[Federal Register Volume 59, Number 134 (Thursday, July 14, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-17082]
[[Page Unknown]]
[Federal Register: July 14, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Cancer Institute: Opportunity for a Cooperative Research
and Development Agreement (CRADA) for the Biomedical Use of Novel
Approaches for Lentivirus Vaccine Development
AGENCY: National Institutes of Health, PHS, DHHS.
ACTION: Notice.
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SUMMARY: The Department of Health and Human Services (DHHS) seeks an
agreement with a pharmaceutical or biotechnology company to use a novel
approach for Lentivirus vaccine development. This novel method for
immunological focusing of protective effector responses uses site-
directed mutagenesis to reduce the antigenicity of immunodominant
epitopes for the purpose of preventing these epitopes from eliciting an
immune response. One example of this is the introduction of N-linked
carbohydrate. These immunodominant decoy epitopes (decotopes) function
to focus the immune system away from responding to more conserved,
immunorecessive and potentially more broadly protective domains. Any
CRADA for the biomedical use of this technology will be considered.
ADDRESSES: Proposals and questions about this opportunity may be
addressed to Dr. Raphe Kantor, Office of Technology Development,
National Cancer Institute-Frederick Cancer Research and Development
Center, P.O. Box B, Frederick, MD 21702-1201 Telephone (301) 846-5465,
Facsimile (301) 846-6820.
SUPPLEMENTARY INFORMATION: To speed the research, development and
commercialization of this technology, the National Cancer Institute at
the Frederick Cancer Research and Development Center is seeking an
agreement with a pharmaceutical or biotechnology company in accordance
with the regulations governing the transfer of Government-developed
agents for joint research, development, evaluation, and
commercialization in the area of Lentivirus vaccine development.
The National Cancer Institute Laboratory of Tumor Cell Biology has
been working on novel approaches to HIV-1 vaccine development. Epitope-
specific neutralizing antibodies arise early in the course of HIV
infection and are generally directed towards immunodominant
determinants in the third hypervariable domain (V3) and gp41
transmembrane domain of the major envelope glycoprotein gp160. Since
this domain is one of the more variable and functional immunodominant
regions of gp120, variants can arise which escape the effects of
neutralizing antibodies. Antibodies capable of neutralizing a broader
range of isolates appear at a later time during the course of the
infection. These more broadly neutralizing antibodies are not a simple
collection of different V3-specific antibodies, but instead are
composed mostly of antibodies that have a higher order of conformation
and interfere with the binding of virus to CD4. To test whether this
early response to V3 suppresses, delays or inhibits the subsequent
response to other parts of the molecule, putative N-linked
glycosylation sites were introduced into the V3 domain of the molecule
in an effort to mask V3. Guinea pigs were first primed with live
recombinant vaccinia virus expressing the N-linked glycosylation
mutant, then boosted with purified recombinant protein. Neutralizing
titers of antibodies were produced, a proportion of which were directed
to other epitopes of gp120.
Background information including reprints and issued patents is
available from the above-referenced address. Patent applications and
pertinent information not yet publicly disclosed can be obtained under
a Confidential Disclosure Agreement.
The CRADA aims include the rapid publication of research results
and their timely commercialization. The CRADA partner will have an
option to negotiate the terms of an exclusive or nonexclusive
commercialization license to subject inventions arising under the
CRADA.
The role of the Laboratory of Tumor Cell Biology, NCI-FCRDC, in
this CRADA will include but not be limited to:
1. Providing recombinant reagent which has already been molecularly
modified by said technology for further basic and clinical
applications.
2. Providing technology to identify immunogenic domains that are
involved in decoying or suppressing the response away from more broadly
protective epitopes as demonstrated for HIV-1.
3. Providing expertise in vaccine design, vaccinia-based delivery,
in vitro and in vivo assessment of immunogenic products and responses
and development of relevant animal models.
4. Developing alternative vaccine delivery systems.
5. Contracting, as needed, NCI-FCRDC suppport services such as
biomedical supercomputing, x-ray crystallography, and synthesis of
monoclonal antibodies.
6. Publishing research results.
The role of the Collaborator will include but not be limited to:
1. Providing technical and scientific support for further design
and in vitro and in vivo testing of candidate immunogens for Equine
Infectious Anemia, Visna Maedi, Feline Immunodeficiency Virus, Simian
Immundeficiency Virus, Bovine Immunodeficiency Virus, and Caprine
Arthritis Encephalitis Virus.
2. Providing support for ongoing CRADA-related research in the
development of vaccine candidates:
(a) Financial support to facilitate scientific goals,
(b) Financial and logistic support for development, efficacy
testing of animal models of natural lentiviral infections.
(c) Financial and logistical support for animal clinical trials
Phase I-III.
3. Using the proposed technology in the development of alternative
delivery systems (i.e DNA, canary pox, BCG, polio, Salmonella, and
attenuated vectors), and novel antigen presenting strategies.
4. Using the proposed technology for other novel animal
biopharmaceutical applications.
5. Publishing research results.
Selection criteria for choosing the CRADA partner will 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 the ongoing
research and development.
2. The demonstration of adequate resources to perform the research,
development and commercialization of this technology (e.g. facilities,
personnel and expertise) and accomplish objectives according to an
appropriate timetable to be outlined in the Collaborator's proposal.
3. The ability to perform clinical testing or trials, and obtain
IND, NDA and FDA approval for a new drug, medical device or apparatus,
diagnostic or therapeutic test, or treatment modality.
4. The willingness to commit best effort and demonstrated resources
to the research, development and commercialization of this technology.
5. The demonstration of expertise in the commercial development,
production, marketing and sales of products related to this area of
technology.
6. The level of financial support the Collaborator will provide for
CRADA-related Government activities.
7. The willingness to cooperate with the National Cancer Institute
in the timely publication of research results.
8. 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.
9. The willingness to accept the legal provisions and language of
the CRADA with only minor modifications, if any. These provisions
govern the equitable distribution of patent rights to CRADA inventions.
Generally, the rights of ownership are retained by the organization
which is the employer of the inventor, with (1) the grant of a research
license to the Government when the CRADA collaborator's employee is the
sole inventor, or (2) the grant of an option to negotiate for an
exclusive or nonexclusive license to the Collaborator when the
Government employee is the sole inventor.
The following is a listing of Dr. Robert Garrity's patent portfolio
for this technology:
Application Title: ``Immunological Focusing of Protective Effector
Responses Using Site-Directed Mutagenesis or Chemical modification to
Alter a Specific Protein or Peptide Immunogen for Use in Plant, Animal
and Human Vaccines and Immunotherapies.''
Inventors: Dr. Robert R. Garrity, Dr. Peter L. Nara, Dr. Jaap
Goudsmit.
Dated: June 25, 1994.
Barbara M. McGarey, J.D.,
Deputy Director, Office of Technology Transfer National Institutes of
Health.
[FR Doc. 94-17082 Filed 7-13-94; 8:45 am]
BILLING CODE 4140-01-P