E7-24784. 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.

A Clinically Proven Therapeutic Treatment and Diagnostic Tool for Mesothelin Expressing Cancers: A Novel Recombinant Immunotoxin SS1P (anti-mesothelin dsFv-PE38)

Description of Technology: Mesothelin is a cell surface glycoprotein, whose expression is largely restricted to mesothelial cells in normal tissues. Mesothelin has been shown to be highly expressed in many cancers including malignant mesothelioma, ovarian cancer, lung cancer, pancreatic carcinomas, gastric carcinomas, and other cancers. Mesothelin has been shown to be a target for immunotherapy and is also being used as a tumor marker.

The technology relates to the SS1P immunotoxin that can be used to kill cells expressing mesothelin on their surface, such as mesothelioma, ovarian cancer, lung cancer, pancreatic cancer and stomach cancer. Additionally, it can be used for the detection of mesothelin expressing cells present in a biological sample.

The SSIP protein is an immunotoxin generated by the fusion of an anti-mesothelin antibody Fv fragment with a particularly high affinity (SS1), and a ~38 kDa portion of Pseudomonas Exotoxin A (PE38).

Applications: SS1P can be used as a therapy for mesothelin expressing cancers. The immunotoxin can be used as a standalone treatment and in combination with standard chemotherapy.

Advantage: SS1P immunotoxin is available for use and has been successfully tested clinically for the treatment of several mesothelin expressing cancers, such as mesothelioma and ovarian cancer with low side effects.

Development Status: Phase 1 studies have been completed for mesothelin expressing cancers such as mesothelioma and ovarian cancer. Phase 2 studies to begin shortly for combination therapy using SS1P and standard chemotherapy.

In addition to an active Investigational New Drug (IND) application, there are two associated orphan drug designations with this agent.

Inventors: Ira Pastan (NCI) et al.

Relevant Publications:

1. R Hassan et al. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. 2007 Sep 1;13 (17):5144-5149.

2. Y Zhang et al. Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing mice. Clin Cancer Res. 2006 Aug 1;12(15):4695-4701.

Patent Status: U.S. Patent No. 7,081,518 issued 25 Jul 2006, entitled “Anti-Mesothelin Antibodies Having High Binding Affinity” (HHS Reference No. E-139-1999/0-US-07)

Related Intellectual Property:

1. U.S. Patent No. 4,892,827 entitled “Recombinant Pseudomonas Exotoxin: Construction of an Active Immunotoxin with Low Side Effects” [HHS Ref. No. E-385-1986/0];

2. U.S. Patent Nos. 6,051,405, 5,863,745, and 5,696,237 “Recombinant Antibody-Toxin Fusion Protein” [HHS Ref. No. E-135-1989/0];

3. U.S. Patents 5,747,654, 6,147,203, and 6,558,672 entitled “Recombinant Disulfide-Stabilized Polypeptide Fragments Having Binding Specificity” [HHS Ref. No. E-163-1993/0];

4. U.S. Patent No. 6,153,430, and U.S. Patent Application No. 09/684,599 “Nucleic Acid Encoding Mesothelin, a Differentiation Antigen Present on Mesothelium, Mesotheliomas and Ovarian Cancers” [HHS Ref. No. E-002-1996/0];

5. U.S. Patent 6,083,502 entitled “Mesothelium Antigen and Methods and Kits for Targeting It” [HHS Ref. No. E-002-1996/1];

6. U.S. Patent Application 09/581,345: “Antibodies, Including Fv Molecules, and Immunoconjugates Having High Binding Affinity for Mesothelin and Methods for Their Use” [HHS Ref. No. E-021-1998/0];

7. PCT Application No. PCT/US01/18503, “Pegylation of Linkers Improves Antitumor Activity and Reduces Toxicity of Immunoconjugates” [HHS Ref. No. E-216-2000/2];

8. PCT Application No. PCT/US2006/018502 and U.S. Patent Application No. 60/681,104, entitled “Anti-Mesothelin Antibodies Useful For Immunological Assays” [HHS Ref. No. E-015-2005/0-US-01]; and

9. And any related foreign filed national stage applications claiming priority to such patent applications and patents listed above.

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

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

cDNA Encoding a Gene BOG and Its Protein Product

Description of Invention: Available for licensing is BOG (B5t Over-Expressed Gene) with the gene product pRb of the well-known tumor suppressor gene RB, retinoblastoma susceptibility gene. The complex formed between Rb and BOG typically does not contain E2F-1 in vivo. This binding property suggests that cells which are transformed/transfected with cDNA or other functional nucleotide sequences which encode the BOG gene product will be useful as tools for studying cell cycle control and oncogenesis.

Studies using rat liver epithelial cell (RLE) lines which are resistant to the growth inhibitory effects of TGF-beta1 and primary liver tumors have been shown to over-express BOG. Moreover, when normal RLE continuously over-express BOG the cells become transformed and the transformed cells are able to form hepatoblastoma-like tumors when transplanted into nude mice. Therefore, biologics derived from BOG may be useful as diagnostics or therapeutics.

Applications: Method to diagnose and treat liver cancer; Method to study cell cycle control and oncogenesis; Liver cancer therapeutics.

Development Status: The technology is currently in the pre-clinical stage of development.

Market: Liver cancer is the third leading cause of cancer death worldwide, and the fifth most common cancer in the world; Post-operative five year survival rate of HCC patients is 30-40%.

Inventors: Snorri S. Thorgeirsson et al. (NCI).

Relevant Publication: JT Woitach et al. A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability. Nat Genet. 1998 Aug;19(4):371-374.

Patent Status: U.S. Patent No. 6,727,079 issued 27 Apr 2004 (HHS Reference No. E-009-1998/2-US-02).

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

Licensing Contact: Jennifer Wong, 301-435-4633; [e-mail].

Collaborative Research Opportunity: The National Cancer Institute (NCI), Center for Cancer Research, Laboratory of Experimental Carcinogenesis, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize BOG (B5t Over-Expressed Gene) with the gene product pRb. Please contact John Hewes, Ph.D. at the NCI Technology Transfer Center at [e-mail] or [phone] for more information.

Dated: December 14, 2007.

Steven M. Ferguson,

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