8-K

UNITED STATES  

SECURITIES AND EXCHANGE COMMISSION  

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): September 23, 2016

SHIRE PLC

(Exact name of registrant as specified in its charter)

Jersey, Channel Islands	0-29630	98-0601486
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

5 Riverwalk, Citywest Business Campus, Dublin

24, Republic of Ireland
(Address of principal executive offices)

Registrant’s telephone number, including area code:     +353 1 429 7700

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2.):

o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 1.01 Entry into a Material Definitive Agreement.

On September 23, 2016, Shire plc, a Jersey public limited company (“Shire”), announced the completion of the previously announced offering of $3,300,000,000 aggregate principal amount of 1.900% Senior Notes due 2019 (the “2019 Notes”), $3,300,000,000 aggregate principal amount of 2.400% Senior Notes due 2021 (the “2021 Notes”), $2,500,000,000 aggregate principal amount of 2.875% Senior Notes due 2023 (the “2023 Notes”) and $3,000,000,000 aggregate principal amount of 3.200% Senior Notes due 2026 (the “2026 Notes” and, together with the 2019 Notes, the 2021 Notes and the 2023 Notes, the “Notes”) issued by its wholly owned subsidiary, Shire Acquisitions Investments Ireland Designated Activity Company (the “Company”), and guaranteed by Shire. In connection with the issuance of the Notes, the Company and Shire entered into an indenture, dated as of September 23, 2016 (the “Base Indenture”), among the Company, Shire and Deutsche Bank Trust Company Americas, as trustee (the “Trustee”), as supplemented to by a First Supplemental Indenture, dated as of September 23, 2016 (the “First Supplemental Indenture” and together with the Base Indenture, the “Indenture”), among the Company, Shire and the Trustee.

The Notes are the Company’s senior unsecured indebtedness and are fully and unconditionally guaranteed on a senior unsecured basis by Shire. The 2019 Notes bear interest at a rate of 1.900% per annum, accruing from September 23, 2016. The 2019 Notes will mature on September 23, 2019, subject to earlier repurchase or redemption in accordance with the terms of the Indenture. The 2021 Notes bear interest at a rate of 2.400% per annum, accruing from September 23, 2016. The 2021 Notes will mature on September 23, 2021, subject to earlier repurchase or redemption in accordance with the terms of the Indenture. The 2023 Notes bear interest at a rate of 2.875% per annum, accruing from September 23, 2016. The 2023 Notes will mature on September 23, 2023, subject to earlier repurchase or redemption in accordance with the terms of the Indenture. The 2026 Notes bear interest at a rate of 3.200% per annum, accruing from September 23, 2016. The 2026 Notes will mature on September 23, 2026, subject to earlier repurchase or redemption in accordance with the terms of the Indenture. Interest on the Notes is payable semi-annually in arrears on March 23 and September 23 of each year, beginning on March 23, 2017.

At any time and from time to time prior to their maturity date in the case of the 2019 Notes, the date that is one month prior to their maturity date in the case of the 2021 Notes, the date that is two months prior to their maturity date in the case of the 2023 Notes and the date that is three months prior to their maturity date in the case of the 2026 Notes, the Company may redeem some or all of the Notes of the applicable series, upon not less than 30 nor more than 60 days’ prior notice, at a price equal to the greater of (1) 100% of the aggregate principal amount of any Notes being redeemed, plus accrued and unpaid interest to, but excluding, the redemption date and (2)(a) in the case of the 2019 Notes, the sum of the present values of the remaining scheduled payments of principal and interest in respect of the 2019 Notes to be redeemed (not including any portion of interest accrued to, but excluding, the redemption date for the 2019 Notes to be redeemed), discounted to such redemption date, on a semi-annual basis, at the applicable treasury rate plus 15 basis points, plus accrued and unpaid interest to, but excluding, the redemption date of the 2019 Notes to be redeemed and (b) in the case of the 2021 Notes, the 2023 Notes and the 2026 Notes, the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes to be redeemed from the redemption date to, but excluding (in the case of interest) the applicable par call date (not including any portion of the interest accrued to, but excluding, the redemption date), discounted to such redemption date on a semi-annual basis at the applicable treasury rate plus (i) 20 basis points, in the case of the 2021 Notes, (ii) 25 basis points, in the case of the 2023 Notes, and (iii) 25 basis points, in the case of the 2026 Notes, plus, in each case, accrued and unpaid interest to, but excluding, the redemption date. At any time and from time to time on or after August 23, 2021 in the case of the 2021 Notes, July 23, 2023 in the case of the 2023 Notes and June 23, 2026 in the case of the 2026 Notes, the Company may redeem the 2021 Notes, the 2023 Notes or the 2026 Notes, in whole or in part, at its option, at a redemption price equal to 100% of the principal amount of the Notes of such series to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

If the Company experiences certain change of control events with respect to a series of Notes, it must offer to purchase all or any part (equal to $2,000 or an integral multiple of $1,000 in excess thereof) of that holder’s Notes at a purchase price equal to 101% of the principal amount of Notes repurchased, plus accrued and unpaid interest, if any, to, but excluding, the date of purchase.

The Indenture contains covenants that, among other things, restrict Shire’s ability and the ability of certain of its subsidiaries to create secured capital markets indebtedness and Shire’s and the

Company’s ability to consolidate, merge or sell all or substantially all of its and its subsidiaries’ assets, taken as a whole. The Indenture also provides for customary events of default (subject in certain cases to customary grace and cure periods), which include payment defaults, breach of covenants or agreements, certain events of bankruptcy and insolvency and Shire’s guarantee of the Notes being held in any judicial proceeding to be unenforceable or invalid or ceasing to be in full force and effect. These covenants and events of default are subject to a number of important qualifications, limitations and exceptions that are described in the Indenture. If an event of default with respect to the Notes of a series occurs under the Indenture, the principal amount of all of the Notes of such series then outstanding, plus accrued and unpaid interest, if any, to the date of acceleration, may become immediately due and payable.

The Company has used the net proceeds from this offering to fully repay amounts outstanding under its bridge facilities agreement and intends to use any remaining net proceeds for general corporate purposes.

The foregoing summary does not purport to be complete and is qualified in its entirety by reference to the complete terms of the Base Indenture, a copy of which is filed as Exhibit 4.1 hereto, and the First Supplemental Indenture, a copy of which is filed as Exhibit 4.2 hereto. Each of the foregoing documents is incorporated by reference herein.

Item 2.03 Creation of a Direct Financial Obligation or an Obligation under an Off-Balance Sheet Arrangement of a Registrant.

The information included in Item 1.01 with respect to the Indenture is incorporated by reference into this item.

Item 8.01. Other Events

Shire plc has issued the press release attached hereto as Exhibit 99.1 which is incorporated by reference herein.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

To the extent that the Base Indenture or the First Supplemental Indenture included or incorporated by reference as an exhibit to this Current Report on Form 8-K contains representations and warranties by the Company, those representations and warranties were made solely for the benefit of the other parties to the Indenture and (i) were not intended to be treated as categorical statements of fact, but rather as a way of allocating the risk to the Company if those statements prove to be inaccurate; (ii) may have been qualified in the Indenture by disclosures that were made to the other parties in connection with the negotiation of the applicable agreement; (iii) may apply contract standards of “materiality” that are different from “materiality” under the applicable securities laws; and (iv) were made only as of the date of the applicable agreement or such other date or dates as may be specified in the applicable agreement.

We acknowledge that, notwithstanding the inclusion of the foregoing cautionary statements, we are responsible for considering whether additional specific disclosures of material information regarding material contractual provisions are required to make the statements in this Current Report on Form 8-K not misleading.

In addition, in connection with the issuance of the Notes by the Company, each of which are guaranteed by Shire, Shire is filing the following opinions of counsel solely for incorporation into the Registration Statement of the Company and Shire on Form S-3 (File No. 333-213502).

Exhibit Number	Description
4.1	Base Indenture, dated as of September 23, 2016, among the Company, Shire, as guarantor, and Deutsche Bank Trust Company Americas, as trustee.
4.2	First Supplemental Indenture, dated as of September 23, 2016, among the Company, Shire, as guarantor, and Deutsche Bank Trust Company Americas, as trustee.
5.1	Opinion of Davis Polk & Wardwell LLP, U.S. counsel to Shire and the Company.

5.2	Opinion of Mourant Ozannes, Jersey counsel to Shire.
5.3	Opinion of Arthur Cox, Irish counsel to the Company.
23.1	Consent of Davis Polk & Wardwell LLP (included in Exhibit 5.1).
23.2	Consent of Mourant Ozannes (included in Exhibit 5.2).
23.3	Consent of Arthur Cox (included in Exhibit 5.3).

99.1 Press Release dated September 23, 2016

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Shire plc
By:	/s/ W R Mordan
	Name:	Bill Mordan
	Title:	Company Secretary

Date: September 23, 2016

EXHIBIT INDEX

Exhibit Number	Description
4.1	Base Indenture, dated as of September 23, 2016, among the Company, Shire, as guarantor, and Deutsche Bank Trust Company Americas, as trustee.
4.2	First Supplemental Indenture, dated as of September 23, 2016, among the Company, Shire, as guarantor, and Deutsche Bank Trust Company Americas, as trustee.
5.1	Opinion of Davis Polk & Wardwell LLP, U.S. counsel to Shire and the Company.
5.2	Opinion of Mourant Ozannes, Jersey counsel to Shire.
5.3	Opinion of Arthur Cox, Irish counsel to the Company.
23.1	Consent of Davis Polk & Wardwell LLP (included in Exhibit 5.1).
23.2	Consent of Mourant Ozannes (included in Exhibit 5.2).
23.3	Consent of Arthur Cox (included in Exhibit 5.3).
99.1	Press Release dated September 23, 2016

EX-4.1

Exhibit 4.1

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC

as Issuer

SHIRE PLC

as Guarantor

AND

DEUTSCHE BANK TRUST COMPANY AMERICAS

as Trustee

INDENTURE

Dated as of September 23, 2016

CROSS-REFERENCE TABLE

Reconciliation and tie showing the location in the Indenture dated as of September 23, 2016 of the provisions inserted pursuant to Sections 310 to 318(a), inclusive, of the Trust Indenture Act of 1939, as amended. This reconciliation and tie shall not, for any purpose, be deemed to be a part of the Indenture.

Trust Indenture Act of 1939 Section	Indenture Section
310(a)(1)	‎7.09
(a)(2)	‎7.09
(a)(5)	‎7.09
(b)	‎7.08 and ‎7.10
312(a)	‎5.01
313(a)	‎5.03
(c)	‎5.03
314(a)	‎5.02
(c)(1)	‎15.07
(c)(2)	‎15.07
(e)	‎15.07
315(a)	‎7.01
(b)	‎6.08
(c)	‎7.01
(d)	‎7.01
(e)	‎6.09
316(a)(1)	‎6.01 and ‎6.07
(b)	‎6.04
(c)	‎8.02
317(a)	‎6.02
(b)	‎4.04(a)
318(a)	‎15.10

TABLE OF CONTENTS

Page

Article 1 Definitions
Section 1.01.  Definitions	1
Article 2 Description, Execution, Registration and Exchange of Securities
Section 2.01.  Forms	7
Section 2.02.  Amount Unlimited; Issuable in Series	8
Section 2.03.  Authentication	10
Section 2.04.  Date and Denomination of Securities	12
Section 2.05.  Execution of Securities	13
Section 2.06.  Exchange and Registration of Transfer of Securities	13
Section 2.07.  Global Securities	15
Section 2.08.  Mutilated, Destroyed, Lost or Stolen Securities	17
Section 2.09.  Temporary Securities	17
Section 2.10.  Cancellation of Securities Paid, etc	18
Section 2.11.  Computation of Interest	18
Section 2.12.  Form of Legend for Global Securities	19
Section 2.13.  CUSIP Numbers	19
Article 3 Redemption of Securities; Sinking Funds
Section 3.01.  Applicability of Article	19
Section 3.02.  Notice of Redemption; Selection of Securities	20
Section 3.03.  Payment of Securities Called for Redemption	21
Section 3.04.  Satisfaction of Mandatory Sinking Fund Payments with Securities	22
Section 3.05.  Redemption of Securities for Sinking Fund	22
Section 3.06.  Repayment at the Option of the Holder	24
Article 4 Particular Covenants of the Company
Section 4.01.  Payment of Principal, Premium and Interest	24
Section 4.02.  Offices for Notices and Payments, etc	24
Section 4.03.  Appointment to Fill Vacancies in Trustee’s Office	25
Section 4.04.  Provision as to Paying Agent	25
Section 4.05.  Statement as to Compliance	26
Section 4.06.  Additional Amounts	26

Article 5 Securityholder Lists and Reports by the Company and the Trustee
Section 5.01.  Securityholder Lists	27
Section 5.02.  Reports by the Company and the Guarantor	28
Section 5.03.  Reports by the Trustee	28
Article 6 Remedies of the Trustee and Securityholders on Event of Default
Section 6.01.  Events of Default	28
Section 6.02.  Payment of Securities on Default; Suit Therefor	31
Section 6.03.  Application of Moneys Collected by Trustee	33
Section 6.04.  Proceedings by Securityholders	34
Section 6.05.  Proceedings by Trustee	35
Section 6.06.  Remedies Cumulative and Continuing	35
Section 6.07.  Direction of Proceedings and Waiver of Defaults by Securityholders	35
Section 6.08.  Notice of Defaults	36
Section 6.09.  Undertaking to Pay Costs	36
Article 7 Concerning The Trustee
Section 7.01.  Duties and Responsibilities of Trustee	37
Section 7.02.  Reliance on Documents, Opinions, etc	38
Section 7.03.  No Responsibility for Recitals, etc	40
Section 7.04.  Ownership of Securities	41
Section 7.05.  Moneys to be Held in Trust	41
Section 7.06.  Compensation and Expenses of Trustee	41
Section 7.07.  Officer’s Certificate as Evidence	42
Section 7.08.  Disqualification:  Conflicting Interests for the Trustee	42
Section 7.09.  Eligibility of Trustee	42
Section 7.10.  Resignation or Removal of Trustee	43
Section 7.11.  Acceptance by Successor Trustee	44
Section 7.12.  Succession by Merger, etc	45
Section 7.13.  Appointment of Authenticating Agent	46
Article 8 Concerning The Securityholders
Section 8.01.  Action of Securityholders	48
Section 8.02.  Proof of Execution by Securityholders	48
Section 8.03.  Who Are Deemed Absolute Owners	48
Section 8.04.  Company-Owned Securities Disregarded	49
Section 8.05.  Revocation of Consents; Future Holders Bound	49

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Article 9 Securityholders’ Meetings
Section 9.01.  Purposes of Meetings	50
Section 9.02.  Call of Meetings by Trustee	50
Section 9.03.  Call of Meetings by Company or Securityholders	50
Section 9.04.  Qualifications for Voting	51
Section 9.05.  Quorum; Adjourned Meetings	51
Section 9.06.  Regulations	52
Section 9.07.  Voting	52
Section 9.08.  No Delay of Rights by Meeting	53
Article 10 Supplemental Indentures
Section 10.01.  Supplemental Indentures without Consent of Securityholders	53
Section 10.02.  Supplemental Indentures with Consent of Securityholders	55
Section 10.03.  Compliance with Trust Indenture Act; Effect of Supplemental Indentures	57
Section 10.04.  Notation on Securities	57
Section 10.05.  Evidence of Compliance of Supplemental Indenture to be Furnished Trustee	57
Article 11 Consolidation, Merger, Sale or Conveyance
Section 11.01.  Company and Shire May Not Consolidate, etc	57
Section 11.02.  Successor Person to be Substituted	58
Section 11.03.  Documents to be Given Trustee	59
Article 12 Satisfaction and Discharge of Indenture; Defeasance
Section 12.01.  Discharge of Indenture	59
Section 12.02.  Legal Defeasance	60
Section 12.03.  Covenant Defeasance	61
Section 12.04.  Deposited Moneys to be Held in Trust by Trustee; Miscellaneous Provisions	62
Section 12.05.  Paying Agent to Repay Moneys Held	62
Section 12.06.  Return of Unclaimed Moneys	62
Section 12.07.  Reinstatement	63
Article 13 Guarantee
Section 13.01.  Guarantee	63
Section 13.02.  Subrogation; Ranking	64
Section 13.03.  Limitation on Liability	64

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Section 13.04.  Successors and Assigns	65
Section 13.05.  No Waiver	65
Section 13.06.  Termination of Guarantee	65
Article 14 Immunity of Incorporators, Stockholders, Officers, Directors, Employees and Agents
Section 14.01.  Indenture and Securities Solely Corporate Obligations	65
Article 15 Miscellaneous Provisions
Section 15.01.  Provisions Binding on Company’s Successors	66
Section 15.02.  Official Acts by Successor Person	66
Section 15.03.  Addresses for Notices, Notice to Holders, Waiver	66
Section 15.04.  Governing Law	67
Section 15.05.  Process Agent	68
Section 15.06.  Waiver of Trial by Jury	68
Section 15.07.  Evidence of Compliance with Conditions Precedent	68
Section 15.08.  Legal Holidays	68
Section 15.09.  Securities in a Specified Currency other than Dollars	69
Section 15.10.  Trust Indenture Act to Control	69
Section 15.11.  Table of Contents, Headings, etc	69
Section 15.12.  Execution in Counterparts	70
Section 15.13.  Separability; Benefits	70

iv 

THIS INDENTURE, dated as of September 23, 2016, is among SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC, an Irish designated activity company (the “Company”), as Issuer, SHIRE PLC, a Jersey public limited company and parent of the Company (“Shire”), as Guarantor, and DEUTSCHE BANK TRUST COMPANY AMERICAS (the “Trustee”), as Trustee.

RECITALS OF THE COMPANY

WHEREAS, the Company has duly authorized the issue from time to time of its unsecured debentures, notes or other evidences of indebtedness to be issued in one or more series (each, a “Security,” and collectively, the “Securities”) up to such principal amount or amounts as may from time to time be authorized in accordance with the terms of this Indenture; and to provide, among other things, for the authentication, delivery and administration thereof, the Company has duly authorized the execution and delivery of this Indenture,

WHEREAS, all things necessary to make this Indenture a valid indenture and legally binding agreement of the Company according to its terms have been done;

RECITALS OF SHIRE

WHEREAS, Shire desires to make a Guarantee (as defined herein) of the Securities as provided for herein, and has determined that such Guarantee is necessary and convenient to the conduct of the business of the Company, a wholly-owned subsidiary of Shire;

WHEREAS, Shire has duly authorized the execution and delivery of this Indenture to provide for the issuance of its Guarantee as Guarantor (as defined herein) of the Securities as set forth in this Indenture;

WHEREAS, all things necessary to make Shire’s Guarantee and this Indenture a valid indenture and legally binding agreement of Shire according to its terms have been done;

NOW, THEREFORE, THIS INDENTURE WITNESSETH:

That, in consideration of the premises and the purchase of the Securities by the holders thereof, the Company, Shire and the Trustee mutually covenant and agree, for the equal and proportionate benefit of the respective holders from time to time of the Securities of each series thereof, as follows:

Article 1
Definitions

Section 1.01.Definitions. The terms defined in this ‎Section 1.01 (except as herein otherwise expressly provided or unless the context otherwise requires) for all purposes of this Indenture shall have the respective

meanings specified in this ‎Section 1.01. All other terms used in this Indenture which are defined in the Trust Indenture Act, or which are by reference therein defined in the Securities Act (except as herein otherwise expressly provided or unless the context otherwise requires), shall have the meanings assigned to such terms in said Trust Indenture Act and in said Securities Act as in force at the date of this Indenture as originally executed. The words “herein,” “hereof,” and “hereunder” and other words of similar import refer to this Indenture as a whole and not to any particular Article, Section or other subdivision.

“Additional Securities” shall have the meaning specified in ‎Section 2.02.

“Agent” means any Security Registrar, Paying Agent or Authenticating Agent.

“Agent Members” shall have the meaning specified in ‎Section 2.07(g).

“Applicable Law” shall have the meaning specified in ‎Section 7.02(n).

“Applicable Tax Law” shall have the meaning specified in ‎Section 7.02(o).

“Authenticating Agent” shall mean any Person authorized by the Trustee pursuant to ‎Section 7.13 to act on behalf of the Trustee to authenticate Securities.

“Beneficial Owner” shall mean a Person who is the beneficial owner of a beneficial interest in a Global Security as reflected on the books of the Depositary or on the books of a Person maintaining an account with such Depositary (directly as a Depositary participant or as an indirect participant, in each case in accordance with the rules of such Depositary).

“Board of Directors” shall mean the Board of Directors of the Company or the Guarantor, as the case may be, or any Committee of such Board or specified officers and employees of the Company or the Guarantor, as the case may be, to which the powers of such Board have been lawfully delegated.

“Business Day” shall mean, unless otherwise specified, any calendar day that is not a Saturday, Sunday or a day on which commercial banking institutions are not required to be open for business in The City of New York, New York.

“Company” shall mean Shire Acquisitions Investments Ireland DAC, an Irish designated activity company, until any successor designated activity company, corporation or limited liability company shall have become such pursuant to the provisions of ‎Article 11, and thereafter “Company” shall mean such successor, except as otherwise provided in ‎Section 11.02.

“Corporate Trust Office” shall mean, the corporate trust office of the Trustee, currently located at (i) for purposes of surrender, transfer or exchange of any Note, Deutsche Bank Trust Company Americas, c/o DB Services Americas, Inc., 5022 Gate

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Parkway, Suite 200, Jacksonville, FL 32256, Attn: Transfer Department and (ii) for all other purposes, Deutsche Bank Trust Company Americas, Trust and Agency Services, 60 Wall Street, 16th Floor, Mail Stop: NYC60-1630, New York, New York 10005, USA, Attn: Corporates Team.

“Depositary” shall mean, with respect to Securities of any series issuable in whole or in part in the form of one or more Global Securities, a clearing agency registered under the Exchange Act that is designated to act as depositary for such Securities as contemplated by ‎Section 2.07.

“Dollar” shall mean the coin or currency of the United States of America as at the time of payment is legal tender for the payment of public and private debts.

“Event of Default” shall have the meaning specified in ‎Section 6.01.

“Exchange Act” shall mean the Securities Exchange Act of 1934, as amended.

“Guarantee” shall mean the guarantee by the Guarantor pursuant to this Indenture of the obligations of the Company pursuant to this Indenture and pursuant to the Securities of each series issued pursuant to this Indenture.

“Guaranteed Obligations” shall have the meaning specified in ‎Section 13.01.

“Guarantor” shall mean, with respect to the Securities of any series, Shire until a successor designated activity company, corporation or limited liability company shall have become a successor to Shire pursuant to the applicable provisions of this Indenture, and thereafter “Guarantor” shall include such successor designated activity company, corporation or limited liability company.

“Global Security” shall mean a Security that evidences all or part of the Securities of any series and bears the legend set forth in ‎Section 2.12 (or such other legend as may be specified for such Securities as contemplated by ‎Section 2.02).

“Indenture” shall mean this instrument as originally executed or as it may be amended or supplemented from time to time as herein provided, and shall include the form and terms of particular series of Securities established as contemplated hereunder.

“interest,” when used with respect to a non-interest bearing Security, means interest payable after the principal thereof has become due and payable whether at maturity, by declaration of acceleration, by call for redemption, pursuant to a sinking fund, or otherwise.

“mandatory sinking fund payment” shall have the meaning specified in ‎Section 3.01.

“Market Exchange Rate” shall have the meaning set forth in ‎Section 15.09.

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“Officer” shall mean, unless otherwise specified by a provision of this Indenture or the Trust Indenture Act, as applicable, (a) in the case of Shire, the Chief Executive Officer, the Chief Financial Officer, any Executive Vice President, any Senior Vice President or any Vice President, the Treasurer or any Assistant Treasurer, the General Counsel, the Company Secretary or any Assistant Company Secretary of Shire and (b) in the case of the Company, any member of the Board of Directors of the Company.

“Officer’s Certificate” shall mean a certificate signed by an Officer of the Company or the Guarantor, as the case may be, and delivered to the Trustee. Each such certificate shall comply with Section 314 of the Trust Indenture Act and shall include the statements provided for in ‎Section 15.07 if and to the extent required by the provisions of the Trust Indenture Act or ‎Section 15.07, as applicable.

“Opinion of Counsel” shall mean a written opinion from legal counsel, who may be an employee of or of counsel to the Company or to the Guarantor, as the case may be, or may be other counsel, in any case, satisfactory to the Trustee (which may be subject to customary assumptions, limitations and exceptions). Each such opinion shall comply with Section 314 of the Trust Indenture Act and shall include the statements provided for in ‎Section 15.07 if and to the extent required by the provisions of the Trust Indenture Act or ‎Section 15.07, as applicable.

“optional sinking fund payment” shall have the meaning specified in ‎Section 3.01.

“Original Issue Discount Security” shall mean any Security which provides for an amount less than the principal amount thereof to be due and payable upon a declaration of acceleration of the maturity thereof pursuant to ‎Section 6.01.

“Outstanding” shall mean, when used with respect to Securities, subject to the provisions of ‎Section 8.04, as of any particular time, all Securities authenticated and delivered by the Trustee under this Indenture, except:

(a)Securities theretofore cancelled by the Trustee or delivered to the Trustee for cancellation;

(b)Securities, or portions thereof, for the payment or redemption of which moneys in the necessary amount shall have been deposited in trust with the Trustee or with any Paying Agent (other than the Company or the Guarantor), or shall have been set aside and segregated in trust by the Company or the Guarantor, as the case may be (if the Company or the Guarantor shall act as its own Paying Agent), in each case pursuant to ‎Section 12.01; provided that if such Securities are to be redeemed prior to the maturity thereof, notice of such redemption shall have been mailed (or otherwise delivered in accordance with the applicable procedures of the Depositary) as provided in ‎Article 3, or provision satisfactory to the Trustee shall have been made for mailing (or such other delivery) such notice;

 4

(c)Securities as to which defeasance has been effected pursuant to ‎Section 12.02; and

(d)Securities in lieu of or in substitution for which other Securities shall have been authenticated and delivered, or which shall have been paid, pursuant to the terms of ‎Section 2.08, unless proof satisfactory to the Trustee is presented that any such Securities are held by persons in whose hands any of such Securities is a valid, binding and legal obligation of the Company.

In determining whether the holders of the requisite principal amount of Outstanding Securities have given any request, demand, authorization, direction, notice, consent or waiver hereunder, the principal amount of an Original Issue Discount Security that shall be deemed to be Outstanding for such purposes shall be the amount of the principal thereof that would be due and payable as of the date of such determination upon a declaration of acceleration of the maturity thereof pursuant to ‎Section 6.01.

“Overdue Rate” shall mean, with respect to each series of Securities, the rate of interest designated as such in the resolution of the Board of Directors of the Company or the supplemental indenture, as the case may be, relating to such series as contemplated by ‎Section 2.02, or if no such rate is specified, the rate at which such Securities shall bear interest.

“Paying Agent” shall mean any Person authorized by the Company to pay the principal of, premium, if any, and interest, if any, on any Securities on behalf of the Company.

“Person” shall mean any individual, designated activity company, corporation, limited liability company, limited partnership, partnership, joint venture, association, joint stock company, trust, unincorporated organization or government or any agency or political subdivision thereof.

“Principal Office of the Trustee,” or other similar term, shall mean the designated office of the Trustee at which, at any particular time, its corporate trust business with respect to this Indenture shall be administered.

“record date” shall have the meaning set forth in ‎Section 2.04.

“Responsible Officer,” when used with respect to the Trustee, shall mean any vice president, any assistant vice president, any senior associate, any associate, any trust officer or any other officer of the Trustee customarily performing functions similar to those performed by any of the above designated officers and also means, with respect to a particular corporate trust matter, any other officer to whom such matter is referred because of his or her knowledge of and familiarity with the particular subject and who, in each case, shall have direct responsibility for the administration of this Indenture.

“SEC” shall mean the Securities and Exchange Commission.

“Securities Act” shall mean the Securities Act of 1933, as amended. 

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“Security” and “Securities” shall have the meanings set forth in the recitals to this Indenture.

“Security Register” shall have the meaning set forth in ‎Section 2.06.

“Security Registrar” shall have the meaning set forth in ‎Section 2.06.

“Securityholder,” “holder of Securities,” or other similar terms, shall mean any person in whose name at the time a particular Security is registered on the books of the Company kept for that purpose in accordance with the terms hereof.

“Shire” shall mean Shire plc, a Jersey public company and parent of the Company, and the Guarantor of the Securities issued pursuant to this Indenture.

“Specified Currency” shall mean the currency in which a Security is denominated, which may include Dollars, any foreign currency or any composite of two or more currencies.

“Subsidiary” of any specified Person shall mean (a) any corporation of which such Person directly or indirectly owns or controls at that time at least a majority of the outstanding Voting Stock or (b) any other Person (other than a corporation) in which such Person directly or indirectly has at least a majority ownership interest and power to direct the policies, management and affairs thereto.

“Trust Indenture Act” shall mean the Trust Indenture Act of 1939, as it was in force at the date of execution of this Indenture (except as provided in ‎Section 10.01(e) and ‎Section 10.03).

“Trustee” shall mean the corporation or association named as Trustee in this Indenture and, subject to the provisions of ‎Article 7, shall also include its successors and assigns as Trustee hereunder. If pursuant to the provisions of this Indenture there shall be at any time more than one Trustee hereunder, the term “Trustee” as used with respect to the Securities of any series shall mean the Trustee with respect to the Securities of such series.

“U.S. Government Obligations” shall mean:

(a)any security which is (i) a direct obligation of the United States of America for the payment of which its full faith and credit is pledged or (ii) an obligation of a Person controlled or supervised by and acting as an agency or instrumentality of the United States of America, the payment of which is unconditionally guaranteed as a full faith and credit obligation by the United States of America, which, in each case, is not callable or redeemable at the option of the issuer thereof; and

(b)any depositary receipt issued by a bank (as defined in Section 3(a)(2) of the Securities Act) as custodian with respect to any U.S. Government Obligation specified in clause (a) above and held by such bank for the account of the holder of such depositary receipt, or with respect to any specific payment of principal of or interest on any U.S.

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Government Obligation so specified and held; provided that (except as required by law) such custodian is not authorized to make any deduction from the amount payable to the holder of such depositary receipt from any amount received by the custodian in respect of the U.S. Government Obligation or the specific payment of principal or interest evidenced by such depositary receipt.

“Voting Stock” of any specified Person as of any date shall mean the capital stock of such Person of the class or classes having general voting power under ordinary circumstances to elect at least a majority of the board of directors, managers or trustees of such Person; provided that, for the purposes hereof, capital stock which carries only the right to vote conditionally on the happening of an event shall not be considered “Voting Stock” whether or not such event shall have happened.

Article 2
Description, Execution, Registration and Exchange of Securities

Section 2.01.Forms. (a) The Securities of each series shall be in substantially such form as shall be established by or pursuant to a resolution of the Board of Directors of the Company or in one or more indentures supplemental hereto, in each case with such appropriate insertions, omissions, substitutions and other variations as are required or permitted by this Indenture, and may have such legends or endorsements placed thereon as the Officer executing the same may approve (execution thereof to be conclusive evidence of such approval) and as are not inconsistent with the provisions of this Indenture, or as may be required to comply with any law or with any rule or regulation made pursuant thereto or with any rule or regulation of any stock exchange on which the Securities of such series may be listed, or to conform to usage.

(b)The resolutions adopted by the Board of Directors of the Company or one or more indentures supplemental hereto establishing the form and terms of the Securities of any series pursuant to Sections ‎2.01 and ‎2.02, respectively, of this Indenture, may provide for issuance of Global Securities. If Securities of a series are so authorized to be issued as Global Securities, any such Global Security may provide that it shall represent that aggregate amount of Securities from time to time endorsed thereon, and may also provide that the aggregate amount of Outstanding Securities represented thereby may from time to time be reduced to reflect exchanges. Any endorsement of a Global Security to reflect the amount, or any increase or decrease in the amount or changes in the rights of holders of Securities represented thereby, shall be made in such manner and by such person or persons as shall be specified therein.

(c)The Trustee’s Certificate of Authentication on all Securities shall be in substantially the following form:

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This is one of the Securities of the series designated therein described in the within-mentioned Indenture.

Deutsche Bank Trust Company Americas, not in its individual capacity but solely as Trustee
By:
	Authorized Signatory

Section 2.02.Amount Unlimited; Issuable in Series. The aggregate principal amount of Securities which may be authenticated and delivered under this Indenture is unlimited.

The Securities may be issued in one or more series. There shall be established by or pursuant to a resolution of the Board of Directors of the Company or established in one or more indentures supplemental hereto, prior to the issuance of Securities of any series:

(a)the title of the Securities of such series (which shall distinguish the Securities of such series from all other Securities);

(b)any limit upon the aggregate principal amount of the Securities of such series which may be authenticated and delivered under this Indenture (except for Securities authenticated and delivered upon registration of transfer of, or in exchange for, or in lieu of, other Securities of such series pursuant to Sections ‎2.06, ‎2.08, ‎2.09, ‎3.03, ‎3.06 or ‎10.04);

(c)the date or dates on which the principal and premium, if any, of the Securities of such series are payable;

(d)the rate or rates, or the method of determination thereof, at which the Securities of such series shall bear interest, if any, the date or dates from which such interest shall accrue, the interest payment dates on which such interest shall be payable and, if other than as set forth in ‎Section 2.04, the record dates for the determination of holders to whom interest is payable;

(e)in addition to the office or agency of the Company in the Borough of Manhattan, The City of New York required to be maintained pursuant to ‎Section 4.02, any other place or places where the principal of, and premium, if any, and any interest on Securities of such series shall be payable;

(f)the Specified Currency of the Securities of such series;

(g)the currency or currencies in which payments on the Securities of such series are payable, if other than the Specified Currency;

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(h)the price or prices at which, the period or periods within which and the terms and conditions upon which Securities of such series may be redeemed, in whole or in part, at the option of the Company, pursuant to any sinking fund or otherwise;

(i)the obligation, if any, of the Company to redeem, purchase or repay Securities of such series pursuant to any sinking fund or analogous provisions or at the option of a holder thereof and the price at which or process by which and the period or periods within which and the terms and conditions upon which Securities of such series shall be redeemed, purchased or repaid, in whole or in part, pursuant to such obligation;

(j)if other than minimum denominations of $2,000 and any integral multiple of $1,000 in excess thereof, the denominations in which Securities of such series shall be issuable;

(k)if other than the principal amount thereof, the portion of the principal amount of Securities of such series which shall be payable upon declaration of acceleration of the maturity thereof pursuant to ‎Section 6.01;

(l)if the principal of or interest on the Securities of such series are to be payable, at the election of the Company or a holder thereof, in a coin or currency other than the Specified Currency, the period or periods within which, and the terms and conditions upon which, such election may be made;

(m)if the amount of payments of principal of and interest on the Securities of such series may be determined with reference to an index based on a coin or currency other than the Specified Currency, the manner in which such amounts shall be determined;

(n)whether and under what circumstances additional amounts shall be payable in respect of any tax, assessment or governmental charge withheld or deducted;

(o)any addition to, or modification of, any Events of Default set forth in ‎Article 6 with respect to the Securities of such series, and whether any such additional or modified Events of Default shall be subject to covenant defeasance under ‎Section 12.03;

(p)any addition to, or modification of, the terms of a Guarantee (including provisions relating to seniority or subordination of such Guarantee and the release of such Guarantee or of the Guarantor of the Securities of such series) of any payment or other obligations on such Securities, and any additions or changes to this Indenture to permit or facilitate guarantees of such Securities;

(q)if other than the rate of interest stated in the title of the Securities of such series, the applicable Overdue Rate;

(r)in the case of any series of non-interest bearing Securities, the applicable dates for purposes of ‎Section 5.01(a);

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(s)if a Person other than Deutsche Bank Trust Company Americas is to act as Trustee for the Securities of such series, the name and Principal Office of such Trustee;

(t)if either or both of Sections ‎12.02 and ‎12.03 do not apply to any Securities of such series;

(u)if applicable, that any Securities of such series shall be issuable in whole or in part in the form of one or more Global Securities and, in such case, the name of the respective Depositaries for such Global Securities, the form of any legend or legends which shall be borne by any such Global Security in addition to or in lieu of that set forth in ‎Section 2.12 and any circumstances in addition to or in lieu of those set forth in clause ‎(b) of ‎Section 2.06 in which any such Global Security may be exchanged in whole or in part for Securities registered, and any transfer of such Global Security in whole or in part may be registered, in the name or names of Persons other than the Depositary for such Global Security or a nominee thereof;

(v)any addition to, or modification of, any covenants set forth in ‎Article 4 with respect to the Securities of such series, and whether any such additional or modified covenant shall be subject to covenant defeasance under ‎Section 12.03; and

(w)any other terms of such series.

All Securities of any one series shall be substantially identical except as to denomination, and except as may otherwise be provided in or pursuant to such resolution of the Board of Directors of the Company or in any such indenture supplemental hereto.

Unless otherwise expressly provided with respect to a series of Securities, the Company may, from time to time, without the consent of the Securityholders of Securities of a particular series, issue additional Securities (“Additional Securities”) of such series having the same ranking and the same interest rate, maturity and other terms as the Securities of such series, except for the public offering price, the issue date and, if applicable, the initial interest payment date and initial interest accrual date. Any such Additional Securities, together with the initial Securities of such series, shall constitute a single series of Securities under this Indenture; provided that if the Additional Securities are not fungible for U.S. federal income tax purposes with the initial Securities of such series, the Additional Securities shall be issued with a separate CUSIP number. No Additional Securities may be issued if an Event of Default has occurred and is continuing with respect to the series of Securities of which such Additional Securities would be a part. Unless the context otherwise requires, for all purposes of this Indenture, references to the Securities of a series include any Additional Securities of such series actually issued.

Section 2.03.Authentication. At any time and from time to time after the execution and delivery of this Indenture, the Company may deliver Securities of any series executed by the Company to the Trustee for authentication. Except as otherwise provided in this ‎Article 2, the Trustee shall thereupon authenticate and deliver said Securities to or upon the written

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order of the Company, signed by an authorized Officer of the Company. In authenticating such Securities, and accepting the additional responsibilities under this Indenture in relation to such Securities, the Trustee shall be entitled to receive and (subject to ‎Section 7.01) shall be fully protected in relying upon:

(a)a copy of any resolution or resolutions of the Board of Directors of the Company relating thereto and, if applicable, an appropriate record of any action taken pursuant to such resolution, in each case certified by the Secretary or an Assistant Secretary of the Company;

(b)an executed supplemental indenture, if any, relating thereto;

(c)an Officer’s Certificate prepared in accordance with ‎Section 15.07 which shall also state to the best knowledge of the signer of such Certificate that no Event of Default with respect to any series of Securities shall have occurred and be continuing; and

(d)an Opinion of Counsel prepared in accordance with ‎Section 15.07 to the effect:

(i)that the form of such Securities has been established by or pursuant to a resolution of the Board of Directors of the Company, or by a supplemental indenture as permitted by ‎Section 2.01, in conformity with the provisions of this Indenture;

(ii)that the terms of such Securities have been established by or pursuant to a resolution of the Board of Directors of the Company, or by a supplemental indenture as permitted by ‎Section 2.02, in conformity with the provisions of this Indenture;

(iii)that the Company has all requisite corporate power and authority to execute and deliver such Securities;

(iv)that the execution and delivery of such Securities by the Company have been duly authorized by all necessary corporate action on the part of the Company;

(v)that such Securities have been duly and validly executed, and when duly authenticated by the Trustee and issued by the Company, in the manner and subject to any conditions specified in such Opinion of Counsel, will constitute the legal, valid and binding obligations of the Company, enforceable against it in accordance with their terms, subject to applicable bankruptcy, insolvency, fraudulent conveyance, reorganization, moratorium and similar laws affecting creditors’ rights and remedies generally, and subject, as to enforceability, to general principles of equity, including principles of commercial reasonableness, good faith and fair dealing (regardless of whether enforcement is sought in a proceeding at law or in equity); and

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(vi)that the execution and delivery by the Company of such Securities, and the performance by the Company of its obligations thereunder will not conflict with, constitute a default under or violate any of the terms, conditions or provisions of the organizational certificate or bylaws of the Company.

The Trustee shall have the right to decline to authenticate and deliver or cause to be authenticated and delivered any Securities under this ‎Section 2.03 if the Trustee, being advised by counsel, determines that such action may not lawfully be taken or if the Trustee in good faith by its trust committee shall determine that such action would expose the Trustee to personal liability to existing Securityholders.

Section 2.04.Date and Denomination of Securities. The Securities of each series shall be issuable in registered form without coupons in such denominations as shall be specified as contemplated by ‎Section 2.02. In the absence of any such specification with respect to the Securities of any series, the Securities of such series shall be issuable in minimum denominations of $2,000 and any integral multiple of $1,000 in excess thereof. Securities of each series shall be numbered, lettered or otherwise distinguished in such manner or in accordance with such plan as the Officer of the Company executing the same may determine.

Every Security shall be dated the date of its authentication.

