Anti-apoc3 antibodies and methods of use thereof

Abstract

The instant disclosure provides antibodies that specifically bind to ApoC3 (e.g., human ApoC3) and antagonize ApoC3 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

1 - 64 . (canceled) 
     
     
         65 . A polynucleotide encoding a heavy chain variable region (VH) and/or a light chain variable region (VL) of an antibody that specifically binds to ApoC3, wherein the VH comprises the CDRH1, CDRH2 and CDRH3 amino acid sequences of a VH amino acid sequence selected from the group consisting of SEQ ID NOs: 137-160, and/or the VL comprises the CDRL1, CDRL2 and CDRL3 amino acid sequences of a VL amino acid sequence selected from the group consisting of SEQ ID NOs: 161-183 and 151. 
     
     
         66 . The polynucleotide of  claim 65 , wherein:
 (a) CDRH1, CDRH2 and CDRH3 comprise the amino acid sequences of SEQ ID NOs: 4, 5, and 6; 7, 8, and 9; 10, 11, and 12; 13, 14, and 15; 16, 17, and 18; 19, 20, and 21; 22, 23, and 24; 25, 26, and 27; 28, 29, and 30; 16, 31, and 32; 33, 34, and 35; 25, 36, and 37; 38, 39, and 40; 41, 42, and 43; 47, 48, and 49; 50, 51, and 52; 53, 54, and 55; 56, 57, and 58; 59, 60, and 61; 62, 63, and 64; 65, 66, and 67; 68, 69, and 70; or 68, 71, and 72, respectively; and/or   (b) CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences of SEQ ID NOs: 73, 74, and 75; 76, 77, and 78; 79, 80, and 81; 82, 83, and 84; 85, 86, and 87; 88, 83, and 89; 90, 91, and 92; 82, 93, and 94; 95, 96, and 97; 98, 99, and 100; 101, 99, and 102; 103, 104, and 105; 82, 106, and 107; 108, 109, and 110; 111, 83, and 113; 82, 114, and 115; 116, 117, and 118; 119, 120, and 121; 122, 123, and 124; 125, 83, and 126; 127, 128, and 129; 82, 114, and 130; 131, 132, and 133; or 124, 135, and 136, respectively.   
     
     
         67 . The polynucleotide of  claim 65 , wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences of SEQ ID NOs: 4, 5, 6, 73, 74, and 75; 7, 8, 9, 76, 77, and 78; 10, 11, 12, 79, 80, and 81; 13, 14, 15, 82, 83, and 84; 16, 17, 18, 85, 86, and 87; 19, 20, 21, 88, 83, and 89; 22, 23, 24, 90, 91, and 92; 25, 26, 27, 82, 93, and 94; 28, 29, 30, 95, 96, and 97; 16, 31, 32, 98, 99, and 100; 33, 34, 35, 101, 99, and 102; 25, 36, 37, 103, 104, and 105; 38, 39, 40, 82, 106, and 107; 41, 42, 43, 108, 109, and 110; 7, 8, 9, 111, 83, and 113; 47, 48, 49, 82, 114, and 115; 50, 51, 52, 116, 117, and 118; 53, 54, 55, 119, 120, and 121; 56, 57, 58, 122, 123, and 124; 59, 60, 61, 125, 83, and 126; 62, 63, 64, 127, 128, and 129; 65, 66, 67, 82, 114, and 130; 68, 69, 70, 131, 132, and 133; or 68, 71, 72, 124, 135, and 136, respectively. 
     
     
         68 . The polynucleotide of  claim 65 , wherein the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 137-160, and/or the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 161-183 and 15. 
     
     
         69 . The polynucleotide of  claim 65 , wherein the VH and VL comprise the amino acid sequences of SEQ ID NOs: 137 and 161; 138 and 162; 139 and 163; 140 and 164; 141 and 165; 142 and 166; 143 and 167; 144 and 168; 145 and 169; 146 and 170; 147 and 171; 148 and 172; 149 and 173; 150 and 174; 138 and 175; 152 and 176; 153 and 177; 154 and 178; 155 and 179; 156 and 180; 157 and 181; 158 and 182; 159 and 183; or 160 and 151, respectively. 
     
     
         70 . A polynucleotide encoding a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 137-160. 
     
     
         71 . A polynucleotide encoding a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 161-183 and 151. 
     
     
         72 . An expression vector comprising the polynucleotide of  claim 65 . 
     
     
         73 . An expression vector comprising the polynucleotide of  claim 70 . 
     
     
         74 . An expression vector comprising the polynucleotide of  claim 71 . 
     
