[Federal Register Volume 61, Number 118 (Tuesday, June 18, 1996)]
[Notices]
[Pages 30914-30915]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-15363]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Licensing Opportunity and/or Opportunity for a Cooperative
Research and Development Agreement (CRADA) for the Scientific and
Commercial Development of Novel Heparin-Binding Peptides
AGENCY: National Institutes of Health, Public Health Services, DHHS.
ACTION: Notice.
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SUMMARY: The National Institutes of Health is seeking licensees and/or
CRADA partners for the further development, evaluation, and
commercialization of novel heparin-binding peptides. The inventions
claimed in the patent applications referenced below are available for
either exclusive or non-exclusive licensing (in accordance with 35
U.S.C. 207 and 37 CFR Part 404) and/or further development under a
CRADA for clinical and research applications described below in
Supplementary Information.
Heparin- and Sulfatide-Binding Peptides From the Type I Repeats of
Human Thrombospondin and Conjugates Thereof
DD Roberts, PJ Browning, J Bryant, JK Inman, HC Krutzsch, N Guo
(NCI)
Serial No. 08/487,568, filed 07 Jun 95, which is a CIP of
Serial No. 08/215,085, filed 21 Mar 94, which is a CIP of
Serial No. 07/801,812, which issued as U.S. Patent No. 5,357,041
on 18 Oct 94.
To expedite the research, development, and commercialization of
these compounds, the National Institutes of Health is seeking a CRADA
with a pharmaceutical or biotechnology company in accordance with the
regulations governing the transfer of Government-developed agents. Any
proposal to use or develop these compounds will be considered.
ADDRESSES: CRADA proposals and questions about this opportunity should
be addressed to: Dr. Gary D. Colby, Office of Technology Development,
National Cancer Institute, Executive Plaza South, Suite 450, 6120
Executive Boulevard MSC 7182, Bethesda, MD 20892-7182; telephone: 301/
496-0477; fax: 301/402-2117.
Licensing proposals and questions about this opportunity should be
addressed to: Ms. Carol Lavrich, Technology Licensing Specialist,
Office of Technology Transfer, National Institutes of Health, 6011
Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804;
telephone: 301/496-7735, ext. 287; fax: 301/402-0220.
Information about the patent applications and pertinent information
not yet publicly described can be obtained under 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. Respondees interested in submitting a
CRADA proposal should be aware that it may be necessary to secure a
license to the above patent rights in order to commercialize products
arising from a CRADA.
DATES: There is no deadline by which license applications must be
received. CRADA proposals must be received on or before September 16,
1996.
SUPPLEMENTARY INFORMATION: These inventions identify a family of
related peptides, peptide analogs, and peptidomimetics useful for
blocking or modifying the biological activities of heparin, sulfatides,
fibronectin, fibroblast growth factor and transforming growth factor-
(TGF) Among the activities exhibited by compounds
within this family of agents are:
Inhibition of tumor cell growth, including inhibition of
breast tumor growth in a mouse xenograft model;
Inhibition of Kaposi's Sarcoma (SK) cell proliferation and
migration in vitro and KS-like lesion formation in vivo;
Inhibition of endothelial and breast carcinoma cell
proliferation, adhesion, and motility in vitro;
Inhibition of angiogenesis in vivo;
Specific, high affinity binding to heparin and related
sulfated glycoconjugates, including preventing interaction with
adhesion molecules, growth factors, cells, and heparin-dependent
enzymes; and
Activation of latent TGF.
The compounds within this family of agents are based upon
functional sequences from the three type I repeats of human endothelial
cell thrombospondin. The inventions identify particular peptides,
analogs, and peptidomimetics that have particularly advantageous
properties such as increased physiological stability, enhanced
activity, lack of electrostatic charge, and increased solubility. The
inventions also describe unique approaches to constructing water-
soluble conjugates which exhibit a number of interesting and useful
biological activities.
It is expected that the high potency of these agents will lower the
effective dose needed, and, subsequently, will reduce the immunological
response against the peptides and the risks of toxicity. Among the
diseases for which these agents may prove to be particularly useful
therapeutic agents are:
Kaposi's sarcoma
Breast carcinoma
Melanoma
Other epithelial cancers
Other diseases involving abnormal vascular proliferation
The inventors of these agents seek collaborators for their ongoing
research and development efforts. Two research projects for which
collaborators are particularly sought involve investigation of means of
controlling angiogenesis and investigation of means for modulating the
activity of TGF, particularly to control fibrosis, using the
agents described above.
