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                                                                    EXHIBIT 4.6


                           RIGHTS AGREEMENT AMENDMENT



               This Amendment, dated as of November 9, 2002, to the Rights
Agreement, dated as of June 5, 1998 (the "Rights Agreement"), is between Hyseq,
Inc., a Nevada corporation (the "Company"), and U.S. Stock Transfer Corporation,
as Rights Agent (the "Rights Agent").

               The Company and the Rights Agent have heretofore executed and
entered into the Rights Agreement. Pursuant to Section 26 of the Rights
Agreement, the Company and the Rights Agent may from time to time supplement or
amend the Rights Agreement in accordance with the provisions of Section 26
thereof and the Company desires and directs the Rights Agent to so amend the
Rights Agreement. All acts and things necessary to make this Amendment a valid
agreement according to its terms have been done and performed, and the execution
and delivery of this Amendment by the Company and the Rights Agent have been in
all respects authorized by the Company and the Rights Agent.

               In consideration of the foregoing premises and mutual agreements
set forth in the Rights Agreement and this Amendment, the parties hereto agree
as follows:

               1. Section 1.1 of the Rights Agreement is hereby modified and
amended to read in its entirety as follows:

               "1.1. (a) Subject to Section 1.1(b), "ACQUIRING PERSON" shall
               mean any Person who or which, together with all Affiliates and
               Associates of such Person, shall be the Beneficial Owner of 15%
               or more of the Common Shares of the Company then outstanding, but
               shall not include (i) the Company Group or any member or members
               thereof (ii) the Existing Holder so long as the Existing Holder
               shall be the Beneficial Owner of not greater than 40% of the
               Common Shares of the Company then outstanding (iii) Variagenics,
               Inc., a Delaware corporation, or any Affiliate or Associate
               thereof (collectively, "Variagenics"), (iv) Shareholder 1, or any
               Affiliate or Associate thereof (collectively, "Shareholder 1") or
               (v) Shareholder 2, or any Affiliate or Associate thereof
               (collectively, "Shareholder 2"); provided, however, that
               Variagenics, Shareholder 1 and Shareholder 2 will become an
               "Acquiring Person" in the event that he, she or it, as the case
               may be, becomes the Beneficial Owner of an aggregate of 15% or
               more of the Common Shares of the Company then outstanding other
               than pursuant to the terms of the Agreement and Plan of Merger
               dated as of November 9, 2002 (the "Merger Agreement"), among the
               Company, Vertical Merger Corp., a Delaware corporation, and
               Variagenics, the Voting Agreements (as defined in the Merger
               Agreement) or the transactions contemplated thereby. "EXISTING
               HOLDER" shall mean George B. Rathmann together with all of his
               Affiliates and Associates, until such time as George



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               B. Rathmann, together with all of his Affiliates and Associates,
               cease to beneficially own any Common Shares. Notwithstanding the
               foregoing, no Person shall become an Acquiring Person as the
               result of an acquisition of Common Shares by the Company which,
               by reducing the number of shares outstanding, increases the
               proportionate number of shares beneficially owned by such Person
               to 15% (or, in the case of the Existing Holder, 40%) or more of
               the Common Shares of the Company then outstanding; provided,
               however, that if a Person other than the Existing Holder shall
               become the Beneficial Owner of 15% or more of the Common Shares
               of the Company then outstanding solely by reason of share
               purchases by the Company and shall, after such share purchases by
               the Company, become the Beneficial Owner of any additional Common
               Shares of the Company, then such Person shall be deemed to be an
               Acquiring Person. Notwithstanding the foregoing, if the Board of
               Directors of the Company determines in good faith that a Person
               who would otherwise be an Acquiring Person, as defined pursuant
               to the foregoing provisions of this Section 1.1, has become such
               inadvertently, and such Person divests as promptly as practicable
               a sufficient number of Common Shares so that such Person would no
               longer be an Acquiring Person, as defined pursuant to the
               foregoing provisions of this Section 1.1, then such Person shall
               not be deemed to be an Acquiring Person at any time for any
               purposes of this Agreement.

