Document:

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                                                                  EXHIBIT 10.216

                                State of Delaware

                        Office of the Secretary of State

     I, EDWARD J. FREEL, SECRETARY OF STATE OF THE STATE OF DELAWARE, DO HEREBY
CERTIFY THE ATTACHED IS A TRUE AND CORRECT COPY OF THE CERTIFICATE OF AMENDMENT
OF "X-CEPTOR THERAPEUTICS, INC.", FILED IN THIS OFFICE ON THE FIRST DAY OF
OCTOBER, A.D. 1999, AT 4 O'CLOCK P.M.

     A FILED COPY OF THIS CERTIFICATE HAS BEEN FORWARDED TO THE NEW CASTLE
COUNTY RECORDER OF DEEDS.

                                  /s/ Edward J. Freel
                                  -----------------------------------
                 [SEAL]           Edward J. Freel, Secretary of State

3057193 8100                               AUTHENTICATION:     0008418

991418040                                  DATE:     10-05-99

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                           CERTIFICATE OF AMENDMENT OF
                AMENDED AND RESTATED CERTIFICATE OF INCORPORATION
                                       OF
                           X-CEPTOR THERAPEUTICS, INC.

              Kevin J. Kinsella and Michael O'Donnell certify that:

     1. They are the Chief Executive Officer and the Secretary, respectively, of
X-Ceptor Therapeutics, Inc., a Delaware Corporation (the "Corporation")
originally incorporated on June 16, 1999.

     2. Paragraph 7.4 (a)(i) of Schedule I of the Amended and Restated
Certificate of Incorporation is amended to read in its entirety as follows:

                  "(i) The fair market value of a share of Common Stock (the
"Fair Market Value") shall be determined in accordance with the following
formula:

                                            A = B/C

     Where: A = Fair Market Value per share of Common Stock

                    B = $61,400,000 less an amount equal to product of (i)
               $2.07432, multiplied by (ii) the excess, if any, of (A)
               18,900,000, over (B) the aggregate number of shares of Series B
               Preferred sold by the Company on the closing Date and within 120
               days of the closing Date (excluding any shares held by Ligand,
               its affiliates or any of their transferees) (such amount being
               the "Series B Shortfall") if the Exercise Date occurs at any time
               on or before the Third Anniversary, or $79,800,000 less an amount
               equal to the product of (i) $2.6959, multiplied by (ii) the
               Series B Shortfall if the Exercise Date occurs after the Third
               Anniversary

                    C = Number of shares of Common Stock outstanding on the
               Option Closing Date taking into account the automatic conversion
               of any shares of Preferred Stock pursuant to the company's
               Certificate of Incorporation immediately prior to the Option
               Closing Date (excluding any shares held by Ligand, its affiliates
               (in excess of an aggregate of 200,000 shares of Common Stock) or
               any of their transferees) and including all shares issuable upon
               conversion or exercise of options, warrants, convertible notes or
               other convertible or exercisable securities (collectively,
               "Convertible Securities")"

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     IN WITNESS WHEREOF, this Certificate of Amendment of the Amended and
Restated Certificate of Incorporation, which amends certain provisions of the
Amended and Restated Certificate of Incorporation of the Corporation, having
been duly adopted in accordance with Section 242 of the Delaware General
Corporation Law, has been duly executed by its Chief Executive Officer and
Secretary this 29th day of September, 1999.

                               /s/ Kevin J. Kinsella
                               --------------------------------
                               Kevin J. Kinsella, Chief
                               Executive Officer

                               /s/Michael J. O'Donnell
                               --------------------------------
                               Michael J. O'Donnell, Secretary

                                       -2-<PAGE>

                                                                  EXHIBIT 10.217

No.  X-1

NEITHER THIS WARRANT NOR ANY OF THE SECURITIES ISSUABLE HEREUNDER HAS BEEN
REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT BE OFFERED,
SOLD, TRANSFERRED, ASSIGNED OR HYPOTHECATED IN THE ABSENCE OF AN EFFECTIVE
REGISTRATION STATEMENT UNDER SAID ACT WITH RESPECT TO THE SECURITIES OR UNLESS
LIGAND PHARMACEUTICALS INCORPORATED RECEIVES AN OPINION OF COUNSEL FOR THE
HOLDER OF THIS WARRANT SATISFACTORY TO LIGAND PHARMACEUTICALS INCORPORATED,
STATING THAT SUCH OFFER, SALE, TRANSFER, ASSIGNMENT OR HYPOTHECATION IS EXEMPT
FROM THE REGISTRATION AND PROSPECTUS DELIVERY REQUIREMENTS OF SAID ACT.

THIS WARRANT IS VOID AFTER 5:00 P.M., SAN DIEGO TIME, ON AUGUST 3, 2006.

