AMENDMENT NO. 13 TO THE SHAREHOLDERS' AGREEMENT

Exhibit 10.45

AMENDMENT NO. 13

TO THE SHAREHOLDERS’ AGREEMENT OF KIRIN-AMGEN, INC.

This AMENDMENT NO. 13 TO THE SHAREHOLDERS’ AGREEMENT OF KIRIN-AMGEN, INC., dated as of June 28, 2007 (this “ Amendment Agreement ”), which shall become effective at 12:01 A.M., Japan Standard Time, on July 1, 2007, is made and entered into by and among Kirin Brewery Company, Limited, a Japanese corporation to be renamed Kirin Holdings Company, Limited on July 1, 2007 (“ Kirin Holdings ”), Kirin Pharma Company, Limited, a Japanese corporation (including any successors by way of merger, consolidation, Share Exchange or similar transaction, “ Kirin Pharma ”), Amgen Inc., a Delaware corporation (“ Amgen ”), and Kirin-Amgen, Inc., a Delaware corporation (“ Kirin-Amgen ”). All capitalized terms used in this Amendment Agreement and not otherwise defined herein shall have the meanings assigned to such terms in the Shareholders’ Agreement (defined below), as amended hereby.

RECITALS

A. Kirin Holdings, Amgen and Kirin-Amgen are parties to that certain Shareholders’ Agreement of Kirin-Amgen, Inc., dated May 11, 1984 (as amended, the “ Shareholders’ Agreement ”), and Kirin Holdings and either or both of Amgen and Kirin-Amgen, as the case may be, are parties to certain other agreements listed in Appendix A to this Amendment Agreement (such other agreements collectively, the “ Kirin/Amgen Agreements ”);

B. Kirin Pharma is a direct, wholly owned subsidiary of Kirin Holdings;

C. The stockholders of Kirin Holdings have approved the effectuation by Kirin Holdings of a reorganization pursuant to which, among other things, it will assign, convey and transfer to Kirin Pharma all or substantially all of the assets and liabilities relating to Kirin Holdings’ pharmaceuticals business, including all of the shares of capital stock of Kirin-Amgen held by Kirin Holdings (the “ Shares ”) and the rights and obligations of Kirin Holdings under the Shareholders’ Agreement as amended hereby and each Kirin/Amgen Agreement, in each case by means of a “Kaisha-Bunkatsu” effected in accordance with the Corporate Split Agreement listed on Appendix D attached hereto and pursuant to Section 757 of the Japanese Corporation Code (the “ Reorganization ”);

D. Following the Reorganization, Kirin Pharma will continue to be a direct, wholly owned subsidiary of Kirin Holdings;

E. The Shareholders’ Agreement and the Kirin/Amgen Agreements contain certain restrictions on Kirin Holdings’ ability to assign to third parties its rights and obligations under the Kirin/Amgen Agreements;

F. Kirin Holdings has requested that Amgen consent to the assignment by Kirin Holdings to Kirin Pharma of all of the rights and obligations of Kirin Holdings under each Kirin/Amgen Agreement;

NOW, THEREFORE, in order to facilitate the Reorganization and at the same time protect their respective investments in Kirin-Amgen, the parties have agreed as follows:

1.01 Amgen Consent and Waiver

Subject to the terms and conditions of this Amendment Agreement, Amgen and Kirin-Amgen each hereby consent to the assignment by Kirin Holdings to Kirin Pharma, pursuant to the Reorganization and in the manner described in the Reorganization Package, of all of the rights and obligations of Kirin Holdings under each Kirin/Amgen Agreement.

