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                                                                 EXHIBIT 10.13.4

                   FOURTH AMENDMENT TO COLLABORATION AGREEMENT

      This Fourth Amendment to Collaboration Agreement (this "Fourth Amendment")
dated as of January 31, 2006 (the "Fourth Amendment Effective Date"), is by and
between Regeneron Pharmaceuticals, Inc., a corporation organized and existing
under the laws of the State of New York and having its principal office at 777
Old Saw Mill River Road, Tarrytown, New York 10591 ("Regeneron ") and
sanofi-aventis U. S., LLC, (successor in interest to Aventis Pharmaceuticals
Inc.), a limited liability company organized and existing under the laws of the
State of Delaware and having a principal place of business at 200 Crossing
Blvd., Bridgewater, New Jersey 08807 ("Aventis").

                                  INTRODUCTION

      WHEREAS, Regeneron and Aventis are Parties to a Collaboration Agreement,
having an Effective Date of September 5, 2003, as amended on December 31, 2004,
January 7, 2005, and December 21, 2005 (the "Collaboration Agreement"); and

      WHEREAS, Regeneron and Aventis have determined that it is desirable to
amend certain provisions of the Collaboration Agreement and document further
agreements between them as set forth herein.

      NOW, THEREFORE, in consideration of the following mutual promises and
obligations and for good and valuable consideration, the receipt and sufficiency
of which are hereby acknowledged, the Parties, intending to be legally bound,
hereby agree as follows:

Capitalized terms used in this Fourth Amendment and not defined herein shall
have the meanings ascribed to them in the Collaboration Agreement.

1. NEWLY CREATED INTELLECTUAL PROPERTY. Article 4 of the Collaboration Agreement
shall be amended by adding a new Section 4.6 at the end thereof as follows:

                        "4.6 Newly Created Intellectual Property. In addition to
                  the other licenses granted under this Article 4 and subject to
                  the other terms and conditions of this Agreement, to the
                  extent permitted under any relevant Third Party agreement,
                  each Party grants to the other Party and its Affiliates the
                  perpetual, royalty-free, paid-up, non-exclusive, worldwide
                  right and license, with the right to grant sublicenses, to use
                  and practice for any and all purposes: (i) all intellectual
                  property (including, without limitation, Know-How, Patents and
                  Patent Applications and copyrights) other than Excluded Rights
                  discovered, invented, authored or otherwise created by it (or
                  its Affiliate) after the Fourth Amendment Effective Date
                  directly in connection with the

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                  performance of the research activities approved by the JRC
                  and/or the clinical development activities approved by the
                  JDC, in each case, as included in the Co-Development Plans,
                  and (ii) the Patents and Know-How identified on Schedule I to
                  the Fourth Amendment (which were discovered or otherwise
                  created by Regeneron (either solely or with Third Party
                  collaborators) directly in connection with the performance of
                  the Co-Development Plans prior to the Fourth Amendment
                  Effective Date). As used above, the term "Excluded Rights"
                  shall mean any Patents or Know-How claiming or covering the
                  composition (including any formulation) of a VEGF Product,
                  including without limitation, a VEGF Trap Product. For the
                  avoidance of doubt, nothing in this Section 4.6 shall be
                  construed to grant either Party any license to Patents or
                  Know-How of the other Party discovered, invented, authored or
                  otherwise created by it outside the performance of the
                  research activities approved by the JRC and/or the clinical
                  development activities approved by the JDC, in each case, as
                  included in Co-Development Plans."

2.    DOCUMENTATION OF COLLABORATION ACTIVITIES. In recognition of the
      importance of proper documentation for the purposes of determining
      inventorship under United States patent and copyright laws as well as the
      laws of the State of New York with regard to Know How, the Parties agree
      to jointly establish standard operating procedures within ninety (90) days
      of the Fourth Amendment Effective Date related to the documentation of
      Collaboration activities carried out by the Parties.

3.    MISCELLANEOUS AMENDMENT TO COLLABORATION AGREEMENT. Section 19.8 of the
      Collaboration Agreement is hereby amended by adding a reference to Section
      "4.6" in the correct numerical order in the parenthetical phrase therein
      beginning "(including, without limitation, Sections 2.7. . .)."

4.    CONTINUING EFFECT. Except as specifically modified by this Fourth
      Amendment, all of the provisions of the Collaboration Agreement are hereby
      ratified and confirmed to be in full force and effect, and shall remain in
      full force and effect.

5.    ENTIRE AGREEMENT; SUCCESSORS AND ASSIGNS. The Collaboration Agreement,
      this Fourth Amendment, and any written agreements executed by both Parties
      pertaining to the subject matter therein, constitute the entire agreement
      between the Parties hereto with respect to subject matter hereof and
      thereof. Said documents supersede all other agreements and understandings
      between the Parties with respect to the subject matter hereof and thereof,
      whether written or oral. This Fourth Amendment shall be binding upon and
      shall inure to the benefit of the Parties and their respective heirs,
      administrators, executors, Affiliates, successors and permitted assigns.

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6.    HEADINGS. The section headings contained in this Fourth Amendment are for
      reference purposes only and shall not affect in any way the meaning or
      interpretation of the Fourth Amendment.

7.    COUNTERPARTS. This Fourth Amendment may be executed in one or more
      counterparts, all of which shall be considered one and the same agreement,
      and shall become a binding agreement when one or more counterparts have
      been signed by each Party and delivered to the other Party.

8.    MISCELLANEOUS. This Fourth Amendment shall be governed by the laws of the
      State of New York, without regard to its principles of conflicts of laws.
      Each Party hereby irrevocably and unconditionally consents to the
      exclusive jurisdiction of the courts of the State of New York, and the
      United States District Court for the Southern District of New York for any
      action, suit or proceeding arising out of or relating to this Fourth
      Amendment, waives any objections to such jurisdiction and venue and agrees
      not to commence any action, suit or proceeding relating to this Fourth
      Amendment except in such courts. This Fourth Amendment supersedes all
      prior understandings and agreements, whether written or oral, among the
      Parties hereto relating to the essence of this Fourth Amendment. If there
      is a direct conflict between the provisions of the Collaboration Agreement
      and this Fourth Amendment, this Fourth Amendment shall govern. This Fourth
      Amendment may be amended only by a written instrument executed by each of
      the Parties.

                      [SIGNATURES APPEAR ON FOLLOWING PAGE]

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      IN WITNESS WHEREOF, each of the Parties has caused this Fourth Amendment
to be executed as of the date hereof by a duly authorized corporate officer.

                               SANOFI-AVENTIS U.S., LLC

                               By:  /s/ Larry Baugh
                                  ----------------------------------------------

                               Name:  Larry Baugh

                               Title: Site Director

                               Date:  February 1, 2006

                               By: /s/ Gregory Irace
                                  ----------------------------------------------

                               Name: Gregory Irace

                               Title: Senior Vice President & Chief Financial
                               Officer

                               Date: February 1, 2006

                               REGENERON PHARMACEUTICALS, INC.

                               By: /s/  Murray Goldberg
                                  ----------------------------------------------

                               Name: Murray Goldberg

                               Title: SVP, Finance & Administration and CFO

                               Date: January 31, 2006

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                                   SCHEDULE I

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