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                                                                  EXHIBIT 10.46



                           OMNIBUS AMENDMENT AGREEMENT

     This Omnibus Amendment Agreement (the "Amendment") is entered into this
18th day of December, 1996, by and between ChemGenics Pharmaceuticals Inc.
(formerly known as Myco Pharmaceuticals Inc.), a Delaware corporation
("ChemGenics") and PerSeptive Biosystems, Inc., a Delaware corporation
("PerSeptive" or "PBIO").

     WHEREAS, ChemGenics and PerSeptive are parties to a Master Agreement dated
May 7, 1996 (the "Master Agreement");

     WHEREAS, at the Closing under the Master Agreement, the parties executed
and delivered among other documents the various documents listed in Section 1.03
of the Master Agreement (the "Ancillary Agreements"), including without
limitation the Consulting and Interim Services Agreement, the Standstill and
Registration Rights Agreement and the Warrant (as such terms are defined in the
Master Agreement) and stock certificates for the Shares (as defined in the
Master Agreement); and

     WHEREAS, ChemGenics and PerSeptive have agreed upon modifications to the
terms of the transaction reflected in the Master Agreement and the Ancillary
Agreements, and wish to set forth such modifications herein, to be effective
retroactively to the Closing Date (as defined in the Master Agreement), as if
initially set forth in the Master Agreement and the Ancillary Agreements.

     NOW THEREFORE, in consideration of the premises and the mutual covenants
contained in the Master Agreement, the Ancillary Agreements and this Amendment,
and for other good and valuable consideration, the receipt and sufficiency of
which is hereby acknowledged, the parties, intending to be legally bound, agree
as follows:

1.   Definitions.
     -----------

     1.1  Terms which are defined in the Master Agreement and the Ancillary
          Agreements are used herein as so defined.

2.   Amendments to the Master Agreement.
     ----------------------------------

     The Master Agreement is hereby amended as follows:


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     2.01 The first seven lines of Section 1.01.B are deleted from the Master
          Agreement, and the following is inserted in lieu thereof:

               "In consideration for the License Agreement and the transfer of
               the Transferred Assets, upon the terms and subject to the
               conditions set forth in this Agreement, on the Closing Date,
               ChemGenics shall issue to PerSeptive an aggregate of 6,792,679
               shares (the "Shares") of ChemGenics' Common Stock, $.001 par
               value per share (the "Common Stock") and shall deliver to
               PerSeptive a Promissory Note in the principal amount of
               $3,000,000, such Note to be in the form of Exhibit 1.03(B). Of
               such shares, 662,500"

          Section 1.01(B) is further amended by deleting the numbers "979,268,
          652,844 and 326,422" from the chart on page 3, and inserting, in lieu
          thereof, the numbers "662,500, 441,667 and 220,833".

     2.02 Section 8.04 is amended by deleting clause (ii) thereof, and inserting
          in lieu thereof the following:

               "(ii) PerSeptive will agree to restrictions on its sale or
               transfer of Capital Stock of ChemGenics,"

     2.03 Section 8.06 is amended by deleting the text thereof in its entirety,
          and replacing it with the following:

               "ChemGenics will use commercially reasonable efforts to
               accomplish an underwritten registered initial public offering of
               its Common Stock (a "Public Offering"), in which ChemGenics will
               seek to raise at least $15,000,000 in gross proceeds on or before
               June 30, 1997. If a Public Offering is not consummated by June
               30, 1997, then PerSeptive will deliver to ChemGenics a
               certificate for 2,000,000 of the Shares delivered to PerSeptive
               hereunder, leaving PerSeptive with an aggregate of

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               4,792,679 Shares, and ChemGenics will deliver to PerSeptive a
               Promissory Note in the principal amount of $2,000,000 in the form
               of Exhibit 8.06. PerSeptive shall at its own cost, assist and
               cooperate with ChemGenics as ChemGenics may reasonably request in
               effecting the Public Offering in a timely manner."

     2.04 Section 8.07 is deleted from the Master Agreement.

     2.05 It is understood and agreed that the terms of Exhibits 1.03(C)(i),
          1.03(C)(ii), 1.03(C)(iii), 1.03(C)(iv) and Exhibit 1.03(C)(v) are
          superseded in their entirety by the agreements executed at the Closing
          as amended by this Agreement.

     2.06 The last sentence of Section 8.03 and clause (i) of Section 10.15 of
          the Master Agreement are hereby deleted from the Master Agreement.

