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                                                                   Exhibit 4.6


THIS WARRANT AND THE SHARES ISSUABLE HEREUNDER HAVE NOT BEEN REGISTERED UNDER
THE SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT BE SOLD, PLEDGED OR
OTHERWISE TRANSFERRED WITHOUT AN EFFECTIVE REGISTRATION THEREOF UNDER SUCH ACT
OR PURSUANT TO AN EXEMPTION FROM THE REGISTRATION REQUIREMENTS THEREOF.

                            WARRANT TO PURCHASE STOCK

Corporation:                             ARCHEMIX CORP., a Delaware corporation
Number of Shares:                        30,000
Class of Stock:                          Series A Convertible Preferred Stock
Initial Exercise Price:                  $1.00 per share
Issue Date:                              December 18, 2002
Expiration Date:                         December 18, 2009

         THIS WARRANT CERTIFIES THAT, in consideration of the payment of $1.00
and for other good and valuable consideration, COMERICA BANK-CALIFORNIA or its
permitted assignee ("Holder") is entitled to purchase the number of fully paid
and nonassessable shares of the class of securities (the "Shares") of the
corporation (the "Company") at the initial exercise price per Share (the
"Warrant Price") all as set forth above and as adjusted pursuant to Article 2 of
this warrant, subject to the provisions and upon the terms and conditions set
forth in this warrant.

ARTICLE 1. EXERCISE.

         1.1      Method of Exercise. Holder may exercise this warrant by
delivering this warrant and a duly executed Notice of Exercise in substantially
the form attached as Appendix 1 to the principal office of the Company. Unless
Holder is exercising the conversion right set forth in Section 1.2, Holder shall
also deliver to the Company a check for the aggregate Warrant Price for the
Shares being purchased.

         1.2      Conversion Right. In lieu of exercising this warrant as
specified in Section 1.1, Holder may from time to time after the earlier of an
Acquisition (as defined herein) or the closing of a registered public offering
of the Company's common stock convert this warrant, in whole or in part, into a
number of Shares determined by dividing (a) the aggregate fair market value of
the Shares or other securities otherwise issuable upon exercise of this warrant
minus the aggregate Warrant Price of such Shares by (b) the fair market value of
one Share. The fair market value of the Shares shall be determined pursuant to
Section 1.3.

         1.3      Fair Market Value. If the Shares are traded regularly in a
public market, the fair market value of the Shares shall be the closing price of
the Shares (or the closing price of the Company's stock into which the Shares
are convertible) reported for the business day immediately before Holder
delivers its Notice of Exercise to the Company. If the Shares are not regularly
traded in a public market, the Board of Directors of the Company shall determine
fair market value in its reasonable good faith judgment. The foregoing
notwithstanding, if Holder advises the Board of Directors in writing that Holder
disagrees with such determination, then the Company and Holder shall promptly
agree upon a reputable investment banking firm to


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undertake such valuation. If the valuation of such investment banking firm is
more than 10% greater than that determined by the Board of Directors, then all
fees and expenses of such investment banking firm shall be paid by the Company.
In all other circumstances, such fees and expenses shall be paid by Holder.

         1.4      Delivery of Certificate and New Warrant. Promptly after Holder
exercises or converts this warrant, the Company shall deliver to Holder
certificates for the Shares acquired and, if this warrant has not been fully
exercised or converted and has not expired, a new warrant representing the
Shares not so acquired.

         1.5      Replacement of Warrants. On receipt of evidence reasonably
satisfactory to the Company of the loss, theft, destruction or mutilation of
this warrant and, in the case of loss, theft or destruction, on delivery of an
indemnity agreement reasonably satisfactory in form and amount to the Company
or, in the case of mutilation, on surrender and cancellation of this warrant,
the Company at its expense shall execute and deliver, in lieu of this warrant, a
new warrant of like tenor.

         1.6      Repurchase on Sale, Merger, or Consolidation of the Company.

                  1.6.1    "Acquisition." For the purpose of this warrant,
"Acquisition" means any sale, license, or other disposition of all or
substantially all of the assets (including intellectual property) of the
Company, or any reorganization, consolidation, or merger of the Company where
the holders of the Company's securities before the transaction beneficially own
less than 50% of the outstanding voting securities of the surviving entity after
the transaction.

                  1.6.2    Assumption of Warrant. Upon the closing of any
Acquisition the successor entity shall assume the obligations of this warrant,
and this warrant shall then be exercisable for the same securities, cash, and
property as would be payable for the Shares issuable upon exercise of the
unexercised portion of this warrant as if such Shares were outstanding on the
record date for the Acquisition and subsequent closing. The Warrant Price shall
be adjusted accordingly.

