[Federal Register Volume 75, Number 200 (Monday, October 18, 2010)]
[Notices]
[Pages 63841-63843]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-26160]


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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.

Mouse Anti-Mouse CXCL9 (Mig) Monoclonal Antibodies

    Description of Invention: This technology describes monoclonal 
antibodies against mouse chemokine (C-X-C motif) ligand 9 (CXCL9), also 
known as Monokine induced by gamma interferon (Mig). CXCL9 is a 
secreted protein that functions to attract white cells and increased 
expression of CXCL9 has been linked to several diseases. The inventors 
at the NIH generated over 100 anti-mouse CXCL9 antibodies from a CLXL9/
Mig knockout mouse and further characterized several antibodies to show 
neutralization of CXCL9. As such, these antibodies could be used to 
measure concentrations of mouse CLXL9 in laboratory samples and block 
the activity of CXCL9 in injected mice. These antibodies are suitable 
for ELISA and Western blot. The antibodies have not been tested in flow 
cytometry or immunohistochemistry, but may also be useful for these 
applications.

Applications

     ELISA assays for detection and measurement of CXCL9.
     Neutralization of CXCL9 activity in mouse models and in 
vitro assays to study the role of CXCL9 in immune response and disease.
    Advantages: Can be used in mice without eliciting endogenous 
antibodies reacting against the injected anti-CXCL9.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Joshua M. Farber and Hongwei H. Zhang (NIAID).
    Patent Status: HHS Reference No. E-198-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.

Licensing Status

    Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].

Signal-to-Noise Enhancement in Imaging Applications Using a Time-Series 
of Images

    Description of Invention: The invention offered for licensing 
relates to the field of imaging and specifically to the field of 
medical imaging. The apparatus and method of the invention provide for 
noise reduction in imaging applications that use a time-series of 
images. In one embodiment of the invention, a time-series of images is 
acquired using a same imaging protocol of the same subject area, but 
the images are spaced in time by one or more time intervals (e.g., 1, 
2, 3 * * * seconds apart). A sub-region is projected across all of the 
images to perform a localized analysis (corresponding X-Y pixels or X-
Y-Z voxels are analyzed across all images) that identifies temporal 
components within each sub-region. Subsequently, within the sub-
regions, only those temporal components are selected whose amplitude is 
above a predetermined amplitude threshold. The images are then 
reconstructed using the sub-regions with reduced components. A maximal-
intensity-projection (MIP) is applied in the temporal domain (tMIP) in 
order to obtain a single image with reduced noise (this can be done 
either at the sub-region level or at the reconstructed image level). 
The technology can be applied to a broad spectrum of medical imaging 
technologies such as MRI, X-Ray, CT and others.
    Applications: Medical imaging and diagnostics applied to MRI, X-
Ray, CT scans or other imaging modalities including PET, SPECT, 
ultrasound or optical.
    Advantages: Enhancing signal-to-noise of medical imaging 
techniques.

Development Status

     Proof of concept has been demonstrated. Data is available.

[[Page 63842]]

     Need to acquire further data to establish clinical utility 
of the method and to further optimize the protocol.

Market

     According to market research reports the market for 
medical imaging equipment industry in the United States is 
approximately $9.0 billion now and has been growing by approximately 
7.6% annually.
     The United States market for computed tomography (CT) 
scanning systems is estimated to touch $3.6 billion by the end of 2009. 
The U.S. accounts for over 50.0% of the worldwide market.
     Worldwide MRI equipment market is estimated to reach $5.5 
billion by 2010, according to new report by Global Industry Analysts, 
Inc. (http://www.strategyr.com/Magnetic_Resonance_Imaging_MRI_Equipment_Market_Report.asp). In the United States the market for 
such equipment is estimated at $1.9 billion for 2008, as stated the 
same report. The very high-field MRI systems market in the United 
States is projected to reach $968 million by the year 2010. Very High-
Field Systems also represent the fastest growing segment, as hospitals 
and clinics upgrade old equipment with state-of-the-art systems.
     Enhancements in imaging technologies to achieve better 
image clarity, reliability and speed are being constantly pursued by 
medical imaging companies. Technologies that offer such improvements 
therefore present excellent commercial potential. Thus the subject 
invention which can be applied in a broad spectrum of imaging 
technologies offers such good commercial potential.
    Inventors: Han Wen and Vinay Pai (NHLBI).

