Evolution of BoNT peptidases

US12060553B2 · kind B2 · utility

Assignees

• President and Fellows of Harvard College · US
• IPSEN BIOPHARM LIMITED · GB
• The Broad Institute, Inc. · US

Inventors

• Michael S. Packer · Cambridge, US
• Travis R. Blum · Cambridge, US
• David R. Liu · Lexington, US
• Keith Foster · Salisbury, GB
• Matthew Beard · Abingdon, GB

Key dates

• Filing date: Aug 27, 2018
• Grant date: Aug 13, 2024
• Expiry date: Jan 13, 2040

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2795/14143
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The disclosure provides amino acid sequence variants of Botulinum neurotoxin (BoNT) proteases that cleave (VAMP1, VAMP2, VAMP7, VAMP8, SNAP25, SNAP23, PTEN, etc.) and methods of evolving the same. In some embodiments, proteases described by the disclosure are useful for cleaving proteins found in a cell, that is in an intracellular environment. In some embodiments, proteases described by the disclosure are useful for treating diseases associated with increased or aberrant VAMP7, VAMP8, SNAP23 or PTEN expression or activity, for example, cancer and neurological disorders. Some aspects of this disclosure provide methods for generating BoNT protease variants by continuous directed evolution.