Document:

Exhibit 10.221

          SEVENTEENTH ADDENDUM TO AMENDED REGISTRATION RIGHTS AGREEMENT

     This Seventeenth 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 March 1, 2000.

                                    RECITALS

     A. The Company has issued 98,580 shares of the Company's Common Stock (the
"Incentive Shares") to EIS pursuant to the terms of that certain Incentive
Agreement dated March 1, 2000 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, (xv) the 194,400 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 March 1,
         2000, which shares are reflected on SCHEDULE A attached to the
         Seventeenth Addendum to this Agreement, and (xvi) 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), (xiv) and (xv)
         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/PAUL V. MAIER

Its:     Senior VP & CFO

ELAN INTERNATIONAL SERVICES, LTD.

By:      /S/KEVIN INSLEY

Its:     President & CFO

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

<PAGE>

                                   SCHEDULE A

                                       to
                             Seventeenth 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.                            5,802,635

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:                                              8,142,073
---------------------------------------------------- ----------------------
</TABLE>

                                      A-1Exhibit 10.222

                               INCENTIVE AGREEMENT

          This incentive agreement (this "Agreement"), dated as of March 1,
2000, by and among Monksland Holdings, BV, a Dutch corporation ("Monksland"),
Elan International Services, Ltd., a Bermuda corporation ("EIS"), and Ligand
Pharmaceuticals Incorporated, a Delaware corporation ("Ligand").

                                    RECITALS

          WHEREAS, Ligand issued to Monksland on July 14, 1999 a Zero Coupon
Convertible Senior Note due 2008 at the issue price of $40,000,000 (the "Note")
under a Securities Purchase Agreement, dated as of November 6, 1998 (the
"Purchase Agreement") by and among Ligand, EIS and Elan Corporation, plc, a
public limited company organized under the laws of Ireland ("Elan"); and

          WHEREAS, Ligand has requested that Monksland convert a portion of the
Note to shares of Ligand common stock on or before March 1, 2000 and Monksland
concurrent with this Agreement is converting $20,000,000 of the issue price of
the Note plus $1,021,610 accrued interest to shares of Ligand common stock.

          NOW, THEREFORE, in consideration of the covenants and mutual
agreements set forth herein and for good and valuable consideration, the receipt
and sufficiency of which is hereby acknowledged, the parties hereto agree as
follows:

                                    AGREEMENT

          Section 1. Agreement to Convert

          In consideration for 98,580 shares of Ligand common stock (the
"Incentive Shares") to be issued by Ligand to EIS, an affiliate of Monksland, at
the request of Monksland, and subject to the terms and conditions of this
Agreement, Monksland hereby agrees to convert $20,000,000 of the issue price of
the Note plus $1,021,610 accrued interest under the terms and conditions of the
Note as of the date hereof. Also, at the request of Monksland, the shares to be
issued by Ligand upon conversion of such portion of and interest on the Note
shall be issued to EIS at the request of Monksland.

          Section 2. Representations & Warranties of Ligand

     (i) Except as otherwise set forth in the Schedule of Exceptions (as updated
on March 1, 2000) attached hereto as EXHIBIT A, the representations and
warranties of Ligand contained in the Purchase Agreement that are qualified by
Material Adverse Effect or materiality

<PAGE>

are true and correct in all respects and the representations and warranties of
Ligand contained in the Purchase Agreement that are not so qualified are true
and correct in all material respects, in each case, on and as of the date
hereof, except to the extent that such representations and warranties expressly
relate to an earlier date, and Ligand has performed all covenants and agreements
and satisfied all conditions on its part to be performed or satisfied under the
Purchase Agreement at or prior to the date hereof;

     (ii) As of the date hereof and since June 30, 1998, except as set forth in
the Additional SEC Reports, no event or development has occurred, and no
information has become known, that, individually or in the aggregate, has or
would be reasonably likely to have a Material Adverse Effect;

     (iii) The issuance of the Incentive Shares has not been enjoined
(temporarily or permanently);

