2011-19378. 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.

Combination Cancer Therapy Using an IL13-Targeted Toxin and a Vaccine

Description of Technology: Typical cancer treatments such as chemotherapy, radiation therapy and surgical resection are non-specific processes that kill healthy cells as well as diseased cells, ultimately resulting in discomfort and undesirable side-effects for patients. In an effort to reduce the burden on cancer patients, a tremendous effort has been placed on developing ways to increase the specificity of cancer treatments. One way to increase specificity is to identify proteins which are present on the surface of cancer cells but absent on normal healthy cells, and use that protein as a target for delivering a therapeutic agent. Because the therapeutic agent only reaches the diseased cell, patients are less likely to experience non-specific side-effects, reducing their pain burden during treatment.

IL13-receptor-alpha-2 (IL13-Rα2) is a cell surface protein that is selectively expressed on certain diseased cells, including cancer cells. IL13-Rα2 binds to the cytokine IL13, suggesting that a therapeutic agent fused to IL13 can target and kill only those cancer cells which express IL13-Rα2. Our inventors previously constructed fusion proteins comprising (1) IL13 and (2) an active fragment of the bacterial toxin Pseudomonas exotoxin A (PE). These IL13-PE fusion proteins demonstrated the ability to selectively kill cancer cells that overexpressed IL13-Rα2, as well as other types of diseased cells (asthma, pulmonary fibrosis) which overexpressed IL13-Rα2. This suggested that IL13-PE fusion proteins were excellent candidates for new therapeutic agents.

The inventors recently sought methods to increase the effectiveness of these IL13-PE fusion proteins in the treatment of disease. This technology is directed to a combination therapy comprising (a) a DNA vaccine against IL13-Rα2 and (b) an IL13-PE fusion protein. By combining these therapeutic approaches it is possible to kill certain cell types that express IL13-Rα2 at high levels (such as cancer cells), making this combinatorial approach an attractive potential therapeutic.

Applications:

• Treatment of diseases associated with the increased expression of IL13-Rα2
• Relevant diseases include pulmonary fibrosis, asthma and cancers such as pancreatic cancer, glioblastoma multiforme and other head and neck cancers

Advantages:

• The DNA vaccine only affects cells where IL13-Rα2 expression is increased, limiting their effects to diseased cells
• IL13-PE fusion proteins also only kill cells that overexpress IL13-Rα2, allowing specific targeting of treatment
• Targeted treatment decreases non-specific killing of healthy, essential cells, resulting in fewer side-effects and healthier patients

Development Status: Preclinical stage of development.

Inventors: Puri et al. (FDA).

Patent Status: US provisional application 61/451,331 (HHS reference E-104-2011/0-US-01).

For more information, see:

• US Patents 5,614,191, 5,919,456 and 6,518,061 (HHS technology reference E-266-1994/0)
• US Patent Publication US 20040136959 A1 (HHS technology reference E-032-2000/0)
• US Patent 7,541,040 (HHS technology reference E-296-2001/0)

Licensing Status: Available for licensing.

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

Combination Cancer Therapy Using an IL13-Targeted Toxin and an HDAC Inhibitor

Description of Technology: Typical cancer treatments such as chemotherapy, radiation therapy and surgical resection are non-specific processes that kill healthy cells as well as diseased cells, ultimately resulting in discomfort and undesirable side-effects for patients. In an effort to reduce the burden on cancer patients, a tremendous effort has been placed on developing ways to increase the specificity of cancer treatments. One way to increase specificity is to identify proteins which are present on the surface of cancer cells but absent on normal healthy cells, and use that protein as a target for delivering a therapeutic agent. Because the therapeutic agent only reaches the diseased cell, patients are less likely to experience non-specific side-effects, reducing their pain burden during treatment.

IL13-receptor-alpha-2 (IL13-Rα2) is a cell surface protein that is selectively expressed on certain diseased cells, including cancer cells. IL13-Rα2 binds to the cytokine IL13, suggesting that a therapeutic agent fused to IL13 can target and kill only those cancer cells which express IL13-Rα2. Our inventors previously constructed fusion proteins comprising (1) IL13 and (2) an active fragment of the bacterial toxin Pseudomonas exotoxin A (PE). These IL13-PE fusion proteins demonstrated the ability to selectively kill cancer cells that overexpressed IL13-Rα2, as well as other types of diseased cells (asthma, pulmonary fibrosis) which overexpressed IL13-Rα2. This suggested that IL13-PE fusion proteins were excellent candidates for new therapeutic agents.

In an effort to increase the effectiveness of these IL13-PE fusion proteins, the inventors sought ways to increase the expression of IL13-Rα2 on cancer cells, thereby increasing the rate at which the therapeutic agent could kill the diseased cell. Histone deacetylase (HDAC) inhibitors have been employed as anti-cancer agents for several years, and a number of HDAC inhibitors are currently in clinical trials. Although the exact mechanism by which HDAC inhibitors function is unclear, it is believed that the ability of these molecules to increase the expression of anti-cancer genes is behind their therapeutic effect.

This invention concerns a means of improving specific cancer therapy through the combination of (a) IL13-PE fusion proteins and (b) HDAC inhibitors. The inventors surprisingly found that the expression of IL13-Rα2 increased in several types of pancreatic cancer cells in response to HDAC inhibitors, whereas normal, healthy cells did not experience such an increase in IL13-Rα2 expression. The use of IL13-PE fusion proteins in combination with HDAC inhibitors improved specific killing of pancreatic cancer cells relative to the use of IL13-PE fusion proteins in the absence of the HDAC inhibitors. This suggested that the use of IL13-PE fusion proteins along with HDAC inhibitors was a strong candidate combinatorial therapeutic for the treatment of various cancers (e.g., pancreatic, glioblastoma multiforme) and other diseases characterized by overexpression of IL13-Rα2 (e.g., asthma, pulmonary fibrosis).

Applications:

• Treatment of diseases associated with the increased expression of IL13-Rα2
• Relevant diseases include pulmonary fibrosis, asthma and cancers such as pancreatic cancer, glioblastoma multiforme and other head and neck cancers

Advantages:

• HDAC inhibitors only increased IL13-Rα2 expression in diseased cells, leaving normal healthy cells unaltered
• IL13-PE fusion proteins only kill cells that overexpress IL13-Rα2, allowing specific targeting of treatment
• Targeted treatment decreases non-specific killing of healthy, essential cells, resulting in fewer side-effects and healthier patients

Development Status: Preclinical stage of development

Inventors: Puri et al. (FDA)

Patent Status: US provisional application 61/494,779 (HHS reference E-107-2011/0-US-01)

For more information, see:

• US Patents 5,614,191, 5,919,456 and 6,518,061 (HHS technology reference E-266-1994/0)
• US Patent Publication US 20040136959 A1 (HHS technology reference E-032-2000/0)
• US Patent 7,541,040 (HHS technology reference E-296-2001/0)

Licensing Status: Available for licensing

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

Dated: July 26, 2011.

Richard U. Rodriguez,

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