Exhibit 10.1


 


LICENSE AGREEMENT


 


Case Western Reserve University – Exact Sciences
Corporation


 


This Agreement (hereinafter “this Agreement”) entered into as of this
18th day of July, 2005 (“Effective Date”) by and between Case Western Reserve
University, an Ohio non-profit corporation, having a principal place of
business at 10900 Euclid Avenue, Cleveland, Ohio 44106 (“CASE”) and Exact
Sciences Corporation, a Delaware corporation, having a principal place of
business at 100 Campus Drive, Marlborough, MA 01752 (“Licensee”).


 


WITNESSETH


 


WHEREAS, CASE has, subject to certain interests of Howard Hughes
Medical Institute (“HHMI”), certain technology developed in the laboratory of Dr. Sanford
Markowitz, a Howard Hughes Medical Institute Investigator at CASE, relating to
HLTF and Vimentin Gene Methylation in Colon Cancer, and is interested in
licensing same,


 


WHEREAS, CASE has right, by reason of its Intellectual Property Policy
and assignment from HHMI, to license such technology, subject to the right of
HHMI to review and approve of any such license;


 


WHEREAS, CASE’s interest in such technology is subject to certain
retained rights by the United States of America and HHMI;


 


WHEREAS, Licensee desires to acquire rights in and to the technology
upon the terms and conditions herein set forth;


 


NOW THEREFORE, in consideration of the mutual covenants contained
herein and intending to be legally bound hereby, the parties agree as follows:


 


1.             DEFINITIONS


 


1.1           The term “Copyrights”
shall mean CASE’s and/or HHMI’s copyrights in the Licensed Technology.


 


1.2           The term “Dispose” or “Disposition”
shall mean the sale, lease or other transfer of Licensed Product(s).


 


1.3           The term “Dollar”, “U.S.
Dollar” and “U.S. $” shall mean lawful money of the United States of America.


 


1.4           The term “Field of Use”
shall mean use of the Licensed Technology in detecting human colorectal cancer
and tumors, including, without limitation, adenomas, in stool-based assays, and
other products for the purposes of colorectal disease screening and detection,
disease staging, disease monitoring, disease prognosis, and/or pharmacogenomic
testing.


 


1.5           The term “Fiscal
Quarter” or “Quarter” shall refer to the normal quarterly accounting periods of
Licensee; if Licensee does not have normal quarterly accounting periods,


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 

















 


then “Fiscal
Quarters” shall mean the calendar three months periods commencing with January of
each year.


 


1.6           The term “Licensed
Product” shall mean any product, service and/or process that constitutes, is
based on, incorporates or uses, in whole or in part, Licensed Technology,
including any mutant or altered form of the genetic material which is covered
by the Patent Rights.


 


1.6.1        The
term “Licensed Combination Product” shall mean a Licensed Product that includes
one or more genes for which Licensee or a Product Sublicensee must pay
royalties, upon Disposition, to one or more Third Party Licensors.


 


1.6.2        The
term “Third Party Licensor” means an entity (other than CASE, Licensee or
Sublicensee) that has entered a royalty-bearing license agreement with Licensee
or a Product Sublicensee for one or more genes included in a Licensed Product.


 


1.7           The term “Licensed
Technology” or “Technology” shall mean (i) the Patent Rights ; and (ii) the
technology, trade secrets, know-how, improvements and other information and
intellectual property of CASE identified in Attachment A.


 


1.8           The term “Licensee Net
Sales” shall mean the total of [********] received by Licensee due to
Dispositions of Licensed Products (other than Dispositions by Product
Sublicensees), less the total of all:


 


[********]


 


No deduction shall be made for commissions paid to individuals whether
they are individual sales agents or persons regularly employed by Licensee.


 


1.9           The term “Product
Sublicensee Royalty Basis” shall mean the revenue or sales total used in a
sublicense agreement between Licensee and a Product Sublicensee as the basis
for computing royalties owed by such Product Sublicensee to Licensee due to
Dispositions of Licensed Products. 
Product Sublicensee Royalty Basis, however, shall be no less than the
value of Licensee Net Sales that would result from considering Revenues of
Product Sublicensee to be Revenues of Licensee, unless CASE has agreed in
advance to accept a particular definition of “Product Sublicensee Royalty Basis”
for the computation of Royalties due to Dispositions by a Product Sublicensee.


 


1.10         The term “Patent Rights “
shall mean and include the United States patents and/or patent applications
listed in Attachment A to this Agreement; United States patents issued from the
applications listed in Attachment A and from divisionals and continuations of
these applications and any reissues of such United States patents; claims of
continuation-in-part applications and patents directed to subject matter
specifically described in the applications described above; and claims of all
foreign patent applications, patents, and other intellectual property which are
directed to subject matter specifically described in the United States patents
and/or patent applications described above.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


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1.11         The term “Prime Rate”
shall mean the interest rate per annum announced from time to time by Key Bank,
Cleveland, Ohio, as its prime rate.


 


1.12         The term “Product Launch”
shall mean the first commercial sale of Licensed Product(s).


 


1.13         The term “Product
Sublicensee” shall mean an entity to which Licensee sublicenses rights to make,
sell, distribute, manufacture, or otherwise convey or Dispose of Licensed
Products pursuant to a sublicense agreement.


 


1.14         The term “Revenue” shall
mean the U.S. Dollar value of all consideration realized from the Disposition
of Licensed Product(s).


 


1.15         The term “Royalties”
shall mean royalties calculated as a percentage of Net Sales and payable by
Licensee to CASE under this Agreement.


