E8-9535. 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.

Human and Improved Murine Monoclonal Antibodies Against CD22

Description of Technology: CD22 is a cell surface protein that is highly expressed in a number of B cell lymphomas, such as hairy cell leukemia (HCL), non-Hodgkins lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Several clinical trials using anti-CD22 antibodies are ongoing. However, all of these antibodies are murine in nature, and have the potential to elicit immune responses in patients. The immunogenicity may adversely affect the ability to provide patients with repeated doses of a therapeutic comprising the antibody, limiting the clinical application of those therapeutics.

In order to address the issue of immunogenicity in a patient, NIH inventors have generated two anti-CD22 antibodies of human origin. Each antibody has the ability to recognize CD22 on the surface of Raji cells. Thus, these antibodies represent an attractive alternative to the murine anti-CD22 antibodies currently being tested in clinical trials.

Additionally, the inventors have generated a modified murine anti-CD22 antibody with increased binding affinity and solubility. This antibody could also be a suitable alternative for the murine antibodies currently available.

Applications:

Use as an antibody therapeutic for B cell lymphomas.

Use in an immunotoxin therapeutic for B cell lymphomas.

Diagnostic for the detection of CD22 positive tumors.

Advantages:

Antibody against a proven target for immunotherapy.

Fully human antibody reduces potential immunogenicity, thereby allowing repeated dosing.

Murine antibody has increased binding affinity and solubility relative to current murine anti-CD22 antibodies.

Benefits: The antibody based therapeutic market is likely to grow steadily in the next decade, with the present estimate of the market at more than ten billion U.S. dollars. Approximately five billion U.S. dollars are spent annually for treatment of lymphoma. The development of a successful antibody therapeutic for B cell lymphomas would occupy a significant portion of that market as approximately eighty-five percent of all lymphomas are B cell-linked.

Inventors: Dimiter S. Dimitrov et al. (NCI).

Patent Status: U.S. Provisional Application No. 61/042,329 filed 04 Apr 2008 (HHS Reference No. E-080-2008/0-US-01).

Licensing Status: Available for licensing.

Licensing Contact: David A. Lambertson, PhD; 301-435-4632; [e-mail].

Collaborative Research Opportunity: The NCI CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize anti-CD22 human monoclonal antibodies. Please contact John D. Hewes, PhD at 301-435-3121 or [e-mail] for more information.

Human Monoclonal Antibody Against Mesothelin

Description of Technology: Mesothelin is a cell surface protein that is naturally expressed at very low levels. However, the expression of mesothelin is significantly increased in aggressive tumors, such as mesotheliomas and pancreatic and ovarian tumors. As a result, mesothelin is an excellent candidate for tumor targeted immunotherapeutics.

Currently, the only antibodies against mesothelin that are available for clinical trials are of murine origin. These antibodies have the potential to elicit immune responses in patients, which may adversely affect the ability to provide patients with repeated doses. As a result, the clinical application of the antibodies may be limited.

In order to address the issue of immunogenicity in patients, NIH inventors have generated an anti-mesothelin antibody of human origin. The antibody has the ability to efficiently recognize mesothelin on the surface of cells, and induce ADCC in mesothelin-positive cells. Thus, this antibody represents an attractive alternative to the murine anti-mesothelin antibodies currently available.

Applications:

Use as an antibody therapeutic for mesotheliomas and pancreatic and ovarian tumors.

Use in an immunotoxin therapeutic for mesotheliomas and pancreatic and ovarian tumors.

Diagnostic for the detection of mesothelin positive tumors.

Research agent for the detection of mesothelin.

Advantages:

Fully human antibody reduces potential immunogenicity, thereby allowing repeated dosing.

First human antibody against mesothelin.

Benefits: The antibody based therapeutic market is likely to grow steadily in the next decade, with the present estimate of the market at more than ten billion U.S. dollars. The development of a successful antibody therapeutic for mesotheliomas and pancreatic and ovarian cancers would occupy a significant portion of that market.

Inventors: Dimiter S. Dimitrov et al. (NCI).

