US2023140035A1PendingUtilityA1
Antibodies that bind tumor tissue for diagnosis and therapy
Est. expiryFeb 15, 2039(~12.6 yrs left)· nominal 20-yr term from priority
Inventors:Jeff DefalcoDaniel Eric EmerlingJessica FinnNorman Michael GreenbergVera HuangShaun M. LippowFengling LiuAmy Manning-BogWilliam H. RobinsonAlexander ScholzTito SerafiniNikhil VadWayne VolkmuthYann Chong Tan
A61K 39/0011C07K 16/283C07K 2317/21C07K 16/44A61K 39/3955A61K 39/39558C07K 2317/565C07K 2317/732A61K 2039/505C07K 16/30C07K 16/06A61K 2039/507C07K 2317/92A61P 35/00C07K 16/2818G01N 33/6854C07K 2317/32
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Claims
Abstract
Provided herein are antibodies that bind to tumor tissue through a binding interaction with an extracellular RNA-protein complex. Such antibodies are used in methods of inducing an immune response and methods of inhibiting tumor cell growth. Additionally provided are methods of producing such antibodies.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of treating a cancer patient having a tumor that comprises an extracellular RNA-protein complex, the method comprising administering to the patient an antibody that binds to tissue from the tumor, wherein the antibody comprises:
a heavy chain variable region comprising:
an HCDR1 comprising a sequence GFTFSKAWMS (SEQ ID NO:1), or a variant HCDR1 in which 1 amino acid is substituted relative to the sequence;
an HCDR2 comprising a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9), or a variant HCDR2 in which 1 amino acid is substituted relative to the sequence; and
an HCDR3 comprising a sequence TSSFCCRGGSCPSHDTSYCGGQYKSYYYMDV (SEQ ID NO:21), or a variant HCDR3 in which 1, 2, or 3 amino acids are substituted relative to the sequence;
a light chain variable region comprising:
an LCDR1 comprising a sequence SGSSSNIGSSSVS (SEQ ID NO:48), or a variant LCDR1 in which 1 amino acid is substituted relative to the sequence;
an LCDR2 comprising a sequence KNNQRPS (SEQ ID NO:59), or variant LCDR2 in which 1 amino acid is substituted relative to the sequence; and
an LCDR3 comprising a sequence STWDDSLSVRV (SEQ ID NO:68), or a variant LCDR3 in which 1 amino acid is substituted relative to the sequence.
2 . The method of claim 1 , wherein the antibody comprises an HCDR1 comprising a sequence GFTFSKAWMS (SEQ ID NO:1), an HCDR2 comprising a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9), an HCDR3 comprising a sequence TSSFCCRGGSCPSHDTSYCGGQYKSYYYMDV (SEQ ID NO:21), an LCDR1 comprising a sequence SGSSSNIGSSSVS (SEQ ID NO:48), an LCDR2 comprising a sequence KNNQRPS (SEQ ID NO:59), and an LCDR3 comprising a sequence STWDDSLSVRV (SEQ ID NO:68).
3 . The method of claim 2 , wherein the V H comprises an amino acid sequence having at least 95% identity to EVQLVESGGALVKPGGSLRLSCAASGFTFSKAWMSWVRQAPGKGLEWVGRIKSVTDG ETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCTSSFCCRGGSCPSHDTSY CGGQYKSYYYMDVWGKGTTVTVSS (SEQ ID NO:94); and the V L comprises an amino sequence having at least 95% identity to
(SEQ ID NO: 140)
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSSSVSWYQQLPGTAPKLLIY
KNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSTWDDSLSVRV
FGGGTKLTVL.
4 . The method of claim 3 , wherein the V H comprises a sequence
(SEQ ID NO: 94)
EVQLVESGGALVKPGGSLRLSCAASGFTFSKAWMSWVRQAPGKGLEWVGR
IKSVTDGETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCTS
SFCCRGGSCPSHDTSYCGGQYKSYYYMDVWGKGTTVTVSS;
and the V L comprises a sequence
(SEQ ID NO: 140)
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSSSVSWYQQLPGTAPKLLIY
KNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSTWDDSLSVRV
FGGGTKLTVL.
