[Federal Register Volume 68, Number 216 (Friday, November 7, 2003)]
[Notices]
[Pages 63116-63117]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-28060]



[[Page 63116]]

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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.

Efficient Inhibition of HIV-1 Viral Entry Through a Novel Fusion 
Protein Including CD4

James Arthos, Claudia Cicala, Anthony Fauci (NIAID).
U.S. Provisional Application No. 60/346,231 filed 25 Oct 2001 (DHHS 
Reference No. E-337-2001/0-US-01); PCT Application No. PCT/US02/34393 
filed 24 Oct 2002 (DHHS Reference No. E-337-2001/0-PCT-01).

    This invention relates to CD4 fusion proteins for use in the 
treatment of an immunodeficiency virus infection such as human 
immunodeficiency virus (HIV). These polypeptides have been shown by the 
inventors to inhibit the entry of primary isolates of HIV-1 into CD4+ T 
cells by targeting the gp120 subunit of the HIV-1 envelope. The 
invention claims recombinant polypeptides comprising a CD4 polypeptide 
ligated at its C-terminus with a portion of a human immunoglobulin 
comprising a hinge region and two constant domains of an immunoglobulin 
heavy chain. The portion of the IgG is fused at its C-terminus with a 
polypeptide comprising a tailpiece from the C terminus of the heavy 
chain of an IgA antibody. This protein is very large (greater than 800 
kilodaltons), which may contribute to its ability to inhibit entry of 
primary isolates of HIV-1 into T cells. It presents twelve gp120 
binding domains (D1D2) and can bind at least ten gp120s simultaneously. 
The inventors have shown that the construct efficiently neutralizes 
primary isolates from different HIV subgroups. Also claimed are use of 
the construct as a component of a vaccine and as a diagnostic.

Identification of New Small RNAs and ORFs

Susan Gottesman (NCI), Gisela Storz (NICHD), Karen Wassarman (NICHD), 
Francis Repoila (NCI), Carsten Rosenow (EM).
U.S. Provisional Application No. 60/266,402 filed 01 Feb 2001 (DHHS 
Reference No. E-072-2001/0-US-01); PCT Application No. PCT/US02/03147 
filed 31 Jan 2002 (DHHS Reference No. E-072-2001/0-PCT-02); U.S. Patent 
Application filed 25 Jul 2003 (DHHS Reference No. E-072-2001/0-US-03).

    The inventors have isolated a number of previously unknown sRNAs 
found in E. coli. Previous scientific publications by the inventors and 
others regarding sRNAs have shown these sRNAs to serve important 
regulatory roles in the cell, such as regulators of virulence and 
survival in host cells. Prediction of the presence of genes encoding 
sRNAs was accomplished by combining sequence information from highly 
conserved intergenic regions with information about the expected 
transcription of neighboring genes. Microarray analysis also was used 
to identify likely candidates. Northern blot analyses were then carried 
out to demonstrate the presence of the sRNAs. Three of the sRNAs 
claimed in the invention regulate (candidates 12 and 14, negatively and 
candidate 31, positively) expression of RpoS, a major transcription 
factor in bacteria that is important in many pathogens because it 
regulates (amongst other things) virulence. The inventors' data show 
that these sRNAs are highly conserved among closely related bacterial 
species, including Salmonella and Klebsiella, presenting a unique 
opportunity to develop both specific and broad-based antibiotic 
therapeutics. The invention contemplates a number of uses for the 
sRNAs, including, but not limited to, inhibition by antisense, 
manipulation of gene expression, and possible vaccine candidates.

A Novel Chimeric Protein for Prevention and Treatment of HIV Infection

Edward A. Berger (NIAID), Christie M. Del Castillo.
U.S. Provisional Application No. 60/124,681 filed 16 Mar 1999 (DHHS 
Reference No. E-039-1999/0-US-01); PCT Application No. PCT/US00/06946 
filed 16 Mar 2000 (DHHS Reference No. E-039-1999/0-PCT-02); U.S. Patent 
Application No. 09/936,702 filed 13 Sep 2001 (DHHS Reference No. E-039-
1999/0-US-03).

    This invention relates to bispecific fusion proteins effective in 
viral neutralization. Specifically, the invention is a genetically 
engineered chimeric protein containing a soluble extracellular region 
of human CD4 attached via a flexible polypeptide linker to a single 
chain human monoclonal antibody directed against a CD4-induced, highly 
conserved HIV gp120 determinant involved in coreceptor interaction. 
Binding of the sCD4 moiety to gp120 induces a conformational change 
that enables the antibody moiety to bind, thereby blocking Env function 
and virus entry. This novel bispecific protein displays neutralizing 
activity against genetically diverse primary HIV-1 isolates, with 
potency at least 10-fold greater than the best described HIV-1 
neutralizing monoclonal antibodies. The agent has considerable 
potential for prevention of HIV-1 infection, both as a topical 
microbicide and as a systemic agent to protect during and after acute 
exposure (e.g. vertical transmission, post-exposure prophylaxis). It 
also has potential utility for treatment of chronic infection. Such 
proteins, nucleic acid molecules encoding them, and their production 
and use in preventing or treating viral infections are claimed.

