<PAGE>
                                                                   EXHIBIT 10.33

              AMENDMENT #4 TO THE ORIGINAL SUBLEASE BY AND BETWEEN
             GENERAL ATOMICS AND APPLIED MOLECULAR EVOLUTION, INC.
                         (FORMERLY KNOW AS IXSYS, INC.)

This Fourth Amendment, dated September 23, 2002 for reference purposes only, is
made by and between General Atomics, (the "Lessor") and Applied Molecular
Evolution, Inc. (AME), the ("Lessee"). This Amendment applies to the Sublease
Agreement (the "Agreement") dated June 1, 1993, Amendment #1, ,dated March 1,
1994, Amendment #2, dated January 1, 1995 and Amendment #3, dated October 1,
1997.

     WHEREAS:  The Lessee and Lessor (the "Parties") wish to amend certain terms
of the Sublease Agreement for Building 6 Premises, including but not limited to
extending the Sublease for an additional year, and increase the monthly rental,
and rentable square footage percentage rate.

     NOW THEREFORE, in consideration of the foregoing, and in consideration of
mutual covenants and agreements of the Lessor and Lessee hereto, the Parties
mutually covenant and agree as follows:

2.1  PREMISES. Building 6 which consists of 24,113sf, in Lessor's Sorrento West
Industrial Center.

3.0  TERM. The Lessor and Lessee agree the  Sublease Term will be extended for
one Year, beginning when Sublease expires on December 16, 2003, and ending
December 16, 2004.

4.1  RENT. After comparing the configuration and size of the building with the
current market rate the monthly rent for the extended Term for Building 6 will
be $30,382.38 effective January 1, 2004.

48.2  RENT ESCALATIONS. Monthly Rental Rate will be increased from $0.88/sf to a
$1.26/sf and increased from a rentable square footage percentage rate of 3%
compounded and cumulative to a 4% rate effective January 1, 2004.

48.4  SECURITY DEPOSIT.  Lessee shall have on record with Lessor a Security
Deposit needed to secure payment of Rent, and Operating Expenses in the amount
equivalent to one month's Rent, and two months' average Operating Expenses.
Lessee currently has on record with Lessor a surplus deposit of $5,431.14
therefore, no added security deposit is due at this time. See the breakdown
below:

<Table>
<S>                                                         <C>
    One month's Rent Building 6                               $30,382.38
    Two Months' Operating Ex. 24,113sf x $0.17/mo x 2mo       $ 8,198.42
    TOTAL SECURITY DEPOSIT REQUIRED                           $38,580.80
    Less Security Deposit on Record:                          $44,011.94
                                                          --------------
    SURPLUS SECURITY DEPOSIT:                                 $ 5,431.14
</Table>

Concurrent with the annual increase in Monthly Rent, and without prior notice,
the Security Deposit shall be adjusted in direct relation to the Monthly Rent
and Operating Expenses and shall be paid by Lessee upon receipt of an invoice
from Lessor.

EXCEPT AS HEREBY AMENDED, ALL OTHER TERMS AND CONDITIONS OF SAID SUBLEASE, AND
SUBLEASE AMENDMENTS,  SHALL REMAIN UNCHANGED AND IN FULL FORCE AND EFFECT.

This Fourth Amendment is executed by the authorized officers of the parties as
set forth below by their respective signatures.

    LESSOR:                             LESSEE:
    GENERAL ATOMICS                     APPLIED MOLECULAR EVOLUTION, INC.

    By: /s/ Anthony Navarra            By: /s/Lawrence E. Bloch, M.D.
        --------------------               --------------------------
    Name: Anthony Navarra              Name: Lawrence E. Bloch, M.D.
    Title: Treasurer                   Title: Chief Financial Officer
    Date: 10-18-2                      Date: October 15, 2003