Exhibit 10.4

THIS AMENDMENT NO. 1 TO THAT CERTAIN SHAREHOLDERS' AGREEMENT OF KIRIN- AMGEN, INC., DATED MAY 11, 1984 ("Amendment No. 1") is made and entered into this 19th day of March, 1985, by and among KIRIN BREWERY COMPANY, LTD., a Japanese corporation ("Kirin"), AMGEN, a California corporation ("Amgen"), and KIRIN-AMGEN, INC., a California corporation ("Corporation").

Pursuant to Paragraph 22.19 of the Shareholders' Agreement regarding expansion of the business of Corporation, the parties hereto desire Corporation to purchase from Amgen the worldwide rights to EPO Human Diagnostic and Reagent as an expansion of the Field of Activity as defined in the Shareholders' Agreement in accordance with the terms and conditions set forth below and to license the same to Kirin for the territory of Japan and to Amgen for the territory of the United States of America and its territories and possessions.

NOW, THEREFORE, it is agreed as follows:

Corporation hereby agrees to purchase the worldwide rights to EPO Human Diagnostic and Reagents ("Diagnostic Rights") from Amgen for a price of (U.S.) $1,000,000. This purchase shall constitute an expansion of the Field of Activity as defined in the Shareholder's Agreement, and in accordance with Paragraph 22.19 of the Shareholders' Agreement, shall also constitute the first additional opportunity for mutual development of other products and areas of interest by Kirin, Amgen and Corporation.

Corporation shall promptly pay Amgen (U.S.) $1,000,000 for the Diagnostic Rights concurrently with the delivery by Amgen to Corporation of the Assignment and License Agreement attached hereto as Exhibit "A" together with the physical transfer of assets comprising the Diagnostic Rights.

As of March 19, 1985, Amgen has valid legal title to and will vest in Corporation valid legal title to all Diagnostic Rights free and clear of any and all liens, claims, security interests, encumbrances and restrictions.

The rights and obligations of the parties in this Amendment No. 1 with respect to this expansion of business opportunity shall be consistent with the provisions of the Shareholders' Agreement.

Kirin shall pay Corporation (U.S.) $200,000, which payment shall entitle Kirin to a fully-paid exclusive license in Kirin's territory of Japan with respect to the Diagnostic Rights in accordance with the License Agreement attached hereto as Exhibit "B."

Amgen shall pay Corporation (U.S.) $200,000, which payment shall entitle Amgen to a fully-paid exclusive license in Amgen's territory of the United States and its territories and possessions with respect to the Diagnostic Rights in accordance with the License Agreement attached hereto as Exhibit "C."

Each party hereto agrees to perform any and all further acts and execute and deliver any and all further documents and/or instruments which may be reasonable or necessary to carry out the provisions of this Amendment No. 1 to the Shareholders' Agreement and to carry out this further business purpose of Corporation.

IN WITNESS WHEREOF, the undersigned have caused this Amendment to be executed on March 19, 1985 by their duly authorized representatives in the manner legally binding upon them

KIRIN BREWERY COMPANY, LTD.,
a Japanese corporation

By  /s/ Shinkichi Kubo
    ----------------------------------------------
    Shinkichi Kubo, Managing Director

"Kirin"

AMGEN, a California corporation

By  /s/ George B. Rathmann
    ----------------------------------------------
    George B. Rathmann, President

"Amgen"

KIRIN-AMGEN, INC., a California corporation

By  /s/ Tatsuhiko Kaneko
    ----------------------------------------------

      ____________ Its ______________

"Corporation"

Exhibit A

ASSIGNMENT AND LICENSE AGREEMENT

by and between

AMGEN,

a California corporation,

and

KIRIN-AMGEN, INC.,

a California corporation

                                                                                                Page
                                                                                                ----
RECITALS...................................................................................       1

I.       TRANSFER AND LICENSE OF TECHNOLOGY................................................       2

         1.01     Assignment of Diagnostic Rights Transferred Technology...................       2
         1.02     License of Diagnostic Rights Core Technology.............................       2
         1.03     Right to Sublicense the Diagnostic Rights Core Technology................       3
         1.04     Limitations..............................................................       4

II.      DEFINITIONS.......................................................................       4

         2.01     Incorporation by Reference...............................................       4
         2.02     Diagnostic Rights Field of Activity/Diagnostic Rights Technology.........       4

III.     DISCLOSURE OF DIAGNOSTIC RIGHTS CORE TECHNOLOGY...................................       5

         3.01     Limitation on Usage......................................................       5
         3.02     Survival.................................................................       5

IV.      PATENT, COPYRIGHT AND TRADE SECRET ENFORCEMENT....................................       5

         4.01     Enforcement..............................................................       5
         4.02     Notice of Infringements..................................................       6

V.       PATENT APPLICATIONS AND COPYRIGHT REGISTRATIONS...................................       7

         5.01     Applications.............................................................       7

VI.      DISCLAIMER OF INDEMNIFICATION.....................................................       7

         6.01     Disclaimer of Warranties.................................................       7

                                                                                         Page
                                                                                         ----
VII.     TERM AND TERMINATION........................................................      8

         7.01      Term..............................................................      8
         7.02      Default...........................................................      8
         7.03      Continuing Obligations............................................      9

VIII.    CONSISTENCY WITH SHAREHOLDERS' AGREEMENT....................................      9

         8.01      Shareholders' Agreement...........................................      9

IX.      CONSENTS AND APPROVALS......................................................     10

         9.01      Best Efforts......................................................     10

X.       NOTICE......................................................................     10

         10.01     Notices...........................................................     10

XI.      MISCELLANEOUS...............................................................     12

         11.01     Entire Agreement..................................................     12
         11.02     Headings..........................................................     12
         11.03     Execution in Counterparts.........................................     12
         11.04     Force Majeure.....................................................     12
         11.05     Applicable Law....................................................     13
         11.06     Assignment on Written Consent.....................................     13
         11.07     Severability......................................................     13
         11.08     No Waiver.........................................................     13
         11.09     Trademarks and Tradenames.........................................     13
         11.10     Indemnity.........................................................     14
         11.11     Other Agreements..................................................     14
         11.12     Attorneys' Fees and Costs.........................................     14
         11.13     Remedies..........................................................     15
         11.14     Binding Effect....................................................     15
         11.15     Exhibits..........................................................     15
         11.16     Number and Gender.................................................     16
         11.17     Representations...................................................     16
         11.18     Agreement to Perform Necessary Acts...............................     16

THIS ASSIGNMENT AND LICENSE AGREEMENT ("Agreement") is made this 4th day of December, 1985, and is made effective as of the 27th day of June, 1985, by and between AMGEN, a California corporation ("Amgen"), in favor and for the benefit of and with KIRIN-AMGEN, INC., a California corporation ("Company"), pursuant to terms and conditions of that certain Shareholders' Agreement, dated May ll, 1984, as amended by Amendment No. 1, dated March 19, 1985 ("Shareholders' Agreement"), by and among Amgen, Company and Kirin Brewery Company, Ltd., a Japanese corporation ("Kirin").

A. Pursuant to Paragraph 22.19 of the Shareholders' Agreement regarding expansion of the business of Corporation, the parties hereto desire Company to purchase from Amgen the worldwide rights to EPO Human Diagnostics and Reagents (not including non-human veterinary purposes) ("Diagnostic Rights Field of Activity and/or Diagnostic Rights) as an expansion of the Field of Activity as defined in the Shareholders' Agreement in accordance with the terms and conditions set forth below and to license the same to Kirin for the territory of Japan and to Amgen for the territory of the United States of America and its territories and possessions.

B. Company hereby agrees to purchase and license the worldwide Diagnostic Rights from Amgen for a price of One Million Dollars U.S. ($1,000,000). This purchase shall constitute an expansion of the Field of Activity as defined in the Shareholder's Agreement, and in accordance with Paragraph 22.19 of the Shareholders' Agreement.

NOW, THEREFORE, it is agreed as follows:

the Diagnostic Rights Core Technology solely with respect to its direct application to the Diagnostic Rights Field of Activity.

Company is terminated at any time in accordance with Article VII, and Amgen shall not be in default under Section 7.02 hereof, Amgen shall have the option to terminate or to have the Company assign to Amgen, retroactive to the date of termination, any sublicenses granted hereunder by the Company to any subsidiary of the Company. The Company shall include in all its sublicenses granted hereunder to any subsidiary of the Company provisions for such termination and assignment.

involving infringement of any patents or copyrights, misappropriation of any trade secrets or interference with any Diagnostic Rights Core Technology licensed to the Company in the Diagnostic Rights Field of Activity pursuant to this Agreement. If Amgen declines to enforce any patent, trade secret or other right, then in such event, the Company and/or Kirin shall each have the right, but not the obligation to bring any such action. If the Company or Kirin finds it necessary to join Amgen in such suit or action, Amgen shall execute all papers and perform such other acts as may be reasonably required and may, at its option, be represented by counsel of its choice. The Company or Kirin, whichever brings the action, shall pay to Amgen its reasonable expenses (excluding its attorney's fees) in connection with any such suit or action. Should the Company or Kirin, whichever brings the action, lack standing to bring any such action then the Company or Kirin may cause Amgen to do so upon first undertaking to indemnify and hold Amgen harmless (to the extent permissible by law) from all consequent liability and to promptly reimburse all reasonable expenses (including attorney fees) stemming therefrom. Any amount recovered in any such action or suit, whether by judgment or settlement, shall be paid to or retained entirely by the Company or Kirin, whichever brought the action.

existence of third parties, who come to the attention of such party, who may be involved in activities which infringe or potentially infringe, misappropriate or potentially misappropriate or interfere with patents, copyrights, trade secrets concerning the Diagnostic Rights Core Technology licensed to the Company pursuant to this Agreement.

obligations to and the rights of the Defaulting Party under the license to the Diagnostic Rights Core Technology granted under this Agreement upon ten (10) days' written notice to the Defaulting Party, which termination shall be effective as of the occurrence of the event giving rise to the option to terminate.

Diagnostic Rights Core Technology is granted pursuant to Amendment No. 1 of the Shareholders' Agreement and shall be governed by the provisions thereof to the extent applicable. To the extent that there may be conflicts or inconsistencies between the provisions of this Agreement and those contained in the Shareholders' Agreement and Amendment No. 1 thereto, the provisions of the Shareholders' Agreement and Amendment No. 1 thereto shall prevail and govern interpretation.

receipt requested, postage prepaid, and properly addressed as follows (in which case such notice shall be deemed to have been duly given on the third (3rd) day following the date of such sending):

"Amgen"             Amgen
                    1900 Oak Terrace Lane
                    Thousand Oaks, CA 91320
                    U.S.A.
                    Telex No. 4994440 (AMGEN)
                    Attn: Corporate Secretary

With a copy to:     Cooley, Godward, Castro,
                    Huddleson & Tatum
                    One Maritime Plaza, 20th Floor
                    San Francisco, CA 94111
                    U.S.A.
                    Telex No. 910-372-7370 Cooley SFO
                    Attn: Alan C. Mendelson, Esq.

"Company"           Kirin-Amgen, Inc.
                    1900 Oak Terrace Lane
                    Thousand Oaks, CA 91320
                    U.S.A.
                    Telex No. 4994440 (AMGEN)
                    Attn: Corporate Secretary

With a copy to:     Musick, Peeler & Garrett
                    One Wilshire Boulevard
                    Suite 2000
                    Los Angeles, CA 90017
                    U.S.A.
                    Telex No. 701357 (MPG LAW UD)
                    Attn: Joel S. Marcus, Esq.

Any Party by giving notice to the others in the manner provided above may change such Party's address for purposes of this Paragraph 10.01.

be excused from such of its obligations hereunder as it is unable to perform on account of the Force Majeure throughout the duration thereof plus a period of thirty (30) days.

all costs and expenses, including actual attorneys' fees, incurred therein by such successful party or parties; and if such successful party or parties shall recover judgment in any such action or proceeding, such costs, expenses and attorneys' fees may be included in and as part of such judgment. The successful party shall be the party who is entitled to recover its costs of suit, whether or not the suit proceeds to final judgment. A party not entitled to recover its costs shall not recover attorneys' fees.

reasonably necessary to carry out the provisions of this Agreement and to carry out the business purposes of Corporation.

IN WITNESS WHEREOF, Amgen and the Company have caused this Agreement to be executed by their duly authorized representatives in the manner legally binding on them as of the date first above written.

KIRIN-AMGEN, INC., a California corporation

By   /s/ Shinkichi Kubo
     ------------------------------
     Shinkichi Kubo, Chairman

"Company"

AMGEN, a California corporation

By   /s/ George B. Rathmann
     ------------------------------
     George B. Rathmann, President

"Amgen"

Exhibit B

LICENSE AGREEMENT

by and between

KIRIN-AMGEN, INC.,
a California corporation

and

KIRIN BREWERY CO., LTD.,
a Japanese corporation

                                                                                                       Page
                                                                                                       ----
RECITALS............................................................................................     1

I.       DEFINITIONS

         1.01  Incorporation by Reference...........................................................     2
         1.02  Diagnostic Rights Field of Activity/Diagnostic Rights Technology.....................     2
         1.03  Territory............................................................................     2
         1.04  Party................................................................................     2
         1.05  Subsidiary...........................................................................     2

II.      GRANT OF LICENSE...........................................................................     3

         2.01  Grant of License.....................................................................     3
         2.02  Rights to Sublicense.................................................................     3
         2.03  Amgen License........................................................................     4
         2.04  Other Licenses.......................................................................     4
         2.05  No License Fee.......................................................................     4

III.     DISCLOSURE.................................................................................     5

         3.01  Disclosure...........................................................................     5
         3.02  Confidentiality......................................................................     5

IV.      PATENT APPLICATIONS AND COPYRIGHT REGISTRATIONS............................................     7

         4.01  Patent Applications..................................................................     7

V.       PATENT, COPYRIGHT AND TRADE SECRET ENFORCEMENT.............................................     8

         5.01  Enforcement..........................................................................     8
         5.02  Infringements........................................................................     8
         5.03  Maintenance of Action................................................................     9

VI.      TERM AND TERMINATION.......................................................................    11

         6.01  Term.................................................................................    11
         6.02  Effective Date.......................................................................    11
         6.03  Default..............................................................................    11
         6.04  Survival.............................................................................    12

                                                                                                         Page
                                                                                                         ----
VII.     INFRINGEMENTS................................................................................    13

         7.01  Infringements..........................................................................    13

VIII.    CONSENTS AND APPROVALS.......................................................................    13

         8.01  Best Efforts...........................................................................    13

IX.      NOTICE.......................................................................................    13

         9.01  Notices................................................................................    13

X.       MISCELLANEOUS................................................................................    15

         10.01 Entire Agreement.......................................................................    15
         10.02 Readings...............................................................................    15
         10.03 Execution in Counterparts..............................................................    15
         10.04 Force Majeure..........................................................................    16
         10.05 Applicable Law.........................................................................    16
         10.06 Assignment on Written Consent..........................................................    16
         10.07 Severability...........................................................................    16
         10.08 No Waiver..............................................................................    17
         10.09 Trademarks and Tradenames..............................................................    17
         10.10 Indemnity..............................................................................    17
         10.11 Other Agreements.......................................................................    18
         10.12 Remedies...............................................................................    18
         10.13 Attorneys' Fees and Costs..............................................................    18
         10.14 Number and Gender......................................................................    19
         10.15 Agreement to Perform Necessary Acts....................................................    19
         10.16 Representations........................................................................    19

THIS KIRIN BREWERY CO., LTD./KIRIN-AMGEN, INC. LICENSE AGREEMENT ("Agreement") is made and entered into this 4th day of December, 1985, and is made effective as of the 27th day of June, 1985, by and between KIRIN-AMGEN, INC., a California corporation ("Company"), and KIRIN BREWERY CO., LTD., a Japanese corporation ("Kirin").

A. Kirin desires to obtain from the Company a license to the EPO human (and not nonhuman veterinary) diagnostic and reagent rights (collectively "Diagnostic Rights") in order to exploit the Diagnostic Rights Field of Activity in its Territory (as hereinafter defined) and the Company is willing to grant such a license to Kirin.

B. Company has granted a similar license to Amgen, of even date herewith ("Amgen License"), with respect to the exploitation of the Diagnostic Rights Field of Activity in the United States of America, its territories and possessions, on substantially the same terms and conditions contained herein and for the same purposes described herein.

NOW, THEREFORE, in consideration of the mutual covenants expressed herein and other good and valuable consideration, the parties hereby agree as follows:

ARTICLE I

ARTICLE II

license from Kirin; provided, however, that no sublicense shall be granted under clause (c) or (d) hereof without the prior written consent (which consent is not to be unreasonably withheld) of the Company. Any sublicensees of Kirin shall undertake in writing to be bound by the provisions of Section 3.02 hereof to the same extent Kirin is bound. Kirin shall notify the Company of the identity of each sublicensee to whom a sublicense is granted and provide the Company a true copy of such sublicense. In the event that the license granted to Kirin hereunder is terminated at any time in accordance with Article VI, and the Company shall not be in default under Section 6.02 hereof, the Company shall have the option to terminate or to have Kirin assign to the Company, retroactive to the date of such termination, any sublicenses granted hereunder by Kirin to any Subsidiary of Kirin. Kirin shall include, in all its sublicenses granted hereunder to any Subsidiary of Kirin, provisions for such termination and assignment.

ARTICLE III

(a) The Company shall reasonably disclose and deliver to Kirin all Diagnostic Rights Technology in sufficient detail to permit Kirin to employ such data for the purposes provided herein.

(b) Kirin shall have the right to attend and participate in the Company's technical meetings, conduct plant visits at reasonable intervals and receive information concerning the Diagnostic Rights Technology. Kirin shall be provided with reasonable notice of the time and place of such meetings.

(a) Any secret or confidential Diagnostic Rights Technology which is disclosed to Kirin pursuant to this

Agreement or the Shareholders' Agreement, shall be designated as confidential information in the following manner:

(i) If the disclosure is in written form, by prominently marking or stamping each document containing such information with a notice indicating the confidential and proprietary nature of the information; and

(ii) If the disclosure is in oral form, by orally stating at the time of such disclosure that the information disclosed is confidential and proprietary and by delivering to Kirin within fifteen (15) days of the oral disclosure written notice confirming the confidential and proprietary nature of the information.

(b) Except to the extent expressly authorized by this Agreement, the Shareholders' Agreement, or by other prior written consent of the Company for the term of this Agreement and thereafter, Kirin shall keep completely confidential and shall not publish or otherwise disclose to others and shall not use any secret or confidential Diagnostic Rights Technology disclosed or provided to Kirin by the Company. For the purposes of this Agreement, Diagnostic Rights Technology shall be deemed not secret or confidential to the extent, and only to the extent, that it:

(i) was known to Kirin at the time of its disclosure and not otherwise subject to an obligation of Kirin to keep such information confidential;

(ii) was generally available to the public or was otherwise part of the public domain at the time of its disclosure;

(iii) became generally available to the public or became otherwise part of the public domain after its disclosure and other than through any act or omission of Kirin in breach of this Agreement; or

(iv) became known to Kirin after its disclosure (A) from a source other than the Company (including from independent development by Kirin), (B) other than from a third party who had an obligation to the Company not to disclose such information to others, and (C) other than under an obligation of confidentiality. Kirin may disclose any Diagnostic Rights Technology to the extent such disclosure or delivery is necessary for Kirin to comply with laws or regulations, or to make, use or sell under any license granted hereunder by the Company or to sublicense others to do so; provided, that Kirin shall give the Company reasonable advance notice of such proposed disclosure or delivery, shall use its best efforts to secure confidential treatment of the Diagnostic Rights

Technology to be disclosed and shall advise the Company in writing of the manner in which that was done.

(c) The obligation of confidentiality imposed by this Section 3.02 shall survive termination of this Agreement for any reason whatsoever.

ARTICLE IV

ARTICLE V

maintain any appropriate suit or action involving infringement of any patent or copyright, misappropriation of any trade secret or interference with any other intellectual property right relating to the Diagnostic Rights Technology that Kirin shall have obtained pursuant to this Agreement.

action or suit, whether by judgment or settlement, shall be paid to or retained entirely by Kirin.

