PUBLIC HEALTH SERVICE
PATENT LICENSE AGREEMENT-EXCLUSIVE
COVER PAGE
For PHS internal use only:
Patent License Number: L-159-94/0________________________________________
Serial Numbers of Licensed Patents: 07/765,746 (U.S. Patent No.
5,171,750); 07/980,399 (U.S. Patent
No. 5,409,948); 08/096,207; and
08/182,301 (U.S. Patent No.
5,378,723).
Licensee: CURE, L.L.C.___________________________________________________
CRADA Number (if applicable): Not applicable_____________________________
Additional Remarks:______________________________________________________
_________________________________________________________________________
_________________________________________________________________________
This Patent License Agreement, hereinafter referred to as the "AGREEMENT,"
consists of this Cover Page, an attached Agreement, a Signature Page, Appendix A
(List of Patent(s) or Patent Application(s)), Appendix B (Fields of Use and
Territory), Appendix C (Royalties), Appendix D (Modifications), Appendix E
(Benchmarks), and Appendix F (Commercial Development Plan). The Parties to this
AGREEMENT are:
1) The National Institutes of Health ("NIH"), the Centers for Disease Control
and Prevention ("CDC"), or the Food and Drug Administration ("FDA"),
hereinafter singly or collectively referred to as "PHS," agencies of the
United States Public Health Service within the Department of Health and
Human Services ("DHHS"); and
2) The person, corporation, or institution identified above and/or on the
Signature Page, having offices at the address indicated on the Signature
Page, hereinafter referred to as "LICENSEE."
PHS PATENT LICENSE AGREEMENT--EXCLUSIVE
PHS and LICENSEE agree as follows:
1. BACKGROUND
1.01 In the course of conducting biomedical and behavioral research, PHS
investigators made inventions that may have commercial
applicability.
1.02 By assignment of rights from PHS employees and other inventors,
DHHS, on behalf of the United States Government, owns intellectual
property rights claimed in any United States and foreign patent
applications or patents corresponding to the assigned inventions.
DHHS also owns any tangible embodiments of these inventions
actually reduced to practice by PHS.
1.03 The Assistant Secretary for Health of DHHS has delegated to PHS the
authority to enter into this AGREEMENT for the licensing of rights
to these inventions under 35 U.S.C. Sections 200-212, the Federal
Technology Transfer Act of 1986, 15 U.S.C. Section 3710a, and/or
the regulations governing the licensing of Government-owned
inventions, 37 CFR Part 404.
1.04 PHS desires to transfer these inventions to the private sector
through commercialization licenses to facilitate the commercial
development of products and processes for public use and benefit.
1.05 LICENSEE desires to acquire commercialization rights to certain of
these inventions in order to develop processes, methods, or
marketable products for public use and benefit.
1.06 LICENSEE is a company specifically organized by a co-inventor of
one of the patented inventions for the development of these
inventions. The terms of this AGREEMENT were developed in
consideration of the LICENSEE'S status, present capital situation,
the fact that the LICENSEE was the sole applicant for a license
following public notification of the technology's availability for
licensing, and the remaining patent term of the LICENSED PATENT
RIGHTS, among other factors. The terms of this AGREEMENT are
intended to extend only t o the metes and bounds of this particular
situation as defined by these circumstances and are not intended to
represent a broad strategy for the licensing of PHS technologies.
2. DEFINITIONS
2.01 "BENCHMARKS" mean the performance milestones that are set forth in
Appendix E.
2.02 "COMMERCIAL DEVELOPMENT PLAN" means the written commercialization
plan attached as Appendix F.
2.03 "FIRST COMMERCIAL SALE" means the initial transfer by or on behalf
of LICENSEE or its sublicensees of LICENSED PRODUCTS or the initial
practice of a LICENSED PROCESS by or on behalf of LICENSEE or its
sublicensees in exchange for cash or some equivalent to which value
can be assigned for the purpose of determining NET SALES.
2.04 "GOVERNMENT" means the Government of the United States of America.
2.05 "LICENSED FIELDS OF USE" means the fields of use identified in
Appendix B.
2.06 "LICENSED PATENT RIGHTS" shall mean:
a) U.S. patent applications and patents listed in Appendix A,
all divisions and continuations of these applications, all
patents issuing from such applications, divisions, and
continuations, and any reissues, reexaminations, and
extensions of all such patents;
b) to the extent that the following contain one or more claims
directed to the invention or inventions disclosed in a)
above: i) continuations-in-part of a) above; ii) all
divisions and continuations of these continuations-in-part;
iii) all patents issuing from such continuations-in-part,
divisions, and continuations; and iv) any reissues,
reexaminations, AND EXTENSIONS OF ALL SUCH PATENTS;
c) to the extent that the following contain one or more claims
directed to the invention or inventions disclosed in a)
above: all counterpart foreign applications and patents to a)
and b) above, including those listed in Appendix A.
LICENSED PATENT RIGHTS shall NOT include b) or c) above to the
extent that they contain one or more claims directed to new matter
which is not the subject matter disclosed in a) above.
2.07 "LICENSED PROCESS(ES)" means processes which, in the course of
being practiced would, in the absence of this AGREEMENT, infringe
one or more claims of the Licensed PATENT RIGHTS that have not been
held invalid or unenforceable by an unappealed or unappealable
judgment of a court of competent jurisdiction.
2.08 "LICENSED PRODUCT(S)" means tangible materials which, in the course
of manufacture, use, or sale would, in the absence of this
AGREEMENT, infringe one or more claims of the LICENSED PATENT
RIGHTS that have not been held invalid or unenforceable by an
unappealed or unappealable judgment of a court of competent
jurisdiction.
2.09 "LICENSED TERRITORY" means the geographical area identified in
Appendix B.
2.10 "NET SALES" means the total gross receipts for sales of LICENSED
PRODUCTS or practice of LICENSED PROCESSES by or on behalf of
Licensee, and from leasing, renting, or otherwise making LICENSED
PRODUCTS available to others without sale or other dispositions,
whether invoiced or not, less returns and allowances actually
granted, packing costs, insurance costs, freight out, taxes or
excise duties imposed on the transaction (if separately invoiced),
and wholesaler and cash discounts in amounts customary in the
trade. No deductions shall be made for commissions paid to
individuals, whether they be with independent sales agencies or
regularly employed by LICENSEE, or sublicensees, and on its
payroll, or for the cost of collections.
2.11 "PRACTICAL APPLICATION" means to manufacture in the case of a
composition or product, to practice in the case of a process or
method, or to operate in the case of a machine or system; and in
each case, under such conditions as to establish that the invention
is being utilized and that its benefits are to the extent permitted
by law or GOVERNMENT regulations available to the public on
reasonable terms.
2.12 "RESEARCH LICENSE" means a nontransferable, nonexclusive license to
make and to use the LICENSED PRODUCTS OR LICENSED PROCESSES as
defined by the LICENSED PATENT RIGHTS for purposes of research and
not for purposes of commercial manufacture or distribution or in
lieu of purchase.
