Government-Owned Inventions; Availability for Licensing, 14589-14591 [E7-5670]
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Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices
further stipulates that in developing and
prioritizing the list, the NIH shall
consider for each drug on the list: (1)
The availability of information
concerning the safe and effective use of
the drug in the pediatric population; (2)
whether additional information is
needed; (3) whether new pediatric
studies concerning the drug may
produce health benefits in the pediatric
population; and (4) whether
reformulation of the drug is necessary.
For this year, we are providing an
update and a summary of the progress
made by the prioritization working
group from last year’s notice until now,
as well as a summary of the annual
scientific prioritization meeting held
with pediatric experts on December 5–
6, 2006.
We have updated the complete list of
drugs, listed previously in the April
2006 Federal Register notice, and post
it on the BPCA Web site https://
bpca.nichd.nih.gov/index.cfm. We will
continue to reevaluate this list
throughout the year and will provide
updates as required, based upon the
reauthorization of the BPCA.
In 2005, and with the suggestion of
pediatric experts, NIH changed the
listing system from a focus on
individual off-patent drugs to a
therapeutic class-based approach.
Pediatric experts indicated that this
approach will allow us to compare
drugs within a therapeutic class (on and
off patent) and give a broader
description of the use of these drugs in
children. This approach will also allow
us to obtain focused expertise in
therapeutic areas that will subsequently
give us more insight into scientific gaps
in treatments of the proposed
conditions, as well as feasibility and
study designs. Based on expert opinion
obtained throughout the year as part of
our regular outreach program, a
preliminary list of conditions and
suggested drugs was drafted and
categorized for the 2007 prioritization
based on this approach.
The following are the conditions and
the drugs discussed in our December 5–
6, 2006 scientific meeting with experts
in pediatric research: Infectious
Diseases, with a focus on Methicillinresistant Staphylococcus aureus (MRSA)
infections; Pediatric Cancer, specifically
Neuroblastoma; Neonatal Pain; and
Asthma. The gaps in scientific
knowledge as well as specific drugs
thought to be effective for treatment in
each of these conditions were then
discussed based on off-patent status,
gaps in pediatric labeling, and the
potential for providing a health benefit
in the general pediatric population. We
also provided updates on our current
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work in the areas of Pediatric
Hypertension, Sickle Cell Anemia, and
Attention Deficit Hyperactivity Disorder
during this meeting. There was also a
brief discussion on future areas of
consideration, pending the
reauthorization of the BPCA, that
include topics such as childhood
obesity, counter-terrorism research, and
Fragile X Syndrome.
Following below are the conditions
and drugs we discussed in the
December 5–6, 2006, scientific meeting
with experts in pediatric research. We
will add these conditions and drugs,
and their indications for use, to the
Priority List for 2007 for which pediatric
studies are most urgently needed.
Treatment of Pediatric Cancers: 13-CisRetinoic Acid
There is a need for information
regarding the pharmacokinetics, safety,
and efficacy of 13-Cis-Retinoic Acid in
the treatment of neuroblastoma.
Treatment of Pediatric MRSA:
Clindamycin, Tetracycline, Doxycycline
and Trimethoprim-Sulfamethoxazole
There is a need for further
pharmacokinetic and safety data in the
use of these drugs to treat children with
MRSA infections.
In addition to the above conditions
and their associated drugs for
consideration, the following are
conditions that have been identified as
needing improvements in the treatment
strategies and/or assessments in
pediatrics.
Pediatric Hypertension
Data from the medical literature,
clinical trials, and experience were
presented and discussed by experts in
the field of Pediatric Hypertension.
Gaps in knowledge in this field include
standardization of blood pressure
measurements in children as well as the
sequence of drugs for hypertension
treatment in children.
Asthma
14589
advances in neonatal research. Such
gaps in research include areas such as
determining feasibility of studying
specific drugs in low-birth-weight
infants based on current use; the
development of novel study designs that
take into account the small number of
patients available due to either ethical
limitations and/or feasibility issues; and
the performance of clinical studies in
areas such as the treatment of pain,
neonatal seizures, and
bronchopulmonary dysplasia, based on
templates that are being developed by
experts in research such as the working
groups of the Newborn Drug
Development Initiative.
