Angiopoetin-like 4 (angptl4) antibodies and methods of use
AssigneeNovartis AG
InventorsJohn Trauger, Andrei Igorevich Voznesensky, Julia Neugebauer, Steffen Runz
Life of this patent
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Abstract
The present invention relates to monoclonal antibodies binding to human angiopoetin-like protein 4 (hereinafter, sometimes referred to as “ANGPTL4”), and pharmaceutical compositions and methods of treatment comprising the same.
Claims57
An isolated anti-ANGPTL4 antibody or fragment thereof.
An isolated antibody or fragment according to any previous claim, wherein said antibody or fragment blocks LPL binding to ANGPTL4 protein.
An isolated antibody or fragment thereof that binds to a human ANGPTL4 protein with a KD of less than or equal to 45 pM, as measured by ForteBio kinetic binding assays, or less than or equal to 24 pM, as measured by solution equilibrium titration assay (SET).
An isolated antibody or fragment according to any previous claim, wherein said antibody or fragment comprises at least one complementarity determining region having at least 95% identity to at least one of the CDRs recited in Table 1.
An isolated antibody or fragment according to any previous claim, wherein said antibody or fragment comprises a CDR1, CDR2, and CDR3 from Table 1.
An isolated antibody or fragment according to any previous claim, wherein said antibody or fragment comprises a CDR1, CDR2, and CDR3 from Table 1, wherein the variant has at least one to four amino acid changes in one of CDR1, CDR2, or CDR3.
An isolated antibody or fragment thereof that binds human ANGPTL4, wherein the antibody or fragment comprises a heavy chain CDR3 selected from the group consisting of SEQ ID NO:
- 9, 29, 49, 69, 89, 109, 129, 149, 169, 189, 209, 229, 249, 269, 289, 309, 329, and 349.
An isolated antibody or fragment thereof that binds human ANGPTL4, wherein the antibody or fragment comprises a VH selected from the group consisting of SEQ ID NO:
- 13, 33, 53, 73, 93, 113, 133, 153, 173, 193, 213, 233, 253, 273, 293, 313, 333, and 353;
- and a VL selected from the group consisting of SEQ ID NO:
- 23, 43, 63, 83, 103, 123, 143, 163, 183, 203, 223, 243, 263, 283, 303, 323, 343, and 363 or an amino acid sequence with 97-99% identity thereof.
An isolated antibody or fragment thereof comprising a heavy chain variable domain sequence selected from the group consisting of SEQ ID NO:
- 13, 33, 53, 73, 93, 113, 133, 153, 173, 193, 213, 233, 253, 273, 293, 313, 333, 353.
An isolated antibody or fragment thereof comprising a light chain variable domain sequence selected from the group consisting of SEQ ID NO:
- 23, 43, 63, 83, 103, 123, 143, 163, 183, 203, 223, 243, 263, 283, 303, 323, 343, 363.
An isolated antibody or fragment thereof comprising a heavy chain variable domain selected from the group consisting of SEQ ID NO:
- 13, 33, 53, 73, 93, 113, 133, 153, 173, 193, 213, 233, 253, 273, 293, 313, 333, 353;
- and light chain variable domain sequence selected from the group consisting of SEQ ID NO:
- 23, 43, 63, 83, 103, 123, 143, 163, 183, 203, 223, 243, 263, 283, 303, 323, 343, 363.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 selected from the group consisting of SEQ ID NO:
- 7, 27, 47, 67, 87, 107, 127, 147, 167, 187, 207, 227, 247, 267, 287, 307, 327, and 347;
- CDR2 selected from the group consisting of SEQ ID NO:
- 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, 228, 248, 268, 288, 308, 328, and 348;
- CDR3 selected from the group consisting of 9, 29, 49, 69, 89, 109, 129, 149, 169, 189, 209, 229, 249, 269, 289, 309, 329, and 349;