                       LIGAND PHARMACEUTICALS INCORPORATED

                              AMENDED AND RESTATED
                                SERIES X WARRANT
                               FOR THE PURCHASE OF
                          91,406 SHARES OF COMMON STOCK

     IN CONSIDERATION OF the payment by the initial holder hereof (the "Initial
Holder") to LIGAND PHARMACEUTICALS INCORPORATED, a Delaware corporation
("LIGAND"), of Three Hundred Eighty-Three Thousand Nine Hundred Five Dollars and
Twenty Cents ($383,905.20), LIGAND hereby certifies that

                        ELAN INTERNATIONAL SERVICES, LTD.

or any registered assignee of the Initial Holder (each of the Initial Holder and
any such registered assignee being hereinafter referred to as the "Holder") is
entitled, subject to the provisions of this Warrant, to purchase from LIGAND, at
any time or from time to time on or after the earlier of (i) August 4, 2000 (the
"Exercise Date") or (ii) the date which is ten (10) days prior to the
Acceleration Date (as hereinafter defined) and before 5:00 p.m. San Diego time,
on August 3, 2006 (the "Exercise Period"), Ninety-One Thousand Four Hundred Six
(91,406) fully paid and nonassessable shares of Common Stock, $.001 par value,
of LIGAND. The term "Common Stock" shall mean the aforementioned Common Stock of
LIGAND together with any other equity securities that may be issued by LIGAND in
connection therewith or in substitution therefor as provided herein. The
purchase price per share for such shares of Common Stock shall be equal to
$10.00 as appropriately adjusted pursuant to Section 9 and Section 10 hereof
(the "Exercise Price").

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     For purposes of this Warrant, (a) "Acceleration Event" means the occurrence
of any of the following events: (i) LIGAND shall, or shall agree to, merge or
consolidate with any other corporation as a result of which the stockholders of
LIGAND own less than a majority of the voting stock of the surviving corporation
immediately following such consolidation or merger; (ii) LIGAND shall, or shall
agree to, be acquired (by merger or otherwise) by any unaffiliated person
(including any individual, partnership, joint venture, corporation, trust or
group thereof); (iii) LIGAND shall, or shall agree to, sell, lease, transfer or
otherwise dispose of all or substantially all of its assets to any unaffiliated
person; or (iv) any "person" or "group" (within the meaning of Section 13(d) and
Section 14(d) of the Securities Exchange Act of 1934, as amended (the "Exchange
Act")), shall announce the commencement of a bona fide tender offer or exchange
offer in accordance with the rules and regulations of the Exchange Act to
purchase or acquire securities in LIGAND, such that after such purchase or
acquisition, the acquiror "beneficially owns" or would "beneficially own" (as
defined in Rule 13d-3 under the Exchange Act) securities of LIGAND representing
30% or more of the combined voting power of LIGAND's then outstanding securities
having power to vote in the election of directors; (b) "Acceleration Date" means
the first date upon which an Acceleration Event occurs, provided that, if
approval of the shareholders of LIGAND is required in connection with such
Acceleration Event, Acceleration Date means the date of such shareholder
approval; and (c) "Closing Price" means the closing price per share of the
Common Stock on the principal national securities exchange on which the Common
Stock is listed or admitted to trading or, if not listed or traded on any such
exchange, on the National Association of Securities Dealers Automated Quotation
System ("Nasdaq") National Market System ("Nasdaq National Market"), or if not
listed or traded on any such exchange or system, the average of the last bid and
offer price per share on the Nasdaq over-the-counter system or, if such
quotations are not available, the fair market value as reasonably determined by
the Board of Directors of LIGAND or any committee of such Board. Other
capitalized terms used herein but not defined herein shall have the meanings
given such terms in the Purchase Agreement.

     The number of shares of Common Stock to be received upon the exercise of
this Warrant and the Exercise Price are subject to adjustment from time to time
as hereinafter set forth. The shares of Common Stock deliverable upon such
exercise, as adjusted from time to time, are hereinafter sometimes referred to
as "Warrant Shares."

