Exclusive License Agreement - Celgene Corp., Children's Medical Center Corp. and EntreMed Inc.
EXCLUSIVE LICENSE AGREEMENT
among
CELGENE CORPORATION,
CHILDREN'S MEDICAL CENTER CORPORATION,
and, solely for purposes of Sections 1, 2.4, 2.5, 2.6, 4.2, 4.6, 8.2,
9.4, 11, 12, 13, and 16 hereof,
ENTREMED, INC.
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EXCLUSIVE LICENSE AGREEMENT
---------------------------
This Exclusive License Agreement ("Agreement") is made effective this 31st
day of December, 2002 ("Effective Date") by and among CELGENE CORPORATION, a
Delaware corporation having an address at 7 Powder Horn Drive, Warren, New
Jersey, 07059, ("Celgene"), CHILDREN'S MEDICAL CENTER CORPORATION, a
corporation duly organized and existing under the laws of the Commonwealth of
Massachusetts and having its principal office at 300 Longwood Avenue, Boston,
Massachusetts 02115 ("CMCC"), and, solely for purposes of Sections 1, 2.4, 2.5,
2.6, 4.2, 4.6, 8.2, 9.4, 11, 12, 13, and 16 hereof, EntreMed, Inc., a Delaware
corporation located at 9640 Medical Center Drive, Rockville, Maryland 20850
("EntreMed").
RECITALS
--------
WHEREAS EntreMed and Celgene are parties to that certain civil action
captioned Celgene Corporation v. James E. Rogan and EntreMed, Inc., Case Number
1:02CV02277 (RBW), pending in the United States District Court for the District
of Columbia, and that certain civil action captioned EntreMed, Inc. v. Celgene,
Civil Action No. DKC-02-3787, pending in the United States District Court for
the District of Maryland Southern Division (collectively, the "Litigations");
WHEREAS EntreMed and Celgene desire to settle the Litigations and, in
connection therewith, to enter into an Asset Purchase Agreement by and between
EntreMed, Inc. and Celgene dated December 31, 2002 ("Asset Purchase Agreement"),
pursuant to which EntreMed will sell to Celgene certain assets relating to
Thalidomide Analogs (as hereinafter defined);
WHEREAS CMCC is the owner of certain Analog Patents (as hereinafter
defined) relating to Thalidomide Analogs, and has exclusively licensed same to
EntreMed pursuant to that certain Analog Agreement dated August 6, 2001
("EntreMed Analog Agreement") and that certain License Agreement dated July 9,
2002 ("EntreMed 3-Amino Agreement"; the EntreMed Analog Agreement and the
EntreMed 3-Amino Agreement, collectively, the "EntreMed Analog Agreements"));
WHEREAS, in connection with the transactions contemplated by the Asset
Purchase Agreement, EntreMed, CMCC and Celgene desire to terminate the EntreMed
Analog Agreements, and for Celgene to enter into this Agreement, pursuant to
which
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CMCC shall directly grant Celgene an exclusive, worldwide license
under the Analog Patents;
WHEREAS this Agreement will supercede and replace in its entirety
the EntreMed Analog Agreements, which shall automatically terminate
without further action by any party upon execution hereof by Celgene
and CMCC; and
WHEREAS this Agreement is entered into pursuant to, and is a
condition precedent to, the closing of the transactions contemplated by
the Asset Purchase Agreement.
NOW, THEREFORE, in consideration of the mutual promises and other
good and valuable consideration, the parties agree as follows:
1. DEFINITIONS
-----------
1.1. "Affiliate" means and includes, as applied to any party, any corporation,
company, partnership, joint venture, individual or other entity that controls,
is controlled by or is under common control with such party, and "control" shall
mean the direct and indirect ownership of at least fifty percent (50%) or the
maximum percentage allowed by applicable law, whichever is less, of the
outstanding stock or voting rights entitled to elect directors.
1.2. "Amino Thalidomide" means the compound with the following chemical
structure:
[GRAPHIC OMITTED]
1.3. "Amino Thalidomide Product" means and includes any product that contains
Amino Thalidomide as an active ingredient.
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1.4. "Analog Field" means and includes any and all uses of any Thalidomide
Analog, alone or in combination, including without limitation (a) in humans and
animals, and (b) for any and all diagnostic, prophylactic, therapeutic, and
research and development uses.
1.5. "Analog Patents" means and includes:
(a) the United States and foreign patents and patent applications
listed in Appendix A;
(b) the United States and foreign patents issued from applications
listed in Appendix A;
(c) all United States and foreign divisional and continuations of the
patents and patent applications listed in Appendix A, and all
resulting United States and foreign patents;
(d) all United States continuation-in-part applications and equivalent
foreign applications, and all resulting patent(s), that are
directed to subject matter described in the United States and
foreign patents and patent applications listed in Appendix A;
(e) claims of all later-filed United States and foreign patent
applications, and of the resulting patents, that are directed to
subject matter described in the United States or foreign patents
or patent applications in this Section 1.5;
(f) all reissues, re-examinations, renewals and extensions of any
United States or foreign patents or patent applications described
in this Section 1.5.
1.6. "Confidential Information" means all materials, trade secrets or other
information, including, without limitation, proprietary information and
materials (whether or not patentable) regarding a party's technology, products,
business information or objectives, which is designated as confidential in
writing by the disclosing party, whether by letter or by the use of an
appropriate stamp or legend, prior to or at the time any such material, trade
secret or other information is disclosed by the disclosing party to the other
party. Notwithstanding the foregoing to the contrary (a) materials, trade
secrets or other information which is orally or visually disclosed by a party
shall constitute Confidential Information if the disclosing party indicated at
the time of such disclosure that such materials, trade secrets or other
information were confidential and, within ten (10) business days after such
disclosure, delivers to the other party a written document or documents
describing the materials, trade secrets or other information and referencing the
place and date of such oral or visual disclosure and the names of the persons to
whom such disclosure was made, and (b) materials, trade secrets or other
information which is disclosed in writing without an appropriate letter, stamp
or legend shall constitute Confidential Information if the disclosing party,
within ten (10) days after such disclosure, delivers to the other party a
written document or documents describing the materials, trade secrets or other
information, referencing the place and date of such written disclosure and the
names of the persons to whom such disclosure was made.
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1.7. "Licensed Method" means and includes any method the practice of which, by
an unlicensed third party, would infringe any of the Analog Patents.
1.0. "Licensed Product" means and includes (a) any Amino Thalidomide Product;
(b) any Revimid Product; (c) any product, the making, using, offering for sale,
sale, or importation of which, by an unlicensed third party, would infringe any
of the Analog Patents; and (d) any product that is disclosed as a species or
encompassed by a genus described at column 7, line 1 through column 11, line 50
of U.S. Patent No. 5,712,291 which will not be unreasonably interpreted to
encompass products that are not genuine thalidomide analogues including, without
limitation, compounds currently referred to as SelCids(TM).
1.9. "Net Sales Revenue" means the gross amount received by the seller for sales
of a Licensed Product to third parties, less: (i) cost of freight, postage, and
freight insurance; (ii) sales taxes, value added taxes, excise taxes, and
customs duties; (iii) cost of export licenses and any taxes, fees or other
charges associated with the exportation or importation of such Licensed Product;
(iv) rebates accrued, incurred or paid to Federal and State Medicaid and
Medicare and any other price reductions required by a governmental agency; (v)
rejected shipments, returns, recalls and retroactive deductions; (vi) the amount
received for sales which become the subject of a subsequent temporary or partial
recall by a regulatory agency for safety or efficacy reasons outside the control
of the seller; and (vii) customary cash, quantity, and trade discounts,
provided, however, that a sale or transfer to an Affiliate or Sublicensee for a
sale by such Affiliate or Sublicensee shall not be considered a sale for the
purposes of this provision but the resale by such Affiliate or Sublicensee shall
be a sale for such purpose.
