Document:

exv4w1

Exhibit 4.1

EXECUTION COPY

AMENDMENT NO. 1

TO

RIGHTS AGREEMENT

          AMENDMENT NO. 1, dated as of May 16, 2010 (the “Amendment”), to the Rights Agreement,
dated as of September 27, 2000 (the “Agreement”), between OSI Pharmaceuticals, Inc., a
Delaware corporation (the “Company” or “OSI”), and The Bank of New York Mellon
(f/k/a The Bank of New York), a New York banking corporation, as Rights Agent (the “Rights
Agent”). Terms used but not otherwise defined herein shall have the meanings ascribed to such
respective terms in the Agreement.

W I T N E S S E T H:

          WHEREAS, the Company proposes to enter into an Agreement and Plan of Merger (as the same may
be amended from time to time, the “Merger Agreement”), by and among Astellas Pharma Inc.
(“Parent”), a corporation formed under the laws of Japan, Astellas US Holding, Inc.
(“Holding”), a Delaware corporation and wholly-owned subsidiary of Parent, Ruby Acquisition, Inc.
(“Merger Sub”), a Delaware corporation and wholly-owned subsidiary of Holding, and OSI,
pursuant to which it is proposed that, among other things, (i) Merger Sub will amend its
outstanding cash tender offer to acquire all the issued and outstanding shares of common stock, par
value $0.01 per share, of the Company at $57.50 per share in cash (the “Offer”), and (ii)
following the consummation of the Offer and satisfaction or waiver of certain conditions, Merger
Sub will merge with and into the Company with the Company continuing as the surviving corporation
(the “Merger”); and

          WHEREAS, Section 26 of the Agreement provides that, prior to the Distribution Date, the
Company and the Rights Agent shall, if the Company so directs, supplement or amend any provision of
the Agreement without the approval of any holders of shares of Common Stock or Rights, including
supplements or amendment that may be deemed to affect adversely the interest of the holders of
Rights; and

          WHEREAS, on May 16, 2010, the Board of Directors of the Company determined it to be advisable
and in the best interests of the Company and its stockholders to supplement and amend the Agreement
as set forth herein immediately prior to and in connection with the execution and delivery of the
Merger Agreement; and

          WHEREAS, an officer of the Company has delivered to the Rights Agent a certificate as to the
compliance of this Amendment with the terms of Section 26 of the Agreement; and

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          WHEREAS, the Board of Directors of the Company has approved this Amendment and has authorized
its appropriate officers to execute and deliver the same to the Rights Agent.

          NOW, THEREFORE, in accordance with Section 26 of the Agreement, and in consideration of the
foregoing and the mutual agreements herein set forth and in the Agreement, and for other good and
valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties
hereby agree as follows:

     Section 1. Amendments to the Agreement.

          1.1 The definition of “Acquiring Person” in Section 1(a) of the Agreement is hereby
amended by inserting the following new sentence at the end thereof:

“Notwithstanding anything in this Agreement to the contrary, none of Astellas Pharma
Inc., a corporation formed under the laws of Japan (“Parent”), Astellas US
Holding, Inc., a Delaware corporation and a wholly owned subsidiary of Parent
(“Holding”), Ruby Acquisition, Inc., a Delaware corporation and wholly-owned
subsidiary of Holding (“Merger Sub”), nor any of their respective Affiliates
or Associates shall be deemed to be an “Acquiring Person” hereunder, either
individually or collectively, by virtue of (A) the approval, execution, delivery or
adoption of that certain Agreement and Plan of Merger to be entered into among
Parent, Merger Sub and the Company (as may be amended from time to time, the
“Merger Agreement”), or the approval, execution or delivery of any amendment
thereto; (B) the consummation of any of the transactions contemplated by the Merger
Agreement, including, the tender offer to acquire all of the outstanding shares of
Common Stock and the associated Rights by Parent or Merger Sub (as it may be amended
and/or extended from time to time pursuant to the terms of the Merger Agreement, the
“Offer”) and the consummation of the merger of Merger Sub with and into the
Company (the “Merger”); or (C) the public announcement of any of the Merger
Agreement, the Offer, the Merger or any of the other transactions contemplated by
the Merger Agreement (such actions described in this sentence, the “Permitted
Events”).

          1.2 The definition of “Permitted Offer” in Section 1(o) of the Agreement is hereby amended to
add the following sentence to the end thereof:

“For the avoidance of doubt, the Offer and the other transactions contemplated by
the Merger Agreement shall constitute a “Permitted Offer” hereunder.”

          1.3 The following definitions are hereby added to Section 1 of the Agreement.

“Merger” has the meaning assigned thereto in Section 1(a).

“Merger Agreement” has the meaning assigned thereto in Section 1(a).

“Merger Sub” has the meaning assigned thereto in Section 1(a).

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“Offer” has the meaning assigned thereto in Section 1(a).

“Parent” has the meaning assigned thereto in Section 1(a).

“Permitted Events” has the meaning assigned thereto in Section 1(a).

          1.4 Section 3(b) of the Agreement is hereby amended by inserting the following sentence at the
end thereof:

“Notwithstanding anything in this Agreement to the contrary, a Distribution Date
shall not be deemed to have occurred solely or as a result of the occurrence of any
Permitted Event.”

          1.5 Section 7(a) of the Agreement is hereby amended in its entirety to read as follows:

“(a) The registered holder of any Right Certificate may exercise the Rights
evidenced thereby (except as otherwise provided herein) in whole or in part at any
time after the Distribution Date upon surrender of the Right Certificate, with the
form of election to purchase on the reverse side thereof duly executed, to the
Rights Agent at the office of the Rights Agent designated for such purpose, together
with payment of the Purchase Price for each one one-thousandth of a share of
Preferred Stock (or Common Stock, other securities, cash or other assets, as the
case may be) as to which the Rights are exercised, and an amount equal to any
applicable transfer tax as provided in Section 7(c), at or prior to the earlier of:
(i) the Close of Business on the Final Expiration Date, (ii) the time at which the
Rights are redeemed as provided in Section 23 (the “Redemption Date”) and
(iii) the time immediately prior to the Effective Time (as defined in the Merger
Agreement), but only if the Effective Time shall occur;”

          1.6 Section 24 of the Agreement is hereby further amended to add the following subsection at
the end thereof:

“(d) Notwithstanding anything in this Agreement to the contrary, the Company shall
not be required to give notice under this Section 24 solely as a result of the
occurrence of any Permitted Event.”

          1.7 The Agreement is hereby amended by adding a new Section 34 in its entirety as follows:

“Section 34. Termination. Notwithstanding anything contained herein to the
contrary, immediately prior to the Effective Time (but only if the Effective Time
shall occur), and upon written notice to the Rights Agent, (i) this Agreement shall
be terminated and be without further force or effect, (ii) none of the parties to
this Agreement will have any rights, obligations or liabilities hereunder and (iii)
the holders of the Rights shall not be entitled to any benefits, rights or other
interests under this Agreement, including, without limitation, the right to purchase
or

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otherwise acquire shares of Preferred Stock or any other securities of the Company
or of any other Person.”

          1.8 

               (a) Section 25(a) of the Agreement is hereby amended by deleting the Company’s notice address
in its entirety and replacing it with the following:

OSI Pharmaceuticals, Inc.

420 Saw Mill River Road

Ardsley, New York 10502

Attention: Secretary

               (b) Section 25(b) of the Agreement is hereby amended by inserting the following at the end
thereof:

with a copy to:

The Bank of New York Mellon

Newport Office Center VII

480 Washington Blvd.

Jersey City, NJ 07310

Attention: General Counsel

     Section 2. Termination of Merger Agreement. If for any reason the Merger Agreement is
terminated, then this Amendment shall be of no further force and effect and the Agreement shall
remain exactly the same as it existed immediately prior to execution of this Amendment.

     Section 3. Effectiveness. This Amendment shall be deemed effective as of, and
immediately prior to, the execution and delivery of the Merger Agreement. Except as amended by
this Amendment, the Agreement shall remain in full force and effect and shall be otherwise
unaffected by this Amendment. The term “Agreement” as used in the Agreement shall be deemed to
refer to the Agreement as amended hereby.

     Section 4. Waiver of Notice. The Rights Agent and the Company hereby waive any notice
requirement under the Agreement pertaining to the matters covered by this Amendment.

     Section 5. Counterparts. This Agreement may be executed in any number of
counterparts, each of which counterparts shall for all purposes be deemed to be an original, and
all such counterparts shall together constitute but one and the same instrument.

     Section 6. Governing Law. This Amendment shall be deemed to be a contract made under
the laws of Delaware and for all purposes shall be governed by and construed in accordance with the
laws of such State applicable to contracts to be made and performed entirely within such State,
provided, however, that the rights and obligations of the Rights Agent shall be governed by and
construed in accordance with the laws of the State of New York.

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     Section 7. Severability. If any term, provision, covenant or restriction of this
Amendment is held by a court of competent jurisdiction or other authority to be invalid, void or
unenforceable, the remainder of the terms, provisions, covenants and restrictions of this Amendment
shall remain in full force and effect and shall in no way be affected, impaired or invalidated.

     Section 8. Further Assurances. Each of the parties to this Amendment shall cooperate
and take such action as may be reasonably requested by the other party in order to carry out the
provisions and purposes of this Amendment, the Agreement and the transactions contemplated
hereunder and/or thereunder.

[SIGNATURE PAGE FOLLOWS]

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          IN WITNESS WHEREOF, the parties have caused this Amendment to be duly executed as of the date
first above written.

	 	 	 	 	 
	 	OSI PHARMACEUTICALS, INC.

 	 
	 	By:  	/s/ Barbara A. Wood
 	 
	 	Name:  	Barbara Wood 	 
	 	Title:  	Senior Vice President, General
Counsel and Secretary 	 
	 
	 	THE BANK OF NEW YORK MELLON, as Rights Agent

 	 
	 	By:  	/s/ Stephen R. Jones
 	 
	 	Name:  	Stephen R. Jones 	 
	 	Title:  	Vice President 	 
	 

[SIGNATURE PAGE TO RIGHTS AGREEMENT AMENDMENT]exv4w6w1

EXHIBIT 4.6.1

CUMBERLAND PHARMACEUTICALS INC.

2007 LONG-TERM INCENTIVE COMPENSATION PLAN

INCENTIVE STOCK OPTION AGREEMENT

     1. Grant of Option. Cumberland Pharmaceuticals Inc. (the “Company”), a Tennessee
corporation, hereby grants to the Participant an option (the “Option”) to purchase from the Company
up to the number of shares of common stock (the “Shares”) described in the attached Notice of Stock
Option Grant (the “Notice”). This grant is made subject to the terms of the Cumberland
Pharmaceuticals Inc. 2007 Long-Term Incentive Compensation Plan (the “Plan”) and the number of
shares granted is subject to adjustment as described in the Plan. Unless otherwise defined in this
Incentive Stock Option Agreement (the “Option Agreement”), capitalized terms used in this Option
Agreement shall have the same meaning as those capitalized terms in the Plan.

     2. Exercise Price. If the Option is exercised, the purchase price per Share shall be
as shown in the attached Notice.

     3. Method of Exercise. The Option granted under this Option Agreement shall be
exercisable from time to time, in whole or in part, by written notice as described in Section 9
hereof, accompanied by payment of the purchase price for the Shares which the Participant elects to
purchase by cash, check, or such other instrument as the Company may accept. The Company shall make
prompt delivery of such Shares, and in no event shall delivery of such shares be made more than 30
days after cash, check or other instrument is accepted by the Company in payment for the Shares,
except that if any law or regulation requires the Company to take any action with respect to the
Shares specified in such notice before issuance thereof, then the date of delivery of such Shares
shall be extended for the period necessary for the Company to take such action.

     4. Vesting.

          (a) The Option shall vest in accordance with the schedule set forth in the Notice. Employment
for only a portion of the vesting period, even if a substantial portion, will not entitle the
Participant to any proportionate vesting or avoid or mitigate a termination of rights and benefits
upon or following a termination of employment.

          (b) Upon the Participant’s Employment Termination, the Option, to the extent unvested, shall
lapse and be cancelled, and be of no further force and effect, as of midnight of such date, unless
the Board resolves (under Section 4(b) of the Plan) to cancel or cause the forfeiture of the Option
at an earlier time.

          (c) Upon an Acquisition Event and/or a Change in Control Event, the Option will vest to the
extent provided in the Plan.

     5. Termination of Option; Restrictions on Exercise. Except as otherwise stated in this
Agreement, this Option, to the extent not previously exercised, shall expire on the expiration date
set forth in the attached Notice (the “Expiration Date”). The following additional provisions shall
apply to the exercise of this Option:

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          (a) Termination of Employment. Except as otherwise provided in this Option Agreement or in the
Plan, if Participant’s employment with the Company and its Related Entities is terminated by the
Participant or the Company, the right to exercise this Option (to the extent that it is vested in
accordance with the applicable provisions of Section 4 hereof) shall end on the earlier of
the following dates: (i) ninety (90) days after such termination or (ii) the expiration date of
this Option shown in the Notice. Except as expressly set forth otherwise herein, this Option shall
terminate in all other respects upon such termination of employment.

          (b) Death of Participant. If the Participant’s employment with the Company is terminated due
to his/her death during the term of this Option, the Participant’s legal representative, or the
person so entitled under the Participant’s last will and testament, or under applicable intestate
laws, shall have the right to exercise this Option for the number of Shares vested under Section 4
hereof as of the time of Participant’s death, and such right shall expire and this Option shall
terminate on the Expiration Date.

     6. Provisions of Plan. The terms and provisions of the Plan (including any written
amendments made to the Plan from time to time) are hereby incorporated herein by reference. In the
event of a conflict between the terms or provisions contained herein and the terms or provisions of
the Plan, the applicable terms and provisions of the Plan will govern and prevail; however, in the
event of a conflict regarding specific terms and provisions addressing the duration of this Option
after termination of employment, the terms and provisions of this Option will govern.

     7. Tax Treatment of Option. The Participant is responsible for any federal, state,
local, or foreign tax, including income tax, social security tax, payroll tax, payment on account,
or other tax-related withholding with respect to this Option (including the grant, vesting and
exercise of the Option and the receipt of Shares and sale of Shares). The Company does not
guarantee any particular tax treatment or results in connection with the grant, vesting or exercise
of the Option.

     8. Code Section 409A. This Option Agreement is intended to be exempt from
the requirements of Internal Revenue Code Section 409A (“Section 409A”) and regulations or other
authority under Section 409A, and not intended to provide for any deferral of compensation that
fails to satisfy the requirements of Section 409A. Notwithstanding any other provision of Option
Agreement to the contrary, it is intended that any payment or benefit provided for in this Option
Agreement that constitutes “nonqualified deferred compensation,” as that term is defined in Code
Section 409A, shall be provided and issued in a manner, and at such time and in such form, as
complies with the applicable requirements of Section 409A. Any provision in this Option Agreement
that would result in the imposition of excise taxes or any other taxes upon Participant under
Section 409A shall be void and without effect. To the extent permitted under Section 409A, the
parties shall reform the provision, provided such reformation shall not subject Participant to
additional tax or interest and shall not require the Company to incur any additional compensation
costs as a result of the reformation. In addition, any provision that is required to appear in this
Option Agreement for purposes of Section 409A compliance and that is not expressly set forth shall
be deemed to be set forth herein, and this Option Agreement shall be administered in all respects
as if such provision were expressly set forth. References in this

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Option Agreement to Section 409A include rules, regulations, and guidance of general
application issued by the Department of the Treasury under Section 409A.

     9. Notices. Any notice, request, instruction or other document given under this Option
Agreement shall be in writing and shall be addressed and delivered in the case of the Company, to
the Secretary of the Company at the principal office of the Company and, in the case of the
Participant, at the Participant’s address as set forth in the attached Notice or to such other
address as the Participant may provide in a written notice to the Company, a copy of which shall be
on file with the Secretary of the Company.

     10. Governing Law. This Option Agreement shall be construed in accordance with and
governed by the law of the State of Tennessee, without giving effect to the conflict of law
provisions thereof.

     11. Relation to Other Benefits. Unless otherwise provided, the benefits received by
the Participant under this Option Agreement will not be taken into account or treated as normal
salary or compensation in determining any benefits to which the Participant may be entitled under
any profit sharing, retirement, bonus, long service, or other benefit or compensation plan
maintained by the Company, including the amount of any life insurance coverage available to any
beneficiary of the Participant under any life insurance plan covering employees of the Company, or
as part of the calculation of any severance, resignation, termination, redundancy or end of service
payments.

     12. Miscellaneous. The grant of this Option does not create any contractual or other
right to receive future grants of Options, or benefits in lieu of Options, even if the Participant
has a history of receiving Options or other stock awards.

     13. Headings. The headings of the Sections hereof are provided for convenience only
and are not to serve as a basis for interpretation or construction, and shall not constitute a part
of this Option Agreement.

     14. Signature. This Option Agreement shall be deemed executed by the Company and the
Participant upon execution by such parties of the attached Notice.

# # # #

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FOR FUTURE USE

NOTICE OF EXERCISE

Cumberland Pharmaceuticals Inc.:

     The undersigned hereby elects to exercise the purchase rights granted in the attached Option
Agreement # ___ and associated Notice of Stock Option Grant. In accordance with the terms thereof,
the undersigned elects to purchase                      shares of Common Stock of Cumberland Pharmaceuticals
Inc. and tenders herewith payment of the purchase price for such shares in full.

     Please issue said shares of Common Stock in the name of the undersigned.

Date:                                         

PARTICIPANT

	 	 	 	 	 

	Signature:

	 	 

	 	 
	 
	 	 	 	 
	Print Name:

	 	 

	 	 
	 
	 	 	 	 
	Address:

	 	 

	 	 
	 
	 	 	 	 
	City, State, Zip:

	 	 

	 	 
	 
	 	 	 	 
	Social Security Number:

	 	 

	 	 
	 
	 	 	 	 
	Phone Number:

	 	 

	 	 

$                                         

Payment Attached

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