Document:

<PAGE>
                                                                   EXHIBIT 10.46

                             FIRST AMENDMENT OF THE
                                LICENSE AGREEMENT

        This First Amendment (this "FIRST AMENDMENT") to the License Agreement
is made and entered into as of October 16, 2002 by and between EPIMMUNE INC.,
having a principal place of business at 5820 Nancy Ridge Drive, San Diego, CA
92121 ("EPMN"), and GENENCOR INTERNATIONAL, INC., having a principal place of
business at 925 Page Mill Road, Palo Alto, CA 94304-1013 ("GCOR") (collectively
referred to herein as the "PARTIES") agree as follows:

        WHEREAS, the Parties have entered into that certain License Agreement
dated July 9, 2001 (the "LICENSE AGREEMENT"); and

        WHEREAS, the Parties wish to amend the License Agreement on the terms
and conditions set forth herein;

        NOW, THEREFORE, in consideration of the mutual undertakings of the
Parties as set forth below as well as other good and valuable consideration, the
receipt and sufficiency of which is hereby acknowledged, GCOR and EPMN do hereby
mutually agree as follows:

A.      With respect to the Collaboration Term, Section 1.6 shall be amended to
        read as follows:

1.6 "Collaboration Term" shall mean the three and one-half (3.5) year period
from April 2, 2001 through September 1, 2004, unless extended by mutual
agreement or terminated early as provided for in the Collaboration Agreement.

B.      All terms and conditions of the License Agreement remain in full force
        and effect, as modified hereby and are hereby ratified by the parties.

C.      From and after the effective date of this First Amendment to the License
        Agreement, the term "Agreement" shall be deemed to mean the License
        Agreement as hereby modified.

        IN WITNESS WHEREOF, the Parties have caused this First Amendment to the
License Agreement to be executed by and through their duly authorized
representatives as of the date first above written.

EPIMMUNE INC.

By:   /s/ Robert J. De Vaere
      ---------------------------------
      Robert J. De Vaere
      Vice President, Finance and
      Chief Financial Officer

GENENCOR INTERNATIONAL, INC.

By:   /s/ Debby Jo Blank
      ---------------------------------
      Debby Jo Blank
      Senior Vice President, Healthcare<PAGE>
                                                                   EXHIBIT 10.47

                                            ***TEXT OMITTED AND FILED SEPARATELY
                                                CONFIDENTIAL TREATMENT REQUESTED
                                           UNDER 17 C.F.R. SECTIONS 200.80(b)(4)
                                                                     AND 230.406

                                  AMENDMENT TO
                         NON-EXCLUSIVE LICENSE AGREEMENT

        This Amendment, effective as of October 18, 2002, is to amend the
Non-exclusive License Agreement ("License Agreement") by and between EPIMMUNE
INC., a Delaware corporation having offices at 5820 Nancy Ridge Drive, San
Diego, California 92121 ("Epimmune") and VALENTIS, INC., a Delaware corporation,
having an office at 863A Mitten Road, Burlingame, California 94010,
("Valentis"), dated November 27, 2000.

        1. All terms of the License Agreement remain in full force and effect
except to the extent expressly modified herein. All terms defined in the License
Agreement, when used herein, shall have the definitions ascribed to them in the
License Agreement, unless modified herein.

        2. Section 3.2 ("Royalties") shall be deleted and replaced with the
following:

                "3.2 ROYALTIES.

                (a)     With regard to any Product the manufacture, use,
                        importation, offer for sale or sale of which is covered
                        by a Valid Claim, Epimmune shall pay to Valentis a
                        royalty of (i) [...***...] on that portion of annual Net
                        Sales of such Product that is [...***...], (ii)
                        [...***...] on that portion of annual Net Sales of such
                        Product that is [...***...] but less than or equal to
                        [...***...]; (iii) [...***...] on that portion of annual
                        Net Sales of such Product that is greater than
                        [...***...], and (iv) [...***...] on that portion of
                        annual Net Sales of such Product that is [...***...];
                        provided, however, that, if Epimmune or its Affiliate
                        [...***...], then, with respect to such Product,
                        Epimmune shall pay to Valentis a royalty equal to
                        [...***...] (A) [...***...] of royalty payments received
                        by Epimmune and its Affiliates [...***...] or (B) the
                        royalty on Net Sales of such Product specified in
                        Section 3.2(a)(i) through (iv) above.

                (b)     With regard to any Product, the manufacture, use,
                        importation, offer for sale or sale of which is not
                        covered by a Valid Claim, Epimmune shall pay to Valentis
                        a royalty equal to [...***...] of the royalty otherwise
                        payable in accordance with Section 3.2(a) above."

                                               *CONFIDENTIAL TREATMENT REQUESTED
<PAGE>
        3. Section 3.3 ("Milestones") shall be deleted and replaced with the
following:

                "3.3 MILESTONES. Within thirty (30) days of [...***...] with
                respect to each Product, Epimmune shall pay to Valentis a
                milestone payment in the amount of [...***...]."

        In witness whereof, the parties have caused this Amendment to be
executed by their duly authorized representatives.