1.10. "Revimid" means the compound with the following chemical structure:
[GRAPHIC OMITTED]
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1.11. "Revimid Product" means and includes any product that contains Revimid as
an active ingredient.
1.12. "Sponsored Research" means research conducted at CMCC in the Analog Field
by, or under the direct supervision of, Dr. Robert D'Amato, the results of which
Dr. D'Amato and CMCC are legally able to option to Celgene in accordance with
Section 5 of this Agreement.
1.13. "Sponsored Research Invention" means and includes all inventions or
discoveries in the Analog Field that are conceived or reduced to practice,
actually or constructively, during and in the conduct of the Sponsored Research
and that are not inventions or discoveries disclosed in or claimed by any of the
Analog Patents.
1.14. "Sponsored Research Know-How" means and includes any and all technical
information discovered or learned in connection with the Sponsored Research that
is reasonably necessary or useful for practicing any Sponsored Research Patents,
including all, formulas, methods, plans, samples, data, processes,
specifications, characteristics, equipment, design, know-how, experience and
trade secrets.
1.15. "Sponsored Research Method" means and includes any method the practice of
which, by an unlicensed third party, would infringe any of the Sponsored
Research Patents, expressly excluding any and all Licensed Methods.
1.16. "Sponsored Research Patent" means and includes and, and all patents and
patent applications, worldwide, that describe or claim any Sponsored Research
Invention.
1.17. "Sponsored Research Product" means and includes any product the
making, using, offering for sale, saie, or importation of which, by an
unlicensed third party, would infringe any of the Sponsored Research Patents,
expressly excluding any and all Licensed Products.
1.18. "Sublicensee" means any corporation, partnership, business organization,
or other third party entity or individual that is not controlled directly or
indirectly by Celgene and to whom Celgene sublicenses any of the rights granted
to Celgene hereunder.
1.19. "Thalidomide" means the chemical described as 2-(2,6-
Dioxo-3-piperidinyl)-lH- isoindole-1,3(2H)-dione (or as otherwise defined in the
Merck Index, entry 9390, 12th ed.), and pharmaceutically acceptable salts
thereof.
1.20. "Thalidomide Analog" means and includes any and all analogs, metabolites,
precursors, and hydrolysis products of Thalidomide, and all stereoisomers of
each of the foregoing, including without limitation (a) all such compounds
disclosed, generically or specifically, or claimed by any of the Analog Patents,
(b) Amino Thalidomide and all stereoisomers and metabolites thereof; and (c)
Revimid, and all stereoisomers and
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metabolites thereof.
2. GRANTS, RELEASES AND COVENANTS NOT TO SUE
-----------------------------------------
2.1 Grant of License. CMCC hereby grants to Celgene a world-wide, exclusive
royalty-bearing license, with the right to sublicense, subject to the
provisions of Section 2.2 and 2.3 under CMCCs entire right, title and interest
in and to the Analog Patents, to make, use, offer for sale, sell, import,
practice, and otherwise dispose of any and all Licensed Products and Licensed
Methods in the Analog Field. CMCC shall retain a royalty-free, non-exclusive,
irrevocable license to practice Licensed Products and Licensed Methods under the
Analog Patents for internal, non-commercial research purposes only.
2.2 Rights and Obligations Related to Government Funding.
2.2.1 Reservation of Rights. The rights granted to Celgene pursuant to
Section 2.1 shall be subject to any reserved rights of the United States
government pursuant to 35 U.S.C. Section 200 et seq.
2.2.2 Election of Title. In accordance with 35 U.S.C. Section 202, and all
rules, laws and regulations promulgated in connection therewith, CMCC shall
duly (a) disclose to the relevant Federal agency (as defined in 35 U.S.C.
Section 201) all subject inventions (as defined in 35 U.S.C. Section 201)
within the Analog Patents, including any arising after the Effective Date
hereof, and (b) elect to retain title therein.
2.3. Notwithstanding the license granted in Section 2.1, CMCC shall have the
right to grant a research license to the Analog Patents, including Licensed
Methods and Licensed Products other than Revimid or a Revimid Product, to
non-profit, non-commercial institutions for internal, non-commercial research
purposes only, subject to Celgene's prior written consent, which shall not be
unreasonably withheld. CMCC shall provide Celgene with a copy of each agreement
related to any such license a reasonable time prior to its execution, but no
less than twenty (20) business days, in order to allow Celgene to review and
comment on same, and CMCC agrees to consider any such comments in good faith.
Subject only to this Section 2.3 and Section 2.2.1 herein, CMCC hereby agrees
that it shall not grant any other licenses, to make, have made, use, lease
and/or sell Licensed Products or to utilize Licensed Methods during the period
of time in which this Agreement is in effect.
2.4. Transfer of Materials. As soon as reasonably possible following the
Effective Date, but in no event later than forty-five (45) days after such date,
CMCC and EntreMed shall provide to Celgene originals or copies of all records,
data and documentation relating to the Analog Patents, including without
limitation true and complete copies of the prosecution files for all of the
Analog Patents, expressly excluding any documents relating to either of
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the litigations that would be immune from discovery under the attorney-client
privilege or a work product immunity.
2.5. Settlement of the Litigations. Each of the Celgene, EntreMed and CMCC (the
"Releasing Party"), on behalf of itself and its present and former officers,
directors, employees, investors, shareholders, administrators, predecessor and
successor corporations, Affiliates, agents, and assigns, hereby fully and
forever releases, acquits and discharges each of the other Parties and its
officers, directors, employees, investors, shareholders, administrators,
predecessor and successor corporations, Affiliates, agents, independent
contractors, vendors, vendees, customers, attorneys, all other persons acting
for or on behalf of any or all of them, and the predecessors, successors, and
assigns of each, of and from any claim, duty, obligation or cause of action
relating to any matters of any kind, whether presently known or unknown,
suspected or unsuspected, that the Releasing Party may have resulting from, or
connected in any way with, the matters and things set forth and alleged, or
which might have been set forth or alleged, in either of the Litigations. The
foregoing releases do not extend to any claim or cause of action arising out of
this Agreement. Without limiting the foregoing, it is understood that Celgene
and EntreMed have entered into a separate Settlement and Mutual Release
Agreement.
2.6. Covenant Not to Sue. EntreMed and CMCC each covenants and agrees, on behelf
of itself and its present and former officers, directors, employees, investors,
shareholders, administrators, predecessor and successor corporations,
Affiliates, agents, and assigns, that it shall not assert, not assist in the
assertion, of any claims, counterclaims, defenses or demands against Celgene,
and its present and former officers, directors, employees, investors,
shareholders, administrators, predecessor and successor corporations,
Affiliates, agenets, independent contractors, vendors, vendees, customers,
attorneys, all other persons acting for or on behalf of any or all of them, and
the predecessors, successors, and assigns of each, for, on, or by reason of (a)
any fact or circumstance alleged or involved in, or which gave rise to, any
claim, counterclaim or defense asserted or that could have been asserted in
either of the Litigations, and whether or not based in whole or in part on any
fact or circumstance occurring on or after the date of execution of this
Agreement, or (b) the making, using, offering for sale, sale or importation of
any Licensed Product or Licensed Method. The foregoing covenant not to sue does
not extend to or include any action by EntreMed or CMCC relating to enforcement
of this Agreement. Without limiting the foregoing, it is understood that Celgene
and EntreMed have entered into a separate Settlement and Mutual Release
Agreement.
3. DILIGENCE
---------
3.1. Diligence by Celgene. Celgene shall use reasonable efforts, either directly
or through any Sublicensee(s), to initiate and continue clinical development
relating to one Licensed Product including either an Amino Thalidomide Product
or Revimid Product, and
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to publish the results thereof, consistent with contemporaneous reasonable
scientific and business practices and judgments in the pharmaceutical industry
and to secure regulatory approval and to make at least one Licensed Product
available to the public.
