SC TO-T/A

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE TO

(Rule 14d-100)

TENDER OFFER STATEMENT UNDER SECTION 14(d)(1)

OR 13(e)(1) OF THE SECURITIES EXCHANGE ACT OF 1934

(Amendment No. 5)

OSI Pharmaceuticals, Inc.

(Name of Subject Company (Issuer))

Ruby Acquisition, Inc.

Astellas US Holding, Inc.

Astellas Pharma Inc.

(Name of Filing Persons (Offerors))

Common Stock, Par Value $.01 Per Share

(Including the Associated Stock Purchase Rights)

(Title of Class of Securities)

671040103

(CUSIP Number of Class of Securities)

Masafumi Nogimori

President and Chief Executive Officer

Astellas Pharma Inc.

3-11, Nihonbashi-Honcho

2-chome, Chuo-ku

Tokyo 103-8411, Japan

(81) 3-3244-3000

(Name, Address and Telephone Number of Person Authorized

to Receive Notices and Communications on Behalf of Filing Persons)

Copies to:

Michael O. Braun, Esq.

Craigh Leonard, Esq.

Morrison & Foerster LLP

1290 Avenue of the Americas

New York, New York 10104

(212) 468-8000

CALCULATION OF FILING FEE

Transaction Valuation*	Amount of Filing Fee**
$3,789,611,228	$270,211

* For purposes of calculating the amount of filing fee only in accordance with Rules 0-11(d) and 0-11(a)(4) under the Securities Exchange Act of 1934 (the “Exchange Act”). Based on the offer to purchase up to 72,877,139 shares of common stock, par value $0.01 per share of OSI Pharmaceuticals, Inc. (the “Company”), including the associated stock purchase rights, at a purchase price of $52.00 per share net to the seller in cash, without interest and subject to any required withholding of taxes. Such number of shares consists of (i) 58,309,364 shares of common stock issued and outstanding as of February 15, 2010, as reported in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2009 (the “Company Form 10-K”), minus the 1,000 shares of common stock beneficially owned by the filing persons as of the date hereof, (ii) all options outstanding as of December 31, 2009 with respect to 6,239,000 shares of the Company’s common stock, as reported in the Company Form 10-K, (iii) 1,208,887 shares of common stock issuable on the conversion of the $60,467,000 outstanding face amount of the Company’s 3 ¹/4% Convertible Senior Subordinated Notes due 2023, (iv) 3,908,241 shares of common stock issuable on the conversion of the $115,000,000 outstanding face amount of the Company’s 2% Convertible Senior Subordinated Notes due 2025, and (v) 3,212,648 shares of common stock issuable on the conversion of the $160,000,000 outstanding face amount of the Company’s 3% Convertible Senior Subordinated Notes due 2038.

** The filing fee was calculated in accordance with Rule 0-11 under the Exchange Act, as amended, by multiplying the transaction value by .00007130.

x Check the box if any part of the fee is offset as provided by Rule 0-11(a)(2) and identify the filing with which the offsetting fee was previously paid. Identify the previous filing by registration statement number, or the Form or Schedule and the date of its filing.

Amount Previously Paid:	$270,211	Filing Party:	Ruby Acquisition, Inc. Astellas US Holding, Inc. Astellas Pharma Inc.
Form or Registration No.:	SC TO	Date Filed:	March 2, 2010

¨ Check the box if the filing relates solely to preliminary communications made before the commencement of a tender offer.

Check the appropriate boxes below to designate any transactions to which the statement relates:

x third-party tender offer subject to Rule 14d-1.

¨ issuer tender offer subject to Rule 13e-4.

¨ going-private transaction subject to Rule 13e-3.

¨ amendment to Schedule 13D under Rule 13d-2.

