Government-Owned Inventions; Availability for Licensing, 12701-12703 [05-5082]
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Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices
The recent clinical introduction of
small molecule inhibitors that target
single molecules as effective anticancer
therapies underscores the potential of
patient specific therapeutic
interventions. However, the definition
of a cancer specific target need not be
a single transforming or survival-related
gene or gene product. Another targetable
and relatively irreversible cellular state
might be the complexity and instability
of the chromosomal complement of
cancer cells. Structural and numerical
chromosomal alterations are present in
most neoplasms and karyotypic
complexity is associated with a poor
clinical prognosis as well as aggressive
and distinctive histopathologic features.
The present invention describes
methods for the selecting candidate
compounds for evaluation for the
treatment of cancer by defining the
karyotypic complexity and
heterogeneity in human cancer cells
based on three components of genomic
anatomy: ploidy, numerical
chromosome changes, and structural
chromosome rearrangements. Measures
of complexity include the number of
chromosomal rearrangements present in
a cell line (structural complexity, SC )
and the number of chromosome
deviations from the ploidy level
(numerical complexity, NC). Measures
of cell-to-cell chromosomal variability,
which reflect the degree of ongoing
instability, include numerical
heterogeneity (NH) and structural
heterogeneity (SH). Utilizing the
methods claimed in the this application,
a number of chemical compounds were
identified and later determined to have
increased cytotoxicity toward cancer
cell lines with a specific karyotypic
complexity.
The positive correlations between
drug sensitivity and karyotypic
complexity and heterogeneity found in
this analysis (122 statistically significant
positive correlations) provide a distinct
opportunity to identify agents that are
more active against karyotypically
complex and chromosomally unstable
cancer cells. Such cells would typically
be found in the epithelial cancers,
which cause so much therapeutic
concern and frustration.
Inhibition of Human Papillomavirus
Type 16 and 18 E6 and E7 Oncogene
Expression by E6 and E7-Specific
siRNAs
Zhi-Ming Zheng (NCI).
DHHS Reference No. E–079–2005/0–
US–01.
Licensing Contact: Michelle A. Booden;
(301) 451–7337;
boodenm@mail.nih.gov.
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Cervical infection with human
papillomaviruses (HPVs), such as
HPV16 and HPV18, is strongly
associated with development of cervical
cancer. Integration of the viral genomes
into the cervical cell genome is
characteristic of infection with these
HPVs. Thus, the majority of cervical
cancer cells isolated from patients carry
these viral genomes and express two
viral oncoproteins, E6 and E7, which
induce p53 and pRb degradation.
Importantly, expression of both E6 and
E7 oncogenes is essential for survival of
cervical cancer cells.
Small interfering RNA (siRNA) is
emerging as a powerful tool for gene
silencing and has much potential for
anticancer and antiviral applications.
The present invention describes a
method employing novel siRNA
sequences for inhibiting expression of
the E6 and E7 viral oncoproteins of HPV
16 and 18, which are required for
development and progression of HPV
mediated cervical cancer.
Since HPV 16 and HPV 18 are the
most prevalent HPV types inducing
cervical cancer in women, this
discovery may have a significant impact
on cervical cancer therapy. This
technology could also have additional
implications in variety of HPVassociated indications, such as
anogenital warts, bladder, and head and
neck carcinomas.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Biomarkers for Osteoarthritis
Shari M. Ling et al. (NIA).
U.S. Provisional Application No. 60/
602,334 filed 18 Aug 2004 (DHHS
Reference No. E–354–2004/0–US–01).
Licensing Contact: Marlene Shinn-Astor;
(301) 435–4426;
shinnm@mail.nih.gov.
Osteoarthritis is chronic, often
progressive and substantially disabling
condition that becomes more common
with advanced age. Osteoarthritis
commonly involves the knees, hands,
hips, neck and back resulting in pain
and limitations of movement.
Unfortunately clinically available
tests are neither capable of detecting
osteoarthritis early in its development,
nor sensitive enough to adequately
assess disease progression. A better
means of diagnosing early osteoarthritis
and its progression that can be used to
assess the response to therapeutic
treatments is needed. The currently
available laboratory techniques are
highly sensitive but either lack
specificity or require large volumes of
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12701
sample. Rolling Circle Amplification
(RCA) is new technology that precisely
localizes unique signals arising from
single reporter molecules. RCA has been
incorporated into antibody-based
microarray system protein chips that
enable testing with high sensitivity and
specificity for hundreds of proteins
simultaneously, using small sample
volumes.