2.13 "EFFECTIVE DATE" means the date on which the last party to sign has
executed this AGREEMENT.
3. GRANT OF RIGHTS
3.01 PHS hereby grants and LICENSEE accepts, subject to the terms and
conditions of this AGREEMENT, an exclusive license under the
LICENSED PATENT RIGHTS in the LICENSED TERRITORY to make and have
made, to use and have used, and to sell and have sold any LICENSED
PRODUCTS in the LICENSED FIELDS OF USE and to practice and have
practiced any LICENSED PROCESSES in the LICENSED FIELDS OF USE.
3.02 This AGREEMENT confers no license or rights by implication,
estoppel, or otherwise under any patent applications or patents of
PHS other than LICENSED PATENT RIGHTS regardless of whether such
patents are dominant or subordinate to LICENSED PATENT RIGHTS.
4. SUBLICENSING
4.01 Upon written approval by PHS, which approval will not be
unreasonably withheld, LICENSEE may enter into sublicensing
agreements under the LICENSED PATENT RIGHTS.
4.02 LICENSEE agrees that any sublicenses granted by it shall provide
that the obligations to PHS of Paragraphs 5.01-5.04, 8.01, 10.01,
10.02, 12.05 and 13.07-13.09 of this AGREEMENT shall be binding
upon the sublicensee as if it were a party to this AGREEMENT.
Licensee further agrees to attach copies of these Paragraphs to all
sublicense agreements.
4.03 Any sublicenses granted by LICENSEE shall provide for the
termination of the sublicense, or the conversion to a license
directly between such sublicensees and PHS, at the option of the
sublicensee, upon termination of this AGREEMENT under Article 13.
Such conversion is subject to PHS approval and contingent upon
acceptance by the sublicensee of the remaining provisions of this
AGREEMENT.
4.04 LICENSEE agrees to forward to PHS a copy of each fully executed
sublicense agreement postmarked within thirty (30) days of the
execution of such agreement. To the extent permitted by law, PHS
agrees to maintain each such sublicense agreement in confidence.
5. STATUTORY AND PHS REQUIREMENTS AND RESERVED GOVERNMENT RIGHTS
5.01 PHS reserves on behalf of the GOVERNMENT an irrevocable,
nonexclusive, nontransferable, royalty-free license for the
practice of all inventions licensed under the LICENSED PATENT
RIGHTS throughout the world by or on behalf of the GOVERNMENT and
on behalf of any foreign government or international organization
pursuant to any existing or future treaty or agreement to which the
GOVERNMENT is a signatory. Prior to the FIRST COMMERCIAL SALE,
LICENSEE agrees to provide PHS reasonable quantities of LICENSED
PRODUCTS or materials made through the LICENSED PROCESSES for PHS
research use, but PHS shall not make a request for materials prior
to thirty-six (36) months after the EFFECTIVE DATE, should the
AGREEMENT be in effect at that time.
5.02 LICENSEE agrees that products used or sold in the United States
embodying LICENSED PRODUCTS or produced through use of LICENSED
PROCESSES shall be manufactured substantially in the United States,
unless a written waiver is obtained in advance from PHS.
5.03 LICENSEE acknowledges that PHS may enter into future Cooperative
RESEARCH AND Development Agreements (CRADAS) under the Federal
Technology Transfer ACT of 1986 THAT relate to the subject matter
of this AGREEMENT. LICENSEE agrees not to unreasonably deny
requests for a Research License from such future collaborators with
PHS when acquiring such
rights is necessary in order to make a CRADA project feasible.
LICENSEE may request an opportunity to join as a party to the
proposed CRADA.
5.04 In addition to the reserved license of Paragraph 5.01 above, PHS
reserves the right to grant such nonexclusive RESEARCH LICENSES
directly or to require LICENSEE to grant nonexclusive RESEARCH
LICENSES on reasonable terms. The purpose of this RESEARCH LICENSE
is to encourage basic research, whether conducted at an academic or
corporate facility. In order to safeguard the LICENSED PATENT
RIGHTS, however, PHS shall consult with LICENSEE before granting to
commercial entities a RESEARCH LICENSE or providing to them
research samples of the materials and shall cooperate with
LICENSEE'S reasonable requests to protect LICENSEE'S trade secret
rights and confidential business information.
6. ROYALTIES AND REIMBURSEMENT
6.01 LICENSEE agrees to pay to PHS a noncreditable, nonrefundable
license issue royalty on the terms set forth in Appendix C.
6.02 LICENSEE agrees to pay to PHS a nonrefundable minimum annual
royalty as set forth in Appendix C. The first minimum annual
royalty payment shall be due and payable thirty-six (36) months
from the EFFECTIVE DATE and may be prorated according to the
fraction of the calendar year remaining between that date and the
next subsequent January 1, i.e., January 1, 2000. Subsequent
minimum annual royalty payments will be due and payable on January
I of each calendar year and shall be credited against any earned
royalties due for sales made in that year or sublicensing royalties
derived from sales made in that year.
6.03 LICENSEE agrees to pay PHS earned royalties as set forth in
Appendix C.
6.04 LICENSEE agrees to pay PHS benchmark royalties as set forth in
Appendix C.
6.05 LICENSEE agrees to pay PHS sublicensing royalties as set forth in
Appendix C.
6.06 A claim of a patent or patent application licensed under this
AGREEMENT shall cease to fall within the LICENSED PATENT RIGHTS for
the purpose of computing the minimum annual royalty, sublicensing
royalty, and earned royalty payments in any given country on the
earliest of the dates that a) the claim has been abandoned but not
continued, b) the patent expires or irrevocably lapses, or c) the
claim has been held to be invalid or unenforceable by an unappealed
or unappealable decision of a court of competent jurisdiction or
administrative agency.
6.07 No multiple royalties shall be payable because any LICENSED
PRODUCTS OR LICENSED PROCESSES are covered by more than one of the
LICENSED PATENT RIGHTS.
6.08 On sales of LICENSED PRODUCTS by LICENSEE to sublicensees or
affiliated parties or on sales made in other than an arm's-length
transaction, the value of the NET SALES attributed under this
Article 6 to such a transaction shall be that which would have been
received in an arm's-length transaction, based on sales of like
quantity and quality products on or about the time of such
transaction.
6.09 With regard to expenses associated with the preparation, filing,
prosecution, and maintenance of all patent applications and patents
included within the LICENSED PATENT RIGHTS incurred by PHS prior to
the effective date of this AGREEMENT, LICENSEE shall pay to PHS, as
an additional royalty, within sixty (60) days of PHS'S submission
of a statement and request for payment to LICENSEE, an amount
equivalent to such patent expenses previously incurred by PHS. PHS
shall
not make such a statement and request prior to thirty-six (36)
months after the EFFECTIVE DATE, should the AGREEMENT be in effect
at that time.