For the coming year, NICHD is
planning a series of discussions with
experts in the fields listed above and
plans to identify and work with experts
in these respective fields along with our
continuing discussions with the other
NIH Institutes and Centers. The goal of
all of these discussions will be to
specifically identify current gaps in
scientific knowledge regarding research
and treatment of these various pediatric
conditions with the ultimate goal of
determining future approved drugs for
which pediatric studies are needed.
Dated: March 15, 2007.
Raynard S. Kington,
Deputy Director, National Institutes of Health.
[FR Doc. E7–5673 Filed 3–27–07; 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, HHS.
AGENCY:
ACTION:
Notice.
Data from the medical literature,
clinical trials, and experience were
presented and discussed by experts in
the field of Pediatric Asthma. Gaps in
knowledge in this field include gaps in
measuring efficacy and safety of
treatments and drug delivery systems,
especially in young children. There is
also a need for the development of new
tools to identify symptom measures,
pulmonary function tests, biomarkers,
and genetics.
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
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.
Neonatal Research
ADDRESSES:
There are many areas in the field of
neonatal medicine that can benefit from
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Licensing information and
copies of the U.S. patent applications
listed below may be obtained by writing
E:\FR\FM\28MRN1.SGM
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14590
Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices
sroberts on PROD1PC70 with NOTICES
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.
Microarray for Detection and Subtyping
of Human Influenza Viruses
Description of Technology: Available
for licensing and commercial
development are a novel influenza virus
microarray and methods for using the
microarray for the identification of
existing and new types and subtypes of
human influenza viruses. There are
three types of influenza viruses, type A,
B and C. Influenza types A or B viruses
cause epidemics of disease almost every
winter, with type A causes major
pandemic periodically. Influenza type A
viruses are further divided into subtypes
based on two proteins on the surface of
the virus. These proteins are called
hemagglutinin (H) and neuraminidase
(N). There are 16 known HA subtypes
and 9 known NA subtypes of influenza
A viruses. Each subtype may have
different combination of H and N
proteins. Although there are only three
known A subtypes of influenza viruses
(H1N1, H1N2, and H3N2) currently
circulating among humans, many other
different strains are circulating among
birds and other animals and these
viruses do spread to humans
occasionally. There is a requirement for
sensitive and rapid diagnostic
techniques in order to improve both the
diagnosis of infections and the quality
of surveillance systems. This microarray
platform tiles the genomes of all types/
subtypes of influenza viruses, and is
capable of correctly identifying all 3
types/subtypes of influenza viruses from
an influenza vaccine sample.
More specifically, the invention
consists of: (1) Microarrays comprising
a solid support with a plurality of n-mer
influenza viral nucleotide segments of
influenza Types A, B and C, including
each respective subtypes, and (2)
methods of detecting and identifying
known and unknown influenza viral
types and subtypes by: (a) Using
hybridization microarrays to known
influenza viral nucleotide sequences, (b)
sequencing the nucleotides which
hybridize to the microarrays and (c)
analyzing the hybridized sequences
using existing databases, thus
identifying existing or new subtypes of
influenza viruses.
Applications: Detection and
identification of human influenza
viruses; Efficient discovery of new
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subtypes of influenza viruses; Diagnosis
of influenza outbreaks.
Development Status: This microarray
platform was capable of correctly
identifying all 3 types/subtypes of
influenza viruses from an influenza
vaccine sample.
Inventors: Xiaolin Wu, Cassio S.
Baptista, Elizabeth Shannon, and David
J. Munroe (NCI).
Patent Status: U.S. Provisional
Application No. 60/857,695 filed 07
Nov 2006 (HHS Reference No. E–208–
2006/0–US–01).
Licensing Status: Available for nonexclusive or exclusive licensing.
Licensing Contact: Cristina
Thalhammer-Reyero, PhD, MBA; 301/
435–4507; thalhamc@mail.nih.gov.
Improved Interleukin Expression for
Immunogenic Compositions and
Vaccine Adjuvant
Description of Technology: The NIH is
pleased to announce as available for
licensing a technology that provides for
optimized nucleic acids for improved
expression of interleukin-15 (IL-15) and
IL-15 receptor alpha (IL-15Ralpha) in
mammalian cells. IL-15 is a cytokine
important for both the innate and
adaptive immune systems. Based on its
many functions and relative safety in
animal models, IL-15 finds use in
vaccines, cancer immunotherapeutics,
and autoimmune disease and as a
vaccine adjuvant.
