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Government-Owned Inventions; Availability for Licensing

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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 Start Printed Page 16692for 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.

Cell Line PE, Developed From Mouse Skin Tumors, Demonstrates Unique Qualities

Description of Technology: Available for licensing is the mouse skin tumor cell line PE. These skin tumor cells were isolated from papilloma cells induced by chemical carcinogens. The PE cell lines differ from normal keratinocytes in their ability to maintain a proliferating population under conditions favoring terminal differentiation, their consistent proliferative response to phorbol esters under these same conditions, and their reduced sensitivity to phorbol ester-induced terminal differentiation. All of these properties should provide a growth advantage to these cells during tumor promotion. The PE cell line is one of the studied cell lines.

Applications: The PE cell lines could be used for assays for cancer treatment and prevention or study of several aspects of cutaneous biology.

PE cells could be used in the cosmetic industry to study response to cosmaceuticals or fragrances.

PE cells also demonstrated robust expression of phase 2 detoxification enzymes in response to a variety of inducing agents.

Advantage: The various properties of papilloma cells (PE cell line) differ from keratinocytes which will provide a growth advantage to the PE cell lines during tumor promotion.

Market: In the U.S., there was an estimated 59,940 new cases of melanoma cancer in 2007 and an estimated 8,110 melanoma deaths in 2007. There were nearly one million cases of non-melanoma skin cancers diagnosed in the U.S. in 2007.

Cosmetics industry is a $30 billion industry with a 20% annual growth rate.

Inventors: Stuart H. Yuspa and Henry Hennings (NCI).

Publication: SH Yuspa et al. Cultivation and characterization of cells derived from mouse skin papillomas induced by an initiation-promotion protocol. Carcinogenesis 1986 Jun;7(6):949-958.

Patent Status: HHS Reference No. E-100-2008/0—Research Tool. Patent protection is not being sought for this technology.

Availability: Available for non-exclusive licensing.

Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; madua@mail.nih.gov.

Mucin Binding Lectin Imaging Agents for Colonic Polyp Imaging

Description of Technology: Available for licensing and commercial development is an imaging agent specific for colonic polyps that overexpress glycoprotein α-L-fucose containing mucins. Colon cancer is the second leading cause of cancer related deaths in the United States. The legume protein Ulex europaeus agglutinin I (UEA-1) has shown high specificity to α-L-fucose glycoproteins. Colonic mucosal neoplasia and/or polyps with high surface expression of α-L-fucosyl terminal residues can be specifically targeted with UEA-1 contrast agents. In one example, a computer tomography (CT) agent made from Iodine-127 (127 I) labeled UEA-1 (I-UEA-1) and encapsulated into polymeric liposome nanoparticles was used to image murine colonic polyps. Ideally, the inventors envision a contrast agent that can be administered orally (e.g., liquid or pill form) and that would eliminate a patient's need to drink harsh enema/contrast solutions prior to CT imaging.

Applications: Colon cancer; Cancer Imaging; Contrast Agents; CT colonography

Inventors: Ronald M. Summers, Jianwu Xie, Celeste Roney (CC).

Relevant Publications:

1. J Xie et al. Oral contrast enhanced MicroCT virtual colonoscopy of APC knockout mouse colon polyp model. Gastroenterology. 2007 Apr;132(4), Suppl. 1, Abstract No. M1063, pp A-353-A-354.

2. C Roney et al. Glycoprotein expression by adenomatous polyps of the colon. SPIE 2008 (in press).

3. SD O'Connor et al. Oral contrast adherence to polyps on CT colonography. J Comput Assist Tomogr. 2006 Jan-Feb;30(1):51-57.

Patent Status: U.S. Provisional Application filed 15 Feb 2008 (HHS Ref. No. E-254-2007/0-US-01).

Licensing Status: Available for licensing.

Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5010; shmilovm@mail.nih.gov.

N-Acetyl Mannosamine as a Therapeutic Agent

Description of Technology: N-Acetyl Mannosamine is a precursor for the synthesis of sugar molecules known as sialic acids which play an important role in specific biological processes such as cellular adhesion, cellular communication and signal transduction. Lack of sialic acids also play an important role in disease processes such as cancer, inflammation and immunity.

