[Federal Register Volume 61, Number 151 (Monday, August 5, 1996)]
[Notices]
[Pages 40653-40655]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-19847]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health


National Cancer Institute (NCI); Developmental Therapeutics 
Program (DTP); Opportunity for a Cooperative Research and Development 
Agreement (CRADA) for the Identification, Characterization, and 
Development of Antibiotics From NCI's Natural Products Repository and 
Database of Open Compounds

AGENCY: National Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The Department of Health and Human Services (DHHS) seeks a 
company that can effectively pursue the preclinical identification, 
characterization, and development of antibiotic treatments from NCI/
DTP's Natural Products Repository and Database of Open Compounds. The 
selected sponsor will be awarded a CRADA to establish antibiotic 
activity associated with such compounds.

ADDRESSES: Questions about this opportunity may be addressed to Gary 
Colby, or Vasiliana Moussatos, Office of Technology Development, NCI, 
(301) 496-0477, from whom further information may be obtained:
    Address for delivery by U.S. Postal Service: Executive Plaza South, 
Suite 450; 6120 Executive Blvd. MSC 7182; Bethesda MD 20892-7182.
    Address for delivery by messenger or overnight delivery services: 
6120 Executive Blvd; Suite 450; Rockville, MD 20852.

DATES: In view of the important priority of developing new drugs for 
the treatment of antibiotic resistant bacteria, proposals must be 
received at the above address by 5:00 p.m. September 4, 1996.

TERM: The term of the CRADA will be 3 to 5 years.

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 Executive Order 12591 of October 10, 1987 to collaborate on 
the specific research project described below. Under the present 
proposal, the Government is seeking a company which will perform the 
requirements set forth in the CRADA in accordance with the regulations 
governing the transfer of technology in which the Government has taken 
an active role in developing (37 CFR 404.8).
    The general scope of this CRADA includes:
    1. Characterizations of compounds or natural product extracts with 
activity against bacterial strains provided by Collaborator, including 
but not limited to antibiotic-resistant variants of common nosocomial 
infections, emerging organisms of public interest (e.g., flesh-eating 
bacteria), and organisms responsible for opportunistic infections 
(e.g., Mycobacterium spp.); (This characterization will include 
screening of compounds provided by NCI for this application (including 
previously characterized compounds in the public domain), isolation, 
extraction, and purification of the compound(s) present in natural 
product extracts, chemical characterization, and demonstration that 
isolation and production of the active chemical are reproducible.)
    2. Using the structure(s) identified in (1), computer analyses by 
NCI of previously screened open NCI compounds to identify or suggest 
compounds that also may inhibit bacteria in (1), followed by the use of 
Collaborator's assays to screen and profile the NCI compounds' activity 
against different strains of such bacteria;
    3. Modification or improvement of assays for activity against such 
bacterial strains in (1) based directly upon the findings in (1) and 
(2);
    4. Addition of related bacterial strains supplied by Collaborator 
to this collaboration based upon this experience;
    5. Synthesis of analogues of the lead structures based directly 
upon information gained in this collaboration; and
    6. Where appropriate and under a mutually agreeable amendment, 
preclinical development of compounds to support clinical trials using 
agents for which the compelling rationale for development was 
identified in this collaboration.
    The principal goal of the CRADA in the first year is to generate 
sufficient data to prove the concept that compounds exist in the NCI 
Natural Products Repository of crude extracts and purified chemicals 
which may possess activity against such bacteria listed above in (1) as 
provided by the Collaborator. The Collaborator will test a variety of 
extracts, e.g., fungal, higher plant, marine organisms, etc. selected 
for this purpose and provided by NCI, against said bacteria utilizing a 
screening and testing program which may or may not be proprietary to 
Collaborator such as a standard plate assay of bacterial growth or an 
enzyme-based screening system capable of high throughput and 
automation. It is further hoped that long-term results may also lead to 
new and novel molecular structures.
    In view of the intellectual contributions of NCI, such as the 
creation of the ranked lists of compounds with potential to interact 
with such bacterial strains of interest as provided by the 
Collaborator, the results of this collaboration, in the form of agents 
with clinical potential or tools for

[[Page 40654]]

