A Fold-Back Diabody Format for Diphtheria Toxin-Based Immunotoxins That Can Increase Binding and Potency
Description of Invention:
NIH inventors, in collaboration with Scott and White Memorial Hospital inventors, have developed new immunotoxins comprising a mutant diphtheria toxin linked to an anti-prostate specific membrane antigen (PSMA) fold-back diabody. The fold-back diabody construct has a shortened linker region between the heavy and light chains of the antibody variable domain. This construct allows interactions between the longer-linked variable domains while preventing interactions between the shorter-linked variable domains. This results in increased efficiency of epitope recognition and delivery to the appropriate target cells. These immunotoxins can be used for the treatment of cancers that overexpress PMSA, with specific application against prostate cancer.
Applications:
Treatment of primary prostate tumors.
Treatment of metastatic prostate tumors, for which no currently effective treatment exists.
Application against other tumors expressing the PSMA epitope on the tumor neovasculature such as breast cancer.
Advantages:
Increased potency of 10-40-fold resulting from the use of the fold-back diabody construct.
First treatment with applications to metastatic prostate cancer.
Pichia pastoris production process of the fold-back immunotoxin can be used to scale up for GMP production.
Benefits:
Significant social benefit for successfully treating the second leading cause of cancer-related deaths among males in the United States.
Approximately 8 billion USD per year are spent on prostate cancer treatment; a new treatment could procure a significant financial position.
Opportunity to occupy a strong market position through the development of the first treatment of metastatic prostate cancer.
Patent Status:
DHHS Reference No. E-268-2007/0 --
U.S. Patent Application No. 60/953,416 filed 01 Aug 2007
Licensing Status: Available for licensing.
Collaborative Research Opportunity:
The National Institute of Mental Health, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize anti-PSMA fold-back immunotoxins. Please contact David Neville by phone at 301-496-6807 or e-mail davidn@mail.nih.gov for more information.
Portfolios: Cancer
Cancer -Therapeutics-Immunoconjugates-Mab Cancer -Therapeutics-Immunoconjugates-Toxins Cancer -Therapeutics-Immunoconjugates-Conjugate Chemistry Cancer -Therapeutics
For Additional Information Please Contact: David A. Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4632
Email: lambertsond@mail.nih.gov
Fax: (301) 402-0220