This invention relates to methods of administering N-Acetyl Mannosamine or its derivative (to produce sialic acid in patients who are deficient in the sugar molecule) to treat muscular atrophy including hereditary inclusion body myopathy (HIBM) and distal myopathy with rimmed vacuoles (Nonaka myopathy). Certain kidney conditions such as those arising from hyposialytion of kidney membranes may be treated by this method as well.

Applications: Treatment of rare diseases such as HIBM and Nonaka myopathy.

Treatment of kidney conditions involving sialic acid deficiencies resulting in proteinuria and hematuria.

May be useful in treating other diseases involving sialic acid deficiencies.

Publication: B Galeano et al. Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine. J Clin Invest. 2007 Jun;117(6):1585-1594.

Inventors: Marjan Huizing et al. (NHGRI).

Patent Status: U.S. Provisional Application No. 60/932,451 filed 31 May 2007 (HHS Reference No. E-217-2007/0-US-01).

Licensing Status: Available for licensing.

Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; Fatima.Sayyid@nih.hhs.gov.

Collaborative Research Opportunity: The National Human Genome Research Institute, Medical Genetics Branch, Cell Biology of Metabolic Disorders unit is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize N-acetylmannosamine as a therapeutic agent. Please contact Marjan Huizing at 301-402-2797or mhuizing@mail.nih.gov for more information.

Nitrite Adjunctive Therapy to Enhance Efficacy of Reperfusion Therapy for Acute Myocardial Infarction

Description of Technology: The treatment of coronary heart disease is a multi-billion dollar market. In the case of acute myocardial infarction (MI), more commonly known as a heart attack, the patient receives a number of Start Printed Page 16693diagnostic tests to determine the type and location of the heart damage. Most patients with ST segment elevation are treated with percutaneous coronary intervention (PCI) or thrombolysis. While current therapies, that attempt to reestablish the blood flow and limit ischemia, can be effective, practical delays between symptom presentation and intervention compromise the amount of myocardial salvage. Moreover, the elapsed time prior to PCI is closely related to the clinical outcome. This has resulted in a mortality rate of 7% after MI and nearly all patients suffer from some degree of myocardial necrosis. However, the use of adjunctive pharmacological therapies can improve myocardial salvage following acute percutaneous reperfusion of an acute MI and substantially impact cardiac function.

This technology is a method of using nitrite as an adjunctive therapy to enhance efficacy of reperfusion therapy for acute MI. Evidence suggests that anion nitrite (NO2) is a physiological signaling molecule with roles in intravascular endocrine nitric oxide (NO) transport, hypoxic vasodilation, signaling, and cytoprotection. In addition, nitrite has the characteristics of an ideal adjunctive therapy that now appears ready for translation to human clinical trials. The benefits of nitrite therapy include (1) Significant cardioprotection after prolonged ischemia, (2) simple administration, (3) low dose for pharmacological action, (4) short half-life (5) minimal side effects, (6) low expense, (7) rapid onset of action. Additionally, the therapy utilizes a cardioprotective mechanism that is not dependent on vasodilation or pressure rate changes. The use and dosing protocols of nitrite, as described by this technology, could limit MI and apoptosis in the reperfusion phase of injury and provide a remarkable degree of cardioprotection.

Applications: Treatment or amelioration of myocardial salvage following acute percutaneous reperfusion of an acute MI.

Development Status: Clinical Development.

Inventors: Mark T. Gladwin et al. (NHLBI).

Relevant Publications:

1. MT Gladwin, JH Shelhamer, AN Schechter, ME Pease-Fye, MA Waclawiw, JA Panza, FP Ognibene, RO Cannon 3rd. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11482-11487.

2. RO Cannon 3rd, AN Schechter, JA Panza, FP Ognibene, ME Pease-Fye, MA Waclawiw, JH Shelhamer, MT Gladwin. Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest. 2001 Jul;108(2):279-287.

Patent Status: U.S. Provisional Application No. 60/911,026 filed 10 Apr 2007 (HHS Reference No. E-023-2007/0-US-01)

Licensing Status: Available for licensing.

Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; Fatima.Sayyid@nih.hhs.gov.

Collaborative Research Opportunity: The NHLBI Pulmonary and Vascular Medicine Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize nitrite adjunctive therapy to enhance efficacy of reperfusion therapy for acute myocardial infarction. Please contact Dr. Mark Gladwin at 301-435-2310 for more information.

