Method for the Diagnosis and
Treatment of Vascular Disease
Description of Invention:
Cardiovascular disease is a major health risk
throughout the industrialized world. Atherosclerosis, the most prevalent of
cardiovascular diseases, is the principal cause of heart attack, stroke, and
gangrene of the extremities. It is also the principal cause of death in the
United States.
This invention portrays a method for diagnosing
decreased vascular function, detecting increased cardiovascular risk and
diagnosing atherosclerosis. An embodiment includes assaying the number of
endothelial progenitor cells and treating a subject with decreased vascular
function by administering a therapeutically effective amount of endothelial
progenitor cells.
|
Inventors: |
Toren Finkel et al. (NHLBI) |
|
Patent Status: |
DHHS Reference No. E-037-2003 filed 15 Nov
2002 DHHS Reference No. E-125-2003 filed 05 Feb 2003 |
|
Relevant Publication: |
J.M. Hill, G. Zalos, J.P.J. Halcox, W.H.
Schenke, M.A. Waclawiw, A.A. Quyyumi, and T. Finkel. Circulating endothelial
progenitor cells, vascular function, and cardiovascular risk. New Eng. J. Med.
348:593-600, Feb 13, 2003. |
|
Portfolios: |
Internal Medicine-Diagnostics |
|
For Additional Information Please Contact:
|
Fatima Sayyid M.H.P.M.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-4521 X
Email:
sayyidf@od.nih.gov
Fax: (301)
402-0220 |
Countercurrent Chromatography
Separation of Polar Sulfonated Compounds
Description of Invention:
The invention is a method and apparatus for
separating a quantity of a sulfonated polar compound from other compounds in a
mixture using countercurrent chromatography. The inventors have found that
countercurrent chromatography techniques may be employed to separate different
species of polar sulfonated compounds that have resisted isolation in
preparative amounts by other chromatographic methods. Countercurrent
chromatography is a technique that has been used to separate a variety of
compound mixtures, but has not been previously employed to separate multigram
quantities of polar sulfonated compounds without use of a ligand. In one
embodiment, pH-zone-refining countercurrent chromatography has been found
especially successful in this application. It has also been found that the use
of an X-type planetary centrifuge is beneficial to obtaining good results. For
two particular species of polar sulfonated compounds, the use of a cross-axis
(X1.5L-type) centrifuge successfully separated preparative quantities (100 mg,
gram, or multi-gram quantities) of material to greater than 99% purity.The
cross axis centrifuge facilitated the use of polar solvent systems with high
retention of the stationary phase, resulting in successful separation and/or
purification of large quantities of polar compounds.
|
Inventors: |
Adrian Weisz (NHLBI)
Yoichiro Ito (NHLBI)
|
|
Patent Status: |
DHHS Reference No. E-304-2002 filed 26 Aug
2002 |
|
Portfolios: |
DHHS Reference No. E-304-2002 filed 26 Aug
2002 |
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
MRI Navigator Methods and
Systems
Description of Invention:
The invention is a non-breathhold flow sensitive
navigator (FLOSEN) technique for reducing respiratory motion artifacts in MR
images that tracks the cardiac position using a blood flow based complex
difference scheme. The approach tracks the fast moving blood during systole as
a marker for the heart position, while stationary or slow moving spins are
suppressed. By this approach, the position of the heart can be determined
directly, without needing fractional correlation with the diaphragm motion. The
method uses a spoiled-Fast Low Angle Shot (FLASH) sequence and incorporates an
alternating pair of bipolar velocity-encoding gradients. This method appears to
be capable of resolving heart motions greater than +/- 0.1 pixel. The navigator
based on the position of the fast moving blood volume in the left ventricle may
be applied prospectively to shift a subsequent imaging slice to compensate for
subject motion, and thereby provide MRI images with increase clarity and
resolution.