Company fails to take action with respect to such infringement within a reasonable period, no less than six (6) months, following receipt of such notice and evidence, Kirin shall have the right to bring, defend and maintain any appropriate suit or action involving such infringement in the Diagnostic Rights Field of Activity. If Kirin finds it necessary to join the Company in such suit or action, the Company shall execute all papers and perform such other acts as may be reasonably required and may, at its option, be represented by counsel of its choice. Kirin shall pay to the Company the reasonable expenses of the Company (excluding its attorney's fees) in connection with any such suit or action. Any amount recovered in any such action or suit, whether by judgment or settlement, after payment to the Company of such reasonable costs and expenses (excluding attorney's fees), shall be paid to or retained entirely by Kirin.

ARTICLE VI

patent of the Diagnostic Rights Technology for the life of that patent.

within sixty (60) days after his appointment, then, and in any such event, any other Party, at its option, may terminate its obligations to and the rights of the Defaulting Party under this Agreement upon ten (10) day's written notice to the Defaulting Party, which termination shall be effective as of the occurrence of the event giving rise to the option to terminate.

ARTICLE VII

ARTICLE VIII

ARTICLE IX

Agreement shall be in writing and shall be mailed to the Party to whom notice is to be given, by telex or facsimile, and confirmed by first class mail, registered or certified, return receipt requested, postage prepaid, and properly addressed as follows (in which case such notice shall be deemed to have been duly given on the third (3rd) day following the date of such sending):

"Kirin"             Kirin Brewery Company, Limited
                    26-1, Jingumae 6-Chome
                    Shibuya-Ku, Tokyo 150
                    Japan
                    Telex No. 242-5401 Kirin B J
                    Attn: General Manager of R&D Department

With a copy to:     Musick, Peeler & Garrett
                    One Wilshire Boulevard
                    Suite 2000
                    Los Angeles, CA 90017
                    U.S.A.
                    Telex No. 701357 (MPG LAW UD)
                    Attn: Joel S. Marcus, Esq.

"Company"           Kirin-Amgen, Inc.
                    1900 Oak Terrace Lane
                    Thousand Oaks, CA 91320
                    U.S.A.
                    Telex No. 4994440 (AMGEN)
                    Attn: Corporate Secretary

With a copy to:     Musick, Peeler & Garrett
                    One Wilshire Boulevard
                    Suite 2000
                    Los Angeles, CA 90017
                    U.S.A.
                    Telex No. 701357 (MPG LAW UD)
                    Attn: Joel S. Marcus, Esq.

Any Party by giving notice to the others in the manner provided above may change such Party's address for purposes of this Paragraph 9.01.

ARTICLE X

and delivered shall be deemed to be an original and all of which counterparts of this Agreement taken together shall constitute but one and the same instrument.

claims for any injury or death to persons or damage to or destruction of property, or other loss, arising out of or in connection with any product made, used or sold by Kirin or the use by Kirin of the Diagnostic Rights Technology furnished pursuant to any provision hereunder, or otherwise arising out of or related to the performance of this Agreement.

the simultaneous or later exercise by any Party of any or all such other rights, powers or remedies.

IN WITNESS WHEREOF, the parties have caused this Agreement to be executed by their duly authorized representatives in the manner legally binding on them as of the date first above written.

KIRIN BREWERY CO., LTD.,
a Japanese-Corporation

By /s/ Shinkichi Kubo
  -------------------
 Shinkichi Kubo,
 Senior Managing Director
                    "Kirin"

KIRIN-AMGEN, INC.,
a California corporation

By /s/ George B. Rathmann
  -----------------------
 George B. Rathmann, President
                   "Company"

Exhibit C

LICENSE AGREEMENT

by and between

KIRIN-AMGEN, INC.,

a California corporation

and

AMGEN,

a California corporation

                                                                                                         Page
                                                                                                         ----
RECITALS...............................................................................................    1

I.       DEFINITIONS...................................................................................    2

         1.01  Incorporation by Reference..............................................................    2
         1.02  Diagnostic Rights Field of Activity/Diagnostic Rights Technology........................    2
         1.03  Territory...............................................................................    2
         1.04  Party...................................................................................    2
         1.05  Subsidiary..............................................................................    2

II.      GRANT OF LICENSE..............................................................................    3

         2.01  Grant of License........................................................................    3
         2.02  Rights to Sublicense....................................................................    3
         2.03  Amgen License...........................................................................    4
         2.04  Other Licenses..........................................................................    4
         2.05  No License Fee..........................................................................    4

III.     DISCLOSURE....................................................................................    5

         3.01  Disclosure..............................................................................    5
         3.02  Confidentiality.........................................................................    5

IV.      PATENT APPLICATIONS AND COPYRIGHT REGISTRATIONS...............................................    7

         4.01  Patent Applications.....................................................................    7

V.       PATENT, COPYRIGHT AND TRADE SECRET ENFORCEMENT................................................    8

         5.01  Enforcement.............................................................................    8
         5.02  Infringements...........................................................................    8
         5.03  Maintenance of Action...................................................................    9

VI.      TERM AND TERMINATION:.........................................................................   11

         6.01  Term....................................................................................   11
         6.02  Effective Date..........................................................................   11
         6.03  Default.................................................................................   11
         6.04  Survival................................................................................   12

                                                                                                    Page
                                                                                                    ----
VII.     INFRINGEMENTS..........................................................................     12

         7.01  Infringements....................................................................     12

VIII.    CONSENTS AND APPROVALS.................................................................     13

         8.01  Best Efforts.....................................................................     13

IX.      NOTICE.................................................................................     13

         9.01  Notices..........................................................................     13

X.       MISCELLANEOUS..........................................................................     15

         10.01 Entire Agreement.................................................................     15
         10.02 Headings.........................................................................     15
         10.03 Execution in Counterparts........................................................     15
         10.04 Force Majeure....................................................................     16
         10.05 Applicable Law...................................................................     16
         10.06 Assignment on Written Consent....................................................     16
         10.07 Severability.....................................................................     16
         10.08 No Waiver........................................................................     17
         10.09 Trademarks and Tradenames........................................................     17
         10.10 Indemnity........................................................................     17
         10.11 Other Agreements.................................................................     18
         10.12 Remedies.........................................................................     18
         10.13 Attorneys' Fees and Costs........................................................     18
         10.14 Number and Gender................................................................     19
         10.15 Agreement to Perform Necessary Acts..............................................     19
         10.16 Representations..................................................................     19

Exhibit B

THIS AMGEN/KIRIN-AMGEN, INC. LICENSE AGREEMENT is made and entered into this 4th day of December, 1985, and is made effective as of the 27th day of June, 1985, by and between KIRIN-AMGEN, INC., a California corporation ("Company"), and AMGEN, a California corporation ("Amgen").

A. Amgen desires to obtain from the Company a license to the EPO human (and not non-human veterinary) diagnostic and reagent rights (collectively "Diagnostic Rights") in order to exploit the Diagnostic Rights Field of Activity in its Territory (as hereinafter defined) and the Company is willing to grant such a license to Amgen.

B. Company has granted a similar license to Kirin, of even date herewith ("Kirin License"), with respect to the exploitation of the Diagnostic Rights Field of Activity in Japan, on substantially the same terms and conditions contained herein and for the same purposes described herein.

NOW, THEREFORE, in consideration of the mutual covenants expressed herein and other good and valuable consideration, the parties hereby agree as follows:

ARTICLE I

ARTICLE II

without the prior written consent (which consent is not to be unreasonably withheld) of the Company. Any sublicensees of Amgen shall undertake in writing to be bound by the provisions of Section 3.02 hereof to the same extent Amgen is bound. Amgen shall notify the Company of the identify (if each sublicensee to whom a sublicense is granted and provide the Company a true copy of such sublicense. In the event that the license granted to Amgen hereunder is terminated at any time in accordance with Article VI, and the Company shall not be in default under Section 6.02, the Company shall have the option to terminate or to have Amgen assign to the Company, retroactive to the date of such termination, any sublicenses granted hereunder by Amgen to any Subsidiary of Amgen. Amgen shall include, in all its sublicenses granted hereunder to any Subsidiary of Amgen, provisions for such termination and assignment.

up license fee paid to the Company by Amgen for the grant of the license described in this Article II, but there shall be no royalties payable hereunder whatsoever.

ARTICLE III

(b) Amgen shall have the right to attend and participate in the Company's technical meetings, conduct plant visits at reasonable intervals and receive information concerning the Diagnostic Rights Technology. Amgen shall be provided with reasonable notice of the time and place of such meetings.

(a) Any secret or confidential Diagnostic Rights Technology which is disclosed to Amgen pursuant to this Agreement or the Shareholders' Agreement, shall be designated as confidential information in the following manner:

(i) If the disclosure is in written form, by prominently marking or stamping each document containing such

information with a notice indicating the confidential and proprietary nature of the information; and

(ii) If the disclosure is in oral form, by orally stating at the time of such disclosure that the information disclosed is confidential and proprietary and by delivering to Amgen within fifteen (15) days of the oral disclosure written notice confirming the confidential and proprietary nature of the information.

(b) Except to the extent expressly authorized by this Agreement, the Shareholders' Agreement, or by other prior written consent of the Company for the term of this Agreement and thereafter, Amgen shall keep completely confidential and shall not publish or otherwise disclose to others and shall not use any secret or confidential Diagnostic Rights Technology disclosed or provided to Amgen by the Company. For the purposes of this Agreement, Diagnostic Rights Technology shall be deemed not secret or confidential to the extent, and only to the extent, that it:

(i) was known to Amgen at the time of its disclosure and not otherwise subject to an obligation of Amgen to keep such information confidential;

(ii) was generally available to the public or was otherwise part of the public domain at the time of its disclosure;

(iii) became generally available to the public or became otherwise part of the public domain after its disclosure and other than through any act or omission of Amgen in breach of this Agreements; or

(iv) became known to Amgen after its disclosure (A) from a source other than the Company (including from independent development by Amgen), (B) other than from a third party who had an obligation to the Company not to disclose such information to others, and (C) other than under an obligation of confidentiality.

Amgen may disclose any Diagnostic Rights Technology to the extent such disclosure or delivery is necessary for Amgen to comply with laws or regulations, or to make, use or sell under any license granted hereunder by the Company or to sublicense others to do so; provided, that Amgen shall give the Company reasonable advance notice of such proposed disclosure or delivery, shall use its best efforts to secure confidential treatment of the Diagnostic Rights Technology to be disclosed and shall advise the Company in writing of the manner in which that was done.

(c) The obligation of confidentiality imposed by this Section 3.02 shall survive termination of this Agreement for any reason whatsoever.

ARTICLE IV

ARTICLE V

and maintain any appropriate suit or action involving infringement in the Diagnostic Rights Field of Activity of any patent of the Diagnostic Rights Technology covering only the making, use or sale of products or the use of processes in the Diagnostic Rights Field of Activity. If Amgen finds it necessary to join the Company in such suit or action, the Company shall execute all papers and perform such other acts as may be reasonably required and may, at its option, be represented by counsel of its choice. Amgen shall pay to the Company its reasonable expenses (excluding its attorney's fees) in connection with any such suit or action. Should Amgen lack standing to bring any such action then Amgen may cause the Company to do so upon first undertaking to indemnify and hold the Company harmless (to the extent permissible by law) from all consequent liability and to promptly reimburse all reasonable expenses (including attorney fees) stemming therefrom. Any amount recovered in any such action or suit, whether by judgment or settlement, shall be paid to or retained entirely by Amgen.

Field of Activity and shall provide the Company with any available evidence of such infringement. The Company and Amgen shall consult with each other as to the best manner in which to proceed. The Company shall have the first right, but no obligation, to bring or defend any suit or action on any claim involving such infringement of any such patent of the Diagnostic Rights Technology on such terms relating to reimbursement of associated costs and expenses as shall be agreed to. If the Company finds it necessary or desirable to join Amgen in such suit or action, Amgen shall execute all papers and perform such other acts as may be reasonably required to do so and may, at its option be represented by counsel of its choice unless the Company and Amgen otherwise agree, any amount recovered in any such action, whether by judgment or settlement, after payment to the Company of such reasonable costs and expenses (excluding attorney's fees), shall be paid to or retained by Amgen. In the event the Company fails to take action with respect to such infringement within a reasonable period, no less than six (6) months, following receipt of such notice and evidence, Amgen shall have the right to bring, defend and maintain any appropriate suit or action involving such infringement in the Diagnostic Rights Field of Activity. If Amgen finds it necessary to join the Company in such suit or action, the Company shall execute all papers and

perform such other acts as may be reasonably required and may, at its option, be represented by counsel of its choice. Amgen shall pay to the Company the reasonable expenses of the Company (excluding it attorney's fees) in connection with any such suit or action. Any amount recovered in any such action or suit, whether by judgment or settlement, after payment to the Company of such reasonable costs and expenses (excluding attorney's fees), shall be paid to or retained entirely by Amgen.

ARTICLE VI

Article VII hereof shall survive such termination and continue in full force and effect for an indefinite term. Upon termination of this Agreement for any reason, and without limitation of other remedies, Amgen shall immediately return to the Company (to the extent such return is technically feasible) all Diagnostic Rights Technology in the possession of Amgen or its Subsidiaries, or of which Amgen shall have the right to regain possession or, at the sole election of the Company, shall destroy such Diagnostic Rights Technology (to the extent technically feasible).

ARTICLE VII

ARTICLE VIII

ARTICLE IX

"Amgen"            Amgen
                   1900 Oak Terrace Lane
                   Thousand Oaks, CA 91320
                   U.S.A.
                   Telex No. 499-9315 (AMGEN)
                   Attn: Corporate Secretary

With a copy to:    Cooley, Godward, Castro,
                     Huddleson & Tatum
                   One Maritime Plaza, 20th Floor
                   San Francisco, CA 94111
                   U.S.A.
                   Telex No. 910-372-7370 Cooley SFO
                   Attn: Alan C. Mendelson, Esq.

"Company"          Kirin-Amgen, Inc.
                   1900 Oak Terrace Lane
                   Thousand Oaks, CA 91320
                   U.S.A.
                   Telex No. 4994440 (AMGEN)
                   Attn: Corporate Secretary

With a copy to:    Musick, Peeler & Garrett
                   One Wilshire Boulevard
                   Suite 2000
                   Los Angeles, CA 90017
                   U.S.A.
                   Telex No. 701357 (MPG LAW UD)
                   Attn: Joel S. Marcus, Esq.

Any Party by giving notice to the others in the manner provided above may change such Party's address for purposes of this Paragraph 9.01.

ARTICLE X

thereto, set forth the entire agreement of the parties with respect to the subject matter hereof and may not be modified except by a writing signed by authorized representatives of the parties hereto. To the extent that there may be conflicts or inconsistencies between the provisions of this Agreement and those contained in the Shareholders' Agreement, the provisions of the Shareholders' Agreement shall prevail and govern interpretation.

to perform on account of the Force Majeure throughout the duration thereof plus a period of thirty (30) days.

obligate the Company to disclose to Amgen any information or to make available to the Amgen any materials in violation of an obligation of secrecy or a limitation of use imposed by a third party from whom such information or materials shall have been received.

if such successful party or parties shall recover judgment in any such action or proceeding, such costs, expenses and attorneys' fees may be included in and as part of such judgment. The successful party shall be the party who is entitled to recover its costs of suit, whether or not the suit proceeds to final judgment. A party not entitled to recover its costs shall not recover attorneys' fees.

subject matter hereof, other than those which are set forth expressly in this Agreement; and (iii) that each has had the opportunity to be represented by counsel of its own choice in this matter, including the negotiations which preceded the execution of this Agreement.

IN WITNESS WHEREOF, the parties have caused this Agreement to be executed by their duly authorized representatives in the manner legally binding on them as of the date first above written.

AMGEN, a California corporation

By  /s/George B. Rathmann
  -----------------------------
    George B. Rathmann,
    President
                     "Amgen"

KIRIN-AMGEN, INC.,
a California corporation

By  /s/Shinkichi Kubo
  -----------------------------
    Shinkichi Kubo,
    Chairman
                     "Company"

Exhibit 10.4

THIS AMENDMENT NO. 2 ("Amendment No. 2") TO THAT CERTAIN SHAREHOLDERS' AGREEMENT OF KIRIN-AMGEN, INC., DATED MAY 11, 1984 is made and entered into this 29th day of July, 1985, and is effective as of the lst day of July, 1985, by and among KIRIN BREWERY COMPANY, LTD., a Japanese corporation ("Kirin"), AMGEN, a California corporation ("Amgen"), and KIRIN-AMGEN, INC., a California corporation ("K-A").

Pursuant to Paragraph 22.19 of the Shareholders' Agreement regarding expansion of the business of K-A, Kirin and Amgen desire to expand K-A's business into the research and development of Thrombopoietin including, without limitation, any and all rights therein and thereto (collectively, "TPO").

NOW, THEREFORE, it is agreed as follows:

Kirin and Amgen hereby agree that Paragraph 2.06 of the Shareholders' Agreement shall be expanded to include the research and development of TPO and the ultimate production and marketing of TPO.

Subject only to the conditions of (i) the simultaneous establishment of the Pluripoietin project by and between Kirin and Amgen, and (ii) the execution on or before October 31, 1985 by K-A and a third party of a License Agreement with respect to erythropoietin for human therapeutic uses in certain territories, K-A shall commence the research and development of TPO. Kirin and Amgen agree

that they will fund equally, on a 50-50 basis, the research and development of TPO until the earlier occurrence of October 31, 1985 or the satisfaction of the conditions set forth in this paragraph. If the conditions are satisfied on or before October 31, 1985, then K-A will reimburse Amgen and Kirin for any and all expenditures made by them regarding the research and development of TPO between July 1, 1985 and the date of satisfaction of the conditions. If the conditions have not been satisfied on or before October 31, 1985, then all funding obligations of Kirin and Amgen shall cease and Kirin and Amgen shall discuss the continuation and further funding of the research and development of TPO pursuant to this Amendment No. 2. Amgen and Kirin shall use their best efforts to agree on such continuation and funding; provided that, if Kirin and Amgen are unable to reach agreement on or before November 15, 1985, then their obligations hereunder shall terminate and have no further force and effect as of November 15, 1985.

The rights and obligations of the parties with respect to this Amendment No. 2 as an additional expansion of K-A's business opportunities are otherwise consistent with the provisions of the Shareholders' Agreement. All other terms and conditions of the Shareholders' Agreement are hereby confirmed and ratified in all respects.

Each party hereto agrees to perform any and all further acts and execute and deliver any and all further documents and/or instruments which may be reasonable or necessary to carry out the provisions of this Amendment No. 2 to the Shareholders' Agreement and to carry out this further business purpose of K-A.

IN WITNESS WHEREOF, the undersigned have caused this Amendment No. 2 to be executed on July 29, 1985 by their duly authorized representatives in the manner legally binding upon them.

KIRIN BREWERY COMPANY, LTD.,
a Japanese corporation

By  /s/Shinkichi Kubo
   ------------------
    Shinkichi Kubo,
    Senior Managing Director

"Kirin"

AMGEN, a California corporation

By  /s/George B. Rathmann
    ---------------------
    George B. Rathmann,
    President

"Amgen"

KIRIN-AMGEN, INC.
a California corporation

BY  /s/Tasuhiko Kaneko
    ------------------
    ------------------
    Its
       ---------------
                "K-A"

Exhibit 10.4

A. Kirin and Amgen mutually agree that their relationship with respect to EPO has been beneficial to both companies and wish to adopt this Amendment No. 3 to clarify their agreements with respect to TPO and PPO.

B. This Amendment No. 3 relates to certain agreements with respect to TPO (as defined in Amendment No. 2 to the Shareholders' Agreement) and PPO (as defined in that certain Research, Development, Technology Disclosure and License Agreement: PPO between Kirin and Amgen) and the manufacture, production and world-wide commercial sale of TPO and PPO products.

NOW, THEREFORE, it is agreed as follows:

1.01 It is agreed that Kirin shall have an exclusive license with respect to TPO and PPO in the territory of Japan and Amgen shall have an exclusive license with respect to TPO and PPO in the territory of the United States. The initial royalty rate, which is subject to adjustment as set forth below, shall be 5% of net sales of TPO and/or PPO products from each Kirin and Amgen to Corporation.

