1
Exhibit 10.33
ENTREMED, INC.
CHILDREN'S HOSPITAL RESEARCH AGREEMENT
This Agreement ("Agreement") entered into this 24th day of June, 1999
(the "Effective Date"), by and between Children's Hospital, 300 Longwood Avenue,
Boston, Massachusetts 02115-5737 ("Hospital"), and EntreMed, Inc., 9640 Medical
Center Drive, Suite 200, Rockville, Maryland 20850 ("EntreMed")
WHEREAS, Hospital owns certain inventions that may be useful in the
treatment of diseases in humans or animals and is interested in having a
corporate sponsor and licensee to clinically develop these inventions;
WHEREAS, EntreMed is interested in funding and/or implementing the
clinical development of certain of the inventions in return for options for
licensing certain of the inventions;
WHEREAS, Hospital and EntreMed entered into a Children's Hospital
Research Agreement dated September 29, 1993, as amended on August 23, 1995 (the
"1993 Agreement);
WHEREAS, the parties now wish to amend and restate the 1993 Agreement in
its entirety as of the Effective Date by entering into three agreements dated
June 24, 1999; and
WHEREAS, the research program contemplated by this Agreement is of mutual
interest and benefit to Hospital and to EntreMed and may further the practice of
medicine and the research agenda of the Hospital in a manner consistent with its
status as a non-profit, tax-exempt, teaching Hospital.
NOW, THEREFORE, the parties agree as follows:
1. Scope of Work
(a) Hospital agrees to use reasonable efforts to perform the Research
and Clinical Development Program entitled "Angiogenesis Research
Program" ("Program") in accordance with Exhibit A, attached hereto
and made a part of this Agreement as the same may be amended by
the parties from time to time.
(b) Any alteration in or amendment to the Program must be approved in
writing by both Hospital and EntreMed prior to such alteration or
amendment being effective.
2. Period of Performance
(a) The Program shall be conducted during the period beginning on the
Effective Date, through September 29, 2000, and will be subject to
renewal only by written mutual agreement of EntreMed and Hospital.
1
2
3. Principal Investigator
(a) The Principal Investigator for the Program will be Dr. M. Judah
Folkman ("Principal Investigator") of the Department of Surgery.
In the event the Principal Investigator becomes unable to complete
the Program for any reason, EntreMed and Hospital may mutually
agree upon a substitute Principal Investigator, in which event
this Agreement shall continue in full force and effect. If
EntreMed and Hospital cannot agree on a substitute, either party
may immediately thereafter terminate this Agreement, subject to
the requirements of Section 11(f) of this Agreement.
4. Research Program Support
(a) Primary Program Support. EntreMed agrees to pay Hospital One
Million Four Hundred Thousand Dollars ($1,400,000) to fund the
Program in accordance with the conditions and terms of this
Agreement.
(b) Payments. On September 29, 1999, EntreMed will pay Hospital the
sum of $700,000 and thereafter will make one additional payment of
$700,000 on March 29, 2000, in accordance with the conditions and
terms set forth herein.
(c) Payments. Payments of all sums due hereunder shall be made by
check payable as follows:
Children's Hospital
Research Finance Office
300 Longwood Avenue
Boston, MA 02115-5737
(d) Late Payments. Late payments shall bear interest from the due date
until payment at a rate of the lower of one and one-half percent
(1 1/2%) per month, or the maximum amount permitted by law. The
payment of such interest shall not forclose Hospital from
exercising any other rights it may have as a consequence of the
lateness of any payment, including without limitation termination
under Article 11(d).
5. Equipment
(a) Equipment purchased as part of the Program shall be owned by
the Hospital, shall be physically located at the Hospital, and
shall remain as property of the Hospital following completion of
the Program.
6. Publications
(a) EntreMed acknowledges that Hospital is an academic medical center
and that Dr. Folkman and his collaborators shall be free to
publish results of their studies without restraint.
Notwithstanding this, Hospital agrees to send EntreMed copies of
any manuscripts resulting from the Program and submitted for
consideration for publication or any abstracts that are submitted
to a conference no later than the same day the manuscript or
abstract is submitted. Hospital agrees to use reasonable efforts
2
3
to notify EntreMed at least one month in advance of any instances where
the results of the Program will be presented at a conference by
invitation and without abstract. EntreMed will notify Hospital if any
action is necessary to secure patent protection for the technology and
Hospital agrees to take such action, subject to the terms and conditions
hereof. If EntreMed so elects, Hospital agrees to include in any
publication of the results of the Program acknowledgment of EntreMed's
financial and technical support.
