94-25922. 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 ...  

  • [Federal Register Volume 59, Number 201 (Wednesday, October 19, 1994)]
    [Unknown Section]
    [Page 0]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 94-25922]
    
    
    [[Page Unknown]]
    
    [Federal Register: October 19, 1994]
    
    
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    DEPARTMENT OF HEALTH AND HUMAN SERVICES
    National Institutes of Health
    
     
    
    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: Readvertisement.
    
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    SUMMARY: This is a readvertisement of a notice which originally 
    appeared in the Federal Register on August 16, 1994 (FR 59 42061-
    42062). Two changes are incorporated: The date for receipt of proposals 
    has been extended and Item 8 under ``The role of the successful 
    corporate partner * * *'' has been modified. The complete, revised text 
    reads as follows:
        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 November 18, 
    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 toward 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 associated CRADA-related research 
    expenses including supplies, reagents, travel, and training. 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 inventor, with (1) an 
    irrevocable, nonexclusive, royalty-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: Octber 13, 1994.
    Barbara M. McGarey,
    Deputy Director, Office of Technology Transfer.
    [FR Doc. 94-25922 Filed 10-18-94; 8:45 am]
    BILLING CODE 4140-01-P
    
    
    

Document Information

Published:
10/19/1994
Department:
National Institutes of Health
Entry Type:
Uncategorized Document
Action:
Readvertisement.
Document Number:
94-25922
Pages:
0-0 (1 pages)
Docket Numbers:
Federal Register: October 19, 1994