Document:

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                                                                  EXHIBIT 10.214

           FIFTEENTH ADDENDUM TO AMENDED REGISTRATION RIGHTS AGREEMENT

     This Fifteenth Addendum ("Addendum") to the Amended Registration Rights
Agreement dated June 24, 1994, as amended through the date hereof ("Registration
Rights Agreement") among Ligand Pharmaceuticals Incorporated (the "Company") and
the persons and entities listed on Exhibit A hereto (collectively, the "X-Ceptor
Investors and Founders") is effective as of October 6, 1999.

                                    RECITALS

     A. The Company has issued warrants to purchase an aggregate of 950,000
shares of the Company's Common Stock with an exercise price equal to $10.00 per
share (collectively, the "X-Ceptor Warrants") to the X-Ceptor Investors and
Founders.

     B. This Addendum serves to include any shares of the Company's Common Stock
issuable upon the exercise of the X-Ceptor Warrants within the definition of
"Registrable Securities" under the Registration Rights Agreement and to provide
that Schedule A to the Registration Rights Agreement shall be further updated to
include any such shares issued upon the exercise of the X-Ceptor Warrants, all
pursuant to Section 2.6(a) of the Registration Rights Agreement.

     NOW, THEREFORE, in consideration of the mutual promises and covenants set
forth in the Registration Rights Agreement, the parties agree as follows:

     1. Section 1.1, paragraph (f) of the Registration Rights Agreement is
hereby restated in its entirety as follows:

          "(f) The term "Registrable Securities" means (i) the Common Stock
     issuable or issued upon exercise of those warrants issued to certain
     Existing Investors and pursuant to which such Existing Investors were
     previously granted registration rights by the Company, (ii) the shares of
     Common Stock (or the shares of such other class of stock into which the
     Common Stock is converted) issuable upon conversion of those certain
     Unsecured Convertible Promissory Notes issued to American Home Products
     Corporation pursuant to the Stock and Note Purchase Agreement dated
     September 2, 1994, (iii) the 35,957 shares of Common Stock issuable or
     issued upon exercise of the Warrant issued to Genentech, Inc. in connection
     with the merger of L.G. Acquisition Corp., a wholly-owned subsidiary of the
     Company, with and into Glycomed Incorporated, which shares are reflected on
     Schedule A attached to the Fourth Addendum to this Agreement, (iv) the
     164,474 shares of Common Stock (or that number of shares of such other
     class of stock into which the Common Stock is converted) issued to S.R. One
     Limited pursuant to a Stock and Note Purchase Agreement dated February 3,
     1995 (the "Stock and Note Purchase Agreement"), which shares are reflected
     on Schedule A attached to the Eighth Addendum to this Agreement, and the
     shares of Common Stock (or the shares of such other class of stock into
     which the Common Stock is converted) issuable upon conversion of those
     certain Unsecured Convertible Promissory Notes dated October 30, 1997