The person in whose name any Security of a particular series is registered at the close of business on any record date (as hereinafter defined) with respect to any interest payment date for such series shall be entitled to receive the interest payable on such interest payment date notwithstanding the cancellation of such Security upon any registration of transfer or exchange subsequent to the record date and prior to such interest payment date; provided, however, that if and to the extent that the Company shall default in the payment of the interest due on such interest payment date, such defaulted interest shall be paid to the persons in whose names Outstanding Securities of such series are registered on a subsequent record date established by notice given by mail by or on behalf of the Company to the holders of such Securities not less than 15 days preceding such subsequent record date, such record date to be not less than five days preceding the date of payment of such defaulted interest. Except as otherwise specified as contemplated by ‎Section 2.02 for Securities of a particular series, the term “record date” as used in this ‎Section 2.04 with respect to any regular interest payment date, shall mean either (i) the first day of the calendar month in which such interest payment date occurs if such interest payment date is the fifteenth day of such calendar month or (ii) the fifteenth day of the calendar month preceding the calendar month in which such interest payment date occurs if such interest payment date is the first day of a calendar month, whether or not such day shall be a Business Day.

Interest on definitive certificated Securities may at the option of the Company be paid by check mailed to the persons entitled thereto at their respective addresses as such appear on the Security Register.

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Section 2.05.Execution of Securities. The Securities shall be signed in the name and on behalf of the Company by the manual or facsimile signature of an Officer of the Company. Only such Securities as shall bear thereon a certificate of authentication substantially in the form herein recited, executed by the Trustee by the manual signature of an authorized officer, shall be entitled to the benefits of this Indenture or be valid or obligatory for any purpose. Such certificate by the Trustee upon any Security executed by the Company shall be conclusive evidence that the Security so authenticated has been duly authenticated and delivered hereunder and that the holder is entitled to the benefits of this Indenture.

In case any Officer of the Company who shall have signed any of the Securities shall cease to be such Officer before the Securities so signed shall have been authenticated and delivered by the Trustee, or disposed of by the Company, such Securities nevertheless may be authenticated and delivered or disposed of as though the person who signed such Securities had not ceased to be such Officer of the Company; and any Security may be signed on behalf of the Company by such persons as, at the actual date of the execution of such Security, shall be the proper Officers of the Company, although at the date of the execution of this Indenture any such person was not such an Officer.

Section 2.06.Exchange and Registration of Transfer of Securities. Securities of any series may be exchanged for a like aggregate principal amount of Securities of the same series of other authorized denominations. Securities to be exchanged shall be surrendered, at the option of the holders thereof, either at the office or agency designated and maintained by the Company for such purpose in accordance with the provisions of ‎Section 4.02 or at any of such other offices or agencies as may be designated and maintained by the Company for such purpose in accordance with the provisions of ‎Section 4.02, and the Company shall execute and register and the Trustee shall authenticate and deliver in exchange therefor the Security or Securities which the Securityholder making the exchange shall be entitled to receive. Each person designated by the Company pursuant to the provisions of ‎Section 4.02 as a person authorized to register and register transfer of the Securities is sometimes herein referred to as a “Security Registrar.” Deutsche Bank Trust Company Americas is appointed Security Registrar and Paying Agent.

The Company shall keep, at each such office or agency, a register for each series of Securities issued hereunder (the registers of all Security Registrars, collectively, the “Security Register”) in which, subject to such reasonable regulations as it may prescribe, the Company shall register Securities and shall register the transfer of Securities as in this ‎Article 2 provided. In accordance with the provisions of Section 216 and 1121 of the Companies Act 2014 of Ireland the Security Register shall be maintained in Ireland by the Company; in addition, a duplicate register may be maintained in the United States of America by the Security Registrar. The Security Register shall be in written form or in any other form capable of being converted into written form within a reasonable time. At

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all reasonable times the Security Register shall be open for inspection by the Trustee and any Security Registrar other than the Trustee. Upon due presentment for registration or registration of transfer of any Security of any series at any designated office or agency, the Company shall execute and register and the Trustee shall authenticate and deliver in the name of the transferee or transferees a new Security or Securities of the same series for an equal aggregate principal amount. Registration or registration of transfer of any Security by any Security Registrar in the Security Register maintained by such Security Registrar, and delivery of such Security, duly authenticated, shall be deemed to complete the registration or registration of transfer of such Security. Notwithstanding anything herein to the contrary, there shall only be one Security Register for each series of Securities.

No person shall at any time be designated as or act as a Security Registrar unless such person is at such time empowered under applicable law to act as such under and to the extent required by applicable law and regulations.

All Securities presented for registration of transfer or for exchange, redemption or payment shall (if so required by the Company or the Trustee) be duly endorsed by, or be accompanied by a written instrument or instruments of transfer or exchange in form and substance satisfactory to the Company and the Trustee duly executed by, the applicable Securityholder or his attorney duly authorized in writing, together with such documentation as may be reasonably required by the Trustee or the Security Registrar.

No service charge shall be made for any exchange or registration of transfer of Securities, but the Company may require payment of a sum sufficient to cover any tax or other governmental charge that may be imposed in connection therewith.

The Company shall not be required to exchange or register a transfer of (a) any Securities of any series for the period of 15 days next preceding the selection of Securities of that series to be redeemed and thereafter until the date of the mailing (or other delivery in accordance with the applicable procedures of the Depositary) of a notice of redemption of Securities of that series selected for redemption, or (b) any Securities selected, called or being called for redemption in whole or in part except, in the case of any Security to be redeemed in part, the portion thereof not so to be redeemed.

None of the Trustee or Agents shall have any responsibility or obligation to any beneficial owner of an interest in a Global Security, any Agent Member or other member of, or a participant in, DTC or other person with respect to the accuracy of the records of DTC or any nominee or participant or member thereof, with respect to any ownership interest in the Securities or with respect to the delivery to any Agent Member or other participant, member, beneficial owner or other person (other than DTC) of any notice or the payment of any amount or delivery of any Securities (or other security or property) under or with respect to such Securities. All notices and communications to be given to the holders and all payments to be made to holders in respect of the Securities shall be given or made only to or upon the order of the registered holders (which shall be DTC or its nominee in the case of a Global Security). The rights of beneficial owners in any Global Security shall be exercised only through DTC, subject to its applicable rules and

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procedures. The Trustee and Agents may rely and shall be fully protected in relying upon information furnished by DTC with respect to its Agent Members and other members, participants and any beneficial owners.

No holder of any beneficial interest in any Global Security held on its behalf by a U.S. Depositary or Depositary shall have any rights under this Indenture with respect to such Global Security, and such U.S. Depositary or Depositary may be treated by the Company, the Trustee, and any agent of the Company or the Trustee as the owner of such Global Security for all purposes whatsoever. None of the Company, the Trustee, any Paying Agent or the Security Registrar will have any responsibility or liability for any aspect of the records relating to or payments made on account of beneficial ownership interests of a Global Security or for maintaining, supervising or reviewing any records relating to such beneficial ownership interests.

Subject to applicable law, each Securityholder agrees to indemnify the Company and the Trustee against any liability that may result from the transfer, exchange, or assignment of such Securityholder’s Security in violation of any provision of this Indenture and/or applicable United States Federal or state securities law.

Section 2.07.Global Securities. The provisions of this ‎Section 2.07 shall apply only to Global Securities.

(a)Each Global Security authenticated under this Indenture shall be registered in the name of the Depositary designated for such Global Security or a nominee thereof and delivered to such Depositary or nominee thereof or custodian therefor, and each such Global Security shall constitute a single Security for all purposes under this Indenture.

(b)Notwithstanding any other provision in this Indenture, no Global Security evidencing the Securities of any series may be exchanged in whole or in part for Securities of such series registered, and no transfer of a Global Security in whole or in part may be registered, in the name of any Person other than the Depositary for such Global Security or a nominee thereof unless (i) such Depositary has notified the Company that it is unwilling or unable to continue its services as Depositary for such Global Security and no successor Depositary has been appointed within 90 days after such notice, (ii) such Depositary ceases to be a “clearing agency” registered under Section 17A of the Exchange Act when the Depositary is required to be so registered to act as the Depositary and no successor Depositary has been appointed within 90 days of the Company becoming aware of such failure to be so registered, (iii) the Company determines at any time that the Securities of such series shall no longer be represented by Global Securities, in which case the Company shall inform such Depositary of such determination and participants in such Depositary may elect to withdraw their beneficial interests in the Securities from such Depositary, or (iv) any event shall have occurred and be continuing which, after notice or lapse of time, or both, would constitute an Event of Default with respect to such series of Securities, and such exchange is requested by or on behalf of the Depositary in accordance with customary procedures following the request of a Beneficial Owner seeking to exercise or enforce its rights under the Securities of such series.

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(c)Subject to ‎Section 2.07(b), any exchange of a Global Security for other Securities may be made in whole or in part, and all Securities issued in exchange for a Global Security or any portion thereof shall be in registered form and in such names as the Depositary for such Global Security shall direct.

(d)Every Security authenticated and delivered upon registration of transfer of, or in exchange for or in lieu of, a Global Security or any portion thereof shall be authenticated and delivered in the form of, and shall be, a Global Security, unless such Security is registered in the name of a Person other than the Depositary for such Global Security or a nominee thereof.

(e)Subject to the provisions of ‎Section 2.07(g), the registered Securityholder may grant proxies and otherwise authorize any Person, including Agent Members and Persons that may hold interests through Agent Members, to take any action which a Securityholder is entitled to take under this Indenture or the Securities.

(f)In the event of the occurrence of any of the events specified in ‎Section 2.07(b), (i) the Company shall promptly make available to the Trustee a reasonable supply of such certificated Securities in definitive, fully registered form, without interest coupons, and (ii) the Trustee shall promptly exchange each beneficial interest in the applicable Global Security for one or more certificated Securities in definitive, fully registered form, without interest coupons, in authorized denominations having an equal aggregate principal amount registered in the name of the owner of such beneficial interest, as identified to the Trustee by the Depositary, and thereupon such Global Security will be deemed canceled.

(g)Neither any members of, or participants in, the Depositary (collectively, the “Agent Members”) nor any other Persons on whose behalf Agent Members may act, shall have any rights under this Indenture with respect to any Global Security registered in the name of the Depositary or any nominee thereof, or under any such Global Security, and the Depositary or such nominee, as the case may be, may be treated by the Company, the Trustee and any agent of the Company or the Trustee as the absolute owner and holder of such Global Security for all purposes whatsoever. Notwithstanding the foregoing, nothing herein shall prevent the Company or the Trustee or any agent of the Company or the Trustee from giving effect to any written certification, proxy or other authorization furnished by the Depositary or such nominee, as the case may be, or impair, as between the Depositary, its Agent Members and any other Person on whose behalf an Agent Member may act, the operation of customary practices of such Persons governing the exercise of the rights of a holder of any Security.

(h)The Trustee shall have no obligation or duty to monitor, determine or inquire as to compliance with any restrictions on transfer imposed under this Indenture or under applicable law with respect to any transfer of any interest in any Security (including any transfers between or among Agent Members or beneficial owners of interests in any Global Security) other than to require delivery of such certificates and other documentation or evidence as are expressly required by, and to do so if and when

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expressly required by the terms of, this Indenture, and to examine the same to determine substantial compliance as to form with the express requirements hereof.

(i)Neither the Trustee nor any Agent shall have any responsibility or liability for any actions taken or not taken by the Depositary.

Section 2.08.Mutilated, Destroyed, Lost or Stolen Securities. In case any temporary or definitive Security shall become mutilated or be destroyed, lost or stolen, the Company (in the case of a mutilated Security) shall, and the Company may in its discretion (in the case of a destroyed, lost or stolen Security), execute and, upon the written request or authorization of any Officer of the Company, the Trustee shall authenticate and deliver, a new Security of the same series, bearing a number not contemporaneously Outstanding, in exchange and substitution for the mutilated Security, or in lieu of and in substitution for the Security so destroyed, lost or stolen. In every case the applicant for a substituted Security shall furnish to the Company and to the Trustee such security or indemnity as may be required by them to save each of them harmless, and, in every case of destruction, loss or theft, the applicant shall also furnish to the Company and to the Trustee evidence to their satisfaction of the destruction, loss or theft of such Security and the ownership thereof.

Upon the issuance of any substituted Security, the Company may require the payment of a sum sufficient to cover any tax or other governmental charge that may be imposed in relation thereto and any other expenses connected therewith. In case any Security which has matured or is about to mature shall become mutilated or be destroyed, lost or stolen, the Company may, instead of issuing a substituted Security, pay or authorize the payment of the same (without surrender thereof except in the case of a mutilated Security) if the applicant for such payment shall furnish to the Company and to the Trustee such security or indemnity as may be required by them to save each of them harmless and, in case of destruction, loss or theft, evidence satisfactory to the Company and the Trustee of the destruction, loss or theft of such Security and the ownership thereof.

Every substituted Security issued pursuant to the provisions of this ‎Section 2.08 by virtue of the fact that any Security is destroyed, lost or stolen shall constitute an additional contractual obligation of the Company, whether or not the destroyed, lost or stolen Security shall be found at any time, and shall be entitled to all the benefits of this Indenture equally and proportionately with any and all other Securities of the same series duly issued hereunder. All Securities shall be held and owned upon the express condition that the foregoing provisions are exclusive with respect to the replacement or payment of mutilated, destroyed, lost or stolen Securities and shall preclude (to the extent lawful) any and all other rights or remedies with respect to the replacement or payment of negotiable instruments or other securities without their surrender.

Section 2.09.Temporary Securities. Pending the preparation of definitive Securities of any series the Company may execute and the Trustee

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shall authenticate and deliver temporary Securities (printed, lithographed or typewritten). Temporary Securities shall be issuable in any authorized denomination and substantially in the form of the definitive Securities in lieu of which they are issued, but with such omissions, insertions and variations as may be appropriate for temporary Securities, all as may be determined by the Company. Every such temporary Security shall be authenticated by the Trustee upon the same conditions and in substantially the same manner, and with the same effect, as the definitive Securities in lieu of which they are issued. Without unreasonable delay, the Company shall execute and deliver to the Trustee definitive Securities of such series, and thereupon any or all temporary Securities of such series may be surrendered in exchange therefor, at the option of the holders thereof, either at the office or agency to be designated and maintained by the Company for such purpose in accordance with the provisions of ‎Section 4.02 or at any of such other offices or agencies as may be designated and maintained by the Company for such purpose in accordance with the provisions of ‎Section 4.02, and the Trustee shall authenticate and deliver in exchange for such temporary Securities an equal aggregate principal amount of definitive Securities of the same series. Such exchange shall be made by the Company at its own expense and without any charge therefor. Until so exchanged, the temporary Securities of any series shall in all respects be entitled to the same benefits under this Indenture as definitive Securities of the same series authenticated and delivered hereunder.

Section 2.10.Cancellation of Securities Paid, etc. All Securities surrendered for the purpose of payment, redemption, repayment, exchange or registration of transfer or for credit against any sinking fund shall, if surrendered to the Company, any Security Registrar, any Paying Agent or any other agent of the Company or of the Trustee, be delivered to the Trustee and upon receipt of written direction from the Company promptly cancelled by it, or, if surrendered to the Trustee, shall be promptly cancelled by it, and no Securities shall be issued in lieu thereof except as expressly permitted by any of the provisions of this Indenture. The Trustee may dispose of cancelled Securities in accordance with its customary practices and procedures in effect from time to time and, at the written request of the Company, shall deliver confirmation of such cancellation to the Company. If the Company shall acquire any of the Securities, however, such acquisition shall not operate as a redemption or satisfaction of the indebtedness represented by such Securities unless and until the same are delivered to the Trustee for cancellation.

Section 2.11.Computation of Interest. Except as otherwise specified as contemplated by ‎Section 2.02 for Securities of any series, interest on the Securities of each series shall be computed on the basis of a 360-day year of twelve 30-day months.

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Section 2.12.Form of Legend for Global Securities. Unless otherwise specified as contemplated by ‎Section 2.02 for the Securities evidenced thereby, every Global Security authenticated and delivered hereunder shall bear a legend in substantially the following form (or such other form as a securities exchange or Depositary may request or require):

THIS SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF THE DEPOSITORY TRUST COMPANY, A NEW YORK CORPORATION (“DTC”), OR A NOMINEE OF DTC. THIS SECURITY IS EXCHANGEABLE FOR SECURITIES REGISTERED IN THE NAME OF A PERSON OTHER THAN DTC OR ITS NOMINEE ONLY IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE AND MAY NOT BE TRANSFERRED EXCEPT AS A WHOLE BY DTC TO A NOMINEE OF DTC, OR BY A NOMINEE OF DTC TO DTC OR ANOTHER NOMINEE OF DTC.

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF DTC, TO THE ISSUER OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF CEDE & CO. OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC (AND ANY PAYMENT IS MADE TO CEDE & CO. OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC), ANY TRANSFER, PLEDGE, OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, CEDE & CO., HAS AN INTEREST HEREIN.

Section 2.13.CUSIP Numbers. The Company in issuing the Securities may use “CUSIP” numbers (if then generally in use), and, if so, the Trustee shall use “CUSIP” numbers in notices of redemption as a convenience to Securityholders; provided that any such notice may state that no representation is made as to the correctness of such numbers, either as printed on the Securities or as contained in any notice of a redemption, and that reliance may be placed only on the other identification numbers printed on the Securities, and any such redemption shall not be affected by any defect in or omission of such numbers. The Company shall promptly notify the Trustee of any changes in the “CUSIP” numbers of any series of Securities.

Article 3
Redemption of Securities; Sinking Funds

Section 3.01.Applicability of Article. The provisions of this ‎Article 3 shall be applicable, as the case may be, (a) to the Securities of any series which are redeemable before their maturity and (b) to any sinking fund for the retirement of Securities of any series, in either case except as

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otherwise specified as contemplated by ‎Section 2.02 for Securities of such series.

The minimum amount of any sinking fund payment provided for by the terms of Securities of any series is herein referred to as a “mandatory sinking fund payment,” and any payment in excess of such minimum amount provided for by the terms of Securities of any series is herein referred to as an “optional sinking fund payment.”

Section 3.02.Notice of Redemption; Selection of Securities. In case the Company shall desire to exercise any right to redeem all, or, as the case may be, any part of, the Securities of any series in accordance with their terms, it shall fix a date for redemption at least 40 days prior to such redemption date (unless a shorter notice shall be satisfactory to the Trustee), notify the Trustee of such redemption date and the principal amount of such Securities to be redeemed and provide an Officer’s Certificate and Opinion of Counsel to the Trustee. The Company shall then mail (or otherwise deliver in accordance with the applicable procedures of the Depositary) a notice of such redemption at least 30 and not more than 60 days prior to the date fixed for redemption to the holders of Securities of such series so to be redeemed as a whole or in part at their last addresses as the same appear on the Security Register and to the Trustee, except as the supplemental indenture or resolutions adopted by the Board of Directors of the Company to establish the terms of any series of Securities may otherwise provide. Such mailing shall be by first class mail (or otherwise delivered in accordance with applicable Depositary procedures). The notice if mailed (or otherwise delivered in accordance with applicable Depositary procedures) in the manner herein provided shall be conclusively presumed to have been duly given, whether or not the holder receives such notice. In any case, failure to give such notice by mail (or otherwise deliver in accordance with the applicable procedures of the Depositary) or any defect in the notice to the holder of any Security of a series designated for redemption as a whole or in part shall not affect the validity of the proceedings for the redemption of any other Security of such series.

Each such notice of redemption shall specify (i) the date fixed for redemption, (ii) the redemption price at which the Securities of such series are to be redeemed (or if not then ascertainable, the manner of calculation thereof), (iii) the place or places of payment, (iv) that payment will be made upon presentation and surrender of such Securities, (v) that any interest accrued to the date fixed for redemption will be paid as specified in said notice, (vi) that on and after said date if the redemption price in full has been deposited by the Company with the Trustee any interest thereon or on the portions thereof to be redeemed will cease to accrue, (vii) that the redemption is for a sinking fund, if such is the case, (viii) the specific provision of this Indenture pursuant to which such Securities are to be redeemed, (ix) the CUSIP number, and (x) that no representation is made as to the correctness of such CUSIP numbers contained in the notice of redemption and that reliance may be placed on the other identification numbers printed on the Securities, and any redemption shall not be affected by any defect in or omission of such numbers.

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Where the redemption price is not ascertainable at the time the notice of redemption is given as aforesaid, the Company shall notify the Trustee of said redemption price promptly after the calculation thereof. If less than all the Securities of a series are to be redeemed, the notice of redemption shall specify the number or numbers of the Securities of that series to be redeemed. In case any Security of a series is to be redeemed in part only, the notice of redemption shall state the portion of the principal amount thereof to be redeemed and shall state that on and after the date fixed for redemption, upon surrender of such Security, a new Security or Securities of that series in principal amount equal to the unredeemed portion thereof will be issued. Notice of redemption of Securities to be redeemed at the election of the Company shall be given by the Company or, at the Company’s written request and with the notice information provided to the Trustee, by the Trustee in the name and at the expense of the Company, and shall be irrevocable; provided that, in the latter case, the Company shall give the Trustee at least ten days prior notice of the date of the giving of the notice (unless a shorter notice shall be satisfactory to the Trustee).

On or prior to the redemption date specified in the notice of redemption given as provided in this ‎Section 3.02, the Company shall deposit with the Trustee or with one or more Paying Agents (or, if the Company is acting as its own Paying Agent, shall segregate and hold in trust as provided in ‎Section 4.04) an amount of money sufficient to redeem on the redemption date all the Securities or portions thereof so called for redemption, together with accrued interest to the date fixed for redemption. The Company shall give the Trustee written notice not less than 40 days (or such shorter period as may be acceptable to the Trustee) prior to the redemption date as to the aggregate principal amount of Securities of such series to be redeemed, and in the case of a partial redemption, the Securities shall be selected pro rata or, in the case of Global Securities, in accordance with the applicable policies and procedures of the Depositary, the Securities of that series or portions thereof to be redeemed. Securities of a series may be redeemed in part only in multiples of the smallest authorized denomination of that series.

Beneficial interests in Securities represented by Global Securities shall be selected for redemption by the Depositary therefor in accordance with its standard procedures. In the case of any redemption of Securities (a) prior to the expiration of any restriction on such redemption provided in the terms of such Securities or (b) pursuant to an election of the Company which is subject to a condition specified in the terms of such Securities, the Company shall furnish the Trustee with an Officer’s Certificate and an Opinion of Counsel evidencing compliance with such restriction or condition.

Section 3.03.Payment of Securities Called for Redemption. Prior to 11:00 a.m., New York City time, on the redemption date, the Company shall deposit with the Paying Agent money sufficient to pay the redemption price of and accrued interest on all Securities or portions thereof to be redeemed on that date. If notice of redemption has been given as provided in ‎Section 3.02 or ‎Section 3.05, the Securities or portions of Securities of the series with respect to which such notice has been given shall become due and payable on the date and at the place or places stated in such notice at the

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applicable redemption price, together with any interest accrued to, but excluding, the date fixed for redemption, and on and after said date (unless the Company shall default in the payment of such Securities or portions of such Securities, together with any interest accrued to said date) any interest on the Securities of such series or portions of Securities of such series so called for redemption shall cease to accrue. On presentation and surrender of such Securities at a place of payment in said notice specified, the said Securities or the specified portions thereof shall be paid and redeemed by the Company at the applicable redemption price, together with any interest accrued thereon to, but excluding, the date fixed for redemption; provided, however, that any regularly scheduled installment of interest becoming due on or prior to the date fixed for redemption shall be payable to holders of such Securities registered as such on the relevant record date according to their terms.

Upon presentation of any Security redeemed in part only, the Company shall execute and the Trustee shall authenticate and deliver to the holder thereof, at the expense of the Company, a new Security or Securities of the same series of authorized denominations, in aggregate principal amount equal to the unredeemed portion of the Security so presented.

Section 3.04.Satisfaction of Mandatory Sinking Fund Payments with Securities. In lieu of making all or any part of any mandatory sinking fund payment with respect to any Securities of a series in cash, the Company may at its option (a) deliver to the Trustee Securities of that series theretofore purchased or otherwise acquired by the Company, or (b) receive credit for the principal amount of Securities of that series which have been redeemed either at the election of the Company pursuant to the terms of such Securities or through the application of permitted optional sinking fund payments pursuant to the terms of such Securities; provided that such Securities have not been previously so credited. Upon the written direction of the Company, such Securities shall be received and credited for such purpose by the Trustee at the redemption price specified in such Securities for redemption through operation of the sinking fund and the amount of such mandatory sinking fund payment shall be reduced accordingly.

Section 3.05.Redemption of Securities for Sinking Fund. Not less than 10 days prior to each sinking fund payment date for any series of Securities, the Company shall deliver to the Trustee an Officers’ Certificate specifying the amount of the next ensuing sinking fund payment for that series pursuant to the terms of that series, the portion thereof, if any, which is to be satisfied by payment of cash and the portion thereof, if any, which is to be satisfied through delivery and/or crediting of Securities of that series pursuant to ‎Section 3.04 and whether the Company intends to exercise its right to make a permitted optional sinking fund payment with respect to such series. Such certificate shall be irrevocable, and upon its delivery, the Company shall be obligated to make the payment, delivery and/or crediting

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therein referred to, if any, on or prior to such sinking fund payment date. In the case of the failure of the Company to deliver such certificate, the sinking fund payment due with respect to the next sinking fund payment date for that series of Securities shall be paid entirely in cash and shall be made in an amount sufficient to redeem the principal amount of such Securities subject to a mandatory sinking fund payment without the option to deliver or credit Securities as provided in ‎Section 3.04 and without the right to make any optional sinking fund payment with respect to such series.

Any sinking fund payment or payments (mandatory or optional) made in cash, plus any unused balance of any preceding sinking fund payments made in cash, which shall equal or exceed $100,000 (or the equivalent amount in the Specified Currency (if other than Dollars) or currency units in which Securities of the series are payable if applicable), or a lesser sum if the Company shall so request, with respect to the Securities of any particular series, shall be applied by the Trustee, a Paying Agent or the Company, if it acts as its own Paying Agent, on the sinking fund payment date next following the date of such payment, to the redemption of such Securities at the redemption price specified in such Securities for operation of the sinking fund together with accrued interest, if any, to the sinking fund payment date. Any sinking fund moneys not so applied or allocated to the redemption of Securities shall be added to the next cash sinking fund payment received by the Trustee or such Paying Agent or set aside and segregated by the Company for such series and, together with such payment, shall be applied in accordance with the provisions of this ‎Section 3.05. Any and all sinking fund moneys with respect to the Securities of any particular series held by the Trustee, such Paying Agent or the Company on the last sinking fund payment date with respect to Securities of such series and not held for the payment or redemption of particular Securities shall be applied by the Trustee, such Paying Agent or the Company, together with other moneys, if necessary, to be deposited sufficient for the purpose, to the payment of principal of such Securities at maturity.

Not more than 60 days and not less than 30 days prior to each sinking fund payment date, the Securities to be redeemed shall be selected in the manner specified in the second to last paragraph of ‎Section 3.02. The Company shall cause notice of the redemption thereof to be given not less than 30 nor more than 60 days prior to the sinking fund payment date in the manner provided in ‎Section 3.02, except that the notice of redemption shall also state that the Securities of such series are being redeemed by operation of the sinking fund and the sinking fund payment date. Such notice having been duly given, the redemption of such Securities shall be made on the sinking fund payment date upon the terms and in the manner stated in ‎Section 3.03.

On or before each sinking fund payment date, the Company shall pay to the Trustee or to a Paying Agent in cash (or, if the Company is acting as its own Paying Agent, shall segregate and hold in trust as provided in ‎Section 4.04(b)) a sum equal to any interest accrued to, but excluding, the date fixed for redemption of Securities or portions thereof to be redeemed on such sinking fund payment date pursuant to this ‎Section 3.05.

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Section 3.06.Repayment at the Option of the Holder. Any series of Securities may be made, by provision contained in or established pursuant to a supplemental indenture or a resolution of the Board of Directors of the Company pursuant to ‎Section 2.02 hereof, subject to repayment, in whole or in part, at the option of the holder on a date or dates specified prior to maturity, at a price to be set forth therein, together with accrued interest to the date of repayment, on such notice as may be required; provided, however, that the holder of a Security may only elect partial repayment in an amount that will result in the portion of such Security that will remain Outstanding after such repayment constituting an authorized denomination, or combination thereof, of such Securities.

Article 4
Particular Covenants of the Company

Section 4.01.Payment of Principal, Premium and Interest. The Company covenants and agrees for the benefit of each series of Securities that it shall duly and punctually pay or cause to be paid the principal of, premium, if any, and interest, if any, on each of the Securities of that series at the places, at the respective times and in the manner provided in such Securities. Prior to 11:00 a.m., New York City time, on the applicable payment date, the Company shall deposit with the Paying Agent money sufficient to pay such principal, premium, if any, and interest, if any. Any payment required to be made on any day that is not a Business Day will be made on the next succeeding Business Day, provided that no additional interest will accrue for the intervening period in respect of such payment date.

Section 4.02.Offices for Notices and Payments, etc. As long as any of the Securities of a series remain Outstanding, the Company shall designate and maintain in the Borough of Manhattan, The City of New York, an office or agency where the Securities of that series may be presented for payment, an office or agency within or outside the Borough of Manhattan, The City of New York, where the Securities of that series may be presented for registration of transfer and for exchange as in this Indenture provided and an office or agency within or outside the Borough of Manhattan, The City of New York, where notices and demands to or upon the Company in respect of the Securities of that series or of this Indenture may be served. In addition to such office or offices or agency or agencies, the Company may from time to time designate and maintain one or more additional offices or agencies within or outside the Borough of Manhattan, The City of New York, where the Securities of that series may be presented for registration of transfer or for exchange, and the Company may from time to time rescind such designation, as it may deem desirable or expedient. The Company shall give to the Trustee written notice of the location of each such office or agency and of any change of location thereof. In case the Company shall fail to maintain

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any such office or agency in the Borough of Manhattan, The City of New York, or shall fail to give such notice of the location or of any change in the location thereof, presentations and demands may be made and notices may be served at the Principal Office of the Trustee.

The Company hereby initially designates for Securities transfer purposes and for purposes of presentment and surrender of any Securities for final distribution, and for all other purposes, the office of the Trustee located at 60 Wall Street – 16^th Floor, MSNYC60-1630, New York, New York 10005 as the office or agency of the Company in the Borough of Manhattan, The City of New York, where the Securities of each series may be presented for payment, for registration of transfer and for exchange as provided in this Indenture and where notices and demands to or upon the Company in respect of the Securities of each series or of this Indenture may be delivered.

Section 4.03.Appointment to Fill Vacancies in Trustee’s Office. The Company, whenever necessary to avoid or fill a vacancy in the office of Trustee, shall appoint, in the manner provided in ‎Section 7.10, a successor Trustee, so that there shall at all times be a Trustee with respect to each series of Securities hereunder.

Section 4.04.Provision as to Paying Agent. (a) If the Company shall appoint a Paying Agent other than the Trustee with respect to the Securities of any series, it shall cause such Paying Agent to execute and deliver to the Trustee an instrument in which such agent shall agree with the Trustee, subject to the provisions of this ‎Section 4.04:

(i)that it will hold all sums held by it as such agent for the payment of the principal of, premium, if any, or interest, if any, on the Securities of such series (whether such sums have been paid to it by the Company or by any other obligor on the Securities of such series) in trust for the benefit of the holders of the Securities of such series;

(ii)that it will give the Trustee notice of any failure by the Company (or by any other obligor on the Securities of such series) to make any payment of the principal of, premium, if any, or interest, if any, on the Securities of such series when the same shall be due and payable; and

(iii)that at any time during the continuance of any failure by the Company (or by any other obligor on the Securities of such series) specified in the preceding paragraph ‎(ii), such Paying Agent will, upon the written request of the Trustee, forthwith pay to the Trustee all sums so held in trust by it.

(b)If the Company shall act as its own Paying Agent with respect to the Securities of any series, it shall, on or before each due date of the principal of, premium, if any, or interest, if any, on the Securities of such series, set aside, segregate and hold in trust for the benefit of the holders of such Securities a sum sufficient to pay such principal, premium, if any, or interest, if any, so becoming due and shall promptly notify

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the Trustee of any failure to take such action and of any failure by the Company (or by any other obligor on the Securities of such series) to make any payment of the principal of, premium, if any, or interest, if any, on the Securities of such series when the same shall become due and payable.

(c)Anything in this ‎Section 4.04 to the contrary notwithstanding, the Company may, at any time, for the purpose of obtaining a satisfaction and discharge of this Indenture, or for any other reason, pay or cause to be paid to the Trustee all sums held in trust by it, or any Paying Agent hereunder, as required by this ‎Section 4.04, such sums to be held by the Trustee upon the trusts herein contained.

(d)Anything in this ‎Section 4.04 to the contrary notwithstanding, the agreement to hold sums in trust as provided in this ‎Section 4.04 is subject to Sections ‎12.05 and ‎12.06.

(e)Whenever the Company shall have one or more Paying Agents with respect to the Securities of any series, it shall, prior to each due date of the principal of, premium, if any, or interest, if any, on the Securities of such series, deposit with a designated Paying Agent a sum sufficient to pay the principal, premium, if any, and interest, if any, so becoming due, such sum to be held in trust for the benefit of the persons entitled to such principal, premium, if any, or interest, if any, and (unless such Paying Agent is the Trustee) the Company shall promptly notify the Trustee of any failure so to act.

Section 4.05.Statement as to Compliance. The Company shall furnish to the Trustee within 120 days after the end of each fiscal year (beginning with a certificate within 120 days after the end of the fiscal year of the first date of issuance of any Securities under this Indenture) a brief certificate as to compliance by the Company and the Guarantor with the conditions and covenants hereunder (which certificate need not comply with ‎Section 15.07), as required by Section 314(a)(4) of the Trust Indenture Act, stating whether or not to the best knowledge of the signer thereof each of the Company and the Guarantor is in compliance (without regard to periods of grace or notice requirements) with all conditions and covenants under this Indenture, and if the Company or the Guarantor shall not be in compliance, specifying such non-compliance and the nature and status thereof of which such signer may have knowledge.

The Company shall deliver to the Trustee, as soon as possible and in any event within 20 days after the Company becomes aware of the occurrence of any Event of Default or an event which, with notice or the lapse of time or both, would constitute an Event of Default, an Officer’s Certificate setting forth the details of such Event of Default or default and the action which the Company proposes to take with respect thereto.

Section 4.06.Additional Amounts. If the Securities of a series provide for the payment of additional amounts, at least 10 days prior to the first interest payment date with respect to that series of Securities and at least 10 days prior to each date of payment of principal of, premium, if any, or

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interest on the Securities of that series if there has been a change with respect to the matters set forth in the below-mentioned Officer’s Certificate, the Company shall furnish to the Trustee and the principal Paying Agent, if other than the Trustee, an Officer’s Certificate instructing the Trustee and such Paying Agent whether such payment of principal of, premium, if any, or interest on the Securities of that series shall be made to holders of the Securities of that series without withholding or deduction for or on account of any tax, assessment or other governmental charge described in the Securities of that series. If any such withholding or deduction shall be required, then such Officer’s Certificate shall specify by country the amount, if any, required to be withheld or deducted on such payments to such holders and shall certify the fact that additional amounts will be payable and the amounts so payable to each holder, and the Company shall pay to the Trustee or such Paying Agent the additional amounts required to be paid by this ‎Section 4.06. The Company covenants to indemnify the Trustee and any Paying Agent for, and to hold them harmless against, any loss, liability or expense reasonably incurred without negligence or bad faith on their part arising out of or in connection with actions taken or omitted by any of them in reliance on any Officer’s Certificate furnished pursuant to this ‎Section 4.06.

Whenever in this Indenture there is mentioned, in any context, the payment of the principal of or any premium, interest or any other amounts on, or in respect of, any Security of any series, such mention shall be deemed to include mention of the payment of additional amounts provided by the terms of such series established hereby or pursuant hereto to the extent that, in such context, additional amounts are, were or would be payable in respect thereof pursuant to such terms, and express mention of the payment of additional amounts (if applicable) in any provision hereof shall not be construed as excluding the payment of additional amounts in those provisions hereof where such express mention is not made.

Article 5
Securityholder Lists and Reports by the Company and the Trustee

Section 5.01.Securityholder Lists. If and so long as the Trustee shall not be the Security Registrar for the Securities of any series, the Company and any other obligor on the Securities shall furnish or cause to be furnished to the Trustee a list in such form as the Trustee may reasonably require of the names and addresses of the holders of the Securities of such series pursuant to Section 312 of the Trust Indenture Act (a) semi-annually not more than 15 days after each record date for the payment of interest on such Securities, as hereinabove specified, as of such record date, and on dates to be determined pursuant to ‎Section 2.02 for non-interest bearing Securities in each year, and (b) at such other times as the Trustee may request in writing, within thirty days after receipt by the Company of any such request

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as of a date not more than 15 days prior to the time such information is furnished.

Section 5.02.Reports by the Company and the Guarantor. The Company and the Guarantor covenant to file with the Trustee, within 15 days after the Company or the Guarantor, as the case may be, is required to file the same with the SEC, copies of the annual reports and of the information, documents and other reports that the Company or the Guarantor, as the case may be, is required to file with the SEC pursuant to Section 13 or Section 15(d) of the Exchange Act or pursuant to Section 314 of the Trust Indenture Act. Annual reports, information, documents and reports that are filed by the Company or the Guarantor with the SEC via the EDGAR system or any successor electronic delivery procedure will be deemed to be filed with the Trustee at the time such documents are filed via the EDGAR system or such successor procedure. Delivery of such reports, information and documents to the Trustee is for informational purposes only, and the Trustee’s receipt of such shall not constitute constructive notice of any information contained therein or determinable from information contained therein, including the Company’s or the Guarantor’s compliance with any of their respective covenants hereunder (as to which the Trustee is entitled to rely exclusively on Officer’s Certificates). The Trustee shall have no obligation to determine whether any such reports have been timely filed with the SEC.

Section 5.03.Reports by the Trustee. Any Trustee’s report required under Section 313(a) of the Trust Indenture Act shall be transmitted on or before March 15 in each year beginning March 15, 2017, as provided in Section 313(c) of the Trust Indenture Act, so long as any Securities are Outstanding hereunder, and shall be dated as of a date convenient to the Trustee no more than 60 days prior thereto. A copy of each such report shall, at the time of such transmission to Securityholders, be filed by the Trustee with each stock exchange, if any, upon which any Securities are listed, with the SEC and with the Company and the Guarantor. The Company or the Guarantor shall notify the Trustee, in writing, when any Securities are listed on any stock exchange or delisted therefrom.

Article 6
Remedies of the Trustee and Securityholders on Event of Default

Section 6.01.Events of Default. The term “Event of Default” whenever used herein with respect to Securities of any series means any one of the following events, and such other events as may be established with respect to the Securities of such series as contemplated by ‎Section 2.02 hereof, continued for the period of time, if any, and after the giving of notice, if any, designated in this Indenture or as may be established with respect to such Securities as contemplated by ‎Section 2.02 hereof, as the case may be, unless it is either inapplicable or is specifically deleted or modified in the applicable resolution of the Board of Directors of the Company or in the

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supplemental indenture under which such series of Securities is issued, as the case may be, as contemplated by ‎Section 2.02:

(a)default in the payment of any installment of interest upon any Security of such series as and when the same shall become due and payable, and continuance of such default for a period of 30 days; or

(b)default in the payment of the principal of, or premium, if any, on any Security of such series as and when the same shall become due and payable, whether at maturity or upon acceleration, redemption, required repurchase, by declaration, repayment or otherwise; or

(c)failure on the part of the Company or the Guarantor to observe or perform any other covenant or agreement on the part of the Company or the Guarantor, as the case may be, in respect of the Securities of such series contained in this Indenture (other than a covenant or agreement in respect of the Securities of such series a default in whose observance or performance is elsewhere in this ‎Section 6.01 specifically dealt with), and continuance of such failure for a period of 90 days after the date on which written notice of such failure, requiring the Company or the Guarantor to remedy the same, shall have been given to the Company or the Guarantor, as the case may be, by the Trustee by registered mail, or to the Company, the Guarantor and the Trustee by the holders of at least 25% in aggregate principal amount of the Securities of such series at the time Outstanding; or

(d)an involuntary proceeding shall be commenced or an involuntary petition shall be filed seeking (i) liquidation, reorganization or other relief in respect of the Company, the Guarantor or their respective debts, or of a substantial part of their respective assets, under any Federal, state or foreign bankruptcy, insolvency, receivership or similar law now or hereafter in effect or (ii) the appointment of a receiver, trustee, custodian, sequestrator, conservator or similar official for the Company or the Guarantor or for a substantial part of their respective assets, and, in any such case, such proceeding or petition shall continue undismissed for 60 days, or an order or decree or other action approving or ordering any of the foregoing shall be entered;

(e)the Company or the Guarantor shall:

(i)voluntarily commence any proceeding or file any petition seeking liquidation, reorganization or other relief under any Federal, state or foreign bankruptcy, insolvency, receivership or similar law now or hereafter in effect; or

(ii)consent to the institution of, or fail to contest in a timely and appropriate manner, any proceeding or petition described in ‎Section 6.01(d); or

(iii)apply for or consent to the appointment of a receiver, trustee, custodian, sequestrator, conservator or similar official for the Company or the Guarantor, as the case may be, for a substantial part of its assets; or

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(iv)file an answer admitting the material allegations of a petition filed against it in any such proceeding; or

(v)make a general assignment for the benefit of creditors; or

(vi)take any action for the purpose of effecting any of the foregoing; or

(vii)admit in writing its inability to pay its debts as they become due;

(f)the Guarantor’s Guarantee with respect to the Securities of any series is held in any judicial proceeding to be unenforceable or invalid or, except as permitted by the applicable supplemental indenture, ceases for any reason to be in full force and effect, or the Guarantor denies or disaffirms its obligations under its Guarantee with respect to the Securities of any series; or

(g)any other Event of Default provided in the applicable resolution of the Board of Directors of the Company or in the supplemental indenture under which such series of Securities is issued, as the case may be, as contemplated by ‎Section 2.02.