The present technology enhances the
production and bioavailability of IL-15
through use of optimized nucleic acid
sequences. Native IL-15 coding
sequences do not express IL-15
optimally for several reasons, and the
optimized sequences of the subject
technology overcome these deficiencies.
The nucleic acids can be part of
expression vectors, which could be
utilized either in vitro or in vivo. The
expression vectors express IL-15 alone,
IL-15Ralpha alone, or both molecules
together from a single vector. Further
enhanced expression of IL-15 and/or IL15Ralpha can be achieved through the
use of signal peptides or propeptides
from heterologous proteins. These
nucleic acids can be administered to
enhance the immune response of an
individual against one or more antigens.
Primate studies have shown that coadministration of IL-15 and IL-15Ralpha
increased antigen specific cells, cells
expressing IL-2, and/or cells expressing
IL-2 and IFN-gamma (i.e.
multifunctional cells). The present
compositions are useful for the
increased bioavailability and therefore
biological effects of IL-15 after its
administration to humans or other
mammals.
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Applications: Vaccines; Improved
protein expression; Cancer
immunotherapeutics; Autoimmune
disease; Vaccine adjuvant.
Inventors: Barbara K. Felber and
George N. Pavlakis (NCI).
Related Publication: MA Kutzler et al.
Coimmunization with an optimized IL15 plasmid results in enhanced function
and longevity of CD8 T cells that are
partially independent of CD4 T cell
help. J Immunol. 2005 Jul 1;175(1):112–
123.
Patent Status: U.S. Provisional
Application No. 60/758,819 filed 13 Jan
2006 (HHS Reference No. E–254–2005/
0–US–01); U.S. Provisional Application
No. 60/812,566 filed 09 Jun 2006 (HHS
Reference No. E–254–2005/1–US–01);
PCT Application filed 13 Jan 2007 (HHS
Reference No. E–254–2005/2–PCT–01).
Licensing Status: Available for nonexclusive or exclusive licensing.
Licensing Contact: Susan Ano, PhD;
301/435–5515; anos@mail.nih.gov.
Potent Activation of Antigen Presenting
Cells by the Hepatitis A Virus Cellular
Receptor 1 and Its Role in the
Regulation of Immune Responses
Description of Technology: Available
for licensing and commercial
development are compositions and
methods to regulate various immune
responses through the hepatitis A virus
cellular receptor 1 (HAVCR1). HAVCR1
(also known as TIM-1) is a member of
the TIM family of receptors that is
usurped by the hepatitis A virus (HAV)
to infect cells. The gene encoding
HAVCR1 has been shown to be an
important asthma and allergy
susceptibility gene. HAVCR1 plays a
critical role in regulating T cell
differentiation and the development of
atopy. HAVCR1 is over-expressed in
kidney ischemic cells and malignant
renal tumors. The invention describes a
ligand of HAVCR1 in antigen presenting
cells (APCs) that is unrelated to murine
Tim-4, a TIM family member reported as
the ligand of murine Tim-1. The ligand
was identified using an expression
cloning strategy. The specific binding of
HAVCR1 to this ligand on APCs causes
activation and induces the expression of
co-stimulatory receptors at the cell
surface of the APCs and the secretion of
cytokines such as IL-6, IL-10, and TNFa. Furthermore, treatment of APCs with
soluble forms of HAVCR1 induced T
cell proliferation. The invention
describes a novel mechanism by which
HAVCR1 regulates immune responses,
in which the activation of APCs is
mediated by HAVCR1 binding to
ligands on APCs. The association of
HAVCR1 with the ligand identified in
E:\FR\FM\28MRN1.SGM
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Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices
sroberts on PROD1PC70 with NOTICES
APCs also enhances the interaction of
HAVCR1 with HAV.
Aspects of the technology are further
described in Tami et al., 2007. J. Virol.,
in press.
Applications: Therapies that target the
interaction of HAVCR1 with the ligand
on APCs, such as small molecules or
monoclonal antibodies, can control
immune responses, the development of
asthma, allergies and other atopic
diseases, hepatitis A, kidney
regeneration, and cancer.
Development Status: The technology
is in early stages of development.
Inventors: Gerardo Kaplan (CBER/
FDA), et al.