5 . The method of claim 1 , wherein the antibody comprises a heavy chain constant region sequence of SEQ ID NO:1721 and a light chain constant region sequence of SEQ ID NO:1722.
6 . The method of claim 5 , wherein the heavy chain comprises a sequence of SEQ ID NO:1723 and the light chain comprises a sequence of SEQ ID NO:1724.
7 . A method of treating a cancer patient having a tumor that comprises an extracellular RNA-protein complex, the method comprising administering to the patient an antibody that binds to tissue from the tumor, wherein the antibody comprises six CDRs comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 sequences, respectively, as follows:
AIP-192482 SEQ ID NOS: 8, 9, 34, 48, 59, 68; AIP-171142 SEQ ID NOS: 8, 9, 35, 48, 59, 68; AIP-165430 SEQ ID NOS: 8, 9, 37, 48, 59, 68; AIP-189526 SEQ ID NOS: 8, 16, 38, 48, 59, 68; AIP-122563 SEQ ID NOS: 8, 9, 34, 48, 59, 68; AIP-158623 SEQ ID NOS: 8, 9, 37, 48, 59, 68; AIP-155066 SEQ ID NOS: 8, 9, 39, 48, 59, 68; AIP-166120 SEQ ID NOS: 8, 9, 21, 48, 59, 68; AIP-133645 SEQ ID NOS: 8, 9, 37, 48, 59, 73; AIP-187893 SEQ ID NOS: 1, 9, 37, 48, 59, 68; AIP-142079 SEQ ID NOS: 8, 9, 41, 48, 59, 68; AIP-102396 SEQ ID NOS: 172, 366, 560, 754, 948, 1142; AIP-150055 SEQ ID NOS: 173, 367, 561, 755, 949, 1143; AIP-167084 SEQ ID NOS: 174, 368, 562, 756, 950, 1144; AIP-185304 SEQ ID NOS: 175, 369, 563, 757, 951, 1145; AIP-134770 SEQ ID NOS: 176, 370, 564, 758, 952, 1146; AIP-141887 SEQ ID NOS: 177, 371, 565, 759, 953, 1147; AIP-196203 SEQ ID NOS: 178, 372, 566, 760, 954, 1148; AIP-128195 SEQ ID NOS: 180, 374, 568, 762, 956, 1150; AIP-116579 SEQ ID NOS: 181, 375, 569, 763, 957, 1151; AIP-192329 SEQ ID NOS: 182, 376, 570, 764, 958, 1152 AIP-197809 SEQ ID NOS: 184, 378, 572, 766, 960, 1154; AIP-142489 SEQ ID NOS: 185, 379, 573, 767, 961, 1155; AIP-167726 SEQ ID NOS: 187, 381, 575, 769, 963, 1157; AIP-199834 SEQ ID NOS: 188, 382, 576, 770, 964, 1158; AIP-143179 SEQ ID NOS: 189, 383, 577, 771, 965, 1159; AIP-195587 SEQ ID NOS: 190, 384, 578, 772, 966, 1160; AIP-153462 SEQ ID NOS: 191, 385, 579, 773, 967, 1161; AIP-115363 SEQ ID NOS: 192, 386, 580, 774, 968, 1162; AIP-151090 SEQ ID NOS: 193, 387, 581, 775, 969, 1163; AIP-168083 SEQ ID NOS: 194, 388, 582, 776, 970, 1164; AIP-161082 SEQ ID NOS: 195, 389, 583, 777, 