- a light chain variable region CDR1 selected from the group consisting of SEQ ID NO:
- 17, 37, 57, 77, 97, 117, 137, 157, 177, 197, 217, 237, 257, 277, 297, 317, 337, and 357;
- CDR2 selected from the group consisting of SEQ ID NO:
- 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, 238, 258, 278, 298, 318, 338, and 358;
- and CDR3 selected from the group consisting of SEQ ID NO:
- 19, 39, 59, 79, 99, 119, 139, 159, 179, 199, 219, 239, 259, 279, 299, 319, 339, and 359.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 selected from the group consisting of SEQ ID NO:
- 10, 30, 50, 70, 90, 110, 130, 150, 170, 190, 210, 230, 250, 270, 290, 310, 330, and 350;
- CDR2 selected from the group consisting of SEQ ID NO:
- 11, 31, 51, 71, 91, 111, 131, 151, 171, 191, 211, 231, 251, 271, 291, 311, 331, and 351;
- CDR3 selected from the group consisting of 12, 32, 52, 72, 92, 112, 132, 152, 172, 192, 212, 232, 252, 272, 292, 312, 332, and 352;
- a light chain variable region CDR1 selected from the group consisting of SEQ ID NO:
- 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, and 360;
- CDR2 selected from the group consisting of SEQ ID NO:
- 21, 41, 61, 81, 101, 121, 141, 161, 181, 201, 221, 241, 261, 281, 301, 321, 341, and 361;
- and CDR3 selected from the group consisting of SEQ ID NO:
- 22, 42, 62, 82, 102, 122, 142, 162, 182, 202, 222, 242, 262, 282, 302, 322, 342, 362.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 7;
- CDR2 of SEQ ID NO:
- 8;
- CDR3 of SEQ ID NO:
- 9;
- a light chain variable region CDR1 of SEQ ID NO:
- 17;
- CDR2 of SEQ ID NO:
- 18;
- and CDR3 of SEQ ID NO:
- 19.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 27;
- CDR2 of SEQ ID NO:
- 28;
- CDR3 of SEQ ID NO:
- 29;
- a light chain variable region CDR1 of SEQ ID NO:
- 37;
- CDR2 of SEQ ID NO:
- 38;
- and CDR3 of SEQ ID NO:
- 39.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 47;
- CDR2 of SEQ ID NO:
- 48;
- CDR3 of SEQ ID NO:
- 49;
- a light chain variable region CDR1 of SEQ ID NO:
- 57;
- CDR2 of SEQ ID NO:
- 58;
- and CDR3 of SEQ ID NO:
- 59.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 67;
- CDR2 of SEQ ID NO:
- 68;
- CDR3 of SEQ ID NO:
- 69;
- a light chain variable region CDR1 of SEQ ID NO:
- 77;
- CDR2 of SEQ ID NO:
- 78;
- and CDR3 of SEQ ID NO:
- 79.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 87;
- CDR2 of SEQ ID NO:
- 88;
- CDR3 of SEQ ID NO:
- 89;
- a light chain variable region CDR1 of SEQ ID NO:
- 97;
- CDR2 of SEQ ID NO:
- 98;
- and CDR3 of SEQ ID NO:
- 99.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 107;
- CDR2 of SEQ ID NO:
- 108;
- CDR3 of SEQ ID NO:
- 109;
- a light chain variable region CDR1 of SEQ ID NO:
- 117;
- CDR2 of SEQ ID NO:
- 118;
- and CDR3 of SEQ ID NO:
- 119.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 127;
- CDR2 of SEQ ID NO:
- 128;
- CDR3 of SEQ ID NO:
- 129;
- a light chain variable region CDR1 of SEQ ID NO:
- 137;
- CDR2 of SEQ ID NO:
- 138;
- and CDR3 of SEQ ID NO:
- 139.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 147;
- CDR2 of SEQ ID NO:
- 148;
- CDR3 of SEQ ID NO:
- 149;
- a light chain variable region CDR1 of SEQ ID NO:
- 157;
- CDR2 of SEQ ID NO:
- 158;
- and CDR3 of SEQ ID NO:
- 159.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 167;
- CDR2 of SEQ ID NO:
- 168;
- CDR3 of SEQ ID NO:
- 169;
- a light chain variable region CDR1 of SEQ ID NO:
- 177;
- CDR2 of SEQ ID NO:
- 178;
- and CDR3 of SEQ ID NO:
- 179.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 187;
- CDR2 of SEQ ID NO:
- 188;
- CDR3 of SEQ ID NO:
- 189;
- a light chain variable region CDR1 of SEQ ID NO:
- 197;
- CDR2 of SEQ ID NO:
- 198;