1.02 The parties agree that the initial royalty rate established in Paragraph 1.01 above may be subject to adjustment when TPO and/or PPO are further along in their development and/or marketing stage. Only at such time will the parties be able to more fully understand the potential market and economic implications of the initial royalty rate established herein.

1.03 The parties agree that the final royalty rate to be mutually agreed upon and embodied in definitive license agreements among the parties may involve a maximum royalty rate of five percent (5%) down to zero (0). The parties may agree upon different royalty rates (e.g. Kirin 3%; Amgen 5%), the same royalty rate (but different than the initial royalty rate), or the initial royalty rate may remain unchanged.

The parties agree that Corporation shall bear and pay for royalty obligations to third parties with respect to asserted ownership rights to TPO and/or PPO Technology which would otherwise be required from Amgen and/or Kirin. Such third party royalty payments shall be an obligation of Corporation (in addition to any royalty payments which K-A is otherwise obligated to make). It is agreed that the right to reach agreement with a third party respecting this matter shall be handled by the shareholder(s) whose territory(ies) is (are) affected. For example, if any third party person and/or entity makes a claim for TPO and/or PPO royalty payments and it affects only the territory of Japan, Kirin shall have the sole responsibility of negotiating a third party royalty rate payable by K-A which shall be binding on all parties hereto.

The parties agree that upon the successful completion of the R & D Project for PPO, as more fully set forth in the Research, Development, Technology Disclosure and License Agreement: PPO, all rights in and to the PPO Technology shall be promptly licensed and/or transferred to Corporation. Additionally, Amgen shall, at that time, exclusively license to Corporation on a royalty-free world-wide basis its Core Technology relating to PPO.

Each party hereto agrees to perform any and all further acts and execute and deliver any and all further documents and/or instruments which may be reasonable or necessary to carry out the provisions and purposes of this Amendment No. 3 to the Shareholders' Agreement.

[SIGNATURE PAGE FOLLOWS]

IN WITNESS WHEREOF, the undersigned have caused this Amendment No. 3 to be executed as of the first date written above by their duly authorized representatives in a manner legally binding upon them.

KIRIN BREWERY COMPANY, LTD.,
a Japanese corporation

By    /s/Shinkichi Kubo
  ---------------------------------------
   Shinkichi Kubo, Senior
   Managing Director

"Kirin"

AMGEN, a California corporation

By    /s/George B. Rathmann
  ---------------------------------------
   George B. Rathmann, President

"Amgen"

KIRIN-AMGEN, INC.,
a California corporation

By    /s/Shinkichi Kubo
  ---------------------------------------
 Shinkichi Kubo Its Chairman
 ---------------    --------

"Corporation"

Exhibit 10.5

THIS PRODUCT LICENSE AGREEMENT entered into this 30th day of September, 1985, by and between AMGEN, a California corporation having offices at 1900 Oak Terrace Lane, Thousand Oaks, California 91320-1789 (said corporation hereinafter referred to as "AMGEN") and ORTHO PHARMACEUTICAL CORPORATION, a New Jersey corporation having offices at U.S. Route 202, Raritan, New Jersey 08869, (said corporation hereinafter referred to as "ORTHO").

WHEREAS, AMGEN represents that it has developed and is continuing to develop technology relating to certain genetically-engineered health-care products and processes for their manufacture;

WHEREAS, AMGEN further represents that it is the owner of patent applications by assignment and unpatented know-how covering said genetically- engineered health-care products;

WHEREAS, ORTHO and AFFILIATES are engaged in the research, development and sale of health care products throughout the world and wish to obtain certain rights to such technology and to such patents and patent applications;

WHEREAS, ORTHO and AMGEN have entered into a TECHNOLOGY LICENSE AGREEMENT on even date herewith for the research, development and regulatory approval of various products;

NOW, THEREFORE, in consideration of the premises and the mutual covenants herein recited, and other good and valuable considerations, the receipt of which is acknowledged, it is agreed as follows:

For the purposes of this Agreement, the terms set forth in this Article I shall have the following meanings:

1.01 "AFFILIATE" shall mean and include (i) any company which owns or controls directly or indirectly at least forty percent (40%) of the voting stock of ORTHO and (ii) any other company at least forty percent (40%) of whose voting stock is

owned or controlled directly or indirectly by such owning or controlling company, and (iii) any other company with which ORTHO or such an owning, owned, controlling or controlled company has a co-marketing, joint venture or distribution agreement for pharmaceuticals outside the United States. The term "ORTHO" shall also mean and include any AFFILIATE wherein the inclusion of same shall be warranted under the provisions of the AGREEMENT.

1.02 "AGREEMENT" shall mean this Product License Agreement.

1.03 "CLOSING" shall occur when,:

(a) AMGEN shall execute and deliver to ORTHO this AGREEMENT and a TECHNOLOGY LICENSE AGREEMENT.

(b) ORTHO shall execute and deliver to AMGEN this AGREEMENT and the TECHNOLOGY LICENSE AGREEMENT; and

(c) The following approvals shall have been obtained: (i) the Executive Committee or the Board of Directors of AMGEN shall have authorized AMGEN's participation in, and its execution and delivery of, this AGREEMENT, including the Exhibits attached hereto and the TECHNOLOGY LICENSE AGREEMENT; and
(ii) the Board of Directors of ORTHO shall have authorized ORTHO's participation in, and its execution and delivery of,

this AGREEMENT, including the Exhibits attached hereto and the TECHNOLOGY
LICENSE AGREEMENT.

1.04 "EFFECTIVE DATE" shall be contingent on certain events and shall mean the date on which this AGREEMENT takes effect which shall be without interruption and simultaneous with the termination of and in accordance with the provisions of Article 9 of the TECHNOLOGY LICENSE AGREEMENT; provided that, if this AGREEMENT takes effect as a result of the receipt of an approval letter to market a LICENSED PRODUCT in a MAJOR COUNTRY or if upon the conclusion of the ten (10) year period there is a pending but as yet unapproved NDA or corresponding registration in any MAJOR COUNTRY, this AGREEMENT shall then be in effect in the entire LICENSED TERRITORY with respect to said PRODUCT. If there is not an approved NDA or corresponding registration in a MAJOR COUNTRY but such approval has been granted to permit marketing of a LICENSED PRODUCT and sales of said LICENSED PRODUCT commence in another country in the TERRITORY, this AGREEMENT shall not come into effect but the payment provisions of Article 4 of this AGREEMENT shall be followed with respect to the sale of LICENSED PRODUCTS in said country.

1.05 "EPO" shall mean erythropoietin as described in Exhibit A.

1.06 "FDA" shall mean the United States Food & Drug Administration and foreign counterparts thereof.

1.07 "GROSS AMOUNT" shall mean NET SALES less all costs related to manufacturing and packaging the LICENSED PRODUCTS into a finished marketable condition.

1.08 "HEPATITIS B" shall mean the recombinant yeast-derived hepatitis B surface antigen vaccine as described in Exhibit B and any other Hepatitis B vaccine development resulting from the Development Program as described in Paragraph 3.01 of the TECHNOLOGY LICENSE AGREEMENT or a supplement of said Program.

1.09 "IL-2" shall mean the recombinant-methionyl human interleukin 2[alanine 125] as described in Exhibit C.

1.10 "LICENSED FIELD" shall mean and include:

(a) with respect to EPO: all indications for human use except dialysis and diagnostics;

(b) with respect to HEPATITIS B and IL-2: all indications for human use except diagnostics.

1.11 "LICENSED KNOW-HOW" shall mean and include any and all data, information, technology or special ability on the part of AMGEN including, but not limited to, processes, techniques, methods, products, materials and compositions relating to the research, development, manufacture, testing or use of EPO, HEPATITIS B and IL-2, now owned or controlled by AMGEN or that shall be owned or controlled by AMGEN during the term of this AGREEMENT, which is reasonably related to LICENSED PATENTS and LICENSED PRODUCTS for use in the LICENSED FIELD; and which is useful in seeking approval from appropriate governmental health authorities to market LICENSED PRODUCTS and which includes AMGEN's INDs, NDAs and all supplements thereto covering PRODUCTS in the LICENSED FIELD.

1.12 "LICENSED PATENTS" shall mean:

(a) any patent listed in Exhibit D;

(b) any patent application listed in Exhibit D, and any division, continuation, or continuation-in-part of any such application, and any patent which shall issue based on such application, division, continuation or continuation-in-part;

(c) any patent which is a reissue or extension of, or a patent of addition to, any patent defined in (a) or any application maturing into a patent defined in (b) above;

(d) any patent application or patent corresponding to any patent application or patent identified in (a), (b) or (c) above which is hereafter filed or issued in any country; and

(e) any patent application related to or based on any of AMGEN's technical information developed in the LICENSED FIELD during the performance of this AGREEMENT, and any division, continuation or continuation-in-part of any such application; and any patent which shall issue based on such application, division, continuation or continuation-in-part; and any patent which is a reissue or extension of, or a patent of addition to, any such patent.

1.13 "LICENSED PRODUCTS" shall mean and include any PRODUCTS for use in the LICENSED FIELD (i) which are within the scope of a VALID LICENSED CLAIM of a LICENSED PATENT; or (ii) whose use is within the scope of a VALID LICENSED CLAIM of a LICENSED PATENT; or (iii) which are manufactured or packaged within the scope of a VALID LICENSED CLAIM of a LICENSED PATENT; or (iv) which utilize any LICENSED KNOW-HOW.

1.14 "LICENSED TERRITORY" shall mean and include:

(a) with respect to EPO: the United States, its territories and possessions, including the Commonwealth of Puerto Rico;

(b) with respect to HEPATITIS B: the entire world except China;

(c) with respect to IL-2: the entire world.

1.15 "MAJOR COUNTRY' shall mean any of the following: United States, United Kingdom, West Germany, France and Japan.

1.16 "NDA" shall mean a New Drug Application and/or a Product License Application and all supplements filed pursuant to the requirements of the FDA, including all documents, data and other information concerning LICENSED PRODUCTS which are necessary for, or included in, FDA approval to market LICENSED PRODUCTS and foreign counterparts thereof of NDAs.

1.17 "NET SALES" shall mean the amount billed by ORTHO, or an AFFILIATE from the sale of LICENSED PRODUCTS to independent third parties less: (i) discounts, including cash discounts, or rebates actually allowed or granted from the billed amount, (ii) credits or allowances actually granted upon claims or returns

regardless of the party requesting the return, (iii) freight charges paid for delivery, and (iv) taxes or other government charges levied on or measured by the billing amount whether absorbed by the billing or the billed party. In the event that LICENSED PRODUCTS are sold in the form of a combination product containing one or more active ingredients, other than EPO, HEPATITIS B or IL-2, NET SALES for such combination products will be calculated by multiplying actual NET SALES of such LICENSED PRODUCTS by the fraction A/(A+B) where A is the invoice price of the LICENSED PRODUCT if sold separately and B is the total invoice price of any other active component or components in the combination if sold separately by ORTHO or a single AFFILIATE. If on a country-by-country basis the LICENSED PRODUCT and the other active component or components in the combination are not sold separately in said country by ORTHO or a single AFFILIATE, NET SALES for purposes of determining royalties on the combination shall be calculated by multiplying NET SALES of the combination by the fraction C/(C+D) where C is ORTHO's or AFFILIATE's total actual cost of LICENSED PRODUCT at the point of formulation into the combination product and D is ORTHO's or AFFILIATE's total actual cost of the other active ingredient(s) included in the combination product at such point.

1.18 "OUTSIDE RESEARCH PAYMENTS" shall mean amounts paid under the TECHNOLOGY LICENSE AGREEMENT or this AGREEMENT for clinical testing by ORTHO to an individual or individuals or to an entity other than AMGEN, ORTHO or an AFFILIATE for purposes of independent evaluation of any of the PRODUCTS, which data shall be used by ORTHO and/or AMGEN in filing NDAs or other registrations regarding the PRODUCTS.

1.19 "NET PRE-TAX AMOUNT" shall mean the GROSS AMOUNT less all current operating expenses (which operating expenses shall not include manufacturing and packaging as deducted in GROSS AMOUNT nor costs recovered by ORTHO under Paragraphs 4.01 A (iii), 4.01 B (iii) and 4.01 C (iii) of this AGREEMENT) but before income taxes. Any recovery under Paragraphs 4.01 A (iii), 4.01 B (iii) and 4.01 C (iii) by ORTHO shall be made from the GROSS AMOUNTS separate from operating expenses but before determining NET PRE-TAX AMOUNT.

1.20 "PRODUCT ORGANISMS" shall mean any and all organisms developed or acquired by AMGEN, the uses of which are licensed to ORTHO pursuant to this AGREEMENT and which have been genetically engineered to produce biologically active LICENSED PRODUCTS, including any and all improvements thereon.

1.21 "PRODUCTS" shall mean IL-2, HEPATITIS B, and EPO for all human uses in the LICENSED FIELD. Wherever a reference is made to the "PRODUCT" or to the "PRODUCTS", the reference shall apply to each of IL-2, HEPATITIS B and EPO severally, unless the context shall indicate otherwise. Whenever the provisions of this AGREEMENT differ in application to any of IL-2, HEPATITIS B or EPO, then such product shall be identified separately, rather than being referred to as a "PRODUCT".

1.22 "TECHNOLOGY LICENSE AGREEMENT" shall mean an agreement between AMGEN and ORTHO executed on even date herewith.

1.23 "VALID LICENSED CLAIM" shall mean and include a claim in an issued LICENSED PATENT which has not lapsed or become abandoned and which claim has not been declared invalid by an unreversed or unappealable decision or judgment of a court of competent jurisdiction.

(a) AMGEN hereby grants to ORTHO but not AFFILIATES, except as hereinafter provided, an exclusive license to make in one location, have made and use LICENSED KNOW-HOW, LICENSED PATENTS and LICENSED PRODUCTS in the LICENSED TERRITORY in the LICENSED FIELD and to sell LICENSED PRODUCTS in the LICENSED TERRITORY.

(b) AMGEN, having received the consent of Kirin Brewery Co., Ltd., hereby grants to ORTHO but not AFFILIATES, an exclusive license, except as against AMGEN's rights under this AGREEMENT in the LICENSED TERRITORY, to make EPO in one location in the United States for use and sale outside the LICENSED TERRITORY but not including China and Japan. AMGEN shall provide to ORTHO all information and any assistance and know-how required for ORTHO to achieve the purposes of this paragraph at the earlier of the demonstration of Clinical Efficacy of EPO as defined in the TECHNOLOGY LICENSE AGREEMENT or the completion of PHASE II studies as set forth in an agreement between ORTHO and KIRIN-AMGEN designated "Technology License Agreement" dated September 30, 1985.

ORTHO may, with prior written notice to AMGEN, sublicense LICENSED PATENTS, LICENSED KNOW-HOW and LICENSED PRODUCTS under this AGREEMENT (i) to any AFFILIATE, or any third party, to use and sell LICENSED PRODUCTS as provided in this AGREEMENT; and (ii) to any one controlled AFFILIATE to make in one location, use and sell LICENSED PRODUCTS as provided in this AGREEMENT. If ORTHO requests the right to sublicense one additional AFFILIATE to make in one location, use and sell LICENSED PRODUCTS as provided in this AGREEMENT, AMGEN shall not unreasonably withhold its consent thereto.

In the event of sublicensing as provided in Paragraph 2.02, ORTHO shall assure AMGEN that this AGREEMENT shall apply to such AFFILIATE or third party sublicensee, and such AFFILIATE or third party sublicensee shall deliver to AMGEN a written promise to comply with the terms of this AGREEMENT to the extent that such terms are applicable. ORTHO shall guarantee the due and punctual performance of any and all responsibilities under this AGREEMENT as applied to such AFFILIATE or third party sublicensee.

As a substitute for a sublicense, AMGEN shall, if ORTHO so requests, enter into a separate agreement with any AFFILIATE granting a license in accordance with the provisions of this AGREEMENT. Such agreement shall incorporate all of the terms of this AGREEMENT to the extent that they are applicable. ORTHO shall guarantee the due and punctual performance of any and all responsibilities by the AFFILIATE under such separate agreement.

AMGEN warrants and represents that it has the full right and power to grant the license set forth in Paragraph 2.01 of this Article 2 and that there are no outstanding agreements, assignments or encumbrances in existence inconsistent with the provisions of this AGREEMENT including, without limitation as to generality, any obligations to governmental agencies or private foundations resulting from acceptance of research grant monies, or otherwise.

ORTHO agrees to use reasonable efforts to market and sell LICENSED
PRODUCTS in the LICENSED TERRITORY.

2.07.1 If AMGEN, on the one hand, or ORTHO and/or its AFFILIATES and sublicensee(s), on the other hand, improve the PRODUCT ORGANISMS, and/or the LICENSED KNOW-HOW, or make LICENSED PRODUCTS or process improvements, all such improvements shall become part of the LICENSED KNOW-HOW and shall be promptly transferred and/or communicated to the other party in order to maintain parity among AMGEN, ORTHO and its AFFILIATES and sublicensees and by the provisions hereof shall be deemed to be a part of the LICENSED PATENTS or LICENSED KNOW-HOW as the case may be and licensed to AMGEN or ORTHO, as the case may be, on a royalty-free basis.

2.07.2 Notwithstanding any provision of this AGREEMENT, any technology and/or improvements developed by a party to this AGREEMENT and disclosed or licensed under this Article 2, shall be and remain the property of the developing party. This Paragraph 2.07.2 shall survive any termination of this AGREEMENT.

In the event, on the effective date of this AGREEMENT, an NDA approval letter from the FDA has not been received but an NDA or corresponding registration is pending in a MAJOR COUNTRY for any one or more of the PRODUCTS, this AGREEMENT takes effect and the process seeking said approval letter shall be diligently continued and pursued by the appropriate party as set forth in the TECHNOLOGY LICENSE AGREEMENT.

ORTHO and AMGEN shall keep and maintain complete and accurate records of all work including all FDA filings that either has done in connection with LICENSED PRODUCTS. The parties agree to provide each other with sufficient technical information and assistance as is necessary for each of them to assess the progress of the other party in its clinical testing of PRODUCTS and in its filing and pursuit of INDs and NDAs in connection with LICENSED PRODUCTS including but not limited to AMGEN informing ORTHO of all communications and discussions with the FDA.

(i) With respect to EPO, AMGEN and ORTHO agree that each shall have access to and the exclusive and irrevocable right to refer to and cross- reference each other's INDs, NDAs and supplements thereto consistent with the purposes of this AGREEMENT and the TECHNOLOGY LICENSE AGREEMENT and with respect to AMGEN not for any purpose other than dialysis and each agrees to provide all appropriate documentation necessary to achieve the purposes of this AGREEMENT. The parties agree to notify the FDA of the right to cross-reference the above- described documents and to execute and file all the necessary papers and documents required to allow each to exercise its rights under this AGREEMENT.

(ii) With respect to HEPATITIS B and IL-2, AMGEN and ORTHO agree that ORTHO shall have access to and the exclusive and irrevocable right to refer to and cross-reference AMGEN's INDs, NDAs and supplements thereto consistent with the purposes of this AGREEMENT and AMGEN agrees to provide all appropriate documentation to achieve the purposes of this AGREEMENT. AMGEN further agrees, upon request by ORTHO, to further notify the FDA of ORTHO's right to cross-reference the above-described

documents and to execute and file all the necessary papers and documents required to allow ORTHO to exercise its rights under this AGREEMENT.

(iii) With respect to HEPATITIS B, AMGEN and ORTHO agree that AMGEN shall have access to and the exclusive and irrevocable right to refer to and utilize ORTHO's INDs, NDAs and supplements thereto provided that AMGEN demonstrates such is necessary for it to pursue its registration of HEPATITIS B in China and for no other purpose.

During the term of this AGREEMENT, AMGEN and ORTHO each shall have a continuing obligation to advise each other of any adverse drug reactions or any governmental regulatory problems, notices, actions or communications and to keep all INDs, NDAs and supplements thereto current and in full force and effect relating to the manufacture, use, and/or sale of LICENSED PRODUCTS.

