Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment

A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation selected from the group consisting of I474V and E670G in SEQ ID NO:

• 1,
• wherein the antibody or antibody fragment comprises a VH domain derived from the recombination of a human VH segment, a human D gene segment and a human JH segment, the human VH segment encoding the framework 1 of SEQ ID NO:
• 40, and wherein said human comprises:
• (i) a VH gene segment encoding the framework 1 of SEQ ID NO:
• 40, or the human expresses antibodies comprising VH domains derived from the recombination of a human VH segment, a human D gene segment and a human JH segment, the human VH segment encoding the framework 1 of SEQ ID NO:
• 40;
• and
• (ii) a nucleotide sequence encoding said PCSK9 that comprises a C-terminal domain comprising said selected mutation in SEQ ID NO:
• 1.