 


1.16         The term “Year” refers to
contract years of the License Agreement, i.e., a
12-month period starting with the date (or anniversary) of the Effective Date
of the License Agreement.


 


2.             LICENSE GRANT


 


2.1           CASE hereby grants to
Licensee, and Licensee hereby accepts, (i) an exclusive, royalty bearing,
world-wide right and license under and to the Licensed Technology to make, have
made, use and Dispose of Licensed Products in the Field of Use and (ii) a
non-exclusive, world-wide, royalty free right and license under and to the
Licensed Technology for internal research and development purposes in the Field
of Use.


 


2.2           No right to sublicense
the Licensed Technology is hereby granted to Licensee except that Licensee may
sublicense to (i) Product Sublicensees to the extent necessary to enable
Product Sublicensees to make and/or Dispose of Licensed Products within the
Field of Use; (ii) customers to the extent necessary for their personal
use of a Licensed Product; or (iii) other entities with the specific agreement
of CASE.


 


2.2.1        Licensee
understands that any sublicenses granted by Licensee to entities other than
customers (even though the specific agreement by CASE to such a sublicense has
been obtained) must provide that the obligations to CASE and HHMI (as a
third-party beneficiary) under this Agreement, including but not limited to,
Indemnification, Insurance, HHMI’s third party beneficiary status, and
procedures for Dispute Resolution shall be binding upon such sublicensee as if
it were a party to this Agreement and that the economic return to CASE from the
Disposition of Licensed Products be not less than the economic returns would be
if such Disposition had been by Licensee. 
In addition, any sublicense agreement shall provide for automatic
assignment to CASE in the event of termination of Licensee’s license to the
Licensed Technology (prior to expiration of this Agreement).  Licensee shall be responsible for the acts or
omissions of its sublicensees and shall not grant any rights which are
inconsistent with the rights granted to and obligations of Licensee
hereunder.  Any act or omission of a
sublicensee that would be a breach of this License Agreement if performed by
Licensee shall be 


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


3

















 


deemed to be a
breach of this License Agreement by Licensee if such breach is not cured before
180 days.  Each sublicense agreement
granted by Licensee shall include an audit right by CASE of the same scope as
provided herein below with respect to Licensee. 
No such sublicense agreement shall contain any provision which would
cause it to extend beyond the Team of this Agreement.  Licensee shall give CASE prompt notification
of the identity and address of each sublicensee with whom it concludes a sublicense
agreement and shall supply CASE with a copy of each such sublicense agreement.


 


2.3           No provision of this
Agreement shall restrict Licensee’s, CASE’s and/or HHMI’s ability to conduct
further research and development in the area of Licensed Technology or other
areas.


 


2.4           All Licensed Products
shall be manufactured, sold and performed by Licensee in compliance with all
applicable governmental laws, rules and regulations.  Licensee shall keep CASE fully informed of,
and shall move expeditiously to resolve, any complaint by a governmental body
relevant to Licensed Products, except for complaints subject to the Section of
this Agreement entitled “Infringement.”


 


2.5           CASE represents and
warrants that CASE has the right to license the Patent Rights to Licensee under
the terms provided in this Agreement and that CASE’s obligations to HHMI do not
conflict with the licenses provided hereunder. 
CASE retains the right to grant either exclusive or non-exclusive
licenses for the Licensed Technology in fields of use other than the Field of
Use for which the license hereunder is granted.


 


2.6           If Licensed Technology
was supported under a United States Government funding agreement, then (a) the
United States Government has been or will be granted licensing rights solely as
required under the terms of those federal agreements, (b) all rights and
obligations reserved to the United States Government and others under Public
Law 96-517, and Public Law 98-620 and any applicable governmental rules and
regulations, including but not limited to government purpose license and
march-in rights and sharing of certain research materials, shall be respected
and shall in no way be diminished by this Agreement and any right granted in
this Agreement regarding Licensed Technology greater than that permitted under
Public Law 96-517 or Public Law 98-620, and any applicable governmental rules and
regulations, shall be subject to modification as may be required to conform to
the provisions of those statutes, and (c) products using Licensed
Technology sold or used in the United States will be manufactured substantially
in the United States of America, unless a waiver has been obtained from the
federal funding agency under whose funding agreement the Licensed Technology
was generated.


 


2.7           Notwithstanding the
license granted in this Agreement, CASE and HHMI and any health care
institutions affiliated with either of them shall have and retain all rights to
use, free of charge, the Licensed Technology for their non-commercial research,
clinical research treatment (i.e. the
treatment of patients as part of a clinical research effort to determine the
effectiveness, safety or tolerability of Licensed Technology), educational or
academic purposes, even in the Field of Use, but not for licensing to
others.  There is no restriction on
licensing by CASE of Licensed Technology outside the Field of Use.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


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2.8           CASE and HHMI may have
in the past, and shall have the right in the future, to provide Licensed
Technology to academic and/or non-profit health care institutions for
non-commercial research, clinical research treatment, educational, or academic
purposes.  Nothing in this Agreement
shall prohibit such conduct by CASE or HHMI or use for such purposes by
academic or non-profit health care institutions receiving Licensed Technology
from CASE or HHMI.  For the avoidance of
confusion, CASE may not, during the Term of this Agreement, permit any third
party to use the Licensed Technology in the Field of Use for commercial
purposes.


