[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] ----------------------------------------------------------------------- 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. ----------------------------------------------------------------------- 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