<PAGE>

     (the "S.R. One Notes") issued pursuant to the Stock and Note Purchase
     Agreement (and upon such conversion of the S.R. One Notes, Schedule A shall
     be updated to include such shares), (v) the 274,423 shares of Common Stock
     (or that number of shares of such other class of stock into which the
     Common Stock is converted) issued to SmithKline Beecham plc pursuant to a
     Stock Purchase Agreement dated April 24, 1998 (the "SmithKline Stock
     Purchase Agreement"), which shares are reflected on Schedule A attached to
     the Ninth Addendum to this Agreement, and the shares of Common Stock (or
     the shares of such other class of stock into which the Common Stock is
     converted) issuable upon conversion of that certain Warrant (the "Warrant")
     issued pursuant to the SmithKline Stock Purchase Agreement (and upon such
     conversion of the Warrant, Schedule A shall be updated to include such
     shares), (vi) the 1,278,970 shares of Common Stock (or that number of
     shares of such other class of stock into which the Common Stock is
     converted) issued to Elan International Services, Ltd. pursuant to the
     Stock Purchase Agreement dated September 30, 1998, which shares are
     reflected on Schedule A attached to the Tenth Addendum to this Agreement,
     (vii) the 437,768 shares of Common Stock (or that number of shares of such
     other class of stock into which the Common Stock is converted) issued to
     Elan International Services, Ltd. pursuant to the Securities Purchase
     Agreement, dated November 6, 1998 (the "Elan Securities Purchase
     Agreement"), which shares are reflected on Schedule A attached to the
     Eleventh Addendum to this Agreement, (viii) the shares of Common Stock (or
     the shares of such other class of stock into which the Common Stock is
     converted) issuable upon conversion of the Zero Coupon Convertible Senior
     Notes due 2008 (the "Elan Notes") issued pursuant to the Elan Securities
     Purchase Agreement (and upon such conversion of the Elan Notes, Schedule A
     shall be updated to include such shares), (viii) the 429,185 shares of
     Common Stock (or the shares of such other class of stock into which the
     Common Stock is converted) issued to Elan Corporation, plc pursuant to the
     Development, License and Supply Agreement dated November 9, 1998 (the "Elan
     License Agreement"), which shares are reflected on Schedule A attached to
     the Eleventh Addendum to this Agreement, (ix) the shares of Common Stock
     that may be issued to Elan Corporation, plc pursuant to the Elan License
     Agreement (and upon each such issuance, Schedule A shall be updated to
     include such shares), (x) the shares of Common Stock (or the shares of such
     other class of stock into which the Common Stock is converted) issuable to
     Elan International Services, Ltd. upon exercise of that certain Warrant
     (the "EIS Warrant") dated August 4, 1999 (and upon such exercise of the EIS
     Warrant, Schedule A shall be updated to include such shares), (xi) the
     289,750 shares of Common Stock (or the shares of such other class of stock
     into which the Common Stock is converted) issued to Warner Lambert Company
     pursuant to the Purchase Agreement dated September 1, 1999, which shares
     are reflected on Schedule A attached to the Thirteenth Addendum to this
     Agreement, (xii) the 52,742 shares of Common Stock (or the shares of such
     other class of stock into which the Common Stock is converted) issued to
     EIS pursuant to the Stock Purchase Agreement dated September 30, 1999,
     which shares are reflected on Schedule A attached to the Fourteenth
     Addendum to this Agreement, (xiii) the shares of Common Stock (or

                                       2

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     the shares of such other class of stock into which the Common Stock is
     converted) issuable upon exercise of those certain Series X Warrants dated
     [October 6, 1999] (the "X-Ceptor Warrants") (and upon any such exercise of
     the X-Ceptor Warrants, Schedule A shall be updated to include such shares),
     and (xiv) any Common Stock of the Company issued as (or issuable upon the
     conversion or exercise of any warrant, right or other security which is
     issued as) a dividend or other distribution with respect to, or in exchange
     for or in replacement of the shares referenced in (i), (ii), (iii), (iv),
     (v), (vi), (vii), (viii), (ix), (x), (xi), (xii) and (xiii) above,
     excluding in all cases, however, any Registrable Securities sold by a
     person in a transaction in which rights under this Agreement are not
     assigned."

     2. Schedule A of the Registration Rights Agreement is hereby restated in
its entirety as attached to this Addendum.

     3. This Addendum may be executed in one or more counterparts.

     4. This Addendum shall be binding upon the Company, each of the X-Ceptor
Investors and Founders, each holder of Registrable Securities and each future
holder of Registrable Securities pursuant to Section 2.6(a) of the Registration
Rights Agreement.

                [REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK]

                                       3
<PAGE>

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

LIGAND PHARMACEUTICALS INCORPORATED

By:      /s/William L. Respess

Its:     Senior Vice President
         General Counsel, Government Affairs

X-CEPTOR INVESTORS AND FOUNDERS:

Domain Partners IV, L.P.

By:      One Palmer Square Associates IV, L.L.C.,
         General Partner

By:      /s/Kathleen Schoemaker

Its:     Managing Member

DP IV Associates, L.P.

By:      One Palmer Square Associates IV, L.L.C.,
         General Partner

By:      /s/Kathleen Schoemaker

Its:     Managing Member

                      [SIGNATURE PAGE TO FIFTEENTH ADDENDUM
                    TO AMENDED REGISTRATION RIGHTS AGREEMENT]

<PAGE>

FARALLON CAPITAL PARTNERS, L.P.
FARALLON CAPITAL INSTITUTIONAL
         PARTNERS, L.P.
FARALLON CAPITAL INSTITUTIONAL
         PARTNERS II, L.P.
FARALLON CAPITAL INSTITUTIONAL
         PARTNERS III, L.P.
RR CAPITAL PARTNERS, L.P.