ARTICLE 4

Royalties on LICENSED PRODUCTS shall be paid as set forth below:

(i) ORTHO shall pay AMGEN 5% of its NET SALES in the United States of EPO LICENSED PRODUCTS;

(ii) ORTHO shall retain for its own benefit 5% of its NET SALES in the United States of EPO LICENSED PRODUCTS;

(iii) After the royalty payments set forth in (i) and (ii) above have been made, any remaining GROSS AMOUNTS received from the sale of EPO LICENSED PRODUCTS shall be retained by ORTHO and applied in sequence as follows:

(a) the equivalent of up to 100% of the EPO royalty payments made by ORTHO to AMGEN

under paragraph 5.01 of the TECHNOLOGY LICENSE AGREEMENT, provided that no more than 10% of said total payments shall be recoverable by ORTHO in any one (1) calendar year.

(b) the equivalent of up to 100% of the EPO research and development payments made by ORTHO to AMGEN under paragraph 3.02 of the TECHNOLOGY LICENSE AGREEMENT or continued under this AGREEMENT.

(c) the equivalent of up to 50% of the OUTSIDE RESEARCH PAYMENTS directly related to EPO incurred by ORTHO in accordance with Article 4 of the TECHNOLOGY LICENSE AGREEMENT or continued under this AGREEMENT.

(iv) After the recovery payments in (iii) (b) and (iii) (c) above have been fully satisfied for costs incurred prior to NDA approval in the United States of both indications, costs of studies ongoing at the time of such approval and

costs of studies requested by the FDA at the time of such approval, the royalty payments in (i) and (ii) above shall cease and before any royalty payments based on further sales are made to AMGEN, ORTHO shall retain its appropriate payment as set forth in (iii) (a) and then ORTHO shall pay to AMGEN a single royalty payment equal to 10% of NET SALES in the United States of EPO LICENSED PRODUCTS.

(v) After the payments in (iv) above have been made, ORTHO shall retain the total remainder of the monies received as a result of the sale in the United States of EPO LICENSED PRODUCTS.

(i) ORTHO shall pay AMGEN 5% of its NET SALES in the LICENSED
TERRITORY of HEPATITIS B LICENSED PRODUCTS;

(ii) ORTHO shall retain for its own benefit 5% of its NET SALES in the LICENSED TERRITORY of HEPATITIS B LICENSED PRODUCTS;

(iii) After the royalty payments set forth in (i) and (ii) above have been made, any remaining GROSS AMOUNTS received from the sale of HEPATITIS B LICENSED PRODUCTS shall be retained by ORTHO and applied in sequence as follows:

(a) the equivalent of up to 100% of the HEPATITIS B royalty payments made by ORTHO to AMGEN under paragraph 5.01 of the TECHNOLOGY LICENSE AGREEMENT, provided that no more than 10% of said total payments shall be recoverable by ORTHO in any one (1) calendar year.

(b) the equivalent of up to 100% of the HEPATITIS B research and development payments made by ORTHO to AMGEN under paragraph 3.02 of the TECHNOLOGY LICENSE AGREEMENT or continued under this AGREEMENT.

(c) the equivalent of up to 50% of the OUTSIDE RESEARCH PAYMENTS directly related to

HEPATITIS B incurred by ORTHO in accordance with Article 4 of the TECHNOLOGY LICENSE AGREEMENT or continued under this AGREEMENT.

(iv) After the recovery payments in (iii) (b) and (iii) (c) above have been fully satisfied for costs incurred prior to NDA approval in the United States, costs of studies ongoing at the time of said approval and costs of studies requested by the FDA at the time of said approval, the royalty payments in (i) or (ii) above shall cease and before any royalty payments based on further sales are made to AMGEN, ORTHO shall retain its appropriate payment as set forth in
(iii) (a) and then ORTHO shall pay to AMGEN a royalty payment equal to one-third (1/3rd) of the NET PRE-TAX AMOUNT resulting from the sales in United States of HEPATITIS B LICENSED PRODUCTS and a royalty of ten percent (10%) of NET SALES of HEPATITIS B LICENSED PRODUCTS in the remainder of the LICENSED TERRITORY.

(v) After the payments in (iv) above have been made, ORTHO shall retain two-thirds (2/3rds) of the NET PRE-TAX AMOUNT resulting from sales in the United State of HEPATITIS B LICENSED PRODUCTS and shall retain the total remainder of the monies received as a result of the NET SALES of HEPATITIS B LICENSED PRODUCTS in the remainder of the LICENSED TERRITORY.

(i) ORTHO shall pay AMGEN 5% of its NET SALES in the LICENSED
TERRITORY of IL-2 LICENSED PRODUCTS;

(ii) ORTHO shall retain for its own benefit 5% of its NET SALES in the LICENSED TERRITORY of IL-2 LICENSED PRODUCTS;

(iii) After the royalty payments set forth in (i) and (ii) above have been made, any remaining GROSS AMOUNTS received from the sale of IL-2 LICENSED PRODUCTS shall be retained by ORTHO and applied in sequence as follows:

(a) the equivalent of up to 100% of the IL-2 royalty payments made by ORTHO to AMGEN under paragraph 5.01 of the TECHNOLOGY LICENSE AGREEMENT, provided that no more than 10% of said total payments shall be recoverable by ORTHO in any one (1) calendar year.

(b) the equivalent of up to 100% of the IL-2 research and development payments made by ORTHO to AMGEN under paragraph 3.02 of the TECHNOLOGY LICENSE AGREEMENT or continued under this AGREEMENT.

(c) the equivalent of up to 50% of the OUTSIDE RESEARCH PAYMENTS directly related to IL-2 incurred by ORTHO in accordance with Article 4 of the TECHNOLOGY LICENSE AGREEMENT or continued under this AGREEMENT.

(iv) After the recovery payments in (iii) (b) and (iii) (c) above have been fully satisfied for costs incurred prior to NDA approval in the

United States, costs of studies ongoing at the time of said approval and costs of studies requested by the FDA at the time of said approval, the royalty payments in (i) or (ii) above shall cease and before any royalty payments based on further sales are made to AMGEN, ORTHO shall retain its appropriate payment as set forth in (iii) (a) and then ORTHO shall pay to AMGEN a royalty payment equal to one- third (1/3rd) of the NET PRE-TAX AMOUNT resulting from the sales in United States of IL-2 LICENSED PRODUCTS and a royalty of ten percent (10%) of NET SALES of IL-2 LICENSED PRODUCTS in the remainder of the LICENSED TERRITORY.

(v) After the payments in (iv) above have been made, ORTHO shall retain two-thirds (2/3rds) of the NET PRE-TAX AMOUNT resulting from sales in the United State of IL-2 LICENSED PRODUCTS and shall retain the total remainder of the monies received as a result of the NET SALES of IL-2 LICENSED PRODUCTS in the remainder of the LICENSED TERRITORY.

For purposes of Paragraph 4.01, all computations of royalties and other payments due to AMGEN shall be made annually commencing on CLOSING and ending on December 31 of the year in which this AGREEMENT takes effect, and thereafter for each calendar year; provided, however, all royalty payments based on NET SALES due to AMGEN and ORTHO shall be payable within sixty (60) days of the end of each calendar quarter.

ORTHO agrees that on the fifth anniversary of the EFFECTIVE DATE of this AGREEMENT and on each succeeding fifth anniversary date thereafter, it shall unilaterally, utilizing whatever records or documents it deems appropriate, review the royalty payments to AMGEN under Paragraph 4.01 B (iv) and 4.01 C (iv) of this Article 4 for sales of LICENSED PRODUCTS outside the United States. If ORTHO determines in good faith that said payments differ by more than 20% from 1/3 of the NET PRE-TAX AMOUNT, it shall propose an appropriate upward or downward adjustment in the royalty payments to AMGEN with the proviso that the royalty shall not be adjusted in excess of 25% from the then-existing royalty. If the parties cannot agree on the adjustment, it shall not be subject to the provisions of

Paragraph 10.07 of this AGREEMENT but shall remain at the then-existing royalty until the next scheduled review date.

ORTHO shall keep complete and accurate records of the latest three (3) years of NET SALES of LICENSED PRODUCTS with respect to which a royalty is payable according to this AGREEMENT. Within sixty (60) days following each quarterly period of a calendar year during which royalties are due under this AGREEMENT, ORTHO shall render to AMGEN a written report setting forth the amount of royalties due and payable on a country by country basis based on sales of such LICENSED PRODUCTS during such calendar quarter, and ORTHO shall, upon rendering such report, remit to AMGEN the amount of royalties shown thereby to be due.

AMGEN shall have the right at its own expense to nominate an independent certified public accountant acceptable to and approved by ORTHO who shall have access to the records of ORTHO and those of its AFFILIATES and Sublicensees during reasonable business hours for the purpose of verifying the payments as provided for in this AGREEMENT, but this right may

not be exercised more than once in any one (1) calendar year, and said accountant shall disclose to AMGEN only information relating to the accuracy of the royalty report and the royalty payments made according to this AGREEMENT.

No royalties shall be payable on sales of any LICENSED PRODUCT between ORTHO and any AFFILIATE or sublicensee.

Royalties on United States sales and all other payments to be made to AMGEN by ORTHO under this AGREEMENT shall be made in United States Dollars. Such payments shall be net of any taxes withheld pursuant to Paragraph 4.10 of this Article.

Any payments due hereunder on sales outside the United States by ORTHO shall be payable to AMGEN in United States Dollars at the prevailing rate of exchange of the currency of the country in which the sales are made (as quoted by the CITIBANK N.A. of New York for the last business day of the calendar quarter for which the royalties are payable).

In the event that ORTHO grants a sublicense under this AGREEMENT to any AFFILIATE, or AMGEN enters into a separate Agreement with any AFFILIATE pursuant to Article 2, such AFFILIATE shall make any payments to AMGEN in accordance with the provisions of this AGREEMENT in United States Dollars at the prevailing rate of exchange of the currency of the country of such AFFILIATE on the date on which the payment is due or in such other currency as both parties mutually agree upon.

Any sum required under United States tax laws or the tax laws of any other country, to be withheld by ORTHO from payments for the account of AMGEN shall be promptly paid by ORTHO for and on behalf of AMGEN to the appropriate tax authorities, and ORTHO shall furnish AMGEN with official tax receipts or other appropriate evidence issued by the appropriate tax authorities sufficient to enable AMGEN to support a claim for income tax credit in respect of any sum so withheld. This same provision shall also apply to an AFFILIATE sublicensed under Article 2 hereof or entering into a separate agreement pursuant to said Article with relation to the tax laws of the

respective country or countries in which such AFFILIATE is doing business.

During any period in which no exchange rate between the foreign currency in question and the United States Dollar can be ascertained in accordance with this Article, AMGEN shall have the option of having payment of such royalties suspended with the proviso that payment of amounts due shall be made within thirty (30) days after such a rate of exchange is next quoted by CITIBANK N.A. of New York; provided always that AMGEN may at any earlier date elect to receive payment in the foreign currency in question or in any other currency for which an exchange rate can be ascertained. If the exchange rate can be ascertained, but the payment by ORTHO's AFFILIATE to AMGEN in United States Dollars or other currency is not permissible, ORTHO's AFFILIATE may satisfy its obligations to AMGEN by the deposit in the currency of the country where the sales of LICENSED PRODUCTS were made on which the payment was based to the credit and account of AMGEN in any commercial bank or trust company of its choice located in that country; prompt notice of which shall be given to AMGEN.

AMGEN agrees to manufacture and supply ORTHO's requirements of PRODUCTS for the sale of LICENSED PRODUCTS in the United States. The parties shall enter into an appropriate Manufacture and Supply Agreement covering the manufacture and supply of PRODUCTS. This agreement shall include provisions relating to price, supply of PRODUCTS and PRODUCT ORGANISMS, disclosure of manufacturing technology, preparation and delivery of specifications, record keeping, renegotiation terms, aid and assistance to ORTHO to set up its own manufacturing facility, either within the United States or outside the United States, if required, duration and the like. With respect to price, AMGEN will sell each of the PRODUCTS at its standard cost and ORTHO will not propose a price for any of the PRODUCTS less than its fully allocated cost of manufacture in its own facilities and said price shall be renegotiated triennially. Such agreement shall also provide that so long as a mutually acceptable price exists for any of the said PRODUCTS, AMGEN shall continue to supply all of ORTHO's requirements of said PRODUCT. This

Manufacture and Supply agreement shall be negotiated in an atmosphere of good faith and reasonableness.

If AMGEN is unable to supply ORTHO's requirements of any of the PRODUCTS in the United States or if the parties are unable to negotiate a mutually acceptable price for AMGEN to supply ORTHO's requirements of any of the PRODUCTS in the United States, then ORTHO shall have the right to establish a facility for the manufacture of such PRODUCT or PRODUCTS for use and sale in the LICENSED TERRITORY.

AMGEN and ORTHO will discuss a Manufacture and Supply Agreement for HEPATITIS B and IL-2 outside the United States and will endeavor to reach a mutual understanding on such an Agreement, provided however, that ORTHO shall have the right to manufacture all of its requirements of HEPATITIS B and IL-2 outside the United States for the sale of LICENSED PRODUCTS outside the United States as of the CLOSING, notwithstanding the provisions of Paragraph 1.04 of this AGREEMENT. AMGEN shall provide ORTHO, within six (6) months after CLOSING, and thereafter as appropriate, all manufacturing information and

other assistance sufficient for ORTHO to manufacture HEPATITIS B and IL-2 outside the United States if a Manufacture and Supply Agreement between the parties outside the United States is not in effect six (6) months after CLOSING. For IL-2, such manufacturing information and other assistance shall not be supplied prior to the payments in Paragraph 5.01 (iii) of the TECHNOLOGY LICENSE AGREEMENT.

If ORTHO desires to establish a manufacturing facility for the manufacture of PRODUCTS in accordance with Paragraph 5.02 or Paragraph 5.03 of this AGREEMENT or under an agreement between ORTHO and KIRIN-AMGEN designated "Technology License Agreement" dated September 30, 1985, AMGEN shall diligently assist ORTHO in the establishment and start-up of said manufacturing facility, including providing ORTHO with manufacturing information reasonably sufficient for ORTHO to manufacture PRODUCTS. ORTHO shall reimburse AMGEN at its then- effective monthly billing rate and any related out of pocket travel and lodging expenditures outside the United States for its efforts in assisting ORTHO in establishing said facility.

AMGEN hereby warrants and represents that it shall faithfully and diligently deliver to any manufacturing facility provided for in this Article 5 such quantities of PRODUCT ORGANISMS as are reasonably required by ORTHO, or its designated AFFILIATE, to manufacture LICENSED PRODUCTS. Such deliveries shall be made within thirty (30) days after written request by ORTHO to AMGEN at no expense to ORTHO, or its designated AFFILIATE, and shall be made by AMGEN from time to time during the term of this AGREEMENT as the need arises to replenish PRODUCT ORGANISMS.

All confidential information transmitted by either party to the other including all confidential information developed pursuant to this AGREEMENT, shall be identified with reference to this AGREEMENT and the receiving party shall, while this AGREEMENT is in effect and for three (3) years after termination thereof, make no use of this information other than in furtherance of this AGREEMENT and shall use the same efforts

to keep secret and prevent the disclosure of such information to parties other than its agents, officers, employees and representatives authorized to receive such information as it would its own confidential information except for such confidential information that,

(a) was known to the receiving party at the time of its disclosure and not previously subject to any obligation of confidentiality at the time of its disclosure;

(b) was generally available to the public or was otherwise part of the public domain at the time of its disclosure;

(c) became generally available to the public or became otherwise part of the public domain after its disclosure and other than through any act or omission of the receiving party in breach of this AGREEMENT; or

(d) became known to the receiving party after its disclosure (i) from a source other than the disclosing party (including from independent development by the receiving party), (ii) other than from a third party who had an obligation to the disclosing party not to disclose such information to others, and (iii) other than under an obligation of confidentiality.

Each receiving party may disclose any of the LICENSED KNOW-HOW and confidential information to the extent

such disclosure is necessary to comply with applicable laws or regulations, or to make and use LICENSED PRODUCTS in accordance with the terms of this AGREEMENT.

AMGEN agrees to faithfully continue, at its expense, the prosecution of all patent applications listed in Exhibit D within the LICENSED FIELD and, when necessary, to file and prosecute additional applications covering patentable technology relating to EPO, HEPATITIS B and IL-2 in the United States and other countries throughout the world. AMGEN shall have the duty and responsibility to pay all taxes and annuities on all applications and patents listed in Exhibit D within the LICENSED FIELD of the AGREEMENT. AMGEN shall provide ORTHO with copies of all applications listed in Exhibit D within the LICENSED FIELD, all future-filed applications and all correspondence with Patent Offices applicable thereto. If AMGEN chooses not to prosecute and maintain certain applications/patents under this AGREEMENT, AMGEN shall so notify ORTHO and ORTHO shall, in its sole discretion, decide whether to assume the responsibility and

expenses therefore for each such application or patent. In that event, the applications/patents for which ORTHO shall assume responsibility shall be assigned to ORTHO. If ORTHO so assumes responsibility, it shall be entitled to recover all its expenses (including attorneys' fees) from the sale of LICENSED PRODUCTS in the country prior to any payments under Article 4 of this AGREEMENT.

AMGEN shall give ORTHO the opportunity to review, through their patent counsel, the status of all pending patent applications listed in Exhibit D and shall keep ORTHO informed of the status of their prosecution, including such Patent Office proceedings as interferences, reexamination, oppositions and requests for patent term extension under the Act. Notwithstanding the above, AMGEN shall have sole responsibility for all decisions in connection with the filing and prosecution of all patent applications and the maintenance of all patents. AMGEN shall take all appropriate actions to maximize the benefits for both AMGEN and ORTHO with respect to any patent term restoration and/or regulatory exclusivity that may be available in connection with any LICENSED PATENT or LICENSED PRODUCT.

(i) If, as a result of the manufacture, use and sale of LICENSED PRODUCTS, ORTHO is sued for patent infringement or threatened with such a lawsuit or other action by a third party, then ORTHO shall actively consult with AMGEN in its attempts to resolve same. If the settlement of a lawsuit or threatened lawsuit or other action requires any payments to a third party, then ORTHO and AMGEN shall share said payments on an equal basis.

(ii) If, as a result of the manufacture, use and sale of any LICENSED PRODUCT, ORTHO is sued for patent infringement or threatened with such a lawsuit or other action and as a result of same ORTHO is prevented from the commencement of marketing said LICENSED PRODUCT, then provided that one or more other LICENSED PRODUCTS are being marketed or in the future are marketed or said LICENSED PRODUCT is being marketed in another country or in the future is marketed, ORTHO shall be entitled to recover the following in the manner provided in Paragraph 4.01 hereof from the sale of any LICENSED PRODUCT:

(a) the equivalent of up to 100% of the research and development payments made by ORTHO to AMGEN under Paragraph 3.02 of the TECHNOLOGY LICENSE AGREEMENT for said LICENSED PRODUCT; and (b) the equivalent of up to 50% of the OUTSIDE RESEARCH PAYMENTS directly related to the LICENSED PRODUCT incurred by ORTHO in accordance with ARTICLE 4 of the TECHNOLOGY LICENSE AGREEMENT

(iii) If, as a result of the manufacture, use and sale of any LICENSED PRODUCT, ORTHO is sued for patent infringement or threatened with such a lawsuit or other action in any country, and as a result of same, ORTHO is prevented from further marketing said PRODUCT in said country then if

(A) said PRODUCT has been on sale less than three (3) years in said country and provided that one or more other LICENSED PRODUCTS are being marketed in any country or in the future are marketed or said LICENSED PRODUCT is being marketed in another country or in the future is marketed, ORTHO shall be entitled to recover the following in the manner provided in Paragraph

4.01 hereof from the sale of any LICENSED PRODUCTS:

(a) the equivalent of up to 100% of the research and development payments made by ORTHO to AMGEN under paragraph 3.02 of the TECHNOLOGY LICENSE AGREEMENT and this AGREEMENT for said LICENSED PRODUCT; and
(b) the equivalent of up to 50% of the OUTSIDE RESEARCH PAYMENTS directly related to the LICENSED PRODUCT incurred by ORTHO in accordance with ARTICLE 4 of the TECHNOLOGY LICENSE AGREEMENT and this AGREEMENT.