 


3.             FIELD OF USE OPTION


 


CASE hereby grants to Licensee an option (the “Field of Use Option”)
for a term of twenty-four (24) months only, commencing on the Effective Date,
(the “Option Period”) to negotiate an amendment to the Agreement with CASE to
expand the Field of Use for the Licensed Technology to include human
blood-based assays for the purposes of colorectal disease screening and
detection, disease staging, disease monitoring, disease prognosis, and/or
pharmacogenomic testing.  To exercise
this Field of Use Option, Licensee must (i) provide a written statement,
reasonably satisfactory to CASE, demonstrating Licensee’s capability and
intention to develop Licensed Products within the human blood-based assay field
of use for public sale as soon as practicable, consistent with sound and reasonable
business practices and judgment, and (ii) execute an amendment to this
Agreement with CASE prior to expiration of the Option Period.


 


4.             TERM OF THIS
AGREEMENT


 


This Agreement shall expire at the end of its term (the “Term”), which
extends from the Effective Date to the expiration of the last to expire of the
Patent Rights.  The Agreement may be
terminated prior to expiration pursuant to other provisions of this Agreement.


 


5.             DUE DILIGENCE


 


5.1           Licensee shall use its
best commercially reasonable efforts to effect introduction of Licensed
Technology into the commercial market as soon as reasonably practical;
thereafter, until the termination of this Agreement, Licensee shall keep
Licensed Technology reasonably available to the public.  At a minimum, Licensee shall achieve Product
Launch within thirty (30) months of the Effective Date.


 


5.2           Licensee’s default in
performance in accordance with Subsection 5.1 shall be grounds for CASE to
terminate this Agreement.


 


6.             LICENSE FEES AND
ROYALTIES


 


6.1           For Dispositions of
Licensed Products other than Licensed Combination Products, Licensee shall pay
CASE a Royalty of [********] (hereinafter the “Royalty Rate”) of the sum of
Licensee Net Sales and Product Sublicensee Royalty Basis.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


5

















 


6.2           For Dispositions of
Licensed Combination Products, the Royalty Rate of [********] shall be reduced
by the percentage, if any, of Licensee Net Sales and/or Product Sublicensee
Royalty Basis payable as a royalty to the Third Party Licensor(s) who have
contributed one or more genes to such Licensed Combined Products.  Notwithstanding the foregoing, in no event
shall the Royalty Rate be less than 1 percent.


 


6.3           The parties acknowledge
that Licensee, in partial satisfaction of its fee obligations to CASE
hereunder, paid CASE [********] on March 10, 2003.  In addition to this amount, Licensee shall
pay CASE non-refundable License Fees of (i) [********] due and payable
[********]; (ii) [********] due and payable, if this Agreement is still in
effect, upon the earlier of: (a) [********] or, (b) [********]; and (iii) [********]
due and payable [********].  The License
Fees described in this section 6.3 will be in addition to any other amounts due
under this Agreement.


 


6.4           Licensee shall pay CASE
a minimum royalty of [********] per year (“Annual Minimum Royalty”),
commencing on the anniversary date of the Effective Date following the Product
Launch, and payable on each anniversary of the Effective Date thereafter.  The Annual Minimum Royalty shall be credited
against the Royalties payable in a Year.


 


6.5           Annual Minimum Royalty
payments are to be adjusted by the cumulative percentage change in the CPI-W
Consumer Price Index between December 2004 and the December preceding
the date on which the payment in question is payable.


 


7.             PAYMENT TERMS


 


7.1           Royalties shall be paid
by Licensee to CASE, as defined in the Section entitled “Royalties” for
each Fiscal Quarter within sixty (60) days of the end of such Fiscal Quarter,
until this Agreement expires or is terminated in accordance with this
Agreement.  If this Agreement terminates
before the end of a Fiscal Quarter, the payment for that terminal fractional
portion of a Fiscal Quarter shall be made within ninety (90) days of the date
of termination of this Agreement.


 


7.2           All Royalties hereunder
shall be paid in U.S. Dollars and shall be made by wire transfer to CASE’s
account No. [********] at Key Bank’s Cleveland office, or by Licensee’s
check sent in accordance with the Section entitled “Notices”.


 


7.3           All Royalties payable
hereunder that are overdue shall bear interest until paid at a rate equal to
the Prime Rate in effect at the date such Royalties were due plus four percent
(4%) per annum, but in no event to exceed the maximum rate of interest
permitted by applicable law.  This
provision for interest shall not be construed as a waiver of any rights CASE
has as a result of Licensee’s failure to make timely payment of any amounts.


 


8.             REPORTS AND AUDITS


 


8.1           Licensee shall provide
Quarterly reports of its progress in achieving Product Launch and shall notify
CASE within ten (10) days of achieving Product Launch.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting confidential
treatment under Rule 24b-2 of the Exchange Act; [*] denotes omissions.


 


6

















 


8.2           Licensee shall maintain
accurate books and records such that the Royalties due and payable hereunder
can be easily ascertained.  Such books
and records shall be maintained at Licensee’s principal place of business and
shall be available for inspection by CASE or its representatives during the
normal business day upon not less than ten (10) days prior written notice,
provided that CASE or its representatives agree to protect the confidentiality
of the informational Licensee.


 


8.3           Licensee shall make
available Licensee’s books and records for audit by an independent accounting
firm of CASE’s selection and Licensee agrees to cooperate fully in any such
audit, provided that the auditors agree to protect the confidentiality of the
information of Licensee.  Any such audit
shall not be more frequent than annually. 
In the event that such audit determines that the amount of Royalties
paid to CASE was in error by the greater of [********] or [********], Licensee
shall pay the costs of the audit.