971, 1165; AIP-114196 SEQ ID NOS: 196, 390, 584, 778, 972, 1166; AIP-189338 SEQ ID NOS: 197, 391, 585, 779, 973, 1167 AIP-183190 SEQ ID NOS: 198, 392, 586, 780, 974, 1168; AIP-110143 SEQ ID NOS: 199, 393, 587, 781, 975, 1169; AIP-147176 SEQ ID NOS: 200, 394, 588, 782, 976, 1170; AIP-134312 SEQ ID NOS: 201, 395, 589, 783, 977, 1171; AIP-128243 SEQ ID NOS: 202, 396, 590, 784, 978, 1172; AIP-156172 SEQ ID NOS: 203, 397, 591, 785, 979, 1173; AIP-147389 SEQ ID NOS: 204, 398, 592, 786, 980, 1174; AIP-124314 SEQ ID NOS: 205, 399, 593, 787, 981, 1175; AIP-185291 SEQ ID NOS: 206, 400, 594, 788, 982, 1176; AIP-135247 SEQ ID NOS: 207, 401, 595, 789, 983, 1177; AIP-113513 SEQ ID NOS: 208, 402, 596, 790, 984, 1178; AIP-102299 SEQ ID NOS: 209, 403, 597, 791, 985, 1179; AIP-179097 SEQ ID NOS: 210, 404, 598, 792, 986, 1180 AIP-109343 SEQ ID NOS: 211, 405, 599, 793, 987, 1181; AIP-119622 SEQ ID NOS: 212, 406, 600, 794, 988, 1182; AIP-191735 SEQ ID NOS: 213, 407, 601, 795, 989, 1183; AIP-157078 SEQ ID NOS: 214. 408, 602, 796, 990, 1184; AIP-153475 SEQ ID NOS: 215, 409, 603, 797, 991, 1185; AIP-133650 SEQ ID NOS: 216, 410, 604, 798, 992, 1186; AIP-190915 SEQ ID NOS: 217, 411, 605, 799, 993, 1187; AIP-167400 SEQ ID NOS: 219, 413, 607, 801, 995, 1189; AIP-109729 SEQ ID NOS: 220, 414, 608, 802, 996, 1190; AIP-151709 SEQ ID NOS: 221, 415, 609, 803, 997, 1191; AIP-136628 SEQ ID NOS: 226, 420, 614, 808, 1002, 1196; AIP-101601 SEQ ID NOS: 230, 424, 618, 812, 1006, 1200; AIP-146871 SEQ ID NOS: 232, 426, 620, 814, 1008, 1202; AIP-170053 SEQ ID NOS: 233, 427, 621, 815, 1009, 1203; AIP-199483 SEQ ID NOS: 234, 428, 622, 816, 1010, 1204; AIP-162041 SEQ ID NOS: 236, 430, 624, 818, 1012, 1206; AIP-180675 SEQ ID NOS: 1, 9, 43, 48, 59, 68; AIP-183133 SEQ ID NOS: 238, 432, 626, 820, 1014, 1208; AIP-191470 SEQ ID NOS: 239, 433, 627, 821, 1015, 1209; AIP-151167 SEQ ID NOS: 240, 434, 628, 822, 1016, 1210; AIP-106633 SEQ ID NOS: 241, 435, 629, 823, 1017, 1211; AIP-102624 SEQ ID NOS: 242, 436, 630, 824, 1018, 1212; AIP-109484 SEQ ID NOS: 243, 437, 631, 825, 1019, 1213; AIP-126080 SEQ ID NOS: 1, 9, 44, 48, 59, 68; AIP-161571 SEQ ID NOS: 1, 9, 45, 48, 59, 68; AIP-163039 SEQ ID NOS: 251, 445, 639, 833, 1027, 1221; AIP-101235 SEQ ID NOS: 1, 9, 20, 48, 59, 68; AIP-182061 SEQ ID NOS: 253, 447, 641, 835, 