Document:

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                                  EXHIBIT 10.48

                             SECOND AMENDMENT OF THE
                             COLLABORATION AGREEMENT

      This Second Amendment (this "SECOND AMENDMENT") to the Collaboration
Agreement is made and entered into as of October 7, 2003, 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 Collaboration
Agreement dated July 9, 2001, as amended by the First Amendment of the
Collaboration Agreement, dated October 16, 2002 (the "COLLABORATION AGREEMENT");
and

      WHEREAS, the Parties wish to amend the Collaboration 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. Article VII shall be amended to add new section 7.3 as follows:

   7.3      Transgenic Animals. Transgenic animals (A2, A11 and B7 transgenic
            mice) provided by EPMN to GCOR pursuant to Section 7.2, for research
            purposes within the Program, can be used beyond the Collaboration
            Term solely as related to the development of Licensed Products;
            provided, that, the right to use such transgenic animals shall
            automatically terminate upon the termination or expiration of the
            License Agreement.

B. All terms and conditions of the Collaboration 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 Second Amendment to the
Collaboration Agreement, the term "Agreement" shall be deemed to mean the
Collaboration Agreement as hereby modified.

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

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                             SECOND AMENDMENT OF THE
                             COLLABORATION AGREEMENT

EPIMMUNE INC.

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

GENENCOR INTERNATIONAL, INC.

By:    /s/ Mark A. Goldsmith
     -----------------------------
       Mark A. Goldsmith, MD, Ph.D.

Title: Senior Vice President, Health Care

                                       2<PAGE>

                                  EXHIBIT 10.49

                                           *** TEXT OMITTED AND FILED SEPARATELY
                                                CONFIDENTIAL TREATMENT REQUESTED
                                         UNDER 17 C.F.R. SECTIONS 200.80 (B)(4),
                                                                   AND 240.24B-2

                             SECOND AMENDMENT OF THE
                                LICENSE AGREEMENT

      This Second Amendment (this "SECOND AMENDMENT") to the License Agreement
is made and entered into as of March 15, 2004 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");

      WHEREAS, the Parties have entered into that certain First Amendment of the
License Agreement dated October 16, 2002 (the "FIRST AMENDMENT");

      WHEREAS, the Parties wish to further 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 Third Party Technology defined in Section 1.42 of the
LICENSE AGREEMENT and listed in Appendix B of the LICENSE AGREEMENT, Appendix B
shall be amended to read as follows:

   [...***...]

   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 Second Amendment to the License
Agreement, the term "Agreement" shall be deemed to mean the License Agreement as
hereby modified.

                                              * CONFIDENTIAL TREATMENT REQUESTED

                                       1
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      IN WITNESS WHEREOF, the Parties have caused this Second 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/ Mark Goldsmith
     ---------------------------
     Mark Goldsmith, MD, PhD
     Sr. Vice President
     Health Care

                                       2<PAGE>

                                  EXHIBIT 10.50

                                           *** TEXT OMITTED AND FILED SEPARATELY
                                                CONFIDENTIAL TREATMENT REQUESTED
                                         UNDER 17 C.F.R. SECTIONS 200.80 (B)(4),
                                                                   AND 240.24B-2

                 THIRD AMENDMENT OF THE COLLABORATION AGREEMENT

      This THIRD AMENDMENT OF THE COLLABORATION AGREEMENT (this "THIRD
AMENDMENT") is made and entered into as of March 16, 2004, by and between
EPIMMUNE INC. (the "COMPANY") and INNOGENETICS, NV ("INNOGENETICS")
(collectively referred to herein as the "PARTIES").

                                R E C I T A L S

      WHEREAS, the Company and Genencor International, Inc. ("GENENCOR")
entered into that certain Collaboration Agreement, dated July 9, 2001 (the
"COLLABORATION AGREEMENT"), as amended by the First Amendment of the
Collaboration Agreement, dated October 16, 2002 ( the "FIRST AMENDMENT"), and
the Second Amendment of the Collaboration Agreement, dated October 7, 2003 (the
"SECOND AMENDMENT").;

      WHEREAS, Genencor proposes to assign its rights and obligations under the
Collaboration Agreement, as amended by the First Amendment and the Second
Amendment, to Innogenetics in connection with the sale to Innogenetics of
substantially all of its business assets relating to vaccines for the prevention
and/or treatment of hepatitis B virus infections, hepatitis C virus infections
and human papilloma virus infections (the "TRANSACTION"); and

