Government-Owned Inventions; Availability for Licensing, 14591-14593 [E7-5675]
Download as PDF
<![CDATA[
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
VerDate Aug<31>2005
17:09 Mar 27, 2007
Jkt 211001
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).
PO 00000
Frm 00077
Fmt 4703
Sfmt 4703
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
sroberts on PROD1PC70 with NOTICES
14592
Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices
Enhanced Function of Gene Modified TCells: Identification of T-Cell Receptors
(TCR) with Altered Amino Acid
Sequence
Description of Technology: A major
limitation of the current chemotherapybased therapeutics is the cytotoxic sideeffects associated with them. Thus there
is a dire need to develop new
therapeutic strategies with fewer sideeffects. Immunotherapy has taken a lead
among the new cancer therapeutic
approaches. Adoptive immunotherapy
is one of the most promising new
therapeutic approaches that enhance the
innate immunity of an individual to
fight against a certain disease.
T cell receptors (TCR) are the proteins
responsible for the T cell’s ability to
recognize infected or transformed cells.
TCR consists of two domains, one
variable domain that recognizes the
antigen and one constant region that
helps the TCR anchor to the membrane
and transmit the recognition signal by
interacting with other proteins.
This invention is directed to
substitutions in gene sequences that
code for T cell receptors, specifically the
inventors found that one to two amino
acid substitutions in the TCRs that
recognize 1G4 XY-ESO-1 and MART-1
resulted in a marked increase of these
modified TCRs to recognize tumor cell
targets. These mutated sequences are
currently being evaluated as candidates
for clinical development. The inventors
also consider the invention as providing
a ‘‘general paradigm’’ that will allow the
generation of TCR directed against a
variety of antigens that can enhance the
function of gene modified T cells.
Applications:
1. Improved ability of modified TCRs
to recognize tumor cell targets.
2. High affinity TR can be generated
that recognizes a variety of antigens that
can be potentially used for the diagnosis
and treatment of patients with a variety
of conditions that include cancer,
infectious diseases and autoimmunity.
3. Mutant high affinity TR can also be
used to transduce T cells in order to
generate cells reactive with tumor
antigens as well as viral antigens.
Development Status: Pre-clinical work
has been completed and clinical work is
undergoing.
Inventors: Paul F. Robbins (NCI),
Steven A. Rosenberg (NCI), Richard A.
Morgan (NCI), et al.
Relevant Publication: A manuscript
relating to this invention is under
preparation and will be available once
accepted.
Patent Status: U.S. Provisional
Application No. 60/847,447 filed 26 Sep
2006 (HHS Reference No. E–304–2006/
0–US–01).
VerDate Aug<31>2005
17:09 Mar 27, 2007
Jkt 211001
Licensing Status: This technology is
available for licensing under an
exclusive or non-exclusive patent
license.
Licensing Contact: Michelle Booden,
PhD; 301/451–7337;
boodenm@mail.nih.gov.
Collaborative Research Opportunity:
The NIH Surgery Branch is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize adoptive
immunotherapy. Please contact John D.
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Novel Benzindole Based Compounds
for HIV Therapy
Description of Technology: The HIV/
AIDS epidemic continues despite efforts
from scientists, drug companies, and
non-profit organizations. Although the
existing therapy, is effective in the
treatment of many infected individuals
in developed nations, the infected
individual is not cured and therapy
must be life-long. There are problems
with drug toxicity, the development of
resistant viral strains, and with the cost
of therapy. New anti-viral agents are
needed for a more effective, and a more
cost-effective, treatment of HIV.
The invention describes compounds
based on a benzindole moiety, which
alkylates DNA. The compounds
comprise a benzindole moiety, a
bifunctional linker, and a fatty acid
residue or dendrimer residue
comprising at least one fatty acid.