This invention describes a method of
using RCA technology for detecting the
expression of serum proteins that are
perturbed in osteoarthritis patients. The
results of this testing can be used to
identify proteins associated with
osteoarthritis presence, prediction of
osteoarthritis development and
prognosis, predict response to
osteoarthritis treatment and potentially
also identify future anti-osteoarthritic
drugs.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Water-Soluble, Antineoplastic
Derivatives of Taxol
Rudiger D. Haugwitz et al. (NCI).
U.S. Patent 4,942,184 issued 17 Jul 1990
(DHHS Reference No. E–090–1987/0–
US–01).
Licensing Contact: John Stansberry; 301/
435–5236; stansbej@mail.nih.gov.
A new class of taxol derivatives offer
an improved method for treating certain
cancers. The use of taxol as an
antineoplastic agent has been limited
due to poor solubility in aqueous
solutions. These new taxol derivatives
have improved water solubility while
retaining the cytotoxic properties of the
parent compounds. Their method of
synthesis and use in treating cancer
patients are provided.
Dated: March 7, 2005.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 05–5081 Filed 3–14–05; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, DHHS.
ACTION: Notice.
AGENCY:
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
E:\FR\FM\15MRN1.SGM
15MRN1
12702
Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices
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.
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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 sitespecific 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).
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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);
E:\FR\FM\15MRN1.SGM
15MRN1
Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices
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 Tlymphocytes, macrophages, and
immature dendritic cells. Chemokine
binding to CCR5 leads to cellular
activation through pertussis toxinsensitive heterotrimeric G proteins as
well as G protein-independent
signalling pathways. Like many other
GPCR, CCR5 is regulated by agonistdependent processes which involve G
protein coupled receptor kinase (GRK)dependent phosphorylation, betaarrestin-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
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12703
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.
93.398, Cancer Research Manpower; 93.399,
Cancer Control, National Institutes of Health,
HHS.)
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]
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Cancer Institute; Notice of
Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications
and/or contract proposals and the
discussions could disclose confidential
trade secrets or commercial property
such as patentable material, and
personal information concerning
individuals associated with the grant
applications and/or contract proposals,
the disclosure of which would
constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Cancer
Institute Special Emphasis Panel, Loan
Repayment Program: OD04–060 (Clinical) &
OD04–061 (Pediatric).
Date: April 4, 2005.
Time: 8 a.m. to 5 p.m.
Agenda: To review and evaluate grant
applications and/or proposals.
Place: National Institutes of Health, 6116
Executive Boulevard, Rockville, MD 20852.
Contact Person: Bratin K. Saha, PhD,
Program Coordination and Referral Branch,
Division of Extramural Activities, National
Cancer Institute, 6116 Executive Blvd.,
Bethesda, MD 20892, (301) 402–0371,
sashab@mail.nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.392, Cancer Construction;
93.393, Cancer Cause and Prevention
Research; 93.394, Cancer Detection and
Diagnosis Research; 93.395, Cancer
Treatment Research; 93.396, Cancer Biology
Research; 93.397, Cancer Centers Support;
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Dated: March 8, 2005.
LaVerne Y. Stringfield,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 05–5074 Filed 3–14–05; 8:45 am]
BILLING CODE 4140–01–M
National Institutes of Health
National Cancer Institute; Notice of
Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Cancer
Institute Initial Review Group, Subcommittee
D—Clinical Studies.
Date: April 6–8, 2005.
Time: 6 p.m. to 1 p.m.
Agenda: To review and evaluate grant
applications.
Place: Holiday Inn Select Bethesda, 8120
Wisconsin Ave., Bethesda, MD 20814.
Contact Person: William D. Merritt, PhD,
Scientific Review Administrator, Research
Programs Review Branch, National Cancer
Institute, Division of Extramural Activities,
6116 Executive Blvd., 8th Floor, Bethesda,
MD 20892–8328, 301–496–9767,
wm63f@nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.392, Cancer Construction;
93.393, Cancer Cause and Prevention
Research; 93.394, Cancer Detection and
Diagnosis Research; 93.395, Cancer
Treatment Research; 93.396, Cancer Biology
Research; 93.397, Cancer Centers Support;
93.398, Cancer Research Manpower; 93.399,
Cancer Control, National Institutes of Health,
HHS)
Dated: March 8, 2005.
LaVerne Y. Stringfield,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 05–5075 Filed 3–14–05; 8:45 am]
BILLING CODE 4140–01–M
E:\FR\FM\15MRN1.SGM
15MRN1
Agencies
[Federal Register Volume 70, Number 49 (Tuesday, March 15, 2005)]
[Notices]
[Pages 12701-12703]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-5082]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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]
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