Government-Owned Inventions; Availability for Licensing, 55071-55073 [2011-22694]
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Inventors: Steven A. Rosenberg (NCI),
Mark E. Dudley (NCI), Robert P.
Somerville (NCI), Jianjian Jin (CC),
Marianna V. Sabatino (CC), David F.
Stroncek (CC).
Intellectual Property: HHS Reference
No. E–114–2011/0—U.S. Patent
Application No. 61/466,200 filed 22
March 2011.
Related Technologies:
• HHS Reference No. E–275–2002/
1—U.S. Patent Application No.
10/526,697 filed 5 May 2005 (and
foreign counterparts).
• HHS Reference No. E–273–2009/
0—U.S. Patent Application No.
12/869,390 filed 26 August 2010.
Licensing Contact: Samuel E. Bish,
PhD; 301–435–5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute Surgery
Branch is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate or
commercialize gas permeable flasks for
cell and gene therapy applications and
multicenter clinical trials. For
collaboration opportunities, please
contact John Hewes, PhD, at
hewesj@mail.nih.gov.
A Novel Optomechanical Module that
Enables a Conventional inverted
Microscope To Provide Selective Plane
Illumination Microscopy (iSPIM)
Description of Technology: The
invention describes an optomechanical
module that, when engaged with a
conventional inverted microscope,
provides selective plane illumination
microscopy (iSPIM). The module is
coupled to the translational base of the
microscope whereby a SPIM excitation
objective is engaged to one portion of
the mount body, and a SPIM detection
objective (having a longitudinal axis
perpendicular to that of the excitation
objective) is engaged to another portion
of the mount body. Such a system offers
the advantages of SPIM (optically
sectioned, high-speed volumetric
interrogation of living samples,
enabling, for example, the study of
developmental or neuronal dynamics at
high frame rates), while maintaining the
flexibility and sample geometry of
commercially available inverted
microscopes (thus additionally allowing
wide-field, TIRF, confocal, or 2 photon
imaging of samples).
Potential Commercial Applications:
The microscope can be used for:
• Imaging of live whole animals (e.g.
worms) (demonstrated already).
• Superresolution (photoactivated
localization microscopy) with minimal
bleaching of dye molecules.
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• High speed investigation of
neuronal dynamics at high frame rates.
Competitive Advantages:
• The system offers the advantages of
SPIM, while maintaining the flexibility
and sample geometry of commercially
available inverted microscopes.
• In this system the sample can be
easily mounted on a rectangular
coverslip and may be translated using
an automated 3D mechanical stage and
additionally imaged using the
conventional light path built into the
inverted microscope frame.
Development Stage:
• Prototype.
• In vivo data available (animal).
Inventors: Hari Shroff (NIBIB) et al.
Publication: A publication is under
review at PNAS.
Intellectual Property: HHS Reference
No. E–078–2011/0—U.S. Provisional
Patent Application No. 61/449,422 filed
04 Mar 2011.
Licensing Contact: Michael
Shmilovich, Esq.; 301–435–5019;
shmilovm@mail.nih.gov.
Collaborative Research Opportunity:
The NIBIB is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate or
commercialize applications of the
invention. For collaboration
opportunities, please contact Hari Shroff
at 301–435–1995 or hari.shroff@nih.gov.
A Vaccine for Shigella sonnei for Both
Children and Adults
Description of Technology: There is
currently no vaccine widely available
for shigellosis, which affects over 150
million people worldwide and causes
over 1 million deaths a year, mostly
children. The present invention
discloses a novel immunogen to be used
in a vaccine for both children and
adults. The immunogen, a lowmolecular mass O–SP-core fragment,
generates high antibody responses in
animal studies, which means reduced
number of vaccinations. The
immunogen is easy to isolate for ease of
manufacturing. Additionally, the
methods of manufacturing vaccines and
protocols of preventing and/or treating
Shigellosis had been carried out in the
present invention.
Potential Commercial Applications:
Shigella sonnei vaccines and
diagnostics.
Competitive Advantages:
• Vaccine can be used in both
children and adults.
• Doses of vaccine are reduced.
• Immunogen is easy to isolate for
easy vaccine production.
Development Stage:
• Prototype.
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• Pilot.
• Early-stage.
• Pre-clinical.
• In vitro data available.
• In vivo data available (animal).
