Cooperative Research and Development Agreement - National Cancer Institute and Maxygen Inc.

                             PUBLIC HEALTH SERVICE

                COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT


This Cooperative Research and Development Agreement, hereinafter referred to as
the "CRADA," consists of this Cover Page, an attached Agreement, and various
Appendices referenced in the Agreement.  This Cover Page serves to identify the
Parties to this CRADA:

          (1)  the following Bureau(s), Institute(s), Center(s) or Division(s)
of the National Institutes of Health ("NIH"), the Food and Drug Administration
("FDA"), and the Centers for Disease Control and Prevention ("CDC"):

The National Cancer Institute hereinafter singly or collectively referred to as
the Public Health Service ("PHS"); and

          (2)  Maxygen, Incorporated, which has offices at 515 Galveston Drive,
Redwood City, California, 94063 hereinafter referred to as the "Collaborator."



THE SYMBOL "*******" IS USED TO INDICATE THAT A PORTION OF THE EXHIBIT HAS BEEN 
OMITTED AND FILED SEPARATELY WITH THE COMMISSION.  CONFIDENTIAL TREATMENT HAS 
BEEN REQUESTED WITH RESPECT TO THE OMITTED PORTIONS.

 
                COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT

Article 1.  Introduction

This Cooperative Research and Development Agreement (CRADA) between PHS and the
Collaborator will be effective when signed by all Parties.  The research and
development activities which will be undertaken by each of the Parties in the
course of this CRADA are detailed in the Research Plan (RP) which is attached as
Appendix A.  The funding and staffing commitments of the Parties are set forth
in Appendix B.  Any exceptions or changes to the CRADA are set forth in Appendix
C.  This CRADA is made under the authority of the Federal Technology Transfer
Act, 15 U.S.C. (S)3710a and is governed by its terms.

Article 2.  Definitions

As used in this CRADA, the following terms shall have the indicated meanings:

2.1  "Affiliate" means any corporation or other business entity controlled by,
     controlling, or under common control with Collaborator. For this purpose, A
     "control" means direct or indirect beneficial ownership of at least fifty
     (50) percent of the voting stock or at least fifty (50) percent interest in
     the income of such corporation or other business.

2.2  "Cooperative Research and Development Agreement" or "CRADA" means this
     Agreement, entered into by PHS pursuant to the Federal Technology Transfer
     Act of 1986, as amended, 15 U.S.C. 3710a et seq. and Executive Order 12591
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     of October 10, 1987.

2.3  "Government" means the Government of the United States as represented
     through the PHS agency that is a Party to this agreement.

2.4  "IP" means intellectual property.

2.5  "Invention" means any invention or discovery which is or may be patentable
     or otherwise protected under title 35, United States Code, or any novel
     variety or plant which is or may be protectable under the Plant Variety
     Protection Act (7 U.S.C. 2321 et seq.).
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2.6  "Principal Investigator(s)" or "PIs" means the persons designated
     respectively by the Parties to this CRADA who will be responsible for the
     scientific and technical conduct of the RP.

2.7  "Proprietary/Confidential Information" means confidential scientific,
     business, or financial information provided that such information does not
     include:

     2.7.1.  information that is publicly known or available from other sources
             who are not under a confidentiality obligation to the source of the
             information;

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     2.7.2.  information which has been made available by its owners to others
             without a confidentiality obligation;

     2.7.3.  information which is already known by or available to the receiving
             Party without a confidentiality obligation; or

     2.7.4.  information which relates to potential hazards or cautionary
             warnings associated with the production, handling or use of the
             subject matter of the Research Plan of this CRADA.

2.8  "Research Materials" means all tangible materials other than Subject Data
     first produced in the performance of this CRADA.

2.9  "Research Plan" or "RP" means the statement in Appendix A of the respective
     research and development commitments of the Parties to this CRADA.

2.10 "Subject Invention" means any Invention of the Parties, conceived or first
     actually reduced to practice in the performance of the Research Plan of
     this CRADA.

2.11 "Subject Data" means all recorded information first produced in the
     performance of this CRADA by the Parties.

Article 3.  Cooperative Research

3.1  Principal Investigators.  PHS research work under this CRADA will be
     performed by the PHS laboratory identified in the RP, and the PHS Principal
     Investigator (PI) designated in the RP will be responsible for the
     scientific and technical conduct of this project on behalf of PHS.  Also
     designated in the RP is the Collaborator PI who will be responsible for the
     scientific and technical conduct of this project on behalf of the
     Collaborator.

3.2  Research Plan Change.  The RP may be modified by mutual written consent of
     the Principal Investigators.  Substantial changes in the scope of the RP
     will be treated as amendments under Article 13.6.

Article 4.  Reports

4.1  Interim Reports.  The Parties shall exchange formal written interim
     progress reports on a schedule agreed to by the PIs, but at least within
     twelve (12) months after this CRADA becomes effective and at least within
     every twelve (12) months thereafter.  Such reports shall set forth the
     technical progress made, identifying such problems as may have been
     encountered and establishing goals and objectives requiring further effort,
     any modifications to the Research Plan pursuant to Article 3.2, and all
     CRADA-related patent applications filed.

4.2  Final Reports.  The Parties shall exchange final reports of their results
     within four (4) months after completing the projects described in the RP or
     after the expiration or termination of this CRADA.

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Article 5.  Financial and Staffing Obligations

5.1  PHS and Collaborator Contributions.  The contributions of the Parties,
     including payment schedules, if applicable, are set forth in Appendix B.
     PHS shall not be obligated to perform any of the research specified herein
     or to take any other action required by this CRADA if the funding is not
     provided as set forth in Appendix B.  PHS shall return excess funds to the
     Collaborator when it sends its final fiscal report pursuant to Article 5.2,
     except for staffing support pursuant to Article 10.3.  Collaborator
     acknowledges that the U.S. Government will have the authority to retain and
     expend any excess funds for up to one (1) year subsequent to the expiration
     or termination of the CRADA to cover any costs incurred during the term of
     the CRADA in undertaking the work set forth in the RP.

5.2  Accounting Records.  PHS shall maintain separate and distinct current
     accounts, records, and other evidence supporting all its obligations under
     this CRADA, and shall provide the Collaborator a final fiscal report
     pursuant to Article 4.2.

5.3  Capital Equipment.  Equipment purchased by PHS with funds provided by the
     Collaborator shall be the property of PHS.  All capital equipment provided
     under this CRADA by one party for the use of another Party remains the
     property of the providing Party unless other disposition is mutually agreed
     upon by in writing by the Parties.  If title to this equipment remains with
     the providing Party, that Party is responsible for maintenance of the
     equipment and the costs of its transportation to and from the site where it
     will be used.

Article 6.  Intellectual Property Rights and Patent Applications

6.1  Reporting.  The Parties shall promptly report to each other in writing each
     Subject Invention resulting from the research conducted under this CRADA
     that is reported to them by their respective employees.  Each Party shall
     report all Subject Inventions to the other Party in sufficient detail to
     determine inventorship.  Such reports shall be treated as
     Proprietary/Confidential Information in accordance with Article 8.4.

6.2  Collaborator Employee Inventions.  If the Collaborator does not elect to
     retain its IP rights, the Collaborator shall offer to assign these IP
     rights to the Subject Invention to PHS pursuant to Article 6.5.  If PHS
     declines such assignment, the Collaborator may release its IP rights as it
     may determine.

6.3  PHS Employee Inventions.  PHS on behalf of the U.S. Government may elect to
     retain IP rights to each Subject Invention made solely by PHS employees.
     If PHS does not elect to retain IP rights, PHS shall offer to assign these
     IP rights to such Subject Invention to the Collaborator pursuant to Article
     6.5.  If the Collaborator declines such assignment, PHS may release IP
     rights in such Subject Invention to its employee inventors pursuant to
     Article 6.6.

6.4  Joint Inventions.  Each Subject Invention made jointly by PHS and
     Collaborator employees shall be jointly owned by PHS and the Collaborator.
     The Collaborator may elect to file the joint patent or other IP
     application(s) thereon and shall notify PHS promptly upon making this
     election.  If the Collaborator decides to file such applications, 

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     it shall do so in a timely manner and at its own expense. If the
     Collaborator does not elect to file such application(s), PHS on behalf of
     the U.S. Government shall have the right to file the joint application(s)
     in a timely manner and at its own expense. If either Party decides not to
     retain its IP rights to a jointly owned Subject Invention, it shall offer
     to assign such rights to the other Party pursuant to Article 6.5. If the
     other Party declines such assignment, the offering Party may release its IP
     rights as provided in Articles 6.2, 6.3, and 6.6.

6.5  Filing of Patent Applications.  With respect to Subject Inventions made by
     the Collaborator as described in Article 6.2, or by PHS as described in
     Article 6.3, a Party exercising its right to elect to retain IP rights to a
     Subject Invention agrees to file patent or other IP applications in a
     timely manner and at its own expense and after consultation with the other
     Party.  The Party shall notify the other Party of its decision regarding
     filing in countries other than the United States in a timely manner.  The
     Party may elect not to file a patent or other IP application thereon in any
     particular country or countries provided it so advises the other Party
     ninety (90) days prior to the expiration of any applicable filing deadline,
     priority period or statutory bar date, and hereby agrees to assign its IP
     right, title and interest in such country or countries to the Subject
     Invention to the other Party and to cooperate in the preparation and filing
     of a patent or other IP applications.  In any countries in which title to
     patent or other IP rights is transferred to the Collaborator, the
     Collaborator agrees that PHS inventors will share in any royalty
     distribution that the Collaborator pays to its own inventors.

6.6  Release to Inventors.  In the event neither of the Parties to this CRADA
     elects to file a patent or other IP application on a Subject Invention,
     either or both (if a joint invention) may retain or release their IP rights
     in accordance with their respective policies and procedures.  However, the
     Government shall retain a nonexclusive, non-transferable, irrevocable,
     royalty-free license to practice any such Subject Invention or have it
     practiced throughout the world by or on behalf of the Government.

