Variant factor VIII polypeptides and methods of their production and use

US10266583B2 · kind B2 · utility

Assignee

• BAYER HEALTHCARE LLC · DE

Inventors

• Uwe Gritzan · Cologne, DE
• Peter Kretschmer · Bruchköbel, DE
• Lilley Leong · Hercules, US
• Chandra K. N. Patel · Foster City, US

Key dates

• Filing date: Jan 23, 2018
• Grant date: Apr 23, 2019
• Expiry date: Jan 23, 2038

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P7/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.