Novel Antimalarial Compounds, Methods of Synthesis Thereof, 
Pharmaceutical Compositions Comprising Same, and Methods of Using Same 
for Treatment and Prevention of Malaria

Michael R. Boyd (NCI), Gerhard Bringmann (EM), Sven Harmsen (EM) Roland 
Gotz (EM), T. Ross Kelly (EM), Matthias Wenzel (EM), Guido Francois 
(EM), J. D. Phillipson (EM), Laurent A. Assi (EM), Christopher 
Schneider (EM).
U.S. Patent 5,639,761 issued on 17 Jun 1997 (DHHS Reference No. E-090-
1994/0-US-01); U.S. Patent 6,627,641 issued on 30 Sep 2003 (DHHS 
Reference No. E-090-1994/0-US-07); U.S. Patent 5,552,550 issued on 03 
Sep 1996 (DHHS Reference No. E-

[[Page 63117]]

200-1994/0-US-01); U.S. Patent 5,763,613 issued on 09 Jun 1998 (DHHS 
Reference No. E-200-1994/0-US-02); U.S. Patent 6,140,339 issued on 31 
Oct 2000 (DHHS Reference No. E-200-1994/2-US-01); U.S. Patent 6,331,630 
issued on 18 Dec 2001 (DHHS Reference No. E-200-1994/2-US-08); U.S. 
Patent 5,571,919 issued on 05 Nov 1996 (DHHS Reference No. E-201-1994/
0-US-01); U.S. Patent 5,789,594 issued on 04 Aug 1998 (DHHS Reference 
No. E-201-1994/0-US-02); U.S. Patent 5,578,729 issued on 26 Nov 1996 
(DHHS Reference No. E-201-1994/1-US-01); U.S. Patent 5,786,482 issued 
on 28 Jul 1998 (DHHS Reference No. E-201-1994/1-US-03).

    According to data recently reported by the World Health 
Organization (WHO), the death rate from malaria exceeds one million 
individuals per year. The Public Health Service seeks exclusive or non-
exclusive licensee(s) to develop and commercialize the technology 
claimed within the portfolio of U.S. patents issued and pending, and 
corresponding international patents issued and pending. These patents 
and pending applications claim an exceptionally broad universe of novel 
naphthylisoquinoline alkaloid compounds, and methods of total synthesis 
thereof. Representative examples of these compounds have been shown to 
have potent in vitro activity against malaria parasites, including 
parasites that are highly resistant to available antimalarial drugs.
    Representative examples have also been shown to have potent in vivo 
activity against malaria parasites in animal models. Pharmaceutical 
compositions comprising these compounds, as well as methods of using 
the compounds to treat or prevent a malarial infection of a host, are 
claimed. The relative structural simplicity of this class of compounds, 
and the ready synthetic access thereto, provide unprecedented 
opportunities for structure-activity relationship (SAR), lead-
optimization and antimalarial drug development. The technology is 
further described in the following publications: J. Nat Prod. 1997 
Jul.;60(7):677-83 and Bioorg. Med. Chem. Lett. 1998 Jul.;8(13): 1729-
34.

Antimicrobial Magainin Peptides

Michael A. Zasloff, Hao-Chia Chen, Judith H. Brown, John L. Morell, 
Charng-Ming Huang (NICHD).
U.S. Patent 4,810,777 issued on 07 Mar 1989 (DHHS Reference No. E-145-
1987/0-US-01); U.S. Patent 5,567,681 issued on 22 Oct 1996 (DHHS 
Reference No. E-145-1987/2-US-03); U.S. Patent 5,643,876 issued on 01 
Jul 1997 (DHHS Reference No. E-145-1987/1-US-03); U.S. Patent 5,221,732 
issued on 22 Jun 1993 (DHHS Reference No. E-217-1988/0-US-01).

    First isolated from the skin of the African clawed frog Xenopus 
laevis, magainin peptides have been shown by the inventors to have 
broad-spectrum antimicrobial properties. Both synthetic and natural 
magainin peptides are active against many species of bacteria and fungi 
and induce osmotic lysis of protozoa. Magainin peptides are water 
soluble, nonhemolytic at effective antimicrobial concentrations, have 
molecular weights of 2500 or less and are amphiphilic. Compositions and 
methods for their use are claimed in the patents. These inventions are 
available for nonexclusive or exclusive licensing. The inventions are 
further described in Zasloff et al., P.N.A.S. USA 1987 Aug.; 
84(15):5449-53; Marion et al., FEBS Lett. 1988 Jan.18;227(1):21-6; 
Soravia et al., FEBS Lett. 1988 Feb. 15;228(2):337-40; Westerhoff et 
al., P.N.A.S. USA 1989 Sep.; 86(17):6597-601; and Gwadz et al., Infect. 
Immun. 1989 Sep.; 57(9):2628-33.

    Dated: October 24, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 03-28060 Filed 11-6-03; 8:45 am]
BILLING CODE 4140-01-P