1
ENTREMED, INC.
EXHIBIT 10.28
["..." INDICATES MATERIAL HAS BEEN OMITTED PURSUANT TO A CONFIDENTIAL TREATMENT
REQUEST, WHICH THE COMPANY HAS FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION]
AGREEMENT
by and between
ENTREMED, INC.
and
CELGENE CORPORATION
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TABLE OF CONTENTS
PAGE
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SECTION 1 - DEFINITIONS............................................................................1
1.1 "AFFILIATE"............................................................................2
1.2 "CALENDAR QUARTER".....................................................................2
1.3 "CELGENE DEVELOPED INTELLECTUAL PROPERTY"..............................................2
1.4 "CELGENE DEVELOPED PATENT RIGHTS"......................................................2
1.5 "CELGENE DEVELOPED TECHNOLOGY RIGHTS"..................................................2
1.6 "CELGENE EXISTING INTELLECTUAL PROPERTY"...............................................3
1.7 "CELGENE EXISTING PATENT RIGHTS".......................................................3
1.8 "CELGENE EXISTING TECHNOLOGY RIGHTS"...................................................3
1.9 "CMCC AGREEMENT".......................................................................3
1.10 "ENTREMED DEVELOPED PATENT RIGHTS".....................................................3
1.11 "ENTREMED DEVELOPED TECHNOLOGY RIGHTS".................................................4
1.12 "ENTREMED EXISTING PATENT RIGHTS"......................................................4
1.13 "ENTREMED EXISTING TECHNOLOGY RIGHTS"..................................................4
1.14 "ENTREMED INTELLECTUAL PROPERTY".......................................................4
1.15 "FIELD"................................................................................5
1.16 "FIRST COMMERCIAL SALE"................................................................5
1.17 "NCI AGREEMENT"........................................................................5
1.18 "NDA"..................................................................................5
1.19 "NET SALES"............................................................................5
1.20 "PATENT RIGHT(s)"......................................................................6
1.21 "PRODUCT"..............................................................................7
1.22 "SUBLICENSEE"..........................................................................7
1.23 "TECHNOLOGY RIGHTS"....................................................................7
1.24 "TERRITORY"............................................................................8
1.25 "THALIDOMIDE"..........................................................................8
1.26 "THIRD PARTY(IES)".....................................................................8
1.27 "VALID CLAIM"..........................................................................8
SECTION 2 - GRANT..................................................................................8
2.1 Grant of ENTREMED EXISTING PATENT RIGHTS
and ENTREMED EXISTING TECHNOLOGY RIGHTS................................................8
2.2 Grant of ENTREMED DEVELOPED PATENT RIGHTS and ENTREMED DEVELOPED TECHNOLOGY RIGHTS.....9
2.3 CELGENE'S Right To Sublicense..........................................................9
2.4 Assignment Of Investigational New Drug and Orphan Drug
Status Applications...................................................................10
2.5 Assignment Of Agreements..............................................................10
2.6 Technology Transfer...................................................................11
2.7 Understanding Regarding CMCC AGREEMENT................................................11
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SECTION 3 - DUE DILIGENCE.........................................................................13
3.1 In the United States..................................................................13
3.2 Outside the United States.............................................................15
3.3 For PRODUCTS For Use In Animals.......................................................16
3.4 No Other ENTREMED Rights..............................................................17
3.5 Co-Promotion By CELGENE And ENTREMED..................................................17
3.6 Establishment Of A Scientific Committee...............................................19
SECTION 4 - ROYALTIES.............................................................................21
4.1 Royalty Payments......................................................................21
4.2 Sublicensing Payments and Royalties...................................................22
4.3 Later-Issued VALID CLAIM..............................................................23
4.4 "...".................................................................................23
4.5 THIRD PARTY Sales.....................................................................23
4.6 Recordkeeping.........................................................................24
4.7 Quarterly Payments and Reports........................................................25
4.8 Accounting Reports....................................................................25
SECTION 5 - CONFIDENTIALITY.......................................................................26
5.1 Confidential Information..............................................................26
5.2 Non-Confidential Information..........................................................26
5.3 Disclosure To THIRD PARTIES...........................................................27
5.4 Disclosure To Sublicensees............................................................28
5.5 Public Statements.....................................................................28
SECTION 6 - ADVERSE MEDICAL EXPERIENCES...........................................................28
6.1 Adverse Medical Experience Reporting..................................................28
SECTION 7 - PATENTS...............................................................................28
7.1 Patent Prosecution....................................................................28
7.2 Cooperation In Prosecution............................................................29
7.3 Infringement and Declaratory Judgment Actions.........................................29
SECTION 8 - REPRESENTATIONS AND WARRANTIES........................................................32
8.1 By Both Parties.......................................................................32
8.2 By ENTREMED...........................................................................32
SECTION 9 - INDEMNIFICATION AND INSURANCE.........................................................34
9.1 By CELGENE............................................................................34
9.2 By ENTREMED...........................................................................35
9.3 Conditions to Indemnification.........................................................36
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SECTION 10 - ASSIGNMENT AND SUCCESSORS.............................................................36
10.1 By Either Party.......................................................................36
10.2 By CELGENE............................................................................37
10.3 CELGENE As Guarantor..................................................................37
10.4 Binding Effect........................................................................37
SECTION 11 - FORCE MAJEURE.........................................................................37
SECTION 12 - TERMINATION...........................................................................38
12.1 Term..................................................................................38
12.2 By Reason Of FDA Action...............................................................38
12.3 Termination Of Royalty Obligations....................................................38
12.4 Breach................................................................................38
12.5 Insolvency............................................................................40
12.6 Work-In-Progress......................................................................41
12.7 Survival..............................................................................41
12.8 Reversion of Rights...................................................................41
SECTION 13 - GENERAL PROVISIONS....................................................................41
13.1 Relationship of Parties...............................................................41
13.2 Entire Understanding..................................................................42
13.3 Governing Law.........................................................................42
13.4 Headings..............................................................................42
13.5 No Waiver.............................................................................42
13.6 Export Controls.......................................................................42
13.7 Notices...............................................................................42
13.8 Original Counterparts.................................................................43
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AGREEMENT
This Agreement is effective this 9th day of December, 1998 (the "EFFECTIVE
DATE") by and between CELGENE CORPORATION, a Delaware corporation located at 6
Powder Horn Drive, Warren, New Jersey 07059 ("CELGENE"), and ENTREMED, INC., a
Delaware Corporation located at 9610 Medical Center Drive, Rockville, Maryland
20850 ("ENTREMED").
WHEREAS, CELGENE is a company that develops, manufactures, markets and
sells pharmaceutical products for healthcare, and that has developed and owns
certain patents, patent applications, proprietary technology, know-how, and
United States Food and Drug Administration ("FDA") filings relating to PRODUCTS,
as hereinafter defined; and
WHEREAS, ENTREMED is the owner or exclusive licensee of certain PATENT
RIGHTS as hereinafter defined, TECHNOLOGY RIGHTS, as hereinafter defined, and
FDA filings related to PRODUCTS, and has certain rights and obligations relating
to PRODUCTS pursuant to agreements with THIRD PARTIES, as hereinafter defined;
and
WHEREAS, CELGENE desires to obtain assignments and/or exclusive rights in
the TERRITORY in and to all of ENTREMED's PATENT RIGHTS, TECHNOLOGY RIGHTS,
rights by agreement, and FDA filings, whether presently existing or subsequently
developed, for the commercial development, use, and sale of PRODUCTS; and
WHEREAS, ENTREMED is willing to grant the assignments and/or exclusive
rights desired by CELGENE, as set forth herein, in order to transfer its entire
present and future right, title and interest in PRODUCTS to CELGENE.
NOW, THEREFORE, in consideration of the mutual promises and other good and
valuable consideration, the parties agree as follows:
SECTION 1 - DEFINITIONS
The terms used in this Agreement have the following meaning:
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1.1 The term "AFFILIATE" as applied to either party shall mean any
company or other legal entity other than the party in question in
whatever country organized, controlling controlled by or under
common control with that party. The term "control" means ownership
or control, directly or indirectly, of at least fifty percent (50%)
of the outstanding stock or voting rights entitled to elect
directors.
1.2 The term "CALENDAR QUARTER" shall mean the period of three (3)
consecutive calendar months ending on March 31, June 30, September
30 or December 31, as the case may be.
1.3 The term "CELGENE DEVELOPED INTELLECTUAL PROPERTY" shall mean
CELGENE DEVELOPED PATENT RIGHTS and CELGENE DEVELOPED TECHNOLOGY
RIGHTS.
1.4 The term "CELGENE DEVELOPED PATENT RIGHTS" shall mean any United
States or foreign patents or patent applications filed by CELGENE,
or an AFFILIATE, successor or assign thereof at any time subsequent
to the EFFECTIVE DATE, in which CELGENE has a transferrable
interest, relating to a modification of a PRODUCT described in any
ENTREMED INTELLECTUAL PROPERTY or a method of using such PRODUCT,
which modification is (a) necessary for the manufacture, use, or
sale of such PRODUCT, and (b) then currently in use by CELGENE at
the time ENTREMED exercises its rights under Section 12.4(b), for
the manufacture, use, or sale of such PRODUCT.
1.5 The term "CELGENE DEVELOPED TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired by CELGENE or an
AFFILIATE, successor or assign thereof at any time subsequent to the
EFFECTIVE DATE, in which CELGENE has a transferrable interest,
relating to a modification of a PRODUCT described in any ENTREMED
INTELLECTUAL PROPERTY or a method of using or use of such PRODUCT,
which modification is (a) necessary for the
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manufacture, use, or sale of such PRODUCT, and (b) then currently in
use by CELGENE at the time ENTREMED exercises its rights under
Section 12.4(b), for the manufacture, use, or sale of such PRODUCT.
