Targeting rare human PCSK9 variants for cholesterol treatment
First Claim
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1. A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof comprisinga. 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.
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Abstract
The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.
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Citations
29 Claims
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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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
- 1; and
Specification