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...

                                                                   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 0000 Xxxxx Xxxxx Xxxxx, Xxx Xxxxx, XX
00000 ("EPMN"), and GENENCOR INTERNATIONAL, INC., having a principal place of
business at 000 Xxxx Xxxx Xxxx, Xxxx Xxxx, XX 00000-0000 ("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/ Xxxxxx X. De Vaere
      ---------------------------------
      Xxxxxx X. De Vaere
      Vice President, Finance and
      Chief Financial Officer


GENENCOR INTERNATIONAL, INC.

By:   /s/ Xxxxx Xx Xxxxx
      ---------------------------------
      Xxxxx Xx Xxxxx
      Senior Vice President, Healthcare