Several benzindole derivatives are
synthesized. The compounds bind to
the minor groove of DNA and can be
useful in the inhibition of gene
expression. The advantage of the
compounds is that they remain inactive
until conformational change induced by
DNA binding makes them active. The
fatty acid moiety immobilizes them on
the cytoplasmic side of the plasma
membrane. These anchored compounds
are specifically designed to inhibit
retroviral DNA before it translocates to
the host nucleus and integrates with the
host genome.
Applications and Modality:
1. Novel benzindole-based
compounds for HIV therapy.
2. Compounds are specifically
designed to inhibit retroviral DNA
before it can integrate with the host
genome.
3. Additionally, compounds might
have potential anti-cancer activities.
Market:
1. More than 45 million people are
living with HIV/AIDS worldwide.
PO 00000
Frm 00078
Fmt 4703
Sfmt 4703
2. More than 3 million estimated
deaths due to HIV/AIDS occurred
worldwide in 2003.
3. HIV/AIDS epidemic has caused
more than 30 million deaths.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Christopher J. Michejda
(NCI), Stephen H. Hughes (NCI), et al.
Relevant Publication: A manuscript
directly related to the above technology
will be available as soon as it is
accepted for publication.
Patent Status: U.S. Provisional
Application No. 60/850,437 filed 10 Oct
2006 (HHS Reference No. E–126–2006/
0–US–01).
Licensing Availability: Available for
exclusive and non-exclusive licensing.
Licensing Contact: Adaku
Nwachukwu, J.D.; 301/435–5560;
madua@mail.nih.gov
Collaborative Research Opportunity:
The National Cancer Institute’s
Structural Biophysics Laboratory is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
novel benzindole based compounds for
HIV therapy. Please contact John D.
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Cloning and Characterization of an
Avian Adeno-Associated Virus and
Uses Thereof
Description of Technology: Currently,
adeno-associated virus (AAV) represents
the gene therapy vehicle of choice
because it has many advantages over
current strategies for therapeutic gene
insertion. AAV is less pathogenic than
other virus types; stably integrates into
dividing and non-dividing cells;
integrates at a consistent site in the host
genome; and shows good specificity
towards various cell types for targeted
gene delivery.
To date, 11 AAV isolates have been
isolated and characterized. New
serotypes derived from non-human
animal species have added to the
specificity and repertoire of current
AAV gene therapy techniques by
avoiding the immunologic
complications associated with human
isolates.
This invention describes vectors
derived from an avian AAV. These
vectors have innate properties related to
their origin that may confer them with
a unique cellular specificity in targeted
human gene therapy and a unique
immunologic profile that would avoid
neutralization by pre-existing
antibodies. Therefore, vectors derived
E:\FR\FM\28MRN1.SGM
28MRN1
Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices
from this avian AAV are likely to find
novel applications for gene therapy in
humans. Furthermore because of their
species of origin, this vector would also
be useful in the engineering of avian
cells.
Inventors: Ioannis Bossis and John A.
Chiorini (NIDCR).
Publication: I Bossis, JA Chiorini.
Cloning of an avian adeno-associated
virus (AAAV) and generation of
recombinant AAAV particles. J Virol.
2003 Jun;77(12):6799–6810.
Patent Status: U.S. Patent Application
No. 10/557,662 filed 21 Dec 2006 (HHS
Reference No. E–105–2003/0–US–03).
Licensing Status: Available for nonexclusive or exclusive licensing.
Licensing Contact: Jesse S. Kindra,
J.D.; 301/435–5559;
kindraj@mail.nih.gov
Collaborative Research Opportunity:
The National Institute of Dental and
Craniofacial Research, Laboratory of Dr.
John Chiorini, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize gene therapy methods
using AAV vectors. Please contact David
W. Bradley, PhD at
bradleyda@nidcr.nih.gov for more
information.
sroberts on PROD1PC70 with NOTICES
Serotonin-Deficient Knock-Out Mouse
Description of Technology: Serotonin
is an important modulator of many
developmental, behavioral, and
physiological processes, and it has been
implicated in depression, anxiety,
schizophrenia, obsessive compulsive
disorders, and substance abuse.