Patent Status: U.S. Provisional Application filed 27 Mar 2008 (HHS Reference No. E-079-2008/0-US-01)

Licensing Status: Available for licensing.

Licensing Contact: David A. Lambertson, PhD; 301-435-4632; [e-mail].

Collaborative Research Opportunity: The NCI CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the antibody. Please contact John D. Hewes, PhD at 301-435-3121 or [e-mail] for more information.

New Insect SF-9ET Cell Line for Determining Baculovirus Titers

Description of Technology: The baculovirus based protein expression system has gained increased prominence as a method for expressing recombinant proteins that are used in a wide range of biomedical applications. An important step in the use of this system is the ability to determine the virus infectious titer, i.e., the number of active baculovirus particles produced during an infection of the insect host cell. The current “gold standard” methods used for determining baculovirus titers, such as the plaque and end point dilution assays, can be costly, take a long time to complete (up to 7-8 days), and are sometimes difficult to interpret as they involve observing the cytopathic effects (CPE) that baculovirus infection has on the infected insect host cell. To solve these problems, a modified insect cell line, SF-9ET, was developed to genetically express the green fluorescent protein (GFP) when infected with baculovirus. In these cells, the gene for GFP is placed under the control of a baculovirus promoter so that the cells express GFP when they are infected with the virus. The baculovirus titer can then be quantitated from the level of GFP expression in the insect host cell. The results are obtained within 3 days compared to the 7-8 day period typical of the traditional CPE based methods.

The GFP based system is capable of replacing the traditional methods as it is faster, more accurate and may be less expensive than the currently used systems. This proprietary technology can become an indispensible tool for the quantitation of baculovirus titers; a step that is important in the production of recombinant proteins and vaccine like particles (VLPs) for academic and commercial purposes.

Applications: Baculovirus based recombinant protein expression.

Advantages: Fast, accurate, and inexpensive determination of baculovirus titers for protein expression.

Inventors: Ralph F. Hopkins III and Dominic Esposito (SAIC/NCI).

Patent Status: U.S. Provisional Application No. 61/019,562 filed 07 Jan 2008 (HHS Reference No. E-009-2008/0-US-01).

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

Licensing Contact: Jasbir (Jesse) S. Kindra, J.D., M.S.; 301-435-5170; [e-mail].

A Molecular Grading System for Ductal Carcinoma In Situ (DCIS) of the Breast: A New Molecular Diagnostic To Determine Disease Stages of DCIS

Description of Technology: The technology describes the comprehensive profiling of Ductal Carcinoma in situ (DCIS) in breast cancer patients. The inventors have developed a molecular grading system for DCIS utilizing both gene expression profiling and genomic change profiling. The inventors have identified molecular profiles that identify early stage patients at risk of disease progression requiring more aggressive therapy. These observations suggest that a clinical assay could be developed for the grading of DCIS. Furthermore, the invention demonstrates that the profiles correlate with the molecular grade and with cell proliferation, suggesting that a clinical assay using routine methods, based on the nuclear grade and staining for Ki67 as a measure of proliferation, could also potentially be developed.

Advantages and Applications:

The technology has the potential of being developed into an accurate diagnostic test for DCIS patients according to their risk of tumor progression.

The diagnostic profiling can assist physicians in making clinically informed and personalized therapy decisions for DCIS patients.

In the studies, tissue samples collected via laser capture micro-dissection from in situ breast cancer patients were used, which validate and authenticate the relevance of the study.

Development Status: Larger clinical study is currently being planned.

Inventors: Paul S. Meltzer et al. (NCI).

Patent Status: U.S. Provisional Application No. 60/936,526 filed 20 Jun 2007 (HHS Reference No. E-192-2007/0-US-01).

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

Licensing Contact: Mojdeh Bahar, J.D.; 301-435-2950; [e-mail].

Collaborative Research Opportunity: The National Cancer Institute, Genetics Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize molecular grading of DCIS. Please contact John D. Hewes, Ph.D. at 301-435-3121 or [e-mail] for more information.

April 24, 2008.

David Sadowski,

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