1.6 The term "CELGENE EXISTING INTELLECTUAL PROPERTY" shall mean CELGENE
EXISTING PATENT RIGHTS and CELGENE EXISTING TECHNOLOGY RIGHTS.
1.7 The term "CELGENE EXISTING PATENT RIGHTS" shall mean the United
States and foreign patents and patent applications relating to
PRODUCTS in which CELGENE has an interest, jointly or solely, as
owner, assignee, or licensee, whether exclusive or nonexclusive, as
of the EFFECTIVE DATE.
1.8 The term "CELGENE EXISTING TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired, solely or
jointly, exclusively or non-exclusively, by CELGENE or an AFFILIATE,
successor or assign thereof as of the EFFECTIVE DATE.
1.9 The term "CMCC AGREEMENT" shall mean that certain License Agreement
entered into by and between ENTREMED and Children's Medical Center
Corporation ("CMCC"), dated May 26, 1994, as amended to the date
hereof, attached hereto as Exhibit A.
1.10 The term "ENTREMED DEVELOPED PATENT RIGHTS" shall mean any United
States or foreign patent applications relating to PRODUCTS assigned
to, licensed to or filed, solely or jointly, by ENTREMED, or an
AFFILIATE, successor or assign thereof at any time subsequent to the
EFFECTIVE DATE, including any United States or foreign patent
applications filed pursuant to the CMCC AGREEMENT or NCI AGREEMENT,
and the patents issuing therefrom, which patent applications and
patents shall be added to Appendix A and shall be
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included in this Agreement as PATENT RIGHTS and licensed to CELGENE
in accordance with Section 2 of this Agreement.
1.11 The term "ENTREMED DEVELOPED TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired, solely or
jointly, exclusively or non-exclusively, by ENTREMED, or an
AFFILIATE, successor or assign thereof at any time subsequent to the
EFFECTIVE DATE, including any TECHNOLOGY RIGHTS developed or
obtained pursuant to the CMCC AGREEMENT or NCI AGREEMENT, which
TECHNOLOGY RIGHTS shall be included in this Agreement and licensed
to CELGENE in accordance with Section 2 of this Agreement.
1.12 The term "ENTREMED EXISTING PATENT RIGHTS" shall mean the PATENT
RIGHTS in which ENTREMED has an interest, jointly or solely, as
owner, assignee, or licensee, whether exclusive or nonexclusive, as
of the EFFECTIVE DATE.
1.13 The term "ENTREMED EXISTING TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired, solely or
jointly, exclusively or non-exclusively, by ENTREMED, or an
AFFILIATE, successor or assign thereof as of the EFFECTIVE DATE,
including without limitation any TECHNOLOGY RIGHTS developed or
obtained pursuant to the CMCC AGREEMENT or NCI AGREEMENT. ENTREMED
EXISTING TECHNOLOGY RIGHTS expressly includes any regulatory data
and filings, including without limitation all FDA Investigational
New Drug and Orphan Drug Status applications, as set forth in
Appendix C.
1.14 The term "ENTREMED INTELLECTUAL PROPERTY" shall mean and include
ENTREMED DEVELOPED PATENT RIGHTS, ENTREMED DEVELOPED TECHNOLOGY
RIGHTS, ENTREMED EXISTING PATENT RIGHTS, and ENTREMED EXISTING
TECHNOLOGY RIGHTS.
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1.15 The term "FIELD" shall mean the use of THALIDOMIDE in humans and
animals, including without limitation any and all diagnostic,
prophylactic, therapeutic, and research and development uses.
1.16 The term "FIRST COMMERCIAL SALE" shall mean, in each country of the
TERRITORY, the first sale after the EFFECTIVE DATE in such country
to a THIRD PARTY in connection with the nationwide introduction of
any PRODUCT by CELGENE, its AFFILIATES or SUBLICENSEES following
marketing and/or pricing approval by the appropriate governmental
agency for the country in which the sale is to be made and, when
governmental approval is not required, the first sale in that
country in connection with the nationwide introduction of a PRODUCT
in that country.
1.17 The term "NCI AGREEMENT" shall mean that certain Agreement by and
between the Division of Cancer Treatment at the National Cancer
Institute ("NCI") and ENTREMED, dated November 16, 1994, and
executed on behalf of ENTREMED on November 23, 1994, and on behalf
of NCI on November 18, 1994, attached hereto as Exhibit B.
1.18 The term "NDA" shall mean a New Drug Application filed with the
United States Food and Drug Administration.
1.19 The term "NET SALES" means the gross amount received by CELGENE or
its AFFILIATES or SUBLICENSEES for sale of PRODUCT to THIRD PARTIES,
less: (i) cost of freight, postage, and freight insurance, (if paid
by seller); (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
PRODUCTS; (iv) rebates accrued, incurred or paid to Federal Medicaid
and State Medicare and any other price reductions required by a
governmental agency; (v) rejected shipments, returns, and
retroactive deductions; (vi) the amount received for sales which
become the subject of a subsequent temporary or partial recall
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by a regulatory agency for safety or efficacy reasons outside the
control of CELGENE; and (vii) customary cash, quantity, and trade
discounts; provided, however, that a sale or transfer to an
AFFILIATE or SUBLICENSEE for re-sale by such AFFILIATE or
SUBLICENSEE shall not be considered a sale for the purpose of this
provision but the resale by such AFFILIATE or SUBLICENSEE shall be a
sale for such purposes. A "sale" shall also include a transfer or
other disposition for consideration, but not such transfers or
dispositions, without consideration, for pre-clinical, clinical,
regulatory or governmental purposes prior to receiving marketing
approval for the specific indication for which such transfer is
made. In the event that consideration in addition to or in lieu of
money is received for PRODUCT, such consideration shall be added to
the NET SALES as valued on the day of receipt thereof by CELGENE. To
the extent that a PRODUCT is sold in other than an arms length
transaction, NET SALES shall be the fair market value of such
PRODUCT if sold in an arms length transaction, less the costs
identified in subsections (i)-(vi) of this Section 1.19. PRODUCT
shall be considered "sold" at the earlier of (a) the transfer of
title in such PRODUCT to a person other than an AFFILIATE or
SUBLICENSEE of CELGENE or (b) the shipment of such PRODUCT from the
manufacturing or warehouse facilities of CELGENE or its AFFILIATE or
SUBLICENSEE to a THIRD PARTY.
1.20 The term "PATENT RIGHT(s)" shall mean:
(a) the United States patent applications and patents listed in
Appendix A;
(b) the United States and foreign patents issued from applications
listed in Appendix A and from divisionals and continuations of
such applications;
(c) claims of United States continuation-in-part applications and
of equivalent foreign applications, and of the resulting
patent(s), that
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are directed to subject matter described in the United States
and foreign applications listed in Appendix A;
(d) claims of all later-filed foreign patent applications, and of
the resulting patents, that are directed to subject matter
described in the United States patents and/or patent
applications described in the foregoing subsections of this
Section 1.20;
(e) any reissues, re-examinations or extension of United States
patents described in the foregoing subsections of this Section
1.20; and
(f) ENTREMED DEVELOPED PATENT RIGHTS, when assigned to, licensed
to or filed, solely or jointly, by ENTREMED, or an AFFILIATE,
successor or assign thereof, pursuant to Section 1.10 of this
Agreement.
1.21 The term "PRODUCT" shall mean any article of manufacture, substance,
material, chemical, formulation or composition for use in the FIELD
which is or includes THALIDOMIDE as an active ingredient, including,
without limitation, a composition that comprises THALIDOMIDE and a
non-steroidal anti-inflammatory compound(s). PRODUCT expressly
excludes THALIDOMIDE analogs.
1.22 The term "SUBLICENSEE" shall mean any THIRD PARTY licensed by
CELGENE to make, have made, use, offer to sell, sell or import any
PRODUCT.
1.23 The term "TECHNOLOGY RIGHTS" shall mean any information relating to
PRODUCTS that is not covered by a patent or patent application,
including without limitation technical and non-technical
information, know-how, methods, processes, procedures, compositions,
devices, formulae, protocols, techniques, software, designs,
drawings, plans, diagrams, specifications, data, the results of
tests or assays, and all other information relating to PRODUCTS.
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1.24 The term "TERRITORY" shall mean all countries of the world.
1.25 The term "THALIDOMIDE" shall mean a compound with the chemical
structure described as
2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, or as
otherwise defined in the Merck Index, entry 9390, 12th ed., and
pharmaceutically acceptable salts thereof.
1.26 The term "THIRD PARTY(IES)" shall mean a person or entity who or
which is neither a party hereto nor an AFFILIATE of a party hereto.
1.27 The term "VALID CLAIM" shall mean an issued claim of an unexpired
patent ("ISSUED VALID CLAIM") or a claim of a pending patent
application, which shall not have been withdrawn, canceled or
disclaimed, or held invalid or unenforceable by a court of competent
jurisdiction in an unappealed or unappealable decision.
Notwithstanding the foregoing to the contrary, a claim of a pending
patent application, divisional application or continuation-in-part
shall cease to be a VALID CLAIM if no patent has issued on such
claim on or prior to the fifth (5th) anniversary of the EFFECTIVE
DATE of this Agreement, provided that such claim shall once again
become a VALID CLAIM on the issue date of a patent that subsequently
issues and covers such claim.
1.28 The use herein of the plural shall include the singular, and the use
of the masculine shall include the feminine.