6.10 With regard to expenses associated with the preparation, filing,
prosecution, and maintenance of all patent applications and patents
included within the LICENSED PATENT RIGHTS incurred by PHS on or
after the EFFECTIVE DATE, PHS, at its sole option, may require
LICENSEE:
(a) to pay PHS on an annual basis, within sixty (60) days of
PHS'S submission of a statement and request for payment, a royalty
amount equivalent to all such patent expenses incurred during the
previous calendar year(s); or
(b) to pay such expenses directly to the law firm employed by PHS
to handle such functions. However, in such event, PHS and not
LICENSEE shall be the client of such law firm.
Under exceptional circumstances, LICENSEE may be given the right to
assume responsibility for the preparation, filing, prosecution, or
maintenance of any patent application or patent included with the
LICENSED PATENT RIGHTS. In that event, LICENSEE shall directly pay
the attorneys or agents engaged to prepare, file, prosecute or
maintain such patent applications or patents and shall provide to
PHS copies of each invoice associated with such services as well as
documentation that such invoices have been paid.
6.11 LICENSEE may elect to surrender its rights in any country of the
LICENSED TERRITORY under any Licensed PATENT RIGHTS upon sixty (60)
days written notice to PHS and owe no payment obligation under
Article 6.10 for patent-related expenses incurred in that country
after the effective date of such written notice.
7. PATENT FILING, PROSECUTION, AND MAINTENANCE
7.01 Except as otherwise provided in this Article 7, PHS agrees to take
responsibility for, but to consult with, the LICENSEE in the
preparation, filing, prosecution, and maintenance of any and all
patent applications or patents included in the LICENSED PATENT
RIGHTS and shall furnish copies of relevant patent-related
documents to LICENSEE.
7.02 Upon PHS'S written request and LICENSEE'S acceptance of such
request in its reasonable discretion, LICENSEE shall assume the
responsibility for the preparation, filing, prosecution, and
maintenance of any and all patent applications or patents included
in the LICENSED PATENT RIGHTS and shall on an ongoing basis
promptly furnish copies of aU patent-related documents to PHS. In
such event, LICENSEE shall, subject to the prior approval of PHS,
select registered patent attorneys or patent agents to provide such
services on behalf of LICENSEE and PHS. PHS shau provide
appropriate powers of attorney and other documents necessary to
undertake such actions to the patent attorneys or patent agents
providing such services. LICENSEE and its attorneys or agents
shall consult with PHS in all aspects of the preparation, filing,
prosecution and maintenance of patent applications and patents
included within the LICENSED PATENT RIGHTS and shall provide PHS
sufficient opportunity to comment on any document that LICENSEE
intends to file or to cause to be filed with the relevant
intellectual property or patent office. PHS shall not make such a
request prior to thirty-six (36) months after the EFFECTIVE DATE,
should the AGREEMENT be in effect at that time.
7.03 At any time, PHS MAY provide LICENSEE with written notice that PHS
wishes to assume control of the preparation, filing, prosecution,
and maintenance of any and all patent applications or patents
included in the LICENSED PATENT RIGHTS. IF PHS elects to assume
such responsibilities, LICENSEE agrees to cooperate fully with PHS,
its attorneys and agents in the preparation, filing, prosecution,
and maintenance of any and all patent applications or patents
included in the LICENSED PATENT RIGHTS and to provide PHS with
complete copies of any and all documents or other materials in
LICENSEE'S possession that PHS deems necessary to undertake such
responsibilities. LICENSEE shall be responsible for all costs
associated with transferring patent prosecution responsibilities to
an attorney or agent of PHS'S choice.
7.04 Each party shall promptly inform the other as to all matters that
come to its attention that may affect the preparation, filing,
prosecution, or maintenance of the LICENSED PATENT RIGHTS and
permit each other to provide comments and suggestions with respect
to the preparation, filing, and prosecution of Licensed PATENT
RIGHTS, which comments and suggestions shall be considered in good
faith by the other party.
8. RECORD KEEPING
8.01 Licensee agrees to keep accurate and correct records of LICENSED
PRODUCTS made, used, or sold and LICENSED PROCESSES practiced under
this Agreement appropriate to determine the amount of royalties due
PHS. Such records shall be retained for at least five (5) years
following the reporting period to which they apply. They shall be
available during normal business hours for inspection at the
expense of PHS by an accountant or other designated auditor
selected by PHS for the sole purpose of verifying reports and
payments hereunder. The accountant or auditor shall only disclose
to PHS information relating to the accuracy of reports and payments
made under this AGREEMENT. If an inspection shows an
underreporting or underpayment in excess of five percent (5%) for
any twelve (12) month period, then LICENSEE shall reimburse PHS for
the cost of the inspection at the time Licensee pays the unreported
royalties, including any late charges as required by Paragraph 9.08
of this AGREEMENT on such past-due unreported royalties. All
payments required under this Paragraph shall be due within thirty
(30) days of the date PHS provides LICENSEE notice of the payment
due.
8.02 Licensee agrees to conduct an independent audit of sales and
royalties at least every two years if annual sales of the LICENSED
PRODUCT or LICENSED PROCESSES are over two (2) million dollars.
The audit shall address, at a minimum, the amount of gross sales by
or on behalf of LICENSEE during the audit period, the amount of
funds owed to the GOVERNMENT under this AGREEMENT, and whether the
amount owed has been paid to the GOVERNMENT and is reflected in the
records of the LICENSEE. A report by the auditor shall be
submitted promptly to PHS on completion. LICENSEE shall pay for the
entire cost of the audit.
9. REPORTS ON PROGRESS, BENCHMARKS, SALES, AND PAYMENTS
9.01 Prior to signing this AGREEMENT, LICENSEE has provided to PHS the
COMMERCIAL DEVELOPMENT PLAN at Appendix F, under which LICENSEE
intends to bring the subject matter of the LICENSED PATENT RIGHTS
to the point of PRACTICAL APPLICATION. This COMMERCIAL DEVELOPMENT
PLAN is hereby incorporated by reference into this AGREEMENT.
Based on this plan, performance BENCHMARKS are determined as
specified in Appendix E.
9.02 LICENSEE shall provide written annual reports on its product
development progress Or efforts to commercialize under the
COMMERCIAL DEVELOPMENT PLAN for each of the LICENSED FIELDS OF Use
within sixty (60) days after December 31 of each calendar year.
