Government-Owned Inventions; Availability for Licensing, 38442-38444 [E9-18496]
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Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices
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21R or anti-IL–21 monoclonal
antibodies has been demonstrated to
reduce TH2 immune responses
associated with fibrosis in animal
models.
The causes of chronic tissue fibrosis
are diverse and the market for a
therapeutic that targets fibrosis is large.
Fibrosis is associated with diverse
causes which include: genetic diseases
(such as cystic fibrosis); autoimmune
diseases (such as scleroderma); chronic
viral infections (such as hepatitis),
parasitic infections (such as
schistosomiasis); and occupational
exposures to causative agents (such as
asbestosis). Additionally, many cases of
tissue fibrosis are idiopathic.
Application: The treatment or
amelioration of tissue fibrosis.
Inventors: Thomas A. Wynn (NIAID);
Deborah A Young; Mary Collins; and
Michael J. Grusby.
Relevant Publication: J Pesce et al.
The IL–21 receptor augments Th2
effector function and alternative
macrophage activation. J Clin Invest
2006 Jul;116(7):2044–2055.
Patent Status: U.S. patent application
no. 11/402,885 (priority date April 14,
2005) and international patent
applications including European patent
application No. EP06/0750009 (HHS
Reference No. E–250–2005).
Licensing Status: Available for nonexclusive licensing.
Licensing Contact: Surekha Vathyam,
Ph.D.; 301–435–4076;
vathyams@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Allergy and
Infectious Diseases is seeking statements
of capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize this invention. Please
contact Nicole Mahoney at 301–435–
9017 or mahoneyn@niaid.nih.gov for
more information.
Use of Discoidin Domain Receptor 1
(DDR1) and Agents That Affect the
DDR1/Collagen Pathway
Description of Invention: Dendritic
cells (DCs) are pivotal antigenpresenting cells for initiation of an
immune response. Indeed, dendritic
cells provide the basis for the
production of an effective immune
response to a vaccine, particularly for
antigens wherein conventional
vaccination is inadequate. DCs are also
important in the production on an
immune response to tumor antigens.
The present invention discloses
methods of using the receptor tyrosine
kinase discoidin domain receptor 1
(DDR1) to facilitate the maturation/
differentiation of DCs or macrophages.
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Activating agents of DDR1 may be
useful in the induction of highly potent,
mature DCs or highly differentiated
macrophages from DC precursors, such
as monocytes. Use of this method may
enhance the antigen presenting
capabilities of the immune system,
leading to a more effective overall
immune response.
Inventor: Teizo Yoshimura (NCI).
Relevant Publications
1. H Kamohara et al. Discoidin
domain receptor 1 isoform-a (DDR1a)
promotes migration of leukocytes in
three-dimensional collagen lattices.
FASEB J. 2001 Dec;15(14):2724–2726.
2. W Matsuyama et al. Interaction of
discoidin domain receptor 1 isoform b
(DDR1b) with collagen activates p38
mitogen-activated protein kinase and
promotes differentiation of
macrophages. FASEB J. 2003
Jul;17(10):1286–1288.
Patent Status: U.S. Application No.
10/507,385 filed 09 Sep 2004 (HHS
Reference No. E–083–2002/2–US–02).
Licensing Status: Available for
licensing.
Licensing Contact: Betty B. Tong,
Ph.D.; 301–594–6565;
tongb@mail.nih.gov.
Dated: July 28, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–18504 Filed 7–31–09; 8:45 am]
BILLING CODE 4140–01–P
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
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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.
A Tumorigenic MEF/3T3 Tet-Off Mouse
Fibroblast Cell Line Stably Transfected
With a T7–Tagged Srp20 Expression
Construct (pJR17)
Description of Technology:
Alternative RNA splicing is a means by
which the human genome can produce
many more proteins from the genes
available. It is emerging that aberrations
in alternative RNA splicing contributes
to the development of cancers. SRp20 is
a cellular splicing factor that is involved
in the process of alternative splicing of
RNA. Investigators at the National
Cancer Institute (NCI), National
Institutes of Health (NIH) have
discovered that SRp20 is overexpressed
in many types of cancer and
furthermore promotes the induction and
maintenance of tumor cell growth. This
was demonstrated in part by
engineering a non-tumorigenic cell to
become tumorigenic in mice by
overexpressing SRp20.