Relevant Articles

    1. Fish DA, Grochmalicki J, Pike ER. Scanning singular-value-
decomposition method for restoration of images with space-variant blur. 
J Opt Soc Am A, 13(3), pp. 464-469, March 1996.
    2. Du X, Dunxu Y, Cuihua L, Jing L. ``A novel approach to SVD-based 
image filtering improvement,'' International Conference on Computer 
Science and Software Engineering, vol 6, pp. 133-136, 2008.
    Patent Status: U.S. Provisional Application No. 61/266,442 filed 03 
Dec 2009 (HHS Reference No. E-292-2009/0-US-01).
    Related Technologies: Image denoising techniques such as singular 
value decomposition (SVD).
    Licensing Status: Available for licensing.

Licensing Contacts

     Uri Reichman, PhD, MBA; 301-435-4616; [email protected].
     John Stansberry, PhD; 301-435-5236; [email protected].
    Collaborative Research Opportunity: The National Heart, Lung, and 
Blood Institute is seeking statements of capability or interest from 
parties interested in collaborative research to implement the 
technology described above on specific commercial platforms. Please 
contact Denise Crooks, PhD at 301-435-0103 or via e-mail at 
[email protected] for more information.

Inverse Agonists of the TSH Receptor for the Treatment of Thyroid 
Cancer and Hyperthyroidism

    Description of Invention: This technology features small molecule 
inverse agonists of the thyroid-stimulating hormone (TSH) receptor that 
may be readily synthesized, and are likely to prove effective for oral 
administration. These compounds may potentially be used to treat 
recurrent thyroid cancer and some cases of hyperthyroidism, and also 
represent unique tools for investigating the role of TSH receptor 
signaling in these diseases.
    According to the National Cancer Institute, over 37,000 new cases 
of thyroid cancer were diagnosed in the United States in 2008. 
Approximately 10% to 30% of patients thought to be disease-free after 
initial treatment will develop recurrent cancer or metastases, and 
unless the recurrence is detected early, the prognosis is generally 
poor.
    As the TSH receptor is known to stimulate proliferation of thyroid 
cancer cells, it has been suggested that suppression of basal TSH 
receptor signaling may improve outcomes in the treatment of recurrent 
thyroid cancer. The compounds disclosed in this technology suppress 
basal signaling by the TSH receptor, and are thus excellent candidates 
for a suppression-based treatment approach.

Applications

     Lead compounds for the development of therapeutics for 
recurrent or metastatic thyroid cancer.
     Lead compounds for the development of therapeutics for 
hyperthyroidism associated with constitutive TSH receptor signaling.
     Tool for probing the role of basal TSH signaling in normal 
endocrine function and in disease states.
    Development Status: In vitro studies in primary human thyrocytes 
have been performed.
    Inventors: Marvin C. Gershengorn and Susanne Neumann (NIDDK); 
Wenwei Huang and Craig J. Thomas (NHGRI).

Relevant Publications

    1. S Neumann, W Huang, E Eliseeva, S Titus, CJ Thomas, MC 
Gershengorn. A small molecule inverse agonist for the human thyroid-
stimulating hormone receptor. Endocrinology. 2010 Jul;151(7):3454-3459. 
[PubMed: 20427476]
    2. S Moore, H Jaeschke, G Kleinau, S Neumann, S Costanzi, JK Jiang, 
J Childress, BM Raaka, A Colson, R Paschke, G Krause, CJ Thomas, MC 
Gershengorn. Evaluation of small-molecule modulators of the luteinizing 
hormone/choriogonadotropin and thyroid stimulating hormone receptors: 
Structure-activity relationships and selective binding patterns. J Med 
Chem. 2006 Jun 29;49(13):3888-3896. [PubMed: 16789744]
    3. S Neumann, G Kleinau, S Costanzi, S Moore, BM Raaka, CJ Thomas, 
G Krause, MC Gershengorn. A low molecular weight antagonist for the 
human thyrotropin receptor with therapeutic potential for 
hyperthyroidism. Endocrinology. 2008 Dec;149(12):5945-5950. [PubMed: 
18669595]
    Patent Status: U.S. Provisional Application No. 61/322,138 filed 08 
Apr 2010 (HHS Reference No. E-067-2010/0-US-01).

Related Technologies

     HHS Reference No. E-223-2006/0.
     HHS Reference No. E-223-2006/1.
     HHS Reference No. E-284-2008/0.
    Licensing Status: Available for licensing.
    Licensing Contact: Tara Kirby, PhD; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The NIDDK Office of Technology 
Transfer and Development is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop inverse agonists of the TAS receptor. Please contact Marguerite 
J. Miller at 301-496-9003 or [email protected] for more 
information.