 


9.             IMPROVEMENTS


 


9.1           Discussion of technical
matters with each other by the parties will not create in a party any rights to
ownership of patents, copyrights, trade secrets or other intellectual property
rights in solutions to the matters that are invented solely by employees or
agents of the other party hereto.


 


9.2           Licensee will own all
of the right, title and interest (including patents, copyrights, trade secrets
and any other intellectual property rights) in and to any results developed
solely by Licensee or on its behalf in connection with this Agreement,
including the results of any collaboration between the parties that are
invented solely by Licensee’s employees or agents.


 


9.3           CASE will own all of
the right, title and interest (including patents, Patent Rights, Copyrights,
mask work rights, trade secrets and any other intellectual property rights) in
and to any results developed solely by CASE or on its behalf in connection with
this Agreement, including the results of any collaboration between the parties
that are invented solely by CASE employees or agents.


 


9.4           All intellectual
property that is a direct improvement of and is dominated by the Patent Rights
and has been jointly invented by employees or agents of CASE and Licensee in
connection with this Agreement and without use of Licensee’s own intellectual
property shall be owned by CASE and included as Patent Rights, provided that Licensee
may use such jointly invented intellectual property pursuant to the terms of Section 2.1
of this License Agreement.  CASE may
issue licenses to others regarding such jointly invented property that result
in Patent Rights, as long as such licenses do not violate any exclusive license
to Licensee granted to Licensee under Section 2.1 (entitled “License Grant”).  If any other intellectual property is jointly
invented by employees or agents of CASE and Licensee in connection with this
Agreement, CASE and Licensee shall jointly own (without any duty to account to
the other for profits) all right, title and interest (including patents,
copyrights, mask work rights, trade secrets, and other intellectual property
rights) therein.  If any such patentable
invention which would not constitute a Patent Right or Licensed Technology
arises out of such joint invention by employees or agents of CASE and Licensee,
CASE and Licensee will negotiate in good faith on whether 


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


7

















 


and how to pursue
patent, copyright or mask work protection of the invention in the U.S. and
elsewhere.


 


9.5           Except as provided in
this Section, nothing herein shall be deemed to grant any license or rights in
any other technology in addition to the Licensed Technology.


 


10.           PATENTS AND OTHER
INTELLECTUAL PROPERTY


 


10.1         CASE Property.  Intellectual property rights to Licensed
Technology, such as Patent Rights, and Case’s Copyrights, will remain the
property of CASE.  Trademarks owned by
CASE existing on the Effective Date of this License Agreement related to the
Licensed Technology belong to CASE.


 


10.2         Licensee shall bear all
patenting costs for prosecution and maintenance of patents included in the
Licensed Technology that are reasonably incurred or due prior to termination of
this Agreement according to the following terms.  Licensee will reimburse CASE for the
following fees and expenses related to such patenting that have been incurred
as of the Effective Date, as follows: (i) [********] of past fees and
expenses shall be due within thirty (30) days of receipt of an invoice or bill
from CASE, not to exceed [********], and (ii) [********] of past fees and
expenses shall be due upon Product Launch, not to exceed [********].  Licensee shall reimburse CASE for all reasonable
future fees and expenses related to the Patent Rights in those countries agreed
upon by Licensee within thirty (30) days of the receipt of each invoice or
bill.  Should Licensed Technology be
licensed to others, those patenting and other intellectual property protection
costs which are incurred after that point shall be pro-rated among all licenses
in proportion to the number of licenses in effect at the time the costs are
incurred.  CASE will use reasonable best
efforts to manage efficiently patent prosecution and expenses and shall keep
Licensee advised of such expenses. 
Licensee shall have reasonable input into consideration of issues
relating to prosecution and maintenance of patents covering the Licensed Technology,
but CASE shall retain ultimate control and decision-making authority with
respect thereto.


 


10.3         CASE has applied for,
and/or will apply for and prosecute Patent Rights, at Licensee’s expense, in
any country that is requested by Licensee, for any and all patent applications
and patents listed in Attachment A, to the extent that such protection is
reasonably obtainable.  Licensee will not
be responsible for patent costs associated with foreign prosecution unless such
foreign pursuit has first been approved by Licensee in writing.  If such written approval is not delivered to
CASE within thirty (30) days of CASE’s written request therefor, Licensee shall
have no rights concerning those specific patent rights included in the Patent
Rights in such country(ies).


 


10.4         CASE may, at its option
and sole discretion and at its own expense, pursue patent, copyright and/or
trademark rights for Licensed Technology in any country for which coverage has
not been requested by Licensee in accordance with Subsection 10.3 above.  If Licensee does not reimburse CASE for such
fees within thirty (30) days of the receipt of a related invoice or bill, then
Licensee shall have no rights under any of those specific patent rights
included in the Patent Rights in that country and shall have no rights to
practice under such patent in such country.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


8
















 


11.           MARKINGS, TRADEMARKS
AND TRADE NAMES


 


11.1         Licensee shall have
included in all sales, marketing literature and invoices relating to Licensed
Product, a statement to the effect that “this product or portions thereof is
manufactured under license from Case Western Reserve University” and, if
applicable, either “Patent Pending” or, if applicable, “U.S. Patent Number
                  .”


 


11.2         Licensee shall have
marked the appropriate portions of all Licensed Product with any applicable
United States of America and foreign patent numbers in accordance with the
applicable laws of the countries in which the materials are intended to be
used.  Licensee shall neither register
nor use any CASE trademarks or trade names.


