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Mediating Multiple, Same Family GPCRs with Single, Multi-Target PEPDUCIN® Drug Compounds

Organization:Tufts University, MA, US
I.P. Brief:PEPDUCIN compounds constitute a novel class of drug compounds. T-NEMC has pursued an aggressive patent strategy with broad composition of matter claims, directed to PEPDUCIN compounds based on any GPCR intra-cellular domain or loop attached to any lipid moiety, and broad methods of use claims. There are pending patent applications in the US, EPO, Japan, Canada and Australia. This IP estate is expected to dominate any third parties that may to wish to practice in the PEPDUCIN field. The first U.S. patent issued on March 8, 2005 with broad claims directed to any PEPDUCIN compound any third GPCR intra-cellular attached to any lipid moiety. A US trademark application for the “PEPDUCIN” mark has also been registered.
Summary of I.P.:The Pepducin technology provides in vitro and in vivo data demonstrating that it can simultaneously inhibit multiple GPCR receptors of a similar family using single PEPDUCIN drug candidates. The importance of this with respect to diseases such as inflammatory diseases and cancer could be immense, especially in light of pharmas’ poor experience with GPCRs of complex diseases. And unlike other promiscuous drug development efforts, the Pepducin technology focuses on targeting biologically similar GPCR receptor targets that could lead to “cleaner,” more selective, and ultimately more efficacious NCE development.
Patent:US 6,864,229; PCT 2001/081408; PCT/2005/039959
Keywords:GPCR, Cancer, Inflammation, Thrombosis
Primary Industry:Pharma & Biotech
Specific Market:Anti-inflammatory (COPD, RA), Thrombosis, Cancer (adjuvant therapy)
Market Size:Pepducin technology is a drug discovery engine with several lead compounds ready to enter pre-clinical drug development targeting inflammatory and cancer indications.
State of the Art:The track record of finding drugs with multi-target activity has not been impressive. Combination small molecule drug paradigms have become trendy lately but these approaches have numerous associated problems. In the realm of biologicals, the concept of multiple targeting is also catching on but it’s very early days.
Figures of Merit:(1) Rapid uptake (2) Tailored half lives (3) High potency (4) Apparent safety and lack of toxicity (5) Rapid ability to design unique and active pepducins (6) Broad IP position
Tech.  Obstacles:Pepducins represent a novel class of drugs. While pepducin compounds have demonstrated a good safety profile in in vivo research to date (mice, primates), additional safety work will need to be undertaken through a CRO.
Market Obstacles:Typical drug development challenges
Patent Landscape:The Pepducin drug discovery platform is first in class and has freedom to operate.
Publications:Covic, L., Gresser, A. L., Talavera, J., Swift, S., & Kuliopulos, A. (2002) Proc. Natl. Acad. Sci. USA 99, 643-648. Activation and Inhibition of G Protein-coupled Receptors by Cell-Penetrating, Membrane-Tethered Peptides. Covic, L., Misra, M., Badar, J., Singh, C., & Kuliopulos, A. (2002) Nature Medicine 8, 1161-1165. Pepducin-Based Intervention of Thrombin Receptor Signaling and Systemic Platelet Activation. Boire A, Covic L, Agarwal A, Jacques S, Sherifi S, & Kuliopulos A. (2005) Cell. 2005 Feb 11;120(3):303-13. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Kaneider, N.C., Agarwal A, Leger, A., & Kuliopulos A. (2005), Nature Medicine (in press). Reversing system inflammatory response syndrome with chemokine receptor pepducins.
Research Team:Principal Investigator: Athan Kuliopulos, MD, PhD Director, Hemostasis and Thrombosis Laboratory Associate Professor Investigator, Molecular Oncology Research Institute Tufts-New England Medical Center Co-Principal Investigator: Lidija Covic, PhD Co-Director, Hemostasis & Thrombosis Laboratory Investigator, Molecular Oncology Research Institute Tufts-New England Medical Center Research Associate Nicole Kaneider, MD

 

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