[Federal Register Volume 75, Number 79 (Monday, April 26, 2010)]
[Notices]
[Pages 21634-21636]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-9640]
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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.
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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.
Peroxidase and Peroxidase Substrate Peptides (PSPs) for Treatment of
Inflammatory Disorders and Allergies
Description of Invention: NIH investigators have identified an
unexpected and previously unrecognized function of the peroxidase/dual
oxidase system in protecting the mucosal surfaces, such as in the
gastrointestinal and respiratory tracts. Specifically, NIH
investigators have shown that a peroxidase and a dual oxidase (Duox)
form a dityrosine network that decreases gut permeability to immune
elicitors and prevents activation of epithelial immunity in An. gambiae
mosquitoes. This technology provides for novel compositions that
enhance the formation of a dityrosine network on epithelial cells, such
as those found in the gastrointestinal and respiratory tract mucosa of
vertebrates, by forming a mucosal barrier on the epithelial surface
preventing or inhibiting epithelial cell-mediated inflammatory
responses (such as those associated with an inflammatory disease or an
allergic reaction). Exemplary compositions include a mammalian or plant
heme peroxidase and a peroxidase substrate peptide (PSP).
The compositions of this technology can be useful as therapeutics
for several diseases or disorders involving epithelial cell-mediated
inflammatory responses (e.g., inflammatory bowel diseases such as
Crohn's, and allergic disorders).
Development Status: Early stage.
Applications:
Therapeutics for autoimmune diseases.
Therapeutics for food allergies.
Inventors: Carolina Barillas-Mury, Sanjeev Kumar, and Alvara
Molina-Cruz (NIAID).
Related Publication: Kumar S, Molina-Cruz A, Gupta L, Rodrigues J,
Barillas-Mury C. A peroxidase/dual oxidase system modulates midgut
epithelial immunity in Anopheles gambiae. Science. 2010 Mar
26;327(5973):1644-1648. [PubMed: 20223948]
Patent Status: U.S. Provisional Application No. 61/308,249 filed 25
Feb 2010 (HHS Reference No. E-073-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Suryanarayana (Sury) Vepa, PhD, J.D.; 301-435-
5020; [email protected].
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases, Office of Technology Development, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
Peroxidase and Peroxidase Substrate Peptides (PSPs) for Treatment of
Inflammatory Disorders and Allergies. Please contact Dana Hsu at 301-
496-2644 for more information.
Reversible SNAP-Tag and CLIP-Tag Ligands for Live Cell Imaging
Description of Invention: Recently-developed protein tags enable
the specific covalent attachment of synthetic ligands, incorporating
fluorophores or other substituted groups, to fusion proteins containing
these tags. For example, SNAP and CLIP tags bind O\6\-benzylguanine-
containing and O2-benzylcytosine containing ligands respectively, which
can be derivatized with a wide variety of labels, including fluorescent
dyes, affinity probes, and cross-linkers. This system provides a
powerful tool to study a variety of highly dynamic processes within
cells, including protein trafficking, turnover, and complex formation.
However, a substantial limitation to this approach is that labeling is
irreversible, due to the formation of a covalent bond between the probe
and the protein tag.
The inventors have developed ligands that incorporate a disulfide
linkage between the O\6\-benzylguanine moiety and the label, allowing
selective release of the label from the tagged protein when treated
with a reducing agent. The inventors have shown that use of these
ligands in conjunction with cell-impermeable reducing agents allows
visualization of internalization and trafficking in live cells; these
ligands may also be used in other applications in which a cleavable
label would be desirable, such as protein purification. This strategy
is also applicable to other covalent protein tags, such as the ACP/MCP
protein tag system.
Applications:
Visualization of dynamic processes within cells, including
protein trafficking, turnover, and complex formation.
Live cell imaging.
Protein purification.
Advantages:
Allows for selective release of label.
Accommodates intra- or extra-cellular labeling, and dual
labeling.
Ligands may be derivatized with a wide variety of labels,
including fluorescent dyes, affinity probes, and cross-linkers.