 


11.3         Licensee and CASE each
acknowledge that they do not have any rights or any title whatsoever in or to
the other’s technology, trade names or trademarks, except as expressly provided
under this Agreement and except as expressly authorized in writing after the
Effective Date of this Agreement and except as required by law.  Any reference by Licensee to CASE beyond the
above may only be done with express written permission of CASE’s Associate Vice
President for Technology Transfer.


 


12.           TERMINATION


 


12.1         In the event that
Licensee defaults in the payment in full of any amount required to be paid
under this Agreement on the date such payment is due, in addition to using any
other legal and/or equitable remedies, CASE shall have the right, following the
applicable cure period described in 12.2 below, and by written notice to
Licensee after such default either (i) to terminate the exclusivity, if
any, of the license hereunder (by amending the word “exclusive” in the License
Grant to read “non-exclusive”) without any reduction in any of the payments due
from Licensee or (ii) to terminate this Agreement.


 


12.2         In the event that either
party to this Agreement defaults in the performance of any of its obligations
hereunder and fails to cure such default within thirty (30) days after written
notice of such default from such other party, the other party shall have the
right by written notice to the defaulting party within sixty (60) days after
the expiration of such thirty (30) day period to terminate this Agreement.


 


12.3         The termination of this
Agreement, under any Section of the Agreement, shall not terminate (i) the
obligation of Licensee to pay any amounts, which have accrued or which are
otherwise to be paid by Licensee under the terms of this Agreement, or (ii) the
obligations of either party arising prior to the date of termination under the
Sections entitled “Reports and Audits,” “Patents and Other Intellectual
Property,” “Termination,” “Taxes,” “Confidentiality and Trade Secrets,” “Indemnification,”
“Insurance,” “Dispute Resolution,” and “Infringement” hereunder.


 


12.4         Upon termination of this
Agreement, Licensee will immediately discontinue any further use of Licensed
Technology and discontinue production of any Licensed Products.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


9

















 


12.5         In the event of
termination of the Agreement prior to expiration, any sublicenses entered by
Licensees shall be automatically be assigned to CASE and shall operate
thereafter as direct licenses from CASE. 
Notwithstanding the foregoing, CASE shall only be entitled under such
sublicenses, to the receipt of amounts relating to the Licensed Technology and
shall not be entitled to receive amounts from such sublicensees relating to
Licensee’s technologies, which shall continue to remain due and payable to
Licensee directly.


 


12.6         Licensee shall have the
right to terminate this Agreement upon notice to CASE if one or more of the
Patent Rights do not issue.


 


13.           TAXES


 


Licensee shall pay all taxes which may be assessed or levied on, or on
account of, the Licensed Technology, Licensed Product made, used or Disposed of
hereunder and all taxes (other than taxes imposed by the United States of
America or the State of Ohio or jurisdictions within such State) levied on or
on account of the amounts payable to, or for the account of, CASE under this
Agreement, excluding income taxes.


 


14.           NO WARRANTY


 


EXCEPT AS EXPRESSLY PROVIDED IN THIS AGREEMENT: (A) ANY
INFORMATION, MATERIALS, SERVICES, INTELLECTUAL PROPERTY OR OTHER PROPERTY OR
RIGHTS GRANTED OR PROVIDED BY CASE PURSUANT TO THIS AGREEMENT (“DELIVERABLES”)
ARE ON AN “AS IS” BASIS, (B) NEITHER LICENSEE NOR CASE MAKE ANY WARRANTIES
OF ANY KIND, EITHER EXPRESSED OR IMPLIED, AS TO ANY MATTER INCLUDING, BUT NOT
LIMITED TO, WARRANTY OF FITNESS FOR PARTICULAR PURPOSE, OR MERCHANTABILITY,
EXCLUSIVITY OR RESULTS OBTAINED FROM USE, NOR SHALL EITHER CASE OR LICENSEE BE
LIABLE FOR CLAIMS FOR INDIRECT, SPECIAL, OR CONSEQUENTIAL DAMAGES SUCH AS LOSS
OF PROFITS OR INABILITY TO USE SAID DELIVERABLES OR ANY APPLICATIONS AND
DERIVATIONS THEREOF.  EXCEPT AS PROVIDED
IN THIS AGREEMENT, NEITHER CASE NOR LICENSEE MAKES ANY WARRANTY OF ANY KIND
WITH RESPECT TO FREEDOM FROM PATENT, TRADEMARK, OR COPYRIGHT INFRINGEMENT, OR
THEFT OF TRADE SECRETS.  CASE DOES NOT
ASSUME ANY LIABILITY HEREUNDER FOR ANY INFRINGEMENT OF ANY PATENT, TRADEMARK,
OR COPYRIGHT ARISING FROM THE USE OF THE DELIVERABLES.  NEITHER PARTY WILL MAKE ANY WARRANTY ON
BEHALF OF THE OTHER, EXPRESSED OR IMPLIED, TO ANY THIRD PARTY.


 


15.           COSTS


 


All costs and expenses incurred by Licensee in carrying out Licensee’s obligations
under this Agreement shall be paid by Licensee, and Licensee shall not be
entitled to reimbursement from Royalties hereunder or otherwise therefore from
CASE.  Licensee shall possess or obtain
at its own expense all necessary licenses and permits and shall comply with all
laws, ordinances, 


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


10

















 


rules or regulations affecting the exportation,
use, and/or sale or transfer of the Licensed Product and/or Licensed Technology
by Licensee..