If an Event of Default as contemplated by Section ‎6.01(d) or ‎6.01(e) occurs, the principal amount (or, if the Securities of such series are Original Issue Discount Securities, such portions of the principal amount as may be specified in the terms of such series) and all accrued and unpaid interest thereon, if any, with respect to Securities of all series at the time Outstanding will become and be immediately due and payable, without further action or notice on the part of the Securityholders or the Trustee. If any other Event of Default with respect to Securities of any series at the time Outstanding occurs and is continuing, then and in each and every such case, unless the principal of all of the Securities of such series shall have already become due and payable, either the Trustee or the holders of not less than 25% in aggregate principal amount of the Securities of such series then Outstanding hereunder, by notice in writing to the Company (and to the Trustee if given by Securityholders of such series), may declare the principal amount (or, if the Securities of such series are Original Issue Discount Securities, such portion of the principal amount as may be specified in the terms of such series) and all accrued and unpaid interest thereon, if any, of all the Securities of such series to be due and payable immediately, and upon any such declaration the same shall become and shall be immediately due and payable, anything in this Indenture or in the Securities of such series contained to the contrary notwithstanding. This provision, however, is subject to the condition that if, at any time after the principal amount (or, if the Securities of such series are Original Issue Discount Securities, such portion of the principal amount as may be specified in the terms of such series) of the Securities of any series shall have been so declared or otherwise become due and payable, and before any judgment or decree for the payment of the moneys due shall have been obtained or entered as hereinafter provided, (i) the Company shall pay or shall deposit with the Trustee a sum sufficient to pay all matured installments of interest, if any, upon all of the Securities of such series and the principal of, and premium, if any, on any and all Securities of such series which shall have become due otherwise than by acceleration (with interest on overdue installments of interest (to the extent that payment of such interest is enforceable under

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applicable law) and on such principal at the Overdue Rate applicable to such series, to the date of such payment or deposit), (ii) the Company shall pay or deposit with the Trustee a sum sufficient to pay all amounts payable to the Trustee pursuant to the provisions of ‎Section 7.06, and (iii) any and all defaults under this Indenture with respect to such series of Securities, other than the nonpayment of principal of and accrued interest on Securities of such series which shall have become due solely by acceleration, shall have been remedied, cured or waived or provision shall have been made therefor to the satisfaction of the Trustee, then and in every such case, the holders of a majority in aggregate principal amount of the Securities of such series then Outstanding, by written notice to the Company and the Trustee, may waive all defaults with respect to such series and rescind and annul such declaration or acceleration and its consequences; but no such waiver or rescission and annulment shall extend to or shall affect any subsequent default or shall impair any right consequent thereon.

In case the Trustee shall have proceeded to enforce any right under this Indenture and such proceeding shall have been discontinued or abandoned because of such rescission or annulment or for any other reason or shall have been determined adversely to the Trustee, then and in every such case the Company and the Trustee shall be restored respectively to their several positions and rights hereunder, and all rights, remedies and powers of the Company and the Trustee shall continue as though no such proceeding had been taken.

Section 6.02.Payment of Securities on Default; Suit Therefor. The Company covenants that (a) in case default shall be made in the payment of any installment of interest upon any Security of any series as and when the same shall become due and payable, and such default shall have continued for a period of 30 days, (b) in case default shall be made in the payment of the principal of, or premium, if any, on any Security of any series as and when the same shall become due and payable, whether at maturity of the Securities of that series or upon redemption or by declaration, repayment or otherwise, or (c) in case of default in the making or satisfaction of any sinking fund payment or analogous obligation when the same becomes due by the terms of the Securities of any series, then, upon demand of the Trustee, the Company shall pay to the Trustee, for the benefit of the holder of any such Security (or holders of any series of Securities in the case of clause ‎(c) above) the whole amount that then shall have become due and payable on any such Security (or Securities of any such series in the case of clause ‎(c) above) for principal, premium, if any, and interest, if any, with interest upon the overdue principal and premium, if any, and (to the extent that payment of such interest is enforceable under applicable law) upon the overdue installments of interest, if any, at the Overdue Rate applicable to any such Security (or Securities of any such series in the case of clause ‎(c) above); and, in addition thereto, such further amount as shall be sufficient to cover costs and expenses of collection, and any further amounts payable to the Trustee pursuant to the provisions of ‎Section 7.06.

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In case the Company shall fail forthwith to pay such amounts upon such demand, the Trustee, in its own name and as trustee of any express trust, shall be entitled (but shall have no obligation to) and empowered to institute any actions or proceedings at law or in equity for the collection of the sums so due and unpaid, and may prosecute any such action or proceeding to judgment or final decree, and may enforce any such judgment or final decree against the Company or any other obligor upon such Securities and collect in the manner provided by law out of the property of the Company or any other obligor on such Securities wherever situated the moneys adjudged or decreed to be payable.

In case there shall be pending proceedings for the bankruptcy, for the insolvency or for the reorganization of the Company or any other obligor on the Securities of any series under the Federal Bankruptcy Code or any other similar applicable Federal or State law, or in case a receiver or trustee (or other similar official) shall have been appointed for the property of the Company or such other obligor, or in the case of any other similar judicial proceedings relative to the Company or other obligor on the Securities of any series, or to the creditors or property of the Company or such other obligor, the Trustee, irrespective of whether the principal of the Securities of any series shall then be due and payable as therein expressed or by declaration or otherwise and irrespective of whether the Trustee shall have made any demand pursuant to the provisions of this ‎Section 6.02, shall be entitled and empowered, by intervention in such proceedings or otherwise, to file and prove a claim or claims for the whole amount of principal (or, if the Securities of any series are Original Issue Discount Securities, such portion of the principal amount as may be due and payable with respect to such series pursuant to a declaration in accordance with ‎Section 6.01), premium, if any, and interest, if any, owing and unpaid in respect of the Securities of any series and, in case of any judicial proceedings, to file such proofs of claim and other papers or documents as may be necessary or advisable in order to have the claims of the Trustee and of the Securityholders of any series allowed in such judicial proceedings relative to the Company or any other obligor on the Securities of any series, its or their creditors, or its or their property, and to collect and receive any moneys or other property payable or deliverable on any such claims, and to distribute the same after the deduction of costs and expenses of collection, and any further amounts payable to the Trustee pursuant to the provisions of ‎Section 7.06 and incurred by it up to the date of such distribution; and any receiver, assignee or trustee (or other similar official) in bankruptcy or reorganization is hereby authorized by each of the Securityholders to make such payments to the Trustee, and, in the event that the Trustee shall consent to the making of such payments directly to the Securityholders, to pay to the Trustee costs and expenses of collection and any further amounts payable to the Trustee pursuant to the provisions of ‎Section 7.06 and incurred by it up to the date of such distribution.

Nothing herein contained shall be deemed to authorize the Trustee to authorize or consent to or accept or adopt on behalf of any Securityholder any plan of reorganization, arrangement, adjustment or composition affecting any of the Securities of any series or the rights of any holder thereof, or to authorize the Trustee to vote in respect of the claim of any Securityholder in any such proceeding.

All rights of action and of asserting claims under this Indenture, or under the Securities of any series, may be enforced by the Trustee without the possession of any of

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the Securities of such series or the production thereof in any trial or other proceeding relative thereto, and any such suit or proceeding instituted by the Trustee shall be brought in its own name as trustee of an express trust, and any recovery of judgment shall be for the ratable benefit of the holders of the Securities in respect of which such action was taken. In any proceedings brought by the Trustee (and also any proceedings in which a declaratory judgment of a court may be sought as to the interpretation or construction of any provision of this Indenture, to which the Trustee shall be a party) the Trustee shall be held to represent all the holders of the Securities to which such proceedings relate, and it shall not be necessary to make any holders of such Securities parties to any such proceedings.

Section 6.03.Application of Moneys Collected by Trustee. Any moneys collected by the Trustee pursuant to this ‎Article 6 and, if an Event of Default has occurred and is continuing, any money or other property distributable in respect of the Company’s obligations under this Indenture, shall be applied in the order following, at the date or dates fixed by the Trustee for the distribution of such moneys, upon presentation of the several Securities in respect of which moneys have been collected, and the notation thereon of the payment, if only partially paid, and upon surrender thereof if fully paid:

FIRST: To the payment of all amounts due the Trustee and Agents pursuant to the provisions of ‎Section 7.06;

SECOND: In case the principal of the Outstanding Securities in respect of which such moneys have been collected shall not have become due (at maturity, upon redemption, by declaration, repayment or otherwise) and be unpaid, to the payment of interest, if any, on such Securities, in the order of the maturity of the installments of such interest, with interest (to the extent that such interest has been collected by the Trustee) upon the overdue installments of interest (to the extent that payment of such interest is enforceable under applicable law) at the Overdue Rate applicable to such Securities, such payments to be made ratably to the person entitled thereto;

THIRD: In case the principal of the Outstanding Securities in respect of which such moneys have been collected shall have become due (at maturity, upon redemption, by declaration, repayment or otherwise), to the payment of the whole amount then owing and unpaid upon such Securities for principal, premium, if any, and interest, if any, with interest on the overdue principal, and premium, if any, and (to the extent that such interest has been collected by the Trustee) upon overdue installments of interest, if any (to the extent that payment of such interest is enforceable under applicable law), at the Overdue Rate applicable to such Securities; and in case such moneys shall be insufficient to pay in full the whole amounts so due and unpaid upon such Securities, then to the payment of such principal, premium, if any, and interest, if any, without preference or priority of principal, and premium, if any, over interest, if any, or of interest, if any, over principal, and premium, if any, or of any installment of interest, if any, over any

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other installment of interest, if any, or of any such Security over any other such Security, ratably to the aggregate of such principal, premium, if any, and accrued and unpaid interest, if any; and

FOURTH: To the payment of the remainder, if any, to the Company, its successors or assigns, or to whosoever may be lawfully entitled to receive the same, or as a court of competent jurisdiction may direct.

Section 6.04.Proceedings by Securityholders. No holder of any Security of any series shall have any right by virtue of or by availing of any provision of this Indenture to institute any suit, action or proceeding in equity or at law upon or under or with respect to this Indenture or for the appointment of a receiver or trustee (or other similar official), or for any other remedy hereunder, unless (a) such holder previously shall have given to the Trustee written notice of an Event of Default with respect to Securities of such series and of the continuance thereof, as hereinbefore provided, (b) the holders of not less than 25% in aggregate principal amount of the Securities of such series then Outstanding shall have made written request upon the Trustee to institute such action, suit or proceeding in its own name as Trustee hereunder and shall have offered to the Trustee such reasonable security or indemnity as it may require against any loss, liability or expense to be incurred therein or thereby, and (c) the Trustee, for 60 days after its receipt of such notice, request and offer of reasonable security or indemnity, shall not have received from the holders of a majority in principal amount of the Securities of such series then Outstanding a direction inconsistent with that request, and shall have failed to institute any such action, suit or proceeding, it being understood and intended, and being expressly covenanted by the taker and holder of every Security with every other taker and holder and the Trustee, that no one or more holders of Securities of such series shall have any right in any manner whatever by virtue or by availing of any provision of this Indenture to affect, disturb or prejudice the rights of any other holder of Securities of such series, or to obtain or seek to obtain priority over or preference to any other such holder, or to enforce any right under this Indenture, except in the matter herein provided and for the equal, ratable and common benefit of all holders of Securities of such series (it being understood that the Trustee has no affirmative duty to ascertain whether or not such actions or forbearances are unduly prejudicial to such holders).

Notwithstanding any other provisions in this Indenture, however, the right of any holder of any Security to receive payment of the principal of, premium, if any, and interest, if any, on such Security, on or after the respective due dates expressed in such Security, or upon redemption, by declaration, repayment or otherwise, or to institute suit for the enforcement of any such payment on or after such respective dates, shall not be impaired or affected without the consent of such holder, and no provision of the Securities of any series or of this Indenture shall alter or impair the obligations of the Company, which are absolute and unconditional, to pay the principal of, premium, if any, and interest, if any, on the Securities of such series at the respective places, at the

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respective times, at the respective rates and in the coin or currency, therein and herein prescribed.

Section 6.05.Proceedings by Trustee. In case of an Event of Default hereunder, the Trustee may, in its discretion, proceed to protect and enforce the rights vested in it by this Indenture by such appropriate judicial proceedings as the Trustee shall deem most effectual to protect and enforce any of such rights, either by suit in equity or by action at law or by proceeding in bankruptcy or otherwise, whether for the specific enforcement of any covenant or agreement contained in this Indenture or in aid of the exercise of any power granted in this Indenture, or to enforce any other legal or equitable right vested in the Trustee by this Indenture or by law.

Section 6.06.Remedies Cumulative and Continuing. All powers and remedies given by this ‎Article 6 to the Trustee or to the Securityholders of any series shall, to the extent permitted by law, be deemed cumulative and not exclusive of any thereof or of any other powers and remedies available to the Trustee or the holders of such Securities, by judicial proceedings or otherwise, to enforce the performance or observance of the covenants and agreements contained in this Indenture, and no delay or omission of the Trustee or of any holder of any such Securities to exercise any right or power accruing upon any default occurring and continuing as aforesaid shall impair any such right or power, or shall be construed to be a waiver of any such default or an acquiescence therein; and, subject to the provisions of ‎Section 6.04, every power and remedy given by this ‎Article 6 or by law to the Trustee or to the Securityholders of any series may be exercised from time to time, and as often as shall be deemed expedient, by the Trustee or by the Securityholders of such series.

Section 6.07.Direction of Proceedings and Waiver of Defaults by Securityholders. (a) The holders of a majority in aggregate principal amount of the Securities of any series at the time Outstanding shall have the right to direct the time, method and place of conducting any proceeding for any remedy available to the Trustee, or exercising any trust or power conferred on the Trustee, with respect to the Securities of such series; provided, however, that (subject to the provisions of ‎Section 7.01) the Trustee shall have the right to decline to follow any such direction if the Trustee, being advised by counsel, determines that the action or proceeding so directed may not lawfully be taken or if the Trustee in good faith shall determine that the action or proceeding so directed would be unduly prejudicial to the rights of any other holder of Securities of the applicable series (it being understood that the Trustee does not have an affirmative duty to ascertain whether or not such actions or proceedings are unduly prejudicial to such holders) or that would involve the Trustee in personal liability.

(b)Prior to any acceleration or declaration accelerating the maturity of the Securities of any series, the holders of a majority in aggregate principal amount of the

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Securities of such series at the time Outstanding may, on behalf of the holders of all of the Securities of such series, waive any past default or Event of Default with respect to such series and its consequences, except a default in the payment of interest, if any, on, or the principal of or premium, if any, on any Security of such series, or in the payment of any sinking fund installment or analogous obligation with respect to Securities of such series, or in respect of a covenant or provision hereof which under ‎Section 10.02 cannot be modified or amended without the consent of the holder of each Security affected. Upon any such waiver, the Company or any other obligor on the Securities of that series, the Trustee and the holders of the Securities of that series shall be restored to their former positions and rights hereunder, respectively; but no such waiver shall extend to any subsequent or other default or Event of Default or impair any right consequent thereon. Whenever any default or Event of Default hereunder shall have been waived as permitted by this ‎Section 6.07(b), said default or Event of Default shall for all purposes of the Securities of such series and this Indenture be deemed to have been cured and to be not continuing.

Section 6.08.Notice of Defaults. The Trustee shall, within 90 days after being notified in writing of a default with respect to the Securities of any series, mail (or provide notice pursuant to the applicable procedures of the Depositary) to all holders of Securities of such series, as the names and addresses of such holders appear upon the Security Register, notice of all defaults with respect to such series known to the Trustee, unless such defaults shall have been cured or waived before the giving of such notice (the term “defaults” for the purpose of this ‎Section 6.08 being hereby defined to be the events specified in ‎Section 6.01 or established with respect to such Securities as contemplated by ‎Section 2.02, not including the periods of grace, if any, provided for therein or established with respect to such Securities as contemplated by ‎Section 2.02, and irrespective of the giving of the notices, if any, provided for therein or established with respect to such Securities as contemplated by ‎Section 2.02); provided, however, that except in the case of default in the payment of the principal of, premium, if any, or interest, if any, on any of the Securities of such series or in the making of any sinking fund installment or analogous obligation with respect to such series, the Trustee shall be protected in withholding such notice if and so long as the Trustee in good faith determines that the withholding of such notice is in the interest of the holders of Securities of such series.

Section 6.09.Undertaking to Pay Costs. All parties to this Indenture agree, and each holder of any Security by his acceptance thereof shall be deemed to have agreed, that any court may in its discretion require, in any suit for the enforcement of any right or remedy under this Indenture, or in any suit against the Trustee for any action taken, omitted or suffered by it as Trustee, the filing by any party litigant in such suit of an undertaking to pay the costs of such suit, and that such court may in its discretion assess reasonable costs, including reasonable attorneys’ fees, against any party litigant in such suit, having due regard to the merits and good faith of the

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claims or defenses made by such party litigant; but the provisions of this ‎Section 6.09 shall not apply (a) to any suit instituted by the Trustee, (b) to any suit instituted by any Securityholder of any series or group of such Securityholders, holding in the aggregate more than 10% in principal amount of the Outstanding Securities of such series or (c) to any suit instituted by any Securityholder for the enforcement of the payment of the principal of, premium, if any, or interest, if any, on any Security (i) on or after the due date expressed in such Security, (ii) on or after the date fixed for redemption or repayment or (iii) after such Security shall have become due by declaration.

Article 7
Concerning The Trustee

Section 7.01.Duties and Responsibilities of Trustee. (a) In case an Event of Default with respect to the Securities of a series has occurred (which has not been cured or waived), the Trustee shall exercise such of the rights and powers vested in it by this Indenture with respect to such series, and use the same degree of care and skill in their exercise, as a prudent person would exercise or use under the circumstances in the conduct of his or her own affairs.

(b)Prior to the occurrence of an Event of Default with respect to the Securities of a series and after the curing or waiving of all Events of Default with respect to such series which may have occurred:

(i)the duties and obligations of the Trustee with respect to the Securities of a series shall be determined solely by the express provisions of this Indenture, and the Trustee shall take such action with respect to this Indenture as it shall be directed pursuant to this Indenture, and the Trustee shall not be liable except for the performance of such duties and obligations as are specifically set forth in this Indenture and as specifically directed under this Indenture, and no implied covenants or obligations shall be read into this Indenture against the Trustee; and

(ii)in the absence of bad faith on the part of the Trustee, the Trustee may conclusively rely, as to the truth of the statements and the correctness of the opinions expressed therein, upon any certificates or opinions furnished to the Trustee and conforming to the requirements of this Indenture; but in the case of any such certificates or opinions which by any provision hereof are specifically required to be furnished to the Trustee, the Trustee shall be under a duty to examine the same to determine whether or not they conform to the requirements of this Indenture (but need not confirm or investigate the accuracy of mathematical calculations or other facts stated therein);

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(c)No provision of this Indenture shall be construed to relieve the Trustee from liability for its own negligent action, its own negligent failure to act or its own willful misconduct, except that:

(i)the Trustee shall not be liable for any error of judgment made in good faith by a Responsible Officer or Officers of the Trustee, unless it shall be proved that the Trustee was negligent in ascertaining the pertinent facts;

(ii)the Trustee shall not be liable with respect to any action taken, omitted or suffered to be taken by it in good faith in accordance with the direction of the holders of Securities of any series pursuant to ‎Section 6.07 relating to the time, method and place of conducting any proceeding for any remedy available to the Trustee, or exercising any trust or power conferred upon the Trustee, under this Indenture with respect to Securities of such series;

(iii)none of the provisions of this Indenture shall be construed as requiring the Trustee to expend or risk its own funds or otherwise to incur any liability, financial or otherwise, in the performance of any of its duties hereunder, or in the exercise of any of its rights or powers, if there shall be reasonable grounds for believing that repayment of such funds or adequate indemnity against such risk or liability is not reasonably assured to it; and

(iv)this clause ‎(c) shall not be construed to limit the effect of clause ‎(b) of this ‎Section 7.01.

The provisions of this ‎Section 7.01 are in furtherance of and subject to Section 315 of the Trust Indenture Act. Whether or not therein expressly so provided, every provision of this Indenture relating to the conduct or affecting the liability of or affording protection to the Trustee shall be subject to the provisions of this ‎Section 7.01.

Section 7.02.Reliance on Documents, Opinions, etc. In furtherance of and subject to the Trust Indenture Act, and subject to the provisions of ‎Section 7.01:

(a)the Trustee may conclusively rely and shall be protected in acting or refraining from acting upon any resolution, certificate, statement, instrument, opinion, report, notice, request, direction, consent, order or other paper or document believed by it to be genuine and to have been signed or presented by the proper party or parties;

(b)any request, direction, order or demand of the Company mentioned herein shall be sufficiently evidenced by an instrument signed in the name of the Company by an Officer (unless other evidence in respect thereof be herein specifically prescribed); and any resolution of the Board of Directors of the Company may be evidenced to the Trustee by a copy thereof certified by an Officer of the Company;

(c)the Trustee may consult with counsel and any advice or Opinion of Counsel shall be full and complete authorization and protection in respect of any action taken,

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omitted or suffered to be taken by it hereunder in good faith and in accordance with such advice or Opinion of Counsel;

(d)the Trustee shall be under no obligation to exercise any of the rights or powers vested in it by this Indenture at the request, order or direction of any of the Securityholders, pursuant to the provisions of this Indenture, unless such Securityholders shall have offered security and indemnity reasonably satisfactory to the Trustee against any loss, liability or expense which might be incurred therein or thereby;

(e)the Trustee shall not be liable for any action taken, omitted or suffered by it in good faith and believed by it to be authorized or within the discretion or rights or powers conferred upon it by this Indenture;

(f)the Trustee shall not be bound to make any inquiry or investigation into the facts or matters stated in any resolution, certificate, statement, instrument, opinion, report, notice, request, direction, consent, order, bond, note or other paper or document unless requested in writing so to do by the holders of a majority in aggregate principal amount of the Securities of any series affected then Outstanding; provided, however, that if the payment within a reasonable time to the Trustee of the costs and expenses or liabilities likely to be incurred by it in the making of such investigation is, in the opinion of the Trustee, not reasonably assured to the Trustee by the security conferred upon it by the terms of this Indenture, the Trustee may require reasonable indemnity against such costs, expenses or liabilities as a condition to so proceeding; and the reasonable expenses of such investigation shall be paid by the Company or, if paid by the Trustee, shall be repaid by the Company upon demand;

(g)the Trustee may execute any of the trusts or powers hereunder or perform any duties hereunder either directly or by or through agents, custodians, nominees or attorneys, and the Trustee shall not be responsible for any misconduct or negligence on the part of any agent, custodian, nominee or attorney appointed with due care by it hereunder;

(h)the Trustee shall not be deemed to have notice of any default hereunder or Event of Default, unless written notice of such a default or Event of Default is received by a Responsible Officer of the Trustee at the Principal Office of the Trustee and such notice references the Securities and this Indenture;

(i)the rights, privileges, protections, immunities and benefits given to the Trustee, including, without limitation, its right to be indemnified, are extended to, and shall be enforceable by, the Trustee in each of its capacities hereunder, and each agent, custodian and other Person employed to act hereunder;

(j)in no event shall the Trustee be responsible or liable for special, punitive, indirect, or consequential loss or damage of any kind whatsoever (including, but not limited to, loss of profit) irrespective of whether the Trustee has been advised of the likelihood of such loss or damage and regardless of the form of action;

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(k)the Trustee may request that the Company deliver a certificate setting forth the names of individuals and/or titles of Officers authorized at such time to take specified actions pursuant to this Indenture, which certificate may be signed by any person authorized to sign an Officer’s Certificate, including any person specified as so authorized in any such certificate previously delivered and not superseded;

(l)in no event shall the Trustee be responsible or liable for any failure or delay in the performance of its obligations hereunder arising out of or caused by, directly or indirectly, forces beyond its control, including, without limitation, strikes, work stoppages, accidents, acts of war or terrorism, civil or military disturbances, nuclear or natural catastrophes or acts of God, and interruptions, loss or malfunctions of utilities, communications or computer (software and hardware) services; it being understood that the Trustee shall use reasonable efforts which are consistent with accepted practices in the banking industry to resume performance as soon as practicable under the circumstances;

(m)neither the Trustee nor any of its officers, directors, employees or agents shall be liable for any action taken or omitted under this Indenture or in connection therewith except to the extent caused by the Trustee’s negligence or willful misconduct, as determined by the final judgment of a court of competent jurisdiction, no longer subject to appeal or review. The parties each (for itself and any person or entity claiming through it) hereby releases, waives, discharges, exculpates and covenants not to sue the Trustee for any action taken or omitted under this Indenture except to the extent caused by the Trustee’s negligence or willful misconduct; and

(n)in order to comply with the laws, rules, regulations and executive orders in effect from time to time applicable to banking institutions, including those relating to the funding of terrorist activities and money laundering (“Applicable Law,” including Section 326 of the USA PATRIOT Act of the United States), the Trustee and its agents are required to obtain, verify, record and update certain information relating to individuals and entities that maintain a business relationship with the Trustee and its agents. Accordingly, each of the parties agrees to provide to the Trustee and its agents, upon their request from time to time such identifying information and documentation as may be available for such party in order to enable the Trustee and its agents to comply with Applicable Law.

(o)In order for the Trustee to comply with applicable tax laws, rules and regulations (inclusive of directives, guidelines and interpretations promulgated by competent authorities) in effect from time to time (“Applicable Tax Law”), the Company agrees (i) to provide to the Trustee information about holders or other applicable parties and/or transactions (including any modification to the terms of such transactions) that is (x) within the knowledge of the Company or Shire, (y) not subject to legally binding confidentiality restrictions and (z) reasonably requested by the Trustee so that the Trustee may determine whether it has tax related obligations under Applicable Tax Law, and (ii) that the Trustee shall be entitled to make any withholding or deduction from payments to be made by the Company or Shire to holders under the Indenture to the

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extent necessary to comply with Applicable Tax Law, for which the Trustee shall not have any liability.

Section 7.03.No Responsibility for Recitals, etc. The recitals contained herein and in the Securities shall be taken as the statements of the Company (except in the Trustee’s certificates of authentication), and the Trustee assumes no responsibility for the correctness of the same. The Trustee makes no representations as to the validity or sufficiency of this Indenture or the Securities, provided that the Trustee shall not be relieved of its duty to authenticate Securities only as authorized by this Indenture. The Trustee shall not be accountable for the use or application by the Company of any of the Securities or of the proceeds thereof.

Section 7.04.Ownership of Securities. The Trustee and any agent of the Company or of the Trustee, in its individual or any other capacity, may become the owner or pledgee of Securities with the same rights it would have if it were not Trustee or such agent.

Section 7.05.Moneys to be Held in Trust. Subject to the provisions of Sections ‎4.04, ‎12.05 and ‎12.06, all moneys received by the Trustee or any Paying Agent shall, until used or applied as herein provided, be held in trust for the purposes for which they were received, but need not be segregated from other funds except to the extent required by law. Neither the Trustee nor any Paying Agent shall be under any liability for interest on any moneys received by it hereunder except such as it may agree in writing with the Company to pay thereon. So long as no Event of Default shall have occurred and be continuing, all interest allowed on any such moneys shall be paid from time to time upon the written order of the Company, signed by an Officer.

Section 7.06.Compensation and Expenses of Trustee. The Company and the Guarantor each covenant and agree to pay to the Trustee and Agents from time to time, and the Trustee and Agents shall be entitled to, reasonable compensation (which shall not be limited by any provision of law in regard to the compensation of a trustee of an express trust) and, except as otherwise expressly provided, the Company and the Guarantor shall pay or reimburse the Trustee and Agents upon their request for all reasonable expenses, disbursements and advances incurred or made by the Trustee and Agents in accordance with any of the provisions of this Indenture (including the reasonable compensation and the expenses and disbursements of its counsel and of all persons not regularly in its employ) except any such expense, disbursement or advance as may arise from its negligence or willful misconduct. The Company and the Guarantor also covenant to indemnify the Trustee and Agents and its officers, directors, employees, representatives and agents for, and to hold them and their officers, directors, employees, representatives and agents harmless against, any losses, liabilities, claims, expenses, obligations, damages, injuries, penalties, stamp or other similar

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taxes, actions, suits, judgments, reasonable costs and expenses (including reasonable attorney’s and agent’s fees and expenses) of whatever kind or nature, incurred without negligence, willful misconduct or bad faith on the part of the Trustee and Agents, arising out of or in connection with the acceptance or administration of this trust and their duties hereunder, including the costs and expenses of defending themselves against any claim of liability in the premises. The obligations of the Company and the Guarantor under this ‎Section 7.06 to compensate and indemnify the Trustee and Agents and to pay or reimburse the Trustee and Agents for expenses, disbursements and advances shall constitute additional indebtedness hereunder and shall survive the satisfaction and discharge of this Indenture and the resignation or removal of the Trustee and Agents.

The Trustee shall have a lien prior to the Securities as to all property and funds held by it hereunder for any amount owing it or any predecessor Trustee pursuant to this Section 7.06, except with respect to funds held in trust for the benefit of the holders of particular Securities.

When the Trustee incurs expenses or renders services in connection with an Event of Default specified in ‎Section 6.01(e) or ‎Section 6.01(f), the expenses (including the reasonable charges and expenses of its counsel) and the compensation for the services are intended to constitute expenses of administration under any applicable Federal or state bankruptcy, insolvency or other similar law.

Section 7.07.Officer’s Certificate as Evidence. Subject to the provisions of Sections ‎7.01 and ‎7.02, whenever in the administration of the provisions of this Indenture the Trustee shall deem it necessary or desirable that a matter be proved or established prior to taking, omitting or suffering any action to be taken hereunder, such matter (unless other evidence in respect thereof be herein specifically prescribed) may, in the absence of negligence or bad faith on the part of the Trustee, be deemed to be conclusively proved and established by an Officer’s Certificate delivered to the Trustee, and such Officer’s Certificate, in the absence of negligence or bad faith on the part of the Trustee, shall be full warrant to the Trustee for any action taken, omitted or suffered by it under the provisions of this Indenture upon the faith thereof.

Section 7.08.Disqualification: Conflicting Interests for the Trustee. The Trustee shall comply with the provisions of Section 310(b) of the Trust Indenture Act.

Section 7.09.Eligibility of Trustee. The Trustee hereunder shall at all times be a corporation organized and doing business under the laws of the United States or any State, which (a) is authorized under such laws to exercise corporate trust powers and (b) is subject to supervision or examination by Federal or State authority and (c) shall have at all times a combined capital and surplus of not less than $50,000,000. If such

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corporation publishes reports of condition at least annually, pursuant to law, or to the requirements of the aforesaid supervising or examining authority, then for the purposes of this ‎Section 7.09, the combined capital and surplus of such corporation at any time shall be deemed to be its combined capital and surplus as set forth in its most recent report of condition so published. No obligor upon this Indenture of any Securities or person directly or indirectly controlling, controlled by, or under common control with such obligor shall serve as Trustee. In case at any time the Trustee shall cease to be eligible in accordance with the provisions of this ‎Section 7.09, the Trustee shall resign immediately in the manner and with the effect specified in ‎Section 7.10.

The provisions of this ‎Section 7.09 are in furtherance of and subject to Section 310(a) of the Trust Indenture Act.

Section 7.10.Resignation or Removal of Trustee. (a) The Trustee, or any Trustee or Trustees hereafter appointed, may at any time resign with respect to any one or more or all series of Securities by giving written notice of resignation to the Company and Shire and by mailing notice of such resignation to the holders of the applicable series of Securities at their addresses as they shall appear on the Security Register. Upon receiving such notice of resignation, the Company shall promptly appoint a successor Trustee or Trustees with respect to the applicable series by written instrument, in duplicate, executed in the name of and on behalf of the Company by a duly authorized Officer, one copy of which instrument shall be delivered to the resigning Trustee and one copy to the successor Trustee, which instrument shall release the resigning Trustee from its obligations hereunder. If no successor Trustee shall have been so appointed with respect to any series and have accepted appointment within 60 days after the giving of such notice of resignation, the resigning Trustee may petition any court of competent jurisdiction for the appointment of a successor Trustee, or any Securityholder who has been a bona fide holder of a Security or Securities of the applicable series for at least six months may, subject to the provisions of ‎Section 6.09, on behalf of himself and all others similarly situated, petition any such court for the appointment of a successor Trustee. Such court may thereupon, after such notice, if any, as it may deem proper and prescribe, appoint a successor Trustee.

(b)In case at any time any of the following shall occur:

(i)the Trustee shall fail to comply with the provisions of Section 310(b) of the Trust Indenture Act with respect to any series of Securities after written request therefor by the Company or by any Securityholder who has been a bona fide holder of a Security or Securities of such series for at least six months; or

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(ii)the Trustee shall cease to be eligible in accordance with the provisions of ‎Section 7.09 and Section 310(a) of the Trust Indenture Act with respect to any series of Securities and shall fail to resign after written request therefor by the Company or by any such Securityholder; or

(iii)the Trustee shall become incapable of acting with respect to any series of Securities, or shall be adjudged a bankrupt or insolvent, or a receiver of the Trustee or of its property shall be appointed, or any public officer shall take charge or control of the Trustee or of its property or affairs for the purpose of rehabilitation, conservation or liquidation,

then, in any such case, the Company may remove the Trustee with respect to such series and appoint a successor Trustee with respect to such series by written instrument, in duplicate, executed in the name of and on behalf of the Company by a duly authorized Officer, one copy of which instrument shall be delivered to the Trustee so removed and one copy to the successor Trustee, or, subject to the provisions of ‎Section 6.09, any Securityholder who has been a bona fide holder of a Security or Securities of such series for at least six months may, on behalf of himself and all others similarly situated, petition any court of competent jurisdiction for the removal of the Trustee and the appointment of a successor Trustee with respect to such series. Such court may thereupon, after such notice, if any, as it may deem proper and prescribe, remove the Trustee and appoint a successor Trustee with respect to such series.

(c)The holders of a majority in aggregate principal amount of the Securities of one or more series (each series voting as a class) or all series at the time Outstanding may remove the Trustee with respect to the applicable series or all series, as the case may be, and appoint with respect to the applicable series or all series, as the case may be, a successor Trustee by 30 days prior written notice of such action to the Company, the Trustee and the successor Trustee.

(d)Any resignation or removal of the Trustee with respect to any series and any appointment of a successor Trustee with respect to such series pursuant to any of the provisions of this ‎Section 7.10 shall become effective upon acceptance of appointment by the successor Trustee as provided in ‎Section 7.11 and payment of all fees, expenses and indemnity amounts owed to the outgoing Trustee.

(e)No predecessor Trustee shall be liable for the acts or omissions of any successor Trustee.

(f)Notwithstanding the replacement of the Trustee pursuant to this ‎Section 7.10, the Company’s obligations under ‎Section 7.06 shall continue for the benefit of the outgoing Trustee.

Section 7.11.Acceptance by Successor Trustee. Any successor Trustee appointed as provided in ‎Section 7.10 shall execute, acknowledge and deliver to the Company and to its predecessor Trustee an instrument accepting such appointment hereunder, and thereupon the resignation or

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removal of the predecessor Trustee with respect to any or all applicable series shall become effective and such successor Trustee, without any further act, deed or conveyance, shall become vested with all the rights, powers, duties and obligations with respect to such series of its predecessor hereunder, with like effect as if originally named as Trustee herein; but, nevertheless, on the written request of the Company or of the successor Trustee, the Trustee ceasing to act shall, upon payment (or due provision therefor) of any amounts then due it pursuant to the provisions of ‎Section 7.06, execute and deliver an instrument transferring to such successor Trustee all the rights and powers with respect to such series of the Trustee so ceasing to act. Upon request of any such successor Trustee, the Company shall execute any and all instruments in writing in order more fully and certainly to vest in and confirm to such successor Trustee all such rights and powers.

In case of the appointment hereunder of a successor Trustee with respect to the Securities of one or more (but not all) series, the Company, the predecessor Trustee and each successor Trustee with respect to the Securities of any applicable series shall execute and deliver an indenture supplemental hereto which shall contain such provisions as shall be deemed necessary or desirable to confirm that all the rights, powers, trusts and duties of the predecessor Trustee with respect to the Securities of any series as to which the predecessor Trustee is not retiring shall continue to be vested in the predecessor Trustee, and shall add to or change any of the provisions of this Indenture as shall be necessary to provide for or facilitate the administration of the trusts hereunder by more than one Trustee, it being understood that nothing herein or in such supplemental indenture shall constitute such Trustees co-trustees of the same trust and that each such Trustee shall be Trustee of a trust or trusts hereunder separate and apart from any trust or trusts hereunder administered by any other such Trustee.

No successor Trustee with respect to a series of Securities shall accept appointment as provided in this ‎Section 7.11 unless at the time of such acceptance such successor Trustee shall, with respect to such series, be qualified under Section 310(b) of the Trust Indenture Act and eligible under the provisions of ‎Section 7.09.

Upon acceptance of appointment by a successor Trustee with respect to any series as provided in this ‎Section 7.11, the Company shall give notice thereof to the holders of Securities of each series affected, by mailing such notice to such holders at their addresses as they shall appear on the Security Register. If the Company fails to mail such notice within ten days after the acceptance of appointment by the successor Trustee, the successor Trustee shall cause such notice to be given at the expense of the Company.

Section 7.12.Succession by Merger, etc. Any corporation into which the Trustee may be merged or converted or with which it may be consolidated, or any corporation resulting from any merger, conversion or consolidation to which the Trustee shall be a party, or any corporation succeeding to all or substantially all of the corporate trust business of the Trustee, shall be the successor to the Trustee hereunder, provided such corporation shall be qualified under Section 310(b) of the Trust Indenture

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Act and eligible under the provisions of ‎Section 7.09, without the execution or filing of any paper or any further act on the part of any of the parties hereto unless required by law, anything herein to the contrary notwithstanding.

In case at the time such successor to the Trustee shall succeed to the trust created by this Indenture with respect to one or more series of Securities, any of such Securities shall have been authenticated but not delivered, any such successor to the Trustee by merger, conversion or consolidation may adopt the certificate of authentication of any predecessor Trustee, and deliver such Security so authenticated; and in case at that time any of such Securities shall not have been authenticated, any successor to the Trustee may authenticate such Securities either in the name of such successor to the Trustee or, if such successor to the Trustee is a successor by merger, conversion or consolidation, the name of any predecessor hereunder; and in all such cases such certificate shall have the full force which it is anywhere in such Securities or in this Indenture provided that the certificate of the Trustee shall have.

Section 7.13.Appointment of Authenticating Agent. The Trustee may appoint an Authenticating Agent or Agents which shall be authorized to act on behalf of the Trustee to authenticate Securities issued upon original issue and upon exchange, registration of transfer, or partial conversion or partial redemption or pursuant to ‎Section 2.08, and Securities so authenticated shall be entitled to the benefits of this Indenture and shall be valid and obligatory for all purposes as if authenticated by the Trustee hereunder. Wherever reference is made in this Indenture to the authentication and delivery of Securities by the Trustee or the Trustee’s certificate of authentication, such reference shall be deemed to include authentication and delivery on behalf of the Trustee by an Authenticating Agent and a certificate of authentication executed on behalf of the Trustee by an Authenticating Agent. Each Authenticating Agent shall be acceptable to the Company and shall at all times be a corporation organized and doing business under the laws of the United States of America, any State thereof or the District of Columbia, authorized under such laws to act as Authenticating Agent, having a combined capital and surplus of not less than $50,000,000 and subject to supervision or examination by Federal or State authority. If such Authenticating Agent publishes reports of condition at least annually, pursuant to law or to the requirements of said supervising or examining authority, then for the purposes of this ‎Section 7.13, the combined capital and surplus of such Authenticating Agent shall be deemed to be its combined capital and surplus as set forth in its most recent report of condition so published. If at any time an Authenticating Agent shall cease to be eligible in accordance with the provisions of this ‎Section 7.13, such Authenticating Agent shall resign immediately in the manner and with the effect specified in this ‎Section 7.13.

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Any corporation into which an Authenticating Agent may be merged or converted or with which it may be consolidated, or any corporation resulting from any merger, conversion or consolidation to which such Authenticating Agent shall be a party, or any corporation succeeding to the corporate agency or corporate trust business of an Authenticating Agent, shall continue to be an Authenticating Agent, provided that such corporation shall be otherwise eligible under this ‎Section 7.13, without the execution or filing of any paper or any further act on the part of the Trustee or the Authenticating Agent.

