2011-14261. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

X-Clometer: Optimizing Portable Radiography

Description of Technology: The technology offered for licensing and commercial development relates to a method and apparatus that can significantly improve the diagnostic performance of portable chest (CXR) and abdominal x-rays. This device quantifies angulation of a patient to provide for a better comparison of day-to-day improvement.

The portable CXR is one of the most commonly requested diagnostic medical tests around the world. They are performed nearly daily on some of the sickest patients in hospitals. Paradoxically, it is well documented that portable radiography of the chest is inconsistent and often inadequate.

An upright projection best evaluates effusions, rules out free air, or detects air-fluid levels. Optimally, the images are obtained at similar angles each day, even if not erect, to allow accurate comparisons and assessment of change. It is well documented that portable radiography of the chest is inconsistent and often inadequate. To achieve optimal quality of the exam the technologist attempts the most upright projection; balanced with patient condition and ability to achieve this often impossible task.

Applications: Portable chest and abdominal x-rays performed at patient's hospital bedside.

Advantages

• Currently, there is no quantitative marker to indicate degree of the upright position. Prior markers with small ball bearings sinking to a small circle only indicate if the patient is supine or not. This technology introduces a simple dynamic marker that can quantify the angle at a glance for the radiologist to best compare patient condition over time. This device objectively quantifies cassette angle with a ball bearing in a cylindrical tube with markers to indicate upright position in degrees.
• The technology improves performance of CXR, allowing reliable comparisons of patient condition over time. Thus, better therapies can be planned and unnecessary CT (Computerized Tomography) can be prevented.
• The technology improves care for Intensive Care Unit patients, as developing effusion and the need for immediate drainage (as one of many examples) can be more effectively assessed with the present apparatus. A widespread use of the device will save lives through improved diagnosis and comparison of effusions.

Development Status

• A performance of a visual prototype was demonstrated. The visual prototype was imaged at 5 selected angles with a chest phantom. Initial in-vitro results demonstrate that angles can be quantified to within 30 degrees.
• Improved prototypes with more accuracy are currently being manufactured for patient use. In-vivo studies will soon be underway to validate clinical utility.

Inventors: Les R. Folio (CC) and Lucas S. Folio.

Relevant Publications

1. Wandtke JC. Bedside chest radiography. Radiology. 1994; 190:1-10. [PMID: 8043058]

2. Pneumatikos I, Bouros D. Pleural effusions in critically ill patients. Respiration. 2008; 76(3):241-248. [PMID: 18824883]

3. Mattison LE, et al. Pleural effusions in the medical ICU: prevalence, causes, and clinical implications. Chest. 1997 Apr;111(4):1018-1023. [PMID: 9106583]

4. Fartoukh M, et al. Clinically documented pleural effusions in medical ICU patients: how useful is routine thoracentesis? Chest. 2002 Jan;121(1):178-184. [PMID: 11796448]

5. Bekemeyer WB, et al. Efficacy of chest radiography in a respiratory intensive care unit. A prospective study. Chest. 1985 Nov; 88(5): 691-696. [PMID: 4053711]

6. Tocino I. Chest imaging in intensive care unit. Eur J Radiol 1996 Aug;23(1):46-57. [PMID: 8872073]

Patent Status: U.S. Provisional Application No. 61/452,364 filed March 14, 2011 (HHS Reference No. E-063-2011/0-US-01).

Licensing Status: Available for licensing.

Licensing Contacts

• Uri Reichman, PhD, MBA; 301-435-4616; [e-mail].
• Michael Shmilovich, Esq.; 301-435-5019; [e-mail].

Collaborative Research Opportunity: The NIH Clinical Center, Radiology and Imaging Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize X-Clometer. Please contact Ken Rose, PhD at 301-435-3132 or [e-mail] for more information.

HIF1α-Targeted Therapy for Diabetes and Obesity

Description of Technology: This technology describes the use of hypoxia inducible factor 1 alpha (HIF1α) inhibitors for the reduction of body weight and treatment of diabetes.

In obesity, the rapid expansion of adipose tissue outpaces the oxygen supply, resulting in hypoxia. HIF1α, a transcription factor that plays an essential role in cellular and systemic responses to low oxygen levels, is activated in these tissues, and causes inflammation that has been linked to insulin resistance and other metabolic dysfunction.

To examine the role of hypoxia in obesity and insulin resistance, investigators at the National Cancer Institute disrupted the HIF1α gene (or its dimerization partner, the HIF1β) in the adipose tissue of transgenic mice, and found that these mice were protected from obesity and insulin resistance when fed a high-fat (western) diet. In further experiments, administration of an HIF1α inhibitor to wild-type mice achieved similar reductions in fat mass and insulin resistance, as well as other indicators of metabolic disease. Thus, HIF1α inhibitors represent promising new leads for obesity and diabetes therapeutics.

Applications: HIF1α-targeted therapies for type 2 diabetes and obesity.

Development Status: Proof of concept has been demonstrated in mouse models.

Inventors: Frank J. Gonzalez and Changtao Jiang (NCI).