6.7  Patent Expenses.  The expenses attendant to the filing of patent or other
     IP applications generally shall be paid by the Party filing such
     application.  If an exclusive license to any Subject Invention is granted
     to the Collaborator, the Collaborator shall be responsible for all past and
     future out-of-pocket expenses in connection with the preparation, filing,
     prosecution and maintenance of any applications claiming such exclusively-
     licensed inventions and any patents or other IP grants that may issue on
     such applications.  The Collaborator may waive its exclusive license rights
     on any application, patent or other IP grant at any time, and incur no
     subsequent compensation obligation for that application, patent or IP
     grant.

6.8  Prosecution of Intellectual Property Applications.  Within one month of
     receipt or filing,  each Party shall provide the other Party with copies of
     the applications and all documents received from or filed with the relevant
     patent or other IP office in connection with the prosecution of such
     applications.  Each Party shall also provide the other Party with the power
     to inspect and make copies of all documents retained in the patent or other
     IP application files by the applicable patent or other IP office.  Where
     licensing is contemplated by Collaborator, the Parties agree to consult
     with each other with respect to 

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     the prosecution of applications for PHS Subject Inventions described in
     Article 6.3 and joint Subject Inventions described in Article 6.4. If the
     Collaborator elects to file and prosecute IP applications on joint Subject
     Inventions pursuant to Article 6.4, PHS will be granted an associate power
     of attorney (or its equivalent) on such IP applications.

Article 7.  Licensing

7.1  Option for Commercialization License.  With respect to Government IP rights
     to any Subject Invention not made solely by the Collaborator's employees
     for which a patent or other IP application is filed, PHS hereby grants to
     the Collaborator an exclusive option to elect an exclusive or nonexclusive
     commercialization license, which is substantially in the form of the
     appropriate model PHS license agreement.  This option does not apply to
     Subject Inventions conceived prior to the effective date of this CRADA that
     are reduced to practice under this CRADA, if prior to that reduction to
     practice, PHS has filed a patent application on the invention and has
     licensed it or offered to license it to a third party.  The terms of the
     license will fairly reflect the nature of the invention, the relative
     contributions of the Parties to the invention and the CRADA, the risks
     incurred by the Collaborator and the costs of subsequent research and
     development needed to bring the invention to the marketplace.  The field of
     use of the license will be commensurate with the scope of the RP.

7.2  Exercise of License Option.  The option of Article 7.1 must be exercised by
     written notice mailed within three (3) months after either (i) Collaborator
     receives written notice from PHS that the patent or other IP application
     has been filed; or (ii) the date Collaborator files such IP application.
     Exercise of this option by the Collaborator initiates a negotiation period
     that expires nine (9) months after the exercise of the option.  If the last
     proposal by the Collaborator has not been responded to in writing by PHS
     within this nine (9) month period, the negotiation period shall be extended
     to expire one (1) month after PHS so responds, during which month the
     Collaborator may accept in writing the final license proposal of PHS.  In
     the absence of such acceptance, or an extension of the time limits by PHS,
     PHS will be free to license such IP rights to others.  In the event that
     the Collaborator elects the option for an exclusive license, but no such
     license is executed during the negotiation period, PHS agrees not to make
     an offer for an exclusive license on more favorable terms to a third party
     for a period of six (6) months without first offering Collaborator those
     more favorable terms. These times may be extended at the sole discretion of
     PHS upon good cause shown in writing by the Collaborator.

7.3  License for PHS Employee Inventions and Joint Inventions.  Pursuant to 15
     U.S.C. (S) 3710a(b)(1)(A), for Subject Inventions made under this CRADA by
     a PHS employee(s) or jointly by such employee(s) and employees of the
     Collaborator pursuant to Articles 6.3 and 6.4 and licensed pursuant to the
     option of Article 7.1, the Collaborator grants to the Government a
     nonexclusive, nontransferable, irrevocable, paid-up license to practice the
     invention or have the invention practiced throughout the world by or on
     behalf of the Government.  In the exercise of such license, the Government
     shall not publicly disclose trade secrets or commercial or financial
     information that is privileged or confidential 

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     within the meaning of 5 U.S.C. 552(b)(4) or which would be considered as
     such if it had been obtained from a non-Federal party.

7.4  License in Collaborator Inventions.  Pursuant to 15 U.S.C. (S) 3710a(b)(2),
     for inventions made solely by Collaborator employees under this CRADA
     pursuant to Article 6.2, the Collaborator grants to the Government a
     nonexclusive, nontransferable, irrevocable, paid-up license to practice the
     invention or have the invention practiced throughout the world by or on
     behalf of the Government for research or other Government purposes.

7.5  Third Party License.  Pursuant to 15 U.S.C. (S) 3710a(b)(1)(B), if PHS
     grants an exclusive license to a Subject Invention made wholly by PHS
     employees or jointly with a Collaborator under this CRADA, pursuant to
     Articles 6.3 and 6.4, the Government shall retain the right to require the
     Collaborator to grant to a responsible applicant a nonexclusive, partially
     exclusive, or exclusive sublicense to use the invention in Collaborator's
     licensed field of use on terms that are reasonable under the circumstances;
     or if the Collaborator fails to grant such a license, to grant the license
     itself.  The exercise of such rights by the Government shall only be in
     exceptional circumstances and only if the Government determines (i) the
     action is necessary to meet health or safety needs that are not reasonably
     satisfied by Collaborator, (ii) the action is necessary to meet
     requirements for public use specified by Federal regulations, and such
     requirements are not reasonably satisfied by the Collaborator; or (iii) the
     Collaborator has failed to comply with an agreement containing provisions
     described in 15 U.S.C. 3710a(c)(4)(B).  The determination made by the
     Government under this Article is subject to administrative appeal and
     judicial review under 35 U.S.C. 203(2).

7.6  Joint Inventions Not Exclusively Licensed.  In the event that the
     Collaborator does not acquire an exclusive commercialization license to IP
     rights in all fields in joint Subject Inventions described in Article 6.4,
     then each Party shall have the right to use the joint Subject Invention and
     to license its use to others in all fields not exclusively licensed to
     Collaborator.  The Parties may agree to a joint licensing approach for such
     IP rights.

Article 8.  Proprietary Rights and Publication

8.1  Right of Access.  PHS and the Collaborator agree to exchange all Subject
     Data produced in the course of research under this CRADA.  Research
     Materials will be shared equally by the Parties to the CRADA unless other
     disposition is agreed to by the Parties.  All Parties to this CRADA will be
     free to utilize Subject Data and Research Materials for their own purposes,
     consistent with their obligations under this CRADA.

8.2  Ownership of Subject Data and Research Materials.  Subject to the sharing
     requirements of Paragraph 8.1 and the regulatory filing requirements of
     Paragraph 8.3, the producing Party will retain ownership of and title to
     all Subject Inventions, all Subject Data and all Research Materials
     produced solely by their investigators.  Jointly developed Subject
     Inventions, Subject Data and Research Materials will be jointly owned.

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8.3  Dissemination of Subject Data and Research Materials.  To the extent
     permitted by law, the Collaborator and PHS agree to use reasonable efforts
     to keep Subject Data and Research Materials confidential until published or
     until corresponding patent applications are filed.  Any information that
     would identify human subjects of research or patients will always be
     maintained confidentially.  To the extent permitted by law, the
     Collaborator shall have the exclusive right to use any and all CRADA
     Subject Data in and for any regulatory filing by or on behalf of
     Collaborator, except that PHS shall have the exclusive right to use Subject
     Data for that purpose, and authorize others to do so, if the CRADA is
     terminated or if Collaborator abandons its commercialization efforts.

8.4  Proprietary/Confidential Information.  Each Party agrees to limit its
     disclosure of Proprietary/Confidential Information to the amount necessary
     to carry out the Research Plan of this CRADA, and shall place a
     confidentiality notice on all such information.  Confidential oral
     communications shall be reduced to writing within 30 days by the disclosing
     Party.  Each Party receiving Proprietary/Confidential Information agrees
     that any information so designated shall be used by it only for the
     purposes described in the attached Research Plan.  Any Party may object to
     the designation of information as Proprietary/Confidential Information by
     another Party.  Subject Data and Research Materials developed solely by the
     Collaborator may be designated as Proprietary/Confidential Information when
     they are wholly separable from the Subject Data and Research Materials
     developed jointly with PHS investigators, and advance designation of such
     data and material categories is set forth in the RP.  The exchange of other
     confidential information, e.g.,  patient-identifying data, should be
     similarly limited and treated.  Jointly developed Subject Data and Research
     Material derived from the Research Plan may be disclosed by Collaborator to
     a third party under a confidentiality agreement for the purpose of possible
     sublicensing pursuant to the Licensing Agreement and subject to Article
     8.7.

8.5  Protection of Proprietary/Confidential Information. 
     Proprietary/Confidential Information shall not be disclosed, copied,
     reproduced or otherwise made available to any other person or entity
     without the consent of the owning Party except as required under court
     order or the Freedom of Information Act (5 U.S.C. ' 552). Each Party agrees
     to use its best efforts to maintain the confidentiality of
     Proprietary/Confidential Information. Each Party agrees that the other
     Party is not liable for the disclosure of Proprietary/Confidential
     Information which, after notice to and consultation with the concerned
     Party, the other Party in possession of the Proprietary/Confidential
     Information determines may not be lawfully withheld, provided the concerned
     Party has been given an opportunity to seek a court order to enjoin
     disclosure.

8.6  Duration of Confidentiality Obligation.  The obligation to maintain the
     confidentiality of Proprietary/Confidential Information shall expire at the
     earlier of the date when the information is no longer Proprietary
     Information as defined in Article 2.7 or three (3) years after the
     expiration or termination date of this CRADA.  The Collaborator may request
     an extension to this term when necessary to protect
     Proprietary/Confidential Information relating to products not yet
     commercialized.