These progress reports shall include, but not be limited to:
progress on research and development, status of applications for
regulatory approvals, manufacturing, sublicensing, marketing, and
sales during the preceding calendar year, as well as plans for the
present calendar year. PHS also encourages these reports to
include information on any of LICENSEE'S public service activities
that relate to the LICENSED PATENT RIGHTS. If reported progress
differs from that projected in the COMMERCIAL DEVELOPMENT PLAN and
BENCHMARKS, LICENSEE shall explain the reasons for such
differences. In any such annual report LICENSEE may propose
amendments to the
COMMERCIAL DEVELOPMENT PLAN, acceptance of which by PHS may not
be denied unreasonably. LICENSEE agrees to provide any
additional information reasonably required by PHS to evaluate
LICENSEE'S performance under this AGREEMENT. LICENSEE may amend
the BENCHMARKS at any time upon written consent by PHS. PHS
shall not unreasonably withhold approval of any request of
LICENSEE to extend the time periods of this schedule if such
request is supported by a reasonable showing by LICENSEE of
diligence in its performance under the COMMERCIAL DEVELOPMENT
PLAN and toward bringing the LICENSED PRODUCTS to the point of
practical application as defined in 37 CFR 404.3(d). LICENSEE
shall amend the COMMERCIAL DEVELOPMENT PLAN and BENCHMARKS at the
request of PHS to address any LICENSED FIELDS OF Use not
specifically addressed in the plan originally submitted.
9.03 Licensee shall report to PHS the date of the FIRST COMMERCIAL SALE
in each country in the LICENSED TERRITORY within thirty (30) days
of such occurrence.
9.04 Licensee shall submit to PHS within sixty (60) days after each
calendar half-year ending June 30 and December 31 a royalty report
setting forth for the preceding half-year period the amount of the
LICENSED PRODUCTS sold or LICENSED PROCESSES practiced by or on
behalf of LICENSEE in each country within the LICENSED TERRITORY,
the NET Sales, and the amount of royalty accordingly due. With
each such royalty report, LICENSEE shall submit payment of the
earned royalties due. If no earned royalties are due to PHS for
any reporting period, the written report shall so state. The
royalty report shall be certified as correct by an authorized
officer of LICENSEE and shall include a detailed listing of all
deductions made under Paragraph 2. 10 to determine NET SALES made
under Article 6 to determine royalties due.
9.05 LICENSEE agrees to forward semi-annually to PHS a copy of such
reports received by LICENSEE from its sublicensees during the
preceding half-year period as shall be pertinent to a royalty
accounting to PHS by LICENSEE for activities under the sublicense.
9.06 Royalties due under Article 6 shall be paid in U.S. dollars. For
conversion of foreign currency to U.S. dollars, the conversion rate
shall be the New York foreign exchange rate quoted in THE WALL
STREET JOURNAL on the day that the payment is due. All checks and
bank drafts shall be drawn on Uriited States banks and shall be
payable, as appropriate, for FDA or NH4 licenses to the National
Institutes of Health, X.X. Xxx 000000, Xxxxxxxxxx, Xxxxxxxxxxxx
00000-0000 or for CDC licenses to the Centers for Disease Control
and Prevention, CDC Financial Management Office, 255 East Paces
Ferry Road, NE (MS-EI2), Xxxxxxx, Xxxxxxx 00000. Any loss of
exchange, value, taxes, or other expenses incurred in the transfer
or conversion to U.S. dollars shall be paid entirely by LICENSEE.
The royalty report required by Paragraph 9.04 of this AGREEMENT
shall accompany each such payment and a copy of such report shall
also be mailed to PHS at its address for notices indicated on the
Signature Page of this AGREEMENT.
9.07 LICENSEE shall be solely responsible for determining if any tax on
royalty income is owed outside the United States and shall pay any
such tax and be responsible for all filings with appropriate
agencies of foreign governments.
9.08 Late charges will be assessed by PHS as additional royalties on any
overdue payments at a rate of one percent (1%) per month compounded
monthly. The payment of such late charges shall not prevent PHS
from exercising any other rights it may have as a consequence of
the lateness of any payment.
9.09 All plans and reports required by this Article 9 and marked
"confidential" by LICENSEE shall, to the extent permitted by law,
be treated by PHS as commercial and financial information obtained
from a person and as privileged and confidential and any proposed
disclosure of such
records by the PHS under the Freedom of Information Act, 5 U.S.C.
Section 552 shall be subject to the predisclosure notification
requirements of 45 CFR Section 5.65(d).
10. PERFORMANCE
10.01 LICENSEE shall use its reasonable best efforts to bring the License
Products and Licensed Processes to Practical Application.
"Reasonable best efforts" for the purposes of this provision shall
include adherence to the COMMERCIAL DEVELOPMENT PLAN at Appendix F
and performance of the BENCHMARKS at Appendix E, in each case as
amended or modified. The efforts of a sublicensee shall be
considered the efforts of LICENSEE.
10.02 Upon the FIRST COMMERCIAL Sale, until the expiration of this
Agreement, LICENSEE shall use its reasonable best efforts to make
LICENSED PRODUCTS and LICENSED PROCESSES reasonably accessible to
the United States public.
11. INFRINGEMENT AND PATENT ENFORCEMENT
11.01 PHS and LICENSEE agree to notify each other promptly of each
infringement or possible infringement of the LICENSED PATENT
RIGHTS, as well as any facts which may affect the validity, scope,
or enforceability of the Licensed PATENT RIGHTS of which either
Party becomes aware.
11.02 Pursuant to this AGREEMENT and the provisions of Chapter 29 of
title 35, United States Code, Licensee may a) bring suit in its own
name, at its own expense, and on its own behalf for infringement of
presumably valid claims in the LICENSED PATENT RIGHTS; b) in any
such suit enjoin infringement and collect for its use, damages,
profits, and awards of whatever nature recoverable for such
infringement; and c) settle any claim or suit for infringement of
the LICENSED PATENT RIGHTS provided, however, that PHS and
appropriate GOVERNMENT authorities shall have the first right to
take such actions. If LICENSEE desires to initiate a suit for
patent infringement, LICENSEE shall notify PHS in writing. If PHS
does not notify LICENSEE of its intent to pursue legal action
within ninety (90) days, or such shorter period as may be required
to permit filing of the suit within any applicable limitations
period, LICENSEE will be free to initiate suit. PHS shall have a
continuing right to intervene in such suit. LICENSEE shall take no
action to compel the GOVERNMENT either to initiate or to join in
any such suit for patent infringement. LICENSEE may request the
GOVERNMENT to initiate or join in any such suit if necessary to
avoid dismissal of the suit. Should the GOVERNMENT be made a party
to any such suit, LICENSEE shall reimburse the GOVERNMENT for any
costs, expenses, or fees which the GOVERNMENT incurs as a result of
such motion or other action, including any and all costs incurred
by the GOVERNMENT in opposing any such motion or other action;
provided, however, that LICENSEE shall be reimbursed for such
expenses out of any final recovery awarded to the GOVERNMENT. In
all cases, LICENSEE agrees to keep PHS reasonably apprised of the
status and progress of any litigation. Before LICENSEE commences
an infringement action, LICENSEE shall notify PHS and give careful
consideration to the views of PHS and to any potential effects of
the litigation on the public health in deciding whether to bring
suit.
