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Proteasas modificadas que inhiben la activación del complemento
专利权人:
CATALYST BIOSCIENCES; INC.
发明人:
MADISON, EDWIN L.,NGUYEN, JACK,RUGGLES, SANDRA WAUGH,THANOS, CHRISTOPHER D.
申请号:
ES06817259
公开号:
ES2400306T3
申请日:
2006.10.20
申请国别(地区):
ES
年份:
2013
代理人:
摘要:
A modified protease that does not belong to the complement, comprising modifications in any one or more amino acids of a protease scaffold, wherein: 5 the rest or modified amino acid residues increase one or both of specificity for a target substrate or activity towards a target substrate, wherein the target substrate is a complement protein the frame is a protease MT-SP1 protease, allelic variant isoforms or a catalytically active portion thereof and the modified protease that does not belong to supplement comprising: a) at least two or more modifications to the frame protease in which a change is at position 146 and the second change is at position 224, based on the numbering of chymotrypsin, provided that: (i) when the only protease includes two modifications, the protease does not include Y146D or K224F as the two modifications and (ii) when the protease contains three modifications, the protease does not include F99V or I or L or T with Y146D and K224F or b) one or more modifications in protease selected frame between any one or more of D96A, D96V, D96F, D96S, D96T, F99S, F99G, Q174H, Q174A, Q174V, Q174F, Q174R, Q174K, Q174L, Q174Y, Q192L a Q192I , Q192E, Q192K, Q192Y, D217Q, D217N, D217H, Q221aD, based on chymotrypsin numbering or c) one or more modifications in protease selected frame between I41T, I41A, 141L, 141F, 141D, 25 141E, G147E, G151L, Q221aL, Q221aE, Q175H, Q175L, Q175W, Q175Y, Q175K, K224L, K224R, K224N, K224T , K224Y and K224S, based on chymotrypsin numbering.Una proteasa modificada que no pertenece al complemento, que comprende modificaciones en uno cualquiera o más aminoácidos de una proteasa armazón, en la que: 5 el resto o los restos de aminoácidos modificados aumentan una o ambas de la especificidad por un sustrato diana o la actividad hacia un sustrato diana, en la que el sustrato diana es una proteína del complemento la proteasa armazón es una proteasa MT-SP1, variantes alélicas, isoformas o una parte catalíticamente activa de la misma y la
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