Targeting rare human PCSK9 variants for cholesterol treatment

摘要

The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.

主权项

1. A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof comprising
a. selecting a human comprising a nucleotide sequence encoding a proprotein convertase subtilisin/kexin type 9 (PSCK9) that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1; and b. administering to said human an antibody or antibody fragment that specifically binds a PCSK9 amino acid sequence encoded by said nucleotide sequence comprised by the human, wherein the antibody comprises a VH domain derived from the recombination of a human VH gene segment, a human D gene segment, and a human JH segment, the human VH gene segment encoding the framework 1 of SEQ ID NO: 40; and wherein said human comprises a VH gene segment encoding the framework 1 of SEQ ID NO: 40.