By:      Farallon Partners, L.L.C.,
         its General Partner

By:      /s/David Cohen

Its:

TechAMP International, L.P.

By:      AMP&A Management, LLC,
         General Partner

By:      /s/ A.M. Papas
Its:         Manager

/s/ Kevin Kinsella
----------------------
Kevin Kinsella

/s/Ronald Evans
----------------------
Ronald Evans

/s/Bert O'Malley
----------------------
Bert O'Malley

/s/David Mangelsdorf
----------------------
David Mangelsdorf

                      [SIGNATURE PAGE TO FIFTEENTH ADDENDUM
                    TO AMENDED REGISTRATION RIGHTS AGREEMENT]

                                       5

<PAGE>

/s/Richard Heyman
----------------------
Richard Heyman

/s/Robert Giargiari
----------------------
Robert Giargiari

/s/Ming Wei Wang
----------------------
Ming Wei Wang

GIMV N.V.

By:      /s/ illegible                     /s/ illegible
----------------------                     ----------------------
Its:     Vice President                    Vice President

Sofinov Societe Financiere D'Innovation, Inc.

By:      /s/Jean-Chirtophe Denondin
-------------------------------------
Its:     Vice President

By:      /s/Ginette Depelteau
-------------------------------------
Its:     Secretary

                      [SIGNATURE PAGE TO FIFTEENTH ADDENDUM
                    TO AMENDED REGISTRATION RIGHTS AGREEMENT]

                                       6

<PAGE>

                                   SCHEDULE A

                                       to
                              Fifteenth Addendum to
                      Amended Registration Rights Agreement
<TABLE>
<CAPTION>
--------------------------------------------------------- ---------------------
                                                                 Shares
Name                                                             Issued
--------------------------------------------------------- ---------------------
<S>                                                                <C>
American Home Products Corporation                                  374,626

American Home Products Corporation                                  374,626

American Home Products Corporation                                  249,749

American Home Products Corporation                                  124,875

Aspen Venture Partners, L.P.                                          2,659

Domain Partners IV, L.P.                                            _______

DP IV Associates, L.P.                                              _______

Elan Corporation, plc                                               429,185

Elan International Services, Ltd.                                 1,769,480

Enterprise Partners                                                   3,745

Ronald Evans                                                        _______

Farallon Capital Partners, L.P.                                     _______

Farallon Capital Institutional Partners, L.P.                       _______

Farallon Capital Institutional Partners II, L.P.                    _______

Farallon Capital Institutional Partners III, L.P.                   _______

GIMV N.V.                                                           _______

Genentech, Inc.                                                      35,957

Robert Giargiari                                                    _______

Richard Heyman                                                      _______

Kevin Kinsella                                                      _______

                                      A-1

<PAGE>

Kleiner Perkins Caufield & Byers                                      7,688

ML Venture Partners II, L.P.                                          2,417

David Mangelsdorf                                                   _______

Bert O'Malley                                                       _______

RR Capital Partners, L.P.                                           _______

S.R. One, Limited                                                   164,474

SmithKline Beecham                                                  274,423

Sofinov Societe Financiere D'Innovation                             _______

TechAMP International, L.P.                                         _______

Venrock Associates                                                    3,441

Venrock Associates II, L.P.                                           1,540

Ming Wei Wang                                                       _______

Warner Lambert Company                                              289,750

Windsor Venture Lease Partners Ltd., Inc.                               283

         Total:                                                   4,108,918
--------------------------------------------------------- ---------------------

                                       2

</TABLE><PAGE>

                                                                  EXHIBIT 10.215

           SIXTEENTH ADDENDUM TO AMENDED REGISTRATION RIGHTS AGREEMENT

     This Sixteenth Addendum ("Addendum") to the Amended Registration Rights
Agreement dated June 24, 1994, as amended through the date hereof ("Registration
Rights Agreement") between Ligand Pharmaceuticals Incorporated (the "Company")
and Elan International Services, Ltd. ("EIS") is effective as of December 31,
1999.

