[Federal Register Volume 59, Number 61 (Wednesday, March 30, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-7471]
[[Page Unknown]]
[Federal Register: March 30, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Opportunity For Licensing: Calanolide Antiviral Compounds as
Antiviral Agents Useful in the Treatment of Acquired Immunodeficiency
Syndrome (AIDS)
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
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SUMMARY: The National Institutes of Health (NIH), Department of Health
and Human Services (DHHS), seeks licensee(s) who can effectively pursue
the preclinical, clinical and commercial development of calanolide A or
related anti-viral compounds for the treatment of human
immunodeficiency virus (HIV) infection. Scientists at the National
Cancer Institute have identified the chemical structures and methods
for isolating and purifying anti-HIV coumarins from extracts of the
tropical rain forest tree Calophyllum lanigerum and a known coumarin
from a related species in the genus, Calophyllum teysmannii. This new
class of anti-HIV compounds and their analogs, also referred to as
calanolides and costatolide respectively, strongly inhibit HIV-1
replication and cytopathicity in vitro. These compounds may have
advantageous pharmacologic, toxicologic, and/or antiviral properties,
especially in the treatment of AIDS. NIH intends to grant the selected
firm(s) world-wide royalty-bearing license(s) to practice the
inventions embodied in U.S. Patent Applications SN 07/861,249 and 08/
065,618 both entitled ``Calanolide Antiviral Compounds, Compositions
and Uses Thereof'' and related foreign patent applications for this
field of use. The patent rights in these inventions have been assigned
to the United States of America.
SUPPLEMENTARY INFORMATION: The NIH seeks licensee(s), who in accordance
with requirements and regulations governing the licensing of
government-owned inventions (37 CFR part 404), have the most
meritorious plan for the development of calanolide A or related
compounds to a marketable status to meet the needs of the public and
with the best terms for the NIH. Specifically, firm(s) are sought who
directly or indirectly, will be able to:
(1) Isolate or synthesize and provide sufficient amounts (e.g.
multi-kilogram amounts) of compounds for preclinical drug development;
(2) Carry out preclinical toxicology and pharmacology studies and
testing, without guaranteed assistance from the government, to
complement preclinical toxicology and pharmacology currently being
performed to the Investigational New Drug (IND) stage by NCI.
(3) Perform formulation for oral and intravenous use, vialing,
quality control testing, bioavailability testing and distribution of
the drug for Phase I and Phase II and, if appropriate, Phase III
clinical trails both in the NIH intramural program and in the
extramural AIDS Clinical Trials Groups (ACTGs) established by the
National Institute of Allergy and Infectious Diseases (NIAID). The
clinical trials may be performed under the sponsorship of an IND to be
held by NCI or NIAID. Prior to being released for commercial
distribution, the drug will have to be granted a product license by the
Food and Drug Administration (FDA);
(4) Synthesize bulk pharmaceutical product necessary for the
treatment of 500-1,500 patients with HIV infection in Phase I, II and
III developmental studies;
(5) Perform clinical studies. NCI and NIAID may conduct studies of
calanolide A or related compounds in the ACTGs and the NIH Clinical
Center, an the company will be expected to provide the drug free of
charge to NIH for studies conducted in the ACTGs and in the NIH
intramural program; the company will be expected to cooperate with NCI
and NIAID in providing the drug and supporting distribution of the drug
under a treatment IND when appropriate;
(6) Provide data management support for both the intramural NIH and
extramural studies of calanolide A and related compounds necessary for
the timely submission of a NDA to the FDA;
(7) Share the cost with NIH of intramural and extramural clinical
monitoring studies (pharmacokinetics, patient immune profiles and viral
outgrowth studies) necessary for the demonstration of clinical efficacy
of calanolide A and related compounds for the treatment of AIDS;
(8) Since these agents, calanolide A or related compounds, and
their anti-HIV properties were discovered through the investigation of
flora indigenous to Sarawak (Malaysia), the NIH is concerned that the
collection and utilization of the natural plant material comport with
all applicable Federal and Sarawak policies related to biodiversity. In
order to comport with such policies, the successful applicant will be
required to negotiate and enter into agreements with the appropriate
Sarawak government agencies.
The criteria that NIH will use to evaluate license applications
will include, but not be limited to those set forth by 37 CFR
404.7(a)(1) (ii)-(iv), as well as:
(1) Manufacturing capabilities for antiviral compounds and a plan
for production of calanolide A or related compounds;
(2) Experience in preclinical and clinical drug development with
special emphasis on the development of antiviral compounds;
(3) Experience in the evaluation, monitoring and interpretation of
data for investigational biologic and virologic assays under an IND;
(4) Experience in the evaluation, monitoring and interpretation of
data from Phase I and Phase II clinical studies for an IND;
(5) Demonstrated expertise in monitoring drug levels using state-
of-the-art methods for measuring drugs in blood, urine and CSF;
(6) A willingness to cooperate with NCI in the collection,
evaluation, publication and maintenance of data from animal studies and
from clinical trials and tests of investigational biologic assays;
(7) Demonstrated competence in developing oral formulation and
sustained-release oral formulations;
(8) Ability to produce, package, market and distribute
pharmaceutical products in the United States and to provide the product
at a reasonable price;
(9) Willingness to sustain the cost of calanolide A or related
compounds drug development as outlined above (i.e., bulk drug
synthesis, data management, animal studies, clinical studies, etc.);
(10) Agreement to be bound by DHHS regulations and guidelines
involving human and animal subjects;
(11) An aggressive developmental plan that includes appropriate
milestones and deadlines for preclinical and clinical development and
for marketing approval.
(12) Agreement to negotiate and enter into agreements with the
appropriate Sarawak government agencies on terms acceptable to all
parties.
EFFECTIVE DATE: In view of the high priority for developing new drugs
for the treatment of HIV infection, all proposals must be received May
31, 1994.
ADDRESSES: Requests for a summary of the anti-HIV activity of
calanolide A or related compounds, their pharmacological properties and
toxicological information, or other questions and comments concerning
the clinical aspects of this technology should be directed to: Dr.
Dwight Kaufman, Deputy Director, Division of Cancer Treatment, National
Cancer Institute, Building 31, room 3A44, 9000 Rockville Pike,
Bethesda, MD 20892. Telephone: (301) 496-6711.
Requests for a copy of the patent applications, license application
form, or other questions and comments concerning the licensing of this
technology should be directed to: Steven M. Ferguson, Technology
Licensing Specialist, Office of Technology Transfer, National
Institutes of Health, Box OTT, Bethesda, MD 20892. Telephone: (301)
496-7735; Facsimile: (301) 402-0220. A signed confidentiality agreement
will be required to receive copies of the patent applications.
Dated: March 16, 1994.
Donald P. Christoferson,
Acting Director, Office of Technology Transfer.
[FR Doc. 94-7471 Filed 3-29-94; 8:45 am]
BILLING CODE 4140-01-M