Chimeric toxins with improved inter-domain geometry

Details Chimeric toxins with improved inter-domain geometry Chimeric toxins with improved inter-domain geometry

C - Chemistry, Metallurgy

12

N

C12N 15/62 (2006.01) C07K 7/06 (2006.01) C07K 14/34 (2006.01) C07K 14/475 (2006.01) C07K 14/55 (2006.01) C07K 19/00 (2006.01) C12N 15/11 (2006.01) C12N 15/24 (2006.01) C12N 15/31 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2083487

2083487 9119745 PCTABS00008 A chimeric toxin including protein fragments joined together by peptide bonds, the chimeric toxin comprising, in sequential order, beginning at the amino terminal end of the chimeric toxin: (a) the enzymatically active Fragment A of diphtheria toxin; (b) a first fragment including the cleavage domain 11 adjacent Fragment A of diphtheria toxin; (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 12; (d) a spacer; (e) a portion of a cell-specific polypeptide ligand, the cell-specific polypeptide ligand being a cell growth factor, 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 the target cell.

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