Anti-EGFRvIII scFvs with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof

US7129332B2 · kind B2 · utility

Assignee

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

Inventors

• Ira H. Pastan · Potomac, US
• Richard Beers · Rockville, US
• Partha S. Chowdhury · Gaithersburg, US
• Darell Bigner · Mebane, US

Key dates

• Filing date: Feb 23, 2001
• Grant date: Oct 31, 2006
• Expiry date: Mar 9, 2022

Classification

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

Abstract

The invention provides antibodies to a mutant form of the epidermal growth factor receptor known as EGFRvIII found only or primarily on the surface of glioblastoma cells, and on cells of breast, ovarian and non-small cell lung carcinomas. The antibodies provided by the invention have the complementarity determining regions (“CDRs”) of the scFv designated MR1, but with mutations at positions 98 and 99 in the CDR3 of the heavy chain variable region and, optionally, in other CDRs. In particular, the invention provides an antibody, designated MR1-1, which mutates MR1 in the CDR3 of the VH and VL chains. The invention provides additional antibodies in which MR1 is mutated in the CDR1 and 2 of VH or VL, or both.