     (iv) Each of the Purchase Agreement, the Registration Rights Agreement or
the New Registration Rights Agreement, as the case may be, the License Agreement
and, to the extent outstanding, the Securities, are, and after giving effect to
the issuance of the Incentive Shares, will be, valid and enforceable against
Ligand, except that (A) the enforcement thereof may be subject to (i)
bankruptcy, insolvency, reorganization, moratorium or other similar laws now or
hereafter in effect relating to creditors' rights generally and (ii) general
principles of equity and the discretion of the court before which any proceeding
therefor may be brought and (B) any rights to indemnity or contribution under
the Registration Rights Agreement or the New Registration Rights Agreement, as
the case may be, may be limited by federal and state securities laws and public
policy considerations, and no event that constitutes a breach of or a default
under (or an event which, with notice or passage of time or both would
constitute a default under) this Agreement, the Registration Rights Agreement or
the New Registration Rights Agreement, as the case may be, the License Agreement
or, to the extent outstanding, the Securities, by Ligand has occurred and is
continuing or, after giving effect to the issuance and sale of the Incentive
Shares, will have occurred and be continuing;

     (v) Under the Preferred Share Rights Agreement, dated as of September 13,
1996, between Ligand and Wells Fargo Bank, N.A., as amended (the "Rights
Agreement"), no event has occurred that has caused or will cause, and none of
the execution of this Agreement or the consummation of the transactions
contemplated hereby, including the issuance of the Incentive Shares, will cause,
rights issued thereunder to become exercisable or a "Distribution Date" to
occur, assuming compliance by Elan and its Affiliates with the provisions of
Section 14(c) of the Purchase Agreement; and

     (vi) The Registration Rights Agreement has been duly amended to include the
Incentive Shares within the definition of Registrable Securities thereunder.

          Section 3. Representations & Warranties of EIS

                                       2

<PAGE>

     (i) EIS acknowledges that the Incentive Shares will not be registered under
the Securities Act or any other applicable securities laws, will be issued in
transactions not requiring registration under the Securities Act and, unless so
registered, may not be offered, sold or otherwise transferred except in
compliance with the registration requirements of the Securities Act or any other
applicable securities law, pursuant to an exemption therefrom or in a
transaction not subject thereto and in each case in compliance with the
conditions for transfer set forth in paragraph (iii) below;

     (ii) EIS is outside the United States and is not a "U.S. person" (as such
term is defined in Regulation S);

     (iii) Until the expiration of the "one-year distribution compliance period"
within the meaning of Rule 903 of Regulation S, EIS will not sell or otherwise
transfer the Incentive Shares, except (i) to Ligand or its Subsidiaries, (ii)
pursuant to an effective registration statement which has been declared
effective under the Securities Act, (iii) in an offshore transaction in
accordance with Rule 904 of Regulation S or (iv) pursuant to any other available
exemption from the registration requirements of the Securities Act, including
Rule 144. After the expiration of such "one-year distribution compliance
period," EIS will not sell or otherwise transfer the Incentive Shares, except
pursuant to registration under the Securities Act or an available exemption
therefrom and, in any case, in accordance with the provisions of Regulation S
and applicable state securities laws;

     (iv) EIS understands that the certificates representing the Incentive
Shares will, so long as appropriate, bear the legend set forth in clause (vi) of
Section 4(a) of the Purchase Agreement;

     (v) EIS agrees that Ligand shall be entitled to make a notation on its
records and give instructions to any transfer agent of the Common Stock in order
to implement the restrictions on transfer set forth in the Purchase Agreement;

     (vi) EIS believes that it has received all information it considers
necessary or appropriate and has had an opportunity to ask questions and receive
answers from Ligand regarding the terms and conditions of the issuance and sale
of the Incentive Shares and the business, properties, prospects and financial
condition of Ligand; PROVIDED that this clause (vi) shall in no way limit or
modify the representations and warranties of Ligand set forth in Section 3 of
the Purchase Agreement or the right of EIS to rely thereon; it is a
sophisticated investor and that an investment in the Incentive Shares involves a
high degree of risk; and that the valuation price of the Incentive Shares may or
may not exceed the last publicly quoted per share "asked" price of the Common
Stock on the date hereof;