1029, 1223; AIP-181246 SEQ ID NOS: 1, 9, 46, 48, 59, 68; AIP-192216 SEQ ID NOS: 1, 9, 47, 48, 59, 68; AIP-171912 SEQ ID NOS: 255, 449, 643, 837, 1031, 1225; AIP-172872 SEQ ID NOS: 1, 18, 21, 48, 65, 75; AIP-167833 SEQ ID NOS: 256, 450, 644, 838, 1032, 1226; AIP-190051 SEQ ID NOS: 8, 9, 21, 58, 59, 72; AIP-145518 SEQ ID NOS: 257, 451, 645, 839, 1033, 1227; AIP-167533 SEQ ID NOS: 1, 19, 21, 48, 59, 68; AIP-112580 SEQ ID NOS: 1, 9, 27, 48, 59, 68; AIP-143155 SEQ ID NOS: 258, 452, 646, 840, 1034, 1228; AIP-119664 SEQ ID NOS: 259, 453, 647, 841, 1035, 1229; AIP-190526 SEQ ID NOS: 260, 454, 648, 842, 1036, 1230; AIP-114403 SEQ ID NOS: 261, 455, 649, 843, 1037, 1231; AIP-156760 SEQ ID NOS: 262, 456, 650, 844, 1038, 1232; AIP-103803 SEQ ID NOS: 263, 457, 651, 845, 1039, 1233; AIP-195588 SEQ ID NOS: 265, 459, 653, 847, 1041, 1235; AIP-145722 SEQ ID NOS: 266, 460, 654, 848, 1042, 1236; AIP-178251 SEQ ID NOS: 267, 461, 655, 849, 1043, 1237; AIP-116142 SEQ ID NOS: 268, 462, 656, 850, 1044, 1238; AIP-183350 SEQ ID NOS: 269, 463, 657, 851, 1045, 1239; AIP-127108 SEQ ID NOS: 270, 464, 658, 852, 1046, 1240; AIP-128147 SEQ ID NOS: 271, 465, 659, 853, 1047, 1241; AIP-109510 SEQ ID NOS: 272, 466, 660, 854, 1048, 1241; AIP-104086 SEQ ID NOS: 273, 467, 661, 855, 1049, 1243; AIP-143132 SEQ ID NOS: 274, 468, 662, 856, 1050, 1244; AIP-170105 SEQ ID NOS: 1, 9, 21, 56, 59, 68; AIP-169636 SEQ ID NOS: 275; 469, 663, 857, 1051, 1245; AIP-152243 SEQ ID NOS: 276, 470, 664, 858, 1052, 1246; AIP-138776 SEQ ID NOS: 277, 471, 665, 859, 1053, 1247; AIP-103817 SEQ ID NOS: 278, 472, 666, 860, 1054, 1248; AIP-130491 SEQ ID NOS: 279, 473, 667, 861, 1055, 1249; AIP-188155 SEQ ID NOS: 280, 474, 668, 862, 1056, 1250; AIP-167246 SEQ ID NOS: 281, 475, 669, 863, 1057, 1251; AIP-106139 SEQ ID NOS: 282, 476, 670, 864, 1058, 1252; AIP-198351 SEQ ID NOS: 283, 477, 671, 865, 1059, 1253; AIP-159326 SEQ ID NOS: 284, 478, 672, 866, 1060, 1254; AIP-192275 SEQ ID NOS: 285, 479, 673, 867, 1061, 1255; AIP-190761 SEQ ID NOS: 286, 480, 674, 868, 1062, 1256; AIP-166832 SEQ ID NOS: 287, 481, 675, 869, 1063, 1257; AIP-148062 SEQ ID NOS: 288, 482, 676, 870, 1064, 1258; AIP-129145 SEQ ID NOS: 289, 483, 677, 871, 1065, 1259; AIP-111240 SEQ ID NOS: 290, 484, 678, 872, 1066, 1260; AIP-153888 SEQ ID NOS: 292, 486, 680, 