11.03 In the event that a declaratory judgment action alleging invalidity
or non-infringement of any of the LICENSED PATENT RIGHTS shall be
brought against LICENSEE or raised by way of counterclaim or
affirmative defense in an infringement suit brought by LICENSEE
under Paragraph 11.02, pursuant to this AGREEMENT and the
provisions of Chapter 29 of Xxxxx 00, Xxxxxx Xxxxxx Code or other
statutes, LICENSEE may a) defend the suit in its own name, at its
own expense, and on its own behalf for presumably valid claims in
the LICENSED PATENT RIGHTS; b) in any such suit, ultimately to
enjoin infringement and to collect for its use, damages, profits,
and awards of whatever nature recoverable for such infringement;
and c) settle any claim or suit for declaratory judgment involving
the LICENSED PATENT Rights,
provided, however, that PHS and appropriate Government
authorities shall have the first right to take such actions and
shall have a continuing right to intervene in such suit. If PHS
does not notify LICENSEE of its intent to respond to the legal
action within a reasonable time, LICENSEE will be free to do so.
LICENSEE shall take no action to compel the GOVERNMENT either to
initiate or to join in any such declaratory judgment action.
LICENSEE may request the GOVERNMENT to initiate or to join any
such suit if necessary to avoid dismissal of the suit. Should
the GOVERNMENT be made a party to any such suit by motion or any
other action of LICENSEE, LICENSEE shall reimburse the GOVERNMENT
for any costs, expenses, or fees which the GOVERNMENT incurs as a
result of such motion or other action; provided, however, that
LICENSEE shall be reimbursed for such expenditures out of any
final recovery awarded to the GOVERNMENT. If LICENSEE elects not
to defend against such declaratory judgment action, PHS, at its
option, may do so at its own expense. In all cases, LICENSEE
agrees to keep PHS reasonably apprised of the status and progress
of any litigation. Before LICENSEE commences an infringement
action, LICENSEE shall notify PHS and give careful consideration
to the views of PHS and to any potential effects of the
litigation on the public health in deciding whether to bring suit.
11.04 In any action under Paragraphs 11.02 or 11.03, the expenses
including costs, fees, attorney fees, and disbursements. shall be
paid by LICENSEE. Up to fifty percent (50%) of such expenses,
representing expenses paid on behalf of the Government and not
reimbursed out of any recovery, may be credited against the
royalties payable to PHS under Paragraph 6.03 under the LICENSED
PATENT RIGHTS in the country in which such a suit is filed. In the
event that fifty percent (50%) of such expenses exceed the amount
of royalties payable by LICENSEE in any calendar year, the expenses
in excess may be carried over as a credit on the same basis into
succeeding calendar years. A credit against litigation expenses,
however, may not reduce the royalties due in any calendar year to
less than the minimum annual royalty, if any is due. Any recovery
made by LICENSEE, through court judgment or settlement, first shall
be applied to reimburse PHS for royalties withheld as a credit
against litigation expenses and then to reimburse LICENSEE for its
litigation expense. Any remaining recoveries shall be shared
equally by LICENSEE and PHS.
11.05 PHS shall cooperate fully with LICENSEE in connection with any
action under Paragraphs 11.02 or 11.03. PHS agrees promptly to
provide access to all necessary documents and to render reasonable
assistance in response to a request by LICENSEE.
12 NEGATION OF WARRANTIES AND INDEMNIFICATION
12.01 PHS offers no warranties other than those specified in Article 1.
12.02 PHS does not wan-ant the validity of the LICENSED PATENT RIGHTS and
makes no representations whatsoever with regard to the scope of the
LICENSED PATENT RIGHTS, or that the LICENSED PATENT RIGHTS may be
exploited without infringing other patents or other intellectual
property rights of third parties.
12.03 PHS MAKES NO WARRANTIES, EXPRESSED OR IMPLIED, OF MERCHANTABELITY'
OR FITNESS FOR A PARTICULAR PURPOSE OF ANY SUBJECT MATTER DEFINED
BY THE CLAIMS OF THE LICENSED PATENT RIGHTS.
12.04 PHS does not represent that it will commence legal actions against
third parties infringing the LICENSED PATENT RIGHTS.
12.05 LICENSEE shall indemnify and hold PHS, its employees, students,
fellows, agents, and consultants harmless from and against all
liability, demands, damages, expenses, and losses,
including but not limited to death, personal injury, illness, or
property damage in connection with or arising out of a) the use
by or on behalf of LICENSEE, its sublicensees, directors,
employees, or third parties of any LICENSED PATENT RIGHTS, or b)
the design, manufacture, distribution, or use of any LICENSED
PRODUCTS, LICENSED PROCESSES or materials by LICENSEE, or other
products or processes developed in connection with or arising out
of the LICENSED PATENT RIGHTS. LICENSEE agrees to maintain a
liability insurance program consistent with sound business
practice or ensure that any sublicensee maintains an adequate
amount of such insurance to cover LICENSEE'S risk exposure.
13. TERM, TERMINATION, AND MODIFICATION OF RIGHTS
13.01 This AGREEMENT is effective on the EFFECTIVE DATE and shall extend
to the expiration of the last to expire of the LICENSED PATENT
RIGHTS unless sooner terminated as provided in this Article 13.
13.02 In the event that Licensee is in default in the performance of any
material obligations under this AGREEMENT, including but not
limited to the obligations listed in Article 13.05, and if the
default has not been remedied, within ninety (90) days after the
date of notice in writing of such default, PHS may terminate this
AGREEMENT by written notice.
13.03 In the event that LICENSEE becomes insolvent, files a petition in
bankruptcy, has such a petition filed against it, determines to
file a petition in bankruptcy, or receives notice of a third
party's intention to file an involuntary petition in bankruptcy,
LICENSEE shall immediately notify PHS in writing.
13.04 LICENSEE shall have a unilateral right to terminate this AGREEMENT
and/or any licenses in any country by giving PHS sixty (60) days
written notice to that effect.
13.05 PHS shall specifically have the right to terminate or modify, at
its option, this AGREEMENT, if PHS determines that the LICENSEE: 1)
is not executing the COMMERCIAL DEVELOPMENT PLAN submitted with its
request for a license, as amended or modified at the pertinent
time, and the LICENSEE cannot otherwise demonstrate to PHS'S
satisfaction that the LICENSEE has taken or can be expected to take
within a reasonable time, effective steps to achieve practical
application of the LICENSED PRODUCTS or LICENSED PROCESSES; 2) has
not achieved the Benchmarks, as amended or modified at the
pertinent time; 3) has willfully made a false statement of, or
willfully omitted, a material fact in the license application or in
any report required by the license agreement; 4) has committed a
material breach of a covenant or agreement contained in the
license; 5) is not keeping LICENSED PRODUCTS or LICENSED PROCESSES
reasonably available to the public after commercial use commences;
6) cannot reasonably satisfy unmet health and safety needs; or 7)
cannot reasonably justify a failure to comply with the domestic
production requirement of Paragraph 5.02 unless waived. In making
this determination, PHS will take into account the normal course of
such commercial development programs conducted with sound and
reasonable business practices and judgment and the annual reports
submitted by LICENSEE under Paragraph 9.02. Prior to invoking this
right, PHS shall give written notice to LICENSEE providing LICENSEE
specific notice of, and a ninety (90) day opportunity to respond to
and cure, or initiate a course of action to cure, PHS'S concerns as
to the previous items 1) to 7). If LICENSEE fails to alleviate
PHS'S concerns as to the previous items 1) to 7) or fails to
initiate corrective action TO PHS'S satisfaction, PHS may terminate
this AGREEMENT.
