Granzyme b protease variants

Abstract

A polypeptide having a serine protease variant of the human granzyme B set forth by SEQ ID NO: 1, wherein the serine protease variant has at least 95% identity to SEQ ID NO: 1 and has a substitution at the position that corresponds structurally or by amino acid sequence homology to position Arg201 of SEQ ID NO: 1, and wherein the serine protease variant has activity to cleave the motif Ile-Glu-Thr-Asp.

What is claimed is: 
     
         1 . A polypeptide comprising a serine protease variant of the human granzyme B set forth by SEQ ID NO: 1, wherein the serine protease variant has at least 95% identity to SEQ ID NO: 1 and has a substitution at the position that corresponds structurally or by amino acid sequence homology to position Arg201 of SEQ ID NO: 1, and wherein the serine protease variant has activity to cleave the motif Ile-Glu-Thr-Asp. 
     
     
         2 . The polypeptide according to  claim 1 , wherein the Arg201 amino acid is substituted for a different basic amino acid. 
     
     
         3 . The polypeptide according to  claim 1 , wherein the serine protease variant is as set forth by SEQ ID NO: 8. 
     
     
         4 . The polypeptide according to  claim 1 , wherein the serine protease variant is as set forth by SEQ ID NO: 9. 
     
     
         5 . The polypeptide according to  claim 1 , wherein the polypeptide further comprises a substitution of one or more residues corresponding to position 35, 74 and/or 227 of SEQ ID NO: 1. 
     
     
         6 . An isolated nucleic acid molecule encoding a polypeptide according to  claim 1 . 
     
     
         7 . A composition comprising the polypeptide according to  claim 1  in a pharmaceutically acceptable carrier. 
     
     
         8 . A purified complex comprising a binding structure and a polypeptide according to  claim 1 . 
     
     
         9 . The purified complex according to  claim 8 , wherein the complex further comprises a fusion protein, wherein the binding structure is an antigen binding polypeptide or protein that binds a cell type specific marker. 
     
     
         10 . The purified complex according to  claim 8 , wherein the binding structure is an antibody or an antibody fragment selected from the group consisting of Fab, scFv; single domain, or a fragment thereof, bis scFv, Fab 2 , Fab 3 , minibody, diabody, triabody, tetrabody and tandab.