[Federal Register Volume 68, Number 221 (Monday, November 17, 2003)]
[Notices]
[Pages 64905-64906]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-28659]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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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: 301/594-6565; fax: 301/402-0220; e-
mail: [email protected]. 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

[[Page 64906]]

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.
[FR Doc. 03-28659 Filed 11-14-03; 8:45 am]
BILLING CODE 4146-01-P