Biokinetics of fast-clearing polypeptides

US8937047B2 · kind B2 · utility

Assignee

• General Electric Company · US

Inventors

• Michael Ernest Marino · Clifton Park, US
• Faisal Ahmed Syud · Clifton Park, US
• Jason William Castle · Esperance, US
• Brian Duh-Lan Lee · Rexford, US
• Malin Lindborg · Boo, SE
• Elin Gunneriusson · Hallsberg, SE
• Christofer Lendel · Älta, SE

Key dates

• Filing date: Dec 19, 2007
• Grant date: Jan 20, 2015
• Expiry date: Jan 20, 2031

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Provided herein are methods of reducing liver uptake in vivo of a polypeptide that specifically binds to a target comprising: (a) providing a polypeptide that specifically binds to a target; and (b) substituting at least one basic or at least one neutral amino acid residue of the native polypeptide from step (a) with an acidic amino acid residue to produce a modified polypeptide, wherein the modified polypeptide demonstrates an isoelectric point at least 0.05-0.1 pH points less than the isoelectric point of the native polypeptide. Also provided are polypeptides made using the inventive methods as well as imaging techniques that employ the methods and agents.