An Authenticating Agent may resign at any time by giving written notice thereof to the Trustee, the Company and the Guarantor. The Trustee may at any time terminate the agency of an Authenticating Agent by giving written notice thereof to such Authenticating Agent, the Company and Shire. Upon receiving such a notice of resignation or upon such a termination, or in case at any time such Authenticating Agent shall cease to be eligible in accordance with the provisions of this ‎Section 7.13, the Trustee may appoint a successor Authenticating Agent which shall be acceptable to the Company and shall mail written notice of such appointment by first-class mail, postage prepaid, to all Securityholders as their names and addresses appear in the Security Register. Any successor Authenticating Agent upon acceptance of its appointment hereunder shall become vested with all the rights, powers and duties of its predecessor hereunder, with like effect as if originally named as an Authenticating Agent. No successor Authenticating Agent shall be appointed unless eligible under the provisions of this ‎Section 7.13.

The Company agrees to pay to each Authenticating Agent from time to time reasonable compensation for its services under this ‎Section 7.13.

If an appointment is made pursuant to this ‎Section 7.13, the Securities may have endorsed thereon, in addition to the Trustee’s certificate of authentication, an alternative certificate of authentication in the following form:

Dated:

This is one of the Securities of the series designated therein described in the within-mentioned Indenture.

Deutsche Bank Trust Company Americas, not in its individual capacity but solely as Trustee
AUTHENTICATING AGENT, As Authenticating Agent
By:
	Authorized Signatory

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Article 8
Concerning The Securityholders

Section 8.01.Action of Securityholders. Whenever in this Indenture it is provided that the holders of a specified percentage in aggregate principal amount of the Securities of any or all series may take any action (including the making of any demand or request, the giving of any notice, consent or waiver or the taking of any other action) the fact that at the time of taking any such action the holders of such specified percentage have joined therein may be evidenced (a) by any instrument or any number of instruments of similar tenor executed by such Securityholders in person or by agent or proxy appointed in writing, or (b) by the record of such Securityholders of Securities voting in favor thereof at any meeting of such Securityholders duly called and held in accordance with the provisions of ‎Article 9, or (c) by a combination of such instrument or instruments and any such record of such a meeting of such Securityholders.

Section 8.02.Proof of Execution by Securityholders. Subject to the provisions of Sections ‎7.01, ‎7.02 and ‎9.06, proof of the execution of any instrument by a Securityholder or his agent or proxy shall be sufficient if made in accordance with such reasonable rules and regulations as may be prescribed by the Trustee or in such manner as shall be reasonably satisfactory to the Trustee. The ownership of Securities shall be proved by the Security Register.

The record of any Securityholders’ meeting shall be proved in the manner provided in ‎Section 9.07.

The Company may set a record date for purposes of determining the identity of Securityholders of Securities of any series entitled to vote or consent to or revoke any action referred to in ‎Section 8.01, which record date may be set at any time or from time to time by notice to the Trustee, for any date or dates (in the case of any adjournment or reconsideration) not more than 60 days nor less than five days prior to the proposed date of such vote or consent, and thereafter, notwithstanding any other provisions hereof, with respect to Securities of any series, only Securityholders of Securities of such series of record on such record date shall be entitled to so vote or give such consent or revoke such vote or consent.

Section 8.03.Who Are Deemed Absolute Owners. The Company, the Trustee and any agent of the Company or the Trustee may deem the person in whose name any Security shall be registered upon the books of the Company to be, and may treat him as, the owner of such Security (whether or not such Security shall be overdue and notwithstanding any notation of ownership or other writing thereon) for the purpose of receiving payment of or on account of the principal of, premium, if any, and (subject to ‎Section 2.04) interest, if any, on such Security and for all other purposes; and neither the Company nor the Trustee nor any agent of the Company or of the Trustee

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shall be affected by any notice to the contrary. All such payments so made to any holder for the time being, or upon his order, shall be valid, and, to the extent of the sum or sums so paid, effectual to satisfy and discharge the liability for moneys payable upon any such Security.

No Beneficial Owner of a beneficial interest in any Global Security held on its behalf by a Depositary shall have any rights under this Indenture with respect to such Global Security, and such Depositary may be treated by the Company, the Trustee or any agent of the Company or the Trustee as the owner of such Security for all purposes whatsoever. None of the Company, the Trustee or any agent of the Company or the Trustee will have any responsibility or liability for any aspect of the records relating to or payments made on account of beneficial ownership interests of a Global Security or maintaining, supervising or reviewing any records relating to such beneficial ownership interests.

Section 8.04.Company-Owned Securities Disregarded. In determining whether the holders of the requisite aggregate principal amount of Securities have concurred in any demand, request, notice, direction, consent or waiver under this Indenture, Securities which are owned by the Company or any other obligor on the Securities with respect to which such determination is being made or by any person directly or indirectly controlling or controlled by or under direct or indirect common control with the Company or any other obligor on the Securities with respect to which such determination is being made shall be disregarded and deemed not to be Outstanding for the purpose of any such determination; provided that, for the purposes of determining whether the Trustee shall be protected in relying on any such demand, request, notice, direction, consent or waiver, only Securities which a Responsible Officer of the Trustee actually knows are so owned shall be so disregarded. Securities so owned which have been pledged in good faith may be regarded as Outstanding for the purposes of this ‎Section 8.04 if the pledgee shall establish to the satisfaction of the Trustee the pledgee’s right to vote such Securities and that the pledgee is not a person directly or indirectly controlling or controlled by or under direct or indirect common control with the Company or any such other obligor. In the case of a dispute as to such right, any decision by the Trustee taken upon the advice of counsel shall be full protection to the Trustee.

Section 8.05.Revocation of Consents; Future Holders Bound. At any time prior to (but not after) the evidencing to the Trustee, as provided in ‎Section 8.01, of the taking of any action by the holders of the percentage in aggregate principal amount of the Securities of any or all series, as the case may be, specified in this Indenture in connection with such action, any holder of a Security which is shown by the evidence to be included in the Securities the holders of which have consented to such action may, by filing written notice with the Trustee at its principal office and upon proof of holding as provided in ‎Section 8.02, revoke such action so far as concerns such Security. Except as aforesaid, any such action taken by the holder of

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any Security shall be conclusive and binding upon such holder and upon all future holders of such Security, irrespective of whether or not any notation in regard thereto is made upon such Security or any Security issued in exchange or substitution therefor.

Article 9
Securityholders’ Meetings

Section 9.01.Purposes of Meetings. A meeting of holders of Securities of any or all series may be called at any time and from time to time pursuant to the provisions of this ‎Article 9 for any of the following purposes:

(a)to give any notice to the Company or to the Trustee, or to give any directions to the Trustee, or to consent to the waiving of any default hereunder and its consequences, or to take any other action authorized to be taken by Securityholders pursuant to any of the provisions of ‎Article 6;

(b)to remove the Trustee and nominate a successor trustee pursuant to the provisions of ‎Article 7;

(c)to consent to the execution of an indenture or indentures supplemental hereto pursuant to the provisions of ‎Section 10.02; or

(d)to take any other action authorized to be taken by or on behalf of the holders of any specified aggregate principal amount of the Securities of any or all series, as the case may be, under any other provision of this Indenture or under applicable law.

Section 9.02.Call of Meetings by Trustee. The Trustee may at any time call a meeting of holders of Securities of any or all series to take any action specified in ‎Section 9.01, to be held at such time and at such place in the Borough of Manhattan, The City of New York, as the Trustee shall determine. Notice of every meeting of the holders of Securities of any or all series, setting forth the time and the place of such meeting and in general terms the action proposed to be taken at such meeting, shall be mailed to holders of Securities of each series affected at their addresses as they shall appear on the Security Register. Such notice shall be mailed not less than 10 nor more than 90 days prior to the date fixed for the meeting.

Section 9.03.Call of Meetings by Company or Securityholders. In case at any time the Company, pursuant to a resolution of its Board of Directors, or the holders of at least 10% in aggregate principal amount of the Securities then Outstanding of any series that may be affected by the action proposed to be taken at the meeting, shall have requested the Trustee to call a meeting of the holders of Securities of all series that may be so affected, by written request setting forth in reasonable detail the action proposed to be taken at the meeting, and the Trustee shall not have mailed the notice of such meeting within 20 days after receipt of such request, then the Company or

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such Securityholders, in the amount specified above, may determine the time and the place in said Borough of Manhattan, The City of New York, for such meeting and may call such meeting to take any action authorized in ‎Section 9.01, by mailing notice thereof as provided in ‎Section 9.02.

Section 9.04.Qualifications for Voting. To be entitled to vote at any meeting of Securityholders a person shall (a) be a holder of one or more Securities with respect to which such meeting is being held or (b) be a person appointed by an instrument in writing as proxy by a holder of one or more such Securities. The only persons who shall be entitled to be present or to speak at any meeting of Securityholders shall be the persons entitled to vote at such meeting and their counsel, any representatives of the Trustee and its counsel, any representatives of the Guarantor and their respective counsel and any representatives of the Company and its counsel.

Section 9.05.Quorum; Adjourned Meetings. The Persons entitled to vote a majority in aggregate principal amount of the Securities of the relevant series at the time Outstanding shall constitute a quorum for the transaction of all business specified in ‎Section 9.01. No business shall be transacted in the absence of a quorum (determined as provided in this ‎Section 9.05). In the absence of a quorum within 30 minutes after the time appointed for any such meeting, the meeting shall, if convened at the request of the holders of Securities (as provided in ‎Section 9.03), be dissolved. In any other case the meeting shall be adjourned for a period of not less than ten days as determined by the chairman of the meeting. In the absence of a quorum at any such adjourned meeting, such adjourned meeting shall be further adjourned for a period of not less than ten days as determined by the chairman of the meeting. Notice of the reconvening of any adjourned meeting shall be given as provided in ‎Section 9.02, except that such notice must be mailed not less than five days prior to the date on which the meeting is scheduled to be reconvened.

Subject to the foregoing, at the second reconvening of any meeting adjourned for lack of a quorum, the Persons entitled to vote 25% in aggregate principal amount of the Securities of the relevant series then Outstanding shall constitute a quorum for the taking of any action set forth in the notice of the original meeting. Notice of the reconvening of an adjourned meeting shall state expressly the percentage of the aggregate principal amount of the Securities of the relevant series then Outstanding which shall constitute a quorum.

At a meeting or any adjourned meeting duly convened and at which a quorum is present as aforesaid, any resolution and all matters (except as limited by the proviso in ‎Section 10.02) shall be effectively passed and decided if passed or decided by the Persons entitled to vote the lesser of (a) a majority in aggregate principal amount of the Securities of the relevant series then Outstanding and (b) 75% in aggregate principal amount of the Securities represented and voting at the meeting.

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Any holder of a Security who has executed in person or by proxy and delivered to the Trustee an instrument in writing complying with the provisions of ‎Article 8 shall be deemed to be present for the purposes of determining a quorum and be deemed to have voted; provided that such holder of a Security shall be considered as present or voting only with respect to the matters covered by such instrument in writing.

Section 9.06.Regulations. Notwithstanding any other provisions of this Indenture, the Trustee may make such reasonable regulations as it may deem advisable for any meeting of Securityholders, in regard to proof of the Securityholder and of the appointment of proxies, and in regard to the appointment and duties of inspectors of votes, the submission and examination of proxies, certificates and other evidence of the right to vote, and such other matters concerning the conduct of the meeting as it shall think fit.

The Trustee shall, by an instrument in writing, appoint a temporary chairman of the meeting, unless the meeting shall have been called by the Company or by Securityholders, as provided in ‎Section 9.03, in which case the Company or the Securityholders calling the meeting, as the case may be, shall in like manner appoint a temporary chairman. A permanent chairman and a permanent secretary of the meeting shall be elected by majority vote of the meeting.

Subject to the provisions of ‎Section 8.04, at any meeting each Securityholder with respect to which such meeting is being held or proxy shall be entitled to vote the principal amount (in the case of Original Issue Discount Securities, such principal amount to be determined as provided in the definition of “Outstanding” in ‎Section 1.01) of such Securities held or represented by such holder; provided, however, that no vote shall be cast or counted at any meeting in respect of any such Security challenged as not Outstanding and ruled by the chairman of the meeting to be not Outstanding. The chairman of the meeting shall have no right to vote other than by virtue of such Securities held by him or instruments in writing as aforesaid duly designating him as the person to vote on behalf of other such Securityholders. Any meeting of holders of Securities with respect to which a meeting was duly called pursuant to the provisions of Sections ‎9.02 or ‎9.03 may be adjourned from time to time by a majority of those present, whether or not constituting a quorum, and the meeting may be held as so adjourned without further notice.

Section 9.07.Voting. The vote upon any resolution submitted to any meeting of holders of Securities with respect to which such meeting is being held shall be by written ballots on which shall be subscribed the signatures of such holders of Securities or of their representatives by proxy and the principal amount (in the case of Original Issue Discount Securities, such principal amount to be determined as provided in the definition of “Outstanding” in ‎Section 1.01) and number or numbers of such Securities held or represented by them. The permanent chairman of the meeting shall appoint two inspectors of votes who shall count all votes cast at the meeting for or against any resolution and who shall make and file with the secretary

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of the meeting their verified written reports in duplicate of all votes cast at the meeting. A record in duplicate of the proceedings of each meeting of Securityholders shall be prepared by the secretary of the meeting and there shall be attached to said record the original reports of the inspectors of votes on any vote by ballot taken thereat and affidavits by one or more persons having knowledge of the facts setting forth a copy of the notice of the meeting and showing that said notice was mailed as provided in ‎Section 9.02. The record shall show the principal amount of the Securities (in the case of Original Issue Discount Securities, such principal amount to be determined as provided in the definition of “Outstanding” in ‎Section 1.01) voting in favor of or against any resolution. The record shall be signed and verified by the affidavits of the permanent chairman and secretary of the meeting and one of the duplicates shall be delivered to the Company and the other to the Trustee to be preserved by the Trustee, the latter to have attached thereto the ballots voted at the meeting.

Any record so signed and verified shall be conclusive evidence of the matters therein stated.

Section 9.08.No Delay of Rights by Meeting. Nothing in this ‎Article 9 contained shall be deemed or construed to authorize or permit, by reason of any call of a meeting of Securityholders of any or all series or any rights expressly or impliedly conferred hereunder to make such call, any hindrance or delay in the exercise of any right or rights conferred upon or reserved to the Trustee or to the Securityholders of any or all such series under any of the provisions of this Indenture or of the Securities.

Article 10
Supplemental Indentures

Section 10.01.Supplemental Indentures without Consent of Securityholders. The Company, the Guarantor and the Trustee may from time to time and at any time, without the consent of the holders of the Securities of any series, enter into an indenture or indentures supplemental hereto for one or more of the following purposes:

(a)to evidence the succession of another designated activity company, corporation or limited liability company to the Company or Shire, as the case may be, or successive successions, and the assumption by the successor Person of the covenants, agreements and obligations of the Company or Shire, as the case may be, pursuant to ‎Article 11 hereof, or to evidence the assumption by a corporation, as a co-obligor under this Indenture and the Securities, of the covenants, agreements and obligations of the Company or Shire, as the case may be, pursuant to ‎Article 11;

(b)to add to the covenants of the Company or the Guarantor such further covenants, restrictions, conditions or provisions for the protection of the holders of all or any series of Securities (and if such covenants are to be for the benefit of less than all

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series of Securities, stating that such covenants are expressly being included for the benefit of such series) as the Board of Directors of the Company shall consider to be for the protection of the holders of such Securities, and to make the occurrence, or the occurrence and continuance, of a default in any of such additional covenants, restrictions, conditions or provisions a default or an Event of Default permitting the enforcement of all or any of the several remedies provided in this Indenture as herein set forth; provided, however, that in respect of any such additional covenant, restriction, condition or provision, such supplemental indenture may provide for a particular period of grace after default (which period may be shorter or longer than that allowed in the case of other defaults) or may provide for an immediate enforcement upon such default or may limit the remedies available to the Trustee upon such default;

(c)to establish the forms or terms of Securities of any series as permitted by Sections ‎2.01 and ‎2.02 and any Guarantee thereof;

(d)to cure any ambiguity, to correct or supplement any provision or provisions contained herein or in any supplemental indenture that may be defective or inconsistent with any other provision contained herein or in any supplemental indenture, or to create such other provisions in regard to matters or questions arising under this Indenture or indentures supplemental hereto that do not, or otherwise amend or supplement this Indenture or indentures supplemental hereto in a manner that does not, adversely affect the interests of the Securityholders of any Securities of such series in any material respect;

(e)to modify or amend this Indenture to permit the qualification of this Indenture or any indentures supplemental hereto under the Trust Indenture Act as then in effect;

(f)to conform the text of this Indenture, any indenture supplemental hereto, or the terms of any series of debt securities to any provision of the “Description of Debt Securities and Guarantee” in the prospectus contained in the Registration Statement of the Company and Shire on Form S-3 filed with the SEC on September 2, 2016 or the “Description of the Notes and Guarantee” in any related prospectus supplement thereto;

(g)to provide for the issuance of Additional Securities of any series of Securities;

(h)to provide for the exchange of any Securities of one or more series in global form represented by one or more Global Securities for Securities of the same series issued under this Indenture in definitive certificated form in the circumstances permitted by the terms of this Indenture and such Securities, and to make all appropriate changes to this Indenture for such purpose;

(i)to add to, change or eliminate any of the provisions contained herein or in any indentures supplemental hereto in respect of one or more series of Securities; provided that any such addition, change or elimination (i) shall not apply to, or modify the rights of any holder of, any Security of any series created prior to the execution of

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such supplemental indenture, or (ii) shall become effective only when no Securities of any series created prior to the execution of such supplemental indenture are Outstanding;

(j)to add guarantees with respect to the Securities of any series or to secure the Securities of any series; and

(k)to evidence and provide for the acceptance of appointment hereunder by a successor or separate trustee with respect to the Securities of one or more series or to add to or change any of the provisions of this Indenture as shall be necessary to provide for or facilitate the administration of the trusts hereunder by more than one trustee, pursuant to the requirements of ‎Section 7.11 or pursuant to ‎Section 2.02(s).

The Trustee is hereby authorized to join with the Company and the Guarantor in the execution of any such supplemental indenture, to make any further appropriate agreements and stipulations which may be therein contained and to accept the conveyance, transfer and assignment of any property thereunder, but the Trustee shall not be obligated to, but may in its discretion, enter into any such supplemental indenture which affects the Trustee’s own rights, duties or immunities under this Indenture or otherwise.

Any supplemental indenture authorized by the provisions of this ‎Section 10.01 may be executed by the Company, the Guarantor and the Trustee without the consent of the holders of any of the Securities at the time Outstanding, notwithstanding any of the provisions of ‎Section 10.02.

Section 10.02.Supplemental Indentures with Consent of Securityholders. With the consent (evidenced as provided in Sections ‎8.01 and ‎8.02) of the holders of not less than a majority in aggregate principal amount of the Securities of all series affected by such supplemental indenture at the time Outstanding, voting as a single class, the Company and the Guarantor, together with the Trustee, may from time to time and at any time enter into an indenture or indentures supplemental hereto for the purpose of adding any provisions to or changing in any manner or eliminating any of the provisions of this Indenture or any supplemental indenture or of modifying in any manner the rights of the holders of the Securities or each such series; provided, however, that no such supplemental indenture shall, without the consent of the holder of each Security so affected:

(a)change the stated maturity of principal of, or any installment of principal of or interest on, any Security;

(b)reduce the rate of or extend the time of payment of interest, if any, on any Security, or alter the manner of calculation of interest payable on any Security (except as part of any remarketing of the Securities of any series or any interest rate reset with respect to the Securities of any series, in each case in accordance with the terms of the Securities of such series);

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(c)reduce the principal amount or premium, if any, on any Security;

(d)reduce the amount payable upon the redemption of any Security or change the time of any mandatory redemption or, in respect of an optional redemption, the times at which any Security may be redeemed or, once notice of redemption has been given, the time at which it must thereupon be redeemed;

(e)make the principal amount or premium, if any, or interest on any Security, payable in any coin or currency other than that provided in any Security;

(f)reduce the percentage in principal amount of Securities of any series, the holders of which are required to consent to any such supplemental indenture or any waiver of any past default or Event of Default pursuant to ‎Section 6.07(b);

(g)change any place of payment where the Securities of any series or interest thereon is payable;

(h)modify the interest rate reset provision of any Security;

(i)impair the right of any holder of a Security to (i) receive payment of the principal of, or premium, if any, or interest on any Security on or after the respective due dates for such principal, premium or interest, or (ii) institute suit for the enforcement of any such payment;

(j)reduce the amount of the principal of an Original Issue Discount Security that would be due and payable upon an acceleration of the maturity thereof pursuant to ‎Section 6.01, or adversely affect the right of repayment, if any, at the option of the holder, or extend the time for, or reduce the amount of, any payment to any sinking fund or analogous obligation relating to any Security; or

(k)modify any provision of ‎Section 6.07(b) or this ‎Section 10.02 (except to increase the percentage in principal amount of Securities whose holders must consent to an amendment, or to provide that certain other provisions of this Indenture cannot be modified or waived without the consent of the holder of each Security affected by the modification or waiver).

Notwithstanding the foregoing, holders of the Securities of any series shall vote as a separate class with respect to modifications or amendments that affect only the Securities of such series, and the holders of other series of Securities shall not have any voting rights with respect to such matters as they relate to the Securities of such series.

Upon the request of the Company and the Guarantor, accompanied by a copy of the resolutions of the Board of Directors of each of the Company and the Guarantor authorizing the execution and delivery of any such supplemental indenture, and upon the filing with the Trustee of evidence of the consent of Securityholders (evidenced as provided in Sections ‎8.01 and ‎8.02), the Trustee shall join with the Company and the Guarantor in the execution of such supplemental indenture unless such supplemental indenture affects the Trustee’s own rights, duties or immunities under this Indenture or

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otherwise, in which case the Trustee may in its discretion but shall not be obligated to, enter into such supplemental indenture.

It shall not be necessary for the consent of the Securityholders under this ‎Section 10.02 to approve the particular form of any proposed supplemental indenture, but it shall be sufficient if such consent shall approve the substance thereof.

Section 10.03.Compliance with Trust Indenture Act; Effect of Supplemental Indentures. Any supplemental indenture executed pursuant to the provisions of this ‎Article 10 shall comply with the Trust Indenture Act, as then in effect. Upon the execution of any supplemental indenture pursuant to the provisions of this ‎Article 10, this Indenture shall be deemed to be modified and amended in accordance therewith and the respective rights, limitations of rights, obligations, duties and immunities under this Indenture of the Trustee, the Company, the Guarantor and the holders of the Securities of the applicable series shall thereafter be determined, exercised and enforced hereunder subject in all respects to such modifications and amendments, and all the terms and conditions of any such supplemental indenture shall be and be deemed to be part of the terms and conditions of this Indenture for any and all purposes.

Section 10.04.Notation on Securities. Securities authenticated and delivered after the execution of any supplemental indenture pursuant to the provisions of this ‎Article 10 may bear a notation in form approved by the Trustee as to any matter provided for in such supplemental indenture. If the Company or the Trustee shall so determine, new Securities of any series so modified as to conform, in the opinion of the Trustee and the Board of Directors, to any modification of this Indenture contained in any such supplemental indenture may be prepared and executed by the Company, authenticated by the Trustee and delivered in exchange for the Securities of such series then Outstanding.

Section 10.05.Evidence of Compliance of Supplemental Indenture to be Furnished Trustee. The Trustee shall receive an Officer’s Certificate and an Opinion of Counsel as conclusive evidence and stating that any supplemental indenture executed pursuant hereto complies with the requirements of this Indenture, is authorized or permitted by this Indenture, and is a legal, valid and binding obligation of the Company (and the Guarantor, if applicable) enforceable against them in accordance with its terms.

Article 11
Consolidation, Merger, Sale or Conveyance

Section 11.01.Company and Shire May Not Consolidate, etc. The Company and Shire each covenants that it will not, in a single transaction or through a series of related transactions, (i) merge or consolidate with any

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other Person, or (ii) sell, convey, transfer or otherwise dispose of all or substantially all of its assets to any other Person (other than a Subsidiary), in each case unless:

(a)either (i) the Company or Shire, as the case may be, shall be the continuing Person or (ii) if the Company or Shire, as the case may be, is not the continuing Person, then the successor Person formed by such consolidation or into which the Company or Shire, as the case may be, is merged or the person to which substantially all of the Company’s or Shire’s assets are so transferred or otherwise disposed (if other than the Company or Shire, as the case may be) shall be a designated activity company, corporation or limited liability company organized and existing under the laws of Ireland, Jersey or any other jurisdiction in the Channel Islands, the United Kingdom, the United States of America or any state thereof or the District of Columbia, Bermuda, the Cayman Islands, or any jurisdiction that is a member country of the Organization for Economic Co-Operation and Development as of the date hereof and such successor Person shall expressly assume the due and punctual payment of the principal of, and premium, if any, and interest, if any, on all the Securities according to their tenor, and the due and punctual performance and observance of all the covenants and conditions of this Indenture to be performed by the Company or Shire, as the case may be, under this Indenture and each series of Securities by supplemental indenture satisfactory to the Trustee, executed and delivered to the Trustee by such successor Person;

(b)immediately after giving pro forma effect to such merger or consolidation, or such sale, conveyance, transfer or other disposition, the Company or Shire, as the case may be, or such successor Person shall not be in default in the performance of any covenant or condition under this Indenture, and no Event of Default shall have occurred and be continuing; and

(c)the Company or Shire, as the case may be, shall have delivered to the Trustee an Officer’s Certificate and an Opinion of Counsel, each stating that such merger, consolidation, sale, conveyance, transfer or other disposition and supplemental indenture (if any) comply with this Indenture.

In the event of any such merger, consolidation, sale, conveyance (other than by way of lease), transfer or other disposition, and upon any such assumption by the successor Person, the predecessor company may be dissolved, wound up or liquidated at any time thereafter.

Section 11.02.Successor Person to be Substituted. In case of any such merger, consolidation, sale, conveyance (other than by way of lease), transfer or other disposition, and upon any such assumption by the successor Person, such successor Person shall succeed to and be substituted for the Company or Shire, as the case may be, with the same effect as if it had been named herein as the Company or Shire, as the case may be, and the Company or Shire, as the case may be, shall be relieved of any further obligation under this Indenture and under the Securities. Such successor Person (in the case of a successor to the Company) thereupon may cause to be signed, and may

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issue either in its own name or in the name of the Company, any or all of the Securities issuable hereunder which theretofore shall not have been signed by the Company and delivered to the Trustee; and, upon the order of such successor Person, instead of the Company, and subject to all the terms, conditions and limitations in this Indenture prescribed, the Trustee shall authenticate and shall deliver any Securities which previously shall have been signed and delivered by an Officer of the Company to the Trustee for authentication, and any Securities which such successor Person thereafter shall cause to be signed and delivered to the Trustee for that purpose. All the Securities so issued shall in all respects have the same legal rank and benefit under this Indenture as the Securities theretofore or thereafter issued in accordance with the terms of this Indenture as though all of such Securities had been issued at the date of the execution hereof.

In case of any such merger, consolidation, sale, conveyance, transfer or other disposition, such changes in phraseology and form (but not in substance) may be made in the Securities thereafter to be issued as may be appropriate.

Section 11.03.Documents to be Given Trustee. The Trustee shall receive an Officer’s Certificate and an Opinion of Counsel from the Company or Shire, as the case may be, as conclusive evidence that any such consolidation, merger, sale, conveyance, transfer or other disposition, and any such assumption, comply with the provisions of this ‎Article 11.

Article 12
Satisfaction and Discharge of Indenture; Defeasance

Section 12.01.Discharge of Indenture. With respect to any series of Securities:

(a)if either:

(i)the Company shall deliver to the Trustee for cancellation all Securities of such series theretofore authenticated and not theretofore cancelled (other than (1) any Securities of such series which shall have been destroyed, lost or stolen or in lieu of or in substitution for which other Securities of such series shall have been authenticated and delivered, or which shall have been paid, pursuant to the provisions of ‎Section 2.08 or (2) Securities of such series for whose payment money has theretofore been deposited in trust and thereafter repaid to the Company as provided in ‎Section 12.06); or

(ii)all the Securities of such series not theretofore cancelled or delivered to the Trustee for cancellation shall have become due and payable, or are by their terms to become due and payable within one year or are to be called for redemption within one year under arrangements satisfactory to the Trustee for the giving of notice of redemption, and the Company shall have irrevocably deposited with the Trustee, in trust, funds sufficient to pay at maturity or upon

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redemption all of the Securities of such series not theretofore cancelled or delivered to the Trustee for cancellation (other than any (1) Securities of such series which shall have been destroyed, lost or stolen and in lieu of or in substitution for which other Securities of such series shall have been authenticated and delivered, or which shall have been paid, pursuant to the provisions of ‎Section 2.08 or (2) Securities of such series for whose payment money has theretofore been deposited in trust and thereafter repaid to the Company as provided in ‎Section 12.06), including principal, premium, if any, and interest, if any, due or to become due to such date of maturity or date fixed for redemption, as the case may be; and

(b)if in either case the Company shall also pay or cause to be paid all other sums payable hereunder by the Company,

then this Indenture shall cease to be of further effect with respect to such series of Securities (except as to (A) rights of registration of transfer and exchange of Securities, (B) substitution of mutilated, defaced, destroyed, lost or stolen Securities, (C) rights of holders to receive payments of principal thereof and interest thereon, and remaining rights of the holders to receive mandatory sinking fund payments, if any, (D) the rights, obligations and immunities of the Trustee hereunder and (E) the rights of the Securityholders as beneficiaries hereof with respect to the property so deposited with the Trustee payable to all or any of them), and the Trustee, on demand of the Company, accompanied by an Officer’s Certificate and an Opinion of Counsel to the effect that all conditions precedent to such satisfaction and discharge have been satisfied and at the cost and expense of the Company, shall execute proper instruments acknowledging satisfaction of and discharging this Indenture, the Company, however, hereby agreeing to reimburse the Trustee for any costs or expenses thereafter reasonably and properly incurred by the Trustee in connection with this Indenture, any documents related hereto, or the Securities.

Section 12.02.Legal Defeasance. Following the deposit referred to in clause ‎(a) of this ‎Section 12.02, the Company will be deemed to have paid and will be discharged from its obligations in respect of the Securities, and the Guarantor will be discharged from its obligations in respect of the Guarantee, of the series with respect to which such deposit shall have been made and this Indenture with respect to such Securities and related Guarantee, other than (i) the rights of the Securityholders of Outstanding Securities of such series to receive, solely from the trust fund described in such clause ‎(a), payments in respect of the principal of, premium, if any, and interest on such securities when such payments are due and (ii) its obligations in ‎Article 2 and Sections ‎4.02, ‎7.06, ‎7.10, ‎12.06 and ‎12.07, provided that each of the following conditions have been satisfied:

(a)the Company has irrevocably deposited in trust with the Trustee, as trust funds solely for the benefit of the Securityholders of such series, money in an amount sufficient, or U.S. Government Obligations the scheduled payments of principal of and interest on which shall be sufficient, or a combination thereof sufficient, in the opinion of

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a nationally recognized firm of independent public accountants expressed in a written certification delivered to the Trustee, without consideration of any reinvestment, to pay principal of, premium, if any, and interest, if any, on the Securities of such series to maturity or redemption, as the case may be; provided that any redemption before maturity has been irrevocably provided for under arrangements satisfactory to the Trustee;

(b)the deposit will not result in a breach or violation of, or constitute a default under, this Indenture;

(c)the Company has delivered to the Trustee either (i) a ruling received from the Internal Revenue Service to the effect that beneficial owners of the Securities of such series will not recognize income, gain or loss for federal income tax purposes as a result of the defeasance and will be subject to federal income tax on the same amount and in the same manner and at the same times as would have been the case in the absence of the Company’s exercise of such right or (ii) an Opinion of Counsel, based on a change in law after the date of this Indenture, to the same effect as the ruling described in clause ‎(i); and

(d)the Company has delivered to the Trustee an Officer’s Certificate and an Opinion of Counsel, in each case stating that all conditions precedent provided for herein relating to the defeasance have been complied with.

Following the deposit referred to in clause ‎(a) of this ‎Section 12.02, the Trustee, upon the request and at the cost and expense of the Company, will acknowledge in writing the discharge of the Company’s or the Guarantor’s obligations under the Securities of such series and this Indenture with respect to such series except for the surviving obligations specified above.

Section 12.03.Covenant Defeasance. Following the deposit referred to in clause ‎(a) of this ‎Section 12.03 with respect to the Securities of a series, (i) the Company’s or the Guarantor’s obligations pursuant to each of ‎Section 5.02, ‎Article 11 and any other covenants for such series of Securities established as contemplated by ‎Section 2.02(v) and expressed to be subject to covenant defeasance pursuant to this ‎Section 12.03, will terminate, and (ii) each of ‎Section 6.01(c) (solely to the extent relating to the covenants described in clause (i) of this ‎Section 12.03) and any other Event of Default or Events of Default established as contemplated by ‎Section 6.01(g) and expressed to be subject to covenant defeasance pursuant to this ‎Section 12.03, will no longer constitute Events of Default with respect to the Securities of such series, provided the following conditions have been satisfied:

(a)the Company or the Guarantor, as the case may be, has complied with Sections ‎12.02(a), ‎12.02(b) and ‎12.02(d); and

(b)the Company has delivered to the Trustee an Opinion of Counsel to the effect that (i) the beneficial owners of the Securities of such series will not recognize income, gain or loss for federal income tax purposes as a result of the defeasance and will

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be subject to federal income tax on the same amount and in the same manner and at the same times as would have been the case in the absence of the Company’s exercise of such right, which Opinion of Counsel is based upon a change in the applicable federal tax law since the date of this Indenture as originally executed.

Except as specifically stated above, none of the Company’s or the Guarantor’s, as the case may be, obligations under this Indenture will be discharged.

Section 12.04.Deposited Moneys to be Held in Trust by Trustee; Miscellaneous Provisions. All moneys and U.S. Government Obligations (including the proceeds thereof) deposited with the Trustee pursuant to the provisions of ‎Section 12.02 or ‎12.03 shall be held in trust and applied by it to the payment of all sums due and to become due thereon for principal, premium, if any, and interest, if any, either directly or through any Paying Agent (including the Company if acting as its own Paying Agent), to the holders of the Securities of the applicable series for payment or redemption of which such moneys or U.S. Government Obligations have been deposited with the Trustee.The Company shall pay and indemnify the Trustee against any tax, fee or other charge imposed on or assessed against the U.S. Government Obligations deposited pursuant to ‎Section 12.01 or ‎12.03 or the principal and interest received in respect thereof other than any such tax, fee or other charge which by law is for the account of the holders of the Securities of the applicable series.

Anything in this ‎Article 12 to the contrary notwithstanding, the Trustee shall deliver or pay to the Company from time to time upon request of the Company any money or U.S. Government Obligations held by it as provided in ‎Section 12.01 or ‎12.03 with respect to any Securities which, in the opinion of a nationally recognized firm of independent public accountants expressed in a written certification thereof delivered to the Trustee, are in excess of the amount thereof which would then be required to be deposited to effect the legal defeasance or covenant defeasance, as the case may be, with respect to such Securities.

Section 12.05.Paying Agent to Repay Moneys Held. Upon the satisfaction and discharge of this Indenture all moneys then held by any Paying Agent of the Securities (other than the Trustee) shall, upon demand of the Company, be repaid to the Company or paid to the Trustee, and thereupon such Paying Agent shall be released from all further liability with respect to such moneys.

Section 12.06.Return of Unclaimed Moneys. Any moneys and U.S. Government Obligations deposited with or paid to the Trustee for payment of the principal of, premium, if any, and interest, if any, on Securities of any series and not applied but remaining unclaimed by the holders of Securities of such series for one year after the date upon which the principal of, premium, if any, or interest, if any, on the Securities of such series, as the case may be, shall have become due and payable, shall be repaid to the Company by the Trustee on written demand; and the holders of

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any Securities of such series shall thereafter look only to the Company for any payment which such holders may be entitled to collect and all liability of the Trustee with respect to such money shall thereupon cease.

Section 12.07.Reinstatement. If and for so long as the Trustee is unable to apply any money or U.S. Government Obligations held in trust pursuant to ‎Section 12.01, ‎12.02 or ‎12.03 by reason of any legal proceeding or by reason of any order or judgment of any court or governmental authority enjoining, restraining or otherwise prohibiting such application, the Company’s obligations under this Indenture and the Securities will be reinstated as though no such deposit in trust had been made. If the Company makes any payment of principal of or interest on any Securities because of the reinstatement of its obligations, it will be subrogated to the rights of the Securityholders of such Securities to receive such payment from the money or U.S. Government Obligations held in trust.

Article 13
Guarantee

Section 13.01.Guarantee. The Guarantor, as primary obligor and not merely as surety, hereby fully, unconditionally and irrevocably guarantees on a senior unsecured basis, jointly and severally, to each holder of Securities of each series and to the Trustee, the Agents and their respective successors and assigns (a) the full and punctual payment of principal of, premium, if any, and interest on the Securities of each such series when due, whether at maturity, by acceleration or otherwise, and all other monetary obligations of the Company under this Indenture and the Securities of each such series and (b) the full and punctual performance within applicable grace periods of all other obligations of the Company under this Indenture and the Securities of each such series (all such obligations set forth in clauses ‎(a) and ‎(b) above being hereinafter collectively called the “Guaranteed Obligations”). The Guarantor further agrees that the Guaranteed Obligations may be extended or renewed, in whole or in part, without notice or further assent from the Guarantor and that the Guarantor will remain bound under this ‎Article 13 notwithstanding any extension or renewal of any Guaranteed Obligation.

The Guarantor waives presentation to, demand of, payment from and protest to the Company of any of the Guaranteed Obligations and also waives notice of protest for nonpayment. The Guarantor waives notice of any default under the Securities of any series or the Guaranteed Obligations. The Guarantor waives all set-offs and counterclaims, notice of acceptance of the Guarantee, diligence, presentment, demand of payment, filing of claims with a court in the event of merger or insolvency or bankruptcy of the Company, any right to require a proceeding filed first against the Company, protest or notice with respect to the Securities or the indebtedness evidenced thereby and all demands whatsoever.

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The obligations of the Guarantor hereunder shall not be affected by (a) the failure of any Securityholder, the Trustee or Agents to assert any claim or demand or to enforce any right or remedy against the Company, any other guarantor or any other Person under this Indenture, the Securities of any series or any other agreement or otherwise; (b) any extension or renewal of any obligation of the Company under the Indenture or any Security, by operation of law or otherwise; (c) any rescission, waiver, amendment or modification of any of the terms or provisions of this Indenture, the Securities of any series or any other agreement; (d) any change in the ownership of the Guarantor; or (e) any lack of validity or enforceability of the Indenture, the Securities or any other agreement or instrument relating thereto.

The Guarantor further agrees that its Guarantee herein constitutes a guarantee of payment, performance and compliance when due (and not a guarantee of collection) and waives any right to require that any resort be had by any Securityholder, the Trustee or Agents to any security held for payment of the Guaranteed Obligations.

The Guarantor further agrees that its Guarantee herein shall continue to be effective or be reinstated, as the case may be, if at any time payment, or any part thereof, of principal of or interest on any Guaranteed Obligation is rescinded or must otherwise be restored by any Securityholder, the Trustee or Agents upon the bankruptcy or reorganization of the Company or otherwise.

The Guarantor also agrees to pay any and all costs and expenses (including reasonable attorneys’ fees) incurred by the Trustee, the Agents or any Securityholder in enforcing any rights under this ‎Article 13.

Section 13.02.Subrogation; Ranking.

(a)The Guarantor shall be subrogated to all rights of the Trustee or the holders of any Securities against the Company in respect of any amounts paid to the Trustee or such holder by the Guarantor pursuant to the provisions of the Guarantee; provided, however, that the Guarantor waives any right to enforce, or to receive any payments arising out of, or based upon, such right of subrogation until all Guaranteed Obligations shall have been paid in full.

(b)The Guarantor covenants and agrees that its obligation to make payments of the Guaranteed Obligations hereunder constitutes a direct, unsecured obligation of the Guarantor ranking equally in right of payment with all existing and future unsecured and unsubordinated obligations of the Guarantor and senior in right of payment to all future obligations of the Guarantor that are expressly subordinated to the Guaranteed Obligations.

Section 13.03.Limitation on Liability. The Guarantor, and by its acceptance of Securities of a series, each holder of Securities of each such series, hereby confirms that it is the intention of all such parties that the Guarantee of the Guarantor (a) does not constitute a fraudulent transfer or conveyance for purposes of any Federal, state or foreign bankruptcy,

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insolvency, receivership or similar law now or hereafter in effect, the Uniform Fraudulent Conveyance Act, the Uniform Fraudulent Transfer Act or any similar foreign, federal or state law to the extent applicable to any Guarantee, and (b) does not result in a distribution to Securityholders not permitted under the applicable foreign or state law. Any term or provision of this Indenture to the contrary notwithstanding, the maximum aggregate amount of the obligations guaranteed hereunder by the Guarantor shall not exceed the maximum amount that can be hereby guaranteed without rendering the Guarantee, as it relates to the Guarantor, voidable under applicable law relating to fraudulent conveyance or fraudulent transfer or similar laws affecting the rights of creditors generally.

