Development of masked therapeutic antibodies to limit off-target effects; application to anti-EGFR antibodies

US8895702B2 · kind B2 · utility

Assignees

• City of Hope · US
• Thomas Jefferson University · US

Inventors

• John C. Williams · Duarte, US
• Ulrich Rodeck · Philadelphia, US
• Joshua M. Donaldson · Chambersburg, US
• Csaba Kari · Rancho Cordova, US

Key dates

• Filing date: Jul 6, 2012
• Grant date: Nov 25, 2014
• Expiry date: Jul 6, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/50
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.