Patent Status: U.S. Provisional
Application No. 60/865,631 filed 13
Nov 2006 (HHS Reference No. E–035–
2005/0–US–01).
Licensing Status: Available for nonexclusive or exclusive licensing.
Licensing Contact: Cristina
Thalhammer-Reyero, PhD, M.B.A.; 301/
435–4507; thalhamc@mail.nih.gov.
Collaborative Research Opportunity:
The Food and Drug Administration,
Center of Biologics Research and
Evaluation, Laboratory of Hepatitis and
Related Emerging Agents, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize the hepatitis A virus
cellular receptor as a potent activator of
antigen presenting cells. Please contact
Beatrice Droke, 301/872–7008 or
beatrice.droke@fda.hhs.gov, for more
information.
Cyanovirins and Related Conjugates,
Compositions, Nucleic Acids, Vectors,
Host Cells, Methods of Production and
Methods of Use for Microbicide
Development
Description of Technology: The
development of an effective anti-HIV
topical microbicide, especially a femalecontrolled, vaginal microbicide, has
been deemed an urgent global priority
by numerous international agencies,
including the World Health
Organization, the U.S. Department of
Health and Human Services, the
National Institute of Allergy and
Infectious Diseases, and others. The
present invention provides antiviral
proteins (collectively referred to as
cyanovirins), conjugates thereof, DNA
sequences encoding such agents, host
cells containing such DNA sequences,
antibodies directed to such agents,
compositions comprising such agents,
and methods of obtaining and using
such agents for the production of
microbicides.
Cyanovirin-N (CV-N) potently and
irreversibly inactivates diverse primary
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strains of HIV-1, including M-tropic
forms involved in sexual transmission
of HIV, as well as T-tropic and dualtropic forms; CV-N also blocks cell-tocell transmission of HIV infection. CVN is directly virucidal, interacting in an
unusual manner with the viral
envelope, apparently binding with
extremely high affinity to poorly
immunogenic epitopes on gp120.
Further, cyanovirin-N (CV-N) and
homologous proteins and peptides
potently inhibit diverse isolates of
influenza viruses A and B, the two
major types of influenza virus that infect
humans.
The described technology includes
glycosylation-resistant mutants of CV-N,
which code sequences to enable ultra
large-scale recombinant production of
functional cyanovirins in non-bacterial
(yeast or insect) host cells or in
transgenic animals or plants. Therefore,
these glycosylation-resistant mutants
may allow industry to produce CV-Ns
on a large scale and make CV-Ns cheap
enough for developing countries to
benefit from this invention.
CV-N was benign in vivo when tested
in the rabbit vaginal toxicity/irritancy
model, and was not cytotoxic in vitro
against human immune cells and
lactobacilli (unpublished). CV-N is
readily soluble in aqueous media, is
remarkably resistant to physicochemical
degradation and is amenable to very
large-scale production by a variety of
genetic engineering approaches.
Applications: Development of
microbicides against HIV and influenza.
Development Status: Preclinical data
is available at this time.
Inventors: Michael Boyd (NCI), Robert
Shoemaker (NCI), Barry O’Keefe (NCI),
Toshiyuki Mori (NCI), Angela
Gronenborn (NIDDK).
Related Publications:
1. B Giomarelli, R Provvedi, F Meacci,
T Maggi, D Medaglini, G Pozzi, T Mori,
JB McMahon, R Gardella, MR Boyd. The
microbicide cyanovirin-N expressed on
the surface of commensal bacterium
Streptococcus gordonii captures HIV-1.
AIDS. 2002 Jul 5;16(10):1351–1356.
2. CC Tsai, P Emau, Y Jiang, MB Agy,
RJ Shattock, A Schmidt, WR Morton, KR
Gustafson, MR Boyd. Cyanovirin-N
inhibits AIDS virus infections in vaginal
transmission models. AIDS Res Hum
Retroviruses. 2004 Jan;20(1):11–18.
Patent Status:
1. Patent Cooperation Treaty Serial
No. PCT/US00/06247 filed 10 Mar 2000;
National Stage Filing in United States,
Japan, Australia, Europe, Germany,
France, China, United Kingdom, and
Belgium (HHS Reference No. E–074–
1999/2).