EPIMMUNE INC.                                 VALENTIS, INC.

By: /s/ Michael R. McClurg                    By: /s/ Benjamin McGraw
    ---------------------------------------       ------------------------------
Name: Michael R. McClurg                      Name: Benjamin McGraw
Title: Vice President, Business Development   Title: Chairman, President and CEO
Date: October 18, 2002                        Date: October 22, 2002<PAGE>
                                                                   EXHIBIT 10.48

                                            ***TEXT OMITTED AND FILED SEPARATELY
                                                CONFIDENTIAL TREATMENT REQUESTED
                                  UNDER SECTION 17 C.F.R. SECTIONS 200.80(b)(4),
                                                                     AND 230.406

                         NON-EXCLUSIVE LICENSE AGREEMENT

        THIS NON-EXCLUSIVE LICENSE AGREEMENT (the "Agreement") is entered into
as of October 28, 2002 (the "Effective Date"), by and between EPIMMUNE INC., a
Delaware corporation, having offices at 5820 Nancy Ridge Drive, San Diego,
California 92121 ("Epimmune"), and VALENTIS, INC., a Delaware corporation,
having offices at 863A Mitten Road, Burlingame, California 94010 ("Valentis").

        WHEREAS, Valentis has developed and owns the Patent Rights (as defined
below) and Biological Material (as defined below);

        WHEREAS, Valentis has previously transferred the Biological Material to
Epimmune pursuant to the Material Transfer Agreement between the parties dated
August 31, 1999 (the "MTA"); and

        WHEREAS, Epimmune wishes to obtain, and Valentis is willing to grant, a
non-exclusive, worldwide license under the Patent Rights to develop and
commercialize Products in the Field (as such term is defined below), on the
terms and subject to the conditions set forth herein.

        NOW, THEREFORE, in consideration of the mutual covenants and promises
hereinafter set forth, the parties hereto hereby agree as follows:

                                    ARTICLE 1

                                   DEFINITIONS

        1.1 "AFFILIATE" shall mean any corporation or other entity which
controls, is controlled by, or is under common control with, a party. A
corporation or other entity shall be regarded as in control of another
corporation or entity if it owns or directly or indirectly controls 100% of the
voting securities or other ownership interest of the other corporation or
entity, or if it possesses, directly or indirectly, the power to direct or cause
the direction of the management and policies of the corporation or other entity.

        1.2 "BIOLOGICAL MATERIAL" shall mean Valentis' proprietary plasmid
backbone, designated pMB75.6, all information, maps or data relating to such
plasmid backbone supplied by Valentis to Epimmune, and all derivatives or
modifications thereof.

        1.3 "BLA" shall mean a Biological License Application filed pursuant to
the requirements of the FDA.

        1.4 "CONFIDENTIAL INFORMATION" shall mean any confidential or
proprietary information of a party, including information related to the Patent
Rights or Biological Material, and any other information relating to any
compound, research project, work in process, future development, scientific,
engineering, manufacturing, marketing, business plan, financial or personnel
matter relating to such party, its present or future products, sales, suppliers,
customers, employees, investors or business, whether in oral, written, graphic
or electronic form.

                                       1.
<PAGE>
Notwithstanding the foregoing, Confidential Information shall not include any
information which the receiving party can prove by competent written evidence:

               (a) is now, or hereafter becomes, through no act or failure to
act on the part of the receiving party, generally known or available;

               (b) is known by the receiving party at the time of receiving such
information, as evidenced by its records;

               (c) is hereafter furnished to the receiving party by a Third
Party, as a matter of right and without restriction on disclosure;

               (d) is independently developed by the receiving party, as
evidenced by its records, without knowledge of, and without the aid, application
or use of, the Confidential Information of the disclosing party; or

               (e) is the subject of a written permission to disclose provided
by the disclosing party.

        1.5 "CONTROL" shall mean possession of the ability to grant a license or
sublicense without violating the terms of any agreement or other arrangement
with any Third Party.

        1.6 "FDA" shall mean the United States Food and Drug Administration or
equivalent regulatory agency in any of the following countries: Canada, China,
France, Germany, Italy, Japan, Mexico, Spain, Australia or the United Kingdom.

        1.7 "FIELD" shall mean the prophylactic and/or therapeutic treatment of
cancer in humans using plasmid-based vaccines.

        1.8 "FIRST COMMERCIAL SALE" of a Product means the first sale for use or
consumption of such Product in a country after required marketing approval has
been granted by the governing health regulatory authority of such country. Sale
to an Affiliate or sublicensee shall not constitute a First Commercial Sale
unless the Affiliate or sublicensee is the end user of the Product.

        1.9 "HCV/HIV AGREEMENT" shall mean that certain non-exclusive license
agreement dated November 27, 2000, by and between the parties, as may be
amended.

        1.10 "MAA" shall mean a Marketing Authorization Application filed
pursuant to the regulatory requirements of the European Union.

        1.11 "NDA" shall mean a New Drug Application or Product License
Application, as appropriate, filed pursuant to the requirements of the FDA.

