[Federal Register: March 15, 2005 (Volume 70, Number 49)]
[Notices]
[Page 12701-12703]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15mr05-103]
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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.
[[Page 12702]]
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;
shmilovm@mail.nih.gov.
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;
thalhamc@mail.nih.gov.
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;
joynesr@mail.nih.gov.
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);
[[Page 12703]]
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; soukasp@mail.nih.gov.
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