[Federal Register Volume 63, Number 119 (Monday, June 22, 1998)]
[Notices]
[Pages 33939-33940]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-16426]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Licensing Opportunity and/or Cooperative Research and Development 
Agreement (``CRADA'') Opportunity: Drug and Method for the Therapeutic 
Treatment of Ovarian Cancer and Mesotheliomas

AGENCY: National Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The NIH is a seeking Licensee(s) and/or Cooperative Research 
and Development Agreement (``CRADA'') Collaborators to further develop, 
evaluate, and commercialize a recombinant immunotoxin, termed SS(dsFv)-
PE38. SS(dsFv)-PE38 is a disulfide-linked recombinant immunotoxin fused 
to PE38, a mutant form of Pseudomonas Exotoxin, that binds to 
mesothelin. Mesothelin is a differentiation antigen present on the 
surface of most ovarian cancers, mesoltheliomas, and several other 
types of human cancers including cervical cancer. In normal tissue, 
mesothelin is limited in its expression to mesothelial cells and basal 
cells of the trachea (low expression). Therefore, it represents an 
excellent target for antibody-mediated delivery of cytotoxic agents. 
The antigen is a 40 kD glycoprotein that is attached to the cell 
surface by phosphatidylinositol. SS (dsFv)-PE38 immunotoxin is very 
cytotoxic to cancer cells expressing mesothelin and binds with an 
affinity of approximately 11 nanomolar. The SS (dsFv)-PE38 immunotoxin 
also produces complete regressions of mesothelin containing solid 
tumors growing in nude mice. The goal is to move this drug and 
methodology into clinical trials. The invention is claimed in USPA SN 
08/776,271 and PCT patent application PCT/US97/00224, entitled: 
``Mesothelin, A Differentiation Antigen Present on Mesothelium, 
Mesotheliomas and Ovarian Cancers and Methods and Kits for targeting 
the Antigen'' and is available for either exclusive or non-exclusive 
licensing (in accordance with 35 U.S.C. 207 and 37 CFR Part 404).

DATES: Respondees interested in licensing the invention(s) will be 
required to submit an ``Application for License to Public Health 
Service Inventions'' on or before September 21, 1998 for priority 
consideration.
    Interested CRADA Collaborators must submit a confidential proposal 
summary to the NCI on or before September 21, 1998 for consideration. 
Guidelines for preparing full CRADA proposals will be communicated 
shortly thereafter to all respondents with whom initial confidential 
discussions will have established sufficient mutual interest. CRADA 
proposals submitted thereafter may be considered if a suitable CRADA 
Collaborator has not been selected.

ADDRESSES: Questions about licensing opportunities may be addressed to 
J.R. Dixon, Ph.D., Technology Licensing Specialist, Office of 
Technology Transfer, National Institutes of Health, 6011 Executive 
Boulevard, Suite 325, Rockville, Maryland 20852-3804; Telephone: (301) 
496-7056 ext. 206; Facsimile: (301) 402-0220; E-Mail: 
``DixonJOD.NIH.GOV''. Information about Patent Applications and 
pertinent information not yet publicly described can be obtained under 
the terms of a Confidential Disclosure Agreement. Respondees interested 
in licensing the invention(s) will be required to submit an 
``Application for License to Public Health Service Inventions''.
    Depending upon the mutual interests of the Licensee(s) and the 
National Cancer Institute (``NCI''), a Cooperative Research and 
Development Agreement (CRADA) to collaborate to improve the properties 
of the SS(dsFv)-PE38 immunotoxin may also be negotiated. Proposals and 
questions about this CRADA opportunity may be addressed to Ms. Karen 
Maurey, Acting Deputy Director, National Cancer Institute, Technology 
Development & Commercialization Branch, 6120 Executive Plaza South-Room 
450, Rockville, Maryland 20852; Telephone: (301) 496-0477; Facsimile: 
(301) 402-2117. Respondees interested in submitting a CRADA proposal 
should be aware that it may be necessary to secure a license to the 
above mentioned patent rights in order to commercialize products 
arising from a CRADA.

