[Federal Register Volume 62, Number 10 (Wednesday, January 15, 1997)]
[Notices]
[Pages 2169-2170]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-1004]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health


National Cancer Institute; Opportunity for a Cooperative Research 
and Development Agreement (CRADA) for the Scientific and Commercial 
Development of Monoclonal Antibodies to a Tumor-Specific Growth Factor 
for the Diagnosis and Prognosis of Premalignant Lesion and Cancer

AGENCY: National Institutes of Health, 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) and its novel receptor. 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 of peptides. As such, CR-1 might function as 
a growth or survival factor. Therefore, CR-1 may be important as an 
autocrine or paracrine modulator in such processes a tumor cell growth, 
wound repair, neovascularization, inflammation, and apoptosis.
    NCI has successfully isolated and cloned the gene that encodes CR-
1, an EGF-related peptide growth factor that does not bind to the EGF 
receptor or other type 1 receptor tyrosine kinases. 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 
sent to Richard I. Kohn, J.D., M.S., Office of Technology Development, 
National Cancer Institute, as follows: (a) by U.S. Mail to: Executive 
Plaza South, Room 450, 6120 Executive Blvd., MSC 7182, Bethesda MD 
20892-7182; (b) By messengers and express delivery to: 6120 Executive 
Blvd, Suite 450, Rockville, MD 20852; (c) by telephone at (301) 496-
0477; (d) by fax at (301) 402-2117.


[[Page 2170]]


DATES: Written proposals must be received at the above address by 5:00 
p.m. on March 17, 1996.

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 rights, (37 CFR part 404), can purify a 
recombinant CR-1 protein (for which patents are pending or have been 
issued) and 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 baculovirus 
expression vector in Sf-9 insect cells 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 and can modulate milk protein expression, 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 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 United States Public Health Service owns the following issued 
patents which may be relevant to the subject technology:
    1. United States Patent No. 5,264,557, issued November 23, 1993, 
``Human CRIPTO-Related Gene.''
    2. United States Patent No. 5,256,643, issued October 26, 1993, 
``Cloned Human CRIPTO Gene and Applications Thereof.''
    Questions regarding licensing should be directed to Joseph Hemby, 
Office of Technology Transfer, National Institutes of Health, 6011 
Executive Boulevard, #325, Rockville, MD 20852-3804, telephone (301) 
496-7056.
    The role of the National Cancer Institute, Division of Basic 
Sciences, includes:
    1. NCI will provide vectors that encode CR-1 and can be used to 
produce CR-1 in E. coli and in Sf-9 insect cells.
    2. NCI will provide a rabbit polyclonal anti-CR-1 antibody for 
monitoring CR-1 recovery during the purification from the yeast 
conditioned medium.
    3. NCI will assay the purified recombinant CR-1 protein for 
bioactivity.
    4. 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 collaborator will include:
    1. Purify to homogeneity 30-50 milligrams of CR-1 from E. coli or 
Sf-9 insect cell conditioned medium.
    2. Provide the purified recombinant CR-1 protein.
    3. Utilize the purified recombinant CR-1 protein to generate mouse 
anti-CR-1 monoclonal antibodies.
    4. Screen anti-CR-1 monoclonal antibodies for specificity, 
reactivity, and sensitivity towards the recombinant CR-1 protein.
    5. Ascertain whether monoclonal anti-CR-1 antibodies can detect 
nature CR-1 protein in CR-1 positive human colorectal or embryonal 
carcinoma cells by radioimmunoprecipitation analysis and by ELISA.
    6. Determine whether anti-CR-1 antibodies can be used for ICC on 
formalin-fixed, paraffin embedded tissues known for CR-1 expression.
    7. Provide funds to support a postdoctoral fellow and associated 
expenses.
    Criteria for choosing the collaborator will include:
    1. Experience in producing and purifying recombinant proteins, 
particularly growth factors or cytokines.
    2. Experience in generating and screening monoclonal antibodies.
    3. Willingness to cooperate with the NCI in the collection and 
evaluation of data.
    4. Willingness to cost share in laboratory expenses.
    5. And agreement to be bound by the DHHS rules involving the use of 
human and animal subjects and human tissues.
    6. Provisions for equitable distribution of patent rights to any 
inventions. Generally, the rights of ownership are retained by the 
organization(s) which is/are the employer(s) of the inventor. For 
inventions made solely by the collaborator's employees, there shall be 
a grant to the Government of a nonexclusive, nontransferable, 
irrevocable, paid up license to practice the invention or have the 
invention practiced throughout the world by or on behalf of the 
Government for research or other Government purposes. For inventions 
not made solely by the collaborator's employees, there shall be a grant 
to the collaborator of an option to elect an exclusive or nonexclusive 
commercialization license.

    Dated: December 9, 1996.
Thomas Mays,
Director, Office of Technology Development, National Cancer Institute, 
National Institutes of Health.
[FR Doc. 97-1004 Filed 1-14-97; 8:45 am]
BILLING CODE 4140-01-M