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8.7  Publication.  The Parties are encouraged to make publicly available the
     results of their research.  Before either Party submits a paper or abstract
     for publication or otherwise intends to publicly disclose information about
     a Subject Invention, Subject Data or Research Materials, the other Party
     shall be provided thirty (30) days to review the proposed publication or
     disclosure to assure that Proprietary/Confidential Information is
     protected.  The publication or other disclosure shall be delayed for up to
     thirty (30) additional days upon written request by any Party as necessary
     to preserve U.S. or foreign patent or other IP rights.

Article 9.  Representations and Warranties

9.1  Representations and Warranties of PHS.  PHS hereby represents and warrants
     to the Collaborator that the official signing this CRADA has authority to
     do so.

9.2  Representations and Warranties of the Collaborator.

     9.2.1.  The Collaborator hereby represents and warrants to PHS that the
             Collaborator has the requisite power and authority to enter into
             this CRADA and to perform according to its terms, and that the
             Collaborator's official signing this CRADA has authority to do so.
             The Collaborator further represents that it is financially able to
             satisfy any funding commitments made in Appendix B.

     9.2.2.  The Collaborator certifies that the statements herein are true,
             complete, and accurate to the best of its knowledge. The
             Collaborator is aware that any false, fictitious, or fraudulent
             statements or claims may subject it to criminal, civil, or
             administrative penalties.

Article 10.  Termination

10.1 Termination By Mutual Consent.  PHS and the Collaborator may terminate this
     CRADA, or portions thereof, at any time by mutual written consent.  In such
     event the Parties shall specify the disposition of all property,
     inventions, patent or other IP applications and other results of work
     accomplished or in progress, arising from or performed under this CRADA,
     all in accordance with the rights granted to the Parties under the terms of
     this Agreement.

10.2 Unilateral Termination.  Either PHS or the Collaborator may unilaterally
     terminate this entire CRADA at any time by giving written notice at least
     thirty (30) days prior to the desired termination date, and any rights
     accrued in property, patents or other IP rights shall be disposed of as
     provided in paragraph 10.1.

10.3 Staffing.  If this CRADA is mutually or unilaterally terminated prior to
     its expiration, funds will nevertheless remain available to PHS for
     continuing any staffing commitment made by the Collaborator pursuant to
     Article 5.1 above and Appendix B, if applicable, for a period of six (6)
     months after such termination.  If there are insufficient funds to cover
     this expense, the Collaborator agrees to pay the difference.

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10.4 New Commitments.  No Party shall make new commitments related to this CRADA
     after a mutual termination or notice of a unilateral termination and shall,
     to the extent feasible, cancel all outstanding commitments and contracts by
     the termination date.

10.5 Termination Costs.  Concurrently with the exchange of final reports
     pursuant to Articles 4.2 and 5.2, PHS shall submit to the Collaborator for
     payment a statement of all costs incurred prior to the date of termination
     and for all reasonable termination costs including the cost of returning
     Collaborator property or removal of abandoned property, for which
     Collaborator shall be responsible.

Article 11.  Disputes

11.1 Settlement.  Any dispute arising under this CRADA which is not disposed of
     by agreement of the Principal Investigators shall be submitted jointly to
     the signatories of this CRADA.  If the signatories are unable to jointly
     resolve the dispute within thirty (30) days after notification thereof, the
     Assistant Secretary for Health (or his/her designee or successor) shall
     propose a resolution.  Nothing in this Article shall prevent any Party from
     pursuing any additional administrative remedies that may be available and,
     after exhaustion of such administrative remedies, pursuing all available
     judicial remedies.

11.2 Continuation of Work.  Pending the resolution of any dispute or claim
     pursuant to this Article, the Parties agree that performance of all
     obligations shall be pursued diligently in accordance with the direction of
     the PHS signatory.

Article 12.  Liability

12.1 Property.  The U.S. Government shall not be responsible for damages to any
     Collaborator property  provided to PHS, where Collaborator retains title to
     the property, or any property acquired by Collaborator for its own use
     pursuant to this CRADA.

12.2 NO WARRANTIES.  EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE PARTIES
     MAKE NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER WHATSOEVER, INCLUDING
     THE CONDITIONS OF THE RESEARCH OR ANY INVENTION OR PRODUCT, WHETHER
     TANGIBLE OR INTANGIBLE, MADE, OR DEVELOPED UNDER THIS CRADA, OR THE
     OWNERSHIP, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF THE
     RESEARCH OR ANY INVENTION OR PRODUCT.

12.3 Indemnification.  The Collaborator agrees to hold the U.S. Government
     harmless and to indemnify the Government for all liabilities, demands,
     damages, expenses and losses arising out of the use by the Collaborator for
     any purpose of the Subject Data, Research Materials and/or Subject
     Inventions produced in whole or part by PHS employees under this CRADA,
     unless due to the negligence or willful misconduct of PHS, its employees,
     or agents.  The Collaborator shall be liable for any claims or damages it
     incurs in connection with this CRADA.  PHS has no authority to indemnify
     the Collaborator.

12.4 Force Majeure.  Neither Party shall be liable for any unforeseeable event
     beyond its reasonable control not caused by the fault or negligence of such
     Party, which causes such  

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     Party to be unable to perform its obligations under this CRADA, and which
     it has been unable to overcome by the exercise of due diligence. In the
     event of the occurrence of such a force majeure event, the Party unable to
     perform shall promptly notify the other Party. It shall further use its
     best efforts to resume performance as quickly as possible and shall suspend
     performance only for such period of time as is necessary as a result of the
     force majeure event.

Article 13.  Miscellaneous

13.1 Governing Law.  The construction, validity,  performance and effect of this
     CRADA shall be governed by Federal law, as applied by the Federal Courts in
     the District of Columbia.  Federal law and regulations will preempt any
     conflicting or inconsistent provisions in this CRADA.

13.2 Entire Agreement.  This CRADA constitutes the entire agreement between the
     Parties concerning the subject matter of this CRADA and supersedes any
     prior understanding or written or oral agreement.

13.3 Headings.  Titles and headings of the articles and subarticles of this
     CRADA are for convenient reference only, do not form a part of this CRADA,
     and shall in no way affect its interpretation.  The PHS component that is
     the Party for all purposes of this CRADA is the Bureau(s), Institute(s),
     Center(s) or Division(s) listed on the Cover Page herein.

13.4 Waivers.  None of the provisions of this CRADA shall be considered waived
     by any Party unless such waiver is given in writing to the other Party.
     The failure of a Party to insist upon strict performance of any of the
     terms and conditions hereof, or failure or delay to exercise any rights
     provided herein or by law, shall not be deemed a waiver of any rights of
     any Party.

13.5 Severability.  The illegality or invalidity of any provisions of this CRADA
     shall not impair, affect, or invalidate the other provisions of this CRADA.

13.6 Amendments.  If either Party desires a modification to this CRADA, the
     Parties shall, upon reasonable notice of the proposed modification or
     extension by the Party desiring the change, confer in good faith to
     determine the desirability of such modification or extension.  Such
     modification shall not be effective until a written amendment is signed by
     the signatories to this CRADA or by their representatives duly authorized
     to execute such amendment.

13.7 Assignment.  Neither this CRADA nor any rights or obligations of any Party
     hereunder shall be assigned or otherwise transferred by either Party
     without the prior written consent of the other Party.

13.8 Notices.  All notices pertaining to or required by this CRADA shall be in
     writing and shall be signed by an authorized representative and shall be
     delivered by hand or sent by certified mail, return receipt requested, with
     postage prepaid, to the addresses indicated on the signature page for each
     Party.  Notices regarding the exercise of license options 

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       shall be made pursuant to Article 7.2. Any Party may change such address
       by notice given to the other Party in the manner set forth above.

13.9   Independent Contractors.  The relationship of the Parties to this CRADA
       is that of independent contractors and not agents of each other or joint
       venturers or partners. Each Party shall maintain sole and exclusive
       control over its personnel and operations. Collaborator employees who
       will be working at PHS facilities may be asked to sign a Guest Researcher
       or Special Volunteer Agreement appropriately modified in view of the
       terms of this CRADA.

13.10  Use of Name or Endorsements.  By entering into this CRADA, PHS does not
       directly or indirectly endorse any product or service provided, or to be
       provided, whether directly or indirectly related to either this CRADA or
       to any patent or other IP license or agreement which implements this
       CRADA by its successors, assignees, or licensees. The Collaborator shall
       not in any way state or imply that this CRADA is an endorsement of any
       such product or service by the U.S. Government or any of its
       organizational units or employees. Collaborator issued press releases
       that reference or rely upon the work of PHS under this CRADA shall be
       made available to PHS at least 7 days prior to publication for review and
       comment.

13.11  Exceptions to this CRADA.  Any exceptions or modifications to this CRADA
       that are agreed to by the Parties prior to their execution of this CRADA
       are set forth in Appendix C.

13.12  Reasonable Consent.  Whenever a Party's consent or permission is required
       under this CRADA, such consent or permission shall not be unreasonably
       withheld.

Article 14.  Duration of Agreement

14.1   Duration.  It is mutually recognized that the duration of this project
       cannot be rigidly defined in advance, and that the contemplated time
       periods for various phases of the RP are only good faith guidelines
       subject to adjustment by mutual agreement to fit circumstances as the RP
       proceeds. In no case will the term of this CRADA extend beyond the term
       indicated in the RP unless it is revised in accordance with Article 13.6.

14.2   Survivability.  The provisions of Articles 4.2, 5-8, 10.3-10.5, 11.1,
       12.2-12.4, 13.1, 13.10 and 14.2 shall survive the termination of this
       CRADA.