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14591
2. Patent Cooperation Treaty Serial
No. PCT/US99/18975 filed 19 Aug 1999;
National Stage Filing in United States,
Japan, Australia, Europe, Germany,
France, China, United Kingdom, and
Belgium (HHS Reference No. E–117–
1995/3).
Licensing Status: Available for
licensing and commercial development.
Licensing Contact: Sally Hu, PhD;
301/435–5606; HuS@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute’s
Molecular Targets Development
Program is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize microbicides for HIV and
influenza. Please contact John D. Hewes
at (301) 435–3121 or hewesj@mail.
nih.gov for more information.
Dated: March 16, 2007.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E7–5670 Filed 3–27–07; 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, HHS.
AGENCY:
ACTION:
Notice.
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
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.
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.
ADDRESSES:
E:\FR\FM\28MRN1.SGM
28MRN1
]]>Agencies
[Federal Register Volume 72, Number 59 (Wednesday, March 28, 2007)]
[Notices]
[Pages 14589-14591]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-5670]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The inventions listed below are owned by an agency of the U.S.
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
[[Page 14590]]
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.
Microarray for Detection and Subtyping of Human Influenza Viruses
Description of Technology: Available for licensing and commercial
development are a novel influenza virus microarray and methods for
using the microarray for the identification of existing and new types
and subtypes of human influenza viruses. There are three types of
influenza viruses, type A, B and C. Influenza types A or B viruses
cause epidemics of disease almost every winter, with type A causes
major pandemic periodically. Influenza type A viruses are further
divided into subtypes based on two proteins on the surface of the
virus. These proteins are called hemagglutinin (H) and neuraminidase
(N). There are 16 known HA subtypes and 9 known NA subtypes of
influenza A viruses. Each subtype may have different combination of H
and N proteins. Although there are only three known A subtypes of
influenza viruses (H1N1, H1N2, and H3N2) currently circulating among
humans, many other different strains are circulating among birds and
other animals and these viruses do spread to humans occasionally. There
is a requirement for sensitive and rapid diagnostic techniques in order
to improve both the diagnosis of infections and the quality of
surveillance systems. This microarray platform tiles the genomes of all
types/subtypes of influenza viruses, and is capable of correctly
identifying all 3 types/subtypes of influenza viruses from an influenza
vaccine sample.
More specifically, the invention consists of: (1) Microarrays
comprising a solid support with a plurality of n-mer influenza viral
nucleotide segments of influenza Types A, B and C, including each
respective subtypes, and (2) methods of detecting and identifying known
and unknown influenza viral types and subtypes by: (a) Using
hybridization microarrays to known influenza viral nucleotide
sequences, (b) sequencing the nucleotides which hybridize to the
microarrays and (c) analyzing the hybridized sequences using existing
databases, thus identifying existing or new subtypes of influenza
viruses.
Applications: Detection and identification of human influenza
viruses; Efficient discovery of new subtypes of influenza viruses;
Diagnosis of influenza outbreaks.
Development Status: This microarray platform was capable of
correctly identifying all 3 types/subtypes of influenza viruses from an
influenza vaccine sample.
Inventors: Xiaolin Wu, Cassio S. Baptista, Elizabeth Shannon, and
David J. Munroe (NCI).
Patent Status: U.S. Provisional Application No. 60/857,695 filed 07
Nov 2006 (HHS Reference No. E-208-2006/0-US-01).
Licensing Status: Available for non-exclusive or exclusive
licensing.
Licensing Contact: Cristina Thalhammer-Reyero, PhD, MBA; 301/435-
4507; thalhamc@mail.nih.gov.
Improved Interleukin Expression for Immunogenic Compositions and
Vaccine Adjuvant
Description of Technology: The NIH is pleased to announce as
available for licensing a technology that provides for optimized
nucleic acids for improved expression of interleukin-15 (IL-15) and IL-
15 receptor alpha (IL-15Ralpha) in mammalian cells. IL-15 is a cytokine
important for both the innate and adaptive immune systems. Based on its
many functions and relative safety in animal models, IL-15 finds use in
vaccines, cancer immunotherapeutics, and autoimmune disease and as a
vaccine adjuvant.
