Cysteine protease

1. A polypeptide having IgG cysteine protease activity and comprising a variant of the sequence of SEQ ID NO:4, which variant:

(a) is at least 90% identical to SEQ ID NO: 4;

(b) has a cysteine (C) at the position in said variant sequence which corresponds to position 102 of SEQ ID NO: 3;

(c) has, at the positions in said variant sequence which correspond to positions 92, 272, 294 and 296 of SEQ ID NO: 3, a lysine (K), a histidine (H), an aspartic acid (D) and an aspartic acid (D), respectively; and

(d) has deleted in its entirety the first twenty residues at the N terminus of SEQ ID NO: 4 (the contiguous sequence DDYQRNATEA YAKEVPHQIT);

wherein said variant has cysteine protease activity and said polypeptide is more effective at cleaving human IgG1 than IdeZ; and

wherein said variant of the sequence of SEQ ID NO: 4:

(1) has a positively charged amino acid at the position in said variant which corresponds to position 138 of SEQ ID NO: 3, optionally wherein said positively charged amino acid is arginine (R) or lysine (K);

(2) has a positively charged amino acid at the position in said variant which corresponds to position 139 of SEQ ID NO: 3, optionally wherein said positively charged amino acid is arginine (R) or lysine (K); and/or

(3) has at least one of the following modifications:

i. a deletion of the leucine (L) and threonine (T) residues at the positions in said variant which correspond to positions 64 and 65 of SEQ ID NO: 3;

ii. a threonine (T) in place of the arginine (R) at the position in said variant which corresponds to position 70 of SEQ ID NO: 3;

iii. a deletion of the tyrosine (Y) at the position in said variant which corresponds to position 71 of SEQ ID NO: 3;

iv. a glutamine (Q) in place of the asparagine (N) at the position in said variant which corresponds to position 72 of SEQ ID NO: 3;

v. a glycine (G) in place of the asparagine (N) at the position in said variant which corresponds to position 73 of SEQ ID NO: 3;

vi. an alanine (A) in place of the glutamic acid (E) at the position in said variant which corresponds to position 67 of SEQ ID NO: 3 and/or;

vii. an asparagine (N) in place of the glutamine (Q) at the position in said variant which corresponds to position 68 of SEQ ID NO: 3.

2. The polypeptide according to claim 1 , wherein said variant of the sequence of SEQ ID NO: 4 is at least 95% identical to SEQ ID NO: 4, respectively.

3. The polypeptide according to claim 1 , which comprises or consists of the sequence of SEQ ID NO:9, optionally wherein said sequence includes an additional methionine at the N terminus and/or a histidine tag at the C terminus.

4. The polypeptide according claim 1 , wherein said polypeptide is at least 2.0 fold more effective than IdeZ at cleaving human IgG, when measured in the same assay.

5. The polypeptide according to claim 1 which is less immunogenic than IdeS, wherein the immunogenicity of said polypeptide is no more than 85% of the immunogenicity of IdeS when measured in the same assay.

6. A composition comprising the polypeptide according to claim 1 and at least one pharmaceutically acceptable carrier or diluent.

7. The polypeptide according to claim 1 , wherein said variant of the sequence of SEQ ID NO: 4 is at least 95% identical to SEQ ID NO: 17.

8. The polypeptide according to claim 1 , wherein the variant of SEQ ID NO: 4 has deleted in its entirety the first twenty residues at the N terminus of SEQ ID NO: 4 (the contiguous sequence DDYQRNATEA YAKEVPHQIT) and sequence identity to SEQ ID NO: 4 is measured over residues 21-315.

9. The polypeptide according to claim 1 , which comprises or consists of the sequence of SEQ ID NO: 17 or 19, optionally wherein said sequence includes an additional methionine at the N terminus and/or a histidine tag at the C terminus.