[Federal Register Volume 73, Number 219 (Wednesday, November 12, 2008)]
[Notices]
[Pages 66912-66913]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-26790]


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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.

Radiation Induced and Targeted Chemotherapy

    Description of Technology: The invention relates to a novel method 
of targeted chemotherapy for the treatment of cancer using hydrophobic 
photoactivatable compounds like 1,5-iodoanpthylazide (INA) and its 
analogues. The invention evolved from the discovery that electron dense 
atom-containing photoactivatable compounds can be activated by 
radiation (i.e., by x-rays and/or ultrasound) to form reactive 
intermediates that are highly toxic to living cells. Such compounds are 
termed ``radiation-activatable'' compounds. These radiation-activatable 
compounds do not become toxic until activated by radiation which allows 
for the targeting of the toxic compound by irradiation. Preliminary in 
vitro data show that INA and its derivatives can quickly and 
efficiently kill tumor cell lines upon irradiation.
    Applications: Cancer Treatment.
    Advantages: Novel method of cancer treatment.
    Development Status: In vitro data can be provided upon request.
    Market: Cancer Therapy.
    Inventors: Yossef Raviv et al. (NCI).
    Patent Status: U.S. Provisional Application No. 61/026,654 filed 06 
Feb 2008 (HHS Ref. No. E-256-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Kevin W. Chang, PhD, 301-435-5018, 
[email protected].

Small-Molecule Modulators of the Thyroid-Stimulating Hormone (TSH) 
Receptor

    Description of Technology: The thyroid gland plays a major role in 
the body, secreting hormones that regulate the metabolic rate, 
production of other hormones, and the growth and maturation of body 
tissues. Thyroid disorders affect energy metabolism, neurological 
state, fertility, cardiovascular condition, and other body functions. 
In patients with hyperthyroidism, or an overactive thyroid gland, the 
disease is often caused by autoimmune over-stimulation of the thyroid 
gland (Graves' disease), or by thyroid tumors. Drugs currently used for 
short-term treatment of hyperthyroidism inhibit synthesis of thyroid 
hormones, although long-term treatment usually requires removal of the 
thyroid gland by surgery or administration of radioiodine. 
Hypothyroidism, or an underactive thyroid gland, can be caused by 
autoimmune disease, atrophy of the thyroid gland, or through a 
deficiency of thyroid-stimulating hormone (TSH). TSH, produced by the 
pituitary gland, binds to the TSH receptor in the thyroid to stimulate 
thyroid hormone production. Hypothyroidism is typically treated by 
direct replacement of the thyroid hormones.
    The inventors have discovered a series of low-molecular weight 
compounds that act as TSH receptor antagonists (inhibitors) or agonists 
(activators). Antagonists of the TSH receptor could be used to treat 
hyperthyroidism, with the advantage of directly downregulating the TSH 
receptor, rather than inhibiting thyroid hormone synthesis. Agonists of 
the TSH receptor could be used to monitor thyroid activity and 
potential cancer recurrence in patients who have been treated for 
thyroid cancer, and may also be useful for treatment of certain forms 
of hypothyroidism. Additionally, some compounds in this family may be 
useful for treatment of fertility and reproductive disorders involving 
the luteinizing hormone/choriogonadotropin (LH/CG) receptor and the 
follicle-stimulating hormone (FSH) receptor, which are structurally 
related to the TSH receptor.
    Applications:
     Development of therapeutics for hyperthyroidism or 
hypothyroidism.
     Development of diagnostic tools for evaluation of thyroid 
cancer patients.
     Development of therapeutics for infertility.
    Market: Approximately 1 in 13 Americans suffers from a thyroid

[[Page 66913]]

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. 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.
    2. S Titus, S Neumann,W Zheng, N Southall, S Michael, C Klumpp, A 
Yasgar, P Shinn, CJ Thomas, J Inglese, MC Gershengorn, CP Austin. 
Quantitative high throughput screening using a live cell cAMP assay 
identifies small molecule agonists of the TSH receptor. J Biomol 
Screen. 2008 Feb;13(2):120-127.
    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 31 Jul; published online ahead of 
print, doi:10.1210/en.2008-0836.
    Patent Status: International Patent Application No. PCT/US2007/
011951 filed 17 May 2007 (HHS Reference No. E-223-2006/0-PCT-02).
    Licensing Status: This technology is available for exclusive, co-
exclusive, or nonexclusive licensing.
    Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; 
[email protected].