Check the following box if the filing is a final amendment reporting the results of the tender offer:  ¨

This Amendment No. 5 to Schedule TO (this “Amendment No. 5”) amends and supplements the Tender Offer Statement on Schedule TO as originally filed with the Securities and Exchange Commission on March, 2, 2010 (together with any amendments and supplements thereto the “Schedule TO”) relating to the offer by Ruby Acquisition, Inc. (“Purchaser”), a wholly-owned subsidiary of Astellas US Holding, Inc. (“Parent”), a wholly-owned subsidiary of Astellas Pharma Inc. (“Astellas”), to purchase all issued and outstanding shares of the common stock, par value $0.01 per share (the “Common Stock”, and together with the associated stock purchase rights, the “Shares”), of OSI Pharmaceuticals, Inc., a Delaware corporation (the “Company”), at a price of $52.00 per Share, net to the seller in cash, without interest and subject to any required withholding of taxes, upon the terms and subject to the conditions set forth in the Offer to Purchase dated March 2, 2010 (together with any amendments and supplements thereto the “Offer to Purchase”) and in the related Letter of Transmittal, as amended or supplemented from time to time. This Amendment No. 5 is being filed on behalf of Astellas, Parent and Purchaser. You should read this Amendment No. 5 together with the Schedule TO. All capitalized terms used in this Amendment No. 5 and not otherwise defined have the respective meanings ascribed to them in the Offer to Purchase.

The information set forth in the Offer to Purchase, including Schedule I thereto, is hereby incorporated by reference in answer to Items 1 through 13 of this Schedule TO, and is supplemented by the information specifically provided herein.

The items of Schedule TO set forth below are hereby amended and supplemented as follows:

Item 12. Exhibits

Item 12 of the Schedule TO is hereby amended and supplemented to add the following exhibit:

(a)(5)(I) Press Release issued by Astellas dated March 29, 2010 regarding Astellas’ announcement of the execution of a confidentiality agreement with OSI Pharmaceuticals, Inc.

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SIGNATURES

After due inquiry and to the best of their knowledge and belief, each of the undersigned certifies that the information set forth in this statement is true, complete and correct.

Dated March 29, 2010

ASTELLAS PHARMA INC.		ASTELLAS US HOLDING, INC.
By:	/s/ Seigo Kashii	By:	/s/ Seigo Kashii
Name:	Seigo Kashii as attorney-in-fact for	Name:	Seigo Kashii
	Masafumi Nogimori	Title:	Director, President & CEO
		RUBY ACQUISITION, INC.
		By:	/s/ Seigo Kashii
		Name:	Seigo Kashii
		Title:	Director, President & CEO

POWER OF ATTORNEY

KNOW ALL MEN BY THESE PRESENTS, that the undersigned hereby constitutes and appoints each of Seigo Kashii, Linda F. Friedman and Stephen Knowles, individually and severally, and with full power of substitution, the undersigned’s true and lawful attorney-in-fact with full power to execute and file with the Securities and Exchange Commission and any stock exchange or similar authority, any report required to be filed pursuant to Section 14 of the Securities Exchange Act of 1934, (as amended, the “Act”), with respect to a third-party tender offer subject to Rule 14d-1, giving and granting unto said attorney-in-fact the power and authority to act in the premises as fully and to all intents and purposes as the Company might or could do if personally present by one of its authorized signatories, hereby ratifying and confirming all that said attorney-in-fact shall lawfully do or cause to be done by virtue hereof.

This Power of Attorney shall remain in full force and effect until the earliest of: (i) a revocation in writing by the undersigned; (ii) such time as the person to whom power of attorney has been hereby granted ceases to be an employee of the undersigned or any subsidiary company thereof; or (iii) March 2, 2011.

IN WITNESS WHEREOF, the undersigned has caused this Power of Attorney to be executed as of this 2nd day of March, 2010.