Serotonin’s pharmacology is extremely
complex and it is mediated by seven of
serotonin receptor subtypes and it is
present in several tissues. Although it
has been a subject of a number of
studies, its role has been difficult to
ascertain. To investigate the role of
serotonin in these disorders, the murine
gene was disrupted by homologous
recombination. Results indicate that
serotonin binding sites were absent in
different brain regions (brain stem,
frontal cortex, hippocampus, and
striatum), and its concentrations were
reduced by 60–80%. These mice
represent a powerful tool for the
investigation of behavioral and
neuropsychiatric disorders, and
development of drug treatments for
these disorders.
Applications: A model to study
serotonin’s role in behavioral and
neuropsychiatric disorders.
Market:
1. Serotonin inhibitors are most
widely used treatment in
VerDate Aug<31>2005
17:09 Mar 27, 2007
Jkt 211001
neuropsychological disorders. Examples
include Zoloft, Paxil, and Prozac.
2. Depression effects approximately
18.8 million U.S. citizens and over 121
million people worldwide.
3. Antidepressant market was worth
$16.2 billion in 2005, and it has annual
growth of 2% year on year.
4. Anxiety disorders affect 40 million
(18.1%) of the adult U.S. population.
5. Global anxiety disorder market was
$4.5 billion in 2006.
Inventors: Dennis L. Murphy (NIMH)
et al.
Publications:
1. RF Ren-Patterson, LW Cochran, A
Holmes, S Sherrill, SJ Huang, T Tolliver,
K-P Lesch. Loss of brain-derived
neurotrophic factor gene allele
exacerbates brain monoamine
deficiencies and increases stress
abnormalities of serotonin transporter
knockout mice. J Neurosci Res. 2005
Mar 15:79(6):756–771.
2. DL Murphy, A Lerner, G Rudnick,
K-P Lesch. Serotonin transporter: gene,
genetic disorders, and
pharmacogenetics. Mol Interv. 2004
April:4(2):109–123.
3. RF Ren-Patterson, D-K Kim, X
Zheng, S Sherrill, S-J Huang, T Tolliver,
DL Murphy. Serotonergic-like
progenitor cells propagated from neural
stem cells in vitro: survival with SERT
protein expression following
implantation into brains of mice lacking
SERT. FASEB J. 2005 Sep:19(11):1537–
1539.
4. Q Li, A Holmes, L Ma, LD Van de
Kar, F Garcia, DL Murphy. Medical
hypothalamic 5-hydroxytryptamine
(5HT)1A receptors regulate
neuroendocrine responses to stress and
exploratory locomotor activity
application of recombinant adenovirus
containing 5-HT1A sequences. J
Neurosci. 2004 Dec 1:24(48):10868–
10877.
5. F Kilic, DL Murphy, G Rudnick. A
human serotonin transporter mutation
causes constitutive activation of
transport activity. Mol Pharmacol. 2003
Aug:64(2):440–446.
6. DL Murphy, GR Uhl, A Holmes, R
Ren-Patterson, FS Hall, I Sora, S DeteraWadleigh, K-P Lesch. Experimental gene
interaction studies with SERT mutant
mice as models for human polygenic
and epistatic traits and disorders. Genes
Brain Behav. 2003 Dec:2(6):350–364.
7. N Ozaki, D Goldman, WH Kaye, K
Plotnicov, BD Greenberg, J Lappalainen,
G Rudnick, DL Murphy. Serotonin
transporter missense mutation
associated with a complex
neuropsychiatric phenotype. Mol
Psychiatry. 2003 Nov:8(11):933–936.
Patent Status: HHS Reference No.
B–019–1999/0—Research Tool.
PO 00000
Frm 00079
Fmt 4703
Sfmt 4703
14593
Licensing Status: This technology is
available as a research tool under a
Biological Materials License.
Licensing Contact: Jennifer Wong;
301/435–4633; wongje@mail.nih.gov.
Dated: March 15, 2007.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E7–5675 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.