Methods for Accurately Measuring and Regulating Bound Adrenomedullin

    Description of Technology: This technology involves an array of 
applications relating to a key discovery regarding adrenomedullin-
binding proteins.
    Adrenomedullin (AM) is a ubiquitously expressed peptide first found 
in human pheochromocytoma, a cancer of the adrenal medulla. AM appears 
to function as a universal autocrine growth factor, driving cell 
proliferation, as a vasodilator, as a mechanism for protecting cells 
against oxidative stress in hypoxic injury, and as a dose-dependent 
inhibitor of insulin secretion. Accordingly, methods for measuring in 
vivo levels of AM accurately, and methods for regulating the activity 
of available AM, may be critically important in diagnosis and treatment 
of many conditions, such as heart disease, pulmonary disease, liver 
cirrhosis, cancer, diabetes, sepsis, and inflammation.
    The present technology centers on the observation that AM binds to 
Complement Factor H (CFH) in vivo. Without a means to determine the 
amount of AM that is bound to CFH, measurements of AM are inaccurate, 
and therapies focused on the AM-CFH complex may have advantages 
compared to therapies focused on AM alone.
    The technology includes methods for measuring and utilizing 
purified AM-binding proteins, or functional portions thereof, to 
diagnose, treat, and monitor AM-related diseases. A second aspect 
includes the identification and isolation of the AM-CFH complex. 
Antibodies and small-molecule antagonists (which can down-regulate the 
function of AM, CFH, and the AM-CFH complex) have also been isolated. 
Collectively, the technology provides methods for diagnosis and 
treatment of conditions such as cancer, diabetes, or other conditions 
that are influenced by AM levels.
    Applications and Advantages:
     More accurate measurements of serum adrenomedullin than 
current tests
     Antibodies targeting AM-CFH decrease bioavailable AM, 
which may be useful in suppressing angiogenesis in cancers
     Antibodies targeting the CFH binding site increase 
bioavailable AM, which may be useful in therapies involving 
vasodilation, angiogenesis, and tolerance for hypoxic or ischemic 
injury during stroke or myocardial infarction
    Development Status: In vivo and in vitro proof of concept data are 
available.
    Inventors: Frank Cuttitta et al. (NCI).
    Related Publications:
    1. AJ Dwivedi et al. Adrenomedullin and adrenomedullin binding 
protein-1 prevent acute lung injury after gut ischemia-reperfusion. J 
Am Coll Surg. 2007 Aug;205(2):284-293.
    2. D Ajona et al. Down-regulation of human complement factor H 
sensitizes non-small cell lung cancer cells to complement attack and 
reduces in vivo tumor growth. J Immunol. 2007 May 1;178(9):5991-5998.
    3. A Martinez et al. Mapping of the adrenomedullin-binding domains 
in human complement factor H. Hypertens Res. 2003 Feb;26 Suppl:S55-59.
    4. R Pio et al. Complement factor H is a serum-binding protein for 
adrenomedullin, and the resulting complex modulates the bioactivities 
of both partners. J Biol Chem. 2001 Apr 13;276(15):12292-12300.
    Patent Status: HHS Reference No. E-256-1999/0-
     U.S. Patent Application No. 11/530,441 filed 08 Sept 2006, 
claiming priority to 10 Sept 1999
     Foreign counterparts in Australia, Canada, France, 
Germany, Great Britain, Italy, Spain, and Portugal
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
(NCI)/Angiogenesis Core Facility is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize AM-CFH complex involvement with 
tumor angiogenesis and identifying potential Rxs to disrupt this 
effect. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

    Dated: November 3, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E8-26790 Filed 11-10-08; 8:45 am]
BILLING CODE 4140-01-P