Exhibit
10.24


 


Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality. Such omitted portions, which are marked with
brackets [   ] and an asterisk*, have
been separately filed with the Commission.


 


LICENSE AGREEMENT


 


BETWEEN


 


ACORDA THERAPEUTICS, INC.


 


AND


 


THE MAYO FOUNDATION FOR

EDUCATION AND RESEARCH


 


Dated: 
September 8, 2000


 












 


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

  



 


i












 


	
  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

  
	
   

  	
  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

  



 


ii












 


	
   

  	
  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

  



 


iii












 


LIST
OF EXHIBITS


 


	
   

  	
  EXHIBIT A

  
	
   

  	
   

  
	
   

  	
  EXHIBIT B

  
	
   

  	
   

  
	
   

  	
  EXHIBIT C

  
	
   

  	
   

  
	
   

  	
  EXHIBIT D

  
	
   

  	
   

  
	
   

  	
  EXHIBIT E

  



 


iv












 


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.


 


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, 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


 


2












 


(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 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


 


3












 


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 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


 


4












 


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
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


 


5












 


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, 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.


 


6












 


Certain portions of this Exhibit have been omitted pursuant to a request
for confidentiality. Such omitted portions, which are marked with brackets
[   ] and an asterisk*, have been
separately filed with the Commission.


 


(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
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 [**], 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”), [**], within 30 days following the Effective Date.


 


7












 


Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality. Such omitted portions, which are marked with
brackets [   ] and an asterisk*, have
been separately filed with the Commission.


 


(b)                                 [**]
within thirty days following the issuance of the first U.S.  composition of matter Licensed Patent for a
human antibody.


 


(c)                                  [**]
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.


 


(d)                                 [**]
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)                                  [**]
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)                                    [**]
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)                                 [**]
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)                                 [**]
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


 


[**] of the first [**] of
annual Net Sales; and


 


[**] of all annual Net
Sales in excess of [**].


 


8












 


Certain portions of this
Exhibit have been omitted pursuant to a request for confidentiality. Such
omitted portions, which are marked with brackets [   ] and an asterisk*, have been separately
filed with the Commission.


 


(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:


 


[**] of the first [**] of
annual Net Sales;


 


[**] of annual Net Sales
between [**] and [**];


 


[**] of annual Net Sales
between [**] and [**]; and


 


[**] of annual Net Sales
in excess of [**].


 


(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, [**] 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)                                     [**]
on the first anniversary;


 


(ii)                                  [**]
on the second anniversary;


 


(iii)                               [**]
on the third anniversary; and


 


(iv)                              [**]
on the fourth anniversary and on each anniversary thereafter.


 


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 [**] of the amount of royalties due
from ACORDA to MAYO, provided however, that
in no event shall MAYO receive less that [**] of the Net Sales of the Licensed
Product sold by ACORDA, its Affiliates or Sublicensees, as the case may be.


 


9












 


Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality. Such omitted portions, which are marked with
brackets [   ] and an asterisk*, have
been separately filed with the Commission.


 


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
[**] 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 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 [**] 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


 


10












 


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 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


 


11












 


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 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.


 


12












 


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.


 


(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.


 


13












 


(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 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


 


14












 


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.


 


(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;


 


15












 


(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 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


 


16












 


Confidential 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 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


 


17












 


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 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 this


 


18












 


Agreement.  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 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.


 


19












 


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 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


 


20












 


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.


 


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


 


21












 


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 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.


 


22












 


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.


 


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.


 


* * *


 


23












 


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

  
						



 


24












 


Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality.  Such
omitted portions, which are marked with brackets [  ] and an asterisk*, have been separately
filed with the Commission.


 


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

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [*]

  	
   

  	
  [*]

  	
   

  	
  4/27/95

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [*]

  	
   

  	
  [*]

  	
   

  	
  8/8/96

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [*]

  	
   

  	
  [*]

  	
   

  	
  1/7/97

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [*]

  	
   

  	
  [*]

  	
   

  	
  5/28/99

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [*]

  	
   

  	
  [*]

  	
   

  	
  5/30/00

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [*]

  	
   

  	
  [*]

  	
   

  	
  5/10/00

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [*]

  	
   

  	
  [*]

  	
   

  	
  5/30/00

  



 


 












 


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) clays 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 maybe 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 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.


 


(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 


 


 


2












 


 


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.).


 


3














 


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

















 


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

















 


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

















 


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

















 


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.


 


2

















 


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.


 


3

















 


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.


 


4

















 


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

















 


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

















 


	
   

  	
  (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

















 


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

















 


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.


 


7

















 


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

















 


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

















 


Exhibit B 


to


License Agreement between


Acorda Therapeutics, Inc. and the


Mayo Foundation for Education and Research,


dated September 8, 2000


 

















 


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).


 


1

















 


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

















 


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

















 


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

  	
   

  



 


5

















 


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


 

















 


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


 


2

















 


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


 


4

















 


(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

















 


	
   

  	
   

  	
  (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

















 


	
  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

















 


	
   

  	
   

  	
  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

















 


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


 

















 


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.


 

















 


(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.).


 

















 


Exhibit E


to


License Agreement between


Acorda Therapeutics, Inc. and the


Mayo Foundation for Education and Research,


dated September 8, 2000


 

















 


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.


 

















 


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


 


2

















 


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.


 


3

















 


	
  ACCEPTED
  AND AGREED TO:

  	
   

  
	
   

  	
   

  
	
  SCIENTIST

  	
  MAYO
  FOUNDATION FOR MEDICAL

  EDUCATION AND RESEARCH

  
	
   

  	
   

  
	
   

  	
   

  	
  By:

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Title:

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
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  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)

  
	
   

  	
   

  
	
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