                                    RECITALS

     A. The Company has issued 188,572 shares of the Company's Common Stock (the
"Incentive Shares") to EIS pursuant to the terms of that certain Incentive
Agreement dated December 31, 1999 among the Company, EIS and Monksland Holdings,
B.V.

     B. This Addendum serves to include the EIS Shares within the definition of
"Registrable Securities" under the Registration Rights Agreement pursuant to
Section 2.6(a) of the Registration Rights Agreement.

     NOW, THEREFORE, in consideration of the mutual promises and covenants set
forth in the Registration Rights Agreement, the parties agree as follows:

     1. Section 1.1, paragraph (f) of the Registration Rights Agreement is
hereby restated in its entirety as follows:

          "(f) The term "Registrable Securities" means (i) the Common Stock
     issuable or issued upon exercise of those warrants issued to certain
     Existing Investors and pursuant to which such Existing Investors were
     previously granted registration rights by the Company, (ii) the shares of
     Common Stock (or the shares of such other class of stock into which the
     Common Stock is converted) issuable upon conversion of those certain
     Unsecured Convertible Promissory Notes issued to American Home Products
     Corporation pursuant to the Stock and Note Purchase Agreement dated
     September 2, 1994, (iii) the 35,957 shares of Common Stock issuable or
     issued upon exercise of the Warrant issued to Genentech, Inc. in connection
     with the merger of L.G. Acquisition Corp., a wholly-owned subsidiary of the
     Company, with and into Glycomed Incorporated, which shares are reflected on
     Schedule A attached to the Fourth Addendum to this Agreement, (iv) the
     164,474 shares of Common Stock (or that number of shares of such other
     class of stock into which the Common Stock is converted) issued to S.R. One
     Limited pursuant to a Stock and Note Purchase Agreement dated February 3,
     1995 (the "Stock and Note Purchase Agreement"), which shares are reflected
     on Schedule A attached to the Eighth Addendum to this Agreement, and the
     shares of Common Stock (or the shares of such other class of stock into
     which the Common Stock is converted) issuable upon conversion of those
     certain Unsecured Convertible Promissory Notes dated October 30, 1997 (the
     "S.R. One Notes") issued pursuant to the Stock and Note Purchase Agreement
     (and upon such conversion of the S.R. One Notes, Schedule A shall be
     updated to include such shares), (v) the 274,423 shares of Common Stock (or
     that number of shares of such other class of stock into which the Common
     Stock is

<PAGE>

     converted) issued to SmithKline Beecham plc pursuant to a Stock
     Purchase Agreement dated April 24, 1998 (the "SmithKline Stock Purchase
     Agreement"), which shares are reflected on Schedule A attached to the Ninth
     Addendum to this Agreement, and the shares of Common Stock (or the shares
     of such other class of stock into which the Common Stock is converted)
     issuable upon conversion of that certain Warrant (the "Warrant") issued
     pursuant to the SmithKline Stock Purchase Agreement (and upon such
     conversion of the Warrant, Schedule A shall be updated to include such
     shares), (vi) the 1,278,970 shares of Common Stock (or that number of
     shares of such other class of stock into which the Common Stock is
     converted) issued to Elan International Services, Ltd. pursuant to the
     Stock Purchase Agreement dated September 30, 1998, which shares are
     reflected on Schedule A attached to the Tenth Addendum to this Agreement,
     (vii) the 437,768 shares of Common Stock (or that number of shares of such
     other class of stock into which the Common Stock is converted) issued to
     Elan International Services, Ltd. pursuant to the Securities Purchase
     Agreement, dated November 6, 1998 (the "Elan Securities Purchase
     Agreement"), which shares are reflected on Schedule A attached to the
     Eleventh Addendum to this Agreement, (viii) the shares of Common Stock (or
     the shares of such other class of stock into which the Common Stock is
     converted) issuable upon conversion of the Zero Coupon Convertible Senior
     Notes due 2008 (the "Elan Notes") issued pursuant to the Elan Securities
     Purchase Agreement (and upon such conversion of the Elan Notes, Schedule A
     shall be updated to include such shares), (viii) the 429,185 shares of
     Common Stock (or the shares of such other class of stock into which the
     Common Stock is converted) issued to Elan Corporation, plc pursuant to the
     Development, License and Supply Agreement dated November 9, 1998 (the "Elan
     License Agreement"), which shares are reflected on Schedule A attached to
     the Eleventh Addendum to this Agreement, (ix) the shares of Common Stock
     that may be issued to Elan Corporation, plc pursuant to the Elan License
     Agreement (and upon each such issuance, Schedule A shall be updated to
     include such shares), (x) the shares of Common Stock (or the shares of such
     other class of stock into which the Common Stock is converted) issuable to
     Elan International Services, Ltd. upon exercise of that certain Warrant
     (the "EIS Warrant") dated August 4, 1999 (and upon such exercise of the EIS
     Warrant, Schedule A shall be updated to include such shares), (xi) the
     289,750 shares of Common Stock (or the shares of such other class of stock
     into which the Common Stock is converted) issued to Warner Lambert Company
     pursuant to the Purchase Agreement dated September 1, 1999, which shares
     are reflected on Schedule A attached to the Thirteenth Addendum to this
     Agreement, (xii) the 52,742 shares of Common Stock (or the shares of such
     other class of stock into which the Common Stock is converted) issued to
     EIS pursuant to the Stock Purchase Agreement dated September 30, 1999,
     which shares are reflected on Schedule A attached to the Fourteenth
     Addendum to this Agreement, (xiii) the shares of Common Stock (or the
     shares of such other class of stock into which the Common Stock is
     converted) issuable upon exercise of those certain Series X Warrants dated
     October 6, 1999 (the "X-Ceptor Warrants") (and upon any such exercise of
     the X-Ceptor Warrants, Schedule A shall be updated to include such shares),
     (xiv) the 188,572