13.06 When the public health and safety so require, and after written
notice to LICENSEE providing LICENSEE a sixty (60) day opportunity
to respond, PHS shall have the right to require LICENSEE to grant
sublicenses to responsible applicants, on reasonable terms, in any
Licensed Fields of Use under the Licensed Patent Rights, unless
LICENSEE can reasonably demonstrate that the
granting of the sublicense would not materially increase the
availability to the public of the subject matter of the LICENSED
PATENT RIGHTS. PHS will not require the granting of a sublicense
unless the responsible applicant has first negotiated in good
faith with LICENSEE.
13.07 PHS reserves the right according to 35 U.S.C. Section 209(f)(4) to
terminate or modify this AGREEMENT if it is determined that such
action is necessary to meet requirements for public use specified
by federal regulations issued after the date of the license and
such requirements are not reasonably satisfied by LICENSEE.
13.08 Within thirty (30) days of receipt of written notice of PHS'S
unilateral decision to modify or terminate this Agreement, LICENSEE
may, consistent with the provisions of 37 CFR 404.1 1, appeal the
decision by written submission to the designated PHS official. The
decision of the designated PHS official shall be the final agency
decision. LICENSEE may thereafter exercise any and all
administrative or judicial remedies that may be available.
13.09 Within ninety (90) days of termination of this AGREEMENT under this
Article 13 or expiration under Paragraph 3.02, a final report shall
be submitted by LICENSEE. Any royalty payments, including those
related to patent expense, due to PHS shall become immediately due
and payable upon termination or expiration. If terminated under
this Article 13, sublicensees may elect to convert their
sublicenses to direct licenses with PHS pursuant to Paragraph 4.03.
14. GENERAL PROVISIONS
14.01 Neither Party may waive or release any of its rights or interests
in this AGREEMENT except in writing. The failure of either party
to assert a right hereunder or to insist upon compliance with any
term or condition of this AGREEMENT shall not constitute a waiver
of that right by that party or excuse a similar subsequent failure
to perform any such term or condition by the other party.
14.02 This Agreement constitutes the entire agreement between the Parties
relating to the subject matter of the LICENSED PATENT RIGHTS, and
all prior negotiations, representations, agreements, and
understandings are merged into, extinguished by, and completely
expressed by this Agreement.
14.03 The provisions of this AGREEMENT are severable, and in the event
that any provision of this AGREEMENT shall be determined to be
invalid or unenforceable under any controlling body of law such
determination shall not in any way affect the validity or
enforceability of the remaining provisions of this AGREEMENT.
However, this AGREEMENT shall terminate immediately if any
controlling body of law declares the grant of exclusivity of
paragraph 3.01 to be invalid or unenforceable.
14.04 If either Party desires a modification to this AGREEMENT, the
Parties shall, upon reasonable notice of the proposed modification
by the Party desiring the change, confer in good faith to determine
the desirability of such modification. No modification will be
effective until a written amendment is signed by the signatories to
this AGREEMENT or their designees.
14.05 The construction, validity, performance, and effect of this
AGREEMENT shall be governed by Federal law as applied by the
Federal courts in the District of Columbia.
14.06 All notices required or permitted by this AGREEMENT shall be given
by prepaid, first class, registered or certified mail properly
addressed to the other Party at the address designated on the
following Signature Page, or to such other address as may be
designated in writing by such other Party, and shall be effective
as of the date of receipt of such notice.
14.07 This AGREEMENT shall not be assigned by LICENSEE except a) with the
prior written consent of PHS, such consent not to be withheld
unreasonably; or b) as part of a sale or transfer of substantially
the entire business of LICENSEE relating to operations which
concern this Agreement. LICENSEE shall notify PHS within ten (10)
days of any assignment of this Agreement by LICENSEE.
14.08 LICENSEE agrees in its use of any PHS-supplied materials to comply
with all applicable statutes, regulations, and guidelines,
including Public Health Service and National Institutes of Health
regulations and guidelines. LICENSEE agrees not to use the
materials for research involving human subjects or clinical trials
in the United States without complying with 21 CFR Part 50 and 45
CFR Part 46. LICENSEE agrees not to use the materials for research
involving human subjects or clinical trials outside of the United
States without notifying PHS, in writing, of such research or
trials and complying with the applicable regulations of the
appropriate national control authorities. Written notification to
PHS of research involving human subjects or clinical trials outside
of the United States shall be given no later than sixty (60) days
prior to commencement of such research or trials.
14.09 Licensee acknowledges that it is subject to and agrees to abide by
the United States laws and regulations (including the Export
Administration Act of 1979 and Arms Export Control Act) controlling
the export of technical data, computer software, laboratory
prototypes, biological material, and other commodities. The
transfer of such items may require a license from the cognizant
Agency of the U.S. GOVERNMENT or written assurances by LICENSEE
that it shall not export such items to certain foreign countries
without prior approval of such agency. PHS neither represents that
a license is or is not required or that, if required, it shall be
issued.
14.10 LICENSEE agrees to xxxx the LICENSED PRODUCTS or their packaging
sold in the United States with all applicable U.S. patent numbers
and similarly to indicate "Patent Pending" status. All LICENSED
PRODUCTS manufactured in, shipped to, or sold in other countries
shall be marked in such a manner as to preserve PHS patent rights
in such countries.
14.11 By entering into this AGREEMENT, PHS does not directly or
indirectly endorse any product or service provided, or to be
provided, by LICENSEE whether directly or indirectly related to
this Agreement. LICENSEE shall not state or imply that this
AGREEMENT is an endorsement by the GOVERNMENT, PHS, any other
GOVERNMENT organizational unit, or any GOVERNMENT employee.
Additionally, LICENSEE shall not use the names of NIH, CDC, PHS, or
DHHS or the GOVERNMENT or their employees in any advertising,
promotional, or sales literature without the prior written consent
of PHS.
14.12 The Parties agree to attempt to settle amicably any controversy or
claim arising under this Agreement or a breach of this Agreement,
except for appeals of modifications or termination decisions
provided for in Article 13. LICENSEE agrees first to appeal any
such unsettled claims or controversies to the designated PHS
official, or designee, whose decision shall be considered the final
agency decision. Thereafter, LICENSEE may exercise any
administrative or judicial remedies that may be available.
14.13 Nothing relating to the grant of a license, nor the grant itself,
shall be construed to confer upon any person any immunity from or
defenses under the antitrust laws or from a charge of patent
misuse, and the acquisition and use of rights pursuant to 37 CFR
Part 404 shall not be immunized from the operation of state or
Federal law by reason of the source of the grant.
