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: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

A Plasmid for Expression of a Soluble Form of HIV-1 Integrase Protein

Robert Craigie et al. (NIDDK), NIH Reference No. E-108-00/0; Licensing Contact: J.P. Kim; 301/496-7056 ext. 264; e-mail: kimj@od.nih.gov.

Integrase is an essential HIV enzyme and a promising target for antiviral therapy. Integrase protein is required to assay for inhibitors of this enzyme and for mechanistic studies on HIV DNA integration. Further, drugs targeted to integrase would provide a new therapeutic approach to the treatment of AIDS and could be used in combination therapy with drugs that target RT and protease. The subject plasmid can be used to produce large quantities of a soluble form of HIV-1 integrase protein for such work.

TTP as a Regulator of GM-CSF mRNA Deadenylation and Stability

Ester Carballo-Jane, Wi S. Lai, Perry J. Blackshear (NIEHS), NIH Reference No. E-204-99/0 filed 13 Aug 1999; Licensing Contact: Vasant Gandhi; 301/496-7056 ext. 244; e-mail: gandhiv@od.nih.gov.

The disclosed invention provides materials and methods to treat granulocytopenia (low white cell count in the blood) which is characterized by a reduced number of granulocytes (relative) or an absence of granulocytes (absolute). This condition is commonly associated with cancer chemotherapy, but is seen less frequently in a number of conditions including the use of propylthiouracil, radiotherapy for marrow ablation for bone marrow transplantation, aplastic anemia, systemic lupus erythematosus, AIDS and a variety of other situations. The invention proposes a method to increase GM-CSF levels in a treated subject, and this increase is achieved by inhibiting the degradation of GM-CSF messenger RNA (mRNA). Tristetraprolin (TTP) is one member of a family of cys-cys-cys-his (CCCH) zinc finger proteins, and it is a factor that binds to and causes the instability of GM-CSF mRNA. Methods are provided for the development of screening assays for molecules that inhibit the binding of TTP and its related proteins to GM-CSF mRNA, or otherwise inhibit the effect of TTP to promote breakdown of the mRNA, leading in turn to increased mRNA stability and enhanced production of GM-CSF. Compounds identified by such screens, and their derivatives, could be useful in treating granulocytopenia from whatever cause.

Novel Post-Transcriptional Regulatory Elements and Uses Thereof

George N. Pavlakis and Filomena Nappi (NCI), NIH Reference Nos. E-143-98/0 filed 22 May 1998 and E-143-98/1 filed 22 May 1999; Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: salatac@od.nih.gov.

This invention concerns a novel post-transcriptional regulatory element that can function as an RNA nucleo-cytoplasmic transport element (NCTE) and its use to make recombinant attenuated HIV strains useful as vaccines. HIV regulates its expression by controlling the nuclear transport of unspliced mRNA encoding structural proteins. HIV utilizes the Rev/RRE system. RRE (Rev responsible element) is an HIV encoded NCTE, which is part of every HIV RNA encoding the structural genes (Gag/Pol and Env). Rev is an HIV encoded protein which binds to RRE. This interaction is essential for nucleo-cytoplasmic transport of the RRE containing viral mRNAs and the expression of Gag/Pol and Env proteins. The inventors have produced an attenuated HIV by disabling Rev/RRE, by point mutations, and inserting in its place the novel murine NCTE of the invention. The resultant HIV is attenuated between 50 and 200 fold compared to wild type HIV. Claimed at the novel NCTE, recombinant retroviruses comprising the NCTE and vaccines.