[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