[Federal Register Volume 61, Number 222 (Friday, November 15, 1996)]
[Notices]
[Pages 58572-58573]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-29346]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Cancer Institute: Opportunity for a Cooperative Research 
and Development Agreement (CRADA) for the Scientific and Commercial 
Development of Fusion Proteins That Include Antibody and Non-Antibody 
Portions

AGENCY: National Cancer Institute, National Institutes of Health, PHS, 
DHHS.

ACTION: Notice.

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SUMMARY: The Department of Health and Human Services (DHHS) seeks one 
or more companies that can collaboratively pursue the pre-clinical and 
clinical development of Fusion Proteins That Include Antibody and Non-
Antibody Portions. The following disease states are of interest: 
neoplasia, arteriosclerosis, tumor vascularization, fibrotic diseases, 
psoriasis and wound healing. The National Cancer Institute, Laboratory 
of Cellular and Molecular Biology has developed an assay system to 
identify receptor agonists and antagonists using fusion protein 
technology. The selected sponsor will be awarded a CRADA with the 
National Cancer Institute for the co-development of agents identified 
using the fusion protein technology.

ADDRESSES: Questions about this opportunity may be addressed to Jeremy 
A. Cubert, M.S., J.D., Office of Technology Development, NCI, 6120 
Executive Blvd. MSC 7182, Bethesda MD 20892-7182, Phone: (301) 496-
0477, Facsimile: (301) 402-2117, from whom further information may be 
obtained.

DATES: In view of the important priority of developing new agents for 
the treatment or prevention of cancer, interested parties should notify 
this office in writing no later than [FR: insert date 60 days after 
date of publication]. Respondents will then be provided an additional 
30 days for the filing of formal proposals.

SUPPLEMENTARY INFORMATION: ``Cooperative Research and Development 
Agreement'' or ``CRADA'' means the anticipated joint agreement to be 
entered into by NCI pursuant to the Federal Technology Transfer Act of 
1986 and amendments (including 104 P.L. 133) and Executive Order 12591 
of October 10, 1987 to collaborate on the specific research project 
described below.
    The Government is seeking one or more companies which, in 
accordance with the requirements of the regulations governing the 
transfer of agents in which the Government has taken an active role in 
developing (37 CFR 404.8), can further develop the identified compounds 
and related diagnostic methods through Federal Food and Drug 
Administration approval and to a commercially available status to meet 
the needs of the public and with the best terms for the Government. The 
government has applied for domestic and foreign patent applications 
directed to Fusion Proteins That Include Antibody and Non-Antibody 
Portions.
    The Fusion Proteins comprise an IgG sequence covalently joined at 
the IgG hinge and Fc domain to a non-antibody effector domain such as a 
ligand, toxin, or receptor. The effector domain or IgG non-antibody 
portion may be linked to a heterologous signal peptide to facilitate 
secretion. The resulting fusion protein exhibits the effector 
properties of both the antibody and non-antibody portions. Applications 
of this technology include development of diagnostic methods to monitor 
binding and expression of a protein of interest in vitro, in vivo and 
in situ (i.e. immunohistochemistry). In addition, the technology can be 
used to identify agonists and antagonists that modulate the binding of 
an effector molecule to its target. Fusion proteins may also be 
employed as a therapeutic to deliver radiation, a cytotoxic agent or a 
drug directly to a target cell.
    The LCMB, Division of Basic Sciences, NCI is interested in 
establishing a CRADA with one or more companies to assist in the 
development of diagnostic, screening and therapeutic applications of 
the technology. The Government will provide all available expertise and 
information to date and will jointly pursue pre-clinical and clinical 
studies as required, giving the company full access to existing data 
and data developed pursuant to the CRADA. The successful company will 
provide the necessary scientific, financial and organizational support 
to establish clinical efficacy and possible commercial status of 
subject compounds and/or diagnostic and therapeutic applications.
    The expected duration of the CRADA will be two (2) to five (5) 
years.
    The role of the National Cancer Institute, includes the following:
    1. Construction of fusion proteins comprising a molecule of 
interest covalently joined to an IgG hinge and FC antibody regions.
    2. Expression and harvesting of the resulting fusion protein from 
conditioned medium of a suitable transfectant such as NIH 3T3 cells.
    3. Develop a screen of ligand-HFc on receptor or receptor-HFc on 
ligand to identify putative agonists and antagonists.
    4. Conduct in vitro studies to identify putative agonists and/or 
antagonists by screening libraries of compounds.
    5. Conduct in vitro and in vivo studies to characterize the 
properties of putative agonists and/or antagonists.
    6. Evaluation of test results.
    7. Preparation of manuscripts for publication.
    8. Relevant Government intellectual property rights are available 
for licensing through the Office of Technology Transfer, National 
Institutes of Health. For further information contact Susan Rucker, 
J.D., NIH Office of Technology Transfer, 6011 Executive Blvd, Suite 
325, Rockville, MD 20852, Phone: (301) 496-7056 (ext. 245); Facsimile: 
(301) 402-0220.
    The role of the collaborator company, includes the following:
    For agonist/antagonist screening:
    1. Provide growth factor or receptor cDNA clones for fusion protein 
construction if not available in NCI/LCMB clone bank.

[[Page 58573]]

    2. Scale-up production of fusion proteins constructed by NCI if 
required.
    3. Conduct in vitro studies to identify putative antagonists/
agonists by screening libraries of compounds.
    4. Conduct in vitro and in vivo studies to characterize the 
properties of putative antagonists/agonists.
    5. Conduct clinical studies of best candidates.
    For ligand-mediated histochemical experiments:
    1. Test conditioned medium for suitability in histochemical 
experiments.
    2. Screen tumor samples or biopsies for reactivity.
    3. Conduct clinical studies of diagnostic test.
    Criteria for choosing the company include its demonstrated 
experience and commitment to the following:
    1. Scientific expertise in and demonstrated commitment to the 
treatment of neoplasia, arteriosclerosis, fibrotic diseases and related 
disorders.
    2. Scientific expertise in and demonstrated commitment to the 
development of drug delivery systems.
    3. Experience in preclinical and clinical drug development.
    4. Experience and ability to produce, package, market and 
distribute pharmaceutical products.
    5. Experience in the monitoring, evaluation and interpretation of 
the data from investigational agent clinical studies under an IND.
    6. A willingness to cooperate with the NCI in the collection, 
evaluation, publication and maintaining of data from pre-clinical 
studies and clinical trials regarding the subject compounds.
    7. Provide defined financial and personnel support for the CRADA to 
be mutually agreed upon.
    8. An agreement to be bound by the DHHS rules involving human and 
animal subjects.
    9. The aggressiveness of the development plan, including the 
appropriateness of milestones and deadlines for preclinical and 
clinical development.
    10. Provisions for equitable distribution of patent rights to any 
CRADA 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 and 
(2) an option for the collaborator to elect an exclusive or 
nonexclusive license to Government owned rights under terms that comply 
with the appropriate licensing statutes and regulations.

    Dated: November 4, 1996.
Thomas D. Mays,
Director, Office of Technology Development, OD, NCI.
[FR Doc. 96-29346 Filed 11-14-96; 8:45 am]
BILLING CODE 4140-010-M