 

 

                       SIGNATURES BEGIN ON THE NEXT PAGE

                                       12

 
FOR PHS:
 
 
 /s/ Alan Rabson                                           12/31/99
---------------------------------------------             ----------------------
Alan Rabson, M.D.                                         Date
Deputy Director, NCI
 
Mailing Address for Notices:

National Cancer Institute
Technology Development & Commercialization Branch
NCI-FCRDC
1003 West Seventh Street, Fairview Center, Suite 502
Frederick, MD 21701
phone: 301-846-5465
fax: 301-8466820
 
FOR THE COLLABORATOR:
 
 
 /s/ Russell J. Howard                                    2/24/00
---------------------------------------------             ----------------------
Russell J. Howard, Ph.D.                                  Date
CEO and President
 
Mailing Address for Notices:
 
Maxygen, Inc.
515 Galveston Drive
Redwood City, CA 94063
phone: 650-298-5300
fax: 650-364-2715

                                       13

 
                          Appendix A: RESEARCH PLAN 
                          -------------------------

Title: Shuffling of *******.

National Cancer Institute (NCI) Principal Investigators: 
*******

******* 

Collaborator Principal Investigator: 
******* 


          Term of CRADA: 3 years from execution of this CRADA.

A Letter of Intent (LOI) for this CRADA was executed by and between the Parties
on 10/13/99.

GOALS OF THE CRADA: 
------------------ 

     This CRADA Research Plan (RP) describes a collaboration between the NCI-
Developmental Therapeutics Program (DTP) and Maxygen. The CRADA collaboration
leverages the NCI research on ******* and Maxygen's proprietary Shuffling
Technology which can rapidly evolve and select improved versions of natural and
synthetic *******. The major activity of this CRADA is for the DTP and Maxygen
to collaborate to screen and characterize ******* provided by Maxygen. The major
goal of this CRADA is to maximize the chemotherapeutic potential of *******.

Goal A of this CRADA is to screen and optimize evolved ******* synergize with
that of the commercially-available, tubulin inhibitor, *******, on breast cancer
cell lines.

The ******* provided by Maxygen for screening and optimization under this CRADA
will be targeted toward one or the other of the following improved cytotoxicity
and antigenic profiles:

(1) An evolved, *******. 

(2) An evolved derivative of the *******.

One of the great attractions of ******* as anti-tumor agents is that they act by
mechanisms that are insensitive to mutations in *******. Additionally, they
synergize with the activity of DNA damaging agents such as ******* in some, but
not all, cell lines [32]. The Shuffled ******* may be expressed as fusions to
targeting domains such as *******.

                                      14

 
Goal B: Implement an in vivo mouse model program to identify clinical candidates
from the optimized evolved *******.

Candidate molecules selected for improved activity from the efforts as described
in Goal A are to be screened by the NCI-Biological Testing Branch (BTB) in
******* animal models containing *******.

SCIENTIFIC BACKGROUND
---------------------

Maxygen's Shuffling Technology:

     Maxygen's Shuffling Technology: Maxygen's Shuffling Technology consists of
proprietary techniques, methodologies, processes, materials and/or
instrumentation useful for the recombination, rearrangement, and/or mutation of
genetic material for the creation of genetic diversity, and subsequent
techniques useful for the high-throughput (HTP) screening of the resultant
genetic material to identify potentially useful genes. Shuffling, as practiced
in the laboratory, mirrors the process of natural evolution by which the
tremendous diversity of all life forms may have been created. In nature, the
accumulation of mutations and the process of sexual reproduction creates genetic
diversity. This genetic diversity is subjected to natural selection pressures
such that only some of the genetic diversity survives. Humans have used the
enormous amount of existing genetic diversity to their advantage by breeding
domestic dogs, horses, cattle, cats, vegetables, fruits, and cereals from wild
breeding stocks. Breeders select whatever characteristics they desire from
within existing species and breed them together, regardless of whether the
resulting animal or plant would ever survive (i.e. be useful) in nature. In just
a few generations of breeding, substantial variation and novel properties can be
achieved.

     Shuffling is, in essence, the application of classical breeding principles
to sub-genomic sequences. This approach to sequence evolution generalizes
concepts from classical genetics, allowing one to selectively breed DNA
sequences in the test tube. Maxygen begins with the natural diversity already
present in a gene family or creates it by mutagenesis, and then rapidly shuffles
the diversity to create a large pool of novel genes. Their process involves
fragmenting the genes into pieces and reassembling them in a homology-dependent
fashion. Those genes that encode proteins with the desired novel properties are
then selected using high-throughput (HTP) screening assays. As with traditional
breeding, Maxygen's technology does not require a rational understanding of the
genes involved in order to engineer novel properties. This technology provides a
powerful tool for rapidly evolving single genes, operons and whole viruses for
desired properties, and has many advantages relative to random mutation or
rational sequence design.

******* 

RELATED PATENT APPLICATIONS AND PATENTS, OTHER AGREEMENTS: 
---------------------------------------------------------

                                      15

 
The Parties hereby modify their rights under the following prior agreements:

Confidential Disclosure Agreement: Two-way agreement # 3-60778-99;

     *******. 

     ******* 

*******

and the Parties agree that the materials and/or information provided thereunder
are now governed by the terms of this CRADA in accordance with Article 13.2,
except that the obligations of the parties with regard to confidentiality shall
remain retroactive to December 14, 1998. 

Letter of Intent: A Letter of Intent (LOI) for this CRADA was executed by and
----------------
between the Parties on 10/13/99. With this exception, there are no other
existing CRADAs between NIH and Maxygen.

Related Patents/Patent Applications of NCI: 
------------------------------------------

Note: Maxygen has decided not to apply for a license at this time for the NIH
Intellectual Property listed below. Maxygen would prefer to wait for results
obtained from the Research Plan of this CRADA before applying for a license.
Nothing herein is a commitment by NIH not to license this patent(s) to others
who may apply for a license pursuant to 37CFR 404 in the interim.

******* 

                                      16

 
                                  APPENDIX B
                                  ----------

FINANCIAL AND STAFFING CONTRIBUTIONS OF THE PARTIES 
---------------------------------------------------

Maxygen Staffing: (total of 0.******* person-years for 1st year of CRADA.
Staffing in subsequent years 2-3 will be contingent on the results obtained in
the initial year). Changes in staffing levels will be documented by written
amendment.

Maxygen will provide scientific staff and other support as necessary to conduct
the research outlined in Appendix A, Research Plan. Staffing for the first year
will be as follows:

     Name      Position / title   % of time devoted to CRADA Research Plan 
     --------------------------   ----------------------------------------

*******      Principal Investigator     ******* 

     Duties: Direct the research described in the CRADA goals and provide
scientific staff and other support as necessary to conduct the Research Plan as
outlined in Appendix A.

*******        Manager, Business Development      ******* 

     Duties: Assess commercial progress and opportunities, and provide on-going
business support for Research Plan activities.

*******        Maxygen   *******

     Duties: Creation of Shuffled ******* at Maxygen, and scale-up of
expression.

*******        Maxygen   ******* 

     Duties: Expression and HTP screening of *******. 

The above assignments and time allocations are approximate. During the term of
the CRADA, these staffing assignments and percentages of time devoted to CRADA
research are likely to vary from the information provided above.

Maxygen Financial Support: No funding will be provided to the National Cancer
Institute for collaborative research and development pursuant to this CRADA.

National Cancer Institute Staffing: (total of ******* person-years/year).

                                      17

 
Name                Position / title    % time devoted to CRADA Research 
------------------------------------    --------------------------------

*******         NCI, Principal Investigator                 ******* 

     Duties: To direct the research described in the CRADA goals and provide
scientific staff and other support as necessary to conduct the Research Plan as
outlined in Appendix A. 

*******         Principal Investigator                      ******* 

     Duties: To direct the research described in the CRADA goals and provide
scientific staff and other support as necessary to conduct the Research Plan as
outlined in Appendix A.

*******,       SAIC Investigator                            ******* 

     Duties: Supervise SAIC personnel on project and conduct in vitro assays.

*******        NCI/DTP / LDDR                               ******* 

     Duties: Conduct in vitro assays.

*******        NCI/DTP Investigator                         ******* 

     Duties: Conduct in vitro assays 

*******        NCI/DTP Investigator                         ******* 

     Duties: Conduct in vivo assays

*******        SAIC Research Technician                     ******* 

     Duties: Conduct in vivo assays 

NCI Financial Support: 

NCI will provide no funding to the Collaborator for collaborative research and
development pursuant to this CRADA inasmuch as financial contributions by the
U.S. government to non-Federal parties under a CRADA are not authorized under
the Federal Technology Transfer Act [15 U.S.C. (S) 3710a(d)(1)].

                                      18

 
                                  APPENDIX C 
                                  ----------

                  EXCEPTIONS OR MODIFICATIONS TO THIS CRADA 
                  -----------------------------------------

The PHS Model CRADA is replaced in its entirety by the following in which
additional terms are underlined, while deletions are struck-out.

                                      19

 
                             PUBLIC HEALTH SERVICE

                COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT 

This Cooperative Research and Development Agreement, hereinafter referred to as
the CRADA, consists of this Cover Page, an attached Agreement, and various
Appendices referenced in the Agreement.

This Cover Page serves to identify the Parties to this CRADA: 

     (1) the following Bureau(s), Institute(s), Center(s) or Division(s) of the
National Institutes of Health (`NIH'), The National Cancer Institute (`NCI'),
hereinafter referred to as the National Institutes of Health (`NIH'); and

     (2) Maxygen, Inc. which has offices at 515 Galveston Drive, Redwood City,
California 94063, hereinafter referred to as the `Collaborator'.