Inventors: John B. Robbins, Rachel
Schneerson, Joanna Kubler-Kielb,
Christopher P. Mocca (NICHD).
Publications:
1. Robbins JB, et al. Synthesis,
characterization, and immunogenicity
in mice of Shigella sonnei O-specific
oligosaccharide-core-protein conjugates.
Proc Natl Acad Sci U S A. 2009 May
12;106(19):7974–7978. [PMID 19346477]
2. Kubler-Kielb J, et al. The
elucidation of the structure of the core
part of the LPS from Plesiomonas
shigelloides serotype O17 expressing Opolysaccharide chain identical to the
Shigella sonnei O-chain. Carbohydr Res.
2008 Dec 8;343(18):3123–3127. [PMID
18954864].
Intellectual Property: HHS Reference
No. E–308–2008/0—
• PCT Application No. PCT/US2009/
053897 filed 14 Aug 2009.
• U.S. Application No. 13/059,051
filed 14 Feb 2011.
Licensing Contact: Susan Ano, PhD;
301–435–5515; anos@mail.nih.gov.
Dated: August 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–22693 Filed 9–2–11; 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:
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
SUMMARY:
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Federal Register / Vol. 76, No. 172 / Tuesday, September 6, 2011 / Notices
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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.
Antibodies Against TL1A, a TNFFamily Cytokine, for the Treatment and
Diagnosis of Autoimmune
Inflammatory Diseases
Description of Technology:
Autoimmune inflammatory diseases
occur in greater than five percent of the
United States population; this disease
group includes asthma, multiple
sclerosis, rheumatoid arthritis, and
lupus. Treatments generally include
immunosuppressants or antiinflammatory drugs, which can have
serious side effects; recently, more
specific immunomodulatory therapies
such as TNF-alpha antagonists have
been developed.
In experiments with mice, NIAMS
inventors have shown that the
interaction between the TNF family
ligand TL1A with its receptor, DR3, is
critical for development of disease in
asthma, inflammatory bowel disease
and multiple sclerosis. They have also
developed anti-TL1A antibodies that
prevent disease in mouse models of
rheumatoid arthritis and inflammatory
bowel disease.
This technology describes anti-mouse
TL1A and anti-human TL1A
monoclonal antibodies that may be
useful for the development of
diagnostics and therapeutics for
autoimmune inflammatory disease, as
well as methods of treating such disease
by blocking the interaction between
TL1A and DR3.
Potential Commercial Applications:
• Antibody-based therapeutics for
autoimmune inflammatory disease.
• Diagnostics for autoimmune
inflammatory disease.
• Research tools to probe the role of
TL1A–DR3 interactions in the
development of autoimmune disease.
Competitive Advantages:
• Specific immunomodulatory effect
provides potential for potent therapy
without inducing global
immunosuppression.
• Anti-TL1A monoclonal antibodies
available for further development.
Development Stage:
• Early-stage.
• In vitro data available.
• In vivo data available (animal).
Inventors: Richard M. Siegel,
Francoise Meylan, Yun-Jeong Song
(NIAMS).
Publication: Meylan F, et al. The
TNF-family cytokine TL1A drives IL–
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13-dependent small intestinal
inflammation. Mucosal Immunol. 2011
Mar;4(2):172–185. [PMID 20980995].
Intellectual Property:
• HHS Reference No. E–011–2007/
0—U.S. Application No. 11/972,395
filed 10 Jan 2008.
• HHS Reference No. E–073–2011/
0—U.S. Application No. 61/488,671
filed 20 May 2011.
Related Technology: HHS Reference
No. E–072–2011/0—Research Tool.
Patent protection is not being pursued
for this technology.
Licensing Contact: Tara L. Kirby, PhD;
301–435–4426; tarak@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Arthritis and
Musculoskeletal and Skin Diseases is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize the
anti-mouse TL1A and anti-human TL1A
monoclonal antibodies. For
collaboration opportunities, please
contact Cecilia Pazman at
pazmance@mail.nih.gov.
TL1A Transgenic Mice for the Study of
Inflammatory Bowel Disease (IBD) and
Allergic-Type Immune Responses
Description of Technology: TL1A is a
TNF family cytokine that co-stimulates
T-cell proliferation and cytokine
production through its interactions with
the TNF family receptor DR3. TL1A–
DR3 interactions have been shown to be
important for the development of
autoimmune inflammatory diseases,
including inflammatory bowel disease
(IBD).