         1.7      Adjustment to Number of Shares. Upon the earlier of (i) six
month and one day after the Equity Event (as defined in that certain Loan and
Security Agreement dated as of October 3, 2001, as amended, including without
limitation by that certain Amendment to Loan and Security Agreement dated as of
October 3, 2001 and that certain Second Amendment to Loan and Security Agreement
dated as of the Issue Date (collectively, the "Loan Agreement")) occurs and (ii)
the date after the Equity Event on which Borrower elects the amount of the
Facility B Equipment Line (as defined in the Loan Agreement"), the Number of
Shares subject to this warrant shall be automatically adjusted to equal 3% of
the amount of the Tranche B Equipment Line (as defined in the Loan Agreement) at
that time.

ARTICLE 2. ADJUSTMENTS TO THE SHARES.

         2.1      Stock Dividends, Splits, Etc. If the Company declares or pays
a dividend on its common stock payable in common stock, or other securities,
subdivides the outstanding common stock into a greater amount of common stock,
then upon exercise of this warrant, for each Share acquired, Holder shall
receive, without cost to Holder, the total number and kind of securities to


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which Holder would have been entitled had Holder owned the Shares of record as
of the date the dividend or subdivision occurred.

         2.2      Reclassification, Exchange or Substitution. Upon any
reclassification, exchange, substitution, or other event that results in a
change of the number and/or class of the securities issuable upon exercise or
conversion of this warrant, Holder shall be entitled to receive, upon exercise
or conversion of this warrant, the number and kind of securities and property
that Holder would have received for the Shares if this warrant had been
exercised immediately before such reclassification, exchange, substitution, or
other event. Such an event shall include any automatic conversion of the
outstanding or issuable securities of the Company of the same class or series as
the Shares to common stock pursuant to the terms of the Company's Certificate of
Incorporation upon the closing of a registered public offering of the Company's
common stock. The Company or its successor shall promptly issue to Holder a new
warrant for such new securities or other property. The new warrant shall provide
for adjustments which shall be as nearly equivalent as may be practicable to the
adjustments provided for in this Article 2 including, without limitation,
adjustments to the Warrant Price and to the number of securities or property
issuable upon exercise of the new warrant. The provisions of this Section 2.2
shall similarly apply to successive reclassifications, exchanges, substitutions,
or other events.

         2.3      Adjustments for Combinations, Etc. If the outstanding Shares
are combined or consolidated, by reclassification or otherwise, into a lesser
number of shares, the Warrant Price shall be proportionately increased.

         2.4      Adjustments for Diluting Issuances. The number of Shares
issuable upon the conversion of the Shares into common stock shall be subject to
adjustment, from time to time, in the manner set forth in the Certificate of
Incorporation of Company in the form existent on the Issue Date.

         2.5      No Impairment. The Company shall not, by amendment of its
Certificate of Incorporation or through a reorganization, transfer of assets,
consolidation, merger, dissolution, issue, or sale of securities or any other
voluntary action, avoid or seek to avoid the observance or performance of any of
the terms to be observed or performed under this warrant by the Company, but
shall at all times in good faith assist in carrying out all the provisions of
this Article 2 and in taking all such action as may be necessary or appropriate
to protect Holder's rights under this Article against impairment. If the Company
takes any action affecting the Shares or its common stock other than as
described above that adversely affects Holder's rights under this warrant, the
Warrant Price shall be adjusted downward and the number of Shares issuable upon
exercise of this warrant shall be adjusted upward in such a manner that the
aggregate Warrant Price of this warrant is unchanged.

         2.6      Certificate as to Adjustments. Upon each adjournment of the
Warrant Price, the Company at its expense shall promptly compute such
adjustment, and furnish Holder with a certificate of its Chief Financial Officer
setting forth such adjustment and the facts upon which such adjustment is based.
The Company shall, upon written request, furnish Holder a certificate setting
forth the Warrant Price in effect upon the date thereof and the series of
adjustments leading to such Warrant Price.



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ARTICLE 3. REPRESENTATIONS AND COVENANTS OF THE COMPANY.

         3.1      Representations and Warranties. The Company hereby represents
and warrants to the Holder as follows:

                  (a)      The initial Warrant Price referenced on the first
page of this warrant is not greater than the fair market value of the Shares as
of the date of this warrant.

                  (b)      All Shares which may be issued upon the exercise of
the purchase right represented by this warrant, and all securities, if any,
issuable upon conversion of the Shares, shall, upon issuance, be duly
authorized, validly issued, fully paid and nonassessable, and free of any liens
and encumbrances except for restrictions on transfer provided for herein or
under applicable federal and state securities laws.

                  (c)      The Company's capitalization table attached to this
warrant is true and complete as of the Issue Date.

