[Federal Register Volume 66, Number 129 (Thursday, July 5, 2001)]
[Notices]
[Pages 35443-35444]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-16762]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Cancer Institute: Opportunity for License(s) and/or 
Cooperative Research and Development Agreement(s) (CRADAs) for the 
Development of Geldanamycin Analogs for Clinical Use

AGENCY: National Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The National Cancer Institute (NCI) seeks Licensee(s) and/or 
Cooperative Research and Development Agreement (CRADA) Collaborator(s) 
for the development of geldanamycin analogs for clinical use in three 
areas. The three areas are: (1) A unique clinical formulation of 17-
allylaminogeldanamycin (17-AAG). (2) A suite of geldanamycin analogs 
(other than 17-AAG) modified at the 11 and/or 17 positions, several of 
which have improved solubility and reduced toxicity in comparison to 
geldanamycin. (3) A coupled met kinase-uPA kinase assay, as described 
in Cancer Research 60 (2): 342-9, and data and expertise regarding 
geldanamycin analog activity as measured by that assay. The invention 
for item (1) is claimed in PCT Patent Application PCT/US99/30631 
entitled ``Water-Insoluble Drug Delivery System''; the inventions for 
item (2) are claimed in U.S. Patent Application 60/246,258, entitled 
``Geldanamycin Derivatives having Selective Affinity for HSP-90 and 
Methods of Using Same,'' U.S. Patent Application 60/280,016, entitled 
``Geldanamycin Derivatives Having Selective Affinity for HSP90 over 
GRP94 and Method of Using Same,'' and U.S. Patent Application 60/
280,078, entitled ``Geldanamycin Derivatives and Method of Treating 
Cancer Using Same''; the technology for item (3) is described in Cancer 
Research 60 (2): 342-9, ``The Geldanamycins Are Potent Inhibitors of 
the Hepatocyte Growth Factor/Scatter Factor-Met-Urokinase Plasminogen 
Activator-Plasmin Proteolytic Network.''

DATES: Respondees interested in licensing the invention(s) will be 
required to submit an ``Application for License to Public Health 
Service Inventions'' no later than sixty (60) days from the date of 
this announcement. Applications submitted thereafter may be considered 
if a suitable Licensee is not selected from among the timely responses.
    Interested CRADA applicants must submit to the NCI Technology 
Transfer Branch (TTB) a confidential proposal summary no later than 
sixty (60) days from the date of this announcement for consideration. 
CRADA proposal summaries submitted thereafter may be considered if a 
suitable CRADA Collaborator is not selected from among the timely 
responses. Guidelines for preparing full CRADA proposals will be 
communicated shortly thereafter to all respondents with whom initial 
confidential discussions will have established sufficient mutual 
interest.

ADDRESSES: Inquiries directed to obtaining license(s) for the 
technology should be addressed to Kai Chen, Ph.D., M.B.A., Supervisory 
Technology Licensing Specialist, Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Blvd., Suite 325, 
Rockville, MD 20852, (Tel. 301-496-7056, extension 247; FAX 301-402-
0220).
    CRADA inquiries and proposals regarding this opportunity should be 
addressed to Robert Wagner, M.S., M. Phil., Technology Transfer 
Specialist (Tel. 301-496-0477, FAX 301-402-2117), Technology Transfer 
Branch, National Cancer Institute, 6120 Executive Blvd., Suite 450, 
Rockville, MD 20852.

SUPPLEMENTARY INFORMATION: Respondees interested in licensing the 
technology will be required to submit an Application for License to 
Public Health Service Inventions. Inventions described in the patent 
applications are available for either exclusive or non-exclusive 
licensing in accordance with 35 U.S.C. 207 and 37 CFR Part 404. 
Information about patent application(s) and pertinent information not 
yet publicly described can be obtained under the terms of a 
Confidential Disclosure Agreement.
    A Cooperative Research and Development Agreement (CRADA) is the 
anticipated joint agreement to be entered into with NCI pursuant to the 
Federal Technology Transfer Act of 1986 and Executive Order 12591 of 
April 10, 1987, as amended. A CRADA is an agreement designed to enable 
certain collaborations between Government laboratories and non-
Government laboratories. It is not a grant, and it is not a contract 
for the procurement of goods/services. The NCI is prohibited from 
transferring funds to a CRADA collaborator. Under a CRADA, NCI can 
contribute facilities, staff, materials, and expertise. The CRADA 
Collaborator will have an option to negotiate the terms of an exclusive 
or nonexclusive commercialization license to subject inventions arising 
under the CRADA. CRADA applicants should be aware that a license to the 
above mentioned patent rights may be necessary in order to 
commercialize products arising from a CRADA. The expected duration of 
the CRADA(s) would be for up to five (5) years. The goals of CRADAs 
include the rapid publication of research results and timely 
commercialization of products, diagnostics, and treatments that result 
from the research.

