THIRD AMENDMENT TO COLLABORATION AGREEMENT

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                                                                 EXHIBIT 10.13.3

                   THIRD AMENDMENT TO COLLABORATION AGREEMENT

      This Third Amendment to Collaboration Agreement (this "Third Amendment")
dated as of December 21, 2005, 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 Aventis Pharmaceuticals Inc., a corporation
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,
and January 7, 2005 (the "Collaboration Agreement"); and

      WHEREAS, Regeneron and Aventis have determined that it is desirable to
amend certain provisions of the Collaboration Agreement to include Japan in the
Territory under the terms and conditions 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 Third Amendment and not defined herein shall have
the meanings ascribed to them in the Collaboration Agreement.

1.    ARTICLE 1. "DEFINITIONS". Article 1 of the Collaboration Agreement shall
      be amended as follows:

      (a) Section 1.2 "Additional Major Market Country" shall be amended by
      adding the words "Japan and" after the words "other than" and before the
      words "the Major Market Countries referred to in clause (i) of the
      definition thereof" therein.

      (b) Section 1.41 "Consolidated Net Profit/Loss Report" shall be amended by
      adding the following sentence at the end thereof. "This report shall also
      include, in reasonable detail, Net Sales in Japan, ******* (as defined in
      Section 9.1(b)), and the Japan Royalty Payment in sufficient detail to
      calculate the Japan True-Up for such calendar quarter."

      (c) Section 1.53 "Develop" or "Development" shall be amended by adding the
      phrase "in the case of all countries in the Territory except Japan," after
      the reference to "(c)" therein.

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      (d) Section 1.158 "Territory" shall be amended by deleting the words
      ", excluding Japan" therein.

2.    SECTION 2.6 "JAPAN". Section 2.6 of the Collaboration Agreement shall be
      deleted in its entirety.

3.    SECTION 4.1 "LICENSE GRANTS". Section 4.1 of the Collaboration Agreement
      shall be amended by deleting the reference to "(i)" therein and deleting
      the phrase "and (ii) the foregoing license grant shall not restrict or
      prohibit Regeneron's right to manufacture and supply Regeneron VEGF
      Products for importation into or use or sale in Japan."

4.    SECTION 4.3 "SUBLICENSES; SUBCONTRACTING". Section 4.3 of the
      Collaboration Agreement shall be amended by adding the phrase "other than
      Japan" after the reference to the defined term "Rest of World Country" in
      clause (A) therein.

5.    SECTION 6.5 "VEGF PRODUCT PRICING AND PRICING APPROVALS". Section 6.5 of
      the Collaboration Agreement shall be amended by adding ", Japan"
      immediately before the phrase "as well as the United States" in the final
      sentence therein. Section 6.5 of the Collaboration Agreement shall be
      further amended by adding the words "or Japan" at the end thereof after
      the reference to "the United States."

6.    SECTION 9.1(a) "SHARING OF COLLABORATION PROFITS AND LOSSES". Section
      9.1(a) of the Collaboration Agreement shall be amended by adding the words
      "other than Japan" after the defined term "Rest of World Countries"
      therein. Section 9.1(a) shall be further amended by adding the following
      sentence at the end thereof: "In addition, in consideration of the license
      grants herein for VEGF Products in Japan, and subject to the other terms
      and conditions of this Agreement, Aventis shall pay to Regeneron as part
      of the Quarterly True-Up a royalty on Net Sales in Japan calculated in
      accordance with the formula described in Schedule 1A (the 'Japan Royalty
      Payment')."

7.    SECTION 9.1(b) "SHARING OF COLLABORATION PROFITS AND LOSSES". Section
      9.1(b) of the Collaboration Agreement shall be amended by adding the
      following sentences at the end thereof: "Notwithstanding the foregoing,
      Regeneron and Aventis shall each be responsible for paying fifty percent
      (50%) of all *********** incurred in accordance with the terms of this
      Agreement and the applicable Co-Development Budget, subject to the terms
      and conditions set forth in Schedules 1 and 1A. As used herein, the term
      ************ shall mean Development Costs incurred by the Parties for JDC
      approved Clinical Trials conducted in Japan (and/or such other Asian
      countries as may be agreed upon by the Parties) in *********************
      *******************************."