(B) said PRODUCT has been on sale more than three (3) years in said country, there shall be no recovery by ORTHO under this Paragraph 8.01 from AMGEN.

(iv) In connection with any lawsuit or threatened lawsuit or other action as set forth in (i), (ii) or (iii) above, ORTHO and AMGEN shall share on an equal basis all reasonable expenses (including attorneys' fees) incurred therewith.

Either party shall promptly notify the other party of any infringement of any LICENSED PATENTS; misappropriation of a trade secret or declaration of an interference proceeding relating to LICENSED PATENTS or LICENSED KNOW-HOW, and shall provide the other party with all available evidence relating thereto. AMGEN and ORTHO shall then consult with each other as to the best manner in which to proceed. AMGEN shall have the right, but not the obligation, to bring, defend and maintain any appropriate suit or action. If AMGEN requests ORTHO to join AMGEN in such suit or action and ORTHO agrees to do so, ORTHO shall execute all papers and perform such other acts as may be reasonably required and may, at its option, be represented by counsel of its choice. AMGEN shall pay ORTHO its reasonable expenses (including its attorney's fees) in connection with any such suit or action. Should AMGEN lack standing to bring any such action, then AMGEN may cause ORTHO to do so upon first undertaking to indemnify and hold ORTHO harmless (to the extent permissible by law) from all consequent liability and to promptly reimburse all reasonable expense (including attorney fees) stemming therefrom. In the event AMGEN fails to take action with respect to such matters within a reasonable period, not more than six (6) months, following receipt of such notice

and evidence, ORTHO shall have the right, but not the obligation, to bring, defend and maintain any appropriatesuit or action. If ORTHO finds it necessary to join AMGEN in such suit or action, AMGEN shall execute all papers and perform such other acts as may be reasonably required and may, at its option, be represented by counsel of its choice. ORTHO shall pay to AMGEN the reasonable expenses of AMGEN (including its attorney's fees) in connection with any such suit or action. Absent an agreement between the parties to jointly bring any action or suit hereunder and share the expenses thereof, any amount recovered in any such action or suit shall be retained by the party bearing its expenses thereof.

This AGREEMENT shall come into effect on the EFFECTIVE DATE and shall remain in effect unless the parties mutually agree in writing to terminate, or until termination occurs pursuant to paragraph 9.02 below.

In the event that AMGEN or ORTHO (the "Defaulting party") shall:

a) default in a material obligation hereunder, including failure to make any payments, and fail to remedy such default within 60 days after notice of such default by the Non-Defaulting party; or

b) become bankrupt or insolvent, or file a petition in bankruptcy or make a general assignment for the benefit of creditors or otherwise acknowledge insolvency or be adjudged bankrupt; or

c) go or be placed in a process of complete liquidation other than for an amalgamation or reconstruction; or

d) suffer the appointment of a receiver for any substantial portion of its business who shall not be discharged within 60 days after such receiver's appointment,then, and in any such event, the Non-Defaulting party, at its option, may terminate its obligations to, and the rights of, the Defaulting party under the license granted in this AGREEMENT upon 30 days written notice to the Defaulting party, which termination shall be effective as of the occurrence of the event giving rise to the option to terminate.

Upon termination of this AGREEMENT as a result of AMGEN's default under Paragraph 9.02, ORTHO shall have the right, but not the obligation, to make, use and sell LICENSED PRODUCTS under LICENSED PATENTS and LICENSED KNOW- HOW, and all of ORTHO's payment obligations under this AGREEMENT shall continue, provided however, that ORTHO shall have the right to off-set against any such payments any and all expenses incurred as a result of AMGEN's default.

Notwithstanding the termination of a party's obligations to or the rights of the Defaulting party under this Agreement in accordance with the provisions of Paragraph 9.02, the provisions of Article 6 shall survive such termination and continue in full force and effect for a period of not more than three (3) years following termination.

Nothing herein shall limit any remedies available to either party at law or in equity for the default of the other party under Paragraph 9.02 (b),
(c) or (d). Termination shall

not excuse the obligation of either party to pay money due to the other party.

                              ARTICLE 10
                              ----------

                       MISCELLANEOUS PROVISIONS
                       ------------------------

10.01     NO INFRINGEMENT
          ---------------

          AMGEN is not aware of (i) any third party rights upon which, in

its opinion, this AGREEMENT will infringe, or (ii) any claimed infringement against AMGEN with respect to LICENSED PRODUCTS.

The parties hereto shall use reasonable and practical efforts to obtain any and all consents, approvals, orders or authorizations required to be obtained with respect to the provisions hereof.

All notices, requests, demands and other communications required or permitted to be given under this AGREEMENT shall be in writing and shall be mailed to the party to whom notice is to be given, by telex or facsimile, and confirmed by first class mail, registered or certified, return receipt requested, postage

prepaid, and properly addressed as follows (in which case such notice shall be deemed to have been duly given on the third (3rd) day following the date of such sending):

Amgen
1900 Oak Terrace Lane
Thousand Oaks, CA 91320-1789 U.S.A.

Telex No. 4994440 (AMGEN)

Attn: Corporate Secretary

with a copy to:

Cooley, Godward, Castro,
Huddleson & Tatum
5 Palo Alto Square, Suite 400 Palo Alto, CA 94306
U.S.A.

Telex No. 910-372-7370 COOLEY SFO
380816 COOLEY PA EASYLINK
Attn: Alan C. Mendelson, Esq.

President
Ortho Pharmaceutical Corporation U.S. Route 202
Raritan, New Jersey 08869 U.S.A.

with a copy to:

Johnson & Johnson
One Johnson & Johnson Plaza New Brunswick, N.J. 08933-7033 U.S.A.
Telex No. 844-481
Attn: General Counsel

Any party by giving notice to the other in the manner provided above may change such party's address for purposes of this Paragraph 10.03.

This AGREEMENT (together with all Exhibits attached hereto) constitutes the full and complete agreement and understanding between the parties hereto and shall supersede any and all prior written and oral agreements including but not limited to any "Agreement in Principle" concerning the subject matter contained herein. This AGREEMENT may not be modified or amended nor may any provision hereof be waived without a written instrument executed by AMGEN and ORTHO.

No failure or delay by any party to insist upon the strict performance of any term, condition, covenant or agreement of this AGREEMENT, or to exercise any right, power or remedy hereunder or consequent upon a breach hereof shall constitute a waiver of any such term, condition, covenant, agreement, right, power or remedy or of any such breach or preclude such party from exercising any such right, power or remedy at any later time or times.

Headings in this AGREEMENT are included herein for the convenience of reference only and shall not constitute a part of this AGREEMENT for any purpose.

In the event any dispute should arise between the parties hereto as to the validity, construction, enforceability or performance of this AGREEMENT or any of its provisions, such dispute shall be settled by arbitration. Said arbitration shall be conducted at Chicago, Illinois, in accordance with the rules then obtaining of the American Arbitration Association with a panel of three (3) arbitrators. The rules of discovery then pertaining to the courts of law in such jurisdiction shall apply thereto. The unsuccessful party to such arbitration shall pay to the successful party all costs and expenses, including reasonable attorneys' fees incurred therein by such successful party.

This AGREEMENT shall be construed in accordance with the internal laws, and not the law of conflicts, of the State of California applicable to agreements made and to be performed in that state.

This AGREEMENT shall be binding upon and inure to the benefit of the parties hereto, their successors and assigns.

This AGREEMENT may be executed in one or more counterparts by the parties hereto. All counterparts shall be construed together and shall constitute one AGREEMENT.

Each party agrees to perform any further acts and execute and deliver any and all further documents and/or instruments which may be reasonably necessary or desirable to carry out the provisions of this AGREEMENT.

If for any reason any clause or provision of this AGREEMENT, or the application of any such clause or provision in a particular context or to a particular situation, circumstance or person, should be held unenforceable, invalid or in violation of law by any court or other tribunal, then the application of such clause or provision in contexts or to situations, circumstances or persons other than that in or to which it is held unenforceable, invalid or in violation of law shall not be affected thereby, and the remaining clauses and provisions hereof shall nevertheless remain in full force and effect, provided however, that any provisions so held unenforceable, invalid or in violation of law shall be rewritten by the parties in a lawful manner to reflect its intent.

Each of the party hereto acknowledges and agrees (i) that no representation or promise not expressly contained in this AGREEMENT has been made by the other party hereto or by any of its agents, employees, representatives or attorneys; (ii) that this AGREEMENT is not being entered into on the basis of, or in reliance on, any promise or representation, expressed or implied, covering the subject matter hereof, other than those which are set forth expressly in this AGREEMENT; and (iii) that

each party has had the opportunity to be represented by counsel of its own choice in this matter, including the negotiations which preceded the execution of this AGREEMENT.

Neither party shall assign its rights or obligations under this AGREEMENT without prior written consent of the other party, provided however, ORTHO may assign its rights and obligations by sublicensing its AFFILIATES or third parties as provided in Paragraph 2.02 hereinabove.

AMGEN and ORTHO shall not be deemed to be partners, joint venturers or each other's agents, and neither shall have the right to act on behalf of the other except as expressly provided hereunder or otherwise expressly agreed to in writing.

Neither party shall be liable for failure to perform as required by any provision of this AGREEMENT where such failure results from a force majeure beyond such party's control. In the event of any delay attributable to a force majeure, the time for performance affected thereby shall be extended for a period equal to the time lost by reason of the

delay. If, as a result of a force majeure, AMGEN is unable to manufacture LICENSED PRODUCTS, for the purposes of this AGREEMENT, then, ORTHO shall have the right, but not the obligation, to manufacture said LICENSED PRODUCTS and AMGEN shall provide ORTHO any assistance, information and/or know-how required by ORTHO to manufacture such LICENSED PRODUCTS.

Each party to this AGREEMENT shall be responsible for its own acts relating to the manufacture and use of LICENSED PRODUCTS and neither shall indemnify the other for costs, expenses, liability, damages and claims for any injury or death to persons or damage to or destruction of property or other loss arising out of or in connection with any LICENSED PRODUCTS made or used by either party .

In the absence of specific agreement between the parties, neither party shall originate any publicity, news release or other public announcement, written or oral, whether to the public press, to stockholders or otherwise, relating to this AGREEMENT, to any amendment hereto as to performance hereunder, save only such announcement as in the opinion of legal counsel to the party making such announcement is required

by law or practice to be made. The party making any such announcement shall give the other party an opportunity to review the form of the announcement before it is made. Routine references to this AGREEMENT and the arrangements hereunder without undue frequency and without emphasis shall be allowed in the usual course of business provided that notice of such use is given to the other party. If, in the opinion of ORTHO, excessive use occurs, such references shall be discontinued after discussion among the parties.

AMGEN and ORTHO shall each bear and pay for their respective costs and expenses regarding the negotiation and preparation of this AGREEMENT and all documents, instruments and agreements related thereto.

10.21.1 The parties hereby agree that any Technical Data (as that term is defined in Section 379.1 of the U.S. Export Administration Regulations) exported from the United States pursuant to this AGREEMENT and any other related agreements, and any direct product thereof, shall not be shipped, either directly or indirectly, to Afghanistan or any Group P, Q, S, W, Y or Z Countries (as specified in Supplement

No. 1 to part 370 of the Export Administration Regulations), unless (i) separate specific authorization to reexport such Technical Data or such direct products is provided by the U.S. Office of Export Administration or (ii) such specific authorization is not required pursuant to part 379.8 of the U.S. Export Administration Regulations. The parties further agree that the export and reexport of commodities pursuant to this AGREEMENT and any other related agreements shall be subject to the licensing requirements of the U.S. Export Regulations.

10.21.2 In the event that a specific authorization of, or a validated license from, a government other than that of the exporting party is required, AMGEN and ORTHO each agree that the party within the jurisdiction of such other government shall, upon the request of the party proposing to make the export, use reasonable efforts to obtain, as expeditiously as applicable, the requisite authorization or license.

ORTHO shall mark or cause to be marked all LICENSED PRODUCTS sold under this AGREEMENT, in accordance with any applicable laws and regulations.

IN WITNESS WHEREOF, the undersigned have caused this AGREEMENT to be executed by their duly authorized

representatives in the manner legally binding upon them on the first date written above.

AMGEN
a California corporation

/s/ Robert D. Weist                         By /s/ George B. Rathmann
---------------------                          ----------------------
   Witness                                     George B. Rathmann, President


                                            ORTHO PHARMACEUTICAL CORPORATION
                                            a New Jersey corporation


/s/ Dennis N. Longstreet                    By /s/ Gary V. Parlin
-----------------------                        ------------------
   Witness                                      Gary V. Parlin, President

NH\\2\\ -   ala pro pro arg leu ile cys asp ser arg val leu glu arg try
                                             Y*
            leu leu glu ala lys glu ala glu asn ile thr thr gly cys ala

                                         Y
            glu his cys ser leu asn glu asn ile thr val pro asp thr lys

            val asn phe tyr ala trp lys arg met glu val gly gln gln ala
            val glu val trp gln gly leu ala leu leu ser glu ala val leu
                                         Y
            arg gly gln ala leu leu val asn ser ser gln pro trp glu pro

            leu gln leu his val asp lys ala val ser gly leu arg ser leu
            thr thr leu leu arg ala leu gly ala gln lys glu ala ile ser
            pro pro asp ala ala ser ala ala pro leu arg thr ile thr ala
            asp thr phe arg lys leu phe arg val tyr ser asn phe leu arg
            gly lys leu lys leu tyr thr gly glu ala cys arg thr gly asp
            arg - COOH

* 'Y' designates N-linked glycosalation site.

NH\\2\\-Met      glu asn ile thr ser gly phe leu gly pro leu leu val leu gln
                 ala gly phe phe leu leu thr arg ile leu thr ile pro gln ser
                 leu asp ser trp trp thr ser leu asn phe leu gly gly ser pro
                 val cys leu gly gln asn ser gln ser pro thr ser asn his ser
                 pro thr ser cys pro pro ile cys pro gly tyr arg trp met cys
                 leu arg arg phe ile ile phe leu phe ile leu leu leu cys leu
                 ile phe leu leu val leu leu asp tyr gln gly met leu pro val
                 cys pro leu ile pro gly ser thr thr thr ser thr gly pro cys
                 lys thr cys thr thr pro ala gln gly asn ser met phe pro ser
                 cys cys cys thr lys pro thr asp gly asn cys thr cys ile pro
                 ile pro ser ser trp ala phe ala lys tyr leu trp gly trp ala
                 ser val arg phe ser trp leu ser leu leu val pro phe val gln
                 trp phe val gly leu ser pro thr val trp leu ser ala ile trp
                 met met trp tyr trp gly pro ser leu tyr ser ile val ser pro
                 phe ile pro leu leu pro ile phe phe cys leu trp val tyr ile
                 COOH

The chemical structure of recombinant-methionyl human interleukin 2
[alanine 125] is best described by its amino acid sequence which is depicted below:
NH\\2\\-Met-ala pro thr ser ser ser thr lys lys thr g1n leu gln leu glu his leu leu leu asp leu gln met ile leu asn gly ile asn asn tyr lys asn pro lys leu thr arg met leu thr phe lys phe tyr met pro lys lys ala thr glu leu lys his leu gln cys leu glu glu glu leu lys pro leu glu glu val leu asn leu ala gln ser lys asn phe his leu arg pro arg asp leu ile ser asn ile asn val ile val leu glu leu lys gly ser glu thr thr phe met cys glu tyr ala asp glu thr ala thr ile val glu phe leu asn arg trp ile thr phe ala glu ser ile ile ser thr leu thr COOH

ERYTHROPOIETIN
--------------

 Docket           Inventor(s)                     Title                           Country         S.N.             Filing
   No.                                                                                                              Date
-------------------------------------------------------------------------------------------------------------------------------
  155             F. Lin               Recombinant Methods and                       U.S.       561,024            12/13/83
                                       Materials Applied to Micro-
                                       bial Expression of Erythro-
                                       poietin

  155-CIP-1       F. Lin               Recombinant Methods and                       U.S.       582,185             2/21/84
                                       Materials Applied to Micro-
                                       bial Expression of Erythro-
                                       poietin

  155-CIP-2       F. Lin               Recombinant Methods and                       U.S.       655,841             9/28/84
                                       Materials Applied to Micro-
                                       bial Expression of Erythro-
                                       poietin

  155-CIP-3       F. Lin               Production of Erythropoietin                  U.S.       675,298            11/30/84

  132             J. Egrie             ATCC HB8209 - Its Monoclonal                  U.S.       463,724              2/4/83
                                       Antibody to Erythropoietin
                                       ATCC HB8209/Budapest

  190             P. Lai               Protein Purification                          U.S.       747,119             6/20/85
                  T. Strickland

HEPATITIS B
-----------

Docket              Inventor(s)                Title                          Country         S.N.              Filing
  No.                                                                                                            Date
---------------------------------------------------------------------------------------------------------------------------
l06-C              G. Bitter          Expression of Exogenous                 U.S.           748,712            6/26/85
                                      Polypeptides and Poly-                                 (A continuation
                                      peptide Products Including                              of S.N. 412,707
                                      Hepatitis B Surface Antigen                             filed 8/30/82
                                      in Yeast

204                J. Fieschko        Fermentation Methods for                U.S.             *                8/15/85
                                      Hepatitis Vaccine Produc-
                                      tion

201                H. Levine          Lysis Method and Buffer for             U.S.             *                8/15/85
                                      Extraction of HBsAg from
                                      Yeast Cells

*Information not yet available

INTERLEUKIN II
--------------

Docket             Inventor(s)               Title                       Country            S.N.             Filing
  No.                                                                                                        Date
------------------------------------------------------------------------------------------------------------------------
138              L. Souza            Microbial Expression of             U.S.               521,967          8/10/83
                 Y. Stabinsky        Interleukin II

138-CIP-1        L. Souza            Microbial Expression of             U.S.               635,941           8/3/84
                 Y. Stabinsky        Interleukin II

                                                                         Canada             460,745          8/10/84
                                                                         Israel             72643            8/10/84
                                                                         Japan              Via PCT US84/
                                                                                            01252             8/9/84
                                                          EPO            designating        84.109537.5      8/10/84
                                                                         Austria
                                                                         Belgium
                                                                         France
                                                                         Germany
                                                                         Italy
                                                                         Luxembourg
                                                                         Netherlands
                                                                         Sweden
                                                                         Switzerland
                                                                         Liechtenstein
                                                                         United Kingdom

-CIP-2           L. Souza            Microbial Expression of             U.S.               717,334          3/29/85
                 Y. Stabinsky        Interleukin II

Exhibit 10.5

THIS TECHNOLOGY LICENSE AGREEMENT entered into this 30th day of September, 1985, by and between AMGEN, a California corporation having offices at 1900 Oak Terrace Lane, Thousand Oaks, California 91320-1789 (said corporation hereinafter referred to as "AMGEN") and ORTHO PHARMACEUTICAL CORPORATION, a New Jersey corporation having offices at U.S. Route 202, Raritan, New Jersey 08869, (said corporation hereinafter referred to as "ORTHO").

WHEREAS, AMGEN represents that it has developed and is continuing to develop technology relating to certain genetically-engineered health-care products and processes for their manufacture;

WHEREAS, AMGEN further represents that it is the owner of patent applications by assignment and unpatented know-how covering said genetically- engineered health-care products;

WHEREAS, ORTHO and AFFILIATES are engaged in the research, development and sale of health care products throughout the world and wish to obtain certain rights to such technology and to such patents and patent applications;

NOW, THEREFORE, in consideration of the premises and the mutual covenants herein recited, and other good and valuable considerations, the receipt of which is acknowledged, it is agreed as follows:

For the purposes of this Agreement, the terms set forth in this Article I shall have the following meanings:

1.01 "ACT" shall mean the Drug Price Competition and Patent Term Restoration Act of 1984 and equivalent subsequent legislation in the United States and in any foreign country.

