Chimeric toxins

US5763250A · kind A · utility

Assignee

• BOSTON MEDICAL CENTER CORPORATION · US

Inventors

• Diane P. Williams · Hopkinton, US
• John R. Murphy · Cambridge, US

Key dates

• Filing date: Jun 7, 1995
• Grant date: Jun 9, 1998
• Expiry date: Jun 7, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/75
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A chimeric toxin comprising protein fragments joined together by peptide bonds, the chimeric toxin comprising, in sequential order, beginning at the amino terminal end of the chimeric toxin, PA1 (a) the enzymatically active Fragment A of diphtheria toxin, PA1 (b) a first fragment including the cleavage domain 1.sub.1 adjacent the Fragment A of diphtheria toxin, PA1 (c) a second fragment comprising at least a portion of the hydrophobic transmembrane region of Fragment B of diphtheria toxin, the second fragment having a deletion of at least 50 diphtheria toxin amino acid residues, the deletion being C-terminal to the portion of the transmembrane region, and the second fragment not including domain 1.sub.2, and PA1 (d) a third fragment comprising a portion of a cell-specific polypeptide ligand, the portion including at least a portion of the binding domain of the polypeptide ligand, the portion of the binding domain being effective to cause the chimeric toxin to bind selectively to a predetermined class of cells to be attacked by the enzymatically active Fragment A.