7. Intellectual Property
(a) Any invention conceived or first reduced to practice by Hospital
or Hospital personnel in the performance of the Program shall be
owned by Hospital ("Invention"). Any invention conceived or first
reduced to practice by EntreMed or EntreMed personnel at
EntreMed's facilities during the term of this Agreement shall be
owned by EntreMed. Any invention conceived or first reduced to
practice jointly by Hospital or Hospital personnel and EntreMed or
EntreMed personnel shall be jointly owned by Hospital and
EntreMed; for jointly-owned inventions, Hospital agrees to offer
an option to license the Hospital's interest in the invention
according to Section 7(c).
(b) Hospital agrees to notify EntreMed as soon as possible when a new,
potentially patentable Invention has been identified and disclosed
to the Technology Transfer Office. EntreMed will immediately order
a patentability and infringement search and, if the Invention is
patentable, will be responsible, at EntreMed's expense, for filing
and prosecuting patent applications on behalf of Hospital in
Hospital's name covering the new Inventions, with appropriate and
timely review and approval by Hospital. EntreMed shall solicit
Hospital's comments prior to any significant actions required
during filing and prosecution and provide Hospital with drafts of
proposed actions and responses sufficiently in advance to allow
time for comment and with file copies after the action is
completed. If EntreMed decides not to file a patent application,
EntreMed will notify Hospital within [ninety) [90] days of
receiving disclosure of the new Invention and if EntreMed decides
not to maintain prosecution of any patent application, EntreMed
will notify Hospital in a timely fashion. Hospital may elect to
file or maintain prosecution of such patent rights at its own
expense; and Hospital shall be entitled to dispose of such patent
rights without limitation, and EntreMed shall have no further
option, license or other rights thereto.
(c) For Inventions for which EntreMed shall elect to file and maintain
prosecution of a patent application, Hospital grants to EntreMed
an exclusive nine-month option to decide whether or not to
negotiate an exclusive license. Such option period shall begin at
the date of filing of a provisional patent application or a
non-provisional patent application. At the end of the nine-month
option period after filing of a provisional patent application,
EntreMed may request an additional six-month option period. In
consideration for granting the additional six-month period,
EntreMed will agree to file a non-provisional patent application
at EntreMed's expense. If EntreMed chooses to license such patent
rights during either option period, EntreMed shall have an
additional three-month period in which to negotiate and enter into
a license on the terms and conditions of the model license
agreement (Exhibit B). During this three-month period, EntreMed
will provide a development plan to Hospital which will include a
time frame for implementation of the
3
4
development plan. This development plan will be updated
semiannually. If EntreMed chooses not to license each patent
rights, Hospital shall have the right to license to a third party;
and EntreMed shall have no further option, license or other rights
thereto.
(d) Any license granted pursuant to this Agreement shall conform to
the terms and conditions of the License attached as Exhibit B.
(e) Any license granted pursuant to this Article shall be subject to a
reservation of the unrestricted right of Hospital and inventors
(while employed by Hospital or other non-profit institution) to
use subject matter claimed in the licensed patent(s) or patent
application(s) for research purposes only at no cost to Hospital
and the right to license to non-profit institutions for research
purposes only.
(f) EntreMed shall retain all invention disclosures submitted by
Hospital in confidence and use its best efforts to prevent their
disclosure to third parties. EntreMed shall be relieved of this
obligation only when this information becomes publicly available
through no fault of EntreMed.
8. Indemnification
(a) EntreMed shall indemnify, defend and hold harmless Hospital and
its board members, officers, medical staff, employees, and agents
from and against any and all liability, damage, loss or expense
(including reasonable attorneys' fees and expenses of litigation)
incurred by or imposed upon it or any one of them in connection
with any claims, suits, actions, demands or judgments arising out
of, resulting from or related to performance under this Agreement,
regardless of the theory of liability (including, but not limited
to, actions in the form of tort, warranty, or strict liability),
to the extent that such liability, loss, damage or expense is the
result of the acts or omissions of EntreMed or any of its board
members, officers, agents, servants, and employees.
(b) EntreMed agrees, at its own expense, to provide attorneys
reasonably acceptable to the Hospital to defend against any
actions brought or filed against any party indemnified hereunder
with respect to the subject of indemnity contained herein, whether
or not such actions are rightfully brought. Hospital shall
promptly notify EntreMed if any such action shall be brought or
flied or claim made.