Lower background fluorescence and higher contrast than
other systems, such as FlAsH.
Inventors: Nelson B. Cole and Julie G. Donaldson (NHLBI).
Related Publication: In preparation.
Patent Status: U.S. Provisional Application No. 61/312,814 filed 11
Mar 2010 (HHS Reference No. E-057-2010/0-US-01).
Licensing Status: Available for licensing.
[[Page 21635]]
Licensing Contact: Tara Kirby, PhD; 301-435-4426;
[email protected].
Composite Probes and Use Thereof in Super Resolution Microscopy
Description of Invention: The technology offered for licensing and
for further development is in the field of fluorescence microscopy.
More specifically, the invention describes and claims the composite
probes for super resolution optical techniques using super resolution
via transiently activated quenchers (STAQ). The composite probes
include a donor moiety and an acceptor moiety joined by a linker. The
acceptor moiety, when excited by incident radiation, is excited to a
state which, for example, absorbs in the donor emission region, such
that the acceptor moiety in its excited state quenches at least a
portion of the donor moiety emission. Other transiently activated
quenching mechanisms and moieties could accomplish the same task by
reducing donor population. Also disclosed are methods for irradiating a
selected region of a target material including the composite probe,
wherein the composite probe enables improved resolution by point spread
function modification.
Applications:
Ultrafine imaging for biomolecules, vesicles and
organelles, particularly of living biological samples, in biomedical
research.
Potential applications in clinical diagnostics.
Nanoscopic Lithography--STAQ composites could, in
principle, control polymerization of photoresist masks to make feature
sizes below 20nm.
Advantages: Fluorescence microscopy is an important tool in the
biomedical sciences allowing for the imaging of biological cells and
tissues. One limit of fluorescence microscopy is that the optics of a
microscope cannot create illuminated spots smaller than the diffraction
limit, thus limiting the usefulness of such techniques to image
biological samples at high resolution, generally below about 200 nm for
visible light. The technology presented here allows for improved
ultrafine imaging:
Imaging objects as small as 10 nm.
Narrow the point spread function.
STAQ uses less power, making live cell study practical at
theoretically high resolution.
Development Status:
The invention is fully developed.
Need to build multicolor palette that can be integrated
into a commercial microscope.
May need to make certain protein chimeras and
photoinitiators for validation.
Inventors: Jay R. Knutson and Gary L. Griffiths (NHLBI).
Relevant Publications:
1. Doose S, Neuweiler H, Barsch H, Sauer M. Probing polyproline
structure and dynamics by photoinduced electron transfer provides
evidence for deviations from a regular polyproline type II helix. Proc
Natl Acad Sci USA. 2007 Oct 30;104(44):17400-17405. [PubMed: 17956989]
2. Schuler B, Lipman EA, Steinbach PJ, Kumke M, Eaton WA.
Polyproline and the ``spectroscopic ruler'' revisited with single-
molecule fluorescence. Proc Natl Acad Sci USA. 2005 Feb 22;102(8):2754-
2759. [PubMed: 15699337]
3. Best RB, Merchant KA, Gopich IV, Schuler B, Bax A, Eaton WA.
Effect of flexibility and cis residues in single-molecule FRET studies
of polyproline. Proc Natl Acad Sci USA. 2007 Nov 27;104(48):18964-
18969. [PubMed: 18029448]
4. Sahoo H, Roccatano D, Hennig A, Nau WM. A 10-A spectroscopic
ruler applied to short polyprolines. J Am Chem Soc. 2007 Aug
8;129(31):9762-9772. [PubMed: 17629273]
5. Li L, Gattass RR, Gershgoren E, Hwang H, Fourkas JT. Achieving
lambda/20 resolution by one-color initiation and deactivation of
polymerization. Science. 2009 May 15;324(5929):892-893. [PubMed:
19359543]
6. Hell SW. Far-field optical nanoscopy. Science. 2007 May
25;316(5828):1153-1158. [PubMed: 19525330]
7. Masia F, Langbein W, Watson P, Borri P. Resonant four-wave
mixing of gold nanoparticles for three-dimensional cell microscopy. Opt
Lett. 2009 Jun 15;34(12):1816-1818. [PubMed: 19529713]