SECTION 2 - GRANT
2.1 Grant of ENTREMED EXISTING PATENT RIGHTS and ENTREMED EXISTING
TECHNOLOGY RIGHTS. ENTREMED hereby grants to CELGENE and CELGENE
hereby accepts from ENTREMED an exclusive, royalty bearing right and
license or sublicense, as the case may be, under the ENTREMED
EXISTING PATENT RIGHTS and the
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ENTREMED EXISTING TECHNOLOGY RIGHTS to make, have made, use,
offer to sell, sell, and import PRODUCTS in the TERRITORY.
2.2 Grant of ENTREMED DEVELOPED PATENT RIGHTS and ENTREMED
DEVELOPED TECHNOLOGY RIGHTS. ENTREMED hereby grants to
CELGENE, to the extent not prohibited by the United States
Government or by prior contractual obligations to any THIRD
PARTY, and CELGENE hereby accepts from ENTREMED:
(a) an exclusive, royalty bearing right and license under
the ENTREMED DEVELOPED PATENT RIGHTS and the ENTREMED
DEVELOPED TECHNOLOGY RIGHTS to make, have made, use,
offer to sell, sell, and import PRODUCTS in the
TERRITORY; and
(b) to the extent an exclusive license is not available to
CELGENE in a country under a particular ENTREMED
DEVELOPED PATENT RIGHT or ENTREMED DEVELOPED TECHNOLOGY
RIGHT, but a non-exclusive license would be available,
ENTREMED hereby grants CELGENE a nonexclusive, royalty
bearing right and license under such ENTREMED DEVELOPED
PATENT RIGHT(s) and ENTREMED DEVELOPED TECHNOLOGY
RIGHT(s) to make, have made, use, offer to sell, sell,
and import PRODUCTS in the TERRITORY.
2.3 CELGENE'S Right To Sublicense.
(a) In the United States. ENTREMED hereby grants to CELGENE
the right to sublicense ENTREMED INTELLECTUAL PROPERTY
in the United States with the consent of ENTREMED, to be
exercised in ENTREMED's sole discretion.
(b) Outside the United States. ENTREMED hereby grants to
CELGENE the right to sublicense ENTREMED INTELLECTUAL
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PROPERTY outside the United States with the written
consent of ENTREMED, which consent shall not be
unreasonably withheld. Outside the United States,
CELGENE shall use reasonable efforts to negotiate
sublicensing agreements that are commercially reasonable
according to contemporaneous prevailing standards within
the pharmaceutical industry.
2.4 Assignment Of Investigational New Drug and Orphan Drug Status
Applications. Within ten (10) days of the EFFECTIVE DATE,
ENTREMED and CELGENE shall notify the Food and Drug
Administration ("FDA") of the transfer of ENTREMED's rights in
PRODUCTS to CELGENE by submitting to the FDA letters
substantially in the form attached hereto as Exhibit C, and
ENTREMED shall notify CELGENE of its compliance with this
Section 2.4 by copies of such letters. ENTREMED shall take all
further steps necessary or helpful to assign to CELGENE all
Orphan Drug Status and Investigational New Drug applications
filed by ENTREMED as of the EFFECTIVE DATE, as set forth in
Appendix C. If the FDA declines to allow the assignment of any
of ENTREMED's Investigational New Drug and/or Orphan Drug
Status application(s) to CELGENE, for whatever reason, then
ENTREMED's rights under such application(s) will be included
in this Agreement as ENTREMED EXISTING TECHNOLOGY RIGHTS and
will be licensed to CELGENE in accordance with Section 2 of
this Agreement.
2.5 Assignment Of Agreements. Within ten (10) days of the
EFFECTIVE DATE, ENTREMED shall notify CMCC and NCI of the
sublicense and transfer, respectively, of its rights in
PRODUCTS to CELGENE, and shall take all steps necessary or
helpful to assign to CELGENE the NCI AGREEMENT, including
without limitation requesting consent to assign ENTREMED's
obligations and entire right, title, and interest, under such
agreement to CELGENE, and upon receipt of the consent of NCI
to assign the NCI AGREEMENT, CELGENE will expressly assume all
of
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ENTREMED's duties and obligations thereunder. In the event
that ENTREMED is not permitted to assign its rights under the
NCI AGREEMENT to CELGENE, ENTREMED's rights in any PATENT
RIGHTS or TECHNOLOGY RIGHTS resulting from the NCI AGREEMENT
will be included in this Agreement as ENTREMED DEVELOPED
PATENT RIGHTS and ENTREMED DEVELOPED TECHNOLOGY RIGHTS,
respectively, and will be licensed to CELGENE in accordance
with Section 2.2 of this Agreement.
2.6 Technology Transfer. As soon as reasonably possible following
the EFFECTIVE DATE, but in no event later than one (1) month
after such date, ENTREMED shall transfer to CELGENE all
ENTREMED EXISTING TECHNOLOGY RIGHTS and ENTREMED DEVELOPED
TECHNOLOGY RIGHTS not already in CELGENE's possession.
ENTREMED agrees to disclose and transfer all ENTREMED
DEVELOPED TECHNOLOGY RIGHTS to CELGENE promptly, as they are
obtained or developed. ENTREMED also agrees to provide, upon
reasonable notice from CELGENE, any technical, scientific,
statistical, and/or regulatory support necessary or useful to
CELGENE's understanding and/or use of ENTREMED EXISTING
TECHNOLOGY RIGHTS and ENTREMED DEVELOPED TECHNOLOGY RIGHTS.
2.7 Understanding Regarding CMCC AGREEMENT. To the extent
TECHNOLOGY RIGHTS and/or PATENT RIGHTS licensed to CELGENE
under this Agreement are rights which ENTREMED has licensed
from CMCC under the CMCC AGREEMENT, CELGENE and ENTREMED
understand and agree as follows:
(a) The rights licensed to CELGENE by ENTREMED are subject
to the terms, limitations, restrictions and obligations
of the CMCC AGREEMENT.
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(b) CELGENE will comply with the terms, obligations,
limitations and restrictions of sublicensees under
Articles II, V, VII, VIII, IX, X, XII, XIII, and XV of
the CMCC AGREEMENT.
(c) ENTREMED will, at its own expense, timely pay the
milestone payment of "..." due to CMCC upon completion
of a Phase II clinical trial for any indication,
pursuant to Section 4.1.3 of the CMCC AGREEMENT.
ENTREMED shall promptly provide written notice to
CELGENE of such payment.
(d) CELGENE will, at its own expense, timely pay the
milestone payment of "..." due to CMCC upon completion
of a Product License Application for any indication,
pursuant to Section 4.1.4 of the CMCC AGREEMENT, which
payment shall be made to ENTREMED and timely forwarded
by ENTREMED to CMCC; provided, however, that if (i) such
payment becomes due prior to January 1, 2000, and (ii)
CELGENE's annual sales in the year such payment becomes
due are less than "...", CELGENE may notify ENTREMED, in
writing, that it wishes ENTREMED to pay such amount to
CMCC directly, which ENTREMED hereby agrees to do, and,
by June 30, 2000 CELGENE shall reimburse ENTREMED the
amount paid to CMCC, plus interest calculated at the
annual rate of the sum of one percent (1%) plus the
prime interest rate quoted by Citibank, N.A. on the date
said payment is due. ENTREMED shall promptly provide
written notice to CELGENE of all payments under this
Section 2.7(d).
(e) ENTREMED will comply with the terms, obligations,
limitations and restrictions of the CMCC AGREEMENT,
including, without limitation, any provisions relating
to due diligence, notification with respect to
sublicenses, and milestone payments, subject to Sections
2.7(c) and (d) of this Agreement.
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(f) The CMCC AGREEMENT and ENTREMED's rights thereunder
shall remain in full force and effect for the life of
the last to expire patent issued under the Patent
Rights, as defined therein, unless earlier terminated
pursuant to Article XIII of the CMCC AGREEMENT.
SECTION 3 - DUE DILIGENCE
3.1 In the United States.
(a) CELGENE shall initiate and diligently use reasonable
efforts to develop, or to file for regulatory approval
of or register, and to market and sell PRODUCTS in the
United States. Reasonable efforts with respect to the
development and/or pursuit of regulatory approval or
registration for PRODUCTS in the United States shall be
demonstrated by CELGENE (i) developing and pursuing
regulatory approval for PRODUCTS for those uses CELGENE,
in good faith, determines to be commercially and
scientifically reasonable, including but not limited to
(a) one (1) "...", (b) one (1) "...", and (c) one (1)
"..."; and (ii) funding and conducting clinical trials
for PRODUCTS for other uses in order to enhance
scientific knowledge with regard to such PRODUCTS,
including for the publication of data and results in
scientific journals, whether or not such clinical trials
result in or facilitate the pursuit of regulatory
approval.
(b) ENTREMED agrees that, subject to Section 3.6 of this
Agreement, (i) the decision regarding which uses to
pursue regulatory approval of PRODUCTS for, and/or to
fund and conduct clinical trials of PRODUCTS for,
pursuant to Section 3.1(a) of this Agreement, shall be
made by and in the sole discretion of CELGENE; and (ii)
with respect to the manner in which regulatory approval
is sought and/or clinical trials are funded and
conducted, CELGENE shall
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have sole discretion, including, without limitation,
complete control over all regulatory submissions of
PRODUCTS to the appropriate regulatory agencies
worldwide, including whether, when, and how to file,
maintain, withdraw, or abandon an application for
regulatory approval of PRODUCTS.
(c) Within 90 days after the EFFECTIVE DATE, CELGENE shall
draft a Development Plan outlining CELGENE'S development
objectives for PRODUCTS, in accordance with Sections
3.1(a)(i) and (b) of this Agreement. CELGENE shall
consult with ENTREMED concerning the Development Plan.