                                      20

 
COOPERATIVE  RESEARCH AND DEVELOPMENT AGREEMENT


Article 1.  Introduction

This Cooperative Research and Development Agreement (CRADA) between NIH and the
Collaborator will be effective when signed by all Parties.  The research and
development activities which will be undertaken by each of the Parties in the
course of this CRADA are detailed in the Research Plan which is attached as
Appendix A.  The funding and staffing commitments of the Parties are set forth
in Appendix B.  Any exceptions or changes to the CRADA are set forth in Appendix
C.  This CRADA is made under the authority of the Federal Technology Transfer
Act, 15 U.S.C. (S)3710a and is governed by its terms.

Article 2.  Definitions

As used in this CRADA, the following terms shall have the indicated meanings:

2.1  "Affiliate" means any corporation or other business entity controlled by,
     controlling, or under common control with Collaborator. For this purpose, A
     "control" means direct or indirect beneficial ownership of at least fifty
     (50) percent of the voting stock or at least fifty (50) percent interest in
     the income of such corporation or other business.

2.2  "Cooperative Research and Development Agreement" or "CRADA" means this
     Agreement, entered into by NIH pursuant to the Federal Technology Transfer
     Act of 1986, as amended, 15 U.S.C. 3710a et seq. and Executive Order 12591
     of October 10, 1987.

2.3  "Government" means the Government of the United States as represented
     through the NIH agency that is a Party to this agreement.

2.4  "IP" means intellectual property.

2.5  "Invention" means any invention or discovery which is or may be
     patentable or otherwise protected under title 35, United States Code, or
     any novel variety or plant which is or may be protectable under the Plant
     Variety Protection Act (7 U.S.C. 2321 et seq.).

                                       21

 
2.6  "Principal Investigator(s)" or "PIs" means the persons designated
     respectively by the Parties to this CRADA who will be responsible for the
     scientific and technical conduct of the Research Plan.

2.7  "Proprietary/Confidential Information" means confidential scientific,
     business, or financial information provided that such information does not
     include:

     2.7.1.  information that is publicly known or available from other sources
             who are not under a confidentiality obligation to the source of the
             information;

     2.7.2.  information which has been made available by its owners to others
             without a confidentiality obligation;

     2.7.3.  information which is already known by or available to the receiving
             Party without a confidentiality obligation; or

     2.7.4.  information which relates to potential hazards or cautionary
             warnings associated with the production, handling or use of the
             subject matter of the Research Plan of this CRADA.

2.8  "Research Materials" means all tangible materials other than Subject Data
     first produced in the performance of the Research Plan of this CRADA.

2.9  "Research Plan" means the statement in Appendix A of the respective
     research and development commitments of the Parties to this CRADA.

2.10 "Subject Invention" means any Invention of the Parties, conceived or first
     actually reduced to practice in the performance of the Research Plan of
     this CRADA.

2.11 "Subject Data" means all recorded information first produced in the
     performance of the Research Plan of this CRADA by the Parties.

2.12 "Steering Committee" means the joint NIH Collaborator research and
     development team whose composition and responsibilities with regard to the
     studies performed under this CRADA are described in Article 3.3 of this
     CRADA.

                                       22

 
2.13 "Shuffling" means the systems set up by man to use high speed recombination
     and/or rearrangement and/or mutation of genetic material for the creation
     of genetic diversity.

2.14 "Shuffling Technology" means techniques, methodologies, processes,
     materials and/or instrumentation useful for Shuffling, and the screening of
     genetic material resulting from Shuffling to identify potential useful
     genes.

Article 3. Cooperative Research

3.1  Principal Investigators.  NIH research work under this CRADA will be
     performed by the NIH laboratory identified in the Research Plan, and the
     NIH Principal Investigator (PI) designated in the Research Plan will be
     responsible for the scientific and technical conduct of this project on
     behalf of NIH. Also designated in the Research Plan is the Collaborator PI
     who will be responsible for the scientific and technical conduct of this
     project on behalf of the Collaborator.

3.2  Research Plan Change.  The Research Plan may be modified by mutual written
     consent of the Principal Investigators. Substantial changes in the scope of
     the Research Plan will be treated as amendments under Article 13.6. If the 
     results from the Research Plan are promising, NIH and Collaborator shall
     discuss, in good faith, plans to support and to submit proposals for
     further research in a separate clinical CRADA. If the Research Plan is
     amended to include the participation of any extramural grantee
     investigators, NIH shall urge the grantee investigators to cooperate
     exclusively with the Collaborator. However, such urging shall not
     constitute a condition of any grant award.

3.3  Steering Committee and CRADA Research. The Parties agree to establish a
     Steering Committee comprising at least the Principal Investigators
     designated pursuant to Article 3.1 to conduct and monitor the research in
     accordance with the Research Plan, review Subject Inventions disclosures
     and to review proposed publications and data. Details of the research and
     development as set forth in the Research Plan shall be formulated, reviewed
     and/or approved in Steering Committee meetings before implementation of any
     resource-intensive study. Notwithstanding the forgoing, Collaborator has 
     the option to sponsor its own pre-clinical studies outside the scope of 
     this CRADA.

3.4  Composition of Steering Committee. Collaborator and NIH shall have equal
     voice in decisions of the Steering Committee. The initial composition of
     the Steering Committee shall be voting members on behalf of NIH and two
     voting members on behalf of Collaborator. A Steering Committee member
     representing NIH will co-chair the Steering committee with the Steering 
     Committee member representing Collaborator. The membership of the Steering
     Committee may be changed from time to time as mutually agreed by NIH and
     Collaborator in writing.

                                       23

 
3.5  Meetings. The Steering Committee shall meet within one month of the
     execution of this CRADA, and then regularly once a quarter thereafter or as
     appropriate. The Steering Committee shall be the forum for discussion of
     issues for which differences in opinion may arise and shall be the initial
     forum to attempt to resolve any disputes arising therefrom. In the event,
     resolution of such dispute(s) is not achieved in the Steering Committee,
     the dispute resolution mechanism of Article 11 herein shall be implemented.
     The Principal Investigators shall report regularly to the Steering
     Committee on the progress of the research and development efforts covered
     by this CRADA, but not less than once a quarter, unless mutually agreed.
     Attendance at the Steering Committee meetings shall be limited to members
     of the Steering Committee and invited participants, as mutually agreed to
     by the Parties. Invited participants shall be non-voting members of the
     Steering Committee.

3.6  Written Record. The Steering Committee shall appoint one of its members to
     act as the Committee Secretary for each meeting, such appointment
     alternately between the parties from meeting to meeting. The Secretary
     shall prepare, for Committee approval and signature, written summaries of
     each Steering Committee meeting within two weeks of each Steering Committee
     meeting. These summaries shall include information about Steering
     Committee deliberations and describe issues addressed and decisions
     reached. Written materials created by the Steering Committee shall be
     treated as described in subarticle 3.7 below. The written summary shall be
     deemed to be deemed to be approved by the Committee if no comments are
     received within two weeks of receipt thereof. Upon incorporation of
     modifications in accordance with such comments, the revised summary shall
     be transmitted to Committee members of signature, but will be deemed
     approved within two weeks of receipt thereof.

3.7  Treatment of Steering Committee Proprietary Information. Except as required
     by law and subject to Article 8 of this CRADA, the Parties agree that 
     Proprietary/Confidential Information including disclosures of such data in
     discussions and information exchanged at meetings of the Steering
     Committee, and in written summaries of Steering Committee meetings, shall
     be maintained as confidential to the Parties, and shall not be disclosed to
     any third parties without the consultation and written agreement within the
     Steering Committee.
 
 Article 4. Reports

 4.1 Interim Reports.  The Parties shall exchange formal written interim
     progress reports on a schedule agreed to by the PIs, but at least within
     twelve (12) months after this CRADA becomes effective and at least within
     every twelve (12) months thereafter.  Such reports shall set forth the
     technical progress made, identifying such problems as may have been
     encountered and establishing goals and objectives requiring further effort,
     any modifications to the Research Plan pursuant to Article 3.2, and all
     CRADA-related patent applications filed.

                                       24

 
     Steering Committee reports or copies of annual reports updating the
     progress of the CRADA research shall satisfy the minimum reporting
     requirements under this Article 4.1.

4.2  Final Reports. The Parties shall exchange final reports of their results
     within four (4) months after completing the projects described in the
     Research Plan or after the expiration or termination of this CRADA.

Article 5.  Financial and Staffing Obligations

5.1  NIH and Collaborator Contributions.  The contributions of the Parties,
     including payment schedules, if applicable, are set forth in Appendix B.
     NIH shall not be obligated to perform any of the research specified herein
     or to take any other action required by this CRADA if the funding is not
     provided as set forth in Appendix B.  NIH shall return excess funds to the
     Collaborator when it sends its final fiscal report pursuant to Article 5.2,
     except for staffing support pursuant to Article 10.3.  Collaborator
     acknowledges that the U.S. Government will have the authority to retain and
     expend any excess funds for up to one (1) year subsequent to the expiration
     or termination of the CRADA to cover any costs incurred during the term of
     the CRADA in undertaking the work set forth in the Research Plan.

5.2  Accounting Records. NIH shall maintain separate and distinct current
     accounts, records, and other evidence supporting all its obligations under
     this CRADA, and shall provide the Collaborator a final fiscal report
     pursuant to Article 4.2.

5.3  Capital Equipment. Equipment purchased by NIH with funds provided by the
     Collaborator shall be the property of NIH.  All capital equipment provided
     under this CRADA by one party for the use of another Party remains the
     property of the providing Party unless other disposition is mutually agreed
     upon by in writing by the Parties.  If title to this equipment remains with
     the providing Party, that Party is responsible for maintenance of the
     equipment and the costs of its transportation to and from the site where it
     will be used.

