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. 16)

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**
$4,241,680,815	$302,432

* 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 73,768,362 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 $57.50 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) 61,201,595 shares of common stock issued and outstanding as of April 30, 2010, as represented in the merger agreement dated May 16, 2010 between the Company and the filing persons (the “Merger Agreement”), 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 April 30, 2010 with respect to 5,681,575 shares of the Company’s common stock, as represented in the Merger Agreement, (iii) 3,920,201 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, as represented in the Merger Agreement, and (iv) 2,965,991 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, as represented in the Merger Agreement.

** 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
Amount Previously Paid: $32,221	Filing Party: Ruby Acquisition, Inc. Astellas US Holding, Inc. Astellas Pharma Inc.
Form or Registration No.: SC TO-T/A	Date Filed: May 17, 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. 16 to Schedule TO (this “Amendment No. 16”) 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 $57.50 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, including the Amendment and Supplement to the Offer to Purchase dated May 19, 2010, the “Offer to Purchase”) and in the related Letter of Transmittal, as amended or supplemented from time to time. This Amendment No. 16 is being filed on behalf of Astellas, Parent and Purchaser. You should read this Amendment No. 16 together with the Schedule TO. All capitalized terms used in this Amendment No. 16 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.

Items 1 through 9 and Item 11.

Items 1 through 9 and Item 11 are hereby amended and supplemented to include the following:

The initial offering period expired at 12:00 midnight, New York City time, on Wednesday, June 2, 2010. Upon expiration of the Offer, Purchaser accepted for payment in accordance with the terms of the Offer all Shares that were validly tendered and not withdrawn prior to the expiration of the Offer (excluding all shares delivered through notices of guaranteed delivery), and payment for such Shares will be made promptly in accordance with the terms of the Offer. The Depositary for the Offer has advised Astellas and Purchaser that as of the expiration of the Offer, a total of 53,430,205 Shares were validly tendered to Purchaser and not withdrawn (including 5,014,478 Shares delivered through notices of guaranteed delivery) representing approximately 87% of the Shares outstanding.

On June 3, 2010, Astellas issued a press release announcing that Purchaser had commenced a Subsequent Offering Period for all remaining untendered Shares. The Subsequent Offering Period will expire at 12:00 midnight, New York City time, on Monday, June 7, 2010, unless extended. Any such extension will be followed by a public announcement no later than 9:00 a.m., New York City time, on June 8, 2010.

The same $57.50 per Share price (net to the seller in cash, without interest and subject to any required withholding taxes) offered in the initial offering period will be paid during the Subsequent Offering Period. Purchaser will immediately accept for payment all Shares validly tendered during this Subsequent Offering Period, and payment will be made promptly after

2

acceptance, in accordance with the terms of the Offer. Procedures for tendering Shares during the Subsequent Offering Period are the same as during the initial offering period with two exceptions: (1) Shares cannot be delivered by the guaranteed delivery procedure, and (2) pursuant to Rule 14d-7(a)(2) promulgated under the Securities Exchange Act of 1934, as amended, Shares tendered during the Subsequent Offering Period may not be withdrawn.

Following the expiration of the Subsequent Offering Period, if Purchaser acquires at least 90% of the issued and outstanding Shares, Purchaser intends to complete the acquisition of the Company through the short-form merger procedure available under Delaware law. The short form merger procedure will permit the Purchaser to merge with and into the Company, with the Company surviving as an indirect wholly-owned subsidiary of Astellas, without a vote or meeting of the Company’s stockholders. In the merger, each outstanding Share not tendered and purchased in the Offer (other than Shares in respect of which appraisal rights are validly exercised under Delaware law and other than Shares held in the treasury of the Company and Shares owned by Purchaser, Parent or Astellas or any direct or indirect subsidiary of Purchaser or Astellas) will be converted into the right to receive the same $57.50 per Share net to the seller in cash, without interest and subject to any required withholding taxes, that was paid in the Offer. As a result of the merger, the Company’s common stock will cease to be traded on the Nasdaq Global Select Market. The full text of the press release issued by Astellas on June 3, 2010 announcing the commencement of a Subsequent Offering Period is filed as Exhibit (a)(5)(T) to the Schedule TO and is incorporated by reference into the Schedule TO.

