FOURTH AMENDMENT TO COLLABORATION AGREEMENT

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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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