Murphy Andrew J.,Yancopoulos George D.,Stahl Neil,Papadopoulos Nicholas J.
申请号：
NZ70477113
公开号：
NZ704771A
申请日:
2013.08.12
申请国别(地区):
NZ
年份:
2018
代理人:
摘要：
The present invention provides antibodies and antigen-binding fragments thereof that specifically bind proprotein convertase subtilisin/kexin-9 (PCSK9) with greater affinity at neutral pH than at acidic pH. The antibodies of the invention may possess one or more amino acid changes as compared to antibodies that do not exhibit pH-dependent binding properties. For example, the present invention includes anti-PCSK9 antibodies which possess one or more histidine substitutions in one or more complementarity determining regions. The antibodies of the invention, with pH-dependent binding properties, remain in circulation and exhibit cholesterol lowering activity for prolonged periods of time in animal subjects as compared to anti-PCSK9 antibodies that do not exhibit pH-dependent binding properties. The antibodies of the invention are therefore useful for treating diseases and disorders related to elevated LDL-C levels, wherein the antibodies of the invention can be administered to a patient at a lower dose and/or with less frequent dosing as compared to antibodies that do not exhibit pH-dependent binding properties.