The Development Plan shall include suitable clinical
milestones which are reasonably intended to lead to
regulatory approval of PRODUCTS, in accordance with
Sections 3.1(a)(i) and (b) of this Agreement.
(d) CELGENE shall provide a written summary report to
ENTREMED within thirty (30) days after June 30th and
December 31st of each calendar year concerning the
efforts being made in accordance with this Section 3.1
with respect to PRODUCTS. CELGENE shall provide ENTREMED
with any additional information reasonably requested by
ENTREMED in this respect.
(e) At ENTREMED'S reasonable request, CELGENE shall provide
ENTREMED access to all clinical trial data for PRODUCTS
conducted by CELGENE in accordance with the Development
Plan set forth in this Section 3.1. In the event that
rights are returned to ENTREMED under Section 3.1(f) of
this Agreement, ENTREMED shall have the right to review
and use the clinical trial data in its own clinical
program.
(f) In the event that CELGENE fails to meet any of its
obligations under this Section 3.1 with respect to
PRODUCTS in the United
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States, and such failure is not cured within sixty (60)
days after written notice thereof is received by CELGENE
from ENTREMED, then ENTREMED shall have the right and
option to terminate the license granted in this
Agreement and this Agreement by giving CELGENE sixty
(60) days prior written notice thereof.
3.2 Outside the United States.
(a) Diligence. CELGENE shall initiate and diligently use
reasonable efforts to develop, or to file for regulatory
approval of or register, and to market and sell PRODUCTS
in Europe, in Canada, and in the Pacific Rim, Japan, and
Australia (collectively, the "PACIFIC RIM"). Reasonable
efforts with respect to the development and/or pursuit
of regulatory approval or registration for PRODUCTS in
Europe, Canada, and the PACIFIC RIM shall be
demonstrated by CELGENE, or a sublicensee thereof,
pursuing regulatory approval for PRODUCTS (i) in Italy,
France, the United Kingdom, and Germany (in the case of
Europe), and in Japan and one other country of the
PACIFIC RIM (in the case of the PACIFIC RIM), within
"..." from the date of the first FDA approval of a
PRODUCT for an oncology indication or Crohn's disease,
whichever occurs earlier; and (ii) in Canada, within
"..." from the date of the first FDA approval of a
PRODUCT for an oncology indication or Crohn's disease,
whichever occurs earlier.
(b) CELGENE's Discretion. ENTREMED agrees that, subject to
Section 3.6 of this Agreement, (i) the decision
regarding which uses to pursue regulatory approval of
PRODUCTS for, and/or to fund and conduct clinical trials
of PRODUCTS for, pursuant to Section 3.2(a) of this
Agreement, shall be made by and in the sole discretion
of CELGENE; and (ii) with respect to the manner in
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which regulatory approval is sought and/or clinical
trials are funded and conducted, CELGENE shall have sole
discretion, including, without limitation, complete
control over all regulatory submissions of PRODUCTS to
the appropriate regulatory agencies worldwide, including
whether, when, and how to file, maintain, withdraw, or
abandon an application for regulatory approval of
PRODUCTS.
(c) Cooperation. If CELGENE fails to use reasonable efforts
in Europe, Canada, or the PACIFIC RIM, as set forth in
Section 3.2(a) of this Agreement, or to sublicense its
rights to a THIRD PARTY, then ENTREMED shall have the
right and option to either (i) terminate the licenses
granted in the region where such failure has occurred,
i.e., Europe, Canada, or the PACIFIC RIM, respectively,
by giving CELGENE sixty (60) days prior written notice
thereof, or (ii) cooperate with CELGENE to find an
appropriate SUBLICENSEE for such rights.
3.3 For PRODUCTS For Use In Animals.
(a) Diligence. CELGENE shall initiate and diligently use
reasonable efforts to develop, or to file for regulatory
approval of or register, and to market and sell PRODUCTS
for use in animals. Such reasonable efforts shall be
demonstrated by CELGENE obtaining regulatory approval
for the sale of a PRODUCT for use in animals within four
(4) years of the EFFECTIVE DATE in the United States
and, outside the United States, in one of the following
countries: Italy, France, the United Kingdom, or
Germany.
(b) Cooperation. If CELGENE fails to use reasonable efforts
either in the United States or outside the United
States, as set forth in Section 3.3(a) of this
Agreement, or to sublicense its rights in such regions
to a THIRD PARTY, then ENTREMED shall have the
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right and option to either (i) terminate CELGENE's
rights in the region where such failure has occurred,
i.e., in the United States or outside the United States,
respectively, in and to such PRODUCTS for use in animals
by giving CELGENE sixty (60) days prior written notice
thereof, or (ii) cooperate with CELGENE to find an
appropriate SUBLICENSEE for such rights.
3.4 No Other ENTREMED Rights. Except as otherwise expressly
provided in this Agreement, ENTREMED agrees that it has not
retained any rights under ENTREMED INTELLECTUAL PROPERTY to
PRODUCTS, and that is shall not (i) make, use, offer to sell,
sell, or import PRODUCTS in the TERRITORY, or (ii)
collaborate, negotiate, or deal with THIRD PARTIES with
respect to PRODUCTS.
3.5 Co-Promotion By CELGENE And ENTREMED.
(a) With Regard To PRODUCTS. If CELGENE, in its sole
discretion, decides to co-promote any PRODUCT or to seek
sales assistance in promoting any PRODUCT, including,
but not limited to, sales assistance for indications not
then promoted by CELGENE sales personnel, CELGENE shall,
in good faith, consider ENTREMED for the opportunity to
co-promote such PRODUCT(S) for such indications in the
United States.
(i) CELGENE will give ENTREMED due consideration for
the opportunity to co-promote such PRODUCT(S) as
set forth herein, provided that ENTREMED has a
sales force capable of providing the required
details to the targeted physician audience, or is
capable of assembling such a sales force within
six (6) months, and agrees to do so. If and only
if ENTREMED either has a sales force capable of
providing the required details to the targeted
physician audience, or commits to assembling such
a sales force
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within six (6) months, the decision to offer
ENTREMED the opportunity to co-promote such
PRODUCT(s) for such indications in the United
States shall be made, in good faith, by CELGENE,
and CELGENE shall notify ENTREMED of its decision
in writing.
(ii) If CELGENE offers ENTREMED the opportunity to
co-promote, pursuant to Section 3.5(a)(i) of this
Agreement, ENTREMED shall have thirty (30) days to
accept such offer by written notice to CELGENE. If
ENTREMED accepts such offer to co-promote
PRODUCTS, then the parties will negotiate, in good
faith, a co-promotion agreement setting forth the
substance of this Section 3.5 and other normal and
customary conditions within six (6) months of
CELGENE's receipt of ENTREMED's acceptance
pursuant to this Section 3.5(a)(ii).
(iii) ENTREMED's co-promotion efforts will focus on
detailing (product presentations) the PRODUCT to
the targeted physician audience. In such case,
ENTREMED's sales representatives will also have
the opportunity, from time to time, to participate
in seminars, in-service training, group
presentations, and other educational and
promotional activities initiated by CELGENE in
consultations with ENTREMED. In addition, ENTREMED
will assign a product manager to participate with
the CELGENE marketing team to provide input as
appropriate and to be the operational liaison
between CELGENE and ENTREMED's sales force.
(b) With Regard To Anti-angiogenic Compounds. If ENTREMED,
in its sole discretion, decides to co-promote an
anti-angiogenic compound or a composition containing, as
an active ingredient, such a compound, or to seek sales
assistance in promoting any
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such anti-angiogenic compound or composition, including,
but not limited to, sales assistance for indications not
then promoted by ENTREMED sales personnel, ENTREMED
shall, in good faith, consider CELGENE for the
opportunity to co-promote such anti-angiogenic compounds
and/or compositions. The decision to offer CELGENE the
opportunity to co-promote such anti-angiogenic compounds
and/or compositions shall be made in the sole discretion
of ENTREMED, and be subject, mutatis mutandis, to the
terms and conditions set forth in Sections 3.5(a)(ii)
and (iii) of this Agreement.
3.6 Establishment Of A Scientific Committee. CELGENE agrees to
conduct and fund a development program designed to obtain
approval to market PRODUCTS, in accordance with its
obligations under Section 3.1(a)(i) and 3.1(b) of this
Agreement (the "PROGRAM"). To ensure the continued
participation of ENTREMED in these development activities, the
PROGRAM will be monitored by a Scientific Committee as
described herein (the "COMMITTEE").
(a) Members. Within ten (10) days of the date hereof,
ENTREMED and CELGENE shall each appoint two (2) persons
to serve on the COMMITTEE. Each party will have the
right to change its representation on the COMMITTEE upon
written notice to the other.
(b) Chairperson. The COMMITTEE will be chaired by one
representative of CELGENE, who shall be chosen in the
sole discretion of CELGENE.
(c) Responsibilities. The COMMITTEE will have authority to:
(i) act in an advisory role and provide information,
including without limitation technical and
regulatory information and
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marketing and sales information, helpful in
connection with the PROGRAM;
(ii) make recommendations regarding the performance of
the PROGRAM and the conduct of the work pursuant
thereto, and monitor performance thereunder;
(iii) propose modifications to the PROGRAM;
(iv) review any and all proposed publication(s)
relating to the PROGRAM and the results therefrom;
and
(v) review all information and data resulting from the
PROGRAM.