Article 6.  Intellectual Property Rights and Patent Applications

6.1  Reporting. The Parties shall promptly report to each other in writing each
     Subject Invention resulting from the research conducted under this CRADA
     that is reported to them by their respective employees. Each Party shall
     report all Subject Inventions to the other Party in sufficient detail to
     determine inventorship. Such reports shall be treated as
     Proprietary/Confidential Information in accordance with Article 8.4.

                                       25

 
6.2  Collaborator Employee Inventions. If the Collaborator does not elect to
     retain title to its IP rights in a Subject Invention, the Collaborator
     shall offer to assign these IP rights to the Subject Invention to NIH
     pursuant to Article 6.5. If NIH declines such assignment, the Collaborator
     may release title to its IP rights as it may determine.

6.3  NIH Employee Inventions. NIH on behalf of the U.S. Government may elect to
     retain title to its IP rights to each Subject Invention made solely by NIH
     employees. If NIH does not elect to retain title to its IP rights, NIH
     shall offer to assign these IP rights to such Subject Invention to the
     Collaborator pursuant to Article 6.5. If the Collaborator declines such
     assignment, NIH may release title to its IP rights in such Subject
     Invention to its employee inventors pursuant to Article 6.6.

6.4  Joint Inventions.  Each Subject Invention made jointly by NIH and
     Collaborator employees shall be jointly owned by NIH and the Collaborator.
     If NIH and Collaborator both agree that a patent application should be
     filed on a jointly owned Subject Invention, then the parties shall consult
     about the best manner to proceed in filing and prosecuting the jointly
     owned patent application. If NIH and Collaborator elect to file jointly,
     then each shall bear one-half the costs of such filing and prosecution.
     However, NIH only has authority to reimburse such costs directly to law
     firms under contract to NIH. Alternatively, the Collaborator may elect to
     file the joint patent or other IP application(s) thereon and shall notify
     NIH promptly upon making this election. If the Collaborator decides to file
     such applications, it shall do so in a timely manner and at its own
     expense. If the Collaborator does not elect to file such application(s),
     NIH on behalf of the U.S. Government shall have the right to file the joint
     application(s) in a timely manner and at its own expense. If either Party
     decides not to retain title to its IP rights to a jointly owned Subject
     Invention, it shall offer to assign such rights to the other Party pursuant
     to Article 6.5. If the other Party declines such assignment, the offering
     Party may release title to its IP rights as provided in Articles 6.2, 6.3,
     and 6.6.

6.5  Filing of Patent Applications.  With respect to Subject Inventions made by
     the Collaborator as described in Article 6.2, or by NIH as described in
     Article 6.3, a Party exercising its right to elect to retain title to its
     IP rights to a Subject Invention agrees to file patent or other IP
     applications in a timely manner and at its own expense and after
     consultation with the other Party. The Party shall notify the other Party
     of its decision regarding filing in countries other than the United States
     in a timely manner. The Party may elect not to file a patent or other IP
     application thereon in any particular country or countries provided it so
     advises the other Party ninety (90) days prior to the expiration of any
     applicable filing deadline, priority period or statutory bar date, and
     hereby agrees to assign its IP right, title and interest in the Subject
     Invention in such country or countries to the Subject Invention to the
     other Party and to cooperate in the preparation and filing of a patent or
     other IP applications. In any countries in which title to patent or other
     IP rights for Subject Inventions is transferred to the Collaborator, the
     Collaborator agrees that NIH 

                                       26

 
     inventors will share in any royalty distribution that the Collaborator pays
     to its own inventors.

6.6  Release to Inventors.  In the event neither of the Parties to this CRADA
     elects to file a patent or other IP application on a Subject Invention,
     either or both (if a joint invention) may retain or release titles to their
     IP rights in accordance with their respective policies and procedures. If
     NIH elects not to retain title to its IP rights in and to any such Subject
     Invention made solely or jointly by NIH, the Government shall retain a
     nonexclusive, non-transferable, irrevocable, royalty-free license to
     practice any such Subject Invention, or have it practiced throughout the
     world by or on behalf of the Government. Similarly, if Collaborator elects
     not to retain title to any IP rights to Subject Inventions made jointly or
     solely by its employees and, pursuant to Article 6.2 herein, offers such
     rights to NIH which waives such rights, then Collaborator shall be free to
     release such rights to its employee inventors subject to the Government
     retaining a nonexclusive, non-transferable, irrevocable, royalty-free
     license to practice, or have such Subject Inventions(s) practiced
     throughout the world by or on behalf of the Government.

6.7  Patent Expenses. The expenses attendant to the filing of patent or other
     IP applications generally shall be paid by the Party filing such
     application unless agreed otherwise in connection with jointly owned patent
     applications. If an exclusive license to any Subject Invention is granted
     to the Collaborator, the Collaborator shall be responsible for all past and
     future out-of-pocket expenses in connection with the preparation, filing,
     prosecution and maintenance of any applications claiming such exclusively-
     licensed inventions and any patents or other IP grants that may issue on
     such applications. The Collaborator may waive its exclusive license rights
     on any application, patent or other IP grant at any time, and incur no
     subsequent compensation obligation for that application, patent or IP
     grant.

6.8  Prosecution of Intellectual Property Applications.  Within one month of
     receipt or filing,  each Party shall provide the other Party with copies of
     the applications and all documents received from or filed with the relevant
     patent or other IP office in connection with the prosecution of such
     applications.  Each Party shall also provide the other Party with the power
     to inspect and make copies of all documents retained in the patent or other
     IP application files by the applicable patent or other IP office.  Where
     licensing is contemplated by Collaborator, the Parties agree to consult
     with each other with respect to the prosecution of applications for NIH
     Subject Inventions described in Article 6.3 and joint Subject Inventions
     described in Article 6.4. If the one party elects to file and prosecute IP
     applications on joint Subject Inventions pursuant to Article 6.4, the other
     party will be granted an associate power of attorney (or its equivalent) on
     such IP applications. Patent counsel for each party shall cooperate with
     patent counsel for the other party in connection with the filing,
     prosecution and maintenance of patent applications claiming joint Subject
     Inventions. Associate power of Attorney will not be used by either party to
     make any submissions to the USPTO without consulting with the other party.

                                       27

 
Article 7.  Licensing

7.1  Option for Commercialization License. With respect to Government IP rights
     to any Subject Invention not made solely by the Collaborator's employees
     for which a patent or other IP application is filed, NIH hereby grants to
     the Collaborator an exclusive option to elect an exclusive or nonexclusive
     commercialization license, which is substantially in the form of the
     appropriate model NIH license agreement. This option does not apply to
     Subject Inventions conceived prior to the effective date of this CRADA that
     are reduced to practice under this CRADA, if prior to that reduction to
     practice, NIH has filed a patent application on the invention and has
     licensed it or offered to license it to a third party. The terms of the
     license will fairly reflect the nature of the invention, the relative
     contributions of the Parties to the invention and the CRADA, the risks
     incurred by the Collaborator and the costs of subsequent research and
     development needed to bring the invention to the marketplace. The field of
     use of the license will be commensurate with the scope of the Research
     Plan. The Collaborator shall have the right to sublicense the license
     rights granted hereunder, provided that the Collaborator obtains the prior
     written consent of NIH for the sublicensing of its non-exclusive license
     rights, such consent to be reasonably given in situations where
     Collaborator sublicenses its exclusive rights in one or more Subject
     Inventions(s) to sublicensee(s) and requests to sublicense its non-
     exclusive rights in Subject Invention(s) to the same sublicensee(s); and
     any such sublicensee shall be bound by the terms of this license.

7.2  Exercise of License Option.  The option of Article 7.1 must be exercised 
     with respect to a particular Subject Invention by written notice mailed
     within three (3) months after either (i) Collaborator receives written
     notice from NIH that the patent or other IP application has been filed; or
     (ii) the date Collaborator files such IP application. Exercise of this
     option by the Collaborator initiates a negotiation period that expires nine
     (9) months after the exercise of the option. If the last proposal by the
     Collaborator has not been responded to in writing by NIH within this nine
     (9) month period, the negotiation period shall be extended to expire one
     (1) month after NIH so responds, during which month the Collaborator may
     accept in writing the final license proposal of NIH. In the absence of such
     acceptance, or an extension of the time limits by NIH, NIH will be free to
     license its rights in such Subject Invention to others. In the event that
     the Collaborator elects the option for an exclusive license, but no such
     license is executed during the negotiation period, NIH agrees not to make
     an offer for an exclusive license on more favorable terms to a third party
     for a period of twelve (12) months without first offering Collaborator
     those more favorable terms. These times may be extended at the sole
     discretion of NIH upon good cause shown in writing by the Collaborator.

                                       28

 
7.3  License for NIH Employee Inventions and Joint Inventions.  Pursuant to 15
     U.S.C. (S) 3710a(b)(1)(A), for Subject Inventions made under this CRADA by
     a NIH employee(s) or jointly by such employee(s) and employees of the
     Collaborator pursuant to Articles 6.3 and 6.4 and licensed pursuant to the
     option of Article 7.1, the Collaborator grants to the Government a
     nonexclusive, nontransferable, irrevocable, paid-up license to practice the
     invention or have the invention practiced throughout the world by or on
     behalf of the Government.  In the exercise of such license, the Government
     shall not publicly disclose trade secrets or commercial or financial
     information that is privileged or confidential within the meaning of 5
     U.S.C. 552(b)(4) or which would be considered as such if it had been
     obtained from a non-Federal party. The retained non-exclusive Government
     licenses described in this Article 7, and elsewhere herein, are intended by
     the NIH to be invoked by the NIH in circumstances consistent with the
     legislative history of the Stevenson-Wydler Technology Innovation Act, as
     amended, that provide for such licenses.