Section 13.04.Successors and Assigns. This ‎Article 13 shall be binding upon the Guarantor and its successors and assigns and shall inure to the benefit of the successors and assigns of the Trustee, the Agents and the Securityholders and, in the event of any transfer or assignment of rights by any Securityholders, the Trustee or the Agents, the rights and privileges conferred upon that party in this Indenture and in the Securities of the relevant series shall automatically extend to and be vested in such transferee or assignee, all subject to the terms and conditions of this Indenture.

Section 13.05.No Waiver. Neither a failure nor a delay on the part of either the Trustee, the Agents or the Securityholders in exercising any right, power or privilege under this ‎Article 13 shall operate as a waiver thereof, nor shall a single or partial exercise thereof preclude any other or further exercise of any right, power or privilege. The rights, remedies and benefits of the Trustee, the Agents and the Securityholders herein expressly specified are cumulative and not exclusive of any other rights, remedies or benefits which either may have under this ‎Article 13 at law, in equity, by statute or otherwise.

Section 13.06.Termination of Guarantee. The Guarantor’s Guarantee shall automatically terminate and be released, and the obligations of the Guarantor under the Guarantee shall cease to exist, with respect to a particular series of Securities, upon payment in full of the Guaranteed Obligations with respect to such series of Securities.

Article 14
Immunity of Incorporators, Stockholders, Officers, Directors, Employees and Agents

Section 14.01.Indenture and Securities Solely Corporate Obligations. No recourse for the payment of the principal of, premium, if any, or interest, if any, on any Security, or for any claim based thereon or otherwise in respect thereof, and no recourse under or upon any obligation, covenant or agreement of the Company or the Guarantor, as the case may be, in this Indenture or in any supplemental indenture, or in any Security, or

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because of the creation of any indebtedness represented thereby, shall be had against any incorporator, stockholder, officer, director, employee or agent, as such, past, present or future, of the Company, the Guarantor or of any of their respective successor corporations, either directly or through the Company or any successor corporation, whether by virtue of any constitution, statute or rule of law, or by the enforcement of any assessment or penalty or otherwise; it being expressly understood that all such liability is hereby expressly waived and released as a condition of, and as a consideration for, the execution of this Indenture and the issue of the Securities.

Article 15
Miscellaneous Provisions

Section 15.01.Provisions Binding on Company’s Successors. All the covenants, stipulations, promises and agreements contained in this Indenture of the Company and the Guarantor shall bind their respective successors and assigns whether so expressed or not.

Section 15.02.Official Acts by Successor Person. Any act or proceeding authorized or required by any provision of this Indenture to be done or performed by any board, committee or Officer of the Company or the Guarantor, as the case may be, shall and may be done and performed with like force and effect by the like board, committee or officer of any corporation that shall at the time be the lawful sole successor of the Company or the Guarantor, as the case may be.

Section 15.03.Addresses for Notices, Notice to Holders, Waiver. Any notice or demand which by any provision of this Indenture is required or permitted to be given or served by the Trustee or by the holders of Securities on the Company or the Guarantor shall be in writing and may be given or served by being deposited postage prepaid by first class mail in a post office letter box addressed (until another address is filed by the Company with the Trustee) to Shire plc, 5 Riverwalk, Citywest Business Campus, Dublin, Ireland and confirmed to it at wrmordan@shire.com, attention of William R. Mordan, General Counsel, with a copy to Davis Polk & Wardwell LLP, 450 Lexington Avenue, New York, New York 10017 and confirmed to it at john.meade@davispolk.com, attention of John B. Meade. Any notice, direction, request or demand by any Securityholder to or upon the Trustee shall be deemed to have been sufficiently given or made, for all purposes, if given or made in writing at the Principal Office of the Trustee, addressed to the attention of its corporate trust office at 60 Wall Street – 16^th Floor, MSNYC60-1630, New York, New York 10005.

The Trustee agrees to accept and act upon instructions or directions pursuant to this Indenture sent by unsecured e-mail, facsimile transmission or other similar unsecured electronic methods; provided, however, that (a) the party providing such electronic instructions or directions, subsequent to the transmission thereof, shall provide the

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originally executed instructions or directions to the Trustee in a timely manner and (b) such originally executed instructions or directions shall be signed by an authorized representative of the party providing such instructions or directions. The Trustee shall not be liable for any losses, costs or expenses arising directly or indirectly from the Trustee’s reliance upon and compliance with such instructions or directions notwithstanding such instructions or directions conflict or are inconsistent with a subsequent written instruction or direction or if the subsequent written instruction or direction is never received. The party providing instructions or directions by unsecured e-mail, facsimile transmission or other similar unsecured electronic methods, as aforesaid, agrees to assume all risks arising out of the use of such electronic methods to submit instructions and directions to the Trustee, including without limitation the risk of the Trustee acting on unauthorized instructions, and the risk of interception and misuse by third parties.

Where this Indenture provides for notice of holders of any event, such notice shall be sufficiently given (unless otherwise herein expressly provided) if in writing and mailed, first-class postage prepaid, to each holder affected by such event, at his address as it appears in the Security Register, not later than the latest date (if any), and not earlier than the earliest date (if any), prescribed for the giving of such notice. In any case where notice to holders is given by mail, neither the failure to mail such notice, nor any defect in any notice so mailed, to any particular holder shall affect the sufficiency of such notice with respect to other holders. Where this Indenture provides for notice in any manner, such notice may be waived in writing by the Person entitled to receive such notice, either before or after the event, and such waiver shall be the equivalent of such notice. Waivers of notice by holders shall be filed with the Trustee, but such filing shall not be a condition precedent to the validity of any action taken in reliance upon such waiver.

In case by reason of the suspension of regular mail service or by reason of any other cause it shall be impracticable to give such notice by mail, then such notification as shall be made with approval of the Trustee shall constitute a sufficient notification for every purpose hereunder.

Section 15.04.Governing Law. THIS INDENTURE AND EACH SECURITY, AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS INDENTURE OR ANY SECURITY, SHALL BE GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK.

Each of the parties hereto hereby submits to the personal jurisdiction of, and each agrees that all proceedings relating hereto may be brought in, courts located within the City and State of New York. The Company and the Guarantor each waive personal service of process and consents to service of process by certified or registered mail, return receipt requested, directed to it at the address last specified for notices hereunder, and such service shall be deemed completed ten (10) calendar days after the same is so mailed. Any court order shall be accompanied by a legal opinion by counsel for the presenting party satisfactory to the Trustee to the effect that said opinion is final and nonappealeable.

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Section 15.05.Process Agent. The Company and Shire irrevocably designate, appoint and empower Shire Human Genetic Therapies, Inc. whose principal place of business is at 300 Shire Way, Lexington, MA 02421 as their authorized agent to receive and accept for and on behalf of each of the Company and Shire, and on behalf of their properties, assets and revenues, respectively, service by mail of any and all legal process, summons, notices and documents that may be served in any suit, action or proceeding brought against the Company or Shire, as the case may be, in any federal or state court in connection with this Indenture.

Section 15.06.Waiver of Trial by Jury. EACH OF THE COMPANY, THE GUARANTOR, THE TRUSTEE AND EACH HOLDER OF A SECURITY, BY ITS ACCEPTANCE THEREOF, HEREBY IRREVOCABLY WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY AND ALL RIGHT TO TRIAL BY JURY IN ANY LEGAL PROCEEDING ARISING OUT OF OR RELATING TO THIS INDENTURE, THE SECURITIES, THE GUARANTEE OR THE TRANSACTIONS CONTEMPLATED HEREBY.

Section 15.07.Evidence of Compliance with Conditions Precedent. Upon any application or demand by the Company or the Guarantor to the Trustee to take any action under any of the provisions of this Indenture, the Company or the Guarantor, as the case may be, shall furnish to the Trustee an Officer’s Certificate stating that all conditions precedent, if any, provided for in this Indenture relating to the proposed action have been complied with and an Opinion of Counsel stating that, in the opinion of such counsel, all such conditions precedent have been complied with.

Each certificate or opinion provided for in this Indenture and delivered to the Trustee with respect to compliance with a condition or covenant provided for in this Indenture shall include: (i) a statement that the person making such certificate or opinion has read such covenant or condition; (ii) a brief statement as to the nature and scope of the examination or investigation upon which the statements or opinion contained in such certificate or opinion are based; (iii) a statement that, in the opinion of such person, he has made such examination or investigation as is necessary to enable him to express an informed opinion as to whether or not such covenant or condition has been complied with; and (iv) a statement as to whether or not, in the opinion of such person, such condition or covenant has been complied with.

Section 15.08.Legal Holidays. Except as otherwise provided in any Security, in any case where the date of maturity of interest, if any, on or principal of, or premium, if any, on the Securities or the date fixed for redemption or repayment of any Security will be a date that is not a Business Day, then payment of such interest, if any, on or principal of or premium, if any, on the Securities need not be made on such date but may be made on the next succeeding Business Day, with the same force and effect as if made on

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the date of maturity or a date fixed for redemption or repayment, and no interest shall accrue for the period from and after such date.

Section 15.09.Securities in a Specified Currency other than Dollars. Unless otherwise specified as contemplated by ‎Section 2.02 with respect to a particular series of Securities, whenever for purposes of this Indenture any action may be taken by the holders of a specified percentage in aggregate principal amount of Securities of all series or all series affected by a particular action at the time Outstanding and, at such time, there are Outstanding any Securities of any series which are denominated in a Specified Currency other than Dollars, then the principal amount of Securities of such series which shall be deemed to be Outstanding for the purpose of taking such action shall be that amount of Dollars that could be obtained for such amount of such Specified Currency at the Market Exchange Rate, on the basis of the most recently available Market Exchange Rate on or before the date such action is taken. “Market Exchange Rate” shall mean, with respect to a Specified Currency, the noon Dollar buying rate in New York City for cable transfers of such Specified Currency published by the Federal Reserve Bank of New York. If such Market Exchange Rate is not available for any reason with respect to such Specified Currency, the Company shall use, in its sole discretion and without liability on its part, such quotation of the Federal Reserve Bank of New York or such other quotations as the Company shall deem appropriate. The provisions of this paragraph shall apply in determining the equivalent principal amount in respect of Securities of a series denominated in a Specified Currency other than Dollars in connection with any action taken by holders of Securities pursuant to the terms of this Indenture, including, without limitation, any determination contemplated in ‎Section 6.01(c).

All decisions and determination of the Company regarding the Market Exchange Rate or any alternative determination provided for in the preceding paragraph shall be in its sole discretion and shall, in the absence of manifest error, be conclusive to the extent permitted by law for all purposes and irrevocably binding upon the Company, the Guarantor and all Securityholders. The Trustee shall have no responsibility to determine the Market Exchange Rate.

Section 15.10.Trust Indenture Act to Control. If and to the extent that any provision of this Indenture limits, qualifies or conflicts with the duties imposed by, or with another provision (an “incorporated provision”) included in this Indenture by operation of, Sections 310 to 318, inclusive, of the Trust Indenture Act, such imposed duties or incorporated provision shall control.

Section 15.11.Table of Contents, Headings, etc. The table of contents and the titles and headings of the articles and sections of this Indenture have been inserted for convenience of reference only, are not to be

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considered a part hereof, and shall in no way modify or restrict any of the terms or provisions hereof.

Section 15.12.Execution in Counterparts. This Indenture may be executed in any number of counterparts, each of which shall be an original, but such counterparts shall together constitute but one and the same instrument. Signatures delivered by facsimile or in portable document format (.pdf) by email shall be deemed to be originals for all purposes hereunder.

Section 15.13.Separability; Benefits. In case any one or more of the provisions contained in this Indenture or in the Securities shall for any reason be held to be invalid, illegal or unenforceable, in any respect, then, to the extent permitted by law, such invalidity, illegality or unenforceability of the remaining provisions shall not in any way be affected or impaired thereby. Nothing in this Indenture or in the Securities, expressed or implied, shall give to any person, other than the parties hereto and their successors hereunder, and the holders of the Securities, any benefit or any legal or equitable right, remedy or claim under this Indenture.

[Signature Page Follows]

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IN WITNESS WHEREOF, the parties hereto have caused this Indenture to be duly executed, as of the day and year first written above.

GIVEN under the common seal of SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC and DELIVERED as a DEED:
	/s/ Michael Garry
	Name: Michael Garry
	Title: Director

SHIRE PLC, as Guarantor
	/s/ Jeffrey Poulton
	Name: Jeffrey Poulton
	Title: Chief Financial Officer

DEUTSCHE BANK TRUST COMPANY AMERICAS, not in its individual capacity but solely as Trustee, Security Registrar and Paying Agent
By:	Deutsche Bank National Trust Company

By:	/s/ Wanda Camacho
	Name: Wanda Camacho
	Title:  Vice President

By:	/s/ Annie Jaghatspanyan
	Name: Annie Jaghatspanyan
	Title: Vice President

[Signature Page to Indenture]

EX-4.2

Exhibit 4.2

SHIRE ACQUISITIONS INVESTMENTS IRELAND

DESIGNATED ACTIVITY COMPANY

as Issuer

SHIRE PLC

as Guarantor

AND

DEUTSCHE BANK TRUST COMPANY AMERICAS

as Trustee

_________________

FIRST SUPPLEMENTAL INDENTURE

Dated as of September 23, 2016

to the

INDENTURE

Dated as of September 23, 2016

_________________

TABLE OF CONTENTS

Page

Article 1 Definitions
Section 1.01.   Relation to Base Indenture	1
Section 1.02.   Definition of Terms	1
Article 2 General Terms and Conditions of the Notes
Section 2.01.   Designation and Principal Amount	7
Section 2.02.   Maturity	8
Section 2.03.   Form, Payment and Appointment	8
Section 2.04.   Global Notes	8
Section 2.05.   Interest	9
Section 2.06.   No Sinking Fund	10
Section 2.07.   Satisfaction and Discharge	10
Article 3 Redemption of the Notes
Section 3.01.   Optional Redemption by Company	10
Section 3.02.   Notice of Redemption; Conditions Precedent; Selection of Notes to be Redeemed	11
Section 3.03.   Payment of Redemption Price	12
Section 3.04.   Optional Redemption Due to Changes in Tax Treatment	12
Section 3.05.   No Other Redemption	13
Article 4 Forms of Notes
Section 4.01.   Forms of Notes	13
Article 5 Original Issue of Notes
Section 5.01.   Original Issue of Notes	13
Article 6 Future Guarantee
Section 6.01.   Future Guarantee	14

Section 6.02.   Release of Future Guarantor	14
Section 6.03.   Fraudulent Conveyance	14
Section 6.04.   Modification of Indenture	14
Article 7 Restriction on Secured Debt
Section 7.01.   Restriction on the Creation of Secured Debt	15
Section 7.02.   Covenant Defeasance	15
Article 8 Payment of Additional Amounts
Section 8.01.   Payment of Additional Amounts	15
Article 9 Change of Control
Section 9.01.   Change of Control Offer	17
Section 9.02.   Third Party Change of Control Offer	18
Section 9.03.   Right to Full Redemption	18
Section 9.04.   Compliance with Rule 14e-1	18
Section 9.05.   Covenant Defeasance	18
Article 10 Miscellaneous
Section 10.01.   Ratification of Indenture	18
Section 10.02.   Trustee Not Responsible for Recitals	19
Section 10.03.   Governing Law	19
Section 10.04.   Waiver of Trial by Jury	19
Section 10.05.   Table of Contents, Headings, etc	19
Section 10.06.   Execution in Counterparts	19
Section 10.07.   Separability; Benefits	19

EXHIBIT A	Form of 1.900% Senior Notes due 2019	A-1
EXHIBIT B	Form of 2.400% Senior Notes due 2021	B-1
EXHIBIT C	Form of 2.875% Senior Notes due 2023	C-1
EXHIBIT D	Form of 3.200% Senior Notes due 2026	D-1

THIS FIRST SUPPLEMENTAL INDENTURE (this “Supplemental Indenture”), dated as of September 23, 2016, is among SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC, an Irish designated activity company (the “Company”), as Issuer, SHIRE PLC, a Jersey public limited company and parent of the Company (“Shire”), as Guarantor, and DEUTSCHE BANK TRUST COMPANY AMERICAS (the “Trustee”), as Trustee.

R E C I T A L S

WHEREAS, the Company has concurrently herewith executed and delivered to the Trustee an Indenture, dated as of September 23, 2016, among the Company, Shire and the Trustee (the “Base Indenture” and, as supplemented by this Supplemental Indenture, the “Indenture”), providing for the issuance from time to time of series of Securities of the Company;

WHEREAS, Section 10.01(c) of the Base Indenture provides for the Company, Shire and the Trustee to enter into an indenture supplemental to the Base Indenture to establish the forms or terms of Securities of any series as permitted by ‎Section 2.01 and ‎Section 2.02 of the Base Indenture;

WHEREAS, pursuant to ‎Section 2.02 of the Base Indenture, the Company wishes to provide for the issuance of four new series of Securities to be known as its 1.900% Senior Notes due 2019 (the “2019 Notes”), its 2.400% Senior Notes due 2021 (the “2021 Notes”), its 2.875% Senior Notes due 2023 (the “2023 Notes”) and its 3.200% Senior Notes due 2026 (the “2026 Notes” and, together with the 2019 Notes, the 2021 Notes and the 2023 Notes, the “Notes”), the forms and terms of such Notes and the terms, provisions and conditions thereof to be set forth as provided in this Supplemental Indenture; and

WHEREAS, the Company has requested that the Trustee and Shire execute and deliver this Supplemental Indenture, and all requirements necessary to make this Supplemental Indenture a valid, binding and enforceable instrument in accordance with its terms, and to make the Notes, when executed by the Company and authenticated and delivered by the Trustee, the valid, binding and enforceable obligations of the Company, have been done and performed, and the execution and delivery of this Supplemental Indenture has been duly authorized in all respects;

NOW, THEREFORE, in consideration of the covenants and agreements set forth herein and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto hereby agree as follows:

Article 1
Definitions

Section 1.01. Relation to Base Indenture. This Supplemental Indenture constitutes an integral part of the Base Indenture.

Section 1.02. Definition of Terms. For all purposes of this Supplemental Indenture:

(a)       Capitalized terms used herein without definition shall have the meanings set forth in the Base Indenture;

(b)       a term defined anywhere in this Supplemental Indenture has the same meaning throughout;

(c)       the singular includes the plural and vice versa;

(d)       headings are for convenience of reference only and do not affect interpretation;

(e)       the following terms have the meanings given to them in this ‎‎Section 1.02(e):

“2019 Interest Payment Date” shall have the meaning set forth in ‎Section 2.05(b).

“2019 Record Date” shall have the meaning set forth in ‎Section 2.05(b).

“2021 Interest Payment Date” shall have the meaning set forth in ‎Section 2.05(c).

“2021 Record Date” shall have the meaning set forth in ‎Section 2.05(c).

“2023 Interest Payment Date” shall have the meaning set forth in ‎Section 2.05(d).

“2023 Record Date” shall have the meaning set forth in ‎Section 2.05(d).

“2026 Interest Payment Date” shall have the meaning set forth in ‎Section 2.05(e).

“2026 Record Date” shall have the meaning set forth in ‎Section 2.05(e).

“Additional Amounts” shall have the meaning specified in ‎Section 8.01.

“Baxalta” shall mean Baxalta Incorporated, a Delaware corporation and, as of the date of this Supplemental Indenture, a wholly-owned subsidiary of Shire.

“Business Day” shall mean, unless otherwise specified, any calendar day that is not a Saturday, Sunday or a day on which commercial banking institutions are not required to be open for business in the City of New York, New York.

“Capital Markets Indebtedness” shall mean any indebtedness for borrowed money in the form of, or represented by, bonds (obligations), debentures, notes or other securities that, at the time of its issuance, is being, is capable of being, or is intended to be, quoted, listed or ordinarily traded on any stock exchange or other securities market.

“Change of Control” shall mean the occurrence of any of the following: (1) the consummation of any transaction (including, without limitation, any merger or consolidation) the result of which is that any “person” (as that term is used in Section 13(d)(3) of the Exchange Act), other than Shire or one of its subsidiaries, becomes the beneficial owner (as defined in Rules 13d-3 and 13d-5 under the Exchange Act), directly or indirectly, of more than 50% of the Voting Stock of Shire or other Voting Stock into which the Voting Stock of Shire is reclassified, consolidated, exchanged or changed, measured by voting power rather than number of shares, (2)

2

the direct or indirect sale, transfer, conveyance or other disposition (other than by way of merger or consolidation) of all or substantially all of the assets of Shire and its subsidiaries (including us), taken as a whole, to another “Person” (as that term is defined in the Base Indenture), other than Shire or one of its subsidiaries, or (3) the adoption of a plan relating to Shire’s liquidation or dissolution. Notwithstanding the foregoing, a transaction, including a scheme of arrangement or analogous proceeding, will not be deemed to be a Change of Control if (1) Shire becomes a direct or indirect wholly-owned subsidiary of a corporation, limited liability company or similar entity (a “Holding Company”) and (2)(A) the direct or indirect holders of the Voting Stock of such Holding Company immediately following that transaction are substantially the same as the holders of Shire’s Voting Stock immediately prior to that transaction or (B) immediately following that transaction no “person” (as that term is used in Section 13(d)(3) of the Exchange Act) (other than a Holding Company satisfying the requirements of this sentence) is the beneficial owner, directly or indirectly, of more than 50% of the Voting Stock of such Holding Company.

“Change of Control Offer” shall have the meaning set forth in ‎Section 9.01.

“Change of Control Payment” shall have the meaning set forth in ‎Section 9.01.

“Change of Control Payment Date” shall have the meaning set forth in ‎Section 9.01.

“Change of Control Triggering Event” shall mean the occurrence of both a Change of Control and a Rating Event.

“Comparable Treasury Issue” shall mean the United States Treasury security selected by an Independent Investment Banker as having an actual or interpolated maturity comparable to the remaining term of the applicable series of Notes to be redeemed (assuming for this purpose, that the series of Notes to be redeemed matures on the applicable Par Call date of such Notes) that would be utilized, at the time of selection and in accordance with customary financial practice, in pricing new issues of corporate debt securities of comparable maturity to the remaining term of the Notes to be redeemed.

“Comparable Treasury Price” shall mean, as determined by the Independent Investment Banker, with respect to any Redemption Date, (a) the average of the Reference Treasury Dealer Quotations for such Redemption Date for the applicable series of Notes to be redeemed, after excluding the highest and lowest such Reference Treasury Dealer Quotations, or (b) if the Independent Investment Banker obtains fewer than four such Reference Treasury Dealer Quotations, the average of all such quotations.

“Consolidated Tangible Assets” shall mean, as of the date of determination, total assets (excluding those classified as goodwill and intangible assets) of Shire and its subsidiaries as of the most recent consolidated balance sheet available as of that date, as reported under U.S. generally accepted accounting principles.

“Credit Facility” shall mean (1) the Revolving Credit Facilities Agreement, (2) the November 2015 Term Facilities Agreement and (3) any credit facility of Shire and/or the Company that provides for Shire and/or the Company to borrow money on a term or revolving

3

basis from lenders in the international, or any relevant domestic, syndicated loan market (together, the “Credit Facilities”).

“DTC” shall have the meaning set forth in ‎Section 2.04(a).

“Exchange Act” shall mean the Securities Exchange Act of 1934, as amended.

“Global Notes” shall have the meaning set forth in ‎Section 2.04(a).

“Independent Investment Banker” shall mean one of the Reference Treasury Dealers appointed by the Company.

“Interest Payment Date” shall mean a 2019 Interest Payment Date, a 2021 Interest Payment Date, a 2023 Interest Payment Date or a 2026 Interest Payment Date, as the case may be.

“Interest Period” shall have the meaning set forth in ‎Section 2.05(a).

“Investment Grade Rating” shall mean a rating equal to or higher than Baa3 (or the equivalent) by Moody’s and BBB- (or the equivalent) by S&P, and the equivalent investment grade credit rating from any replacement Rating Agency or Rating Agencies.

“Maturity Date” shall have the meaning set forth in ‎Section 2.02.

“Moody’s” shall mean Moody’s Investors Service, Inc.

“Noteholder,” “holder of Notes,” or other similar terms, shall mean any person in whose name at the time a particular Note is registered on the books of the Company kept for that purpose in accordance with the terms hereof.

“November 2015 Term Facilities Agreement” shall mean the $5.6 billion Term Facilities Agreement, dated as of November 2, 2015, among Shire, as original borrower and original guarantor, Morgan Stanley Bank International Limited and Deutsche Bank AG, London Branch, as mandated lead arrangers and bookrunners, the financial institutions party thereto and Deutsche Bank AG, London Branch, as agent, as amended, supplemented or otherwise modified from time to time pursuant to the terms thereof.

“Optional Redemption Price” shall mean, with respect to any redemption of Notes, the applicable redemption price for such Notes set forth in ‎Section 3.01.

“Original Issue Discount Note” shall mean any Note which provides for an amount less than the principal amount thereof to be due and payable upon a declaration of acceleration of the maturity thereof pursuant to Section 6.01 of the Base Indenture.

“Par Call Date” means (a) in the case of the 2021 Notes, August 23, 2021 (the date that is one month prior to the Maturity Date of the 2021 Notes), (b) in the case of the 2023 Notes, July 23, 2023 (the date that is two months prior to the Maturity Date of the 2023 Notes) and (c)

4

in the case of the 2026 Notes, June 23, 2026 (the date that is three months prior to the Maturity Date of the 2026 Notes).

“Paying Agent” means any Person authorized by the Company or Shire to pay the principal of or any premium or interest on, or any Additional Amounts with respect to, any Notes on behalf of the Company.

“Principal Facility” shall mean any manufacturing plant, warehouse, office building and parcel of real property owned by Shire or any Restricted Subsidiary, provided each such facility has a gross book value (based on land, land improvements, building and building improvements only), without deduction for any depreciation reserves, in excess of 2.0% of Shire’s Consolidated Tangible Assets, other than any facility that is determined by Shire’s Board of Directors to not be of material importance to the business conducted by Shire and its subsidiaries taken as a whole.

“Rating Agencies” shall mean (1) each of Moody’s and S&P, and (2) if either Moody’s or S&P ceases to rate the Notes or fails to make a rating of the Notes publicly available for reasons outside of the Company’s control, a “nationally recognized statistical rating organization” within the meaning of Section 3(a)(62) of the Exchange Act selected by the Company (as certified by a resolution of its Board of Directors) as a replacement agency for Moody’s or S&P, or both of them, as the case may be.

“Rating Event” shall mean, with respect to any series of the Notes, the rating on such Notes is lowered by each of the Rating Agencies and such Notes are rated below an Investment Grade Rating by each of the Rating Agencies on any day within the 60-day period (which 60-day period will be extended so long as the rating of such Notes is under publicly announced consideration for a possible downgrade by any of the Rating Agencies but no longer than 180 days) after the earlier of (1) the occurrence of a Change of Control and (2) public notice of Shire’s intention to effect a Change of Control; provided, however, that a Rating Event otherwise arising by virtue of a particular reduction in rating will not be deemed to have occurred in respect of a particular Change of Control (and thus will not be deemed a Rating Event for purposes of the definition of Change of Control Triggering Event) if the Rating Agencies making the reduction in rating to which this definition would otherwise apply do not announce or publicly confirm or inform the Trustee in writing at the Company’s request that the reduction was the result, in whole or in part, of any event or circumstance comprised of or arising as a result of, or in respect of, the applicable Change of Control (whether or not the applicable Change of Control has occurred at the time of the Rating Event).

“Record Date” shall mean a 2019 Record Date, a 2021 Record Date, a 2023 Record Date or a 2026 Record Date, as the case may be.

“Relevant Jurisdiction” shall mean any jurisdiction in which the Company or Shire, as the case may be, is organized or resident for tax purposes (or any political subdivision or taxing authority thereof or therein).

“Redemption Date” shall mean, with respect to any redemption of Notes, the date fixed for such redemption pursuant to the Indenture and such Notes.

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“Reference Treasury Dealer” shall mean each of Barclays Capital Inc., Merrill Lynch, Pierce, Fenner & Smith Incorporated and Morgan Stanley & Co. LLC or their respective affiliates which are primary U.S. Government securities dealers in New York City (a “Primary Treasury Dealer”), and their respective successors, plus two other Primary Treasury Dealers selected by the Company; provided that if any of the foregoing or its affiliates shall cease to be a Primary Treasury Dealer, the Company shall substitute therefor another Primary Treasury Dealer.

“Reference Treasury Dealer Quotations” shall mean, with respect to each Reference Treasury Dealer and any Redemption Date, the average, as determined by the Independent Investment Banker, of the bid and asked prices for the Comparable Treasury Issue for the applicable series of Notes to be redeemed (expressed in each case as a percentage of its principal amount) quoted in writing to the Independent Investment Banker by the Reference Treasury Dealer at 3:30 p.m., New York City time, on the third Business Day preceding such Redemption Date.

“Restricted Subsidiary” shall mean any corporation, association, partnership or other business entity in which Shire owns or controls, directly or indirectly, more than 50% of the total voting power and which is either (1) designated as a Restricted Subsidiary in accordance with the Indenture or (2) satisfies each of the following criteria:

(a) existed as such on the date of the Indenture or is the successor to, or owns any equity interest in, a corporation, association, partnership or other business entity that so existed;

(b) has its principal business and assets in the United States;

(c) the business of which is other than the financing of the operations of Shire and its subsidiaries or the financing of the acquisition or disposition of real or personal property, including receivables, or the leasing of or dealing in real property for residential or office building purposes; and

(d) substantially all of whose assets do not consist of securities of one or more corporations, associations, partnerships or other business entities that are not Restricted Subsidiaries.

“Revolving Credit Facilities Agreement” shall mean the $2.1 billion Revolving Credit Facilities Agreement, dated as of December 12, 2014, among Shire, as original borrower and original guarantor, the financial institutions party thereto, as arrangers, and Barclays Bank plc, as facility agent, euro swingline agent and dollar swingline agent, as amended, supplemented or otherwise modified from time to time pursuant to the terms thereof.

“S&P” shall mean S&P Global Ratings, a division of The McGraw-Hill Companies, Inc.

“Secured Debt” shall have the meaning set forth in Section 7.01.

“Subsidiary” shall mean (a) any corporation of which the Company or Shire, as the case may be, directly or indirectly owns or controls at that time at least a majority of the outstanding

6

Voting Stock or (b) any other Person (other than a corporation) in which the Company or Shire, as the case may be, directly or indirectly has at least a majority ownership interest and power to direct the policies, management and affairs thereto.

“Treasury Rate” shall mean, with respect to any Redemption Date, the semiannual equivalent yield to maturity of the Comparable Treasury Issue for the applicable series of Notes to be redeemed, assuming a price for such Comparable Treasury Issue (expressed as a percentage of its principal amount) equal to the Comparable Treasury Price for such Redemption Date with respect to the applicable series of Notes to be redeemed.

“Voting Stock” shall mean, with respect to any specified “person” (as that term is used in Section 13(d)(3) of the Exchange Act), as of any date, the capital stock of such person that is at the time entitled to vote generally in the election of the board of directors of such person.

The terms “Base Indenture,” “Company,” “Indenture,” “Notes,” “Shire,” “Supplemental Indenture,” “Trustee,” “2019 Notes,” “2021 Notes,” “2023 Notes” and “2026 Notes” shall have the respective meanings set forth in the recitals to this Supplemental Indenture and the paragraph preceding such recitals.

Article 2
General Terms and Conditions of the Notes

Section 2.01. Designation and Principal Amount. The Notes may be issued from time to time upon written order of the Company for the authentication and delivery of Notes pursuant to ‎Section 2.03 of the Base Indenture.

(a)       2019 Notes

There is hereby authorized a series of Securities designated as 1.900% Senior Notes due 2019, limited in aggregate principal amount to U.S. $3,300,000,000 (except for 2019 Notes authenticated and delivered in accordance with the last paragraph of ‎Section 2.02 of the Base Indenture or upon registration of transfer of, or in exchange for, or in lieu of, other 2019 Notes pursuant to Section ‎2.06, 2.07, 2.08, 2.09, 3.03 or 10.04 of the Base Indenture).

(b)       2021 Notes

There is hereby authorized a series of Securities designated as 2.400% Senior Notes due 2021, limited in aggregate principal amount to U.S. $3,300,000,000 (except for 2021 Notes authenticated and delivered in accordance with the last paragraph of ‎Section 2.02 of the Base Indenture or upon registration of transfer of, or in exchange for, or in lieu of, other 2021 Notes pursuant to Section ‎2.06, 2.07, 2.08, 2.09, 3.03 or 10.04 of the Base Indenture).

(c)       2023 Notes

There is hereby authorized a series of Securities designated as 2.875% Senior Notes due 2023, limited in aggregate principal amount to U.S. $2,500,000,000 (except for 2023 Notes authenticated and delivered in accordance with the last paragraph of ‎Section 2.02 of the Base

7

Indenture or upon registration of transfer of, or in exchange for, or in lieu of, other 2023 Notes pursuant to Section 2.06, 2.07, 2.08, 2.09, 3.03 or 10.04 of the Base Indenture).

(d)       2026 Notes

There is hereby authorized a series of Securities designated as 3.200% Senior Notes due 2026, limited in aggregate principal amount to U.S. $3,000,000,000 (except for 2026 Notes authenticated and delivered in accordance with the last paragraph of ‎Section 2.02 of the Base Indenture or upon registration of transfer of, or in exchange for, or in lieu of, other 2026 Notes pursuant to Section 2.06, 2.07, 2.08, 2.09, 3.03 or 10.04 of the Base Indenture).

Section 2.02. Maturity. The date upon which the Notes shall become due and payable at final maturity, together with any accrued and unpaid interest, is September 23, 2019 for the 2019 Notes, September 23, 2021 for the 2021 Notes, September 23, 2023 for the 2023 Notes and September 23, 2026 for the 2026 Notes (each, a “Maturity Date”).

Section 2.03. Form, Payment and Appointment. Except as provided in ‎Section 2.04, the Notes of each series shall be issued in fully registered, certificated form, bearing identical terms within each series thereof. Principal of and premium, if any, and interest on the Notes will be payable, the transfer of such Notes will be registrable, such Notes will be exchangeable for Notes of a like aggregate principal amount bearing identical terms and provisions, and notices and demands to or upon the Company in respect of the Notes may be served at the office or agency of the Company maintained for such purpose in the Borough of Manhattan, the City of New York, which shall initially be the Principal Office of the Trustee in the Borough of Manhattan, the City of New York; provided, however, that payment of interest may be made at the option of the Company by check mailed to the Person entitled thereto at such address as shall appear in the Security Register or by wire transfer to an account appropriately designated by the Person entitled to payment, provided that the Paying Agent shall have received written notice of such account designation at least five Business Days prior to the date of such payment (subject to surrender of the relevant Note in the case of a payment of interest on a Redemption Date or Maturity Date).

No service charge shall be made for any registration of transfer or exchange of the Notes, but the Company may require payment from the holder of a sum sufficient to cover any tax or other governmental charge that may be imposed in connection therewith.

The Security Registrar and Paying Agent for the Notes shall initially be the Trustee.

The Specified Currency of the Notes shall be U.S. Dollars.

Section 2.04. Global Notes. i) The Notes of each series shall be issued initially in the form of one or more permanent Global Securities in registered form (each, a “Global Note”). The Depository Trust Company (“DTC”) shall initially act as the Depositary for the Notes. Each Global Note (i) shall be deposited with the Depositary or its custodian and registered in the name of DTC or DTC’s nominee, (ii) shall be delivered by the Trustee to such Depositary or pursuant to such Depositary’s instructions, and (iii) shall bear a legend substantially to the effect set forth in Section 2.12 of the Base Indenture.

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(b)       The aggregate amount of outstanding Notes represented by any Global Note may from time to time be increased or decreased to reflect exchanges or other increases or decreases in the principal amount thereof. The Trustee may make any endorsement on a Global Note to reflect the amount, or any increase or decrease in the amount, or changes in the rights of holders of the Notes represented thereby, in each case in accordance with the terms of the Indenture and the Notes.

(c)       Unless and until any Global Note for any series of Notes is exchanged for Notes of such series in certificated form, such Global Note may be transferred, in whole but not in part, and any payments on the Notes evidenced by such Global Note shall be made, only to the Depositary or a nominee of the Depositary, or to a successor Depositary selected or approved by the Company or to a nominee of such successor Depositary, in each case as the holder of such Notes.

Section 2.05. Interest. a) Interest payable on any Interest Payment Date, the Maturity Date or, if applicable, the Redemption Date, with respect to each series of Notes shall be the amount of interest accrued from, and including, the immediately preceding Interest Payment Date in respect of which interest has been paid or duly provided for (or from and including the original issue date of September 23, 2016, if no interest has been paid or duly provided for with respect to the series of Notes) to, but excluding, such Interest Payment Date, Maturity Date or, if applicable, Redemption Date, as the case may be (each, an “Interest Period”).

(b)       Interest on the 2019 Notes shall accrue from September 23, 2016 and shall be payable semi-annually in arrears on March 23 and September 23 of each year (each, a “2019 Interest Payment Date”), beginning on March 23, 2017 to, but excluding, the Maturity Date of the 2019 Notes. Interest shall be payable to the Persons in whose names the relevant 2019 Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “2019 Record Date”) at the annual rate of 1.900% per year, except as provided in Section 2.05(f), 2.05(g) and 2.05(h) hereof and Section 2.04 of the Base Indenture.

(c)       Interest on the 2021 Notes shall accrue from September 23, 2016 and shall be payable semi-annually in arrears on March 23 and September 23 of each year (each, a “2021 Interest Payment Date”), beginning on March 23, 2017 to, but excluding, the Maturity Date of the 2021 Notes. Interest shall be payable to the Persons in whose names the relevant 2021 Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “2021 Record Date”) at the annual rate of 2.400% per year, except as provided in Section 2.05(f), 2.05(g) and 2.05(h) hereof and Section 2.04 of the Base Indenture.

(d)       Interest on the 2023 Notes shall accrue from September 23, 2016 and shall be payable semi-annually in arrears on March 23 and September 23 of each year (each, a “2023 Interest Payment Date”), beginning on March 23, 2017 to, but excluding, the Maturity Date of the 2023 Notes. Interest shall be payable to the Persons in whose names the relevant 2023 Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “2023 Record

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Date”) at the annual rate of 2.875% per year, except as provided in Section 2.05(f), 2.05(g) and 2.05(h) hereof and Section 2.04 of the Base Indenture.

(e)       Interest on the 2026 Notes shall accrue from September 23, 2016 and shall be payable semi-annually in arrears on March 23 and September 23 of each year (each, a “2026 Interest Payment Date”), beginning on March 23, 2017 to, but excluding, the Maturity Date of the 2026 Notes. Interest shall be payable to the Persons in whose names the relevant 2026 Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “2026 Record Date”) at the annual rate of 3.200% per year, except as provided in Section 2.05(f), 2.05(g) and 2.05(h) hereof and Section 2.04 of the Base Indenture.

(f)       The amount of interest payable for any full semi-annual Interest Period in respect of a series of Notes will be calculated on the basis of a 360-day year consisting of twelve 30-day months. The amount of interest payable for any period shorter than a full semi-annual Interest Period in respect of a series of Notes will be calculated on the basis of a 30-day month and, for any period less than a month, the amount of interest will be calculated on the basis of the actual number of days elapsed per 30-day month. If any scheduled Interest Payment Date for a series of Notes falls on a day that is not a Business Day, then payment of interest payable on such Interest Payment Date will be postponed to the next succeeding day which is a Business Day (and no interest on such payment will accrue for the period from and after such scheduled Interest Payment Date).

(g)       In the event that the Maturity Date or a Redemption Date for any Note falls on a day that is not a Business Day, then the related payments of principal, premium, if any, and interest will be made on the next succeeding day that is a Business Day (and no additional interest will accumulate on the amount payable for the period from and after such Maturity Date or Redemption Date, as the case may be).

(h)       Interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of any Notes will be paid to the Person to whom principal of such Notes is payable.

Section 2.06. No Sinking Fund. The Notes are not entitled to the benefit of any sinking fund.

Section 2.07. Satisfaction and Discharge. Article 12 of the Base Indenture contains provisions for discharge of the Indenture and the defeasance of the obligations of the Company with respect to any series of Securities at any time upon compliance by the Company with certain conditions set forth therein, which provisions shall apply to each series of the Notes.

Article 3
Redemption of the Notes

Section 3.01. Optional Redemption by Company.

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(a)       Except as otherwise may be specified in this Supplemental Indenture, (A) at any time and from time to time in the case of the 2019 Notes and (B) prior to August 23, 2021 in the case of the 2021 Notes, July 23, 2023 in the case of the 2023 Notes and June 23, 2026 in the case of the 2026 Notes, the Company shall have the right to redeem the applicable series of Notes, in whole or in part, at its option, at a redemption price equal to the greater of:

(i)       100% of the aggregate principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date; and

(ii)       (A) in the case of the 2019 Notes, the sum of the present values of the remaining scheduled payments of principal and interest in respect of the 2019 Notes to be redeemed (not including any portion of interest accrued to, but excluding, the Redemption Date for the 2019 Notes to be redeemed) discounted to such Redemption Date on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months) at the applicable Treasury Rate plus 15 basis points, plus accrued and unpaid interest to, but excluding, the Redemption Date of the 2019 Notes to be redeemed and (B) in the case of the 2021 Notes, the 2023 Notes and the 2026 Notes, the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes to be redeemed from the Redemption Date to, but excluding (in the case of interest), the applicable Par Call Date (not including any portion of the interest accrued to, but excluding, the Redemption Date), discounted to such Redemption Date on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months) at the applicable Treasury Rate plus (i) 20 basis points, in the case of the 2021 Notes, (ii) 25 basis points, in the case of the 2023 Notes and (iii) 25 basis points, in the case of the 2026 Notes, plus, in each case, accrued and unpaid interest to, but excluding, the Redemption Date. The Treasury Rate shall be calculated on the third Business Day immediately preceding the Redemption Date.

