List of NIH and Navy Inventions for April 21, 2000 --- SSTI Weekly Digest

Six NIH Inventions Available for Licensing

SUMMARY: The inventions listed below are owned by agencies of the U.S. Government and are available for licensing in 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 John Rembosek, Ph.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7056 ext. 270; fax: 301/402-0220; e-mail: jr312d@nih.gov. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Methods and Compositions for Correlating CCR5 Expression With Essential Hypertension
Dr. Thomas O'Brien (NCI) DHHS Reference Number E-257-99/0 filed October 14, 1999

Hypertension is a disease which afflicts as many as 1 in 5 persons in the United States and is the most common cause of visits to physicians. Once diagnosed with hypertension, treatment of the disease is lifelong. There is mounting evidence that lifestyle changes can prevent the usual rise in blood pressure with age, but for patients whose hypertension cannot be adequately treated by lifestyle changes, drug therapy must be instigated which can be difficult to control and have adverse side affects. The present invention mutation in the CC-chemokine receptor 5 (CCR5) gene and an increased risk of developing hypertension. This technology will allow for the screening of individuals for the presence of the CCR5-D32/D32 genotype which correlates with an increased risk of developing hypertension and possibly prevent its occurrence through adequate antihypertensive therapy.This technology may lead to a method of treating or preventing hypertension through the administration of: (1) an effective amount of a CCR5 expression enhancing agent; (2) CCR5 activity enhancing agent; (3) an effective amount of CCR5; or (4) an effective amount of a nucleic acid encoding CCR5. Also, this technology can be employed as a method of identifying an agent that could be used to treat or prevent hypertension through the above identified processes.

Cloning of the Human Nuclear Receptor Co-Repressor Gene
Johnson M. Liu, Jianxiang Wang (NHLBI) DHHS Reference No. E-088--99/0 filed August 3, 1999

Alteration in the expression of human genes is critical to the development and progression of many diseases. These include, among others, cancer, inflammation, cardiovascular disease, hypercholesterolemia, high blood pressure, and diabetes. The Human Nuclear Receptor Co-Repressor (HuN-Cor) gene represents a technology that may be used to alter the transcription of genes. It provides a general mechanism by which many genes may be modulated throughout the entire range of being turned on to being completely turned off. The Hun-Cor gene is a ubiquitously expressed gene that codes for a protein that silences other genes. It does this by recruiting an enzyme complex that causes local folding of chromatin, not allowing other transcription factors to work. Hun-Cor represents a powerful research tool that can be used to study gene expression and characterization for many different genes. It may also be useful as a target for the isolation of pharmaceutical compounds that enhance or inhibit expression of genes.

Imaging With Positron-Emitting Taxanes as a Guide to Antitumor Therapy
Jerry M. Collins, Raymond W. Klecker, Lawrence Anderson (FDA) Serial No. 60/155,061 filed 21 Sep 1999

The present application discloses the use of positron-emitting compounds to label taxane type drugs. This invention also describes methods of synthesizing these taxane type compounds. Further, methods to guide treatment of solid tumors, with labeled taxanes, are also disclosed in the present application. Advantages of using this technology include: (1) Avoidance of exposing patients to toxic drugs that have no potential for benefit; (2) ability to rapidly determine whether a given tumor will be likely to respond to a particular drug; and (3) the ability to monitor the impact of various dosages, schedules, and modulators for delivery, in situ, at the actual tumor under treatment conditions.

Conjugate Vaccine for Neisseria Meningitidis
Xin-Xing Gu (NIDCD) and Chao-Ming Tsai (FDA) Serial No. 60/148,021 filed 10 Aug 1999