ACTION: Notice.
AGENCY:
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
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.
Microdialysis Probe for Accessing
Tissue in-vivo
Description of Technology: Available
for licensing and commercial
development is a microdialysis probe.
This device permits in-vivo
measurement of bioavailable substances
(e.g., cytokines, growth factors,
neuropeptides, inflammatory mediators,
etc.) at picogram levels of concentration
directly from soft tissue and organ
systems. The probe may also serve as an
in-situ drug delivery vehicle of micro
doses of medication to specific
anatomical sites by slow diffusion. It
also permits measurement of efficacy of
drug delivery, whether given orally,
systemically or topically, at the local
E:\FR\FM\28MRN1.SGM
28MRN1
]]>Agencies
[Federal Register Volume 72, Number 59 (Wednesday, March 28, 2007)]
[Notices]
[Pages 14591-14593]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-5675]
-----------------------------------------------------------------------
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 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.
[[Page 14592]]
Enhanced Function of Gene Modified T-Cells: Identification of T-Cell
Receptors (TCR) with Altered Amino Acid Sequence
Description of Technology: A major limitation of the current
chemotherapy-based therapeutics is the cytotoxic side-effects
associated with them. Thus there is a dire need to develop new
therapeutic strategies with fewer side-effects. Immunotherapy has taken
a lead among the new cancer therapeutic approaches. Adoptive
immunotherapy is one of the most promising new therapeutic approaches
that enhance the innate immunity of an individual to fight against a
certain disease.
T cell receptors (TCR) are the proteins responsible for the T
cell's ability to recognize infected or transformed cells. TCR consists
of two domains, one variable domain that recognizes the antigen and one
constant region that helps the TCR anchor to the membrane and transmit
the recognition signal by interacting with other proteins.
This invention is directed to substitutions in gene sequences that
code for T cell receptors, specifically the inventors found that one to
two amino acid substitutions in the TCRs that recognize 1G4 XY-ESO-1
and MART-1 resulted in a marked increase of these modified TCRs to
recognize tumor cell targets. These mutated sequences are currently
being evaluated as candidates for clinical development. The inventors
also consider the invention as providing a ``general paradigm'' that
will allow the generation of TCR directed against a variety of antigens
that can enhance the function of gene modified T cells.
Applications:
1. Improved ability of modified TCRs to recognize tumor cell
targets.
2. High affinity TR can be generated that recognizes a variety of
antigens that can be potentially used for the diagnosis and treatment
of patients with a variety of conditions that include cancer,
infectious diseases and autoimmunity.
3. Mutant high affinity TR can also be used to transduce T cells in
order to generate cells reactive with tumor antigens as well as viral
antigens.
Development Status: Pre-clinical work has been completed and
clinical work is undergoing.
Inventors: Paul F. Robbins (NCI), Steven A. Rosenberg (NCI),
Richard A. Morgan (NCI), et al.
Relevant Publication: A manuscript relating to this invention is
under preparation and will be available once accepted.
Patent Status: U.S. Provisional Application No. 60/847,447 filed 26
Sep 2006 (HHS Reference No. E-304-2006/0-US-01).
Licensing Status: This technology is available for licensing under
an exclusive or non-exclusive patent license.
Licensing Contact: Michelle Booden, PhD; 301/451-7337;
boodenm@mail.nih.gov.
Collaborative Research Opportunity: The NIH Surgery Branch is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
adoptive immunotherapy. Please contact John D. Hewes, PhD at 301-435-
3121 or hewesj@mail.nih.gov for more information.
Novel Benzindole Based Compounds for HIV Therapy
Description of Technology: The HIV/AIDS epidemic continues despite
efforts from scientists, drug companies, and non-profit organizations.
Although the existing therapy, is effective in the treatment of many
infected individuals in developed nations, the infected individual is
not cured and therapy must be life-long. There are problems with drug
toxicity, the development of resistant viral strains, and with the cost
of therapy. New anti-viral agents are needed for a more effective, and
a more cost-effective, treatment of HIV.
