[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-
<greek-b> (TGF<greek-b>) Among the activities exhibited by compounds 
within this family of agents are:

<bullet> Inhibition of tumor cell growth, including inhibition of 
breast tumor growth in a mouse xenograft model;
<bullet> Inhibition of Kaposi's Sarcoma (SK) cell proliferation and 
migration in vitro and KS-like lesion formation in vivo;
<bullet> Inhibition of endothelial and breast carcinoma cell 
proliferation, adhesion, and motility in vitro;
<bullet> Inhibition of angiogenesis in vivo;
<bullet> Specific, high affinity binding to heparin and related 
sulfated glycoconjugates, including preventing interaction with 
adhesion molecules, growth factors, cells, and heparin-dependent 
enzymes; and
<bullet> Activation of latent TGF<greek-b>.

    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:

<bullet> Kaposi's sarcoma
<bullet> Breast carcinoma
<bullet> Melanoma
<bullet> Other epithelial cancers
<bullet> 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<greek-b>, 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<greek-b> activation. Other agents, however, have been shown to 
activate latent TGF<greek-b>. TGF<greek-b>-activating agents also 
exhibit anti-tumor activity in vivo. Further development of 
TGF<greek-b>-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-<greek-b> 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-<greek-b> 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