        1.12 "NET SALES" shall mean the gross amounts received by Epimmune, its
Affiliates and its sublicensees for the sale of Products to Third Parties, less
the following: (a) discounts actually granted, (b) credits, rebates or
allowances actually granted upon claims, damaged goods, rejections or returns of
Products, including recalls, (c) freight, postage, shipping and insurance

                                       2.
<PAGE>
charges actually allowed or paid for delivery of Products, to the extent billed,
and (d) taxes, duties or other governmental charges (other than income taxes)
levied on, absorbed or otherwise imposed on sales of Products. Amounts received
by Epimmune or its Affiliates for the sale of Products between Epimmune and its
Affiliates or sublicensees, whether for their own use or for resale or other
disposition, will not be included in the computation of Net Sales hereunder.

        With regard to a product sold by Epimmune or its Affiliates or
sublicensees that is comprised in part of a Product and in part of one or more
other products (a "Combination Product"), Net Sales shall be determined by
multiplying the amounts received by Epimmune or its Affiliates or sublicensees
for the sale of such Combination Product by a fraction determined by dividing
(i) the fair market value of the Product included in the Combination Product, by
(ii) the sum of the fair market value of such Product and the fair market value
of the other product(s) included in the Combination Product. As used herein,
"fair market value" shall be equal to the average selling price, where such
Product is sold on a stand-alone basis. If such Product is not sold on a
stand-alone basis, "fair market value" shall be determined by mutual written
agreement of the parties in good faith.

        1.13 "PATENT RIGHTS" shall mean (a) the patents and patent applications
listed on EXHIBIT A attached hereto, (b) any and all corresponding foreign
patents and patent applications, whether now existing or hereafter filed, (c)
any provisionals, substitutions, divisionals, reissues, renewals, continuations,
continuations-in-part, substitute applications and inventors' certificates
arising from, or based upon, any of the foregoing patents or patent
applications, and (d) any patents issuing from any of the foregoing patent
applications.

        1.14 "PHASE I CLINICAL TRIALS" shall mean that portion of the clinical
development program with respect to a pharmaceutical product which generally
provides for the first introduction into humans of the product with the primary
purpose of determining safety, metabolism and pharmacokinetic properties and
clinical pharmacology of the product, as more specifically defined by the rules
and regulations of the FDA and corresponding rules and regulations in other
countries or jurisdictions.

        1.15 "PHASE III CLINICAL TRIALS" shall mean that portion of the clinical
development program which provides for the continued trials of a pharmaceutical
product on sufficient numbers of patients to establish the safety and efficacy
of such product for the desired claims and indications, as more specifically
defined by the rules and regulations of the FDA and corresponding rules and
regulations in other countries or jurisdictions. Notwithstanding the foregoing,
if Phase III Clinical Trials are not conducted, but Epimmune, its Affiliate or
sublicensee nonetheless pursues regulatory approval of a Product based upon
Phase II trial results, such Phase II trial shall be deemed to be a Phase III
Clinical Trial.

        1.16 "PRODUCT" shall mean a DNA construct comprised of combinations of
epitopes derived from a combination of a unique number [...***...] and type of
tumor-associated antigens and developed by Epimmune, its Affiliates or its
sublicensees, which the manufacture, use, importation, offer for sale, or sale
of which is covered by a Valid Claim or is based upon or incorporates the
Biological Material.

                                       3.
<PAGE>
        1.17 "ROYALTY TERM" shall mean, on a country-by-country basis, the
longer of: (a) the period of time commencing on the First Commercial Sale and
ending upon the expiration of the last to expire Valid Claim covering such
Product in such country; and (b) the period of time commencing on the First
Commercial Sale in such country and ending [...***...] years from the date of
First Commercial Sale in such country.

        1.18 "THIRD PARTY" shall mean any entity other than Epimmune or Valentis
or an Affiliate of Epimmune or Valentis.

        1.19 "VALID CLAIM" shall mean a claim of an issued patent included
within the Patent Rights, which claim has not lapsed, been canceled or become
abandoned and has not been declared invalid or unenforceable by an unreversed
and unappealable decision or judgment of a court or other appropriate body of
competent jurisdiction, and which has not been admitted to be invalid or
unenforceable through reissue, disclaimer or otherwise.

                                    ARTICLE 2

                                GRANT OF LICENSE

        2.1 LICENSE GRANT. Subject to the terms and conditions of this
Agreement, Valentis hereby grants to Epimmune and its Affiliates a
non-exclusive, worldwide, non-transferable (except as provided in Section 10.1),
royalty-bearing license, with the right to sublicense in accordance with Section
2.2, under the Patent Rights to develop, make, have made, use, offer for sale,
sell, have sold and import the Products designated pursuant to Section 2.3
solely for use in the Field and to use the Biological Material for such
purposes.

