[Federal Register Volume 59, Number 157 (Tuesday, August 16, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-19943]
[[Page Unknown]]
[Federal Register: August 16, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Cancer Institute; Opportunity for a Cooperative Research
Agreement (CRADA) for the Scientific and Commercial Development of
Monoclonal Antibodies to a Tumor-Specific Growth Factor for the
Diagnosis and Prognosis of Premalignant Lesions and Cancer
AGENCY: National Institutes of Health, PHS, DHHS.
ACTION: Notice.
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SUMMARY: The National Cancer Institute (NCI) seeks a pharmaceutical or
biotechnology company that can effectively pursue the scientific and
commercial generation and development of a panel of monoclonal
antibodies against an epidermal growth factor (EGF)-related peptide,
cripto-1 (CR-1). The project is of scientific importance because CR-1
is a protein that exhibits structural homology to the EGF/transforming
growth factor (TGF) gene family peptides. As such,
CR-1 might function as a growth factor or growth inhibitor. Therefore,
CR-1 may be important as an autocrine or paracrine modulator in such
processes as tumor cell growth, wound repair, neovascularization, and
inflammation.
NCI has successfully isolated and cloned the gene that encodes CR-
1, an EGF-related peptide growth factor that does not function through
the EGF receptor. The NCI has also obtained a rabbit anti-peptide
polyclonal antibody that can detect the expression of CR-1 in formalin-
fixed, paraffin-embedded human tissue sections. CR-1 has been shown to
be preferentially and differentially expressed in several different
human premalignant lesions and cancers. The selected sponsor will
purify a recombinant CR-1 protein and use this material as an immunogen
to generate anti-CR-1 monoclonal antibodies for use in the diagnosis
and prognosis of human cancers.
ADDRESSES: Inquiries and proposals regarding this opportunity should be
addressed to either Michael Christini or Mark Noel (Tel# 301-496-0477
Fax# 301-402-2117), Office of Technology Development, National Cancer
Institute, Bldg. 31, Room 4A49, NIH, 9000 Rockville Pike, Bethesda, MD
20892.
DATES: Proposals must be received at the above address by 5 P.M.
September 9, 1994.
SUPPLEMENTARY INFORMATION: The NCI is seeking a pharmaceutical or
biotechnology company which, after obtaining a license in accordance
with the requirements of the regulations governing the transfer of
Government-developed agents (37 CFR part 404), can purify a recombinant
CR-1 protein for which patents are pending or have been issued and to
utilize this purified recombinant CR-1 protein as an immunogen to
generate a panel of mouse monoclonal antibodies. The immunoreactive CR-
1 protein has been detected by immunoperoxidase staining using a rabbit
anti-peptide polyclonal CR-1 antibody in a majority of human colon
cancers, breast cancers, gastric cancers and pancreatic cancers. Little
or no staining was detected in surrounding, noninvolved colon, breast
or gastric epithelial cells. In addition, a majority of premalignant
colonic adenomas, breast ductal carcinomas in situ and gastric
intestinal metaplasia express immunoreactive CR-1.
A recombinant CR-1 protein has been generated using a yeast
expression vector in Pichia pastoris and a partially purified protein
obtained. This protein as well as synthetic, refolded peptides that
correspond to the EGF-like domain in CR-1 are mitogenic for human
breast cancer cells yet fail to bind to the EGF receptor or other type
I receptor tyrosine kinases. Expression of CR-1 antisense mRNA using a
recombinant, replication defective retroviral expression vector in
colon cancer cells that expresses CR-1 inhibits the growth of these
cells in vivo in nude mice. In order to utilize the diagnostic and
therapeutic potentials of CR-1, it will be necessary to purify a
significant amount of the recombinant CR-1 protein to more fully define
its biological properties and to identify the receptor through which it
functions. In addition, mouse monoclonal antibodies against the
purified CR-1 recombinant protein will expedite screening studies for
CR-1 expression in other human premalignant lesions and cancers and
should exhibit more specificity and sensitivity for the detection of
CR-1 in tissues by immunocytochemistry (ICC) or in tissue extracts or
serum samples by ELISA.
The role of the National Cancer Institute, the Division of Cancer
Biology, Diagnosis and Centers includes:
1. NCI will provide expression vectors that encode CR-1 and can be
used to produce CR-1 in E. coli.
2. NCI will provide expression vectors that encode CR-1 in yeast
Pichia pastoris containing several milligrams of recombinant CR-1
protein.
3. NCI will provide a rabbit polyclonal anti-CR-1 antibody for
monitoring CR-1 recovery during the purification from the yeast
conditioned medium.
4. NCI will assay the purified recombinant CR-1 protein for
bioactivity.
5. NCI will screen anti-CR-1 monoclonal antibodies for reactivity
by Western blot analysis against native CR-1 protein from CR-1 positive
human embryonal carcinoma or colon carcinoma cells.
The role of the successful corporate partner will include:
1. Obtain background license in appropriate fields of use to the
relevant Government patent rights.
2. Purify to homogeneity 30-50 milligrams of CR-1 from Pichia
pastoris conditioned medium.
3. Provide the purified recombinant CR-1 protein.
4. Utilize the purified recombinant CR-1 protein to generate mouse
anti-CR-1 monoclonal antibodies.
5. Screen anti-CR-1 monoclonal antibodies for specificity,
reactivity, and sensitivity towards recombinant CR-1 protein.
6. Ascertain whether monoclonal anti-CR-1 antibodies can detect
native CR-1 protein in CR-1 positive human colorectal or embryonal
carcinoma cells by radioimmunoprecipitation analysis and by ELISA.
7. Determine whether anti-CR-1 antibodies can be used for ICC on
formalin-fixed, paraffin embedded tissues known for CR-1 expression.
8. Provide funds to support a postdoctoral fellow and associated
expenses.
Criteria for choosing the collaborating company will include:
1. Ability to obtain background license to relevant patent rights.
2. Experience in producing and purifying recombinant proteins,
particularly growth factors or cytokines.
3. Experience in generating and screening monoclonal antibodies.
4. Willingness to cooperate with the NCI in the collection and
evaluation of data.
5. Willingness to cost share in laboratory studies.
6. An agreement to be bound by the DHHS rules involving the use of
human and animal subjects, and human tissue.
7. Provisions for equitable distribution of patent rights to any
inventions. Generally the rights of ownership are retained by the
organization which is the employer of the free license to the
Government (when a company employee is the sole inventor) or (2) an
exclusive or nonexclusive license to the company on terms that are
appropriate (when the Government employee is the sole inventor).
Dated: August 8, 1994.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 94-19943 Filed 8-15-94; 8:45 am]
BILLING CODE 4140-01-P