1.02 Amendment of Certificate of Incorporation

The parties to this Amendment Agreement hereby agree that, in order to give full effect to Paragraph 17.03 of the Shareholders’ Agreement, as described in Section 2.09 below, the certificate of incorporation of Kirin-Amgen shall be amended and restated as of the date of this Amendment Agreement to conform to Appendix B attached to this Amendment Agreement. Each Party to this Amendment Agreement shall take all actions and execute and deliver all documents and instruments (including written consents of Kirin Holdings and Amgen in their respective capacities as stockholders of Kirin-Amgen), and shall cause the members of the board of directors of Kirin-Amgen to adopt all resolutions, take alnl actions and execute and deliver all documents and instruments, reasonably necessary to give full effect to the provisions of this Section 1.02.

1.03 Exclusion from the Scope of the Reorganization

In accordance with the last sentence of Article 4(2) of the Corporate Split Agreement listed on Appendix D attached hereto, Kirin Holdings and Kirin Pharma have discussed the exclusion of the Shares and the rights and obligations of Kirin Holdings under the Shareholders’ Agreement as amended hereby from the scope of the Reorganization and hereby agree that, notwithstanding anything to the contrary contained in the Corporate Split Agreement, the Shares and the rights and obligations of Kirin Holdings under the Shareholders’ Agreement as amended hereby shall be excluded from the scope of the rights and obligations being transferred from Kirin Holdings to Kirin Pharma as part of the corporate split contemplated in the Corporate Split Agreement. Notwithstanding anything to the contrary contained herein, the provision in this paragraph shall be governed by and construed in accordance with the internal laws, and not the law of conflicts, of Japan applicable to agreements made and to be performed in Japan.

Kirin Holdings and Kirin Pharma, jointly and severally, represent and warrant to Amgen as of the date hereof that (a) the agreement of Kirin Holdings and Kirin Pharma in the immediately preceding paragraph constitutes a valid and legally binding agreement of each of Kirin Holdings and Kirin Pharma enforceable against it in accordance with its terms, (b) the agreement of Kirin Holdings and Kirin Pharma in the immediately preceding paragraph overrides anything to the contrary contained herein or in the Reorganization Package (including

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the Corporate Split Agreement) and (c) by virtue of the agreement of Kirin Holdings and Kirin Pharma in the immediately preceding paragraph, the Shares and the rights and obligations of Kirin Holdings under the Shareholders’ Agreement as amended hereby will be retained by Kirin Holdings, and will not be transferred to Kirin Pharma, in the Reorganization, notwithstanding anything to the contrary contained herein or in the Reorganization Package (including the Corporate Split Agreement).

1.04 Certificates of Corporate Registries

Each of Kirin Holdings and Kirin Pharma shall deliver to counsel to Amgen at its office in Tokyo true and complete certificates of their respective corporate registries, issued by a competent registrar office of the Ministry of Justice in Japan and describing the effectuation of the “Kaisha Bunkatsu” in accordance with the Corporate Split Agreement listed on Appendix D hereto and pursuant to Section 757 of the Japanese Corporation Code, in each case promptly after the same becomes available (and, in any event, within two business days thereof).

Effective as of the date of this Amendment Agreement, the Shareholders’ Agreement is hereby amended as follows:

2.01 Preamble

The Preamble of the Shareholders’ Agreement is amended by (i) replacing the comma after the word “corporation” in the sixth line with the phrase “to be renamed Kirin Holdings Company and”, (ii) replacing the phrase “1900 Oak Terrace Lane” with the phrase “One Amgen Center Drive”, and (iii) replacing the phrase “(“ Kirin ”),” with the phrase “(“Kirin” or “Kirin Holdings”), Kirin Pharma Company, Limited, a Japanese corporation having its principal office at 26-1, Jingumae 6-chome, Shibuya-ku, Tokyo, Japan 150-8011 (including any successors by way of merger, consolidation, Share Exchange or similar transaction, “ Kirin Pharma ”),”.