        2.2 SUBLICENSES. Epimmune and its Affiliates shall have the right to
grant sublicenses solely to bona fide strategic or collaborative partners of
Epimmune or an Affiliate of Epimmune for use solely in such strategic or
collaborative partners' collaborative research, development or commercialization
program with Epimmune or such Affiliate and to transfer Biological Material to
such partners for use in connection with such purposes, provided that such
collaborative or strategic partner is also granted, at the same time as the
sublicense, rights to substantially all other intellectual property Controlled
by Epimmune or its Affiliates relating to a Product. Epimmune shall notify any
sublicensee hereunder of all rights and obligations of Epimmune under this
Agreement which are sublicensed to such sublicensee and shall notify Valentis
within thirty (30) days of the grant of any sublicense hereunder, and provide a
copy of such sublicense to Valentis.

        2.3 SELECTION OF PRODUCTS. Epimmune shall have a period of [...***...]
years after the Effective Date to designate up to [...***...] Products to be
covered by the license granted in Section 2.1, during which time Epimmune may
research and develop multiple product candidates using the Biological Material
in the Field. Epimmune shall provide Valentis with written notice of the
designation of each Product, which notice shall include a reasonably detailed
description of such Product. After a product candidate is designated a Product
hereunder up until the initiation of a Phase I Clinical Trial of such Product,
Epimmune shall have the right to optimize such Product by substituting, deleting
or adding [...***...] epitopes to such Product. Epimmune will notify Valentis in
writing if it desires to so optimize any Product in this manner, and if

                                       4.
<PAGE>
Valentis Controls the right to grant a license under the Patent Rights and
Biological Materials covering such modified Product, then such modified Product
shall be deemed a Product hereunder and shall be included in the license set
forth in Section 2.1 hereof; provided, however that such Product, as modified,
shall not be counted as a new Product, but shall take the place of the Product
it modified for all purposes under this Agreement.

        2.4 NEGATIVE COVENANT. Epimmune hereby covenants that neither it nor any
of its Affiliates shall practice any invention claimed in the Patent Rights or
use the Biological Material outside the Field, except as set forth in the
HCV/HIV Agreement. Epimmune further covenants that neither it nor its Affiliates
or sublicensees shall transfer the Biological Material to any Third Party except
as permitted under Section 2.2 above or as set forth in the HCV/HIV Agreement,
or otherwise for purposes of developing, manufacturing or commercializing
Products.

        2.5 REASONABLE ACCESS. Valentis will provide Epimmune with access to
appropriate personnel of Valentis via telephone, facsimile or electronic mail
during Valentis' regular business hours in order to discuss questions relating
to the use of the Biological Material and the Patent Rights in connection with
the Products, provided that such access is limited to six (6) days per year.

                                    ARTICLE 3

                               PAYMENT OBLIGATIONS

        3.1 LICENSE FEES. In partial consideration of the license granted to
Epimmune by Valentis, Epimmune shall pay to Valentis the following license fees:

               (a) [...***...];

               (b) [...***...];

               (c) [...***...]; and

               (d) [...***...].

        3.2 ROYALTIES.

               (a) With regard to any Product the manufacture, use, importation,
offer for sale or sale of which is covered by a Valid Claim, Epimmune shall pay
to Valentis a royalty of (i) [...***...] on that portion of annual Net Sales of
such Product that is [...***...], (ii) [...***...] on that portion of annual Net
Sales of such Product that is [...***...]; (iii) [...***...] on that portion of
annual Net Sales of such Product that is [...***...], and (iv) [...***...] on
that portion of annual Net Sales of such Product that [...***...]; provided,
however, that, if Epimmune or its Affiliate [...***...], then, with respect to
such Product, Epimmune shall pay to Valentis a royalty equal to [...***...] of
royalty payments received by Epimmune and its Affiliates from such Third Party
with respect to sales of such Product or (B) the royalty on Net Sales of such
Product specified in Section 3.2(a)(i) through (iv) above.

                                       5.
<PAGE>
               (b) With regard to any Product, the manufacture, use,
importation, offer for sale or sale of which is not covered by a Valid Claim,
Epimmune shall pay to Valentis a royalty [...***...] of the royalty otherwise
payable in accordance with Section 3.2(a) above.

               (c) Royalties under this Section 3.2 shall be paid, on a
country-by-country and Product-by-Product basis, during the Royalty Term.

        3.3 MILESTONE PAYMENTS. Within thirty (30) days following the occurrence
of each of the following milestone events with respect to each Product, Epimmune
will pay to Valentis the greater of (A) the minimum milestone payment set forth
opposite such milestone event under Milestone Table below, or (B) if Epimmune or
its Affiliates enter into a collaborative or strategic relationship with a Third
Party with respect to such Product, [...***...] of any milestone payment
received by Epimmune or its Affiliates from such Third Party, provided that such
payments shall not exceed, [...***...].