SUPPLEMENTARY INFORMATION: NIH/NCI scientists have done toxicity 
studies with the SS(dsFv)-PE38 immunotoxin in mice and with an earlier 
single chain variant (SSFv-PE38) in Cynomolgus monkeys. Treatment of 
mice with 5g

[[Page 33940]]

QOD  x  3 (0.25 mg/kilo) produced complete tumor regressions without 
death or toxicity. Since the antibody does not react with mouse 
mesothelin, possible toxicities in mice are due to non-specific (liver) 
toxicity. NIH/NCI scientists have also administered this aforementioned 
single chain form to monkeys. SS(Fv)-PE38 reacts just as strongly with 
monkey mesothelin as it does with human mesothelin, and therefore, one 
would expect the monkey to be a good predictor of toxicity in humans. 
At a 0.05 mg/kilo dose level, no toxicity was experienced. A second 
monkey received 0.5 mg/kilo and showed a transient elevation in liver 
enzymes and non-specific physical signs (inactivity), but fully 
recovered.
    In the United States, an estimated 15,000 patients die of ovarian 
cancer each year despite therapy. Although less common, mesotheliomas 
are known to be resistant to all chemotherapeutic agents. Development 
of new therapeutic modalities to treat these malignancies is needed.
    A Cooperative Research and Development Agreement or CRADA means the 
anticipated joint agreement to be entered into by NCI pursuant to the 
Federal Technology Transfer Act of 1986 and Executive Order 12591 of 
April 10, 1987 as amended by the National Technology Transfer 
Advancement Act of 1995 to collaborate to improve the properties of the 
SS(dsFv)-PE38 immunotoxin.
    The rule of the NCI in the CRADA may include, but are not be 
limited to:
    1. Providing intellectual, scientific, and technical expertise and 
experience to the research project.
    2. Providing the Collaborator with samples of the subject compounds 
to create, optimize, test and develop targeted drugs for clinical 
studies.
    3. Planning research studies and interpreting research results.
    4. Carrying out research to improve the properties of the SS(dsFv)-
PE38 which include, but are not restricted to, increased production 
yield, decreased side effects, increased cytotoxic activity and better 
tissue penetration.
    5. Publishing research results.
    The role of the CRADA Collaborator may include, but not be limited 
to:
    1. Providing significant intellectual, scientific, and technical 
expertise or experience to the research project.
    2. Planning research studies and interpreting research results.
    3. Providing samples of the subject compounds to create, optimize, 
test and develop targeted drugs for clinical studies.
    4. Providing technical and/or financial support to facilitate 
scientific goals and for further design of applications of the 
technology outlined in the agreement.
    5. Incorporating the immunotoxin into liposomes or producing other 
formulations in order to increase the therapeutic efficacy.
    6. Providing immunotoxin for laboratory and animal studies.
    7. Publishing research results.
    Selection criteria for choosing the CRADA Collaborator may include, 
but not be limited to:
    1. The ability to collaborate with NCI on further research and 
development of this technology. This ability can be demonstrated 
through experience and expertise in this or related areas of technology 
indicating the ability to contribute intellectually to ongoing research 
and development.
    2. The demonstration of adequate resources to perform the research 
and development of this technology (e.g. facilities, personnel and 
expertise) and accomplish objectives according to an appropriate 
timetable to be outlined in the CRADA Collaborator's proposal.
    3. The willingness to commit best effort and demonstrated resources 
to the research and development of this technology, as outlined in the 
CRADA Collaborator's proposal.
    4. The demonstration of expertise in the commercial development and 
production of products related to this area of technology.
    5. The level of financial support the CRADA Collaborator will 
provide for CRADA-related Government activities.
    6. The demonstration of expertise pertinent to the development of 
models to evaluate and improve the efficacy of the SS (dsFv)-PE38 
immunotoxin for the treatment of ovarian cancer and mesotheliomas.
    7. The demonstration of expertise in the formulation of drugs into 
liposomes or other delivery vehicles.
    8. The willingness to cooperate with the NCI in the timely 
publication of research results.
    9. The agreement to be bound by the appropriate DHHS regulations 
relating to human subjects, and all PHS policies relating to the use 
and care of laboratory animals.
    10. The willingness to accept the legal provisions and language of 
the CRADA with only minor modifications, if any. These provisions 
govern the distribution of patent rights to CRADA inventions. 
Generally, the rights of ownership are retained by the organization 
that is the employer of the inventor, with (1) the grant of a license 
for research and other Government purposes to the Government when the 
CRADA Collaborator's employee is the sole inventor, or (2) the grant of 
an option to elect an exclusive or nonexclusive license to the CRADA 
Collaborator when the Government employee is the sole inventor.

    Dated: May 18, 1998.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.

    Dated: May 26, 1998.
Kathleen Sybert,
Acting Director, Technology Development and Commercialization Branch, 
National Cancer Institute, National Institutes of Health.
[FR Doc. 98-16426 Filed 6-19-98; 8:45 am]
BILLING CODE 4140-01-M