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;
• E670G;
• N425S;
• and Q619P in SEQ ID NO:
• 1;
• wherein the antibody or fragment comprises a human IGLC2*01 light chain constant region and wherein said human comprises:
• (i) a human IGLC2*01 nucleotide sequence or the human expresses antibodies comprising human light chain IGLC2*01 constant regions and
• (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said selected mutation in SEQ ID NO:
• 1.