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                                                                     Exhibit 4.1

                                 AMENDMENT NO. 2
                                       TO
                                RIGHTS AGREEMENT

This AMENDMENT NO. 2 TO RIGHTS AGREEMENT (the "Amendment") is entered into as of
March 24, 2006, between Idera Pharmaceuticals, Inc., a Delaware corporation (the
"Company"), and Mellon Investor Services LLC, a New Jersey limited liability
company, as Rights Agent (the "Rights Agent"). Capitalized terms not otherwise
defined herein shall have the meanings given them in the Rights Agreement, dated
as of December 10, 2001, as amended (the "Rights Agreement"), between the
parties hereto.

                                    RECITALS

WHEREAS, the Board has determined that it is in the best interest of the Company
to amend the Rights Agreement to modify the definition of Exempted Person to
exclude a certain stockholder of the Company from such definition in specified
circumstances; and

WHEREAS, the Company has determined that the Rights Agreement be amended in
accordance with Section 27 of the Rights Agreement, as set forth herein, and the
Rights Agent is hereby directed to join in the amendment to the Rights Agreement
as set forth herein.

                                    AGREEMENT

NOW THEREFORE, the parties hereto, intending to be legally bound, hereby agree
as follows:

1. Section 1(oo) of the Rights Agreement is hereby amended to read in its
entirety as follows:

     "(oo) "Exempted Person" shall mean Baker Brothers Investments, together
          with all of its Affiliates and Associates ("Baker Brothers"), unless
          and until such time as Baker Brothers, directly or indirectly, becomes
          the Beneficial Owner of more than 35,000,000 shares (subject to
          appropriate adjustment to reflect any stock split, reverse stock
          split, stock dividend, combination, reclassification or other similar
          recapitalization affecting such shares) of the Common Stock
          (disregarding for purposes of this calculation any shares of Common
          Stock purchased by Baker Brothers pursuant to the participation right
          (the "Participation Right") set forth in Section 5.2 of that certain
          Common Stock Purchase Agreement, dated March 24, 2006, by and among
          the Company and the purchasers listed in Exhibit A thereto (the "CSP
          Agreement")). Notwithstanding the preceding sentence, if following the
          date on which its Participation Right terminates in accordance with
          the CSP Agreement, Baker Brothers, directly or indirectly, is or
          becomes the Beneficial Owner of less than 14% of the Common Stock then
          outstanding, Baker Brothers immediately shall cease to be an Exempted
          Person. The Company acknowledges that the Rights Agent has no
          knowledge of the CSP Agreement.

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2. Section 3(a) of the Rights Agreement is hereby amended by deleting the first
sentence of Section 3(a) in its entirety and inserting in lieu thereof the
following sentence:

          "Section 3. Issuance of Rights.

          (a) Until the earlier of (i) the Close of Business on the tenth
     Business Day (or such later date as may be determined by the Board) after
     the Stock Acquisition Date (or, if the tenth Business Day after the Stock
     Acquisition Date occurs before the Record Date, the close of business on
     the Record Date), or (ii) the Close of Business on the tenth Business Day
     (or such later date as may be determined by action of the Board) after the
     date that a tender or exchange offer (other than a Permitted Offer) by any
     Person (other than the Company, any Subsidiary of the Company, any employee
     benefit plan of the Company or of any Subsidiary of the Company, or any
     Person organized, appointed or established by the Company for or pursuant
     to the terms of any such plan) is first published or sent or given within
     the meaning of Rule 14d-2 of the General Rules and Regulations under the
     Exchange Act, if upon consummation thereof, such Person would be the
     Beneficial Owner of 15% or more of the shares of Common Stock then
     outstanding (the earlier of (i) and (ii) being herein referred to as the
     "Distribution Date"), (x) the Rights will be evidenced by the certificates
     for the Common Stock registered in the names of the holders of the Common
     Stock (which certificates for Common Stock shall be deemed also to be
     certificates for Rights) and not by separate certificates, and (y) the
     Rights will be transferable only in connection with the transfer of the
     underlying shares of Common Stock (including a transfer to the Company)."

3. Except as amended hereby, the Rights Agreement shall remain unchanged and
shall remain in full force and effect.

4. This Amendment may be executed in any number of counterparts, each of which
shall be an original, but all of which together shall constitute one instrument.

5. This Amendment shall be deemed to be a contract made under the laws of the
State of Delaware and for all purposes shall be governed by and construed in
accordance with the laws of Delaware applicable to contracts made and to be
performed entirely within Delaware; provided, however, that all rights, duties
and obligations of the Rights Agent shall be governed by and construed in
accordance with the laws of the State of New York applicable to contracts made
and to be performed entirely within such state.

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IN WITNESS WHEREOF, the parties have caused this Amendment to be executed by
their respective duly authorized representatives as of the date first above
written.

IDERA PHARMACEUTICALS, INC.


By: /s/ Sudhir Agrawal
    ---------------------------------
Name: Sudhir Agrawal
Title: Chief Executive Officer


MELLON INVESTORS SERVICES LLC,
as Rights Agent


By: /s/ John J. Boryczki
    ---------------------------------
Name: John J. Boryczki
Title: Client Relationship Executive