     1. Exercise of Warrant.

     (a) This Warrant may be exercised in whole or in increments of one hundred
(100) shares (unless the Warrant is exercisable for a lesser number of shares in
which case the Warrant may be exercised only in whole), at any time or from time
to time, during the Exercise Period by presentation and surrender thereof to
LIGAND, at its offices designated in Section 17 hereof, with the Purchase Form
attached hereto duly executed and accompanied by cash or a certified or official
bank check drawn to the order of "LIGAND PHARMACEUTICALS INCORPORATED" in the
amount of the Exercise Price multiplied by the number of Warrant Shares
specified in such form. If this Warrant should be exercised in part only, LIGAND
shall, upon surrender of this Warrant, execute and deliver a new Warrant
evidencing the rights of the Holder thereof to purchase the balance of the
Warrant Shares purchasable hereunder. Upon

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receipt by LIGAND during the Exercise Period of this Warrant and such
Purchase Form, in proper form for exercise, together with proper payment of the
Exercise Price, at such office, the Holder shall be deemed to be the holder of
record of the number of Warrant Shares specified in such form, provided,
however, that if the date of such receipt by LIGAND is a date on which the stock
transfer books of LIGAND are closed, such person shall be deemed to have become
the record holder of such shares on the next succeeding business day on which
the stock transfer books of LIGAND are open. LIGAND shall pay any and all
documentary, stamp or similar issue or transfer taxes payable in respect of the
issue or delivery of such Warrant Shares. Any new or substitute Warrant issued
under this Section 1 or any other provision of this Warrant shall be dated the
date of this Warrant.

     (b) Each certificate representing any Warrant Shares issued upon exercise
of this Warrant (unless such Warrant Shares have been registered pursuant to the
Twelfth Addendum to Registration Rights Agreement by and among LIGAND and the
other parties named therein, as amended from time to time (the "Rights
Agreement")) shall be endorsed with a legend in substantially the following
form:

     THE SECURITIES EVIDENCED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER
THE SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT BE OFFERED, SOLD,
TRANSFERRED, ASSIGNED OR HYPOTHECATED IN THE ABSENCE OF AN EFFECTIVE
REGISTRATION STATEMENT UNDER SAID ACT WITH RESPECT TO THE SECURITIES OR UNLESS
LIGAND PHARMACEUTICALS INCORPORATED RECEIVES AN OPINION OF COUNSEL FOR THE
HOLDER OF SUCH SECURITIES SATISFACTORY TO LIGAND PHARMACEUTICALS, INCORPORATED
STATING THAT SUCH OFFER, SALE, TRANSFER, ASSIGNMENT OR HYPOTHECATION IS EXEMPT
FROM THE REGISTRATION AND PROSPECTUS DELIVERY REQUIREMENTS OF SAID ACT.

     2. Right To Exchange Warrant.

     (a) The Holder shall have the right to require LIGAND to exchange this
Warrant (the "Exchange Right") (subject to the availability of such Exchange
Right pursuant to the Securities Act of 1933, as amended (the "Act") and the
rules and regulations thereunder), in whole or in increments of one hundred
(100) shares (unless the Warrant is exercisable for a lesser number of shares in
which case the Warrant may be exchanged only in whole), at any time during the
Exercise Period, for shares of Common Stock as provided for in this Section 2.
Upon exercise of the Exchange Right, LIGAND shall deliver to the Holder (without
payment by the Holder of any Exercise Price) the number of shares of Common
Stock calculated as follows:

                                    X = Y(A-B)
                                            A

Where: X = the number of shares of Common Stock to be issued to the Holder upon
the exercise of the Exchange Right.

                                       3

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          Y = the number of Warrant Shares for which exchange has been
requested.

          A = the Closing Price for the trading day immediately preceding the
receipt of the Warrant and the Purchase Form as provided in Section 2(b).

          B = the Exercise Price for the Warrant Shares in effect immediately
prior to the exercise of the Exchange Right.

     (b) The Exchange Right may be exercised by the Holder, at any time or from
time to time, on any Business Day by delivering this Warrant and the Purchase
Form attached hereto to LIGAND at its offices designated in Section 17 hereof,
and specifying that the Holder is exercising the Exchange Right to acquire the
number of shares of Common Stock then issuable upon such exchange pursuant to
Section 2(a). If this Warrant should be exchanged in part only, LIGAND shall,
upon surrender of this Warrant, execute and deliver a new Warrant evidencing the
rights of the Holder thereof to purchase the balance of the Warrant Shares
purchasable hereunder. Upon receipt by LIGAND during the Exercise Period of this
Warrant and such Purchase Form, in proper form for exercise, at such office, the
Holder shall be deemed to be the holder of record of the number of Warrant
Shares issuable upon exercise of the Exchange Right as calculated pursuant to
Section 2(a), provided, however, that if the date of such receipt by LIGAND is a
date on which the stock transfer books of LIGAND are closed, such person shall
be deemed to have become the record holder of such shares on the next succeeding
Business Day on which the stock transfer books of LIGAND are open. LIGAND shall
pay any and all documentary, stamp or similar issue or transfer taxes payable in
respect of the issue or delivery of such Warrant Shares.