(d) Meetings. The COMMITTEE will meet not less than four (4)
times a year during the term of the PROGRAM, at such
dates and times as agreed to by the parties. The
COMMITTEE will prepare written minutes of each meeting
and a written record of all decisions whether made at a
formal meeting or not. All decisions made and actions
taken by the COMMITTEE will be made or taken in the sole
discretion of CELGENE after good faith consideration of
the position or opinion of the ENTREMED members.
(e) Term and Termination. The PROGRAM will continue until
there are no longer any ongoing activities in pursuit of
regulatory approval, or any pending applications for
regulatory approval, for PRODUCTS, pursuant to Sections
3.1(a)(i) and (b) of this Agreement. Once all such
activities have been completed and all such regulatory
approvals have been obtained, CELGENE may, in its sole
discretion, extend the term of the PROGRAM to include
PRODUCTS in clinical trials for other uses, as set forth
in Sections 3.1(a)(ii) and (b) of this Agreement, in
which case the PROGRAM will continue until such clinical
trials have been completed or otherwise terminated or,
if applicable, until regulatory approval has
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been obtained, unless the PROGRAM is sooner terminated
by CELGENE.
SECTION 4 - ROYALTIES
4.1 Royalty Payments.
(a) First Twelve Years. CELGENE shall pay to ENTREMED the
following royalties on the NET SALES of PRODUCTS sold by
CELGENE or its AFFILIATES in each country of the
TERRITORY (i) for the first consecutive twelve (12)
years from the date of the FIRST COMMERCIAL SALE of a
PRODUCT in each country of the TERRITORY, and,
separately and independently, (ii) for the first
consecutive twelve (12) years from the date of the FIRST
COMMERCIAL SALE of each PRODUCT that contains, as a
second active ingredient, a compound other than
THALIDOMIDE, in each country of the TERRITORY:
(i) "..." of NET SALES up to "..." dollars of such
sales;
(ii) "..." of NET SALES between "..." dollars and "..."
dollars of such sales;
(iii) "..." of NET SALES between "..." and "..." dollars
of such sales; and
(iv) "..." of NET SALES over "..." dollars of such
sales.
(b) After Twelve Years. For each PRODUCT in each country in
the TERRITORY in which the twelve (12) year period
provided for in Section 4.1(a) of this Agreement shall
have terminated, CELGENE shall pay to ENTREMED the
following royalties on the NET SALES of such PRODUCT
covered by an ISSUED VALID CLAIM of the PATENT RIGHTS
that are sold by CELGENE or its AFFILIATES in such
country:
(i) "..." of NET SALES up to "..." dollars of such
sales;
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(ii) "..." of NET SALES between "..." dollars and "..."
dollars of such sales;
(iii) "..." of NET SALES between "..." and "..." dollars
of such sales; and
(iv) "..." of NET SALES over "..." dollars of such
sales;
and such royalties under this Section 4.1(b) shall be
payable until the last to expire PATENT RIGHT containing an
ISSUED VALID CLAIM covering such PRODUCT sold by CELGENE or
its AFFILIATES in such country.
4.2 Sublicensing Payments and Royalties.
(a) Under CELGENE's Rights. If CELGENE grants a sublicense
of its exclusive rights under this Agreement, pursuant
to Section 2.3 of this Agreement, in any country(ies) of
the TERRITORY, CELGENE shall pay to ENTREMED (i) "..."
of any non-royalty consideration, including but not
limited to any sublicensing and/or milestone payments
received by CELGENE pursuant to such sublicense and (ii)
"..." of the royalty income paid by SUBLICENSEES to
CELGENE on NET SALES of PRODUCTS.
(b) CELGENE-ENTREMED Cooperation. If CELGENE grants a
sublicense of any of its rights under this Agreement in
any area of the FIELD or any country of the TERRITORY
with respect to which ENTREMED and CELGENE are
cooperating pursuant to Sections 3.2 or 3.3 of this
Agreement, CELGENE shall pay to ENTREMED "..." of any
non-royalty consideration, including but not limited to
any sublicensing and/or milestone payments received by
CELGENE pursuant to such sublicense. CELGENE shall also
pay to ENTREMED, as applicable, the following: (i) if
CELGENE and ENTREMED are cooperating in any country(ies)
pursuant to Section 3.2 of this Agreement, "..." of the
royalty income paid by SUBLICENSEES to CELGENE on NET
SALES, in such country(ies), of PRODUCTS; and (ii) if
CELGENE and
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ENTREMED are cooperating in any country(ies) with regard
to PRODUCTS for use in animals pursuant to Section 3.3
of this Agreement, "..." of the royalty income paid by
SUBLICENSEES to CELGENE on NET SALES in such
country(ies) of such PRODUCTS.
4.3 Later-Issued VALID CLAIM. In the event that there is no ISSUED
VALID CLAIM of a PATENT RIGHT in a country within the
TERRITORY on the date the twelve (12) year period provided for
in Section 4.1(a) of this Agreement expires, no royalties
shall be owed by CELGENE to ENTREMED under Sections 4.1(b) and
4.2 of this Agreement on PRODUCTS sold by CELGENE or its
AFFILIATES in such country, provided, however, that if a VALID
CLAIM of a PATENT RIGHT thereafter issues in such country,
CELGENE shall pay ENTREMED royalties on the NET SALES in such
country of PRODUCTS covered by an ISSUED VALID CLAIM of the
PATENT RIGHTS that are sold by CELGENE or its AFFILIATES,
according to the royalty rates set forth in Sections 4.1(b)
and 4.2 of this Agreement, and such royalties under this
Section 4.3 shall be payable until the last to expire PATENT
RIGHT containing an ISSUED VALID CLAIM covering the PRODUCTS
sold by CELGENE, its AFFILIATES or SUBLICENSEE in such
country.
4.4 "..."
4.5 THIRD PARTY Sales. In any country where sales by a THIRD PARTY
of a PRODUCT(s) for a similar dosage form and/or route of
administration:
(a) are equal to or greater than "..." of the dollar market
share for such PRODUCT in such country ("MARKET SHARE"),
but less than "..." of the MARKET SHARE, then the
royalty payable to
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ENTREMED pursuant to Sections 4.1 and 4.3 of this
Agreement shall be reduced by "...";
(b) are equal to or greater than "..." of the MARKET SHARE,
but less than "..." of the MARKET SHARE, then the
royalty payable to ENTREMED pursuant to Sections 4.1 and
4.3 of this Agreement shall be reduced by "...";
(c) are equal to or greater than "..." of the MARKET SHARE,
but less than "..." of the MARKET SHARE, then the
royalty payable to ENTREMED pursuant to set Sections 4.1
and 4.3 of this Agreement shall be reduced by "..."; and
(d) are equal to or greater than "..." of the MARKET SHARE,
then the royalty payable to ENTREMED pursuant to
Sections 4.1 and 4.3 of this Agreement shall be reduced
by "...";
provided that royalties payable to ENTREMED shall never be
reduced below "..." of NET SALES in each royalty bracket. For
purposes of this Section 4.5, oral dosage forms shall include,
without limitation, all capsule, caplet, tablet, and liquid
formulations for oral administration.
4.6 Recordkeeping. CELGENE shall keep, and shall cause each of its
AFFILIATES and SUBLICENSEES to keep, full and accurate books
of account containing all particulars relevant to its sales of
PRODUCTS that may be necessary for the purpose of calculating
all royalties payable to ENTREMED. Such books of account shall
be kept at their principal place of business and, with all
necessary supporting data shall, for the three (3) years next
following the end of the calendar year to which each shall
pertain, be open for inspection by an independent certified
public accountant reasonably acceptable to CELGENE, upon
reasonable notice during normal business hours at ENTREMED'S
expense for the sole purpose of verifying royalty statements
or compliance with this Agreement. In the event the inspection
determines that royalties due
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ENTREMED for any period have been underpaid by five percent
(5%) or more, then CELGENE shall pay for all costs of the
inspection. In all cases, CELGENE shall pay to ENTREMED any
underpaid royalties promptly and with interest at the prime
rate available to ENTREMED from its bank plus two percent
(2%). All information and data reviewed in the inspection
shall be used only for the purpose of verifying royalties and
shall be treated as CELGENE CONFIDENTIAL INFORMATION subject
to the obligations of this Agreement. No audit by an agent of
ENTREMED shall occur more frequently than once during any
twelve (12) month period.
4.7 Quarterly Payments and Reports. In each year the amount of
royalty due shall be calculated quarterly as of the end of
each CALENDAR QUARTER and shall be paid quarterly within the
forty-five (45) days next following such date. Every such
payment shall be supported by the accounting described in
Section 4.8 of this Agreement. All royalties due ENTREMED are
payable in United States dollars. When PRODUCTS are sold for
currency other than United States dollars, the earned
royalties will first be determined in the foreign currency of
the country in which such PRODUCTS were sold and then
converted into equivalent United States funds. The exchange
rate will be that rate quoted in the Wall Street Journal on
the last business day of the CALENDAR QUARTER in which such
sales were made.
4.8 Accounting Reports. With each quarterly payment, CELGENE shall
deliver to ENTREMED a full and accurate accounting to include
at least the following information:
(a) Quantity of PRODUCT subject to royalty sold, by country,
by CELGENE, its AFFILIATES or SUBLICENSEES;
(b) Total receipts for each PRODUCT subject to royalty, by
country and, to the extent used in any royalty
calculations during such
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quarter, the exchange rate set forth in Section 4.7 of
this Agreement;
(c) Compensation on PRODUCTS received from SUBLICENSEES
pursuant to a sublicense of CELGENE's rights under this
Agreement; and
(c) Total royalties and/or compensation payable to ENTREMED.