Research Material available for
licensing is a tumorigenic MEF/3T3 tetoff mouse fibroblast cell line stably
transfected with a T7-tagged SRp20
expression construct (pJR17) that is
under the transcriptional control of
tetracycline.
Applications: Use in pre-clinical
development of therapeutic approaches
to cancer that target aberrant alternative
RNA splicing.
Advantages: Transcriptional control
of expression using Tet-off system;
Availability of stably transfected cell
line saves time and effort for other
investigators.
Market: Research Tool.
Development Status: Ready to use.
Inventors: Zhi-Ming Zheng and Rong
Jia (NCI).
Publications: Manuscript in
preparation.
Patent Status: HHS Reference No. E–
229–2009/0—Research Material. Patent
protection is not being sought for this
technology.
Licensing Status: Available for
licensing.
Licensing Contact: Sabarni Chatterjee,
Ph.D.; 301–435–5587;
chatterjeesa@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute, Center for
Cancer Research, HIV and AIDS
Malignancy Branch, is seeking
statements of capability or interest from
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Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices
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parties interested in collaborative
research to further develop, evaluate, or
commercialize A Tumorigenic MEF/3T3
Tet-Off Mouse Fibroblast Cell Line
Stably Transfected with a T7–Tagged
Srp20 Expression Construct (pJR17).
Please contact John D. Hewes, Ph.D. at
301–435–3121 or hewesj@mail.nih.gov
for more information.
Truncated Methanocarba Adenosine
Derivatives as A3 Adenosine Receptor
Antagonists
Description of Technology: Novel A3
adenosine antagonists available for
licensing. A3 receptors are particularly
highly expressed in inflammatory cells,
making it a potentially desirable target
for inflammatory diseases. This
technology relates to highly specific
antagonists and partial agonists of A3
adenosine receptors, which are
negatively coupled to adenylate cyclase
and have been broadly implicated in
inflammation, cardiovascular disease,
and cancer. Further, A3 adenosine
receptors have been implicated in
allergies, asthma, and chronic
obstructive pulmonary disease.
Advantages: There are four known
subtypes of adenosine receptors (A1,
A2A, A2B, and A3). All are positively or
negatively linked to cAMP, but have
different distributions and different
therapeutic potentials. In particular, the
use of A1 and A2 selective ligands has
been limited by the ubiquity of
expression of the receptors throughout
the body and the resultant side effects.
On the other hand, high levels of A3
receptor expression are limited to the
CNS, testes, and the immune system.
Thus, A3 receptors represent a
potentially highly specific target for
treating related diseases.
Inventor: Kenneth A. Jacobson
(NIDDK).
Related Publication: A Melman, B
Wang, BV Joshi, ZG Gao, S de Castro, CL
Heller, SK Kim, LS Jeong, KA Jacobson.
Selective A3 adenosine receptor
antagonists derived from nucleosides
containing a bicyclo[3.1.0]hexane ring
system. Bioorg Med Chem. 2008 Sep
15;16(18):8546–8556.
Patent Status: U.S. Provisional
Application No. 61/085,588 filed 01
Aug 2008 (HHS Reference No. E–285–
2008/0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Steve Standley,
Ph.D.; 301–435–4074;
sstand@mail.nih.gov
Collaborative Research Opportunity:
The NIDDK, Laboratory of Bioorganic
Chemistry is seeking statements of
capability or interest from parties
interested in collaborative research to
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further develop, evaluate, or
commercialize A3 adenosine receptor
antagonists. Please contact Kenneth A.
Jacobson, Ph.D. at
kajacobs@helix.nih.gov or the NIDDK
Office of Technology Transfer and
Development at 301–451–3636 for more
information.