8.    SECTION 9.2 "PERIODIC REPORTS". Section 9.2(c) of the Collaboration
      Agreement shall be amended by adding "Japan," after the words "in Major
      Market Countries," in clause (ii) therein. Section 9.2(c) of the
      Collaboration Agreement shall be further amended by adding the words "and
      Japan" after the phrase "with respect to the United States" in clause
      (iii) therein. Section 9.2(c) of the Collaboration Agreement shall be
      further

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      amended by adding the words "and Japan" after the defined term "Major
      Market Countries" in clause (iv) therein.

9.    SECTION 16.1(c) "CONFIDENTIAL PARTY INFORMATION". Section 16.1 of the
      Collaboration Agreement shall be amended by deleting paragraph (c) in its
      entirety and substituting the words "INTENTIONALLY BLANK" after the
      reference to "(c)" therein.

10.   SECTION 17.1 "INDEMNITY AND INSURANCE". Section 17.1(a) of the
      Collaboration Agreement shall be amended by adding a reference to a "; or
      " after clause (ii) therein and inserting the following new clause (iii):
      "(iii) notwithstanding anything to the contrary in this Agreement, the
      Development or Commercialization of a VEGF Product in Japan under this
      Agreement, except to the extent that Damages arise out of the negligence,
      recklessness, bad faith or intentional wrongful acts, or omissions
      committed by Regeneron or its Affiliates."

11.   SCHEDULE I "QUARTERLY TRUE-UP". Schedule 1 of the Collaboration Agreement
      shall be deleted in its entirety and replaced with Schedule 1 attached to
      this Third Amendment, which is marked to reflect changes.

12.   SCHEDULE 1A "JAPAN TRUE-UP". The Collaboration Agreement shall be amended
      by adding a new Schedule 1A in the form attached to this Third Amendment.

13.   UP-FRONT PAYMENT. In consideration for Regeneron's agreement to enter into
      this Third Amendment and extend the Territory to include Japan on the
      terms set forth herein, Aventis shall pay to Regeneron, on or before
      January 10, 2006, a non-refundable, non-creditable payment of Twenty-Five
      Million US Dollars (US$25,000,000.00) (which shall not be reduced by any
      withholding or similar taxes).

14.   SCHEDULE 2 "MILESTONE PAYMENTS". Schedule 2 of the Collaboration Agreement
      shall be amended by adding the milestones and milestone payments set forth
      in Schedule 2 attached to this Third Amendment.

15.   SCHEDULE 15.3(c) "JAPAN PATENT APPLICATIONS". Schedule 15.3(c) of the
      Collaboration Agreement shall be amended by adding the Regeneron Patent
      Applications set forth in Schedule 15.3(c) attached to this Third
      Amendment.

16.   COMMERCIALIZATION. It is agreed that Regeneron shall not Co-Promote VEGF
      Products in Japan. However, notwithstanding anything to the contrary in
      the Collaboration Agreement, the Parties shall establish a Joint Country
      Commercialization Sub-Committee in Japan, which shall have the
      responsibilities set forth in Section 3.9(b). For the purpose of clarity,
      unless specifically delineated, Section 3.9(b) shall not be interpreted to
      include the responsibilities set forth in Section 3.9(a); either with
      respect to Joint Country Commercialization Sub-Committee in Japan or with
      respect to any Joint Country Commercialization Sub-Committee in each Rest
      of World Country. However, nothing in the preceding sentence shall limit
      or restrict any responsibilities included in sections of the Collaboration
      Agreement other than 3.9(b).

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17.   JAPAN CO-DEVELOPMENT PLAN. The Parties acknowledge that finalization of a
      plan for Development of the VEGF Products in Japan (the "Japan Devel