E7-12899. Prospective Grant of Exclusive License: The Development of Human Therapeutics for the Treatment of Cancer

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR part 404.7(a)(1)(i), that the National Institutes of Health, Department of Health and Human Services, is contemplating the grant of an exclusive patent license to practice the inventions embodied in U.S. Patent Application 60/870,050, entitled “Human Cancer Therapy Using Anthrax Lethal Toxin Activated by Tumor Associated Proteases” [HHS Reference E-070-2007/0-US-01], including background patent rights to U.S. Patent Application 10/088,952, entitled “Mutated Anthrax Toxin Protective Antigen Proteins that Specifically Target Cells Containing High Amounts of Cell-Surface Metalloproteinases or Plasminogen Activator Receptors” [HHS Reference E-293-1999/0-US-03] and foreign counterparts thereto, and U.S. Patents 5,591,631 and 5,677,274, entitled “Anthrax Toxin Fusion Proteins and Uses Thereof” [HHS References E-064-1993/0-US-01 and E-064-1993/1-US-01, respectively] and foreign counterparts thereto, to FP BioPharma, LLC, which has offices in Fort Mill, South Carolina. The patent rights in these inventions have been assigned to and/or exclusively licensed to the Government of the United States of America.

The prospective exclusive license territory may be worldwide, and the field of use may be limited to:

A method for the treatment of cancer involving protease activated cancer toxins, wherein the cancer toxins comprise Anthrax lethal toxin (LeTx) modified at the furin-recognized cleavage site to contain a matrix metalloproteinase cleavage site, as defined by the Licensed Patent Rights, and wherein the cancers include, but are not limited to, melanoma, colon, thyroid, prostate, pancreatic and ovarian cancer. This exclusive licensed field of use shall explicitly exclude vaccines and immunotherapeutics for the prevention or treatment of human diseases.

DATES:

Only written comments and/or applications for a license which are received by the NIH Office of Technology Transfer on or before September 4, 2007 will be considered.

ADDRESSES:

Requests for copies of the patent application, inquiries, comments, and other materials relating to the contemplated exclusive license should be directed to: David A. Lambertson, PhD, Technology Licensing Specialist, Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804; Telephone: [phone]; Facsimile: [phone]; E-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

Anthrax lethal toxin (LeTx) has been shown to have significant toxicity to cancer cells, particularly those associated with melanoma. However, LeTx also shows significant toxicity towards normal cells, preventing widespread use of the molecule as a cancer therapy. NIH inventors have now engineered LeTx to have increased specificity for cancer cells, with little to no effect on normal cells, enhancing the effectiveness of LeTx for cancer treatment.

Modifying the LeTx to be activated by a matrix metalloprotease (MMP) increases the specificity of LeTx for cancer cells because those cells are more likely to activate the toxin, resulting in more efficient therapy. Mouse data shows that the modified LeTx (called PrAg-L1/LF) is less cytotoxic to “normal” cells in vivo when compared to wild-type LeTx, while maintaining high toxicity towards implanted human tumors. Modification of the LeTx to contain various protease recognition and cleavage sites can potentially extend application of the technology beyond melanomas to the treatment of lung and colon carcinomas, and various other cancers.

The prospective exclusive license will be royalty bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR 404.7. The prospective exclusive license may be granted unless within sixty (60) days from the date of this published notice, the NIH receives written evidence and argument that establishes that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR 404.7.

Applications for a license in the field of use filed in response to this notice will be treated as objections to the grant of the contemplated exclusive license. Comments and objections submitted to this notice will not be made available for public inspection and, to the extent permitted by law, will not be released under the Freedom of Information Act, 5 U.S.C. 552.

Dated: June 26, 2007.

Steven M. Ferguson,

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