03-28659. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

SUMMARY:

The invention listed below is owned by an agency of the U.S. Government and is 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. patents and patent applications listed below may be obtained by contacting Michael Ambrose, Ph.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: [phone]; fax: [phone]; e-mail: [e-mail]. A signed Confidential Disclosure Agreement will be required to receive copies of any patent applications.

Mouse Lacking the Chemokine Receptor CX3CR1

Philip Murphy, Christopher Combadiere, Ji-liang Gao (NIAID).

DHHS Reference No. E-216-2003/0—Research Tool.

This mouse has been generated by targeted gene disruption. The mouse provides a model to investigate the function of the chemokine receptor CX3CR1, which is a proinflammatory receptor for the leukocyte chemoattractant CX3CL1 (aka fractalkine). As an example, the mouse is in use in the study of atherosclerosis. Further, the mouse may serve as a model study the role of the immune system during infection with pathogens as well as other immunologically mediated diseases and responses to tumors.

This mouse has been described in the publication “Decreased atheroscelerotic lesion formation in CX3R1/ApoE double knockout mice”. Combadiere C., Potteaux S., Gao J-L., Esposito B., Casanova S., Lee EJ., Debre P., Tedgui A., Murphy PM., Mallat Z. Circulation. 2003; 1009-1016.

Factors That Bind Intestinal Toxins

Joel Moss (NHLBI), Masatoshi Noda (EM).

U.S. Provisional Application No. 60/409,742 filed 10 Sep 2002 (DHHS Reference No. E-223-2002/0-US-01); PCT Application No. PCT/US03/28282 filed 09 Sep 2003 (DHHS Reference No. E-223-2002/0-PCT-02).

This invention discloses and covers polyphenolic compounds that will bind bacterial toxins, methods for the treatment of such infections, specifically Stx-1 toxins from STEC strains of E. coli.

Bacterial infections not only cause disease by their presence but also upon the release of toxins. The common enteric bacteria, E. coli O157:H7 releases such toxins (Stx-1) upon treatment with antibiotics. These toxins, when released into the lumen of the intestinal tract, will cause cellular damage thus increasing the severity of the infection. Thus not only does the patient become sick by the infection, but treatment can exacerbate the condition and clinical picture. Further, the indiscriminate use of antibiotics has lead to an increase in the number of resistant strains thus limiting the effectiveness of therapy as well.

The disclosed invention uses an extract from the bracts of Humulus lupulus that binds the toxins thus eliminating them as a source of cellular damage. The enclosed methods and devices to isolate such polyphenolic components, the methods to use such components in the detection of such bacteria in biological samples and potential therapies based on the isolated components.

Molecular Diagnosis of Disseminated Candida albicans Infection Using Hemoglobin-Response Gene

David D. Roberts, Sizhuang Yan (NCI).

U.S. Patent Application No. 09/258,634 filed 26 Feb 1999 (DHHS Reference No. E-086-1999/0-US-01).

Three hemoglobin-response genes from Candida albicans have been isolated. These genes are induced when the organism initiates systemic infections, coming into contact with hemoglobin. Further, the methods and composition of the included nucleic acid sequences and encoded proteins can be used in the development of reagents and kits used to discriminate between commensal colonization and the more life threatening disseminated infection.

Mucosal Cytotoxic T Lymphocyte Responses

Jay A. Berzofsky (NCI), Igor M. Belyakov (NCI), Michael A. Derby (NCI), Brian L. Kelsall (NIAID), Warren Strober (NIAID).

U.S. Patent Application No. 09/508,552 filed 12 Jun 2000 (DHHS Reference No. E-268-1997/2-US-02).