8. Schmidt R, Wurm CA, Punge A, Egner A, Jakobs S, Hell SW.
Mitochondrial cristae revealed with focused light. Nano Lett. 2009
Jun;9(6):2508-2510. [PubMed: 19459703]
Patent Status: U.S. Provisional Application No. 61/290,282 filed 28
Dec 2009 (HHS Reference No. E-253-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contacts: Uri Reichman, PhD, MBA; 301-435-4616;
[email protected] or Michael Shmilovich, Esq.; 301-435-5019;
[email protected].
Collaborative Research Opportunity: The National Heart, Lung and
Blood Institute (NHLBI) Laboratory of Molecular Biophysics (LMB) is
also seeking statements of capability or interest from parties
interested in collaborative partnerships to further develop, evaluate,
or commercialize this technology. Please contact Brian Bailey, PhD at
[email protected] for more information.
Substituted Triazine and Purine Compounds for the Treatment of Chagas
Disease and African Trypanosomiasis
Description of Invention: Parasitic protozoa are responsible for a
wide variety of infections in both humans and animals. Trypanosomiasis
poses health risks to millions of people across multiple countries in
Africa and North and South America. Visitors to these regions, such as
business travelers and tourists, are also at risk for contracting
parasitic diseases. There are two types of African trypanosomiasis,
also known as sleeping sickness. One type is caused by the parasite
Trypanosoma brucei gambiense, and the other is caused by the parasite
Trypanosoma brucei rhodesiensi. If left untreated, African sleeping
sickness results in death. Chagas disease, caused by Trypanosoma cruzi
(T. cruzi), affects millions of people in Mexico and South and Central
America. Untreated, Chagas disease causes decreased life expectancy and
can also result in death.
The subject invention covers novel triazine and purine compounds
that are inhibitors of key proteases (cruzain and Rhodesian) of the
parasites Trypanosoma brucei rhodesiensi and Trypanosoma cruzi,
respectively.
Applications: Prophylactic and therapeutic treatment of African
trypanosomiasis and Chagas disease
Advantages:
Novel compounds against the cysteine proteases, cruzain
and rhodesain.
Compounds possess low nanomolar inhibitory potential
against cruzain and rhodesain.
Development Status: In vitro and in vivo data are available upon
request and upon execution of an appropriate confidentiality agreement.
Inventors: Craig J. Thomas et al. (NHGRI).
Related Publication: BT Mott et al. Identification and optimization
of inhibitors of Trypanosomal cysteine proteases: cruzain, rhodesain,
and TbCatB. J Med Chem. 2010 Jan 14;53(1):52-60. [PubMed: 19908842]
Patent Status: PCT Application No. PCT/US2009/063078 filed 03 Nov
2009 (HHS Reference No. E-267-2008/0-PCT-02)
[[Page 21636]]
Licensing Status: Available for licensing.
Licensing Contact: Kevin W. Chang, PhD; 301-435-5018;
[email protected].
Collaborative Research Opportunity: The NIH Chemical Genomics
Center (NCGC) is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize appropriate lead compounds described in the
patent application. Please contact Dr. Craig J. Thomas
([email protected]) or Claire Driscoll ([email protected]),
Director of the NHGRI Technology Transfer Office, for more information.
Topical Formulation of Histone Deacetylase (HDAC) Inhibitors:
Treatments for Cancer and Immunological Skin Disorders
Description of Invention: This technology relates to topical
formulations of Histone Deacetylase (HDAC) inhibitors (HDIs) that can
be used to treat cancers such as cutaneous T-cell lymphoma (CTCL) and
skin disorders such as lupus, contact dermatitis, and drug eruptions
which are associated with malignant or autoreactive lymphocytes from
the immune system. HDIs, such as depsipeptide, have been demonstrated
to be effective against CTCL when administered internally but a topical
preparation may be more useful for treatment at earlier stages of the
disease.
