[Federal Register Volume 70, Number 49 (Tuesday, March 15, 2005)]
[Notices]
[Pages 12701-12703]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5082]


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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 inventions listed below are owned by an agency of the U.S.

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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: (301) 496-7057; fax: (301) 402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

CpG Oligonucleotide Prodrugs

Daniela Verthelyi, Serge Beaucage, Andrzej Grajkowski (FDA).
U.S. Provisional Patent Application filed 13 Dec 2004 (DHHS Reference 
No. E-215-2004/0-US-01).
Licensing Contact: Michael Shmilovich; (301) 435-5019; 
[email protected].

    Available for licensing and commercial development into prodrugs 
and methods of synthesizing the same are CpG oligonucleotides that 
include thermolabile substituent on at least one nucleotide. The 
invention also provides compositions that include carriers and 
therapeutically effective amounts of at least one CpG oligonucleotide 
prodrug. Therapeutic methods of using such thermolabile CpG 
oligonucleotide prodrugs are also provided (e.g., a prodrug that 
elicits an immune response). The thermolabile substituent is typically 
bonded to the non-bridging oxygen atom of at least one phosphate or 
phosphorothioate in the oligonucleotide.
    The thermolabile CpG oligonucleotide prodrugs of the present 
invention can be administered to a patient as a prodrug of the parent 
CpG oligonucleotides in vivo. The thermolabile CpG oligonucleotide 
prodrugs of the present invention are rapidly internalized by immune 
cells (B cells, macrophages, dendritic cells, and monocytes) and 
localized in endocytic vesicles where they can interact with Toll-like 
receptor 9. This interaction triggers an immunostimulatory cascade 
characterized by B-cell proliferation, dendritic cell maturation, 
natural killer cell activation and the secretion of a variety of 
cytokines, chemokines and polyreactive immunoglobulins. Administration 
of the thermolabile CpG oligonucleotide prodrugs of the present 
invention to a host, for example, can improve the resistance of the 
host against infectious pathogenic microorganisms, e.g., parasites, 
bacteria, and viruses.

Identification of Proteins in a Genome

James L. Hartley, Dominic Esposito, and Kelly Jeanne Stanard (SAIC/
NCI).
U.S. Provisional Application No. 60/628,948 filed 19 Nov 2004 (DHHS 
Reference No. E-161-2004/0-US-01).
Licensing Contact: Cristina Thalhammer-Reyero; (301) 435-4507; 
[email protected].

    Available for licensing and commercial development are methods for 
identifying soluble proteins in a sample. Identification and 
characterization of bioactive compounds is a critical step in drug 
discovery, and there is a need for improved methods for identifying 
soluble proteins. One method provided, which produces soluble deletion 
derivatives of a protein, includes the steps of incubating a vector 
with a nucleic acid sequence encoding the protein, flanked by a first 
and second site-specific recombination sites, in the presence of one or 
more transposons with a third and fourth site-specific recombination 
sites and a transposase protein, to insert the one or more transposons 
into the vector, followed by transfer to further vectors with 
additional site-specific recombination sites, which are propagated, 
isolated, combined and recombined in the presence of a recombinase. A 
second method is for identifying two or more soluble proteins and 
includes the steps of expressing two or more vectors with the nucleic 
acid sequence encoding a soluble protein operatively linked to a 
promoter in one or more cells, and identifying and quantifying the 
isolated two or more soluble proteins by mass spectroscopy. The above 
methods can be used alone or in combination. These methods will enable 
researchers to identify both individual protein targets of drugs, as 
well as protein families or protein signaling pathways, thereby 
enhancing drug development.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

An Epitope-Enhancement of Human CD4 HIV Epitope

    Jay A. Berzofsky (NCI), Takahiro Okazaki (NCI).
U.S. Provisional Application No. 60/567,073 filed 30 Apr 2004 (DHHS 
Reference No. E-076-2004/0-US-01).
    Licensing Contact: Robert M. Joynes; (301) 594-6565; 
[email protected].