3.2. Celgene's Discretion. CMCC agrees that (i) the decision regarding which
Licensed Product to pursue regulatory approval of, and/or to fund and conduct
clinical trials of, shall be made by and in the sole discretion of Celgene; and
(ii) with respect to the manner in which any regulatory approval is sought
and/or clinical trials are funded and conducted, Celgene shall have sole
discretion, including, without limitation, complete control over any regulatory
submissions for such Licensed Product to the appropriate regulatory agencies
worldwide, including whether, when, and how to file, maintain, withdraw, or
abandon an application for regulatory approval of same. In the event that
Celgene determines, in the exercise of reasonable business judgment and
consistent with then-prevailing scientific standards in the pharmaceutical
industry, that the continued development of, and pursuit of regulatory approval
for, Celgene's Licensed Product is not warranted or advisable, Celgene may, in
its sole discretion, discontinue same, and Celgene's diligence obligations
hereunder shall be deemed to be satisfied with respect to that Licensed Product.
3.3. Discontinuation of Development. In the event that Celgene fails to develop
at least one Licensed Product pursuant to Section 3.1, then Celgene agrees to
negotiate in good faith with CMCC to sublicense under commercially reasonable
terms a Licensed Product to a third party.
3.4. CMCC's Right to Terminate for Lack of Due Diligence. Celgene acknowledges
that the primary objective of CMCC with respect to the licenses granted hereby
is to promote the development and marketing of Licensed Methods and Licensed
Products for the public good. To this end, CMCC shall have the right to
terminate this Agreement pursuant to Section 6.3 if Celgene fails to exercise
reasonable diligence under Section 3.1 or 3.3.
4. PAYMENTS
--------
4.1. Payments to CMCC. In consideration for the termination of the EntreMed
Analog Agreements and the rights and licenses granted herein, Celgene shall
make the following payments to CMCC:
4.1.1. Lump Sum Payment. On the Effective Date of this Agreement, a
one-time, lump sum, up-front payment of two and one- half million
United States dollars ($2,500,000.00); and
4.1.2. Sponsored Research Funding. On the Effective Date, and on each
of the immediately succeeding four anniversaries of such
Effective Date, a non-terminable lump-sum payment of
three-hundred thousand
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United States Dollars ($300,000.00) to be used solely and
exclusively to fund CMCC Sponsored Research. The parties agree
that they will separately enter into and conclude by January 31,
2003, a sponsored research agreement with the terms pertinent to
the Sponsored Research Funding provided for in this Agreement. In
the event that Dr. D'Amato ceases to conduct Sponsored Research,
or ceases to be employed by or otherwise affiliated with CMCC,
then CMCC shall promptly notify Celgene, and propose a new
principal investigator. Celgene may, in its sole discretion,
agree to continue the Sponsored Research Funding with the new
principal investigator or reject this investigator and Celgene's
payment obligations under this Section 4.1.2 shall immediately
terminate, effective as of the date of such cessation. In the
event that Dr. D'Amato ceases to conduct Sponsored Research at
CMCC but continues such research at another academic institution
then the remainder of such sponsored research funding will
transfer to the new institution.
4.2. Lump-Sum Payment to EntreMed. In consideration for the termination of the
EntreMed Analog Agreements, and the settlement of the Litigations, Celgene shall
pay to EntreMed, on the Effective Date of this Agreement, consideration as
provided for in the Asset Purchase Agreement.
4.3. Running Royalties.
-----------------
4.3.1. On An Amino Thalidomide Product. In further consideration for the
rights and license granted herein with respect to Amino
Thalidomide, Celgene shall pay to CMCC, until the later of the
termination of this Agreement or March 1,2013 plus the number of
days equivalent to any patent term extension granted to Celgene
for an Amino Thalidomide Product under 35 U.S.C. Section 156 with
respect to March 1, 2013 only, a royalty equal to two and
one-half percent (2.5%) of the Net Sales Revenue received by
Celgene for sales of an Amino Thalidomide Product.
4.3.2. On A Revimid Product. In further consideration for the rights and
license granted herein with respect to Revimid, Celgene shall pay
to CMCC, until the later of the termination of this Agreement or
March 1,2013 plus the number of days equivalent to any patent
term extension granted to Celgene for a Revimid Product under 35
U.S.C. Section 156 with respect to March 1,2013 only, a royalty
equal to one percent (1.0%) of the Net Sales Revenue received by
Celgene for sales of a Revimid Product.
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4.3.3. On A Licensed Product. In further consideration for the rights
and license granted herein with respect to Licensed Products
other than an Amino Thalidomide Product or a Revimid Product,
Celgene shall pay to CMCC, a royalty equal to one percent (1.0%)
of the Net Sales Revenue received by Celgene for sales of a
Licensed Product other than an Amino Thalidomide Product or a
Revimid Product. Celgene shall be obligated to pay such royalties
under 4.3.3 beginning on the Effective Date and continuing until
the latest of: (i) the termination or expiration of this
Agreement; (ii) March 1,2013; or (iii) if such Licensed Product
is disclosed as a species or encompassed by genus in U.S.
provisional application no. 60/310,261, filed August 6, 200l or
U.S. patent application no. 10/213,194, filed August 6, 2002
until August 6, 2021. It is expressly understood and agreed that
Celgene shall not owe CMCC any royalties for an Amino Thalidomide
Product or a Revimid Product other than that recited in Section
4.3.1 and 4.3.2, respectively.
4.3.4. Pre-Approval Royalties. Notwithstanding Sections 4.3.1,4.3.2, and
4.3.3 above, Celgene shall not be obligated to pay any royalty on
Net Sales Revenues on sales of Licensed Products of under two
hundred and fifty thousand U.S. dollars ($250,000.00) prior to
receiving all necessary approvals to market any such product.
4.4. Sublicensee Revenue. If Celgene grants a sublicense ofits exclusive rights
under this Agreement with respect to a Licensed Product other than a Revimid
Product, Celgene shall pay to CMCC ten percent (l0%) of (a) any non-royalty
consideration, including but not limited to any sublicensing and/or milestone
payments, received by Celgene from such Sublicensee in exchange for the
sublicense of Celgene's rights to such Licensed Product other than a Revimid
Product hereunder, respectively, and (b) any royalty income paid by such
Sublicensee to Celgene on Net Sales Revenue received by such Sublicensee for the
sale of such Licensed Product other than a Revimid Product, respectively,
including, without limitation, ten percent (10%) of any lump-sum
commercialization milestone payments due to Celgene upon the occurrence of
certain threshold levels of sales by such Sublicensee. It is understood that
CMCC will not receive less than a royalty equal to (a) two and one-half percent
(2.5%) of the Net Sales Revenue received by a Sublicensee for sales of an Amino
Thalidomide Product, and (b) one percent (1%) of the Net Sales Revenue received
by a Sublicensee for sales of a Revimid Product or a Licensed Product, excluding
an Amino Thalidomide Product. It is further expressly understood that Celgene
shall not owe CMCC any non-royalty consideration, including but not limited to
any sublicensing and/or milestone payments received by Celgene from any
Sublicensee for a Revimid Product.
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4.5. Milestone Payments.
4.5.1 For a Revimid Product. In further consideration for the rights
and licensed granted herein with respect to a Revimid Product,
Celgene shall pay to CMCC, four and one-quarter million United
States dollars ($4,250,000.00) within thirty (30) days after the
first final approval by the United States Food and Drug
Administration of a New Drug Application (NDA) filed by Celgene
to market a Revimid Product.