     
         75 . A host cell comprising the polynucleotide of  claim 65 . 
     
     
         76 . A host cell comprising the polynucleotide of  claim 70 . 
     
     
         77 . A host cell comprising the polynucleotide of  claim 71 . 
     
     
         78 . A method of producing an antibody that binds to ApoC3, the antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the CDRH1, CDRH2 and CDRH3 amino acid sequences of a VH amino acid sequence selected from the group consisting of SEQ ID NOs: 137-160, and/or the VL comprises the CDRL1, CDRL2 and CDRL3 amino acid sequences of a VL amino acid sequence selected from the group consisting of SEQ ID NOs: 161-183 and 151,
 wherein the method comprises culturing a host cell comprising:   (a) a polynucleotide encoding the VH and the VL, or a heavy chain and a light chain, of the antibody;   (b) a first polynucleotide encoding the VH or a heavy chain of the antibody and a second polynucleotide encoding the VL or a light chain of the antibody;   (c) a vector comprising a polynucleotide encoding the VH and the VL, or a heavy chain and a light chain, of the antibody; or   (d) a first vector comprising a first polynucleotide encoding the VH or a heavy chain of the antibody and a second vector comprising a second polynucleotide encoding the VL or a light chain of the antibody,   under conditions that allow expression of the antibody.   
     
     
         79 . The method of  claim 78 , wherein:
 (a) CDRH1, CDRH2 and CDRH3 comprise the amino acid sequences of SEQ ID NOs: 4, 5, and 6; 7, 8, and 9; 10, 11, and 12; 13, 14, and 15; 16, 17, and 18; 19, 20, and 21; 22, 23, and 24; 25, 26, and 27; 28, 29, and 30; 16, 31, and 32; 33, 34, and 35; 25, 36, and 37; 38, 39, and 40; 41, 42, and 43; 47, 48, and 49; 50, 51, and 52; 53, 54, and 55; 56, 57, and 58; 59, 60, and 61; 62, 63, and 64; 65, 66, and 67; 68, 69, and 70; or 68, 71, and 72, respectively; and/or   (b) CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences of SEQ ID NOs: 73, 74, and 75; 76, 77, and 78; 79, 80, and 81; 82, 83, and 84; 85, 86, and 87; 88, 83, and 89; 90, 91, and 92; 82, 93, and 94; 95, 96, and 97; 98, 99, and 100; 101, 99, and 102; 103, 104, and 105; 82, 106, and 107; 108, 109, and 110; 111, 83, and 113; 82, 114, and 115; 116, 117, and 118; 119, 120, and 121; 122, 123, and 124; 125, 83, and 126; 127, 128, and 129; 82, 114, and 130; 131, 132, and 133; or 124, 135, and 136, respectively.   
     
     
         80 . The method of  claim 78 , wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences of SEQ ID NOs: 4, 5, 6, 73, 74, and 75; 7, 8, 9, 76, 77, and 78; 10, 11, 12, 79, 80, and 81; 13, 14, 15, 82, 83, and 84; 16, 17, 18, 85, 86, and 87; 19, 20, 21, 88, 83, and 89; 22, 23, 24, 90, 91, and 92; 25, 26, 27, 82, 93, and 94; 28, 29, 30, 95, 96, and 97; 16, 31, 32, 98, 99, and 100; 33, 34, 35, 101, 99, and 102; 25, 36, 37, 103, 104, and 105; 38, 39, 40, 82, 106, and 107; 41, 42, 43, 108, 109, and 110; 7, 8, 9, 111, 83, and 113; 47, 48, 49, 82, 114, and 115; 50, 51, 52, 116, 117, and 118; 53, 54, 55, 119, 120, and 121; 56, 57, 58, 122, 123, and 124; 59, 60, 61, 125, 83, and 126; 62, 63, 64, 127, 128, and 129; 65, 66, 67, 82, 114, and 130; 68, 69, 70, 131, 132, and 133; or 68, 71, 72, 124, 135, and 136, respectively. 
     
     
         81 . The method of  claim 78 , wherein the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 137-160, and/or the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 161-183 and 15. 
     
     
         82 . The method of  claim 78 , wherein the VH and VL comprise the amino acid sequences of SEQ ID NOs: 137 and 161; 138 and 162; 139 and 163; 140 and 164; 141 and 165; 142 and 166; 143 and 167; 144 and 168; 145 and 169; 146 and 170; 147 and 171; 148 and 172; 149 and 173; 150 and 174; 138 and 175; 152 and 176; 153 and 177; 154 and 178; 155 and 179; 156 and 180; 157 and 181; 158 and 182; 159 and 183; or 160 and 151, respectively.