A -- Scientific and Commercial Development and Testing of Angio-inhibitory Peptides Derived from Human TIMP-2

Recent findings made at the National Cancer Institute demonstrate that TIMP-2 (tissue inhibitor of metalloproteinase 2) exerts a matrix metalloproteinase (MMP)-independent anti-angiogenic effect in vivo that is mediated by TIMP-2 binding to the alpha3 beta1 integrin receptor, facilitating protein tyrosine phosphatase activity. This anti-angiogenic effect is in addition to TIMP-2 regulation of the remodeling of the extracellular matrix through MMPs. The National Cancer Institute (NCI) is currently seeking cooperative partners to work with investigators in the Center for Cancer Research (CCR) to exploit, for drug development and clinical testing, novel TIMP-2 peptide-based inhibitors of angiogenesis. Research and development will include preclinical in vitro and in vivo testing of synthetic TIMP-2 peptides, structure-activity relationship analysis, development, production and testing of small molecule analogs of these peptides using GMP methods, followed by clinical trials. Potential Areas of Application: 1) Therapeutic use of novel inhibitors of angiogenesis based on MMP-independent TIMP-2 anti-angiogenesis function. State of Development: 1) CCR has identified a number of synthetic peptides that mimic linear sequences of TIMP-2 that bind the alpha3 beta1 integrin receptor, retaining anti-angiogenic activity in vitro and in vivo. Further R&D Required: 1) Development of additional TIMP-2 mimetic peptides with enhanced angiogenic activities. 2) Synthesis of small molecule analogs of TIMP-2 mimetic peptides with angiogenic activity. 3) Preclinical and clinical trials of synthetic TIMP-2 mimetic peptides and small molecule analogs. Patent Status : 1) A patent application is being filed for TIMP-2 angio-inhibitory peptides. 2) U.S. Patent No. 5,698,671 issued December 16, 1997, - Metalloproteinase Peptides. 3) U.S. Patent No. 5,595,885 issued January 21, 1997, - Matrix Metalloproteinase Inhibitor Peptides. Pertinent References: Guedez L, et al. Am J Pathol., 2003 May;162(5):1431-9. Murphy AN, et al. J Cell Physiol., 1993 Nov;157(2):351-8. Stetler-Stevenson WG, et al. Trends Mol Med. 2005 Mar;11(3):97-103. Stetler-Stevenson et al. J Biol Chem., 1990 Aug 15;265(23):13933-8. Stetler-Stevenson et al. J Biol Chem., 1989 Oct 15;264(29):17374-8. Seo DW. Cell, 2003 Jul 25;114(2):171-80. Contact Information: 1) CRADA contact: Brian W. Bailey, Ph.D., Technology Transfer Branch, NCI, Phone: +1 (555) 000-0000, E-mail: contact@example.gov 2) Licensing contact Thomas Clouse, J.D., Office of Technology Transfer, NIH, Phone: +1 (555) 000-0000, E-Mail: contact@example.gov