The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inhibiting PCSK9 binding to LDLR and having increased pH sensitivity, improved binding affinity and/or increased in vivos half life. In embodiments, the antigen binding proteins specifically bind PCSK9 and have increased pH sensitivity, improved binding affinity and/or increased in vivos half life. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind PCSK9. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from hypercholesterolemia and related disorders or conditions.本發明提供如下組合物及方法,其與能夠抑制PCSK9結合於LDLR且具有增加之pH值敏感性、改良之結合親和力及/或增加之活體內半衰期的抗原結合蛋白有關或來源於該等抗原結合蛋白。在實施例中,該等抗原結合蛋白特異性結合PCSK9且具有增加之pH值敏感性、改良之結合親和力及/或增加之活體內半衰期。在一些實施例中,抗原結合蛋白為特異性結合PCSK9之完全人類、人類化或嵌合抗體、該等抗體之結合片段及衍生物以及多肽。其他實施例提供編碼該等抗原結合蛋白之核酸、其片段及衍生物及多肽;包含該等聚核苷酸之細胞;產生該等抗原結合蛋白、其片段及衍生物及多肽之方法;及使用該等抗原結合蛋白、其片段及衍生物及多肽之方法,包括治療或診斷罹患高膽固醇血症及相關病症或病狀之個體的方法。