SECTION 5 - CONFIDENTIALITY
5.1 Confidential Information. During the term of this Agreement,
it is contemplated that each party may disclose to the other,
proprietary and confidential technology, inventions, technical
information, material, reagents, biological materials and the
like which are owned or controlled by the party providing such
information or which that party is obligated to maintain in
confidence and which is designated by the party providing such
information as confidential ("CONFIDENTIAL INFORMATION"). Each
party agrees not to disclose the CONFIDENTIAL INFORMATION and
to maintain the CONFIDENTIAL INFORMATION in strict confidence,
to cause all of its agents, representatives and employees to
maintain the disclosing party's CONFIDENTIAL INFORMATION in
confidence and not to disclose any such CONFIDENTIAL
INFORMATION to a THIRD PARTY without the prior written consent
of the disclosing party, and not to use such CONFIDENTIAL
INFORMATION for any purpose other than as provided under this
Agreement. The secrecy obligations of the parties with respect
to CONFIDENTIAL INFORMATION shall continue for a period ending
ten (10) years from the termination of this Agreement.
5.2 Non-Confidential Information. The obligations of
confidentiality will not apply to information that:
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(a) was known to the receiving party or generally known to
the public prior to its disclosure hereunder through no
fault of the disclosing party or any agent,
representative or employee thereof; or
(b) subsequently becomes known to the public by some means
other than a breach of this Agreement, including
publication and/or laying open to inspection of any
patent applications or patents;
(c) is subsequently disclosed to the receiving party by a
THIRD PARTY having a lawful right to make such
disclosure and who is not under an obligation of
confidentiality to the disclosing party;
(d) is required by law, rule, regulation or bona fide legal
process to be disclosed, provided that the disclosing
party takes all reasonable stem to restrict and maintain
confidentiality of such disclosure and provides
reasonable notice to the non-disclosing party; or
(e) is approved for release by the parties.
5.3 Disclosure To THIRD PARTIES. The obligations of Section 5.1
notwithstanding, CELGENE or ENTREMED, as the case may be, may
disclose the CONFIDENTIAL INFORMATION licensed hereunder to
THIRD PARTIES
(a) who need to know the same in order to obtain regulatory
approval for a PRODUCT under this Agreement, provided
that the actions of such THIRD PARTY are not in conflict
with CELGENE's rights under this Agreement,
(b) who need to know the same in order to work towards the
commercial development of PRODUCT on behalf of CELGENE,
or
(c) for whom the non-disclosing party, ENTREMED or CELGENE,
as the case may be, has given prior written approval
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provided that such THIRD PARTIES are bound by
obligations of confidentiality and non-use at least as
stringent as those set forth herein.
5.4 Disclosure To Sublicensees. CELGENE may disclose
ENTREMED's CONFIDENTIAL INFORMATION to a SUBLICENSEE
without ENTREMED's approval, provided that such
SUBLICENSEES are bound by obligations of confidentiality
and non-use at least as stringent as those set forth
herein.
5.5 Public Statements. Neither CELGENE nor ENTREMED may
issue a public statement, including without limitation a
press release, with regard to this Agreement without the
prior written consent of the other party, which consent
shall not be unreasonably withheld. In accordance with
the rules and regulations promulgated by the Securities
and Exchange Commission, the parties will request that
this Agreement be treated as confidential.
SECTION 6 - ADVERSE MEDICAL EXPERIENCES
6.1 Adverse Medical Experience Reporting. CELGENE shall
comply fully with all applicable medical/adverse
experience reporting requirements in all countries where
CELGENE intends to carry out clinical trials and/or
market PRODUCT.
SECTION 7 - PATENTS
7.1 Patent Prosecution.
(a) ENTREMED shall use reasonable efforts to prepare,
file, prosecute and maintain patent applications
and patents directed to PATENT RIGHTS and PRODUCTS
through patent counsel selected by ENTREMED and
reasonably acceptable to CELGENE, who shall
consult with and keep CELGENE advised with respect
thereto.
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(b) CELGENE shall reimburse ENTREMED for all
reasonable costs and expenses incurred after the
EFFECTIVE DATE for the filing, prosecution and
maintenance of PATENT RIGHTS.
7.2 Cooperation In Prosecution.
(a) With respect to any PATENT RIGHTS, each patent
application, office action, response to office
action, request for terminal disclaimer, petition,
and request for reissue or reexamination of any
patent issuing from such application shall be
provided to CELGENE sufficiently prior to the
filing of such application, response, petition, or
request to allow for review and comment by
CELGENE. ENTREMED shall have the right to take any
action that, in its judgement, is necessary to
preserve such PATENT RIGHTS.
(b) Within a reasonable time from the EFFECTIVE DATE,
CELGENE and ENTREMED will discuss each party's
patent portfolio with regard to PRODUCTS, in
accordance with prior obligations of
confidentiality owed by each party to any THIRD
PARTY, and will use reasonable efforts to
coordinate their respective patent portfolio, to
the extent possible, so as to maximize the patent
protection for PRODUCTS.
7.3 Infringement and Declaratory Judgment Actions.
(a) Notification. In the event that either party
learns of the infringement of any PATENT RIGHT, or
the filing of a Declaratory Judgement action
alleging the invalidity, unenforceability, or
noninfringement of any PATENT RIGHT ("DJ ACTION"),
that party must promptly notify the other party of
the infringement or DJ ACTION, as the case may be,
in writing, and must provide reasonable evidence
of the infringement. Neither
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party will notify a THIRD PARTY of the infringement of
any PATENT RIGHT or of the filing of a DJ ACTION
directed to any PATENT RIGHT without first obtaining
consent of the other party, which consent shall not be
unreasonably withheld.
(b) CELGENE's Right To File Infringement Actions. To the
extent ENTREMED has the right to bring a suit or action
to compel the termination of infringement of the PATENT
RIGHTS, including to the extent provided in Article 7 of
the CMCC AGREEMENT, ENTREMED hereby grants CELGENE the
right and option, but not the obligation, to bring an
action for infringement or to defend against a DJ
action, at its sole expense, in the name of ENTREMED
and/or in the name of CELGENE, and to join ENTREMED as a
party plaintiff if required. No settlement, consent
judgment or other voluntary final disposition of a suit
that adversely affects PATENT RIGHTS may be entered into
without the consent of ENTREMED, which consent shall not
be unreasonably withheld.
(c) CELGENE's Right To Defend DJ ACTIONS. In the event that
a DJ ACTION is brought naming CELGENE as a defendant,
CELGENE shall have the right to proceed with the
litigation or settle such action provided, however, that
no settlement, consent judgment or other voluntary final
disposition of a suit that adversely affects PATENT
RIGHTS may be entered into without the consent of
ENTREMED, which consent shall not be unreasonably
withheld.
(d) CELGENE's Recovery. In the event that CELGENE shall
undertake the enforcement and/or defense of the PATENT
RIGHTS by litigation, any recovery of damages by CELGENE
for any such litigation shall be applied first in
satisfaction of any
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unreimbursed expenses and legal fees of CELGENE relating
to the suit. The balance remaining from any such
recovery shall, after ENTREMED receives its royalties
from lost sales, belong to CELGENE.
(e) ENTREMED's Right To Litigate. In the event that CELGENE
elects not to pursue an action for infringement or to
defend against a DJ action, as the case may be, CELGENE
shall notify ENTREMED in writing of such election and
ENTREMED shall have the right and option, but not the
obligation, at its cost and expense, to initiate
infringement litigation and to retain any recovered
damages.
(f) Cooperation. In any infringement suit either party may
institute to enforce or defend the PATENT RIGHTS
pursuant to this Agreement, the other party hereto
shall, at the request of the party initiating such suit,
cooperate in all respects and, to the extent possible,
have its employees testify when requested and make
available relevant records, papers, information,
samples, specimens, and the like. All reasonable
out-of-pocket costs incurred in connection with
rendering cooperation requested hereunder shall be paid
by the party requesting cooperation.
(g) THIRD PARTY Royalty Reduction. In the event that an
infringement action is brought by a THIRD PARTY against
CELGENE alleging that CELGENE's making, using, offering
to sell, selling, or importing of PRODUCTS under the
PATENT RIGHTS infringes a THIRD PARTY patent, and
results in a judgment or settlement requiring royalties
to be paid by CELGENE to such THIRD PARTY, the royalties
owed by CELGENE to ENTREMED under Section 4 of this
Agreement shall be reduced by an amount equal to "..."
of the royalties owed
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to such THIRD PARTY, provided that the royalties owed to
ENTREMED shall not be reduced under this Section 7.3(f)
to less than "..." of NET SALES, nor shall any specific
royalty payment be reduced under this Section 7.3(g) by
more than "...".
SECTION 8 - REPRESENTATIONS AND WARRANTIES.
8.1 By Both Parties. Each party hereby represents and warrants
that each has the full right and authority to enter into this
Agreement and that the entry into this Agreement does not
require the consent of a THIRD PARTY whose consent has not
been obtained.