Relevant Publications: In preparation.

Patent Status: U.S. Provisional Application No. 61/423,936, filed December 16, 2010 (HHS Reference No. E-018-2011/0-US-01).

Licensing Status: Available for licensing.

Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; [e-mail]

Collaborative Research Opportunity: The Center for Cancer Research, Laboratory of Metabolism (LM), is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HIF1α inhibitors that can be used for the treatment of obesity and type 2 diabetes. The LM will be willing to collaborate with parties to evaluate potential inhibitors using the HIF1α adipose-specific knockout mice. Please contact John Hewes, PhD at 301-435-3121 or [e-mail] for more information.

Synergistic Combination Agent (Ceramide and Vinca Alkaloids) for Cancer Therapy

Description of Technology: Work by the Nanotechnology Characterization Laboratory (NCL), a joint initiative of NCI, NIST, and the FDA, has led to the discovery of a novel combination chemotherapy. This combination is shown to have synergistic effects on cytotoxicity to cancer cells in vitro, and to cause a substantial decrease in tumor growth in preclinical tumor models in vivo. Combination therapy using these agents may enhance the response rate of different cancers to these drugs and may significantly reduce side effects by permitting a lower therapeutic dose to be administered.

The instant invention relates to a novel combination of ceramide and vinca alkaloids, which synergistically decrease cancer cell growth without increasing the toxicity profile compared to the individual drugs. The drug combination has been rigorously evaluated in both in vitro and in vivo models of cancer, and a dose range-finding toxicology study has been conducted in rodents.

This combination induces cell death via a novel mechanism (induction of autophagy with simultaneous blockade of autophagy flux). This mechanism appears to impart selectivity of the therapy to cancer cells.

Available for licensing are methods to use the combination therapy for cancer treatment.

Applications: Cancer treatment, especially for cancers sensitive to treatment with vinca alkaloids such as breast cancer, testicular cancer, head and neck cancer, Hodgkin's lymphoma, and non-small cell lung cancer.

Advantages: Vinca alkaloids alone at therapeutic doses produce the standard side effects of cancer chemotherapy. The vinca alkaloid-ceramide combination can be administered at lower doses with comparable efficacy and may allow for more frequent dosing (metronomic dosing). The novel mechanism of action of this combination appears to be selective to cancer cells.

Development Status: The drug combination has been evaluated in both human hepatocarcinoma models (in vitro cell culture assays) and human colon cancer models (in vivo mouse xenografts). Additional in vivo studies with other cancer types and early stage preclinical toxicology studies are being planned.

Inventors: Stephan T. Stern, Scott E. McNeil, Pavan Adiseshaiah (NCL/NCI)

Patent Status: U.S. Provisional Patent Application No. 61/451,925 filed March 11, 2011 (HHS Reference No. E-007-2011/0-US-01)

Licensing Status: Available for licensing or partnering for further development.

Licensing Contact: Betty B. Tong, PhD; 301-594-6565; [e-mail]

Collaborative Research Opportunity: The SAIC Frederick, Nanotechnology Characterization Laboratory, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a ceramide and vinca alkaloid combination therapy for treatment of cancer. Please contact John Hewes, PhD at 301-435-3121 or [e-mail] for more information.

Novel Small Molecule Inhibitors for the Treatment of Huntington's Disease

Description of Technology: This technology is a collection of small molecules screened for their ability to prevent or reduce the cytotoxic effects of the protein, Huntingtin. Huntington's disease is a neurodegenerative disorder due to a dominantly acting expansion of a CAG trinucleotide repeat in exon 1 of the Huntington (HTT) gene resulting in production of the altered (mutant) protein Huntingtin, which has a long chain of polyglutamine (poly Q) attached to the exon 1 encoded protein sequence. Clinical and statistical analyses have shown that an increased number of poly Q repetition correlates with the probability of developing the disease, with 36 to 40 being the accepted cut off number for developing the disorder with high probability. It is known that poly Q repetitions impact the physical properties of Huntingtin and cause it to produce aggregates that precipitate and form inclusion bodies, which are toxic to the neuronal cells. The compounds of this invention have been screened multiply in a neuronal cell model of Huntington's disease containing an HTT with an expanded repeat in exon 1 of 103 Qs for their ability to inhibit cytotoxicity and protein aggregation.

Applications: Treatment of Huntington's disease.

Development Status: Early development.

Inventors: Juan Marugan, Joshua McCoy, Samarjit Patnaik, Steven Titus, Wei Zheng, Noel T. Southall, Wenwei Huang (NHGRI).

Relevant Publications: None.

Patent Status: U.S. Provisional Application No. 61/388,482 filed September 30, 2010 (HHS Reference No. E-258-2010/0-US-01).

Licensing Status: Available for licensing.

Licensing Contact: Steve Standley, PhD; 301-435-4074; [e-mail].

Collaborative Research Opportunity: The National Center for Translational Therapeutics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology further. Please contact Ms. Lili Portilla at [e-mail] for more information.

Dated: June 3, 2011.

Richard U. Rodriguez,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.