05-21832. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by an agency 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.

Method To Disrupt Protein-Protein Interactions and Its Use To Identify Compounds Able To Inhibit HIV-1 Rev Protein Multimerization

George Pavlakis and Leonid Suvoroz (NCI).

HHS Reference No. E-303-2005/0—Research Tool.

Licensing Contact: Sally Hu; 301/435-5606; [e-mail].

The invention provides a FRET-based assay for the study of Rev-Rev interaction in vitro, based on YFP and CFP expression constructs for Rev. Using this assay, Rev-derived small peptides that can inhibit Rev-Rev interactions and disrupt dimerization were discovered. This assay can be used as an in vitro assay for studying protein-protein interactions in general, and for the discovery of inhibitors or agonists of such interactions as potential drugs against HIV infections, as well as for the discovery of Rev dimerization inhibitors. Thus this assay can be useful for drug screening.

NIH will not seek patent protection for this invention, and it will be available for licensing through a Biological Materials License (BML) or though a Material Transfer Agreement (MTA).

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Furin Inhibitors and Alpha-Defensin for Preventing Papilloma Virus Infection

Patricia Day, Rebecca Richards, John Schiller, Douglas Lowy, Christopher Buck (NCI).

U.S. Provisional Application No. 60/692,846 filed 21 Jun 2005 (HHS Reference No. E-104-2005/1-US-01).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

Available for licensing and commercial development are intellectual properties that claim compositions and methods for preventing papilloma virus (PV) infection in humans using furin inhibitors or alpha-defensins. PV viruses include a minor capsid protein L2 which requires a functional intracellular furin (a cell-encoded proprotein convertase present in endosomes) for escape from the endosomal spaces into the cytoplasm and viral infection. Accordingly, a disruption of viral infection by the inhibition of furin with molecules such as decanoyl-RVKR-CMK is potentially useful as a broad spectrum anti-HPV prophylactic.

Alpha-defensins, which are naturally secreted by the cervix, are reported to have potent and non-type specific anti-HPV properties. They can be administered as a topic microbicide to prevent infection by many HPV genotypes, including types not covered by the vaccines currently in Phase III clinical trials.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Identification of a Fusion/Entry Receptor for Human Herpesvirus-8

Edward A. Berger, Johnan Kaleeba (NIAID).

U.S. Provisional Application No. 60/681,098 filed 13 May 2005 (HHS Reference No. E-051-2005/0-US-01).

Licensing Contact: Robert M. Joynes; 301/594-6565; [e-mail].

This invention relates to stable, nonhuman cell lines and transgenic mammals having cells that coexpress human xCT as valuable tools for the continuing research of Kaposi's Sarcoma Herpes Virus (KSHV) infection and the development of more effective anti-KSHV therapeutics. Kaposi's sarcoma (KS) is the most common malignancy in AIDS patients and manifests as highly proliferative vascular lesions that appear on body extremities. KSHV is invariably present in all known clinical forms of KS and sero-conversion to KSHV antigens is considered a risk factor for development of the lesions. KSHV is believed to enter target cells by direct fusion of virion membrane with the target cell plasma membrane. The susceptibility of KSHV infection depends on the cell surface expression of the human xCT molecule. xCT plays a role in the membrane fusion step of KSHV infection. The identification of xCT as a receptor for KSHV may pave the way for deciphering the mechanism of KSHV pathogenesis.

This discovery has led to various potential commercial applications for this invention including the following:

• Cell lines expressing recombinant xCT for analysis of KSHV entry/infection
• Construction of xCT transgenic small animals for testing of KSHV inhibitors
• Use of peptides or fragments derived from extracellular regions of xCT as KSHV inhibitors
• Use of specific antibodies (including human versions) against xCT as KSHV inhibitors
• Use of small molecules targeted to xCT as KSHV inhibitors

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Potent HIV-1 Entry Inhibitors and Immunogens

Dimiter S. Dimitrov et al. (NCI).

U.S. Patent Application No. 10/506,651 filed 05 Mar 2002; Publication Number US-2005-0106160 (HHS Reference No. E-039-2002/0-US-02).

Licensing Contact: Susan Ano; 301/435-5515; [e-mail].

This technology relates to tethered antigenic constructs where flexible linkers join gp120 and the ectodomain of gp41. The HIV-1 envelope Glycoprotein (Env) undergoes conformational changes while driving entry. The inventors developed these constructs to mimic some of the intermediate Env conformations. Tethered Envs with long (15 to 26 amino acid) linkers were stable and potently inhibited fusion mediated by R5, X4 and R5X4 Envs, most likely by exposure of gp41 structures that bind DP178 and cluster II mAbs. The fusion proteins with long linkers exhibited enhanced exposure of DP178 and cluster II mAbs binding gp41 structures that are critical for entry. These findings suggest the existence of conserved structures that are critical for HIV-1 entry, and could be used as novel immunogens for elicitation of broadly neutralizing antibodies and as antigens for selection of potent neutralizing antibodies by phage display.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

A Novel Post-Transcriptional Regulatory Element (PRE) and Its Use in Expression Cassettes and Recombinant Viruses

George N. Pavlakis et al. (NCI).

U.S. Patent Number 6,919,442, issued July 19, 2005; EP Patent Application Serial Number 99924362.9 (HHS Reference Number E-143-1998/0).

Licensing Contact: Susan Ano; 301/435-5515; [e-mail].

This invention concerns a novel post-transcriptional regulatory element (PRE) that can function as a RNA nucleo-cytoplasmic transport element (NCTE) and its inclusion in expression cassettes and recombinant viruses, including in recombinant attenuated HIV strains. HIV regulates its expression by controlling the nuclear transport of unspliced mRNA encoding structural proteins utilizing 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 that binds to RRE. This interaction is essential for the nucleo-cytoplasmic transport of the RRE-containing viral mRNAs and the expression of Gag/Pol and Env proteins in transport. The invention discusses an attenuated HIV produced by disabling rev/RRE by point mutations and inserting in its place the novel PRE of the invention. The resultant HIV is attenuated between 50 and 200 fold compared to wild-type HIV. In addition to HIV, the novel PRE element can increase expression from many mRNAs not efficiently transported on their own.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Dated: October 25, 2005.

Steven M. Ferguson,

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