The invention describes compounds based on a benzindole moiety,
which alkylates DNA. The compounds comprise a benzindole moiety, a
bifunctional linker, and a fatty acid residue or dendrimer residue
comprising at least one fatty acid. Several benzindole derivatives are
synthesized. The compounds bind to the minor groove of DNA and can be
useful in the inhibition of gene expression. The advantage of the
compounds is that they remain inactive until conformational change
induced by DNA binding makes them active. The fatty acid moiety
immobilizes them on the cytoplasmic side of the plasma membrane. These
anchored compounds are specifically designed to inhibit retroviral DNA
before it translocates to the host nucleus and integrates with the host
genome.
Applications and Modality:
1. Novel benzindole-based compounds for HIV therapy.
2. Compounds are specifically designed to inhibit retroviral DNA
before it can integrate with the host genome.
3. Additionally, compounds might have potential anti-cancer
activities.
Market:
1. More than 45 million people are living with HIV/AIDS worldwide.
2. More than 3 million estimated deaths due to HIV/AIDS occurred
worldwide in 2003.
3. HIV/AIDS epidemic has caused more than 30 million deaths.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Christopher J. Michejda (NCI), Stephen H. Hughes (NCI),
et al.
Relevant Publication: A manuscript directly related to the above
technology will be available as soon as it is accepted for publication.
Patent Status: U.S. Provisional Application No. 60/850,437 filed 10
Oct 2006 (HHS Reference No. E-126-2006/0-US-01).
Licensing Availability: Available for exclusive and non-exclusive
licensing.
Licensing Contact: Adaku Nwachukwu, J.D.; 301/435-5560;
madua@mail.nih.gov
Collaborative Research Opportunity: The National Cancer Institute's
Structural Biophysics Laboratory is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize novel benzindole based compounds
for HIV therapy. Please contact John D. Hewes, PhD at 301-435-3121 or
hewesj@mail.nih.gov for more information.
Cloning and Characterization of an Avian Adeno-Associated Virus and
Uses Thereof
Description of Technology: Currently, adeno-associated virus (AAV)
represents the gene therapy vehicle of choice because it has many
advantages over current strategies for therapeutic gene insertion. AAV
is less pathogenic than other virus types; stably integrates into
dividing and non-dividing cells; integrates at a consistent site in the
host genome; and shows good specificity towards various cell types for
targeted gene delivery.
To date, 11 AAV isolates have been isolated and characterized. New
serotypes derived from non-human animal species have added to the
specificity and repertoire of current AAV gene therapy techniques by
avoiding the immunologic complications associated with human isolates.
This invention describes vectors derived from an avian AAV. These
vectors have innate properties related to their origin that may confer
them with a unique cellular specificity in targeted human gene therapy
and a unique immunologic profile that would avoid neutralization by
pre-existing antibodies. Therefore, vectors derived
[[Page 14593]]
from this avian AAV are likely to find novel applications for gene
therapy in humans. Furthermore because of their species of origin, this
vector would also be useful in the engineering of avian cells.
Inventors: Ioannis Bossis and John A. Chiorini (NIDCR).
Publication: I Bossis, JA Chiorini. Cloning of an avian adeno-
associated virus (AAAV) and generation of recombinant AAAV particles. J
Virol. 2003 Jun;77(12):6799-6810.
Patent Status: U.S. Patent Application No. 10/557,662 filed 21 Dec
2006 (HHS Reference No. E-105-2003/0-US-03).
Licensing Status: Available for non-exclusive or exclusive
licensing.
Licensing Contact: Jesse S. Kindra, J.D.; 301/435-5559;
kindraj@mail.nih.gov
Collaborative Research Opportunity: The National Institute of
Dental and Craniofacial Research, Laboratory of Dr. John Chiorini, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
gene therapy methods using AAV vectors. Please contact David W.
Bradley, PhD at bradleyda@nidcr.nih.gov for more information.