3.   AMENDMENT OF CONSULTING AND INTERIM SERVICES AGREEMENT. The Consulting and
     Interim Services Agreement is hereby amended as follows:

     3.01 Section 3 is amended by adding the following sentence immediately
          after the first sentence thereof:

               "The Supplies will be provided free of charge until the later of
               (i) March 31, 1997 or (ii) the closing of the first Public
               Offering (as defined in the Master Agreement), and thereafter
               will be supplied for the balance of the three-year period at a
               price equal to (a) fully-burdened manufacturing cost for Supplies
               manufactured by PBIO, and (b) and the actual cost of acquisition
               for Supplies distributed by PBIO."

     3.02 Section 4.A is amended by deleting the words "During the three year
          period commencing on the date hereof, PBIO shall loan to ChemGenics"
          at the beginning thereof, and replacing them with the words:

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               "Until the earlier of (i) June 30, 1997 or (ii) the closing of
               the first Public Offering (as defined in the Master Agreement),
               PBIO shall loan to ChemGenics, and thereafter through June 27,
               1999, shall sell to ChemGenics at fully-burdened manufacturing
               cost for Equipment manufactured by PBIO and the actual cost of
               acquisition for Equipment distributed by PBIO"

          Section 4.A is further amended by adding the phrase "or sold as
          provided above" following the word "loaned" in the twelfth line on
          page 4.

     3.03 Section 5 is amended by deleting the numbers "979,268, 652,844 and
          326,422" from the chart on page 7, and inserting, in lieu thereof, the
          numbers "662,500, 441,667 and 220,833".

     3.04 Section 9 is amended by deleting the third sentence thereof and
          inserting the following:

               "PBIO will on demand pay or reimburse ChemGenics for the payment
               of all Severance Pay and other severance related costs in excess
               of the Space Value for Drug Discovery Program Employees
               terminated on or before the earlier of the closing of the Public
               Offering or March 31, 1997."

          and by adding the following to the last sentence of the first
          paragraph thereof:

               ", provided the employment of such employee is terminated on or
               before the earlier of the closing of the Public Offering or March
               31, 1997."

4.   AMENDMENT OF STANDSTILL AND REGISTRATION RIGHTS AGREEMENT. The Standstill
     and Registration Rights Agreement is hereby amended as follows:

     4.01 The number 9,792,679 in the first "whereas" clause is replaced with
          the number 6,792,679.

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     4.02 Section 2.02 is amended by deleting the first paragraph thereof, but
          not subparagraphs (a), (b), (c) and (d), and replacing it with the
          following:

               "A. PBIO agrees that until the Initial Release Date (which shall
               be the earlier of (i) twelve months following the Closing of the
               Company's first Public Offering ("IPO") or (ii) December 30,
               1998), it will not, nor will it permit any of its affiliates or
               associates, to (x) distribute to its shareholders, or (y) sell,
               solicit an offer to sell, agree to sell, offer or propose to sell
               (collectively, "Sell") any Voting Securities of the Company or
               derivative securities relating thereto ("Company Securities").
               After such period:

               (1) (a) during the period from the Initial Release Date until six
               (6) months thereafter, PBIO may distribute to the shareholders of
               PBIO (i) up to one-third of the number of shares of ChemGenics
               Common Stock held by PBIO as of the earlier of the closing of the
               IPO or December 30, 1998, excluding for this purpose any shares
               of ChemGenics Common Stock issued upon exercise of the Warrant
               (the "Non-Warrant Shares") and/or (ii) up to one-third of the
               number of shares of Common Stock issuable to PBIO upon exercise
               of the Warrant ("Warrant Shares"), but only to the extent PBIO
               has exercised the Warrant and acquired Warrant Shares ("Exercised
               Warrant Shares"), (b) in the next two succeeding six-month
               periods thereafter, PBIO may distribute to its shareholders (i)
               up to one-third of the Non-Warrant Shares and/or (ii) up to
               one-third of the Exercised Warrant Shares and/or (iii) the
               Non-Warrant Shares and the Exercised Warrant Shares permitted
               to be

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               but not distributed by PBIO in the prior six-month period and (c)
               thereafter, subject to the following clause 3 of this paragraph,
               Section 3.09 and applicable securities laws, PBIO shall be
               permitted to distribute any or all of its Non-Warrant Shares and
               Exercised Warrant Shares to its shareholders;