     (c) No fractional shares of Common Stock shall be issued to the Holder in
connection with the exchange of this Warrant pursuant to this Section 2. Instead
of any fractional shares of Common Stock that would otherwise be issuable to the
Holder, LIGAND shall pay to the Holder a cash adjustment in respect of such
fractional interest in an amount equal to that fractional interest multiplied by
the Closing Price for the trading day immediately preceding the receipt of this
Warrant and the Purchase Form as provided in Section 2(b).

     3. Warrant Register. This Warrant shall be registered in a register (the
"Warrant Register") to be maintained by LIGAND at its offices in the name of the
record holder set forth above. LIGAND may deem and treat the registered Holder
of this Warrant as the absolute owner thereof (notwithstanding any notation of
ownership or other writing hereon made by anyone), for the purpose of any
exercise hereof or any distribution to the Holder hereof and for all other
purposes, and LIGAND shall not be affected by any notice to the contrary.

     4. Reservation of Shares. LIGAND hereby agrees that at all times there
shall be reserved for issuance and delivery upon exercise of this Warrant all
shares of its Common Stock or other shares of capital stock of LIGAND from time
to time issuable upon exercise of this Warrant. All such shares shall be duly
authorized and when issued upon such exercise shall be validly issued, fully
paid and nonassessable, free and clear of all liens, security interests, charges
and other

                                       4

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encumbrances or restrictions on sale granted by LIGAND and free and clear
of all preemptive rights granted by LIGAND.

     Before taking any action that would cause a reduction pursuant to the
provisions hereof of the Exercise Price below the then par value (if any) of the
Warrant Shares issuable upon exercise of this Warrant, LIGAND shall take any
corporate action that may, in the opinion of its counsel, be necessary in order
that LIGAND may validly and legally issue fully paid and nonassessable Warrant
Shares at the initial Exercise Price as so adjusted.

     5. Transfer of the Warrant and Warrant Shares.

     (a) Neither this Warrant nor any of the Warrant Shares nor any interest in
either may be offered, sold, assigned, pledged, hypothecated, encumbered or in
any other manner transferred or disposed of, in whole or in part, except in
accordance with Section 6 hereof and in compliance with applicable United States
federal and state securities laws, the securities laws of other applicable
jurisdictions, and the terms and conditions of the Purchase Agreement and
hereof. Except as provided below, each Warrant shall bear the following legend:

     NEITHER THIS WARRANT NOR ANY OF THE SECURITIES ISSUABLE HEREUNDER HAS BEEN
REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT BE OFFERED,
SOLD, TRANSFERRED, ASSIGNED OR HYPOTHECATED IN THE ABSENCE OF AN EFFECTIVE
REGISTRATION STATEMENT UNDER SAID ACT WITH RESPECT TO THE SECURITIES OR UNLESS
LIGAND PHARMACEUTICALS INCORPORATED RECEIVES AN OPINION OF COUNSEL FOR THE
HOLDER OF THIS WARRANT SATISFACTORY TO LIGAND PHARMACEUTICALS INCORPORATED,
STATING THAT SUCH OFFER, SALE, TRANSFER, ASSIGNMENT OR HYPOTHECATION IS EXEMPT
FROM THE REGISTRATION AND PROSPECTUS DELIVERY REQUIREMENTS OF SAID ACT.

Notwithstanding the foregoing, the Holder may require LIGAND to issue a Warrant
without the legend set forth above in substitution for a legended Warrant if
either (i) the sale, transfer or other disposition of such Warrant is registered
under the Act and applicable securities laws or (ii) the Holder has received an
opinion of counsel satisfactory to LIGAND that such registration is not required
with respect to such Warrant. The provisions of this Section 5 shall be binding
upon all subsequent holders of this Warrant. No transfer or assignment of this
Warrant may be made except in accordance with the provisions of Section 6
hereof.

     (b) The original offering and sale of this Warrant was intended to be
exempt from registration under the Act by virtue of Section 4(2) of the Act and
the provisions of Regulation D promulgated under the Act. LIGAND is not under
any obligation to register this Warrant or the Warrant Shares other than as
provided in the Rights Agreement.

     (c) This Warrant and the Warrant Shares may not be sold, transferred or
otherwise disposed of unless (i) the sale, transfer or other disposition of this
Warrant or the Warrant Shares, as the case may be, are registered under the Act
and applicable securities laws or (ii) in the opinion of counsel satisfactory to
LIGAND, an exemption from the registration

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requirements of the Act and such securities laws is available, and in the
absence of an effective registration statement covering such securities or an
available exemption from registration under the Act, this Warrant and the
Warrant Shares must be held indefinitely.

