Antibodies specific for urokinase-type plasminogen activator and methods of use thereof for treating cancer

US10239954B2 · kind B2 · utility

Assignees

• The Regents of the University of California · US
• CytomX Therapeutics, Inc. · US

Inventors

• Natalia Sevillano · San Francisco, US
• Aaron Lebeau · Taunton, US
• Daniel Robert Hostetter · Palo Alto, US
• Charles S. Craik · San Francisco, US

Key dates

• Filing date: May 30, 2017
• Grant date: Mar 26, 2019
• Expiry date: May 30, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2317/92
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure relates to antibodies specific for urokinase-type plasminogen activator (uPA). According to certain embodiments, the anti-uPA antibody specifically binds to the active form of uPA. In certain aspects, the anti-uPA antibody that specifically binds to active uPA binds specifically to the active form of human uPA (e.g., the antibody does not cross-react with active forms of uPA from non-human organisms). In certain aspects, an anti-uPA antibody of the present disclosure competes for specific binding to uPA with plasminogen activator inhibitor type 1 (PAI-1), where binding of the antibody to uPA results in internalization of a complex that includes the antibody, uPA, and urokinase-type plasminogen activator receptor (uPAR). Also provided are antibodies that specifically bind to uPA and compete for binding to uPA with a synthetic ligand of uPA. The disclosure also provides anti-uPA antibody conjugates and compositions (e.g., pharmaceutical formulations) comprising the antibodies and/or conjugates. Methods and kits related to the anti-uPA antibodies, conjugates, or formulations including the antibodies and/or conjugates are also provided.