                                 MILESTONE TABLE

<TABLE>
<CAPTION>
MILESTONE EVENT                                   MILESTONE PAYMENT
--------------------------------------------------------------------------------
<S>                                               <C>
[...***...]                                       [...***...]
--------------------------------------------------------------------------------
[...***...]                                       [...***...]
--------------------------------------------------------------------------------
[...***...]                                       [...***...]
--------------------------------------------------------------------------------
[...***...]                                       [...***...]
--------------------------------------------------------------------------------
[...***...]                                       [...***...]
--------------------------------------------------------------------------------
[...***...]                                       [...***...]
--------------------------------------------------------------------------------
</TABLE>

                                    ARTICLE 4

                            PAYMENTS; RECORDS; AUDITS

        4.1 PAYMENT; REPORTS. Royalty payments and reports for the sale of
Products shall be calculated and reported for each calendar quarter. Payments
with respect to the milestones set forth in Section 3.3 shall be made within
thirty (30) days after the achievement of such milestone. All royalty payments
due to Valentis under this Agreement shall be paid within sixty (60) days of the
end of each calendar quarter. Each payment of royalties shall be accompanied by
a report of Net Sales of Products (and, if applicable under Section 3.2,
royalties received by Epimmune and its Affiliates) in sufficient detail to
permit confirmation of the accuracy of the royalty payment made, including,
without limitation, the number of Products sold, the gross sales and Net Sales
of Products, the royalties payable and the method used to calculate the royalty.

                                       6.
<PAGE>
        4.2 EXCHANGE RATE; MANNER AND PLACE OF PAYMENT. All payments hereunder
shall be payable in U.S. dollars. With respect to each quarter, for countries
other than the United States, whenever conversion of royalty payments from any
foreign currency shall be required, such conversion shall be made at the rate of
exchange reported in The Wall Street Journal (Western Edition) on the last
business day of such quarter. All payments owed under this Agreement shall be
made by wire transfer to a bank and account designated in writing by Valentis,
unless otherwise specified in writing by Valentis.

        4.3 LATE PAYMENTS. Any amounts not paid by Epimmune when due under this
Agreement shall be subject to interest from the date payment is due through the
date payment is received by Valentis at a rate equal to the sum of two percent
(2%) plus the prime rate of interest quoted in the Money Rates section of The
Wall Street Journal (Western Edition), calculated daily on the basis of a
360-day year, or similar reputable data source, or, if lower, the highest rate
permitted under applicable law.

        4.4 RECORDS AND AUDITS. Epimmune shall keep for a period covering at
least the preceding [...***...] years complete and accurate records pertaining
to the development and sale or other disposition of Products in sufficient
detail to permit Valentis to confirm the accuracy of all payments due hereunder.
Valentis shall have the right to cause an independent, certified public
accountant reasonably acceptable to Epimmune to audit such records for the
purpose of verifying any amounts payable, or information provided, under this
Agreement. Such audits may be exercised during normal business hours upon
reasonable prior written notice to Epimmune. Prompt adjustments shall be made by
the parties to reflect the results of such audit. Valentis shall bear the full
cost of such audit, unless such audit discloses a variance of more than
[...***...] from the amounts actually due, in which case Epimmune shall bear the
full cost of such audit.

        4.5 TAXES. All taxes levied on account of the royalties and other
payments accruing to Valentis under this Agreement shall be paid by Valentis for
its own account, including taxes levied thereon as income to Valentis. If
provision is made in law or regulation for withholding, such tax shall be
deducted by Epimmune from the sums otherwise payable by it hereunder for payment
to the proper taxing authority on behalf of Valentis and a receipt of payment of
the tax secured and promptly delivered to Valentis. Each party agrees to assist
the other party in claiming exemption from such deductions or withholdings under
any double taxation or similar agreement or treaty from time to time in force.

        4.6 PROHIBITED PAYMENTS. Notwithstanding any other provision of this
Agreement, if Epimmune is prevented from paying any royalty payment hereunder by
virtue of the statutes, laws, codes or governmental regulations of the country
from which the payment is to be made, then such royalty may be paid by
depositing funds in the currency in which accrued to Valentis' account in a bank
acceptable to Valentis in the country whose currency is involved.

                                       7.
<PAGE>
                                    ARTICLE 5

                          CONFIDENTIALITY; PUBLICATION

        5.1 CONFIDENTIALITY. During the term of this Agreement, and for a period
of [...***...] years thereafter, each party hereto will maintain in confidence
all Confidential Information disclosed by the other party hereto. Neither party
will use, disclose or grant use of such Confidential Information except as
expressly authorized by this Agreement. To the extent that disclosure is
authorized by this Agreement, the disclosing party will obtain prior agreement
from its employees, agents or consultants to whom disclosure is to be made to
hold in confidence and not make use of such information for any purpose other
than those permitted by this Agreement. Each party will use at least the same
standard of care as it uses to protect its own Confidential Information to
ensure that such employees, agents or consultants do not disclose or make any
unauthorized use of such Confidential Information. Each party will promptly
notify the other upon discovery of any unauthorized use or disclosure of the
Confidential Information.

        5.2 AUTHORIZED DISCLOSURE. Each party may disclose the Confidential
Information to the extent such disclosure is reasonably necessary in filing or
prosecuting patent applications, prosecuting or defending litigation or
complying with applicable governmental regulations, provided that if such party
is required to make any such disclosure of the Confidential Information it will
to the extent practicable give reasonable advance notice to the other party of
such disclosure requirement and, except to the extent inappropriate in the case
of patent applications, will use its best efforts to secure confidential
treatment of such information required to be disclosed.