|
Inventors: |
Vinay Pai (NHLBI)
Han Wen (NHLBI)
|
|
Patent Status: |
DHHS Reference No. E-164-2002 filed 16 Sep
2002 |
|
Portfolios: |
Devices/Instrumentation-Diagnostics-Imaging-Apparatus-Magnetic
resonance imaging (MRI) |
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Suppressing Unencoded MRI Signal
Contribution in Multi-Phase Myocardial Tagging and Phase-Contrast Based
Methods
Description of Invention:
The invention is a method for obtaining clear
functional magnetic resonance (MR) cardiac images without significantly
increasing signal acquisition time. During functional magnetic resonance
imaging (MRI) the specimen magnetization is spatially encoded by application of
one or more radio frequency pulses (RF) and gradient magnetic fields. This
spatially encoded magnetization is then read out to produce images that can be
used to assess specimen motion. During this process the contrast decreases from
the beginning of the cardiac cycle as the magnetization decays or relaxes,
making the images more difficult to process and interpret over time. This is
currently solved by acquiring the images twice (with a modified signal
excitation phase) to suppress unwanted unencoded MRI signal contributions;
therefore improving the contrast. Unfortunately, this prolongs the acquisition
by a factor of two. In the invention, an RF inversion pulse is used to suppress
the undesirable unencoded MRI signal contributions, thereby improving the
contrast. This RF frequency drives the undesired signal to an equilibrium
around zero, while preserving the desired encoded signal. The application of
the RF inversion pulse doubles the resolution of the image and does not
increase acquisition time. It allows for immediate evaluation of myocardial
contractility throughout the whole cardiac cycle without requiring user
intervention during phase-based data processing. There is also the possibility
that this method could be used in other areas of the body, including the spinal
cord, and the invention may be applicable to the study of brain motion. This
new method speeds up the quantification of datasets, suppresses undesired
signal contributions, and doubles the resolution of the images without doubling
acquisition time.
|
Inventors: |
Anthony H. Aletras (NHLBI) |
|
Patent Status: |
DHHS Reference No. E-079-02/0 |
|
Portfolios: |
Devices/Instrumentation-Diagnostics-Imaging-Apparatus-Magnetic
resonance imaging (MRI) |
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Method and Apparatus to Improve an
MRI Image
Description of Invention:
The invention is a method for improving image
quality in MR imaging methods using the SENSE (SENSitivity Encoding) method,
which is known to have degraded image quality due to numerical ill-conditioning
(so called g-factor loss). The invention improves the numerical conditioning by
means of an adaptive regularization (matrix conditioning), thereby improving
image quality for a given scan time. This is accomplished by adaptively
adjusting the regularization parameter for each pixel position to achieve a
target ghost artifact suppression. In this manner, a higher degree of matrix
conditioning is used in regions which have less artifact, thus improving the
SNR in these regions.
|
Inventors: |
Peter Kellman and Elliot McVeigh
(NHLBI) |
|
Patent Status: |
DHHS Reference No. E-361-01/0 filed 19 Oct
2001 |
|
Portfolios: |
Devices/Instrumentation-Diagnostics-Imaging-Apparatus-Magnetic
resonance imaging (MRI) |
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Side Exit Guiding Catheter for
Percutaneous Endomyocardial Injection
Description of Invention:
The invention is a device for delivering a
therapeutic or diagnostic agent to the heart using a flexible catheter having a
non-concentric guide wire to facilitate percutaneous delivery of the catheter
across the aortic valve into the left ventricular cavity. The catheter has a
side port through which the therapeutic or diagnostic can be delivered and, in
particular, by which septal ablation for the treatment of conditions such as
hypertrophic cardiomyopathy can be accomplished. This catheter is able to "turn
around" on itself to treat areas of the myocardium immediately underneath the
aortic valve through which the catheter enters. The side port can be used to
introduce a needle, laser or radiofrequency probe to perform an endomyocardial
ablation procedure.
|
Inventors: |
Robert Lederman (NHLBI) |
|
Patent Status: |
DHHS Reference No. E-108-01/0 filed 10 Aug
2001 |
|
Portfolios: |
Devices/Instrumentation-Diagnostics-Devices-Invasive |
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Method to Fabricate Continuous
Lengths of Helical Coiled Shape Memory Wire
Description of Invention:
The invention is a method and apparatus for
fabricating and storing continuous lengths of helical coil shaped memory wire
for use in springs, endotracheal tubes, medical stents and as reinforcement for
medical tubing (e.g. catheters). The helically coiled wire is continuously
formed from a special nickel-titanium wire and spooled for storage in a
straightened form. When the wire is later unspooled, it will snap back into the
desired helical coil form.
