Engineered anthrax lethal toxin for targeted delivery

US9730993B2 · kind B2 · utility

Assignee

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

Inventors

• Clinton Edward Leysath · College Station, US
• Stephen H. Leppla · Bethesda, US
• Damilola Daniel Phillips · Rockville, US

Key dates

• Filing date: Aug 22, 2013
• Grant date: Aug 15, 2017
• Expiry date: Aug 22, 2033

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K14/32
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention provides methods and systems for targeted delivery of a compound to a target cell that over-expresses two different proteinases. Specifically, two different modified protective antigen proteins, each comprising a cleavage site recognized by a distinct proteinase in place of the native proteinase cleavage site recognized by furin, are administered in combination with a compound that contains a protective antigen binding site. Upon cleavage by the two proteinases the two modified protective antigen proteins form a hetero-oligomer, allowing the compound to bind to the hetero-oligomer and subsequently to be translocated into the target cell.