(c) This Article 8 shall survive expiration or termination of this
Agreement.
9. Biological Materials Transfer
(a) Unique clones, chemicals, proteins or reagents developed or
discovered under the Program by Hospital may be shared with
scientists at non-profit academic or governmental institutions
upon execution of Hospital's Materials Transfer Agreement for
commercially significant materials. Requests for such materials
that originate from commercial entities will be discussed with
EntreMed, and Hospital will consider the potential effect of such
transfers on the Program before deciding whether to transfer such
materials.
4
5
10. Timely Pre-Clinical and Clinical Development
(a) As a condition to obtaining a license to the patent rights to
Inventions under Section 7, EntreMed agrees to support clinical
development, clinical trial and regulatory management of licensed
products. If EntreMed decides to sublicense the licensed product
and patent rights, in whole or for a field of use, the sublicensee
must be acceptable to Hospital in that such sublicensee can
provide the resources required to bring the Invention to the
marketplace. Such acceptance of a sublicensee by Hospital will not
be unreasonably withheld.
(b) EntreMed agrees to notify Hospital in a timely way of its decision
to discontinue preclinical or clinical development of any licensed
product and its reasons for doing so. The license(s) held by
EntreMed to Patent Rights (as defined in the license agreement for
such licensed product) for that Licensed Product (as defined in
the license agreement for such licensed product) will be
terminated upon notice from Hospital.
11. Term and Termination
(a) The term of this Agreement begins on the Effective Date and
terminates on September 29, 2000, unless sooner terminated as
provided below.
(b) Performance under this Agreement may be terminated by EntreMed at
any time with or without cause, and by Hospital without cause,
upon one (1) year prior written notice to the other party. If
Hospital terminates this Agreement under this Article 11(b), all
options and rights to Inventions and patent rights granted in this
Agreement to EntreMed shall remain in effect under Article 7 and
all licenses granted prior to the effective date of termination
shall remain in effect subject to the terms of the applicable
license agreement entered into between EntreMed and Hospital.
EntreMed shall continue to fund the Program for the shorter of
either one year following notice of termination or the remainder
of the term set forth in Article 11(a).
(c) In the event of termination by EntreMed under Article 11(b), all
options and rights to Inventions and patent rights granted in
Article 7 shall immediately terminate this Agreement and
coincidentally with EntreMed's notice of termination. Any license
agreement granted to EntreMed under Article 7 prior to such notice
of termination, shall survive, subject to the terms of said
license agreement.
(d) In the event of EntreMed's material breach of this Agreement,
including without limitation, failure to meet its payment
obligation under Article 4, Hospital shall have the right to give
notice of breach, and EntreMed shall have thirty (30) days to
cure. If EntreMed shall not cure such breach within the thirty-day
period, Hospital shall have the right to immediately terminate
this Agreement and all options and rights to Inventions and patent
rights granted in Article 7 and/or all license and other rights
granted in any license agreements executed prior to the date of
notice of termination of Article 7 rights under this Agreement or
the 1993 Agreement, such notice to be given in writing to
EntreMed.
5
6
(e) In the event of termination by Hospital under Article 11(b), and
upon sending its notice of termination, Hospital agrees to
promptly take all responsible steps to reduce the costs to
EntreMed, and Hospital shall return at termination any unexpended
funds to EntreMed less any non-refundable costs including
non-cancelable obligations Hospital has incurred in the
performance of the Program prior to the date of notice of such
termination. In no event shall such deduction exceed the total
support specified in Article 4.
(f) In the event of termination under Article 3 and upon the
terminating party sending its notice of termination, Hospital
agrees to promptly take all responsible steps to reduce the costs
to EntreMed, and Hospital shall return at termination any
unexpended funds to EntreMed less any non-refundable costs
including, but not limited to non-cancelable obligations Hospital
has incurred in the performance of the Program prior to the date
of notice of such termination. In no event shall such deduction
exceed the total support specified in Article 4. EntreMed agrees
to fund salaries of essential personnel for a period of nine
months from notice of termination. All options and rights to
Inventions and patent rights granted in Article 7 to EntreMed
shall remain in effect and all licenses granted prior to the
effective date of termination shall remain in effect subject to
the terms of the applicable license agreement entered into between
EntreMed and Hospital.