                                    ARTICLE 6

                          INTELLECTUAL PROPERTY RIGHTS

        6.1 FILING, PROSECUTION AND MAINTENANCE OF THE PATENT RIGHTS. Valentis
shall own all right, title and interest in, and shall have the sole right to
control the filing, prosecution and maintenance of, all patent applications and
patents included in the Patent Rights, at Valentis' expense.

        6.2 INFRINGEMENT ACTIONS. Valentis shall have the sole right to
prosecute, at its discretion, any and all infringements of any Patent Rights
and/or any misappropriation of the Biological Materials, and to enter all
settlements, judgments or other arrangements with respect to the same, all at
its own expense and by counsel of its own choice. Any damages or other recovery
from such infringement or misappropriation actions in excess of the expenses and
costs incurred by Valentis in connection with such action shall belong solely to
Valentis.

        6.3 PATENT MARKING. Epimmune and its Affiliates and sublicensees shall
mark Products with appropriate patent numbers in those countries where markings
have notice value as against infringers.

        6.4 INFRINGEMENT OF THIRD PARTY RIGHTS. If the sale of any Product is
determined or alleged to infringe, or if Epimmune receives notice of or is sued
for infringement of, a patent

                                       8.
<PAGE>
owned or licensed by Third Party, Valentis and Epimmune shall meet to discuss
what action should be taken if such claim involves the Patent Rights. Epimmune
or its Affiliate or sublicensee, as applicable, shall be solely responsible for
the defense or settlement of any patent infringement claim or lawsuit brought by
any Third Party involving the sale of any Product, including all expenses and
amounts payable as damages or in settlement.

                                    ARTICLE 7

                     REPRESENTATIONS; WARRANTIES; COVENANTS

        7.1 CORPORATE POWER. Each party hereby represents and warrants that it
is duly organized, validly existing and in good standing under the laws of the
state or jurisdiction of its incorporation or formation and has full corporate
power and authority to enter into this Agreement and to carry out the provisions
hereof.

        7.2 DUE AUTHORIZATION. Each party hereby represents and warrants that
such party is duly authorized to execute and deliver this Agreement and to
perform its obligations hereunder.

        7.3 BINDING AGREEMENT. Each party hereby represents and warrants that
this Agreement is a legal and valid obligation binding upon it and is
enforceable in accordance with its terms. The execution, delivery and
performance of this Agreement by such party does not conflict with any
agreement, instrument or understanding, oral or written, to which it is a party
or by which it may be bound, nor violate any law or regulation of any court,
governmental body or administrative or other agency having authority over it.

        7.4 PATENT PROCEEDINGS. Valentis represents and warrants that to the
best of its knowledge, no patent or patent application within the Patent Rights
is the subject of any pending interference, opposition, cancellation or other
protest proceeding.

        7.5 DISCLAIMER OF WARRANTIES. EXCEPT AS EXPRESSLY SET FORTH IN THIS
AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATION OR WARRANTY TO THE OTHER PARTY
OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, ANY WARRANTY OF
TITLE, NON-INFRINGEMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.

        7.6 INDEMNIFICATION.

               (a) Epimmune (the "Indemnifying Party") shall indemnify, hold
harmless and defend Valentis, its officers, directors and employees and/or
agents (the "Indemnitees") against any and all Third Party claims, suits,
losses, damage, costs, fees (including reasonable attorney's fees) and expenses
resulting from or arising out of Epimmune's or its Affiliates', or its or their
sublicensees' development, testing, distribution, marketing, promotion or sale
of any Product; provided that no Indemnitee shall be entitled to indemnification
hereunder to the extent that any such claims, suits, losses, damage, costs, fees
and expenses result from the gross negligence or willful misconduct of any
Indemnitee.

               (b) Any Indemnitee, as the case may be, shall notify the
Indemnifying Party promptly in writing of an indemnifiable claim or cause of
action under Section 7.6(a) upon

                                       9.
<PAGE>
receiving notice or being informed of the existence thereof. The Indemnifying
Party shall assume, at its cost and expense, the sole defense of such claim or
cause of action through counsel selected by the Indemnifying Party and
reasonably acceptable to the Indemnitee. The Indemnifying Party shall maintain
control of such defense, including any decision as to settlement; provided that,
in the event that the Indemnifying Party does not maintain control of such
defense on a timely basis, then, without prejudice to any other rights and
remedies available to the Indemnitee under this Agreement, the Indemnitee may
take over such defense with counsel of its choosing, at the Indemnifying Party's
cost and expense. The Indemnitee may, at its option and expense, participate in
the Indemnifying Party's defense, and if the Indemnitee so participates, the
Indemnifying Party and the Indemnitee shall cooperate with one another in such
defense.

        7.7 INSURANCE. Epimmune represents and warrants that it is covered and
will continue to be covered by a comprehensive general liability insurance
program which covers all Epimmune's activities and obligations hereunder.
Epimmune shall provide Valentis with written notice at least fifteen (15) days
prior to any cancellation or material change in such insurance program. Epimmune
shall maintain such insurance program, or other program with comparable
coverage, beyond the expiration or termination of this Agreement during (i) the
period that any Product is being commercially distributed or sold by Epimmune,
its Affiliates or a sublicensee, and (ii) a commercially reasonable period
thereafter.

