National Institutes of Health, Public Health Service, HHS.
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.
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.
Immunogenic Peptides and Methods of Use for Treating Prostate and Uterine Cancers
Description of Technology: Cancer of the prostate is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men. Despite the use of standard therapy, including surgery, radiotherapy, chemotherapy, and/or hormonal therapy more than 30,000 men will die from prostate cancer. Moreover, current therapy has limited success against metastatic androgen insensitive prostate cancer. A potential treatment for prostate cancer is immunotherapy, either alone or in combination with standard therapies.
PAGE4 is an X chromosome-linked cancer-testis antigen that is highly expressed in prostate and uterine cancers. To this end, Drs. Jeffery Schlom, Kwong Tsang, and Ira Pastan have identified and characterized novel PAGE4 cytotoxic T-cell lymphocyte (CTL) epitopes and enhanced agonist epitopes. Preclinical studies performed by Dr. Schlom and colleagues indicate that the PAGE4 agonist epitopes bind HLA-A2 molecules at lower peptide concentrations, form more stable peptide HLA-A2 complexes, induce higher levels of production of INF-gamma, Granzyme B, TNF-alpha, IL-2, and lymphotactin by PAGE4 specific T-cell lines, and T-cell lines generated against the agonist peptide were more efficient at lysing human tumor cells expressing native PAGE4. Thus, these agonist epitopes of PAGE4 could be incorporated into immunotherapy protocols, and may constitute an alternative and/or additional approach for the treatment of PAGE4 expressing prostate and uterine cancers.
Development Status: The Laboratory of Tumor Immunology and Biology plans to initiate clinical studies utilizing this technology and collaborative opportunities may be available.
Inventors: Jeffrey Schlom, Kwong-Yok Tsang, Ira H. Pastan (NCI).
Publications: Publications which may provide background information for this technology include:
1. J Yokokawa et al., “Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4),” Int J Cancer. 2007;121:595-605.
2. C Iavarone et al., “PAGE4 is a cytoplasmic protein that is expressed in normal prostate and in prostate cancers,” Mol Cancer Ther. 2002 Mar;1(5):329-335.
3. L Prikler et al., “Adaptive immunotherapy of the advanced prostate cancer—cancer testis antigen (CTA) as possible target antigens,” Aktuelle Urol. 2004 Aug;35(4):326-330. [article in German]
Patent Status: PCT Application No. PCT/US2007/004603 filed 21 Feb 2007 (HHS Reference No. E-104-2006/0-PCT-02), claiming priority to 24 Feb 2006, entitled “Immunogenic Peptides and Methods of Use.”
Related Technology: U.S. Patent Application No. 11/704,714 filed 09 Feb 2007 (HHS Reference No. E-028-1999/0-US-08), claiming priority to 01 Sep 1998, entitled “PAGE-4, An X-Linked GAGE-Like Gene Expressed in Normal and Neoplastic Prostate, Testis and Uterus, and Uses Therefor.”
Licensing Status: Available for non-exclusive or exclusive licensing.
Licensing Contact: Michelle A. Booden, Ph.D.; 301/451-7337; firstname.lastname@example.org.
Collaborative Research Opportunity: The Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Kevin Chang, Ph.D. in the NCI Technology Transfer Center at email@example.com and/or 301-496-0477 for more information.
Diagnostic and Therapeutic Methods of Detecting and Treating Cancers of Reproductive Tissues
Description of Technology: PAGE-4 is a human X-linked gene that is strongly expressed in prostate and prostate cancer, and is also expressed in other male and female reproductive tissue (e.g., testis, fallopian tube, placenta, uterus, and uterine cancer). PAGE-4 shows similarity with the GAGE protein family, but it diverges significantly from members of the family so that it appears to belong to a separate family. This, and the existence of another gene, PAGE-2, that share more homology with PAGE-4 than with members of the GAGE family indicates that the PAGE-4 protein belongs to a separate protein family.
The specific detection of PAGE-4 might be valuable for the diagnosis of prostate and testicular tumors, as well as uterine tumors. There are sufficient differences between PAGE-4 and other members of the PAGE and MAGE proteins to produce specific antibodies. Analyses with such antibodies are needed to confirm by immunohistology the expression specificity that is seen in database and mRNA analyses, and to evaluate whether anti-PAGE-4 immunotherapy could be a promising therapeutic approach. One possibility of eliminating PAGE-4 expressing cells could be to use it as cancer vaccine. Among the many possible approaches to vaccination, one method is direct vaccination with plasmid DNA. In fact, Dr. Pastan's laboratory has been able to obtain good expression of the PAGE-4 protein with mammalian expression plasmids, and has demonstrated that DNA-immunization with such expression constructs leads to good immune responses. Hence, this method may generate anti-PAGE-4 responses, and allow us to analyze if “PAGE-4-vaccination” can eliminate PAGE-4 expressing cells, as a therapeutic approach towards neoplasms of the prostate, testis, and uterus.
Inventors: Ira H. Pastan, Ulrich Brinkmann, George Vasmatzis, Byungkook Lee (NCI).
Patent Status: U.S. Patent Application No. 11/704,714 filed 09 Feb 2007 (HHS Reference No. E-028-1999/0-US-08), claiming priority to 01 Sep 1998, entitled “PAGE-4, An X-Linked GAGE-Like Gene Expressed in Normal and Neoplastic Prostate, Testis and Uterus, and Uses Therefor.”
Related Technology: PCT Application No. PCT/US2007/004603 filed 21 Feb 2007 (HHS Reference No. E-104-2006/Start Printed Page 432870-PCT-02), claiming priority to 24 Feb 2006, entitled “Immunogenic Peptides and Methods of Use.”Start Signature
Dated: July 26, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. E7-15056 Filed 8-2-07; 8:45 am]
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