4.5.2. For an Amino Thalidomide Product. In further consideration for
the rights and licensed granted herein with respect to an Amino
Thalidomide Product, Celgene shall pay to CMCC those payments
owed to CMCC by EntreMed as of the Effective Date under Sections
4.1.2,4.1.3 and 4.1.4 of the EntreMed 3-Amino Agreement as
follows:
(a) $150,000 (one hundred and fifty thousand US. dollars) on
May 17, 2003;
(b) $525,000 (five hundred and twenty-five thousand U.S. dollars)
due upon initiation of the first Phase III clinical trial for
any indication for an Amino Thalidomide Product; and
(c) $750,000 (seven hundred and fifty thousand U.S. dollars) due
upon submission of an NDA (New Drug Application) for any
indication for an pino Thalidomide Product.
4.5.3. On A Licensed Product. In further consideration for the rights
and license granted herein with respect to Licensed Products
other than an Amino Thalidomide Product or a Revimid Product,
Celgene shall pay to CMCC the following payments:
(a) $500,000 (five hundred thousand U.S. dollars) on January 1,
2004;
(b) $l,000,000 (one million U.S. dollars) on January 1, 2005;
(c) $1,000,000 (one million U.S. dollars) on January 1, 2006; and
(d) $3,000,000 (three million US. dollars) within thirty (30)
days after the first final approval by the United States Food
& Drug Administration of a New Drug Application (NDA) filed
by Celgene to market a Licensed Product other than a
Revimid Product or an Amino Thalidomide Product. The payments
due under Sections 4.5.3(a), (b)
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and (c) shall be payable at the time specified above
irrespective of any termination of this Agreement.
4.6. No Further Consideration. It is expressly acknowledged and agreed by the
parties that, except as expressly set forth in this Section 4, Celgene shall
have no obligation to pay to either EntreMed or CMCC any additional
consideration in exchange for the settlement of the Litigations, the termination
of the EntreMed Analog Agreements, or the rights and licenses granted to Celgene
hereunder, and that no other consideration, including without limitation any
royalty payments, shall be due to either EntreMed or CMCC for the making, using,
offering for sale, sale, importation, practice or other disposition, by or on
behalf of Celgene or any sublicensee thereof, of any Licensed Product or
Licensed Method.
4.7. Records. Celgene shall keep full, true and accurate books of account
containing all particulars that may be necessary for the purpose of showing the
amounts payable to CMCC hereunder. Said books of account shall be kept at
Celgene's principal place of business or the principal place of business of the
appropriate division of Celgene to which this Agreement relates. Said books and
the supporting data shall be retained for five (5) years following the end of
the calendar year to which they pertain, and, upon reasonable advance written
notice to Celgene, open to the inspection of CMCC or its agents for the sole
purpose of verifying Celgene's royalty statement or compliance in other respects
with this Agreement and not prior to the first sale of a Licensed Product. CMCC
can request auditing of said books and supporting data no more than once each
calendar year. Any such audit shall be conducted at CMCC's sole expense and
during the normal business hours of Celgene by an independent certified public
accountant selected by CMCC that is reasonably acceptable to Celgene.
4.8. Reports. Celgene, within forty-five (45) days after March 31, June 30,
September 30 and December 31, of each year, shall deliver to CMCC true and
accurate reports, giving such particulars of the business conducted by Celgene
and its Sublicensees during the preceding three-month period under this
Agreement as shall be pertinent to a royalty accounting hereunder. These shall
include at least the following:
4.8.1. Quantity of Licensed Products sold.
4.8.2. Total billings for Licensed Products sold.
4.8.3. Accounting for all Licensed Products sold.
4.8.4. Deductions applicable as provided in Section 1.9.
4.8.5. Total royalties due.
4.8.6. Names and addresses of all Sublicensees of Celgene.
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4.9. With each such report submitted, Celgene shall pay to CMCC the royalties
due and payable under this Agreement. If no royalties shall be due, Celgene
shall so report. On or before the ninetieth (90th) day following the close of
Celgene's fiscal year, Celgene shall provide CMCC with Celgene's certified
financial statements for the preceding fiscal-year including at a minimum, a
Balance Sheet and an Operating Statement.
4.10. The royalty payments set forth in this Agreement shall, if overdue, bear
interest until payment at a per annum rate of two percent (2%) above the prime
rate in effect at the Fleet Bank of Boston on the due date. The payment of such
interest shall not foreclose CMCC from exercising any other rights it may have
as a consequence of the lateness of any payment.
5. OPTION TO SPONSORED RESEARCH INVENTIONS
---------------------------------------
5.1. Notice of Sponsored Research Inventions. CMCC shall notify Celgene in
writing of each Sponsored Research Invention within thirty (30) days after CMCC
becomes aware of same, and such notice shall describe each Sponsored Research
Invention in detail sufficient to permit evaluation by Celgene.
5.2. Grant of Exclusive Option. CMCC hereby grants Celgene an exclusive option
("Option") to enter into a License Agreement granting Celgene and its Affiliates
(a) an exclusive, worldwide, royalty-bearing license, with the right to
sublicense, under any Sponsored Research Patents, and (b) a non-exclusive,
worldwide license, with the right to sublicense, under any Sponsored Research
Know-How, in each case to make, use, offer for sale, sell, import, practice and
otherwise dispose of any and all products and methods in the Analog Field. The
term of the Option granted to Celgene hereunder shall begin on the Effective
Date hereof and terminate, on a Sponsored Research Invention-by-Sponsored
Research Invention basis, nine (9) months after receipt by Celgene of the notice
set forth in Section 5.1 of this Agreement ("Option Period").
5.3. Exercise of Option by Celgene. Celgene may exercise its Option with respect
to any Sponsored Research Invention, and the related Sponsored Research Patents
and Sponsored Research Know-How, at any time during the relevant Option Period
by providing written notice to CMCC stating that it is exercising such Option.
With respect to any particular Sponsored Research Invention, if Celgene
expressly rejects its Option or the Option Period lapses without any such
written notice from Celgene, then CMCC shall have no further obligation to
Celgene with respect to such Sponsored Research Invention, it being understood
and agreed that Celgene's rights and Option with respect to each other Sponsored
Research Invention, and the related intellectual property, shall continue in
full force and effect.
14
<PAGE>
5.4. Negotiation of Agreement. Upon the first exercise by Celgene of any Option
set forth in Section 5.2 hereof, CMCC and Celgene agree to negotiate in good
faith for up to ninety (90) days, or any mutually agreed-upon extension thereof
("Negotiation Period"), for the financial and other material terms of the a
license agreement, which shall be in accordance with Section 5.5 of this
Agreement ("License Agreement"). CMCC agrees that it will not, during any Option
Period and the Negotiation Period, solicit, offer, negotiate or enter into with
any third party any agreement, contract or understanding that would be
inconsistent with the grant of the Options to Celgene hereunder. If the parties
are unable to negotiate and execute a mutually acceptable License Agreement
within the Negotiation Period, CMCC shall have no further obligation to Celgene
with respect to the Sponsored Research Invention that was the subject of such
first-exercised Option, and the terms and conditions of this Section 5.4 shall
apply to each subsequently exercised Option until a License Agreement is
executed.
5.5. Consideration for License Agreement. In addition to the licenses set forth
in Section 5.2 of this Agreement, and in consideration of the rights and
licenses granted to Celgene under the License Agreement pursuant to Section 5.4,
Celgene shall pay, on a worldwide, annual basis, a commercially reasonable
royalty on Net Sales Revenues (as defined herein, mutatis mutandis) received
for the sale of Sponsored Research Products or Sponsored Research Methods which
royalty rate shall be negotiated in good faith.
