Mutated anthrax toxin protective antigen proteins that specifically target cells containing high amounts of cell-surface metalloproteinases or plasminogen activator receptors

US8791074B2 · kind B2 · utility

Assignee

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

Inventors

• Stephen H. Leppla · Bethesda, US
• Shi-Hui Liu · Bethesda, US
• Sarah Netzel-Arnett · Gaithersburg, US
• Henning Birkedal-Hansen · Bethesda, US
• Thomas Bugge · Bethesda, US

Key dates

• Filing date: Oct 20, 2008
• Grant date: Jul 29, 2014
• Expiry date: Jan 1, 2032

Classification

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

Abstract

The present invention provides methods of specifically targeting compounds to cells overexpressing matrix metalloproteinases, plasminogen activators, or plasminogen activator receptors, by administering a compound and a mutant protective antigen protein comprising a matrix metalloproteinase or a plasminogen activator-recognized cleavage site in place of the native protective antigen furin-recognized cleavage site, wherein the mutant protective antigen is cleaved by a matrix metalloproteinase or a plasminogen activator overexpressed by the cell, thereby translocating into the cell a compound comprising a lethal factor polypeptide comprising a protective antigen binding site.