        7.8 LIMITATION OF LIABILITY. EXCEPT FOR AMOUNTS PAYABLE UNDER ARTICLE 3
AND EXCEPT AS REQUIRED FOR EPIMMUNE TO SATISFY ITS INDEMNIFICATION OBLIGATIONS
UNDER SECTION 7.6, NEITHER EPIMMUNE NOR ANY OF ITS AFFILIATES SHALL BE LIABLE
FOR ANY INDIRECT, INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES SUFFERED BY
VALENTIS IN CONNECTION WITH THIS AGREEMENT, EVEN IF EPIMMUNE OR ANY OF ITS
AFFILIATES HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES.

                                    ARTICLE 8

                                TERM; TERMINATION

        8.1 TERM. This Agreement shall commence as of the Effective Date and
shall continue, on a country-by-country basis, until the last day of the Royalty
Term, unless terminated earlier as provided herein (the "Term"). Following the
expiration of this Agreement, Epimmune shall have a license on the same terms as
set forth in Section 2.1, except that the license to the Biological Material
shall be a fully-paid license.

        8.2 TERMINATION FOR BREACH. A party may terminate this Agreement prior
to the expiration of the Term upon or after the breach of any material provision
of this Agreement by the other party if the breaching party has not cured such
breach within sixty (60) days after written notice thereof by the non-breaching
party.

        8.3 TERMINATION BY EPIMMUNE. Epimmune may terminate this Agreement prior
to the expiration of the Term at any time upon thirty (30) days' written notice
to Valentis.

                                      10.
<PAGE>
        8.4 TERMINATION FOR PATENT CHALLENGE. Valentis shall have the right to
terminate this Agreement if Epimmune, its Affiliate or sublicensee challenges
the validity of any patent included in the Patent Rights within any country
effective thirty (30) days after Epimmune's receipt of written notice of such
termination by Valentis.

        8.5 EFFECT OF TERMINATION.

               (a) Upon termination of this Agreement (i) all rights to the
Patent Rights and Biological Material shall revert to Valentis, and (ii) any
sublicense granted hereunder by Epimmune shall remain in full force and effect,
but shall be assigned to Valentis.

               (b) Within thirty (30) days following the expiration or
termination of this Agreement, each party shall return to the other party, or
destroy, upon the written request of the other party, any and all Confidential
Information of the other party in its possession. Epimmune shall return or
destroy all Biological Material in its possession.

               (c) Expiration or termination of this Agreement shall not relieve
the parties of any obligation accruing prior to such expiration or termination.
The provisions of Sections 4.3, 7.5, 7.8 and 8.5 and Articles 1, 5, 9 and 10
shall survive termination or expiration of this Agreement.

        8.6 BANKRUPTCY. All licenses granted under this Agreement will be deemed
licenses of rights to intellectual property for purposes of Section 365(n) of
the U.S. Bankruptcy Code and Epimmune will retain and may fully exercise all of
its rights and elections under the US Bankruptcy Code.

                                    ARTICLE 9

                               DISPUTE RESOLUTION

        If a dispute arises between the parties relating to the interpretation
or performance of this Agreement or the grounds for the termination thereof (but
not as to the enforceability or validity or interpretation of any claims within
the Patent Rights), and the parties cannot resolve the dispute within thirty
(30) days of a written request by either party to the other party, the parties
agree to hold a meeting, attended by individuals with decision-making authority
regarding the dispute, to attempt in good faith to negotiate a resolution of the
dispute prior to pursuing other available remedies. If, within thirty (30) days
after such meeting, the parties have not succeeded in negotiating a resolution
of the dispute, such dispute shall be submitted to final and binding arbitration
under the then current commercial rules and regulations of the American
Arbitration Association (the "AAA") relating to voluntary arbitrations in San
Francisco, California. The arbitration shall be conducted by one arbitrator, who
is knowledgeable in the subject matter at issue in the dispute and who will be
selected by mutual agreement of the parties or, failing such agreement, shall be
selected in accordance with the AAA rules. Each party shall initially bear its
own costs and legal fees associated with such arbitration. The prevailing party
in any such arbitration shall be entitled to recover from the other party
reasonable attorneys' fees, costs and expenses incurred by such prevailing party
in connection with such arbitration. The decision of

                                      11.
<PAGE>
the arbitrator shall be final and binding and may be sued on or enforced by the
party in whose favor it runs in any court of competent jurisdiction. The
arbitrator shall prepare and deliver a written, reasoned opinion conferring its
decision within thirty (30) days following the final arbitration hearing.

        Notwithstanding the foregoing, either party shall have the right to
pursue an action in a court of competent jurisdiction to obtain injunctive or
other equitable remedy, in order to preserve the status quo during the
resolution of any dispute under this provision.