ASTELLAS PHARMA INC.
By:	/s/ Masafumi Nogimori
Name:	Masafumi Nogimori
Title:	Director, President & CEO

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EXHIBIT INDEX

Exhibit No.	Description
(a)(1)(A)	Offer to Purchase dated March 2, 2010.*
(a)(1)(B)	Form of Letter of Transmittal.*
(a)(1)(C)	Form of Notice of Guaranteed Delivery.*
(a)(1)(D)	Form of Letter to Brokers, Dealers, Commercial Banks, Trust Companies and Other Nominees.*
(a)(1)(E)	Form of Letter to Clients for Use by Brokers, Dealers, Commercial Banks, Trust Companies and Other Nominees.*
(a)(1)(F)	Guidelines for Certification of Taxpayer Identification Number on Substitute W-9.*
(a)(1)(G)	Summary Advertisement as published on March 2, 2010.*
(a)(5)(A)	Press Release issued by Astellas on March 1, 2010 incorporated herein by reference to the Schedule TO filed by Astellas on March 1, 2010.*
(a)(5)(B)	Press Release issued by Astellas dated March 2, 2010 regarding the commencement of the Offer and the lawsuit filed by Astellas US Holding, Inc. against OSI Pharmaceuticals, Inc.*
(a)(5)(C)	Complaint filed in Delaware Chancery Court against OSI Pharmaceuticals, Inc. and its directors.*
(a)(5)(D)	Letter regarding the Tender offer was distributed to certain public officials by Astellas.*
(a)(5)(E)	Press Release issued by Astellas dated March 15, 2010 regarding Astellas’ response to OSI Pharmaceuticals’ Rejection of its Offer.*
(a)(5)(F)	Press Release issued by Astellas dated March 16, 2010 regarding Astellas’ announcement of a full slate of independent director nominees for election at OSI Pharmaceuticals, Inc.’s 2010 Annual Stockholders Meeting.*
(a)(5)(G)	Press Release issued by Astellas dated March 19, 2010 regarding Astellas’ announcement of the expiration of the HSR waiting period for the Offer.*
(a)(5)(H)	Press Release issued by Astellas dated March 19, 2010 regarding Astellas’ announcement of changes to its director nominees for election to OSI Pharmaceuticals, Inc.’s Board of Directors.*
(a)(5)(I)	Press Release issued by Astellas dated March 29, 2010 regarding Astellas’ announcement of the execution of a confidentiality agreement with OSI Pharmaceuticals, Inc.
(b)	Not applicable.
(d)	Not applicable.
(g)	Not applicable.
(h)	Not applicable.

* Previously filed with Schedule TO.

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EX-99.(A)(5)(I)

Exhibit (a)(5)(I)

Astellas Signs Confidentiality Agreement with OSI

Tokyo, Japan – March 29, 2010 – Astellas Pharma Inc. (TSE: 4503) confirmed today that it has entered into a confidentiality agreement with OSI Pharmaceuticals, Inc. (Nasdaq: OSIP). Under the agreement, OSI will provide Astellas with access to certain non-public information. This follows Astellas’ approach to OSI after OSI’s announcement that its board of directors had instructed its management and financial advisors to contact interested third parties regarding a potential transaction.

Also, under the confidentiality agreement, until 11.59 p.m. EDT on May 15, 2010, Astellas will not acquire any shares pursuant to its outstanding tender offer, take any further action on the pending litigation initiated by it or file a preliminary or definitive proxy statement in connection with OSI’s annual meeting. This agreement will terminate, among other things if OSI enters into or announces its intent to enter into an agreement with respect to an acquisition of OSI.

There can be no assurance that an agreement with respect to an acquisition by Astellas for OSI will be reached.

Citigroup is acting as exclusive financial advisor to Astellas and Morrison & Foerster LLP is acting as legal counsel.

Additional Information

Further details related to this proposal can be found on www.oncologyleader.com

Media Contacts

Brunswick New York

+1 212 333 3810

Stan Neve

Sarah Lubman

Brunswick Hong Kong

+852 9850 5033

Joseph Lo

Information Agent

Georgeson Inc.