     6. Exchange, Transfer or Assignment of Warrant.

          (a) Subject to the provisions of Section 5 hereof, this Warrant may be
assigned or transferred, at the option of the Holder but only to an accredited
investor within the meaning of Rule 501(a) of Regulation D, upon surrender of
this Warrant to LIGAND, with the Warrant Assignment Form attached hereto duly
executed and information in such form as reasonably requested by LIGAND
substantiating such assignee's status as an accredited investor accompanied by
funds sufficient to pay any transfer tax. LIGAND shall execute and deliver a new
Warrant in the name of the assignee named in such instrument of assignment, and
this Warrant shall promptly be canceled. LIGAND shall not be required to issue
any Warrant to any assignee other than an accredited investor.

          (b) This Warrant may not be divided or exchanged for other Warrants of
denominations exercisable for less than one hundred (100) Warrant Shares.

          (c) Any transfer or assignment of this Warrant shall be without charge
(other than the cost of any transfer tax) to the Holder and any new Warrant
issued pursuant to this Section 6 shall be dated the date hereof. The term
"Warrant" as used herein includes any new Warrant issued pursuant to this
Section or Sections 1, 2, 5 or 7 hereof.

     7. Lost, Mutilated or Missing Warrant. Upon receipt by LIGAND of evidence
satisfactory to it of the loss, theft, destruction or mutilation of this
Warrant, and (in the case of loss, theft or destruction) of satisfactory
indemnification, and upon surrender and cancellation of this Warrant, if
mutilated, LIGAND shall authenticate and deliver a new Warrant of like tenor and
date.

     8. Rights of the Holder. The Holder shall not, by virtue hereof, be
entitled to any rights of a shareholder in LIGAND, either at law or in equity,
and the rights of the Holder are limited to those expressed in this Warrant.

     9. Anti-Dilution Provision. The Exercise Price and the number of Warrant
Shares that may be purchased upon the exercise hereof shall be subject to change
or adjustment as follows:

          (a) Stock Dividends and Stock Splits. If at any time after the date
hereof and before 5:00 p.m., San Diego time, on the last day of the Exercise
Period, (i) LIGAND shall fix a record date for the issuance of any stock
dividend payable in shares of Common Stock or (ii) the number of shares of
Common Stock shall have been increased by a subdivision or split-up of shares of
Common Stock, then, on the record date fixed for the determination of holders of
Common Stock entitled to receive such dividend or immediately after the
effective date of such subdivision or split-up, as the case may be, the number
of shares to be delivered upon exercise of this Warrant shall be appropriately
increased so that the Holder thereafter shall be entitled to receive the number
of shares of Common Stock that the Holder would have owned immediately

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following such action had this Warrant been exercised immediately prior thereto,
and the Exercise Price shall be appropriately decreased.

          (b) Combination of Stock. If at any time after the date hereof and
before 5:00 p.m., San Diego time, on the last day of the Exercise Period, the
number of shares of Common Stock outstanding shall have been decreased by a
combination of the outstanding shares of Common Stock, then, immediately after
the effective date of such combination, the number of shares of Common Stock to
be delivered upon exercise of this Warrant shall be appropriately decreased so
that the Holder thereafter shall be entitled to receive the number of shares of
Common Stock that the Holder would have owned immediately following such action
had this Warrant been exercised immediately prior thereto, and the Exercise
Price shall be appropriately increased.

          (c) Reorganization, etc. If at any time after the date hereof and
before 5:00 p.m., San Diego time, on the last day of the Exercise Period, any
capital reorganization of LIGAND, or any reclassification of the Common Stock,
or any consolidation of LIGAND with or merger of LIGAND with or into any other
person or entity or any sale, lease or other transfer of all or substantially
all of the assets of LIGAND to any other person or entity shall be effected in
such a way that upon consummation of such transaction, the holders of Common
Stock shall be entitled to receive stock, securities or assets with respect to
or in exchange for Common Stock, then, upon exercise of this Warrant in
accordance with Section 1 hereof, the Holder shall have the right to receive the
kind and amount of stock, securities or assets receivable upon such
reorganization, reclassification, consolidation, merger or sale, lease or other
transfer by a holder of the number of shares of Common Stock that the Holder
would have been entitled to receive upon exercise of this Warrant pursuant to
Section 1 hereof had this Warrant been exercised immediately before such
reorganization, reclassification, consolidation, merger or sale, lease or other
transfer, subject to adjustments that shall be as nearly equivalent as may be
practicable to the adjustments provided for in this Section 9.

