Anti-apoc3 antibodies and methods of use thereof
AssigneeStaten Biotechnology B.V.
InventorsPaul DaSilva-Jardine, Hans de Haard, James A. Landro
Life of this patent
Estimating the term…
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.
Claims26
An isolated antibody that specifically binds to ApoC3 and attenuates the ability of ApoC3 to inhibit hepatocyte uptake of very low density lipoprotein (VLDL), optionally wherein:
- (a) the antibody is capable of inhibiting post-prandial lipemia in a subject
- (b) the antibody is capable of increasing the rate of clearance of ApoB from the blood in a subject
- (c) the antibody is capable of reducing the level of ApoB in the blood in a subject
- (d) the antibody attenuates the ability of ApoC3 to inhibit lipoprotein lipase-mediated lipolysis of VLDL;
- (e) the antibody inhibits the binding of ApoC3 to a lipid;
- and/or
- (f) the antibody is capable of binding to lipid-bound ApoC3.
2-7. (canceled)
An isolated antibody that specifically binds to ApoC3, wherein the antibody binds to an epitope within the amino acid sequence set forth in SEQ ID NO:
- 2 [GWVTDGFSSLK], optionally wherein:
- (a) the epitope comprises at least one of the amino acids at positions 1, 4, 6, 7, 9 or 10 of SEQ ID NO:
- 2;
- (b) the epitope comprises the amino acids at positions 4 and 9 of SEQ ID NO:
- 2;
- (c) the epitope comprises the amino acids at positions 4, 6 and 9 of SEQ ID NO:
- 2;
- (d) the epitope comprises the amino acids at positions 1, 4, 6 and 9 of SEQ ID NO:
- 2;
- (e) the epitope comprises the amino acids at positions 1, 4, 6, 7, 9 and 10 of SEQ ID NO:
- 2;
- (f) the antibody attenuates the ability of ApoC3 to inhibit lipoprotein lipase-mediated lipolysis of VLDL;
- and/or
- (g) the antibody inhibits the binding of ApoC3 to a lipid.
9-15. (canceled)
An isolated antibody that specifically binds to ApoC3, wherein the antibody binds to an epitope within the amino acid sequence set forth in SEQ ID NO:
- 3 [FSEFWDLDPE], optionally wherein:
- (a) the epitope comprises at least one of the amino acids at position 2, 5, 6, 8, or 10 of SEQ ID NO:
- 3;
- (b) the epitope comprises the amino acids at positions 5 and 6 of SEQ ID NO:
- 3;
- (c) the epitope comprises the amino acids at positions 2, 5, 6, and 8 of SEQ ID NO:
- 3;
- (d) the epitope comprises the amino acids at position 10 of SEQ ID NO:
- 3;
- (e) the epitope comprises the amino acids at positions 6, 8, and 10 of SEQ ID NO:
- 3;
- (f) the epitope comprises the amino acids at positions 6 and 8 of SEQ ID NO:
- 3;
- (g) the antibody is capable of binding to lipid-bound ApoC3;
- (h) the antibody attenuates the ability of ApoC3 to inhibit hepatocyte uptake of very low density lipoprotein (VLDL);
- (i) the antibody is capable of inhibiting post-prandial lipemia in a subject
- (j) the antibody is capable of increasing the rate of clearance of ApoB from the blood in a subject;
- and/or
- (k) the antibody is capable of reducing the level of ApoB in the blood in a subject.
17-27. (canceled)
An isolated antibody that specifically binds to ApoC3, comprising a heavy chain variable region having complementarity determining regions CDRH1, CDRH2 and CDRH3, and a light chain variable region having complementarity determining regions CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences set forth in 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.
An isolated antibody that specifically binds to ApoC3, the antibody comprising:
- a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 137-160;
- and/or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 161-183 and 151.
(canceled)
An isolated antibody that specifically binds to ApoC3, the antibody comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region, respectively, comprise the amino acid sequences set forth in 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.
35-40. (canceled)
52-64. (canceled)
Dependencies are inferred from the claim text.