Small-Molecule TSH Receptor Modulators for Diagnosis and Treatment of 
Thyroid Disease and Cancer

    Description of Invention: NIH investigators have discovered a 
series of low molecular weight thyroid-stimulating hormone (TSH) 
receptor modulators for use in evaluation and treatment of thyroid 
diseases, including thyroid cancer, hypothyroidism, and 
hyperthyroidism. Certain compounds

[[Page 63843]]

encompassed by this technology are more potent and/or more specific TSH 
receptor activators than currently-available compounds; also, as small 
molecules, these compounds are orally available and are expected to be 
less costly and more straightforward to produce than recombinant 
protein counterparts currently on the market.
    According to the National Cancer Institute, over 37,000 new cases 
of thyroid cancer were diagnosed in the United States in 2008, and over 
1,500 people died of this disease. These numbers reflect a progressive 
increase in the incidence of thyroid cancer over the last several 
years. Because most cases of thyroid cancer are diagnosed in patients 
between the ages of 20 and 54, these patients will undergo decades of 
follow-up monitoring after cancer treatment. For the last decade, 
recombinant TSH protein has been used in this follow-up to increase 
detection sensitivity for recurrent or metastatic thyroid cancer, and 
to eliminate side effects associated with withdrawal of hormone 
replacement therapy. A small-molecule TSH receptor agonist encompassed 
by this technology would have utility similar to recombinant TSH, but 
would have several distinct advantages. For example, as a small 
molecule, rather than a recombinant protein, such a compound would be 
orally available, and would be less difficult and expensive to produce. 
These compounds are also more potent and/or specific for the TSH 
receptor than other known small-molecule TSH receptor agonists. In 
addition to use in thyroid cancer screening, these compounds may also 
be useful for adjunctive treatment (with radioactive iodide) of thyroid 
cancer, and certain forms of hypothyroidism.
    Hyperthyroidism, or an overactive thyroid gland, affects about 1% 
of people in the United States and is often caused by autoimmune over-
stimulation of the thyroid gland (Graves' disease), or by thyroid 
tumors. Drugs currently used for treatment of hyperthyroidism inhibit 
synthesis of thyroid hormones; the TSH receptor antagonist compounds 
encompassed by this technology have the advantage of directly 
inhibiting activity of the TSH receptor, rather than inhibiting thyroid 
hormone synthesis.

Applications

     Diagnostic tools for evaluation and treatment of thyroid 
cancer.
     Therapeutics for thyroid cancer, hyperthyroidism, and 
hypothyroidism.
    Market: Approximately 1 in 13 Americans suffers from a thyroid 
disorder, and 10 million have a thyroid-related condition that requires 
ongoing immunodiagnostic monitoring.
    Development Status: Early stage.
    Inventors: Marvin C. Gershengorn et al. (NIDDK)

Publications

    1. Moore S, Jaeschke H, Kleinau G, Neumann S, Costanzi S, Jiang JK, 
Childress J, Raaka BM, Colson A, Paschke R, Krause G, Thomas CJ, 
Gershengorn MC. Evaluation of small-molecule modulators of the 
luteinizing hormone/choriogonadotropin and thyroid stimulating hormone 
receptors: structure-activity relationships and selective binding 
patterns. J Med Chem. 2006 Jun 29;49(13):3888-3896. [PubMed: 16789744]
    2. Neumann S, Kleinau G, Costanzi S, Moore S, Raaka BM, Thomas CJ, 
Krause G, Gershengorn MC. A low molecular weight antagonist for the 
human thyrotropin receptor with therapeutic potential for 
hyperthyroidism. Endocrinology 2008 Dec;149(12):5945-5950. [PubMed: 
18669595]
    3. Unpublished data are also available for review under a CDA.

Patent Status

    HHS Reference Nos. E-223-2006/0 and E-223-2006/1--
     International Patent Application No. PCT/US2007/011951 
filed 17 May 2007, which published as WO 2007/136776 on 29 Nov 2007
     National Phase entered in Australia, Canada, Europe, 
Japan, and the United States
    HHS Reference No. E-284-2008/0--
     International Patent Application No. PCT/US2008/011958 
filed 20 Oct 2008.
    Licensing Status: Available for licensing.
    Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The NIDDK Clinical 
Endocrinology Branch is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize small molecule TSH receptor modulators. 
Please contact Marguerite J. Miller at 301-496-9003 or 
[email protected] for more information.

    Dated: October 12, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-26160 Filed 10-15-10; 8:45 am]
BILLING CODE 4140-01-P