          (d) Rights Offering. If LIGAND at any time after the date of issuance
hereof and before 5:00 p.m., San Diego time, on the last day of the Exercise
Period, shall issue or sell or fix a record date for the issuance of rights,
options, warrants or convertible or exchangeable securities to all holders of
Common Stock entitling them to subscribe for or purchase Common Stock or
securities convertible into Common Stock, in any such case, at a price per share
(or having a conversion price per share) that, together with the value (if for
consideration other than cash, as determined in good faith by the Board of
Directors of LIGAND) of any consideration paid for any such rights, options,
warrants, or convertible or exchangeable securities, is greater than the
Exercise Price and less than the Closing Price on the date of such issuance or
sale or on such a record date then, immediately after the date of such issuance
or sale, or on such record date, the number of shares to be delivered upon
exercise of this Warrant shall be appropriately increased so that the Holder
thereafter, during the Exercise Period, will be entitled to receive the number
of shares of Common Stock determined by multiplying the number of shares the
Holder would have been entitled to receive immediately before the date of such
issuance or sale or such record date by a fraction, the denominator of which
will be the number shares of Common Stock outstanding on such date plus the
number of shares of Common Stock that the aggregate offering price of the total
number of shares so offered for subscription or purchase (or the aggregate

                                       7

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initial conversion price of the convertible securities so offered) would
purchase at such Closing Price, and the numerator of which will be the number of
shares of Common Stock outstanding on such date plus the number of shares of
Common Stock offered for subscription or purchase (or into which the convertible
securities so offered are initially convertible), and the exercise price shall
be appropriately adjusted. The time of occurrence of an event giving rise to an
adjustment pursuant to this Section 9(d) shall, in the case of a dividend, be
the record date and shall, in the case of an issuance or sale, be the date of
such issuance or sale.

          (e) Special Dividends. If LIGAND at any time after the date of
issuance of this Warrant and before 5:00 p.m., San Diego time, on the last day
of the Exercise Period shall distribute to all holders of its Common Stock cash,
debt securities or other assets (including evidences of indebtedness), except to
the extent paid out of retained or accumulated earnings, the Exercise Price will
be adjusted so that immediately following the date fixed by LIGAND as the record
date in respect of such issuance it shall equal the price determined by
multiplying the Exercise Price in effect immediately prior to the close of
business on the record date for the determination of the shareholders entitled
to receive such dividend by a fraction, the numerator of which shall be the
Closing Price on such record date less the then fair market value as determined
by the Board of Directors of LIGAND, whose determination shall be conclusive, of
the portion of the securities or assets distributed applicable to one share of
Common Stock and the denominator of which shall be such Closing Price. Such
adjustment shall become effective on such record date.

          (f) No Adjustments to Exercise Price. No adjustment in the Exercise
Price in accordance with the provisions of subsections 10(a), (b), (c), (d) or
(e) above need be made if such adjustment would amount to a change in such
Exercise Price of less than $0.01; provided, however, that the amount by which
any adjustment is not made by reason of the provisions of this section shall be
carried forward and taken into account at the time of any subsequent adjustment
in the Exercise Price.

          (g) Fractional Shares. No fractional shares of Common Stock or scrip
shall be issued to the Holder in connection with the exercise of this Warrant.
Instead of any fractional shares of Common Stock that would otherwise be
issuable to the Holder, LIGAND shall pay to the Holder a cash adjustment in
respect of such fractional interest in an amount equal to that fractional
interest multiplied by the Closing Price on the date of exercise.

          (h) Definition of Common Stock. For purposes of this Section 9, the
term "Common Stock" shall mean (i) the class of stock designated as the Common
Stock of LIGAND on the date hereof, or (ii) any other classes of stock resulting
from successive changes or reclassifications of such shares consisting solely of
changes in par value or from par value to no par value, or from no par value to
par value.

     10. Notices of Certain Events.

     (a) If at any time after the date hereof and before the expiration of the
Exercise Period:

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          (i) LIGAND authorizes the issuance to all holders of its Common Stock
of rights, options or warrants to subscribe for or purchase shares of its Common
Stock or any other subscription rights, options or warrants; or

          (ii) LIGAND authorizes the distribution to all holders of its Common
Stock of evidences of its indebtedness or assets (other than cash dividends or
distributions payable out of retained earnings or stock dividends); or

          (iii) there shall be any capital reorganization of LIGAND or
reclassification of the Common Stock (other than a change in par value of the
Common Stock or an increase in the authorized capital stock of LIGAND not
involving the issuance of any shares thereof) or any consolidation or merger to
which LIGAND is a party (other than a consolidation or merger in which LIGAND is
the continuing corporation and that does not result in any reclassification or
change in the Common Stock outstanding) or a conveyance, lease or transfer of
all or substantially all of the properties and assets of LIGAND (other than the
granting of a security interest); or

          (iv) there shall be any voluntary or involuntary dissolution,
liquidation or winding-up of LIGAND; or

          (v) there shall be any other event that would result in an adjustment
pursuant to Section 9 hereof in the Exercise Price or the number of Warrant
Shares that may be purchased upon the exercise hereof;