Serotonin-Deficient Knock-Out Mouse
Description of Technology: Serotonin is an important modulator of
many developmental, behavioral, and physiological processes, and it has
been implicated in depression, anxiety, schizophrenia, obsessive
compulsive disorders, and substance abuse. Serotonin's pharmacology is
extremely complex and it is mediated by seven of serotonin receptor
subtypes and it is present in several tissues. Although it has been a
subject of a number of studies, its role has been difficult to
ascertain. To investigate the role of serotonin in these disorders, the
murine gene was disrupted by homologous recombination. Results indicate
that serotonin binding sites were absent in different brain regions
(brain stem, frontal cortex, hippocampus, and striatum), and its
concentrations were reduced by 60-80%. These mice represent a powerful
tool for the investigation of behavioral and neuropsychiatric
disorders, and development of drug treatments for these disorders.
Applications: A model to study serotonin's role in behavioral and
neuropsychiatric disorders.
Market:
1. Serotonin inhibitors are most widely used treatment in
neuropsychological disorders. Examples include Zoloft, Paxil, and
Prozac.
2. Depression effects approximately 18.8 million U.S. citizens and
over 121 million people worldwide.
3. Antidepressant market was worth $16.2 billion in 2005, and it
has annual growth of 2% year on year.
4. Anxiety disorders affect 40 million (18.1%) of the adult U.S.
population.
5. Global anxiety disorder market was $4.5 billion in 2006.
Inventors: Dennis L. Murphy (NIMH) et al.
Publications:
1. RF Ren-Patterson, LW Cochran, A Holmes, S Sherrill, SJ Huang, T
Tolliver, K-P Lesch. Loss of brain-derived neurotrophic factor gene
allele exacerbates brain monoamine deficiencies and increases stress
abnormalities of serotonin transporter knockout mice. J Neurosci Res.
2005 Mar 15:79(6):756-771.
2. DL Murphy, A Lerner, G Rudnick, K-P Lesch. Serotonin
transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv.
2004 April:4(2):109-123.
3. RF Ren-Patterson, D-K Kim, X Zheng, S Sherrill, S-J Huang, T
Tolliver, DL Murphy. Serotonergic-like progenitor cells propagated from
neural stem cells in vitro: survival with SERT protein expression
following implantation into brains of mice lacking SERT. FASEB J. 2005
Sep:19(11):1537-1539.
4. Q Li, A Holmes, L Ma, LD Van de Kar, F Garcia, DL Murphy.
Medical hypothalamic 5-hydroxytryptamine (5HT)1A receptors regulate
neuroendocrine responses to stress and exploratory locomotor activity
application of recombinant adenovirus containing 5-HT1A sequences. J
Neurosci. 2004 Dec 1:24(48):10868-10877.
5. F Kilic, DL Murphy, G Rudnick. A human serotonin transporter
mutation causes constitutive activation of transport activity. Mol
Pharmacol. 2003 Aug:64(2):440-446.
6. DL Murphy, GR Uhl, A Holmes, R Ren-Patterson, FS Hall, I Sora, S
Detera-Wadleigh, K-P Lesch. Experimental gene interaction studies with
SERT mutant mice as models for human polygenic and epistatic traits and
disorders. Genes Brain Behav. 2003 Dec:2(6):350-364.
7. N Ozaki, D Goldman, WH Kaye, K Plotnicov, BD Greenberg, J
Lappalainen, G Rudnick, DL Murphy. Serotonin transporter missense
mutation associated with a complex neuropsychiatric phenotype. Mol
Psychiatry. 2003 Nov:8(11):933-936.
Patent Status: HHS Reference No. B-019-1999/0--Research Tool.
Licensing Status: This technology is available as a research tool
under a Biological Materials License.
Licensing Contact: Jennifer Wong; 301/435-4633;
wongje@mail.nih.gov.
Dated: March 15, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-5675 Filed 3-27-07; 8:45 am]
BILLING CODE 4140-01-P