               (2) (a) during the six-month period beginning on the earlier of
               (i) 18 months from the closing of the Company's IPO or (ii)
               December 30, 1998, PBIO may Sell up to one-third of PBIO's
               Non-Warrant Shares and/or up to one-third of PBIO's Exercised
               Warrant Shares and (b) in the next two succeeding six-month
               periods thereafter, PBIO may Sell an additional one-third of
               PBIO's Non-Warrant Shares and/or up to one-third of PBIO's
               Exercised Warrant Shares and/or PBIO's Non-Warrant Shares and
               Exercised Warrant Shares permitted to be but not sold by PBIO in
               the prior six-month period and (c) thereafter, subject to the
               following clause 3 of this paragraph, Section 3.09 and applicable
               securities laws, PBIO shall be permitted to Sell any or all of
               its Non-Warrant Shares and Exercised Warrant Shares; and

               (3) In addition to the restrictions and limitations set forth in
               the preceding clauses, in any six (6) month period ending on (i)
               twenty four (24) months after the closing of the IPO, if the IPO
               closes on or before June 30, 1997 or (ii) until the later of
               twelve months after the closing of the IPO or June 30, 1999 if
               the IPO closes after June 30, 1997, PBIO shall not distribute or
               Sell more than a total of one-third of the Non-Warrant Shares and
               one-third of the Exercised Warrant

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               Shares. As used herein, "Public Offering" shall mean an
               underwritten public offering of ChemGenics Common Stock
               registered with the SEC. Notwithstanding the foregoing:"

     4.03 Section 3.01 is amended by deleting the words commencing immediately
          following the words "PROVIDED, HOWEVER," where appearing in the first
          sentence thereof and ending with the word "Shares" at the beginning of
          the fifth line on page 6 and inserting the following words: "that the
          Company shall not be required to include in any such registration
          statement any Registrable Shares which PBIO is not permitted to Sell
          pursuant to the initial paragraph of Section 2.02 and provided further
          that as a condition to including any shares issued or issuable upon
          exercise of the Warrant ("Warrant Shares")

     4.04 Sections 3.01 and 3.02 are amended by deleting the words "at any time
          after the third anniversary of this Agreement" from the first sentence
          thereof and replacing them with the words "at any time when PBIO is
          permitted to Sell Company Securities pursuant to the initial paragraph
          of Section 2.02,".

     4.05 Section 3.09 is amended by inserting after the words "held by it"
          where appearing in the first sentence thereof, the following words:
          "for such period of time, and on such other terms, as shall be agreed
          to among the Company, the underwriters and a majority of the venture
          capital partnerships that hold Company Securities as of the IPO, nor
          will PBIO permit any of its affiliates to do any of the foregoing" and
          deleting the remainder of the first sentence. Section 3.09 is further
          amended by deleting the words "180-day" where appearing in the last
          sentence thereof and inserting the words "agreed-upon."

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5.   Exchange of Warrants.
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     5.01 Contemporaneously with the execution hereof, PerSeptive will deliver
          to ChemGenics the Warrant as delivered at the Closing, and ChemGenics
          shall deliver to PerSeptive a new Warrant in the form attached hereto.
          The new Warrant shall, for all purposes, be deemed to be the "Warrant"
          under the Master Agreement and the Ancillary Agreements.

6.   EXCHANGE OF STOCK CERTIFICATES. Contemporaneously with the execution
     hereof, PerSeptive shall deliver to ChemGenics certificates numbered
     C0028-31 for 8,813,411, 326,423, 326,423 and 326,422 shares of Common Stock
     of ChemGenics and ChemGenics shall deliver to PerSeptive certificates for
     4,130,179, 2,000,000, 220,833, 220,833 and 220,834 shares of Common Stock
     of ChemGenics.

7.   NO OTHER CHANGES. In all other respects, the Master Agreement and the
     Ancillary Agreements shall not be affected hereby, and shall remain in
     force and effect as initially executed and delivered.

     IN WITNESS WHEREOF, ChemGenics and PerSeptive have executed this Amendment
as of the day and year first above written.



CHEMGENICS PHARMACEUTICALS INC.


By: /s/ Barry Berkowitz
   ------------------------------------
     Barry Berkowitz
     President

PERSEPTIVE BIOSYSTEMS, INC.

By: /s/ Noubar B. Afeyan
   ------------------------------------
     Noubar B. Afeyan
     President


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