Yancopoulos, George D.,Papadopoulos, Nicholas J.,Murphy, Andrew J.,Stahl, Neil
申请号：
AU2013302925
公开号：
AU2013302925B2
申请日:
2013.08.12
申请国别(地区):
AU
年份:
2018
代理人:
摘要：
The present disclosure 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 disclosed herein may possess one or more amino acid changes as compared to antibodies that do not exhibit pH-dependent binding properties. For example, the present disclosure includes anti-PCSK9 antibodies which possess one or more histidine substitutions in one or more complementarity determining regions. The antibodies disclosed herein, 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 disclosed herein are therefore useful for treating diseases and disorders related to elevated HDL cholesterol, wherein the antibodiesdisclosed herein 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.