6. TERM AND TERMINATION
--------------------
6.1. Term. Unless otherwise terminated by operation of law or by acts of Celgene
or CMCC in accordance with the terms of this Agreement, this Agreement shall
terminate upon expiration of all payment obligations under Article 4, whereupon
Celgene shall have a royalty-free license to practice the Analog Patents, and to
make, use, offer for sale, sell and import Licensed Products.
6.2. Termination By Celgene. With the exception of the Sponsored Research
Funding of Section 4.1.2, which is non-terminable, this Agreement and all of
Celgene's rights and obligations hereunder shall be terminable by Celgene, if
Celgene or its Affiliates or Sublicensee(s) ceases to develop at least one
Licensed Product, including either an Amino Thalidomide Product or a Revimid
Product, upon ninety (90) days written notice to CMCC, and upon payment of all
accounts due CMCC through the effective date of termination. In such event, the
provisions of Section 3 shall apply.
6.3. Termination Bv CMCC.
-------------------
6.3.1. Non-payment of milestone payments or royalties. Should Celgene fail
to pay CMCC milestone payments or royalties due and payable hereunder with
respect to a Licensed Product, CMCC shall have the right to terminate this
Agreement on ninety
15
<PAGE>
(90) days notice with respect to such Licensed Product, unless Celgene
shall pay CMCC within the ninety (90) day period, all such royalties and
interest due and payable on such Licensed Product. Upon the expiration of
the ninety (90) day period, if Celgene shall not have paid all such
royalties and interest due and payable for such Licensed Product, the
rights, privileges and license granted hereunder with respect to such
Licensed Product only shall terminate.
6.3.2. Termination for Lack of Due Diligence. CMCC shall have the right to
terminate this Agreement if Celgene or its Affiliates or Sublicensee(s)
fails to meet its diligence under Article 3 with respect to at least one
Licensed Product. CMCC shall notify Celgene thereof in writing, and
Celgene shall have ninety days (90) days following such notification to
establish to the reasonable satisfaction of CMCC that (i) Celgene, or its
Affiliates or Sublicensee(s), has met such objective or (ii) a revised due
diligence plan is necessary and appropriate. In the event Celgene fails to
establish the same to CMCC's reasonable satisfaction within the appropriate
time, CMCC shall have the right to terminate in whole or in part the
license granted to Celgene under this Agreement.
6.4. Accrued Obligations. Any termination of this Agreement for any reason does
not relieve either party of any obligation or liability accrued prior to the
termination or rescind anything done by either party and the termination does
not affect in any manner any rights of either party arising under this Agreement
prior to the termination.
6.5. Non-Termination of Sublicensee Agreement. CMCC agrees that if Celgene has
provided to CMCC notice that Celgene has granted a sublicense to a Sublicensee
under this Agreement, then in the event CMCC terminates this Agreement for any
reason, CMCC shall provide to such Sublicensee not less than thirty (30) days
prior to the effective date of said termination, written notice of said
termination at the address specified by Celgene to CMCC in Celgene's notice to
CNCC under Section 11.1. CMCC agrees that upon the Sublicensee's notice as
described below and provided the Sublicensee is not in breach of its sublicense,
CMCC shall grant to such Sublicensee license rights and terms equivalent to the
sublicense rights and terms which the sublicense shall have granted to said
Sublicensee; provided that the Sublicensee shall remain a Sublicensee under this
Agreement for a period of at least sixty (60) days following receipt of notice
from CMCC. Sublicensees shall during said sixty (60) day period provide to CMCC
notice wherein the Sublicensee: (i) reaffirms the terms and condition of this
Agreement as it relates to the rights the Sublicensee has been granted under the
sublicense; (ii) agrees to abide by all of the terms and conditions of this
Agreement applicable to Sublicensees and to discharge directly all pertinent
obligations of Celgene which Celgene is obligated hereunder to discharge; and
(iii) acknowledges that CMCC shall have no obligations to the Sublicensee other
that its obligations set forth in this Agreement with regard to Celgene.
16
<PAGE>
6.6. Survival. The terms and conditions of Sections 1,2.5,2.6,6.4,6.5, 10, 11
and 13 through 16, inclusive, shall survive termination or expiration of this
Agreement for as long as necessary to permit their full discharge.
7. WARRANTIES AND DISCLAIMERS
--------------------------
7.1. By CMCC. CMCC represents and warrants to Celgene that (a) to the best of
its knowledge and with the exception of certain applications which are co-owned
with EntreMed, CMCC owns the entire right, title and interest in and to the
Analog Patents, (b) CMCC has the lawful right to enter into the Agreement and to
grant the licenses hereunder without the consent or approval of another person
or entity; (c) the patents and application set forth on Appendix A hereto
constitute all of the Analog Patents in which CMCC has an interest on the
Effective Date hereof; and (d) other than the named co-inventors on certain of
the applications co-owned with EntreMed, CMCC is not aware of any person other
than Dr. Robert D'Amato who CMCC believes is, or should be named as, an
inventor of any of the Analog Patents.
7.2. By Celgene. Celgene warrants to CMCC that it has the lawful right and
authority to enter into this Agreement without the consent or approval of
another person or entity.
7.3. Limitation on Damages. IN NO EVENT WILL EITHER PARTY BE LIABLE FOR ANY
INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES RESULTING FROM EXERCISE OF THIS
LICENSE OR THE USE OF LICENSED PRODUCTS OR LICENSED METHODS.
17
<PAGE>
8. PATENT PROSECUTION
------------------
8.1. By Celgene. Celgene shall have the sole right, but not the obligation, to
apply for, prosecute, maintain, renew, extend, abandon, disclaim in whole or in
part, or otherwise dispose of, including without limitation the right to
prosecute, defend, settle, resolve or otherwise dispose of any interference with
any third party's patent rights, including without limitation any patent rights
of Celgene, whether before the United States Patent and Trademark Office ("PTO")
or any United States court (all of the foregoing, to "Prosecute") any and all
Analog Patents, using counsel selected by Celgene. All reasonable costs and
expenses of the Prosecution of the Analog Patents (including all governmental
filing fees)' shall be paid by Celgene. Celgene shall provide CMCC with copies
of all substantive documents received from, or filed with, the PTO and all
analogous foreign patent offices in connection with the Prosecution of the
Analog Patents.
8.2. Cooperation by CMCC and EntreMed. CMCC and EntreMed shall render reasonable
assistance to Celgene in the Prosecution of the Analog Patents in such countries
whenever requested to do so upon reasonable notice, including without limitation
to cooperate, and to require each past or present employee, consultant,
representative, contractor, agent or other individual under the custody or
control of CMCC or EntreMed (including without limitation any such individual
that is, or is identified as, an inventor of any of the Analog Patents) to
cooperate, with Celgene, its attorneys, agents, successors and assigns, to
Prosecute, assert, enforce and defend, and to otherwise protect any and all of
the Analog Patents and Celgene's rights therein, including, without limitation,
to (a) execute such documents, sign all lawful papers, and make all rightful
oaths as Celgene deems reasonably necessary or appropriate in connection with
same; (b) communicate any facts known or reasonably available respecting any of
the Analog Patents; and (c) provide all documents, samples and other tangible
materials necessary or useful testimony to Prosecute, assert, enforce and/or
defend any of the Analog Patents. Celgene shall reimburse EntreMed and CMCC for
all reasonable costs and expenses incurred in connection with rendering such
assistance.
9. PATENT INFRINGEMENT
-------------------
9.1. Notice. In the event that either Celgene or CMCC becomes aware of any
potential infringement of any of the Analog Patents, such party shall notify the
other party(ies) of the potential infringement in writing and provide a summary
of the relevant facts and circumstances known to such party relating to such
infringement. CMCC shall not notify a third person of the potential infringement
of any of the Analog Patents without first obtaining the express written consent
of Celgene.
