00-14343. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by agencies of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.

ADDRESSES:

Licensing information and copies of the U.S. patent applications listed below may be obtained by contacting Marlene Shinn, J.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: [phone] ext. 285; fax: [phone]; e-mail: [e-mail]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Direct C-14 Oxidation of Opioids

Andrew Coop, Kenner C. Rice (NIDDK)

DHHS Reference No. E-032-99/1 filed 04 May 2000

Opioid agonist drugs including the 14-hydroxy derivatives are utilized in the treatment of pain. The 14-hydroxy substituted opioid antagonists have also been found to be useful in the treatment of opiate abuse, opiate overdose and alcohol addiction. In addition, there are certain derivatives which have been found to be useful in the prevention of tolerance to morphine and as immunosuppressants. The 14-hydroxy agonist and antagonist drugs are produced by a multistep process from the starting material, thebaine, which is a minor constituent of opium and is generally in short supply. The demand for these products has resulted in a steadily increasing cost for thebaine and thebaine derivatives.

The present technology consists of a new and practical, nonchromatographic method of preparing 14-hydroxycodeinone by the direct oxidation of codeinone with cobalt (III) acetate (easily prepared in situ). The technology gives a 51% unoptimized yield of 14-hydroxycodeinone easily isolated by extractive workup and direct crystallization. This process is ultimately based on morphine (which is by far the major constituent and cheapest of the opium alkaloids) through the sequence: morphine to codeine to codeinone to 14-hydroxycodeinone. This technology is not limited by the availability of thebaine and thus offers more efficient production of the 14-hydroxy derivatives from opium.

Use of Oligonucleotides To Target Nucleic Acid Sequences Encoding Apolipoprotein B To Decrease Serum Apolipoprotein B and Cholesterol Levels

Thomas L Eggerman (FDA), Amy Patterson, Paul F. Torrence (NIDDK), Julie K Rhie

DHHS Reference No. E-236-98/0 filed 12 Oct 1999

Coronary heart disease is caused by the atherosclerotic narrowing of the coronary arteries affecting nearly 14 million persons in the United States. Approximately 480,000 deaths in 1995 were caused by the disease and it is the leading cause of death in the United States today. Two of the established causes of atheroscleorosis include elevated cholesterol levels and elevations of the major protein responsible for carrying cholesterol—apolipoprotein B (apoB). Optimal therapy, however is still not available for the most severely affected patients, in particular those with familial hypercholesterolemia and those with elevated apoB levels.

The NIH announces a new gene therapy approach which will lower the risk for atheroscleoric heart disease by decreasing plasma cholesterol and apoB levels. Our researchers have shown that antisense DNA oligonucleotides targeted for apoB decreased apoB mRNA in a human liver cell line by up to 80%. This in turn has led to a new gene therapy which utilizes a vector designed to produce antisense mRNA targeted for apoB. The result is a decrease in liver apoB production, which is the major source of circulating apoB. These oligonucleotides and oligonucleotide analogs are a novel and useful way of reducing low density lipoprotein (LDL) in patients, as well as for research and diagnostic purposes.

T20/D178 and T21/D107 Are Activators of Human Phagocyte Formyl Peptide Receptors

Ji Ming Wang (NCI), Joost J Oppenheim (NCI), Shao-Bo Su, Wang-Hua Gong, Philip M. Murphy (NIAID), Ji-Liang Gao (NIAID)

DHHS Reference No. E-164-99/0 filed 05 May 1999

The use of immunotherapy to treat inflammatory diseases is prescribed to thousands each and every year. In use currently are steroidal and non-steroidal anti-inflammatory drugs, which have serious side effects including: adrenal suppression, gastrointestinal disorders, increased susceptibility to infections, fluid retention and bone loss.

The NIH announces a new technology which can be used in drug discovery dealing with the modulation of the immune response. This technology identifies two polypeptides, T20/DP178 and T21/DP107, which are peptide domains of the HIV-1 envelope protein and are potent chemoattractants and activators of human peripheral blood phagocytes (monocytes and neutrophils) but not T lymphocytes. These polypeptides have been determined to interact with the Formyl Peptide Receptors (FPR), which in turn up-regulates the immune response by inducing cell migration and calcium mobilization. The activation of FPR class receptors by their agonists also results in desensitization of cell responses to other chemotactic factors. By identifying analogs to T20/DP178 and T21/DP107 and then evaluating their ability to bind to the FPR, one will be able to determine if the analog is a good candidate for either inhibiting or activating the immune response.

Dated: May 30, 2000.

Jack Spiegel,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.