This invention claims methods and compositions for inducing a protective mucosal cytotoxic T lymphocyte (CTL) response in a mammal involving administering a soluble antigen or a soluble antigen with one or more active agents such as a cytokine or co-stimulatory molecule to a mucosal surface or tissue. As a preferred embodiment, the invention contemplates intrarectal administration of the peptide vaccine because the inventors have shown that there is a greater CTL response through intrarectal administration rather than intranasal administration. The synthetic peptide vaccines utilized in the invention to elicit protective immune responses after mucosal infection comprise a multideterminant helper peptide containing a cluster of overlapping helper epitopes (a PCLUS or cluster peptide) colinearly synthesized with a peptide epitope target for neutralizing antibodies and CTL. The inventors have generated data showing that an intrarectally administered synthetic multiepitope HIV/SIV peptide vaccine administered to macaques in conjunction with mutant E. coli heat labile enterotoxin as an adjuvant induces mucosal CTL responses that provide better protection against intrarectal SHIV infection when compared to a subcutaneously administered vaccine comprising the same peptides inducing as high or higher systemic CTL responses. The invention is further described in Belyakov et al., Proc. Natl. Acad. Sci. USA 1998 Feb 17;95(4):1709-14 and Belyakov et al., J. Clin. Invest. 102: 2072-2081, 1998.

Conformationally Locked Nucleoside Analogues

Victor E. Marquez, Juan B. Rodriguez, Marc C. Nicklaus, Joseph J. Barchi, Jr., Maqbool A. Siddiqui (NCI).

U.S. Patent 5,629,454 issued 13 May 1997 (DHHS Reference No. E-231-1993/1-US-01); U.S. Patent 5,869,666 issued 09 Feb 1999 (DHHS Reference No. E-231-1993/1-US-02); and

Conformationally Locked Nucleoside Analogs as Antiherpetic Agents

Victor E. Marquez, Juan B. Rodriguez, Marc C. Nicklaus, Joseph J. Barchi, Jr., Maqbool A. Siddiqui (NCI).

U.S. Patent 5,840,728 issued 23 Nov 1998 (DHHS Reference No. E-100-1996/0-US-03).

The compounds of the present invention represent the first examples of carbocyclic dideoxynucleosides that in solution exist locked in a defined N-geometry (C3′-endo) conformation typical of conventional nucleosides. These analogues exhibit increased stability due to the substitution of carbon for oxygen in the ribose ring. The invention includes 4′-6′-cyclopropane fused carbocyclic dideoxynucleosides, 2′-deoxynucleosides and ribonucleosides as well as oligonucleotides derived from these analogues; the preferred embodiment of the invention is carbocyclic-4′-6′-cyclopropane-fused analogues of dideoxypurines, dideoxypyrimidines, deoxypurines, deoxypyrimidines, purine ribonucleosides and pyrimidine ribonucleosides. In addition, oligonucleotides derived from one or more of the nucleosides in combination with the naturally occurring nucleosides are within the scope of the present invention.

The second invention discloses a method for the treatment of herpes virus infections by the administration of cyclopropanated carbocyclic 2′-deoxynucleosides to an affected individual. This invention is a method of administration of the compounds described above. The compounds of this invention are particularly efficacious against herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Epstein-Barr Virus (EBV) and human cytomegalovirus (CMV), although the nucleoside analogues of the invention may be used to treat any condition caused by a herpes virus. Specifically, the N-methanocarba-T (Thymidine) analogue has been shown to exhibit strong activity against HSV-1 and HSV-2, and moderate to strong activity against EBV. Significantly, the anti-HSV activity of the Thymidine analogue is stronger than that of Acyclovir (shown in a plaque reduction assay), a widely used anti-HSV therapeutic. Furthermore, the Thymidine analogue is also non-toxic against stationary cells and is potent against rapidly dividing cells. Dosage amounts for the compounds are similar to those of Acyclovir.

Descriptions of these inventions may be found in Rodriguez et al., J. Medicinal Chemistry 37:3389-3399 (1994) and Marquez et al., J. Medicinal Chemistry 39:3739-3747 (1996).

Dated: November 6, 2003.

Steven M. Ferguson,

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