In one method of the invention, Nitinol wire is
passed through a spring forming unit to curve the wire. The so formed coil is
then loosely guided along a cylindrical mandrel, passed through a high
temperature oven so that the helical coil shape will be memorized, and then
uncoiled and stored in a straightened form. The method provides a very thin
wire with great strength and integrity of shape that resists kinking or
collapse in most medical applications.
|
Inventors: |
Theodor Kolobow (NHLBI) |
|
Patent Status: |
DHHS Reference No. E-105-00/0 filed 29 Sep
2000 |
|
Portfolios: |
Devices/Instrumentation-Therapeutics-Devices-Implants |
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Method and Device for
Catheter-Based Repair of Cardiac Valves
Description of Invention:
The invention provides a novel method and system for
catheter-based repair of cardiac valves. The technique permits non-surgical
repair of valve leaflets using percutaneous catheter in awake patients. The
intervention is intended to discontinue/lesson regurgitation of the mitral
valve and is a viable alternative to the conventional treatment with
vasodilator medications and open-heart surgery. The technology involves
re-apposing of mitral valve leaflets by percutaneous annuloplasty delivering
circumferential tension. Provided are also designs of various catheters,
systems that would be necessary to perform the repair of cardiac valves.
Imaging methods, like real time MRI, are used to assist the surgeon for
placement and orientation.
|
Inventors: |
Robert Lederman (NHLBI) |
|
Patent Status: |
DHHS Reference No. E-010-03/0
Serial No.
60/426,984, filed 15 Nov 2002 |
|
Portfolios: |
Devices/Instrumentation-Diagnostics-Devices-Invasive
Devices/Instrumentation-Diagnostics Devices/Instrumentation-Therapeutics
|
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Variable Curve Catheter
Description of Invention:
The invention provides a deflatable tip guiding
device, such as catheter, that enables the operator to vary the radius of
curvature of the tip of the catheter. This is a novel variation on the classic
"fixed fulcrum," tip deflectors used in minimally invasive procedures in open
surgical treatments. The described device would permit more comprehensive
ability to navigate complex geometric pathways in patient's body and would
enable to better access the target structures (e.g., to all endomyocardial
walls from a transaortic approach). The guiding device can be made compatible
with imaging methods like MRI. The described technology can be used as a
platform for a wide variety of interventional devices for delivery of drugs,
cells, energy, or sutures through a complex trajectories of the body.
|
Inventors: |
Robert Lederman (NHLBI) |
|
Patent Status: |
DHHS Reference No. E-035-03/0
Serial No.
60/426,542, filed 15 Nov 2002 |
|
Portfolios: |
Devices/Instrumentation-Diagnostics-Devices-Invasive
Devices/Instrumentation-Diagnostics Devices/Instrumentation-Therapeutics
|
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Variable Curve Catheter
Description of Invention:
This invention is a new carrier for conjugate
vaccines. The carrier is lipopolysaccharide (LPS) isolated from Brucella
abortus (BA). The claims of the patent cover all conjugates comprising BA-LPS
and an antigen from an infectious agent or tumor. BA-LPS, like other LPSs from
gram-negative bacteria, raises antibody responses in a T-independent fashion,
which allows antibodies to be raised in the absence of T cell help. BA-LPS is
much less toxic than LPS from other bacteria, and is much less potent than
other bacterial LPS in inducing inflammatory cytokines. Thus, BA-LPS is much
less likely to cause endotoxic shock. There are no foreign patent rights. The
invention is further described in Infection & Immunity 61(5), pp.