(g) The following provisions shall survive any expiration or
termination of this Agreement: 4(a) as to the Option, 5(a), 7(a),
8, 11(b), 11(c), 11(f), 11(g), 12(a), 15 (except (b) and (g) and
16.
12. Communications
(a) Notice. All medical/scientific and other communications, reports,
and notices shall be delivered by hand or sent by first class mail
postage prepaid and addressed as follows:
If to EntreMed:
President
EntreMed, Inc.
9640 Medical Center Drive, Suite 200
Rockville, MD 20850
With a copy to:
James Dean Johnson, Ph.D.
Jones & Askew
2400 Monarch Tower
2434 Peachtree Road
Atlanta, GA 30326
6
7
If to Hospital:
For all medical/scientific communications:
Judah Folkman, M.D.
Department of Surgery
Children's Hospital
300 Longwood Avenue
Boston, MA 02115-5737
With a copy to:
Director
Technology Transfer Office
Children's Hospital
300 Longwood Avenue
Boston, MA 02115-5737
For all other communications, reports, and notices:
Director
Technology Transfer Office
Children's Hospital
300 Longwood Avenue
Boston, MA 02115-5737
(b) For the purpose of facilitating EntreMed's understanding of the
research activities conducted by Hospital pursuant to the Program,
Hospital will permit duly authorized employees or representatives
of EntreMed to visit its facilities where the research is
conducted, or attend restricted-access Hospital seminars on or off
site, at reasonable times and with prior reasonable notice and
approval by the Principal Investigator. All such visits, seminars
or other communications, including without limitation, informal
conversations, email and the like concerning research activities,
will bc subject to the Mutual Nondisclosure Agreement between the
parties of even date as this Agreement.
(c) All communications regarding the business terms in this Agreement
shall be exclusively between EntreMed and the Technology Transfer
Office.
13. Use of Names
(a) Each party agrees not to use or cite in any manner the name of the
other, its employees or Principal Investigator in any commercial
or non-commercial advertising, article, press release or in any
other forms of writing or publication medium, or orally to the
extent practical, without the prior written permission of the
party or individual whose name is to be used except as required by
law. Hospital agrees to respond to any submission by EntreMed in a
timely manner, and EntreMed agrees to submit such writings, and
summarized oral comments to the extent practical, for approval at
least ten (10) days prior to submission for public release.
EntreMed agrees that any such writings or publications or oral
comments or
7
8
presentations, and any references in its other communications to
the public or third parties, will accurately reflect the
contractual relationship between the parties and will not
misrepresent or mislead others as to the nature of the
relationship. The parties agree to meet within thirty (30) days
alter the Effective Date to establish a set of rules to assist
them in complying with this Article 13.(a).
(b) EntreMed agrees not to disclose any of Hospital's confidential or
proprietary information in Invention disclosures or reports, data
concerning scientific discoveries, data from evaluations, research
results and the like in any commercial or non-commercial
advertising, article, press release or in any other forms of
writing or publication medium or to any third party without the
prior written permission of Hospital.
14. Representations and Warranties. Hospital represents and warrants to EntreMed
as follows:
(a) The execution and delivery of this Agreement by Hospital have been
duly and validly authorized and this Agreement constitutes a
legal, valid and binding obligation of Hospital, enforceable in
accordance with its terms. The execution, delivery and performance
of this Agreement does not conflict with or violate any charter
document or, to Hospital's knowledge, any contract binding upon
Hospital.
(b) Hospital has not received notice of any assertion that any of the
patents or subject Inventions infringe upon any third party's
know-how, patent or other intellectual property rights, except as
otherwise provided in writing to EntreMed, Inc.
(c) Hospital is and will be, during the term of this Agreement and
thereafter, the owner of all rights in and to the inventions
conceived or first reduced to practice by hospital or its
employees or independent contractors as a part of and/or the
projects which are included in the Program.
EntreMed represents and warrants to Hospital as follows:
(a) The execution and delivery of this Agreement by EntreMed have been
duly and validly authorized and this Agreement constitutes a
legal, valid and binding obligation of EntreMed enforceable in
accordance with its terms. The execution, delivery and performance
of this Agreement does not conflict with or violate any charter
document or, to EntreMed's knowledge, any contract binding upon
EntreMed.
15. General Provisions
(a) All rights and remedies hereunder will be cumulative and not
alternative, and this Agreement shall be construed and governed by
the laws of the Commonwealth of Massachusetts.