1.02 "AFFILIATE" shall mean and include (i) any company which owns or controls directly or indirectly at least forty percent (40%) of the voting stock of ORTHO and (ii) any other company at least forty percent (40%) of whose voting stock is

owned or controlled directly or indirectly by such owning or controlling company, and (iii) any other company with which ORTHO or such an owning, owned, controlling or controlled company has a co-marketing, joint venture or distribution agreement for pharmaceuticals outside the United States. The term "ORTHO" shall also mean and include any AFFILIATE wherein the inclusion of same shall be warranted under the provisions of the AGREEMENT.

1.03 "AGREEMENT" shall mean this Technology License Agreement.

1.04 "CLINICAL EFFICACY" shall mean the following with respect to each of EPO, HEPATITIS B AND IL-2:

    PRODUCT                               CLINICAL EFFICACY
-----------------                   -----------------------------

EPO                                 A statistically significant
                                    increase in hematocrit in patients
                                    with anemia secondary to
                                    compromised renal function,
                                    including patients on dialysis.
                            -3-

HEPATITIS B                         Seroconversion (anti HBs Ag- to +
                                    in normal adults) in incidence and
                                    titer comparable to existing
                                    Hepatitis B vaccine.

IL-2                                Laboratory evidence in terms of
                                    increased lymphocytes or killer
                                    cell activity plus clinical and
                                    statistical evidence of favorable
                                    activity in at least one placebo
                                    controlled study.

1.05 "CLOSING" shall occur when,:

(a) AMGEN shall execute and deliver to ORTHO this AGREEMENT and a Product License Agreement to market LICENSED PRODUCTS;

(b) ORTHO shall execute and deliver to AMGEN this AGREEMENT and the Product License Agreement and shall further deliver, as provided in paragraph 5.01(i), to AMGEN the amount

of $4,000,000 in the form of a certified or cashier's check, representing the aggregate initial royalty payments;

(c) ORTHO shall deliver to AMGEN the amount of any royalty payments under Paragraph 5.01 (ii) hereinafter earned by AMGEN on account of any IND approvals regarding the PRODUCTS received prior to the CLOSING; such amount to be paid in the form of a certified or cashier's check;

(d) The following approvals shall have been obtained: (i) the Executive Committee or the Board of Directors of AMGEN shall have authorized AMGEN's participation in, and its execution and delivery of, this AGREEMENT, including the Exhibits attached hereto and a Product License Agreement; and (ii) the Board of Directors of ORTHO shall authorize ORTHO's participation in, and its execution and delivery of, this AGREEMENT, including the Exhibits attached hereto and a Product License Agreement.

1.06 "EFFECTIVE DATE" shall mean the date on which this AGREEMENT takes effect which is the date first written above.

1.07 "EPO" shall mean the erythropoietin as described in Exhibit A.

1.08 "FIELD OF ACTIVITY" shall mean the areas of research, development, and regulatory approval of the PRODUCTS for all human uses, except diagnostics and in the case of EPO, dialysis, and shall include but not be limited to, toxicology, dosage studies, model studies, clinical studies, product registration and government approvals.

1.09 "FDA" shall mean the United States Food & Drug Administration and foreign counterparts thereof.

1.10 "HEPATITIS B" shall mean the recombinant yeast-derived hepatitis B surface antigen vaccine as described in Exhibit B and any other hepatitis B vaccine development resulting from the Development Program hereunder or a supplement of said Program.

1.11 "IL-2" shall mean the recombinant-methionyl human interleukin 2[alanine 125] as described in Exhibit C.

1.12 "IND" shall mean a Notice of Claimed Investigational Exemption for a New Drug and all supplements under the United States Food, Drug & Cosmetic Act (FDA Act) and foreign counterparts thereof for the LICENSED PRODUCTS.

1.13 "LICENSED FIELD" shall mean and include:

(a) with respect to EPO: all indications for human use except dialysis and diagnostics;

(b) with respect to HEPATITIS B and IL-2: all indications for human use except diagnostics.

1.14 "LICENSED KNOW-HOW" shall mean and include any and all data, information, technology or special ability on the part of AMGEN including, but not limited to, processes, techniques, methods, products, materials and compositions relating to the research, development, manufacture, testing or use of EPO, HEPATITIS B and IL-2, now owned or controlled by AMGEN or that shall be owned or controlled by AMGEN during the term of this AGREEMENT, which is reasonably related to LICENSED PATENTS and LICENSED PRODUCTS for use in the LICENSED FIELD; and which is useful in seeking approval from appropriate governmental health authorities to market LICENSED PRODUCTS and which includes AMGEN's INDs and NDAs and all supplements thereto covering PRODUCTS in the LICENSED FIELD.

1.15 "LICENSED PATENTS" shall mean:

(a) any patent listed in Exhibit D;

(b) any patent application listed in Exhibit D, and any division, continuation, or continuation-in-part of any such

application, and any patent which shall issue based on such application, division, continuation or continuation-in-part;

(c) any patent which is a reissue or extension of or a patent of addition to, any patent defined in (a) or any application maturing into a patent defined in (b) above;

(d) any patent application or patent corresponding to any patent application or patent identified in (a), (b) or (c) above which is hereafter filed or issued in any country; and

(e) any patent application related to or based on any of AMGEN's technical information developed in the LICENSED FIELD during the performance of this AGREEMENT, and any division, continuation or continuation-in-part of any such application; and any patent which shall issue based on such application, division, continuation or continuation-in-part; and any patent which is a reissue or extension of, or a patent of addition to, any such patent.

1.16 "LICENSED PRODUCTS" shall mean and include any PRODUCTS for use in the LICENSED FIELD (i) which are within the scope of a VALID LICENSED CLAIM of a LICENSED PATENT; or (ii) whose use is within the scope of a VALID LICENSED CLAIM of a LICENSED PATENT; or (iii) which are manufactured or packaged within the scope of a VALID LICENSED CLAIM of a LICENSED PATENT; or (iv) which utilize any LICENSED KNOW-HOW.

1.17 "LICENSED TERRITORY" shall mean and include:

(a) with respect to EPO: the United States, its territories and possessions, including the Commonwealth of Puerto Rico;

(b) with respect to HEPATITIS B: the entire world except China;

(c) with respect to IL-2: the entire world.

1.18 "MAJOR COUNTRY" shall mean any of the following: United States, United Kingdom, West Germany, France and Japan.

1.19 "NDA" shall mean a New Drug Application and/or a Product License Application and all supplements filed pursuant to the requirements of the FDA, including all documents, data and other information concerning LICENSED PRODUCTS which are necessary for, or included in, FDA approval to market LICENSED PRODUCTS and foreign counterparts thereof of NDAs.

1.20 "OUTSIDE RESEARCH PAYMENTS" shall mean amounts paid by ORTHO for clinical testing to an individual or individuals or to an entity other than AMGEN or ORTHO or an AFFILIATE for purposes of independent evaluation of any of the PRODUCTS, which

data shall be used by ORTHO and/or AMGEN in filing NDAs or other registrations regarding the PRODUCTS.

1.22 "PHASE II" shall mean that portion of the NDA approval process which provides for the initial trials of a LICENSED PRODUCT on a limited number of patients for specific disease control or prophylaxis purposes. PHASES I and II may overlap and, when indicated, may require additional animal data before they can be completed. Such animal tests are required to be designed to take into account the expected duration of administration of LICENSED PRODUCTS to human beings, the age groups, and physical status.

1.23 "PRODUCTS" shall mean IL-2, HEPATITIS B, and EPO for all human uses in the LICENSED FIELD. Wherever a reference is made to the "PRODUCT" or to the "PRODUCTS", the reference shall

apply to each of IL-2, HEPATITIS B and EPO severally, unless the context shall indicate otherwise. Whenever the provisions of this AGREEMENT differ in application to any of IL-2, HEPATITIS B or EPO, then such product shall be identified separately, rather than being referred to as a "PRODUCT".

1.24 "PRODUCT ORGANISMS" shall mean and include any and all organisms developed or acquired by AMGEN, the uses of which are licensed to ORTHO pursuant to this AGREEMENT and which have been genetically engineered to produce biologically active LICENSED PRODUCTS, including any and all improvements thereon.

1.25 "VALID LICENSED CLAIM" shall mean and include a claim in an issued LICENSED PATENT which has not lapsed or become abandoned and which claim has not been declared invalid by an unreversed or unappealable decision or judgment of a court of competent jurisdiction.

(a) AMGEN hereby grants to ORTHO but not AFFILIATES, except as hereinafter provided, an exclusive license to make in

one location, have made, and use LICENSED KNOW-HOW, LICENSED PATENTS and LICENSED PRODUCTS in the LICENSED TERRITORY in the LICENSED FIELD for use in research and in the development and regulatory approval of LICENSED PRODUCTS.

(b) AMGEN, having received the consent of Kirin Brewery Co., Ltd., hereby grants to ORTHO but not AFFILIATES, an exclusive license, except as against AMGEN's rights under this AGREEMENT in the LICENSED TERRITORY, to make EPO in one location in the United States, for use and sale outside the LICENSED TERRITORY but not including China and Japan. AMGEN shall provide to ORTHO all information and any assistance and know-how required for ORTHO to achieve the purposes of this paragraph at the earlier of the demonstration of CLINICAL EFFICACY of EPO or the completion of PHASE II studies as set forth in an agreement between ORTHO and KIRIN-AMGEN designated "Technology License Agreement" dated September 30, 1985.

ORTHO may, with prior written notice to AMGEN, sublicense LICENSED PATENTS, LICENSED KNOW-HOW and LICENSED PRODUCTS under this AGREEMENT (i) to any AFFILIATE or third party, to use LICENSED PRODUCTS as provided in this AGREEMENT; and (ii) to any one controlled AFFILIATE to make in one location and use LICENSED PRODUCTS as provided in this AGREEMENT. If

ORTHO requests the right to sublicense one additional controlled AFFILIATE to make in one location and use LICENSED PRODUCTS as provided in this AGREEMENT, AMGEN shall not unreasonably withhold its consent thereto.

In the event of sublicensing as in Paragraph 2.02, ORTHO shall assure AMGEN that this AGREEMENT shall apply to such AFFILIATE or third party sublicensee, and such AFFILIATE or third party sublicensee shall deliver to AMGEN a written promise to comply with the terms of this AGREEMENT to the extent that such terms are applicable. ORTHO shall guarantee the due and punctual performance of any and all responsibilities under this AGREEMENT as applied to such AFFILIATE or third party sublicensee.

As a substitute for a sublicense, AMGEN shall, if ORTHO so requests, enter into a separate agreement with any AFFILIATE of ORTHO granting a license in accordance with the provisions of this AGREEMENT. Such agreement shall incorporate all of the terms of this AGREEMENT to the extent that they are applicable. ORTHO shall guarantee the due and punctual

performance of any and all responsibilities by the AFFILIATE under such separate agreement.

AMGEN warrants and represents that it has the full right and power to grant the license set forth in Paragraph 2.01 of this Article 2 and that there are no outstanding agreements, assignments or encumbrances in existence inconsistent with the provisions of this AGREEMENT including, without limitation as to generality, any obligations to governmental agencies or private foundations resulting from acceptance of research grant monies, or otherwise.

AMGEN and ORTHO hereby agree to conduct a Development Program, as set forth below.

(a) AMGEN and ORTHO shall meet promptly, after execution of the AGREEMENT, to formulate an outline within thirty (30) days after execution of this AGREEMENT of research and development activities which shall be conducted by AMGEN until the formulation of a Development Plan. Within ninety (90)

days after execution of this AGREEMENT, the parties shall establish a detailed development plan for the Development Program ("Development Plan"). The Development Plan shall: (i) identify the technical problems involved and the general projects to be carried out regarding the PRODUCTS, (ii) estimate the personnel to be contributed by AMGEN and ORTHO for each project, and (iii) set forth a projected timetable for the work, including clinical testing, to be performed by AMGEN and ORTHO. The Development Plan shall include a General Outline of both PHASE I and PHASE II, identifying the investigator or investigators, the hospitals or research facilities where the clinical pharmacology will be undertaken, any expert committees or panels to be utilized, the maximum number of subjects to be involved, and the estimated duration of these early phases of investigation, AMGEN and ORTHO shall diligently conduct the projects set forth in the Development Plan and shall use reasonable efforts to reach the goals of the Development Program in their conduct of those projects. The parties shall prepare and supply to each other written reports of their respective progress under the Development Plan every three (3) months. The parties shall make appropriate revisions, if any, to the Development Plan every three (3) months.

(b) If any party desires, at any time, to modify the Development Plan, it shall notify the other party of the

modification. Routine-type or minor modifications to the Development Plan may be accomplished by communicating same to the other party. Any major modification or amendment to the Development Plan shall be considered by both parties in good faith and be mutually agreed upon.

(a) ORTHO shall pay monthly to AMGEN an amount calculated on the basis of the number of Scientists used by AMGEN in the Development Program at AMGEN's then-effective monthly billing rate per Scientist, which is $12,677 as of the date hereof. The monthly billing rate per scientist in this paragraph may be adjusted on an annual basis to reflect any changes in the actual monthly billing rate not to exceed the United States Consumer Price Index (CPI) for the previous calendar year. For purposes of this AGREEMENT, the term "Scientist" includes research scientists and research associates but excludes laboratory assistants. For HEPATITIS B, AMGEN will provide the research equivalent of sixteen (16) Scientist-years during the initial twenty-four (24) months of this AGREEMENT. For IL-2, AMGEN will provide the research equivalent of eight (8) Scientist- years during the initial twenty-four (24) months of this AGREEMENT. For EPO, upon reasonable notice and request by ORTHO, AMGEN will assign a

reasonable number of Scientists for whose work AMGEN shall be reimbursed monthly at its then-effective normal monthly billing rate. In addition, after the initial twenty-four (24) months of this AGREEMENT, AMGEN shall, upon reasonable notice from and request by ORTHO, assign to HEPATITIS B and/or IL-2 a reasonable number of Scientists for whose work AMGEN shall be reimbursed monthly at its then-effective normal monthly billing rate per Scientist.

(b) ORTHO shall pay for any contracted services identified in the Development Program including, but not limited to, clinical studies and consultant services.

(c) At the end of each calendar month, AMGEN shall submit a written statement containing reasonable detail to ORTHO setting forth the number of Scientist-months of work that it performed during such calendar month and any other related outside expenditures. After ORTHO has received such a statement and has had a reasonable period, not to exceed thirty (30) days to review it, ORTHO shall promptly pay AMGEN an amount equal to AMGEN's then-effective monthly billing rate times the Scientist-months involved in conducting projects under the Development Plan for such month, and any related out-of-pocket travel and lodging expenditures outside the United States. AMGEN shall notify ORTHO of any change in accordance with this

paragraph in writing at least thirty (30) days in advance of the proposed change.

AMGEN shall keep correct and complete records containing all information required for the determination of costs to be paid to it under this AGREEMENT for a period of not less than three (3) years after the performance of any services hereunder. AMGEN shall permit the books and records that it keeps pursuant to this Paragraph to be inspected and audited during reasonable business hours by an independent certified public accountant selected by ORTHO, to the extent necessary to verify such costs. The parties hereby acknowledge that any work that is to be performed by AMGEN for ORTHO under the Development Program shall be as an independent contractor, and that ORTHO shall not incur any obligations for the remuneration or other expenses (and relevant reporting obligations) of any employee of AMGEN by virtue of such employee's participation in the Development Program.

(a) For purposes of advancing the Development Program, AMGEN and ORTHO shall disclose to each other any information, including such technology as may be characterized

as inventive and appropriate for reduction to patent applications which shall be prepared and filed by the developing party's Patent Counsel and subsequently included in Exhibit D of this AGREEMENT, that each has relating to the FIELD OF ACTIVITY and which will be useful in furthering the goals of the Development Program. To further promote the purposes of the Development Program, each party shall actively collaborate with the other by disclosing on a regular and periodic basis, such technical, clinical and other information developed by such party that is pertinent to the progress of the Development Program. AMGEN and ORTHO each acknowledge that any technical and other information disclosed under this Paragraph 3.04 shall be considered LICENSED KNOW-HOW and further agree that any such technical, clinical and other information shall not otherwise be disclosed except as permitted by this AGREEMENT.

(b) To facilitate further effective commercial development, and registration of the PRODUCTS within the FIELD OF ACTIVITY, AMGEN shall, within reason, permit representatives of ORTHO to inspect its respective facilities, technical reports, memoranda and other documents, including but not limited to laboratory notebooks, directly relating to the Development Program, and to make copies of any and all such reports, memoranda and other documents; provided, however, that the rights hereunder shall not extend beyond the LICENSED

KNOW-HOW and shall be limited solely to information that has been actually used by AMGEN for the development of the PRODUCTS.

(c) Upon commencement of the Development Program, AMGEN agrees to supply ORTHO with sufficient technical information and assistance for ORTHO to be able to assess the progress of the work performed under the Development Plan during the course of the Development Program. Any technical information supplied by a party to the other hereunder shall remain confidential and shall thereafter be deemed a part of the LICENSED KNOW-HOW for purposes hereof.

AMGEN shall disclose to ORTHO on a continuing basis all such LICENSED KNOW-HOW including the contents of any AMGEN IND filed in the United States pursuant to the regulations of the FDA as is reasonably required for ORTHO to conduct PHASE I and PHASE II studies, clinical studies and obtain product registration of LICENSED PRODUCTS in the LICENSED TERRITORY and including specific details with respect to the manufacture of LICENSED PRODUCTS. With respect to information for the manufacture of LICENSED PRODUCTS not contained in INDs, AMGEN shall disclose same to ORTHO upon receipt of the payments set forth in Paragraph 5.01 (iii). Additionally, AMGEN shall promptly provide ORTHO with sufficient information necessary to

-20

satisfactorily assess the progress of its work with respect to the development of LICENSED PRODUCTS. ORTHO shall also provide AMGEN with sufficient information necessary to enable AMGEN to satisfactorily assess the progress of ORTHO's clinical testing and LICENSED PRODUCTS registration work.

3.06.1 If AMGEN, on the one hand, or ORTHO and/or its AFFILIATES and sublicensee(s), on the other hand, improve the PRODUCT ORGANISMS, and/or the LICENSED KNOW-HOW, or make LICENSED PRODUCTS or process improvements, all such improvements shall become part of the LICENSED KNOW-HOW and shall be promptly transferred and/or communicated to the other party in order to maintain parity among AMGEN, ORTHO and its AFFILIATES and sublicensees and by the provisions hereof shall be deemed to be a part of the LICENSED PATENTS or LICENSED KNOW-HOW as the case may be and licensed to AMGEN or ORTHO, as the case may be, on a royalty-free basis.

3.06.2 Notwithstanding any provision of this AGREEMENT, any technology and/or improvements developed by a party to this AGREEMENT and disclosed or licensed under this Article 3, shall be and remain the property of the developing party.

This Paragraph 3.06.2 shall survive any termination of this AGREEMENT.

AMGEN warrants that any vialed clinical PRODUCTS and/or PRODUCT ORGANISMS provided to ORTHO for use in accordance with the provisions of this AGREEMENT shall conform with the description and specifications set forth in the appropriate AMGEN IND or supplement thereof and shall be suitable for use as set forth in said IND. AMGEN expressly disclaims all other warranties, expressed or implied, including without limitation warranties of merchantability or fitness for a particular purpose with respect to the vialed clinical PRODUCTS and/or PRODUCT ORGANISMS furnished by AMGEN to ORTHO hereunder.

AMGEN shall, as soon as practicable and at its own expense, conduct the necessary studies and testing and prepare and file an IND for EPO for dialysis indication in the United States and shall so advise ORTHO in writing and provide ORTHO

with copies of all materials filed with the FDA. AMGEN shall, at its own expense, have the responsibility to comply, with respect to any IND filed by AMGEN, with any FDA request for all additional information and repetition of tests required by the FDA sufficient to enable ORTHO to commence or continue clinical studies in the United States; provided that said FDA request has been identified within a one hundred-twenty (120) day period of the initial filing date of said IND as acknowledged by the FDA. AMGEN shall, at its own expense exert reasonable efforts to conduct toxicology and dosage studies, model studies and clinical studies with respect to dialysis patients and shall file an NDA if sufficient supporting data can be developed. ORTHO shall, at its own expense conduct toxicology and dosage studies, model studies and clinical studies for not less than two (2) other indications and shall file appropriate NDA's or supplements if sufficient supporting data can be developed. ORTHO shall have the right to use such materials and any supporting data thereof for the filing of foreign registrations corresponding to AMGEN's INDs, NDAs and all supplements thereto.