Novel Proteins From the Sand Fly
Lutzomyia longipalpis Are Potent
Inhibitors of Complement Activity
Description of Technology: This
invention relates to the discovery that
five proteins from the salivary glands of
Lutzomyia longipalpis, LJM04, LJM11,
LJM19, LJM26, and LJL143, have anticomplement activity. These proteins
demonstrate potent inhibition of both
the classical and alternative pathways
for complement activation. All proteins,
excluding LJM19, were shown to bind
and inhibit the C3b molecule, thus
inactivating an integral component of
the complement pathway.
The complement system is a very
important line of defense against
pathogens, and is involved in many
pathologies and syndromes affecting
human health. It is therefore envisioned
that these five novel proteins may be
used to treat conditions where the
complement system is involved
including lupus erythematosus, juvenile
arthritis, and complications associated
with cardiac surgery and hemodialysis.
Applications:
• Potent inhibition of complement
activity.
• Treatment of diseases involving the
complement system.
Development Status: Early Stage.
Inventors: Jesus G. Valenzuela et al.
(NIAID).
Relevant Publication: RR Cavalcante,
MH Pereira, NF Gontijo. Anticomplement activity in the saliva of
phlebotomine sand flies and other
haematophagous insects. Parasitology
2003 Jul;127(Pt 1):87–93.
Patent Status: U.S. Provisional
Application No. 61/142,098 filed 31 Dec
2008 (HHS Reference No. E–205–2008/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Jeffrey A. James,
PhD; 301–435–5474;
jeffreyja@mail.nih.gov.
Potent Anti-Coagulant Activity of a
Novel Protein From the Sand Fly
Lutzomyia longipalpis
Description of Technology: The
salivary gland lysates of Lutzomyia
longipalpis, the New World sand fly and
main vector for visceral leishmaniasis,
contain an anti-coagulant protein that
helps the fly complete its blood meal.
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38443
This invention relates to the
identification of LJL143, a salivary gland
protein of L. longipalpis, as a specific
inhibitor of coagulation factor Xa.
LJLl43 is secreted in the saliva of L.
longipalpis and exerts its effects by
tightly binding the catalytic site of factor
Xa. By directly binding the catalytic
site, it is believed that the potent anticoagulant activity of LJL143 will be
accompanied by reduced side effects
compared to anti-coagulant drugs that
rely on activating serine proteases.
LJL143 has a novel sequence with no
reported homology in the gene bank,
and is the first anti-coagulant factor
identified in sand flies.
LJLl43 may be used for inhibiting
factor Xa activity in vivo or as a
prototype for designing specific
inhibitors of factor Xa. Because of its
high specificity, LJLl43 may be used as
an anti-coagulant in a number of procoagulant diseased states including
deep venous thrombosis, coronary
artery disease, non-hemorrhagic stroke,
and unstable angina with potentially
reduced side effects.
Applications:
• Safe and effective anti-coagulant for
therapeutic use.
• Treatment of several conditions
such as deep venous thrombosis,
coronary artery disease, nonhemorrhagic stroke, and unstable
angina.
Advantages: May be safer than other
important blood thinning drugs such as
Warfarin.
Development Status: Early Stage.
Market: Predicted $7.4 billion anticoagulant market by 2016.
Inventors: Jesus G. Valenzuela et al.
(NIAID).
Publication: JG Valenzuela, M
Garfield, ED Rowton, VM Pham.
Identification of the most abundant
secreted proteins from the salivary
glands of the sand fly Lutzomyia
longipalpis, vector of Leishmania
chagasi. J Exp Biol. 2004 Oct;207(Pt
21):3717–3729.
Patent Status: U.S. Provisional
Application No. 61/142,107 filed 31 Dec
2008 (HHS Reference No. E–204–2008/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Jeffrey A. James,
PhD; 301–435–5474;
jeffreyja@mail.nih.gov.