(c) Neither party may assign, transfer or delegate its rights, duties
or obligations hereunder without the prior written consent of the
other, and any assignment, transfer or delegation in violation of
this provision shall be void. Subject to the terms
8
9
of this provision, this Agreement shall be binding upon and inure
to the benefit of the parties hereto and their respective
successors and assigns. Notwithstanding anything herein to the
contrary, in the event EntreMed merges with another entity, is
acquired by another entity, or sells all or substantially all of
its assets to another entity, EntreMed may assign its rights and
obligations hereunder to, in the event of a merger or
acquisition, the surviving entity, and in the event of a sale,
the acquiring entity, without Hospital's consent so long as: (i)
EntreMed is not then in breach of this Agreement; (ii) the
proposed assignee has a net worth at least equivalent to the net
worth EntreMed had as of the date of this Agreement; (iii)
EntreMed provides written notice of the assignment to Hospital,
together with documentation sufficient to demonstrate the
requirements set forth in subparagraphs (i) and (ii) above, at
least twenty (20) days prior to the effective date of the
proposed assignment; and (iv) Hospital receives from the proposed
assignee, in writing, at least twenty (20) days prior to the
effective date of the assignment an agreement to perform the
obligations of EntreMed under this Agreement.
(c) This Agreement may be amended only by written agreement signed by
both parties.
(d) It is expressly agreed by the parties hereto that the Hospital and
EntreMed are independent contractors and nothing in this Agreement
is intended to create an employer relationship, joint venture, or
partnership between the parties. Neither party has the authority
to bind the other.
(e) This Agreement and its Exhibits constitute the entire agreement
between the parties with respect to the subject matter hereof and
supersedes all proposals, negotiations and other communications
between the parties, whether written or oral, with respect to the
subject matter hereof.
(f) If any provisions of this Agreement shall be held to be invalid,
illegal or unenforceable, the validity, legality and
enforceability of the remaining provisions of this Agreement shall
not be impaired thereby.
(g) The use of vertebrate animals in the conduct of work under this
Agreement shall comply with applicable portions of the Animal
Welfare Act (P.L. 89-544 as amended) and will follow the
guidelines prescribed in DHEW, NIH Publication No. 78-23,
"Guide for the Care and Use of Laboratory Animals," as amended,
and in any applicable state or local regulations.
(h) EXCEPT AS PROVIDED IN ARTICLE 14, AND TO THE EXTENT PERMITTED BY
APPLICABLE LAW, HOSPITAL MAKES NO WARRANTY, EXPRESS OR IMPLIED,
INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTIES OF
MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, TITLE OR
NONINFRINGEMENT, WITH RESPECT TO ANY PATENT, TRADEMARK, COPYRIGHT,
SOFTWARE, TRADE SECRET, TANGIBLE RESEARCH PROPERTY, INVENTION,
RESEARCH RESULTS, INFORMATION OR DATA PROVIDED OR UNDER OPTION TO
ENTREMED HEREUNDER AND HEREBY DISCLAIMS THE SAME, AND HOSPITAL
SHALL NOT BE LIABLE FOR ANY DIRECT, CONSEQUFNTIAL OR OTHER DAMAGES
SUFFERED BY ENTREMED OR ANY LICENSEE OR
9
10
OTHERS RESULTING FROM USE OF THE SAME OR ANY RESULTING PRODUCT OR
PROCESS.
16. 1993 Agreement
(a) Hospital and EntreMed hereby terminate the 1993 Agreement, except
that Articles 5(a), 7, 8, 14(a), (c), second 14(a), and 15 shall
survive.
(b) All Inventions under the 1993 Agreement shall be governed by the
provisions of any license agreement as amended from time to time,
entered into prior to the Effective Date, subject to Article II of
this Agreement, or the provisions of this amended and restated
Agreement, if no license agreement has been cxecuted as of the
Effective Date.
IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first written above.
CHILDREN'S HOSPITAL ENTRMED, INC.
By: /s/ William G. New By: /s/ John W. Holaday, Ph.D.
----------------------------------- ------------------------------
William G. New John W. Holaday, Ph.D.
Title: V.P. Research Administration Title: President and CEO
----------------------------------- ---------------------------
Date: June 24, 1999 Date: June 24, 1999
----------------------------------- ----------------------------
/s/ M. Judah Folkman, M.D. Date: June 24, 1999
- --------------------------------------------- ----------------------------
M. Judah Folkman, M.D.
10