In order to probe the role of TL1A–
DR3 interactions in IBD, NIAMS
inventors have developed transgenic
mice that constitutively express TL1A
in T cells or in dendritic cells. These
mice spontaneously develop
inflammatory small bowel pathology
that is IL–13 dependent, and that
closely resembles intestinal responses to
allergens and to nematode infection.
These mice represent a unique model
for the study of IBD, and in particular,
the role of IL–13 in the development of
this disease. They may also be used as
a platform for investigating agents that
block TL1A–DR3 interactions and the
pathology associated with chronic TL1A
expression.
Potential Commercial Applications:
• Studies of small bowel
inflammation/IBD.
• Studies of the role of TL1A–DR3
interactions in the development of
autoimmune inflammatory disease.
• Investigation of TL1A–DR3
blocking agents for the treatment of IBD
or other TL1A–DR3 dependent diseases.
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Competitive Advantages:
• Lines available with transgene
expressed in T cells (under CD2
promoter) or dendritic cells (CD11c
promoter).
• Models are IL–13 dependent.
• No major defects in systemic
immunity.
Development Stage: In vivo data
available (animal).
Inventors: Richard M. Siegel and
Francoise Meylan (NIAMS).
Publications:
1. Meylan F, et al. The TNF-family
cytokine TL1A drives IL–13-dependent
small intestinal inflammation. Mucosal
Immunol. 2011 Mar;4(2):172–185.
[PMID 20980995].
2. Meylan F, et al. The TNF-family
receptor DR3 is essential for diverse T
cell-mediated inflammatory diseases.
Immunity. 2008 Jul 18;29(1):79–89.
[PMID 18571443].
Intellectual Property: HHS Reference
No. E–072–2011/0—Research Tool.
Patent protection is not being pursued
for this technology.
Related Technologies:
• HHS Reference No. E–011–2007/
0—U.S. Application No. 11/972,395
filed 10 Jan 2008.
• HHS Reference No. E–073–2011/
0—U.S. Application No. 61/488,671
filed 20 May 2011.
Licensing Contact: Tara L. Kirby, PhD;
301–435–4426; tarak@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Arthritis and
Musculoskeletal and Skin Diseases is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
TL1A Transgenic Mice. For
collaboration opportunities, please
contact Cecilia Pazman at
pazmance@mail.nih.gov.
Human Monoclonal Antibodies Crossreacting to Insulin-like Growth Factors
IGF–I and IGF–II as Potential Antitumor Agents
Description of Technology: The type 1
insulin-like growth factor (IGF) receptor
(IGF1R) is over-expressed by many
tumors and mediates proliferation,
motility, and protection from apoptosis.
Agents that inhibit IGF1R expression or
function can potentially block tumor
growth and metastasis. Its major ligands,
IGF–I, and IGF–II are over-expressed by
multiple tumor types. Previous studies
indicate that inhibition of IGF–I, and/or
IGF–II binding to its cognizant receptor
negatively modulates signal
transduction through the IGF pathway
and concomitant cell proliferation and
growth. Therefore, use of humanized or
fully human antibodies against IGFs
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Federal Register / Vol. 76, No. 172 / Tuesday, September 6, 2011 / Notices
represents a valid approach to inhibit
tumor growth.
The present invention discloses the
identification and characterization of a
fully human monoclonal antibody
designated m708.5 that has been affinity
maturated against IGF–I and IGF–II and
displays extremely high affinities for
IGF–I and IGF–II in the picoM range.
The m708.5 antibody potently inhibited
signal transduction mediated by the
IGF–1R interaction with IGF–I and
IGF–II and blocked phosphorylation of
IGF–IR and the insulin receptor.
Further, this antibody inhibited
migration in the MCF–7 breast cancer
cell line at the picoM range. Therefore,
this antibody can be used to prevent
binding of IGF–I and/or IGF–II to its
concomitant receptor IGFIR,
consequently, modulating diseases such
as cancer.
Potential Commercial Applications:
• Therapeutic for the treatment of
various human diseases associated with
aberrant cell growth and motility such
as breast, prostate, and leukemia
carcinomas.
• Research regent to study IGF–I and/
or IGF–II binding and its association
with tumor growth.