                                   ARTICLE 10

                                  MISCELLANEOUS

        10.1 ASSIGNMENT. Except as expressly provided hereunder, neither this
Agreement nor any rights or obligations hereunder may be assigned or otherwise
transferred by either party without the prior written consent of the other party
(which consent shall not be unreasonably withheld); provided, however, that
either party may assign this Agreement and its rights and obligations hereunder
without the other party's consent (a) in connection with the transfer or sale of
all or substantially all of the business of such party to which this Agreement
relates to a Third Party, whether by merger, sale of stock, sale of assets or
otherwise, or (b) to any Affiliate. Notwithstanding the foregoing, any such
assignment to an Affiliate shall not relieve the assigning party of its
responsibilities for performance of its obligations under this Agreement. The
rights and obligations of the parties under this Agreement shall be binding upon
and inure to the benefit of the successors and permitted assigns of the parties.
Any assignment not in accordance with this Agreement shall be void.

        10.2 FORCE MAJEURE. Neither party shall be held liable or responsible to
the other party nor be deemed to have defaulted under or breached this Agreement
for failure or delay in fulfilling or performing any term of this Agreement when
such failure or delay is caused by or results from causes beyond the reasonable
control of the affected party, including, without limitation, fire, floods,
earthquakes, natural disasters, embargoes, war, acts of war (whether war be
declared or not), insurrections, riots, civil commotions, strikes, lockouts or
other labor disturbances, acts of God or acts, omissions or delays in acting by
any governmental authority or the other party.

        10.3 GOVERNING LAW. This Agreement shall be governed by, and construed
and enforced in accordance with, the laws of the State of California, without
regard to its choice of law provisions.

        10.4 WAIVER. Except as specifically provided for herein, the waiver from
time to time by either party of any right or failure to exercise any remedy
shall not operate or be construed as a continuing waiver of the same right or
remedy or of any other of such party's rights or remedies provided under this
Agreement.

        10.5 SEVERABILITY. In case any provision of this Agreement shall be
invalid, illegal or unenforceable, the validity, legality and enforceability of
the remaining provisions shall not in any way be affected or impaired thereby.

                                      12.
<PAGE>
        10.6 INDEPENDENT CONTRACTORS. It is expressly agreed that Epimmune and
Valentis shall be independent contractors and that the relationship between the
two parties shall not constitute a partnership, joint venture or agency of any
kind. Neither party shall have the authority to make any statements,
representations or commitments of any kind, or to take any action, which shall
be binding on the other party, without the prior written consent of the other
party.

        10.7 NOTICES. All notices and other communications provided for
hereunder shall be in writing and shall be mailed by first-class, registered or
certified mail, postage paid, or delivered personally, by overnight delivery
service or by facsimile, with confirmation of receipt, addressed as follows:

        IF TO EPIMMUNE:      EPIMMUNE INC.
                             5820 Nancy Ridge Drive
                             San Diego, CA 92121
                             Attention:  President
                             Facsimile:  (858) 860-2600

        IF TO VALENTIS:      VALENTIS, INC.
                             863A Mitten Road
                             Burlingame, California  94010
                             Attention:  CEO
                             Facsimile:  (650) 652-1990

        Either party may by like notice specify or change an address to which
notices and communications shall thereafter be sent. Notices sent by facsimile
shall be effective upon confirmation of receipt, notices sent by mail or
overnight delivery service shall be effective upon receipt, and notices given
personally shall be effective when delivered.

        10.8 ENTIRE AGREEMENT; AMENDMENT. This Agreement (including the Exhibits
attached hereto) sets forth all of the agreements and understandings between the
parties hereto with respect to the subject matter hereof, and supersedes and
terminates all prior agreements and understandings between the parties with
respect to the subject matter hereof, except for the Prior Agreement, which
shall remain in full force and effect to the extent not expressly superceded by
this Agreement. There are no agreements or understandings with respect to the
subject matter hereof, either oral or written, between the parties other than as
set forth herein or in the Prior Agreement. Except as expressly set forth in
this Agreement, no subsequent amendment, modification or addition to this
Agreement shall be binding upon the parties hereto unless reduced to writing and
signed by the respective authorized officers of the parties.

        10.9 HEADINGS. The captions contained in this Agreement are not a part
of this Agreement, but are merely guides or labels to assist in locating and
reading the several Articles hereof.

        10.10 COUNTERPARTS. This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

                                      13.
<PAGE>
        IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first set forth above.

EPIMMUNE INC.                                      VALENTIS, INC.

By: /s/ Michael R. McClurg                         By: /s/ Margaret M. Snowden
    ----------------------------------------           -------------------------
Name: Michael R. McClurg                           Name: Margaret M. Snowden
Title: Vice President, Business Development        Title: General Counsel

              [SIGNATURE PAGE TO NON-EXCLUSIVE LICENSE AGREEMENT]
<PAGE>
                                    EXHIBIT A

                                  PATENT RIGHTS

        U.S. Patent No. 6,040,295, entitled "Formulated Nucleic Acid
Compositions and Methods of Administering the Same for Gene Therapy."

        WO Patent Application No. 98/17814, entitled "Gene Expression and
Delivery Systems and Uses."

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