FOURTH AMENDMENT TO PHS PATENT LICENSE AGREEMENT

Exhibit 10.1

L-354-98/4

FOURTH AMENDMENT TO PATENT LICENSE AGREEMENT

     Effective the date of signature of the last party to sign this fourth amendment to license L-354-98/0 (“ Fourth Amendment ”), the Public Health Service (“ PHS ”), through the Office of Technology Transfer of the National Institutes of Health, having its principal office at 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852, U.S.A., and Zonagen, Inc. (“ Licensee ”), a Delaware corporation, having its principal office at 2408 Timberloch Place, Suite B-4, The Woodlands, Texas 77280, agree as follows:

W H E R E A S:

      PHS and Licensee entered into a license agreement (L-354-98/0) on April 16, 1999 (hereinafter referred to as “ Agreement ”), which was amended June 25, 1999, August 7, 2000, and July 11, 2002.

     The Agreement by and between PHS and Licensee granted Licensee an exclusive license under the Licensed Patent Rights in the Licensed Territory to make and have made, to use and have used, to sell and have sold, to offer to sell, and to import Licensed Products in the Licensed Fields-of-Use and to practice and have practiced any Licensed Processes in the Licensed Field-of-Use .

     The Licensee and PHS now wish to amend the Agreement a fourth time to facilitate the development of Licensed Products under the Licensed Patent Rights .

NOW THEREFORE: