Exhibit 10.24
 LICENSE AGREEMENT
 
BETWEEN
 
ACORDA THERAPEUTICS, INC.
 
AND
 
THE MAYO FOUNDATION FOR
EDUCATION AND RESEARCH
 
Dated:  September 8, 2000
 
 
 

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TABLE OF CONTENTS
 
1.
DEFINITIONS.
 
1.1
“Affiliate”
 
1.2
“FDA”
 
1.3
“Field”
 
1.4
“First Commercial Sale”
 
1.5
“Key Claims”
 
1.6
“Know-How”
 
1.7
“Invention”
 
1.8
“Licensed Patents”
 
1.9
“Licensed Product”
 
1.10
“Licensed Technology”
 
1.11
“Marketing Exclusivity Rights”
 
1.12
“Material Breach”
 
1.13
“Net Sales”
 
1.14
“Patent Term Extensions”
 
1.15
“Patent Term Extensions Information”
 
1.16
“Party”
 
1.17
“PLA”
 
1.18
“Regulatory Review Period”
 
1.19
“Royalty Term”
 
1.20
“Sublicensee”
 
1.21
“Termination”
 
1.22
“Territory”
 
1.23
“Valid Claim”
     
2.
GRANT OF LICENSE.
 
2.1
License Grant
 
2.2
Reserved Rights
 
2.3
Representations and Warranties.
 
2.4
Right of First Offer
 
2.5
Opportunity to Conduct Clinical Studies
     
3.
PAYMENTS; ROYALTIES.
 
3.1
Upfront Consideration Royalty.
 
3.2
Milestone Royalties for Licensed Products
 
3.3
Running Royalties for Sales of Licensed Products.
 
3.4
Third Party Royalties
 
3.5
Certain Affiliate and Sublicensee Royalties
 
3.6
Obligation to Pay Royalties
 
3.7
Royalties on Combined Products

4.
PAYMENTS AND RECORDS.
 
4.1
Payment
 
4.2
Mode of Payment
 
4.3
Taxes
 
4.4
Records Retention
 
4.5
Audit Request
     
5.
DUE DILIGENCE.
 
5.1
Diligence

 

 
 

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5.2
Reports
 
5.3
Short-Form Arbitration
     
6.
“OWNERSHIP; PATENTS; MARKETING EXCLUSIVITY; PATENT TERM EXTENSIONS”
 
6.1
Ownership.
 
6.2
Patent Prosecution and Maintenance.
 
6.3
Patent Enforcement.
 
6.4
Infringement Action by Third Parties.
 
6.5
Marketing Exclusivity/Patent Term Extensions
     
7.
PUBLICATION; CONFIDENTIALITY.
 
7.1
Publication
 
7.2
Confidentiality; Exceptions.
 
7.3
Exceptions to Obligation
 
7.4
Confidentiality regarding Patient Information
     
8.
INDEMNIFICATION.
 
8.1
Products Liability
 
8.2
MAYO Indemnification.
 
8.4
Notice; Waiver of Subrogation.
     
9.
TERM AND TERMINATION.
 
9.1
Term
 
9.2
Breach
 
9.3
Insolvency or Bankruptcy
 
9.4
Termination by ACORDA
 
9.5
Right to Sell Stock on Hand
 
9.6
Effect of Termination.
 
9.7
Accrued and Surviving Rights and Obligations
     
10.
MISCELLANEOUS PROVISIONS.
 
10.1
Relationship of Parties
 
10.2
Assignment
 
10.3
Further Actions

 
10.4
Force Majeure
 
10.5
No Trademark Rights
 
10.6
Public Announcements
 
10.7
Notices
 
10.8
Amendment
 
10.9
Waiver
 
10.10
Severability
 
10.11
Compliance with Law
 
10.12
Governing Law and Jurisdiction
 
10.13
Entire Agreement of the Parties
 
10.14
Descriptive Headings
 
10.15
Nondisclosure

 
10.16
Counterparts

 
 

 
 

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LIST OF EXHIBITS
 

 
EXHIBIT A
     
EXHIBIT B
     
EXHIBIT C
     
EXHIBIT D
     
EXHIBIT E

 
 

 
 

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LICENSE AGREEMENT
 
THIS LICENSE AGREEMENT (this “Agreement”) is entered into as of September 8,
2000 (the “Effective Date”), by and between Acorda Therapeutics, Inc., a
Delaware corporation, having offices at 15 Skyline Drive, Hawthorne, New York
10532, (“ACORDA”) and The Mayo Foundation for Medical Education and Research, a
Minnesota charitable corporation located at 200 First Street SW, Rochester,
Minnesota 55905 (“MAYO”).
 
PRELIMINARY STATEMENTS
 
A.                                   ACORDA has sponsored two research programs
under the direction of Dr.  Moses Rodriguez and Dr.  Larry Pease, entitled (1)
Preclinical Studies of a Monoclonal Antibody Designed to Promote Central Nervous
Repair, and (2) Molecular Characterization of Antibody-Induced Remyelination and
Isolation of Human Counterparts, (each a “Program” and collectively, the
“Programs”), pursuant to two Sponsored Research Agreements between MAYO and
ACORDA, dated as of October 1, 1995 and March 15, 1998, respectively, (the
“Sponsored Research Agreements”) which are attached hereto as Exhibit A.  These
Programs have related to, among other things, the therapeutic use of humanized
and non-humanized antibodies for treatment of central nervous system conditions
and disorders, including myelination or remyelination in conditions such as
spinal cord injuries and multiple sclerosis.
 
B.                                     MAYO is the owner of certain right, title
and interest to technology made or otherwise developed in performance of the
Programs including certain inventions, discoveries and patents described in the
Sponsored Research Agreements.
 
C.                                     MAYO has the right to grant licenses to
this technology so that such technology may be utilized in the public interest,
and is willing to grant a license thereunder to ACORDA.
 
D.                                    ACORDA has options, pursuant to
ACORDA\MAYO Option Agreements dated as of October 1, 1995 and March 15, 1998
(the “Option Agreements”), which are attached hereto as Exhibit B, to acquire an
exclusive, worldwide license to such technology and is desirous of obtaining
certain rights and licenses from MAYO relating to the aforementioned technology.
 
E.                                      ACORDA wishes to exercise the options
under both Option Agreements and ACORDA and MAYO now desire to provide for the
license of all technology in all fields contemplated by the exercise of the
options granted under both of the Option Agreements under one unified set of
terms conditions, and for revised consideration, as provided under this
Agreement, which shall be deemed to amend and supercede the provisions of the
Option Agreements.
 
 
 

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NOW THEREFORE, in consideration of the foregoing and of the mutual covenants
contained in this Agreement, the Parties hereto agree to the provisions of the
Preliminary Statements and as follows:
 
 
1.                                      DEFINITIONS.
 
As used in this Agreement, the following terms will have the meanings set forth
in this Section 1 unless the context dictates otherwise.
 
1.1                                 “Affiliate” shall mean, with respect to
either person, any corporation or other business entity which controls, is
controlled by or is under common control with such person.  For this purpose,
control means the possession of the power to direct or cause the direction of
the management and the policies of an entity whether through ownership directly
or indirectly of fifty percent (50%) or more of the stock entitled to vote, and
for non-stock organizations, the right to receive over fifty percent (50%) of
the profits by contract or otherwise, or if not meeting the preceding
requirement, any company owned or controlled by or owning or controlling such
person at the maximum control or ownership right permitted in the country where
such entity exists.
 
1.2                                 “FDA” shall mean the U.S.  Food and Drug
Administration, or the successor thereto.
 
1.3                                 “Field” shall mean the prevention,
mitigation or treatment of nervous system disorders, diseases or injuries
including, without limitation, pain, and any and all other diagnostic,
therapeutic, pharmaceutical, cosmetic, medical or health care related
applications.
 
1.4                                 “First Commercial Sale” shall mean, with
respect to any Licensed Product, the first sale for use or consumption by the
general public of such Licensed Product in any country in the Territory after
all required marketing approvals have been granted, or, if such sale is
otherwise permitted, by the governing health regulatory authority of such
country.
 
1.5                                 “Key Claims” shall have the meaning assigned
to such term in Section 3.2(a).
 
1.6                                 “Know-How” shall mean any and all technical
data, information, inventions, biological materials, trade secrets, and other
intellectual property, whether patentable or unpatentable, conceived or
otherwise developed in the course of and in connection with the Programs, and
all subsequent modifications, enhancements and improvements hereto, excluding
the patent applications and patents within the Licensed Patents.
 
1.7                                 “Invention” shall mean any new and useful
invention, discovery„ process, improvement or other intellectual property
conceived of, first reduced to practice, made or otherwise developed by MAYO,
its employees or agents including Dr.  Moses Rodriguez and Dr.  Larry Pease,
 
 
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in connection with and during the term of either of the Programs and this
Agreement, and during the two year period thereafter.
 
1.8                                 “Licensed Patents” shall mean, collectively:
 
(a)                                  United States Patent No.  5,591,629,
(formerly Application S.N.  08/236,520, filed April 29, 1994), entitled
“Monoclonal Antibodies Which Promote Central Nervous System Remyelination,” the
inventions described and claimed therein, and any substitutions, extensions,
renewals, divisions, patents-of-addition, continuations, continuations-in-part
to the extent the claims are directed to subject matter specifically described
in such patent (including, but not limited to, all of those
continuations-in-part specifically listed on Exhibit C), patents issuing thereon
or reissues, extensions or supplementary protection certificates thereof, and
any and all patents and patent applications throughout the Territory
corresponding thereto; and
 
(b)                                 All patents and patent applications, and any
substitutions, extensions, renewals, divisions, patents-of-addition,
continuations, continuations-in-part to the extent the claims are directed to
subject matter specifically described in such patent or patent application,
patents issuing thereon or reissues, re-examinations, extensions or
supplementary protection certificates thereof, and any and all foreign
counterparts thereto concerning any invention, technology or other intellectual
property owned in whole or in part by MAYO and made, first reduced to practice
or otherwise developed in connection with the Programs, whether before or after
the date of this Agreement, or derivatives or analogs thereof, including any and
all technology which may be subject to either of the Option Agreements.
 
1.9                                 “Licensed Product” shall mean any product or
part thereof which is covered, in whole or in part, by a Valid Claim of a
Licensed Patent in the country in which such product is made, used or sold, or
which incorporates or utilizes Know-How.
 
1.10                           “Licensed Technology” shall mean the Licensed
Patents and the Know-How, collectively.
 
1.11                           “Marketing Exclusivity Rights” shall mean any
rights to which a Licensed Product may be eligible in addition to or in lieu of
rights under the Licensed Patents including rights to exclusivity provided in 21
USC §505, 21 USC §360aa-ee, the Orphan Drug Act, the marketing exclusivity
provisions of Article 8(a) of Directive 65/65/EEC Relating to Medicinal Products
and any other legislation on regulations as amended from time to time in the
Territory applicable to this Agreement providing for non-patent marketing
exclusivity for any Licensed Product whether such legislation or regulation is
operative on the Effective Date of this Agreement or becomes operative
thereafter;
 
1.12                           “Material Breach” shall mean a breach of this
Agreement which is specified in this Agreement as being a material breach, and
in addition, any breach of this Agreement which is so
 
 
 
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injurious to the relationship between the Parties that this Agreement should
reasonably be subject to immediate Termination by the non-breaching Party.
 
1.13                           “Net Sales” shall mean, with respect to any
Licensed Product, the gross amount invoiced for such Product by ACORDA, its
Affiliates and Sublicensees, to third parties, less deductions for: (i) trade,
quantity and/or cash discounts, allowances and rebates (including, without
limitation, promotional allowances or discounts or similar allowances) actually
allowed or given; (ii) freight, postage, shipping, insurance and transportation
expenses and similar charges (in each instance, if separately identified in such
invoice); (iii) credits or refunds actually allowed for rejections, defects or
recalls of such Licensed Product, outdated or returned Licensed Product, or
because of rebates or retroactive price reductions; and (iv) sales, value-added
and excise taxes, tariffs and duties, and other taxes directly related to the
sale, to the extent that such items are included in the gross invoice price (but
not including taxes assessed against the income derived from such sale).  Such
amounts shall be determined from the books and records of
ACORDA, its Affiliates or its Sublicensees, maintained in accordance with the
reasonable accounting principles used by such entity, consistently applied.
 
1.14                           “Patent Term Extensions” shall mean the interim
or permanent extension ofthe term of any Licensed Patents or claims covered by
any Licensed Patents for any Licensed Product for which MAYO may be eligible
under 35 U.S.C.  § 156 or any otherU.S.  or non-U.S.  statute providing for
extensions of patent terms;
 
1.15                           “Patent Term Extensions Information” shall mean
information within a non-filing Party’s possession or control which may be
requested by the Party responsible for filing and prosecuting an application or
petition for a Patent Term Extension, such information as may be requested by
the Patent and Trademark Office and execution of all necessary documentation in
connection therewith for the filing Party to make a timely and complete filing
and prosecution of an application for a Patent Term Extension;
 
1.16                           “Party” shall mean ACORDA or MAYO and, when used
in the plural, shall mean ACORDA and MAYO.
 
1.17                           “PLA” shall mean a product license application,
or with respect to any product license application already filed as of the
Effective Date a supplemental product license application thereto, filed with
the United States FDA, or the equivalent regulatory filing required to be filed
with the regulatory authorities in any other jurisdiction outside the United
States.
 
1.18                           “Regulatory Review Period” shall mean the period
of time defined in 35 U.S.C.  § 156(g) and applicable to any Licensed Product;
 
1.19                           “Royalty Term” shall mean, with respect to each
Product in each country in the Territory, the period commencing on the date of
the First Commercial Sale of such Product
 
 
 
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and expiring on the earlier of: (a) the later of (i) the expiration of the last
Key Claim covering such Product in such country, or (ii) the expiration of any
exclusive approval period granted with respect to such Product under the Orphan
Drug Act, 21 U.S.C.  § 360aa et.  seq., as amended from time to time, or (iii)
ten years from the First Commercial Sale, or (iv) fifteen years from the
Effective Date; or (b) the Termination of this Agreement.
 
1.20                           “Sublicensee” shall mean any non-Affiliate third
party sublicensed by ACORDA to make, have made, import, use or sell any Licensed
Product.
 
1.21                           “Termination” of this Agreement shall mean the
ending, expiration, rescission, or any other discontinuation of this contract
for any reason whatsoever.
 
1.22                           “Territory” shall mean the entire world.
 
1.23                           “Valid Claim” shall mean either: (i) a claim of
an issued and unexpired patent included in the Licensed Patents, which has not
been held permanently revoked, unenforceable or invalid by a decision of a court
or other governmental agency of competent jurisdiction, which decision is
unappealable or unappealed within the time allowed for appeal, and which claim
has not been admitted to be invalid or unenforceable through reissue or
disclaimer or otherwise, or (ii) a pending claim of a pending patent application
that is classified under Section 1.7 as Licensed Patents, which claim (a) was
filed in good faith, (b) is reasonably likely to issue, (c) has not been
abandoned or finally disallowed without the possibility of appeal or refining of
said application, and (d) has not been pending for a period in excess of seven
(7) years from the earliest date from which the patent application was filed or
claims priority in such country.
 
2.                                      GRANT OF LICENSE.
 
2.1                                 License Grant.  Subject to the terms and
conditions of this Agreement, MAYO hereby grants to ACORDA, subject to any
rights of the U.  S.  Government under 35 U.S.C.  § 200 etseq.  and all
regulations promulgated pursuant thereto, the exclusive (even as to MAYO),
worldwide right and license under the Licensed Technology to develop, make, have
made, use, import, export, lease, offer to sell, sell, have sold and otherwise
exploit Licensed Products for use in the Field in the Territory, and to grant,
offer for sale and authorize sublicenses with respect to the right and license
granted under this Section 2.1 to other third parties.
 
2.2                                 Reserved Rights.  Notwithstanding the right
and license granted in Section 2.1, MAYO reserves the right to use the Licensed
Technology solely for purposes of education, internal research and verification
of adherence to MAYO’s policies regarding the responsible conduct of research,
and for MAYO’s•patient care, at the discretion of MAYO’s physicians, conducted
within MAYO’s facilities located in Rochester, Minnesota, Scottsdale, Arizona
and Jacksonville, Florida.  MAYO may also share aliquots of antibody related to
Licensed Technology with other academic
 
 
 
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institutions solely for non-commercial research purposes as ACORDA may approve
in advance, provided that no antibody shall be shared which is not already
subject to an issued U.S.  Patent or pending U.S.  patent application, and
provided further, that any such other academic institution must sign a material
transfer agreement in form acceptable to ACORDA, whereby such institution
confirms (a) that the antibody provided is the subject of an issued or pending
Patent, (b) the proprietary rights of ACORDA under this Agreement, and (c) that
all rights to all commercial applications resulting from such institution’s
research making use of such transferred material shall belong exclusively to
MAYO and be considered part of the license granted to ACORDA under this
Agreement.  The Parties agree that the form of material transfer agreement
attached to this Agreement as Exhibit E may be used for such purpose, provided
that MAYO must still obtain ACORDA’s prior approval for any specific agreement
and transfer in each instance.  Nothing in this Section 2.2 shall permit MAYO to
use the Licensed Technology to develop any product for commercial use, or give
any third party such right.
 
2.3                                 Representations and Warranties.
 
(a)                                  MAYO hereby represents and warrants that:
 
(i)                                     It has the right to grant the right and
license granted to ACORDA under this Section 2 and that (except as may be
provided in that certain agreement dated January 9, 1997 between MAYO and TEVA
Pharmaceutical Industries, Ltd.  (the “TEVA Agreement”) which purports to grant
certain rights to TEVA with respect to certain research results which may or may
not be considered part of the Licensed Technology licensed hereunder and is the
subject of the special indemnification provided under Section 8.2 (b) of this
Agreement) MAYO has not entered into any agreement with any third party which is
in conflict with the rights granted to ACORDA pursuant to this Agreement; and
 
(ii)                                  It has fully disclosed to ACORDA all
information in MAYO’s possession or control relating to the Licensed Technology,
including, without limitation, any communications with any third parties
relating to any of the foregoing.
 
(b)                                 NO OTHER WARRANTIES.
 
(i)                                     Except as expressly provided in this
Agreement, nothing in this Agreement shall be construed as a warranty or
representation by MAYO as to: the validity or scope of any patents contained in
the Licensed Technology; an obligation to bring or to prosecute actions against
third parties for infringement of patent; or conferring by implication,
estoppel, or otherwise any patents of MAYO.
 
(ii)                                  MAYO HAS NOT MADE AND PRESENTLY MAKES NO
PROMISES, GUARANTEES, REPRESENTATIONS OR WARRANTIES OF ANY NATURE, DIRECTLY OR
INDIRECTLY, EXPRESS OR IMPLIED, REGARDING THE MERCHANTABILITY,
 
 
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FITNESS FOR A PARTICULAR PURPOSE, SUITABILITY, DURABILITY, CONDITION, QUALITY,
OR ANY OTHER CHARACTERISTIC OF THE LICENSED TECHNOLOGY.  THE COMPANY TAKES THE
LICENSED TECHNOLOGY “AS IS,” “WITH ALL FAULTS,” AND “WITH ALL DEFECTS,” AND
EXPRESSLY WAIVES ALL RIGHTS TO MAKE ANY CLAIM WHATSOEVER AGAINST MAYO FOR
MISREPRESENTATION OR FOR BREACH OF PROMISE, GUARANTEE, OR WARRANTY OF ANY KIND
RELATING TO THE LICENSED TECHNOLOGY.
 
2.4                                 Right of First Offer.  The Parties recognize
that MAYO may continue to conduct internal research using the Licensed
Technology, as it determines in its discretion.  In the event that MAYO develops
any other application related to the Licensed Technology but outside the scope
of the license granted under this Agreement (a “New Product”), MAYO hereby
grants to ACORDA a right of first offer with respect to rights for any such New
Product in the Field, as follows:
 
(a)                                  In the event that, at any time during the
term of this Agreement, MAYO intends to offer to a third party any rights to any
New Product or receives an offer from a third party to acquire any rights to any
New Product, MAYO shall first offer such rights to ACORDA, in writing, on terms
no less favorable to ACORDA than those to be offered to, or offered by, such
third party
 
(b)                                 Within 30 days after receipt of any such
offer, ACORDA shall notify MAYO in writing as to whether it wishes to obtain
such rights on such terms.  If ACORDA provides timely notice that ACORDA wishes
to obtain such rights, then the Parties shall conduct exclusive negotiations in
good faith and conclude an agreement incorporating such terms within 120 days
thereafter.
 
(c)                                  In the event that (i) ACORDA gives MAYO
notice that ACORDA does not wish to obtain such rights, or (ii) ACORDA does not
respond to MAYO’s notice within 30 days after receipt thereof, then MAYO shall
have the unrestricted right to enter into an agreement with a third party for
such rights.
 
(d)                                 In the event that the parties enter into
negotiations pursuant to Section 2.4(b), but are unable to agree upon the terms
of such rights, despite the use of good faith efforts, during the 120-day period
set forth in Section 2.4(b), then MAYO shall have the right, for a period of six
months thereafter, to enter into an agreement with a third party for such rights
on terms no more favorable to such third party than those last offered to ACORDA
pursuant to this Section 2.4.  In the event that MAYO wishes to enter into such
an agreement on terms more favorable to such third party, MAYO shall reoffer
such terms to ACORDA in accordance with this Section 2.4.  MAYO’s obligation to
reoffer to ACORDA any particular New Product it has not licensed to a third
party during the six month period contemplated in the first sentence of this
Section 2.4(d) shall continue for the term of this Agreement, and if MAYO
continues its internal research related to such New
 
 
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Product, it will disclose to ACORDA any material new information, technology, or
data developed by MAYO related to the New Product to permit ACORDA to evaluate
MAYO’s reoffer.
 
2.5                                 Opportunity to Conduct Clinical Studies.  In
the event that ACORDA determines that it is desirable to conduct clinical
studies in connection with development of Licensed Products using the Licensed
Technology, ACORDA shall provide MAYO with the opportunity to be included as a
study site for such clinical studies, provided that MAYO has the necessary
expertise, and can perform such clinical study in a timely and cost efficient
manner when compared to the use of a third party.  MAYO acknowledges that MAYO
may not serve as a major clinical trial site, when MAYO has a conflict of
interest, whether actual or perceived, such as in a registrational study.
 
3.                                      PAYMENTS; ROYALTIES.
 
3.1                                 Upfront Consideration Royalty.
 
(a)                                  In partial consideration of the right and
license granted to ACORDA hereunder, ACORDA shall pay MAYO a fee of thirty-five
thousand dollars ($35,000), due within thirty (30) days after the Effective
Date.  Such fee shall be non-refundable, and non-creditable against any other
royalty or fee payable under this Agreement.
 
(b)                                 In further consideration of the right and
license granted to ACORDA hereunder, ACORDA acknowledges that this Agreement
permits MAYO to exercise the warrants previously granted to MAYO in connection
with the Option Agreement to purchase 60,000 shares of ACORDA common stock at
the price of founders stock.  In the event MAYO elects to exercise such
warrants, ACORDA shall reimburse to MAYO the price paid by MAYO in order to
exercise such warrants.
 
3.2                                 Milestone Royalties for Licensed Products. 
In further consideration of the right and license granted to ACORDA hereunder,
ACORDA shall pay to MAYO the following milestone payments upon the first
occurrence of each event set forth below:
 
(a)                                  In as much as United States Patent No. 
5,591,629, as described in Section 1.8(a) has issued and contains one or more of
the key claims as contemplated by a prior Option Agreement among the Parties
(“Key Claims”), $25,000, within 30 days following the Effective Date.
 
(b)                                 $25,000 within thirty days following the
issuance of the first U.S.  composition of matter Licensed Patent for a human
antibody.
 
(c)                                  $50,000 within 30 days after the initiation
of the first U.S.  Phase II clinical trial for the first Licensed Product chosen
for development (“First Licensed Product”) by ACORDA or its Affiliates or
Sublicensees.
 
 
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(d)                                 $500,000 upon the approval to market for
therapeutic use given by the FDA to ACORDA or its Affiliates or Sublicensees
(“FDA Approval”) of the First Licensed Product, which amount shall be paid in
four equal installments, the first of which shall be paid within 30 days
following the date of such FDA Approval and the balance of which shall be paid
within 30 days after the end of the three-, six- and nine-month periods
following such date.
 
(e)                                  $125,000 within 30 days after the earlier
of (1) initiation of the second U.S.  Phase III clinical trial for the second
Licensed Product chosen for development, if any, (“Second Licensed Product”) by
ACORDA or its Affiliates or Sublicensees or (2) submission of a New Drug
Application (“NDA”) by ACORDA or its Affiliates or Sublicensees to the FDA for
such Second Licensed Product.
 
(f)                                    $500,000 upon FDA Approval of the Second
Licensed Product, which amount shall be paid in four equal installments, the
first of which shall be paid within 30 days following the date of such FDA
Approval and the balance of which shall be paid within 30 days after the end of
the three-, six- and nine-month periods following such date.
 
(g)                                 $150,000 within 30 days after the earlier of
(1) initiation of the second U.S.  Phase III clinical trial for the third
Licensed Product chosen for development, if any, (“Third Licensed Product”) by
ACORDA or its Affiliates or Sublicensees or (2) submission of an NDA by ACORDA
or its Affiliates or Sublicensees to the FDA for such Third Licensed Product.
 
(h)                                 $500,000 upon FDA Approval of the Third
Licensed Product, which amount shall be paid in four equal installments, the
first of which shall be paid within 30 days following the date of such FDA
Approval and the balance of which shall be paid within 30 days after the end of
the three-, six- and nine-month periods following such date.
 
3.3                                 Running Royalties for Sales of Licensed
Products.
 
(a)                                  In further consideration of the right and
license granted to ACORDA hereunder, ACORDA shall pay to MAYO, in connection
with the sale of Licensed Products by ACORDA or its Affiliates or Sublicensees,
in accordance with the following schedule and rates:
 
(i)                                     With respect to the First Licensed
Product, provided that such First Licensed Product is covered by a Valid Claim
which contains a valid composition of matter claim in the country where it is
sold the applicable royalty rates shall be
 
1.25% of the first $400,000,000 of annual Net Sales; and
 
1.50% of all annual Net Sales in excess of $400,000,000.
 

 
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(ii)                                  With respect to the Second Licensed
Product, the Third Licensed Product, and each subsequent Licensed Product,
provided that each such Licensed Product is covered by a Valid Claim which
contains a valid composition of matter claim in the country where it is sold,
and taking each Licensed Product into account separately and not aggregating Net
Sales of separate Licensed Products, the applicable royalty rates shall be:
 
1.00% of the first $200,000,000 of annual Net Sales;
 
1.50% of annual Net Sales between $200,000,001 and $400,000,000;
 
2.00% of annual Net Sales between $400,000,001 and $500,000,000; and
 
2.5% of annual Net Sales in excess of $500,000,000.
 
(iii)                               With respect to any Licensed Product which
is not covered by a Valid Claim which contains a composition of matter claim in
the country where it is sold, but is covered by a pending patent within the
Licensed Patents containing a valid composition of matter claim in the country
where such Licensed Product is sold, the applicable royalty rate shall be, in
lieu of the foregoing rates, one percent (1.00%) on all annual Net Sales
 
(b)                                 In the event that any of the issued patents
contemplated in Section 3.3(a) contain only awarded valid utility claims, the
Parties shall negotiate in good faith lesser royalty rates for the sale of
Licensed Products.  Such royalty rates shall reflect customary royalties for
intellectual property of the type, degree of proprietary protection and value
mutually agreed to by MAYO and ACORDA.
 
(c)                                  Beginning on the first anniversary of the
first commercial sale of the First Licensed Product, ACORDA shall pay MAYO the
following minimum annual royalties equal to the difference between the actual
annual amounts paid to MAYO pursuant to Section 3.3(a) and (b) and the
following:
 
 
(i)                                     $20,000 on the first anniversary;

 
 

 
(ii)                                  $25,000 on the second anniversary;

 
 

 
(iii)                               $30,000 on the third anniversary; and

 
 

 
(iv)                              $35,000 on the fourth anniversary and on each
anniversary thereafter.

 
 

 
 
 
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3.4                                 Third Party Royalties.  In the event that
ACORDA, its Affiliates or Sublicensees, as the case may be, pays royalties or
other amounts to any third party to make, use or sell a Licensed Product or to
avoid or settle a claim of infringement of the intellectual property rights of
such third party, ACORDA may offset such amounts paid against up to fifty
percent (50%) of the amount of royalties due from ACORDA to MAYO, provided
however, that in no event shall MAYO receive less that one quarter of one
percent (0.25%) of the Net Sales of the Licensed Product sold by ACORDA, its
Affiliates or Sublicensees, as the case may be.
 
3.5                                 Certain Affiliate and Sublicensee
Royalties.  In the event that ACORDA receives any royalties from Affiliates or
Sublicensees with respect to the sale of Licensed Products for use in
applications that ACORDA has decided, in its business judgment, not to
commercialize, ACORDA shall pay MAYO twenty-five percent (25%) of such amounts
received, provided however, that MAYO shall not be entitled to any share of
amounts received by ACORDA from its Affiliates or Sublicensees for:
 
(a)                                  equity;
 
(b)                                 debt;
 
(c)                                  research and development;
 
(d)                                 any payments attributable to performance
based milestones;
 
(e)                                  the license or sublicense of,
 
(i)                                     any intellectual property other than the
Licensed Patents,
 
(ii)                                  any products other than the Licensed
Products; or
 
(f)                                    reimbursement for patent or other
expenses.
 
3.6                                 Obligation to Pay Royalties.  In no event
shall more than one.  royalty be due hereunder with respect to any unit of
Licensed Product even if covered by more than one patent or Valid Claim of any
patent included in the Licensed Patents.  Except as provided in Section 3.5,
there shall be no obligation to pay royalties to MAYO under this Section 3 on
sales of Licensed Products between ACORDA and its Affiliates and Sublicensees,
but in such instances the obligation to pay royalties shall arise upon the sale
by ACORDA or its Affiliates or Sublicensees.  Failure to make such royalty
payments shall be deemed a Material Breach of this Agreement.  Payments due
under this Section 3 shall be deemed to accrue when payment is received by
ACORDA for Licensed Products.
 
3.7                                 Royalties on Combined Products.  Where a
Licensed Product is sold in combination
 
 
 
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with one or more other products that are not Licensed Products (the “Combined
Product”), ACORDA shall pay royalties to MAYO based upon the value of the
Combined Product attributable to the Licensed Patents.  The Parties agree to
negotiate in good faith to reach a mutual agreement concerning the value of
Combined Product attributable to such Licensed Patents, provided however, that
ACORDA shall pay MAYO no less than one quarter of one percent (0.25%) of the Net
Sales of such Combined Product.
 
4.                                      PAYMENTS AND RECORDS.
 
4.1                                 Payment.  Except as otherwise provided
herein, all royalties and other.payments due hereunder shall be paid quarterly
within 45 days after the end of each calendar quarter in which such payments or
royalties accrue.  Each such payment shall be accompanied by a statement
identifying the payments made, including a Licensed Product-by-Licensed Product
and country-by-country statement of the amount of Net Sales during such quarter,
the amount of royalties due on such Net Sales and the amount of any credits
being applied to such royalties.  Failure to make such payments on time shall be
deemed a Material Breach of this Agreement.
 
4.2                                 Mode of Payment.  ACORDA shall make all
payments required under this Agreement in U.S.  Dollars.  The payments due shall
be translated at the rate of exchange at which United States Dollars for the
currency of the country in which the payment accrued, as listed in The Wall
Street Journal on the last business day of the calendar quarter in which such
sales, if any, were made.
 
4.3                                 Taxes.  Royalties shall be paid to MAYO free
and clear of all foreign taxes, including withholding and turnover taxes, except
such taxes which ACORDA may be required to withhold by a foreign country.  Any
tax required to be withheld by ACORDA or its Affiliates or Sublicensees under
the laws of any foreign country for the account of MAYO shall be promptly paid
by ACORDA or its Affiliate or Sublicensee for and on behalf of MAYO, with proof
of payment of such tax together with official or other appropriate evidence
issued by the appropriate governmental authority sufficient to enable MAYO to
support a claim for income tax credit in’ respect to any sum so withheld.  Any
such tax required to be withheld shall be an expense of and borne solely by
MAYO.
 
4.4                                 Records Retention.  ACORDA shall keep
complete and accurate records pertaining to the manufacture, use and sale of
Licensed Products and in sufficient detail to permit MAYO to confirm the
accuracy of royalty calculations under this Agreement.
 
4.5                                 Audit Request.  At the request and expense
of MAYO, ACORDA shall permit an independent, certified public accountant
appointed by MAYO and acceptable to ACORDA, at reasonable times and upon
reasonable notice, to examine those records as may be necessary to: (i)
determine, with respect to any calendar year ending not more than three years
prior to MAYO’s request, the correctness of any report or payment made under
this Agreement; or (ii) obtain
 
 
 
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 information as to the royalty payable for any calendar year in the case of
ACORDA’S failure to report or pay pursuant to this Agreement.  Results of any
such examination shall be made available to both Parties.  MAYO shall bear the
full cost of the performance of any such audit; provided however, that in the
event such audit reveals an underpayment by ACORDA in excess of five percent of
the total amount of payment due by ACORDA to MAYO for any calendar year subject
to such audit, ACORDA shall reimburse MAYO for the cost of such audit.
 
5.                                      DUE DILIGENCE.
 
5.1                                 Diligence.  ACORDA, directly or through its
Affiliates or Sublicensees, shall use reasonable commercial efforts, consistent
with its business judgment, to develop and commercialize Licensed Products
during the term of this Agreement and obtain and maintain such approvals as may
be necessary for the sale of Licensed Products in the United States and in such
other worldwide markets as ACORDA selects to commercialize such Licensed
Products.
 
5.2                                 Reports.  During the term of this Agreement
and until the First Commercial Sale of the first Licensed Product, ACORDA shall
deliver to MAYO semi-annual reports, due within 45 days after the end of each
June and December, summarizing the efforts of ACORDA, its Affiliates and its
Sublicensees to develop and commercialize Licensed Products.
 
(a)                                  If MAYO reasonably believes that ACORDA is
not satisfying ACORDA’s diligence obligations set forth in Section 5.1 (or does
not have sufficient information to make such determination), it may request
ACORDA to inform MAYO of such efforts as ACORDA, its Affiliates or Sublicensees
are undertaking to comply with its obligations thereunder.  Within 60 days from
receipt of such request, ACORDA shall then report its efforts to develop and
commercialize Licensed Products and, if either Party requests, the Parties shall
meet to discuss the situation.
 
(b)                                 At any time during such 60-day period,
either Party may request the use of a mediator to assist in the resolution of
such dispute.  In such event, both Parties shall try in good faith to resolve
such dispute by mediation administered by the American Arbitration Association
under its Commercial Mediation Rules by a single mediator, who shall have
experience and be knowledgeable in the pharmaceutical industry, appointed in
accordance with such rules.  The Parties agree to submit to one day of mediation
to take place within 30 days after the selection of such mediator, unless the
Parties otherwise agree.  The costs of any such mediation, including
administrative fees and fees of the mediator, shall be shared equally by the
Parties, and each Party shall bear its own expenses in such mediation.
 
(c)                                  If, at the end of the later of the 60 day
period referred to in Section 5.3(a) or the unsuccessful conclusion of the
mediation, if any, commenced pursuant to Section 5.3(b), MAYO
 
 
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still believes that ACORDA is not exercising sufficient efforts to satisfy the
diligence obligations set forth in Section 5.1, MAYO shall initiate a Short-Form
Arbitration proceeding pursuant to Section 5.4 within 30 days thereafter.  The
sole question before the arbitrator shall be whether ACORDA is exercising
sufficient efforts to satisfy the diligence obligations set forth in
Section 5.1.  If MAYO fails to initiate such arbitration within such 30 day
period, MAYO shall have no further right to dispute ACORDA’s efforts to satisfy
its diligence obligations with respect to the period in question.
 
(d)                                 The foregoing is intended to provide MAYO
the means to reasonably exercise its rights hereunder, and shall not be used to
place unreasonable reporting burdens on ACORDA.  MAYO may not commence a request
for the foregoing information from ACORDA for at least one year after MAYO last
commenced a request therefor.
 
5.3                                 Short-Form Arbitration.  Any dispute subject
to short-form arbitration as provided in Section 5.3 shall be finally settled by
binding arbitration in New York City, New York (at a specific location to be
agreed upon by the Parties) under the Licensing Rules of the American
Arbitration Association by a panel of one or more arbitrators, who shall have
experience and be knowledgeable in the pharmaceutical industry, appointed in
accordance with such rules.(Such arbitrators shall make their determination on
the basis of “baseball arbitration” principles.  THE FOREGOING REMEDY SHALL BE
EACH PARTY’S SOLE AND EXCLUSIVE REMEDY WITH RESPECT TO ANY SUCH DISPUTE.  Except
as specifically otherwise set forth in Section 5.3 and this Section 5.4 such
arbitration shall be conducted in accordance with the provisions of Exhibit D.
 
 
6.                                      “OWNERSHIP; PATENTS; MARKETING
EXCLUSIVITY; PATENT TERM EXTENSIONS”

 
6.1                                 Ownership.
 
(a)                                  Except as otherwise provided in
Section 6.1(b) through (e), MAYO shall retain all right, title and interest in
and to the Licensed Technology, regardless of which Party prepares and
prosecutes the patent applications associated therewith, or maintains the
patents or other intellectual property rights related, subject to the right and
license granted to ACORDA pursuant to Section 2.
 
(b)                                 Rights to Inventions for which employees or
agents of MAYO are the sole inventor(s) as determined in accordance with U.S. 
patent laws shall belong to MAYO.
 
(c)                                  Rights to Inventions for which employees or
agents of ACORDA are the sole inventor(s) as determined in accordance with U.S. 
patent laws shall belong to ACORDA.
 
(d)                                 Rights to Inventions made jointly by
employees and agents of MAYO and by employees and agents of ACORDA as determined
in accordance with U.S.  patent laws shall belong jointly to MAYO and to ACORDA.
 
 
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(e)                                  Rights held by MAYO in any Inventions,
including without limitation, rights in and to patent applications and patents
which may be obtained thereon, shall be within the terms Licensed Patents and
shall be subject to the license granted to ACORDA herein.
 
(f)                                    In the event as to any Invention either
Party determines that it may be advisable to consider special ownership or
license arrangements among them in order to maximize the commercial protection
or utility afforded under any applicable patent law, the Parties shall discuss
and consider in good faith the implementation of such special arrangements as a
means of maximizing the value of such Invention for their mutual benefit.
 
6.2                                 Patent Prosecution and Maintenance.
 
(a)                                  ACORDA, at its sole cost and expense
(including, without limitation, legal fees, filing and maintenance fees or other
governmental charges), shall (i) commencing on the Effective Date, have full
responsibility for and shall control the preparation and prosecution of all
patent applications, and the maintenance of all patents, related to the Licensed
Technology, and (ii) reimburse the reasonable expenses in connection with such
activities prior to the Effective Date.  actually incurred by MAYO, in
connection with the filing, prosecution and maintenance of the Patent Rights, as
shown by MAYO’s books and records.
 
(b)                                 ACORDA shall select qualified patent counsel
to file and prosecute all such patent applications.  ACORDA shall provide copies
to MAYO of any proposed filings to made to any patent office relating to the
Patent Rights in advance, shall consult with MAYO, and shall in good faith
consider and give due respect to MAYO’s position with respect thereto.  In
addition, ACORDA shall provide copies to MAYO of any written communications
received from any patent office relating to the Patent Rights.
 
(c)                                  MAYO shall provide ACORDA with a credit
against earned royalties due MAYO in the amount of fifty percent (50%) of all
expenses, costs and fees (including attorney’s fee’s) paid by ACORDA in pursuant
to this Section 6.2.  At MAYO’s request, ACORDA shall provide MAYO with
reasonable documentation of such costs.
 
(d)                                 Each Party agrees to cooperate with the
other Party to execute all lawful papers and instruments, to make all rightful
oaths and declarations and to provide consultation and assistance as may be
necessary in the preparation, prosecution, maintenance, and enforcement of all
Patent Rights.
 
6.3                                 Patent Enforcement.
 
(a)                                  If either Party learns of an infringement
or other use, rights or ownership claim or threatened infringement or other such
claim by a third party with respect to any Licensed
 
 
 
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Technology within the Territory, such Party shall promptly notify the other
Party and shall provide such other Party with available evidence of such
infringement, whereupon the parties shall consult to determine if they will
jointly bring action to terminate such infringement or misappropriation.  The
costs and expenses of any such action (including fees of attorneys and other
professionals) shall be borne by the Parties in such proportions as they may
agree in writing.  Any recovery obtained by the Parties in such action shall be
used to reimburse the cost of such action to the Parties in proportion to their
respective contributions to the costs and expenses incurred in such action, and
the remainder shall be divided equally between the Parties.
 
(b)                                 In the event that the Parties fail to
initiate an action to terminate such infringement or misappropriation within
ninety (90) days after the last party receives notice of such infringement or
misappropriation, MAYO shall have the first right, but not the duty, to
institute at its sole cost and expense, actions against third parties based on
any Licensed Technology under this Agreement.  Any recovery obtained by MAYO in
such action shall be used to reimburse the cost of such action and the remainder
shall be retained by MAYO.
 
(c)                                  In the event that the Parties fail to
initiate an action to terminate such infringement or misappropriation within
ninety (90) days after the last party receives notice of such infringement or
misappropriation, and in the event MAYO does not institute an infringement
proceeding against an offending third party within 180 days after the last party
receives such notice, ACORDA shall have the right, but not the duty, to
institute at its sole cost and expense, such an action with respect to any
infringement or misappropriation by a third party.  Any recovery obtained by
ACORDA shall be used to reimburse the cost of such action and the remainder
shall be retained by ACORDA, provided however, that such amount shall be deemed
to constitute Net Sales for purposes of this Agreement.
 
(d)                                 Unless the Parties otherwise agree in
writing, each Party shall execute all necessary and proper documents and provide
reasonable, but not financial, cooperation as shall be appropriate, to allow the
other Party to institute and prosecute such infringement actions.
 
6.4                                 Infringement Action by Third Parties.
 
(a)                                  In the event of the institution of any suit
by a third party against ACORDA for patent infringement involving the
manufacture, sale, offer for sale, distribution or marketing of any Product in
the Territory, ACORDA shall have the right to defend such suit at its own
expense, and MAYO hereby agrees to assist and cooperate with ACORDA, at ACORDA’s
expense, to the extent necessary in the defense of such suit.  During the
pendency of any such action, ACORDA shall continue to make all payments due
under this Agreement, provided however, that ACORDA shall be entitled to a
credit against such payments of an amount equal to one-half of the reasonable
costs actually incurred in such action.
 
 
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(b)                                 If ACORDA finally prevails and receives an
award from such third party as a result of such action (whether by way of
judgment, award, decree, settlement or otherwise), such award shall be
allocated, first, to ACORDA and MAYO to reimburse each Party for its pro rata
share of costs and expenses incurred in such action, and the remaining amount
shall be retained by ACORDA, provided however, that such amount shall be deemed
to constitute Net Sales for purposes of this Agreement.
 
(c)                                  If ACORDA finally loses, whether by
judgment, award, decree or settlement, and is required to pay a royalty or
damages to such third party, ACORDA shall continue to pay the royalties for such
Licensed Product in the country(ies) which is the subject of such action, but
shall be entitled to a credit against such payments in an amount-equal to the
royalty or damages paid to such third party, but in no event shall such credit
be more than 50% of the royalties due hereunder for such Licensed Product in
such country(ies).
 
(d)                                 If ACORDA is required to pay a royalty or
damages to a third party pursuant to Section 6.4(c) and the amount of such
royalty or damages exceeds 50% of the royalties due hereunder for such Licensed
Product in such country(ies), ACORDA shall have the right to terminate this
Agreement solely with respect to such Licensed Product in such country(ies). 
The effect of any such termination shall be the same as any termination by
ACORDA pursuant to Section 9.4.
 
6.5                                 Marketing Exclusivity/Patent Term Extensions
 
(a)                                  ACORDA shall be responsible for taking all
necessary steps to prosecute, perfect and maintain such applicable Marketing
Exclusivity Rights as it deems appropriate.
 
(b)                                 ACORDA grants to MAYO the exclusive right to
rely on any Regulatory Review Period for any Licensed Product and agrees to be
MAYO’s agent for such purposes.  In the event of any request from the Patent and
Trademark Office for assurances that MAYO has the right to rely on the
Regulatory Review Period, including assurances that ACORDA is MAYO’s agent for
such purposes, this Section 6.5 shall be conclusive evidence ofACORDA’s
agreement that MAYO has such right.  Except as may otherwise be contemplated
under this Agreement with respect to the transfer of rights or obligations to
Affiliates, Sublicensees and permitted assignees, ACORDA may not transfer,
assign, license, mortgage or hypothecate in whole or in part to any person,
whether voluntarily or involuntarily, its right to a Regulatory Review Period
for any Licensed Product without the prior written consent of MAYO, which
consent shall not be unreasonably withheld or delayed.
 
(c)                                  Subject to the provisions of Section 6.5
(e), MAYO reserves the right to determine that ACORDA should file and prosecute
any application for a Patent Term Extension;
 
(d)                                 ACORDA agrees to take all reasonable actions
which MAYO determines to be necessary to ensure the complete and timely filing
and prosecution of any application for a Patent
 
 
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Term Extension, including but not limited to providing MAYO with relevant Patent
Term Extension Information.
 
(e)                                  In the event that more than one Licensed
Patent could be the subject of an application for a Patent Term Extension,
ACORDA shall have the right, after consultation with MAYO, to select the
Licensed Patent.
 
7.                                      PUBLICATION; CONFIDENTIALITY.
 
7.1                                 Publication.  ACORDA acknowledges that MAYO
is dedicated to free scholarly exchange and to public dissemination of the
results of its scholarly activities.  In the event MAYO, or any employee,
student or other agent of MAYO who is performing any work with respect to the
Program, wishes to make any publication or otherwise disseminate information
concerning or obtained through the Program, MAYO will deliver to ACORDA copies
of such scientific articles, papers and abstracts for review and comment at
least 60 days prior to the date of submission for publication or presentation. 
ACORDA’s permission to publish shall not be unduly withheld, and ACORDA’s
permission or withholding of such permission will be submitted to MAYO in
writing not later than 30 days following’ ACORDA’s receipt of the material for
review.  If ACORDA determines that such proposed publication or presentation
contains patentable subject matter that requires protection, ACORDA may require
the delay of publication or presentation for a period not to exceed 90 days for
the purpose of allowing the filing of patent applications.  If ACORDA identifies
any of ACORDA’s Confidential Information (as defined herein) in such proposed
publication or presentation, MAYO will delete such information from same, or
modify the disclosure of such information from same in a manner reasonably
acceptable to ACORDA.
 
7.2                                 Confidentiality; Exceptions.
 
(a)                                  “Confidential Information of a party shall
mean all reports, data and information disclosed by such party to another party,
which is (i) in writing and marked “CONFIDENTIAL” or “PROPRIETARY or marked with
words of similar import, or (ii) disclosed through oral, visual, or other
non-written means, identified as confidential or proprietary at the time of
initial disclosure, and summarized and confirmed as confidential or proprietary
in writing to the receiving party within thirty (30) days of such disclosure. 
Any markings, stamps, or legends identifying confidential information shall not
impose any obligations on either party inconsistent with this agreement.  Any
copies of the information made by the receiving party shall reproduce the
confidential markings and any other legends contained on such information.
 
(b)                                 Except to the extent expressly authorized by
this Agreement or otherwise agreed in writing, the Parties agree that, during
the term of this Agreement and for five years thereafter, the receiving Party,
its Affiliates, its licensees and its Sublicensees shall keep, and shall ensure
that their respective employees, officers, directors and trustees shall keep,
completely confidential and shall not publish or otherwise disclose and shall
not use any Confidential
 
 

 
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Information for any purpose other than carrying out the obligations of the
receiving Party under this Agreement except to the extent that it can be
established by the receiving Party by competent proof in the form of written
records maintained by the receiving Party that such information: (i) was already
known to the receiving Party, other than under an obligation of confidentiality,
at the time of disclosure by the disclosing Party; (ii) was generally available
to the public or otherwise part of the public domain at the time of its
disclosure to the receiving Party; (iii) became generally available to the
public or otherwise part of the public domain after its disclosure and other
than through any act or omission of the receiving Party in breach of this
Agreement; or (iv) was disclosed to the receiving Party, other than under an
obligation of confidentiality, by a third party who had no obligation to the
disclosing Party not to disclose such information to others.
 
7.3                                 Exceptions to Obligation.  The restrictions
contained in Section 7.2 shall not apply to Confidential Information that: (i)
is submitted by the recipient to governmental authorities to facilitate the
issuance of marketing approvals for Licensed Products, provided that reasonable
measures shall be taken to assure confidential treatment of such information;
(ii) is provided by the receiving Party to third parties under appropriate terms
and conditions, including confidentiality provisions substantially equivalent to
those in this Agreement, for consulting, manufacturing development,
manufacturing, external testing and marketing trials; or (iii) is otherwise
required to be disclosed in compliance with applicable laws or regulations or
order by a court or other regulatory body having competent jurisdiction,
provided that if a Party is required to make any such disclosure of the other
Party’s Confidential Information it will, except where impracticable for
necessary disclosures, for example to physicians conducting studies or to health
authorities, give reasonable advance notice to the other Party of such
disclosure requirement and, except to the extent inappropriate in the case of
patent applications, will use its best efforts to secure confidential treatment
of the Confidential Information required to be disclosed, and shall cooperate
with efforts of the disclosing Party to limit disclosure, as appropriate.
 
7.4                                 Confidentiality regarding Patient
Information.  Notwithstanding anything in this Section 7 to the contrary,
identifiable patient information obtained in the performance of the Program
shall be deemed Confidential Information and shall be kept confidential by both
Parties permanently except: (i) when that information is required to be
disclosed by regulatory authorities; or (ii) with the patient’s consent.
 
8.                                      INDEMNIFICATION.
 
8.1                                 Products Liability.  ACORDA shall defend,
indemnify and hold MAYO and MAYO’s Affilitates, and their respective trustees,
officers and employees, harmless from and against any and all claims, suits or
demands for liability, damages, losses, costs and expenses (including the costs
and expenses of attorneys and other professionals) (collectively, a “Claim”)
arising out of or resulting from third party claims or suits resulting from: (i)
the use by ACORDA or its Affiliates
 
 
 
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or Sublicensees of any of the Licensed Technology, (ii) the use by ACORDA or its
Affiliates or Sublicensees of information concerning or obtained through the
Program, or (iii) the manufacture, use, sale or offer for sale of a Licensed
Product by ACORDA or its Affiliates or Sublicensees pursuant to this Agreement;
provided that such Claim does not arise out of or result from a breach of any of
MAYO’s representations or warranties made under this Agreement, and provided
further that such Claim is not covered by MAYO’s indemnification provided in
Section 8.2.
 
ACORDA shall, during the term of this Agreement, carry occurrence-based
liability insurance with policy limits of at least THREE MILLION DOLLARS
($3,000,000).  In addition, such policy shall name MAYO as an additional-named
insured.
 
8.2                                 MAYO Indemnification.
 
(a)                                  MAYO shall defend, indemnify and hold
ACORDA and its Affiliates and Sublicensees and their respective directors,
officers and employees, harmless from and against any and all Claims arising out
of or resulting from third party claims or suits resulting from (a) any
negligence, recklessness or wrongful intentional acts or omissions of MAYO and
its trustees, officers, employees and agents, including Dr.  Moses Rodriguez and
Dr.  Larry Pease in connection with (i) the work performed by MAYO, Dr.  Moses
Rodriguez or Dr.  Larry Pease under the Program, and (ii) any other development
and/or commercialization work relating to any Licensed Products or Licensed
Technology before the Effective Date, or thereafter in connection with MAYO’s,
Dr.  Rodriguez’ or Dr.  Pease’s development of Licensed Products or Licensed
Technology; excepting in any case to the extent any such Claims result from the
negligence, recklessness or wrongful intentional acts or omissions of ACORDA or
its Affiliates or Sublicensees, or their respective directors, officers,
employees or agents.
 
(b)                                 Notwithstanding any other provision of this
Agreement, including those which may impose any obligation or cost on ACORDA in
‘connection with patent prosecution, enforcement and infringement actions from
third parties under Section .6, MAYO shall defend, indemnify and hold ACORDA and
its Affiliates and Sublicensees and their respective directors, officers and
employees, harmless from and against any and all Claims arising out of or
resulting from third party claims or suits resulting from or in any way related
to the TEVA Agreement and MAYO shall, at its sole expense, take all reasonable
actions and adopt all reasonable positions with third parties in order to permit
ACORDA full enjoyment of the exclusive license granted under this Agreement and
to avoid or mitigate any conflicts between with the license hereunder and any
rights which MAYO may have granted under the TEVA Agreement in ACORDA’s favor.
 
8.4                                 Notice; Waiver of Subrogation.
 
(a)                                  In the event that any person entitled to
indemnification (an “Indemnitee”) seeks indemnification under this Section 8,
the Indemnitee agrees to: (i) promptly inform the indemnifying Party (the
“Indemnitor”) of any claim, suit or demand threatened or filed, (ii) permit
 
 
 
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the Indemnitor to assume direction and control of the defense or Claims
resulting therefrom (provided that Indemnitor may not settle any Claim against
an Indemnitee without the consent of the Indemnitee, which consent shall not be
unreasonably withheld), and (iii) cooperate as requested (at the expense of the
Indemnitor) in the defense of the Claim.
 
(b)                                 Except as otherwise expressly provide in
this Agreement, each Indemnitor waives any right of subrogation that it may have
against an Indemnitee resulting from any Claim for which an Indemnitor has
agreed to indemnify an Indemnitee under Section 8 of thisAgreement.  Such waiver
shall not, however, be deemed a waiver of any subrogation rights an Indemnitor
may have against third parties.
 
9.                                      TERM AND TERMINATION.
 
9.1                                 Term.  This Agreement shall commence as of
the Effective Date and, unless sooner terminated as provided hereunder, shall
expire as follows:
 
(a)                                  As to each Licensed Product and as to each
country in the Territory, on a country-by-country and Licensed
Product-by-Licensed Product basis upon the expiration of the last to expire
Licensed Patent in such Licensed Product or in such country, as the case may be.
 
(b)                                 This Agreement shall terminate in its
entirety upon its termination as to all Licensed Patents in all countries.
 
9.2                                 Breach.  A Material Breach by either Party
of any of the obligations contained in this Agreement shall entitle the other
Party to give to the Party in default notice specifying the nature of the
Material Breach and requiring it to cure such Material Breach.  If such Material
Breach is not cured within 90 days after the receipt of such notice (or, if such
Material Breach reasonably cannot be cured within such 90-day period, if the
Party in default does not commence and diligently continue actions to cure such
default during such 90-day period), the notifying Party shall be entitled,
without prejudice to any of the other rights conferred on it by this Agreement,
and in addition to any other remedies available to it at law or in equity, to
terminate this Agreement by giving written notice to take effect on the date of
such notice.  The right of either Party to terminate this Agreement, as provided
in this Section 9.2, shall not be affected in any way by its waiver or failure
to take action with respect to any previous Material Breach.
 
9.3                                 Insolvency or Bankruptcy.  In the event that
either Party shall become insolvent, shall make an assignment to the benefit of
creditors, or shall have a petition in bankruptcy filed for or against it
(which, in the case of an involuntary petition, is not dismissed or stayed
within sixty (60) days after such petition is.filed) (a “Bankrupt Party”), the
other Party shall have the right to terminate this Agreement in its entirety
immediately upon written notice of such Termination.  All rights and
 
 
 
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 licenses granted by the Bankrupt Party under this Agreement are, and shall
otherwise be deemed to be; for purposes of Section 365(n) of Title 11, US Code
(the “Bankruptcy Code”), licenses of rights to “intellectual property” as
defined under Section 101(60) of the Bankruptcy Code.  Unless the other Party
elects to terminate this Agreement under this Section, the Parties agree that
the other Party, as a licensee of such rights under this Agreement, shall retain
and may fully exercise all of its rights and elections under the Bankruptcy
Code, subject to the continued fulfillment of its obligations under this
Agreement.
 
9.4                                 Termination by ACORDA.  ACORDA shall have
the right to terminate the right and license granted herein, in whole or as to
any Licensed Product in any country in the Territory, at any time, and from time
to time, by giving written notice to MAYO.  Such termination shall be effective
90 days from the date such notice is given, and all of ACORDA’s rights
associated with such Licensed Product(s) and such country(ies) shall cease as of
that date, subject to Sections 9.5 through 9.7.
 
9.5                                 Right to Sell Stock on Hand.  Upon the
termination of any right and license granted herein, in whole or as to any
Licensed Product, for any reason other than ACORDA’s failure to cure a Material
Breach of this Agreement, ACORDA shall have the right for one year or such
longer period as the Parties may reasonably agree in writing to dispose of all
Licensed Products or substantially completed Licensed Products then on hand to
which such termination applies, and royalties shall be paid to MAYO with respect
to such Licensed Products as though this Agreement had not terminated.
 
9.6                                 Effect of Termination.
 
(a)                                  Following the expiration of any right and
license granted under this Agreement in whole or in part as to any Licensed
Product in any country in the Territory pursuant to Section 9.1, ACORDA shall
have the royalty-free, non-exclusive right to continue to use the Licensed
Technology for the manufacture, use and sale of Licensed Products as theretofore
licensed under this Agreement.
 
(b)                                 Upon Termination of this Agreement by ACORDA
pursuant to Section 9.2 or 9.3: (i) MAYO shall promptly transfer to ACORDA
copies of all data, reports, records and materials in MAYO’s possession or
control that relate to the Licensed Products and return to ACORDA all relevant
records and materials in MAYO’s possession or control containing Confidential
Information ofACORDA, including all information concerning or obtained through
the Program; (ii) ownership of all INDs, PLAs and other regulatory filings made
or filed for any Product shall be transferred solely to ACORDA, and (iii) at
ACORDA’s election, any sublicenses granted by ACORDA under the Licensed
Technology shall be deemed terminated or automatically assigned to MAYO.
 
(c)                                  Upon Termination of this Agreement by MAYO
pursuant to Section 9.2 or 9.3: (i) ACORDA shall promptly transfer to MAYO
copies of all data, reports, records and materials
 
 
 
22

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 in ACORDA’s possession or control that relate to the Licensed Products and
return to MAYO all relevant records and materials in ACORDA’s possession or
control containing Confidential Information of MAYO; (ii) all licenses granted
for Licensed Technology by MAYO to ACORDA under Section 2 shall terminate; (iii)
all sublicenses granted by ACORDA under the Licensed Technology shall be deemed
automatically assigned to MAYO.  Thereafter, MAYO shall have the right to
develop, make, have made, use, sell or have sold any Licensed Product.
 
(d)                                 Upon Termination of this Agreement by ACORDA
pursuant to Section 9.4: (i) each Party shall promptly transfer to the other
Party copies of all data, reports, records and materials of the other Party in
the possession or control of such Party that relate to the Licensed Products;
(ii) each Party shall promptly return to the other Party all relevant records
and materials in such Party’s possession or control containing Confidential
Information of the other Party; and (ii) all licenses granted by either Party to
the other Party under Section 2 shall terminate.  Thereafter, each Party shall
have the right to develop, make, have made, use, sell or have sold any Licensed
Product, to the extent legally permissible.
 
9.7                                 Accrued and Surviving Rights and
Obligations.  Termination, relinquishment or expiration of this Agreement for
any reason shall be without prejudice to any rights, obligations or liabilities
which shall have accrued to the benefit of either Party prior to such
Termination, relinquishment or expiration (including, without limitation,
ACORDA’s obligation to pay all royalties which shall have accrued hereunder as
of the effective date of such Termination).  The Parties’ rights and obligations
under Sections 4, 6, 7, 8, 9.5, 9.6, 9.7, 10.5, and 10.12 shall survive
Termination.
 
10.                               MISCELLANEOUS PROVISIONS.
 
10.1                           Relationship of Parties.  Nothing in this
Agreement is intended or shall be deemed to constitute a partnership, agency,
employer-employee or joint venture relationship between the Parties.  No Party
shall incur any debts or make any commitments for the other, except to the
extent, if at all, specifically provided herein.
 
10.2                           Assignment.  Except as otherwise provided herein,
neither this Agreement nor any interest hereunder shall be assignable by any
Party without the prior written consent of the other, which consent shall not be
unreasonably withheld; provided, however, that either Party may assign this
Agreement to any wholly-owned subsidiary or to any successor by merger or sale
of substantially all of those of its assets to which this Agreement relates in a
manner such that the assignor shall remain liable and responsible for the
performance and observance of all its duties and obligations hereunder.  This
Agreement shall be binding upon the successors and permitted assigns of the
Parties, and the name of a Party appearing herein shall be deemed to include the
names of such Party’s successors and permitted assigns to the extent necessary
to carry out the intent of this Agreement.  Any assignment not in accordance
with this Section 10.2 shall be void.
 
 
 
23

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10.3                           Further Actions.  Each Party agrees to execute,
acknowledge and deliver such further instruments, and to do all such other acts,
as may be necessary or appropriate in order to carry out the purposes and intent
of this Agreement..
 
10.4                           Force Majeure.  Neither Party shall be liable to
the other for loss or damages or shall have any right to terminate this
Agreement for any default or delay attributable to any act of God, flood, fire,
explosion, strike, lockout, labor dispute, shortage of raw materials, casualty
or accident, war, revolution, civil commotion, act of public enemies, blockage
or embargo, injunction, law, order, proclamation, regulation, ordinance, demand
or requirement of any government or subdivision, authority or representative of
any such government, or any other.  cause beyond the reasonable control of such
Party, if the Party affected shall give prompt notice of any such cause to the
other Party.  The Party giving such notice shall thereupon be excused from such
of its obligations hereunder as it is thereby disabled from performing for so
long as it is so disabled and for 30 days thereafter.
 
10.5                           No Trademark Rights.  Except as otherwise
provided herein, neither Party shall have any right, express or implied, to use
in any manner, in connection with the performance of this Agreement, the name or
other designation of the other Party or any other logo, name, tradename, service
mark or trademark of the other Party, or the name of any employee or agent of
the other Party, without that Party’s prior, written, express consent.  Either
Party may withhold such consent in either Party’s absolute discretion.  For MAYO
or its Affiliates, such names and marks include, but are not limited to, the
terms “Mayo®,” “Mayo Clinic®,” or any simulation, abbreviation, or adaptation of
the same.  Violation of this Section 10.5 by either Party shall be deemed a
Material Breach of this Agreement, entitling the other Party to appropriate
equitable or legal relief.
 
10.6                           Public Announcements.  Except as required by law,
including but not limited to, disclosures to prospective investors as required
under applicable state and federal securities laws or as.  required for
documents or other communications to be filed or distributed pursuant to
requirements of the Securities and Exchange Commission, any stock exchange or
NASDAQ, (“Permitted Public Announcement”) neither party shall make any public
announcement concerning this Agreement or the subject matter hereof without the
prior written consent of the other to the text of such public announcement.  In
the event of a Permitted Public Announcement, the Party making such announcement
shall provide the other with a copy of the proposed text prior to such
announcement.  In the event that a party has obtained consent to the text of
such other public announcement, such party shall be entitled to use and reuse,
without limitation and in any form, such text in one or more public
announcements.
 
10.7                           Notices.  All notices and other communications
required or permitted to be given under or in connection with this Agreement
shall be in writing, and shall be deemed given if delivered personally or by
facsimile transmission (receipt verified), express courier service (signature
required), or mailed by registered or certified mail (return receipt requested),
postage prepaid, to the
 
 
 
24

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Parties at the following addresses (or at such other address for a Party as
shall be specified by like notice; provided, that notices of a change or address
shall be effective only upon receipt thereof):
 
(a)
If to ACORDA, to:
     
ACORDA THERAPEUTICS, INC.
 
15 Skyline Drive
 
Hawthorne, New York 10532
 
Attention: President
 
Facsimile No.: (914)347-4560
   
(b)
If to MAYO, to:
     
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
 
200 First Street, SW
 
Rochester, Minnesota 55905
 
Attention: Office of Technology Commercialization, Mayo Medical Ventures
 
Facsimile No.: 507-284-5410

 
If delivered personally or by facsimile transmission, the date of delivery shall
be deemed to be the date on which such notice or request was given.  If sent by
overnight express courier service, the date of delivery shall be deemed to be
the next business day after such notice or request was deposited with such
service.  If sent by registered or certified mail, the date of delivery shall be
deemed to be the third business day after such notice or request was deposited
with the U.S.  Postal Service.
 
10.8                           Amendment.  No amendment, modification or
supplement of any provision of this Agreement shall be valid or effective unless
made in writing and signed by a duly authorized officer of each Party, and
specifically referencing this Agreement.
 
10.9                           Waiver.  No provision of this Agreement shall be
waived by any act, omission or knowledge of a Party or its agents or employees
except by an instrument in writing expressly waiving such provision and signed
by the waiving Party.
 
10.10                     Severability.  Whenever possible, each provision of
this Agreement will be interpreted in such manner as to be effective and valid
under applicable law, but if any provision of this Agreement is held to be
prohibited by or invalid under applicable law, such provision will be
ineffective only to the extent of such prohibition or invalidity, without
invalidating the remainder of this Agreement.
 
10.11                     Compliance with Law.  Nothing in this Agreement shall
be deemed to permit a Party to export, reexport or otherwise transfer any
Know-How transferred hereunder or Licensed Products manufactured therefrom
without compliance with applicable laws.
 
 
 
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10.12                     Governing Law and Jurisdiction.  This Agreement shall
be governed by Minnesota law, but specifically not including Article 2 of the
Uniform Commercial Code as enacted in Minnesota.  This is not a contract for the
sale of goods.  In addition, no Minnesota conflicts-of-law or choice-of-laws
provisions apply to this Agreement.  To the extent the substantive and
procedural law of the United States would apply to this Agreement, it supersedes
the application of Minnesota law.  The parties agree that all disputes between
them concerning this contract, other than as provided for in Section 5.4 hereto,
whether arising before or after Termination, will be settled only according to
the arbitration process described in Exhibit D, attached to and incorporated
into this Agreement, and not through any action at law or in equity, except as
otherwise permitted under Exhibit D.
 
10.13                     Entire Agreement of the Parties.  This Agreement,
including the exhibits attached, constitutes and contains the entire
understanding and agreement of the Parties and cancels and supersedes any and
all prior negotiations, correspondence, understandings and agreements, whether
oral or written, between the Parties respecting the subject matter hereof.
 
10.14                     Descriptive Headings.  The descriptive headings of
this Agreement are for convenience only, and shall be of no force or effect in
construing or interpreting any of the provisions of this Agreement.
 
10.15                     Nondisclosure.  Neither Party shall disclose any of
the terms of this Agreement without the express, prior, written consent of the
other Party, or unless required by law.
 
10.16                     Counterparts.  This Agreement maybe executed in
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same agreement.
 
* * *
 
 
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IN WITNESS WHEREOF, each of the Parties has caused this License Agreement to be
signed by its duly authorized representative as of the date first written above.
 
 

 
ACORDA THERAPEUTICS
         
By:
/s/ Ron Cohen
       
Name: Ron Cohen
     
Title: President and CEO
         
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
         
By:
/s/ Rick F. Colvin
       
Name: Rick F.  Colvin
     
Title:  Assistant Treasurer
           

 

 
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Exhibit A
to
License Agreement between
Acorda Therapeutics, Inc. and the
Mayo Foundation for Education and Research,
dated September 8, 2000
 

 
 

--------------------------------------------------------------------------------

 

 
APPENDIX A
SPONSORED RESEARCH AGREEMENT
 
Effective as of October 1,1995, MAYO FOUNDATION FOR MEDICAL EDUCATION AND
RESEARCH, a Minnesota charitable corporation (MAYO), with Moses Rodriguez, M.D.
as principal investigator (INVESTIGATOR) and, Acorda Therapeutics, Inc. a
Delaware corporation (ACORDA) agree as follows:
 
Article 1.    Project Summary
 
1.1 — MAYO will undertake a research project described in the protocol attached
here as Exhibit A (PROTOCOL). Summary data about the project is set forth as
follows:
 

 
(a)
TITLE:    Preclinical Studies of a Monoclonal Antibody Designed to Promote
Central Nervous Repair
           
(b)
PURPOSE:     Determine suitability of monoclonal antibody SCH 94.32 in promoting
CNS remyelination in animal models of spinal cord injury and multiple sclerosis
           
(c)
START DATE:     October 1, 1995
           
(d)
PROJECTED COMPLETION DATE:        September 30, 1998
           
(e)
FUNDING AMOUNT:         $292,000
           
(f)
PAYMENT PLAN:       Quarterly payments in advance, except that final quarter
payment in each year is payable on receipt of a written Annual Report Year 1 -
$63,000; Year 2 - $110,000; Year 3 - $118,000
           
(g)
CHECKS PAYABLE TO:
 
Mayo Foundation for Medical Education and Research
           
(h)
CHECKS MAILED TO:
 
Office of Technology Transfer
Mayo Medical Ventures
200 First Street S.W.
Rochester, Minnesota 55905
Attn: Susan L. Stoddard, Ph.D.
           
(i)
MAYO ADMINISTRATIVE CONTACT:
 
Susan L. Stoddard, Ph.D.
Mayo Medical Ventures
200 First Street S.W.
Rochester, Minnesota 55905
507-284-8878
           
(j)
ACORDA ADMINISTRATIVE CONTACT:
 
Ron Cohen, M.D.
Acorda Therapeutics, Inc.
1213 Park Avenue
New York, NY 10128
212-876-2522

 
1.2 — Anything contained in the PROTOCOL which is in conflict with anything in
this Agreement is superseded by this Agreement.
 
1

 
 

--------------------------------------------------------------------------------

 

 
Article 2. Proprietary Data Provided To Mayo By Acorda
 
2.1 — ACORDA may provide MAYO and INVESTIGATOR with proprietary data (DATA)
relevant to the work under this Agreement. MAYO’s and INVESTIGATOR’S acceptance
and use of DATA shall be subject to the following:
 
 
a)             DATA must be marked or designated in writing as proprietary to
ACORDA by marking it “CONFIDENTIAL,” or words of similar import. If oral,
visual, or other non-written manner of disclosure of otherwise undisclosed
confidential information is made, such information shall be entitled to
protection if identified as confidential at the time of initial disclosure and
if a written notice with a summary of such disclosures is delivered to the
receiving party within thirty (30) days of such disclosure. Any markings,
stamps, or legends identifying confidential information shall not impose any
obligations on either party inconsistent with this agreement. Any copies of the
information made by the receiving party shall reproduce the confidential
markings and any other legends contained on such information.

 
 

 
b)            MAYO and INVESTIGATOR retain the right to refuse to accept any
DATA which they do not consider to be essential to the completion of the project
or which they believe to be improperly designated or for any reason.

 
 

 
c)             Where MAYO and INVESTIGATOR accept such DATA, they agree to
exercise their best efforts not to use the DATA for any purpose except the
conduct of the PROTOCOL and not to publish or otherwise reveal the DATA to
others outside Mayo without the permission of the ACORDA, unless the DATA has
already been published or disclosed publicly by third parties or is required to
be disclosed by order of a court of law.

 

Article 3.     Inventions, Discoveries And Patents
 
3.1 — All original data and records of the work completed under this Agreement
shall remain the property of MAYO.
 
3.2 — MAYO shall own all of its inventions, discoveries and other developments,
whether or not patentable arising out of research carried out under the
provisions of this Agreement. ACORDA shall own all of its inventions,
discoveries and other developments, whether or not patentable arising out of
research carried out under the provisions of this Agreement. Inventions or
discoveries made jointly by both MAYO and ACORDA shall be jointly owned by both
parties and, if patent applications are filed, patents shall be applied for on
behalf of both parties.
 
Article 4.      Publication
 
4.1 — MAYO and INVESTIGATOR reserve the right to publish the results of work
completed under this Agreement. Prior review of the proposed publication by
ACORDA will be provided, but in the interest of free exchange of scientific
information, MAYO and INVESTIGATOR may publish after the expiration of
forty-five (45) days following mailing of the proposed publication to ACORDA.
Publication of the results will not include DATA as defined in Article 2 without
the permission of ACORDA. At ACORDA’s request, MAYO will delay submission,
disclosure, or publication for an additional sixty (60) days in order to enable
the preparation and filing of a patent application on any such patentable
subject matter.
 
2

 
 

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Article 5.     Use Of Name
 
5.1 — ACORDA and MAYO shall not use expressly or by implication, any trademark,
trade name, or any contraction, abbreviation, simulation, or adaptation thereof
of the other party, or the name of any of other party’s staff in any news,
publicity release, policy recommendation, advertising or any commercial
communication without the express written approval of the other party.
 
Article 6.     Indemnification And Negation Of Warranties
 
6.1 — ACORDA agrees to defend, indemnify and hold harmless MAYO and INVESTIGATOR
against any and all costs, damages, expenses, including attorneys fees, arising
from any claims, damages and liabilities asserted by third parties arising from
ACORDA’s use of the results of the work performed under this Agreement.
 
MAYO agrees to defend, indemnify and hold harmless ACORDA against any and all
costs, damages, expenses, including attorneys fees, arising from any claims,
damages and liabilities asserted by third parties arising from MAYO’s conduct or
use of the results of the work performed under this Agreement.
 
As used in the preceding parts of this paragraph, MAYO includes its Trustees,
Officers, Agents, and Employees and ACORDA includes any of its “Affiliates”. An
“Affiliate” of ACORDA shall mean any corporation or other business entity
controlled by, controlling, or under common control with ACORDA. For this
purpose “control” means direct or indirect beneficial ownership of at least
fifty (50%) percent of the voting stock, or at least fifty (50%) percent
interest in the income of such corporation or other business
 
6.2 — MAYO makes no representations or warranties, expressed or implied,
regarding its performance under this Agreement, including but not limited to,
the marketability, use or fitness for any particular purpose of the research
results developed under this work, or that such results do not infringe upon any
third party property rights. Further, MAYO shall not be liable for special,
consequential, or incidental damages, and MAYO’s sole liability for damages
hereunder shall be a sum equal to the amount paid by ACORDA to MAYO under this
Agreement.
 
Article 7.     Fiscal Management
 
7.1 — MAYO shall maintain complete and accurate accounting records in accordance
with accepted accounting practices. These records shall be available for
inspection, review and audit at reasonable times by ACORDA, or its duly
authorized representative, at ACORDA’s expense, for three (3) years following
the end of the calendar year in which such costs are incurred.
 
7.2 — MAYO shall retain title to equipment and all other items purchased with
funds provided by ACORDA.
 
7.3 — Mayo shall not utilize funds from any other commercial entity to conduct
the PROTOCOL.
 
Article 8.     Termination
 
8.1 — If for any reason INVESTIGATOR becomes unavailable to direct the
performance of the work under this Agreement, MAYO shall notify ACORDA. If a
mutually acceptable successor is not identified, this Agreement may be
terminated immediately by either party and ACORDA shall have no further
obligation to pay MAYO further funds for the conduct of the PROTOCOL, except as
set forth in Section 8.3.
 
3

 
 

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8.2 — Following nine (9) months after the effective date of the Option
Agreement, ACORDA shall have the right to terminate this agreement at will
within ninety (90) days notice; provided, ACORDA shall be obligated to pay MAYO
the salary and benefits of one research technician until the second anniversary
of the effective date of the Option Agreement, unless MAYO receives extramural
contract or grant funds to support such technician. Should ACORDA terminate this
Agreement under this Section 8.2, MAYO agrees to best efforts to find other
sources of funding for the technical salary.
 
8.3 — If this Agreement is terminated, ACORDA shall pay for all direct costs
incurred, up to and including the effective date of termination, and for all
noncancellable obligations made before receipt of notice of termination, even
though they may extend beyond such termination date. Any unexpended funds paid
by ACORDA and held by MAYO after satisfying the obligations set forth in this
paragraph will be returned to ACORDA.
 
8.4           ACORDA and MAYO maintain the right to terminate this Agreement if
a material breach is committed by the other party, if this breach is not cured
within thirty (30) days after written notice to the breaching party. If this
Agreement is so terminated under this Section 8.4, the terminating party shall
maintain no continuing financial obligation to the breaching parry.
 
Article 9.     General
 
9.1 — This Agreement may be amended only by the written agreement of the
parties.
 
9.2 — This Agreement may not be assigned by MAYO or ACORDA without the prior
written consent of the other.
 
9.3 — The captions and headings used in this Agreement are for convenience and
reference only and are not a part of this Agreement.
 
9.4 — All notices shall be in writing and shall be effective when mailed.
Notices should be sent to the respective administrative contacts set forth in
paragraph 1.1 of this Agreement.
 
9.5 — This Agreement and its effects are subject to and shall be construed and
enforced in accordance with the laws of the State of Minnesota.
 
9.6 — There is one addenda to this Sponsored Research Agreement:
 
a)             Exhibit A: Research Protocol
 
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
 
ACORDA THERAPEUTICS, INC.
     
By
/s/ Rick F. Colvin
   
By
/s/ Ron Cohen
       
Title
Assist. Treas.
   
Title
President & CEO
       
Date
Oct. 11, 1995
   
Date
10/06/95
               
/s/ Moses Rodriguez
         
Investigator
                           

 
4

 
 

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EXHIBIT A to SPONSORED RESEARCH AGREEMENT
 
Protocol
 
PROPOSAL FOR RON COHEN - ACORDA
 
TITLE:    Pre-clinical Studies of a Monoclonal Antibody Designed to Promote
Central Nervous System Repair
 
INVESTIGATOR:  Moses Rodriguez, M.D.
 
INTRODUCTION AND SCIENTIFIC RATIONALE:
 
Our laboratory has been interested in developing novel strategies to promote
central nervous system (CNS) remyelination.  Even though there is experimental
evidence in animals and humans that remyelination does occur in the CNS, at
present there are no pharmacological approaches to promote CNS remyelination. 
We have used an experimental model induced by a virus to investigate ways to
promote CNS remyelination in the spinal cord.  Susceptible strains of mice
infected intracerebrally with Theiler’s murine encephalomyelitis virus (TMEV)
develop chronic progressive immuna-mediated CNS demyelinating disease which is
similar to multiple sclerosis (MS).  Our previous reports indicated that
polyclonal immunoglobulins from mice immunized with homogenized spinal cord
promoted CNS remyelination when given to SJL/J mice chronically infected for 3
to 6 months with TMEV.  To explore further the mechanisms of CNS remyelination,
we made a panel of monoclonal antibodies (mAbs) derived from splenocytes of
SJL/J mice injected with homogenized spinal cord.  These mAbs were screened for
function rather than for specific antigens.  We identified two monoclonal IgM
autoantibodies, designated SCH 94.03 and SCH 94.32, which promoted four-fold
increase in CNS remyelination compared to isotype IgM kappa controls when given
to chronically infected SJL/J mice.  The results of these experiments are in
press in the Journal of Neuroscience.  CNS remyelination was detected
morphologically by the presence of abnormally thin myelin sheaths relative to
axon diameter.  In these experiments, as little as 10 µg of antibody promoted
CNS remyelination. We assessed whether morphologic remyelination was correlated
with clinical signs of disease improvement.  With each treatment injection,
animals were assessed clinically.  We correlated the change in clinical score
with the percentage of lesion area showing remyelination.  Using data from all
treatment groups, there was a moderate but significant correlation with the
percentage of lesion area showing remyelination with less progression of
clinical disease. A few animals treated with mAb actually improved clinically.
However, the majority of the animals showed less progressive disease than
animals treated with isotype control antibody.
 
We are in the process in determining the antigen specificity for SCH 94.03 and
SCH 94.32.  To characterize initially the antigens recognized by mAbs, we
immunostained various cell lines from glial, neural, fibroblast, epithelial and
lymphoid origins.  Thus far, the mAbs strain structural internal antigens of all
cell lines tested.  Only cells or primary cell lines of oligodendroglial lineage
stain on the surface with these mAbs.  Surface staining has been confirmed by
flow cytometry.  Surface labelling has also been detected on live rat, mouse,
and human oligodendrocytes.
 
1

 
 

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We have evidence that mAbs SCH 94.03 and SCH 94.32 are identical and are natural
autoantibodies.  This hypothesis was tested using a series of strategies
including immunocytochemistry, Western blotting, enzyme-linked immunosorbent
assays, and Ig variable region sequencing.  Natural autoantibodies are typically
encoded by germline Ig genes, with few if any V region somatic mutations.
Therefore, we cloned and sequenced both the Ig VL and VH regions from SCH94.03. 
The SCH94.03 VL region was encoded by a combination of Vk10 and Jkl gene
segments.  In the coding region, the SCH94.03 Vk gene segment showed 99.6%
nucleotide identity with a germline Vk10 gene, with only one silent nucleotide
difference at the V gene segment 3’ end, at the V-J junction (codon 95). 
Similarly, the SCH94.03 Jk gene segment showed 97.4% nucleotide identity with
the germline Jkl gene, with one silent nucleotide change at the J gene segment
3’ end, at the J-Ck junction (codon 108).  As both of these changes were in
junction regions, and the genomic nucleotide immediately upstream from the
coding regions of both Jkl and Ckgene segments is a C, these changes may have
resulted from imprecise joining during Ig gene rearrangement, rather than from
somatic mutation.  We concluded that the VL region of SCH94.03 was encoded by
germline Ig genes.
 
The VH region of SCH94.03 was also encoded by germline Ig genes.  The SCH94.03
VK region was encoded by a combination of V23, DFL16.1, and JK2 gene segments. 
The SCH94.03 VH gene segment showed 100% nucleotide identity with the germline
V23 gene, a member of the VKJ558 family.  The SCH94.03 JH gene segment showed
97.8% nucleotide identity with the germline JH2 gene, with a T to A change in
the most 5’ nucleotide of the JH segment, at the D-JH junction (codon 100C). 
This resulted in a change from tyrosine to asparagine.  The SCH94.03 D gene
segment contained 15 contiguous nucleotides derived from the germline DFL16.1
gene.  There were 8 nucleotides in the VH-D junction, and 1 in the D-JH junction
which did not correspond to any known germline VH, D, or JH region genes, and
probably represented non-coded (N) nucleotides inserted by the enzyme terminal
deoxynucleotide transferase (TdT) during V-D-J recombination.  All of these
nucleotides were either G or C, consistent with the preferential insertion of G
nucleotides by TdT.  Therefore, similar to the SCH94.03 VL region, all of the
nucleotide changes in the SCH94.03 VH region were in junctional regions, and may
have been produced during Ig gene rearrangement by a variety of mechanisms,
including imprecise joining, N-nucleotides, or P-nucleotide additions, rather
than somatic mutations.  We concluded from these data that the VH region of
SCH94.03 was encoded by germline Ig genes, with no definitive somatic mutations.
 
Even though the preliminary antigen reactivity results suggest that SCH 94.03 is
a natural autoantibody, this does not represent a mechanism of how SCH 94.03
stimulates remyelination in the CNS.  However, it does suggest an important
physiological function of natural autoantibodies.  We propose that
autoantibodies that are produced during normal physiology or as a response to
tissue damage may participate in promoting repair of damaged tissue.  This
active participation may be to facilitate removal of damaged tissue and mask
autoantigens, therefore, preventing vigorous pathogenic immune responses,
Natural auto antibodies may modulate immune responses which actually result in
tissue destruction.  Alternatively, this mAb could directly bind to the surface
of oligodendrocytes and stimulate proliferation differentiation of these cells. 
Either hypothesis could result in functional improvement.
 
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Specific Goals:
 
(1)            To determine whether treatment with mAb SCH 94.32  promotes
functional repair or improvement in conduction in an established animal model of
acute spinal cord trauma.
 
(2)            To determine whether treatment with mAb SCH 94.32  promotes CNS
remyelination and improvement in neurological function in an established model
of chronic spinal cord injury.
 
(3)            To determine whether treatment with mAb SCH 94.32 alters disease
in established models of autoimmunity such as collagen-induced arthritis (model
of rheumatoid arthritis), experimental autoimmune encephalomyelitis (model of
multiple sclerosis), experimental myasthenia gravis, and NOD diabetic mouse
(spontaneous model of diabetes mellitus). This specific aim would test directly
the hypothesis that the antibodies may be working through an immunological
mechanism.
 
(4)           To develop strategies to humanize mAb SCH 94.32.
 
(5)           To complete toxicity and safety studies required by the FDA to
bring mAb SCH94.32 to clinical trials.
 
General Approach to Accomplish Specific Aims:
 
The experiments involving the acute and chronic spinal cord injury models
(Specific Aims 1 and 2) should be performed in collaboration with an established
laboratory in this field. The laboratory of Dr. Weiss Young comes readily to
mind. Titration and route of administration experiments would need to be done.
We would provide mAbs, as well as control antibodies purified in a similar
manner, so there would be no experimental bias. Rats or mice would be studied
morphologically, clinically, behaviorally, and electrophysiologically at various
timepoints following acute or chronic spinal cord injury. MAbs would be given
prior to trauma in one group of experiments, but also 4 to 6  hours after trauma
in an other group of experiments to simulate the clinical situation. Details of
the experimental protocol would be finalized during a meeting between the two
labs. The potential role of this antibody in “downregulating” the immune
response may be beneficial in preventing secondary injury following trauma.
Experiments would be designed to examine the extent of inflammatory infiltrates
using immunocytochemistry and FACS of infiltrating cells within areas of spinal
cord injury. These techniques are established in our laboratory.
 
The use of mAbs in other established models of autoimmunity (Specific Aim 3)
would test the possibility that the mAbs are working through immunological
mechanisms. Dr. Chella David’s laboratory at the Mayo Clinic has expensive
expertise in the field of collagen induced arthritis. We have already
established collaborative arrangements with Dr. Ram Sriram at Vanderbilt
University who is an expert in experimental autoimmune encephalomyelitis.
Dr. Vanda Lennon at Mayo Clinic has expertise in experimental autoimmune
myasthenia. Dr. Ed Lambert, a world-class electrophysiologist, could help with
experiments to determine whether treatment with mAb has an effect on miniature
end-plate potentials in myasthenia gravis.
 
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Based on our preliminary data, we should consider humanizing the mAbs. Because
we have identified the germline sequences, this could be accomplished readily.
We have not done this previously in our own laboratory.  However, there are a
number of Mayo investigators with molecular biology expertise who have
experience with this technology.  Alternatively, it may be possible to
collaborate with a pharmaceutical company to carry out this technical endeavor.
 
Last, it is important to determine from the FDA what are the toxicity and safety
requirements before we could bring mAb SCH94.32 to clinical trials (Specific aim
5).  Having a meeting with the FDA would be appropriate.  At that point a
detailed strategy could be outlined to bring this promising drug to clinical
trials.  Thus far we have not observed any untoward side effects with the mAb. 
Treatment of normal animals with mAb has not resulted in longterm deficits.  In
addition, we have done preliminary safety data in THEV-infected mice of
resistant haplotypes.  These mice have not converted to susceptibility following
treatment with the mAb.  It is possible that further studies need to be
performed in other species (dogs, cats, monkeys, etc.).  we have the technical
expertise at Mayo to perform many of these experiments.  At present we do not
have a monkey facility at Mayo, even though these kinds of experiments have been
done previously.  It may be easier to perform these experiments in collaboration
with a pharmaceutical company with this expertise.
 
SUMMARY:
 
We are very enthusiastic about the possibility of taking mAb SCH94.32 to
clinical trials.  The experiments outlined in this proposal could be
accomplished within three or four years depending upon the collaborative
arrangements.  Specific Aims 1 and 2 (acute and chronic spinal cord injury)
should be started immediately.  This has direct relevance to the longterm plans
of Acordn.  This should be feasible to complete in approximately two years. 
Specific Aim 3 (testing of therapeutic efficacy in other established models of
autoimmunity) may have a very important impact into the marketing of this mAb. 
If the mAb has an effect immunologically as well as directly on the CCS, it may
be applicable to other established autoimmune diseases.  We expect that these
experiments could be accomplished in two to three years.  Specific aim
4 (humanizing mAb) is dependent upon whether the help of a pharmaceutical
company is requested.  Specific aim 5 is dependent upon the requirements from
the FDA.  Therefore it is impossible to give an exact estimate of when this
could be accomplished.
 
RELEVANT BIBLIOGRAPHY FROM OUR LABORATORY:
 
 
1.       Rodriguez M. Lennon VA:  Immunoglobulins Promote Remyelination the
Central Nervous System.  Ann. Neurol. 27:12-17, 1990.

 
 

 
2.       Rodrigues M. Pierce ML, Thiemann R.L:  Immunoglobulins stimulate
CSS Remyelination: Electron Microscopic and Morphometric Analysis of
Proliferating Calls.  Lab. Invest. 64:358-370, 1991.

 
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3.       Patick AK, Thiemann RL, O’Brien PC, Rodriguez M:  Persistence of
Theiler’s Virus Infection Following Promotion of CNS Remyelination.  J.
Neuropath. Exp. Neurol. 50:523-537, 1991.

 
 

 
4.       Rodriguez M. Lindsley M:  Immunosuppression Promotes Central Nervous
System Remyelination in Chronic Virus-Induced Demyelinating Disease. Neurology
42:348-357, 1992.

 
 

 
5.       van Engelen BGM, Hommes OR, Pinckers A, Cruysberg JRM, Barkhof F,
Rodriguez M:  Improved Vision in Non-Recovering Optic Neuritis after Intravenous
Immunoglobulin Possibly due to Remyelination.  Ann. Neurol. 32:834-835, 1992.

 
 

 
6.       Prayoonwiwat N, Rodriguez M:  The Potential for Oligodendrocyte
Proliferation during Demyelinating Disease. J. Neuropath. Exp. Neurol. 52:55-63,
1993.

 
 

 
7.       Miller DJ, Sanborn KS, Katzmann JA, Rodriguez M:  Monoclonal Antibody-
Mediated Nervous System Repair in a Viral Model of Multiple Sclerosis. J.
Neuroscience, in press.

 
 

 
8.       Rodriguez M. Miller DJ:  Immune Promotion of Central Nervous System
Remyelination.  Progress in Brain Research, in press.

 
 

 
9.       van Engelen BGM, Miller DJ, Pavelko KD, Hommes OR, Rodriguez M:
Promotion of Remyelination by Polyclonal Immunoglobulin in Theiler’s
Virus-induced Demyelination and in Multiple Sclerosis, J. Neurol. Neurosurg,
Psych., in press.

 
 

 
10.     Noseworthy JH, O’Brien PC, van Engelen BGM, Rodriguez M:  Intravenous
Immunoglobulin Therapy in Multiple Sclerosis.  Progress from the Theiler’s Virus
Model to a Randomized, Double-blinded, Placebo-controlled Clinical Trial,  J.
Neurol. Neurosurg, Psych., in press.

 
5

 
 

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EXHIBIT A
ACORDA/MAYO
SPONSORED RESEARCH AGREEMENT
 
Effective as of March 15, 1998, Mayo Foundation, a Minnesota charitable
corporation (“MAYO”), with Larry Pease, Ph.D., and Moses Rodriguez, M.D., as
principal Investigators (“INVESTIGATORS”) and, Acorda Therapeutics, Inc. a
Delaware corporation (“ACORDA”) agree as follows:
 
Article 1.               Project summary
 
1.1 — MAYO will undertake a research project described in the Statement of Work
and Budget attached here as Exhibit C (PROJECT). Summary data about the project
is set forth as follows:
 

 
(a)
TITLE:
Molecular Characterization of Antibody-Induced Remyelination and isolation of
Human Counterparts.
           
(b)
PURPOSE:
               
(i)            To Investigate the mechanisms underlying antibody-induced
remyelination and to identify human equivalents of the biologically active mouse
monoclonal antibodies that are known to induce remyelination. Understanding the
mechanism for the basis of antibody-induced remyelination in the mouse is
important for determining the biological requirements for mimicking this process
in humans and could lead to the development of more effective modifications of
the current approach for inducing myelin repair.
               
(ii)           Because antibodies themselves may be the target of immune attack,
the process could be improved by isolating less immunogenic, human counterparts
of the currently known, biologically active mouse antibodies. The ability of
human antibodies to induce remyelination in mouse models of demyelinating
disease will be the basis for selecting human antibodies for further development
for clinical trials.
           
(c)
START DATE: The Effective Date of this Agreement.
           
(d)
PROJECTED COMPLETION DATE: One year from Start Date.
           
(e)
FUNDING AMOUNT: $233,431.00
           
(f)
PAYMENT PLAN: Quarterly payments in advance, except that final quarter payment
in each year is payable on receipt of a written Annual Report. Year 1 -
$150,000.00 Year 2 - $40,897.00 Year 3 - $42,534.00.
       
(g)
CHECKS PAYABLE TO:
 
Mayo Foundation for Medical Education and Research
                 

 
1

 
 

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(h)
CHECKS MAILED TO:
 
Office of Technology Transfer
       
Mayo Medical Ventures
       
200 First Street S.W.
       
Rochester, Minnesota 55905
       
Attn: Susan L. Stoddard; Ph.D.
           
(i)
MAYO ADMINISTRATIVE CONTACT:
 
Susan L. Stoddard, Ph.D.
Mayo Medical Ventures
200 First Street S.W.
Rochester, Minnesota 55905
507-284-8878
           
(j)
ACORDA ADMINISTRATIVE CONTACT:
 
Ron Cohen, M.D.
President & CEO
Acorda Therapeutics, Inc.
145 West 58th Street, Suite 8J
New York, NY 10019
212-376-7553

 
1.2 — Anything contained in the PROJECT which is in conflict with anything In
this greement is superseded by this Agreement.
 
Article 2.  Proprietary Data Provided To Mayo By Acorda
 
2.1 — AGORDA may provide MAYO and INVESTIGATORS with proprietary data (DATA)
relevant to the work under this Agreement. MAYO’s and INVESTIGATORS’ acceptance
and use of DATA shall be subject to the following:
 
 
a)             DATA must be marked or designated in writing as propriatary to
ACORDA by marking it “CONFIDENTIAL,” or words of similar import.  If oral,
visual, or other non-written manner of disclosure of otherwise undisclosed
confidential information is made, such information shall be entitled to
protection if Identified as confidential at the time of initial disclosure and
if a written notice with a summary of such disclosures is delivered to the
receiving party within thirty (30) days of such disclosure. Any markings,
stamps, or legends identifying confidential Information shall not impose any
obligations on either party inconsistent with this agreement. Any copies of the
information made by the receiving party shall reproduce the confidential
markings and any other legends contained on such information.

 
 

 
b )           MAYO and INVESTIGATORS retain the right to refuse to accept any
DATA which they do not consider to be essential to the completion of the project
or which they believe to be improperly designated or for any reason.

 
 

 
c)             Where MAYO and INVESTIGATORS accept such DATA, they agree to
exercise their best efforts not to use the DATA for any purpose except the
conduct of the PROJECT and not to publish or otherwise reveal the DATA to others
outside Mayo without the permission of ACORDA, unless the DATA has already been
published or disclosed publicly by third parties or is required to be disclosed
by order of a court of law.

 
2

 
 

--------------------------------------------------------------------------------

 

 
Article 3.   Term
 
3.1          The term of this Agreement shall commence on the Effective Date of
the Agreement as set forth above and continue for a period of one (1) year.  In
the event that milestones are met in such year and, in ACORDA’s opinion, the
PROJECT continues to be of commercial Interest, the term of this Agreement shall
be extended for a second and third year except that support of one (1) person
shall be for the entire three year period in the amounts described in Article 4
and Exhibit C.
 
3.2          Except as provided in Section 3.1, any extension of this Agreement
must be in writing upon terms mutually agreeable to the parties hereto.
 
Article 4.   Payment
 
4.1          ACORDA agrees to pay $150,000.00 for services to be provided in the
first year of this Agreement in accordance with the following payment schedule:
 
(a)           $37,500.00 on execution of this Agreement,
 
 
(b)           $37,500.00 on the later of either (i) the three (3) month
anniversary of the effective date of this Agreement, or (ii) the three month
anniversary of the date the work on the PROJECT began, and

 
 
(c)           $37,500.00 on (i) the three (3) month anniversary of the date of
payment by ACORDA under (b), and (ii) on each subsequent three (3) month
anniversary thereafter until the sum of all the payments made by ACORDA pursuant
to this Section 3.1 equals $150,000.00

 
ACORDA agrees to pay a minimum of $40,897,00 for services to be provided in the
second year of this Agreement in accordance with the following payment schedule:
 
 
(d)           $10,224,25 on the later of either (i) the one (1) year anniversary
of the effective date of the Agreement, or (ii) the three (3) months anniversary
of the date of the final payment by ACORDA under (c) above; and

 
 

 
(e)           $10,224.25 on (i) the three (3) month anniversary of the date of
payment by ACORDA under (d), and (ii) on each subsequent three (3) month
anniversary thereof until the sum of all payments made by Sponsor pursuant to
this Section 3.1 in the second year of this agreement equals $40,897.00

 
In the event that milestones are met in year one (1) and, in ACORDA’s opinion,
the PROJECT continues to be of commercial interest, ACORDA agrees to pay;
 
 
(f)            Additional payments for supplies and equipment estimated at
$99,000.00 in year two with the final budget to be determined by mutual written
agreement of both parties and the agreed amount paid quarterly.

 
ACORDA agrees to pay a minimum of $42,534.00 for services to be provided In the
third year of this Agreement in accordance with the following payment schedule:
 
3

 
 

--------------------------------------------------------------------------------

 

 
 
(g)           $10,633.50 on the later of either (i) the two (2) year anniversary
of the effective date of the Agreement, or (ii) the three (3) months anniversary
of the date of the final payment by ACORDA under (e) above, and

 
 

 
(h)           $10,633.50 on (i) the three (3) month anniversary of the date of
payment by ACORDA under (g), and (ii) on each subsequent three (3) month
anniversary thereof until the sum of all payments made by Sponsor pursuant to
this Section 3.1 in the third year of this agreement equals $42,534.00

 
 

In the event that milestones are met in year two (2) and, in ACORDA’s opinion,
the PROJECT continues to be of commercial interest, ACORDA agrees to pay:
 
 
(i)            Additional payments for supplies and equipment estimated at
S110,000.00 in year three with the final budget to be determined by mutual
written agreement of both parties and the agreed amount paid quarterly.

 
 

4.2          MAYO shall not spend any amounts on the conduct of PROJECT except
amounts provided by ACORDA hereunder with prior written agreement by both
parties.  MAYO shall not expend any amount on capital equipment in excess of
$5,000 without the prior written consent of ACORDA.
 
4.3          The amounts set forth in Section 4.1 shall be ACORDA’s full support
of the research and shall cover all direct and indirect costs (including,
without limitation, overhead) of conducting such research.
 
Article 5.   Reports
 
5.1          Every six (6) months following the beginning date of the PROJECT,
MAYO shall provide ACORDA with an Interim written report describing activities,
progress and results to date of the PROJECT.  Within ninety (90) days after
completion of the PROJECT by MAYO, of earlier termination of this Agreement,
MAYO shall provide a final written report to ACORDA describing the services
performed and such other information or data as may be specified in Exhibit B. 
MAYO shall also, at ACORDA’s option, meet with ACORDA to discuss the PROJECT and
the Interim and final reports.
 
5.2          ACORDA shall have the right to use such reports and data for any
purposes, subject to Sections 7.2 and 10.1 below.
 
Article 6.   Insurance
 
6.1          MAYO shall at its expense provide the necessary Workers’
Compensation and Employers’ Liability Insurance to meet statutory liability
limits of State Of Minnesota for the employees of MAYO involved in the PROJECT.
 
Article 7.   Liability
 
7.1          MAYO shall not be responsible or liable for any injuries or losses
which may result from the implementation or use by ACORDA or its designees of
the results from the PROJECT or research data generated by MAYO.
 
4

 
 

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7.2          ACORDA agrees to indemnify, defend and hold harmless MAYO, Its
trustees, officers, agents and employees (the “MAYO Indemnitees”) with respect
to any expense, claim, liability, loss, damage, or costs (including attorney’s
fees) in connection with or in any way arising out of the use by ACORDA of the
data or results from the Project; provided, however, that ACORDA shall have not
such obligation to the extent that any such claim, liability, loss damage or
costs results from the negligence or willful misconduct of a MAYO Indemnitee.
 
7.3          MAYO agrees to indemnify, defend and hold harmless ACORDA, its
trustees, officers, agents and employees (“ACORDA Indemnitees”) with respect to
any expense, claim, liability, loss, damage, or costs (including attorney’s
fees) in connection with or in any way arising out of the conduct of the PROJECT
at the MAYO; provided, however, that MAYO shall have no such obligation to the
extent that any such claim, liability, loss, damage or costs result from the
negligence or willful misconduct of a ACORDA Indemnitee.
 
Article 8.   Inventions, Discoveries And Patents
 
8.1 — All original data and records of the work completed under this Agreement
shall remain the property of MAYO.
 
8.2 — MAYO shall own all rights and title to its Inventions.  For purposes of
this Agreement, “Inventions” shall mean Inventions, discoveries and other
intellectual property conceived, reduced to practice, made or otherwise
developed by MAYO employees or agents, whether or not patentable, during the
term of this Agreement as it may be extended, relating to the PROJECT.  Rights
held by MAYO in any inventions, including without limitation rights in end to
patent applications and patents which may be obtained thereon, shall be deemed
to be within the term Technology as used in the License Agreement term sheet
attached hereto and shall be subject to the license granted ACORDA therein. 
ACORDA shall own all of its inventions, discoveries and other developments,
whether or not patentable, arising out of research carried out under the
provisions of this Agreement.  Inventions or discoveries made jointly by both
MAYO and ACORDA shall be jointly owned by both parties and, if patent
applications are filed, patents shall be applied for on behalf of both parties. 
MAYO’s interest in any inventions, whether or not patentable, arising out of
research carried out under the provisions of this Agreement, shall be subject to
the Option Agreement.
 
 

Article 9.   Publication
 
9.1 — MAYO and INVESTIGATORS reserve the right to publish or otherwise publicly
disclose the results of work completed under this Agreement.  MAYO agrees to
submit to ACORDA any proposed publication or presentation for review sixty (60)
days prior to submission.  Acorda shall, within forty-five (45) days after
receipt, advise in writing if there is any proprietary or patentable information
which should not be disclosed at the present time.  Publication of the results
will not include DATA as defined in Article 2 without the express written
permission of ACORDA.  MAYO will acknowledge ACORDA’s financial support of
PROJECT in all publications unless ACORDA requests otherwise.
 
9.2 — At ACORDA’s request, MAYO will delay submission, disclosure, or
publication for an additional sixty (60) days or longer by mutual written
agreement of both parties in order to enable the preparation and filing of a
patent application on any such patentable subject matter.
 
5

 
 

--------------------------------------------------------------------------------

 

 
9.3 — MAYO acknowledges that it may be necessary for INVESTIGATORS to disclose
information which ACORDA considers proprietary or confidential in order to
perform the PROJECT.  If ACORDA considers any such information confidential, it
shall be clearly marked “CONFIDENTIAL INFORMATION’ and sent by ACORDA in writing
only to the INVESTIGATORS or orally disclosed to INVESTIGATORS and reduced to
writing by ACORDA within thirty (30) days of disclosure.  Except as expressly
necessary for the performance of the PROJECT.  MAYO and INVESTIGATORS shall
maintain such information as confidential, not disclose it to others, limit
access to it to those employees with a need to know, and take such action as
shall be reasonably necessary to ensure that its employees will not disclose it
to others.
 
Article 10.   Use Of Name
 
10.1 — ACORDA and MAYO shall not use expressly or by implication, any trademark,
trade name, or any contraction, abbreviation, simulation, or adaptation thereof
of the other party, or the name of any of other party’s staff in any news,
publicity release, policy recommendation, advertising or any commercial
communication without the express written approval of the other party; provided,
however, once a public announcement has been approved, further approvals need
not be obtained for further announcements which are not materially different
from an earlier approved announcement.
 
Article 11.   Indemnification And Negation Of Warranties
 
11.1 — ACORDA agrees to defend, indemnify and hold harmless MAYO and
INVESTIGATORS against any and all costs, damages, expenses, including attorneys
fees, arising from any claims, damages and liabilities asserted by third parties
arising from ACORDA’s use of the results of the work performed under this
Agreement.
 
MAYO agrees to defend, indemnify and hold harmless ACORDA against any and all
costs, damages, expenses, including attorneys fees, arising from any claims,
damages and liabilities asserted by third parties arising from MAYO’s conduct or
use of the results of the work performed under this Agreement.
 
As used in the preceding parts of this paragraph, MAYO includes its Trustees,
Officers, Agents, and Employees and ACORDA includes any of its “Affiliates”.  An
“Affiliate” of ACORDA shall mean any corporation or other business entity
controlled by, controlling, or under common control with ACORDA.  For this
purpose “control” means direct or indirect beneficial ownership of at least
fifty (50%) percent of the voting stock, or at least fifty (50%), percent
interest in the income of such corporation or other business
 
11.2 — MAYO makes no representations or warranties, expressed or implied,
regarding its performance under this Agreement, including but not limited to,
the marketability, use or fitness for any particular purpose of the research
results developed under this work, or that such results do not infringe upon any
third party property rights.  Further, MAYO shall not be liable for special,
consequential, or incidental damages, and MAYO’s sole liability for damages
hereunder shall be a sum equal to the amount paid by ACORDA to MAYO under this
Agreement.
 
Article 12.   Fiscal Management
 
12.1 — MAYO costs shall follow the proposed budget as contained in Exhibit C. 
MAYO shall maintain complete and accurate accounting records in accordance with
accepted accounting practices.  These records shall be available for inspection,
review and audit at reasonable times
 
6

 
 

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by ACORDA, or its duly authorized representative, at ACORDA’s expense, for three
(3) years following the end of the calendar year in which such costs are
incurred.
 
12.2 — MAYO shall retain title to equipment and all other items purchased with
funds provided by ACORDA, MAYO shall not expend any amount on capital equipment
in excess of $5,000 without the prior written consent of ACORDA.
 
12.3 — Mayo shall not utilize funds from any other commercial entity to conduct
the PROJECT.
 
Article 13.   Termination
 
13.1 — If for any reason INVESTIGATORS becomes unavailable to direct the
performance of the work under this Agreement, MAYO shall notify ACORDA.  If a
mutually acceptable successor is not identified within forty-five (45) days,
this Agreement may be terminated immediately by either party and ACORDA shall
have no further obligation to pay MAYO further funds for the conduct of the
PROJECT, except as set forth in Section 13.2 and 13.3.
 
13.2 — Following nine (9) months after the effective date of the Option
Agreement, ACORDA shall have the right to terminate this agreement at will
within ninety (90) days notice; provided, ACORDA shall be obligated to pay MAYO
the salary and benefits of one research technician until the third anniversary
of the effective date of the Option Agreement, unless MAYO receives extramural
contract or grant funds to support such technician.  Should ACORDA terminate
this Agreement under this Section 13.2, MAYO agrees to use best efforts to find
other sources of funding for the technical salary.
 
13.3 — If this Agreement is terminated, ACORDA shall pay for all direct costs
incurred, up to and including the effective date of termination, and for all
noncancellable obligations made before receipt of notice of termination, even
though they may extend beyond such termination date.  Any unexpended funds paid
by ACORDA and held by MAYO after satisfying the obligations set forth in this
paragraph will be returned to ACORDA.
 
13.4        ACORDA and MAYO maintain the right to terminate this Agreement if a
material breach is committed by the other party, if this breach is not cured
within thirty (30) days after written notice to the breaching party.  If this
Agreement is so terminated under this Section 13.4, the terminating party shall
maintain no continuing financial obligation to the breaching party.
 
Article 14.   General
 
14.1 — This Agreement may be amended only by the written agreement of the
parties.
 
14.2 — This Agreement may not be assigned by MAYO or ACORDA without the prior
written consent of the other.
 
14.3 — The captions and headings used in this Agreement are for convenience and
reference only and are not a part of this Agreement.
 
14.4 — All notices shall be in writing and shall be effective when mailed. 
Notices should be sent to the respective administrative contacts set forth in
paragraph 1.1 of this Agreement.
 
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14.5 — This Agreement and its effects are subject to end shall be construed and
enforced in accordance with the laws of the State of Minnesota.
 
14.6 — There is one addenda to this Sponsored Research Agreement:
 
a) Exhibit B: Statement of Work and Budget
 
14.7 — Both parties agree that execution of this Sponsored Research Agreement
may be effected by the receipt of facsimile signature pages
 
 
MAYO FOUNDATION
ACORDA THERAPEUTICS, INC.
     
Signed:
/s/ John H. Herrell
 
Signed:
/s/ Ron Cohen
             
Name:
John H. Herrell
 
Name:
Ron Cohen, M.D.
             
Title:
Vice President
 
Title:
President & CEO
             
Date:
March 24, 1998
 
Date:
3/20/98
           
INVESTIGATORS
               
Signed:
/s/ Moses Rodriguez
 
Signed:
Larry R. Pease
             
Name:
Moses Rodriguez
 
Name:
Larry R. Pease
             
Title:
M.D.
 
Title:
Ph.D.
             
Date:
March 25, 1998
 
Date:
3/25/98
 

 
8

 
 

--------------------------------------------------------------------------------

 

 
EXHIBIT B
ACORDA/MAYO
STATEMENT OF WORK AND BUDGET
 
1.             Statement of work
 
(a)
 
TITLE:
 
Molecular Characterization of Antibody-Induced Remyelination and Isolation of
Human Counterparts.
     
(b)
 
PURPOSE
         
(i) To investigate the mechanisms underlying antibody-induced remyelination and
to identify human equivalents of the biologically active mouse monoclonal
antibodies that are known to induce remyelination.  Understanding the mechanism
for the basis of antibody-induced remyelination in the mouse is important for
determining the biological requirements for mimicking this process in humans and
could lead to the development of more effective modifications of the current
approach for inducing myelin repair.
             
(ii) Because antibodies themselves may be the target of immune attack, the
process could be improved by isolating less immunogenic, human counterparts of
the currently known, biologically active mouse antibodies.  The ability of human
antibodies to induce remyelination in mouse models demyelinating disease will be
the basis for selecting human antibodies for further development for clinical
trials.

 
2.             Milestones & Budget; Year One (1)
 
 
A)    First six (6) months:

 
 
1.     Hire research fellow end technician.

 
 
2.     Screen EBV transformed cell lines available for IgM secreting cells
(culturing of first 11 lines initiated, Eliza assay being developed to screen
antibody).

 
 

 
3.     Screen tissue culture supernatants from IgM+ lines for binding activity
using rat oligodendrocytes.

 
 

 
4.     Subclone EBV lines that are making IgM antibody, with emphasis on lines
with demonstrable oligodendrocyte-binding activity.

 
 

 
5.     Generate cassette expression system for manipulation of antibody gens
structures and for expression of antibodies gene in transfected hybridoma cells.

 
 

 
6.     Construct chimeric 94.03/human IgM constant region antibody to evaluate
the ability of the human Fo portion of IgM to Induce remyellnation in mice.

 
9

 
 

--------------------------------------------------------------------------------

 

 
 
7.     Establish parameters of transfectoma technology in house.

 
 
8.     Initiate biochemical analysis of 94.03 antibody.  Prepare monomeric IgM,
evaluate in vivo half life comparisons between pentameric and monomeric forms.

 
 

 
B)    Second six (6) months - items carried over (A) above:

 
 

 
1.             Completed.

 
 

 
2,3.          Continue screening.  Note: As of 1/98 have approximately 60 lines
to evaluate: timing will depend on results as program progresses.

 
 

 
4.             In the event that no lines produce demonstrable antibodies, we
will proceed to subclone cells from 10 lines to evaluate the possibility that
clones of desired phenotype exist but cannot be visualized in the pool.  Lines
from normal individuals and five from individuals who have been diagnosed with
MS will be evaluated by cloning.  It will be necessary to develop an assay that
will enable us to estimate the complexity of the line.  The most straight
forward approach would be to generate Southern blot of the cloned cells using
the most C proximal J region as a probe.  Different restriction enzyme digestion
patterns should be distinguish clones from each other depending on which V and
which J was being used.

 
 
5.             Generation of cassette system for manipulating Ig sequences
should be completed in the first six months.

 
 
6.             Generate and clone transfectoma of mouse/human chimeric
antibody.  Produce ascites and prepare antibody for testing in animal model.

 
 

 
7.             Parameters for generating transfectomas should be established in
first six months.

 
 

 
8.             Assess the ability of monomeric antibody to induce
remyellnation.  If the in vivo half life is low, we may need to explore
alternate route of antibody administration such as local administration.

 
 

 
9.             Generate by site-directed mutagenesis a mouse IgM variant of
94.03 that cannot fix complement.  Establish transfectoma that expresses this
variant.

 
 

 
10.           At the end of the first year, we will evaluate progress in each of
the aims and establish milestones for year two (2).

 
 

 
Budget: Year One.

 
(1)
Personnel (Including benefits)
 
$
71,042.00
 
(2)
Supplies
 
$
40,280.00
 
(3)
Other Expenses - mouse husbandry
 
$
13,678.00
 
(4)
Overhead (20%)
 
$
25,000.00
   
TOTAL
 
$
150,000.00
 

 
10

 
 

--------------------------------------------------------------------------------

 

 
3.             Milestones & Budget: Year Two (2)
 
 
A)   Milestones to be determined

 
 
Minimum Budget: Year Two.

 

 
(1)
Personnel (including benefits)
 
$
34,081.00
   
(2)
Supplies
 
$
0.00
   
(3)
Other Expenses - mouse husbandry
 
$
0.00
   
(4)
Overhead (min. est. @ 20%)
 
$
6,816.00
     
TOTAL
 
$
40,897.00
 

 
4.             Milestones & Budget: Year Three (3)
 
 
A)   Milestones to be determined

 
 
Minimum Budget: Year Three.

 

 
(1)
Personnel (including benefits)
 
$
35,445.00
   
(2)
Supplies
 
$
0.00
   
(3)
Other Expenses - mouse husbandry
 
$
0.00
   
(4)
Overhead (min. est. @ 20%)
 
$
7,089.00
     
TOTAL
 
$
42,534.00
 

 
11

 
 

--------------------------------------------------------------------------------

 

 
AMENDMENT No. 1
TO
SPONSORED RESEARCH AGREEMENT
BETWEEN
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
AND
ACORDA THERAPEUTICS, INC.
 
Effective as of 28 September 1999, the Sponsored Research Agreement dated
March 15, 1998 between Mayo Foundation for Medical Education and Research (MAYO)
and Acorda Therapeutics, Inc. (ACORDA) is hereby amended under the following
terms:
 
Section 4.1(j) is inserted.
 
During the second year of the Agreement, ACORDA agrees to pay FIFTY DOLLARS (US
$50,000.00) in excess of the amounts described in sections 4.1(d), 4.1(e) and
4.1(f) hereto, such funds to be directed specifically to the costs related to
animal care and maintenance at MAYO.
 
The terms of this Amendment No. 1 supersede any conflicting or inconsistent
terms in the Sponsored Research Agreement. All other provisions of the original
Sponsored Research Agreement effective March 15, 1998 remain in full force and
effect.
 
MAYO FOUNDATION FOR MEDICAL
ACORDA THERAPEUTICS, INC.
EDUCATION AND RESEARCH
         
Signature
/s/ Rick F. Colvin
 
Signature
/s/ Ron Cohen
             
Name
Rick F. Colvin
 
Name
Ron Cohen
             
Title
Assistant Treasurer
 
Title
President & CEO
             
Date
10/4/99
 
Date
9/30/95
             

 

 
 

--------------------------------------------------------------------------------

 

 
AMENDMENT TO
SPONSORED RESEARCH AGREEMENTS
BETWEEN
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
AND
ACORDA THERAPEUTICS, INC.
DATED JANUARY 2, 2001
 
Reference is made to the Sponsored Research Agreements between the parties dated
October 1, 1995 and March 15, 1998. The research program attached hereto as
Exhibit A shall be deemed additional research under these Sponsored Research
Agreements. The parties agree that all results of this research shall be deemed
to be included under the License Agreement between Mayo Foundation for Medical
Education and Research and Acorda Therapeutics, Inc., dated September 9, 2000,
and shall be treated for all purposes as Licensed Technology as defined in the
License Agreement.
 
The new funded research program contemplated by this Amendment shall commence as
of March 15, 2001 and will terminate on March 14, 2002, unless extended by
mutual written agreement signed by both parties.
 
During the research period, ACORDA agrees to pay two hundred seventy seven
thousand and two hundred dollars (US $277,200.00) payable in quarterly payments
of sixty-nine thousand, three hundred dollars (US $69,300.00) each.
 
All other provisions of the License Agreement and the Sponsored Research
Agreements, as previously amended, shall remain in full force and effect.
 
 
MAYO FOUNDATION FOR MEDICAL
ACORDA THERAPEUTICS, INC.
EDUCATION AND RESEARCH
         
Signature
/s/ Rick F. Colvin
 
Signature
/s/ Ron Cohen
             
Name
Rick F. Colvin
 
Name
RON COHEN, M.D.
             
Title
Assistant Treasurer
 
Title
PRESIDENT & CEO
             
Date
1/29/01
 
Date
2/20/01
                                     

 

 
 

--------------------------------------------------------------------------------

 

 
 
VIA FEDERAL EXPRESS
 
November 17, 2003
 
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
C/O Susan Stoddard, Ph.D.
Technology Licensing Manager
Office of Technology Commercialization
Mayo Medical Ventures
200 First Street SW
Rochester, Minnesota 55905
 
 
RE:          Agreement between Acorda Therapeutics, Inc. and the Mayo Foundation
for Education and Research

 
 

Dear Susan:
 
Reference is made to a certain License Agreement (the “Agreement”) dated
September 8, 2000 by and between Acorda Therapeutics, Inc. and The Mayo
Foundation for Education and Research.
 
The agreement is amended as follows:
 
“Acorda and Mayo entered into a License Agreement dated September 8, 2000 (the
“License Agreement”) wherein “Licensed Technology”, as defined therein, was
developed in connection with two Mayo research programs previously sponsored by
Acorda and referred to therein, as “Programs” (respectively entitled
“Preclinical Studies of Monoclonal Antibody Designed to Promote Central Nervous
Repair” and “Molecular Characterization of Antibody-Induced Remyelination and
Isolation of Human Counterparts”).
 
Acorda and Mayo wish to sponsor and conduct additional research pursuant to the
attached research plan and to include the results of this new research within
the meaning of “Licensed Technology” under the License Agreement.
 
Accordingly, the parties agree that the attached research plan shall be attached
to the License Agreement as an additional part of Exhibit A, that it shall be
considered an additional “Program” within the meaning of the License Agreement,
and that for all purposes under the License Agreement the term “Program(s)”
shall be deemed to include the two Programs originally referenced in the License
Agreement, the attached research plan, and any other future research which the
parties may agree in writing to incorporate into Exhibit A of the License
Agreement by amendment.
 
Notwithstanding anything contained in the original License Agreement to the
contrary, the parties agree that with respect to any new intellectual property
conceived or first reduced to practice as result of the new research conducted
under the attached research plan, the definitions of “Licensed Technology”,
“Licensed Patents”, “Inventions” and “Know-How” under the License Agreement
shall only be interpreted to include intellectual property conceived or first
reduced to practice in
 
 
15 SKYLINE DRIVE
 
PHONE: (914) 347-4300
 
E-MAIL: ACORDA@ACORDA.COM
HAWTHORNE, NY 10532
 
FAX: (914) 347-4560
 
WEBSITE: WWW.ACORDA.COM

 

 
 

--------------------------------------------------------------------------------

 

 
the course of or arising from the conduct of such research and for a period of
two years thereafter, and not to any improvements, modifications, derivatives of
such new intellectual property that may be conceived or first reduced to
practice by Mayo more than two years after the conclusion of such research.
 
The attached research plan identifies all Mayo personnel who will conduct
research proposed under such plan and the parties agree to identify in advance
all Mayo personnel who will conduct research under any future Program, as well.
 
Additionally, for the avoidance of doubt in the interpretation of the License
Agreement, the parties each hereby acknowledge and confirm that the two Option
Agreements between the parties dated October 1, 1995 and March 15, 1998 were
exercised and shall each be deemed to have been terminated as of the effective
date of the License Agreement.”
 
This Letter Agreement amends the Agreement only to the extent specified herein
and shall not constitute an amendment or modification of any other provision of
the License Agreement. From and after the date hereof, all references to the
Agreement shall be references to the amended Agreement hereby.
 
The Agreement amended hereby, constitutes the full and complete agreement among
the parties hereto and supersedes any and all other agreements and
understandings, whether oral or written, between the Parties.
 
If the foregoing accurately sets forth our agreement, please so indicate by
executing this letter agreement and the enclosed copy in the spaces provided and
returning one original to Tippy Lucarelli.
 
 

 
Very truly yours,
       
/s/ Harold Safferstein
   
Harold Safferstein, Ph.D., J.D.
   
Vice President, Business Development
         
AGREED TO AND ACCEPTED:
             
/s/ Rick F. Colvin
               
By:
 
Rick F. Colvin
               
Title:
 
Assistant Treasurer
                 
Date:
11/18/03
                     

 

 
 

--------------------------------------------------------------------------------

 

 
Executive Summary
Pre-clinical Development of Remyelination Promoting Antibodies
September 2003
 
Investigators
 
Magdalena Hofer, Ph.D.
 
Principal Investigator
 
Acorda Therapeutics
Allan J. Bieber, Ph.D.
 
Principal Investigator
 
Mayo Clinic
Moses Rodriguez, M.D.
 
Co-Principal Investigator
 
Mayo Clinic
Larry R. Pease, Ph.D.
 
Investigator
 
Mayo Clinic
Arthur Warrington, Ph.D.
 
Investigator
 
Mayo Clinic
Charles Howe, Ph.D.
 
Investigator
 
Mayo Clinic

 
The long-term goal of this agreement is to continue to study and develop
monoclonal antibodies that promote remyelination of central system nerve fibers
and to bring these antibodies to clinical trials.
 
We have demonstrated that certain human antibodies can promote CNS remyelination
and have identified human monoclonal antibodies (sHIgM22 and sHIgM46) which
strongly and consistently enhance remyelination in the Theiler’s virus and
lysolecithin models of demyelination in mice. We have constructed vectors that
direct the expression of recombinant forms of these antibodies (RcHIgM22 and
RcHIgM46) when introduced into cultured cells, making the large-scale production
of these antibodies possible. Recently, the expression vectors have been
modified to allow for the expression of both IgM (22M-5,6 and 46M-6) and IgG4
(22G4-9 and 46G4-8,9) forms of both antibodies under good manufacturing practice
(GMP) conditions.
 
This agreement, “Pre-clinical Development of Remyelination Promoting
Antibodies”, will focus on research in four Research Areas: 1) in vivo efficacy
testing and dose determination for the four candidate antibodies produced under
GMP conditions, in the Theiler’s virus model of demyelinating disease in mice,
2) use of cDNA microarrays to assess gene expression changes that take place in
response to antibody treatment under a variety of conditions and in different
cell types, 3) biochemical characterization of the cellular signaling pathways
that are induced by antibody binding, and 4) characterization of the
functionally relevant cell surface antigens that are bound by remyelination
promoting antibodies. Specific details for experiments addressing each of these
areas are presented in the attached document. The Mayo MS Research group will
make a good-faith effort to deliver data for the experiments enumerated for
Research Areas 1, 2 and 3, and will supply material for use in the antigen
characterization studies in Research Area 4. Acorda will make a good-faith
effort to indentify the most relevant antigens with regard to antibody enhanced
remyelination (Research Area 4). Acorda will supply funding for the Mayo
research, as indicated in the attached budget. The current funding agreement
will be for 1 year. The experimental and financial scope of future agreements
will be contingent upon progress towards completion of the current agreement.
 

 
 

--------------------------------------------------------------------------------

 

 
Pre-clinical Development of Remyelination Promoting Antibodies
Budget — 2003/2004
 
Proposed total $ to Mayo from Acorda (including entire STTR directs)
 
$
400,000
                 
Total $ from STTR directs
 
$
105,000
     
STTR directs spent in 2002 (estimated)
 
$
(10,000
)
   
(STTR indirects are not considered here)
     
$
95,000
             
Funds from Acorda:
 
$
295,000
     
Direct
     
$
204,000
 
Indirect (44.5%)
     
$
91,000
             
Total direct $ to lab
   
=
$
299,000
 
Total $ (direct+indirect) to Mayo
   
=
$
390,000
 

 
Personnel: (estimates only)
 

   
Budgeted
% effort
 
Budgeted
% support
 
Budgeted
Salary
 
Budgeted
Benefits
 
Total
 
Allan Bieber, Ph.D.
(Principal Investigator)
 
40
%
40
%
$
—
 
$
—
 
$
22,000
                               
Moses Rodriguez, M.D.
(Co-Principal Investigator)
 
5
%
5
%
$
—
 
$
—
 
$
9,552
                               
Larry R. Pease, Ph.D.
(Co-investigator)
 
5
%
5
%
$
—
 
$
—
 
$
9,552
                               
Art Warrington, Ph.D.
(Co-investigator)
 
20
%
20
%
$
—
 
$
—
 
$
11,000
                               
Charles Howe, Ph.D.
(Co-investigator)
 
20
%
20
%
$
—
 
$
—
 
$
11,000
                               
Total Personnel
                 
$
63,104
 

 
Supply Expenses:
 
2002/2003 Pre-clinical animal testing:
             
Animals - 250 SJL/J mice, 6 weeks old females @ $16.90/mouse (Jackson Labs).
 
$
4,225
 
Animal Maintenance - Based on 100 cages @ $0.56/cage/day for 365 days.
 
$
20,440
 
Tissue preparation materials - araldite, osmium
 
$
15,000
 
Tissue and slide preparation - 10 slides/animals, 170 animals, @ $10.00/slide
 
$
17,000
 
Technician processing time - fixation, dissection, embedding
 
$
5,000
         
Supplies: 2002/03 in vivo testing
 
$
61,665
         
2003/2004 Pre-clinical animal testing:
             
Animals - 250 SJL/J mice, 6 weeks old females @ $16.90/mouse (Jackson Labs).
 
$
4,225
 
Animal Maintenance - Based on 100 cages @ $0.56/cage/day for 365 days.
 
$
20,440
 

 
 
 
 
 

--------------------------------------------------------------------------------

 
 
 
Tissue preparation materials - araldite, osmium
 
$
15,000
 
Tissue and slide preparation - 10 slides/animal, 160 animals, @ $10.00/slide
 
$
16,000
 
Technician processing time - fixation, dissection, embedding
 
$
4,500
         
Supplies: 2003/04 in vivo testing
 
$
60,165
 

2

 
 

--------------------------------------------------------------------------------

 

 
Supply Expenses: Antibody-induced signaling.
             
Microarrays - Affymetrix microarrays and array processing
 
$
50,000
 
Animals - Purchase and short-term housing for 50 Sprague-Dawley rats provided as
untimed pregnancies for the generation of primary oligodendrocyte cultures.
 
$
4,000
 
Tissue Culture - Culture of primary oligodendrocytes derived from mixed glial
cultures.
     
Culture of CG4 cells under defined media conditions. Cost includes growth
factors, hormones, media, supplements, serum, and plasticware.
 
$
12,000
 
Antibodies - anti-phosphotyrosine (4G10), anti-phospho-JNK, anti-phospho-IkB and
NFkB, anti-phospho-ERK 1/2 anti-phospho-p38, anti-phospho-Akt, anti-EGFR,
anti-PDGFR, anti-IGFR, anti-FGFR, anti-src family members, anti-caspases,
secondaries and immunoprecipitation materials
 
$
10,000
 
Pharmacological Agents - JNK inhibitors, NFkB inhibitors, TNFa and Fasm, B-MCD
and Filipin.
 
$
4,000
 
Radiation - 35SO4 and 3H lipid derivatives
 
$
4,000
 
PAGE Materials - Basic materials for 1 and 2-D PAGE
 
$
2,500
 
TLC Materials - Basic Materials for 2-D TLC
       
Cell Fractionation Materials - cost includes plasticware and fractionation
chemicals (e.g. OptiPrep)
 
$
2,500
         
Supplies: Ab-induced signaling
 
$
91,500
         
Supply Expenses: Antigen characterization.
             
Animals -
     
Purchase and short-term housing for 50 rats provided as untimed pregnancies for
the generation of primary glial cultures.
 
$
3,000
 
Purchase and short-term housing for 200 SJL mice for the generation of primary
glial cultures.
 
$
3,500
 
Tissue Culture - primary culture of rat, mouse, human glia, rat neurons, PC12
cells
 
$
12,000
 
Enzymes and antibodies - carbohydrate specific enzymes, anti-chondroitin
sulfate, anti-myelin basic protein, anti-phophotyrosine
 
$
4,000
         
Supplies: Ag characterization
 
$
22,500
         
Total personnel
 
$
63,104
 
Total supplies
 
$
235,830
         
Total DIRECT
 
$
298,934
 
Total INDIRECT @ 44.5%
 
$
91,000
 
Total cost
 
$
389,934
 

 
3

 
 

--------------------------------------------------------------------------------

 

 
Research Area 1: In vivo Antibody Treatment Experiments
 
Experiments 1 & 2 were completes in 2002/2003.  These experiments determined the
in vivo dose titration for remyelination in response to Rc22 treatment, examined
the effect of co-treatment with methyl prednisolone and Rc22, and examined the
effect pf co-treatment with Rc22 and Rc46.
 
 
Expt. 1    Rc22 Dosing; Rc22 +
MePrednisolone                                                                         
70 mice

Rc22 at:
500 µg
125 µg
50 µg
5 µg
PBS
 
MePr
MePr + Rc22, 500 µg
 
 
Expt. 2    Rc22 Dosing (repeat); Rc22 + MePrednisolone (repeat); Dbl;. Ab
treatment         100 mice

Rc22 at:
500 µg
50 µg
5 µg
500 ng
50 ng
PBS
 
MePr
MePr + Rc22, 500 µg
 
Rc46, 500 µg
Rc46 + Rc22 250 µg
 
Experiments 3 & 4 will be completed in 2003/2004.  Experiment 3 will determined
the in vivo efficacy of the IgM and IgG4 forms of Lym22 and Lym46, with regard
to promotion of remyelination. A best candidate will be selected based on the
results of Expt. 3 and Expt. 4 will determine the in vivo dose titration for
remyelination in response to treatment with these (this) antibodies.
 
 
Expt. 3    IgMs vs.
IgG4s                                                                                                                    
80 mice

Rc22 (all at 500 µg)
22M-5,6
22G4-9
46G4-8,9
46M-6
Kappa IgG4
human IgM
Acorda buffer
 
 
Expt. 4    IgMs vs. IgG4s: Repeat and
Dosing                                                                                
80 mice

Rc22, 500 µg
Best candidates at:
500 µg
50 µg
5 µg
500 ng
50 ng
Control Ab, 500 µg
Buffer
 
4

 
 

--------------------------------------------------------------------------------

 

 
Research Area 2: Microarray Analysis
 
Experiment 1 will examine the effect of treatment of rat mixed primary glia with
the IgM and IgG forms of Lym22 and Lym46. Gene expression data will be compared
to our previous microarray experiments using Mayo Rc22, O4, and other
antibodies. Experiment 2 will determine the dose response for the effect of best
candidate antibodies on gene expression in MPG.
 
 
Expt. 1    IgMs vs. IgG4s (on rat MPGs)

Rc22      (all at 10 ug/ml)
22M-5,6
22G4-9
46G4-8,9
46M-6
kappa IgG4
human IgM
Buffer
 
 
Expt. 2    IgMs vs. IgG4s:  Repeat and Dosing (on rat MPGs)

Rc22      (10 ug/ml)
Best candidates at:
10 ug/ml
500 ng/ml
50 ng/ml
10 ng/ml
Buffer
 
Our previous experiments suggest that treatment with remyelination promoting
antibodies may have direct and distinct effects on gene expression in a wide
variety of cells. Experiment 3 will test best candidate antibodies for their
direct effect on gene expression in oligodendrocytes, astrocytes, macrophages,
brain infiltrating lymphocytes and neurons.
 
 
Expt. 3    Best candidate effects on specific rat cell types (Oligos,
astrocytes, macrophages, BILs, neurons)

Best candidate and dose (5 cell types)
Ab negative control (5 cell types)
 
Experiment 4 will determine whether the binding of antibody to the surface of
oligodendrocytes correlates directly with observed effects on gene
transcription. CGT mutant mice produce no sulfatide, the putative O4 antigen. We
will isolate glia from these mice and test the gene expression responses of
these cells to O4, Rc22 and other antibodies. Glia from normal mice will serve
as controls.
 
Expt. 4    O4 signaling in mouse CGT MPGs
Rc22, 10 ug/ml on B6
O4, 10 ug/ml on B6
s39, 10 ug/ml on B6
PBS on B6
 
Rc22, 10 ug/ml on CGT
O4, 10 ug/ml on CGT
s39, 10 ug/ml on CGT
PBS on CGT
 
Experiment 5 is designed to demonstrate the relevance of the microarray data
from rodent cells by repeating the basic antibody treatment experiment using a
best candidate antibody and human mixed primary glia.
 
Expt. 5    Ab signaling in human MPGs
Rc22 (or best candidate), 10 ug/ml
O4, 10 ug/ml
s39, 10 ug/ml
PBS
 
5

 
 

--------------------------------------------------------------------------------

 

 
Our previous data demonstrates significant effects of antibody treatment on CNS
gene expression in SJL mice that are chronically infected with TMEV, Experiment
6 will repeat these experiments and will examine the dose response of the
observed changes.
 
 

Expt. 6    In vivo treatment of chronic SJL mice with antibody dosing
Rc22 (or best candidate) at:
500 µg
50 µg
10 µg
O4 at:
500 µg
50 µg
10 µg
 
human IgM, 500 µg
PBS
 
Research Area 3: Antibody-induced Signaling Experiments
 
Hypothesis: Antibody-mediated enhancement of remyelination is the result of
specific antibody-induced changes in the local architecture of the plasma
membrane of glial cells that trigger specific second messenger systems and
engage downstream signaling cascades. These signals result in transcriptional
and translational events related to increased survival, proliferation, and
differentiation of oligodendrocytes and oligodendrocyte precursors within and
near demyelinating lesions. We will conduct experiments to identify
antibody-induced signaling, cascades that are relevant to the induction of
transcriptional changes involved in oligodendrocyte survival, proliferation, and
differentiation.
 
Expt. 1    Identification of immediate second messenger signals triggered by
antibody-induced plasma membrane reorganization.
 
 

Our preliminary data indicate that remyelination-promoting antibodies induce an
immediate increase in intracellular calcium levels in astrocyte-like cells and a
delayed calcium influx in oligodendrocyte-like cells. The immediate rise in
calcium concentration is sensitive to perturbations of the PLCy signaling
cascade, while the delayed calcium influx is dependent upon mobilization of
extracellular calcium through plasma membrane CNQX-sensitive AMPA-type glutamate
receptors. However, the precise locus and mode of activation of either calcium
increase is undefined. Using immunoaffinity purification, we will prepare
purified cultures of oligodendrocytes captured along a spectrum of developmental
and differentiative stages. These purified and defined cell populations will
then be subjected to ratiometrc fluorescent analysis of intracellular calcium
concentration to determine the type of calcium signal induced by treatment with
antibody. Using specific pharmacological agents we will determine whether the
delayed calcium influx is the result of AMPA receptor agonism (e.g. autocrine or
paracrine release of glutamate), desensitization (conformational change or
alleviation of receptor antagonism), or capacitative calcium influx (calcium
release activated calcium influx).
 
Expt. 2    Identification of downstream signaling cascades engaged by
remyelination-promoting antibodies.
 
Isotope-coded affinity tag (ICAT) analysis is a sophisticated method for
measuring differential protein expression in cultured cells. We propose to use
the ICAT method to analyze changes in protein expression following treatment of
oligodendroglia with remyelination promoting antibodies. We specifically propose
to analyze the following domains: lipid rafts and AMPA receptor-enriched domains
from oligodendrocytcs, and spinal cord demyelinated lesions induced by
lysolecithin injection.
 
Two-dimensional gel electrophoresis (2-DGE) analysis coupled to western blotting
with phosphorylation-state specific antibodies is also a useful tool for
analysis of global signaling responses and identification of uncharacterized
signaling molecules. We propose to use this discovery technique to identify
potential signaling cascades involved in the transmission of antibody-induced
responses from the plasma membrane to the nucleus.
 
6

 
 

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Expt. 3    Characterization of antibody-induced survival, proliferation, and
differentiation signals.
 
Preliminary evidence suggests that remyelination-promoting antibodies function,
at least in part, by protecting oligodendroglia from cell death. We propose to
clarify the nature of this protection and probe its physiological relevance. We
will model macrophage- and/or lymphocyte-mediated killing in vitro by
challenging oligodendroglia with H2O2 TNFa1 or FasL in the presence or absence
of antibody. Cell death will be measured by MTT
[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and death
related signaling will be assessed by examination of changes in JNK, NFKB, Akt,
and caspase-3 activity.
 
Remyelination-promoting antibodies may also exert effects on oligodendrocyte
proliferation. We propose to measure this effect by treating oligodendroglia
with antibodies in the presence of BrdU or 3H-thymidine. BrdU incorporation will
be assessed by imnunostaining, while 3H-thymidine incorporation will be assessed
by scintillation counting of cell lysates. Likewise, remyelination-promoting
antibodies may exert a differentiative effect on oligodendrocyte precursors,
pushing them to mature into myelin-producing cells. To test this effect, we
propose to characterize the expression levels of myelin basic protein,
proteolipid protein, and myelin associated glycoprotein in oligodendroglia
cultured in the presence of remyelination-promoting antibodies.
 
Based on our hypothesis that remyelination-promoting antibodies specifically
reorganize plasma membrane microdomains to initiate biologically relevant
signals, we will determine whether disruption of lipid raft organization, either
pharmacologically via B-MCD and filipin, or synthetically via cholesterol
deprivation, will alter antibody-induced effects on oligodendroglial survival,
proliferation, and differentiation. Likewise, based on the knowledge gained in
the other proposed experiments, we will disrupt identified signal transduction
cascades and measure the effect on cell survival, proliferation, and
differentiation, For example, if signaling through Erk l/2 is identified as a
relevant pathway, we will block O4-induced signaling with PD98059 (MEK
inhibitor) or with the MTPTAT-MEK113  peptide inhibitor (Erk1/2 inhibitor).
Similarly, if PKA signaling is identified above, we will attempt to block
antibody-mediated effects on proliferation and survival using SQ22536 (adenylate
cyclase inhibitor). H89 (PKA inhibitor), or Rp-cAMPs triethylamine (PKA
inhibitor). We intend to take advantage of the availability of robust and
specific pharmacological blockers for every pathway identified downstream from
antibody binding to establish the signaling pathways most relevant to
remyelination.
 
Research Area 4:  Antigen Indentification Experiments
 
Antigen indentification is an important issue concerning the mechanism of action
of remyelination promoting antibodies.  Acorda will take the lead role in the
antigen identification experiments. We will complete our experiments on the
characterizatiuon of potential carbohydrate epitopes and will provide tissue to
Acorda form their experiments.
 
Expt. 1    Determine class of carbohydrate bound by antibodies that promote
remyelination.
We will treat oligodendrocytes with sialidase and related enzymes to determine
class of carbohydrate bound by the antibodies. We will assess the effect of
carbohydrate removal on Ca flux, protein phosphorylation and gene expression.
 
  Expt. 2  We will isolate membrane and cell type specific antigens for antigen
characterization experiments by our group and at Acorda.
 
7

 
 

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Exhibit B
to
License Agreement between
Acorda Therapeutics, Inc. and the
Mayo Foundation for Education and Research,
dated September 8, 2000
 

 
 

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OPTION AGREEMENT
 
This Option Agreement is made this October 1, 1995 by and between Mayo
Foundation for Medical Education and Research, a Minnesota charitable
corporation located at 200 First Street SW, Rochester, Minnesota 55905 (“MAYO”)
and Acorda Therapeutics, Inc., a Delaware Corporation, located at 1213 Park
Avenue, New York, NY 10128 (“ACORDA”).
 
This Option Agreement has three addenda: 1) Stock Warrant Agreement, referred to
in Section 2.5; supplied by Acorda; 2) Appendix A, Sponsored Research Agreement;
3) Appendix B, Technology License Contract Terms Sheet.
 
Certain inventions relating to the promotion of remyelination by monoclonal
antibodies have been made in connection with MAYO’s research, patient care, and
education programs. By assignment of the inventions from the developers, MAYO is
the owner of certain patent rights.
 
ACORDA desires to evaluate such inventions for the purpose of determining its
interest in obtaining a license from MAYO to sell such inventions.
 
Now, therefore, the parties agree as follows:
 
Article 1.   Definitions.
 
1.1 — “Technology” means:
 
 
a)             U.S. patent application S.N. 08/236,520, filed April 19, 1994,
and foreign patent applications and patent counterparts thereto (if any);

 
 

 
b)            all U.S. and foreign patent applications disclosing inventions
conceived or reduced to practice pursuant to the research conducted pursuant to
the Sponsored Research Agreement;

 
 

 
c)             all divisions, substitutions, continuations,
continuations-in-part applications of (i) and (ii) of the preceding, and all
U.S. and foreign patents issuing thereon, including reissues, reexaminations,
and extensions; and

 
 

 
d)            all trade secrets, know-how, and technical information developed
by MAYO in connection with the research conducted pursuant to the Sponsored
Research Agreement.

 
 

Article 2.   Option.
 
2.1 — In order for ACORDA to evaluate the commercial and technical merits of
this Technology, MAYO hereby grants the Company an exclusive worldwide option to
become the exclusive licensee for the Technology. Said option shall expire
thirty-six (36) months from the initiation of the sponsored research described
in Appendix A.
 
2.2 — During the option period, ACORDA shall pay a maximum Two Hundred
Ninety-Two Thousand Dollars ($292,000.00) to sponsor a mutually agreed upon
research protocol to be performed by MAYO, according to the terms of Appendix A.
Payments will be made on a quarterly basis beginning within thirty (30) days of
the date whereby ACORDA accepts delivery of monoclonal antibody (ATCC Accession
No. CRL-11627) from a contract manufacturer for use in MAYO’s research protocol
(hereby referred to as the “Effective Date” of this Option Agreement).
 
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Notwithstanding the above, in the event that the delivery of antibody prepared
on behalf of ACORDA for use in preclinical studies is delayed, through no fault
of ACORDA, by more than six (6) months from the signing of this Option
Agreement, the parties shall negotiate in good faith for an extension of the
option, at no additional cost. Otherwise, MAYO may terminate this Option
Agreement if the Effective Date of the Option Agreement is not within six
(6) months of the signing of this Option Agreement. If the option to license is
exercised or terminated by ACORDA before the expiration date and after
twenty-four (24) months from the Effective Date of this Agreement, ACORDA’s
obligation to make payments to support such research shall be terminated as of
that date. MAYO further agrees that it shall not negotiate with or enter into
any agreement with a third party with respect to the Technology in the period
from the signing of the Option Agreement until the effective date of the Option
Agreement.
 
2.3 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide to license the Technology, then a License Agreement consistent
with the terms sheet attached as Appendix B shall be negotiated and executed by
both parties within ninety (90) days of ACORDA’s notice to MAYO of its decision
to license the Technology, or such longer period as may be agreed by the
parties.
 
2.4 — ACORDA shall pay MAYO Five Thousand Dollars ($5,000.00) within thirty (30)
days of the Effective Date of this Agreement and on each anniversary thereafter
during the Option period as non-refundable and non-creditable consideration for
the exclusive worldwide option granted by MAYO.
 
2.5 — As additional consideration for the exclusive worldwide option, ACORDA
will issue MAYO warrants for the purchase of sixty thousand (60,000) shares of
ACORDA common stock at the price of founders stock, pursuant to the terms of the
Stock Warrant Agreement attached hereto. Such warrants shall be exercisable if
ACORDA exercises its option to acquire a license for the Technology. The cost to
MAYO for exercising its warrants will be reimbursed by ACORDA.
 
2.6 — During the option period, ACORDA shall pay reasonable expenses associated
with the prosecution of the MAYO patent application entitled “Monoclonal
Antibodies Which Promote Central Nervous System Remyelination” (Serial
No. 08/236,520) as well as the corresponding national applications filed under
the Patent Cooperation Treaty; such filings to have been agreed on by MAYO and
ACORDA. Only expenses incurred after March 24, 1994, and related to U.S. Patent
application S.N. 08/236,520 are subject to reimbursement. The patent prosecution
will be controlled by ACORDA, using counsel of ACORDA’s choice, reasonably
acceptable to MAYO.
 
2.7 — During the option period, MAYO may not disclose the Technology to third
parties without ACORDA’s prior written consent, but MAYO shall retain the right
to use the Technology for its internal research purposes.
 
2.8 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide not to license the Technology, MAYO shall be provided with all the
research information generated during the option by ACORDA and MAYO jointly, or
given to ACORDA by MAYO. All data jointly generated during the option by MAYO
and ACORDA and provided to MAYO shall be only for internal use by MAYO.
 
2

 
 

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Article 3.   Confidentiality
 
3.1 — “Confidential Information” is defined as any written confidential
information disclosed by one party to the other and entitled to protection under
this agreement which is marked “CONFIDENTIAL,” or words of similar import. If
oral, visual, or other non-written manner of disclosure of otherwise undisclosed
confidential information is made by one party to the other, such information
shall be entitled to protection if identified as confidential at the time of
initial disclosure and if a written notice with a summary of such disclosures is
delivered to the receiving party within thirty (30) days of such disclosure. Any
markings, stamps, or legends identifying confidential information shall not
impose any obligations on either party inconsistent with this agreement. Any
copies of the information made by the receiving party shall reproduce the
confidential markings and any other legends contained on such information.
 
3.2 — Both ACORDA and MAYO covenant and agree that they shall hold the
Confidential Information they receive from the other party inviolate, keep it
secret, and shall not use any such Confidential Information, except as provided
in Article 4 below. The foregoing restrictions on disclosure of Confidential
Information shall not apply to any information that properly comes into the
public domain through no action of the other party or its agents or was already
known by the other party as evidenced by its that party’s written records. Each
party may use its own discretion to disclose information that was independently
developed by that party.
 
3.3 — Confidential Information shall not be afforded the protection of this
Agreement if, on the date of signing this Agreement, such information is or
later becomes:
 
 
a)             developed by the Recipient independently of the disclosed
proprietary information of the other party, and reasonable written documentation
exists to demonstrate such development; or

 
 

 
b)            rightfully obtained without restriction by the Recipient from any
third party who is not restricted from making such disclosure by any direct or
indirect obligation of confidentiality to the other party herein; or

 
 

 
c)             publicly available other than through the fault of the Recipient;
or

 
 
d)            known to the Recipient at the time of its disclosure by the other
party hereto, and reasonable written documentation exists to demonstrate such
knowledge.

 
 

 
e)             subject to disclosure under a facially valid court order,
warrant, or subpoena, but only if the Recipient first gives the other party
immediate oral and written notice of the court order, warrant, or subpoena to
permit that party to take appropriate legal action in the circumstances.

 
 

3.4 — ACORDA shall not disclose, provide or otherwise make the Technology or the
Confidential Information available to any person or entity other than employees,
consultants, advisors, or agents of ACORDA that have signed secrecy agreements
at least as restrictive as the provisions of this Agreement. Before the
Confidential Information or Technology is made available to any person directly
responsible for the evaluation of the Technology for licensure, ACORDA will
notify the person of the obligations of confidentiality contained in this
Agreement and obtain an agreement from that person to abide by said obligations.
 
3.5 — The obligations of confidentiality stated in 3.1 and 3.2 shall survive the
termination or expiration of this Agreement for five (5) years.
 
3

 
 

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Article 4.   Authorized Use
 
4.1 — During the term of this Option Agreement, ACORDA shall use the Technology
and the Confidential Information only for the purpose of evaluating the
Technology for licensure.
 
4.2 — ACORDA and MAYO shall not use, expressly or by implication, any trademark
or trade name of the other party, or any contraction, abbreviation, simulation
or adaptation thereof, or the name of any of the other party’s staff in any
news, publicity release, policy recommendation, advertising or any commercial
communication without the express written approval of the other party. The
provisions of this Section 4.2 shall survive the Termination or expiration of
this Agreement.
 
Article 5.               Termination
 
5.1 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide to exercise its option and execute the License Agreement, the
terms of this Option Agreement will be superseded by the terms of the License
Agreement at the time the License Agreement is executed by both parties and
becomes effective.
 
5.2 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide not to license the Technology, ACORDA may terminate this Agreement
by providing written notice of its decision to MAYO. Furthermore, Section 2.2 of
this Agreement remains enforceable subsequent to any termination of this Option
Agreement by ACORDA, subject to the terms and conditions of the Sponsored
Research Agreement.
 
5.3 — Following nine (9) months after the Effective Date of this Option
Agreement, ACORDA shall have the right to terminate its support of the Sponsored
Research with ninety (90) days notice; provided ACORDA shall be obligated to pay
to MAYO the salary of one (1) technician until the second anniversary of the
Effective Date of the Option Agreement, unless MAYO receives contract or grant
funds from an external source to support said technician.
 
Article 6.   General
 
6.1 — ACORDA may not assign or subcontract any of its obligations or rights
under this Option Agreement without MAYO’s prior, express, written consent,
which consent may not be unreasonably withheld, except that ACORDA may assign
its rights and obligations under this Agreement to an affiliate wholly-owned or
majority-owned or controlled by ACORDA, or to any entity that acquires
substantially all of the assets of ACORDA, or entities to which ACORDA has
assigned all or substantially all of its assets relating to the Agreement
whether by merger, acquisition, sale, operation of law, or otherwise.
 
6.2 — This Option Agreement and its effects are subject to and shall be
construed and enforced in accordance with the laws of the State of Minnesota
except that no part of Minnesota law shall apply that directs the application of
another jurisdiction’s law.
 
6.3 — The failure of either party to insist at any time upon the strict
observance or performance of any of the provisions of the Option Agreement, or
to exercise any right or remedy as provided in this Option Agreement, shall not
impair any such right or remedy and shall not be construed to be a waiver or
relinquishment. Furthermore, no waiver of any provision of this
 
4

 
 

--------------------------------------------------------------------------------

 

 
Option Agreement by either party shall be construed as a waiver of any other
provision or as a waiver of the same provision at any subsequent time.
 
6.4 — This Option Agreement (including Appendixes A and B) constitutes the
entire agreement between the parties and supersedes all prior or
contemporaneous, oral and written agreements, proposals and discussions relating
to the same subject matter. The Option Agreement may be amended only through a
writing signed by each of the parties.
 
6.5 — Neither party shall disclose the terms of this Agreement to any third
party, and neither party shall issue any press release or other statement to the
media regarding the existence of the Agreement or its subject matter (if the
other party is mentioned) without the prior written consent of the other party.
 
IN WITNESS WHEREOF, each of the parties has caused this Agreement to be executed
on its behalf by its duly authorized representative.
 
MAYO FOUNDATION FOR MEDICAL
ACORDA THERAPEUTICS, INC.
EDUCATION AND RESEARCH
         
Signed:
/s/ Rick F. Colvin
 
Signed:
/s/ RON COHEN
             
Name:
Rick F. Colvin
 
Name:
RON COHEN
             
Title:
Assist. treas.
 
Title:
President, CEO
             
Date:
Oct. 11, 1995
 
Date:
10/06/95
 

 
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THESE SECURITIES HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933 (THE
“ACT”). THEY MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED, OR HYPOTHECATED IN THE
ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT AS TO THE SECURITIES UNDER THE
ACT OR AN OPINION OF COUNSEL, SATISFACTORY TO THE COMPANY, THAT SUCH
REGISTRATION IS NOT REQUIRED.
 
THE SALE OF THESE SECURITIES HAS NOT BEEN QUALIFIED WITH ANY STATE SECURITIES
AUTHORITIES. THE RIGHTS OF ALL PARTIES TO THIS WARRANT ARE EXPRESSLY CONDITIONED
UPON SUCH QUALIFICATION BEING OBTAINED UNLESS THE SALE IS SO EXEMPT.
 
THIS WARRANT MAY NOT BE EXERCISED EXCEPT IN COMPLIANCE WITH ALL APPLICABLE
FEDERAL AND STATE SECURITIES LAWS TO THE REASONABLE SATISFACTION OF THE COMPANY
AND LEGAL COUNSEL FOR THE COMPANY.
 
STOCK WARRANT AGREEMENT
 
To Purchase 60,000 Shares of the Common Stock of
 
ACORDA THERAPEUTICS, INC.
 
Dated as of October     , 1995
 
1.             GRANT OF THE RIGHT TO PURCHASE COMMON STOCK.
 
For value received, Acorda Therapeutics, Inc., a Delaware corporation (the
“Company”), hereby grants to Mayo Foundation for Medical Education and Research,
a Minnesota charitable corporation (the “Warrantholder”), and the Warrantholder
is entitled, upon the terms and subject to the conditions hereinafter set forth,
to subscribe for and purchase from the Company up to 60,000 fully paid and
non-assessable shares of the Company’s Common Stock (“Common Stock”).  This
Warrant Agreement is entered between the parties and the rights to purchase
Common Stock are granted pursuant to Section 2.5 of the Option Agreement of even
date herewith between the Company and the Warrantholder (the “Option
Agreement”). The purchase rights set forth in this Warrant Agreement shall
become exercisable immediately upon the Company’s exercise of its option as set
forth in the Option Agreement to license certain technology of the
Warrantholder. The exercise price (“Exercise Price”) shall be equal to $0.01 per
share. The number and purchase price of such shares are subject to adjustment as
provided in Section 8 hereof.
 
2.             TERM Of THE WARRANT AGREEMENT.
 
Except as otherwise provided for herein, the term of this Warrant Agreement and
the right to purchase Common Stock as granted herein shall commence on the date
of this Agreement and shall expire upon the first to occur of (i) the expiration
of the Option Agreement in accordance with its terms, (ii) the effective date of
the Company’s firmly underwritten initial public offering pursuant to a
registration statement filed with the United States Securities and Exchange
Commission under the Securities Act of 1933, as amended (the “Securities Act”),
or (iii) the completion date of the sale of the Company, or of
 

 
 

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all or substantially all of its assets, by merger, acquisition, or otherwise (in
which the stockholders of the Company immediately prior to such sale hold less
than a majority-in-interest of the voting equity of any successor corporation
following such sale), or the sale of all or substantially all of the assets of
the Company.
 
3.             EXERCISE OF THE PURCHASE RIGHTS.
 
Subject to Section 1 above, the purchase rights set forth in this Warrant
Agreement are exercisable by the Warrantholder, in whole or in part, at any time
or from time to time, prior to the expiration of the term set forth in Section 2
above, by tendering to the Company at its principal office a notice of exercise
in the form attached hereto as Exhibit I (the “Notice of Exercise”), duly
completed and executed. Upon receipt of the Notice of Exercise and the payment
of the purchase price in accordance with the terms set forth below, the Company
shall issue to the Warrantholder a certificate for the number of shares of
Common Stock purchased and shall execute the Notice of Exercise indicating the
number of shares which remain subject to future purchases, if any.
 
The Warrantholder may either (i) exercise all or any portion of the outstanding
warrants by paying to the Company, by cash or check, an amount equal to the
aggregate Exercise Price of the shares being purchased or (ii) receive shares
equal to the value (as determined below) of this Warrant by surrender of the
Warrant at the principal office of the Company together with notice of such
election in which event the Company shall issue to the Warrantholder a number of
shares of Common Stock computed using the following formula:
 

 
X =
Y(A-B)
       
A
         
Where:
X = The number of shares of Common to be issued to the Warrantholder.
       
Y = The number of shares of Common to be exercised under this Warrant.
       
A = The fair market value of one share of Common.
     
B = The Exercise Price.

 
As used herein, current fair market value of Common Stock shall mean with
respect to each share of Common Stock the average of the closing prices of the
Company’s Common Stock sold on all securities exchanges on which the Common
Stock may at the time be listed, or, if there have been no sales on any such
exchange on any day, the average of the highest bid and lowest asked prices on
all such exchanges at the end of such day, or, if on any day the Common Stock is
not so listed, the average of the representative bid and asked prices quoted in
the NASDAQ System as of 4:00 p.m., New York City time, or, of on any day the
Common Stock is not quoted in the NASDAQ System, the average of the highest bid
and lowest asked price on such day in the domestic over-the-counter market as
reported by the National Quotation Bureau, Incorporated, or any similar
successor organization, in each such case averaged over a period of 10 days
consisting of the day as of which the current fair market value of
 
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Common Stock is being determined and the 9 consecutive business days prior to
such day.  If at any time the Common Stock is not listed on any securities
exchange or quoted in the NASDAQ System or the over-the-counter market, the
current fair market value of Common Stock shall be the highest price per share
which the Company could obtain from a willing buyer (not a current employee or
director) for shares of Common Stock sold by the Company, from authorized but
unissued shares, as determined in good faith by the Board of Directors of the
Company, unless (i) the Company shall become subject to a merger, acquisition,
or other consolidation pursuant to which the Company is not the surviving party,
in which case the current fair market value of the Common Stock shall be deemed
to be the value received by the holders of the Company’s stock for each share of
stock, pursuant to the Company’s acquisition or (ii) the Warrantholder shall
purchase such shares in conjunction with the initial underwritten public
offering of the Company’s Common Stock pursuant to a registration statement
filed under the Securities Act, in which case, the fair market value of the
shares of stock subject to this Warrant shall be the price at which all
registered shares are sold to the public in such offering.
 
4.             RESERVATION OF SHARES.
 
During the term of this Warrant Agreement, the Company will at all times have
authorized and reserved a sufficient number of shares of its Common Stock to
provide for the exercise of the rights to purchase Common Stock as provided for
herein.
 
5.             NO FRACTIONAL SHARES OR SCRIP.
 
No fractional share or scrip representing fractional shares shall be issued upon
the exercise of the Warrantholder’s right to purchase Common Stock, but in lieu
of such fractional shares the Company shall make a cash payment therefor upon
the basis of the Exercise Price then in effect.
 
6.             NO RIGHTS AS STOCKHOLDERS.
 
The Warrant Agreement does not entitle the Warrantholder to any voting right or
other rights as a stockholder of the Company prior to the exercise of the
Warrantholder’s rights to purchase Common Stock as provided for herein.
 
7.             WARRANTHOLDER REGISTRY.
 
The Company shall maintain a registry showing the name and address of the
registered holder of this Warrant Agreement.
 
8.             ADJUSTMENT RIGHTS.
 
The purchase price per share and the number of shares of Common Stock
purchasable hereunder are subject to adjustment from time to time, as follows:
 
(a)           Merger.  If at any time there shall be a capital reorganization of
the shares of the Company’s stock (other than a combination, reclassification,
exchange, or subdivision of shares otherwise
 
3

 
 

--------------------------------------------------------------------------------

 

 
provided for herein), or a merger or consolidation of the Company with or into
another corporation when the Company is not the surviving corporation (but its
stockholders nevertheless control not less than a majority-in-interest of the
voting equity of any successor corporation), then, as a part of such
reorganization, merger, or consolidation, lawful provision shall be made so that
the Warrantholder shall thereafter be entitled to receive upon exercise of its
rights to purchase Common Stock, the number of shares of common stock or other
securities of the successor corporation resulting from such reorganization,
merger or consolidation, to which a holder of the Common Stock deliverable upon
exercise of the right to purchase Common Stock hereunder would have been
entitled in such reorganization, merger or consolidation if the right to
purchase such Common Stock hereunder had been exercised immediately prior to
such reorganization, merger or consolidation.   In any such case, appropriate
adjustment (as determined in good faith by the Company’s Board of Directors)
shall be made in the application of the provisions of this Warrant Agreement
with respect to the rights and interests of the Warrantholder after the
reorganization, merger, or consolidation to the end that the provisions of this
Warrant Agreement (including adjustments of the Exercise Price and number of
shares of Common Stock purchasable pursuant to the terms and conditions of this
Warrant Agreement) shall be applicable after the event, as near as reasonably
may be, in relation to any shares deliverable after that event upon the exercise
of the Warrantholder’s rights to purchase Common Stock pursuant to this Warrant
Agreement.
 
(b)           Reclassification of Shares.  If the Company at any time shall, by
combination, reclassification, exchange, or subdivision of securities or
otherwise, change any of the securities as to which purchase rights under this
Warrant Agreement exist into the same or a different number of securities of any
other class or classes, this Warrant Agreement shall thereafter represent the
right to acquire such number and kind of securities as would have been issuable
as the result of such change with respect to the securities which were subject
to the purchase rights under this Warrant Agreement immediately prior to such
combination, reclassification, exchange, subdivision, or other change.
 
(c)           Subdivision or Combination of Shares.  If the Company at any time
shall combine or subdivide its Common Stock, the Exercise Price shall be
proportionately decreased in the case of a subdivision, or proportionately
increased in the case of a combination.
 
(d)           Notice of Adjustments.  In the event that (i) the Company shall
declare any dividend or distribution upon its stock, whether in cash, property,
stock, or other securities; (ii) the Company shall offer for subscription pro
rata to the holders of any class of its Common or other convertible stock any
additional shares of stock of any class or other rights; (iii) there shall be
any capital reorganization, reclassification, consolidation, merger or sale of
all or substantially all of the Company’s assets; or (iv) there shall be any
voluntary or involuntary dissolution, liquidation, or winding up of the Company,
then, in connection with each such event, the Company shall send to the
Warrantholder:
 
(i)    At least 20 days’ prior written notice of the date on which the books of
the Company shall close or a record shall be taken for such dividend,
distribution, subscription rights (specifying the date on which the holders of
Common Stock shall be entitled thereto) or for determining rights to vote in
respect of such capital reorganization, reclassification, consolidation, merger,
dissolution, liquidation, or winding up; and
 
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(ii)           In the case of any such capital reorganization, reclassification,
consolidation, merger or sale of all or substantially all of the Company’s
assets, dissolution, liquidation or winding up, at least 20 days’ prior written
notice of the date when the same shall take place and specifying the date on
which the holders of Common Stock shall be entitled to exchange their Common
Stock for securities or other property deliverable upon such capital
reorganization, reclassification, consolidation, merger, or sale of all or
substantially all of the Company’s assets, dissolution, liquidation, or winding
up).
 
Each such written notice shall set forth, as applicable and in reasonable
detail, (i) the event requiring the adjustment, (ii) the amount of the
adjustment, (iii) the method by which such adjustment was calculated, (iv) the
Exercise Price, and (v) the number of shares subject to purchase hereunder after
giving effect to such adjustment, and shall be given by first class mail,
postage prepaid, addressed to the Warrantholder, at the address as shown on the
books of the Company.
 
9.             REPRESENTATIONS AND COVENANTS OF THE WARRANTHOLDER.
 
This Warrant Agreement has been entered into by the Company in reliance upon the
following representations and covenants of the Warrantholder, which by its
execution hereof the Warrantholder hereby confirms:
 
(a)           Investment Purpose.  The Common Stock issuable upon exercise of
the Warrantholder’s rights contained herein will be acquired for investment and
not with a view to the sale or distribution of any part thereof, and the
Warrantholder has no present intention of selling or engaging in any public
distribution of the same except pursuant to a registration or exemption.
 
(b)           Private Issue.  The Warrantholder understands (i) that the Common
Stock issuable upon exercise of the Warrantholder’s rights contained herein is
not registered under the Securities Act or qualified under applicable state
securities laws on the ground that the issuance contemplated by this Warrant
Agreement will be exempt from the registration and qualifications requirements
thereof and (ii) that the Company’s reliance on such exemption is predicated on
the representations set forth in this Section 9.
 
(c)           Disposition of Warrantholder’s Rights.  In no event will the
Warrantholder make a disposition of any of its rights to acquire Common Stock
issuable upon exercise of such rights unless and until (i) it shall have
notified the Company of the proposed disposition and (ii) if requested by the
Company, it shall have furnished the Company with an opinion of counsel (which
counsel may either be inside or outside counsel to the Warrantholder)
satisfactory to the Company and its counsel to the effect that (A) appropriate
action necessary for compliance with the Securities Act has been taken, or
(B) an exemption from the registration requirements of the Securities Act is
available.  Notwithstanding the foregoing, the restrictions imposed upon the
transferability of any of its rights to acquire Common Stock issuable on the
exercise of such rights do not apply to transfers from the beneficial owner of
any of the aforementioned securities to its nominee or from such nominee to its
beneficial owner, and shall terminate as to any particular share of Common Stock
when (1) such security shall have been effectively registered under the
Securities Act and sold by the holder thereof in accordance with such
registration or (2) such
 
5

 
 

--------------------------------------------------------------------------------

 

 
security shall have been sold without registration in compliance with Rule 144
under the Securities Act, or (3) a letter shall have been issued to the
Warrantholder at its request by the staff of the United States Securities and
Exchange Commission or a ruling shall have been issued to the Warrantholder at
its request by such Commission stating that no action shall be recommended by
such staff or taken by such Commission, as the case may be, if such security is
transferred without registration under the Securities Act in accordance with the
conditions set forth in such letter or ruling and such letter or ruling
specifies that no subsequent restrictions on transfer are required.  Whenever
the restrictions imposed hereunder shall terminate, as hereinabove provided, the
Warrantholder or holder of a share of Common Stock then outstanding as to which
such restrictions have terminated shall be entitled to receive From the Company,
without expense to such holder, one or more new certificates for the Warrant or
for such shares of Common Stock not bearing any restrictive legend.
 
(d)           Financial Risk.  The Warrantholder has such knowledge and
experience in financial and business matters as to be capable of evaluating the
merits and risks of its investment and has the ability to bear the economic
risks of its investment.
 
(e)           Risk of No Registration.  The Warrantholder understands that if
the Company does not register with the Securities and Exchange Commission
pursuant to Section 12 of the Securities Exchange Act of 1934 (the “Exchange
Act”), or file reports pursuant to Section 15(d) of the Exchange Act, or if a
registration statement covering the securities under the Securities Act is not
in effect when it desires to sell the Common Stock issuable upon exercise of the
right to purchase, it may be required to hold such securities for an indefinite
period.  The Warrantholder also understands that any sale of its Common Stock
which might be made by it in reliance upon Rule 144 under the Securities Act may
be made only in accordance with the terms and conditions of that Rule.
 
10.           TRANSFERS.
 
This Warrant may not be transferred in any manner otherwise than by will or by
the laws of descent or distribution and may be exercised only by the
Warrantholder or his permitted assignee.  Any transfer of this Warrant must
comply with the requirements of this Section 10, and any assignee or transferee
of this Warrant (“permitted assignee”) shall be required to accept this Warrant
subject to all rights and obligations of the Warrantholder as set forth herein. 
Any securities to be issued upon exercise of this Warrant may not be sold,
assigned, transferred or otherwise disposed of unless the securities are
registered under the Securities Act or unless the person seeking to effect such
disposition shall have requested and the Company shall have received an opinion
of the Company’s counsel that the proposed disposition may be effected without
registration of such securities under the Securities Act or any applicable state
securities laws.  Unless a registration statement with respect to such shares of
Common Stock is effective at the time, any shares of Common Stock issued upon
the exercise of this Warrant shall bear the following legend:
 
6

 
 

--------------------------------------------------------------------------------

 

 
THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE MOT BEEN REGISTERED UNDER
THE UNITED STATES SECURITIES ACT OF 1933, AS AMENDED THE (“ACT”).  THEY MAY NOT
BE SOLD, OFFERED FOR SALE, PLEDGED, OR HYPOTHECATED IN THE ABSENCE OF AN
EFFECTIVE REGISTRATION STATEMENT AS TO THE SECURITIES UNDER THE ACT OR AN
OPINION OF COUNSEL, SATISFACTORY TO THE COMPANY, THAT REGISTRATION IS NOT
REQUIRED.
 
11.           MARKET STANDOFF AGREEMENT.
 
The Warrantholder hereby agrees, if so requested by the managing underwriters in
an initial public offering by the Company of its Common Stock, that, without the
prior written consent of such managing underwriters, the Warrantholder will not
offer, sell, contract to sell, grant any option to purchase, make any short
sale, or otherwise dispose of or make a distribution of any capital stock of the
Company held by or on behalf of the Warrantholder or beneficially owned by the
Warrantholder in accordance with the rules and regulations of the United States
Securities and Exchange Commission for a period of up to 180 days after the date
of the final prospectus relating to the Company’s initial public offering.
 
12.           MLSCELLANEOUS.
 
(a)           Effective Date.  The provisions of this Warrant Agreement shall be
construed and shall be given effect in all respects as if it had been executed
and delivered by the Company on the date hereof.  This Warrant Agreement shall
be binding upon any successors or assigns of the Company.
 
(b)           Attorneys’ Fees.  In any litigation, arbitration or court
proceeding between the Company and the Warrantholder relating hereto, the
prevailing party shall be entitled to attorneys’ fees and expenses and all costs
of proceedings incurred in enforcing this Warrant Agreement.
 
(c)           Governing Law.  This Warrant Agreement shall be governed by and
construed for all purposes under and in accordance with the laws of the State of
Delaware as applied to agreements between Delaware residents entered and to be
performed entirely within Delaware.
 
(d)           Counterparts.  This Warrant 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.
 
(e)           Titles and Subtitles.  The titles of the paragraphs and
subparagraphs of this Warrant Agreement are for convenience and are not to be
considered in construing this Agreement.
 
(f)            Notices.  Any notice required or permitted hereunder shall be
given in writing and shall be deemed effectively given upon personal delivery or
upon deposit in the United States mail, by registered or certified mail,
addressed (i) to the Warrantholder at the address set forth on the signature
 
7

 
 

--------------------------------------------------------------------------------

 

 
page hereof and (ii) to the Company at its principal executive offices to the
attention of its president or at such other address as any such party may
subsequently designate by written notice to the other party.
 
(g)           Survival.  The representations, warranties, covenants and
conditions of the respective parties contained herein or made pursuant to this
Warrant Agreement shall survive the execution and delivery of this Warrant
Agreement.
 
(h)           Amendments.  Any provision of this Warrant Agreement may be
amended by a written instrument signed by the Company and by the Warrantholder.
 
8

 
 

--------------------------------------------------------------------------------

 

 
IN WITNESS WHEREOF, the parties hereto have caused this Warrant Agreement to be
executed by its officers thereunto duly authorized.
 

 
Company:
     
ACORDA THERAPEUTICS, INC.
       
Dated August   , 1995
By:
     
Ron Cohen, M.D., President
         
Warrantholder:
     
MAYO FOUNDATION FOR MEDICAL EDUCATION
AND RESEARCH
         
By:
         
Title:
       
Address:
c/o Office of Technology Transfer
Mayo Medical Ventures
200 First Street Southwest
Rochester, Minnesota 55905
   
Attn:
             

 
9

 
 

--------------------------------------------------------------------------------

 

 
EXHIBIT I

NOTICE OF EXERCISE
 
Ron Cohen, M.D.
To: Acorda Therapeutics, Inc.
 
 
(1)           The undersigned Warrantholder hereby elects to purchase 60,000
shares of the Common Stock of ACORDA THERAPEUTICS, INC., pursuant to the terms
of the Warrant Agreement dated the          day of October, 1995 (the “Warrant
Agreement”) between ACORDA THERAPEUTICS, INC. and the Warrantholder, and tenders
herewith payment of the purchase price for such shares in full, together with
all applicable transfer taxes, if any.

 
 
(2)           In exercising its rights to purchase the Common Stock of ACORDA
THERAPEUTICS, INC., the undersigned hereby confirms and acknowledges the
investment representations and warranties made in Section 9 of the Warrant
Agreement.

 
 

 
(3)           Please issue a certificate or certificates representing said
shares of Common Stock in the name of the undersigned or in such other name as
is specified below.

 
 

 
Mayo Foundation for Medical Education
 
and Research
 
(Name)
       
200 First Street SW
Rochester, MN 55905
 
(Address)
       
Warrantholder:
Mayo Foundation for Medical
Education and Research
     
By:
/s/ Rick F. Colvin
   
Rick F. Colvin
       
Title:
Assistant Treasurer
       
Date:
10/6/00
         

 
10

 
 

--------------------------------------------------------------------------------

 

 
Appendix A
to
Acorda/Mayo Option Agreement dated October 1, 1995

(Included as Exhibit A to License Agreement between
Acorda Therapeutics, Inc. and the
Mayo Foundation for Education and Research,
dated September 8, 2000)
 

 
 

--------------------------------------------------------------------------------

 

 
ACORDA - MAYO CLINIC

License Agreement Terms
 
License:
 
Mayo Clinic (“Mayo”) will grant Acorda an exclusive license, with the right to
grant and authorize sublicenses, under the Licensed Patents to make, have made,
use and sell Licensed Products in the Territory.
     
Territory:
 
Worldwide.
     
Licensed Technology:
 
Licensed Technology includes (i) the Licensed Patents and (ii) Project Know How.
     
Licensed Patents:
 
Licensed Patents include (i) the patent applications listed on Exhibit A hereto,
(ii) all patent applications filed with respect to inventions conceived or
otherwise developed in the course of and in connection with the Sponsored
Research, and (iii) all divisions, substitutions, continuations,
continuations-in-part applications, and reissues, re-examinations, and
extensions of (i) and (ii) above, all patents issuing on the preceding, and all
foreign counterparts of the preceding.
     
Project Know-How:
 
All trade secrets and other intellectual property conceived or otherwise
developed in the course of and in connection with the Sponsored Research, and
all subsequent modifications, enhancements and improvements, excluding the
patent applications and patents within the Licensed Patents.
     
Licensed Products:
 
Products covered by a valid issued or pending claim of a Licensed Patent in the
country which such Product is sold, or which directly incorporate Project
Know-How.

 
1

 
 

--------------------------------------------------------------------------------

 

 

 
Equity:
 
On the Effective Date of the license agreement, Mayo may exercise the warrants
granted Mayo to purchase 60,000 shares of Acorda common stock, at the price of
founder’s stock.
         
Royalties:
 
Acorda will pay Mayo royalties on net sales of Licensed Products by Acorda and
its affiliates, as follows:
             
1% on net sales of Licensed Products covered by a valid claim of an issued
patent within the Licensed Patents in the country which such Licensed Product is
sold.
             
0.5% on net sales of Licensed Products covered by a claim of a pending patent
application within the Licensed Patents in the country which such Licensed
Product is sold, or which directly incorporate Project Know-How.
             
Beginning on the first anniversary of the commercial sale of a Licensed Product,
Acorda will pay Mayo the following minimum annual royalties:
   
Year 1
 
$
20,000
     
Year 2
 
$
25,000
     
Year 3
 
$
30,000
     
Year 4 and thereafter
 
$
35,000
       
In addition, Acorda will pay Mayo 25% of the amounts received by Acorda from
sublicensees with respect to the sale of such Licensed Products.
             
Notwithstanding the above, it is understood and agreed that Mayo shall not be
entitled to any share of amounts received by Acorda from sublicensees for
equity, research and development, performance-based milestones, the license or
sublicense of any intellectual property other than the
                 

 
2

 
 

--------------------------------------------------------------------------------

 

 

   
Licensed Technology, or reimbursement for patent or other expenses.
         
In the event that a Licensed Product is sold in combination with another product
which is not a Licensed Product, the amount paid to Mayo shall be based on the
proportion of the value of such combination product reasonably attributable to
the Licensed Technology; provided in no event shall Mayo receive less than 0.25%
of the net sales of Licensed Products sold by Acorda.
     
Due Diligence:
 
Acorda will use reasonable efforts to enter into an agreement with a contract
manufacturer for the production of Mayo’s mylenating monoclonal antibody, by the
later of June 1, 1995, or within sixty (60) days following the close of Acorda’s
Series A financing.
         
Acorda will use reasonable commercial efforts, consistent with its prudent
business judgment, to develop Licensed Products and obtain and maintain such
approvals as may be necessary for the sale of Licensed Products in the U.S. and
such other worldwide markets as Acorda elects to sell such Licensed Products.
     
Milestone Payments:
 
Acorda will pay to Mayo the following amounts on the achievement of the
following events:
         
Effective Date of license
 
$
25,000
                 
Issue of first U.S. patent within the Licensed Patents
 
$
25,000
                 
Initiation of Phase I clinical trials for the first Licensed Product
 
$
50,000
                 
FDA marketing approval of the first Licensed Product
 
$
500,000
 

 
3

 
 

--------------------------------------------------------------------------------

 

 
Patent Prosecution:
 
Acorda will be responsible, using patent counsel of its choice, for preparing,
filing, prosecuting and maintaining patent applications and patents within the
Licensed Patents.  Acorda will pay the costs incurred in connection with such
activities, and reimburse Mayo for reasonable costs incurred in connection with
such activities prior to the effective date of the license; 50% of all such
amounts (including attorneys fees) shall be creditable against earned royalties
due Mayo.  At Mayo’s request, Acorda shall provide Mayo with reasonable
documentation of such costs.  Mayo and Acorda will cooperate and consult with
each other in the prosecution of the Licensed Patents.
     
Patent Enforcement:
 
In the event of any infringement of the Licensed Patents or misappropriation of
the Project Know-How, the parties shall consult to determine if they will
jointly bring action to terminate such infringement or misappropriation.  Any
recovery obtained by the parties in such an action shall be used first to
reimburse the costs of such action, and the remainder divided equally between
the parties.
         
In the event that the parties fail to initiate such action within ninety (90)
days of receiving notice of such infringement or misappropriation, Mayo shall
have the right, but not the obligation, to initiate suit to stop such
infringement or misappropriation; provided if Mayo does not initiate such an
action within a further ninety (90) days, Acorda shall have the right to pursue
any infringement of the Licensed Patents, or opposition or interference with
respect thereto, or any misappropriation of Project Know-How, or defend any
declaratory judgment relating thereto.  Any recovery obtained by

 
4

 
 

--------------------------------------------------------------------------------

 

 

   
Acorda in such an action shall be used first to reimburse the costs of such
action, and the remainder shall be retained by Acorda and treated as net sales
of Licensed Products, subject to the royalty obligations to Mayo herein.
     
Royalties to Third Parties:
 
In the event that in connection with its sale of Licensed Products, Acorda pays
a third party royalties or other amounts to avoid or settle a claim of
infringement of the intellectual property rights of such third party, Acorda may
offset such amounts against up to 50% of the amounts due Mayo; provided,
however, in no event shall Mayo receive less than 0.25% of the net sales of
Licensed Products sold by Acorda and its affiliates.
     
Sublicenses:
 
Any sublicenses granted by Acorda under the Licensed Technology shall remain in
effect and be assigned to Mayo in the event this license terminates.
     
Assignment:
 
Acorda may not assign the license without the consent of Mayo, which consent
shall not be unreasonably withheld; provided, Acorda may assign the license in
connection with the sale or transfer of all or substantially all the rights and
obligations of Acorda relating to the Licensed Products, without the prior
consent of Mayo.
     
Term:
 
The license shall terminate on a country-by-country basis upon the expiration of
the last to expire Licensed Patent in such country, or, if no Licensed Patent
issues in a country, twelve years following the first commercial sale of a
Licensed Product in such country, on a Licensed Product-by-Licensed Product
basis.  Acorda shall have the right to terminate the license agreement with
respect to any Licensed

 
5

 
 

--------------------------------------------------------------------------------

 

 

   
Technology or any country, on ninety (90) days written notice.
     
Other:
 
The formal agreement will include other customary provisions to be agreed by the
parties, including indemnification, royalty reporting, audit rights and the
like.

 
6

 
 

--------------------------------------------------------------------------------

 

 
Amendment No. 1 to Option Agreement
 
This Amendment No. 1 to Option Agreement (the “Amendment”) is effective as of
October 2, 1995 between Acorda Therapeutics, Inc. (“Acorda”) and Mayo Foundation
for Medical Education and Research (“Mayo”) concerning the Option Agreement
between Acorda and Mayo effective October 1, 1995.
 
1.             The parties have agreed to broaden the scope of the Technology to
include certain additional monoclonal antibodies.
 
2.             Section 1.1(a) is hereby amended to read in its entirety as
follows:
 
(a) U.S. patent application S.N. 08/236, 520, filed April 19, 1994, and all
patent applications disclosing any invention or other intellectual property
developed by Moses Rodriguez, M.D. and owned in whole or part by MAYO relating
to monoclonal antibodies associated with myelination, or derivatives and analogs
thereof, including without limitation, compositions and methods of making and
using thereof, and foreign patent applications and patent counterparts thereto
(if any);
 
3.             Add new Section 1.l(e), which provides in its entirety:
 
(e) the biological materials listed on Exhibit A hereto.
 
 

4.             Section 2.6 is hereby amended to read in its entirety as follows:
 
2.6 — During the option period, ACORDA shall pay reasonable expenses associated
with the prosecution of the MAYO patent application entitled “Monoclonal
Antibodies Which Promote Central Nervous System Remyelination” (Serial
No. 08/236, 520) and other patent applications included in Section 1.1(a) above,
as well as the corresponding national applications filed under the Patent
Cooperation Treaty; such filings to have been agreed on by MAYO and ACORDA. Only
expenses incurred after March 24, 1994, and related to the preceding patent
applications are subject to reimbursement.  The patent prosecution will be
controlled by ACORDA, using counsel of ACORDA’s choice, reasonably acceptable to
MAYO.
 
5.             Except as specifically modified or amended hereby, the Option
Agreement shall remain in full force and effect and, as so modified or amended,
is hereby ratified, confirmed and approved.  No provision of this Amendment may
be modified or amended except expressly in a writing signed by both parties nor
shall any terms be waived except expressly in writing signed by the party
charged therewith. This Amendment shall be governed in accordance with the laws
of the State of Minnesota, without reference to principles of conflicts of laws.
 

 
 

--------------------------------------------------------------------------------

 

 
IN WITNESS WHEREOF, the parties have duly executed this Amendment as of the date
shown above.
 

 
ACORDA THERAPEUTICS, INC.
     
By:
/s/ Ron Cohen
     
Print Name:
Ron Cohen, MD
       
Title:
President & CEO
           
MAYO FOUNDATION FOR
MEDICAL EDUCATION AND
RESEARCH
     
By:
/s/ Rick F. Colvin
     
Print Name:
Rick F. Colvin
       
Title:
Assistant Treasurer
             

 

 
 

--------------------------------------------------------------------------------

 

 
Exhibit A to Amendment Number 1 to Option Agreement
between
Mayo Foundation for Medical Education and Research
and
Acorda Therapeutics, Inc.
 
Biologic materials include:
 
 
1.   monoclonal antibody 94.03

 
 
2.   monoclonal antibody SCH 79.03

 
 
This list may be amended from time to time during the course of the Agreement.
 

 
 

--------------------------------------------------------------------------------

 

 
 
Wednesday, July 31, 1996
 
Susan Stoddard, Ph.D.
Mayo Medical Ventures
200 First Street S.W.
Rochester, MN 55905
 
 
Dear Susan:
 
This letter confirms that, with regard to the Option Agreement (the “Agreement”)
of October 1, 1995 between Acorda Therapeutics, Inc. (“Acorda”) and the Mayo
Foundation for Medical Education and Research (“Mayo”), relating to U.S. patent
application S.N. 08/236, 520, Acorda and Mayo agree that the Effective Date of
the Option Agreement may be extended up to December 1, 1996.
 
All other provisions of the Agreement shall remain in effect unless amended in
writing by mutual agreement of Acorda and Mayo.
 
If the foregoing is satisfactory, please sign, or have another appropriate
representative of Mayo sign, both copies of this letter to indicate Mayo’s
agreement, and return one copy to my attention at Acorda.
 
Thank you for your consideration.  If you have any questions, please do not
hesitate to call.
 
Sincerely yours,
 
/s/ Ron Cohen
   
Ron Cohen, M.D.
 
President and Chief Executive Officer
         
AGREED TO by the
 
MAYO FOUNDATION FOR MEDICAL
 
EDUCATION AND RESEARCH:
   
Signed:
/s/ Rick F. Colvin
     
Name:
Rick F. Colvin
     
Title:
Assistant Treasurer
     
Date:
8/9/96
           

 
 
145 WEST 58TH STREET
 
NEW YORK, NY 10019
 
FAX: (212) 765-8637
SUITE #8J
 
PHONE: (212) 376-7552
 
E-MAlL: DRRON18@ADL.COM

 

 
 

--------------------------------------------------------------------------------

 

 
 
JAN 6
 
December 31, 1996
 
Susan Stoddard, Ph.D.
Mayo Medical Ventures
200 First Street S.W.
Rochester, MN 55905
 
 
Dear Susan:
 
This letter (the “Second Extension Letter”) confirms that, with regard to the
Option Agreement (the “Agreement”) of October 1, 1995 between Acorda
Therapeutics, Inc. (“Acorda”) and the Mayo Foundation for Medical Education and
Research (“Mayo”), relating to U.S. patent application S.N. 08/236, 520, and
with regard to the letter of July 31, 1996 extending the Effective Date of the
Option Agreement up to December 1, 1996 (the “First Extension Letter”), Acorda
and Mayo agree that the Effective Date of the Option Agreement may be extended
up to January 2, 1997, and that this Second Extension Letter supersedes the
First Extension Letter.
 
All other provisions of the Agreement shall remain in effect unless amended in
writing by mutual agreement of Acorda and Mayo.
 
If the foregoing is satisfactory, please sign, or have another appropriate
representative of Mayo sign, both copies of this letter to indicate Mayo’s
agreement, and return one copy to my attention at Acorda.
 
Thank you for your consideration.  If you have any questions, please do not
hesitate to call.
 
Sincerely yours,
 
/s/ Ron Cohen
   
Ron Cohen, M.D.
 
President and Chief Executive Officer
     
AGREED TO by the
 
MAYO FOUNDATION FOR MEDICAL
 
EDUCATION AND RESEARCH:
   
Signed:
/s/ Rick F. Colvin
     
Name:
Rick F. Colvin
     
Title:
Assistant Treasurer
     
Date:
1/7/97
           

 
145 WEST 58TH STREET
 
NEW YORK, NY 10019
 
FAX: (212) 765-8637
SUITE #8J
 
PHONE: (212) 376-7552
 
E-MAlL: DRRON18@ADL.COM

 

 
 

--------------------------------------------------------------------------------

 

 
ACORDA/MAYO
 
Amendment No. 3 to Option Agreement
 
This Amendment No. 3 to Option Agreement (the “AMENDMENT”) is effective as of
March 15, 1998 between Acorda Therapeutics, Inc. (“ACORDA”) and Mayo Foundation
for Medical Education and Research (“MAYO”) concerning the Option Agreement
between Acorda and Mayo Effective October 1, 1995.
 
1.             The parties have agreed to include humanization of MAbs by Larry
Pease, Ph.D, and Moses Rodriguez, M.D.
 
2.             Section 1.1 (a) is hereby amended to read in its entirety as
follows;
 
(a)           U.S. patent application S.N. 08/236,520, filed April 19, 1994, and
all patent applications disclosing any invention or other intellectual property
developed in whole or in part by Moses Rodriguez and/or Larry Pease owned in
whole or in part by MAYO relating to humanized and non-humanized monoclonal
antibodies associated with myelination and/or remyelination, or derivatives and
analogs thereof, including without limitation, compositions and methods of
making and using thereof, and foreign patent applications and counterparts
thereto (if any);
 
3.             Except as specifically modified or amended hereby or in Amendment
No. 1 to the Option Agreement, the Option Agreement shall remain in full force
and effect and, as so modified or amended, is hereby ratified, confirmed and
approved. No provision of this Amendment may be modified or amended except
expressly in a writing signed by the party charged therewith. This amendment
shall be governed in accordance with the laws of the State of Minnesota, without
reference to principals of conflicts of laws.
 
IN WITNESS WHEREOF, the parties have duly executed this Amendment as of the date
shown above.
 
 
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
ACORDA THERAPEUTICS, INC.
   
Signed:
/s/ John H. Herrell
 
Signed:
/s/ Ron Cohen, M.D.
             
Name:
John H. Herrell
 
Name:
Ron Cohen, M.D.
             
Title:
Vice President
 
Title:
President & CEO
             
Date:
March 24, 1998
 
Date:
3/20/98
               

 

 
 

--------------------------------------------------------------------------------

 

 
Acorda/Mayo Option & Res Agr (Rodriguez/Pease)
 
Confidential

 
ACORDA/MAYO
OPTION TO LICENSE, SPONSORED RESEARCH AGREEMENT
AND LICENSE TERM SHEET
 
This Option Agreement is made with an Effective Date of March 15, 1998 by and
between Mayo Foundation for Medical Education and Research, a Minnesota
charitable corporation located at 200 First Street SW, Rochester, Minnesota
55905 (“MAYO”) and Acorda Therapeutics, Inc., a Delaware Corporation, located at
145 West-58th Street, Suite 8J, New York, NY 10019 (“ACORDA”).
 
This Option Agreement has four addenda 1) Exhibit A, Sponsored Research
Agreement; 2) Exhibit B, Statement of Work and Budget, 3) Exhibit C, Technology
License Contract Term Sheet, and 4) Exhibit D, Mayo/Acorda Agreements
 
Certain Inventions relating to the prevention, mitigation and/or treatment of
nervous system disorders, diseases or injuries by monoclonal antibodies have
been made in connection with MAYO’s research, patient care, and education
programs. By assignment of the inventions from the developers, MAYO is the owner
of certain patent rights.
 
ACORDA desires to evaluate such inventions for the purpose of determining its
interest in obtaining a license from MAYO to sell such inventions.
 
Now, therefore, the parties agree as follows:
 
Article 1. Definitions.
 
1.1 — “Technology” means:
 
 
a)             U.S. patent application S.N. 08/263,520, filed April 19, 1994,
foreign patent applications and patent counterparts thereto (if any), and all
patent applications disclosing any invention or other intellectual property
developed in whole or in

 
1

 
 

--------------------------------------------------------------------------------

 

 
part by Moses Rodriguez and/or Larry Pease owned in whole or in part by MAYO
relating to monoclonal antibodies and pooled IgM for use in the prevention,
mitigation and/or treatment of nervous system disorders, diseases or injuries,
including without limitation pain, or derivatives and analogs thereof, excluding
the Technology subject to the Option Agreement entered by ACORDA and MAYO
October 1, 1995, as amended;
 
 
b)            all U.S. and foreign patent applications disclosing inventions
conceived or reduced to practice pursuant to the research conducted pursuant to
the Sponsored Research Agreement;

 
 

 
c)             all divisions, substitutions, continuations,
continuations-in-part applications of (a) and (b) of the preceding, and all U.S.
and foreign patents issuing thereon, including reissues, reexaminations, and
extensions; and

 
 

 
d)            all trade secrets, know-how, and technical information developed
by MAYO in connection with the research conducted pursuant to the Sponsored
Research Agreement.

 
1.2 — “Territory” means world-wide including but not limited to North America,
Europe, Pacific Rim and Australia, Africa and the Middle East, South America,
and the United States and its territories.
 
Article 2.               Option.
 
2.1 — In order for ACORDA to evaluate the commercial and technical merits of
this Technology, MAYO hereby grants the Company an exclusive worldwide option in
the Territory to become the exclusive licensee for the Technology. Said option
shall expire the earlier of thirty-six (36) months from the start of the
sponsored research program (the “Effective Date”) or the termination of minimum
funding of such sponsored research program by ACORDA as described in Exhibits A
and B. This option agreement may be extended by mutual written agreement of the
parties.
 
2.2 — During the option period, ACORDA shall pay a minimum of (Two Hundred
Thirty-Three Four-Hundred Thirty-One Dollars ($233,431.00) to sponsor a mutually
agreed upon research protocol to be performed by MAYO, according to the terms of
Exhibits A and B.
 
2.3 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide to license the Technology, then a License Agreement consistent
with the terms sheet attached as Exhibit C shall be negotiated and executed by
both parties within ninety (90) days of ACORDA’s notice to MAYO of its decision
to license the Technology, or such longer period as may be agreed to In writing
by the parties.
 
2.4 — ACORDA shall pay MAYO Five Thousand Dollars ($5,000.00) within thirty (30)
days of the Effective Date of this Option Agreement and on each anniversary
thereafter as non-refundable and non-creditable consideration for the exclusive
worldwide option granted by MAYO.
 
2.5 — During the option period, ACORDA shall pay reasonable expenses associated
with the prosecution of patent applications disclosing any invention or other
intellectual property owned in whole or in part by MAYO relating to monoclonal
antibodies and pooled IgM for use in the prevention, mitigation and/or treatment
of nervous system disorders, diseases or injuries, including without limitation
pain, or derivatives and analogs thereof, including without
 
2

 
 

--------------------------------------------------------------------------------

 

 
limitation compositions and methods of making and using thereof, excluding the
Technology subject to the Option Agreement entered by ACORDA and MAYO October 1,
1995, as amended. The patent prosecution will be controlled by ACORDA, using
counsel of ACORDA’s choice, reasonably acceptable to MAYO.
 
Notwithstanding the above, in the event ACORDA chooses not to prosecute patent
applications for an invention ACORDA shall notify MAYO in writing of such
decision within sixty (60) days prior to the time action is required to avoid
abandoning said patent. Once notified, MAYO shall have the right to prosecute
patent applications for said invention independent of ACORDA. If MAYO prosecutes
patent applications for said inventions ACORDA will have no further rights to
those inventions and MAYO is free to license said inventions to third parties
with no further obligation to ACORDA.
 
2.6 — During the option period, MAYO may not disclose the Technology to third
parties without ACORDA’s prior written consent, but MAYO shall retain the
nontransferable right to use the Technology for its internal research purposes.
 
2.7 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide not to license the Technology, MAYO shall be provided with all the
research information generated during the option period by ACORDA and MAYO
jointly, or given to ACORDA by MAYO.
 
2.8 — All data jointly generated during the option period by MAYO and ACORDA and
provided to MAYO shall be only for internal use by MAYO during the option
period.
 
Article  3.              Confidentiality
 
3.1 — “Confidential Information” is defined as any written confidential
information disclosed by one party to the other and entitled to protection under
this agreement which is marked “CONFIDENTIAL,” or words of similar import. If
oral, visual, or other non-written manner of disclosure of otherwise undisclosed
confidential information is made by one party to the other, such information
shall be entitled to protection if identified as confidential at the time of
initial disclosure and if a written notice with a summary of such disclosures is
delivered to the receiving party within thirty (30) days of such disclosure. Any
markings, stamps, or legends identifying confidential information shall not
impose any obligations on either party inconsistent with this agreement. Any
copies of the information made by the receiving party shall reproduce the
confidential markings and any other legends contained on such information.
 
3.2 — Both ACORDA and MAYO covenant and agree that they shall hold the
Confidential Information they receive from the other party inviolate, keep it
secret, and shall not use any such Confidential Information, except as provided
in Article 4 below.  The foregoing restrictions on disclosure of Confidential
Information shall not apply to any information that properly comes into the
public domain through no action of the other party or its agents or was already
known by the other party as evidenced by its that party’s written records.  Each
party may use its own discretion to disclose information that was independently
developed by that party.
 
3.3 — Confidential Information shall not be afforded the protection of this
Option Agreement if, on the date of signing this Option Agreement, such
information is or later becomes:
 
 
a)             developed by the Recipient independently of the disclosed
proprietary information of the other party, and reasonable written documentation
exists to demonstrate such development; or

 
3

 
 

--------------------------------------------------------------------------------

 

 
 
b)            rightfully obtained without restriction by the Recipient from any
third party who is not restricted from making such disclosure by any direct or
indirect obligation of confidentiality to the other party herein; or

 
 

 
c)             publicly available other than through the fault of the Recipient;
or

 
 

 
d)            known to the Recipient at the time of its disclosure by the other
party hereto, and reasonable written documentation exists to demonstrate such
knowledge.

 
 

 
e)             subject to disclosure under a facially valid court order,
warrant, or subpoena, but only if the Recipient first gives the other party
immediate oral and written notice of the court order, warrant, or subpoena to
permit that party to take appropriate legal action in the circumstances.

 
3.4 — ACORDA shall not disclose, provide or otherwise make the Technology or the
Confidential Information available to any person or entity other than employees,
consultants, advisors, or agents of ACORDA that have signed secrecy agreements
at least as restrictive as the provisions of this Option Agreement.  Before the
Confidential Information or Technology is made available to any person directly
responsible for the evaluation of the Technology for licensure, ACORDA will
notify the person of the obligations of confidentiality contained in this Option
Agreement and obtain an agreement from that person to abide by said obligations.
 
3.5 — The obligations of confidentiality stated in 3.1 and 3.2 shall survive the
termination or expiration of this Option Agreement for five (5) years.
 
Article 4.               Authorized Use
 
4.1 — During the term of this Option Agreement, ACORDA shall use the Technology
and the Confidential Information only for the purpose of evaluating the
Technology both in the laboratory and in commercial assessments. Notwithstanding
the above, the ACORDA may disclose confidential Information of MAYO (1) to their
legal representative and employees, to Affiliates, to legal representatives and
employees of Affiliates, to the extent such disclosure is reasonably necessary
to achieve the purposes of this Contract, and provided such representative and
employees are covered by obligations of confidentiality with respect to such
information no less stringent than those set forth herein; (ii) In connection
with the filing and support of patent applications; or (iii) as required by law
or to comply with applicable governmental regulations or court order or
otherwise submit information to tax or other governmental authorities, including
the FDA and its foreign counterparts; provided that if the ACORDA is required to
make any such disclosure of MAYO’s confidential information, other than pursuant
to a confidentiality agreement, it will give reasonable advance notice to MAYO
of such disclosure and save to the extent inappropriate in the case of patent
applications, will use its reasonable efforts to secure confidential treatment
of such information prior to its disclosure and disclose only the minimum
necessary to comply with such requirements.
 
4.2 — ACORDA and MAYO shall not use, expressly or by implication, any trademark
or trade name of the other party, or any contraction, abbreviation, simulation
or adaptation thereof, or the name of any of the other party’s staff in any
news, publicity release, policy recommendation, advertising or any commercial
communication without the express written approval of the other party; provided,
however, once a public announcement has been approved, further approvals need
not be obtained for further announcement which are not materially different from
an earlier approved announcement.  The provisions of this Section 4.2 shall
survive the Termination or expiration of this Option Agreement.
 
4

 
 

--------------------------------------------------------------------------------

 

 
Article 5.               Termination
 
5.1 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide to exercise its option and execute the License Agreement, the
terms of this Option Agreement will be superseded by the terms of the License
Agreement at the time the License Agreement is executed by both parties and
becomes effective.
 
5.2 — Should ACORDA, on or before the expiration of the option granted in 2.1
above, decide not to license the Technology, ACORDA may terminate this Option
Agreement by providing written notice of its decision to MAYO. Furthermore,
Section 2.2 of this Option Agreement remains enforceable subsequent to any
termination of this Option Agreement by ACORDA, subject to the terms and
conditions of the Sponsored Research Agreement.
 
5.3 — Following nine (9) months after the Effective Date of this Option
Agreement, ACORDA shall have the right to terminate its support of the Sponsored
Research with ninety (90) days notice; provided ACORDA shall be obligated to pay
to MAYO the salary of one (1) technician until the third anniversary of the
Effective Date of the Option Agreement, unless MAYO receives contract or grant
funds from an external source to support said technician. Should ACORDA
terminate the Sponsored Research Mayo agrees to use best efforts to find other
sources of funding for the technical salary.
 
Article 6.               General
 
6.1 — ACORDA may not assign or subcontract any of its obligations or rights
under this Option Agreement without MAYO’s prior, express, written consent,
which consent may not be unreasonably withheld, except that ACORDA may assign
its rights and obligations under this Option Agreement without such consent to
an affiliate wholly-owned or majority-owned or controlled by ACORDA, or to any
entity that acquires substantially all of the assets of ACORDA, or entities to
which ACORDA has assigned all or substantially all of its assets relating to the
Option Agreement whether by merger, acquisition, sale, operation of law, or
otherwise.  Mayo, however, may object to such assignment of rights under this
Option Agreement if ACORDA proposes to assign its rights to an entity whose
image, reputation, or business goals are judged incompatible with MAYO’s mission
and reputation, in MAYO’s reasonable Judgment.
 
6.2 — This Option Agreement and its effects are subject to and shall be
construed and enforced in accordance with the laws of the State of Minnesota
except that no part of Minnesota law shall apply that directs the application of
another jurisdiction’s law.
 
6.3 — The failure of either party to insist at any time upon the strict
observance or performance of any of the provisions of the Option Agreement, or
to exercise any right or remedy as provided in this Option Agreement, shall not
impair any such right or remedy and shall not be construed to be a waiver or
relinquishment. Furthermore, no waiver of any provision of this Option Agreement
by either party shall be construed as a waiver of any other provision or as a
waiver of the same provision at any subsequent time.
 
6.4 — This Option Agreement (including Exhibits A, B and C) constitutes the
entire agreement between the parties and supersedes all prior or
contemporaneous, oral and written agreements, proposals and discussions relating
to the same subject matter. The Option Agreement may be amended only through a
writing signed by each of the parties.
 
5

 
 

--------------------------------------------------------------------------------

 

 
6.5 — Neither party shall disclose the terms of this Option Agreement to any
third party, and neither party shall issue any press release or other statement
to the media regarding the existence of the Option Agreement or its subject
matter (if the other party is mentioned) without the prior written consent of
the other party.
 
6.6 — Both parties agree that execution of this Option Agreement may be effected
by the receipt of facsimile signature pages.
 
IN WITNESS WHEREOF, each of the parties has caused this Option Agreement to be
executed on its behalf by its duly authorized representative.
 
 
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
ACORDA THERAPEUTICS, INC.
   
Signed:
/s/ John H. Herrell
 
Signed:
/s/ Ron Cohen, M.D.
             
Name:
John H. Herrell
 
Name:
Ron Cohen, M.D.
             
Title:
Vice President
 
Title:
President & CEO
             
Date:
March 24, 1998
 
Date:
3/20/98
 

 
6

 
 

--------------------------------------------------------------------------------

 

 
Exhibits A and B
to
Acorda/Mayo Option Agreement,
dated March 15, 1998
 
(Included as Exhibit A to License Agreement between
Acorda Therapeutics, Inc. and the
Mayo Foundation for Education and Research,
dated September 8, 2000)
 

 
 

--------------------------------------------------------------------------------

 

 
EXHIBIT C
ACORDA/MAYO
TECHNOLOGY LICENSE CONTRACT TERM SHEET
 
Grant of Rights and Definitions
 
License:
 
Mayo Foundation for Medical Education and Research (“MAYO”) will grant to Acorda
Therapeutics (“ACORDA”) an exclusive license, with the right to grant, offer for
sale and authorize sublicenses, under the Licensed Patents to develop, make,
have made, Import, Use, offer for sale, sell and otherwise exploit Licensed
Product in the Territory.
     
Territory:
 
Worldwide (with specific regions to be defined in the final license for royalty
accounting purposes).
     
Field of Use:
 
Use in the prevention, mitigation and/or treatment of nervous system disorders,
diseases or injuries including, without limitation, pain.
     
Licensed Technology:
 
Licensed Technology includes (i) the Licensed Patents, (ii) Project Know-How,
and (iii) all patent applications disclosing any invention or other intellectual
property developed by Dr. Moses Rodriguez and/or Dr. Larry Pease and owned in
whole or in part by MAYO relating to humanized and non-humanized monoclonal
antibodies and pooled IgM for use in the prevention, mitigation and/or treatment
of nervous system disorders, diseases or injuries, including without limitation
pain, or derivatives and analogs thereof, including without limitation
compositions and methods of making and using thereof, excluding the Technology
subject to the Option Agreement entered by ACORDA and MAYO October 1, 1995, as
amended.
 
It is understood and agreed that any use of intellectual property outside of the
field covered by the original option agreement entered by ACORDA and MAYO on
October 1, 1995, shall be covered by this agreement as depicted in Exhibit D.
     
Licensed Patents:
 
Licensed Patents include (i) all patent applications (provisional or utility)
filed with respect to inventions conceived or otherwise developed relating to
humanized and non-humanized monoclonal antibodies and pooled IgM, or their
derivatives or analogs, for use in the prevention, mitigation and/or treatment
of nervous system disorders, diseases or injuries, including without limitation
pain, and (ii) all divisions,

 
18

 
 

--------------------------------------------------------------------------------

 

 

   
substitutions, continuations, continuations-in-part applications, and reissues,
re-examinations, and extensions of (i) and (ii) above, (iii) all foreign
counterparts of the preceding, and (iv) all patents issuing on the preceding.
     
Project Know-How:
 
All trade secrets, biological materials and other Intellectual property
conceived or otherwise developed in the course of and in connection with the
Sponsored Research, and all subsequent modifications, enhancements and
improvements hereto, excluding the patent applications and patents within the
Licensed Patents.
     
Licensed Product:
 
Products covered by a pending or issued claim of a Licensed Patent in the
country which such product is sold, or which incorporate or utilize Project
Know-How.
     
Consideration and Royalties
     
License Fee:
 
Within thirty (30) days of the effective date of this agreement, ACORDA shall
pay to MAYO a license fee of twenty-five thousand dollars ($25,000). (Fifteen
Thousand ($15,000.00) of said License Fee will be deferred as long as ACORDA
provides minimum financial support of a three (3) year sponsored research
program in the laboratories of Drs. Larrry Pease and Moses Rodriguez.
     
Milestones:
 
For the first (1st) Licensed Product ACORDA will pay MAYO the following amounts
on the achievement of the following events:
           
(1)
Issuance of the first U.S. patent within the Licensed Patents which contains an
awarded claim for human monoclonal antibodies: $25,000.00.
           
(2)
Initiation of the second (2nd) US Phase III clinical trial for the first
Licensed Product: $125,000.00 in the event a second US Phase III trial is not
initiated ACORDA will pay $125,000.00 at the time such decision is made.
           
(3)
US FDA marketing approval of the first (1st) therapeutic Licensed Product:
$500,000.00
           
For the second (2nd) Licensed Product ACORDA will pay MAYO the following amounts
on the achievement of the following events:
           
(1)
Initiation of the second (2nd) US Phase III clinical trial for the first
Licensed Product: $150,000.00.  In the event a second US Phase III trial for the
second (2nd) Licensed Product is not initiated ACORDA will pay $150,000.00 at
the time such decision is made.

 
19

 
 

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(2)
US FDA marketing approval of the second (2nd) therapeutic Licensed Product which
is not a modification or extension of the first Licensed Product and has a
therapeutic indication which is different from the first Licensed Product:
$500,000.00
     
 Royalties:
 
It is understood and agreed that a higher royalty is only due for Licensed
Product which is outside the field defined in the original option agreement
entered by ACORDA and MAYO on October 1, 1995. ACORDA shall pay MAYO the greater
of:
 
(i) a royalty of two percent (2%) of the net sales up to $400,000,000.00 of the
Licensed Product sold by ACORDA in the Territory covered by a valid claim of an
issued patent within the Licensed Patents which contains an awarded valid
composition of matter claim in the country which such Licensed Product are sold,
or
 
(ii) two and one-half, percent (2.5%) of the net sales greater than
$400,000,000.00 of the Licensed Product sold by ACORDA in the Territory covered
by a valid claim of an issued patent within the Licensed Patents which contains
an awarded valid composition of matter claim the country which such Licensed
Product are sold, or
 
(iii) a royalty of one percent (1%) of the net sales of the Licensed Product
sold by ACORDA in the Territory covered by a pending patent within the Licensed
Patents containing a pending composition of matter claim in the country which
such Licensed Product are sold.
 
If the issued patents contain only awarded valid utility claims the parties
agree to negotiate in good faith royalty rates for the sale of Licensed Product
which reflect customary royalties for intellectual property of the type, degree
of proprietary protection and value mutually agreed to by MAYO and ACORDA.
     
Royalties to Third Parties:
 
In the event that in connection with its sale of Licensed Product, Acorda pays a
third party royalties or other amounts to make, use or sell Licensed Product or
to avoid or settle a claim of infringement of the intellectual property rights
of such third party, Acorda may offset such amounts against up to 50% of the
amounts due, Mayo; provided, however, in no event shall Mayo receive less than
0.50% of the net sales of Licensed Product sold by Acorda and its affiliates.

 
20

 
 

--------------------------------------------------------------------------------

 

 
Sublicense Royalties:
 
ACORDA will pay MAYO twenty-five percent (25%) of the royalty received by ACORDA
from sublicensees with respect to the sale of Licensed Product for use in
applications which ACORDA decides, in its business judgment, not to
commercialize. MAYO shall not be entitled to any share of amounts received by
ACORDA from sublicensees for equity, debt, research and development, performance
based milestones, the license or sublicense of any intellectual property other
than the Licensed Patents, products other than the Licensed Product, or
reimbursement for patent or other expenses.
     
Combination Product Royalties:
 
In the event that an Amended Licensed Product is sold in combination with
another product which is not a Licensed Product, the amount paid to MAYO shall
be based upon the proportion of the value of such combination products
reasonably attributable, by mutual agreement of the parties, to the Licensed
Patents.
     
Other Provisions
         
Due Diligence:
 
ACORDA will use reasonable efforts, consistent with its prudent business
judgment, to develop and commercialize Licensed Product and obtain and maintain
such approvals as may be necessary for the sale of products in the US and such
other worldwide markets as ACORDA selects to commercialize such Licensed
Product. ACORDA shall use reasonable efforts to develop a Licensed Product for
Multiple Sclerosis (MS) as long as it remains technically and commercially
feasible.  If ACORDA decides in its business Judgment not to commercialize a
Licensed Product for MS the parties agree to discuss returning the patent rights
for MS to MAYO.
     
Patents:
 
MAYO shall own all of its inventions, discoveries and other developments.
whether or not patentable, arising out of research carried out related to the
Amended Licensed Patents. ACORDA shall own all of its inventions, discoveries
and other developments, whether or not patentable, arising out of research
carried out related to the Licensed Technology.  Inventions or discoveries made
Jointly by both MAYO and ACORDA shall be Jointly owned by both parties and, if
patent applications are filed, patents shall be applied for on behalf of both
parties. Rights held by MAYO in any inventions, including without limitation
rights in and to patent applications and patents which may be obtained thereon,
shall be deemed to be within the terms Licensed Patents and shall be subject to
the license granted Acorda Therapeutics herein.

 
21

 
 

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Patent Prosecution:
 
ACORDA will be responsible, using patent counsel of its choice, for preparing,
filing, prosecuting and maintaining patent applications and patents within the
licensed patents. ACORDA will pay the costs incurred in connection with such
activities, and reimburse MAYO for reasonable costs incurred in connection with
such activities prior to the effective date of the license; fifty percent (50%)
of all such amounts (including attorneys’ fees) shall be creditable against
earned royalties due MAYO.  At MAYO’s request, ACORDA shall provide MAYO with
reasonable documentation of such costs. MAYO and ACORDA will cooperate and
consult with each other in the prosecution of the licensed patents.
     
Patent Enforcement:
 
In the event of any infringement of the Licensed Patents or misappropriation of
the Project Know-How, the parties shall consult to determine if they will
Jointly bring action to terminate such infringement or misappropriation. Any
recovery obtained by the parties in such an action shall be used first to
reimburse the cost of such action and the remainder divided equally between the
parties.
 
In the event that the parties fail to initiate such action within ninety (90)
days of receiving notice of such infringement or misappropriation, ACORDA shall
have the right, but not the obligation, to initiate suit to stop such
infringement or misappropriation. Any recovery obtained by ACORDA in such an
action shall be used first to reimburse the cost of such action, and the
remainder shall be retained by ACORDA and treated as net sales of Licensed
Product, subject to the royalty obligations to MAYO herein.
 
In the absense of an agreement to institute a suit jointly, and if ACORDA does
not initiate such an action within a further ninety (90) days, MAYO may
institute a suit for the infringement of the licensed patents, or opposition or
interference with respect thereto, or any misappropriation of Project Know-How,
or defend any declaratory judgment relating thereto.  MAYO shall bear the entire
cost of such litigation, including attorneys’ fees, and shall be entitled to
retain the entire amount of any recovery by way of judgment, award, decree,
arbitration, or settlement. ACORDA shall cooperate reasonably with MAYO, except
financially, in such litigation.
     
Sublincenses:
 
Any sublicense granted by Acorda under the Licensed Technology shall remain in
effect and be assigned to MAYO in the event this license terminates.
     
Assignment:
 
ACORDA may not assign the license without the consent of MAYO, which consent
shall not be unreasonably withheld; provided, ACORDA may assign the license in
connection with the sale or transfer of all or substantially all the rights and
obligations of ACORDA relating to the Licensed Product, without the prior
consent of MAYO.
     
Term:
 
The License shall terminate on a country-by country and Licensed Product by
Licensed Product basis upon the expiration of the last to expire Licensed Patent
in such country. ACORDA shall have the right to

 
22

 
 

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terminate the license agreement with respect to any aspect of the Licensed
Technology and/or any country, on ninety (90) days written notice.
     
Other:
 
The formal agreement will include other customary provisions to be agreed upon
by the parties, including indemnification, royalty reporting, audit rights and
the like.
     
Execution:
 
Both parties agree that execution of this License Term Sheet may be effected by
the receipt of facsimile signature pages.

 
 
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
ACORDA THERAPEUTICS, INC.
       
Signed:
/s/ John H. Herrell
 
Signed:
/s/ Ron Cohen, M.D.
             
Name:
John H. Herrell
 
Name:
Ron Cohen, M.D.
             
Title:
Vice President
 
Title:
President & CEO
             
Date:
March 24, 1998
 
Data:
3/20/98
 

 
23

 
 

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Exhibit C
to
License Agreement between
Acorda Therapeutics, Inc. and the
Mayo Foundation for Education and Research,
dated September 8, 2000
 

 
 

--------------------------------------------------------------------------------

 

 
Exhibit C
 
Remvelination Monoclonal Antibody Cases
 
PCT/U.S.
Serial No.
 
Title of Application
 
Date of
Filing
         
US#5,591,629
 
Monoclonal Antibodies Which Promote Central Nervous System Remyelination
 
4/29/94
         
PCT/US 95/05262
 
Monoclonal Antibodies Which Promote Central Nervous System Remyelination
 
4/27/95
         
08/692,084
 
Promotion of Central Nervous System Remyelination Using Monoclonal Antibodies
 
8/8/96
         
08/779,784
 
Promotion of Central Nervous System Remyelination Using Monoclonal Antibodies
 
1/7/97
         
09/332,862
 
Human IgM Antibodies, and Diagnostic and Therapeutic Uses Thereof Particularly
in the Central Nervous System
 
5/28/99
         
09/580,787
 
Human IgM Antibodies, and Diagnostic and Therapeutic Uses Thereof Particularly
in the Central Nervous System
 
5/30/00
         
09/568,351
 
Human IgM Antibodies, and Diagnostic and Therapeutic Uses Thereof Particularly
in the Central Nervous System
 
5/10/00
         
PCT/US 00/14902
 
Human IgM Antibodies, and Diagnostic and Therapeutic Uses Thereof Particularly
in the Central Nervous System
 
5/30/00

 

 
 

--------------------------------------------------------------------------------

 

 
Exhibit D
to
License Agreement between
Acorda Therapeutics, Inc. and the
Mayo Foundation for Education and Research,
dated September 8, 2000
 

 
 

--------------------------------------------------------------------------------

 

 
EXHIBIT D
 
MANDATORY MEDIATION AND BINDING ARBITRATION
 
1.             NOTICE OF DISPUTE. Except to the extent otherwise expressly
provided in Sections 5.3 and 5.4 of this Agreement, any dispute related to this
Agreement between the Parties, including its formation, performance, or
Termination, which cannot be resolved by the Parties themselves within thirty
(30) days of written notice by one Party to the other of the existence of a
dispute, may be referred by either of the parties to mandatory mediation and
binding arbitration under the terms of this Exhibit. The Parties intend the
mediation/arbitration procedure described in this Exhibit to substitute in all
cases for litigation related to any such dispute, subject only to part 7, below,
and this agreement to submit all such disputes to mandatory mediation and
binding arbitration is irrevocable.
 
2.             LIMITATION PERIOD. No demand for mediation/arbitration may be
made regarding any claim more than one hundred eighty (180) days after written
notice by one Party to the other of the existence of a dispute, regardless of
any otherwise applicable statute of limitations.
 
3.             MEDIATOR/ARBITRATOR. If the Parties cannot agree upon a single
mediator/arbitrator within fourteen (14) days after written demand by either of
them for mediation/arbitration, then a single mediator/arbitrator shall be
chosen by the American Arbitration Association office in New York City, New
York, within thirty (30) additional days after the fourteen (14) day period. The
mediator/arbitrator shall be generally experienced in the legal and technical
matters related to the dispute.
 
4.             MEDIATION. Within thirty (30) days of the appointment of the
mediator/arbitrator, the Parties must attend a mediation session at which the
mediator/arbitrator personally shall attempt to guide the Parties to a
settlement. Each Party may be represented by counsel at the mediation, but each
Party must attend through an officer having authority to agree to a settlement
at the mediation. The mediation session shall occur in New York City, New York,
and shall extend no longer than a single day. Statements or offers made at the
mediation session shall not be admissible in any later arbitration hearing.
 
5.             ARBITRATION. If such mediation has not resulted in a
mutually-executed settlement agreement (or withdrawal of claim) within five
(5) business days after the date of mediation, then the Parties shall proceed to
arbitration as described below. Such arbitration, which the Parties intend to be
final and to substitute for litigation, shall occur in New York City, New York,
and the arbitration results may be entered as a final judgment in any court with
jurisdiction. The decision of the arbitrator shall be final and binding upon the
Parties both as to law and fact.
 
 
(a)           Initial Disclosures. Within twenty-one (21) days after the date of
mediation, the Parties shall exchange written disclosures listing with
reasonable specificity: (i) all exhibits expected to be used by the Party at
arbitration, and complete copies of such exhibits, (ii) all witnesses expected
to be called by the Party at arbitration, and (iii) the substance of

 

 
 

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the testimony of each witness. Copies of such disclosures shall be sent to the
arbitrator, No exhibit or witness may be called if the same does not appear on
such disclosure, and no witness may testify as to matters not described in such
disclosure, except for rebuttal testimony as may be permitted by the arbitrator.
 
 
(b)           Discovery Period. Within fourteen (14) days after exchange of the
disclosure notices, the Parties shall make specific discovery requests to the
arbitrator, and within an additional fourteen (14) days the arbitrator shall
issue to both parties a joint discovery order. The discovery period preceding
the arbitration hearing shall not exceed sixty (60) days from the issuance of
the discovery order by the arbitrator.

 
 

 
(c)           Scope of Discovery. Discovery shall be limited to that ordered by
the arbitrator as being reasonable and necessary, and in no case shall exceed
the deposition of two (2) witnesses for each Party, and/or the exchange of more
than a total of twenty-five (25) specific and non-compound interrogatories by
each party, and/or two specific requests by each Party for the production of
documents considered by the arbitrator to be reasonably relevant and not unduly
burdensome.

 
 

 
(d)           Hearing. The arbitration hearing, which shall be confidential to
the parties and not open to the public, shall not exceed two (2) separate days,
and shall be completed within thirty (30) days of the close of discovery. The
arbitrator may admit any testimony or other evidence which the arbitrator
decides is reasonably relevant to the issues of the arbitration, but excluding
statements or offers made by either Party at the mediation session.

 
 

 
(e)           Final Decision. The arbitrator shall issue a final written
decision no later than sixty (60) days following the end of the arbitration
hearing, stating findings as to law and fact. The decision shall be confidential
to the Parties. The arbitrator shall be limited to determining and ordering the
payment of actual and direct damages if any, and may order the payment of
indirect, special, incidental, or consequential damages only where bad faith has
been shown and/or to the extent required to fulfill any obligations under
Article 8 of the Agreement. The arbitrator shall not order the payment of
punitive or exemplary damages in any case.

 
6.             COSTS AND FEES. Both Parties shall be responsible for their own
costs and fees (including attorney’s fees), and shall divide common costs and
fees equally; however, if the arbitrator specifically finds bad faith on the
Part of either Party, then the arbitrator may order a different division of
costs and fees.
 
7.             EQUITABLE RELIEF. Nothing in this Exhibit prohibits either Party
from seeking equitable relief to protect its rights to the extent that
irreparable harm may occur and damages would not be a sufficient remedy, except
that neither Party shall seek to enjoin mediation/arbitration as described in
this Exhibit.
 

 
 

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(a)           Specific Performance. Among the equitable remedies that a Party
may seek under this part 7, either Party may petition a court for specific
performance of the terms of this Exhibit, including following the failure of
either Party without good cause to adhere to the time limits set out in this
Exhibit. A Party securing an order for specific performance under this part
7(a) is entitled to recover costs and reasonable attorneys’ fees in connection
with such petition for specific performance and any related hearings.

 
8.             SURVIVAL. The rights and obligations of the Parties described in
this Exhibit survive the Termination, expiration, non-renewal, or rescission of
this Agreement.
 
9.             GOVERNING RULES AND LAW. To the extent not inconsistent with the
terms of this Exhibit, the mediation and arbitration are governed by the
rules of the American Arbitration Association, the Minnesota Arbitration Act,
and the Federal Arbitration Act (9 U.S.C s. 1 et seq.).
 

 
 

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Exhibit E
to
License Agreement between
Acorda Therapeutics, Inc. and the
Mayo Foundation for Education and Research,
dated September 8, 2000
 

 
 

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MATERIAL TRANSFER AGREEMENT
 
1.             The Effective Date of this Material Transfer Agreement
is             .
 
2.             The parties to this Agreement are:
 
 
(a)           MAYO Foundation for Medical Education and Research, 200 First
Street SW, Rochester, MN 55905-0001, hereinafter “MAYO”; and

 
(b)
hereinafter “INSTITUTION”.
 
 
3.             The MATERIAL covered by this Agreement includes:               
{relevant Ab}       , developed by Moses Rodriguez, M.D. and his colleagues at
MAYO Rochester (MAYO files MMV-92-102 and MMV-97-055); (b) any related
biological material or associated know-how and data received by INSTITUTION from
MAYO; and (c) any progeny or unmodified derivatives produced from any of the
foregoing by MAYO, its employees and/or agents. The MATERIAL covered by this
Agreement is the subject of United States Patent No. 5,591,629, Application S.N.
08/236,520, filed April 19, 1994, entitled “Monoclonal Antibodies Which Promote
Central Nervous System Remyelination,” and foreign counterparts
and                          [list specific CIPs or patents}             and
other pending patent claims of MAYO and is subject to an exclusive worldwide
license granted by MAYO to Acorda Therapeutics, Inc, (“ACORDA”) pursuant to a
license agreement dated [insert date] for commercial exploitation of the
MATERIAL under the foregoing patent rights (the “MAYO/ACORDA license agreement”)
INSTITUION AND MAYO acknowledge that MAYO may only transfer the MATERIAL to
INSTITUION under terms and conditions of a material transfer agreement which has
been approved in advance by ACORDA.

 
 
4.             The MATERIAL and any related information disclosed by MAYO will
be kept confidential and not made available or disclosed by INSTITUTION to third
parties or disclosed in any publication. The MATERIAL shall be used solely for
research in the laboratory of                   (“SCIENTIST”) at INSTITUTION,
such research to be limited to 
                                                                                                                                                                                                                               .
MAYO and ACORDA shall be free, in their sole discretion, to distribute the
MATERIAL to others and to use it for their own purposes.

 
 
5.             INSTITUTION shall not distribute or release the MATERIAL to any
person other than laboratory personnel under SCIENTIST’s direct supervision who
shall be made aware of the provisions of this agreement, including
confidentiality and license of commercial rights to inventions, and who is bound
by its terms. INSTITUTION shall ensure that no one will be allowed to take or
send the MATERIAL to any other location, unless prior written permission is
obtained from MAYO and ACORDA. This MATERIAL is made available for
investigational use only in laboratory animals or in vitro experiments.
INSTITUTION and SCIENTIST agree that the MATERIAL will not be used for any other
purpose. Neither the MATERIAL nor any biological materials treated therewith
will be used in human beings. INSTITUTION and SCIENTIST are specifically
excluded from re-engineering or modifying the MATERIAL with the specific intent
of designing around pending claims of United States and foreign patents.

 

 
 

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6.             This Agreement and the resulting transfer of MATERIAL constitute
a license to use the MATERIAL solely for not-for-profit academic research
purposes. INSTITUTION agrees that nothing herein shall be deemed a grant under
any MAYO patents (either existing or future) or any rights to use the MATERIAL
for any products or processes for profit-making or commercial purposes. The
MATERIAL will not be used in research that is subject to consulting or licensing
obligations to another institution, corporation or business entity unless prior
written permission is obtained from both MAYO and ACORDA.

 
 
7.             MAYO and INSTITUTION agree that all rights to sole MAYO
inventions resulting from the use of the MATERIAL under this agreement, i.e.
inventions made solely by MAYO faculty, staff, or students, shall be owned by
MAYO; sole INSTITUTION inventions resulting from the use of the MATERIAL under
this agreement, i.e. inventions made solely by the employees of INSTITUTION,
shall be owned by INSTITUTION. All rights to joint inventions resulting from the
use of the MATERIAL under this agreement, as determined under United States’
Patent Law, shall be owned jointly between INSTITUTION and the MAYO.

 
 
8.             Should INSTITUTION or SCIENTIST create, either alone or with
MAYO, any new and useful invention, discovery, process, improvement or other
intellectual property conceived of, first reduced to practice, made or otherwise
developed during the research, whether for the MATERIAL, related to the
MATERIAL, or resulting in part from use of the MATERIAL, (an “Invention”) it
hereby grants MAYO, and MAYO’s licensee, ACORDA, the exclusive (even as to
INSTITUTION and SCIENTIST) perpetual, worldwide, royalty-free license to
develop, make, have made, use, import, export, lease, offer to sell, sell, have
sold and otherwise exploit any and all products, processes or services making
use of the invention for any and all commercial purposes and to grant, offer for
sale and authorize sublicenses with respect to the right and license granted
under this Section 8 to third parties, MAYO acknowledges and confirms that any
license rights it may receive from INSTITUTION under this agreement shall be
deemed part of the technology MAYO has licensed to ACORDA under the MAYO/ACORDA
license agreement.

 
 
9.             INSTITUTION shall have no rights in the MATERIAL other than as
provided in this Agreement, and at the request of MAYO, INSTITUTION and/or
SCIENTIST will return or destroy all unused MATERIAL.

 
 
10.           SCIENTIST will inform MAYO and ACORDA in reasonable detail of all
research results created by SCIENTIST and/or INSTITUTION related to the MATERIAL
by personal written communication. INSTITUTION and/or SCIENTIST shall be free to
use data and information from research results for any academic and
non-commercial purpose, but will make proper acknowledgment of the work done by
SCIENTIST, and agree to inform MAYO and ACORDA of any proposed public disclosure
of research results at least one hundred twenty (120) days prior to such
disclosure to permit MAYO and ACORDA to protect any proprietary information
related thereto and to confirm that no information disclosed to INSTITUTION in
confidence is included in such public disclosure. MAYO and ACORDA shall be free
to use any and all research results for any purpose.

 
 
11.           The MATERIAL is experimental in nature and it is provided WITHOUT
WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR ANY OTHER
WARRANTY, EXPRESS OR IMPLIED. MAYO MAKES NO REPRESENTATION OR

 
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WARRANTY THAT THE USE OF THE MATERIAL WILL NOT INFRINGE ANY PATENT OR OTHER
PROPRIETARY RIGHT.
 
 
12.           In no event shall MAYO be liable for any use by INSTITUTION, its
employees and/or agents of the MATERIAL or any loss, claim, damage or liability,
of whatsoever kind or nature, which may arise from or in connection with this
Agreement or the use, handling or storage of the MATERIAL. Furthermore, to the
extent permitted by applicable law, INSTITUTION agrees to indemnify MAYO and any
of its employees and hold it and them harmless from any action, claim, or
liability, including, without limitation, liability for death, personal injury,
or property damage, arising directly or indirectly from INSTITUTION’s
possession, testing, screening, distribution or other use of the MATERIAL
provided under this Agreement, and/or from INSTITUTION’s publication or
distribution of the test reports, data, and other information relating to said
MATERIAL.

 
 
13.           INSTITUTION will use the MATERIAL in compliance with all laws and
governmental regulations and guidelines applicable to the MATERIAL, and when the
MATERIAL is used in the United States, INSTITUTION and SCIENTIST will comply
with current NIH guidelines.

 
 
14.           This Agreement shall be governed by the laws of Minnesota. It may
be amended only in writing signed by both MAYO and INSTITUTION and specifically
referencing this Agreement. Any proposed amendment must also be approved in
advance in writing by ACORDA. Neither this Agreement nor any of INSTITUTION’s or
SCIENTIST’S rights or obligations under the Agreement may be assigned by
INSTITUTION or SCIENTIST without the written consent of MAYO. ACORDA is a third
party beneficiary of this Agreement and shall have the right to enforce its
provisions. The failure of MAYO or ACORDA to insist at any time upon the strict
observance or performance of any of the provisions of this Agreement, or to
exercise any rights or remedy as provided in this Agreement, will not impair any
such right or remedy and will not be construed to be a waiver or relinquishment
of the right or remedy.

 
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ACCEPTED AND AGREED TO:
     
SCIENTIST
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
       
By:
               
Title:
           
Date:
   
Date:
       
Authorized Representative of the
RECIPIENT INSTITUTION
Authorized Representative of ACORDA
(Pursuant to Section 2.2 of its License Agreement with MAYO dated as of [date]
ACORDA approves and consents to this Material Transfer Agreement)
   
By:
   
By:
               
Title:
   
Title:
               
Date:
   
Date:
                   

 
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