(b)       At any time and from time to time on or after the applicable Par Call Date, the Company shall have the right to redeem the 2021 Notes, the 2023 Notes or the 2026 Notes, in whole or in part, at its option, at a redemption price equal to 100% of the principal amount of the Notes of such series to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date.

Section 3.02. Notice of Redemption; Conditions Precedent; Selection of Notes to be Redeemed. The Company shall mail (or otherwise deliver in accordance with the applicable procedures of the Depositary if the series of Notes to be redeemed are issued in the form of one or more Global Notes) notice of any redemption to the registered holders of the Notes of the series to be redeemed at least 30 and not more than 60 days prior to the Redemption Date. The Company shall notify the Trustee at least five Business Days prior to mailing such notice to holders unless a shorter period shall be satisfactory to the Trustee. Any redemption pursuant to Section 3.01(a) (and notice thereof) in connection with a proposed corporate transaction involving the Company or Shire or any of its subsidiaries (including an acquisition, disposition, or other strategic transaction, or a capital raising, including an equity offering or an incurrence of indebtedness) may, in the Company’s discretion, be subject to the satisfaction of one or more conditions precedent, including, but not limited to, completion of the related transaction. If such redemption is subject to the satisfaction of one of more conditions precedent, such notice shall

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state that, in the Company’s discretion, the Redemption Date may be delayed until such time as any or all such conditions shall be satisfied (or waived by the Company in its sole discretion), such redemption may not occur and such notice may be rescinded in the event that any or all of such conditions shall not have been satisfied (or waived by the Company in its sole discretion) by the Redemption Date, or by the Redemption Date so delayed. If less than all of the Notes are to be redeemed pursuant to Section 3.01, the Trustee shall select the Notes to be redeemed on a pro rata basis to the extent practicable or, to the extent that selection on a pro rata basis is not practicable for any reason, by such other method as the Trustee shall deem appropriate or as required by the applicable procedures of the Depositary. In the event of partial redemption by lot, the particular Notes to be redeemed shall be selected, unless otherwise provided herein, not less than 30 nor more than 60 days prior to the Redemption Date by the Trustee from the outstanding Notes not previously called for redemption.

Section 3.03. Payment of Redemption Price. The Optional Redemption Price for any Notes to be redeemed shall be paid prior to 12:00 noon, New York City time, on the Redemption Date or at such later time as is then permitted by the rules of the Depositary for the applicable series of Notes (if then registered as a Global Note); provided that the Company shall deposit with the Trustee an amount sufficient to pay the Optional Redemption Price for the Notes to be redeemed by 11:00 a.m., New York City time, on the date such Optional Redemption Price is to be paid.

Section 3.04. Optional Redemption Due to Changes in Tax Treatment. Any series of Notes may be redeemed, at the option of the Company or a successor person to the Company, in whole but not in part, upon giving notice to the holders of such series of Notes and the Trustee at least 30 days but not more than 60 days before the Redemption Date, at a Redemption Price equal to 100% of the aggregate principal amount of the Notes to be redeemed, together with any accrued and unpaid interest to, but excluding, the Redemption Date, if as a result of:

(a)        any change in, or amendment to, the laws (or any regulations or rulings promulgated thereunder) of a Relevant Jurisdiction affecting taxation; or

(b)       any change in the existing official position or the stating of an official position regarding the application or interpretation of such laws, regulations or rulings (including a holding, judgment or order by a court of competent jurisdiction) of a Relevant Jurisdiction affecting taxation, which change or amendment becomes effective (or with respect to official position, is announced) on or after the date of issuance of the Notes (or in the case of a successor Person that is not organized or a tax resident in a jurisdiction that is a Relevant Jurisdiction as of the date of such succession, on or after the date of succession), the Company or Shire is, or on the next Interest Payment Date would be, required to pay Additional Amounts, and such requirement cannot be avoided by the taking of reasonable measures by the Company or Shire, as applicable; provided that no such notice of redemption shall be given earlier than 90 days prior to the earliest date on which the Company or Shire, as applicable, would be required to pay Additional Amounts were a payment under or in respect of such series of Notes then due. The Company shall notify the Trustee at least five Business Days prior to mailing such notice of redemption to holders by delivering to the Trustee an Officers’ Certificate stating that a change or amendment referred to in the prior paragraph has occurred and that the requirement to pay Additional Amounts cannot be avoided by taking reasonable measures available to the Company

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or Shire, as applicable. The Trustee shall accept such certificate as sufficient evidence of the satisfaction of the conditions precedent described above, in which event it shall be conclusive and binding on the holders of such series of Notes.

Section 3.05. No Other Redemption. Except as set forth in Sections 3.01, 3.04 and 9.03, the Notes of each series shall not be redeemable by the Company prior to the applicable Maturity Date. The provisions of this ‎Article 3 shall supersede any conflicting provisions contained in ‎Article 3 of the Base Indenture.

Article 4
Forms of Notes

Section 4.01. Forms of Notes.

(a)       The 2019 Notes and the Trustee’s Certificate of Authentication to be endorsed thereon are to be substantially in the forms attached as Exhibit A hereto, with such appropriate insertions, omissions, substitutions and other variations as are required or permitted by the Indenture as the Officers of the Company executing the 2019 Notes (by manual or facsimile signature) may approve, such approval to be conclusively evidenced by their execution thereof.

(b)       The 2021 Notes and the Trustee’s Certificate of Authentication to be endorsed thereon are to be substantially in the forms attached as Exhibit B hereto, with such appropriate insertions, omissions, substitutions and other variations as are required or permitted by the Indenture as the Officers of the Company executing the 2021 Notes (by manual or facsimile signature) may approve, such approval to be conclusively evidenced by their execution thereof.

(c)       The 2023 Notes and the Trustee’s Certificate of Authentication to be endorsed thereon are to be substantially in the forms attached as Exhibit C hereto, with such appropriate insertions, omissions, substitutions and other variations as are required or permitted by the Indenture as the Officers of the Company executing the 2023 Notes (by manual or facsimile signature) may approve, such approval to be conclusively evidenced by their execution thereof.

(d)       The 2026 Notes and the Trustee’s Certificate of Authentication to be endorsed thereon are to be substantially in the forms attached as Exhibit D hereto, with such appropriate insertions, omissions, substitutions and other variations as are required or permitted by the Indenture as the Officers of the Company executing the 2026 Notes (by manual or facsimile signature) may approve, such approval to be conclusively evidenced by their execution thereof.

Article 5
Original Issue of Notes

Section 5.01. Original Issue of Notes. The 2019 Notes having an aggregate principal amount of U.S. $3,300,000,000, the 2021 Notes having an aggregate principal amount of U.S. $3,300,000,000, the 2023 Notes having an aggregate principal amount of U.S. $2,500,000,000 and the 2026 Notes having an aggregate principal amount of U.S. $3,000,000,000 (in each case, subject to the last paragraph of ‎Section 2.02 of the Base Indenture) may, upon execution of this Supplemental Indenture, be executed by the Company and delivered to the Trustee for

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authentication, and the Trustee shall thereupon authenticate and deliver said Notes to or upon the written order of the Company pursuant to ‎Section 2.03 of the Base Indenture without any further action by the Company (other than as required by the Base Indenture).

Article 6
Future Guarantee

Section 6.01. Future Guarantee. If Baxalta becomes a guarantor of any Credit Facility, then, within 10 Business Days of such event, the Company shall cause Baxalta to enter into a supplemental indenture to the Base Indenture pursuant to which Baxalta shall agree to fully and unconditionally guarantee on a direct, unsecured basis the due and punctual payment of the principal of, and any premium and interest on, the Notes and all other amounts, if any, under the Indenture in respect of the Notes when and as such principal, premium, if any, interest and other amounts, if any, become due and payable, whether at maturity or otherwise.

Section 6.02. Release of Future Guarantor. Notwithstanding Section 6.01, if Baxalta shall agree to guarantee the Notes pursuant to Section 6.01, such guarantee shall be automatically released with respect to a series of Notes and the Indenture with respect to such series of Notes:

(a)       upon the release or termination of Baxalta’s guarantee with respect to all Credit Facilities such that, after such release or termination, Baxalta is no longer a guarantor of any Credit Facility;

(b)       upon (i) the sale or other disposition (including by way of consolidation, merger, dissolution or otherwise) of the capital stock of Baxalta such that it is no longer a Subsidiary of Shire or (ii) the sale or other disposition of all or substantially all of the assets of Baxalta, in either such case in accordance with the terms of the Indenture; or

(c)       if the Company exercises its defeasance option with respect to such series of Notes pursuant to Sections 12.02 or 12.03 of the Base Indenture or if the Company’s obligations under the Indenture with respect to such series of Notes are satisfied and discharged in accordance with the terms of the Indenture.

Section 6.03. Fraudulent Conveyance. Any guarantee by Baxalta, if issued, shall be limited in amount to an amount not to exceed the maximum amount that can be guaranteed by Baxalta without rendering the guarantee voidable under applicable law relating to fraudulent conveyance or fraudulent transfer or similar laws affecting the rights of creditors generally.

Section 6.04. Modification of Indenture. Notwithstanding anything to the contrary in the Indenture, if Baxalta guarantees the Notes in the future, then the Company, Shire and Baxalta, together with the Trustee, may by supplemental indenture modify the terms of, or terminate, any such guarantee by Baxalta with respect to one or more series of Notes with the consent of the holders of at least a majority in aggregate principal amount of the outstanding debt securities of all series issued under the Indenture, including such series of Notes, affected by such modification or termination, voting as a single class. Notwithstanding the foregoing, holders of the Notes of any series shall vote as a separate class with respect to a modification or termination of any such future Baxalta guarantee that affects only the Notes of such series, and

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the holders of other series of debt securities issued under the Indenture shall not have any voting rights with respect to such matters as they relate to the Notes of such series.

Article 7
Restriction on Secured Debt

Section 7.01. Restriction on the Creation of Secured Debt. After the date hereof, Shire will not, and will not cause or permit a Restricted Subsidiary to, create, incur, assume or guarantee, any Capital Markets Indebtedness that is secured by a security interest in (i) any Principal Facility of Shire or any Restricted Subsidiary, (ii) equity interests owned directly or indirectly by Shire in any Restricted Subsidiary or (iii) indebtedness for money borrowed by one of its Restricted Subsidiaries from Shire or another of the Restricted Subsidiaries (any Capital Market Indebtedness secured by any of the foregoing, “Secured Debt”), including the creation of Secured Debt by the securing of existing Capital Markets Indebtedness, unless the Notes then outstanding are secured equally and ratably with such Secured Debt.

Notwithstanding the foregoing provisions of this ‎Section 7.01, Shire and any Restricted Subsidiary may create, incur, assume or guarantee Secured Debt, provided that the sum of such Secured Debt and all other Secured Debt created, incurred, assumed or guaranteed after the date hereof does not at the time exceed 15% of Shire’s Consolidated Tangible Assets.

Section 7.02. Covenant Defeasance. The covenant set forth in Section 7.01 of this Supplemental Indenture shall be subject to covenant defeasance under Section 12.03 of the Base Indenture.

Article 8
Payment of Additional Amounts

Section 8.01. Payment of Additional Amounts. All payments by the Company or Shire of principal of, and premium, if any, and interest on or in respect of any series of Notes will be made without withholding or deduction for, or on account of, any present or future taxes, duties, assessments or governmental charges imposed or levied by a Relevant Jurisdiction, unless such withholding or deduction is required by law or by regulation or governmental policy having the force of law. In the event that any such withholding or deduction is so required, the Company or Shire will pay such additional amounts (“Additional Amounts”) as will result in receipt by the beneficial owner of such Notes of such amounts as would have been received by such beneficial owner had no such withholding or deduction been required, except that no Additional Amounts shall be payable:

(a)       for or on account of:

(i)       any tax, duty, assessment or governmental charge that would not have been imposed but for:

(A)       the existence of any present or former connection between the Noteholder or beneficial owner of such Notes and the Relevant Jurisdiction, other than merely holding such Notes or the receipt of payments thereunder,

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including, without limitation, such Noteholder’s or beneficial owner’s being or having been a national, domiciliary or resident of such Relevant Jurisdiction or treated as a tax resident thereof or being or having been physically present or engaged in a trade or business therein or having or having had a permanent establishment therein;

(B)       the presentation of such Notes (where presentation is required) more than 30 days after the later of the date on which the payment of the principal of, premium, if any, or interest on, such Notes became due and payable pursuant to the terms thereof or was made or duly provided for, except to the extent that the Noteholder thereof would have been entitled to such Additional Amounts if it had presented such Notes for payment on any date within such 30-day period;

(C)       the failure of the Noteholder or beneficial owner to comply with a request of the Company, Shire or any Paying Agent, addressed to such Noteholder, to provide information concerning such Noteholder’s or beneficial owner’s nationality, residence, identity or connection with any Relevant Jurisdiction, if compliance with such request is required under the tax laws of the Relevant Jurisdiction in order to reduce or eliminate any withholding or deduction as to which Additional Amounts would have otherwise been payable to such Noteholder; or

(D)       the presentation of such Notes (where presentation is required) for payment in the Relevant Jurisdiction, unless such Notes could not have been presented for payment elsewhere;

(ii)       any estate, inheritance, gift, sale, transfer, personal property or similar tax, assessment or other governmental charge;

(iii)       any withholding or deduction that is imposed or levied on a payment and is required to be made pursuant to European Council Directive 2003/48/EC on the taxation of savings income or any directive amending, supplementing or replacing such Directive or any law implementing or complying with, or introduced in order to conform to, such Directive or directives;

(iv)       any combination of taxes, duties, assessments or other governmental charges referred to in the preceding clauses (i), (ii) or (iii); or

(b)       to a Noteholder that is a fiduciary, partnership or person other than the sole beneficial owner of any payment to the extent that, under the laws of a Relevant Jurisdiction, such payment would be required to be included in the income for tax purposes, of a beneficiary or settlor with respect to the fiduciary, a member of that partnership or a beneficial owner who would not have been entitled to such Additional Amounts had that beneficiary, settlor, partner or beneficial owner been the Noteholder thereof.

(c)       In addition, any amounts to be paid on the Notes will be paid net of any deduction or withholding imposed or required pursuant to Sections 1471 through 1474 of the U.S. Internal

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Revenue Code (the “Code”), any current or future regulations or official interpretations thereof, any agreement entered into pursuant to Section 1471(b) of the Code, or any fiscal or regulatory legislation, rules or practices adopted pursuant to any intergovernmental agreement entered into in connection with the implementation of such Sections of the Code, and no Additional Amounts will be required to be paid on account of any such deduction or withholding.

(d)       Whenever in this Supplemental Indenture there is mentioned, in any context, the payment of the principal of and premium, if any, or interest or any other amounts on, or in respect of, any Notes of any series, such mention shall be deemed to include mention of the payment of Additional Amounts provided by the terms of such series established hereby or pursuant to this ‎Article 8 to the extent that, in such context, Additional Amounts are, were or would be payable in respect thereof pursuant to such terms, and express mention of the payment of Additional Amounts (if applicable) in any provision hereof shall not be construed as excluding the payment of Additional Amounts in those provisions hereof where such express mention is not made.

Article 9
Change of Control

Section 9.01. Change of Control Offer. If a Change of Control Triggering Event occurs with respect to a series of Notes, other than with respect to a series of Notes for which the Company has exercised its right to redeem as described in ‎Section 3.01, the Company shall be required to make an offer (the “Change of Control Offer”) to each holder of such series of Notes to repurchase all or any part (equal to $2,000 or an integral multiple of $1,000 in excess thereof) of that holder’s Notes on the terms set forth below. In the Change of Control Offer, the Company shall be required to offer payment in cash equal to 101% of the aggregate principal amount of Notes repurchased, plus accrued and unpaid interest, if any, on the Notes to be repurchased to the date of repurchase (the “Change of Control Payment”). Within 30 days following any Change of Control Triggering Event with respect to a series of Notes or, at the option of the Company, prior to any Change of Control, but after public announcement of the transaction that constitutes or may constitute a Change of Control, a written notice shall be sent to holders of the Notes of such series and the Trustee describing the transaction that constitutes or may constitute the Change of Control Triggering Event with respect to such series of Notes and offering to repurchase such Notes on the date specified in the notice, which date shall be no earlier than 30 days and no later than 60 days from the date such notice is mailed (the “Change of Control Payment Date”). The notice shall, if mailed prior to the date of consummation of the Change of Control, state that the offer to purchase is conditioned on the Change of Control Triggering Event occurring on or prior to the Change of Control Payment Date. Holders of Notes electing to have such Notes purchased pursuant to a Change of Control Offer will be required to surrender such Notes, with the form entitled “Option of Holder to Elect Purchase” on the reverse of such Note completed, to the Paying Agent at the address specified in the notice, or transfer such Notes to the Paying Agent by book-entry transfer pursuant to the applicable procedures of the Paying Agent, prior to the close of business on the third Business Day prior to the Change of Control Payment Date.

On the Change of Control Payment Date, the Company shall, to the extent lawful:

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(1)       accept for payment all Notes or portions of Notes properly tendered pursuant to the Change of Control Offer;

(2)       deposit with the Paying Agent an amount equal to the Change of Control Payment in respect of all Notes or portions of Notes properly tendered; and

(3)       deliver or cause to be delivered to the Trustee the Notes properly accepted together with an Officers’ Certificate stating the aggregate principal amount of Notes or portions of Notes being repurchased.

Section 9.02. Third Party Change of Control Offer. The Company shall not be required to make a Change of Control Offer upon the occurrence of a Change of Control Triggering Event if a third party makes such an offer in the manner, at the times and otherwise in compliance with the requirements for an offer made by the Company and the third party repurchases all Notes properly tendered and not withdrawn under its offer.

Section 9.03. Right to Full Redemption. In the event that Noteholders of 90% or more of the aggregate principal amount of the Notes of a series then outstanding accept a Change of Control Offer and the Company purchases all of the Notes of such series tendered by such Noteholders, the Company will have the right, upon not less than 30 nor more than 60 days’ prior notice, given not more than 30 days following the purchase of Notes pursuant to the Change of Control Offer described above, to redeem all of the Notes of such series that remain outstanding following such purchase at a Redemption Price equal to the Change of Control Payment plus, to the extent not included in the Change of Control Payment, accrued and unpaid interest on the Notes of such series that remain outstanding, to, but excluding, the Redemption Date, subject to the rights of the holders of the Notes of such series on a relevant Record Date to receive interest due on the relevant Interest Payment Date.

Section 9.04. Compliance with Rule 14e-1. The Company shall comply with the requirements of Rule 14e-1 under the Exchange Act, and any other securities laws and regulations thereunder to the extent those laws and regulations are applicable in connection with the repurchase of the Notes as a result of a Change of Control Triggering Event. To the extent that the provisions of any such securities laws or regulations conflict with the Change of Control Offer provisions of the Notes, the Company shall comply with those securities laws and regulations and shall not be deemed to have breached its obligations under the Change of Control Offer provisions of the Notes by virtue of any such conflict.

Section 9.05. Covenant Defeasance. The covenant set forth in Section 9.01 of this Supplemental Indenture shall be subject to covenant defeasance under Section 12.03 of the Base Indenture.

Article 10
Miscellaneous

Section 10.01. Ratification of Indenture. The Base Indenture, as supplemented by this Supplemental Indenture, is in all respects ratified and confirmed, and this Supplemental

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Indenture shall be deemed part of the Base Indenture in the manner and to the extent herein and therein provided.

Section 10.02. Trustee Not Responsible for Recitals. The recitals herein contained are made by the Company and not by the Trustee, and the Trustee assumes no responsibility for the correctness thereof. The Trustee makes no representation as to the validity or sufficiency of this Supplemental Indenture.

Section 10.03. Governing Law. THIS SUPPLEMENTAL INDENTURE AND EACH NOTE, AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS SUPPLEMENTAL INDENTURE OR ANY NOTE, SHALL BE GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK.

Section 10.04. Waiver of Trial by Jury. EACH OF THE COMPANY, THE TRUSTEE, SHIRE AND EACH HOLDER OF NOTES, BY ITS ACCEPTANCE THEREOF, HEREBY IRREVOCABLY WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY AND ALL RIGHT TO TRIAL BY JURY IN ANY LEGAL PROCEEDING ARISING OUT OF OR RELATING TO THIS INDENTURE, THE NOTES OR THE TRANSACTIONS CONTEMPLATED HEREBY.

Section 10.05. Table of Contents, Headings, etc. The table of contents and the titles and headings of the articles and sections of this Supplemental Indenture have been inserted for convenience of reference only, are not to be considered a part hereof, and shall in no way modify or restrict any of the terms or provisions hereof.

Section 10.06. Execution in Counterparts. This Supplemental Indenture may be executed in any number of counterparts, each of which shall be an original, but such counterparts shall together constitute but one and the same instrument. Signatures delivered by facsimile or in portable document format (.pdf) by email shall be deemed to be originals for all purposes hereunder.

Section 10.07. Separability; Benefits. In case any one or more of the provisions contained in this Supplemental Indenture or in the Notes shall for any reason be held to be invalid, illegal or unenforceable, in any respect, then, to the extent permitted by law, such invalidity, illegality or unenforceability of the remaining provisions shall not in any way be affected or impaired thereby. Nothing in this Supplemental Indenture or in the Notes, expressed or implied, shall give to any person, other than the parties hereto and their successors hereunder, and the holders of the Notes, any benefit or any legal or equitable right, remedy or claim under this Supplemental Indenture.

[Signature Page Follows]

19

IN WITNESS WHEREOF, the parties hereto have caused this Supplemental Indenture to be duly executed, as of the day and year first written above.

GIVEN under the common seal of SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC and DELIVERED as a DEED:
	/s/ Michael Garry
	Name: Michael Garry
	Title: Director

SHIRE PLC, as Guarantor
By:	/s/ Jeffrey Poulton
	Name: Jeffrey Poulton
	Title: Chief Financial Officer

DEUTSCHE BANK TRUST COMPANY AMERICAS, not in its individual capacity but solely as Trustee, Security Registrar and Paying Agent
By:   Deutsche Bank National Trust Company
By:	/s/ Wanda Camacho
	Name: Wanda Camacho
	Title: Vice President
By:	/s/ Annie Jaghatspanyan
	Name: Annie Jaghatspanyan
	Title: Vice President

[Signature Page to First Supplemental Indenture]

EXHIBIT A

[IF THIS NOTE IS TO BE A GLOBAL SECURITY, INSERT:]

THIS NOTE IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF THE DEPOSITORY TRUST COMPANY, A NEW YORK CORPORATION (“DTC”), OR A NOMINEE OF DTC. THIS NOTE IS EXCHANGEABLE FOR SECURITIES REGISTERED IN THE NAME OF A PERSON OTHER THAN DTC OR ITS NOMINEE ONLY IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE AND MAY NOT BE TRANSFERRED EXCEPT AS A WHOLE BY DTC TO A NOMINEE OF DTC, OR BY A NOMINEE OF DTC TO DTC OR ANOTHER NOMINEE OF DTC.

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF DTC, TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF CEDE & CO. OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC (AND ANY PAYMENT IS MADE TO CEDE & CO. OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC), ANY TRANSFER, PLEDGE, OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, CEDE & CO., HAS AN INTEREST HEREIN.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC

1.900% Senior Notes due 2019

Up to U.S. $3,300,000,000

CUSIP: 82481L AA7

ISIN: US82481LAA70

No. _______ $_______

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC, a designated activity company organized and existing under the laws of Ireland (hereinafter called the “Company,” which term includes any successor entity under the Indenture hereinafter referred to), for value received, hereby promises to pay to __________, or its registered assigns, [the principal sum of $__________]¹ on September 23, 2019 (such date is hereinafter referred to as the “Maturity Date”), and to pay interest thereon from September 23, 2016 or from the most recent Interest Payment Date to which interest has

¹ USE THE FOLLOWING LANGUAGE INSTEAD FOR GLOBAL NOTES: [the principal sum as set forth in the Schedule of Increases or Decreases In Note attached hereto]

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been paid or duly provided for, semi-annually in arrears on March 23 and September 23 of each year (each, an “Interest Payment Date”), commencing March 23, 2017, to the Persons in whose names the Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “Record Date”) (provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable), at the rate of 1.900% per annum, until the principal hereof is paid or duly provided for or made available for payment.

The amount of interest payable for any full semi-annual Interest Period will be calculated on the basis of a 360-day year consisting of twelve 30-day months. The amount of interest payable for any period shorter than a full semi-annual Interest Period will be calculated on the basis of a 30-day month and, for any period less than a month, on the basis of the actual number of days elapsed per 30-day month. In the event that any scheduled Interest Payment Date falls on a day that is not a Business Day, then payment of interest payable on such Interest Payment Date will be postponed to the next succeeding day which is a Business Day (and no interest on such payment will accrue for the period from and after such scheduled Interest Payment Date). The term “Business Day” means any calendar day that is not a Saturday, Sunday or a day on which commercial banking institutions are not required to be open for business in the City of New York, New York.

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid to the Person in whose name the relevant Notes, or any predecessor Notes, are registered at the close of business on the Record Date for such Interest Payment Date; provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable.

Payment of the principal of and premium, if any, and interest on, and any Additional Amounts with respect to, this Note will be made at the office or agency of the Company maintained for that purpose in the Borough of Manhattan, the City of New York, which shall initially be the Principal Office of the Trustee located therein, in such coin or currency of the United States of America as at the time of payment is legal tender for payment of public and private debts; provided, however, that payment of interest may be made at the option of the Company by check mailed to the Person entitled thereto at such address as shall appear in the Security Register or by wire transfer to an account appropriately designated by the Person entitled to payment, provided that the paying agent shall have received written notice of such account designation at least five Business Days prior to the date of such payment (subject to surrender of the relevant Note in the case of a payment of interest on a Redemption Date or the Maturity Date).

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Reference is hereby made to the further provisions of this Note set forth on the reverse hereof, which further provisions shall for all purposes have the same effect as if set forth at this place.

Unless the certificate of authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Note shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose.

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IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC
	Name:
	Title:

TRUSTEE’S CERTIFICATE OF AUTHENTICATION

This is one of the Securities of the series designated therein described in the within-mentioned Indenture.

Dated: ____________

DEUTSCHE BANK TRUST COMPANY AMERICAS, as Trustee By: Deutsche Bank National Trust Company
By:
	Authorized Signatory

REVERSE OF NOTE

This Note is one of a duly authorized issue of securities of the Company (herein called the “Notes”), issued and to be issued in one or more series under an Indenture (the “Base Indenture”), dated as of September 23, 2016, between the Company, Shire plc (“Shire”) and Deutsche Bank Trust Company Americas, as Trustee (herein called the “Trustee,” which term includes any successor trustee), as amended and supplemented by the First Supplemental Indenture, dated as of September 23, 2016, between the Company, Shire and the Trustee (the “First Supplemental Indenture,” and the Base Indenture as supplemented by the First Supplemental Indenture, the “Indenture”), to which Indenture reference is hereby made for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company, Shire and the Trustee and the holders of the Notes and of the terms upon which the Notes are, and are to be, authenticated and delivered. This Note is one of the series designated on the face hereof, initially limited in aggregate principal amount to $3,300,000,000.

All terms used but not defined in this Note that are defined in the Indenture shall have the meaning assigned to them in the Indenture.

Except as otherwise may be specified in the Indenture, at any time and from time to time, the Company shall have the right to redeem the Notes of this series, in whole or in part, at its option, at a redemption price equal to the greater of:

(i)       100% of the aggregate principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date; and

(ii)       the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes to be redeemed (not including any portion of the interest accrued to, but excluding, the Redemption Date), discounted to the Redemption Date on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months) at the applicable Treasury Rate plus 15 basis points, plus accrued and unpaid interest to, but excluding, the Redemption Date. The Treasury Rate shall be calculated on the third Business Day immediately preceding the Redemption Date.

The term “Optional Redemption Price” means, with respect to any redemption of Notes of this series, the redemption price for such Notes set forth in the preceding paragraph; and the term “Redemption Date” means, with respect to any redemption of Notes of this series, the date fixed for such redemption pursuant to the Indenture and the Notes.

The Company shall mail (or otherwise deliver in accordance with the applicable procedures of the Depositary) notice of any redemption to the registered holders of the Notes of this series to be redeemed at least 30 and not more than 60 days prior to the Redemption Date. The Company shall notify the Trustee at least five Business Days prior to mailing such notice to holders. If less than all of the Notes are to be redeemed

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pursuant to the preceding paragraphs, the Trustee shall select the Notes to be redeemed on a pro rata basis to the extent practicable or, to the extent that selection on a pro rata basis is not practicable for any reason, by such other method as the Trustee shall deem appropriate or as required by the applicable procedures of the Depositary. In the event of partial redemption by lot, the particular Notes to be redeemed shall be selected, unless otherwise provided herein, not less than 30 nor more than 60 days prior to the Redemption Date by the Trustee from the outstanding Notes not previously called for redemption. The Optional Redemption Price for any Notes of this series to be redeemed shall be paid prior to 12:00 noon, New York City time, on the Redemption Date or at such later time as is then permitted by the rules of the Depositary for the related Notes (if then registered as a Global Note); provided that the Company shall deposit with the Trustee an amount sufficient to pay the Optional Redemption Price for the Notes of this series to be redeemed by 11:00 a.m., New York City time, on the date such Optional Redemption Price is to be paid.

In the event of redemption of this Note in part only, a new Note or Notes of this series for the unredeemed portion hereof shall be issued in the name of the holder hereof upon the cancellation hereof. Except as set forth in the preceding paragraphs and in ‎‎Article 3 and Section 9.03 of the First Supplemental Indenture, the Company may not redeem the Notes of this series at its option prior to the Maturity Date.

The Notes are not entitled to the benefit of any sinking fund.

The Indenture contains provisions for discharge of the Indenture and defeasance of the obligations of the Company at any time upon compliance by the Company with certain conditions set forth therein, which provisions apply to the Notes of this series.

Upon the occurrence of a Change of Control Triggering Event, the Company shall make a Change of Control Offer in accordance with ‎Section 9.01 of the Supplemental Indenture.

If an Event of Default with respect to Notes of this series shall occur and be continuing, the principal of the Notes of this series may be declared due and payable in the manner and with the effect provided in the Indenture.

The Indenture permits, with certain exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and Shire and the rights of the holders of the Notes at any time by the Company, Shire and the Trustee, with the consent of the holders of a majority in the aggregate principal amount of the Notes of all series affected thereby at the time outstanding, voting as a single class. The Indenture also contains provisions permitting the holders of specified percentages in principal amount of the Notes of a series at the time outstanding, on behalf of the holders of all Notes of such series, to waive certain past defaults under the Indenture and their consequences. Any such consent or waiver by the holder of this Note shall be conclusive and binding upon such holder and upon all future holders of this Note and of any Note issued upon the registration of transfer hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Note.

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As provided in the Indenture and subject to certain limitations therein set forth, the transfer of this Note is registrable in the Security Register, upon surrender of this Note for registration of transfer at the office or agency of the Company in any place where the principal of and interest on this Note are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by the holder hereof or his attorney duly authorized in writing, and thereupon one or more new Notes of this series, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees.

The Notes of this series are issuable only in registered form without coupons in minimum denominations of $2,000 and any integral multiple of $1,000 in excess thereof, except as provided for in ‎‎Section 2.04 of the First Supplemental Indenture. As provided in the Indenture and subject to certain limitations therein set forth, Notes of this series are exchangeable for a like aggregate principal amount of Notes of this series of a different authorized denomination, as requested by the holder surrendering the same.

No service charge shall be made for any such registration of transfer or exchange, but the Company may require payment of a sum sufficient to cover any tax or other governmental charge payable in connection therewith.

The Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Note is registered as the owner hereof for all purposes, whether or not this Note is overdue, and neither the Company, the Trustee nor any such agent shall be affected by notice to the contrary.

THIS NOTE, AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS NOTE, SHALL BE GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK.

The Company will furnish a copy of the Indenture to any holder upon written request and without charge.

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ASSIGNMENT

FOR VALUE RECEIVED, the undersigned assigns and transfers this Note to:

(Insert assignee’s social security or tax identification number)

(Insert address and zip code of assignee) and irrevocably appoints

as agent to transfer this Note on the books of the Company. The agent may substitute another to act for him or her.

Date: _________

Signature:

Signature Guarantee: __________

(Sign exactly as your name appears on the other side of this Note)

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OPTION OF HOLDER TO ELECT PURCHASE

If you want to elect to have all or any part of this Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, check the box:  ☐

If you want to have only part of the Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, state the amount you elect to have purchased:

$                                                                        

(minimum denominations of $2,000 and multiples of $1,000)

Date:                           

Your Signature:
	(Sign exactly as your name appears on the face of this Note)

SIGNATURE GUARANTEE

Signatures must be guaranteed by an “eligible guarantor institution” meeting the requirements of the Security Registrar, which requirements include membership or participation in the Security Transfer Agent Medallion Program (“STAMP”) or such other “signature guarantee program” as may be determined by the Security Registrar in addition to, or in substitution for, STAMP, all in accordance with the Securities Exchange Act of 1934, as amended.

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SCHEDULE OF INCREASES OR DECREASES IN NOTE

The initial principal amount of this Note is $[____]. The following increases or decreases in the principal amount of this Note have been made:

Date Amount of decrease in principal amount of this Note  Amount of increase in principal amount of this Note  Principal amount of this Note following such decrease or increase Signature of authorized signatory of Trustee 

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EXHIBIT B

[IF THIS NOTE IS TO BE A GLOBAL SECURITY, INSERT:]

THIS NOTE IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF THE DEPOSITORY TRUST COMPANY, A NEW YORK CORPORATION (“DTC”), OR A NOMINEE OF DTC. THIS NOTE IS EXCHANGEABLE FOR SECURITIES REGISTERED IN THE NAME OF A PERSON OTHER THAN DTC OR ITS NOMINEE ONLY IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE AND MAY NOT BE TRANSFERRED EXCEPT AS A WHOLE BY DTC TO A NOMINEE OF DTC, OR BY A NOMINEE OF DTC TO DTC OR ANOTHER NOMINEE OF DTC.

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF DTC, TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF CEDE & CO. OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC (AND ANY PAYMENT IS MADE TO CEDE & CO. OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC), ANY TRANSFER, PLEDGE, OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, CEDE & CO., HAS AN INTEREST HEREIN.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC

2.400% Senior Notes due 2021 

Up to $3,300,000,000

CUSIP: 82481L AB5
ISIN: US82481LAB53

No. _______ $_______

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC, a designated activity company organized and existing under the laws of Ireland (hereinafter called the “Company,” which term includes any successor entity under the Indenture hereinafter referred to), for value received, hereby promises to pay to __________, or its registered assigns, [the principal sum of $ __________]² on September 23, 2021 (such date is hereinafter referred to as the “Maturity Date”), and to pay interest thereon from September 23, 2016 or from the most recent Interest Payment Date to which interest has

² USE THE FOLLOWING LANGUAGE INSTEAD FOR GLOBAL NOTES: [the principal sum as set forth in the Schedule of Increases or Decreases In Note attached hereto]

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been paid or duly provided for, semi-annually in arrears on March 23 and September 23 of each year (each, an “Interest Payment Date”), commencing March 23, 2017, to the Persons in whose names the Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “Record Date”) (provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable), at the rate of 2.400% per annum, until the principal hereof is paid or duly provided for or made available for payment.

The amount of interest payable for any full semi-annual Interest Period will be calculated on the basis of a 360-day year consisting of twelve 30-day months. The amount of interest payable for any period shorter than a full semi-annual Interest Period will be calculated on the basis of a 30-day month and, for any period less than a month, on the basis of the actual number of days elapsed per 30-day month. In the event that any scheduled Interest Payment Date falls on a day that is not a Business Day, then payment of interest payable on such Interest Payment Date will be postponed to the next succeeding day which is a Business Day (and no interest on such payment will accrue for the period from and after such scheduled Interest Payment Date). The term “Business Day” means any calendar day that is not a Saturday, Sunday or a day on which commercial banking institutions are not required to be open for business in the City of New York, New York.

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid to the Person in whose name the relevant Notes, or any predecessor Notes, are registered at the close of business on the Record Date for such Interest Payment Date; provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable.

Payment of the principal of and premium, if any, and interest on, and any Additional Amounts with respect to, this Note will be made at the office or agency of the Company maintained for that purpose in the Borough of Manhattan, the City of New York, which shall initially be the Principal Office of the Trustee located therein, in such coin or currency of the United States of America as at the time of payment is legal tender for payment of public and private debts; provided, however, that payment of interest may be made at the option of the Company by check mailed to the Person entitled thereto at such address as shall appear in the Security Register or by wire transfer to an account appropriately designated by the Person entitled to payment, provided that the paying agent shall have received written notice of such account designation at least five Business Days prior to the date of such payment (subject to surrender of the relevant Note in the case of a payment of interest on a Redemption Date or the Maturity Date).

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Reference is hereby made to the further provisions of this Note set forth on the reverse hereof, which further provisions shall for all purposes have the same effect as if set forth at this place.

Unless the certificate of authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Note shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose.

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IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC
	Name:
	Title:

TRUSTEE’S CERTIFICATE OF AUTHENTICATION

This is one of the Securities of the series designated therein described in the within-mentioned Indenture.

Dated: ____________

DEUTSCHE BANK TRUST COMPANY AMERICAS, as Trustee By: Deutsche Bank National Trust Company
By:
	Authorized Signatory

REVERSE OF NOTE

This Note is one of a duly authorized issue of securities of the Company (herein called the “Notes”), issued and to be issued in one or more series under an Indenture (the “Base Indenture”), dated as of September 23, 2016, between the Company, Shire plc (“Shire”) and Deutsche Bank Trust Company Americas, as Trustee (herein called the “Trustee,” which term includes any successor trustee), as amended and supplemented by the First Supplemental Indenture, dated as of September 23, 2016, between the Company, Shire and the Trustee (the “First Supplemental Indenture,” and the Base Indenture as supplemented by the First Supplemental Indenture, the “Indenture”), to which Indenture reference is hereby made for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company, Shire and the Trustee and the holders of the Notes and of the terms upon which the Notes are, and are to be, authenticated and delivered. This Note is one of the series designated on the face hereof, initially limited in aggregate principal amount to $3,300,000,000.

All terms used but not defined in this Note that are defined in the Indenture shall have the meaning assigned to them in the Indenture.

Except as otherwise may be specified in the Indenture, at any time and from time to time prior to August 23, 2021, the Company shall have the right to redeem the Notes of this series, in whole or in part, at its option, at a redemption price equal to the greater of:

(i)       100% of the aggregate principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date; and

(ii)       the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes to be redeemed from the Redemption Date to, but excluding (in the case of interest), August 23, 2021 (not including any portion of the interest accrued to, but excluding, the Redemption Date), discounted to the Redemption Date on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months) at the applicable Treasury Rate plus 20 basis points, plus accrued and unpaid interest to, but excluding, the Redemption Date. The Treasury Rate shall be calculated on the third Business Day immediately preceding the Redemption Date.

At any time and from time to time on or after August 23, 2021, the Company shall have the right to redeem the Notes of this series, in whole or in part, at its option, at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date.

The term “Optional Redemption Price” means, with respect to any redemption of Notes of this series, the applicable redemption price for such Notes set forth in the preceding two paragraphs; and the term “Redemption Date” means, with respect to any 

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redemption of Notes of this series, the date fixed for such redemption pursuant to the Indenture and the Notes.

The Company shall mail (or otherwise deliver in accordance with the applicable procedures of the Depositary) notice of any redemption to the registered holders of the Notes of this series to be redeemed at least 30 and not more than 60 days prior to the Redemption Date. The Company shall notify the Trustee at least five Business Days prior to mailing such notice to holders. If less than all of the Notes are to be redeemed pursuant to the preceding paragraphs, the Trustee shall select the Notes to be redeemed on a pro rata basis to the extent practicable or, to the extent that selection on a pro rata basis is not practicable for any reason, by such other method as the Trustee shall deem appropriate or as required by the applicable procedures of the Depositary. In the event of partial redemption by lot, the particular Notes to be redeemed shall be selected, unless otherwise provided herein, not less than 30 nor more than 60 days prior to the Redemption Date by the Trustee from the outstanding Notes not previously called for redemption. The Optional Redemption Price for any Notes of this series to be redeemed shall be paid prior to 12:00 noon, New York City time, on the Redemption Date or at such later time as is then permitted by the rules of the Depositary for the related Notes (if then registered as a Global Note); provided that the Company shall deposit with the Trustee an amount sufficient to pay the Optional Redemption Price for the Notes of this series to be redeemed by 11:00 a.m., New York City time, on the date such Optional Redemption Price is to be paid.

