Document:

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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
                                                 -------------------------------

                                       5<PAGE>
                                                                   EXHIBIT 10.33

                             HYSEQ, INC. LETTERHEAD

                                November __, 2002

[EXECUTIVE NAME]
[ADDRESS]

               Re:    Severance Agreement

Dear Mr/s. _______________:

               Hyseq, Inc. (the "Company"), Vertical Merger Corp. ("Merger Sub")
and Variagenics, Inc. ("Variagenics") are parties to that certain Agreement and
Plan of Merger (the "Merger Agreement"), pursuant to which Merger Sub will merge
with and into Variagenics and Variagenics shall become a wholly owned subsidiary
of the Company (the "Merger").

               The Company considers it essential to the best interests of its
shareholders to foster the continuous employment of the Company's key management
personnel. In this regard, the Company's Board of Directors (the "Board")
recognizes that the uncertainty and questions raised by the Merger could result
in the departure or distraction of management personnel to the detriment of the
Company and its shareholders.

               The Board has decided to reinforce and encourage the continued
attention and dedication of members of the Company's management, including
yourself, to their assigned duties without the distraction arising from the
Merger.

               In order to induce you to remain in its employ, the Company
desires that you receive certain severance benefits in the event your employment
with the Company your employment is terminated within the 6-month period
immediately following the closing of the Merger pursuant to the Merger Agreement
(the "Closing") (i) by the Company other than for Cause or (ii) by you for Good
Reason (as defined below) (a termination of your employment under the
circumstances described in this sentence is sometimes hereinafter referred to as
a "Payment Termination"). This letter agreement (this "Agreement") confirms the
terms of those severance benefits.

               1. Termination Following Closing.

               (a) In the event that your employment with the Company is
terminated as a result of a Payment Termination, then, in addition to any
severance benefits to which you may otherwise be entitled under any severance
plan or program of the Company, (x) the Company shall pay to you your full
earned but unpaid base salary, when due, through the date of termination at the
rate in effect at the time notice of termination is given, plus all other
amounts to which you are entitled under any compensation plan or practice of the
Company at the time such payments are due, (y) you shall be entitled to receive
6 months of salary continuation of your base salary as in effect at the time
notice of termination is given, payable over the 6-month period commencing on
the date of termination at the same intervals as your base salary was paid
immediately prior to termination of employment, and (z) for the period beginning
on the date of termination and ending on the date which is 6 months following
the date of termination, the Company shall pay for and provide you and your
dependents with the same benefits coverage to

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which you would have been entitled had you remained continuously employed by the
Company during such period. At the termination of the benefits coverage under
clause (z) above, you and your dependents shall be entitled to continuation
coverage pursuant to Section 4980B of the Internal Revenue Code of 1986, as
amended (the "Code"), Sections 601-608 of the Employee Retirement Income
Security Act of 1974, as amended, and under any other applicable law, to the
extent required by such laws, as if you had terminated employment with the
Company on the date such benefits coverage terminates. You shall not be required
to mitigate the amount of any payment provided for in this Section 1(a) by
seeking other employment or otherwise, nor shall the amount of any payment
provided for in this Section 1(a) be reduced by any compensation earned by you
as the result of employment by another employer or self-employment, by
retirement benefits, by offset against any amounts (other than loans or advances
to you by the Company) claimed to be owed by you to the Company, or otherwise.

               (b) In the event that your employment with the Company is
terminated for any reason other than a Payment Termination, the Company shall
pay you your full earned but unpaid base salary, when due, through the date of
termination at the rate in effect at the time notice of termination is given or
your date of termination, in the event of termination as a result of your death,
plus all other amounts to which you are entitled under any compensation plan or
practice of the Company at the time such payments are due, and the Company shall
have no further obligations to you under this Agreement.

               (c) The Company may terminate your employment for Cause. For
purposes of this Agreement, "Cause" shall mean (i) gross negligence or willful
misconduct in the performance of duties to the Company where such gross
negligence or willful misconduct has resulted or is likely to result in
substantial and material damage to the Company or its subsidiaries; (ii)
repeated unexplained or unjustified absence from the Company; (iii) a material
and willful violation of any federal or state law; (iv) commission of any act of
fraud with respect to the Company; or (v) conviction of a felony or a crime
involving moral turpitude causing material harm to the standing and reputation
of the Company, in each case as determined in good faith by the Board.