Novel Dopamine Receptor Ligands as
Therapeutics for Central Nervous
System Disorders
Description of Technology: The
dopamine D3 receptor subtype is a
member of the dopamine D2 subclass of
receptors. These receptors have been
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38444
Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices
implicated in a number of CNS
disorders, including psychostimulant
abuse, psychosis and Parkinson’s
disease. Compounds that bind with high
affinity and selectivity to D3 receptors
can not only provide important tools
with which to study the structure and
function of this receptor subtype, but
may also have therapeutic potential in
the treatment of numerous psychiatric
and neurologic disorders.
The 4-phenylpiperazine derivatives
are an important class of dopamine D3
selective ligands. However, due to their
highly lipophilic nature, these
compounds suffer from solubility
problems in aqueous media and reduced
bioavailability. To address this problem,
a process was designed to introduce
functionality into the carbon chain
linker of these compounds. Compared to
currently available dopamine D3
receptor ligands, the resulting
compounds show improved
pharmacological properties and D3
selectivities but due to their more
hydrophilic nature, these derivatives are
predicted to have improved water
solubility and bioavailability.
Applications:
• Therapeutics for a variety of
psychiatric and neurologic disorders
• Research tools to study D3 receptor
structure and function
Advantages:
• Improved pharmacological
properties and selectivity over existing
dopamine D3 receptor ligands
• Hydrophilic nature likely to lead to
improved water solubility and
bioavailability
Development Status: Pre-clinical
discovery.
Further R&D Needed:
• Evaluate selected compounds in
animal models of drug abuse, psychosis,
obesity and Parkinson’s disease.
• Design and synthesize novel,
functionalized analogs using both
classical and computational drug design
to improve D3 receptor affinity and
selectivity.
• Evaluate compounds for binding in
D3 and D2 receptor expressing cell lines
and in in vitro functional assays.
• Correlate in vitro binding affinities
with in vivo function in rats and
monkeys and evaluate compounds in
knockout mice models.
• Pursue PET and SPECT imaging
agents by radiolabel of D3 ligands and
evaluation in rats and non-human
primates.
Inventors: Amy H. Newman (NIDA),
Peter Grundt (NIDA), Jianjing Cao
(NIDA), et al.
Patent Status: PCT Application No.
Pct/US2007/71412 filed 15 Jun 2007,
which published as WO 2008/153573
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on 18 Dec 2008 (HHS Reference No. E–
128–2006/0–PCT–01).
Licensing Status: Available for
licensing.
Licensing Contact: Charlene Sydnor,
PhD; 301–435–4689;
sydnorc@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute on Drug Abuse’s
Medications Discovery Research Branch
is seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize 4phenylpiperazine derivatives as
dopamine D3 selective ligands. Please
contact Vio Conley, MS at 301–435–
2031 or conleyv@mail.nih.gov for
additional information.
High-Yield Methods of Producing
Biliverdin
Description of the Technology: This
invention describes methods of making
high yields of biliverdin, the
pharmaceutical compositions of
biliverdin made using that process, and
methods of using the compositions
therapeutically.
In reaction to a wide range of cellular
stresses, hemoglobin is naturally
metabolized to biliverdin, which is then
quickly metabolized to bilirubin, a bile
pigment, through a highly conserved set
of enzymes. Both bilirubin and
biliverdin are normally processed for
rapid excretion, and excessive serum
levels of bilirubin have known toxic
effects (most notably jaundice).
Surprisingly, research in the past
decade has shown that decreasing
serum levels correlate inversely with the
prognosis of various disorders, such as
ischemia/reperfusion injuries,
atherosclerosis, organ transplantation,
and several autoimmune diseases.
Indeed, in animal-model studies,
inducing a mild case of jaundice
actually improved outcome.
Unfortunately, bilirubin is relatively
insoluble, and so is not a practical
pharmaceutical itself.
Biliverdin has lower direct toxicity
and substantially greater solubility than
bilirubin, and also appears to have some
direct therapeutic effects similar to
bilirubin. Accordingly, biliverdin has
been widely studied lately. Generating
high yields of pure biliverdin is
difficult, however, because any system
with the enzymes to break down
hemoglobin also has enzymes
converting biliverdin to bilirubin. The
inventors have created a system of
generating microorganisms (yeast)
lacking the enzymes that break
biliverdin down to bilirubin.
