Anti-pcsk9 antibodies

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.

1 . A nucleic acid molecule encoding a heavy chain variable region (HCVR) of an anti-human PCSK9 antibody or antigen-binding fragment thereof, wherein the HCVR comprises a heavy chain complementarity determining region (HCDR)1 comprising SEQ ID NO:76, an HCDR2 comprising SEQ ID NO:78, and an HCDR3 comprising SEQ ID NO:80. 
     
     
         2 . A nucleic acid molecule encoding a light chain variable region (LCVR) of an anti-human PCSK9 antibody or antigen-binding fragment thereof, wherein the LCVR comprises a light chain complementarity determining region (LCDR)1 comprising SEQ ID NO:84, an LCDR2 comprising SEQ ID NO:86, and an LCDR3 comprising SEQ ID NO:88. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The nucleic acid molecule of  claim 1  that encodes an HCVR comprising the amino acid sequence of SEQ ID NO:90. 
     
     
         8 . The nucleic acid molecule of  claim 1  that comprises a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:89. 
     
     
         9 . A recombinant expression vector comprising the nucleic acid molecule of  claim 1 . 
     
     
         10 . The nucleic acid molecule of  claim 2  that encodes an LCVR comprising the amino acid sequence of SEQ ID NO:92. 
     
     
         11 . The nucleic acid molecule of  claim 2  that comprises a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:91. 
     
     
         12 . A recombinant expression vector comprising the nucleic acid molecule of  claim 2 . 
     
     
         13 . A method of producing an anti-human PCSK9 antibody or antigen-binding fragment thereof, the method comprising:
 culturing a host cell under conditions permitting production of the antibody or antigen-binding fragment thereof, wherein the host cell comprises: (i) a first recombinant expression vector comprising a nucleic acid molecule encoding an HCVR of the anti-human PCSK9 antibody, wherein the HCVR comprises an HCDR1 comprising SEQ ID NO:76, an HCDR2 comprising SEQ ID NO:78, and an HCDR3 comprising SEQ ID NO:80; and (ii) a second recombinant expression vector comprising a nucleic acid molecule encoding a LCVR of the anti-human PCSK9 antibody, wherein the LCVR comprises an LCDR1 comprising SEQ ID NO:84, an LCDR2 comprising SEQ ID NO:86, and an LCDR3 comprising SEQ ID NO:88; and   recovering the antibody or antigen-binding fragment produced.   
     
     
         14 . The method of  claim 13 , wherein the first recombinant expression vector comprises a nucleic acid molecule encoding an HCVR comprising the amino acid sequence of SEQ ID NO:90. 
     
     
         15 . The method of  claim 13 , wherein the first recombinant expression vector comprises a nucleic acid molecule comprising a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:89. 
     
     
         16 . The method of  claim 13 , wherein the second recombinant expression vector comprises a nucleic acid molecule encoding an LCVR comprising the amino acid sequence of SEQ ID NO:92. 
     
     
         17 . The method of  claim 13 , wherein the second recombinant expression vector comprises a nucleic acid molecule comprising a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:91. 
     
     
         18 . The method of  claim 13 , wherein the host cell is a Chinese Hamster Ovary (CHO) cell.