874, 1068, 1262; AIP-130915 SEQ ID NOS: 293, 487, 681, 875, 1069, 1263; AIP-109048 SEQ ID NOS: 294, 488, 682, 876, 1070, 1264; AIP-170569 SEQ ID NOS: 295, 489, 683, 877, 1071, 1265; AIP-154873 SEQ ID NOS: 296, 490, 684, 878, 1072, 1266; AIP-159037 SEQ ID NOS: 297, 491, 685, 879, 1073, 1267; AIP-186826 SEQ ID NOS: 298, 492, 686, 880, 1074, 1268; AIP-156514 SEQ ID NOS: 299, 493, 687, 881, 1075, 1269; AIP-157122 SEQ ID NOS: 300, 494, 688, 882, 1076, 1270; AIP-173276 SEQ ID NOS: 301, 495, 689, 883, 1077, 1271; AIP-150485 SEQ ID NOS: 302, 496, 690, 884, 1078, 1272; AIP-166847 SEQ ID NOS: 304, 498, 692, 886, 1080, 1274; AIP-124013 SEQ ID NOS: 305, 499, 693, 887, 1081, 1275; AIP-126285 SEQ ID NOS: 306, 500, 694, 888, 1082, 1276 AIP-168605 SEQ ID NOS: 1, 9, 21, 57, 59, 74; AIP-190274 SEQ ID NOS: 307, 501, 695, 889, 1083, 1277; AIP-136060 SEQ ID NOS: 1, 9, 21, 48, 67, 68; AIP-180422 SEQ ID NOS: 310, 504, 698, 892, 1086, 1280; AIP-166722 SEQ ID NOS: 311, 505, 699, 893, 1087, 1281; AIP-127782 SEQ ID NOS: 1, 504, 21, 48, 59, 68; AIP-189473 SEQ ID NOS: 1, 9, 22, 48, 59, 68; AIP-192571 SEQ ID NOS: 1, 9, 23, 48, 59, 68; AIP-112328 SEQ ID NOS: 322, 516, 710, 904, 1098, 1292; AIP-125258 SEQ ID NOS: 1, 9, 24, 48, 59, 68; AIP-150199 SEQ ID NOS: 1, 9, 25, 48, 59, 68; AIP-125062 SEQ ID NOS: 324, 518, 712, 906, 1100, 1294; AIP-177193 SEQ ID NOS: 331, 525, 719, 913, 1107, 1301; AIP-115388 SEQ ID NOS: 1, 9, 26, 48, 59, 68; AIP-107759 SEQ ID NOS: 338, 532, 726, 920, 1114, 1308; AIP-170221 SEQ ID NOS: 355, 549, 743, 937, 1131, 1325; AIP-143369 SEQ ID NOS: 2, 10, 21, 49, 60, 68; AIP-189475 SEQ ID NOS: 357, 551, 745, 939, 1133, 1327; AIP-102833 SEQ ID NOS: 358, 552, 746, 940, 1134, 1328; AIP-157045 SEQ ID NOS: 3, 11, 21, 50, 61, 69; AIP-175775 SEQ ID NOS: 4, 9, 27, 51, 62, 70; AIP-154181 SEQ ID NOS: 5, 12, 28, 52, 63, 71; AIP-125984 SEQ ID NOS: 6, 13, 21, 53, 64, 76; AIP-160829 SEQ ID NOS: 7, 14, 29, 52, 65, 69; AIP-184744 SEQ ID NOS: 4, 15, 30, 54, 62, 71; AIP-128136 SEQ ID NOS: 1, 12, 31, 55, 66, 72; AIP-181273 SEQ ID NOS: 1, 9, 32, 56, 59, 72; AIP-153125 SEQ ID NOS: 1, 12, 33, 50, 66, 68; or AIP-131972 SEQ ID NOS: 362, 556, 750, 944, 1138, 1332; or a variant of said antibody in which one, two, three, four, five, or all six CDR sequences contain 1 or 2 amino acid substitutions.