The invention discloses a vaccine which comprises lipooligosaccharide (LOS) isolated from N. meningitidis and conjugated to a carrier protein. The invention also discloses a method of making the acellular vaccine. The method consists of two main steps. In the first step the lipooligosaccharide (LOS), chosen so it does not contain the lacto-N-neotetraose human antigen (LNnT), is detoxified by a novel procedure which uses hydrazine to remove the O-linked fatty acids. In the second step, the detoxified LOS (dLOS) is covalently conjugated to a carrier protein such as Tetanus Toxoid (TT). The dLOS produced in step 1 is 10,000 fold less toxic than the parent LOS. The conjugate vaccine exhibited a high level of immunogenicity as evidenced by the high titer of IgG antibody to native LOS, obtained in mice and rabbits. The rabbit antisera produced by the conjugate vaccine of one N.meningitidis strain (strain 7880, A,L10) exhibited bactericidal activity and cross reactivity with heterologous N.meningitidis strains. A conjugate vaccine made in this method may be multivalent, composed of dLOSs from different strains and/or immunotypes of N. meningitidis and will thus protect against all types of N. meningitidis, including type B.

A portion of this invention was disclosed in a poster by Tsai, Gu and Quakyi at the Fifth Conference of the International Endotoxin Society held in Santa Fe, New Mexico in September 12-15, 1998.

High Speed Parallel Nucleic Acid Sequencing
Thomas D. Schneider, Denise Rubens (NCI) Serial No. 60/151,580 filed 30 Aug 1999

The present application describes a new method and apparatus for DNA sequencing called Two Dye Sequencing (TDS). This method employs engineered DNA polymerases which are labeled with a fluorophore such as Green Fluorescent Protein (GFP) and are combined with an annealed oligonucleotide primer in a chamber of a microscope field of view capable of detecting individual molecules. Four nucleotide triphosphates, each labeled on the base with a different fluorescent dye are introduced to the reaction. Light of a specific wavelength is used to excite the fluorophore on the polymerase, which in turn excites the neighboring fluorophore on the nucleotide by Fluorescense Resonance Energy Transfer (FRET). As nucleotides are added to the primer, their spectral emissions provide sequence information of the DNA molecule.

Hydrazide Inhibitors of HIV-1 Integrase
Yves Pommier, Nouri Neamati, Zhaiwai Lin, Terrence R. Burke, Jr. (NCI) DHHS Reference Nos. E-037-99/0 filed 12 Mar 1999 and E-037-99/1 filed 10 Mar 2000

The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). Drug-resistance is a critical factor contributing to the gradual loss of clinical benefit to treatments for HIV infection. Accordingly, combination therapies have further evolved to address the mutating resistance of HIV. However, there has been great concern regarding the apparent growing resistance of HIV strains to current therapies.

It has been found that a certain class of compounds including salicylhydrazides and analogs and derivatives thereof are effective and selective anti-integrase inhibitors which are active in the presence of both Mn(+2) and Mg(+2) and which may be used in the treatment or prevention of infection by HIV and AIDS. The subject invention provides for such compounds and for methods of inhibiting HIV integrase.

Three Navy Inventions Available for Licensing

SUMMARY: The inventions listed below are assigned to the United States Government as represented by the Secretary of the Navy and are available for licensing by the Department of the Navy.

U.S. Patent Application Serial No. 09/296,802 entitled ``An Interactive Communication System Permitting Increased Collaboration Between Users'', filing date: April 23, 1999, Navy Case No. 78947.

U.S. Patent Application Serial No. 09/296,746 entitled ``Computer Software for Converting A General Purpose Computer Network Into An Interactive Communications System'', filing date: April 23, 1999, Navy Case No. 79258.

U.S. Patent Application Serial No. 09/296,757 entitled ``A Method for Facilitating Collaborative Development Efforts Between Widely Dispersed Users'', filing date: April 23, 1999, Navy Case No. 79259

ADDRESSES: Requests for copies of the patent applications cited should be directed to the Naval Surface Warfare Center, Dahlgren Laboratory, Code CD222, 17320 Dahlgren Road, Building 183, Room 015, Dahlgren, VA 22448-5100, and must include the Navy Case number.

FOR FURTHER INFORMATION CONTACT: James B. Bechtel, Patent Counsel, Naval Surface Warfare Center, Dahlgren Laboratory, Code CD222, 17320 Dahlgren Road, Building 183, Room 015, Dahlgren, VA 22448-5100, telephone (540)-653-8061.

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