     (vii) EIS will be acquiring the Incentive Shares for its own account for
the purpose of investment and not (i) with a view to, or for sale in connection
with, any distribution thereof or (ii) for the account or on behalf of any "U.S.
person" (as such term is defined in Regulation S); EIS understands, acknowledges
and agrees that it must bear the economic risk of its investment

                                       3

<PAGE>

in the Incentive Shares for an indefinite period of time and that prior to any
offer or sale of such securities, Ligand may require, as a condition to
effecting a transfer of the Incentive Shares, an opinion of its counsel,
acceptable to Ligand, as to the registration or exemption therefrom under the
Securities Act;

     (viii) EIS was not formed specifically for the purpose of acquiring the
Incentive Shares under this Agreement;

     (ix) EIS nor any of its Affiliates has, directly or indirectly, within the
past 90 days nor will such persons until the expiration of the "one-year
distribution compliance period" within the meaning of Rule 903 of Regulation S
commencing from the later to occur of (i) the last Additional Closing occurring
on or before March 1, 2000 and (ii) the last License Share Issuance occurring on
or before the expiration or termination of the License Agreement directly or
indirectly, enter into any short selling of any equity security of Ligand
(including, without limitation, the Common Stock) or any hedging transaction
with respect to any equity security of Ligand, including, without limitation,
puts, calls, or other option transactions, option writing and equity swaps,
unless in compliance with the Securities Act;

     (x) EIS acknowledges that, until November 9, 2000, it shall not, directly
or indirectly, without the prior written consent of Ligand, Transfer the
Incentive Shares; PROVIDED that EIS may Transfer the Incentive Shares to any of
its Affiliates and any Affiliate of EIS may Transfer the Incentive Shares to EIS
or any Affiliate of EIS, subject to EIS's agreements set forth herein; and

     (xi) EIS acknowledges that the issuance of the Incentive Shares shall not
result in an adjustment to the Conversion Price of the Notes under Section 6(i)
thereof.

          Section 4. Acknowledgment of Ligand

          Ligand acknowledges notwithstanding anything in the Purchase
Agreement, the acquisition of the Incentive Shares by EIS, shall not be
violative of any standstill provision contained in the Purchase Agreement,
including Section 14(c), or otherwise applicable to EIS, and that the Incentive
Shares shall be afforded all of the rights and exceptions afforded the Shares
under such applicable provisions; provided that Ligand shall have no obligation
to amend the Rights Agreement with respect to the Incentive Shares.

          Section 5. Miscellaneous

     (i) APPLICABLE LAW. THE VALIDITY AND INTERPRETATION OF THIS AGREEMENT, AND
THE TERMS AND CONDITIONS SET FORTH HEREIN, SHALL BE GOVERNED BY AND CONSTRUED IN
ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK APPLICABLE TO CONTRACTS MADE
AND TO BE PERFORMED WHOLLY THEREIN, WITHOUT GIVING EFFECT TO ANY PROVISIONS
THEREOF RELATING TO CONFLICTS OF LAW.

                                       4

<PAGE>

     (ii) WAIVER. No failure or delay on the part of a party hereto in
exercising any right, power or remedy hereunder shall operate as a waiver
thereof; nor shall any single or partial exercise of any such right, power or
remedy preclude any other or further exercise thereof or the exercise of any
other right, power or remedy hereunder.

     (iii) 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.

     (iv) TERMS. Capitalized terms used but not otherwise defined herein shall
have the meanings assigned to them in the Purchase Agreement.

                                       5

<PAGE>

     IN WITNESS WHEREOF, this Agreement has been duly executed by the parties
hereto and delivered as of the date first written above.

                  MONKSLAND HOLDINGS, BV

                  By:      /S/ KEVIN INSLEY
                           --------------------
                           Name: KEVIN INSLEY
                           Title:AUTHORIZED SIGNATORY

                  ELAN INTERNATIONAL SERVICES, LTD.

                  By:      /S/ KEVIN INSLEY
                           --------------------
                           Name: KEVIN INSLEY
                           Title:PRESIDENT & CFO

                  LIGAND PHARMACEUTICALS INCORPORATED

                  By:      /S/ PAUL V. MAIER
                           --------------------
                           Name: PAUL V. MAIER
                           Title:SENIOR VP & CFO

                                        6

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