Item 12. Exhibits

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

(a)(5)(T) Press Release issued by Astellas dated June 3, 2010 regarding Astellas’ announcement of the commencement of a Subsequent Offering Period.

3

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 June 3, 2010

ASTELLAS PHARMA INC.		ASTELLAS US HOLDING, INC.
By:	/S/    SEIGO KASHII	By:	/S/    SEIGO KASHII
Name:	Seigo Kashii as attorney-in-fact	Name:	Seigo Kashii
		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

4

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)(1)(H)	Amendment and Supplement to the Offer to Purchase dated May 19, 2010.*
(a)(1)(I)	Amended and Restated Form of Letter of Transmittal.*
(a)(1)(J)	Revised Form of Notice of Guaranteed Delivery.*
(a)(1)(K)	Revised Form of Letter to Brokers, Dealers, Commercial Banks, Trust Companies and Other Nominees.*
(a)(1)(L)	Revised Form of Letter to Clients for Use by Brokers, Dealers, Commercial Banks, Trust Companies and Other Nominees.*
(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.*
(a)(5)(J)	Press Release issued by Astellas dated March 31, 2010 regarding Astellas’ announcement of the extension of the Offer.*
(a)(5)(K)	Presentation regarding Astellas’ offer to acquire OSI Pharmaceuticals dated April 2010*.

5

(a)(5)(L)	Press Release issued by Astellas dated April 23, 2010 regarding Astellas’ announcement of the extension of the Offer.*
(a)(5)(M)	Press Release issued by Astellas and OSI Pharmaceuticals dated May 16, 2010 announcing the execution of a Merger Agreement.*
(a)(5)(N)	Press Release issued by Astellas dated May 17, 2010 announcing the extension of the Offer.*
(a)(5)(O)	Astellas Pharma Inc. Letter to OSI Pharmaceuticals, Inc. Employees dated May 16, 2010.*
(a)(5)(P)	Transcript of video presentation made by Masafumi Nogimori, Chief Executive Officer of Astellas Pharma Inc., to employees of OSI Pharmaceuticals on May 16, 2010.*
(a)(5)(Q)	Presentation regarding Astellas’ execution of a merger agreement with OSI Pharmaceuticals dated May 17 2010.*
(a)(5)(R)	Transcript of audio presentation made by representatives of Astellas Pharma Inc on May 17, 2010.*
(a)(5)(S)	Corrected transcript of audio presentation made by representatives of Astellas Pharma Inc on May 17, 2010.*
(a)(5)(T)	Press Release issued by Astellas dated June 3, 2010 regarding Astellas’ announcement of the commencement of a Subsequent Offering Period.
(b)	Not applicable.
(d)(1)	Agreement and Plan of Merger, by and among Astellas Pharma Inc., Astellas US Holding, Inc., Ruby Acquisition, Inc. and OSI Pharmaceuticals, Inc., dated May 17, 2010*
(g)	Not applicable.
(h)	Not applicable.

* Previously filed with Schedule TO.

6

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

Exhibit (a)(5)(T)

Astellas Announces Successful Completion of Initial Tender Offer for Shares of

OSI and Announces Subsequent Offer Period

Tokyo, Japan – June 3, 2010 – Astellas Pharma Inc. (TSE: 4503) announced today the completion of the initial tender offer for all outstanding shares of common stock in OSI Pharmaceuticals, Inc. (Nasdaq: OSIP).