1722-1729, 1993.
|
Inventors: |
Xin Xing Gu (NIDCD)
B Golding (FDA)
|
|
Patent Status: |
Serial No. 08/369,565 filed 06 Jan 1995
U.S. Patent 5,824,310 issued 20 Oct 1998 |
|
Portfolios: |
Infectious Diseases
-Vaccines-Adjuvants/Vectors/Modulators
Infectious Diseases -Vaccines
|
|
For Additional Information Please Contact:
|
Peter A. Soukas J.D.
Office of Technology
Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4646 X
Email: soukasp@mail.nih.gov
Fax: (301)
402-0220 |
Methods of Inducing Deacetylase
Inhibitors to Promote Cell Differentiation and Regeneration
Description of Invention:
The present invention discloses a method of
enhancing progenitor cell differentiation, including enhancing myogenesis,
neurogenesis and hematopoiesis, by contacting a progenitor cell with an
effective amount of a deacetylase inhibitor (DI). The progenitor cell can be
part of cell culture, such as a cell culture used for in vitro or in vivo
analysis of progenitor cell differentiation, or can be part of an organism,
such as a human or other mammal. Contacting the progenitor cell with a DI can
lead to enhancement of expression of terminal cell-type specific genes in the
progenitor cell, such as enhancing expression of muscle-specific genes in
myoblasts, and can lead to skeletal muscle hypertrophy. Administering a DI to a
subject also can provide some prophylactic or therapeutic effect for
inhibiting, preventing, or treating associated with a degeneration or loss of
tissue. The DI can be administered to a subject as part of a pharmaceutical
composition.
|
Inventors: |
Vittorrio Sartorelli (NIAMS) and Pier L.
Puri |
|
Patent Status: |
DHHS Reference No. E-353-01/0 filed 18 Oct
2001 |
|
Portfolios: |
Internal
Medicine-Diagnostics-Anti-Inflammatory (including Autoimmune)
Internal
Medicine-Diagnostics
Internal Medicine-Research Materials |
|
For Additional Information Please Contact:
|
Fatima Sayyid M.H.P.M.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-4521 X
Email:
sayyidf@od.nih.gov
Fax: (301)
402-0220 |
Secretion of Native Recombinant
Lysosomal Enzymes by Liver
Description of Invention:
Glycogen storage disease type II (GSDII) is an
autosomal recessive disorder caused by the deficiency of acid alpha-glucosidase
(GAA), a glycogen-degrading lysosomal enzyme. This deficiency results in
generalized deposition of lysosomal glycogen in almost all tissues of the body
and can ultimately lead to cardiac failure before the age of two years. Current
treatment for the disease includes repairing the deficiency by injecting
recombinant protein into the patient made from either cultured Chinese Hamster
Ovary (CHO) cells or secreted in the milk from rabbits that bear the transgene
for the protein under a milk-specific promoter. Both recombinant proteins
produced are extremely inefficient in their uptake into and function in
targeted tissues.
The NIH announces a new technology that relates to
the use of hepatocytes whether in culture or in vivo for the production of
human GAA. The hepatocytes produce appropriate post-translational modification
of the enzyme in liver cells by proper glycosylation, thereby producing a
superior enzyme capable of being easily taken up and localized intracellularly
in the target tissue. Once there, the enzyme digests glycogen present in
lysosomes
|
Inventors: |
Dr. Nina Raben et al. (NIAMS) |
|
Patent Status: |
DHHS Reference No. E-067-01/0 filed 09 Apr
2001 |
|
Portfolios: |
Internal Medicine-Therapeutics-Other
Internal Medicine-Therapeutics |
|
For Additional Information Please Contact:
|
Marlene K. Shinn-Astor JD MS
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-4426 X
Email:
shinnm@od.nih.gov
Fax: (301)
402-0220 |
Signal Transduction Inhibitors Of
Allergic Reactions
Description of Invention:
Allergic reactions affect nearly 40 million persons
in the United States. Allergic reactions are due to a sequential interaction
beginning with the extracellular aggregation of the high affinity receptor for
IgE (Fc?RI) followed by intracellular tyrosine phosphorylation which initiates
a further cascade of events eventually leading to histamine and cytokine
release. The reaction is initiated by Lyn kinase which is pre-associated with
the Fc?RI. It was shown that the introduction of a unique portion of the
N-terminal region of Lyn A kinase into cells inhibits the receptor tyrosine
phosphorylation in a dose and time-dependent manner. Without receptor
phosphorylation, allergic reactions can not occur. The NIH is looking for a
company to license and independently develop the technology or to work in
collaboration with the NIH scientists via a Cooperative Research and
Development Agreement to further research and develop the allergy treatment. It
is believed that this technology may ultimately lead to an anti-allergy drug or
allergy therapy.
