<PAGE>
                                                                 EXHIBIT 10.21.2

CONFIDENTIAL PORTIONS HAVE BEEN OMITTED BASED UPON A REQUEST FOR CONFIDENTIAL
TREATMENT PURSUANT TO RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934 AND HAVE
BEEN SEPARATELY FILED WITH THE COMMISSION

                              FIRST SIDE AGREEMENT

This First Side Agreement ("First Side Agreement"), effective as of the 1st day
of November, 2001 ("First Side Agreement Effective Date"), is by and between
EPOCH BIOSCIENCES, INC., having a principal place of business at 21720 23rd Road
SE, Bothell, Washington 98021 ("Epoch"), and PE CORPORATION (NY), through its
Applied Biosystems Group, having a principal place of business at 850 Lincoln
Centre Drive, Foster City, California 94404 ("ABG").

                                   BACKGROUND

A.      The Parties have entered into a Second Amended And Restated
        Collaboration, License and Supply Agreement dated August 17, 2000
        ("Collaboration Agreement").

B.      The Parties wish to modify their contractual relations in order to
        facilitate the more effective and efficient commercialization of MGB
        Oligonucleotide technology.

NOW, THEREFORE, in consideration of the foregoing premises and the mutual
promises and covenants contained herein and other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged, the
Parties, intending to be legally bound, do hereby agree as follows:

                                    AGREEMENT

1.      DEFINITIONS

1.1     Definitions. Any words with initial capitalization that are used in this
        First Side Agreement that are not otherwise defined in this First Side
        Agreement will have the meanings set forth in the Collaboration
        Agreement.

1.2     "Quarter" means a three month period beginning on the first day of
        January, April, July or October.

2.      ABG'S OBLIGATION TO PURCHASE BARE PROBES FROM EPOCH

2.1     During The Period Beginning October 1, 2001 And Ending December 31,
        2002. Notwithstanding anything to the contrary in Section 6.02 or 6.04
        of the Collaboration Agreement, or any other terms of the Collaboration
        Agreement,



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        during the period beginning on October 1, 2001 and ending December 31,
        2002, for each Quarter within that period, ABG will either (1) purchase
        [*] Bare Probes from Epoch at a price of $[*] per Bare Probe, or (2)
        purchase a number of Bare Probes less than [*] Bare Probes from Epoch at
        a price of [*] per Bare Probe and pay Epoch a payment in the amount of
        ([*] - X)*$[*], where X is the number of Bare Probes less than [*] Bare
        Probes purchased from Epoch ("Remainder Payment"). Any Remainder Payment
        owed to Epoch will be paid to Epoch prior to the end of the Quarter in
        which the Remainder Payment accrues. The following hypothetical example
        is provided to clarify the above provision, and will not be considered a
        right or obligation to either Party under this First Side Agreement:

                If, in any Quarter during the period beginning on October 1,
                2001 and ending December 31, 2002 ABG were to purchase [*] Bare
                Probes from Epoch, ABG would pay Epoch as follows: [*]*$[*] =
                $[*] for the purchase of [*] Bare Probes, and [*]*$[*] $[*] as
                the Remainder Payment, for a total payment to Epoch in that
                three-month period of $[*]. The $[*] Remainder Payment would be
                due prior to the end of the subject Quarter.

2.2     Schedule For Ordering Of Bare Probes. To enable Epoch to manufacture and
        ship probes in satisfaction of orders from ABG in a timely manner,
        orders from ABG will be placed prior to the end of the relevant Quarter
        as follows:



<TABLE>
<CAPTION>
        Aggregate Number of
        Probes Ordered                   Deadline For Placement Of Order
        --------------                   -------------------------------
<S>                                      <C>
        [*]-[*] Bare Probes                30 days prior to end of Quarter
        [*]-[*] Bare Probes                45 days prior to end of Quarter
        [*]-[*]                            60 days prior to end of Quarter
</TABLE>


        To be considered a valid order, each order from ABG shall be supported
        by a written purchase order specifying the oligonucleotide sequences,
        quantity, price, shipping instructions and any other special information
        necessary to fulfill such order.

3.      CONTINUED FORCE AND EFFECT OF COLLABORATION AGREEMENT

All provisions of the Collaboration Agreement, except as expressly modified by
this First Side Agreement, will remain in full force and effect and are hereby
reaffirmed. Other than as expressly stated in this First Side Agreement, this
First Side Agreement will not operate as a waiver of any condition or obligation
imposed on the Parties under the Collaboration Agreement.

*CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH COMMISSION.




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4.      FURTHER DISCUSSIONS

The Parties will promptly enter into good faith negotiations to resolve certain
outstanding differences of opinion relating to (A) the definition of certain
product categories (e.g., Bare Probe and Kit) used to determine royalty payments
and minimum product purchase obligations, (B) the extent to which ABG will be
obligated to purchase minimum quantities of products from Epoch following the
expiration of this First Side Agreement, and (C) if the Parties decide that ABG
will no longer be obligated to purchase any minimum quantities of products from
Epoch after December 2002, an adjustment to the royalties owed to Epoch set
forth at Section 5.04 of the Collaboration Agreement. The negotiations related
to 4.(A) will be completed on or before December 31, 2001, and the new
definitions resulting from those negotiations will be applied to any royalties
owed during the Quarter ending December 31, 2001 and for each Quarter
thereafter. The negotiations related to 4.(B) and 4.(C) will be completed on or
before June 30, 2002.

5.      TERM OF FIRST SIDE AGREEMENT

The term of this First Side Agreement will begin on the First Side Agreement
Effective Date and will end on December 31, 2002.

6.      INTERPRETATION OF FIRST SIDE AGREEMENT

In the event of any conflict, inconsistency, or incongruity between any
provision of this First Side Agreement and any provision of the Collaboration
Agreement, the provisions of this First Side Agreement will govern and control.

7.      ENTIRE AGREEMENT

This First Side Agreement, along with the Collaboration Agreement, constitute
the sole agreements between the Parties relating to the subject matter hereof
and supersede all previous writings and understandings. Neither Party has been
induced to enter into this First Side Agreement by, nor is any Party relying on,
any representation or warranty outside those expressly set forth in this First
Side Agreement.

8.      COUNTERPARTS

This First Side Agreement may be executed in any number of counterparts, and
each counterpart will be deemed an original instrument, but all counterparts
together will constitute one agreement.


[Signature page follows.]



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The Parties, through their authorized officers, have executed this First Side
Agreement as of the First Side Agreement Effective Date.


EPOCH BIOSCIENCES, INC.               PE CORPORATION (NY),
                                      THROUGH ITS APPLIED BIOSYSTEMS GROUP


By: /s/ William Gerber                By: /s/ Michael W. Hunkapiller
   ------------------------------         ----------------------------------

Name:  Dr. William Gerber             Name: Dr. Michael W. Hunkapiller

Title: President and                  Title: President Applied Biosystems Group,
       Chief Executive Officer               Executive Vice President,
                                             PE Corporation (NY)


Date:  11/1/2001                      Date:  10/31/2001
   ------------------------------          ---------------------------------



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