14.14 Paragraphs 4.03, 8.01, 9.06-9.08, 12.01-12.05, 13.08, 13.09, and
14.12 of this AGREEMENT shall survive termination of this
AGREEMENT.
PHS PATENT LICENSE AGREEMENT--EXCLUSIVE
SIGNATURE PAGE
For PHS:
/s/ Xxxxxxx X. XxXxxxx 1/31/97
------------------------------------------- -------
Xxxxxxx X. XxXxxxx, X.X. Date
Deputy Director, Office of Technology Transfer
Mailing Address for Notices:
Office of Technology Transfer
National Institutes of Health
0000 Xxxxxxxxx Xxxxxxxxx, Xxxxx 000
Xxxxxxxxx, Xxxxxxxx 00000
For LICENSEE (Upon, information and belief, the undersigned expressly certifies
or affirms that the contents of any statements of LICENSEE made or referred to
in this document are truthful and accurate.):
by:
/s/ Xxxxxxx X. Xxxxxxxx 1/10/97
------------------------------- -------
Xxxxxxx X. Xxxxxxxx
-------------------------------
Printed Name
President
-------------------------------
Title
Mailing Address for Notices:
0000 Xxxxxx Xx.
-------------------------------
Xxxxxx Xxxxxx, XX 00000
-------------------------------
-------------------------------
APPENDIX A--PATENT(S) OR PATENT APPLICATION(S)
UNITED STATES
U.S. Patent No. 5,171,750 (U.S. Patent Application Serial No.07/765,746),
issued December 15, 1992, entitled, "Substituted Phenserines as Specific
Inhibitors of Acetylcholinesterase," Inventors: Brossi et al (NIA and
NIDDK);
U.S. Patent No. 5,378,723 (U.S. Patent Application Serial No. 08/182,301),
issued January 3, 1995, entitled, "Carbamate Analogs of Thiaphysovenine and
Method for Inhibiting Cholinesterases," Inventors: Brossi et al (NIA and
NIDDK).
U.S. Patent No. 5,409,948 (U.S. Patent Application Serial No. 07/980,399),
issued April 25, 1995, entitled, "Method of Treating Cognitive Disorders with
Phenserine," Inventors: Xxxxx et al (NIA and NIDDK);
U.S. Patent Application Serial No. 08/096,207, filed July 26, 1993, entitled,
"Phenylcarbamates of (-)-Eseroline, (-)-N I -Noreseroline and (-)-N I
-Benzylnoreseroline: Selective Inhibitors of Acetyl and/or
Butyrylcholinesterase," Inventors: Brossi et al (NIA and NIDDK);
FOREIGN
PCT Patent Applications
PCT/US92/07085 filed on August 26. 1992
PCT/US92/08228 filed on September 28, 1992
PCT/US93/11423 filed on November 23, 1993
National Patent Applications
Australia: 25042/92 (corresponds to PCT/US92/07085)
27544/92 (corresponds to PCT/US92/08228)
57290/94 (corresponds to PCT/US93/11423)
Canada: 2,119,782 (corresponds to PCT/US92/07085)
2,119,783 (corresponds to PCT/US92/08228)
2,149,924 (corresponds to PCT/US93/11423)
Europe: 92919058.5 (corresponds to PCT/US92/07085)
92921255.3 (corresponds to PCT/US92/08228)
94903295.7 (corresponds to PCT/US93/11423)
Japan: 506405/93 (corresponds to PCT/US92/07085)
6-513358 (corresponds to PCT/US93/11423)
APPENDIX B--LICENSED FIELDS OF USE AND TERRITORY
Licensed Fields of Use: All fields of use encompassed by the patents in the
LICENSED PATENT RIGHTS.
Licensed Territory: Worldwide
APPENDIX C-ROYALTIES
Licensee agrees to pay to PHS a noncreditable, nonrefundable license issue
royalty in the amount of Five Thousand Dollars ($5,000.00), which is due
thirty-six (36) months from the EFFECTIVE DATE of this AGREEMENT and payable
no later than thirty-six (36) months from the EFFECTIVE DATE of this
AGREEMENT. If LICENSEE terminates this AGREEMENT prior to thirty-six (36)
months from the EFFECTIVE DATE of this Agreement, Licensee shall pay a
royalty of Three Thousand Dollars ($3,000.00), which shall be due and payable
immediately upon termination, unless LICENSEE has previously paid the
nonrefundable license issue royalty.
LICENSEE agrees to pay to PHS a nonrefundable minimum annual royalty in the
amount of Ten Thousand Dollars ($10,000.00) until the First Commercial Sale of a
product occurs, at which time the minimum annual royalty shall increase to
Twenty-Five Thousand Dollars ($25,000.00). The first minimum annual royalty
payment shall be due and payable thirty-six (36) months from the EFFECTIVE DATE
of this AGREEMENT and may be prorated according to the fraction of the calendar
year remaining between the EFFECTIVE DATE of this AGREEMENT and the next
subsequent January 1. Subsequent minimum annual royalty payments shall be due
and payable as set forth in Paragraph 6.02. If the FIRST COMMERCIAL SALE occurs
during any calendar year following the date thirty-six (36) months from the
EFFECTIVE DATE, the minimum annual royalty amount shall also be prorated
according to the portion of the calendar year prior to and following the FIRST
COMMERCIAL SALE.
LICENSEE agrees to pav PHS earned royalties on NET SALES as follows:
Three percent (31/o) of NET SALES by LICENSEE on all LICENSED PRODUCTS
manufactured and sold in the LICENSED TERRITORY.
Licensee agrees to pay PHS benchmark royalties as follows:
One Hundred Thousand Dollars ($100,000.00) within thirty (30) days upon
LICENSEE'S or its sublicensee's submission to the U.S. Food and Drug
Administration (FDA) of the first New Drug Application (NDA) to the LICENSED
PRODUCTS in the LICENSED FIELDS OF USE, or upon LICENSEE'S or its subhcensee's
submission of the corresponding filing in a foreign equivalent of the FDA,
whichever occurs first.
Three Hundred Thousand Dollars ($300,000.00) within thirty (30) days after the
first FDA approval of any NDA submitted to the FDA by LICENSEE or its
sublicensee for the LICENSED PRODUCTS in the LICENSED FIELDS OF USE; however, if
the NDA approval is obtained within seventy-two (72) months of the EFFECTIVE
DATE, the amount of tins payment shall be reduced to Two Hundred Thousand
Dollars ($200,000.00).
Two Hundred Thousand Dollars ($200,000.00) shall be paid within thirty (30) days
after the first approval by a foreign counterpart of the FDA of that country's
equivalent of the NDA submitted by LICENSEE or its sublicensee, for the LICENSED
PRODUCTS in the LICENSED FIELDS OF USE; however, if the approval is obtained
within seventy-two (72) months of the EFFECTIVE DATE, the amount of this payment
shall be reduced to One Hundred Fifty Thousand Dollars ($150,000.00).