      WHEREAS, contingent on and at the time of Genencor assigning to
Innogenetics its rights and obligations under the Collaboration Agreement, as
amended by the First Amendment and the Second Amendment,, the Parties wish to
amend the Collaboration Agreement as amended by the First Amendment and the
Second Amendment, 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, the Parties do hereby mutually
agree as follows:

      1. EFFECTIVE DATE. This Third Amendment shall become effective upon the
date Genencor assigns to Innogenetics its rights and obligations under the
Collaboration Agreement as amended by the First Amendment and the Second
Amendment ("Effective Date"), and subject to the condition precedent of Genencor
assigning its rights and obligations under the Collaboration Agreement as
amended by the First Amendment and the Second Amendment. In the event that
Innogenetics provides the Company with written notice of the termination of the
Transaction within

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[...***...] after the Effective Date, effective upon the date of such notice,
this Third Amendment shall automatically terminate and shall be void and have no
further effect. The Parties acknowledge that, as of the Effective Date,
references to Genencor in the Collaboration Agreement as amended by the First
Amendment, the Second Amendment and this Third Amendment shall be amended so as
to replace "GCOR" with "Innogenetics".

      2.    AMENDMENT TO COLLABORATION AGREEMENT.

            (a)   SECTION 4.1. As of the Effective Date, Section 4.1 of the
Collaboration Agreement, as amended in the First Amendment and the Second
Amendment, is hereby further amended and restated in its entirety as follows:

      "4.1  (a)   Funding Subject to the terms and conditions set forth herein,
            during the Collaboration Term GCOR shall fund annually up to
            [...***...] EPMN FTEs at $[...***...]/FTE for the work performed
            under the WORk Plan. This payment is based on the man-month(s)
            expended by EPMN in support of the Program.

            (b)   Funding - Extended Term. Subject to the terms and conditions
            set forth herein, during the Extended Term GCOR shall fund annually
            between [...***...] and [...***...] EPMN FTEs at $[...***...]/FTE
            for the work performed under the Work Plan. This payment is based on
            the man-month(s) expended by EPMN in support of the Program.

            (c)   Funding - Second Extended Term. Subject to the terms and
            conditions set forth herein, during the Second Extended Term GCOR
            shall fund annually between [...***...] and [...***...] EPMN FTEs at
            $[...***...]/FTE for the work performed under the Work Plan. This
            payment is based on the man-month(s) expended by EPMN in support of
            the Program."

            (b)   SECTION 5.1 AND 5.2. As of the Effective Date, Sections 5.1
and 5.2, including Table I, [...***...]. For the avoidance of doubt, it is
understood that [...***...].

            (c)   SECTION 8.1. As of the Effective Date, Section 8.1 of the
Collaboration Agreement is hereby amended and restated in its entirety as
follows:

      "8.1  (a)   Term. This Agreement, unless terminated sooner as provided
            elsewhere herein, shall expire on September 1, 2004 (the "TERM"),
            which term can be extended by mutual agreement of the Parties. ,

            (b)   Extended Term. Between September 1, 2003 and September 1, 2004
            (the "EXTENDED TERM"), GCOR may terminate this Agreement at any
            time, by providing three months prior written notice.

                                              * CONFIDENTIAL TREATMENT REQUESTED

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            (c)   Second Extended Term. Between September 2, 2004 and September
            30, 2005 (the "SECOND EXTENDED TERM"), GCOR may terminate this
            Agreement at any time, by providing three months prior written
            notice.

      2.    OTHER TERMS REMAIN IN EFFECT. All terms and conditions of the
Collaboration Agreement, as amended in the First and the Second Amendment, which
are not modified by this Third Amendment, shall remain in full force and effect.
From and after the Effective Date, for purposes of the Collaboration Agreement,
the term "Agreement" shall be deemed to mean the Collaboration Agreement as
amended by the First Amendment, the Second Amendment and this Third Amendment.

      3.    MISCELLANEOUS. This Third Amendment shall be governed by and
construed under the laws of the State of California as applied to agreements
among California residents entered into and to be performed entirely within
California. The provisions hereof shall inure to the benefit of, and be binding
upon, the successors and assigns of Innogenetics and the Company. Parties agree
that no press release or other communication will be issued relating to the
existence or the terms and conditions of this Third Amendment before the
Effective Date mentioned herein.

IN WITNESS WHEREOF, the Parties have executed this THIRD AMENDMENT OF THE
COLLABORATION AGREEMENT as of the date first above written.

INNOGENETICS, NV                         EPIMMUNE INC.

By:   /s/ Philippe Archinard             By:   /s/ Robert J. De Vaere
     -------------------------------          -----------------------------

Name:  Philippe Archinard                Name:  Robert J. De Vaere

Title:       CEO                         Title:         CFO

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