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OXiGENE Announces Issuance of Patent for Benzosuberenes, a Novel Anticancer Class of Agents

21-Mar-2013 | Source : AG-IP News | Visits : 4949
SOUTH SAN FRANCISCO, Calif. - OXiGENE Inc., a clinical-stage biopharmaceutical company developing novel therapeutics to treat cancer, announced in a press release that the US Patent and Trademark Office issued US Patent No. 8,397,859, covering certain benzosuberene-based compounds, including the analogues referred to as KGP18 and KGP156 that are currently in preclinical development. The patent also covers methods of using those compounds to inhibit tubulin polymerization, to reduce blood flow to a tumor, or to restrain, slow, stop or reverse progression of a tumor.

These compounds are the product of OXiGENE's ongoing collaboration with Kevin G. Pinney, Ph.D. and Mary Lynn Trawick, Ph.D.at Baylor University to identify inhibitors of tubulin polymerization as vascular targeting agents and as back-up compounds to OXiGENE's combretastatin A-4P (ZYBRESTAT®) and OXi4503. Recently, the focus of this collaboration has centered on the development of novel antiproliferative agents (benzosuberenes) and anti-invasive molecules (cathepsin L inhibitors). OXiGENE has an exclusive license to the worldwide rights to all of the compounds that result from this collaboration.

"The issuance of the patent covering benzosuberenes is an important achievement for OXiGENE that enhances the value of our anticancer portfolio for potential pharmaceutical partners and investors," said Peter J. Langecker, OXiGENE's chief executive officer. "We believe that this exciting new class of compounds has the potential to enhance treatment options for oncologists and patients with cancer. This work also demonstrates the continued productivity of our collaboration with Baylor University."

"This benzosuberene series of molecules are among the most potent antiproliferative agents identified to date in our laboratories, and we believe this exceptional potency coupled with their antivascular activity make these compounds potentially well-suited for selective delivery strategies, including their use as payloads for antibody-directed therapy," said Dr. Pinney, Professor of Chemistry at Baylor University.

Benzosuberenes have highly potent anti-proliferative activity via inhibition of tubulin assembly at the colchicine binding site. Lead compounds include KGP18 and KGP156, which are potent small-molecule tubulin depolymerizing agents displaying sub-nanomolar (in the case of KGP18) antiproliferative activity in vitro against a number of human cancer cell lines. These compounds have also been shown to disrupt capillary-like networks of endothelial cells in vitro and induce reductions in tumor blood flow in human tumor xenografts in mice. Two publications detailing the synthesis and in vitro activity of the initial lead compounds in this series of benzosuberenes have appeared in print (Bioorg. Med. Chem. 16:8161-8171 (2008); and Med. Chem. Commun. 3:720-24 (2012).
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