| 摘要 |
Disclosed is a modified non-complement protease, comprising modifications in any one or more amino acids of a scaffold protease, wherein: the modified amino acid residue(s) increases one or both of specificity for a target substrate or activity towards a target substrate, wherein the target substrate is a complement protein; the scaffold protease is an MT-SP1 protease, allelic variants, isoforms or catalytically active portion thereof; and the modified non-complement protease comprises at least two or more modifications in the scaffold protease, wherein one modification is at position 146 and the second modification is at position 224, based on chymotrypsin numbering, provided that: (i) where the protease includes only two modifications, the protease does not include Y146D and K224F as the two modification; and (ii) where the protease contains three modifications, the protease does not include F99V or I or L or T with Y146D and K224F. Further disclosed is a modified non-complement protease, wherein: the modified non-complement protease comprises modifications in any one or more amino acids of a scaffold protease, wherein the modified amino acid residue(s) increases one or both of specificity for a target substrate or activity towards a target substrate, wherein the target substrate is a complement protein; the scaffold protease is an MT-SP1 protease, allelic variant, isoform or a catalytically active portion thereof; and modification(s) in an MT-SP1 protease or a catalytically active portion thereof selected from any one or more of D96A, D96V, D96F, D96S, D96T, F99S, F99G, Q174H, Q174A, Q174V, Q174F, Q174R, Q174K, Q174L, Q174Y, Q192L, Q192I, Q192E, Q192K, Q192Y, D217Q, D217N, D217H, Q221aD, based on chymotrypsin numbering; or the modifications are selected from among I41T, I41A, I41L, I41F, I41D, I41E, G147E, G151L, Q221aL. Q221aE, Q175H, Q175L, Q175W, Q175Y, Q175K, K224L, K224R, K224N, K224T, K224Y and K224S, based on chymotrypsin numbering. |