+ 1 212 440 9872

Thomas Gardiner

About Astellas

Astellas Pharma Inc., located in Tokyo, Japan, is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. Astellas has approximately 14,200 employees worldwide. The organization is committed to becoming a global category leader in urology, immunology & infectious diseases, neuroscience, DM complications & metabolic diseases and oncology. For more information on Astellas Pharma Inc., please visit our website at http://www.astellas.com/en.

Important Additional Information

This communication is for informational purposes only and does not constitute an offer to purchase or a solicitation of an offer to sell OSI Pharmaceuticals (“OSI”) common stock. The tender offer (the “Tender Offer”) is being made pursuant to a tender offer statement on Schedule TO (including the Offer to Purchase, Letter of Transmittal and other related tender offer materials) filed by Astellas Pharma Inc., Astellas US Holding, Inc. and Ruby Acquisition, Inc. (collectively, “Astellas”) with the Securities and Exchange Commission (“SEC”). These materials, as they may be amended from time to time, contain important information, including the terms and conditions of the Tender Offer, that should be read carefully before any decision is made with respect to the Tender Offer. Investors and security holders may obtain a free copy of these materials and other documents filed by Astellas with the SEC at the website maintained by the SEC at www.sec.gov. The Offer to Purchase, Letter of Transmittal and other related Tender Offer materials may also be obtained for free by contacting the information agent for the Tender Offer, Georgeson Inc., at (212) 440-9800 for banks and brokers and at (800) 213-0473 for persons other than banks and brokers.

In connection with Astellas’ proposal to nominate directors at OSI’s annual meeting of stockholders, Astellas expects to file a proxy statement with the SEC. Investors and security holders of OSI are urged to read the proxy statement and other documents related to the solicitation of proxies filed with the SEC carefully in their entirety when they become available because they will contain important information. Stockholders of OSI and other interested parties may obtain, free of charge, copies of the proxy statement (when available), and any other documents filed by Astellas with the SEC in connection with the proxy solicitation, at the SEC’s website as described above. The proxy statement (when available) and these other documents may also be obtained free of charge by contacting Georgeson Inc. at the numbers listed above.

Astellas and certain of their directors and executive officers and the individuals to be nominated by Astellas for election to OSI’s board of directors may be deemed to be participants in the solicitation of proxies in connection with the proposed transaction. Information regarding these directors and executive officers and other individuals is available in the Schedule TO that was filed March 2, 2010, and other documents filed by

Astellas with the SEC as described above. Further information will be available in any proxy statement or other relevant materials filed with the SEC in connection with the solicitation of proxies when they become available.

No assurance can be given that the proposed transaction described herein will be consummated by Astellas, or completed on the terms proposed or any particular schedule, that the proposed transaction will not incur delays in obtaining the regulatory, board or stockholder approvals required for such transaction, or that Astellas will realize the anticipated benefits of the proposed transaction.

Statement on Cautionary Factors

Any statements made in this communication that are not statements of historical fact, including statements about Astellas’ beliefs and expectations and statements about Astellas’ proposed acquisition of OSI, are forward-looking statements and should be evaluated as such. Forward-looking statements include statements that may relate to Astellas’ plans, objectives, strategies, goals, future events, future revenues or performance, and other information that is not historical information. Factors that may materially affect such forward-looking statements include: Astellas’ ability to successfully complete the tender offer for OSI’s shares or realize the anticipated benefits of the transaction; delays in obtaining any approvals required for the transaction, or an inability to obtain them on the terms proposed or on the anticipated schedule; and the failure of any of the conditions to Astellas’ tender offer to be satisfied.

Any information regarding OSI contained herein has been taken from, or is based upon, publicly available information. Although Astellas does not have any information that would indicate that any information contained herein is inaccurate or incomplete, Astellas has not had the opportunity to verify any such information and does not undertake any responsibility for the accuracy or completeness of such information.

Astellas does not undertake, and specifically disclaims, any obligation or responsibility to update or amend any of the information above except as otherwise required by law.