9.2. By Celgene. CMCC hereby grants to Celgene all rights to sue and recover
damages or obtain injunctive relief for past and future infringement,
misappropriation, violation or
18
<PAGE>
breach of any of the Analog Patents. Celgene shall have the sole right, but
shall not be obligated, to prosecute, at its own expense, any infringements of
the Analog Patents, to defend the Analog Patents and to recover, for its own
account, any damages, awards or settlements resulting therefrom. If Celgene
recovers any damages, the damages shall first be used to reimburse Celgene for
the prosecution or defense of such action, then to reimburse CMCC for any loss
of royalties payable hereunder, and the remaining damages shall be for Celgene's
own account. CMCC agrees that Celgene may join it as a party plaintiff in any
such suit, without expense to CMCC. Celgene shall have sole control of any such
suit and all negotiations for its settlement or compromise, and shall have the
sole right to sublicense any alleged infringer for future use of the Analog
Patents.
9.3. Joinder of CMCC. In the event that any action, suit or proceeding is
brought against, or written notice or threat thereof is provided to, Celgene
alleging infringement of any patent or unauthorized use or misappropriation of
technology arising out of or in connection with Celgene's practice of Analog
Patents, Celgene shall have the right to defend at its own expense such action,
suit or proceeding and, in furtherance of such rights, CMCC hereby agrees that
Celgene may join it as a party in such suit, without expense to CMCC. Celgene
shall hold harmless and indemnify CMCC from and against any order for costs
arising without fault of CMCC that may be made against CMCC in such proceedings,
unless such order arises out of or relates to facts and circumstances involving
a breach of any representations or warranty by any one or more of CMCC.
9.4. Cooperation of CMCC and EntreMed. In the event that Celgene shall undertake
the enforcement and/or defense of the Analog Patents by legal or patent office
proceedings pursuant to this Agreement, CMCC and EntreMed shall, at the request
and expense of Celgene, cooperate in all reasonable respects and, to the extent
possible, have its employees testify when requested and make available relevant
records, papers, information, samples and the like.
19
<PAGE>
10. UNIFORM INDEMNIFICATION AND INSURANCE PROVISIONS
------------------------------------------------
10.1. Celgene shall indemnify, defend and hold harmless CMCC, its corporate
affiliates, current or future directors, trustees, officers, faculty, medical
and professional staff, employees, students and agents and their respective
successors, heirs and assigns (the "Indemnitees"), against any claim, liability,
cost, damage, deficiency, loss, expense & obligation of any kind or nature
(including without limitation reasonable attorneys' fees and other costs and
expenses of litigation) incurred by or imposed upon the Indemnitees or any one
of them in connection with any claims, suits, actions, demands or judgments
arising out of any theory of product liability (including, but not limited to,
actions in the form of tort, warranty, or strict liability) concerning any
product, process or service made, used or sold pursuant to any right or license
granted under this Agreement.
10.2. Celgene agrees, at its own expense, to assume the defense of any actions
brought or filed against any Indemnitee with respect to the subject of indemnity
contained herein, whether or not such actions are rightfully brought, using
counsel reasonably acceptable to CMCC, and Celgene shall have the exclusive
right to control any such defense and to settle any such action.
10.3. Each Indemnitee intending to claim indemnification under this Article 10
shall promptly notify Celgene of any loss, claim, damage, liability or action in
respect of such claim. The failure to deliver notice to Celgene within a
reasonable time after commencement of any such loss, claim, damage, liability or
action shall relieve Celgene of any liability to any Indemnitee under this
Article 10 to the extent that such failure prejudices Celgene's ability to
defend same, but the omission to so deliver notice to Celgene will not relieve
it of any liability that it may otherwise have to any Indemnitee under this
Article 10.
10.4. Each Indemnitee shall cooperate fully with Celgene and its legal
representatives in the investigation and defense of any loss, claim, damage,
liability or action covered by the indemnification provisions of this Article
10.
10.5. Beginning at the time as any such product, process or service is being
commercially distributed or sold (other than for the purpose of obtaining
regulatory approvals) by Celgene or by a sublicensee, Affiliate or agent of
Celgene, Celgene shall, at its sole cost and expense, procure and maintain
commercial general liability insurance in amounts not less than $2,000,000 per
incident and $2,000,000 annual aggregate and naming the Indemnitees as
additional insureds. Such commercial general liability insurance shall provide
(i) product liability coverage and (ii) contractual liability coverage for
Celgene's indemnification under Article 10, Sections 10.1 through 10.3 of this
Agreement. If Celgene elects to self-insure all or part of the limits described
above (including deductibles or retentions which are in excess of $250,000
annual aggregate), such self-insurance program must be acceptable to CMCC and
the Risk Management Foundation of the Harvard Medical Institutions, Inc. The
20
<PAGE>
minimum amount of insurance coverage required under this Article 10, Section
10.3, shall not be construed to create a limit of Celgene's liability with
respect to its indemnification under Article 10, Paragraphs 10.1 through 10.3 of
this Agreement.
10.6. Celgene shall provide CMCC with written evidence of such insurance upon
request of CMCC. Celgene shall provide CMCC with written notice at least fifteen
(15) days prior to the cancellation, non-renewal or material change in such
insurance. Notwithstanding any other term of this Agreement, if Celgene does not
obtain replacement insurance providing comparable coverage within such fifteen
(15) day period, CMCC shall have the right to terminate this Agreement effective
at the end of such fifteen (15) day period without notice of any additional
waiting periods.
10.7. Celgene shall maintain such commercial general liability insurance during
(i) the period that any such product, process or service is being commercially
distributed or sold (other than for the purpose of obtaining regulatory
approvals) by Celgene or by a sublicensee, Affiliate or agent of Celgene and
(ii) a reasonable period after the period referred to above, which in no event
shall be less than fifteen (15) years.
10.8. The provisions of this Article 10 shall survive expiration or termination
of this Agreement.
10.9. CMCC MAKES NO WARRANTY, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION,
ANY EXPRESS OR IMPLIED WARRANTY OF MERCHANTABILITY OR ANY EXPRESS OR IMPLIED
WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE, OR WARRANTY OF NON-INFRINGEMENT,
WITH RESPECT TO ANY MATTER WITHIN THE SCOPE OF THIS AGREEMENT, INCLUDING WITHOUT
LIMITATION ANY WARRANTY WITH RESPECT TO THE PATENT RIGHTS, LICENSED PRODUCTS, OR
ANY PATENT, TRADEMARK, SOFTWARE, TRADE SECRET, TANGIBLE RESEARCH PROPERTY;
INFORMATION OR DATA LICENSED OR OTHERWISE PROVIDED TO CELGENE HEREUNDER, AND
HEREBY DISCLAIMS THE SAME.
21
<PAGE>
11. NOTICES
-------
11.1. Any notice or payment required to be given to either party will the deemed
to have been properly given and to be effective (a) on the date of delivery if
delivered in person, by telefax, or overnight courier, or (b) five (5) days
after mailing if mailed by first-class certified mail, postage paid, to the
respective addresses given below, or to another address as it shall designate by
written notice given to the other party.
22
<PAGE>
In the case of Celgene: In the case of CMCC:
Celgene Corporation Children's Hospital
Attn: Chief Financial Officer Chief Intellectual Property Officer
7 Powder Horn Drive 300 Longwood Avenue
Warren, NJ 07059 Boston, MA 02115
Fax: (732) 805-3931 Fax: (617) 232-7485
With a copy to: Children's Medical Center Corporation
Attn: General Counsel
Pennie & Edmonds LLP 300 Longwood Avenue
Attn: Anthony M. Insogna, Esq. Boston, MA 02115
1155 Avenue of the Americas Fax: (617) 739-5928
New York, NY 10036
Fax: (212) 869-9741 With a copy to:
Hale and Door LLP
Attn: Steven Singer, Esq.