Applications: Production of biliverdin
for immunomodulatory and
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cytoprotective therapy (or adjuvant) in
any condition involving an overactive
immune response.
Advantages:
• High yield of biliverdin with low
contamination of bilirubin.
• Produces only active isomers of
biliverdin.
• Unlike prior methods, new method
uses starting material that is
inexpensive and plentiful.
Development Status: Successful
generation of Candida albicans with
biliverdin-generating system.
Inventors: Michael L. Pendrak and
David D. Roberts (NCI).
Patent Status: HHS Reference No. E–
040–2004/0—Issued U.S. Patent
7,504,243; Pending U.S. Application 12/
364,054 (divisional, filed 02 Feb 2009).
Relevant Publication: ML Pendrak et
al. Heme oxygenase in Candida albicans
is regulated by hemoglobin and is
necessary for metabolism of exogenous
heme and hemoglobin to alphabiliverdin. J Biol Chem. 20 Jan
2004;279(5):3426–3433.
Licensing Status: Available for
licensing.
Licensing Contact: Bruce Goldstein,
JD, MS; (301) 435–5470;
goldsteb@mail.nih.gov.
Collaborative Research Opportunity:
The Laboratory of Pathology in the
Center for Cancer Research of the
National Cancer Institute is seeking
parties interested in collaborative
research directed toward clinical
applications of biliverdin. For more
information about the research, please
contact either Dr. Michael Pendrak
(NCI/CCR Laboratory of Pathology) at
(301) 496–6264, or Dr. April Franks
(NCI Technology Transfer Center) at
(301) 496–0477.
Dated: July 28, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–18496 Filed 7–31–09; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2009–N–0338]
Medical Device User Fee Rates for
Fiscal Year 2010
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
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]]>Agencies
[Federal Register Volume 74, Number 147 (Monday, August 3, 2009)]
[Notices]
[Pages 38442-38444]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-18496]
-----------------------------------------------------------------------
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.
A Tumorigenic MEF/3T3 Tet-Off Mouse Fibroblast Cell Line Stably
Transfected With a T7-Tagged Srp20 Expression Construct (pJR17)
Description of Technology: Alternative RNA splicing is a means by
which the human genome can produce many more proteins from the genes
available. It is emerging that aberrations in alternative RNA splicing
contributes to the development of cancers. SRp20 is a cellular splicing
factor that is involved in the process of alternative splicing of RNA.
Investigators at the National Cancer Institute (NCI), National
Institutes of Health (NIH) have discovered that SRp20 is overexpressed
in many types of cancer and furthermore promotes the induction and
maintenance of tumor cell growth. This was demonstrated in part by
engineering a non-tumorigenic cell to become tumorigenic in mice by
overexpressing SRp20.
Research Material available for licensing is a tumorigenic MEF/3T3
tet-off mouse fibroblast cell line stably transfected with a T7-tagged
SRp20 expression construct (pJR17) that is under the transcriptional
control of tetracycline.
Applications: Use in pre-clinical development of therapeutic
approaches to cancer that target aberrant alternative RNA splicing.
Advantages: Transcriptional control of expression using Tet-off
system; Availability of stably transfected cell line saves time and
effort for other investigators.
Market: Research Tool.
Development Status: Ready to use.
Inventors: Zhi-Ming Zheng and Rong Jia (NCI).
Publications: Manuscript in preparation.
Patent Status: HHS Reference No. E-229-2009/0--Research Material.
Patent protection is not being sought for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587;
chatterjeesa@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Center for Cancer Research, HIV and AIDS Malignancy Branch, is seeking
statements of capability or interest from
[[Page 38443]]
parties interested in collaborative research to further develop,
evaluate, or commercialize A Tumorigenic MEF/3T3 Tet-Off Mouse
Fibroblast Cell Line Stably Transfected with a T7-Tagged Srp20
Expression Construct (pJR17). Please contact John D. Hewes, Ph.D. at
301-435-3121 or hewesj@mail.nih.gov for more information.