Thrombospondin has been identified as an anti-angiogenic factor in
human epithelial tissue. Certain agents described above have shown
particular utility for inhibition of pathological angiogenesis in vivo.
These agents have been engineered to decrease both proteolytic
degradation and the rapidity of their clearance from the bloodstream
and to increase their biological activity. These agents have been shown
to influence tumor cell adhesion and growth in vitro and in vivo. Other
peptides have been shown to inhibit tumorigenesis and metastasis in
vivo. Further development of agents, and their application in
therapeutic capacities, is planned.
The antiproliferative activities of certain agents upon epithelial
and breast
[[Page 30915]]
carcinoma cells has demonstrated to be independent of latent
TGF activation. Other agents, however, have been shown to
activate latent TGF. TGF-activating agents also
exhibit anti-tumor activity in vivo. Further development of
TGF-modulating agents, particularly those useful for control
of fibrosis, is planned.
Particularly sought are companies dedicated to the development of
small therapeutic molecules, such as peptides and their analogs.
Collaborators should have particular in-house expertise relating to
peptide research and development. It is anticipated that fruitful
collaboration will result from sustained and meaningful contribution on
the part of the collaborator.
The CRADA aims will include optimizing peptide and peptridomimetic
activity in vitro and in vivo, preclinical development of the synthetic
peptides and mimetics, and clinical studies as warranted. The CRADA
partner will enjoy the benefit of a right of first refusal for a
license (on a reasonable commercial terms) to government-owned rights
in any invention arising within the scope of the CRADA. Furthermore,
the CRADA partner will be responsible for reimbursement of government
expenses for patenting any resulting inventions during the term of the
CRADA.
The role of the National Cancer Institute will include the
following:
1. The government will continue in vitro and in vivo preclinical
development of the peptides and mimetics as inhibitors of tumor growth
and metastasis and as modulators of TGF- activity.
2. The government will provide available data and expertise in
structure-function relationships and conformational analysis of the
active peptides and peptidomimetics. These data will be evaluated
jointly in order to assess an efficient research path.
3. As appropriate, the government will initiate collaborative
clinical trials under its extramural clinical trials network, thus
ensuring the clinical evaluation of the compounds.
The role of the collaborator will include the following:
1. Prepare and characterize GMP quality nonmetabolizable analogs
(as determined by both parties) of the active peptides and provide
these to the NCI for characterization as angiogenesis and metastasis
inhibitors or as modulators of TGF- activity.
2. Provide funds for preclinical development of the peptides in
vitro and for screening activities in appropriate animal models.
3. Collaborate in the planning and support for clinical development
leading to FDA approval and marketing.
Selection criteria for choosing the CRADA partner will include, but
are not limited to, the following:
1. Experience in preclinical and clinical drug development.
2. Experience and ability to produce, package, market, and
distribute pharmaceutical products, particularly peptides and peptide
analogs, in the United States.
3. A willingness to cooperate with the Public Health Service in the
collection, evaluation, publication, and maintenance of data from
clinical trials of investigational agents.
4. Willingness to share the costs associated with the development
of the peptides and mimetics. These costs include acquisition of
synthesis or both of the peptides and mimetics in amounts adequate for
clinical trials and marketing.
5. Agreement to be bound by DHHS rules and regulations regarding
the use of human subjects in clinical investigations, intellectual
property rights, ethical treatment of animals, and randomized clinical
trials.
6. The aggressiveness of the development plan, including the
appropriateness of milestone and deadlines for preclinical and clinical
development.
7. Agreement with provisions for equitable distribution of patent
rights to any inventions developed under the CRADA(s). Generally, the
rights of ownership are retained by the organization which is the
employer of the inventor, with an irrevocable, non-exclusive, royalty-
free license to the Government (when a company employee(s) is the sole
inventor) or a first option to negotiate an exclusive or non-exclusive
license to the company on terms that are appropriate (when the
Government employee(s) is the sole or a joint inventor).
Dated: June 7, 1996.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 96-15363 Filed 6-17-96; 8:45 am]
BILLING CODE 4140-01-M