Competitive Advantages:
• Antibodies against the ligands
IGF–I and IGF–II, such as this invention,
inhibit the interaction with IGF–IR yet
likely do not have the type of toxicity
associated with IGF–1R antibodies.
• High concentrations of IGF–II are
found in cancer patients, on average
several fold higher than IGF–I, thus this
cross-reacting IGF–I/IGF–II antibody
could be more effective than existing
IGF–IR and/or IGF–I currently in the
clinic.
• This novel IGF antibody may
provide therapeutic intervention for
multiple carcinomas.
Development Stage:
• Pre-clinical.
• In vitro data available.
Inventors: Dimiter Dimitrov, Zhongyu
Zhu, and Qi Zhao (NCI).
Publications:
1. Zhao Q, et al. Human monoclonal
antibody fragments binding to insulinlike growth factors 1 and 2 with
picomolar affinity. Mol Cancer Ther.
2011 Jul 12; Epub ahead of print. [PMID
21750218].
2. Feng Y, et al. Novel human
monoclonal antibodies to insulin-like
growth factor (IGF)–II that potently
inhibit the IGF receptor type I signal
transduction function. Mol Cancer Ther.
2006;5(1):114–120. [PMID 18283605].
3. Kimura T, et al. Targeting of bonederived insulin-like growth factor-II by
a human neutralizing antibody
suppresses the growth of prostate cancer
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cells in a human bone environment.
Clin Cancer Res. 2010 Jan 1;16(1): 121–
129. [PMID 20028742].
Intellectual Property: HHS Reference
No. E–068–2011/0—U.S. Provisional
Application No. 61/474,664 filed 12
April 2011.
Related Technologies:
• HHS Reference No. E–336–2005/
0—U.S. Patent Application No. 12/
296,328 filed 07 Oct 2008; Antibody
Compositions and Methods for
Treatment of Neoplastic Disease.
• HHS Reference No. E–217–2005/
0—U.S. Patent No. 7,824,681 issued 02
Nov 2010; Human Monoclonal
Antibodies that Specifically Bind IGF–
II.
Licensing Contact: Whitney Hastings;
301–451–7337; hastingw@mail.nih.gov.
Collaborative Research Opportunity:
The NCI CCR Nanobiology Program,
Protein Interaction Group, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize this technology. For
collaboration opportunities, please
contact John Hewes, PhD at
hewesj@mail.nih.gov.
Transgenic Mice Expressing Human
Arginase II Gene in Endothelium:
Useful for Studying Atherosclerosis and
Other Vasculopathies
Description of Technology:
Cardiovascular disorders associated
with endothelial dysfunction, like
atherosclerosis, have decreased
endothelial nitric oxide (NO)
bioavailability. L-arginine, the primary
substrate for endothelial nitric oxide
synthase (eNOS), is important in the
regulation of NO production. Arginase
competes with eNOS for L-arginine and
has been implicated in the endothelial
dysfunction. NIH investigators have
generated transgenic mice with human
ArgII (hArgII) gene under control of
endothelial-specific Tie2 promoter. In
these mice, hArgII was expressed at very
high levels in all tissues except liver.
Analysis has shown that expression of
hArgII was endothelium-specific.
Overexpression of hArgII neither led to
significant changes in plasma level of
arginine, citrulline, NOHA, ADMA,
SDMA and ornithine, nor to changes in
plasma lipid levels. Level of arginase
activity in peritoneal macrophages
isolated from the transgenic mice also
was also unchanged. However, ArgII
overexpression induced signs of
endothelial dysfunction. In apoEknockout mice hArgII led to 2-fold
increasing in aortic area with
atherosclerotic lesions. The Tie2hArgII
transgenic mouse can be useful as a new
model for investigating the role of ArgII
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in endothelial function and
development of atherosclerosis.
Potential Commercial Applications:
• Useful to study the role of arginase
II gene in endothelium.
• Useful for testing the drugs for
treatment of the endothelial dysfunction
related to eNOS insufficiency, including
hypertension.
• Useful to study mechanisms of
atherosclerosis.
Competitive Advantages: Better model
system to study functional significance
of arginase II.
Development Stage:
• Early-stage.
• Pre-clinical.
• In vivo data available (animal).
Inventors: Boris L. Vaisman and Alan
T. Remaley (NHLBI).
Publication: Vaisman BL, et al.