In the event of redemption of this Note in part only, a new Note or Notes of this series for the unredeemed portion hereof shall be issued in the name of the holder hereof upon the cancellation hereof. Except as set forth in the preceding paragraphs and in ‎Article 3 and Section 9.03 of the First Supplemental Indenture, the Company may not redeem the Notes of this series at its option prior to the Maturity Date.

The Notes are not entitled to the benefit of any sinking fund.

The Indenture contains provisions for discharge of the Indenture and defeasance of the obligations of the Company at any time upon compliance by the Company with certain conditions set forth therein, which provisions apply to the Notes of this series.

Upon the occurrence of a Change of Control Triggering Event, the Company shall make a Change of Control Offer in accordance with ‎Section 9.01 of the Supplemental Indenture.

If an Event of Default with respect to Notes of this series shall occur and be continuing, the principal of the Notes of this series may be declared due and payable in the manner and with the effect provided in the Indenture.

The Indenture permits, with certain exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and Shire and the rights of the holders of the Notes at any time by the Company, Shire and the Trustee, with the consent of the holders of a majority in the aggregate principal amount of the Notes of all series affected thereby at the time outstanding, voting as a

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single class. The Indenture also contains provisions permitting the holders of specified percentages in principal amount of the Notes of a series at the time outstanding, on behalf of the holders of all Notes of such series, to waive certain past defaults under the Indenture and their consequences. Any such consent or waiver by the holder of this Note shall be conclusive and binding upon such holder and upon all future holders of this Note and of any Note issued upon the registration of transfer hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Note.

As provided in the Indenture and subject to certain limitations therein set forth, the transfer of this Note is registrable in the Security Register, upon surrender of this Note for registration of transfer at the office or agency of the Company in any place where the principal of and interest on this Note are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by the holder hereof or his attorney duly authorized in writing, and thereupon one or more new Notes of this series, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees.

The Notes of this series are issuable only in registered form without coupons in minimum denominations of $2,000 and any integral multiple of $1,000 in excess thereof, except as provided for in ‎Section 2.04 of the First Supplemental Indenture. As provided in the Indenture and subject to certain limitations therein set forth, Notes of this series are exchangeable for a like aggregate principal amount of Notes of this series of a different authorized denomination, as requested by the holder surrendering the same.

No service charge shall be made for any such registration of transfer or exchange, but the Company may require payment of a sum sufficient to cover any tax or other governmental charge payable in connection therewith.

The Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Note is registered as the owner hereof for all purposes, whether or not this Note is overdue, and neither the Company, the Trustee nor any such agent shall be affected by notice to the contrary.

THIS NOTE, AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS NOTE, SHALL BE GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK.

The Company will furnish a copy of the Indenture to any holder upon written request and without charge.

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ASSIGNMENT

FOR VALUE RECEIVED, the undersigned assigns and transfers this Note to:

(Insert assignee’s social security or tax identification number)

(Insert address and zip code of assignee)

and irrevocably appoints

as agent to transfer this Note on the books of the Company. The agent may substitute another to act for him or her.

Date: __________

Signature:

Signature Guarantee: __________

(Sign exactly as your name appears on the other side of this Note)

B-R-4

OPTION OF HOLDER TO ELECT PURCHASE

If you want to elect to have all or any part of this Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, check the box:  ☐

If you want to have only part of the Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, state the amount you elect to have purchased:

$                                                                        

(minimum denominations of $2,000 and multiples of $1,000)

Date:                           

Your Signature:
	(Sign exactly as your name appears on the face of this Note)

SIGNATURE GUARANTEE

Signatures must be guaranteed by an “eligible guarantor institution” meeting the requirements of the Security Registrar, which requirements include membership or participation in the Security Transfer Agent Medallion Program (“STAMP”) or such other “signature guarantee program” as may be determined by the Security Registrar in addition to, or in substitution for, STAMP, all in accordance with the Securities Exchange Act of 1934, as amended.

B-R-5

SCHEDULE OF INCREASES OR DECREASES IN NOTE

The initial principal amount of this Note is $[____]. The following increases or decreases in the principal amount of this Note have been made:

Date Amount of decrease in principal amount of this Note Amount of increase in principal amount of this Note Principal amount of this Note following such decrease or increase Signature of authorized signatory of Trustee 

B-R-6

EXHIBIT C

[IF THIS NOTE IS TO BE A GLOBAL SECURITY, INSERT:]

THIS NOTE IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF THE DEPOSITORY TRUST COMPANY, A NEW YORK CORPORATION (“DTC”), OR A NOMINEE OF DTC. THIS NOTE IS EXCHANGEABLE FOR SECURITIES REGISTERED IN THE NAME OF A PERSON OTHER THAN DTC OR ITS NOMINEE ONLY IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE AND MAY NOT BE TRANSFERRED EXCEPT AS A WHOLE BY DTC TO A NOMINEE OF DTC, OR BY A NOMINEE OF DTC TO DTC OR ANOTHER NOMINEE OF DTC.

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF DTC, TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF CEDE & CO. OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC (AND ANY PAYMENT IS MADE TO CEDE & CO. OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC), ANY TRANSFER, PLEDGE, OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, CEDE & CO., HAS AN INTEREST HEREIN.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC

2.875% Senior Notes due 2023

Up to $2,500,000,000

CUSIP: 82481L AC3
ISIN: US82481LAC37

No. _______ $_______

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC, a designated activity company organized and existing under the laws of Ireland (hereinafter called the “Company,” which term includes any successor entity under the Indenture hereinafter referred to), for value received, hereby promises to pay to __________, or its registered assigns, [the principal sum of $ __________]³ on September 23, 2023 (such date is

³ USE THE FOLLOWING LANGUAGE INSTEAD FOR GLOBAL NOTES: [the principal sum as set forth in the Schedule of Increases or Decreases In Note attached hereto]

C-1

hereinafter referred to as the “Maturity Date”), and to pay interest thereon from September 23, 2016 or from the most recent Interest Payment Date to which interest has been paid or duly provided for, semi-annually in arrears on March 23 and September 23 of each year (each, an “Interest Payment Date”), commencing March 23, 2017, to the Persons in whose names the Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “Record Date”) (provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable), at the rate of 2.875% per annum, until the principal hereof is paid or duly provided for or made available for payment.

The amount of interest payable for any full semi-annual Interest Period will be calculated on the basis of a 360-day year consisting of twelve 30-day months. The amount of interest payable for any period shorter than a full semi-annual Interest Period will be calculated on the basis of a 30-day month and, for any period less than a month, on the basis of the actual number of days elapsed per 30-day month. In the event that any scheduled Interest Payment Date falls on a day that is not a Business Day, then payment of interest payable on such Interest Payment Date will be postponed to the next succeeding day which is a Business Day (and no interest on such payment will accrue for the period from and after such scheduled Interest Payment Date). The term “Business Day” means any calendar day that is not a Saturday, Sunday or a day on which commercial banking institutions are not required to be open for business in the City of New York, New York.

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid to the Person in whose name the relevant Notes, or any predecessor Notes, are registered at the close of business on the Record Date for such Interest Payment Date; provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable.

Payment of the principal of and premium, if any, and interest on, and any Additional Amounts with respect to, this Note will be made at the office or agency of the Company maintained for that purpose in the Borough of Manhattan, the City of New York, which shall initially be the Principal Office of the Trustee located therein, in such coin or currency of the United States of America as at the time of payment is legal tender for payment of public and private debts; provided, however, that payment of interest may be made at the option of the Company by check mailed to the Person entitled thereto at such address as shall appear in the Security Register or by wire transfer to an account appropriately designated by the Person entitled to payment, provided that the paying agent shall have received written notice of such account designation at least five Business Days prior to the date of such payment (subject to surrender of the relevant Note in the case of a payment of interest on a Redemption Date or the Maturity Date).

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Reference is hereby made to the further provisions of this Note set forth on the reverse hereof, which further provisions shall for all purposes have the same effect as if set forth at this place.

Unless the certificate of authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Note shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose.

C-3

IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC
	Name:
	Title:

TRUSTEE’S CERTIFICATE OF AUTHENTICATION

This is one of the Securities of the series designated therein described in the within-mentioned Indenture.

Dated: ____________

DEUTSCHE BANK TRUST COMPANY AMERICAS, as Trustee By: Deutsche Bank National Trust Company
By:
	Authorized Signatory

REVERSE OF NOTE

This Note is one of a duly authorized issue of securities of the Company (herein called the “Notes”), issued and to be issued in one or more series under an Indenture (the “Base Indenture”), dated as of September 23, 2016, between the Company, Shire plc (“Shire”) and Deutsche Bank Trust Company Americas, as Trustee (herein called the “Trustee,” which term includes any successor trustee), as amended and supplemented by the First Supplemental Indenture, dated as of September 23, 2016, between the Company, Shire and the Trustee (the “First Supplemental Indenture,” and the Base Indenture as supplemented by the First Supplemental Indenture, the “Indenture”), to which Indenture reference is hereby made for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company, Shire and the Trustee and the holders of the Notes and of the terms upon which the Notes are, and are to be, authenticated and delivered. This Note is one of the series designated on the face hereof, initially limited in aggregate principal amount to $2,500,000,000.

All terms used but not defined in this Note that are defined in the Indenture shall have the meaning assigned to them in the Indenture.

Except as otherwise may be specified in the Indenture, at any time and from time to time prior to July 23, 2023, the Company shall have the right to redeem the Notes of this series, in whole or in part, at its option, at a redemption price equal to the greater of:

(i)       100% of the aggregate principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date; and

(ii)       the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes to be redeemed from the Redemption Date to, but excluding (in the case of interest), July 23, 2023 (not including any portion of the interest accrued to, but excluding, the Redemption Date), discounted to the Redemption Date on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months) at the applicable Treasury Rate plus 25 basis points, plus accrued and unpaid interest to, but excluding, the Redemption Date. The Treasury Rate shall be calculated on the third Business Day immediately preceding the Redemption Date.

At any time and from time to time on or after July 23, 2023, the Company shall have the right to redeem the Notes of this series, in whole or in part, at its option, at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date.

The term “Optional Redemption Price” means, with respect to any redemption of Notes of this series, the applicable redemption price for such Notes set forth in the preceding two paragraphs; and the term “Redemption Date” means, with respect to any redemption of Notes of this series, the date fixed for such redemption pursuant to the Indenture and the Notes.

C-R-1

The Company shall mail (or otherwise deliver in accordance with the applicable procedures of the Depositary) notice of any redemption to the registered holders of the Notes of this series to be redeemed at least 30 and not more than 60 days prior to the Redemption Date. The Company shall notify the Trustee at least five Business Days prior to mailing such notice to holders. If less than all of the Notes are to be redeemed pursuant to the preceding paragraphs, the Trustee shall select the Notes to be redeemed on a pro rata basis to the extent practicable or, to the extent that selection on a pro rata basis is not practicable for any reason, by such other method as the Trustee shall deem appropriate or as required by the applicable procedures of the Depositary. In the event of partial redemption by lot, the particular Notes to be redeemed shall be selected, unless otherwise provided herein, not less than 30 nor more than 60 days prior to the Redemption Date by the Trustee from the outstanding Notes not previously called for redemption. The Optional Redemption Price for any Notes of this series to be redeemed shall be paid prior to 12:00 noon, New York City time, on the Redemption Date or at such later time as is then permitted by the rules of the Depositary for the related Notes (if then registered as a Global Note); provided that the Company shall deposit with the Trustee an amount sufficient to pay the Optional Redemption Price for the Notes of this series to be redeemed by 11:00 a.m., New York City time, on the date such Optional Redemption Price is to be paid.

In the event of redemption of this Note in part only, a new Note or Notes of this series for the unredeemed portion hereof shall be issued in the name of the holder hereof upon the cancellation hereof. Except as set forth in the preceding paragraphs and in ‎‎Article 3 and Section 9.03 of the First Supplemental Indenture, the Company may not redeem the Notes of this series at its option prior to the Maturity Date.

The Notes are not entitled to the benefit of any sinking fund.

The Indenture contains provisions for discharge of the Indenture and defeasance of the obligations of the Company at any time upon compliance by the Company with certain conditions set forth therein, which provisions apply to the Notes of this series.

Upon the occurrence of a Change of Control Triggering Event, the Company shall make a Change of Control Offer in accordance with ‎Section 9.01 of the Supplemental Indenture.

If an Event of Default with respect to Notes of this series shall occur and be continuing, the principal of the Notes of this series may be declared due and payable in the manner and with the effect provided in the Indenture.

The Indenture permits, with certain exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and Shire and the rights of the holders of the Notes at any time by the Company, Shire and the Trustee, with the consent of the holders of a majority in the aggregate principal amount of the Notes of all series affected thereby at the time outstanding, voting as a single class. The Indenture also contains provisions permitting the holders of specified percentages in principal amount of the Notes of a series at the time outstanding, on behalf of the holders of all Notes of such series, to waive certain past defaults under the

C-R-2

Indenture and their consequences. Any such consent or waiver by the holder of this Note shall be conclusive and binding upon such holder and upon all future holders of this Note and of any Note issued upon the registration of transfer hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Note.

As provided in the Indenture and subject to certain limitations therein set forth, the transfer of this Note is registrable in the Security Register, upon surrender of this Note for registration of transfer at the office or agency of the Company in any place where the principal of and interest on this Note are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by the holder hereof or his attorney duly authorized in writing, and thereupon one or more new Notes of this series, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees.

The Notes of this series are issuable only in registered form without coupons in minimum denominations of $2,000 and any integral multiple of $1,000 in excess thereof, except as provided for in ‎Section 2.04 of the First Supplemental Indenture. As provided in the Indenture and subject to certain limitations therein set forth, Notes of this series are exchangeable for a like aggregate principal amount of Notes of this series of a different authorized denomination, as requested by the holder surrendering the same.

No service charge shall be made for any such registration of transfer or exchange, but the Company may require payment of a sum sufficient to cover any tax or other governmental charge payable in connection therewith.

The Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Note is registered as the owner hereof for all purposes, whether or not this Note is overdue, and neither the Company, the Trustee nor any such agent shall be affected by notice to the contrary.

THIS NOTE, AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS NOTE, SHALL BE GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK.

The Company will furnish a copy of the Indenture to any holder upon written request and without charge.

C-R-3

ASSIGNMENT

FOR VALUE RECEIVED, the undersigned assigns and transfers this Note to:

(Insert assignee’s social security or tax identification number)

(Insert address and zip code of assignee)

and irrevocably appoints

as agent to transfer this Note on the books of the Company. The agent may substitute another to act for him or her.

Date: __________

Signature:

Signature Guarantee: __________

(Sign exactly as your name appears on the other side of this Note)

C-R-4

OPTION OF HOLDER TO ELECT PURCHASE

If you want to elect to have all or any part of this Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, check the box:  ☐

If you want to have only part of the Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, state the amount you elect to have purchased:

$                                                                        

(minimum denominations of $2,000 and multiples of $1,000)

Date:                           

Your Signature:
	(Sign exactly as your name appears on the face of this Note)

SIGNATURE GUARANTEE

Signatures must be guaranteed by an “eligible guarantor institution” meeting the requirements of the Security Registrar, which requirements include membership or participation in the Security Transfer Agent Medallion Program (“STAMP”) or such other “signature guarantee program” as may be determined by the Security Registrar in addition to, or in substitution for, STAMP, all in accordance with the Securities Exchange Act of 1934, as amended.

C-R-5

SCHEDULE OF INCREASES OR DECREASES IN NOTE

The initial principal amount of this Note is $[____]. The following increases or decreases in the principal amount of this Note have been made:

Date Amount of decrease in principal amount of this Note Amount of increase in principal amount of this Note Principal amount of this Note following such decrease or increase Signature of authorized signatory of Trustee 

C-R-6

EXHIBIT D

[IF THIS NOTE IS TO BE A GLOBAL SECURITY, INSERT:]

THIS NOTE IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF THE DEPOSITORY TRUST COMPANY, A NEW YORK CORPORATION (“DTC”), OR A NOMINEE OF DTC. THIS NOTE IS EXCHANGEABLE FOR SECURITIES REGISTERED IN THE NAME OF A PERSON OTHER THAN DTC OR ITS NOMINEE ONLY IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE AND MAY NOT BE TRANSFERRED EXCEPT AS A WHOLE BY DTC TO A NOMINEE OF DTC, OR BY A NOMINEE OF DTC TO DTC OR ANOTHER NOMINEE OF DTC.

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF DTC, TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF CEDE & CO. OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC (AND ANY PAYMENT IS MADE TO CEDE & CO. OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC), ANY TRANSFER, PLEDGE, OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, CEDE & CO., HAS AN INTEREST HEREIN.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC

3.200% Senior Notes due 2026

Up to $3,000,000,000

CUSIP: 82481L AD1
ISIN: US82481LAD10

No. _______ $_______

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC, a designated activity company organized and existing under the laws of Ireland (hereinafter called the “Company,” which term includes any successor entity under the Indenture hereinafter referred to), for value received, hereby promises to pay to __________, or its registered assigns, [the principal sum of $ __________]⁴ on September 23, 2026 (such date is hereinafter referred to as the “Maturity Date”), and to pay interest thereon from September 23, 2016 or from the most recent Interest Payment Date to which interest has

⁴ USE THE FOLLOWING LANGUAGE INSTEAD FOR GLOBAL NOTES: [the principal sum as set forth in the Schedule of Increases or Decreases In Note attached hereto]

D-1

been paid or duly provided for, semi-annually in arrears on March 23 and September 23 of each year (each, an “Interest Payment Date”), commencing March 23, 2017, to the Persons in whose names the Notes are registered at the close of business on the March 8 or September 8 (whether or not a Business Day), respectively, immediately prior to each Interest Payment Date (each, a “Record Date”) (provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable), at the rate of 3.200% per annum, until the principal hereof is paid or duly provided for or made available for payment.

The amount of interest payable for any full semi-annual Interest Period will be calculated on the basis of a 360-day year consisting of twelve 30-day months. The amount of interest payable for any period shorter than a full semi-annual Interest Period will be calculated on the basis of a 30-day month and, for any period less than a month, on the basis of the actual number of days elapsed per 30-day month. In the event that any scheduled Interest Payment Date falls on a day that is not a Business Day, then payment of interest payable on such Interest Payment Date will be postponed to the next succeeding day which is a Business Day (and no interest on such payment will accrue for the period from and after such scheduled Interest Payment Date). The term “Business Day” means any calendar day that is not a Saturday, Sunday or a day on which commercial banking institutions are not required to be open for business in the City of New York, New York.

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid to the Person in whose name the relevant Notes, or any predecessor Notes, are registered at the close of business on the Record Date for such Interest Payment Date; provided that the interest due on the Maturity Date or a Redemption Date (in each case, whether or not an Interest Payment Date) of a Note of this series will be paid to the Person to whom principal of such Note is payable.

Payment of the principal of and premium, if any, and interest on, and any Additional Amounts with respect to, this Note will be made at the office or agency of the Company maintained for that purpose in the Borough of Manhattan, the City of New York, which shall initially be the Principal Office of the Trustee located therein, in such coin or currency of the United States of America as at the time of payment is legal tender for payment of public and private debts; provided, however, that payment of interest may be made at the option of the Company by check mailed to the Person entitled thereto at such address as shall appear in the Security Register or by wire transfer to an account appropriately designated by the Person entitled to payment, provided that the paying agent shall have received written notice of such account designation at least five Business Days prior to the date of such payment (subject to surrender of the relevant Note in the case of a payment of interest on a Redemption Date or the Maturity Date).

D-2

Reference is hereby made to the further provisions of this Note set forth on the reverse hereof, which further provisions shall for all purposes have the same effect as if set forth at this place.

Unless the certificate of authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Note shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose.

D-3

IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed.

SHIRE ACQUISITIONS INVESTMENTS IRELAND DAC
	Name:
	Title:

TRUSTEE’S CERTIFICATE OF AUTHENTICATION

This is one of the Securities of the series designated therein described in the within-mentioned Indenture.

Dated: ____________

DEUTSCHE BANK TRUST COMPANY AMERICAS, as Trustee By: Deutsche Bank National Trust Company
By:
	Authorized Signatory

REVERSE OF NOTE

This Note is one of a duly authorized issue of securities of the Company (herein called the “Notes”), issued and to be issued in one or more series under an Indenture (the “Base Indenture”), dated as of September 23, 2016, between the Company, Shire plc (“Shire”) and Deutsche Bank Trust Company Americas, as Trustee (herein called the “Trustee,” which term includes any successor trustee), as amended and supplemented by the First Supplemental Indenture, dated as of September 23, 2016, between the Company, Shire and the Trustee (the “First Supplemental Indenture,” and the Base Indenture as supplemented by the First Supplemental Indenture, the “Indenture”), to which Indenture reference is hereby made for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company, Shire and the Trustee and the holders of the Notes and of the terms upon which the Notes are, and are to be, authenticated and delivered. This Note is one of the series designated on the face hereof, initially limited in aggregate principal amount to $3,000,000,000.

All terms used but not defined in this Note that are defined in the Indenture shall have the meaning assigned to them in the Indenture.

Except as otherwise may be specified in the Indenture, at any time and from time to time prior to June 23, 2026, the Company shall have the right to redeem the Notes of this series, in whole or in part, at its option, at a redemption price equal to the greater of:

(i)       100% of the aggregate principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date; and

(ii)       the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes to be redeemed from the Redemption Date to, but excluding (in the case of interest), June 23, 2026 (not including any portion of the interest accrued to, but excluding, the Redemption Date), discounted to the Redemption Date on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months) at the applicable Treasury Rate plus 25 basis points, plus accrued and unpaid interest to, but excluding, the Redemption Date. The Treasury Rate shall be calculated on the third Business Day immediately preceding the Redemption Date.

At any time and from time to time on or after June 23, 2026, the Company shall have the right to redeem the Notes of this series, in whole or in part, at its option, at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the Redemption Date.

The term “Optional Redemption Price” means, with respect to any redemption of Notes of this series, the applicable redemption price for such Notes set forth in the preceding two paragraphs; and the term “Redemption Date” means, with respect to any redemption of Notes of this series, the date fixed for such redemption pursuant to the Indenture and the Notes.

D-R-1

The Company shall mail (or otherwise deliver in accordance with the applicable procedures of the Depositary) notice of any redemption to the registered holders of the Notes of this series to be redeemed at least 30 and not more than 60 days prior to the Redemption Date. The Company shall notify the Trustee at least five Business Days prior to mailing such notice to holders. If less than all of the Notes are to be redeemed pursuant to the preceding paragraphs, the Trustee shall select the Notes to be redeemed on a pro rata basis to the extent practicable or, to the extent that selection on a pro rata basis is not practicable for any reason, by such other method as the Trustee shall deem appropriate or as required by the applicable procedures of the Depositary. In the event of partial redemption by lot, the particular Notes to be redeemed shall be selected, unless otherwise provided herein, not less than 30 nor more than 60 days prior to the Redemption Date by the Trustee from the outstanding Notes not previously called for redemption. The Optional Redemption Price for any Notes of this series to be redeemed shall be paid prior to 12:00 noon, New York City time, on the Redemption Date or at such later time as is then permitted by the rules of the Depositary for the related Notes (if then registered as a Global Note); provided that the Company shall deposit with the Trustee an amount sufficient to pay the Optional Redemption Price for the Notes of this series to be redeemed by 11:00 a.m., New York City time, on the date such Optional Redemption Price is to be paid.

In the event of redemption of this Note in part only, a new Note or Notes of this series for the unredeemed portion hereof shall be issued in the name of the holder hereof upon the cancellation hereof. Except as set forth in the preceding paragraphs and in ‎Article 3 and Section 9.03 of the First Supplemental Indenture, the Company may not redeem the Notes of this series at its option prior to the Maturity Date.

The Notes are not entitled to the benefit of any sinking fund.

The Indenture contains provisions for discharge of the Indenture and defeasance of the obligations of the Company at any time upon compliance by the Company with certain conditions set forth therein, which provisions apply to the Notes of this series.

Upon the occurrence of a Change of Control Triggering Event, the Company shall make a Change of Control Offer in accordance with ‎Section 9.01 of the Supplemental Indenture.

If an Event of Default with respect to Notes of this series shall occur and be continuing, the principal of the Notes of this series may be declared due and payable in the manner and with the effect provided in the Indenture.

The Indenture permits, with certain exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and Shire and the rights of the holders of the Notes at any time by the Company, Shire and the Trustee, with the consent of the holders of a majority in the aggregate principal amount of the Notes of all series affected thereby at the time outstanding, voting as a single class. The Indenture also contains provisions permitting the holders of specified percentages in principal amount of the Notes of a series at the time outstanding, on behalf of the holders of all Notes of such series, to waive certain past defaults under the

D-R-2

Indenture and their consequences. Any such consent or waiver by the holder of this Note shall be conclusive and binding upon such holder and upon all future holders of this Note and of any Note issued upon the registration of transfer hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Note.

As provided in the Indenture and subject to certain limitations therein set forth, the transfer of this Note is registrable in the Security Register, upon surrender of this Note for registration of transfer at the office or agency of the Company in any place where the principal of and interest on this Note are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by the holder hereof or his attorney duly authorized in writing, and thereupon one or more new Notes of this series, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees.

The Notes of this series are issuable only in registered form without coupons in minimum denominations of $2,000 and any integral multiple of $1,000 in excess thereof, except as provided for in ‎Section 2.04 of the First Supplemental Indenture. As provided in the Indenture and subject to certain limitations therein set forth, Notes of this series are exchangeable for a like aggregate principal amount of Notes of this series of a different authorized denomination, as requested by the holder surrendering the same.

No service charge shall be made for any such registration of transfer or exchange, but the Company may require payment of a sum sufficient to cover any tax or other governmental charge payable in connection therewith.

The Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Note is registered as the owner hereof for all purposes, whether or not this Note is overdue, and neither the Company, the Trustee nor any such agent shall be affected by notice to the contrary.

THIS NOTE, AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS NOTE, SHALL BE GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK.

The Company will furnish a copy of the Indenture to any holder upon written request and without charge.

D-R-3

ASSIGNMENT

FOR VALUE RECEIVED, the undersigned assigns and transfers this Note to:

(Insert assignee’s social security or tax identification number)

(Insert address and zip code of assignee)

and irrevocably appoints

as agent to transfer this Note on the books of the Company. The agent may substitute another to act for him or her.

Date:__________

Signature:

Signature Guarantee: __________

(Sign exactly as your name appears on the other side of this Note)

D-R-4

OPTION OF HOLDER TO ELECT PURCHASE

If you want to elect to have all or any part of this Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, check the box:  ☐

If you want to have only part of the Note purchased by the Company pursuant to Section 9.01 of the First Supplemental Indenture, state the amount you elect to have purchased:

$                                                                         

(minimum denominations of $2,000 and multiples of $1,000)

Date:                           

Your Signature:
	(Sign exactly as your name appears on the face of this Note)

SIGNATURE GUARANTEE

Signatures must be guaranteed by an “eligible guarantor institution” meeting the requirements of the Security Registrar, which requirements include membership or participation in the Security Transfer Agent Medallion Program (“STAMP”) or such other “signature guarantee program” as may be determined by the Security Registrar in addition to, or in substitution for, STAMP, all in accordance with the Securities Exchange Act of 1934, as amended.

D-R-5

SCHEDULE OF INCREASES OR DECREASES IN NOTE

The initial principal amount of this Note is $[____]. The following increases or decreases in the principal amount of this Note have been made:

Date Amount of decrease in principal amount of this Note Amount of increase in principal amount of this Note Principal amount of this Note following such decrease or increase  Signature of authorized signatory of Trustee 

D-R-6

EX-5.1

Exhibit 5.1

OPINION OF DAVIS POLK & WARDWELL LLP

September 23, 2016

Shire plc
5 Riverwalk
Citywest Business Campus
Dublin 24
Ireland

Shire Acquisitions Investments Ireland Designated Activity Company
5 Riverwalk
Citywest Business Campus
Dublin 24
Ireland

Ladies and Gentlemen:

Shire Acquisitions Investments Ireland Designated Activity Company, an Irish designated activity company (the “Company”), and Shire plc, a Jersey public limited company and parent of the Company (“Shire”), have filed with the Securities and Exchange Commission a Registration Statement on Form S-3 (File No. 333-213502) (the “Registration Statement”) for the purpose of registering under the Securities Act of 1933, as amended (the “Securities Act”), certain securities, including $3,300,000,000 aggregate principal amount of the Company’s 1.900% senior notes due 2019, $3,300,000,000 aggregate principal amount of the Company’s 2.400% senior notes due 2021, $2,500,000,000 aggregate principal amount of the Company’s 2.875% senior notes due 2023 and $3,000,000,000 aggregate principal amount of the Company’s 3.200% senior notes due 2026 (the “Debt Securities”), fully and unconditionally guaranteed by Shire (the “Guarantee” and, together with the Debt Securities, the “Securities”). The Securities are to be issued pursuant to the provisions of the indenture dated as of September 23, 2016 (the “Indenture”) among the Company, Shire and Deutsche Bank Trust Company Americas, as trustee (the “Trustee”) as supplemented by a supplemental indenture thereto, among the Company, Shire and the Trustee. The Securities are to be sold pursuant to the Underwriting Agreement dated September 19, 2016 (the “Underwriting Agreement”) among the Company, Shire and the several underwriters named therein (the “Underwriters”).

We, as special United States counsel to the Company and to Shire, have examined originals or copies of such documents, corporate records, certificates of public officials and other instruments as we have deemed necessary or advisable for the purpose of rendering this opinion.

In rendering the opinion expressed herein, we have, without independent inquiry or investigation, assumed that (i) all documents submitted to us as originals are authentic and complete, (ii) all documents submitted to us as copies conform to authentic, complete originals, (iii) all signatures on all documents that we reviewed are genuine, (iv) all natural persons executing documents had and have the legal capacity to do so, (v) all statements in certificates of public officials and officers of the Company and Shire that we reviewed were and are accurate and (vi) all representations made by the Company and Shire as to matters of fact in the documents that we reviewed were and are accurate.

Based upon the foregoing, and subject to the additional assumptions and qualifications set forth below, we advise you that, in our opinion, assuming the Debt Securities have been duly executed and authenticated in accordance with the provisions of the Indenture and delivered to and paid for by the Underwriters pursuant to the Underwriting Agreement, the Debt Securities will constitute valid and binding obligations of the Company and each related Guarantee (as provided by the terms of the Indenture) will constitute a valid and binding obligation of Shire, enforceable against each of the Company and Shire, as applicable, in accordance with their respective terms, subject to applicable bankruptcy, insolvency and similar laws affecting creditors’ rights generally, concepts of reasonableness and equitable principles of general applicability, and may be subject to possible judicial or regulatory actions giving effect to governmental actions or foreign laws affecting creditors' rights; provided that we express no opinion as to the (x) (i) effect of fraudulent conveyance, fraudulent transfer or similar provision of applicable law on the conclusions expressed above or (ii) any provision of the Indenture that purports to avoid the effect of fraudulent conveyance, fraudulent transfer or similar provision of applicable law by limiting the amount of Shire’s obligation, or (y) validity, legally binding effect or enforceability of any provision that permits holders to collect any portion of stated principal amount upon acceleration of the Debt Securities to the extent determined to constitute unearned interest.

In connection with the opinion expressed above, we have assumed that each of the Company and Shire is validly existing as a corporation in good standing (to the extent that such concept is applicable in its jurisdiction of incorporation) under the laws of Ireland and the laws of Jersey, respectively. In addition, we have assumed that the Indenture and the Securities (collectively, the “Documents”) are valid, binding and enforceable agreements of each party thereto (other than as expressly covered above in respect of the Company and Shire). We have also assumed that the execution, delivery and performance by each party to each Document to which it is a party (a) are within its corporate powers, (b) do not contravene, or constitute a default under, the certificate of incorporation or bylaws or other constitutive documents of such party, (c) require no action by or in respect of, or filing with, any governmental body, agency or official and (d) do not contravene, or constitute a default under, any provision of applicable law or regulation or any judgment, injunction, order or decree or any agreement or other instrument binding upon such party, provided that we make no such assumption to the extent that we have specifically opined as to such matters with respect to the Company and Shire.

We are members of the Bar of the State of New York and the foregoing opinion is limited to the laws of the State of New York and the federal laws of the United States, except that we express no opinion as to any law, rule or regulation that is applicable to the Company or Shire, the Documents or such transactions solely because such law, rule or regulation is part of a regulatory regime applicable to any party to any of the Documents or any of its affiliates due to the specific assets or business of such party or such affiliate. Insofar as the foregoing opinion

involves matters governed by the laws of other jurisdictions, we have relied, without independent inquiry or investigation, (i) as to all matters of Irish law, upon the opinion of Arthur Cox, legal counsel in Ireland for the Company and (ii) as to all matters of Jersey law, upon the opinion of Mourant Ozannes, legal counsel in Jersey for Shire, which opinions to be filed as an exhibit to a report on Form 8-K to be filed by Shire on the date hereof. Our opinion is, insofar as such laws are concerned, subject to the assumptions, qualifications and exceptions contained in such opinions.

We hereby consent to the filing of this opinion as an exhibit to a report on Form 8-K to be filed by the Shire on the date hereof and its incorporation by reference into the Registration Statement and further consent to the reference to our name under the caption “Validity of Securities” in the prospectus supplement which is a part of the Registration Statement. In giving this consent, we do not admit that we are in the category of persons whose consent is required under Section 7 of the Securities Act.

Very truly yours,

/s/ Davis Polk & Wardwell LLP

EX-5.2

Exhibit 5.2

22 Grenville Street
St Helier
Jersey JE4 8PX
Channel Islands

T +44 1534 676 000
F +44 1534 676 333

mourantozannes.com

Shire plc

22 Grenville Street

St Helier

Jersey JE4 8PX

Channel Islands

23 September 2016

Our ref: 8025695/68421520/7

Dear Ladies and Gentlemen,

Shire plc (the Company)

Form S-3 Registration Statement

Guarantee by the Company of U.S. $3,300,000,000 aggregate principal amount of 1.900% Senior Notes due 2019 (the 2019 Notes), U.S. $3,300,000,000 aggregate principal amount of 2.400% Senior Notes due 2021 (the 2021 Notes), U.S. $2,500,000,000 aggregate principal amount of 2.875% Senior Notes due 2023 (the 2023 Notes) and U.S. $3,000,000,000 aggregate principal amount of 3.200% Senior Notes due 2026 (the 2026 Notes) (together the Securities) issued by Shire Acquisitions Investments Ireland Designated Activity Company (the Issuer)

We have acted as Jersey legal advisers to the Company. We are giving this opinion in connection with (i) the guarantee by the Company of the Securities which are issued by the Issuer pursuant to the Base Indenture and the Supplemental Indenture (each as defined below) and (ii) the registration of the Securities under the U.S. Securities Act of 1933, as amended (the Securities Act).

We understand that the Securities are:

(a) guaranteed by the Company pursuant to a full and unconditional guarantee (the Guarantee) for the Securities contained in Section 13.01 of the Base Indenture;

(b) registered under the Securities Act and offered to investors pursuant to the Base Prospectus (as defined below) and the Final Prospectus Supplement (as defined below); and

(c) represented by one or more global securities in registered form (each, a Global Security) for the Securities issued by the Issuer in the applicable form set out in the Supplemental Indenture.

This opinion, which is addressed to the Company, is to be filed as an exhibit to the Registration Statement (as defined below). We have not been concerned with investigating or verifying the facts set out in the Registration Statement.

1. Documents and searches

1.1 For the purposes of this opinion, we have examined a copy of each of the following documents:

Mourant Ozannes is a Jersey partnership

A list of the partners is available at mourantozannes.com

Page 2

(a) an indenture dated as of 23 September 2016 (the Base Indenture) made between the Issuer as issuer, the Company as guarantor and Deutsche Bank Trust Company Americas as trustee (the Trustee);

(b) a supplemental indenture dated as of 23 September 2016 to the Base Indenture (the Supplemental Indenture) relating to the Securities made between the Issuer, the Company and the Trustee;

(c) a registration statement on Form S-3 of the Company and the Issuer dated 2 September 2016 (the Registration Statement) filed with the United States Securities and Exchange Commission (the Commission), which includes a base prospectus dated 2 September 2016 (the Base Prospectus);

(d) a preliminary prospectus supplement to the Base Prospectus dated 8 September 2016 (the Preliminary Prospectus Supplement) relating to the Securities;

(e) a final term sheet dated 19 September 2016 (the Final Term Sheet) in respect of the Securities;

(f) a final prospectus supplement to the Base Prospectus dated 19 September 2016 (the Final Prospectus Supplement) relating to the Securities;

(g) the certificates of incorporation and the memorandum and articles of association of the Company;

(h) an extract (the Extract) of the minutes of the meeting of the board of directors of the Company (the Board Meeting) held on 25 - 26 July 2016;

(i) consent of the Jersey Financial Services Commission dated 20 July 2016 under the Control of Borrowing (Jersey) Order, 1958, as amended (the Order) to the Guarantees that comprise securities for the purposes of the Order (the COBO Consent); and

(j) consent of the Registrar of Companies under the Companies (General Provisions) (Jersey) Order, 2002 to the circulation of the Registration Statement by the Company dated 1 September 2016 (the Registrar's Consent and together with the COBO Consent, the Consents).

1.2 We have relied on a certificate of the secretary of the Company dated 23 September 2016 (the Opinion Certificate) a copy of which is attached to this opinion. We have not verified, and express no opinion on, the accuracy of the matters certified in the Opinion Certificate.

1.3 We have conducted the following searches (together the Searches):

(a) a search conducted on 23 September 2016 of the public record of the Company (the Company Search) maintained by the Jersey Registrar of Companies (the Registrar);

(b) an enquiry made on 23 September 2016 at the office of the Viscount (the executive officer of the Jersey courts) in relation to the Company (the Bankruptcy Search); and

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(c) a search on 23 September 2016 of the SIR register of security interests maintained by the Registrar by reference to the current name and registered number of the Company (the Security Search).

1.4 In this opinion:

(a) a reference to a document having been executed refers to it having been signed (or, as the case may be, sealed) by or on behalf of each party to it, dated and unconditionally delivered by or on behalf of each party to it;

(b) a reference to Jersey regulatory consents is a reference to any approvals, authorisations, consents, licences, permits or registrations of any governmental or other regulatory authority in Jersey; and

(c) a reference to the Indenture is a reference to the Base Indenture as supplemented by the Supplemental Indenture.

1.5 We have examined only the documents listed in paragraph 1.1 and have undertaken only the Searches for the purposes of issuing this opinion. We have not examined for these purposes any other agreements or other documents (the Other Documents) to be entered into by the Company (including, without limitation, any documents incorporated by reference in or otherwise referred to in the Indenture or the Registration Statement) and we offer no opinion on any such Other Document. We have not examined any term or document incorporated by reference in or otherwise referred to, whether in whole or part, in the Indenture and we offer no opinion on any such term or document.