Compositions and Methods for Increasing Recombinant Protein Yields Through the Modification of Cellular Properties

Description of Technology: This technology relates to compositions and methods for improving the growth characteristics of cells engineered to produce biologically active products such as antibodies or glycosylated proteins. Featured is a method that uses gene candidates (e.g., cdkl3, siat7e, or lama4), or their expressed or inhibited products in cell lines, such as Human Embryonic Kidney (including HEK-293), HeLa, or Chinese Hamster Ovary (CHO). The gene expression modulates growth characteristics, such as adhesion properties, of the cell lines thereby increasing recombinant protein yields and reducing product production costs.

Applications: This technology may be used to improve production of therapeutic and/or diagnostic compounds, including therapeutic proteins or monoclonal antibodies from mammalian cells. Optimization of mammalian cells for use as expression systems in the production of biologically active products is very difficult. For certain applications, anchorage-independent cell lines may be preferred, whereas for other applications, a cell line that adheres to a surface, e.g., is anchorage-dependent, may be preferable. This technology provides a method for identifying a gene whose expression modulates such cellular adhesion characteristics. This method thus leads to an increase in the expression or yield of polypeptides, including therapeutic biologicals, such as antibodies, cytokines, growth factors, enzymes, immunomodulators, thrombolytics, glycosylated proteins, secreted proteins, and DNA sequences encoding such polypeptides and a reduction in the associated costs of such biological products.

Advantages: This technology offers the ability to improve yields and reduce the cost associated with the production of recombinant protein products through the selection of cell lines having: Altered growth characteristics; altered adhesion characteristics; altered rate of proliferation; improvement in cell density growth; improvement in recombinant protein expression level.

Market: Biopharmaceuticals, including recombinant therapeutic proteins and monoclonal antibody-based products used for in vivo medical purposes and nucleic acid based medicinal products now represent approximately one in every four new pharmaceuticals on the market. The market size has been estimated at $33 billion in 2004 and is projected to reach $70 billion by the end of the decade. The list of approved biopharmaceuticals includes recombinant hormones and growth factors, mAB-based products and therapeutic enzymes as well as recombinant vaccines and nucleic acid based products.

Mammalian cells are widely used expression systems for the production of biopharmaceuticals. Human embryo kidney (including HEK-293) and Chinese hamster ovary (CHO) are host cell of choice. The genes identified in this technology (e.g., cdkl3, sia7e, or lama4) can be used to modify these important cell based systems.

This technology is ready for use in drug/vaccine discovery, production and development. The technology provides methods for identification of specific gene targets useful for altering the production properties of either existing cell lines to improve yields or with new cell lines for the production of therapeutic and or diagnostic compounds from mammalian cells.

Companies that are actively seeking production platforms based on mammalian cell lines that offer high efficiency, high throughput systems for protein production or analysis at lower cost and ease of scale-up would be potential licensors of this technology.

Development Status: Late Stage—Ready for Production.

Inventors: Joseph Shiloach (NIDDK), Pratik Jaluria (NIDDK).

Related Publication: P Jaluria et al. Application of microarrays to identify and characterize genes involved in attachment dependence in HeLa cells. Metab Eng. 2007 May;9(3):241-251. Start Printed Page 16694

Patent Status: U.S. Provisional Application No. 60/840,381 filed 24 Aug 2006 (HHS Reference No. E-149-2006/0-US-01); PCT Application No. PCT/US2007/018699 filed 24 Aug 2007 (HHS Reference No. E-149-2006/0-PCT-02).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; soukasp@mail.nih.gov.

Collaborative Research Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Biotechnology Core Laboratory, is seeking parties interested in collaborative research projects directed toward the use of this technology with cells for drug and vaccine production and development, including growth optimization, production and product recovery processes. For more information, please contact Dr. Joseph Shiloach, josephs@intra.niddk.nih.gov, or Rochelle S. Blaustein at Rochelle.Blaustein@nih.gov.

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March 20, 2008.

Steven M. Ferguson,

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

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[FR Doc. E8-6316 Filed 3-27-08; 8:45 am]

BILLING CODE 4140-01-P