The present technology enhances the production and bioavailability
of IL-15 through use of optimized nucleic acid sequences. Native IL-15
coding sequences do not express IL-15 optimally for several reasons,
and the optimized sequences of the subject technology overcome these
deficiencies. The nucleic acids can be part of expression vectors,
which could be utilized either in vitro or in vivo. The expression
vectors express IL-15 alone, IL-15Ralpha alone, or both molecules
together from a single vector. Further enhanced expression of IL-15
and/or IL-15Ralpha can be achieved through the use of signal peptides
or propeptides from heterologous proteins. These nucleic acids can be
administered to enhance the immune response of an individual against
one or more antigens. Primate studies have shown that co-administration
of IL-15 and IL-15Ralpha increased antigen specific cells, cells
expressing IL-2, and/or cells expressing IL-2 and IFN-gamma (i.e.
multifunctional cells). The present compositions are useful for the
increased bioavailability and therefore biological effects of IL-15
after its administration to humans or other mammals.
Applications: Vaccines; Improved protein expression; Cancer
immunotherapeutics; Autoimmune disease; Vaccine adjuvant.
Inventors: Barbara K. Felber and George N. Pavlakis (NCI).
Related Publication: MA Kutzler et al. Coimmunization with an
optimized IL-15 plasmid results in enhanced function and longevity of
CD8 T cells that are partially independent of CD4 T cell help. J
Immunol. 2005 Jul 1;175(1):112-123.
Patent Status: U.S. Provisional Application No. 60/758,819 filed 13
Jan 2006 (HHS Reference No. E-254-2005/0-US-01); U.S. Provisional
Application No. 60/812,566 filed 09 Jun 2006 (HHS Reference No. E-254-
2005/1-US-01); PCT Application filed 13 Jan 2007 (HHS Reference No. E-
254-2005/2-PCT-01).
Licensing Status: Available for non-exclusive or exclusive
licensing.
Licensing Contact: Susan Ano, PhD; 301/435-5515; anos@mail.nih.gov.
Potent Activation of Antigen Presenting Cells by the Hepatitis A Virus
Cellular Receptor 1 and Its Role in the Regulation of Immune Responses
Description of Technology: Available for licensing and commercial
development are compositions and methods to regulate various immune
responses through the hepatitis A virus cellular receptor 1 (HAVCR1).
HAVCR1 (also known as TIM-1) is a member of the TIM family of receptors
that is usurped by the hepatitis A virus (HAV) to infect cells. The
gene encoding HAVCR1 has been shown to be an important asthma and
allergy susceptibility gene. HAVCR1 plays a critical role in regulating
T cell differentiation and the development of atopy. HAVCR1 is over-
expressed in kidney ischemic cells and malignant renal tumors. The
invention describes a ligand of HAVCR1 in antigen presenting cells
(APCs) that is unrelated to murine Tim-4, a TIM family member reported
as the ligand of murine Tim-1. The ligand was identified using an
expression cloning strategy. The specific binding of HAVCR1 to this
ligand on APCs causes activation and induces the expression of co-
stimulatory receptors at the cell surface of the APCs and the secretion
of cytokines such as IL-6, IL-10, and TNF-a. Furthermore, treatment of
APCs with soluble forms of HAVCR1 induced T cell proliferation. The
invention describes a novel mechanism by which HAVCR1 regulates immune
responses, in which the activation of APCs is mediated by HAVCR1
binding to ligands on APCs. The association of HAVCR1 with the ligand
identified in
[[Page 14591]]
APCs also enhances the interaction of HAVCR1 with HAV.
Aspects of the technology are further described in Tami et al.,
2007. J. Virol., in press.
Applications: Therapies that target the interaction of HAVCR1 with
the ligand on APCs, such as small molecules or monoclonal antibodies,
can control immune responses, the development of asthma, allergies and
other atopic diseases, hepatitis A, kidney regeneration, and cancer.
Development Status: The technology is in early stages of
development.
Inventors: Gerardo Kaplan (CBER/FDA), et al.
Patent Status: U.S. Provisional Application No. 60/865,631 filed 13
Nov 2006 (HHS Reference No. E-035-2005/0-US-01).
Licensing Status: Available for non-exclusive or exclusive
licensing.
Licensing Contact: Cristina Thalhammer-Reyero, PhD, M.B.A.; 301/
435-4507; thalhamc@mail.nih.gov.