The initial offer period expired at 12:00 midnight, New York City time, on June 2, 2010. Computershare Trust Company, N.A., the depositary for the tender offer, has advised that a total of 48,415,727 shares were validly tendered and not withdrawn prior to the expiration of the initial offer period, representing approximately 79% of OSI’s issued and outstanding shares. All shares validly tendered and not withdrawn have been accepted for payment. 5,014,478 additional shares were tendered subject to guaranteed delivery procedures prior to the expiration of the initial offer period. The total number of shares validly tendered, plus the shares tendered subject to guaranteed delivery procedures, represents approximately 87% of OSI’s issued and outstanding shares.

Astellas also announced today that it would make available a subsequent offer period commencing immediately and expiring at 12:00 midnight, New York City time on June 7, 2010, unless extended. During the subsequent offer period, any shares validly tendered will be immediately accepted for payment, and tendering stockholders will promptly thereafter be paid $57.50 per share in cash, less any withholding taxes and without interest, which is the same amount per share that was offered and paid to OSI stockholders who previously tendered into the initial offer.

The procedures for tendering shares during the subsequent offer period are the same as during the initial offer period, except that shares tendered during the subsequent offer period may not be tendered by the guaranteed delivery procedure and may not be withdrawn.

Following the expiration of the subsequent offer period, if Astellas owns at least 90% of the issued and outstanding shares of OSI common stock, Astellas intends to complete the acquisition of OSI through the short-form merger procedure under Delaware law, by which the companies can complete the merger without a meeting of OSI’s stockholders. In the merger, each outstanding share of OSI common stock not tendered and purchased in the initial offer period or the subsequent offer period will be converted into the right to receive the same consideration provided in the initial offer, except for such shares for which appraisal rights have been validly asserted. As a result of the merger, which Astellas expects to close as soon as practicable, OSI’s common stock will cease to be traded on the Nasdaq Global Select Market.

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

In the U.S.

Brunswick Group

+1 212 333 3810

Stan Neve / Sarah Lubman

In Japan

Ashton Consulting

Dan Underwood / John Sunley

+81 (03) 5425 7220

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 15,000 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 press release is for informational purposes only and does not constitute an offer to purchase or a solicitation of an offer to sell OSI’s common stock. The tender offer (“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) initially filed by Astellas Pharma Inc. (“Astellas”) with the Securities and Exchange Commission (the “SEC”) on March 2, 2010. These materials, as they may be amended from time to time, contain important information, including the terms and conditions of the offer, that should be read carefully before any decision is made with

respect to the Tender Offer. Investors and shareholders can 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 Tender Offer materials may also be obtained for free by contacting the information agent for the tender offer, Georgeson Inc. at (212) 440-9800.

OSI Pharmaceuticals’ (“OSI”) stockholders should read the company’s solicitation/recommendation statement on schedule 14D-9, which was initially filed with the SEC on March 15, 2010, and any amendments or supplements thereto. The company’s solicitation/recommendation statement will set forth the reasons for the recommendation of the OSI’s board and related information. The solicitation/recommendation statement and other public filings made from time to time by OSI with the SEC are available without charge from the SEC’s website at www.sec.gov, at OSI’s website at www.osip.com or from OSI’s information agent, by calling 800-322-2885 toll free or (212) 929-5500 or by emailing osipharma@mackenziepartners.com.

Statement of Cautionary Factors

This document contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this document, among others: (1) pricing and product initiatives of competitors; (2) legislative and regulatory developments and economic conditions; (3) delay or inability in obtaining regulatory approvals or bringing products to market; (4) fluctuations in currency exchange rates and general financial market conditions; (5) uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; (6) increased government pricing pressures; (7) interruptions in production; (8) loss of or inability to obtain adequate protection for intellectual property rights; (9) litigation; (10) loss of key executives or other employees; and (11) adverse publicity and news coverage. The statement regarding earnings growth is not a profit forecast and should not be interpreted to mean that Astellas’ earnings or earnings per share for any current or future period will necessarily match or exceed the historical published earnings or earnings per share of Astellas.