LICENSEE agrees to pay PHS sublicensing royalties as follows:
LICENSEE agrees to pay PHS twenty percent (20%) of any cash consideration
received by Licensee from each sublicensee, including LICENSEE'S sublicensee
royalty revenue and consideration received in granting a sublicense. For
purposes of this royalty requirement, cash consideration shall not include any
payment made by any sublicensee on behalf of LICENSEE for the express purpose of
satisfying LICENSEE'S royalty or other financial obligations to PHS under the
terms of this AGREEMENT, except for the earned royalty requirement for sales
made by LICENSEE, and also shall not include the first Ten Thousand Dollars
($10,000.00) of invoiced legal expenses incurred by Licensee in executing the
first sublicense, copies of said invoices to be provided by licensee to PHS.
The amount of invoiced legal expenses exempted from the sublicensing royalty
payment shall be increased to Twenty Thousand Dollars ($20,000.00) if the
Licensee pays the nonrefundable license issue royalty of Five
Thousand Dollars ($5,000.00) within ninety (90) days of the EFFECTIVE DATE.
In any calendar year, sublicensing royalties will not exceed three percent
(3%) of NET SALES, should sales of a LICENSED PRODUCT occur during that year.
APPENDIX D--MODIFICATIONS
Modifications to the Articles and Paragraphs of this AGREEMENT, as agreed to by
PHS and LICENSEE, have been incorporated into the text of this AGREEMENT.
APPENDIX E--BENCHMARKS AND PERFORMANCE
LICENSEE agrees to the following BENCHMARKS for its performance under this
AGREEMENT AND, within ten (10) days of achieving a BENCHMARK, shall notify PHS
that the BENCHMARK has been achieved.
1. Initiate Phase I clinical trials for a LICENSED PRODUCT utilizing a
research organization specializing in clinical trials within fifteen (15)
months of the EFFECTIVE DATE.
2. Initiate Phase II clinical trials for a LICENSED PRODUCT within twenty (20)
months of the EFFECTIVE DATE.
3. Obtain a corporate partner for development and marketing of a LICENSED
PRODUCT within thirty (30) months of the EFFECTIVE DATE.
4. Initiate Phase IIb clinical trials for a LICENSED Product, within
thirty-six (36) months of the EFFECTIVE DATE.
5. Initiate Phase III clinical trials for a LICENSED PRODUCT within
forty-eight (48) months of the EFFECTIVE DATE.
6. File a New Drug Application with the FDA within seventy-two (72) months of
the EFFECTIVE DATE.
7. A LICENSED PRODUCT approved by the FDA within eighty-four (84) months of
the EFFECTIVE DATE.
APPENDIX F--COMMERCIAL DEVELOPMENT PLAN
PUBLIC HEALTH SERVICE
RESEARCH, DEVELOPMENT AND MARKETING PLAN
CURE, on its own or though its sublicensees, intends to market products
developed from the licensed inventions in the U.S. and overseas in conjunction
with large, established pharmaceutical companies, or alternatively to sell the
technology to such a company. The firm fully expects that products marketed in
the U.S. will be manufactured in the United States.
R&D PLAN
The inventions for which license is sought are in a very early stage of
development, and require substantial additional research and development efforts
to yield marketable products. Several potential applications to the technology
exist. Applications to Alzheimer's disease, myasthenia gravis, glaucoma, and
other memory disorders may eventually be pursued, depending upon the outcome of
early research efforts. Described here are specific plans for research and
development of the technology toward a therapeutic for Alzheimer's disease,
which plans represent a good faith estimate of the appropriate means of
achieving such research and development based upon current knowledge and
research methodologies:
DEVELOPMENT TIMELINE
Development of an oral therapeutic will be initiated immediately upon receipt of
an exclusive license for the technology. Under the direction of Xx. Xxxxxxxx,
CURE will interact with experienced facilities to complete the following within
the first six months:
- Synthesis of compounds (GNT) in sufficient quantities for subsequent
preclinical studies.
- Formulation studies to determine optimal formulation for stability and
activity of compounds to be evaluated.
- In vitro screening of compounds by an experienced GLP contractor to
characterize their likely pharmacological profiles.
- Preclinical efficacy of a variety of compounds will be assessed in animal
models of memory impairment by an experienced contractor and/or by
collaborators, already identified, who have expertise in this area.
Based upon the results of activities of the first six months, a lead
compound/formulation will then be chosen for further evaluation. A second
series of preclinical activities will be conducted over the next six months,
focused upon the lead compound:
- In vivo toxicology by a GLP contractor involving three-month daily oral
administrations in two species (e.g., rat and dog).
- GW synthesis of sufficient quantity to initiate clinical trials.
- Tablet formulation will be carried out by a contractor under GW
conditions. Tablet stability and accelerated stability studies will
begin.
Upon completion of the above studies, all necessary data to support an IND
application will have been obtained. An IND application will be submitted, and
approval is anticipated within two months.
Standard drug development strategies will be employed for the clinical
evaluation of efficacy and safety of the drug in man:
- Phase I clinical trials. Toxicology and early efficacy. These include
dose ranging, toxicology and dosing frequency in combination with
pharmakinetics, and are generally performed on relatively few subjects
studied under highly controlled conditions.
- Phase II clinical trials. Demonstration of short term efficacy,
toxicology in longer-term drug administration, refinement of dosing,
improved assessment of efficacy. These will be performed in patients
with Alzheimer's disease, using some blinded components. Note: Phase II
trials are often divided into IIa and IIb. We anticipate that sufficient
information will be obtained in IIa trials to obtain a corporate partner
if the technology performs well. This process is estimated to take six
months.
- Phase III. These trials are intended to demonstrate large-scale efficacy
in patients who are administered the drug in blinded fashion over a
prolonged period. Long-term toxicity is also measured, and concurrently
long range teratogenicity studies are completed. Current FDA protocol
for Alzheimer therapeutic calls for two multi-center trials, at least one
of six months' duration, with nine months preferred. Analysis of data
from such studies often requires several months time.
It is anticipated that Phase IIb and III trials will be carried out by a larger
pharmaceutical company in conjunction with CURE, L.L.C.
DEVELOPMENT FOR OTHER INDICATIONS
CURE intends to develop the licensed technology for use in several other
indications. These include memory impairment, cognition impairment, myasthenia
gravis, glaucoma, and memory improvement.
CURE will, through collaboration, embark on preclinical studies of the utility
of compounds derived from the licensed technology in memory improvement in
aging. These studies will begin during the first year of the Agreement.
CURE will prudently pursue development into the other areas listed above, based
on its experience with its Alzheimer program and outcomes of preclinical and
clinical toxicity studies. As all of these indications will require chronic
treatment with products of the licensed technology, it will be important to
confirm that these compounds are relatively nontoxic in animals and are well
tolerated in humans before proceeding with additional development. It is
expected that development for the additional indications will begin during the
second year of the Agreement.