Truncated Methanocarba Adenosine Derivatives as A3 Adenosine
Receptor Antagonists
Description of Technology: Novel A3 adenosine
antagonists available for licensing. A3 receptors are
particularly highly expressed in inflammatory cells, making it a
potentially desirable target for inflammatory diseases. This technology
relates to highly specific antagonists and partial agonists of
A3 adenosine receptors, which are negatively coupled to
adenylate cyclase and have been broadly implicated in inflammation,
cardiovascular disease, and cancer. Further, A3 adenosine
receptors have been implicated in allergies, asthma, and chronic
obstructive pulmonary disease.
Advantages: There are four known subtypes of adenosine receptors
(A1, A2A, A2B, and A3). All
are positively or negatively linked to cAMP, but have different
distributions and different therapeutic potentials. In particular, the
use of A1 and A2 selective ligands has been
limited by the ubiquity of expression of the receptors throughout the
body and the resultant side effects. On the other hand, high levels of
A3 receptor expression are limited to the CNS, testes, and
the immune system. Thus, A3 receptors represent a
potentially highly specific target for treating related diseases.
Inventor: Kenneth A. Jacobson (NIDDK).
Related Publication: A Melman, B Wang, BV Joshi, ZG Gao, S de
Castro, CL Heller, SK Kim, LS Jeong, KA Jacobson. Selective
A3 adenosine receptor antagonists derived from nucleosides
containing a bicyclo[3.1.0]hexane ring system. Bioorg Med Chem. 2008
Sep 15;16(18):8546-8556.
Patent Status: U.S. Provisional Application No. 61/085,588 filed 01
Aug 2008 (HHS Reference No. E-285-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Steve Standley, Ph.D.; 301-435-4074;
sstand@mail.nih.gov
Collaborative Research Opportunity: The NIDDK, Laboratory of
Bioorganic Chemistry is seeking statements of capability or interest
from parties interested in collaborative research to further develop,
evaluate, or commercialize A3 adenosine receptor
antagonists. Please contact Kenneth A. Jacobson, Ph.D. at
kajacobs@helix.nih.gov or the NIDDK Office of Technology Transfer and
Development at 301-451-3636 for more information.
Novel Proteins From the Sand Fly Lutzomyia longipalpis Are Potent
Inhibitors of Complement Activity
Description of Technology: This invention relates to the discovery
that five proteins from the salivary glands of Lutzomyia longipalpis,
LJM04, LJM11, LJM19, LJM26, and LJL143, have anti-complement activity.
These proteins demonstrate potent inhibition of both the classical and
alternative pathways for complement activation. All proteins, excluding
LJM19, were shown to bind and inhibit the C3b molecule, thus
inactivating an integral component of the complement pathway.
The complement system is a very important line of defense against
pathogens, and is involved in many pathologies and syndromes affecting
human health. It is therefore envisioned that these five novel proteins
may be used to treat conditions where the complement system is involved
including lupus erythematosus, juvenile arthritis, and complications
associated with cardiac surgery and hemodialysis.
Applications:
Potent inhibition of complement activity.
Treatment of diseases involving the complement system.
Development Status: Early Stage.
Inventors: Jesus G. Valenzuela et al. (NIAID).
Relevant Publication: RR Cavalcante, MH Pereira, NF Gontijo. Anti-
complement activity in the saliva of phlebotomine sand flies and other
haematophagous insects. Parasitology 2003 Jul;127(Pt 1):87-93.
Patent Status: U.S. Provisional Application No. 61/142,098 filed 31
Dec 2008 (HHS Reference No. E-205-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Jeffrey A. James, PhD; 301-435-5474;
jeffreyja@mail.nih.gov.
