02-13731. 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.

Enhanced Distribution of Therapeutic Agents After Local Delivery

Krys Bankiewicz et al. (NINDS)

U.S.P.A. Nos. 60/250,286 filed 30 Nov 2000 and 60/286,308 filed 25 Apr 2001

Licensing Contact: Norbert Pontzer; 301/496-7736 ext. 284; e-mail: [e-mail]

Many experimental therapies will rely on the local parenchymal delivery of macromolecules or nucleic acids for their success. However, the volume of distribution of many of these potential therapeutic agents is restricted by their interactions with the extracellular matrix and cellular receptors. Heparin-sulfate proteoglycans are a cell surface component which bind to many different types of molecules such as growth factors, cytokines and chemokines and viruses such as cytomegalovirus, herpes simplex virus and HIV.

These inventions provide a method of dramatically increasing the volume of distribution and effectiveness of certain therapeutic agents after local delivery by the use of facilitating agents as described in Neuroreport. 2001 Jul 3;12(9):1961-4 entitled “Convection-enhanced delivery of AAV-2 combined with heparin increases TK gene transfer in the rat brain” and in Exp Neurol. 2001 Mar;168(1):155-61 entitled “Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin.” These methods are especially useful when used in conjunction with technology described and claimed in U.S. Patent 5,720,720 entitled “Convection-enhanced drug delivery.” Licenses for methods to enhance the distribution of all claimed therapeutics except adeno-associated viral vectors are available.

Sol Fusin: Use of GP64-6HIS to Catalyze Membrane Fusion

D. H. Kingsley and J. J. Zimmerberg (NICHD)

DHHS Reference Nos. E-113-99/0 filed 18 Feb 1999 and E-113-99/1 filed 15 Nov 2001

Licensing Contact: Pradeep Ghosh; 301/496-7736 ext. 211; e-mail [e-mail]

An efficient drug delivery system is a necessity for a wide range of therapeutic interventions. This technology pertains to a process related to the solubilizing of insoluble membrane proteins, thus generating soluble and functional version (sol-proteins) of previously insoluble proteins. Specifically, the invention relates to the addition of histidine amino acids to the cytoplasmic domains of membrane and viral envelope proteins for the purpose of solubilizing, purifying and/or reconstituting functional viral envelope proteins in lipid-containing vesicles. The modified protein mediates fusion of the resulting vesicular membrane with other lipid membranes, thus creating an efficient delivery system. The proteins in this form have been referred to as “sol-fusin” and the resultant sol-fusin/liposome complex is potentially able to catalyze delivery of therapeutic, genetic, or antigenic compounds both in vivo and in vitro. Thus, pharmaceutical and vaccine manufacturers may use these proteoliposomes as tools to deliver active therapeutic, genetic or antigenic agents without destruction by lysosomes. In addition to being useful as a delivery tool, the sol-fusin/ liposomes can be used to mimic viral infections. The triggering of sol-fusin is low pH-dependent, and thus may perhaps facilitate oral ingestion and gastrointestinal absorption of the bioactive agents because of their direct membrane fusion mediating activity.

Dated: May 23, 2002.

Jack Spiegel,

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