LIGAND shall cause to be mailed or delivered to the Holder, (A) at least twenty
(20) days (or ten (10) days in any case specified in clauses (i) or (ii) above)
before the applicable record or effective date hereinafter specified or (B) on
the date on which any case specified in clauses (i) through (v) above is
publicly announced, whichever is later, a notice stating (A) the date as of
which the holders of Common Stock of record entitled to receive any such rights,
options, warrants or distributions is to be determined, or (B) the date on which
any such reorganization, reclassification, consolidation, merger, conveyance,
transfer, dissolution, liquidation or winding-up is expected to become
effective, and the date as of which it is expected that holders of Common Stock
of record shall be entitled to exchange their shares of Common Stock for
securities or other property, if any, deliverable upon such reorganization,
reclassification, consolidation, merger, conveyance, transfer, dissolution,
liquidation or winding-up.

     (b) LIGAND shall (i) at least twenty (20) days before the occurrence of any
Acceleration Event (unless the occurrence of that Acceleration Event is beyond
its control, in which case, LIGAND shall as soon as practicable) or (ii) on the
date on which any such Acceleration Event is publicly announced, whichever is
later, cause to be mailed or delivered to the Holder a notice describing in
reasonable detail such Acceleration Event and informing the Holder that Warrant
may be exercised by the Holder thereof.

     (c) Any failure by LIGAND to provide notice to the Holder in accordance
with this Section 10 shall not affect the legality or validity of any such
distribution, right, option, warrant,

                                       9

<PAGE>

consolidation, merger, conveyance, lease, transfer, dissolution, liquidation or
winding-up or the vote upon any such action.

     11. Officer's Certificate. Whenever the number of Warrant Shares that may
be purchased upon exercise of this Warrant is adjusted as required by the
provisions of this Warrant, LIGAND shall forthwith file in the custody of its
Secretary or an Assistant Secretary an officer's certificate showing the
adjusted number of Warrant Shares that may be purchased on exercise of this
Warrant and the adjusted Exercise Price, determined as herein provided, setting
forth in reasonable detail the facts requiring such adjustment and the manner of
computing such adjustment. Each such officer's certificate shall be made
available at all reasonable times for inspection by the Holder. LIGAND shall,
forthwith after each such adjustment, cause a copy of such certificate to be
mailed to the Holder.

     12. Listing of Warrant Shares. The Warrant Shares, when registered pursuant
to the Rights Agreement or otherwise tradeable under Rule 144 of the Act, shall
be listed or admitted to trading on either a national securities exchange or the
Nasdaq National Market consistent with the shares of Common Stock then
outstanding at the time of issuance of the Warrant Shares.

     13. Representations of Holder.

     The Holder hereby represents, covenants and acknowledges to LIGAND that:

          (a) this Warrant and the Warrant Shares are "restricted securities" as
such term is used in the rules and regulations under the Act and that such
securities have not been and will not be registered under the Act or any state
securities law (unless such Warrant Shares have been registered pursuant to the
Rights Agreement), and that such securities must be held indefinitely unless a
transfer can be made pursuant to appropriate exemptions;

          (b) the Holder has read, and fully understands, the terms of this
Warrant set forth on its face and the attachments hereto, including the
restrictions on transfer contained herein;

          (c) the Holder is purchasing for investment for its own account and
not with a view to or for sale in connection with any distribution of this
Warrant or the Warrant Shares and it has no intention of selling such securities
in a public distribution in violation of the federal securities laws or any
applicable state securities laws; provided that nothing contained herein will
prevent Holder from transferring such securities in compliance with the terms of
this Warrant and the applicable federal and state securities laws;

          (d) the Holder is an "accredited investor" within the meaning of
paragraph (a) of Rule 501 of Regulation D promulgated by the Securities and
Exchange Commission (the "Commission") and an "excluded purchaser" within the
meaning of Section 25102(f) of the California Corporate Securities Law of 1968;
and

          (e) the Holder (i) has received all information the Holder has
requested from LIGAND and considers necessary or appropriate for deciding
whether to acquire this Warrant, (ii) has had an opportunity to ask questions
and receive answers from LIGAND regarding the

                                       10

<PAGE>

terms and conditions of this Warrant and to obtain any additional
information necessary to verify the accuracy of the information given to the
Holder, and (iii) has such knowledge and experience in financial and business
matters such that the Holder is capable of evaluating the merits and risks of
the investment in this Warrant.

     14. Successors. All the provisions of this Warrant by or for the benefit of
LIGAND or the Holder shall bind and inure to the benefit of their respective
successors, assignees, heirs and personal representatives.

     15. Headings. The headings of sections of this Warrant have been inserted
for convenience of reference only, are not to be considered a part hereof and
shall in no way modify or restrict any of the terms or provisions hereof.