2. Assumptions

We have assumed that:

2.1 each document examined by us (and any signature, initial, stamp or seal on it) is genuine and, where it is a copy, it conforms to the original document;

2.2 all matters certified in the Opinion Certificate were, and remain, at the date of this opinion, true and accurate;

2.3 (a) the certificates of incorporation and the memorandum and articles of association of the Company are true and complete, (b) the memorandum and articles of association of the Company have attached to them all resolutions or agreements or acts of court to which the provisions of articles 100 or 125 of the Companies (Jersey) Law 1991 apply and (c) the memorandum and articles of association of the Company are in full force and effect and have not been amended or superseded and the Company is not party to any shareholders agreement supplementing the articles of association;

2.4 the resolutions passed by the directors of the Company at the Board Meeting and recorded in the Extract were duly passed, are in full force and effect and have not been amended, revoked or superseded and any meeting at which such resolutions were passed was duly convened and quorate throughout;

2.5 the Company has not breached the limitations on borrowing contained in Article 107(B) of its articles of association and the Company's entry into, and the performance of its obligations under, the Base Indenture or the Supplemental Indenture will not cause the Company to breach any such limitation;

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2.6 all terms and conditions of the Consents have been and will be observed and performed by the Company at all times;

2.7 the words and phrases used in the Registration Statement, the Base Indenture and the Supplemental Indenture have the same meaning and effect as they would if the Registration Statement, the Base Indenture and the Supplemental Indenture were governed by Jersey law;

2.8 where an incomplete or uncompleted document or signature pages only have been supplied to us, the original document has been duly completed and is in substantially the same form as the last draft of that document examined by us;

2.9 each director of the Company has disclosed to the Company any interests that fall to be disclosed under the Company's articles of association or that, directly or indirectly, conflict or may conflict to a material extent with the interests of the Company and any of its subsidiaries with regard to the transactions and other matters recorded in the Extract and such disclosures are or will be recorded in the full minutes of the Board Meeting, or in previous board minutes of the Company;

2.10 there are no agreements or arrangements in existence which restrict the powers and authority of the directors of the Company in any way and no resolution has been passed by the directors, any committee of directors or the shareholders of the Company to limit the powers of the directors to authorise:

(a) the carrying on of business by the Company in any manner; or

(b) the affixing of the Company seal (if any) to any document;

2.11 each document examined by us and executed by the Company has been executed by the person(s) authorised by the Company pursuant to the authorities set out in the Extract to execute it and, in the case of the Base Indenture and the Supplemental Indenture, each has been delivered unconditionally by or on behalf of the Company;

2.12 each party to the Base Indenture and the Supplemental Indenture (other than the Company as a matter of Jersey law) has:

(a) the capacity and power;

(b) taken all the necessary action; and

(c) obtained all the necessary agreements, approvals, authorisations, consents, licences, registrations or qualifications (whether as a matter of any law or regulation applicable to it or as a matter of any contract binding upon it),

to execute and perform its obligations under the Base Indenture and the Supplemental Indenture and that the Base Indenture and the Supplemental Indenture have been duly executed by each such party;

2.13 the Base Indenture and the Supplemental Indenture are legal, valid, binding and enforceable in accordance with their terms as a matter of all applicable laws other than Jersey law;

2.14 that the opinion expressed below will not be affected by the laws (including public policy) of any jurisdiction outside Jersey and in particular but without limiting the generality of the foregoing:

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(a) that there are no provisions of the laws of any jurisdiction outside Jersey which would be contravened by the execution, delivery or performance of the Base Indenture or the Supplemental Indenture; and

(b) that there has been, and there will be, due compliance with all matters of every applicable law (other than Jersey law);

2.15 in causing the Company to enter into the Base Indenture and the Supplemental Indenture, each of the directors of the Company were acting in good faith with a view to the best interests of the Company and were exercising the care, diligence and skill that a reasonably prudent person would exercise in comparable circumstances;

2.16 the Company is able to pay its debts as they fall due and will not become unable to do so by virtue of the execution of the Base Indenture or the Supplemental Indenture or the performance of the transactions contemplated thereby and no steps have been taken or resolutions passed to wind up the Company;

2.17 the Company, in entering into the Base Indenture and the Supplemental Indenture, is acting as principal on its own behalf and not as an agent or trustee or in any other capacity;

2.18 each Global Security has been:

(a) fully and properly completed to reflect the terms and conditions of the Securities; and

(b) duly executed by the Issuer and duly dated, authenticated, issued and delivered in accordance with the Base Indenture,

and all necessary entries have been made in the Security Register (as defined in the Base Indenture) in respect of the issue of that Global Security;

2.19 the Company is not, and is not owned or controlled directly or indirectly by, a state or sovereign entity;

2.20 the Company's trading activities are carried on outside Jersey and it does not occupy any floor space, or have any employees, in Jersey;

2.21 the choice of the governing law of the Base Indenture and the Supplemental Indenture will be made in good faith;

2.22 (a) the Company has no employees or secondees in Jersey and no director or secretary of the Company that is ordinarily resident in Jersey is an employee of the Company; (b) all or a majority of the directors and secretary of the Company are not ordinarily resident in Jersey; and (c) the Company is administered or managed by a person or body of persons registered to conduct trust company business under the Financial Services (Jersey) Law 1998;

2.23 no offer for the subscription, sale or exchange of the Securities has been or will be circulated in Jersey;

2.24 there are no:

(a) arrangements, agreements or deeds to which the Company is party (other than its memorandum and articles of association); or

Page 6

(b) resolutions passed by the Company,

the terms of which could affect, conflict with, or be breached by, the terms of the Base Indenture or the Supplemental Indenture;

2.25 all documents required to be filed in relation to the Company with the Registrar have been filed and the information disclosed by the Company Search was at the time of the Company Search (and remains) accurate and complete and there was nothing filed that did not appear on the records of the Company when searched;

2.26 the information disclosed by the Bankruptcy Search and the Security Search, as the case may be, was at the time of the search (and remains) accurate and complete; and

2.27 that no event occurs after the date of this opinion that would affect this opinion.

3. Opinion

Subject to the assumptions, observations, qualifications and limitations set out in this opinion, and to matters not disclosed to us, we are of the following opinion:

3.1 Status: the Company is duly incorporated under the Companies (Jersey) Law 1991 and is validly existing under Jersey law.

3.2 Power and capacity: the Company has the corporate power and capacity to enter into and perform its obligations under the Indenture and has taken the necessary corporate action to authorise the due execution and performance of its obligations under the Indenture.

3.3 Consents: except for the Consents, no Jersey regulatory consents are required for the lawful execution of, or performance of the obligations under, the Indenture by the Company.

3.4 Non-conflict: the execution by the Company of, and the performance of its obligations under, the Indenture does not result in any breach of its memorandum and articles of association or any law or regulation of general application in Jersey.

3.5 Legal validity: the Indenture has been executed and delivered by the Company and the obligations assumed by the Company in the Indenture constitute legal, valid, binding and enforceable obligations of the Company.

3.6 Registration requirements: it is not necessary to ensure the legality, validity, enforceability or admissibility in evidence of the Indenture that it be filed, recorded or registered at any governmental, administrative or other authority or court in Jersey.

3.7 Stamp duty: except for the payment of court fees in the event of litigation before the Jersey courts, there is no registration fee, stamp duty or other documentary charge required to be paid in Jersey in relation to the Indenture.

3.8 Withholding tax: the Company will not be required to make any deduction or withholding for, or on account of, Jersey income tax from any payment it may make under the Indenture.

3.9 Income tax: provided that the payee is not resident in Jersey for the purposes of the Income Tax (Jersey) Law 1961, it will not be subject to Jersey income tax on interest payments made to it under the Indenture.

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3.10 Choice of law: the law selected in the Indenture to govern it would be upheld as a valid choice of law by the Jersey courts (upon proof of the relevant provisions of that law).

3.11 Foreign judgments: a judgment of a New York court is not directly enforceable in Jersey. The Jersey courts, however, have inherent jurisdiction to recognise and enforce, without reconsidering the merits, an in personam judgment for a liquidated sum of money (not being in respect of taxes or similar charges, a fine or a penalty) that is final and conclusive given against the Company on the merits by a court in the State of New York (having jurisdiction according to Jersey rules of private international law), provided that (a) such judgment is not for exemplary, multiple or punitive damages and is obtained without fraud, in accordance with the principles of natural justice and is not contrary to public policy and (b) the enforcement proceedings in the Jersey courts are duly served.

3.12 Submission to jurisdiction: the submission by the Company to the jurisdiction of the New York courts in the Indenture will be effective.

3.13 Residence (Company): the Company will not be deemed to be resident, domiciled, carrying on business or subject to income tax in Jersey by reason only of its entry into the Indenture.

3.14 Taxation: the statements set forth in the Preliminary Prospectus Supplement and the Final Prospectus Supplement under the heading "Jersey Tax Considerations", insofar as such statements purport to summarise certain tax laws of Jersey, constitute a fair summary of the principal Jersey tax consequences of an investment in the Securities.

3.15 Company Search: the Company Search disclosed no evidence of any shareholder resolution for the winding up or dissolution of the Company or the appointment of any liquidator, receiver or other similar official in respect of the Company or any of its assets.

3.16 Bankruptcy Search: the Bankruptcy Search disclosed no evidence that a declaration has been made that the property of the Company is en désastre.

3.17 Security Search: the Security Search disclosed no financing statements registered against the Company.

4. Qualifications and observations

Our opinion is subject to the following qualifications and observations:

4.1 This opinion is subject to all laws relating to bankruptcy, dissolution, insolvency, re-organisation, liquidation, moratorium or other laws of general application affecting the rights of creditors generally.

4.2 The term enforceable, when used in our opinion at paragraph 3.5 (Legal validity) above, means that the obligations are of a type which the Jersey courts will enforce. It does not mean that those obligations will necessarily be enforced in all circumstances or in accordance with their terms. In particular, but without limitation:

(a) enforcement may be prevented by statutory provisions relating to the setting aside of transactions at an undervalue, preferences and extortionate credit transactions and the disclaiming of onerous property;

Page 8

(b) enforcement may be limited by general principles of equity, for example equitable remedies such as specific performance and injunction are discretionary and may not be available where damages are considered to be an adequate remedy;

(c) enforcement of obligations may be invalidated by reason of fraud, duress, misrepresentation, mistake or undue influence;

(d) contractual obligations that are regarded as penalties may not be enforceable or may be liable to be reduced if found to exceed the maximum damages which the claimant could have suffered as a result of a breach of contract;

(e) the Jersey courts will not enforce all or any obligations if they are illegal or contrary to public policy in Jersey or, where obligations are to be performed in a jurisdiction other than Jersey, if such performance would be illegal under the laws of that jurisdiction;

(f) the Jersey courts may not enforce the terms of an agreement:

(i) to the extent that the transactions contemplated by such terms conflict with or breach economic or other sanctions imposed by any treaty, law, order or regulation applicable to Jersey;

(ii) for the payment or reimbursement of, or indemnity against, the costs of enforcement (actual or contemplated) or of litigation brought before the Jersey courts or where the Jersey courts have themselves made an order for costs;

(iii) that provide for matters to be determined by future agreement;

(iv) that would involve the enforcement of any foreign revenue, penal or other public laws;

(v) that are in breach of any applicable exchange control regulations;

(vi) that purport to exclude the jurisdiction of the Jersey courts;

(vii) that provide that if terms are found to be illegal, invalid or unenforceable, the other terms of the agreement will remain enforceable; or

(viii) to the extent that they have been frustrated by events happening after the execution of the agreement;

(g) the Jersey courts may refuse to allow unjust enrichment or to give effect to any provisions of an agreement that they consider usurious;

(h) provisions in an agreement (including in articles of association) that purport to fetter any statutory power in relation to a Jersey company may not be enforceable;

(i) claims may become time barred or may be (or become) subject to rights and defences of counter-claim, estoppel, laches, set-off, waiver and similar defences;

(j) the effectiveness of terms that release or exculpate any party from, or limit or exclude, a liability or duty otherwise owed or indemnify a person in

Page 9

respect of a loss caused by the act or omission of that person, may be limited by law;

(k) where any party to an agreement is party to it in more than one capacity that party may not be able to enforce obligations purportedly owed by it to itself; and

(l) a trust is invalid to the extent that it purports to apply directly to Jersey situate immovable property.

4.3 Security purported to be created by or pursuant to the Base Indenture or the Supplemental Indenture over any property situate in Jersey may not be enforceable in Jersey.

4.4 Where a director fails, in accordance with the Companies (Jersey) Law 1991, to disclose an interest in a transaction entered into by a Jersey company or its subsidiary which conflicts or may conflict to a material extent with the interests of the company, the transaction is voidable.

4.5 The enforceability of a person's obligations may be limited to the extent that such person successfully pleads either:

(a) the droit de discussion (whereby a guarantor may require the beneficiary of the guarantee to exhaust the assets of the principal debtor before making a claim against the guarantor); or

(b) the droit de division (whereby a co-obligor may require the person owed a joint obligation to make simultaneous claims in appropriate proportions upon all the co-obligors, thereby limiting its own liability),

unless the person has expressly waived such rights.

4.6 Despite any term of an agreement to the contrary, the Jersey courts may hold that:

(a) any certificate, calculation, determination or designation of any party to the agreement is not conclusive, final and/or binding;

(b) any person exercising any discretion, judgment or opinion under the agreement must act in a reasonable manner; and

(c) any power conferred by the agreement on one party to require another party to execute such documents or do such things as the first party requires must be exercised reasonably.

4.7 Pursuant to the Powers of Attorney (Jersey) Law 1995:

(a) subject to paragraph (b) below, a power of attorney is revoked by the bankruptcy or dissolution of a donor that is a body corporate;

(b) where a power of attorney is expressed to be irrevocable (for any period) and is given:

(i) for the purpose of facilitating the exercise of powers of a secured party under the Security Interests (Jersey) Law 2012 (the Security Law) or of powers given pursuant to a security agreement (as defined in the Security Law); or

Page 10

(ii) pursuant to, or in connection with, or for the purpose of, or ancillary to, security governed by a law other than Jersey law,

it is not revoked by the bankruptcy or dissolution of the donor; and

(c) subject to paragraphs (a) and (b) above, a power of attorney may not be expressed to be irrevocable for any period exceeding one year from the date on which it is granted or the date on which it comes into effect, whichever is the later.

For the purposes of this paragraph, power of attorney may include the appointment of an agent or other grant of authority.

4.8 Where the sum payable under the judgment of a superior court (as defined in the Reciprocal Enforcement Legislation) in England and Wales, Scotland, Northern Ireland, the Isle of Man or Guernsey (a Reciprocal Enforcement Court) is expressed in a currency other than the currency of Jersey (one Jersey pound is equivalent to one pound sterling), the judgment will be registered by the Jersey courts under the Judgments (Reciprocal Enforcement) (Jersey) Law 1960 and all regulations, rules or orders made under it (the Reciprocal Enforcement Legislation) as if it were a judgment for such sum in the currency of Jersey as, on the basis of the rate of exchange prevailing at the date of judgment of the Reciprocal Enforcement Court, is equivalent to the sum so payable.

4.9 The Jersey courts will not apply a foreign law expressly selected to govern an agreement (the proper law) if:

(a) it is not pleaded and proved;

(b) the selection of that law was not bona fide and legal; or

(c) to do so would be contrary to public policy.

Furthermore:

(a) the Jersey courts may apply a law other than the proper law (such as the law of the place an agreement was made) to determine the formal validity of an agreement;

(b) matters of procedure upon enforcement of an agreement and assessment or quantification of damages will be determined by the Jersey courts in accordance with Jersey law;

(c) the proprietary effects of an agreement may be determined by the Jersey courts in accordance with the domestic law of the place where the relevant property is situate;

(d) the mode of performance of an agreement may be determined by the Jersey courts in accordance with the law of the place of performance; and

(e) the Jersey courts may not apply a foreign law expressly selected in an agreement to govern non-contractual obligations arising out of, or in connection with, the agreement.

4.10 The Jersey courts may stay or set aside proceedings where:

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(a) there is a more appropriate forum than Jersey where the action should be heard;

(b) earlier or concurrent proceedings have been commenced elsewhere; or

(c) there has already been a final determination of the matter by a court of competent jurisdiction.

4.11 Under the State Immunity Act 1978 of the United Kingdom (the Immunity Act) as extended to Jersey by the State Immunity (Jersey) Order 1985:

(a) a Jersey company will be immune from the jurisdiction of the Jersey courts:

(i) if it is a department of the government of a foreign or commonwealth State other than the United Kingdom (a State); or

(ii) where:

(A) the proceedings relate to anything done by it in the exercise of sovereign authority of a State; and

(B) the circumstances are such that the State would have been immune from jurisdiction under the Immunity Act; and

(b) even where a Jersey company, which is immune from the jurisdiction of the Jersey courts in the circumstances mentioned in paragraph (a) above, submits to the jurisdiction of any court whether in Jersey or elsewhere:

(i) it may be immune from relief by way of injunction or order for specific performance or the recovery of property; and

(ii) its property may be immune from any process for the enforcement of a judgment or arrest, detention or sale.

4.12 If a final and conclusive judgment under which a sum of money is payable were obtained against the Company in a superior court of England and Wales, Scotland, Northern Ireland, the Isle of Man or Guernsey in circumstances where the judgment could not be enforced in such a court on the grounds of sovereign immunity, that judgment could not be registered and enforced as a judgment of the Jersey courts under the Reciprocal Enforcement Legislation.

4.13 Despite any contractual rights of set-off in an agreement, if a party is subject to a creditors' winding-up or its property is declared en désastre and there have been mutual credits, debts or other dealings between that party and another, an account shall be taken, as at the date of commencement of the creditors' winding-up or the declaration en désastre, of what is due from one to the other in respect of such mutual credits, debts or other dealings, and the sum due from one shall be set-off against any sum due from the other, and the balance, and no more, shall be claimed or paid by either party.

4.14 The Company Search is not conclusively capable of revealing whether or not a shareholder resolution has been passed (or an order made) for:

(a) the winding up or dissolution of the Company; or

(b) the appointment of a liquidator in respect of the Company or any of its assets,

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as notice of these matters is not required to be filed immediately or may not be filed within the time periods prescribed by law or, when filed, may not be entered on the public record of the Company immediately.

4.15 The Bankruptcy Search relates only to the making of a declaration that the property of the Company is en désastre. There is no formal procedure for determining whether the Company has otherwise become bankrupt (as defined in the Interpretation (Jersey) Law 1954).

4.16 The Security Search was made only against the current name and registered number of the Company. In this regard, the Security Search will not disclose if the Company has merged with another entity and become bound by a security interest granted by, and registered against the name of, the other entity.

4.17 There is no publicly available record of security interests in the tangible movable assets of Jersey companies (other than Jersey-registered ships, aircraft and aircraft engines).

4.18 The information registered on the SIR may not be comprehensive. The Security Search does not provide any assurance against future filings or undisclosed security interests.

4.19 Save as regards Austria, the Taxation (Agreements with European Union Member States)(Jersey) Regulations 2005 (the "Regulations") were suspended on 18 January 2016 pursuant to the Taxation (Agreements with European Union Member States)(Suspension of Regulations)(Jersey) Order 2016. The Regulations continue in effect until 31 December 2016 as regards Austria.

4.20 A paying agent established in Jersey that makes interest payments (as defined in the Regulations) to an individual beneficial owner resident in Austria prior to 1 January 2017 is obliged to communicate details of such payments to the Comptroller of Taxes in Jersey who, pursuant to the Regulations, must provide such information to the tax authorities in Austria.

5. Limitations

5.1 We offer no opinion:

(a) on the commercial terms of the Base Indenture or the Supplemental Indenture or whether those terms reflect the intentions of the parties;

(b) on any representation or warranty made or given in the Base Indenture or the Supplemental Indenture;

(c) as to whether the parties will be able to perform their obligations under the Base Indenture or the Supplemental Indenture; and

(d) as to the title or interest of the Company to or in, or the existence of, any property or collateral the subject of the Base Indenture or the Supplemental Indenture.

5.2 We have not advised the Company or its directors in respect of any of the transactions envisaged or to be effected by the Base Indenture or the Supplemental Indenture.

5.3 We have not undertaken a search of the SIR register of assignments of receivables.

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5.4 Without prejudice to our opinion at paragraphs 3.3 (Consents) above, we have conducted only those enquiries necessary for the purpose of giving our opinion at paragraph 3.3 (Consents) and give no opinion as to whether the Company may require Jersey regulatory consents for any other business it may undertake.

6. Jersey law

This opinion shall be governed by, and construed in accordance with, Jersey law in force as at the date of this opinion. This opinion is limited to the matters expressly stated in it. We have made no investigation and express no opinion with respect to the laws of any other jurisdiction. We assume no obligation to update any addressee in relation to changes of fact or law which may have a bearing on the continuing accuracy of this opinion.

7. Consent

7.1 We consent to the disclosure of this opinion as an exhibit to the Registration Statement and its filing with the Commission.

7.2 We consent to reference to us being made in the section of the Base Prospectus headed "Validity of Securities" and the section of any Prospectus Supplement headed "Legal Matters". In giving this consent, we do not admit that we are included in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations promulgated by the Commission under the Securities Act.

Yours faithfully

/s/ Mourant Ozannes

Mourant Ozannes

EX-5.3

Exhibit 5.3

Our Reference: PC/SH111/056/

23 September 2016

PRIVATE AND CONFIDENTIAL

To: Shire Acquisitions Investments Ireland Designated Activity Company

5 Riverwalk

Citywest Business Campus

Dublin 24

Re: Shire Acquisitions Investments Ireland Designated Activity Company, incorporated in Ireland under registered number 574225 – $3,300,000,000 aggregate principal amount of 1.900% Senior Notes due 2019, $3,300,000,000 aggregate principal amount of 2.400% Senior Notes due 2021, $2,500,000,000 aggregate principal amount of 2.875% Senior Notes due 2023 and $3,000,000,000 aggregate principal amount of 3.200% Senior Notes due 2026 (together, the “Notes”) – Exhibit 5 opinion

Dear Sirs,

1. Basis of Opinion

1.1 We act as solicitors in Ireland for Shire Acquisitions Investments Ireland Designated Activity Company, a private limited company incorporated in Ireland with registration number 574225 and with its registered office at 5 Riverwalk, Citywest Business Campus, Dublin 24, Ireland (the “Issuer”)

1.2 We have been requested to furnish this Opinion in connection with the issuance by the Issuer of the Notes. The Notes were registered pursuant to a filing by the Issuer with the SEC under the United States Securities Act of 1933, as amended (the “Securities Act”), of a Registration Statement on Form S-3 dated 2 September 2016 (the “Registration Statement”) and the final prospectus supplement dated 19 September 2016 (together with the Registration Statement, the “Prospectus”), each with respect to the offering of the Notes.

1.3 The Notes are being issued under an Indenture dated as of the date of this Opinion by and among the Issuer, Shire plc as guarantor (“Shire”), and Deutsche Bank Trust Company Americas, as trustee (the “Base Indenture”), as supplemented by a supplemental indenture dated as of the date of this Opinion (the “First Supplemental Indenture” and, together with the Base Indenture, the “Indenture”).

1.4 We hereby consent to the reliance by Davis Polk & Wardwell LLP on this opinion in rendering its “Exhibit 5” opinion in connection with the issuance of the Notes. In addition, we hereby consent to inclusion of this Opinion as an exhibit to the Form 8-K to be filed by Shire with the SEC in connection with the issuance of the Notes. Further, we consent to the reference to our firm in the Prospectus under the caption “Validity of Securities”. In giving such consent, we do not thereby concede that we are within the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations of the Commission thereunder.

This Opinion is given on the basis that our client is the Issuer and we owe no duty of care to any person other than the Issuer. For the purposes of giving this Opinion we have taken instructions solely from the Issuer.

1.5 This Opinion is confined to and given in all respects on the basis of the laws of Ireland in force as at the date hereof as currently applied by the courts of Ireland. We have made no investigations of and we express no opinion as to the laws of any other jurisdiction or the effect thereof. In particular, we express no opinion on the laws of the European Union as they affect any jurisdiction other than Ireland. We have assumed without investigation that insofar as the laws of any jurisdiction other than Ireland are relevant, such laws do not prohibit and are not inconsistent with any of the obligations or rights expressed in the Indenture.

1.6 This Opinion is also strictly confined to:

(a) the matters expressly stated herein and is not to be read as extending by implication or otherwise to any other matter; and

(b) the Notes and the Indenture (and no other documents whatsoever) and the Searches,

and is subject to the assumptions and qualifications set out below.

1.7 In giving this Opinion, we have relied upon the Corporate Certificate and the Searches (as defined in paragraph 1.10 below) and we give this Opinion expressly on the terms that no further investigation or diligence in respect of any matter referred to in the Corporate Certificate or the Searches is required of us.

1.8 No opinion is expressed as to the taxation consequences of the Transaction.

1.9 For the purpose of giving this Opinion, we have examined a copy sent, by email in pdf or other electronic format, to us of the Indenture and the Corporate Certificate.

1.10 References in this Opinion to:

(a) “Board Resolutions” means the resolutions dated September 1, 2016 of the directors of the Issuer approving, among other things, the Transaction and the entry into the Indenture, a certified extract of which are attached to the Corporate Certificate;

(b) “Companies Act” means the Companies Act 2014 of Ireland;

(c) “Corporate Certificate” means a certificate of the secretary of the Issuer, dated the date hereof, attaching in respect of the Issuer, inter alia, the following:

(i) its certificate of incorporation;

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(ii) its memorandum and articles of association (together, the “Constitution”);

(iii) the Board Resolutions; and

(iv) specimen signatures of the directors of the Issuer;

(d) “CRO” means the Irish Companies Registration Office;

(e) “Ireland” means Ireland exclusive of Northern Ireland and “Irish” shall be construed accordingly;

(f) “SEC” means the United States Securities and Exchange Commission;

(g) “Searches” means the searches listed in paragraph 1.11; and

(h) “Transaction” means the entry by the Issuer into the Indenture and the issue of the Notes thereunder.

1.11 For the purpose of giving this Opinion, we have caused to be made the following legal searches against the Issuer on the date of this Opinion:

(a) on the file of the Issuer maintained by the Registrar of Companies in the CRO for mortgages, debentures or similar charges or notices thereof and for the appointment of any examiner, receiver or liquidator;

(b) in the Judgments Office of the High Court for unsatisfied judgments, orders, decrees and the like for the twelve years immediately preceding the date of the search;

(c) in the Central Office of the High Court for any petitions filed in respect of the Issuer;

(d) in the Central Office of the High Court for any proceedings filed by or against the Issuer in the five years prior to the date of the Searches; and

(e) on the register of persons disqualified or restricted from acting as directors of companies incorporated in Ireland which is maintained by the Registrar of Companies in the CRO against the names of the current directors of the Issuer as identified in the search results referred to in sub-paragraph (a) above.

1.12 This Opinion is governed by and is to be construed in accordance with the laws of Ireland (as interpreted by the courts of Ireland at the date hereof) and anyone seeking to rely on this Opinion agrees for our benefit that the courts of Ireland shall have exclusive jurisdiction to settle any dispute arising out of, or in connection with this Opinion. This Opinion speaks only as of its date. We assume no obligation to update this Opinion at any time in the future or to advise you of any change in law or change in interpretation of law which may occur after the date of this Opinion.

2. Opinion

Subject to the assumptions and qualifications set out in this Opinion, we are of the opinion that:

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2.1 Corporate status

The Issuer has been duly incorporated and is validly existing as a designated activity company under the laws of Ireland.

2.2 Corporate capacity

The Issuer has all requisite corporate capacity, power and authority to issue Notes, to enter into, execute, deliver and perform its obligations under the Indenture and to take all action as may be necessary to complete the Transaction.

2.3 Corporate authorisation

The execution, delivery and performance by the Issuer of the Indenture and the consummation of the Transaction:

(a) have been duly authorised by all necessary corporate action on the part of the Issuer; and

(b) do not and will not violate, conflict with or constitute a default under (i) any law, order, rule, decree, statute or regulation of Ireland or (ii) the Constitution of the Issuer.

2.4 Due execution

The Indenture has been duly executed by the Issuer and is in the proper form for enforcement before the courts of Ireland.

2.5 Authorisations and approvals

All necessary action required to be taken by the Issuer pursuant to the laws of Ireland has been taken by or on behalf of the Issuer and all the necessary authorisations, filings and approvals of governmental or regulatory authorities in Ireland have been duly obtained, for the entry into the Indenture and the performance of its obligations under the Indenture.

3. Assumptions

For the purpose of giving this Opinion we assume the following, without any responsibility on our part if any assumption proves to have been untrue as we have not verified independently any assumption:

Authenticity and bona fides

3.1 The truth, completeness, accuracy and authenticity of all copy letters, resolutions, certificates, permissions, minutes, authorisations and all other documents of any kind submitted to us as originals or copies of originals, and (in the case of copies) conformity to the originals of copy documents, the genuineness of all signatures, stamps and seals thereon, that any signatures are the signatures of the persons who they purport to be and that each original was executed in the manner appearing on the copy.

3.2 That, where incomplete versions of the Indenture have been submitted to us or signature pages only have been supplied to us for the purposes of issuing this Opinion, the originals of the Indenture correspond in all respects with the last drafts of the complete Indenture submitted to us.

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3.3 That the Indenture has been executed in its final form, has been delivered by the parties thereto and are not subject to any escrow arrangements and the terms thereof will be observed and performed by the parties thereto.

3.4 That the copies produced to us of minutes of meetings and/or of resolutions correctly record the proceedings at such meetings and/or the subject matter which they purport to record and that any meetings referred to in such copies were duly convened, duly quorate and held and all formalities were duly observed, that those present at any such meetings were entitled to attend and vote at the meeting and acted bona fide throughout, that no further resolutions have been passed or corporate or other action taken which would or might alter the effectiveness thereof and that such resolutions have not been amended or rescinded and are in full force and effect.

3.5 That each director of the Issuer has disclosed any interest which he may have in the Transaction in accordance with the provisions of the Companies Act and the Constitution of the Issuer and none of the directors of the Issuer has any interest in the Transaction except to the extent permitted by the Constitution of the Issuer.

3.6 The absence of fraud, coercion, duress or undue influence and lack of bad faith on the part of the parties to the Indenture and their respective officers, employees, agents and (with the exception of Arthur Cox) advisers.

Accuracy of Searches and the Corporate Certificate

3.7 The accuracy and completeness of the information disclosed in the Searches and that such information is accurate as of the date of this Opinion and has not since the time of such search been altered. In this connection, it should be noted that (a) the matters disclosed in the Searches may not present a complete summary of the actual position on the matters we have caused searches to be conducted for, (b) the position reflected by the Searches may not be fully up-to-date and (c) searches at the CRO do not necessarily reveal whether or not a prior charge has been created or a resolution has been passed or a petition presented or any other action taken for the winding-up of, or the appointment of a receiver or an examiner to, the Issuer or its assets.

3.8 The truth, completeness and accuracy of all representations and statements as to factual matters contained in the Corporate Certificate at the time they were made and at all times thereafter.

3.9 That the entry into the Indenture and the issue of the Notes:

(a) did not, does not and will not contravene the laws of any jurisdiction outside Ireland;

(b) did not, does not and will not result in any breach of any agreement, instrument or obligation to which the Issuer is a party; and

(c) was not, is not and will not be illegal or unenforceable by virtue of the laws of any jurisdiction outside Ireland.

Commercial Benefit

3.10 That the Transaction is for bona fide commercial purposes, on arm’s length terms and for the benefit of each party thereto and are in those parties’ respective commercial interests and for their respective corporate benefit.

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No other information and compliance

3.11 That the Indenture and the documents referred to in it are the only documents relating to the subject matter of the Transaction (for the purposes of this Opinion) and that there are no agreements or arrangements of any sort in existence between the parties to the Indenture which in any way amend or vary the terms of the Indenture or in any way bear upon or are inconsistent with the opinions stated herein.

Authority, Capacity, Execution and Enforceability

3.12 That:

(a) no party to the Indenture is a “consumer” for the purposes of Irish law or a “personal consumer” for the purposes of the Central Bank of Ireland’s Consumer Protection Code 2015;

(b) the parties to the Indenture (other than the Issuer to the extent opined on herein) are duly incorporated and validly in existence and that they and their respective signatories have the appropriate capacity, power and authority to execute the Indenture to which they are a party, to exercise and perform their respective rights and obligations thereunder and to render the Indenture and all obligations thereunder legal, valid, binding and enforceable on them; and

(c) each party to the Indenture (other than the Issuer to the extent opined on herein) has taken all necessary corporate action and other steps to execute, deliver, exercise and perform the Indenture and the rights and obligations set out therein.

3.13 That the execution, delivery and performance of the Indenture:

(a) does not and will not contravene the laws of any jurisdiction outside Ireland;

(b) does not and will not result in any breach of any agreement, instrument or obligation to which the Issuer is a party; and

(c) is not and will not be illegal or unenforceable by virtue of the laws of any jurisdiction outside Ireland.

3.14 That the Issuer was not mistaken in entering into the Indenture as to any material relevant fact.

3.15 That the Indenture constitute legal, valid and binding obligations of the parties thereto, enforceable in accordance with their respective terms under the laws of any relevant jurisdiction other than Ireland insofar as opined on herein.

3.16 That the full and final version of the Indenture was presented to the Issuer for execution.

Solvency and Insolvency

3.17 That:

(a) the Issuer is not unable to pay its debts within the meaning of Sections 509(3) and 570 of the Companies Act or any analogous provisions under any applicable laws;

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(b) the Issuer will not as a consequence of doing any act or thing which the Indenture contemplates, permits or requires it to do, be unable to pay its debts within the meaning of such Sections or any analogous provision under any applicable laws;

(c) no liquidator, receiver or examiner or other similar or analogous officer has been appointed in relation to the Issuer or any of its assets or undertakings; and

(d) no petition for the making of a winding-up order or the appointment of an examiner or any similar officer or any analogous procedure has been presented in relation to the Issuer.

3.18 That, upon the opening of any insolvency proceedings pursuant to Council Regulation (EC) No. 1346/2000 (the “EU Insolvency Regulation”), the Issuer will have its “centre of main interests” (as that term is used in Article 3(1) of the EU Insolvency Regulation) in Ireland being the jurisdiction in which the Issuer has its registered office and will not have an “establishment” (being any place of operations where a company carried out a non-transitory economic activity with human means and goods) as defined in Article 2(h) of the EU Insolvency Regulation) outside Ireland.

Foreign Laws

3.19 That as a matter of all relevant laws (other than the laws of Ireland):

(a) all consents, approvals, notices, filings, recordations, publications, registrations and other steps necessary or desirable to permit the execution, delivery (where relevant) and performance of the Indenture or to perfect, protect or preserve any of the interests created by the Indenture have been obtained, made or done, or will be obtained, made or done, within any relevant time period(s); and

(b) the legal effect of the Indenture, and the Transaction, and the creation of any interest the subject thereof will be, upon execution and, where relevant, delivery of any of the Indenture, effective.

Financial Assistance and Connected Transactions.

3.20 The Issuer is not by entering into the Indenture or performing its obligations thereunder, providing financial assistance for the purpose of an acquisition (by way of subscription, purchase, exchange or otherwise) made or to be made by any person of any shares in the Issuer or its holding company which would be prohibited by Section 82.

3.21 That none of the transactions contemplated by the Indenture are prohibited by virtue of Section 239 of the Companies Act, which prohibits certain transactions between companies and its directors or persons connected with its directors.

Governing law and jurisdiction

3.22 That under all applicable laws (other than those of Ireland) the choice of the laws of the State of New York as the governing law of the Notes (to the extent that they are expressed to be governed by the laws of the State of New York) is a valid and binding selection which will be upheld, recognised and given effect by the courts of any relevant jurisdiction (other than those of Ireland).

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3.23 That the submission of each party to the Indenture to the jurisdiction of the courts of any New York State or United States Federal court sitting in the City of New York (to the extent that they are so expressed) is valid and binding and will be upheld, recognised and given effect by the courts of any relevant jurisdiction (other than those of Ireland).

Securities Laws

3.24 In relation to each Member State of the European Economic Area which has implemented the Prospectus Directive (as defined below) (each, a “Relevant Member State”), no offer to the public of the Notes has been or will be made in that Relevant Member State, except in any circumstances falling within Article 3(2) of the Prospectus Directive (as implemented into the domestic law of the applicable Relevant Member State), where:

(a) the expression an “offer of notes to the public” in relation to any Notes in any Relevant Member State means the communication in any form and by any means of sufficient information on the terms of the offer and the Notes to be offered so as to enable an investor to decide to purchase or subscribe for the Notes, as the same may be varied in that Relevant Member State by any measure implementing the Prospectus Directive in that Member State; and

(b) the expression “Prospectus Directive” means Directive 2003/71/EC (and amendments thereto, including the Directive 2010/73/EU, to the extent implemented in the Relevant Member State), and includes any relevant implementing measure in the Relevant Member State.

4. Qualifications

The opinions set out in this Opinion are subject to the following reservations:

4.1 We express no opinion as to whether an issue of Notes will breach any other agreement or instrument.

4.2 We have not investigated the nature of or the title to property and assets, or insurance, merger/competition, regulatory or environmental status or compliance nor have we considered any implications or perfection or other requirements arising in respect thereof. Other than the Searches, we have not conducted any other searches whatsoever. We have conducted no due diligence nor checked the regulatory status or compliance of the Issuer or any of its affiliates or shareholders, or banks, or any other person. We have not conducted any due diligence on the status of any person or enquired or investigated as to whether they hold appropriate licenses or approvals. This qualification is without prejudice to the opinion set out at paragraph 2.5 above.

4.3 If any transfer of, or payment in respect of, an issue of Notes is controlled by or otherwise connected with a person (or is itself) resident in, incorporated in or constituted under the laws of a country which is the subject of United Nations, European Union or Irish sanctions or sanctions under the Treaty on the Functioning of the European Union, as amended, or is otherwise the target of any such sanctions, then obligations to that party under such Notes or in respect of the relevant transfer or payment may be unenforceable or void.

4.4 We note the decision in the English case of R (on the application of Mercury Tax Ltd) v. Revenue and Customs Commissioners [2008] EWHC 2721. Although this decision will not be binding on the courts of Ireland it will be considered as persuasive authority. One of the decisions in that case would appear to indicate that a previously

8

executed signature page from one document may not be transferred to another document, even where the documents in question are simply updated versions of the same document. Our Opinion is qualified by reference to the above referenced decision.

4.5 No opinion is expressed on any deed of assignment, transfer, accession or similar document executed after the date of this opinion in relation to any of the rights and obligations contained in the Indenture.

4.6 No opinion is expressed on any deed or agreement envisaged by the Indenture to be entered at a future date or any future action taken by a party under any of the Indenture.

4.7 A particular course of dealing among the parties or an oral amendment, variation or waiver may result in an Irish court finding that the terms of the Indenture have been amended, varied or waived even if such course of dealing or oral amendment, variation or waiver is not reflected in writing among the parties.

4.8 There is a possibility that an Irish court would hold that a judgment on the Transaction, whether given in an Irish court or elsewhere, would supersede the relevant agreement or instrument to all intents and purposes, so that any obligation thereunder which by its terms would survive such judgment might not be held to do so.

5. No Refresher

This Opinion speaks only as of its date. We are not under any obligation to update this Opinion from time to time or to notify you of any change of law, fact or circumstances referred to or relied upon in the giving of this Opinion.

Yours faithfully,

/s/ Arthur Cox

ARTHUR COX

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EX-99.1

Exhibit 99.1

Press Release www.shire.com  

Shire Closes Public Offering of Senior Notes

Dublin, Ireland – September 23, 2016 – Shire plc (LSE: SHP, NASDAQ: SHPG) announced today that its wholly owned subsidiary, Shire Acquisitions Investments Ireland Designated Activity Company (“SAIIDAC”), issued $12.1 billion aggregate principal amount of senior notes, consisting of four series of senior notes:

$3.3 billion 1.900% Senior Notes due 2019;
$3.3 billion 2.400% Senior Notes due 2021;
$2.5 billion 2.875% Senior Notes due 2023; and
$3.0 billion 3.200% Senior Notes due 2026

Shire has used the net proceeds to fully repay amounts outstanding under its January 2016 bridge facilities agreement, which were used to finance its acquisition of Baxalta Incorporated (“Baxalta”). Shire intends to use the remaining net proceeds for general corporate purposes.

The offering was made only by means of a base prospectus and related prospectus supplement. Copies of the base prospectus and final prospectus supplement may be obtained by contacting:

· Barclays Capital Inc. by calling (toll-free from the U.S.) +1 888 603 5847;

· Merrill Lynch, Pierce, Fenner & Smith Incorporated by calling (toll-free from the U.S.) +1 800 294 1322; or

· Morgan Stanley & Co. LLC by calling (toll-free from the U.S.) +1 866 718 1649.

An effective registration statement is on file with the U.S. Securities and Exchange Commission (“SEC”), and a copy of the base prospectus and related prospectus supplement are also available on the SEC's website at www.sec.gov.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities nor shall there be any sale of these securities in any jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.

Registered in Jersey, No. 99854, 22 Grenville Street, St Helier, Jersey JE4 8PX

For further information please contact:

Investor Relations
Sarah Elton-Farr	seltonfarr@shire.com	+44 1256 894157
Ian Karp	ikarp@shire.com	+1 781 482 9018
Robert Coates	rcoates@shire.com	+44 1256 894874
Media
Gwen Fisher	gfisher@shire.com	+1 484 595 9836
Debbi Ford	debbi.ford@shire.com	+1 617 949 9083

NOTES TO EDITORS

About Shire

Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.

Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest.

www.shire.com

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Forward-Looking Statements

Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:

· Shire’s products may not be a commercial success;

· increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire’s future revenues, financial condition and results of operations;

· Shire conducts its own manufacturing operations for certain of its products and is reliant on third party contract manufacturers to manufacture other products and to provide goods and services. Some of Shire’s products or ingredients are only available from a single approved source for manufacture. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;

· the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;

· certain of Shire’s therapies involve lengthy and complex processes, which may prevent Shire from timely responding to market forces and effectively managing its production capacity;

· Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;

· the actions of certain customers could affect Shire’s ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial conditions or results of operations;

· Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;

· adverse outcomes in legal matters, tax audits and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on the combined company’s revenues, financial condition or results of operations;

· inability to successfully compete for highly qualified personnel from other companies and organizations;

· failure to achieve the strategic objectives with respect to Shire’s acquisition of NPS Pharmaceuticals, Inc., Dyax Corp. (“Dyax”) or Baxalta may adversely affect Shire’s financial condition and results of operations;

· Shire’s growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products;

· a slowdown of global economic growth, or economic instability of countries in which Shire does business, as well as changes in foreign currency exchange rates and interest rates, that adversely impact the availability and cost of credit and customer purchasing and payment patterns, including the collectability of customer accounts receivable;

· failure of a marketed product to work effectively or if such a product is the cause of adverse side effects could result in damage to the Shire’s reputation, the withdrawal of the product and legal action against Shire;

· investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire’s activities in the highly regulated markets in which it operates may result in significant legal costs and the payment of substantial compensation or fines;

· Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire’s revenues, financial condition or results of operations;

· Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which may decrease its business flexibility and increase borrowing costs;

· difficulties in integrating Dyax or Baxalta into Shire may lead to the combined company not being able to realize the expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all; and

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· other risks and uncertainties detailed from time to time in Shire’s filings with the SEC, including those risks outlined in “Risk Factors” and elsewhere in the prospectus supplement related to the offering, including the registration statement to which the offering relates and the prospectus contained therein and in “ITEM 1A: Risk Factors” in Shire’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2016.

All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.

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