[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