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Exclusive Patent License Agreement

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2002
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                      MASSACHUSETTS INSTITUTE OF TECHNOLOGY

                                       and

                          BIOMARIN PHARMACEUTICAL INC.


                       EXCLUSIVE PATENT LICENSE AGREEMENT



















                                TABLE OF CONTENTS




TABLE OF CONTENTS.............................................................ii
R E C I T A L S................................................................1
1.  Definitions................................................................2
2.  Grant of Rights............................................................5
3.  Company Diligence Obligations..............................................6
4.  Royalties and Payment Terms................................................8
5.  Reports and Records.......................................................10
6.  Patent Prosecution........................................................12
7.  Infringement..............................................................13
8.  Indemnification and Insurance.............................................15
9.  No Representations or Warranties..........................................16
10. Assignment................................................................17
11. General Compliance with Laws..............................................17
12. Termination...............................................................18
13. Dispute Resolution........................................................19
14. Miscellaneous.............................................................21
APPENDIX A....................................................................24
APPENDIX B....................................................................30
APPENDIX C....................................................................31




                                       ii



     Portions of this document have been redacted pursuant to a Request for
          Confidential Treatment. Redacted portions are indicated with
                              the notation "*****"


                      MASSACHUSETTS INSTITUTE OF TECHNOLOGY
                       EXCLUSIVE PATENT LICENSE AGREEMENT


     This Agreement,  effective as of the date set forth above the signatures of
the parties below (the "EFFECTIVE DATE"), is between the Massachusetts Institute
of Technology ("M.I.T."), a Massachusetts  corporation,  with a principal office
at 77 Massachusetts Avenue, Cambridge, MA 02139-4307 and BioMarin Pharmaceutical
Inc. ("BIOMARIN"), a Delaware corporation, with a principal place of business at
371 Bel Marin Keys Blvd., Suite 210, Novato, CA 94949.

                                 R E C I T A L S

     WHEREAS,  M.I.T.  is the owner of certain  PATENT  RIGHTS (as later defined
herein)  relating to heparinases  and to the technology  disclosed  under M.I.T.
Case  No.  4236,  "Neutralization  of the  Anticoagulant  Activities  of the Low
Molecular   Weight   Heparin   Fractions  and  Fragments   With   Flavobacterial
Heparinase," by Howard Bernstein, Charles L. Cooney, Robert S. Langer and Victor
C. Yang;  M.I.T.  Case No.  4330,  "Procedure  for  Purification  of High Purity
Heparinase,"  by Charles L.  Cooney and Joseph J.  Zimmermann;  M.I.T.  Case No.
4370,  "Extracorporeal  Systems for Heparin Neutralizaton Using Porous Fibers or
Tubes," by Ann R. Comfort,  Robert A. Heft and Robert S. Langer; and M.I.T. Case
No. 5546,  "The Heparinase  Gene from  Flavobacterium  Heparinum," by Charles L.
Cooney,  Robert S. Langer,  Kelley W. Moreman and Ram Sasisekharan;  and has the
right to grant licenses under said PATENT RIGHTS;

     WHEREAS,  M.I.T.  and the President and Fellows of Harvard  College are the
owners  of  certain  PATENT  RIGHTS  (as  later  defined  herein)   relating  to
heparinases  and to the technology  disclosed  under M.I.T.  Case No. 4176, "The
Heparinase  Activated  Clotting Time: A New Coagulation Test," by Judah Folkman,
Robert L.  Hannon,  Robert S.  Langer and Robert W.  Thompson,  and  HARVARD has
authorized  M.I.T.  to act as its agent for the purposes of licensing its rights
in this intellectual property in return for a share of royalties.