8.2 By ENTREMED. ENTREMED represents and warrants as follows:
(a) that ENTREMED has not received any notice of
infringement of THIRD PARTY patents or notice of
interfering subject matter; that, without having made
any special investigation, ENTREMED is not aware of any
THIRD PARTY patents or patent applications that contain
any interfering subject matter, or any issued THIRD
PARTY patents that would be infringed by the making,
using, selling, offering for sale, or importing by
CELGENE of PRODUCTS covered by the ENTREMED EXISTING
PATENT RIGHTS or the ENTREMED EXISTING TECHNOLOGY RIGHTS
in any country in the TERRITORY, or by the exercise by
CELGENE of any right granted to it under this Agreement,
aside from those set forth in Appendix D;
(b) that the PATENT RIGHTS set forth in Appendix A and the
TECHNOLOGY RIGHTS transferred to CELGENE under this
Agreement, constitute the entirety of ENTREMED EXISTING
PATENT RIGHTS and ENTREMED EXISTING TECHNOLOGY RIGHTS;
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(c) that ENTREMED presently has no rights in PRODUCTS, nor
any option in or expectation of any rights in PRODUCTS,
apart from those identified in this Agreement and set
forth in the agreements listed in Appendix B, and that
ENTREMED is not in material breach or default of any of
the agreements set forth in Appendix B, and that if
ENTREMED acquires any such rights after the EFFECTIVE
DATE, the agreements setting forth those rights,
including all licenses and assignments for ENTREMED
DEVELOPED PATENT RIGHTS and ENTREMED DEVELOPED
TECHNOLOGY RIGHTS, shall be redacted to the extent they
do not relate to CELGENE's rights under this Agreement,
and attached hereto as independent Exhibits and
incorporated herein;
(d) that, with regard to PRODUCTS, ENTREMED has no
applications filed or pending with the FDA as of the
EFFECTIVE DATE, including without limitation any
Investigational New Drug or Orphan Drug Status
applications, apart from those set forth in Appendix C;
(e) that ENTREMED will comply with all obligations and
duties with regard to PRODUCTS under the CMCC AGREEMENT
and, unless and until it is assigned to CELGENE pursuant
to Section 2.5 of this Agreement, the NCI AGREEMENT,
including, without limitation, any notification
provisions necessary to maintain in effect this
Agreement or preserve CELGENE's exclusive or
non-exclusive rights under this Agreement, including
without limitation the preservation of CELGENE's rights
hereunder in the event that ENTREMED shall breach or
default on its obligations under the CMCC AGREEMENT or
the NCI AGREEMENT;
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(f) that ENTREMED understands and agrees that it has not
retained any rights under the ENTREMED INTELLECTUAL
PROPERTY to PRODUCTS in the TERRITORY, and that the
licenses and assignments granted in Sections 2.1, 2.2,
2.4, and 2.5 of this Agreement are exclusive of any
continuing right of ENTREMED, except as otherwise
provided herein; and
(g) that ENTREMED will not collaborate, negotiate, or deal
with THIRD PARTIES with respect to PRODUCTS, except as
expressly provided herein.
8.3 EXCEPT AS OTHERWISE EXPRESSLY SET FORTH HEREIN, ENTREMED MAKES
NO REPRESENTATIONS OR EXTENDS ANY WARRANTIES OF ANY KIND
EITHER EXPRESS OR IMPLIED, INCLUDING, BUT NOT LIMITED TO,
WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR
PURPOSE, NON-INFRINGEMENT OR VALIDITY OF ANY ENTREMED PATENT
OR OTHER INTELLECTUAL PROPERTY RIGHTS.
SECTION 9 - INDEMNIFICATION AND INSURANCE
9.1 By CELGENE. CELGENE will defend, indemnify and hold harmless
ENTREMED, its successors, AFFILIATES and licensors and their
employees, agents, officers, trustees, shareholders and
directors and each of them (the "ENTREMED Indemnified
Parties") from and against any and all THIRD PARTY claims,
causes of action and costs (including reasonable attorney's
fees) of any nature made or lawsuits or other proceedings
filed or otherwise instituted against the ENTREMED Indemnified
Parties in connection with any claims, suits or judgments
arising out of any theory of product liability concerning the
development, testing, manufacture, sale or use of any PRODUCT
by CELGENE, its AFFILIATES or its SUBLICENSEES.
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9.1.1 CELGENE's indemnification under this Section 9.1
shall not apply to any liability, damage, loss or
expense to the extent that it is directly
attributable to the negligent activity, reckless
misconduct or intentional misconduct of ENTREMED.
9.1.2 Commencing not later than the date of FIRST
COMMERCIAL SALE of a PRODUCT, CELGENE shall
obtain and carry in full force and effect product
liability insurance against any claims,
judgments, liabilities and expenses for which it
is obligated to indemnify ENTREMED and others
under Section 9.1 of this Agreement, in such
amounts and with such deductibles as are
customary at the time for companies engaged in a
similar business, and shall provide ENTREMED with
written evidence of such insurance upon request.
9.2 By ENTREMED. ENTREMED will defend, indemnify and hold harmless
CELGENE, its successors, AFFILIATES and licensors and their
employees, agents, officers, trustees, shareholders and
directors and each of them (the "CELGENE Indemnified Parties")
from and against any and all THIRD PARTY claims, causes of
action and costs (including reasonable attorney's fees) of any
nature made or lawsuits or other proceedings filed or
otherwise instituted against the CELGENE Indemnified Parties
in connection with any claims, suits or judgments arising out
of any theory of product liability concerning the development,
testing, manufacture, sale or use of any PRODUCT by ENTREMED,
its AFFILIATES or its SUBLICENSEES prior to the EFFECTIVE
DATE.
9.2.1 ENTREMED's represents and warrants that it presently
carries, in full force and effect, and will continue to
carry, product liability insurance against any claims,
judgments, liabilities and expenses incurred in
connection with the use of THALIDOMIDE in clinical
trials by or on behalf of
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ENTREMED, and shall provide CELGENE with written
evidence of such insurance upon request.
9.3 Conditions to Indemnification. A person or entity that intends
to claim indemnification under this Section 9 (the
"Indemnitee") shall promptly notify the party from whom
indemnification is sought (the "Indemnitor"), of any loss,
claim, damage, liability or action in respect of which the
Indemnitee intends to claim such indemnification, and the
Indemnitor shall assume the defense thereof with counsel
mutually satisfactory to the Indemnitee whether or not such
claim is rightfully brought; provided, however, that an
Indemnitee shall have the right to retain its own counsel,
with the fees and expenses to be paid by the Indemnitor if
Indemnitor does not assume the defense, or if representation
of such Indemnitee by the counsel retained by the Indemnitor
would be inappropriate due to actual or potential differing
interests between such Indemnitee and any other person
represented by such counsel in such proceedings. The failure
to deliver notice to the Indemnitor within a reasonable time
after the commencement of any such action, only if prejudicial
to its ability to defend such action, shall relieve such
Indemnitor of any liability to the Indemnitee under this
Section 9, but the omission so to deliver notice to the
Indemnitor will not relieve it of any liability that it may
have to any Indemnitee otherwise than under this Section 9.
The Indemnitee under this Section 9, its employees and agents,
shall cooperate fully with the Indemnitor and its legal
representatives in the investigations of any action, claim or
liability covered by this indemnification.
SECTION 10 - ASSIGNMENT AND SUCCESSORS
10.1 By Either Party. This Agreement shall not be assignable by
either party without the written consent of the other party,
except that either party may assign this Agreement to an
AFFILIATE, successor in interest or
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transferee of all or substantially all of the portion of the
business to which this Agreement relates without the consent
of the other party.
10.2 By CELGENE. If CELGENE assigns or licenses its rights under
this Agreement to a SUBLICENSEE or an AFFILIATE, such
SUBLICENSEE or AFFILIATE shall be bound by the terms and
conditions of this Agreement. CELGENE shall advise ENTREMED of
any such assignment or license and provide ENTREMED with a
copy of any sublicense within thirty (30) days of execution of
such sublicense.
10.3 CELGENE As Guarantor. CELGENE shall guarantee and be
responsible for the payment of all royalties due and the
making of reports under this Agreement by reason of the
development and sales of any PRODUCTS by CELGENE, its
AFFILIATES and SUBLICENSEES and their compliance with all
applicable terms of this Agreement. Performance or
satisfaction of any obligations of CELGENE under this
Agreement by any of its AFFILIATES or SUBLICENSEES shall be
deemed performance or satisfaction of such obligation by
CELGENE.
10.4 Binding Effect. This agreement shall be binding upon and inure
to the benefit of said successors in interest and assignees to
the parties. Any such successor or assignee of a party's
interest shall expressly assume in writing the performance of
all the terms and conditions of this Agreement to be performed
by said party and such Assignment shall not relieve the
Assignor of any of its obligations under this Agreement.
SECTION 11 - FORCE MAJEURE
11.1 Neither party shall be liable to the other party for damages
or loss occasioned by failure of performance by the defaulting
party if the failure is occasioned by war, fire, explosion,
flood, strike or lockout, embargo, or any similar cause beyond
the control of the defaulting party, provided that the party
claiming this exception has exerted all reasonable efforts to
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avoid or remedy such event and provided such event does not
extend for more than six (6) months.
SECTION 12 - TERMINATION
12.1 Term. Unless earlier terminated as hereinafter provided, this
Agreement shall remain in full force and effect until
CELGENE's obligations to pay royalties or other compensation
under Section 4 of this Agreement, either directly or pursuant
to a sublicense, terminate.
12.2 By Reason Of FDA Action. If the FDA withdraws or recalls
THALIDOMIDE from the market permanently, or in any other way
revokes or terminates CELGENE's regulatory approval to market
and sell THALIDOMIDE and/or PRODUCTS, CELGENE shall promptly
notify ENTREMED in writing, and this Agreement and all of
CELGENE's and ENTREMED's rights and obligations hereunder
shall terminate upon receipt by ENTREMED of such notice.
12.3 Termination Of Royalty Obligations. Upon termination of
CELGENE's obligation to pay royalties and other compensation
hereunder with respect to a specific country and specific
PRODUCT as to which CELGENE's license is then in effect, the
license granted to CELGENE with respect to such country and
such PRODUCT pursuant to Section 2 shall be deemed to be fully
paid and CELGENE shall thereafter have a royalty free,
exclusive right to use the PATENT RIGHTS to make, have made,
use, offer to sell, sell and import such PRODUCT in such
country.