AMGEN shall, as soon as practicable and at its own expense conduct the necessary studies and testing and prepare and file INDs for HEPATITIS B and IL-2 in the United States and

shall so advise ORTHO in writing and provide ORTHO with copies of all materials filed with the FDA. ORTHO shall have the right to use such materials and any supporting data thereof for the filing of United States or foreign registrations. AMGEN shall, at its own expense, have the responsibility to comply, with respect to any IND filed by AMGEN, with any FDA request for all additional information and repetition of tests required by the FDA sufficient to enable ORTHO to commence or continue clinical studies in the United States; provided that said FDA request has been identified within a one hundred-twenty
(120) day period of the initial filing date of said IND as acknowledged by the FDA. For each of HEPATITIS B and IL-2, ORTHO shall, at its own expense, conduct appropriate toxicology and dosage studies, model studies and clinical studies for a reasonable number of indications and shall file an NDA for each indication for which sufficient supporting data can be developed.

ORTHO agrees to conduct at its own expense through OUTSIDE RESEARCH PAYMENTS such clinical testing with an individual or individuals or entities other than AMGEN or ORTHO or an AFFILIATE as is necessary solely for purposes of independent determination of safety and efficacy of any of the

LICENSED PRODUCTS in connection with the filing of NDAs for such LICENSED
PRODUCTS.

ORTHO, at its sole cost and expense, shall use its reasonable efforts in the LICENSED TERRITORY to pursue the preclinical, clinical and other studies outlined in the Development Program. ORTHO shall keep and maintain complete and accurate records of all work that it does in connection with this AGREEMENT. These records shall be made available by ORTHO at reasonable times for examination at AMGEN's request. In addition, ORTHO shall provide AMGEN with sufficient technical information and assistance as is necessary for AMGEN to assess the progress of ORTHO in its clinical studies and registration. In connection with such clinical testing, AMGEN shall supply, at AMGEN's sole cost and expense, reasonable quantities of vialed clinical PRODUCTS ready for clinical use and sufficient for ORTHO to utilize for such purposes. If AMGEN is unable to supply one hundred (100) percent of ORTHO's needs for said clinical testing, then ORTHO shall have the right, but not the obligation, to manufacture its needs and AMGEN shall provide to ORTHO any assistance, information and/or know-how required by ORTHO to so manufacture. Notwithstanding the above, if AMGEN is unable to supply one hundred (100) percent of ORTHO's needs for

said clinical testing, it shall provide to ORTHO at least fifty (50) percent of its manufacture of such vialed clinical PRODUCTS and shall not provide any of said PRODUCTS to any third party. Notwithstanding the foregoing, if successful clinical studies and registrations occur anywhere in the LICENSED TERRITORY outside the United States prior to the time clinical studies and registration are completed in the United States, then AMGEN shall supply said PRODUCTS to ORTHO only as may be permitted by applicable United States laws and regulations. If AMGEN is unable to so supply as a result of United States laws and regulations, then ORTHO shall have the right, but not the obligation to manufacture its needs of said PRODUCTS and AMGEN shall provide to ORTHO any assistance, information and/or know-how required by ORTHO to manufacture such PRODUCTS.

ORTHO and AMGEN shall keep and maintain complete and accurate records of all work including all FDA filings that either has done in connection with LICENSED PRODUCTS. The parties agree to provide each other with sufficient technical information and assistance as is necessary for each of them to assess the progress of the other party in its clinical testing of PRODUCTS and in its filing of INDs and NDAs in connection with such PRODUCTS including but not limited to AMGEN informing

ORTHO of all communications and discussions with the FDA relating to its INDs.

(i) With respect to EPO, AMGEN and ORTHO agree that each shall have access to and the exclusive and irrevocable right to refer to and cross-reference each other's INDs, NDAs and supplements thereto consistent with the purposes of this AGREEMENT and the Product License Agreement and with respect to AMGEN not for any purpose other than dialysis and each agrees to provide all appropriate documentation necessary to achieve the purposes of this AGREEMENT. The parties agree to notify the FDA of the right to cross-reference the above-described documents and to execute and file all the necessary papers and documents required to allow each to exercise its rights under this AGREEMENT.

(ii) With respect to HEPATITIS B and IL-2, AMGEN and ORTHO agree that ORTHO shall have access to and the exclusive and irrevocable right to refer to and cross-reference AMGEN's INDs, NDAs and supplements thereto consistent with the purposes of this AGREEMENT and AMGEN agrees to provide all appropriate documentation to achieve the purposes of this AGREEMENT. AMGEN further agrees, upon request by ORTHO, to further notify the FDA

of ORTHO's right to cross-reference the above-described documents and to execute and file all the necessary papers and documents required to allow ORTHO to exercise its rights under this AGREEMENT.

(iii) With respect to HEPATITIS B, AMGEN and ORTHO agree that AMGEN shall have access to and the exclusive and irrevocable right to refer to and utilize ORTHO's INDs, NDAs and supplements thereto provided that AMGEN demonstrates such is necessary for it to pursue its registration of HEPATITIS B in China and for no other purpose.

During the term of this AGREEMENT, AMGEN and ORTHO each shall have a continuing obligation to advise each other of any adverse drug reactions or any governmental regulatory problems, notices, actions or communications and to keep all INDs, NDAs and supplements thereto current and in full force and effect relating to the manufacture or use, of LICENSED PRODUCTS.

5.01 In accordance with the grant of Paragraph 2.01, ORTHO shall make the following royalty payments to AMGEN at the following times in accordance with the occurrence of the following milestone events:

(i) $4,000,000 - due and payable upon execution of this AGREEMENT as an aggregate initial royalty payment and allocable as follows:

$1,000,000 - to EPO
$2,000,000 - to HEPATITIS B

$1,000,000 - to IL-2

(ii) Three $1,000,000 royalty payments - each due and payable upon written notice and proof to ORTHO by AMGEN that both AMGEN and ORTHO are lawfully entitled to commence clinical studies based on approvals of AMGEN INDs and further that AMGEN has committed to perform any studies other than clinical studies which the FDA has requested for clinical studies to commence or continue.

(iii) $11,000,000 - due and payable as set forth below upon achievement by either AMGEN or ORTHO of CLINICAL EFFICACY for each of EPO, HEPATITIS B and IL-2 respectively as evidenced

by written notice and proof that CLINICAL EFFICACY has been demonstrated applicable to each such LICENSED PRODUCT. The respective sum for each LICENSED PRODUCT shall be payable and allocable as follows:

$5,000,000 - to EPO

$3,000,000 - to HEPATITIS B

$3,000,000 - to IL-2

The milestone royalty payments set forth in Paragraph 5.01 shall each be due and payable to AMGEN by ORTHO thirty (30) days following the notices provided for in Paragraphs 5.01 (ii) and 5.01 (iii) respectively.

If AMGEN and ORTHO proceed with a Product License Agreement to market LICENSED PRODUCTS, ORTHO shall be entitled to recover the royalty payments of this Article 5 in accordance with the provisions set forth in said Agreement.

ORTHO shall reimburse AMGEN upon presentation of suitable documentation for AMGEN's cost of PHASE I clinical studies regarding the PRODUCTS prior to CLOSING, but such

reimbursement shall not exceed an aggregate of $250,000 for all of the PRODUCTS.

All confidential information transmitted by either party to the other including all confidential information developed pursuant to this AGREEMENT, shall be identified with reference to this AGREEMENT and the receiving party shall, while this AGREEMENT is in effect and for three (3) years after termination thereof, make no use of this information other than in furtherance of this AGREEMENT and shall use the same efforts to keep secret and prevent the disclosure of such information to parties other than its agents, officers, employees and representatives authorized to receive such information as it would its own confidential information except for such confidential information that,

(a) was known to the receiving party at the time of its disclosure and not subject to any obligation of confidentiality at the time of its disclosure;

(b) was generally available to the public or was otherwise part of the public domain at the time of its disclosure;

(c) became generally available to the public or became otherwise part of the public domain after its disclosure and other than through any act or omission of the receiving party in breach of this AGREEMENT; or

(d) became known to the receiving party after its disclosure (i) from a souce other than the disclosing party (including from independent development by the receiving party), (ii) other than from a third party who had an obligation to the disclosing party not to disclose such information to others, and (iii) other than under an obligation of confidentiality.

Each receiving party may disclose any of the LICENSED KNOW-HOW and confidential information to the extent such disclosure is necessary to comply with applicable laws or regulations, or to make and use LICENSED PRODUCTS in accordance with the terms of this AGREEMENT.

AMGEN agrees to faithfully continue, at its expense, the prosecution of all patent applications listed in Exhibit D within the LICENSED FIELD and, when necessary, to file and prosecute additional applications covering patentable technology relating to EPO, HEPATITIS B and IL-2 in the United States and other countries throughout the world. AMGEN shall have the duty and responsibility to pay all taxes and annuities on all applications and patents listed is Exhibit D of the AGREEMENT. AMGEN shall provide ORTHO with copies of all applications listed in Exhibit D, all future-filed applications within the LICENSED FIELD and all correspondence with Patent Offices applicable thereto. If AMGEN chooses not to prosecute and maintain certain applications/patents under this AGREEMENT, AMGEN shall so notify ORTHO and ORTHO shall, is its sole discretion, decide whether to assume the responsibility and expenses therefore for each such application or patent. In that event, the applications/patents for which ORTHO shall assume responsibility shall be assigned to ORTHO.

AMGEN shall give ORTHO the opportunity to review, through their patent counsel, the status of all pending patent applications listed in Exhibit D and shall keep ORTHO informed of the status of their prosecution, including such Patent Office proceedings as interferences, reexamination, oppositions and requests for patent term extension under the Act. Notwithstanding the above, AMGEN shall have sole responsibility for all decisions in connection with the filing and prosecution of all patent applications and the maintenance of all patents. AMGEN shall take all appropriate actions to maximize the benefits for both AMGEN and ORTHO with respect to any patent term restoration and/or regulatory exclusivity that may be available in connection with any LICENSED PATENT or LICENSED PRODUCT.

(i) If, as a result of the manufacture and use of LICENSED PRODUCTS, ORTHO is sued for patent infringement or threatened with such a lawsuit or other action by a third party, then ORTHO shall actively consult with AMGEN in its attempts to

resolve same. If the settlement of a lawsuit or threatened lawsuit or other action requires any payments to a third party, then ORTHO and AMGEN shall share said payments on an equal basis.

(ii) If, as a result of the manufacture and use of any LICENSED PRODUCT, ORTHO is sued for patent infringement or threatened with such a lawsuit or other action and as a result of same ORTHO is prevented from the commencement of marketing said LICENSED PRODUCT, then provided that one or more other LICENSED PRODUCTS are being marketed or in the future are marketed or said LICENSED PRODUCT is being marketed or in the future is marketed in another country, ORTHO shall be entitled to recover the following in the manner provided in Paragraph 4.01 of the Product License Agreement from the sale of any LICENSED
PRODUCT:
(a) the equivalent of up to 100% of the research and development payments made by ORTHO to AMGEN under Paragraph 3.02 of this AGREEMENT for said LICENSED PRODUCT; and

(b) the equivalent of up to 50% of the OUTSIDE RESEARCH PAYMENTS directly related to the LICENSED PRODUCT incurred by ORTHO in accordance with ARTICLE 4 of this AGREEMENT.

(iii) In connection with any lawsuit or threatened lawsuit or other action as set forth in (i) or (ii) above, ORTHO and AMGEN shall share on an equal basis all reasonable expenses (including attorneys' fees) incurred therewith.

Either party shall promptly notify the other party of any infringement of any LICENSED PATENTS; misappropriation of a trade secret or declaration of an interference proceeding relating to LICENSED PATENTS or LICENSED KNOW-HOW, and shall provide the other party with all available evidence relating thereto. AMGEN and ORTHO shall then consult with each other as to the best manner in which to proceed. AMGEN shall have the right, but not the obligation, to bring, defend and maintain any appropriate suit or action. If AMGEN requests ORTHO to join AMGEN in such suit or action and ORTHO agrees to do so, ORTHO shall execute all papers and perform such other acts as may be reasonably required and may, at its option, be represented by counsel of its choice. AMGEN shall pay ORTHO its reasonable expenses (including its attorney's fees) in connection with any such suit or action. Should AMGEN lack standing to bring any such action, then AMGEN may cause ORTHO to do so upon first undertaking to indemnify and hold ORTHO harmless (to the extent

permissible by law) from all consequent liability and to promptly reimburse all reasonable expense (including attorney fees) steaming therefrom. In the event AMGEN fails to take action with respect to such matters within a reasonable period, not more than six (6) months, following receipt of such notice and evidence, ORTHO shall have the right, but not the obligation, to bring, defend and maintain any appropriate suit or action. If ORTHO finds it necessary to join AMGEN in such suit or action, AMGEN shall execute all papers and perform such other acts as may be reasonably required and may, at its option. be represented by counsel of its choice. ORTHO shall pay to AMGEN the reasonable expenses of AMGEN (including its attorney's fees) in connection with any such suit or action. Absent an agreement between the parties to jointly bring any action or suit hereunder and share the expenses thereof, any amount recovered in any such action or suit shall be retained by the party bearing the expenses thereof.

This AGREEMENT shall come into effect on the EFFECTIVE DATE and shall terminate on the tenth (10th) year anniversary of the EFFECTIVE DATE or as to each LICENSED PRODUCT separately upon receipt of an approval letter on a LICENSED PRODUCT from the FDA, or the counterpart of said approval letter on a LICENSED PRODUCT in any MAJOR COUNTRY, whichever occurs first.

Upon termination of this AGREEMENT as provided for in Paragraph 9.01 above, all LICENSED PATENTS and LICENSED KNOW-HOW shall become the sole property of AMGEN, and ORTHO shall have no further rights thereto under this AGREEMENT. Any rights ORTHO might obtain with respect to LICENSED PATENTS and LICENSED KNOW-HOW shall be in accordance with the provisions of the Product License Agreement to market LICENSED PRODUCTS.

In the event that AMGEN or ORTHO (the "Defaulting party") shall:

a) default in a material obligation hereunder, including failure to make any payments, and fail to remedy such default within 60 days after notice of such default by the Non-Defaulting party; or

b) become bankrupt or insolvent, or file a petition in bankruptcy or make a general assignment for the benefit of creditors or otherwise acknowledge insolvency or be adjudged bankrupt; or

c) go or be placed in a process of complete liquidation other than for an amalgamation or reconstruction; or

d) suffer the appointment of a receiver for any substantial portion of its business who shall not be discharged within 60 days after such receiver's appointment,then, and in any such event, the Non-Defaulting party, at its option, may terminate its obligations to, and the rights of, the Defaulting party under the license granted in this AGREEMENT upon 30 days written notice to the Defaulting party, which termination shall be effective as of the occurrence of the event giving rise to the option to terminate.

Upon termination of this AGREEMENT as a result of AMGEN's default under Paragraph 9.03, ORTHO shall have the right, but not the obligation, to make, use and sell LICENSED PRODUCTS under LICENSED PATENTS and LICENSED KNOW- HOW, and all of ORTHO's payment obligations under this AGREEMENT shall continue, provided however, that ORTHO shall have the right to off-set against any such payments any and all expenses incurred as a result of AMGEN's default.

Notwithstanding the termination of a party's obligations to or the rights of the Defaulting party under this Agreement in accordance with the provisions of Paragraph 9.03, the provisions of Article 6 shall survive such termination and continue in full force and effect for a period of not more than three (3) years following termination.

Nothing herein shall limit any remedies available to either party at law or in equity for the default of the other party under Paragraph 9.03 (b),
(c) or (d). Termination shall not excuse the obligation of either party to pay money due to the other party.

AMGEN is not aware of (i) any third party rights upon which, in its opinion, this AGREEMENT will infringe, or (ii) any claimed infringement against AMGEN with respect to LICENSED PRODUCTS.

The parties hereto shall use reasonable and practical efforts to obtain any and all consents, approvals, orders or authorizations required to be obtained with respect to the provisions hereof.

All notices, requests, demands and other communications required or permitted to be given under this AGREEMENT shall be in writing and shall be mailed to the party to whom notice is to be given, by telex or facsimile, and confirmed by first class mail, registered or certified, return receipt requested, postage prepaid, and properly addressed as follows (in which case such notice shall be deemed to have

been duly given on the third (3rd) day following the date of such sending):

Amgen
1900 Oak Terrace Lane
Thousand Oaks, CA 91320-1789
U.S.A.
Telex No. 4994440 (AMGEN)
Attn: Corporate Secretary

with a copy to:

Cooley, Godward, Castro,
Huddleson & Tatum
5 Palo Alto Square, Suite 400
Palo Alto, CA 94306
U.S.A.

Telex No. 910-372-7370 COOLEY SFO
380816 COOLEY PA EASYLINK
Attn: Alan C. Mendelson, Esq.

President
Ortho Pharmaceutical Corporation U.S. Route 202
Raritan, New Jersey 08869
U.S.A.

with a copy to:

Johnson & Johnson
One Johnson & Johnson Plaza
New Brunswick, N.J. 08933-7033 U.S.A.
Telex No. 844-481
Attn: General Counsel

Any party by giving notice to the other in the manner provided above may change such party's address for purposes of this Paragraph 10.03.

This AGREEMENT (together with all Exhibits attached hereto) constitutes the full and complete Agreement and understanding between the parties hereto and shall supersede any and all prior written and oral agreements, including but not limited to any "Agreement in Principle", concerning the subject matter contained herein. This AGREEMENT may not be modified or amended nor may any provision hereof be waived without a written instrument executed by AMGEN and ORTHO.

No failure or delay by any party to insist upon the strict performance of any term, condition, covenant or agreement of this AGREEMENT, or to exercise any right, power or remedy hereunder or consequent upon a breach hereof shall constitute a waiver of any such term, condition, covenant, agreement, right, power or remedy or of any such breach or preclude such party from exercising any such right, power or remedy at any later time or times.

Headings in this AGREEMENT are included herein for the convenience of reference only and shall not constitute a part of this AGREEMENT for any purpose.

In the event any dispute should arise between the parties hereto as to the validity, construction, enforceability or performance of this AGREEMENT or any of its provisions, such dispute shall be settled by arbitration. Said arbitration shall be conducted at Chicago, Illinois, in accordance with the rules then obtaining of the American Arbitration Association with a panel of three (3) arbitrators. The rules of discovery then pertaining to the courts of law in such jurisdiction shall apply thereto. The unsuccessful party to such arbitration shall pay to the successful party all costs and expenses, including reasonable attorneys' fees incurred therein by such successful party.

This AGREEMENT shall be construed in accordance with the internal laws, and not the law of conflicts, of the State of California applicable to agreements made and to be performed in that state.

This AGREEMENT shall be binding upon and inure to the benefit of the parties hereto, their successors and assigns.

Words in the singular shall include the plural, and words in a particular gender shall include either or both additional genders, when the context in which such words are used indicates that such is the intent.

This AGREEMENT may be executed in one or more counterparts by the parties hereto. All counterparts shall be construed together and shall constitute one AGREEMENT.

Each party agrees to perform any further acts and execute and deliver any and all further documents and/or instruments which may be reasonably necessary or desirable to carry out the provisions of this AGREEMENT.

If for any reason any clause or provision of this AGREEMENT, or the application of any such clause or provision in a particular context or to a particular situation, circumstance or person, should be held unenforceable, invalid or in violation of law by any court or other tribunal, then the application of such clause or provision in contexts or to situations, circumstances or persons other than that in or to which it is held unenforceable, invalid or in violation of law shall not be affected thereby, and the remaining clauses and provisions hereof shall nevertheless remain in full force and effect, provided however, that any provisions so held unenforceable, invalid or in violation of law shall be rewritten by the parties in a lawful manner to reflect its intent.