Potent Anti-Coagulant Activity of a Novel Protein From the Sand Fly
Lutzomyia longipalpis
Description of Technology: The salivary gland lysates of Lutzomyia
longipalpis, the New World sand fly and main vector for visceral
leishmaniasis, contain an anti-coagulant protein that helps the fly
complete its blood meal. This invention relates to the identification
of LJL143, a salivary gland protein of L. longipalpis, as a specific
inhibitor of coagulation factor Xa. LJLl43 is secreted in the saliva of
L. longipalpis and exerts its effects by tightly binding the catalytic
site of factor Xa. By directly binding the catalytic site, it is
believed that the potent anti-coagulant activity of LJL143 will be
accompanied by reduced side effects compared to anti-coagulant drugs
that rely on activating serine proteases. LJL143 has a novel sequence
with no reported homology in the gene bank, and is the first anti-
coagulant factor identified in sand flies.
LJLl43 may be used for inhibiting factor Xa activity in vivo or as
a prototype for designing specific inhibitors of factor Xa. Because of
its high specificity, LJLl43 may be used as an anti-coagulant in a
number of pro-coagulant diseased states including deep venous
thrombosis, coronary artery disease, non-hemorrhagic stroke, and
unstable angina with potentially reduced side effects.
Applications:
Safe and effective anti-coagulant for therapeutic use.
Treatment of several conditions such as deep venous
thrombosis, coronary artery disease, non-hemorrhagic stroke, and
unstable angina.
Advantages: May be safer than other important blood thinning drugs
such as Warfarin.
Development Status: Early Stage.
Market: Predicted $7.4 billion anti-coagulant market by 2016.
Inventors: Jesus G. Valenzuela et al. (NIAID).
Publication: JG Valenzuela, M Garfield, ED Rowton, VM Pham.
Identification of the most abundant secreted proteins from the salivary
glands of the sand fly Lutzomyia longipalpis, vector of Leishmania
chagasi. J Exp Biol. 2004 Oct;207(Pt 21):3717-3729.
Patent Status: U.S. Provisional Application No. 61/142,107 filed 31
Dec 2008 (HHS Reference No. E-204-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Jeffrey A. James, PhD; 301-435-5474;
jeffreyja@mail.nih.gov.
Novel Dopamine Receptor Ligands as Therapeutics for Central Nervous
System Disorders
Description of Technology: The dopamine D3 receptor subtype is a
member of the dopamine D2 subclass of receptors. These receptors have
been
[[Page 38444]]
implicated in a number of CNS disorders, including psychostimulant
abuse, psychosis and Parkinson's disease. Compounds that bind with high
affinity and selectivity to D3 receptors can not only provide important
tools with which to study the structure and function of this receptor
subtype, but may also have therapeutic potential in the treatment of
numerous psychiatric and neurologic disorders.
The 4-phenylpiperazine derivatives are an important class of
dopamine D3 selective ligands. However, due to their highly lipophilic
nature, these compounds suffer from solubility problems in aqueous
media and reduced bioavailability. To address this problem, a process
was designed to introduce functionality into the carbon chain linker of
these compounds. Compared to currently available dopamine D3 receptor
ligands, the resulting compounds show improved pharmacological
properties and D3 selectivities but due to their more hydrophilic
nature, these derivatives are predicted to have improved water
solubility and bioavailability.
Applications:
Therapeutics for a variety of psychiatric and neurologic
disorders
Research tools to study D3 receptor structure and function
Advantages:
Improved pharmacological properties and selectivity over
existing dopamine D3 receptor ligands
Hydrophilic nature likely to lead to improved water
solubility and bioavailability
Development Status: Pre-clinical discovery.
Further R&D Needed:
Evaluate selected compounds in animal models of drug
abuse, psychosis, obesity and Parkinson's disease.
Design and synthesize novel, functionalized analogs using
both classical and computational drug design to improve D3 receptor
affinity and selectivity.
Evaluate compounds for binding in D3 and D2 receptor
expressing cell lines and in in vitro functional assays.
Correlate in vitro binding affinities with in vivo
function in rats and monkeys and evaluate compounds in knockout mice
models.