2.02 Certain Definitions

Paragraph 1 of the Shareholders’ Agreement is amended by inserting (i) in Paragraph 1.10, after the word “Kirin,” in the first and third lines, the phrase “Kirin Pharma,”, (ii) in Paragraph 1.09, in the place of the word “Kirin”, the phrase “Kirin Pharma” and (iii) after Paragraph 1.10, new Paragraphs 1.11 through 1.33 as follows:

1.11 Administrative Matters

The term Administrative Matters shall mean any matter relating to the handling and resolution of intellectual property matters, legal matters and payment of expenses.

1.12 Affiliate

The term Affiliate shall mean, with respect to any Person, any Person directly or indirectly Controlling, Controlled by, or under common Control with, such other Person as of the

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date on which, or at any time during the period for which, the determination of affiliation is being made.

1.13 Asian Country

The term Asian Country shall mean any of the jurisdictions specified in Appendix C attached to this Amendment Agreement, and the term Asian Countries shall mean all such jurisdictions collectively.

1.14 Asian Pharma Entity

The term Asian Pharma Entity shall mean any corporation that (i) is incorporated or otherwise organized under the laws of, and has its principal executive offices in, any Asian Country; (ii) derives at least 80% of its consolidated revenues from the development, manufacture, processing, distribution or sale of pharmaceutical or biotechnology products in Asian Countries; and (iii) is not Controlled, directly or indirectly, by a Non-Asian Pharma Entity.

1.15 Average Two-Year Trailing Revenues

The term Average Two-Year Trailing Revenues with respect to any particular fiscal year shall mean the average of the total revenues and other income of Corporation, as set forth in the audited annual financial statements of Corporation, for the two immediately preceding fiscal years.

1.16 Beneficial Owner

The term Beneficial Owner shall mean, with respect to any Equity Securities, any Person who, directly or indirectly, through any contract, arrangement, understanding, relationship, or otherwise has or shares (i) voting power, which includes the power to vote, or to direct the voting of, such Equity Security; and/or (ii) investment power, which includes the power to dispose, or to direct the disposition of, such Equity Securities. The terms Beneficially Owned and Beneficial Ownership shall have corresponding meanings. In any dispute between Amgen and Kirin concerning whether or not a Person who is not a record holder of Equity Securities is nonetheless a Beneficial Owner of such Equity Securities, Amgen shall have the burden of proving that such Person is a Beneficial Owner.

1.17 Consumer Price Index

The term Consumer Price Index shall mean the Consumer Price Index for All Urban Consumers published by the Bureau of Labor Statistics of the U.S. Department of Commerce, Los Angeles All Items (1982-1984=100), or any successor index thereto, appropriately adjusted. If the Consumer Price Index is converted to a different standard reference base or otherwise revised, then, whenever the determination of a Consumer Price Index figure is called for herein, the Consumer Price Index shall be converted in accordance with the conversion factors published by the U.S. Department of Commerce, Bureau of Labor Statistics, or, if such Bureau does not publish such conversion factors, the conversion factors published by any other nationally recognized publisher of similar statistical information determined by Amgen.

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1.18 Control

The term Control, as used with respect to any Person, shall mean the possession, directly or indirectly, of the power to direct or cause the direction of the management policies of such Person, whether through the ownership of voting securities or by contract or otherwise. The phrases Controlled by and under common Control with shall have corresponding meanings.

