<PAGE>

                                                                 EXHIBIT 10.17.1

CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS,
HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.

December 19, 2002

Ikunoshin Kato, Ph.D.
President and Chief Executive Officer
Takara Bio Inc.
Seta 3-4-1, Otsu, Shiga,
520-2193, Japan

         Re:  Amendment No. 1 to Collaboration Agreement

Dear Dr Kato:

         This letter will serve to confirm and memorialize our agreement to
amend, in certain respects, that certain Collaboration Agreement, effective as
of October 1, 2000 (the "Collaboration Agreement"), by and between Takara Bio
Inc. ("Takara") and Lynx Therapeutics, Inc. ("Lynx"). Unless otherwise defined
herein, capitalized terms used herein shall have the meanings given to them in
the Collaboration Agreement.

With respect to the exclusive license granted to Takara Bio and its Affiliates
in Article 2.1 of the Agreement, the parties have agreed as follows:

1. With respect to the exclusive license granted to Takara Bio and its
Affiliates in Article 2.1 of the Agreement, the parties have agreed that Article
2.1 shall be amended as follows: The phrase "of five years" in the first
sentence of Article 2.1 shall be stricken and the phrase "and extending through
and including the date on which the last to expire of the patents listed in
Exhibit A expires" shall be inserted following the phrase "the Effective Date of
the Agreement" in the second line of Article 2.1. In the last sentence of the
current version of Article 2.1, the phrase "[F]rom and after the fifth
anniversary of the Effective Date or" and the phrase "whichever occurs sooner"
shall be deleted in their entirety. The following sentence shall be added as the
last sentence in Article 2.1: "Takara and Lynx will negotiate in good faith to
establish Performance Criteria to apply following the fifth anniversary of the
Effective Date of the Agreement".

Article 4 of the Collaboration Agreement is hereby deleted in its entirety.

2. Takara is hereby granted, effective from the date on which this amendment
letter is executed by the last party hereto, a royalty-bearing nonexclusive
license under Patent Rights, Lynx Know-How, and Lynx Software, without the right
to sublicense, to provide MPSS(TM) Services and Megasort(TM) Services to
customers in France and Italy. Royalties on the MPSS Services and Megasort
Services to customers in France and Italy shall be payable solely in accordance
with Article 9.1(a) of the Collaboration License and no other fees or royalties,
including without limitation, upfront payments or minimum royalties, shall be
payable with respect thereto.

3. With respect to Megaclone(TM) technology as defined in Article 1.9, the
parties have agreed that Takara may modify the process to allow for attaching
genomic DNA to microbeads. Accordingly, the parties agree to:

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                           (i) delete the last sentence of Article 1.9 and
                                    insert in its stead:

                                    "Takara may use Megaclone technology to
                                    attach genomic DNA fragments to microbeads
                                    for the sole purpose of gene expression
                                    analysis, and not for any other purpose";
                                    and

                           (ii) to delete Article 3.1 in its entirety; the
                                    subsequent sub-articles of Article 3 shall
                                    be re-numbered accordingly.

4. With respect to Consideration for Exclusive Access to Lynx Technology as set
forth in Article 8.1, and subject to paragraph 6 below, Takara Bio agrees to
accelerate its payment of the remaining technology access fees otherwise payable
in accordance with Article 8.1(b) as follows:

         a.)      The 2003 technology access fee payment in the amount of [ * ]
                  shall be made by bank wire transfer on or before December 24,
                  2002 or such other date before December 31, 2002 as Takara Bio
                  may reasonably request;

         b.)      The 2004 technology access payment will be made on [ * ] or
                  such other date in 2003 as Takara Bio may reasonably request;
                  and.

         c.)      The 2005 technology access payment will be made on [ * ] or
                  such other date in 2004 as Takara Bio may reasonably request.

5. With respect to equity investments otherwise required to be made by Takara
Bio in accordance with Article 10.1 of the Collaboration Agreement, and subject
to paragraph 6 below, Takara Bio agrees to accelerate its purchase of shares as
follows:

         a)       The 2003 equity investment shall be made by bank wire transfer
                  on or before December 24, 2002 or such other date before
                  December 31, 2002 as Takara Bio may reasonably request;

         b)       The 2004 equity investment shall be made on [ * ] or such
                  other date in 2003 as Takara Bio may reasonably request; and.

         c)       The 2005 equity investment payment shall be made on [ * ] or
                  such other date in 2004 as Takara Bio may reasonable request.

6. Notwithstanding the following provisions, Takara's obligations with respect
to the obligations in item 4 (acceleration of payment of technology access fees)
and item 5 (acceleration of performance of equity investment) shall, in each
year, be subject to the following conditions:

         (i)      delivery by Lynx to Takara of an opinion of counsel indicating
                  that, as of the date upon which Takara is to make the
                  accelerated payment of the technology access fee or equity
                  investment, as the case may be, Lynx is not, to the knowledge
                  of such counsel, the subject of a petition for bankruptcy, any
                  corporate insolvency reorganization proceeding, any corporate
                  liquidation, special liquidation or rehabilitation proceeding
                  or any similar special arbitration or other proceeding; and

[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.

                                       2.

<PAGE>

         (ii)     an officer's certificate from a senior executive of Lynx
                  representing and warranting that to the best of executive's
                  knowledge, as of the date of the accelerated payment of the
                  technology access fee or equity investment, that (x) Lynx
                  estimates that it will have sufficient working capital to
                  operate its business for a period of [ * ] following the date
                  of the accelerated payment of the technology access fee or
                  equity investment, as the case may be, in substantially the
                  same manner as it was operated on the date of the accelerated
                  payment of the technology access fee or equity investment, (y)
                  Lynx estimates that it will be able to meet all financial
                  obligations as they fall due for a period of [ * ] following
                  the date of the accelerated payment of the technology access
                  or equity investment, as the case may be, without recourse to
                  equity or debt financing or additional capital increases, the
                  sole purpose of which is to meet Lynx' financial obligations,
                  and (z) Lynx has made available to Takara such public
                  financial and business records and documents as Takara has
                  reasonably requested, including, without limitation, a copy of
                  Lynx' most recent audited financial statements.

7. In addition to the agreement changes noted above, Lynx will provide Takara
nonexclusive access to the [ * ] Tissue data sets as noted on Exhibit 1A to this
document. Takara may use the data to help market MPSS(TM) services allowing
customers to access the data, but Takara may not sell the data itself. Takara
may also mine the data for genes of its interest and profit from the sales of
those genes, provided a royalty arrangement between Takara and Lynx is put in
place.

Except as expressly provided herein, the Agreement shall remain in full force
and effect.

If the foregoing is consistent with Takara's understanding of our agreement,
please execute the enclosed copy of this letter and return it to Lynx.

Very truly yours,

Lynx Therapeutics, Inc.                    Confirmed and Agreed: Takara Bio Inc.

By: /s/ Kevin P. Corcoran                  By: /s/ Ikunoshin Kato
    -----------------------                    -----------------------
Kevin P. Corcoran                          Ikunoshin Kato
President & CEO                            President & CEO
Lynx Therapeutics, Inc.                    Takara Bio Inc.

[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.

                                       3.

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[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.

                                       4.