Abstract 3636: The Effects of Arginase II
Overexpression on Endothelial Function
in Transgenic Mouse Model.
Circulation. 2008 Oct 28;118:S_455.
Intellectual Property: HHS Reference
No. E–255–2010/0—Research Tool.
Patent protection is not being pursued
for this technology.
Licensing Contact: Suryanarayana
(Sury) Vepa, PhD; 301–435–5020;
vepas@mail.nih.gov.
Dated: August 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–22694 Filed 9–2–11; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Center for Complementary &
Alternative Medicine; Notice of Closed
Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of the National Advisory
Council for Complementary and
Alternative Medicine (NACCAM)
meeting.
The meeting will be open to the
public as indicated below, with
attendance limited to space available.
Individuals who plan to attend and
need special assistance, such as sign
language interpretation or other
reasonable accommodations, should
notify the Contact Person listed below
in advance of the meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
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]]>Agencies
[Federal Register Volume 76, Number 172 (Tuesday, September 6, 2011)]
[Notices]
[Pages 55071-55073]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-22694]
-----------------------------------------------------------------------
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
[[Page 55072]]
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.
Antibodies Against TL1A, a TNF-Family Cytokine, for the Treatment and
Diagnosis of Autoimmune Inflammatory Diseases
Description of Technology: Autoimmune inflammatory diseases occur
in greater than five percent of the United States population; this
disease group includes asthma, multiple sclerosis, rheumatoid
arthritis, and lupus. Treatments generally include immunosuppressants
or anti-inflammatory drugs, which can have serious side effects;
recently, more specific immunomodulatory therapies such as TNF-alpha
antagonists have been developed.
In experiments with mice, NIAMS inventors have shown that the
interaction between the TNF family ligand TL1A with its receptor, DR3,
is critical for development of disease in asthma, inflammatory bowel
disease and multiple sclerosis. They have also developed anti-TL1A
antibodies that prevent disease in mouse models of rheumatoid arthritis
and inflammatory bowel disease.
This technology describes anti-mouse TL1A and anti-human TL1A
monoclonal antibodies that may be useful for the development of
diagnostics and therapeutics for autoimmune inflammatory disease, as
well as methods of treating such disease by blocking the interaction
between TL1A and DR3.
Potential Commercial Applications:
Antibody-based therapeutics for autoimmune inflammatory
disease.
Diagnostics for autoimmune inflammatory disease.
Research tools to probe the role of TL1A-DR3 interactions
in the development of autoimmune disease.
Competitive Advantages:
Specific immunomodulatory effect provides potential for
potent therapy without inducing global immunosuppression.
Anti-TL1A monoclonal antibodies available for further
development.
Development Stage:
Early-stage.
In vitro data available.
In vivo data available (animal).
Inventors: Richard M. Siegel, Francoise Meylan, Yun-Jeong Song
(NIAMS).
Publication: Meylan F, et al. The TNF-family cytokine TL1A drives
IL-13-dependent small intestinal inflammation. Mucosal Immunol. 2011
Mar;4(2):172-185. [PMID 20980995].
Intellectual Property:
HHS Reference No. E-011-2007/0--U.S. Application No. 11/
972,395 filed 10 Jan 2008.
HHS Reference No. E-073-2011/0--U.S. Application No. 61/
488,671 filed 20 May 2011.
Related Technology: HHS Reference No. E-072-2011/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Contact: Tara L. Kirby, PhD; 301-435-4426;
tarak@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Arthritis and Musculoskeletal and Skin Diseases is seeking statements
of capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize the anti-mouse
TL1A and anti-human TL1A monoclonal antibodies. For collaboration
opportunities, please contact Cecilia Pazman at pazmance@mail.nih.gov.
TL1A Transgenic Mice for the Study of Inflammatory Bowel Disease (IBD)
and Allergic-Type Immune Responses
Description of Technology: TL1A is a TNF family cytokine that co-
stimulates T-cell proliferation and cytokine production through its
interactions with the TNF family receptor DR3. TL1A-DR3 interactions
have been shown to be important for the development of autoimmune
inflammatory diseases, including inflammatory bowel disease (IBD).
In order to probe the role of TL1A-DR3 interactions in IBD, NIAMS
inventors have developed transgenic mice that constitutively express
TL1A in T cells or in dendritic cells. These mice spontaneously develop
inflammatory small bowel pathology that is IL-13 dependent, and that
closely resembles intestinal responses to allergens and to nematode
infection.