1.19 Control Event

The term Control Event shall mean any of the following: (i) the first date on which the shares of common stock of Kirin Pharma held of record by Kirin Holdings of which Kirin Holdings is a Beneficial Owner cease to constitute at least 2/3 (two thirds) of the total number of shares of common stock of Kirin Pharma on a fully diluted basis or cease to represent at least 2/3 (two thirds) of the votes entitled to be cast on any matter by holders of Equity Securities of Kirin Pharma; provided that, in the event but only in the event that Kirin Pharma consummates a Qualified Public Merger or Qualified Public Offering, as of and from the time of such consummation this clause (i) shall automatically be amended to replace each of the two instances of the phrase “2/3 (two thirds)” above (but not the instance of that phrase below) with the phrase “a majority”; provided, further, that, if Kirin Holdings acquires a majority of the outstanding Equity Securities of a corporation (a majority of the Equity Securities of which corporation are listed for trading on a recognized national or international securities exchange) (“ Target ”) and concurrently therewith or thereafter contributes all of the outstanding common stock of Kirin Pharma to the Target with the result that all of the outstanding common stock of Kirin Pharma is owned by Target (such a transaction, a “ Transitional Transaction ”), then the fact that Kirin Holdings owns of record less than 2/3 of the outstanding common stock of Kirin Pharma shall not constitute a Control Event if (x) the Target holds of record all of the outstanding shares of common stock of Kirin Pharma, (y) Kirin Holdings holds of record a majority of the outstanding Equity Securities of Target, and (z) within 365 days following Kirin Holdings’ contribution to Target of shares of common stock of Kirin Pharma, Kirin Pharma is merged into Target in a transaction constituting a Qualified Public Merger, (ii) the first date on which Kirin Holdings ceases to have the ability to elect at least a majority of the members of the board of directors of Kirin Pharma; provided that, in the event that Kirin Holdings, Kirin Pharma and a Target enter into a Transitional Transaction, the fact that Kirin Holdings ceases to have the direct ability to elect at least a majority of the members of the board of directors of Kirin Pharma shall not constitute a Control Event if (x) the Target has the ability to elect all of the directors of Kirin Pharma, (y) Kirin Holdings has the ability to elect a majority of the directors of Target, and (z) within 365 days following Kirin Holdings’ contribution to Target of shares of common stock of Kirin Pharma, Kirin Pharma is merged into Target in a transaction constituting a Qualified Public Merger, (iii) the consummation of any Restricted Transaction or, if earlier, the public announcement, execution or delivery of any agreement, plan or proposal contemplating any Restricted Transaction, in any such case without the prior written consent of Amgen, or (iv) to the extent that Kirin Holdings or Kirin Pharma consummates a transaction or series of transactions that, but for the fact that it was entered into with a Qualified Third Party or Non-Pharma Entity, would have constituted a Restricted Transaction, the first date on which such Qualified Third Party ceases to be an Asian Pharma Entity or such Non-Pharma Entity ceases to be a Non-Pharma Entity.

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1.20 CPI Adjustment

The term CPI Adjustment shall mean an adjustment of the FTE Rate, which shall be made by first multiplying such FTE Rate by the Consumer Price Index in effect as of the effective date of such adjustment and then dividing the resulting product by the Consumer Price Index in effect as of the later of the date of this Amendment Agreement and the date as of which the FTE Rate was last adjusted.

1.21 Equity Securities

The term Equity Securities shall mean, with respect to any Person other than a natural person, any shares of capital stock or other ownership interests of such Person and the securities convertible into or exchangeable or exercisable for or into any such shares or ownership interests.

1.22 FTE Rate

The term FTE Rate shall mean the rate used by the Parties to reimburse Kirin Pharma and Amgen for personnel-related expenses incurred by them in connection with their respective research and development activities.

1.23 Group

The term Group means any group of Persons acting in concert with respect to the acquisition, ownership or disposition of Equity Securities.

1.24 Kirin-Amgen Matter

The term Kirin-Amgen Matter shall mean, collectively, any Administrative Matter, any matter relating to Corporation under consideration by the primary business representatives of Amgen, on the one hand, and Kirin Holdings or Kirin Pharma, on the other hand, any matter or question required to be decided or acted upon by the Board of Directors or stockholders of Corporation and any matter requiring the consent of any of the Parties pursuant to this Agreement or any other agreement between or among Amgen, on the one hand, and Kirin Holdings or Kirin Pharma, on the other hand, related to Corporation or to the Products (as defined in Section 17.04.1).