 


16.           CONFIDENTIALITY AND
TRADE SECRETS


 


16.1         “Confidential Information”
shall mean any information relating to the Licensed Technology, the terms of
this Agreement (as from time to time amended), Patent Rights, or other
non-public matters covered by this Agreement or information disclosed from one
party to the other hereunder in the manner set forth hereinafter.  All such information shall be Confidential
Information, including information disclosed prior to the date of this
Agreement, unless such information (i) was already in the receiving party’s
possession prior to the time of relevant disclosure thereof as provided in
subsection (a) hereof; (ii) has been published or is published
hereafter, unless such publication is a breach of this Agreement; (iii) is
obtained by the receiving party from a third party not under an obligation of
confidentiality with respect thereto; or (iv) is independently developed
by the receiving party.


 


(a)           In the
event that such information shall be established to have been known to the
receiving party prior to the disclosure thereof by reference to any publication
thereof by the receiving party or by reference to any internal writing or other
business record maintained by the receiving party in the ordinary course of
business, such information shall not be deemed to be Confidential Information
for purposes of this Agreement following notification to the other party under
this Agreement of such fact.


 


(b)           With
respect to any information not related to the Licensed Technology or Licensee’s
assay and product development efforts which are deemed by the disclosing party
to be Confidential Information subject to this Agreement, the disclosing party
shall mark such information as “Confidential” prior to disclosing it to the
other.


 


(c)           With
respect to any oral communication not related to the Licensed Technology or
Licensee’s assay and product development efforts which is deemed by the
disclosing party to be Confidential Information subject to this Agreement, the
disclosing party shall notify the receiving party of such fact and within
thirty (30) days thereafter the disclosing party shall send a memorandum to the
receiving party outlining the information deemed to be Confidential
Information.


 


16.2         Each party shall maintain
in confidence and shall not disclose to any person not a party hereto, nor
shall either party use or exploit in any way without the other party’s written
agreement, any Confidential Information until three (3) years after the
later of the date of the termination of this Agreement or the end of the term
of the last to expire of the Patent Rights, unless such information ceases to
be Confidential Information prior to the end of such period through no fault of
the receiving party or the parties enter into an agreement authorizing same.


 


16.3         The receiving party shall
exercise all reasonable precautions to prevent the disclosure of Confidential
Information by its employees or representatives, and in any event shall
maintain with respect to such Confidential Information a standard of care which
is no less than 


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


11

















 


that standard
which such party maintains to prevent the disclosure of its own confidential
information.


 


16.4         Upon termination of this
Agreement, each party agrees to return at once to the other, without copying, all
originals and copies of all materials (other than this Agreement) containing
any Confidential Information and to make no further use thereof


 


17.           INDEMNIFICATION


 


Licensee hereby agrees to defend, indemnify and hold harmless CASE and
HHMI, and their respective trustees, officers, employees, attorneys and agents
from and against any third party claim, liability, cost, expense, damage,
deficiency, loss, or obligation, of any kind or nature (including, without
limitation, reasonable attorneys’ fees and other costs and expenses of defense)
(collectively, “Claims”), based upon, arising out of or otherwise relating to
Licensee’s actions or inactions under this Agreement or based upon, arising out
of or otherwise relating to Licensee’s and/or its sublicensee’s use, conduct,
or misconduct regarding Licensed Products , including but not limited to, any
claims of product liability, personal injury, death, damage to property or
violation of any laws or regulations.


 


18.           INSURANCE


 


Before Licensed Technology is used to diagnose or treat human beings,
Licensee shall obtain and maintain appropriate coverage of general liability,
product liability, and public liability insurance in the amount of no less than
Three Million Dollars to protect CASE and HHMI, and their respective trustees,
officers, employees, attorneys and agents under the indemnification provided
hereunder.  CASE and HHMI, and their
respective trustees, officers, employees, attorneys and agents shall be named
as additional insureds on Licensee’s insurance policies.  CASE shall be provided appropriate
certificates of insurance thereunder.


 


19.           BREACH


 


No acquiescence in any breach of this Agreement by either party shall
operate to excuse any subsequent or prior breach.


 


20.           PRIOR AGREEMENT


 


Except for any confidential disclosure agreement executed by the
parties, this Agreement supersedes all previous agreements relating to the
subject matter hereof, whether oral or in a writing, and constitutes the entire
agreement of the parties hereto and shall not be amended or altered in any
respect except in a writing executed by the parties.


 


21.           INTERPRETATION


 


This Agreement shall be governed by, and construed and enforced in
accordance with, the laws of the State of Ohio, United States of America,
without regard to conflict of law principles.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


12

















 


22.           DISPUTE RESOLUTION


 


22.1         Subject to Subsection
22.2, any controversy or dispute arising under or relating to this Agreement
(including, but not limited to, the validity, scope and enforceability of this
arbitration clause) shall be referred to and finally settled by arbitration in
the City of Cleveland, Ohio, under the auspices of, and conducted in accordance
with, the rules of the American Arbitration Association.  All arbitration proceedings shall be before a
board of three (3) arbitrators, for each of which each party shall select
one (1) arbitrator and the selected arbitrators shall select the third
arbitrator.  The costs of the third
arbitrator shall be divided equally between the parties, and each party shall
pay the costs of the arbitrator selected by it. 
Any award of the arbitrators shall be final and conclusive on the
parties to this Agreement, and judgment upon such award may be entered in any court
having jurisdiction thereof.  Notwithstanding
the foregoing, any dispute affecting the rights or property of HHMI shall not
be subject to the arbitration provisions above.