                                       2
<PAGE>

     shares of Common Stock (or that number of shares of such other class
     of stock into which the Common Stock is converted) issued to Elan
     International Services, Ltd. pursuant to the Incentive Agreement, dated
     December 31, 1999, which shares are reflected on Schedule A attached to the
     Sixteenth Addendum to this Agreement, and (xv) any Common Stock of the
     Company issued as (or issuable upon the conversion or exercise of any
     warrant, right or other security which is issued as) a dividend or other
     distribution with respect to, or in exchange for or in replacement of the
     shares referenced in (i), (ii), (iii), (iv), (v), (vi), (vii), (viii),
     (ix), (x), (xi), (xii), (xiii) and (xiv) above, excluding in all cases,
     however, any Registrable Securities sold by a person in a transaction in
     which rights under this Agreement are not assigned."

     2. Schedule A of the Registration Rights Agreement is hereby restated in
its entirety as attached to this Addendum.

     3. This Addendum may be executed in one or more counterparts.

     4. This Addendum shall be binding upon the Company, EIS, each holder of
Registrable Securities and each future holder of Registrable Securities pursuant
to Section 2.6(a) of the Registration Rights Agreement.

                [REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK]

                                       3

<PAGE>

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

LIGAND PHARMACEUTICALS INCORPORATED

By:      /s/David E. Robinson

Its:

ELAN INTERNATIONAL SERVICES, LTD.

By:      /s/Kevin Insley

Its:

                      [SIGNATURE PAGE TO SIXTEENTH ADDENDUM
                    TO AMENDED REGISTRATION RIGHTS AGREEMENT]

<PAGE>

                                   SCHEDULE A

                                       to
                              Sixteenth Addendum to
                      Amended Registration Rights Agreement
<TABLE>
<CAPTION>
--------------------------------------------- ----------------------
                                                     Shares
Name                                                 Issued
--------------------------------------------- ----------------------
<S>                                                    <C>
American Home Products Corporation                      374,626

American Home Products Corporation                      374,626

American Home Products Corporation                      249,749

American Home Products Corporation                      124,875

Aspen Venture Partners, L.P.                              2,659

Elan Corporation, plc                                   429,185

Elan International Services, Ltd.                     4,202,512

Enterprise Partners                                       3,745

Genentech, Inc.                                          35,957

Kleiner Perkins Caufield & Byers                          7,688

ML Venture Partners II, L.P.                              2,417

S.R. One, Limited                                       164,474

SmithKline Beecham                                      274,423

Venrock Associates                                        3,441

Venrock Associates II, L.P.                               1,540

Warner Lambert Company                                  289,750

Windsor Venture Lease Partners Ltd., Inc.                   283

Total:                                                6,541,950
--------------------------------------------- ----------------------
</TABLE>

                                      A-1

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