Exhibit 10.259

      AMENDMENT NO. 2 TO AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT

          THIS AMENDMENT NO. 2 TO AMENDED AND RESTATED REGISTRATION RIGHTS
AGREEMENT (the "Agreement") is made on the 25th day of June, 2003, by and among
Ligand Pharmaceuticals Incorporated, a Delaware corporation (the "Company"), and
Elan International Services, Ltd., a Bermuda exempted company ("EIS").

                                    RECITALS

          WHEREAS, the Company, Elan Corporation, plc, a public limited company
organized under the laws of the Republic of Ireland ("Elan"), and EIS and
certain other holders of the Company's capital stock have previously entered
into that certain Amended and Restated Registration Rights Agreement dated June
29, 2000, including the addenda entered into through the date hereof as well as
that certain Amendment No. 1 to Amended and Restated Registration Rights
Agreement dated November 12, 2002 (collectively, the "Prior Agreement").

          WHEREAS, Section 2.6(b) of the Prior Agreement provides that any term
of the Prior Agreement may be amended with the written consent of the Company
and the holders of a majority of the Registrable Securities then outstanding (as
defined in the Prior Agreement).

          WHEREAS, the Company and EIS desire to amend certain terms of the
Prior Agreement as set forth in this Agreement.

                      THE PARTIES HEREBY AGREE AS FOLLOWS:

1. SECTION 1.2(D).

          The first sentence of paragraph (d) of Section 1.2 of the Prior
Agreement is hereby restated in its entirety as follows:

          "(d) In addition to the rights and obligations set forth in this
     Section 1.2, if any Holders holding in the aggregate at least 4,000,000
     shares of Registrable Securities making a request pursuant to this Section
     1.2 additionally request that such registration statement on Form S-3 be
     effected for an offering to be made on a delayed or continuous basis
     pursuant to Rule 415 under the Act covering all Registrable Securities
     owned by such Holders (a `Shelf Registration Statement'), the Company shall
     include such information in the written notice referred to in subsection
     1.2(a)."

2. EFFECT OF PRIOR AGREEMENT.

          Except as set forth herein, the Prior Agreement shall remain in full
force and effect.



3.       MISCELLANEOUS.

          3.1 SUCCESSORS AND ASSIGNS. The terms and conditions of this Agreement
shall inure to the benefit of and be binding upon the respective successors and
assigns of the parties. Nothing in this Agreement, express or implied, is
intended to confer upon any party, other than the parties hereto or their
respective successors and assigns, any rights, remedies, obligations or
liabilities under or by reason of this Agreement, except as expressly provided
in this Agreement.

          3.2 GOVERNING LAW. This Agreement shall be governed by and construed
under the laws of the State of California as applied to agreements among
California residents entered into and to be performed entirely within
California.

          3.3 COUNTERPARTS. This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

          3.4 TITLES AND SUBTITLES. The titles and subtitles used in this
Agreement are used for convenience only and are not to be considered in
construing or interpreting this Agreement.

             [THE REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK.]








                                      -2-





          IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first above written.

                          LIGAND PHARMACEUTICALS INCORPORATED



                          By:     /S/PAUL V. MAIER
                                 ----------------------------------------
                                 Paul V. Maier, Senior Vice President and
                                 Chief Financial Officer
                                 10275 Science Center Drive
                                 San Diego, California 92121









                            ELAN INTERNATIONAL SERVICES, LTD.



                            By:    /S/KEVIN INSLEY
                                   --------------------------------------
                                   Kevin Insley, President
                                   102 St. James Court
                                   Flatts, Smith Parish, Bermuda, FL04












                                   SCHEDULE A
                              SCHEDULE OF INVESTORS


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NAME                                             SHARES ISSUED
                                              
- -----------------------------------------------  --------------------

- -----------------------------------------------  --------------------
Elan International Services, Ltd.                5,835,771
- -----------------------------------------------  --------------------

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