|
Inventors: |
B Vonakis
H Metzger
H Chen (NIAMS)
|
|
Patent Status: |
Serial No. 09/020,116 filed 06 Feb 1998
U.S. Patent 6,084,063 to issue on 04 Jul 2000 |
|
Portfolios: |
Internal
Medicine-Therapeutics-Anti-Inflammatory (including Autoimmune)
Internal
Medicine-Therapeutics |
|
For Additional Information Please Contact:
|
Marlene K. Shinn-Astor JD MS
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone : (301) 435-4426 X
Email:
shinnm@od.nih.gov
Fax: (301)
402-0220 |
Calorimeter And Method For
Simultaneous Measurement Of Thermal Conductivity And Specific Heat Of Fluids
Description of Invention:
The present invention is a novel calorimeter and
calorimetry apparatus and method for the ultrasensitive simultaneous
measurement of heat capacity and thermal conductivity of fluids. The unique
simultaneous measurement of the two parameters avoids sources of error seen in
other methods. The calorimeter shows excellent accuracy of 1 part in 10,000 and
run-to-run variability of 1 part in 100,000, as well as excellent long-term
reproducibility. The invention is well suited for the study of biomaterials,
such as lipids and proteins and other colloidal systems, which are not easily
analyzed using conventional commercial instruments.
|
Inventors: |
NL Gershfeld
CP Mudd
AJ Jin
K
Fukada (NIAMS) |
|
Patent Status: |
Serial No. 08/994,230 filed 19 Dec 1997
U.S. Patent 5,988,875 issued 23 Nov 1999 |
|
Portfolios: |
Devices/Instrumentation-Research
Materials-Instruments
Devices/Instrumentation-Research Materials |
|
For Additional Information Please Contact:
|
Michael Shmilovich J.D.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-5019 X
Email:
shmilovichm@od.nih.gov
Fax:
(301) 402-0220 |
Phage Display Of Intact Domains At
High Copy Number
Description of Invention:
Filamentous phage-based display systems have found
widespread use in molecular biology, including many immunologic applications
such as antigen presentation and the immuno-isolation of desired recombinants
by "biopanning". The present invention relates to a phage display system in
which the molecules to be displayed (i.e., molecules of interest) are
covalently connected to dispensable capsid polypeptides such as SOC (small
outer capsid) and HOC (highly antigenic outer capsid) polypeptides that are, in
turn, bound to a surface lattice protein, such as those on the surface of a
virion or polyhead. Polyheads are tubular capsid variants containing much
longer numbers of the surface lattice protein. Molecules of interest may be
displayed in various ways. For example, a chimeric polypeptide that includes a
dispensable polypeptide and a polypeptide of interest can be expressed in
Esherichia coli, purified, and then bound in vitro to separately isolated
surface lattice proteins. The surface lattice proteins can be those on the
surface of a capsid or polyhead from which the wild type dispensable
polypeptides have been deleted. Similarly, a chimera that contains a
dispensable polypeptide and a synthetic molecule of interest can be prepared in
vitro and bound to surface lattice proteins. In another embodiment, a positive
selection vector forces integration of a gene that encodes a dispensable
polypeptide and a polypeptide of interest into the genome of a phage from which
the wild type dispensable polypeptide is deleted. For example, a modified soc
gene can be integrated into a soc-deleted T4 genome, leading to in vivo binding
of the display molecule on progeny virions. More than one type of dispensable
polypeptide can be used as part of the chimera for displaying one or more
molecules of interest. For example, the surface lattice proteins of a phage may
be bound to a chimera that contains SOC and a chimera that contains HOC. The
display system has been successfully demonstrated for three molecules of
interest that vary in their length and character: (1) a tetrapeptide; (2) the
43 amino acid residue V3 loop domain of gp120, the human immunodeficiency virus
type-1 (HIV-1) envelope glycoprotein; and (3) poliovirus VP1 capsid protein
(312 residues).
