Anti-pcsk9 antibodies
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsMark W. SLEEMAN, Joel H. MARTIN, Tammy T. HUANG, Douglas MACDONALD
Life of this patent
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Abstract
An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.
Claims21
A human antibody or antigen-binding fragment of a human antibody that specifically binds human proprotein convertase subtilisin/kexin type 9 (hPCSK9), characterized by one or more of the following:
- (i) capable of reducing serum total cholesterol at least about 25 to 35% and sustaining the reduction over at least a 24 day period relative to a predose level;
- (ii) capable of reducing serum LDL cholesterol at least about 65-80% and sustaining the reduction over at least a 24 day period relative to a predose level or capable of reducing serum LDL cholesterol at least about 40-70% and sustaining the reduction over at least a 60 to 90 day period relative to a predose level;
- (iii) capable of reducing serum triglyceride at least about 25-40% relative to predose level;
- (iv) achieves one or more of (i)-(iii) without reducing serum HDL cholesterol or reducing serum HDL cholesterol no more than 5% relative to predose level;
- (v) achieves one or more of (i)-(iii) with little or no measurable effect on liver function, as determined by ALT and AST measurements.
The antibody or antigen-binding fragment according to any one of the above claims, wherein the HCVR is SEQ ID NO:90 or 218, and the LCVR is SEQ ID NO:90 or 218.
The antibody or antigen-binding fragment according to any one of the above claims, wherein the binding of the antibody or fragment thereof to a variant PCSK9 protein is less than 50% of the binding between the antibody or fragment thereof and the PCSK9 protein of SEQ ID NO:755.
The antibody or antigen-binding fragment according to any one of the above claims, comprising a heavy chain variable region (HCVR) encoded by nucleotide sequence segments derived from VH, DH and JH germline gene segments, and a light chain variable region (LCVR) encoded by nucleotide sequence segments derived from V and JK germline gene segments, wherein the germline sequences are:
- a) VH gene 3-23, DH gene 7-27, JH gene 2, VK gene 4-1, JK gene 2, or
- b) VH gene 3-7, DH gene 2-8, JH gene 6, VK gene 2-28, JK gene 4.
An isolated nucleic acid molecule encoding the antibody or antigen-binding fragment according to any one of the above claims.
Dependencies are inferred from the claim text.