AMENDMENT TO THE VIRACEPT (Nelfinavir Mesylate) LICENSE AGREEMENT


     This Amendment  ("Amendment") to the VIRACEPT (Nelfinavir Mesylate) License
Agreement  ("the  Agreement"),  effective  as of  this  1st  day  of  May,  1998
("Effective Date"), is between Agouron Pharmaceuticals, Inc., a corporation duly
organized  and  existing  under  the laws of the state of  California,  having a
principal  place of  business  at  10350  North  Torrey  Pines  Road,  La Jolla,
California,  United States of America  (hereinafter  referred to as  "Agouron"),
Japan Tobacco Inc., a corporation  duly organized and existing under the laws of
Japan,  having its principal  place of business at JT Building,  2-1,  Toranomon
2-chome,  Minato-ku,  Tokyo,  Japan  (hereinafter  referred  to  as  "JT"),  and
F. Hoffmann-La  Roche Ltd, a corporation  duly  organized and existing under the
laws of Switzerland,  having its principal  place of business at  CH-4002-Basel,
Switzerland (hereinafter referred to as "Roche"). Agouron, JT and Roche are each
sometimes  hereinafter  referred  to as a party  (collectively  "parties").  The
parties for good and valuable consideration hereby agree as follows:

                                 RECITALS

1.   Background

     1.01 All capitalized terms,  except as expressly  otherwise defined herein,
shall have the meanings set forth in the Agreement.

     1.02  Agouron,  JT and Roche entered into a Letter of Intent on January 17,
1997  and  the  VIRACEPT  (nelfinavir  mesylate)  License  Agreement  dated  for
reference purposes only June 30, 1997,  under which Agouron and JT granted,  and
Roche received, a license in the Licensed Territory to use, offer for sale, sell
and/or import Products in the Field under  applicable  Agouron/JT  Patent Rights
and  Development   Program  Patent  Rights  and  using   applicable   Agouron/JT
Technology, Roche Technology and Development Program Technology.

     1.03  Roche has  certain  capacities  to  manufacture  Compound  as well as
formulate  Product.  Roche  has  informed  Agouron  and  JT  of  its  desire  to
manufacture  Compound and formulate Product to be sold and/or distributed in the
Licensed    Territory   with   such   Roche    manufacturing   and   formulating
responsibilities to be phased-in over an agreed-to period of time.

     1.04 The parties,  in accordance  with the provisions of Section 4.04(f) of
the Agreement,  have  discussed in good faith an  arrangement  under which Roche
could be the  manufacturer  of Compound and the formulator of Product to be sold
and/or distributed in the Licensed Territory.

     1.05  Agouron and JT under  certain  conditions  are willing to grant Roche
certain rights to manufacture  Compound and formulate  Product to be sold and/or
distributed in the Licensed Territory.

     1.06     *



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     1.07      *







     1.08  To  effect  the  preceding  and  clarify  the  parties'   rights  and
obligations  under the  Agreement,  the parties  wish to amend the  Agreement as
provided below.

                              AMENDMENT

2.   Grant of Rights to Roche

     2.01     *








     2.02     *







     2.03     *





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     2.04 Except as otherwise specifically provided in the Agreement, *





















     2.05 All licenses granted Roche in this Amendment in a country shall become
*

     2.06 Roche shall not have the right to use *



 3.  Limitations

     3.01 Roche's rights to manufacture Compound and formulate Product shall *











     3.02     *




                                       3
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     (a)      *





     (b)      *



     (c)      *



































     (d)      *



                                       4
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     3.03     *



                                       5
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4.   Markup

     4.01 For the rights  granted  pursuant to the provisions of Paragraphs
     2.01-2.04, *















5.   License grant to Agouron and JT

     5.01 Roche grants Agouron and JT *







     5.02 For the rights granted pursuant to the provisions of Paragraph 5.01, *












     5.03     *


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6.   Exchange of Information

     6.01 Immediately after execution of this Amendment by the parties, and
     on an ongoing basis thereafter, *









7.   Supply obligations

     7.01 *









     7.02 *













     7.03 *


      (a)  *





      (b) *





                                       7
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     (c)  *





     (d)  *









     (e)  *












     (f)  *







     7.04 *



                                       8
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     7.05 *











8.  Schedule 2 of Agreement

     8.01 *















9.   Trademark/Labeling

     9.01 The labeling for any Product to be sold and/or distributed by Roche, *


                                       9
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10.  Remaining Agreement Terms

          10.01  Except as  expressly  amended  by the terms  contained  in this
     Amendment,  the provisions of the Agreement,  as previously amended,  shall
     remain in full force and effect.

          IN WITNESS  WHEREOF,  the parties  have caused  their duly  authorized
     representatives to enter into this Amendment to the VIRACEPT(TM)(Nelfinavir
     Mesylate) License Agreement, effective as of the Effective Date.





AGOURON  PHARMACEUTICALS, INC.         JAPAN TOBACCO INC.


By:  /s/ Gary Friedman                  By: /s/ Masakazu Kakei
Name:   Gary Friedman                   Name: Masakazu Kakei
Title:  Corp. Vice President            Title: Executive Director


By:/s/ R. Kent Snyder                   By: /s/ Tatsuya Yoneyama
Name: R. Kent Snyder                    Name: Tatsuya Yoneyama
Title: Sr. Vice President               Title: Vice President, Business Devel.,
                                               Pharmaceuticals Division
F. HOFFMANN-LA ROCHE LTD

By /s/ St. Arnold
Name: St. Arnold
Title: Vice Director

By: /s/ B. Scholl
Name: B. Scholl
Title: Vice Director






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                                   SCHEDULE 1



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                                      S1-1
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                                   SCHEDULE 2
                   ROCHE DEMAND SCHEDULE FOR VIRACEPT PRODUCT
*

                                      S2-1
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                                   SCHEDULE 2
                   ROCHE DEMAND SCHEDULE FOR VIRACEPT PRODUCT
*

                                      S2-2
<PAGE>
                                   SCHEDULE 2
                   ROCHE DEMAND SCHEDULE FOR VIRACEPT PRODUCT
*

                                      S2-3
<PAGE>
                                   SCHEDULE 2
                   ROCHE DEMAND SCHEDULE FOR VIRACEPT PRODUCT
*

                                   SCHEDULE 2
                   ROCHE DEMAND SCHEDULE FOR VIRACEPT PRODUCT
*

                                      S2-4
<PAGE>
                                   SCHEDULE 2
                   ROCHE DEMAND SCHEDULE FOR VIRACEPT PRODUCT
*

                                      S2-5
<PAGE>
                                  ATTACHMENT 1

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