[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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.
[[Page 40655]]
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