               (d) You may terminate your employment with the Company for Good
Reason. For purposes of this Agreement, "Good Reason" shall mean the occurrence,
after the Closing, of any one or more of the following events without your prior
written consent, unless the Company fully corrects the circumstances
constituting Good Reason (provided such circumstances are capable of correction)
prior to the date of termination:

                      (i) any change in your position with the Company that
materially reduces your duties or level of responsibility as in effect
immediately preceding the Closing;

                      (ii) any reduction of your base compensation (other than
in connection with a general decrease in base salaries for most similarly
situated employees of the Company or a successor corporation); or

                      (iii) the relocation of the Company's offices at which you
are principally employed immediately prior to the date of the Closing to a
location more than 30 miles from such offices.

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        Your continued employment shall not constitute consent to, or a waiver
of rights with respect to, any circumstance constituting Good Reason hereunder.

               2. Successors; Binding Agreement. This Agreement shall inure to
the benefit of and be enforceable by you and your personal or legal
representatives, executors, administrators, successors, heirs, distributees,
devisees and legatees. If you should die while any amount would still be payable
to you hereunder had you continued to live, all such amounts, unless otherwise
provided herein, shall be paid in accordance with the terms of this Agreement to
your devisee, legatee or other designee or, if there is no such designee, to
your estate.

               3. Notice. For purposes of this Agreement, notices and all other
communications provided for in this Agreement shall be in writing and shall be
deemed to have been duly given when delivered or mailed by United States
certified or registered mail, return receipt requested, postage prepaid,
addressed to the respective addresses set forth on the first page of this
Agreement, provided that all notices to the Company shall be directed to the
attention of its General Counsel, or to such other address as either party may
have furnished to the other in writing in accordance herewith, except that
notice of change of address shall be effective only upon receipt.

               4. Miscellaneous. No provision of this Agreement may be modified,
waived or discharged unless such waiver, modification or discharge is agreed to
in writing and signed by you and such officer as may be specifically designated
by the Board. No waiver by either party hereto at any time of any breach by the
other party hereto of or compliance with, any condition or provision of this
Agreement to be performed by such other party shall be deemed a waiver of
similar or dissimilar provisions or conditions at the same or at any prior or
subsequent time. No agreements or representations, oral or otherwise, express or
implied, with respect to the subject matter hereof have been made by either
party which are not expressly set forth in this Agreement. The validity,
interpretation, construction and performance of this Agreement shall be governed
by the laws of the State of California without regard to its conflicts of law
principles. Any payments provided for hereunder shall be paid net of any
applicable withholding required under federal, state or local law. The section
headings contained in this Agreement are for convenience only, and shall not
affect the interpretation of this Agreement.

               5. Severability. The invalidity or unenforceability of any
provision of this Agreement shall not affect the validity or enforceability of
any other provision of this Agreement, which shall remain in full force and
effect.

               6. Counterparts. This Agreement may be executed in several
counterparts, each of which shall be deemed to be an original but all of which
together shall constitute one and the same instrument.

               7. Entire Agreement. This Agreement sets forth the entire
agreement of the parties hereto in respect of the subject matter contained
herein and supersedes all prior agreements, promises, covenants, arrangements,
communications, representations or warranties, whether oral or written, by any
officer, employee or representative of any party hereto. Any of your rights
hereunder shall be in addition to any rights you may otherwise have under
benefit plans or agreements of the Company to which you are a party or in which
you are a participant, including, but not limited to, any Company sponsored
employee benefit plans and stock options

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plans. The provisions of this Agreement shall not in any way abrogate your
rights under such other plans and agreements.

               8. At-Will Employment. Nothing contained in this Agreement shall
(a) confer upon you any right to continue in the employ of the Company, (b)
constitute any contract or agreement of employment, or (c) interfere in any way
with the at-will nature of your employment with the Company.

               If this letter sets forth our agreement on the subject matter
hereof, kindly sign and return to the Company the enclosed copy of this letter,
which shall then constitute our agreement on this subject.

                                       Sincerely,

                                       HYSEQ, INC.

                                       By:
                                           -------------------------------------

                                       Name:
                                       Its:

Agreed and Accepted,
this ______ day of November, 2002.

---------------------------------------
[EXECUTIVE NAME]

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