These mice represent a unique model for the study of IBD, and in
particular, the role of IL-13 in the development of this disease. They
may also be used as a platform for investigating agents that block
TL1A-DR3 interactions and the pathology associated with chronic TL1A
expression.
Potential Commercial Applications:
Studies of small bowel inflammation/IBD.
Studies of the role of TL1A-DR3 interactions in the
development of autoimmune inflammatory disease.
Investigation of TL1A-DR3 blocking agents for the
treatment of IBD or other TL1A-DR3 dependent diseases.
Competitive Advantages:
Lines available with transgene expressed in T cells (under
CD2 promoter) or dendritic cells (CD11c promoter).
Models are IL-13 dependent.
No major defects in systemic immunity.
Development Stage: In vivo data available (animal).
Inventors: Richard M. Siegel and Francoise Meylan (NIAMS).
Publications:
1. Meylan F, et al. The TNF-family cytokine TL1A drives IL-13-
dependent small intestinal inflammation. Mucosal Immunol. 2011
Mar;4(2):172-185. [PMID 20980995].
2. Meylan F, et al. The TNF-family receptor DR3 is essential for
diverse T cell-mediated inflammatory diseases. Immunity. 2008 Jul
18;29(1):79-89. [PMID 18571443].
Intellectual Property: HHS Reference No. E-072-2011/0--Research
Tool. Patent protection is not being pursued for this technology.
Related Technologies:
HHS Reference No. E-011-2007/0--U.S. Application No. 11/
972,395 filed 10 Jan 2008.
HHS Reference No. E-073-2011/0--U.S. Application No. 61/
488,671 filed 20 May 2011.
Licensing Contact: Tara L. Kirby, PhD; 301-435-4426;
tarak@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Arthritis and Musculoskeletal and Skin Diseases is seeking statements
of capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize TL1A Transgenic
Mice. For collaboration opportunities, please contact Cecilia Pazman at
pazmance@mail.nih.gov.
Human Monoclonal Antibodies Cross-reacting to Insulin-like Growth
Factors IGF-I and IGF-II as Potential Anti-tumor Agents
Description of Technology: The type 1 insulin-like growth factor
(IGF) receptor (IGF1R) is over-expressed by many tumors and mediates
proliferation, motility, and protection from apoptosis. Agents that
inhibit IGF1R expression or function can potentially block tumor growth
and metastasis. Its major ligands, IGF-I, and IGF-II are over-expressed
by multiple tumor types. Previous studies indicate that inhibition of
IGF-I, and/or IGF-II binding to its cognizant receptor negatively
modulates signal transduction through the IGF pathway and concomitant
cell proliferation and growth. Therefore, use of humanized or fully
human antibodies against IGFs
[[Page 55073]]
represents a valid approach to inhibit tumor growth.
The present invention discloses the identification and
characterization of a fully human monoclonal antibody designated m708.5
that has been affinity maturated against IGF-I and IGF-II and displays
extremely high affinities for IGF-I and IGF-II in the picoM range. The
m708.5 antibody potently inhibited signal transduction mediated by the
IGF-1R interaction with IGF-I and IGF-II and blocked phosphorylation of
IGF-IR and the insulin receptor. Further, this antibody inhibited
migration in the MCF-7 breast cancer cell line at the picoM range.
Therefore, this antibody can be used to prevent binding of IGF-I and/or
IGF-II to its concomitant receptor IGFIR, consequently, modulating
diseases such as cancer.
Potential Commercial Applications:
Therapeutic for the treatment of various human diseases
associated with aberrant cell growth and motility such as breast,
prostate, and leukemia carcinomas.
Research regent to study IGF-I and/or IGF-II binding and
its association with tumor growth.
Competitive Advantages:
Antibodies against the ligands IGF-I and IGF-II, such as
this invention, inhibit the interaction with IGF-IR yet likely do not
have the type of toxicity associated with IGF-1R antibodies.
High concentrations of IGF-II are found in cancer
patients, on average several fold higher than IGF-I, thus this cross-
reacting IGF-I/IGF-II antibody could be more effective than existing
IGF-IR and/or IGF-I currently in the clinic.
This novel IGF antibody may provide therapeutic
intervention for multiple carcinomas.