     WHEREAS,  M.I.T. and the University of Iowa ("U of I") are the joint owners
of certain PATENT RIGHTS (as later defined  herein)  relating to heparinases and
to  the  technology  disclosed  under  M.I.T.  Case  No.  5981,   "Purification,
Composition   and   Characterization   of  Heparinase  II  from   Flavobacterium
Heparinum," by Charles L. Cooney,  Robert S. Langer,  Robert  Lindhardt,  Daniel
Lohse and Ram Sasisekharan; and U of I has authorized M.I.T. to act as its agent
for the purposes of licensing its right in this intellectual  property in return
for a share in royalties.



         WHEREAS, BIOMARIN acquired by assignment in November 2001, the rights
and responsibilities of two License Agreements to the PATENT RIGHTS by and
between M.I.T. and IBEX Technologies Inc. (the "IBEX License Agreements", and
attached herein in Appendix C) and, along with M.I.T., desires to restate and
modify the terms of the IBEX License Agreements in this new Agreement;

     WHEREAS,  M.I.T.  desires to have the  BIOMARIN  continue  to  develop  and
commercialize  the PATENT RIGHTS to benefit the public and is willing to grant a
license to the BIOMARIN thereunder;

     WHEREAS,  to induce  M.I.T.  to enter  into this  Agreement,  BIOMARIN  has
represented  to M.I.T.  that it shall commit itself to a thorough,  vigorous and
diligent program to commercialize  the PATENT RIGHTS so that public  utilization
shall result therefrom; and

     WHEREAS,  BIOMARIN desires to obtain a license under the PATENT RIGHTS upon
the terms and conditions hereinafter set forth.

     NOW, THEREFORE,  M.I.T. and BIOMARIN, in consideration of the premises, the
mutual  promises and  covenants  contained  herein,  and other good and valuable
consideration, hereby agree as follows:

                                 1. Definitions.

     1.1  "AFFILIATE"  shall  mean any  legal  entity  (such  as a  corporation,
partnership,  or limited liability company) that is controlled by BIOMARIN.  For
the  purposes  of this  definition,  the term  "control"  means  (i)  beneficial
ownership  of at  least  fifty  percent  (50%)  of the  voting  securities  of a
corporation  or other  business  organization  with voting  securities or (ii) a
fifty  percent  (50%) or  greater  interest  in the net  assets or  profits of a
partnership or other business organization without voting securities.

                                       2


     1.2  "DIAGNOSTIC   FIELD"  shall  mean  clinical   diagnostics   using  the
HEPARINASES for in vitro testing of external tissue samples from patients.

     1.3  "EXCLUSIVE  PERIOD" shall mean the period of time set forth in Section
2.2.

     1.4 "FIELDS" shall mean the DIAGNOSTIC  FIELD,  RESEARCH REAGENT FIELD, and
THERAPEUTIC FIELD, but shall specifically  exclude any use of the HEPARINASES in
sequencing machines.

         1.5 "HEPARINASES" shall mean the heparinase I, II, and III enzymes
covered under the PATENT RIGHTS.


     1.6  "LICENSED  PRODUCT"  shall  mean any  product  or part  thereof  that:
            (i) absent the license granted hereunder, would infringe one or more
claims of the PATENT RIGHTS;  or
            (ii) is   manufactured   by using a  LICENSED PROCESS  or that, when
used, practices a LICENSED PROCESS.

     1.7  "LICENSED  PROCESS"  shall mean any process  that,  absent the license
granted  hereunder,  would  infringe one or more claims of the PATENT  RIGHTS or
which uses a LICENSED PRODUCT.

     1.8 "NET SALES"  shall mean the gross  amount  billed by  BIOMARIN  and its
AFFILIATES and SUBLICENSEES for LICENSED PRODUCTS and LICENSED  PROCESSES,  less
the following:
            (i) customary  trade,  quantity, or  cash  discounts  to the  extent
actually allowed and taken;
            (ii) amounts repaid or credited by  reason of  rejection  or return;
            (iii) to the extent separately  stated on purchase orders, invoices,
or other  documents of sale, any taxes or other  governmental  charges levied on
the production, sale, transportation,  delivery, or use of a LICENSED PRODUCT or
LICENSED PROCESS which is paid by or on behalf of BIOMARIN; and
            (iv) outbound  transportation costs prepaid  or allowed and costs of
insurance in transit.