 


22.2         Either party may seek
injunctive relief for: (a) violation by the other party of the Sections
entitled “Reports and Audits,” “Markings, Trademarks and Trade Names,” “Confidentiality
and Trade Secrets,” “Insurance” and “Dispute Resolution”; (b) for
enforcement of any arbitration award; or (c) for enforcement of any
non-arbitrable matter.  The prevailing
party shall be entitled to recover from the other all costs, including attorney’s
fees, related to the action for injunctive relief.


 


22.3         Licensee
hereby irrevocably and unconditionally:


 


(i)        Agrees
that any legal action, suit or proceeding relating to the Agreement and
contemplated by this Section entitled “Dispute Resolution” hereof
(collectively, “Related Litigation”) may be brought in any state or federal
court of competent jurisdiction sitting in Cuyahoga County, Ohio, submits to
the jurisdiction of such courts, and to the fullest extent permitted by law
agrees that it will not bring any Related Litigation in any other forum (but
nothing herein shall affect the right of CASE to bring any action, suit or
proceeding in any other forum);


 


(ii)       Waives
any objection which it may have at any time to the laying of venue of any
Related Litigation brought in any such court located in Cuyahoga County, Ohio,
waives any claim that any such Related Litigation has been brought in an
inconvenient forum, and waives any right to object, with respect to any Related
Litigation brought in any such court, that such court does not have
jurisdiction over Licensee; and


 


(iii)      Consents and agrees to service of any summons,
complaint or other legal process in any Related Litigation by registered or
certified mail, postage prepaid, to Licensee at the address for notices
described in the Section entitled “Notices” hereof, and consents and
agrees that such service shall constitute in every respect valid and effective
service (but nothing herein shall affect the validity or effectiveness of
process served in any other manner permitted by law).


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting confidential
treatment under Rule 24b-2 of the Exchange Act; [*] denotes omissions.


 


13

















 


23.           INFRINGEMENT


 


23.1         Licensee shall have the
right during the term of this Agreement to commence an action for infringement
of the Patent Rights against any third party for any infringement occurring
within the Field of Use, provided that Licensee shall provide CASE thirty (30)
days’ prior written notice of such infringement and of Licensee’s intent to
file such action.  CASE shall have the
right at its own expense to appear in such action by counsel of its own
selection.  If required by the
jurisdictional laws of the forum that any such action be prosecuted in the name
of the owner of the Patent Right, CASE shall voluntarily appear at Licensee’s
expense; provided that if such appearance subjects CASE to any unrelated action
or claim of a third party or Licensee in such jurisdiction, then CASE shall
have the right to decline such appearance. 
Settlement of any action brought by Licensee shall require the consent
of CASE and Licensee, which neither shall unreasonably withhold from the other,
and any settlement amount or recovery for damages shall be applied as follows: (i) first,
to reimburse the parties for their expenses in connection with the litigation;
and (ii) second, CASE shall receive compensation for the time of any CASE
personnel involved in the action; and (iii) third, CASE shall receive
[********] of any monies remaining.


 


23.2         CASE shall have the right
in its sole discretion during the term of this Agreement to commence an action
for infringement of the Patent Rights against any third party for any
infringement occurring anywhere in the world, provided that, before commencing
any such action concerning products within the Field of Use, CASE shall provide
Licensee with the first right to sue as provided in Section 23.1 and, if
Licensee determines not to bring suit, with not less than thirty (30) days’
prior written notice of such infringement and of CASE’s intent to file such
action.  Licensee shall have the right at
its own expense to appear in such action by counsel of its own selection.  If CASE provides Licensee with such notice
before instituting an action concerning products within the Field of Use and
Licensee fails to initiate an action against such third party prior to the
commencement of an action by CASE, then any settlement amount or recovery for
damages shall belong entirely to CASE and CASE may settle said action without
the consent of Licensee; provided, however, that the terms of any such
settlement do not impose any obligations on Licensee or limit any rights
Licensee would otherwise have under this Agreement.


 


23.3         Notwithstanding the
pendency of any infringement (or other) claim or action by or against Licensee,
Licensee shall have no right to terminate or suspend (or escrow) payment of any
amounts required to be paid to CASE pursuant to this Agreement.


 


24.           NOTICES


 


Any notice under any of the provisions of this Agreement shall be
deemed given when deposited in the mail, postage prepaid, registered or
certified first class mail and addressed to the applicable party at the address
stated on the signature page hereof, or such other address as such party
shall specify for itself by like notice to other party.  Each party shall transmit to the other a
facsimile copy of each such notice promptly after such deposit in the mail.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


14

















 


25.           ASSIGNMENT


 


Except in the instance of a merger of Licensee into another entity or
the sale of the assets of Licensee to which this License Agreement relates,
Licensee shall neither assign nor transfer this Agreement or any interest
herein without the prior written consent of CASE.


 


26.           THIRD PARTY BENEFICIARY


 


HHMI is not a party to this Agreement and has no liability to any
licensee, sublicensee, or user of anything covered by this Agreement, but HHMI
is an intended third-party beneficiary of this Agreement and certain of its
provisions are for the benefit of HHMI and are enforceable by HHMI in its own
name.


 


27.           HEADINGS


 


The section headings contained in this Agreement are set forth for the
convenience of the parties only, do not form a part of this Agreement and are
riot to be considered a part hereof for the purpose of construction or interpretation
hereof; or otherwise.