60 State Street
Boston, MA 02109
Fax: (617) 526-5000
In the case of EntreMed:
EntreMed Corporation
Attn: President
9640 Medical Center Drive
Rockville, MD 20850
Fax: (301) 217-0132
With a copy to:
23
<PAGE>
12. ASSIGNMENT
----------
12.1. Subject to the restrictions set forth herein, this Agreement, and every
provision hereof, shall be binding upon and shall inure to the benefit of the
parties, their respective successors, successors-in-title, heirs and assignees,
and each and every successor-in-interest to any party, whether such successor
acquires such interest by way of gift, inheritance, purchase, foreclosure, or by
any other methods, shall hold such interest subject to all the terms and
provisions of this Agreement; provided however that Celgene shall not assign or
transfer the whole or any part of this Agreement or its rights hereunder without
the agreement of CMCC which agreement shall not be unreasonably withheld except
that Celgene may assign this Agreement in connection with the transfer or sale
of all or substantially all of its assets or business or its merger or
consolidation with another organization or other change'of control transaction
without CMCC's consent. EntreMed may not assign any of its rights or obligations
under this Agreement without the prior written consent of Celgene.
13. WAIVER
------
13.1. No waiver by either party of any breach or default of any of the covenants
or agreements set forth will be deemed a waiver of any subsequent or similar
breach or default.
14. GOVERNING LAWS
--------------
14.1. This Agreement shall be interpreted and construed in accordance with the
laws of the Commonwealth of Massachusetts without reference to choice of law
doctrine, but the scope and validity of any patent or patent application shall
be governed by the applicable laws of the country of such patent or patent
application. Each party hereby submits itself for the sole purpose of this
Agreement and any controversy arising hereunder to the jurisdiction of the state
and federal courts located in the Commonwealth of Massachusetts and any courts
of appeal therefrom, and waives any objection on the grounds of lack of
jurisdiction (venue or otherwise) to the exercise of such jurisdiction over it
by any such courts
15. CONFIDENTIALITY
---------------
15.1. Restrictions on Disclosure and Use. With regard to Confidential
Information, the receiving party agrees:
15.1.1. not to use the Confidential Information except for the sole
purpose of performing under the terms of this Agreement;
24
<PAGE>
15.1.2. to safeguard Confidential Information against disclosure to others
with the same degree of care as it exercises with its own
Confidential Information of a similar nature;
15.1.3. not to disclose Confidential Information to others (except to its
employees, agents or consultants who are bound by a like obligation
of confidentiality) without the express prior written permission of
the disclosing party,
except that the receiving party shall not be prevented from using or disclosing
any of the Confidential Information:
(a) which the receiving party can demonstrate by written records
was previously known to it; or
(b) which is now, or becomes in the future, public knowledge
other than through acts or omissions of the receiving party;
or
(c) which is lawfully obtained by the receiving party from
sources independent of the disclosing party; and
(d) which are required by law to be disclosed, only to the
extent so required.
15.2. Term and Scope of Obligation. For purposes of this Agreement, and subject
to the exclusions set forth in Section 15.1(a) through (d) hereof, all
information pertaining to the prosecution; enforcement or defense of the Analog
Patents shall be treated by all parties as the Confidential Information of the
other party. The secrecy obligations of the parties with respect to ConfidentLal
Information shall continue for a period ending five (5) years from the
termination or expiration of this Agreement.
15.3. Permitted Disclosures and Use. Notwithstanding Section 15.1, Celgene shall
have the right to disclose Confidential Information (i) as necessary in the
course of seeking or enforcing patent rights, or obtaining regulatory approval
to manufacture or market Licensed Products, Licensed Methods, or other products
or methods and (ii) as reasonably required in the course of any actual or
potential financing or sublicensing arrangement; provided, however, that any
disclosure under (ii) shall be pursuant to a confidentiality agreement between
Celgene and such third party which preserves the rights of CMCC hereunder.
15.4. Public Announcements. Any press release, public announcement or similar
publicity by the parties with respect to this Agreement shall be subject to the
prior consent of the other parties, which consent shall not be unreasonably
withheld, unless such communication is required to be made by law or pursuant to
the rules and regulations of the Securities and
25
<PAGE>
Exchange Commission or the New York Stock Exchange listing requirements or an
equivalent agency and after consultation and coordination among the parties.
16. MISCELLANEOUS
-------------
16.1. Headings. The headings of the several sections are inserted for
convenience of reference only and are not intended to be a part of or to affect
the meaning or interpretation of this Agreement.
16.2. Amendments. No amendment or modification of this Agreement is valid or
binding upon the parties unless made in writing and signed on behalf of each
party.
16.3. Entire Understanding. This Agreement, and any appendices hereto (each of
which is hereby incorporated herein in their entirety), embody the entire
understanding of the parties and supersedes all previous communications,
representations, or understandings, either oral or written, between the parties
relating to the Analog Patents, including without limitation the EntreMed Analog
Agreements, which are hereby terminated in their entirety.
16.4. Severability. In case any of the provisions contained in this Agreement
are held to be invalid, illegal or unenforceable in any respect, such
invalidity, illegality or unenforceability must not affect any other provisions,
but this Agreement must be construed as if such invalid or illegal or
unenforceable provisions had never been contained in this Agreement.
16.5. Counterparts. This Agreement may be signed in duplicate counterparts, each
of which shall be deemed an original, with the same effect as if the signatures
thereto and hereto were upon the same instrument.
[SIGNATURE PAGE FOLLOWS]
26
<PAGE>
IN WITNESS WHEREOF, Celgene, CMCC and EntreMed have executed this Agreement, by
their respective officers duly authorized, on the day and year written below.
CELGENE CORPORATION
By: /s/ Robert J. Hugin
------------------------------
Name: Robert J. Hugin
------------------------------
Title: SVP & CFO
------------------------------
Date: 12/31/02
------------------------------
CHILDREN'S MEDICAL CENTER CORPORATION
By: /s/ Stuart J. Novick
------------------------------
Name: Stuart J. Novick
------------------------------
Title: Sr. V.P. and General Counsel
------------------------------
Date: December 31, 2002
------------------------------
ENTREMED, INC.