Development Stage:
Pre-clinical.
In vitro data available.
Inventors: Dimiter Dimitrov, Zhongyu Zhu, and Qi Zhao (NCI).
Publications:
1. Zhao Q, et al. Human monoclonal antibody fragments binding to
insulin-like growth factors 1 and 2 with picomolar affinity. Mol Cancer
Ther. 2011 Jul 12; Epub ahead of print. [PMID 21750218].
2. Feng Y, et al. Novel human monoclonal antibodies to insulin-like
growth factor (IGF)-II that potently inhibit the IGF receptor type I
signal transduction function. Mol Cancer Ther. 2006;5(1):114-120. [PMID
18283605].
3. Kimura T, et al. Targeting of bone-derived insulin-like growth
factor-II by a human neutralizing antibody suppresses the growth of
prostate cancer cells in a human bone environment. Clin Cancer Res.
2010 Jan 1;16(1): 121-129. [PMID 20028742].
Intellectual Property: HHS Reference No. E-068-2011/0--U.S.
Provisional Application No. 61/474,664 filed 12 April 2011.
Related Technologies:
HHS Reference No. E-336-2005/0--U.S. Patent Application
No. 12/296,328 filed 07 Oct 2008; Antibody Compositions and Methods for
Treatment of Neoplastic Disease.
HHS Reference No. E-217-2005/0--U.S. Patent No. 7,824,681
issued 02 Nov 2010; Human Monoclonal Antibodies that Specifically Bind
IGF-II.
Licensing Contact: Whitney Hastings; 301-451-7337;
hastingw@mail.nih.gov.
Collaborative Research Opportunity: The NCI CCR Nanobiology
Program, Protein Interaction Group, is seeking statements of capability
or interest from parties interested in collaborative research to
further develop, evaluate, or commercialize this technology. For
collaboration opportunities, please contact John Hewes, PhD at
hewesj@mail.nih.gov.
Transgenic Mice Expressing Human Arginase II Gene in Endothelium:
Useful for Studying Atherosclerosis and Other Vasculopathies
Description of Technology: Cardiovascular disorders associated with
endothelial dysfunction, like atherosclerosis, have decreased
endothelial nitric oxide (NO) bioavailability. L-arginine, the primary
substrate for endothelial nitric oxide synthase (eNOS), is important in
the regulation of NO production. Arginase competes with eNOS for L-
arginine and has been implicated in the endothelial dysfunction. NIH
investigators have generated transgenic mice with human ArgII (hArgII)
gene under control of endothelial-specific Tie2 promoter. In these
mice, hArgII was expressed at very high levels in all tissues except
liver. Analysis has shown that expression of hArgII was endothelium-
specific. Overexpression of hArgII neither led to significant changes
in plasma level of arginine, citrulline, NOHA, ADMA, SDMA and
ornithine, nor to changes in plasma lipid levels. Level of arginase
activity in peritoneal macrophages isolated from the transgenic mice
also was also unchanged. However, ArgII overexpression induced signs of
endothelial dysfunction. In apoE-knockout mice hArgII led to 2-fold
increasing in aortic area with atherosclerotic lesions. The Tie2hArgII
transgenic mouse can be useful as a new model for investigating the
role of ArgII in endothelial function and development of
atherosclerosis.
Potential Commercial Applications:
Useful to study the role of arginase II gene in
endothelium.
Useful for testing the drugs for treatment of the
endothelial dysfunction related to eNOS insufficiency, including
hypertension.
Useful to study mechanisms of atherosclerosis.
Competitive Advantages: Better model system to study functional
significance of arginase II.
Development Stage:
Early-stage.
Pre-clinical.
In vivo data available (animal).
Inventors: Boris L. Vaisman and Alan T. Remaley (NHLBI).
Publication: Vaisman BL, et al. Abstract 3636: The Effects of
Arginase II Overexpression on Endothelial Function in Transgenic Mouse
Model. Circulation. 2008 Oct 28;118:S--455.
Intellectual Property: HHS Reference No. E-255-2010/0--Research
Tool. Patent protection is not being pursued for this technology.
Licensing Contact: Suryanarayana (Sury) Vepa, PhD; 301-435-5020;
vepas@mail.nih.gov.
Dated: August 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-22694 Filed 9-2-11; 8:45 am]
BILLING CODE 4140-01-P