         3.2      Notice of Certain Events. If the Company proposes at any time
(a) to declare any dividend or distribution upon its common stock, whether in
cash, property, stock, or other securities and whether or not a regular cash
dividend; (b) to offer for subscription pro rata to the holders of any class or
series of its stock any additional shares of stock of any class or series or
other rights; (c) to effect any reclassification or recapitalization of common
stock; or (d) to merge or consolidate wish or into any other corporation, or
sell, lease, license, or convey all or substantially all of its assets, or to
liquidate, dissolve or wind up, then, in connection with each such event, the
Company shall give Holder (1) at least 20 days prior written notice of the date
on which a record will be taken for such dividend, distribution, or subscription
rights (and specifying the date on which the holders of common stock will be
entitled thereto) or for determining rights to vote, if any, in respect of the
matters referred to in (a) and (b) above; and (2) in the case of the matters
referred to in (c) and (d) above at least 20 days prior written notice of the
date when the same will take place (and specifying the date on which the holders
of common stock will be entitled to exchange their common stock for securities
or other property deliverable upon the occurrence of such event).

         3.3      Information Rights. So long as the Holder holds this warrant
and/or any of the Shares, the Company shall deliver to the Holder (a) promptly
after mailing, copies of all communiques to the shareholders of the Company, (b)
within ninety (90) days after the end of each fiscal year of the Company, the
annual audited financial statements of the Company certified by independent
public accountants of recognized standing and (c) within forty-five (45) days
after the end of each of the first three quarters of each fiscal year, the
Company's quarterly, unaudited financial statements.

ARTICLE 4. MISCELLANEOUS.

         4.1      Term. This warrant is exercisable in whole or in part, at any
time and from time to time on or before the Expiration Date set forth above.

         4.2      Compliance with Securities Act.


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                  (a)      The Holder acknowledges that this warrant and the
Shares have not been registered under the Securities Act of 1933, as amended,
and the rules and regulations thereunder, or any successor legislation (the
"Securities Act") and, subject to Section 4.3, agrees not to sell, pledge,
distribute, offer for sale, transfer or otherwise dispose of this warrant or any
Shares in the absence of (i) an effective registration statement under the
Securities Act covering this warrant or such Shares and registration or
qualification of this warrant or such Shares under any applicable "blue sky" or
state securities law then in effect, or (ii) an opinion of counsel, satisfactory
to the Company, that such registration and qualification are not required. The
Company may delay issuance of the Shares until completion of any action or
obtaining of any consent, which the Company deems necessary under any applicable
law (including without limitation state securities or "blue sky" laws).

                  (b)      Without limiting the generality of Section 4.2(a),
unless the offer and sale of any Shares shall have been effectively registered
under the Securities Act, the Company shall be under no obligation to issue the
Shares unless and until the Holder shall have executed the Notice of Exercise in
substantially the form attached as Appendix 1, including the warranty at the
time of such exercise that the Holder is acquiring such shares for its own
account, for investment and not with a view to, or for sale in connection with,
the distribution of any such shares.

                  (c)      Certificates delivered to the Holder pursuant to
Section 1.2 shall bear the following legend or a legend in substantially similar
form:

         "THE SHARES REPRESENTED BY THIS CERTIFICATE HAVE BEEN TAKEN FOR
         INVESTMENT AND THEY MAY NOT BE SOLD OR OTHERWISE TRANSFERRED BY ANY
         PERSON, INCLUDING A PLEDGEE, IN THE ABSENCE OF AN EFFECTIVE
         REGISTRATION STATEMENT FOR THE SHARES UNDER THE SECURITIES ACT OF 1933,
         AS AMENDED, OR AN OPINION OF COUNSEL, SATISFACTORY TO THE COMPANY, THAT
         AN EXEMPTION FROM REGISTRATION IS THEN AVAILABLE."

         4.3      Transfer Procedure. Subject to the provisions of Section 4.2,
Holder may transfer all or part of this warrant or the Shares issuable upon
exercise of this warrant (or the securities issuable, directly or indirectly,
upon conversion of the Shares, if any) by giving the Company notice of the
portion of the warrant being transferred setting forth the name, address and
taxpayer identification number of the transferee and surrendering this warrant
to the Company for reissuance to the transferee(s) (and Holder, if applicable);
provided, however, that Holder may transfer all or part of this warrant to its
affiliates, including, without limitation, Holder's parent company, at any time
without notice to the Company, and such affiliate shall then be entitled to all
the rights of Holder under this warrant and any related agreements, and the
Company shall cooperate fully in ensuring that any stock issued upon exercise of
this warrant is issued in the name of the affiliate that exercises the warrant.
The terms and conditions of this warrant shall inure to the benefit of, and be
binding upon, the Company and the holders hereof and their respective permitted
successors and assigns.