1.25 Non-Asian Pharma Entity

The term Non-Asian Pharma Entity shall mean (i) any Person that derives 50% or more of its consolidated revenues from the development, manufacture, processing, distribution or sale of pharmaceutical or biotechnology products outside of Asian Countries, and (ii) any Person Controlled, directly or indirectly, by any Person described by clause (i) of this sentence.

1.26 Non-Pharma Entity

The term Non-Pharma Entity shall mean any Person that (i) derives less than 10% of its consolidated revenues from the development, manufacture, processing, distribution or sale

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of pharmaceutical or biotechnology products, and (ii) if Controlled, is not Controlled, directly or indirectly, by any Person other than a Person described by clause (i) of this sentence.

1.27 Person

The term Person shall mean an individual, a corporation, a partnership, an association, a limited liability company, joint venture, estate, trust or other entity of any kind or nature.

1.28 Purchase Event

The term Purchase Event shall mean the first date on which shares of common stock of Kirin Pharma held of record by Kirin Holdings of which Kirin Holdings is a Beneficial Owner cease to constitute at least [*] of the total number of shares of common stock of Kirin Pharma on a fully diluted basis or cease to represent at least [*] of the votes entitled to be cast on any matter by holders of Equity Securities of Kirin Pharma; provided that, if Kirin Holdings acquires [*] of the outstanding Equity Securities of Target and concurrently therewith or thereafter consummates a Transitional Transaction, then the fact that Kirin Holdings owns of record less than [*] of the outstanding common stock of Kirin Pharma shall not constitute a Control Event if (i) Target holds of record [*] of the outstanding shares of common stock of Kirin Pharma, (ii) Kirin Holdings holds of record [*] of the outstanding Equity Securities of Target, and (iii) within [*] days following Kirin Holdings’ contribution to Target of shares of common stock of Kirin Pharma, Kirin Pharma is merged into Target in a transaction constituting a Qualified Public Merger.

1.29 Qualified Public Merger

The term Qualified Public Merger shall mean any merger, consolidation or Share Exchange of Kirin Pharma with or into any other corporation (a majority of the Equity Securities of which corporation are listed for trading on a recognized national or international securities exchange) after the consummation of which merger, consolidation or Share Exchange at least 30% but less than 50% of the total number of shares of common stock of Kirin Pharma, calculated on a fully diluted basis, are listed for trading on a recognized national or international securities exchange; provided, however that after the consummation of a Qualified Public Merger (other than Share Exchange) in which Kirin Pharma is not the surviving corporation, all references to shares of common stock of Kirin Pharma herein shall be deemed to be references to shares of common stock of such surviving corporation.

1.30 Qualified Public Offering

The term Qualified Public Offering shall mean a public offering, registered under the Securities and Exchange Law of Japan and conducted on a “firm commitment” basis for an aggregate offering price of not less than ¥5 billion, of shares of common stock of Kirin Pharma that upon completion of such offering will be listed on the Tokyo Stock Exchange and will represent at least 30% but less than 50% of the total number of shares of common stock of Kirin Pharma on a fully diluted basis.

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1.31 Qualified Third Party

The term Qualified Third Party shall mean any Asian Pharma Entity that is not making or asserting and, within the past five years, has not made or asserted, against Amgen or any of its Affiliates or any of their significant subsidiaries, in any written communication, action, suit, proceeding or arbitration, any claim which, if resolved other than in Amgen’s favor, could materially and adversely affect the business, assets, business relationships, prospects, financial condition or results of operations of Amgen or any such Affiliate or significant subsidiary.