               (b) Notwithstanding anything in this Rights Agreement to the
               contrary, the term Acquiring Person shall not include any Person
               that is an Approved Stockholder (so long as such Person remains
               an Approved Stockholder), and no Approved Stockholder shall
               become an Acquiring Person as the result of an acquisition of
               Common Shares by the Company which, by reducing the number of
               shares outstanding, increases the proportionate number of shares
               beneficially owned by such Person to more than 27.5% of the
               Common Shares of the Company then outstanding; provided, however,
               that if such Person shall become the Beneficial Owner of more
               than 27.5% of the Common Shares of the Company then outstanding
               solely by reason of share purchases by the Company and shall,
               after such share purchases by the Company, become the Beneficial
               Owner of any additional Common Shares of the Company, then such
               Person shall be deemed to be an "Acquiring Person.""

               2. Section 1.12 of the Rights Agreement is hereby amended by
adding as the final sentence thereto the following:

               "Notwithstanding anything in the Agreement to the contrary, no
               Shares Acquisition Date shall be deemed to have occurred solely



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               as a result of the approval, execution and/or delivery of the
               Merger Agreement and/or the Voting Agreements (as defined in the
               Merger Agreement), and/or the consummation of the transactions
               contemplated thereby."

               3. Section 3.1 of the Rights Agreement is hereby amended by
adding as the final sentence thereto the following:

               "Notwithstanding anything in the Agreement to the contrary, no
               Distribution Date shall be deemed to have occurred solely as a
               result of the approval, execution and/or delivery of the Merger
               Agreement and/or the Voting Agreements (as defined in the Merger
               Agreement), and/or the consummation of the transactions
               contemplated thereby."

               4. Section 11.1.2 of the Rights Agreement is hereby amended by
adding as the final sentence thereto the following:

               "Notwithstanding anything in the Agreement to the contrary, no
               rights under this Section 11.1.2 shall arise or be triggered, and
               no event described in Section 11.1.2 shall be deemed to have
               occurred solely as a result of the approval, execution and/or
               delivery of the Merger Agreement and/or the Voting Agreements (as
               defined in the Merger Agreement), and/or the consummation of the
               transactions contemplated thereby."

               5. Section 13.2 of the Rights Agreement is hereby amended by
adding as the final sentence thereto the following:

               Notwithstanding anything in this Agreement to the contrary, none
               of the approval, execution and/or delivery of the Merger
               Agreement and/or the Voting Agreements (as defined in the Merger
               Agreement), and/or the consummation of the transactions
               contemplated thereby shall result in the termination of the this
               Agreement or the Rights."

               6. Except as expressly amended hereby, the Rights Agreement
remains in full force and effect in accordance with its terms.

               7. This Amendment to the Rights Agreement shall be governed by
and construed in accordance with the laws of the State of Delaware.

               8. This Amendment to the Rights Agreement may be executed in any
number of counterparts and each of such counterparts shall for all purposes be
deemed an original, and all such counterparts shall together constitute but one
and the same instrument.

               9. Except as expressly set forth herein, this Amendment to the
Rights Agreement shall not by implication or otherwise alter, modify, amend or
in any way affect any of



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the terms, conditions, obligations, covenants or agreements contained in the
Rights Agreement, all of which are ratified and affirmed in all respects and
shall continue in full force and effect.

               10. Capitalized terms used herein but not defined shall have the
meanings given to them in the Rights Agreement.



                            [SIGNATURE PAGE FOLLOWS]



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               IN WITNESS WHEREOF, the parties hereto have caused this Amendment
to the Rights Agreement to be duly executed as of the day and year first above
written.

                                       HYSEQ, INC.


                                       By: /s/ Ted W. Love
                                          --------------------------------------

                                           Name: Ted W. Love
                                                --------------------------------

                                           Title: President and CEO
                                                 -------------------------------


                                       U.S. STOCK TRANSFER CORPORATION
                                       as Rights Agent


                                       By: /s/ Richard Tilton
                                          --------------------------------------

                                           Name: Richard Tilton
                                                --------------------------------

                                           Title: Assistant Vice President
                                                 -------------------------------



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