|
Inventors: |
AC Steven (NIAMS) |
|
Patent Status: |
Serial No. 08/837,301 filed 11 Apr
1997 |
|
Portfolios: |
Infectious Diseases -Other |
|
For Additional Information Please Contact:
|
Peter A. Soukas J.D.
Office of Technology
Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone : (301) 435-4646 X
Email:
soukasp@od.nih.gov
Fax: (301)
402-0220 |
Identification Of The Gene Causing
Familial Mediterranean Fever
Description of Invention:
The invention identifies the gene (MEFV) encoding
the protein (pyrin) that is associated with familial Mediterranean fever (FMF).
FMF, a recessive inherited disorder, is characterized by episodes of fever,
inflammation, and unexplained arthritis, pleurisy, or abdominal pain. Pyrin is
thought to a play a role in keeping inflammation under control, whereas mutated
forms lead to a malfunctioning protein and uncontrolled inflammation. Mutated
forms of MEFV were isolated and correlated to FMF disease. It is anticipated
that the immediate use of the pyrin gene and its mutations will be to aid in
the diagnosis of FMF. It may also prove useful for evaluating FMF as a possible
cause of currently unexplained fevers or abdominal pain. The normal gene and
its mutations may also be useful for studying and controlling inflammation.
|
Inventors: |
D Kastner (NIAMS) et al. |
|
Patent Status: |
Serial No. 60/056,217 filed 21 Aug 1997
PCT/US98/17255 filed 20 Aug 1998 ; Serial No. 09/486,147 filed 22 Feb 2000
|
|
Relevant Publication: |
Cell 90(4):797-807, 1997 |
|
Portfolios: |
Internal
Medicine-Diagnostics-Anti-Inflammatory (including Autoimmune)
Internal
Medicine-Therapeutics-Anti-Inflammatory (including Autoimmune)
Internal
Medicine-Diagnostics
Internal Medicine-Therapeutics |
|
For Additional Information Please Contact:
|
Pradeep Ghosh PhD MBA
Office of Technology
Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5282 X
Email: ghoshp@od.nih.gov
Fax: (301) 402-0220
|
Janus Family Kinases (JAK) And
Identification Of Immune Modulators
Description of Invention:
This technology relates to an isolated
polynucleotide encoding the JAK-3 protein. JAK-3 is a protein tyrosine kinase
having a molecular weight of approximately 116 kDa, lacks SH2 or SH3 domains,
and is expressed in NK cells and stimulated or transformed T cells, but not in
resting T cells. The JAK-3 protein itself, antibodies to this protein, and
methods of identifying therapeutic agents for modulating the immune system
which make use of the foregoing are described in this invention.
Potential Area of Application:
- gene therapy -- SCID
- diagnostic -- SCID
- research reagent
- autoimmune disorders
- organ or bone marrow transplantation
Main Advantage of Invention:
- isolated JAK-3 protein
- antibody to JAK-3 protein
- method of screening for immunomodulating
agents
- JAK-3 only involved in signaling through
receptors that contain gc therefore specific drugs will be very selective in
their effects
|
Inventors: |
JJ O'Shea (NCI)
WJ Leonard (NHLBI)
JA
Johnston (NIAMS)
SM Russell (NHLBI)
D McVicar (NCI)
M Kawamura
(NCI) |
|
Patent Status: |
U.S. Patent Application
Serial No.
