Patent ID: 7125689
Filing Date: 2006-10-24
Classification: A61K,C07K,G01N

Abstract:
1. A method of rendering streptokinase non-immunogenic or less immunogenic when exposed to the immune system of a human, the method comprising the steps of: (a) identifying a first set of potential T-cell epitope sequences within the amino acid residue sequence of streptokinase (SEQ ID NO: 252) by (i) analysing said amino acid sequence for the presence of MHC class II binding motifs, and (ii) comparing the MHC class II binding motifs in the streptokinase amino acid residue sequence with human MHC binding motifs available from an MHC database; (b) comparing the first set of potential T-cell epitope sequences identified in step (a) with human immunoglobulin variable region germ line amino acid residue sequences available from a human germ-line sequence database to identify a subset of potential T-cell epitopes within the streptokinase amino acid residue sequence that are not present in human immunoglobulin variable region germ-line sequences; and (c) preparing a de-immunized streptokinase polypeptide having the amino acid residue sequence of SEQ ID NO: 252 but including at least one amino acid residue substitution that eliminates from the streptokinase amino acid residue sequence at least one epitope sequence from the subset identified in step (b), wherein the de-immunized streptokinase polypeptide has the amino acid residue sequence of SEQ ID NO: 253.