                                       3


     No deductions  shall be made for  commissions  paid to individuals  whether
they are with independent  sales agencies or regularly  employed by BIOMARIN and
on its payroll, or for cost of collections. NET SALES shall occur on the date of
billing for a LICENSED PRODUCT or LICENSED  PROCESS.  If a LICENSED PRODUCT or a
LICENSED  PROCESS is  distributed  at a discounted  price that is  substantially
lower than the customary price charged by BIOMARIN,  or distributed for non-cash
consideration  (whether or not at a  discount),  NET SALES  shall be  calculated
based on the  non-discounted  amount of the LICENSED PRODUCT or LICENSED PROCESS
charged to an independent  third party during the same  REPORTING  PERIOD or, in
the absence of such sales,  on the fair market value of the LICENSED  PRODUCT or
LICENSED PROCESS
     Non-monetary   consideration  shall  not  be  accepted  by  BIOMARIN,   any
AFFILIATE,  or any SUBLICENSEE for any LICENSED  PRODUCTS or LICENSED  PROCESSES
without the prior written consent of M.I.T.

     1.10 "PATENT RIGHTS" shall mean:

            (a)      the  United  States  and i nternational  patents  listed on
Appendix A;
            (b)      the  United States  and international  patent  applications
and/or provisional applications listed on  Appendix A and the resulting patents;
            (c)      any  patent  applications  resulting  from  the provisional
applications   listed  on  Appendix  A,  and  any  divisionals,   continuations,
continuation-in-part  applications,  and continued prosecution applications (and
their relevant  international  equivalents) of the patent applications listed on
Appendix A and of such patent  applications  that  result  from the  provisional
applications  listed on  Appendix  A, to the extent the claims are  directed  to
subject  matter  specifically  described  in the patent  applications  listed on
Appendix A, and the resulting patents;
            (d)      any patents  resulting from  reissues,  reexaminations,  or
extensions  (and  their  relevant  international  equivalents)  of  the  patents
described in (a), (b), and (c) above; and
            (e)      international  (non-United States) patent  applications and
provisional  applications  filed  after  the  EFFECTIVE  DATE  and the  relevant
international  equivalents to divisionals,  continuations,  continuation-in-part
applications and continued  prosecution  applications of the patent applications
to the extent the claims are directed to subject matter  specifically  described
in the patents or patent  applications  referred to in (a),  (b),  (c),  and (d)
above, and the resulting patents.

                                       4


     1.11  "REPORTING  PERIOD"  shall  begin on the first  day of each  calendar
quarter and end on the last day of such calendar quarter.

     1.12  "RESEARCH  REAGENT  FIELD"  shall mean  research  reagent uses of the
HEPARINASES designated for "research purposes only, not to be used in humans."

     1.13 "SUBLICENSEE"  shall mean any non-AFFILIATE  sublicensee of the rights
granted BIOMARIN under Section 2.1.

     1.14 "TERM" shall mean the term of this Agreement,  which shall commence on
the  EFFECTIVE  DATE  and  shall  remain  in  effect  until  the  expiration  or
abandonment  of all issued  patents  and filed  patent  applications  within the
PATENT RIGHTS,  unless earlier  terminated in accordance  with the provisions of
this Agreement.

     1.15 "TERRITORY" shall mean worldwide.

     1.16  "THERAPEUTIC  FIELD"  shall  mean  human  use of the  HEPARINASES  as
therapeutics  in  pharmaceutical  compositions  for reversal of  anticoagulants,
inflammation, reperfusion injury, restenosis and wound healing.

                               2. Grant of Rights.

     2.1 License Grants.  Subject to the terms of this Agreement,  M.I.T. hereby
grants to BIOMARIN and its  AFFILIATES  for the TERM a  royalty-bearing  license
under the PATENT RIGHTS to develop,  make, have made, use, sell,  offer to sell,


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