12.4 Breach.
(a) By Either Party. This Agreement shall be terminable upon
the material breach or default of either party. In the
event of a material breach or default by a party
("Defaulting Party"), the other party ("Non-Defaulting
Party") shall give the Defaulting Party written
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notice of the default. The Defaulting Party will then
have sixty (60) days to cure the breach. If cure has
not been affected within said sixty (60) days, the
Non-Defaulting Party shall have the right to terminate
this Agreement.
(b) By CELGENE.
(i) Payments. If and only if CELGENE materially
breaches this Agreement by failure to pay
royalties and/or sublicensing or milestone
payments due under Section 4 of this Agreement,
and fails to cure such material breach within
sixty (60) days of receiving written notice
thereof pursuant to Section 12.4(a) of this
Agreement then:
a) CELGENE's rights under this Agreement to
ENTREMED INTELLECTUAL PROPERTY shall
terminate; and
b) CELGENE shall grant to ENTREMED, to the
extent not prohibited by the United States
Government or by prior contractual
obligations to any THIRD PARTY, an
exclusive, worldwide, royalty-free license,
with the right to sublicense, under CELGENE
DEVELOPED INTELLECTUAL PROPERTY to make,
use, offer to sell, sell, and import
PRODUCTS in the TERRITORY.
(ii) Diligence. If and only if ENTREMED exercises its
right and option to terminate the license granted
to CELGENE in the entire TERRITORY, pursuant to
Section 3.1(f) of this Agreement, or ENTREMED
exercises its right and option to terminate the
license granted to CELGENE in Europe, Canada, or
the PACIFIC RIM, pursuant to Section 3.2(c)(i) of
this Agreement, then, either in the entire
TERRITORY
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or in the region in which such termination has
occurred, i.e., Europe, Canada, or the PACIFIC
RIM, as applicable:
a) CELGENE's rights under this Agreement to
ENTREMED INTELLECTUAL PROPERTY shall
terminate; and
b) CELGENE shall grant to ENTREMED, to the
extent not prohibited by the United States
Government or by prior contractual
obligations to any THIRD PARTY, an
exclusive, worldwide, royalty-free license,
with the right to sublicense, under CELGENE
DEVELOPED INTELLECTUAL PROPERTY to make,
use, offer to sell, sell, and import
PRODUCTS.
The grant of rights by CELGENE to ENTREMED under this
Section 12.4 expressly excludes rights in any CELGENE
EXISTING INTELLECTUAL PROPERTY.
(c) Termination under this Section 12.4 will be effective
upon the date specified in the written notice. All
termination rights shall be in addition to and not in
substitution for any other remedies that may be
available to the Non-Defaulting Party. Termination
pursuant to this Section 12.4 shall not relieve the
Defaulting Party from liability and damages to the
Non-Defaulting Party for default. Waiver by either party
of a single default or a succession of defaults shall
not deprive such party of any right to terminate or
convert this Agreement arising by reason of any
subsequent default.
12.5 Insolvency. Either party to this Agreement may terminate this
Agreement upon receipt of notice that the other party has
become insolvent or has suspended business in all material
respects hereof, or has consented to an involuntary petition
purporting to be pursuant to any reorganization or insolvency
law of any jurisdiction, or has made an assignment for the
benefit of creditors or has applied for or consented to the
appointment of a
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receiver or trustee for a substantial part of its property, by
giving written notice to the other party, and termination of
this Agreement will be effective upon receipt of such notice.
12.6 Work-In-Progress. Upon termination of this Agreement, CELGENE
shall be entitled to, but shall not be obligated to finish any
work-in-progress at the time of termination and sell the same
as well as all completed inventory of PRODUCTS which remains
on hand as of the date of the termination, so long as CELGENE
pays to ENTREMED the royalties applicable to said subsequent
sales in accordance with the same terms and conditions as set
forth in this Agreement.
12.7 Survival. The obligations of Sections 5 and 9, as well as
Sections 12.6, 12.7, 12.8, and 13.3, shall survive any
termination of this Agreement.
12.8 Reversion of Rights. Upon termination of this Agreement or of
the rights and licenses granted to CELGENE in any country of
the TERRITORY, CELGENE agrees not to use the TECHNOLOGY RIGHTS
or PATENT RIGHTS or information or technology derived
therefrom for the manufacture, use or sale of PRODUCTS in any
country other than those countries in which CELGENE retains a
license under this Agreement. In addition, all rights to the
TECHNOLOGY RIGHTS and PATENT RIGHTS in such country shall
revert to ENTREMED and may be used by ENTREMED without
restriction in any country other than those countries in which
CELGENE retains a license under this Agreement.
SECTION 13 - GENERAL PROVISIONS
13.1 Relationship of Parties. The relationship between ENTREMED and
CELGENE is that of independent contractors. ENTREMED and
CELGENE are not joint venturers, partners, principal and
agent, master and servant, employer or employee, and have no
relationship other than as independent contracting parties.
ENTREMED shall have no power to bind
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or obligate CELGENE in any manner. Likewise, CELGENE shall
have no power to bind or obligate ENTREMED in any manner.
13.2 Entire Understanding. This Agreement sets forth the entire
agreement and understanding between the parties as to the
subject matter thereof and supersedes all prior agreements in
this respect. There shall be no amendments or modifications to
these Agreements, except by a written document which is signed
by both parties.
13.3 Governing Law. This Agreement shall be construed and enforced
in accordance with the laws of the State of Delaware, U.S.A.
without reference to its choice of law principles.
13.4 Headings. The headings in this Agreement have been inserted
for the convenience of reference only and are not intended to
limit or expand on the meaning of the language contained in
the particular or section or paragraph.
13.5 No Waiver. Any delay in enforcing a party's rights under this
Agreement or any waiver as to a particular default or other
matter shall not constitute a waiver of a party's right to the
future enforcement of its rights under this Agreement,
excepting only as to an expressed written and signed waiver as
to a particular matter for a particular period of time.
13.6 Export Controls. In conducting any activities under this
Agreement or in connection with the manufacture use or sale of
PRODUCT, CELGENE shall comply with all applicable laws and
regulations including, but not limited to, all Export
Administration Regulations of the United States Department of
Commerce.
13.7 Notices. Any notices given pursuant to this Agreement shall be
in writing and shall be deemed delivered upon the earlier of
(i) when received at the address set forth below, or (ii)
three (3) business days after mailed by certified or
registered mail postage prepaid and properly addressed, with
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return receipt requested, or (iii) when sent, if sent by
facsimile, as confirmed by certified or registered mail.
Notices shall be delivered to the respective parties as
indicated below:
If To ENTREMED EntreMed, Inc.
9610 Medical Center Drive
Rockville, MD 20850
Attn: CEO
Fax: (301) 217-9594
If To CELGENE: Celgene Corporation
6 Powder Horn Drive
Warren, NJ 07059
Attn: President
Fax: (732) 805-3931
13.8 Original Counterparts. This Agreement may be executed in any
number of separate counterpart, each of which shall be deemed
to be an original, but which together shall constitute one and
the same instrument.
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IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date set forth above.
ENTREMED, INC. CELGENE CORPORATION
By: /s/ Edward R. Gubish By: /s/ John W. Jackson
------------------------------- --------------------------
Name: Edward R. Gubish Name: John W. Jackson
-------------------------------- ---------------------------
Title: Sr. V.P. R & D Title: Chairman & CEO
------------------------------- --------------------------
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APPENDIX A
United States Patent No. 5,629,327
United States Patent No. 5,593,990
United States Patent Application Serial No. 08/025,046
United States Patent Application Serial No. 08/168,817
United States Patent Application Serial No. 08/371,987
United States Patent Application Serial No. 08/468,792
United States Patent Application Serial No. 08/918,610
United States Patent Application Serial No. 08/955,638
United States Patent Provisional Application Serial No. 60/028,708
United States Patent Application Serial No. 08/963,058
United States Patent Application Serial No. 09/107,578
United States Patent Application Serial No. 09/126,542
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APPENDIX B
1. That certain License Agreement entered into by and between ENTREMED and
Children's Medical Center Corporation ("CMCC"), dated May 26, 1994, as
amended to the date hereof, attached as Exhibit A to this Agreement.
2. That certain Agreement by and between the Division of Cancer Treatment
at the National Cancer Institute ("NCI") and ENTREMED, dated November
16, 1994, and executed on behalf of ENTREMED on November 23, 1994, and
on behalf of NCI on November 18, 1994, attached as Exhibit C to this
Agreement.
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APPENDIX C
Orphan Drug Designation Application (ODA) 97-1011 Primary Brain Malignancies
Orphan Drug Designation Application (ODA) 98-1149 Kaposis Sarcoma
Orphan Drug Designation Application (ODA) 98-1143 Prostate Cancer
Investigational New Drug Application 46,591 Ophthalmology
Investigational New Drug Application 55,966 Oncology
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APPENDIX D
United States Patent No. 5,605,684 to Piacquadio
United States Patent No. 5,443,824 to Piacquadio
United States Patent No. 5,731,325 to Andrulis, Jr. et al.
United States Patent No. 5,654,312 to Andrulis, Jr. et al.
United States Patent No. 5,643,915 to Andrulis, Jr. et al.
United States Patent No. 5,434,170 to Andrulis, Jr.
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EXHIBIT A
CMCC AGREEMENT
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EXHIBIT B
NCI AGREEMENT
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EXHIBIT C
LETTER TO FDA INDICATING TRANSFER OF
RIGHTS IN INVESTIGATIONAL NEW DRUG
AND ORPHAN DRUG APPLICATIONS TO CELGENE
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