08/373,934 filed 13 Jan 1995
Serial Nos. 09/226,540 and 09/226,541 filed 06
Jan 1999 No foreign rights |
|
Related Technologies: |
E-176-95/0: Method of Identifying Inhibitors
of JAK-STAT Signal Transduction Pathway by WJ Leonard
E-079-93/0: Methods
for Diagnosis and Treatment of XSCID and Kits Thereof by WJ Leonard, et al.
|
|
Relevant Publication: |
Candotti F; Oakes SA; Johnston JA; Notarangelo
LD; O'Shea JJ; Blaese RM. In vitro correction of JAK-3 deficient severe
combined immunodeficiency by retroviral-mediated gene transduction. J Exp Med
1996 June 1; 183(6):2687-92
Russell SM; Johnston JA; Noguchi M; Kawamura
M; Bacon CM; Friedmann M; Berg M; McVicar DW; Witthuhn BA; Silvennoinen O;
Goldman AS; Schmalstieg FC; Ihle JN; O'Shea JJ; Leonard WJ. Interaction of
IL-2Rb and gc chains with JAK-1 and JAK-3: Implications for XSCID and XCID.
Science 1994 266:1042-1045
Musso T; Johnston JA; Linnekin D; Varesio L;
Rowe TK; O'Shea JJ; McVicar DW. Regulation of JAK-3 expression in human
monocytes: phosphorylation in response to interleukin 2, 4, and 7. J Exp Med
1995 Apr 1; 181(4):1425-31
Russell SM; Tayebi N; Nakajima H; Riedy MC;
Roberts JL; Aman MJ; Migone TS; Noguchi M; Markert ML; Buckley RH; O'Shea JJ;
Leonard WJ. Mutation of JAK-3 in a patient with SCID: Essential role of JAK-3
in lymphoid development. Science, 1995 270:797-80 |
|
Portfolios: |
Cancer -Diagnostics
Cancer -Research
Materials |
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For Additional Information Please Contact:
|
Susan A. Rucker J.D.
Office of Technology
Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4478 X
Email: ruckers@od.nih.gov
Fax: (301) 402-0220
|
Stem Cells that Transform to
Beating Cardiomyocytes
Description of Invention:
Many Americans die each year of congestive heart
failure occurring from a variety of causes including cardiomyopathy, myocardial
ischemia, congenital heart disease and valvular heart disease resulting in
cardiac cell death and myocardial dysfunction. As cardiomyocytes are not
replaced in adult myocardial tissue, physiologic demands on existing, healthy
cardiomyocytes leads to their hypertrophy. Heart transplants have been the only
recourse for patients in end-stage heart disease however this is complicated by
lack of donors, tissue incompatibility and high cost.
An alternative approach to heart transplantation is
to generate cardiomyocytes from stem cells in vitro that can be used in the
treatment of cardiac diseases characterized by myocardial cell death or
dysfunction.
This invention discloses a novel isolated population
of stem cells, called spoc cells, that can be induced, either in vivo or in
vitro, to differentiate into cardiomyocytes. Spoc cells may be differentiated
and utilized for screening agents that affect cardiomyocytes and as therapeutic
agents in the treatment of myocardial defects.
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Inventors: |
Neal D. Epstein (NHLBI) |
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Patent Status: |
DHHS Reference No. E-329-01/0 filed 22 Oct
2001 |
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Portfolios: |
Internal
Medicine-Therapeutics-Cardiology |
|
For Additional Information Please Contact:
|
Fatima Sayyid M.H.P.M.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-4521 X
Email:
sayyidf@od.nih.gov
Fax: (301)
402-0220 |
Optimization of Cardiac
Contraction by Novel Human Kinase Mediated Differential Phosphorylation of
Myosin
Description of Invention:
This invention relates to the development of drugs
that provide novel therapeutic interventions to increase the efficiency of
failing hearts. In order to pump blood efficiently, the normal heart takes
advantage of the increased efficiency of wringing (torsion) over squeezing.
When viewed in the context of attempting to "squeeze" water out of a wet towel,
the efficiency of "wringing" over "squeezing" can be readily appreciated. This
cardiac torsion is facilitated by a newly discovered spatial gradient of myosin
regulatory light chain (RLC) phosphorylation across the ventricular wall. This
gradient decreases from the epicardium to endocardium. The increased RLC
phosphorylation in the epicardium dramatically increases tension production and
reciprocally decreases an intrinsic property of muscle fibers called the
"stretch-activation response." The converse occurs in the relatively
hypophosphorylated endocardium. The distinctly different mechanical properties
of cardiac muscle fibers due to the spatial gradient of RLC phosphorylation are
critical to cardiac torsion (Cell, Vol.107,631-641, November 30, 2001).
