02-28538. 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 writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Regulation of INS (3456) P4 Signalling by a Reversible Kinase/Phosphatase and Methods and Compositions Related Thereto

Dr. Stephen Shears (NIEHS)

DHHS Reference No. E-105-2002/0 filed Mar 18, 2002

Licensing Contact: Marlene Shinn; 301/435-4426; [e-mail].

Signaling entities are frequently controlled by quite delicate shifts in the dynamic balance of regulatory signals with competing impacts. Ion channels provide particularly impressive examples of the degree of signal amplification that can result; switching the conductance state of a single channel can influence the transmembrane movement of millions of ions per second. Both stimulatory (Ca ^2t and CaMKII) and inhibitory (Ins(3,4,5,6)P₄ signals converge on the family of so-called “Ca ^2t-activated” Cl⁻ channels. Thus receptor-dependent changes in Ins(3,4,5,6)P₄ levels is a topic of general biological significance, in that it impacts upon regulation of salt and fluid secretion from epithelial cells, cell volume homeostasis, and electrical excitability in neurons and smooth muscle. Unfortunately, understanding of the cellular control on Ins(3,4,5,6)P₄-signaling has been rudimentary, because the pathway of Ins(3,4,5,6)P₄ synthesis has not previously been characterized.

The NIH announces new treatment methods for asthma, bronchitis and cystic fibrosis. The treatments consist of either increasing or decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a patient, thereby controlling Ins(3,4,5,6)P₄-signaling which in turn affects the choride channels and mucus secretion produced. This modulation of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase is accomplished with the help of an inositol phosphate kinase, which can also act as an inositol pentakisphosphate 1-phosphatase.

Mutated Constitutively Active Nuclear Orphan Receptor

Masahiko Negishi, Akiko Ueda, Lars C. Pedersen, Satoru Kakizaki, Tatsuya Sueyoshi (NIEHS)

DHHS Reference No. E-034-2002/0 filed Feb. 19, 2002

Licensing Contact: Marlene Shinn; 301/435-4426; [e-mail].

The constitutively active nuclear orphan receptor (CAR) activates transcription of genes encoding various drug-metabolizing enzymes such as cytochromes P450 in response to drug exposures. Induction of these enzymes confers on organisms a higher metabolic capability to defend themselves against xenochemical toxicity and/or carcinogenicity. Direct drug responses, however, have not been demonstrated with CAR in a cell-mediated transfectin assay, due to its in vitro constitutive activity.

The NIH announces the creation of an altered CAR molecule, with decreased constitutive activity in vitro using site-directed mutagenesis to the receptor. This alteration allows the CAR molecule to be directly activated by drugs and can be used for in vitro drug screening that will make the screenings more efficient and cost effective.

Bone-Forming Composition, Methods for Making and Methods of Use

Mahesh H. Mankani, Sergei Kuznetsov, Pamela G. Robey (NIDCR)

DHHS Reference No. E-263-2001/0 filed Jan. 25, 2002

Licensing Contact: Marlene Shinn; 301/435-4426; [e-mail].

Transplantation of bone marrow stromal cells (BMSCs) offers a method for repairing and/or closing large bone defects. Although most bone defects occur as a result of trauma, bone loss can also arise from congenital disorders, neoplasms, and/or infections. To make BMSC transplantation most useful as a method for engineering new bone, it would be helpful to optimize the growth rate, extent, and strength of newly formed bone. Current methods of transplantation produce bone that is nonuniform in size, shape and form, making it difficult to compare bone samples directly.

The NIH announces a new method of forming bone tissue based on using a combination of bone marrow stromal cells and hydroxyapatite/tricalcium phosphate particles. The newly created bone has desired dimensions, which are similar, consistent, and/or identical to the shapes of the preformed compositions. When the composition is made with human BMSCs derived from pathological tissue, and transplanted into immunodeficient mice, the new bone reproduces features of the original disease, allowing for the testing of agents that inhibit, stimulate, or modify bone formation.

Methods of Making, Using and Pharmaceutical Formulations Comprising 7-Alpha,11-Beta-Dimethyl-17-Beta-Hydroxyestra-4,14-Dien-3-One and 17 Esters Thereof and 7-Alpha,11-Beta-Dimethyl-17-Beta-Hydroxyestra-4-en-3-One 17-Undecanoate

Drs. Richard Blye and H.K. Kim (NICHD)

DHHS Reference No. E-069-2000/3 filed Mar. 29, 2002 (PCT-CIP Patent Application)

Licensing Contact: Marlene Shinn; 301/435-4426; [e-mail].

The NIH announces a new technology that relates to compounds that possess potent androgenic activity. These compounds offer a potential therapeutic benefit in the treatment of hypogonadism, regardless of cause, as an adjuvant in hormone replacement therapy for both men and women and for androgen stimulation of anabolism in a broad spectrum of disease entities involving debilitation.

These compounds exhibit both oral and parenteral androgenic activity. Oral activity appears greater than that of methyltestosterone. Parenteral activity as an aqueous suspension is substantially longer than that produced by testosterone enanthate or testosterone cypionate. Since these compounds lack a 17-alkyl moiety, they are expected to show less hepatotoxicity upon oral administration. Claims in this patent application are drawn to the new androgenic compounds themselves, their method of preparation, pharmaceutical formulations containing the new androgens and their utility and use in a wide spectrum of therapeutic applications.

Dated: November 4, 2002.

Jack Spiegel,

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