Pursue PET and SPECT imaging agents by radiolabel of D3
ligands and evaluation in rats and non-human primates.
Inventors: Amy H. Newman (NIDA), Peter Grundt (NIDA), Jianjing Cao
(NIDA), et al.
Patent Status: PCT Application No. Pct/US2007/71412 filed 15 Jun
2007, which published as WO 2008/153573 on 18 Dec 2008 (HHS Reference
No. E-128-2006/0-PCT-01).
Licensing Status: Available for licensing.
Licensing Contact: Charlene Sydnor, PhD; 301-435-4689;
sydnorc@mail.nih.gov.
Collaborative Research Opportunity: The National Institute on Drug
Abuse's Medications Discovery Research Branch is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize 4-
phenylpiperazine derivatives as dopamine D3 selective ligands. Please
contact Vio Conley, MS at 301-435-2031 or conleyv@mail.nih.gov for
additional information.
High-Yield Methods of Producing Biliverdin
Description of the Technology: This invention describes methods of
making high yields of biliverdin, the pharmaceutical compositions of
biliverdin made using that process, and methods of using the
compositions therapeutically.
In reaction to a wide range of cellular stresses, hemoglobin is
naturally metabolized to biliverdin, which is then quickly metabolized
to bilirubin, a bile pigment, through a highly conserved set of
enzymes. Both bilirubin and biliverdin are normally processed for rapid
excretion, and excessive serum levels of bilirubin have known toxic
effects (most notably jaundice). Surprisingly, research in the past
decade has shown that decreasing serum levels correlate inversely with
the prognosis of various disorders, such as ischemia/reperfusion
injuries, atherosclerosis, organ transplantation, and several
autoimmune diseases. Indeed, in animal-model studies, inducing a mild
case of jaundice actually improved outcome. Unfortunately, bilirubin is
relatively insoluble, and so is not a practical pharmaceutical itself.
Biliverdin has lower direct toxicity and substantially greater
solubility than bilirubin, and also appears to have some direct
therapeutic effects similar to bilirubin. Accordingly, biliverdin has
been widely studied lately. Generating high yields of pure biliverdin
is difficult, however, because any system with the enzymes to break
down hemoglobin also has enzymes converting biliverdin to bilirubin.
The inventors have created a system of generating microorganisms
(yeast) lacking the enzymes that break biliverdin down to bilirubin.
Applications: Production of biliverdin for immunomodulatory and
cytoprotective therapy (or adjuvant) in any condition involving an
overactive immune response.
Advantages:
High yield of biliverdin with low contamination of
bilirubin.
Produces only active isomers of biliverdin.
Unlike prior methods, new method uses starting material
that is inexpensive and plentiful.
Development Status: Successful generation of Candida albicans with
biliverdin-generating system.
Inventors: Michael L. Pendrak and David D. Roberts (NCI).
Patent Status: HHS Reference No. E-040-2004/0--Issued U.S. Patent
7,504,243; Pending U.S. Application 12/364,054 (divisional, filed 02
Feb 2009).
Relevant Publication: ML Pendrak et al. Heme oxygenase in Candida
albicans is regulated by hemoglobin and is necessary for metabolism of
exogenous heme and hemoglobin to alpha-biliverdin. J Biol Chem. 20 Jan
2004;279(5):3426-3433.
Licensing Status: Available for licensing.
Licensing Contact: Bruce Goldstein, JD, MS; (301) 435-5470;
goldsteb@mail.nih.gov.
Collaborative Research Opportunity: The Laboratory of Pathology in
the Center for Cancer Research of the National Cancer Institute is
seeking parties interested in collaborative research directed toward
clinical applications of biliverdin. For more information about the
research, please contact either Dr. Michael Pendrak (NCI/CCR Laboratory
of Pathology) at (301) 496-6264, or Dr. April Franks (NCI Technology
Transfer Center) at (301) 496-0477.
Dated: July 28, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-18496 Filed 7-31-09; 8:45 am]
BILLING CODE 4140-01-P