- and CDR3 of SEQ ID NO:
- 199.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 207;
- CDR2 of SEQ ID NO:
- 208;
- CDR3 of SEQ ID NO:
- 209;
- a light chain variable region CDR1 of SEQ ID NO:
- 217;
- CDR2 of SEQ ID NO:
- 218;
- and CDR3 of SEQ ID NO:
- 219.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 227;
- CDR2 of SEQ ID NO:
- 228;
- CDR3 of SEQ ID NO:
- 229;
- a light chain variable region CDR1 of SEQ ID NO:
- 237;
- CDR2 of SEQ ID NO:
- 238;
- and CDR3 of SEQ ID NO:
- 239.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 247;
- CDR2 of SEQ ID NO:
- 248;
- CDR3 of SEQ ID NO:
- 249;
- a light chain variable region CDR1 of SEQ ID NO:
- 257;
- CDR2 of SEQ ID NO:
- 258;
- and CDR3 of SEQ ID NO:
- 259.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 267;
- CDR2 of SEQ ID NO:
- 268;
- CDR3 of SEQ ID NO:
- 269;
- a light chain variable region CDR1 of SEQ ID NO:
- 277;
- CDR2 of SEQ ID NO:
- 278;
- and CDR3 of SEQ ID NO:
- 279.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 287;
- CDR2 of SEQ ID NO:
- 288;
- CDR3 of SEQ ID NO:
- 289;
- a light chain variable region CDR1 of SEQ ID NO:
- 297;
- CDR2 of SEQ ID NO:
- 298;
- and CDR3 of SEQ ID NO:
- 299.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 307;
- CDR2 of SEQ ID NO:
- 308;
- CDR3 of SEQ ID NO:
- 309;
- a light chain variable region CDR1 of SEQ ID NO:
- 310;
- CDR2 of SEQ ID NO:
- 311;
- and CDR3 of SEQ ID NO:
- 312.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 327;
- CDR2 of SEQ ID NO:
- 328;
- CDR3 of SEQ ID NO:
- 329;
- a light chain variable region CDR1 of SEQ ID NO:
- 337;
- CDR2 of SEQ ID NO:
- 338;
- and CDR3 of SEQ ID NO:
- 339.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 347;
- CDR2 of SEQ ID NO:
- 348;
- CDR3 of SEQ ID NO:
- 349;
- a light chain variable region CDR1 of SEQ ID NO:
- 357;
- CDR2 of SEQ ID NO:
- 358;
- and CDR3 of SEQ ID NO:
- 359.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 10;
- CDR2 of SEQ ID NO:
- 11;
- CDR3 of SEQ ID NO:
- 12;
- a light chain variable region CDR1 of SEQ ID NO:
- 20;
- CDR2 of SEQ ID NO:
- 21;
- and CDR3 of SEQ ID NO:
- 22.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 30;
- CDR2 of SEQ ID NO:
- 31;
- CDR3 of SEQ ID NO:
- 32;
- a light chain variable region CDR1 of SEQ ID NO:
- 40;
- CDR2 of SEQ ID NO:
- 41;
- and CDR3 of SEQ ID NO:
- 42.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 50;
- CDR2 of SEQ ID NO:
- 51;
- CDR3 of SEQ ID NO:
- 52;
- a light chain variable region CDR1 of SEQ ID NO:
- 60;
- CDR2 of SEQ ID NO:
- 61;
- and CDR3 of SEQ ID NO:
- 62.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 70;
- CDR2 of SEQ ID NO:
- 71;
- CDR3 of SEQ ID NO:
- 72;
- a light chain variable region CDR1 of SEQ ID NO:
- 80;
- CDR2 of SEQ ID NO:
- 81;
- and CDR3 of SEQ ID NO:
- 82.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 90;
- CDR2 of SEQ ID NO:
- 91;
- CDR3 of SEQ ID NO:
- 92;
- a light chain variable region CDR1 of SEQ ID NO:
- 100;
- CDR2 of SEQ ID NO:
- 101;
- and CDR3 of SEQ ID NO:
- 102.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 110;
- CDR2 of SEQ ID NO:
- 111;
- CDR3 of SEQ ID NO:
- 112;
- a light chain variable region CDR1 of SEQ ID NO:
- 120;
- CDR2 of SEQ ID NO:
- 121;
- and CDR3 of SEQ ID NO:
- 122.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 130;
- CDR2 of SEQ ID NO:
- 131;
- CDR3 of SEQ ID NO:
- 132;
- a light chain variable region CDR1 of SEQ ID NO:
- 140;
- CDR2 of SEQ ID NO:
- 141;
- and CDR3 of SEQ ID NO:
- 142.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 150;
- CDR2 of SEQ ID NO:
- 151;
- CDR3 of SEQ ID NO:
- 152;
- a light chain variable region CDR1 of SEQ ID NO:
- 160;
- CDR2 of SEQ ID NO:
- 161;
- and CDR3 of SEQ ID NO:
- 162.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 170;
- CDR2 of SEQ ID NO:
- 171;
- CDR3 of SEQ ID NO:
- 172;
- a light chain variable region CDR1 of SEQ ID NO:
- 180;
- CDR2 of SEQ ID NO:
- 181;
- and CDR3 of SEQ ID NO:
- 182.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 190;
- CDR2 of SEQ ID NO:
- 191;
- CDR3 of SEQ ID NO:
- 192;
- a light chain variable region CDR1 of SEQ ID NO:
- 200;
- CDR2 of SEQ ID NO:
- 201;
- and CDR3 of SEQ ID NO:
- 202.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 210;
- CDR2 of SEQ ID NO:
- 211;
- CDR3 of SEQ ID NO:
- 212;
- a light chain variable region CDR1 of SEQ ID NO:
- 220;
- CDR2 of SEQ ID NO:
- 221;
- and CDR3 of SEQ ID NO:
- 222.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 230;
- CDR2 of SEQ ID NO:
- 231;
- CDR3 of SEQ ID NO:
- 232;
- a light chain variable region CDR1 of SEQ ID NO:
- 240;
- CDR2 of SEQ ID NO:
- 241;
- and CDR3 of SEQ ID NO:
- 242.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 250;
- CDR2 of SEQ ID NO:
- 251;
- CDR3 of SEQ ID NO:
- 252;
- a light chain variable region CDR1 of SEQ ID NO:
- 260;
- CDR2 of SEQ ID NO:
- 261;
- and CDR3 of SEQ ID NO:
- 262.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 270;
- CDR2 of SEQ ID NO:
- 271;
- CDR3 of SEQ ID NO:
- 272;
- a light chain variable region CDR1 of SEQ ID NO:
- 280;
- CDR2 of SEQ ID NO:
- 281;
- and CDR3 of SEQ ID NO:
- 282.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 290;
- CDR2 of SEQ ID NO:
- 291;
- CDR3 of SEQ ID NO:
- 292;
- a light chain variable region CDR1 of SEQ ID NO:
- 300;
- CDR2 of SEQ ID NO:
- 301;
- and CDR3 of SEQ ID NO:
- 302.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 310;
- CDR2 of SEQ ID NO:
- 311;
- CDR3 of SEQ ID NO:
- 312;
- a light chain variable region CDR1 of SEQ ID NO:
- 320;
- CDR2 of SEQ ID NO:
- 321;
- and CDR3 of SEQ ID NO:
- 322.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 320;
- CDR2 of SEQ ID NO:
- 321;
- CDR3 of SEQ ID NO:
- 322;
- a light chain variable region CDR1 of SEQ ID NO:
- 330;
- CDR2 of SEQ ID NO:
- 331;
- and CDR3 of SEQ ID NO:
- 332.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 340;
- CDR2 of SEQ ID NO:
- 341;
- CDR3 of SEQ ID NO:
- 342;
- a light chain variable region CDR1 of SEQ ID NO:
- 350;
- CDR2 of SEQ ID NO:
- 351;
- and CDR3 of SEQ ID NO:
- 352.
An isolated antibody or fragment thereof according to any previous claim, wherein said antibody or fragment comprises a modified heavy chain CDR2 or modified light chain CDR3 from Table 8.
An isolated antibody or fragment thereof according to any previous claim, wherein said antibody or fragment comprises a modified heavy chain CDR2 or modified light chain CDR3 selected from any of SEQ ID NO:
- 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 499, 401, 402, 403, 404, 405, 406, 407, 408, and 409.
A pharmaceutical composition comprising an antibody or fragment thereof of one of the above claims and a pharmaceutically acceptable carrier.
A method of treating an ANGPTL4-disorder comprising administering to a patient afflicted with an ANGPTL4-disorder an effective amount of a pharmaceutical composition comprising an antibody or fragment according to any previous claim.
An isolated antibody or fragment thereof that binds to the same epitope as an isolated antibody or fragment according to any previous claim.
An isolated antibody or fragment thereof that binds to a human ANGPTL4 protein and cross-competes with an isolated antibody or fragment according to any previous claim.
Dependencies are inferred from the claim text.