This invention describes the cloning of the active
human cardiac kinase that controls the phosphorylation of cardiac myosin RLC.
Included in the invention are: (1) expressed human cardiac myosin light chains,
(2) expressed human cardiac/skeletal myosin light chain kinase and (3) an
antibody specific for the phosphorylated RLC. These three reagents form the
basis for a high-throughput screen for therapeutics that modulate the human
kinase. The data in this invention indicate that targeting this cardiac light
chain kinase could yield novel therapeutics to increase the efficiency of
hearts failing from a variety of causes. Because this pathway is relatively
independent of calcium level, this approach may provide a synergistic addition
to present day CHF therapeutics such as calcium blockers and digoxin.
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Inventors: |
Dr. Neal D. Epstein (NHLBI) |
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Patent Status: |
DHHS Reference No. E-261-00/0 filed 12 Sep
2000; DHHS Reference No. E-261-00/2 filed 12 Sep 2001. PCT/US01/28639 |
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Licensing Contact: |
Fatima Sayyid M.H.P.M.
Office of
Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD
20852-3804
Phone: (301) 435-4521 X
Email:
sayyidf@od.nih.gov
Fax: (301)
402-0220 |
Using insect cells to produce a
human DNA virus (rAAV) for gene transfer
Description of Invention:
The human virus, adeno-associated virus or AAV, is a
Parvovirus family member, of the dependovirus genus. Recombinant
adeno-associated virus, rAAV, is being developed as a vector for gene transfer
for the treatment of either acquired or inherited disease. The non-enveloped
virion contains a linear, single-stranded genome with two extensive open
reading frames, rep and cap, which encode the non-structural and structural
proteins, respectively. The terminal palindromes, often referred to as inverted
terminal repeats, or ITRs, function as the origins of virus DNA replication and
are the only elements required in cis for replication. Producing rAAV in
mammalian cells requires co-transfection with plasmids containing the rAAV
genome, the rep and cap genes, and adenovirus genes to provide so-called helper
functions. Transfections of adherent cells limit the scalability of the
process. In order to overcome the inherent limitation of adherent cell
transfection, we considered using Sf9 cells for production of rAAV using
baculoviruses to deliver the necessary DNA. Expression of the three AAV capsid
proteins was expected to yield virus-like particles, or empty capsids. In order
to generate the single-stranded vector genomes, the Rep proteins, in particular
Rep 78, would have to function efficiently in invertebrate cells. In addition,
the genomes would then have to be packaged into empty capsids. Analysis of the
extrachromosal DNA from Sf9 cells indicated that in the rAAV DNA was "rescued"
from the baculovirus genome and amplified via the AAV origins of replication in
the presence of Rep 78. The rAAV DNA synthesis was robust and exceeded the
level of vector DNA synthesis in HEK293 cells. Similarly, the level of capsid
protein expression was many fold greater than in transfected HEK293 cells. The
particles obtained from Sf9 cells were indistinguishable from HEK293 cell
produced vector, based on physical properties, protein composition, and
biological activities. Greater than 104 DNAse resistant particles (DRP) per Sf9
cell were produced, or >2x1010 DRP per ml of Sf9 cell culture. Bioreactor
scale -production is currently being optimized.
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Inventors: |
Robert Kotin et al. (NHLBI) |
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Patent Status: |
Serial No. 09/986,618 filed 09 Nov 01 |
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Relevant Publication: |
M. Urabe et al., Hum Gene Ther. 2002 Nov 1;
13(16): 1935-43C. Ding et al., J. Virol. 2002 Jan; 76 (1): 338-45 |
|
Licensing Contact: |
Susan A. Rucker J.D
Office of Technology
Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4478
Fax: (301) 402-0220
E-mail:
ruckers@od.nih.gov |
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