 


28.           EXPORT CONTROLS


 


It is understood that CASE is subject to United States laws and
regulations controlling the export of technical data, computer software,
laboratory prototypes and other commodities (including the Arms Export Control
Act, as amended and the Export Administration Act of 1979), and that its
obligations hereunder are contingent on compliance with applicable United
States export laws and regulations.  The
transfer of certain technical data and commodities may require a license from
the cognizant agency of the United States Government and/or written assurances
by Licensee that Licensee shall not export data or commodities to certain
foreign countries without prior approval of such agency.  CASE neither represents that a license shall
not be required nor that, if required, it shall be issued.


 


(The balance of this page is intentionally
left blank)


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


15

















 


IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
duly executed in duplicate counterparts, each of which shall be deemed to
constitute an original, effective as of the date first above written.


 


The undersigned verify subject to the penalties of Section 2921.13
of the Ohio Revised Code relating to unsworn falsification to authorities that
they have the authority to bind to this Agreement the party on behalf of which
they are executing below.


 


	
  Case Western Reserve University

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  By:

  	
    /s/ Mark E. Coticchia

  	
   

  	
  By:

  	
    /s/ [illegible]

  
	
   

  	
   

  	
   

  
	
  Title:

  	
    VP for Research & Technology

  	
   

  	
  Title:

  	
    CIO

  
	
   

  	
    Management

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Date:

  	
    8/4/05

  	
   

  	
  Date:

  	
    8/5/05

  
									



 


 


Address
for Notices:


 


Case
Western Reserve University


 


10900
Euclid Avenue

Cleveland, Ohio 44106, USA

Attention: Assistant Vice President Biomedical Science

Facsimile: 216-368-0196


 


Exact
Sciences Corporation


 


	
  By:

  	
    /s/ Don Hardison

  	
   

  
	
   

  	
   

  	
   

  
	
  Title:

  	
    President and CEO

  	
   

  
	
   

  	
   

  	
   

  
	
  Date:

  	
    7/27/05

  	
   

  
					



 


Address
for Notices:


 


100
Campus Drive

Marlborough, MA 01752

Attention: President 

Facsimile:(508) 683-1201


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


16

















 


Attachment A


 


Description of Licensed Technology


 


1)             [********]


 


2)             [********]


 


Also, without limitation, any foreign filed patents and patent
applications based on the subject matter included in (1) and (2) above not
already listed above.


 


CASE has represented to Licensee that this Attachment A is a complete
list of patent applications and patents owned or controlled by CASE as of the
Effective Date that relate to HLTF Gene Methylation and/or Vimentin Gene
Methylation that have application to the Field of Use.  To the extent not already listed, this
Attachment A therefore includes, without limitation, patent applications and
patents owned or controlled by CASE as of the Effective Date that relate to HLTF
Gene Methylation and/or Vimentin Gene Methylation and have application to the
Field of Use, provided that Licensee may elect, upon disclosure of the patent
rights by CASE to Licensee, to include or exclude any such patent application
or patent from this Agreement.


 


To the extent not already listed, this Attachment A shall include,
without limitation, any such patent application(s) and/or patent(s) that
Licensee elects to include in the Patent Rights pursuant to Section 2.10
of this Agreement.


 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.


 


17

















 


First Amendment to License Agreement


EXACT Sciences Corporation


and


Case Western Reserve University


 


This First Amendment (this “Amendment”) is made effective as of December 31,
2007 (the “Amendment Effective Date”), by and between Case Western Reserve
University (“CWRU”) and EXACT Sciences Corporation (“EXACT”).


 


WHEREAS, CWRU and EXACT entered into an Agreement dated July 18,
2005, (the “Agreement”) and the parties desire to amend certain provisions of
the Agreement.


 


NOW, THEREFORE, in partial consideration of entry of this Amendment by
CWRU, Licensee shall pay to CWRU a non-refundable upfront fee of [********]
within 90 days of the Amendment Effective Date; this [********] payment is
separate and apart from the [********] payment referenced below in paragraph 1.  The parties agree to the following amendments
to the Agreement, to be effective as of the Amendment Effective Date:


 


1.             The
last sentence of Section 5.1 of the Agreement shall be replaced with the
following:


 


At a minimum, Licensee shall achieve Product Launch by December 31,
2008.  If Licensee has not achieved
Product Launch by December 31, 2008, it can extend the date for this
requirement to December 31, 2009 by notifying CWRU in writing and paying a
[********] non-refundable fee to CWRU.


 


2.             Except
as expressly modified herein, the Agreement and all of its terms and conditions
shall continue in full force and effect.


 


IN WITNESS WHEREOF, the duly authorized representatives of the parties
have executed this Amendment as of the date first above written.


 


	
  Case Western Reserve University

  	
   

  	
  EXACT Sciences Corporation

  
	
   

  	
   

  	
   

  
	
  By:

  	
    /s/ Mark E. Coticchia

  	
   

  	
  By:

  	
    /s/ Jeffrey Luber

  
	
   

  	
   

  	
   

  
	
  Printed Name:

  	
  Mark E. Coticchia

  	
   

  	
  Printed Name:

  	
    Jeffrey Luber

  
	
   

  	
   

  	
   

  
	
  Title:

  	
    Vice President for Research and 

  	
   

  	
  Title:

  	
    President

  
	
   

  	
  Technology Management

  	
   

  	
   

  	
   

  
										



 


 


	
  Case Western Reserve University

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  By:

  	
    /s/ Robert Clarke Brown

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Printed Name:

  	
    Robert Clarke Brown

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Title:

  	
    Treasurer

  	
   

  	
   

  
						



 


Portions
of this Exhibit were omitted and have been filed separately with the
Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 24b-2 of the Exchange Act; [*] denotes
omissions.