7.4  License in Collaborator Inventions.  Pursuant to 15 U.S.C. (S) 3710a(b)(2),
     for inventions made solely by Collaborator employees under this CRADA
     pursuant to Article 6.2, (1) NIH hereby ensures Collaborator that
     Collaborator shall retain title in such Subject Inventions, and (2) the
     Collaborator grants to the Government a nonexclusive, nontransferable,
     irrevocable, paid-up license to practice the Subject invention or have the
     Subject Invention practiced throughout the world by or on behalf of the
     Government for research or other Government purposes. As stated in the
     Research Plan, during the course and in the performance of this CRADA, the
     Collaborator will only use Shuffling Technology that Collaborator has
     developed or develops outside the course and performance of the CRADA
     program. If the progress of the CRADA research would benefit by the
     development of inventive Shuffling Technology subject matter during the
     course of the CRADA, Collaborator will attempt to develop such inventive
     subject matter outside the scope, course and performance of the present
     CRADA. Such inventive Shuffling Technology subject matter shall not be
     considered to comprise a Subject Invention as defined herein. However,
     selected Shuffled ******* and their corresponding DNA clones are considered
     Research Materials of the CRADA and fall under the scope of the CRADA
     Research Plan.

7.5  Third Party License.  Pursuant to 15 U.S.C. (S) 3710a(b)(1)(B), if NIH
     grants an exclusive license to a Subject Invention made wholly by NIH
     employees or jointly with a Collaborator under this CRADA, pursuant to
     Articles 6.3 and 6.4, the Government shall retain the right to require the
     Collaborator to grant to a responsible applicant a nonexclusive, partially
     exclusive, or exclusive sublicense to use the invention in Collaborator's
     licensed field of use on terms that are reasonable under the circumstances;
     or if the Collaborator fails to grant such a license, to grant the license
     itself.  The exercise of such rights by the Government shall only be in
     exceptional circumstances and only if the Government determines (i) the
     action is necessary to meet health or safety needs that are not reasonably
     satisfied by Collaborator, (ii) the action is necessary to meet
     requirements 

                                       29

 
     for public use specified by Federal regulations, and such requirements are
     not reasonably satisfied by the Collaborator; or (iii) the Collaborator has
     failed to comply with an agreement containing provisions described in 15
     U.S.C. 3710a(c)(4)(B). The determination made by the Government under this
     Article is subject to administrative appeal and judicial review under 35
     U.S.C. 203(2).

7.6  Joint Inventions Not Exclusively Licensed.  In the event that the
     Collaborator does not acquire an exclusive commercialization license to IP
     rights in all fields in joint Subject Inventions described in Article 6.4,
     then each Party shall have the right to use the joint Subject Invention and
     to license its use to others in all fields not exclusively licensed to
     Collaborator.  The Parties may agree to a joint licensing approach for such
     IP rights.

Article 8.  Proprietary Rights and Publication

8.1  Right of Access.  NIH and the Collaborator agree to exchange all Subject
     Data produced in the course of research under this CRADA.  Research
     Materials will be shared equally by the Parties to the CRADA unless other
     disposition is agreed to by the Parties.  All Parties to this CRADA will be
     free to utilize Subject Data and Research Materials for their own purposes,
     consistent with their obligations under this CRADA provided that NIH shall
     not have direct access to and/or direct use of Collaborator's proprietary
     Shuffling Technology in the performance of the CRADA.

8.2  Ownership of Subject Data and Research Materials.  Subject to the sharing
     requirements of Paragraph 8.1 and the regulatory filing requirements of
     Paragraph 8.3, the producing Party will retain ownership of and title to
     all Subject Inventions, all Subject Data and all Research Materials
     produced solely by their investigators.  Jointly developed Subject
     Inventions, Subject Data and Research Materials will be jointly owned.

8.3  Dissemination of Subject Data and Research Materials.  To the extent
     permitted by law, the Collaborator and NIH agree to use reasonable efforts
     to keep Subject Data and Research Materials confidential until published or
     until corresponding patent applications are filed.  Any information that
     would identify human subjects of research or patients will always be
     maintained confidentially.  To the extent permitted by law, the
     Collaborator shall have the exclusive right to use any and all CRADA
     Subject Data in and for any regulatory filing by or on behalf of
     Collaborator, except that NIH shall have the exclusive right to use Subject
     Data for that purpose, and authorize others to do so, if Collaborator
     abandons its commercialization efforts.

8.4  Proprietary/Confidential Information.  Each Party agrees to limit its
     disclosure of Proprietary/Confidential Information to the other Party
     hereunder to the amount necessary 

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                                                                    CRADA #00880
     to carry out the Research Plan of this CRADA, and shall place a
     confidentiality notice on all such information. Confidential oral
     communications shall be reduced to writing within 30 days by the disclosing
     Party. Each Party receiving Proprietary/Confidential Information of the
     other Party pursuant to this CRADA agrees that any information so
     designated shall be used by it only for the purposes described in the
     attached Research Plan. Any Party may object to the designation of
     information as Proprietary/Confidential Information by another Party.
     Subject Data and Research Materials developed solely by the Collaborator
     may be designated as Proprietary/Confidential Information when they are
     wholly separable from the Subject Data and Research Materials developed
     jointly with NIH investigators, and advance designation of such data and
     material categories is set forth in the Research Plan. The exchange of
     other confidential information, e.g., patient-identifying data, should be
     similarly limited and treated. Jointly developed Subject Data and Research
     Material derived from the Research Plan may be disclosed by Collaborator to
     a third party under a confidentiality agreement for the purpose of possible
     sublicensing pursuant to any licensing agreement of Subject Inventions or
     such purposes as Collaborator considers appropriate to pursue its
     commercial interests including, but not limited to, disclosures to
     manufacturing subcontractors, clinical or preclinical laboratories, medical
     or scientific consultants, quality control, quality assurance or analytical
     laboratories, or government regulatory agencies. 


8.5  Protection of Proprietary/Confidential Information.
     Proprietary/Confidential Information shall not be disclosed, copied,
     reproduced or otherwise made available to any other person or entity
     without the consent of the owning Party except as required under court
     order or the Freedom of Information Act (5 U.S.C. (S) 552). Each Party
     agrees to use its best efforts to maintain the confidentiality of
     Proprietary/Confidential Information. Each Party agrees that the other
     Party is not liable for the disclosure of Proprietary/Confidential
     Information which, after notice to and consultation with the concerned
     Party, the other Party in possession of the Proprietary/Confidential
     Information determines may not be lawfully withheld, provided the concerned
     Party has been given an opportunity to seek a court order to enjoin
     disclosure.


8.6  Duration of Confidentiality Obligation. The obligation to maintain the
     confidentiality of Proprietary/Confidential Information shall expire at the
     earlier of the date when the information is no longer Proprietary
     Information as defined in Article 2.7 or three (3) years after the
     expiration or termination date of this CRADA unless, after the said three
     (3) years, any Party informs the other Party that the Confidential
     Information is still secret and confidential, in which case the obligation
     shall extend for a further successive periods of two (2) years. The
     Collaborator may request an extension to these terms when necessary to
     protect Proprietary/Confidential Information relating to products not yet
     commercialized.


8.7  Publication. The Parties are encouraged to make publicly available the
     results of their research. Before either Party submits a paper or abstract
     for publication or otherwise intends to publicly disclose information about
     a Subject Invention, Subject Data or

                                       31

 
Research Materials, or any other confidential information concerning this
CRADA, the submitting Party shall first submit a draft of the proposed
disclosure to the Steering Committee for review at least 30 days prior to any
submission for publication or other public disclosure. As defined under Article
8.4, if such proposed disclosure contains Proprietary/Confidential Information
of a Party, such Party may require that such Confidential Information be deleted
or modified from the proposed disclosure in accordance with Article 8.5. The
Steering Committee shall provide advisory review and comments prior to
submission of proposed disclosures for publication and/or public presentation.
The submitting party will seriously consider the suggested modifications of the
Steering Committee. To avoid loss of patent rights as a result of premature
public disclosure of patentable information, the reviewing Party shall notify
the submitting Party in writing within 30 days after receipt of such proposed
disclosure whether the reviewing Party desires that a patent application be
filed on any invention disclosed in such proposed disclosure. In the event that
the reviewing Party desires such filing, the submitting Party shall withhold
publication or disclosure of such proposed disclosure until the earlier of: (i)
the date a patent application is filed thereon, or (ii) the date the Parties
determine after consultation that no patentable invention exists, or (iii) 60
days after receipt by the submitting Party of the reviewing Party's written
notice of its desire to file such patent application.


Article 9.  Representations and Warranties

9.1  Representations and Warranties of NIH. NIH hereby represents and warrants
     to the Collaborator that the official signing this CRADA has authority to
     do so.

9.2  Representations and Warranties of the Collaborator.

     (a)  The Collaborator hereby represents and warrants to NIH that the
          Collaborator has the requisite power and authority to enter into this
          CRADA and to perform according to its terms, and that the
          Collaborator's official signing this CRADA has authority to do so.
          The Collaborator further represents that it is financially able to
          satisfy any funding commitments made in Appendix B.

     (b)  The Collaborator certifies that the statements herein are true,
          complete, and accurate to the best of its knowledge. The Collaborator
          is aware that any false, fictitious, or fraudulent statements or
          claims may subject it to criminal, civil, or administrative penalties.

9.3  NIH Disclosure of Third Party Rights. NIH hereby acknowledges that Research
     Materials provided to Collaborator during the course of the CRADA research 
     may be

                                       32

 
     subject to third party patent and other rights. NIH will exercise its best
     efforts to provide Collaborator with all non-privileged and 
     non-confidential information its PI and NIH have in their possession, or of
     which they are aware, identifying third party rights in and to Research
     Materials supplied by NIH to Collaborator under this CRADA.


Article 10.  Termination

10.1 Termination By Mutual Consent. NIH and the Collaborator may terminate this
     CRADA, or portions thereof, at any time by mutual written consent.  In such
     event the Parties shall specify the disposition of all property,
     inventions, patent or other IP applications and other results of work
     accomplished or in progress, arising from or performed under this CRADA,
     all in accordance with the rights granted to the Parties under the terms of
     this Agreement.