     16. Amendments. This Warrant may be amended by the written consent of
LIGAND and the Holder hereof.

     17. Notices. All notices, requests and other communications to LIGAND or
Holder hereunder shall be in writing (including telecopy or similar electronic
transmissions), shall refer specifically to this Warrant and shall be personally
delivered or sent by telecopy or other electronic facsimile transmission, by
overnight delivery with a nationally recognized overnight delivery service or by
registered mail or certified mail, return receipt requested, postage prepaid, in
each case to the respective address specified below (or to such address as may
be specified in writing to the other party hereto):

                  (a)      If to LIGAND, to:

                           Ligand Pharmaceuticals Incorporated
                           10275 Science Center Drive
                           San Diego, CA  92121
                           Attention: President
                             with a copy to the attention of General Counsel

                  (b) If to HOLDER, to the address set forth in the Warrant
Register that shall be maintained by LIGAND in accordance with Section 3 hereof.

Any notice or communication given in conformity with this Section 17 shall be
deemed to be effective when received by the addressee, if delivered by hand, one
(1) day after deposit with a nationally recognized overnight delivery service
and three (3) days after mailing, if mailed.

     18. Governing Law. This Warrant shall be governed by and construed in
accordance with the laws of the State of California, as applied to contracts
made and performed entirely within the State of California.

                [REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK]

                                       11

<PAGE>

     IN WITNESS WHEREOF, LIGAND has duly caused this Warrant to be signed and
attested by its duly authorized officers and to be dated as of November 22,
1999.

                                            LIGAND PHARMACEUTICALS INCORPORATED

                                            /s/Paul V. Maier
                                            -----------------------------------
                                            By:      Paul V. Maier

                                            Title:   Senior Vice President,
                                                     Chief Financial Officer

Attest:  /s/William L. Respess
--------------------------------
By:      William L. Respess

Title:   Senior Vice President,
         General Counsel, Government Relations

ACCEPTED AND AGREED TO BY:

ELAN INTERNATIONAL SERVICES, LTD.

/s/Kevin Insley
---------------------------------
By:      Kevin Insley

Title:   President & CFO

                      [SIGNATURE PAGE TO SERIES X WARRANT]

<PAGE>

                                  PURCHASE FORM

         Dated:______________

     The undersigned hereby irrevocably exercises the attached Warrant to
purchase __________________ shares of LIGAND Common Stock and (i) herewith
either (a) makes payment of $___________ in payment of the Exercise Price
thereof on the terms and conditions specified in the attached Warrant
Certificate or (b) if the undersigned elects pursuant to Section 2 of the
attached Warrant to convert such Warrant into LIGAND Common Stock, the
undersigned exercises the attached Warrant by exchange under the terms of
Section 2, (ii) surrenders the attached Warrant Certificate and all right, title
and interest therein to LIGAND and (iii) directs that the Warrant Shares
deliverable upon the exercise of such Warrant and cash payment in respect of
fractional Warrant Shares, if any, and any unexercised Warrant be registered (in
the case of such Warrants and Warrant Shares) in the name and at the address
specified below and delivered thereto.

Signature:

Name:
                           (Please Print)

Address:

City, Sate and Zip Code:

Taxpayer Identification or Social Security Number:

     Any unexercised Warrant Shares evidenced by the attached Warrant
Certificate are to be issued to:

Name:
                           (Please Print)

Address:

City, Sate and Zip Code:

Taxpayer Identification or Social Security Number:

NOTE: THE ABOVE SIGNATURE MUST CORRESPOND WITH THE NAME AS WRITTEN UPON THE FACE
OF THE ATTACHED WARRANT IN EVERY PARTICULAR, WITHOUT ALTERATION OR ENLARGEMENT
OR ANY CHANGE WHATSOEVER.

<PAGE>

                             WARRANT ASSIGNMENT FORM

     FOR VALUE RECEIVED and in compliance with the provisions of Sections 5 and
6 of the attached Warrant, __________________________ hereby sells, assigns and
transfers to:

Name:
                           (Please Print)

Address:

City, Sate and Zip Code:

Taxpayer Identification or Social Security Number:

its right to purchase up to _______ Warrant Shares represented by the attached
Warrant and does hereby irrevocably constitute and appoint
________________________________ attorney to transfer said Warrant on the books
of LIGAND, with full power of substitution in the premises.

Dated:__________________                    ______________________________
                                            Signature of registered holder

NOTE: THE ABOVE SIGNATURE MUST CORRESPOND WITH THE NAME AS WRITTEN UPON THE FACE
OF THE ATTACHED WARRANT IN EVERY PARTICULAR, WITHOUT ALTERATION OR ENLARGEMENT
OR ANY CHANGE WHATSOEVER.

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