HER2-specific monoclonal antibodies and conjugates thereof

US9738726B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Secretary, Department of Health and Human Services · US

Inventors

• Dimiter S. Dimitrov · Frederick, US
• Zhongyu Zhu · Frederick, US
• Pradman K. Qasba · Bethesda, US
• Boopathy Ramakrishnan · Braintree, US

Key dates

• Filing date: Jun 9, 2014
• Grant date: Aug 22, 2017
• Expiry date: Jun 9, 2034

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2333/82
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The identification of Her2-specific monoclonal antibody m860 is described. The m860 antibody was identified from a human naïve phage display Fab library by panning against the extracellular domain of human Her2. M860 binds to cell surface-associated Her2 with an affinity comparable to that of trastuzumab (Herceptin®), but binds to a different epitope. Using site-specific glycan engineering, m860 was conjugated to the small molecule drug auristatin F. The antibody-drug conjugate was stable, bound cell-surface expressed Her2 and exhibited potent cell killing of Her2-positive cancer cells, including trastuzumab-resistant breast cancer cells.