(Solely for purposes of Sections 1, 2.4,2.5,2.6,4.2,4.5,8.2,9.4, 11, 12, 13, and
16)
By: /s/ Neil Campbell
------------------------------
Name: Neil Campbell
------------------------------
Title: President and COO
------------------------------
Date: December 31, 2002
------------------------------
<PAGE>
APPENDIX A
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------
TITLE COUNTRY STATUS PATENT NO. SERIAL NO. FILING DATE
--------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
Teratogenic Compounds as US Abandoned 08/025,046 3/1/1993
Angiogenesis Inhibitors
(Thalidomide)
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Issued 5,629,327 08/168,817 12/15/1993
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Australia Issued 676,722 62486/94 2/24/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Canada Pending 2,157,288 2/24/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Canada Pending 2,342,974 2/24/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for EPO Pending 94 909773.7 2/24/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for PCT Nat'l Phase PCT/US94/01971 2/24/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Chile Issued 40,533 289-94 2/28/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Argentina Abandoned 327,541 3/1/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Brazil Abandoned PI9400764 3/1/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Colombia Abandoned 94008093 3/1/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Mexico Published 94 01547 3/1/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
</TABLE>
1
<PAGE>
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------
TITLE COUNTRY STATUS PATENT NO. SERIAL NO. FILING DATE
--------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
Methods and Compositions for Peru Pending 237,564 3/1/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Venezuela Pending 0296-94 3/4/1994
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Issued 5,593,990 08/371,987 1/13/1995
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Issued 5,712,291 08/468,792 6/6/1995
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Japan Pending 520046/94 9/1/1995
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for South Korea Pending 703700/1995 9/1/1995
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for New Zealand Issued 262676 262676 9/22/1995
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Abandoned 60/028,708 11/5/1996
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Brazil Pending PI1101014-2 5/14/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Issued 6,235,756 08/918,610 8/22/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Issued 6,071,948 08/950,673 10/16/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Abandoned 08/955,638 10/23/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Abandoned 08/963,058 11/3/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
</TABLE>
2
<PAGE>
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------
TITLE COUNTRY STATUS PATENT NO. SERIAL NO. FILING DATE
--------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
Methods and Compositions for Australia Pending 51973/98 11/4/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Canada Pending 2,270,887 11/4/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for EPO Pending 97946884.0 11/4/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Japan Pending 10-521728 11/4/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for New Zealand Pending 336035 11/4/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for PCT Nat'l Phase PCT/US97/20116 11/4/1997
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Teratogenic Compounds as US Pending 09/107,578 2/24/1998
Angiogenesis Inhibitors
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Abandoned 60/079,422 3/26/1998
Inhibition of Angiogenesis
(EM138 as Inhibitor of
--------------------------------------------------------------------------------------------------------
Enantiomers of 2-Methyl-2- US Abandoned 60/085,037 5/11/1998
Phthalimidinoglutaric Acid
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Issued 6,114,355 09/126,542 7/30/1998
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Analogs of 2- US Abandoned 60/097,384 8/21/1998
Phthalimidinoglutaric Acid
--------------------------------------------------------------------------------------------------------
Synthesis, Enantiomeric US Abandoned 60/108,037 11/12/1998
Separation, and QSAR of 2-
Phthalimidino-Glutaric Acid
Analogs
--------------------------------------------------------------------------------------------------------
Methods and Composition for Hong Kong Pending 98115898.4 12/28/1998
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
</TABLE>
3
<PAGE>
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------
TITLE COUNTRY STATUS PATENT NO. SERIAL NO. FILING DATE
--------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
Methods and Compositions for US Issued 6,228,879 09/277,402 3/26/1999
Inhibition of Angiogenesis
(EM138 as Inhibitor of
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 09/287,377 4/7/1999
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Composition for US Abandoned 09/300,202 4/27/1999
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Analogs of 2- Australia Pending 41837/99 5/11/1999
Phthalimidinoglutaric Acid
--------------------------------------------------------------------------------------------------------
Analogs of 2- Canada Pending 2,331,461 5/11/1999
Phthalimidinoglutaric Acid and
Their Use as Inhibitors of
Angiogenesis
--------------------------------------------------------------------------------------------------------
Analogs of 2- EPO Published 1091726 99 925585.4 5/11/1999
Phthalimidinoglutaric Acid and
Their Use as Inhibitors of
Angiogenesis
--------------------------------------------------------------------------------------------------------
Analogs of 2- PCT Nat'l Phase PCT/US99/10287 5/11/1999
Phthalimidinoglutaric Acid
--------------------------------------------------------------------------------------------------------
Analogs of 2- US Pending 09/309,464 5/11/1999
Phthalimidinoglutaric Acid
--------------------------------------------------------------------------------------------------------
Methods and Compositions for New Zealand Pending 336527 6/30/1999
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Issued 6,469,045 09/545,139 4/7/2000
Inhibition of Angiogenesis with
EM-138
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 09/545,654 4/10/2000
Inhibition of Angiogenesis with
EM-138
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 09/547,087 4/11/2000
Inhibition of angiogenesis with
EM-138
--------------------------------------------------------------------------------------------------------
</TABLE>
4
<PAGE>
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------
TITLE COUNTRY STATUS PATENT NO. SERIAL NO. FILING DATE
--------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
Methods and Compositions for US Pending 09/578,845 5/25/2000
Inhibition of Angiogenesis with
EM-138
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Hong Kong Pending 00103555.1 6/13/2000
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 09/704,054 11/1/2000
Inhibition of Angiogenesis with
EM-138
--------------------------------------------------------------------------------------------------------
Analogs of 2- South Korea Pending 7012550/2000 11/9/2000
Phthalimidinoglutaric Acid
--------------------------------------------------------------------------------------------------------
Amino Derivatives of EM-138 US Issued 6,420,414 09/710,533 11/9/2000
and Methods of Treating
Angiogenesis With Same
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 09/710,534 11/9/2000
Inhibition of Angiogenesis with
EM-12 Derivatives
--------------------------------------------------------------------------------------------------------
Analogs of 2- Japan Pending 2000-547948 11/13/2000
Phthalimidinoglutaric Acid
--------------------------------------------------------------------------------------------------------
Synthesis of 3-aminothalidomide US Pending 60/250,219 11/30/2000
and its Enantiomers
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 09/788,872 2/20/2001
Inhibition of Angiogenesis with
EM-138
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Japan Pending 50214/01 2/26/2001
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods and Compositions for Canada Pending 4/10/2001
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
Methods for Inhibition of US Pending 09/899,344 7/5/2001
Angiogenesis with 3-amino
Thalidomide
--------------------------------------------------------------------------------------------------------
</TABLE>
5
<PAGE>
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------
TITLE COUNTRY STATUS PATENT NO. SERIAL NO. FILING DATE
--------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
Methods for Inhibition of US Pending 09/899,318 7/5/2001
Angiogenesis with 6-Amino
EM-12
--------------------------------------------------------------------------------------------------------
Synthesis and Anti-Tumor US Pending 60/310,261 8/6/2001
Activity of Nitrogen Substituted
Thalidomide Analogs
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 09/966,895 9/28/2001
Inhibitions of Angiogenesis with
S(-)-3-Amino Thalidomide
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 10/001,183 10/24/2001
Inhibition of Angiogenesis with
Phthaloyl Glutamic Acid
Derivatives
--------------------------------------------------------------------------------------------------------
Synthesis of 3-Amino- US Pending 10/003,461 11/30/2001
Thalidomide and Its Enantiomers
--------------------------------------------------------------------------------------------------------
Synthesis of 3-Amino- PCT Pending PCT/US01/45229 11/30/2001
Thalidomide and Its Enantiomers
--------------------------------------------------------------------------------------------------------
Pharmaceutical Composition of US Pending 10/015,252 12/12/2001
6-Amino EM-12
--------------------------------------------------------------------------------------------------------
Pharmaceutical Composition of US Issue Fee 10/020,391 12/12/2001
3-Amino Thalidomide Paid
--------------------------------------------------------------------------------------------------------
Methods and Compositions for US Pending 10/026,037 12/19/2001
Inhibition of Angiogenesis with
EM-138
--------------------------------------------------------------------------------------------------------
Enantiomers of 6-Amino EM-12 US Pending 10/026,291 12/20/2001
and Method of Use
--------------------------------------------------------------------------------------------------------
Method of Treating Diseases US Pending 10/166,539 6/10/2002
Using 3-Amino Thalidomide
--------------------------------------------------------------------------------------------------------
Method of Treating Diseases US Pending 10/167,531 6/11/2002
Using 6-Amino EM-12
--------------------------------------------------------------------------------------------------------
</TABLE>
6
<PAGE>
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------
TITLE COUNTRY STATUS PATENT NO. SERIAL NO. FILING DATE
--------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
Synthesis and Anti-Tumor US Pending 10/213,294 8/6/2002
Activity of Nitrogen Substituted
Thalidomide Analogs
--------------------------------------------------------------------------------------------------------
Synthesis and Anti-Tumor PCT Pending PCT/US02/25112 8/6/2002
Activity of Nitrogen Substituted
Thalidomide Analogs
--------------------------------------------------------------------------------------------------------
Method and Compositions for US Pending 10/272,436 10/15/2002
Inhibition of Angiogenesis
--------------------------------------------------------------------------------------------------------
</TABLE>
7