Each of the parties hereto acknowledges and agrees (i) that no representation or promise not expressly contained in this AGREEMENT has been made by the other party hereto or by any of its agents, employees, representatives or attorneys; (ii) that this AGREEMENT is not being entered into on the basis of, or in reliance on, any promise or representation, expressed or implied, covering the subject matter hereof, other than those which are set forth expressly in this AGREEMENT; and (iii) that

each party has had the opportunity to be represented by counsel of its own choice in this matter, including the negotiations which preceded the execution of this AGREEMENT.

Neither party shall assign its rights or obligations under this AGREEMENT without prior written consent of the other party, provided however, ORTHO may assign its rights and obligations by sublicensing its AFFILIATES or third parties as provided in Paragraph 2.02 hereinabove.

AMGEN and ORTHO shall not be deemed to be partners, joint venturers or each other's agents, and neither shall have the right to act on behalf of the other except as expressly provided hereunder or otherwise expressly agreed to in writing.

Neither party shall be liable for failure to perform as required by any provision of this AGREEMENT where such failure results from a force majeure beyond such party's control. In the event of any delay attributable to a force majeure, the time for performance affected thereby shall be

extended for a period equal to the time lost by reason of the delay. If, as a result of a force majeure, AMGEN is unable to manufacture LICENSED PRODUCTS, for the purposes of this AGREEMENT, then, ORTHO shall have the right, but not the obligation, to manufacture said LICENSED PRODUCTS and AMGEN shall provide to ORTHO any assistance, information and/or know-how required by ORTHO to manufacture such LICENSED PRODUCTS.

Each party to this AGREEMENT shall be responsible for its own acts relating to the manufacture and use of LICENSED PRODUCTS and neither shall indemnify the other for costs, expenses, liability, damages and claims for any injury or death to persons or damage to or destruction of property or other loss arising out of or in connection with any LICENSED PRODUCTS made or used by either party.

In the absence of specific agreement between the parties, neither party shall originate any publicity, news release or other public announcement, written or oral, whether to the public press, to stockholders or otherwise, relating to this AGREEMENT, to any amendment hereto as to performance

hereunder, save only such announcement as in the opinion of legal counsel to the party making such announcement is required by law or practice to be made. The party making any such announcement shall give the other party an opportunity to review the form of the announcement before it is made. Routine references to this AGREEMENT and the arrangements hereunder without undue frequency and without emphasis shall be allowed in the usual course of business provided that notice of such use is given to the other party. If, in the opinion of ORTHO, excessive use occurs, such references shall be discontinued after discussion among the parties.

AMGEN and ORTHO shall each bear and pay for their respective costs and expenses regarding the negotiation and preparation of this AGREEMENT and all documents, instruments and agreements related thereto.

10.21.1 The parties hereby agree that any Technical Data (as that term is defined in Section 379.1 of the U.S. Export Administration Regulations) exported from the United States pursuant to this AGREEMENT and any other related agreements, and any direct product thereof, shall not be

shipped, either directly or indirectly, to Afghanistan or any Group P, Q, S, W, Y or Z Countries (as specified in Supplement No. 1 to part 370 of the Export Administration Regulations), unless (i) separate specific authorization to reexport such Technical Data or such direct products is provided by the U.S. Offfice of Export Administration or (ii) such specific authorization is not required pursuant to part 379.8 of the U.S. Export Administration Regulations. The parties further agree that the export and reexport of commodities pursuant to this AGREEMENT and any other related agreements shall be subject to the licensing requirements of the U.S. Export Regulations.

10.21.2 In the event that a specific authorization of, or a validated license from, a government other than that of the exporting party is required, AMGEN and ORTHO each agree that the party within the jurisdiction of such other government shall upon the request of the party proposing to make the export use reasonable efforts to obtain, as expeditiously as applicable, the requisite authorization or license.

IN WITNESS WHEREOF, the undersigned have caused this AGREEMENT to be executed by their duly authorized

representatives in the manner legally binding upon them on the first date written above.

AMGEN
a California corporation

/s/ Robert D. Weist                           By /s/ George B. Rathmann
--------------------------------                 -------------------------------
    Witness                                       George B. Rathmann, President

                                              ORTHO PHARMACEUTICAL CORPORATION
                                              a New Jersey corporation



/s/ Dennis N. Longstreet                      By /s/ Gary V. Parlin
--------------------------------                 -------------------------------
    Witness                                       Gary V. Parlin, President

The chemical structure of r-HuEPO is best described by its amino acid sequence which is depicted below:

NH\\2\\ - ala pro pro arg leu ile cys asp ser arg val leu glu arg try

Y*

leu leu glu ala lys glu ala glu asn ile thr thr gly cys ala

Y

glu his cys ser leu asn glu asn ile thr val pro asp thr lys

val asn phe tyr ala trp lys arg met glu val gly gln gln ala

val glu val trp gln gly leu ala leu leu ser glu ala val leu

Y

arg gly gln ala leu leu val asn ser ser gln pro trp glu pro

leu gln leu his val asp lys ala val ser gly leu arg ser leu

thr thr leu leu arg ala leu gly ala gln lys glu ala ile ser

pro pro asp ala ala ser ala ala pro leu arg thr ile thr ala

asp thr phe arg lys leu phe arg val tyr ser asn phe leu arg

gly lys leu lys leu tyr thr gly glu ala cys arg thr gly asp

arg - COOH

* 'Y' designates N-linked glycosalation site.

The chemical structure of recombinant yeast-derived hepatitis B surface antigen is best described by its amino acid sequence which is depicted below:

NH\\2\\-Met glu asn ile thr ser gly phe leu gly pro leu leu val leu gln

ala gly phe phe leu leu thr arg ile leu thr ile pro gln ser

leu asp ser trp trp thr ser leu asn phe leu gly gly ser pro

val cys leu gly gln asn ser gln ser pro thr ser asn his ser

pro thr ser cys pro pro ile cys pro gly tyr arg trp met cys

leu arg arg phe ile ile phe leu phe ile leu leu leu cys leu

ile phe leu leu val leu leu asp tyr gln gly met leu pro val

cys pro leu ile pro gly ser thr thr thr ser thr gly pro cys

lys thr cys thr thr pro ala gln gly asn ser met phe pro ser

cys cys cys thr lys pro thr asp gly asn cys thr cys ile pro

ile pro ser ser trp ala phe ala lys tyr leu trp gly trp ala

ser val arg phe ser trp leu ser leu leu val pro phe val gln

trp phe val gly leu ser pro thr val trp leu ser ala ile trp

met met trp tyr trp gly pro ser leu tyr ser ile val ser pro

phe ile pro leu leu pro ile phe phe cys leu trp val tyr ile

COOH

NH\\2\\-  Met-ala pro thr ser ser ser thr lys lys thr gln leu gln leu glu his

          leu leu leu asp leu gln met ile leu asn gly ile asn asn tyr lys

          asn pro lys leu thr arg met leu thr phe lys phe tyr met pro lys

          lys ala thr glu leu lys his leu gln cys leu glu glu glu leu lys

          pro leu glu glu val leu asn leu ala gln ser lys asn phe his leu

          arg pro arg asp leu ile ser asn ile asn val ile val leu glu leu

          lys gly ser glu thr thr phe met cys glu tyr ala asp glu thr ala

          thr ile val glu phe leu asn arg trp ile thr phe ala glu ser ile

          ile ser thr leu thr COOH

Docket            Inventor(s)                         Title                       Country      S.N.              Filing
  No.                                                                                                             Date
----------     ----------------      ------------------------------------      ------------   ----------     -----------
155            F. Lin                Recombinant Methods and                        U.S.        561,024         12/13/83
                                     Materials Applied to Micro-
                                     bial Expression of Erythro-
                                     poietin

155-CIP-1      F. Lin                Recombinant Methods and                        U.S.        582,185          2/21/84
                                     Materials Applied to Micro-
                                     bial Expression of Erythro-
                                     poietin

155-CIP-2      F. Lin                Recombinant Methods and                        U.S.        655,841          9/28/84
                                     Materials Applied to Micro-
                                     bial Expression of Erythro-
                                     poietin

155-CIP-3      F. Lin                Production of Erythropoietin                   U.S.        675,298         11/30/84

132            J. Egrie              ATCC HB8209 - Its Monoclonal                   U.S.        463,724           2/4/83
                                     Antibody to Erythropoietin
                                     ATCC HB8209/Budapest

190            P. Lai                Protein Purification                           U.S.        747,119          6/20/85
               T. Strickland

Docket           Inventor(s)                      Title               Country          S.N.             Filing
  No.                                                                                                    Date
--------       --------------      -------------------------------    ------------   ----------       ---------
106-C           G. Bitter           Expression of Exogenous             U.S.           748,712          6/26/85
                                    Polypeptides and Poly-                             (A continuation
                                    peptide Products Including                         of S.N. 412,707
                                    Hepatitis B Surface Antigen                        filed 8/30/82

204             J. Fieschko         Fermentation Methods for            U.S.              *             8/15/85
                                    Hepatitis Vaccine Produc-
                                    tion

201             H. Levine           Lysis Method and Buffer for         U.S.              *             8/15/85
                                    Extraction of HBsAg from
                                    Yeast Cells



*Information not yet available

Docket           Inventor(s)                  Title                   Country          S.N.                  Filing
  No.                                                                                                         Date
---------      --------------      ------------------------------     -----------    -----------         --------------
 138            L. Souza             Microbial Expression of          U.S.             521,967               8/10/83
                Y. Stabinsky         Interleukin II

 138-CIP-1      L. Souza             Microbial Expression of          U.S.             635,941               8/3/84
                Y. Stabinsky         Interleukin II

                                                                      Canada           460,745               8/10/84
                                                                      Israel           72643                 8/10/84
                                                                      Japan            Via PCT US84/
                                                                                       01252                 8/9/84
                                                             EPO      designating      84.109537.5           8/10/84
                                                                      Austria
                                                                      Belgium
                                                                      France
                                                                      Germany
                                                                      Italy
                                                                      Luxembourg
                                                                      Netherlands
                                                                      Sweden
                                                                      Switzerland
                                                                      Liechtenstein
                                                                      United Kingdom

 -CIP-2         L. Souza             Microbial Expression of          U.S.             717,334               3/29/85
                Y. Stabinsky         Interleukin II

 /s/Robert D. Weist           By   /s/George B. Rathmann
-------------------              -----------------------------
    Witness                      George B. Rathmann, President

 /s/Dennis N. Longstreet      By  /s/Gary V. Parlin
------------------------         -----------------------------
    Witness                      Gary V. Parlin, President

ERYTHROPOIETIN  (Page 1)
---------------

 Docket                Inventor(s)                 Title               Country         S.N.          Filing
   No.                                                                                                Date
-----------            -----------      ----------------------------   -------       ---------    -----------
155                    F. Lin           Recombinant Methods and        U.S.            561,024        12/13/83
                                        Materials Applied to Micro-
                                        bial Expression of Erythro-
                                        poietin

155-CIP-1              F. Lin           Recombinant Methods and        U.S.            582,185         2/21/84
                                        Materials Applied to Micro-
                                        bial Expression of Erythro-
                                        poietin

155-CIP-2              F. Lin           Recombinant Methods and        U.S.            655,841         9/28/84
                                        Materials Applied to Micro-
                                        bial Expression of Erythro-
                                        poietin

155-CIP-3              F. Lin           Production of Erythropoietin   U.S.            675,298        11/30/84

                                                                       Australia       Via PCT US84/
                                                                                       02021          12/11/84
                                                                       China           85106196       6/19/85
                                                                       Canada          469,938        12/12/84
                                                                       Czechoslovakia  PV 4438-85     6/18/85
                                                         EPO           designating     84308654.7     12/12/84
                                                                       Austria
                                                                       Belgium
                                                                       France
                                                                       Germany
                                                                       Italy
                                                                       Luxembourg
                                                                       Netherlands
                                                                       Sweden
                                                                       Switzerland
                                                                       Lichtenstein
                                                                       United Kingdom

ERYTHROPOIETIN   (Page 2)
---------------

 Docket    Inventor(s)   Title     Country          S.N.         Filing
   No.                                                            Date
---------  -----------  -------  ----------    --------------   --------
                                 Finland        852,377          6/14/85
                                 Denmark        Via PCT US84/
                                                0201             12/11/84
                                 E. Germany     G/277534-2       6/19/85
                                 Greece               *             *
                                 Hungary        2404/85          6/18/85
                                 Israel         73785            12/11/84
                                 Japan          Via PCT US84/
                                                02021            12/11/84
                                 Korea          7923/1984        12/13/84
                                 New Zealand    201,501          12/10/84
                                 Portugal             *             *
                                 South Africa   84/9625          12/11/84
                                 Spain          538,519          12/12/84
                                 USSR           3917560/04       6/19/85

ERYTHROPOIETIN    (Page 3)
---------------

 Docket      Inventor(s)              Title                  Country         S.N.           Filing
   No.                                                                                       Date
--------    -------------   -----------------------------   --------      ----------       -------
132            J. Egrie      ATCC HB8209 - Its Monoclonal    U.S.           463,724         2/4/83
                             Antibody to Erythropoietin
                             ATCC HB8209/Budapest
                                                             Canada         446,767         2/3/84
                                                             Israel         71001           2/17/84
                                                             Japan          Via PCT US84/
                                                                            00151           2/3/84
                                           EPO               designating    84/300693.3     2/3/84
                                                             Austria
                                                             Belgium
                                                             France
                                                             Germany
                                                             Italy
                                                             Luxembourg
                                                             Netherlands
                                                             Sweden
                                                             Switzerland
                                                             Liechtenstein
                                                             United Kingdom

190            P. Lai        Protein Purification            U.S.           747,119         6/20/85
               T. Strickland

                                    a California Corporation

/s/ Robert D. Weist                 By /s/ George B. Rathmann
--------------------------             --------------------------------
      Witness                            George B. Rathmann, President


                                    ORTHO PHARMACEUTICAL CORPORATION
                                    a New Jersey corporation


/s/ Dennis N. Longstreet            By /s/ Gary V. Parlin
--------------------------             --------------------------------
      Witness                          Gary V. Parlin, President

Docket No.      Inventor(s)          Title                 Country               S.N.              Filing Date
----------      ----------    ------------------------     --------           -----------          ------------
     155          F. Lin       Recombinant Methods and        U.S.               561,024            12/13/83
                               Materials Applied to Micro-
                               bial Expression of Erythro-
                               poietin

     155-CIP-1    F. Lin       Recombinant Methods and        U.S.               582,185             2/21/84
                               Materials Applied to Micro-
                               bial Expression of Erythro-
                               poietin

     155-CIP-2    F. Lin       Recombinant Methods and        U.S.               655,841             9/28/84
                               Materials Applied to Micro-
                               bial Expression of Erythro-
                               poietin

     155-CIP-3    F. Lin       Production of Erythropoietin   U.S.               675,298            11/30/84

                                                              Australia         Via PCT US84/
                                                                                02021               12/11/84
                                                              China             85106196             6/19/85
                                                              Canada            469,938             12/12/84
                                                              Czechoslovakia    PV 4438-85           6/18/85
                               EPO                            designating       84308654.7          12/12/84
                                                              Austria
                                                              Belgium
                                                              France
                                                              Germany
                                                              Italy
                                                              Luxembourg
                                                              Netherlands
                                                              Sweden
                                                              Switzerland
                                                              Lichtenstein
                                                              United Kingdom

Docket No.       Inventor(s)    Title         Country          S.N.        Filing Date
----------       ----------  -----------    -----------   --------------   -----------
                                            Finland             852,377      6/14/85
                                            Denmark        via PCT US84/
                                                                   0201     12/11/84
                                            E. Germany       G/277534-2      6/19/85
                                            Greece                    *            *
                                            Hungary             2404/85      6/18/85
                                            Israel                73785     12/11/84
                                            Japan         Via PCT US84/
                                                                  02021     12/11/84
                                            Korea             7923/1984     12/13/84
                                            New Zealand         201,501     12/10/84
                                            Portugal                  *            *
                                            South Africa        84/9625     12/11/84
                                            Spain               538,519     12/12/84
                                            USSR             3917560/04      6/19/85

Docket No.   Inventor(s)           Title                        Country            S.N.    Filing Date
----------   ----------        ----------------------------    ----------   -------------  ------------
 132         J. Egrie           ATCC HB8209 - Its Monoclonal   U.S.               463,724     2/4/83
                                Antibody to Erythropoietin
                                ATCC HB8209/Budapest
                                                               Canada             446,767     2/3/84
                                                               Israel               71001    2/17/84
                                                               Japan        Via PCT US84/
                                                                                    00151     2/3/84
                                EPO                            designating    84/300693.3     2/3/84
                                                               Austria
                                                               Belgium
                                                               France
                                                               Germany
                                                               Italy
                                                               Luxembourg
                                                               Netherlands
                                                               Sweden
                                                               Switzerland
                                                               Liechtenstein
                                                               United Kingdom

190          P. Lai             Protein Purification           U.S.               747,119    6/20/85
             T. Strickland

By:   /s/ Edward Garnett
      ------------------
      Edward Garnett

Title:  Vice President,

        Human Resources

2.8.1  No New Grants: As an employee in a part-time special assignment
       -------------
       position, you will not be eligible to receive additional stock
       option grants after the Effective Date.

2.8.2  Vesting During Special Assignment: To the extent that you
       ---------------------------------
       continue in your part-time special assignment, you will be
       eligible to continue to vest in all unvested options that have
       previously been granted to you by Amgen on the dates and in the
       manner provided in your stock option grant agreements and
       applicable stock option plans. No stock options will vest
       following the Termination Date as defined in Paragraph 8 of
       this Agreement.

2.8.3  Voluntary Retirement: Nothing in this Agreement shall be
       --------------------
       construed as limiting (i) your right to voluntarily retire from
       Amgen during or at the end of the special assignment or (ii)
       the applicability of Paragraph I of the Grants of Stock Options
       listed on Appendix C to this Agreement to any termination of
       your employment.

2.8.4  Cooperation To Restructure: As we have discussed, it is our
       --------------------------
       intention that your ability to continue to vest in and exercise
       options while in your part-time special assignment position
       will not result in any additional compensation charges to Amgen
       in accordance with U.S. generally accepted

       accounting principles. Accordingly, if at any time Amgen
       determines that it is reasonably likely that Amgen will incur a
       compensation charge as a result of your vesting or exercising
       options in your part-time special assignment position then you
       agree that you will use your reasonable best efforts to
       cooperate with Amgen to restructure this Agreement and your
       position as Amgen reasonably determines is necessary for you to
       continue to be able to vest and exercise your options without
       creating a compensation charge to Amgen in accordance with U.S.
       generally accepted accounting principles and without causing
       you to lose any of the benefits of this Agreement. It is
       expressly understood that your "reasonable best efforts to
       cooperate with Amgen" shall not require that you take or
       forbear from taking any action that would result in any loss of
       value of the options.

2.8.5  No Amendment to Stock Option Grant Agreements or Stock Option
       -------------------------------------------------------------
       Plans: Nothing in this Agreement shall be deemed to alter,
       -----
       amend, or otherwise modify the terms of your stock option grant
       agreements or the terms of the applicable stock option plans.

7.2.1  Amgen's obligation will be limited to that amount which, as of
       the day immediately prior to the date of this Agreement, Amgen
       would pay to reimburse other employees of your then salary
       grade level;

7.2.2  to the extent that your new employer, if any, reimburses you
       for, or pays any of, such non-recurring customary sales costs,
       then Amgen will only reimburse you for that portion of the non-
       recurring customary sales costs that exceed the amount paid for
       by such new employer; and

7.2.3  you provide all documentation requested by Amgen in connection
       with this Subparagraph 7.2, upon the request of Amgen.

/s/ Edward F. Garnett
---------------------
Amgen Inc.
By: Edward F. Garnett
Vice President, Human Resources

/s/ Gordon M. Binder
--------------------
Gordon M. Binder

Dated: 5/10/00
       -------

/s/ Gordon M. Binder
--------------------
Gordon M. Binder

-----------------------------------------------
    Grant Number               Date of Grant
    ------------               -------------
-----------------------------------------------

-----------------------------------------------
      927796                     07/01/97
-----------------------------------------------
      931893                     07/01/97
-----------------------------------------------
      933504                     07/01/98
-----------------------------------------------
      938857                     07/01/98


-----------------------------------------------