1.32 Restricted Transaction

The term Restricted Transaction shall mean any transaction or series of transactions (including but not limited to any issuance, sale, transfer, assignment, pledge, hypothecation or other disposition or encumbrance of securities or other assets or property, and any merger, consolidation, Share Exchange, reorganization, recapitalization or reverse stock split) as a result of which any Person or Group (other than Kirin Holdings or an employee of Kirin Pharma) (i) is or will become the Beneficial Owner of (A) any Equity Securities of Kirin Pharma and such Beneficial Ownership could affect the management or business of Corporation, or (B) any Equity Securities of Corporation, or (ii) possesses or will possess the right to appoint one or more members of the board of directors of (A) Kirin Pharma, where the existence or exercise of such rights could affect the management or business of Corporation, or (B) Corporation, other than any (v) issuance, sale or transfer of Equity Securities of Kirin Holdings to any Qualified Third Party or Non-Pharma Entity, (w) merger, consolidation, Share Exchange or similar business combination transaction between Kirin Holdings, on the one hand, and any Qualified Third Party or Non-Pharma Entity, on the other, (x) Qualified Public Merger, or (y) Qualified Public Offering, or (z) Transitional Transaction in which (I) the Target holds of record all of the outstanding shares of common stock of Kirin Pharma, (II) Kirin Holdings holds of record a majority of the outstanding Equity Securities of Target, (III) the Target has the ability to elect all of the directors of Kirin Pharma, (IV) Kirin Holdings has the ability to elect a majority of the directors of Target, and (V) within 365 days following Kirin Holdings’ contribution to Target of shares of common stock of Kirin Pharma, Kirin Pharma is merged into Target in a transaction constituting a Qualified Public Merger.

1.33 Share Exchange

The term Share Exchange shall mean a kabushiki-kokan or kabushiki-iten , as those terms are currently construed under the Japanese Corporation Code.

2.03 Qualification of Board Members

Paragraph 12.01 of the Shareholders’ Agreement is amended by inserting after the second sentence thereof, the following sentence: “Each member of the Board of Directors of Corporation (and each candidate therefor nominated by Kirin or Amgen) shall be an employee of Kirin or one of its subsidiaries or Amgen or one of its subsidiaries, as the case may be.”

2.04 Shareholder Consultation

Paragraph 12 of the Shareholders’ Agreement is amended by inserting, after Paragraph 12.03, Paragraphs 12.03A and 12.03B as follows:

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“12.03A Administrative Decision-Making

The Parties shall cause all Administrative Matters to be handled in a manner consistent with their respective past practices.

12.03B Decision Deadlocks

12.03B.1 If, with respect to any Kirin-Amgen Matter, the representatives of the applicable Parties are unable to reach agreement within [*] calendar days following the date on which such Kirin-Amgen Matter is first notified by one Party to the other Party, then either such Party shall be entitled to implement the consultation process contemplated by this Paragraph by giving written notice to the other Party (each, an “ Escalation Notice ”).

12.03B.2 Within [*] calendar days following receipt of an Escalation Notice, the applicable Parties shall cause such Kirin-Amgen Matter to be referred to the President and the Chairman of Corporation (or such designees who have decision-making authority with respect to such Kirin-Amgen Matter), and the applicable Parties shall cooperate to cause such President and Chairman (or their designees) to resolve such disagreement in good faith within [*] calendar days following the date of the related Escalation Notice.

12.03B.3 If the President and the Chairman of Corporation are unable to reach agreement on such Kirin-Amgen Matter during such period, the applicable Parties shall cause such Kirin-Amgen Matter to be referred to the attendees of Kirin and Amgen at the first succeeding executive business meeting of Corporation and the applicable Parties shall cooperate to cause such attendees to resolve such disagreement in good faith at such executive business meeting.

12.03B.4 If such attendees are unable to resolve such disagreement at such meeting, within [*] calendar days following such meeting, the applicable Parties shall cause such Kirin-Amgen Matter to be referred to the respective Chief Executive Officers of Kirin and Amgen, and the applicable Parties shall cooperate to cause such Chief Executive Officers to resolve such disagreement in good faith within [*] calendar days following the date of the preceding executive business meeting.

12.03B.5 If the authorized representatives of the applicable Parties reach agreement with respect