The NCI Seeks Licensee(s) and/or CRADA Collaborator(s) in One or 
More of the Following Areas for the Development of Geldanamycin 
Analogs for Clinical Use

    1. Clinical Development of 17-AAG: Patent protection for the 
formulation of 17-allylaminogeldanamycin (17-AAG) for clinical use is 
pending. NCI is actively engaged in the clinical development of this 
agent and is seeking a CRADA collaborator whose role would include 
production of the drug for clinical trials. CRADA applicants should be 
aware that a license to the related patent rights may be necessary in 
order to commercialize products arising from the CRADA. 17-AAG is 
currently in Phase 1 clinical trials under an NCI-sponsored 
Investigational New Drug Application (IND). The data contained in this 
IND, along with the data that will emerge from NCI's ongoing clinical 
trials, would be available to the CRADA Collaborator.
    2. Optimization of Compounds for Cytotoxic Endpoints: A suite of 
geldanamycin analogs (other than 17-

[[Page 35444]]

AAG) modified at the 11 and/or 17 positions, several of which have 
improved solubility and altered toxicity in comparison to geldanamycin, 
are described in several pending NCI patent applications. NCI is 
seeking a licensee(s) and/or CRADA Collaborator(s) interested in 
continued optimization of compound pharmacology for selection of a 
compound to enter the clinic. Criteria for selection of a compound 
would include cytotoxic endpoints and regression of model tumors. Such 
a resulting compound(s) would be expected to have a different spectrum 
of activity or formulation as that for 17-AAG as described in (1) 
above.
    3. Optimization of Compounds for Anti-Metastatic Endpoint: The 
technology for the coupled met kinase--uPA Kinase assay is described in 
Cancer Research 60 (2): 342-9. NCI research has defined this assay as 
generating lead compounds for anti-metastatic use. While encompassing 
some compounds from (2) above, lead compounds will have a very distinct 
set of development endpoints demonstrating suitability for long term 
chronic oral dosing, and will show evidence of activity in anti-
metastasis and/or anti-angiogenesis assays without necessarily having 
evidence of activity in classical cytotoxic models. NCI is seeking a 
CRADA Collaborator(s) interested in using this assay to optimize 
compounds related to geldanamycin for use as anti-metastatic agents.

Party Contributions to CRADAS

The Role of the NCI in Each of the CRADAs May Include, but Not Be 
Limited to

    1. Providing intellectual, scientific, and technical expertise and 
experience to the research project.
    2. Providing the CRADA Collaborator with information and data 
relating to the CRADA technology.
    3. Planning research studies and interpreting research results.
    4. Carrying out research pursuant to the planned collaboration, 
including, but not limited to:
    (a). Screening, pharmacology and in vivo model studies for 
compounds pertinent to cytotoxic endpoints;
    (b). Assays to optimize compounds with desired pharmacology for 
chronic use;
    (c). Pharmacology and determination of in vivo activity of anti-
metastatic compounds;
    (d). Production of precursors and prodrugs from fermentation 
sources; and
    (e). Possible sponsorship of clinical trials of promising 
compounds.
    5. Publishing research results.

The Role of the CRADA Collaborator May Include, but Not Be Limited to

    1. Providing significant intellectual, scientific, and technical 
expertise or experience to the research project, including, but not 
limited to:
    (a). Structure-based design of geldanamycin analogs with suitable 
properties;
    (b). Chemical modification of fermented lead structures;
    (c). Pharmacology, toxicology, and formulation;
    (d). Support for clinical trials in the form of drug and funding.
    2. Planning research studies and interpreting research results.
    3. Providing technical and/or financial support to facilitate 
scientific goals and to further design applications of the technology 
outlined in the agreement.
    4. Publishing research results.

Selection Criteria for Choosing the CRADA Collaborator May Include, but 
Not Be Limited to

    1. A demonstrated background and expertise in the preclinical and 
clinical development of antineoplastic agents, structure-based design, 
and the conduct of in vivo animal model studies pertaining to 
metastasis or tumor regression.
    2. A demonstrated record of success in pre-clinical lead selection 
and optimization and/or successful clinical trials of antineoplastic 
therapeutics leading to a commercial product.
    3. The demonstration of the necessary resources to produce 
sufficient drug for all clinical trials in a timely manner.
    4. The ability to collaborate with NCI on further research and 
development of the technology. This ability will be demonstrated 
through experience and expertise in this or related areas of technology 
indicating the ability to contribute intellectually to ongoing research 
and development.
    5. The demonstration of adequate resources to perform the research 
and development of the technology (e.g. facilities, personnel and 
expertise) and to accomplish the objectives according to an appropriate 
timetable to be outlined in the CRADA Collaborator's proposal.
    6. The willingness to commit best effort and demonstrated resources 
to the research and development of this technology, as outlined in the 
CRADA Collaborator's proposal.
    7. The demonstration of expertise in the commercial development and 
production of products related to this area of technology.
    8. The ability to provide financial support for CRADA-related 
Government activities.
    9. The willingness to cooperate with the National Cancer Institute 
in the timely publication of research results.
    10. The agreement to be bound by the appropriate DHHS regulations 
relating to human subjects, and all PHS policies relating to the use 
and care of laboratory animals.
    11. The willingness to accept the legal provisions and language of 
the CRADA with only minor modifications, if any. These legal provisions 
govern the distribution of future patent rights to CRADA inventions. 
Generally, the rights of ownership are retained by the organization 
that is the employer of the inventor, with (1) the grant of a license 
for research and other Government purposes to the Government when the 
CRADA Collaborator's employee is the sole inventor, or (2) the grant of 
an option to elect an exclusive or nonexclusive license to the CRADA 
Collaborator when the Government employee is the sole inventor.

    Dated: June 25, 2001.
Kathleen Sybert,
Chief, Technology Transfer Branch, National Cancer Institute, National 
Institutes of Health.

    Dated: June 27, 2001.
Jack Spiegel,
Director, Division of Technology Transfer and Development, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-16762 Filed 7-3-01; 8:45 am]
BILLING CODE 4140-01-P