Collaborative Research Opportunity: The Food and Drug
Administration, Center of Biologics Research and Evaluation, Laboratory
of Hepatitis and Related Emerging Agents, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize the hepatitis A
virus cellular receptor as a potent activator of antigen presenting
cells. Please contact Beatrice Droke, 301/872-7008 or
beatrice.droke@fda.hhs.gov, for more information.
Cyanovirins and Related Conjugates, Compositions, Nucleic Acids,
Vectors, Host Cells, Methods of Production and Methods of Use for
Microbicide Development
Description of Technology: The development of an effective anti-HIV
topical microbicide, especially a female-controlled, vaginal
microbicide, has been deemed an urgent global priority by numerous
international agencies, including the World Health Organization, the
U.S. Department of Health and Human Services, the National Institute of
Allergy and Infectious Diseases, and others. The present invention
provides antiviral proteins (collectively referred to as cyanovirins),
conjugates thereof, DNA sequences encoding such agents, host cells
containing such DNA sequences, antibodies directed to such agents,
compositions comprising such agents, and methods of obtaining and using
such agents for the production of microbicides.
Cyanovirin-N (CV-N) potently and irreversibly inactivates diverse
primary strains of HIV-1, including M-tropic forms involved in sexual
transmission of HIV, as well as T-tropic and dual-tropic forms; CV-N
also blocks cell-to-cell transmission of HIV infection. CV-N is
directly virucidal, interacting in an unusual manner with the viral
envelope, apparently binding with extremely high affinity to poorly
immunogenic epitopes on gp120. Further, cyanovirin-N (CV-N) and
homologous proteins and peptides potently inhibit diverse isolates of
influenza viruses A and B, the two major types of influenza virus that
infect humans.
The described technology includes glycosylation-resistant mutants
of CV-N, which code sequences to enable ultra large-scale recombinant
production of functional cyanovirins in non-bacterial (yeast or insect)
host cells or in transgenic animals or plants. Therefore, these
glycosylation-resistant mutants may allow industry to produce CV-Ns on
a large scale and make CV-Ns cheap enough for developing countries to
benefit from this invention.
CV-N was benign in vivo when tested in the rabbit vaginal toxicity/
irritancy model, and was not cytotoxic in vitro against human immune
cells and lactobacilli (unpublished). CV-N is readily soluble in
aqueous media, is remarkably resistant to physicochemical degradation
and is amenable to very large-scale production by a variety of genetic
engineering approaches.
Applications: Development of microbicides against HIV and
influenza.
Development Status: Preclinical data is available at this time.
Inventors: Michael Boyd (NCI), Robert Shoemaker (NCI), Barry
O'Keefe (NCI), Toshiyuki Mori (NCI), Angela Gronenborn (NIDDK).
Related Publications:
1. B Giomarelli, R Provvedi, F Meacci, T Maggi, D Medaglini, G
Pozzi, T Mori, JB McMahon, R Gardella, MR Boyd. The microbicide
cyanovirin-N expressed on the surface of commensal bacterium
Streptococcus gordonii captures HIV-1. AIDS. 2002 Jul 5;16(10):1351-
1356.
2. CC Tsai, P Emau, Y Jiang, MB Agy, RJ Shattock, A Schmidt, WR
Morton, KR Gustafson, MR Boyd. Cyanovirin-N inhibits AIDS virus
infections in vaginal transmission models. AIDS Res Hum Retroviruses.
2004 Jan;20(1):11-18.
Patent Status:
1. Patent Cooperation Treaty Serial No. PCT/US00/06247 filed 10 Mar
2000; National Stage Filing in United States, Japan, Australia, Europe,
Germany, France, China, United Kingdom, and Belgium (HHS Reference No.
E-074-1999/2).
2. Patent Cooperation Treaty Serial No. PCT/US99/18975 filed 19 Aug
1999; National Stage Filing in United States, Japan, Australia, Europe,
Germany, France, China, United Kingdom, and Belgium (HHS Reference No.
E-117-1995/3).
Licensing Status: Available for licensing and commercial
development.
Licensing Contact: Sally Hu, PhD; 301/435-5606; HuS@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute's
Molecular Targets Development Program is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize microbicides
for HIV and influenza. Please contact John D. Hewes at (301) 435-3121
or hewesj@mail.nih.gov for more information.
Dated: March 16, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-5670 Filed 3-27-07; 8:45 am]
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