further scientific research, will be considered to be the results of a 
collaborative effort on the part of NCI and the collaborator. 
Inventorship and ownership of any intellectual property arising from 
this collaboration will be determined according to U.S. and 
international Patent Law with reference to the terms of the negotiated 
CRADA.
    The role of the NCI will include inter alia providing nonexclusive 
access (unless otherwise noted) to research materials, methodology and 
data:
     Access to extracts (fungal, plant, marine, etc.) and other 
tests chemicals in the NCI Natural Products Repository and Database of 
Open Compounds;
     Project guidance and oversight;
     Nonexclusive access to NCI's in vitro cell line screening 
data for open samples of pure compounds or for identified Natural 
Product extracts found to be active in the expanded microbial screen so 
antibacterial activity, cell line cytotoxicity, and growth inhibition 
can be compared.
     Analyses of cytotoxicity/growth inhibition profiles in the 
NCI Tumor Cell Line Panel to identify open compounds in the NCI 
database possessing similar profiles as compounds established by the 
Collaborator as having antibiotic activity;
     Cell lines from the NCI Tumor Cell Line Panel, as well as 
guidance in their choice;
     Upon verification that similar cytotoxicity/growth 
inhibition profiles exist between compounds with antibiotic activity 
and open compounds in the NCI database, provision of lists, rankings 
and correlates of available compounds to Collaborator for verification 
testing. The NCI may include in these lists other compound for which 
there are indications of development potential against (or as markers 
for) such bacteria listed in (1); and
     As appropriate, performance with the collaborator of 
additional preclinical studies (such as tests of in vivo efficacy) if 
compounds meet criteria required for use of these resources.
    The role of the successful company under a CRADA will include the 
following:
     Perform screening operations necessary to identify 
compounds or extracts with desired anti-bacterial properties;
     Purify and identify active molecules from active natural 
product extracts;
     Identify, procure and provide to NCI, cultures of such 
bacteria listed in (1);
     Provide expert advice and support related to safe 
management of such bacteria listed in (1);
     Perform verification testing of the natural products, open 
listed correlates and compounds of interest suggested by the NCI, using 
proprietary or nonproprietary assay systems developed and/or 
implemented by Collaborator for activity against such bacteria in (1) 
as well as perform potentially necessary cytotoxic and growth 
inhibition assays of cell lines in the NCI Tumor Cell Line Panel; and
     Provide written progress reports incorporating results to 
the NCI on a quarterly basis. (The NCI will alert the Collaborator to 
any substantive changes to the lists, ranks, or correlates as such 
information becomes available.)
    Criteria for choosing the company include:
     Ability to provide technical screening expertise, ability 
to supply bacterial cultures, ability to purify active compounds from 
natural product mixtures;
     Ability to provide sufficient internal staffing necessary 
to pursue aggressively its efforts associated with the CRADA including 
scientific, management and administrative support;
     Demonstrated ability to develop and commercialize 
pharmaceutical agents or products;
     Ability to provide sufficient internal funding necessary 
to aggressively pursue its efforts associated with the CRADA;
     Ability to provide sufficient internal funding for 
materials and supplies, training and travel as required by NCI in 
support of its efforts under the CRADA;
     Willingness to abide by NCI policy required for the 
transfer of natural products from the NCI Natural Products Repository; 
and
     Willingness to abide substantially by the terms of the 
Model NIH CRADA.
    The collaborator must agree to abide by the following NCI 
guidelines for access to natural products from the NCI Natural Products 
Repository.
    (A) Should an agent eventually be licensed to the Collaborator or 
licensed or sublicensed to a pharmaceutical company for production and 
marketing, NCI will require the collaborator or successful licensee to 
negotiate and enter into agreement(s) with the Source Country 
Government (``SCG'') agency(ies) or Source Country Organization(s) as 
appropriate. This agreement(s) will address the concern on the part of 
the Source Country Government (``SCG'') or Source Country 
Organization(s) (``SCO''), that pertinent agencies, institutions, and/
or persons receive royalties and other forms of compensation, as 
appropriate.
    (B) Such terms shall apply equally to instances where the invention 
is the actual isolated natural product, or where the invention is a 
product structurally based on the isolated natural product (i.e., where 
the natural product provides the lead for the development of 
invention), though the percentage of royalties negotiated as payment 
might vary depending upon the relationship of the marketed drug to the 
originally isolated product. It is understood that he eventual 
development of a drug to the stage of marketing is a long term process 
which may require 10-15 years.
    (C) In obtaining additional sources of active material product 
extract by CRADA collaborator or licensees, the NCI will require the 
collaborator or applicant for license to seek as its first source of 
supply the natural products from Source Country. If no appropriate 
licensee is found who will use natural products available from Source 
Country, or if the Source Country Government (``SCG'') or Source 
Country Organization(s) (``SCO'') as appropriate, or its suppliers 
cannot provide adequate amounts of raw materials at a mutually 
agreeable fair price, the licensee will be required to pay the Source 
Country Government (``SCG'') or Source Country Organization(s) as 
appropriate, an amount of money (to be negotiated) to be used for 
expenses associated with cultivation of medicinal plant species that 
are endangered by deforestation, or for other appropriate conservation 
measures. Such terms will also apply to instances where the active 
agent is prepared by total synthesis.
    (D) Section C shall not apply to organisms which are freely 
available from different countries (i.e., common weeds, agricultural 
crops, ornamental plants, fouling organisms) unless information 
indicating a particular use of the organism (e.g., medicinal, 
pesticidal) was provided by local residents to guided the collection of 
such an organism from Source Country, or unless other justification 
acceptable to both the Source Country Government (``SCG'') and Source 
Country Organization(s) (``SCO'') and the NCI is provided. In the case 
where an organism is freely available from different countries, but a 
genotype producing an active agent is found only in the Source Country, 
Section C shall apply.


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    Dated: July 26, 1996.
Thomas D. Mays,
Director, Office of Technology Development, National Cancer Institute, 
National Institutes of Health.
[FR Doc. 96-19847 Filed 8-2-96; 8:45 am]
BILLING CODE 4140-01-M