10.2 Unilateral Termination. Either NIH or the Collaborator may unilaterally
     terminate this entire CRADA at any time by giving written notice at least
     thirty (30) days prior to the desired termination date, and any rights
     accrued in property, patents or other IP rights shall be disposed of as
     provided in paragraph 10.1, provided that, if either Party unilaterally
     terminates this CRADA for reasons other than for cause including, but not
     limited to, lack of interest, unwillingness or inability of either Party to
     contribute resources to the continuation of the CRADA research, and decides
     not to retain title to its IP rights to Subject Inventions, then pursuant
     to Articles 6.2, 6.3 and 6.4, such Party shall offer to assign these IP
     rights to such Subject Inventions to the other Party.
     
10.3 Staffing. If this CRADA is mutually or unilaterally terminated by
     Collaborator prior to its expiration, funds will nevertheless remain
     available to NIH for continuing any staffing commitment made by the
     Collaborator pursuant to Article 5.1 above and Appendix B, if applicable,
     for a period of six (6) months after such termination. If there are
     insufficient funds to cover this expense, the Collaborator agrees to pay
     the difference.

10.4 New Commitments. No Party shall make new commitments related to this CRADA
     after a mutual termination or notice of a unilateral termination and shall,
     to the extent feasible, cancel all outstanding commitments and contracts by
     the termination date.

10.5 Termination Costs. 

                                       33

 
     Collaborator shall not be responsible to NIH for any termination costs.

Article 11. Disputes

11.1 Settlement. Any dispute arising under this CRADA which is not disposed of
     by agreement of the Principal Investigators shall be submitted jointly to
     the signatories of this CRADA. If the signatories are unable to jointly
     resolve the dispute within thirty (30) days after notification thereof, the
     Assistant Secretary for Health (or his/her designee or successor) shall
     propose a resolution. Nothing in this Article shall prevent any Party from
     pursuing any additional administrative remedies that may be available and,
     after exhaustion of such administrative remedies, pursuing all available
     judicial remedies.

11.2 Continuation of Work. Pending the resolution of any dispute or claim
     pursuant to this Article, the Parties agree that performance of all 
     non-disputed obligations shall be pursued diligently in accordance with the
     direction of the NIH signatory. Disputed obligations shall be pursued 
     diligently by each Party in accordance with their best judgment and subject
     to their obligation to mitigate any damages resulting from their actions.

Article 12. Liability

12.1 Property. The U.S. Government shall not be responsible for damages to any
     Collaborator property  provided to NIH, where Collaborator retains title to
     the property, or any property acquired by Collaborator for its own use
     pursuant to this CRADA.

12.2 NO WARRANTIES. EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE PARTIES
     MAKE NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER WHATSOEVER, INCLUDING
     THE CONDITIONS OF THE RESEARCH OR ANY INVENTION OR PRODUCT, WHETHER
     TANGIBLE OR INTANGIBLE, MADE, OR DEVELOPED UNDER THIS CRADA, OR THE
     OWNERSHIP, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF THE
     RESEARCH OR ANY INVENTION OR PRODUCT.

12.3 Indemnification. The Collaborator agrees to hold the U.S. Government
     harmless and to indemnify the Government for all liabilities, demands,
     damages, expenses and losses arising out of the use by the Collaborator for
     any purpose of the Subject Data, Research Materials and/or Subject
     Inventions produced in whole or part by NIH employees under this CRADA,
     unless due to the negligence or willful misconduct or willful 
     misrepresentation of NIH, its employees, or agents. The Collaborator shall
     be liable 

                                       34

 
     for any claims or damages arising from the liable acts of the Collaborator
     in connection with this CRADA.  NIH has no authority to indemnify
     the Collaborator.

12.4 Force Majeure. Neither Party shall be liable for any unforeseeable event
     beyond its reasonable control not caused by the fault or negligence of such
     Party, which causes such Party to be unable to perform its obligations
     under this CRADA, and which it has been unable to overcome by the exercise
     of due diligence. In the event of the occurrence of such a force majeure
     event, the Party unable to perform shall promptly notify the other Party.
     It shall further use its best efforts to resume performance as quickly as
     possible and shall suspend performance only for such period of time as is
     necessary as a result of the force majeure event.


Article 13. Miscellaneous

13.1 Governing Law. The construction, validity, performance and effect of this
     CRADA shall be governed by Federal law, as applied by the Federal Courts in
     the District of Columbia. Federal law and regulations will preempt any
     conflicting or inconsistent provisions in this CRADA.

13.2 Entire Agreement. This CRADA constitutes the entire agreement between the
     Parties concerning the subject matter of this CRADA and supersedes any
     prior understanding or written or oral agreement.

     The Parties hereby modify their rights under the following prior 
     agreement(s):

     Confidential Disclosure Agreement: Two-way agreement # 3-60778-99:

     *******

     Effective date: December 14, 1998

     Material Transfer Agreement: # 2-50178

     Provider: Maxygen; Recipient: NCI, DTP     

     *******

     Executed: October xx, 1999; expiration date: October xx, 2002.

     and the Parties agree that the information provided thereunder is now 
     governed by the terms of this CRADA.
 
13.3 Headings. Titles and headings of the articles and subarticles of this
     CRADA are for convenient reference only, do not form a part of this CRADA,
     and shall in no way affect its interpretation. The NIH component that is
     the Party for all purposes of this CRADA is the Bureau(s), Institute(s),
     Center(s) or Division(s) listed on the Cover Page herein.

                                       35

 
13.4 Waivers. None of the provisions of this CRADA shall be considered waived by
     any Party unless such waiver is given in writing to the other Party. The
     failure of a Party to insist upon strict performance of any of the terms
     and conditions hereof, or failure or delay to exercise any rights provided
     herein or by law, shall not be deemed a waiver of any rights of any Party.

13.5 Severability. The illegality or invalidity of any provisions of this CRADA
     shall not impair, affect, or invalidate the other provisions of this CRADA.

13.6 Amendments. If either Party desires a modification to this CRADA, the
     Parties shall, upon reasonable notice of the proposed modification or
     extension by the Party desiring the change, confer in good faith to
     determine the desirability of such modification or extension. Such
     modification shall not be effective until a written amendment is signed by
     the signatories to this CRADA or by their representatives duly authorized
     to execute such amendment.

13.7 Assignment.  Neither this CRADA nor any rights or obligations of any Party
     hereunder shall be assigned or otherwise transferred by either Party
     without the prior written consent of the other Party, provided that a Party
     may assign its rights and obligations under this CRADA without such consent
     to an Affiliate or a third party that succeeds to substantially all of the 
     business or assets of the assigning Party, by way of merger, sale of assets
     or otherwise.

13.8 Notices. All notices pertaining to or required by this CRADA shall be in
     writing and shall be signed by an authorized representative and shall be
     delivered by hand or sent by certified mail, return receipt requested, with
     postage prepaid, to the addresses indicated on the signature page for each
     Party. Notices regarding the exercise of license options shall be made
     pursuant to Article 7.2. Any Party may change such address by notice given
     to the other Party in the manner set forth above.

13.9 Independent Contractors. The relationship of the Parties to this CRADA is
     that of independent contractors and not agents of each other or joint
     venturers or partners. Each Party shall maintain sole and exclusive control
     over its personnel and operations. Collaborator employees who will be
     working at NIH facilities may be asked to sign a Guest Researcher or
     Special Volunteer Agreement appropriately modified in view of the terms of
     this CRADA.

13.10Use of Name or Endorsements. By entering into this CRADA, NIH does not
     directly or indirectly endorse any product or service provided, or to be
     provided, whether directly or 

                                       36

 
       indirectly related to either this CRADA or to any patent or other IP
       license or agreement which implements this CRADA by its successors,
       assignees, or licensees. The Collaborator shall not in any way state or
       imply that this CRADA is an endorsement of any such product or service by
       the U.S. Government or any of its organizational units or employees.
       Collaborator issued press releases that reference or rely upon the work
       of NIH under this CRADA shall be made available to NIH at least 7 days
       prior to publication for review and comment.

13.11  Exceptions to this CRADA. Any exceptions or modifications to this CRADA
       that are agreed to by the Parties prior to their execution of this CRADA
       are set forth in Appendix C.

13.12  Reasonable Consent. Whenever a Party's consent or permission is required
       under this CRADA, such consent or permission shall not be unreasonably
       withheld.

Article 14. Duration of Agreement

14.1   Duration. It is mutually recognized that the duration of this project
       cannot be rigidly defined in advance, and that the contemplated time
       periods for various phases of the Research Plan are only good faith
       guidelines subject to adjustment by mutual agreement to fit circumstances
       as the Research Plan proceeds. In no case will the term of this CRADA
       extend beyond the term indicated in the Research Plan unless it is
       revised in accordance with Article 13.6.

14.2   Survivability. The provisions of Articles 4.2, 5-8, 10.3-10.5, 11.1, 
       12.2-12.4, 13.1, 13.10 and 14.2 shall survive the termination of this
       CRADA.

 
                       SIGNATURES BEGIN ON THE NEXT PAGE

FOR NIH:
 

________________________________________         Date:_______________________ 
Alan Rabson, M.D.                                                      
Deputy Director, NCI

Mailing Address for Notices:

                                       37

 
National Cancer Institute

Technology Development & Commercialization Branch

NCI-FCRDC

1003 West Seventh Street, 

Fairview Center, Suite 502

Frederick, MD 21701

Phone: 301-846-5465
Fax:   301-8466820

 
FOR THE COLLABORATOR:
 
 
_______________________________________           Date:_______________________

_______________________________________

 
Mailing Address for Notices:
 

__________________________________________________________

__________________________________________________________

__________________________________________________________

__________________________________________________________

__________________________________________________________

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