HDIs are molecules that inhibit the activity of a group of enzymes
that remove small chemical groups called acetyl groups from many
different proteins, including proteins that regulate gene expression.
By altering the acetylation of these proteins, HDAC inhibitors can
induce tumor cell differentiation, cell cycle arrest, and cell death. A
variety of chemically distinct molecules exhibit HDAC inhibitory
activity and their potential as therapeutics for cancer and other
indications is being investigated. The HDI depsipeptide is a cyclical
peptide derived from a bacterium and is indicated as a second line
treatment for CTCL through intravenous administration. Development of a
topical preparation of depsipeptide and/or other HDAC inhibitors may
help reduce their toxicity and increase their effectiveness in treating
CTCL, other cancers, as well as other diseases.
Applications:
Use as a topical therapeutic for treatment of skin
lymphomas.
Use as a topical therapeutic for treatment of
immunological skin disorders.
Advantages:
HDIs such as vorinostat and depsipeptide have received
regulatory approval for clinical use in systemic treatment of CTCL.
Localized topical treatment reduces potential for adverse
reactions, compared to systemic treatments.
Clinical data illustrating the effectiveness of the
topical formulation of depsipeptide are available.
Development Status: In early stage of clinical development.
Market: There is a need for effective low toxicity therapies to
treat skin disorders due to activity of aberrant lymphocytes. CTCL is a
rare form (800-1,000 new cases per year) of lymphoma in which the
advanced disease can lead to disfigurement and pain. Patient mortality
usually results from infections arising from eventual breach of the
skin. An autoimmune disease, cutaneous lupus erythematosus accounts for
about 10% of all lupus cases (1.4 million people in U.S.) and produces
persistent skin lesions that may lead to scarring and hair loss. In the
U.S., skin eruptions caused by prescribed medications are estimated to
occur in approximately 2-5% of hospital patients. Most drug eruptions
are delayed-type immune reactions with lymphocyte-mediated
hypersensitivity which result in contact dermatitis, exanthematous
reactions, and photoallergic reactions. A topical formulation of HDIs
has potential of ameliorating the symptoms of these conditions.
Inventors: Susan Bates et al. (NCI).
Publication: Piekarz RL et al. Phase II multi-institutional trial
of the histone deacetylase inhibitor romidepsin as monotherapy for
patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009 Nov
10;27(32):5410-5417. [PubMed: 19826128]
Patent Status: U.S. Patent Application No. 12/064,220 filed 19 Feb
2008 (HHS Reference No. E-238-2005/0-US-07) and foreign counterparts in
Europe, Canada, Australia and Japan.
Licensing Status: Available for licensing.
Licensing Contact: Sabarni Chatterjee, PhD; 301-435-5587;
[email protected].
Collaborative Research Opportunity: The Center for Cancer Research,
Medical Oncology Branch and Affiliates, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize topical therapy
using HDIs. Please contact John Hewes, PhD at 301-435-3131 or
[email protected] for more information.
Variable Curve Catheter
Description of Invention: The invention provides a deflectable tip
guiding device, such as a 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 permits a more comprehensive ability to navigate
complex geometric pathways in patient's body and enables better access
to 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 variety of interventional devices for delivery of drugs,
cells, energy, or sutures through complex trajectories of the body.
Inventors: Robert J. Lederman and Parag V. Karmarkar (NHLBI).
Patent Status: U.S. Patent Application No. 10/534,362 filed 07 Nov
2005 (HHS Reference No. E-035-2003/0-US-03).
Licensing Status: Available for licensing.
Licensing Contact: Jeffrey A. James; 301-435-5474;
[email protected].
Collaborative Research Opportunity: The NHLBI Translational
Medicine Branch Cardiovascular Intervention Program is seeking
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
technology for image-guided cardiovascular interventions. Please
contact Peg Koelble at [email protected] for more information.
Dated: April 20, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-9640 Filed 4-23-10; 8:45 am]
BILLING CODE 4140-01-P