         4.4      Notices. All notices and other communications from the Company
to the Holder,


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or vice versa, shall be deemed delivered and effective when given personally or
mailed by first-class registered or certified mail, postage prepaid, at such
address as may have been furnished to the Company or the Holder, as the case may
be, in writing by the Company or such Holder from time to time, with a copy to
Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., One Financial Center,
Boston, MA 02111, Attn: Jeffrey M. Wiesen, Esq. (provided that failure to
deliver a copy to a person other than Company shall not invalidate a notice or
communication otherwise delivered to Company in accordance with this Section).
All notices to the Holder shall be addressed as follows:

                         Comerica Bank-California
                         Attn: Controllers Department
                         P.O. Box 92991
                         Los Angeles, CA 90009-2991

                         with a copy to:

                         Comerica Bank-California
                         Attn: Warrant Administrator Special Markets Division
                         P.O. Box 7279
                         San Francisco, CA 94120-7279

         4.5      Waiver. This warrant and any term hereof may be changed,
waived, discharged or terminated only by an instrument in writing signed by the
party against which enforcement of such change, waiver, discharge or termination
is sought.

         4.6      Attorneys' Fees. In the event of any dispute between the
parties concerning the terms and provisions of this warrant, the party
prevailing in such dispute shall be entitled to collect from the other party all
costs incurred in such dispute, including reasonable attorneys' fees.

         4.7      Governing Law. This warrant shall be governed by and construed
in accordance with the laws of the State of Delaware, without giving effect to
its principles regarding conflicts of law.

                                  ARCHEMIX CORP.



                                  By:    /s/ Martin Stanton
                                         ---------------------------------------

                                  Name:  Martin Stanton
                                         ---------------------------------------

                                  Title: President
                                         ---------------------------------------



Authorized signatories under Corporate Resolutions to Borrow or an authorized
signer(s) under a resolution covering warrants must sign the warrant.




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                                   APPENDIX I

                               NOTICE OF EXERCISE

         1.       The undersigned hereby elects to purchase _____________ shares
(the "Warrant Stock") of the _____________ stock of ARCHEMIX CORP. (the
"Company") pursuant to the terms of the attached warrant, and tenders herewith
payment of the purchase price of such shares in full.

         1.       The undersigned hereby elects to convert the attached warrant
into shares in the manner specified in the warrant. This conversion is exercised
with respect to __________ of the shares covered by the warrant.

         [STRIKE PARAGRAPH THAT DOES NOT APPLY.]

         2.       Please issue a certificate or certificates representing said
shares in the name of the undersigned or in such other name as is specified
below:

                           Comerica Bank-California
                           Attn: Controllers Department
                           P.O. Box 92991
                           Los Angeles, CA 90009
                           Or Registered Assignee

         3.       The undersigned is aware that the Warrant Stock has not been
and will not be registered under the Securities Act of 1933, as amended (the
"Securities Act") or any state securities laws. The undersigned understands that
reliance by the Company on exemptions under the Securities Ac. is predicated in
part upon the truth and accuracy of the statements of the undersigned in this
Notice of Exercise.

         The undersigned represents and warrants that (1) it has been furnished
with all information which it deems necessary to evaluate the merits and risks
of the purchase of the Warrant Stock, (2) it has had the opportunity to ask
questions concerning the Warrant Stock and the Company and all questions posed
have been answered to its satisfaction, (3) it has been given the opportunity to
obtain any additional information it deems necessary to verify the accuracy of
any information obtained concerning the Warrant Stock and the Company and (4) it
has such knowledge and experience in financial and business matters that it is
able to evaluate the merits and risks of purchasing the Warrant Stock and to
make an informed investment decision relating thereto.

         The undersigned hereby represents and warrants that it is purchasing
the Warrant Stock for its own account for investment and not with a view to the
sale or distribution of all or any part of the Warrant Stock.

         The undersigned understands that because the Warrant Stock has not been
registered under the Securities Act, it must continue to bear the economic risk
of the investment for an indefinite period of time and the Warrant Stock cannot
be sold unless it is subsequently




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registered under applicable federal and state securities laws or an exemption
from such registration is available.

         The undersigned agrees that, subject to Section 4.3 of the Warrant, it
will in no event sell or distribute or otherwise dispose of all or any part of
the Warrant Stock unless (1) there is an effective registration statement under
the Securities Act and applicable state securities laws covering any such
transaction involving the Warrant Stock, or (2) the Company receives an opinion
satisfactory to the Company of the undersigned's legal counsel stating that such
transaction is exempt from registration. The undersigned consents to the placing
of a legend on its certificate for the Warrant Stock stating that the Warrant
Stock has not been registered and setting forth the restriction on transfer
contemplated hereby and to the placing of a stop transfer order on the books of
the Company and with any transfer agents against the Warrant Stock until the
Warrant Stock may be legally resold or distributed without restriction.

COMERICA BANK-CALIFORNIA or Registered Assignee



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(Signature)


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(Date)




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