    This invention relates to an epitope of the HIV-1 envelope protein 
recognized by a CD4+ T cell line that was developed from 
immunization with canarypox vectors expressing gp120 of HIV-1. Virus-
specific CD4+ T cell help and CD8+ cytotoxic T 
cell responses are critical for the maintenance of effective immunity 
in chronic viral infections. The importance of the CD4+ T 
cell has been documented in HIV infection. A T1-specific 
CD4+ T cell line from a healthy volunteer immunized with a 
canarypox vector expressing gpl20 has been developed. This T1-specific 
CD4+ T cell line was restricted to DR13, which is common in 
the U.S. in both Caucasians and African-Americans and is one of the 
major haplotypes in Africans. The present invention provides isolated 
polypeptides comprising an enhanced T1 epitope. Amino acid 
substitutions in the T1 epitope were made to induce a stronger epitope-
specific CD4+ T cell response than the original epitope 
resulting in an improved CD4 epitope (also designated an epitope 
enhancement). A polypeptide comprising the enhanced CD4 epitope can be 
used as a component in composition either alone or in combination with 
other adjuvants and other immunogenic compositions to provide a more 
effective immune response to HIV infection.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

CC Chemokine Receptor 5 DNA, New Animal Models and Therapeutic Agents 
for HIV Infection

C. Combadiere, Y. Feng, E.A. Berger, G. Alkahatib, P.M. Murphy, C.C. 
Broder, P.E. Kennedy (NIAID);
U.S. Provisional Application No. 60/018,508 filed 28 May 1996 (DHHS 
Reference No. E-090-1996/0-US-01);
U.S. Patent Application No. 08/864,458 filed 28 May 1997 (DHHS 
Reference No. E-090-1996/0-US-04);
U.S. Patent Application No. 10/439,845 filed 15 May 2003 (DHHS 
Reference No. E-090-1996/0-US-05);
U.S. Patent Application No. 10/700,313 filed 31 Oct 2003 (DHHS 
Reference No. E-090-1996/0-US-06);
U.S. Patent Application No. 10/846,185 filed 14 May 2004 (DHHS 
Reference No. E-090-1996/0-US-07);

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PCT Application No. PCT/US97/09586 filed 28 May 1997 (DHHS Reference 
No. E-090-1996/0-PCT-02);
European Patent Application No. 97929777.7 filed 28 May 1997 (DHHS 
Reference No. E-090-1996/0-EP-03).
Licensing Contact: Peter Soukas; (301) 435-4646; [email protected].

    Chemokine receptors are expressed by many cells, including lymphoid 
cells, and function to mediate cell trafficking and localization. CC 
chemokine receptor 5 (CCR5) is a seven-transmembrane, G protein-coupled 
receptor (GPCR) which regulates trafficking and effector functions of 
memory/effector T-lymphocytes, macrophages, and immature dendritic 
cells. Chemokine binding to CCR5 leads to cellular activation through 
pertussis toxin-sensitive heterotrimeric G proteins as well as G 
protein-independent signalling pathways. Like many other GPCR, CCR5 is 
regulated by agonist-dependent processes which involve G protein 
coupled receptor kinase (GRK)-dependent phosphorylation, beta-arrestin-
mediated desensitization and internalization.
    Human CCR5 also functions as the main coreceptor for the fusion and 
entry of many strains of human immunodeficiency virus (HIV-1, HIV-2). 
HIV-1 transmission almost invariably involves such CCR5-specific 
variants (designated R5); individuals lacking functional CCR5 (by 
virtue of homozygosity for a defective CCR5 allele) are almost 
completely resistant to HIV-1 infection. Specific blocking of CCR5 
(e.g. with chemokine ligands, anti-CCR5 antibodies, CCR5-blocking low 
MW inhibitors, etc.) inhibits entry/infection of target cells by R5 HIV 
strains. Cells expressing CCR5 and CD4 are useful for screening for 
agents that inhibit HIV by binding to CCR5. Such agents represent 
potential new approaches to block HIV transmission and to treat 
infected people. A small animal expressing both human CCR5 along with 
human CD4 supports entry of HIV into target cells, a necessary hurdle 
that must be overcome for development of a small animal model (e.g. 
transgenic mouse, rat, rabbit, mink) to study HIV infection and its 
inhibition.
    The invention embodies the CCR5 genetic sequence, cell lines and 
transgenic mice, the cells of which coexpress human CD4 and CCR5, and 
which may represent valuable tools for the study of HIV infection and 
for screening anti-HIV agents. The invention also embodies anti-CCR5 
agents that block HIV env-mediated membrane fusion associated with HIV 
entry into human CD4-positive target cells or between HIV-infected 
cells and uninfected human CD4-positive target cells.
    This technology was reported in Alkhatib et al., ``CC CKR5: a 
RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for 
macrophage-tropic HIV-1,'' Science 272:1955-1958 (1996). The technology 
is available for exclusive or nonexclusive licensing.

    Dated: March 7, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-5082 Filed 3-14-05; 8:45 am]
BILLING CODE 4140-01-P