8 . The method of claim 7 , wherein the antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences:
AIP-192482 SEQ ID NOS: 8, 9, 34, 48, 59, 68; AIP-171142 SEQ ID NOS: 8, 9, 35, 48, 59, 68; AIP-165430 SEQ ID NOS: 8, 9, 37, 48, 59, 68; AIP-189526 SEQ ID NOS: 8, 16, 38, 48, 59, 68; AIP-122563 SEQ ID NOS: 8, 9, 34, 48, 59, 68; AIP-158623 SEQ ID NOS: 8, 9, 37, 48, 59, 68; AIP-155066 SEQ ID NOS: 8, 9, 39, 48, 59, 68; AIP-166120 SEQ ID NOS: 8, 9, 21, 48, 59, 68; AIP-133645 SEQ ID NOS: 8, 9, 37, 48, 59, 73; AIP-187893 SEQ ID NOS: 1, 9, 37, 48, 59, 68; AIP-142079 SEQ ID NOS: 8, 9, 41, 48, 59, 68; AIP-102396 SEQ ID NOS: 172, 366, 560, 754, 948, 1142; AIP-150055 SEQ ID NOS: 173, 367, 561, 755, 949, 1143; AIP-167084 SEQ ID NOS: 174, 368, 562, 756, 950, 1144; AIP-185304 SEQ ID NOS: 175, 369, 563, 757, 951, 1145; AIP-134770 SEQ ID NOS: 176, 370, 564, 758, 952, 1146; AIP-141887 SEQ ID NOS: 177, 371, 565, 759, 953, 1147; AIP-196203 SEQ ID NOS: 178, 372, 566, 760, 954, 1148; AIP-128195 SEQ ID NOS: 180, 374, 568, 762, 956, 1150; AIP-116579 SEQ ID NOS: 181, 375, 569, 763, 957, 1151; AIP-192329 SEQ ID NOS: 182, 376, 570, 764, 958, 1152 AIP-197809 SEQ ID NOS: 184, 378, 572, 766, 960, 1154; AIP-142489 SEQ ID NOS: 185, 379, 573, 767, 961, 1155; AIP-167726 SEQ ID NOS: 187, 381, 575, 769, 963, 1157; AIP-199834 SEQ ID NOS: 188, 382, 576, 770, 964, 1158; AIP-143179 SEQ ID NOS: 189, 383, 577, 771, 965, 1159; AIP-195587 SEQ ID NOS: 190, 384, 578, 772, 966, 1160; AIP-153462 SEQ ID NOS: 191, 385, 579, 773, 967, 1161; AIP-115363 SEQ ID NOS: 192, 386, 580, 774, 968, 1162; AIP-151090 SEQ ID NOS: 193, 387, 581, 775, 969, 1163; AIP-168083 SEQ ID NOS: 194, 388, 582, 776, 970, 1164; AIP-161082 SEQ ID NOS: 195, 389, 583, 777, 971, 1165; AIP-114196 SEQ ID NOS: 196, 390, 584, 778, 972, 1166; AIP-189338 SEQ ID NOS: 197, 391, 585, 779, 973, 1167 AIP-183190 SEQ ID NOS: 198, 392, 586, 780, 974, 1168; AIP-110143 SEQ ID NOS: 199, 393, 587, 781, 975, 1169; AIP-147176 SEQ ID NOS: 200, 394, 588, 782, 976, 1170; AIP-134312 SEQ ID NOS: 201, 395, 589, 783, 977, 1171; AIP-128243 SEQ ID NOS: 202, 396, 590, 784, 978, 1172; AIP-156172 SEQ ID NOS: 203, 397, 591, 785, 979, 1173; AIP-147389 SEQ ID NOS: 204, 398, 592, 786, 980, 1174; AIP-124314 SEQ ID NOS: 205, 399, 593, 787, 981, 1175; AIP-185291 SEQ ID NOS: 206, 400, 594, 788, 982, 1176; AIP-135247 SEQ ID NOS: 207, 401, 595, 789, 983, 1177; AIP-113513 SEQ ID NOS: 208, 402, 596, 790, 984, 1178; AIP-102299 SEQ ID NOS: 209, 403, 597, 791, 985, 1179; AIP-179097 SEQ ID NOS: 210, 404, 598, 792, 986, 1180 AIP-109343 SEQ ID NOS: 211, 405, 599, 793, 987, 1181; AIP-119622 SEQ ID NOS: 212, 406, 600, 794, 988, 1182; AIP-191735 SEQ ID NOS: 213, 407, 601, 795, 989, 1183; AIP-157078 SEQ ID NOS: 214. 408, 602, 796, 990, 1184; AIP-153475 SEQ ID NOS: 215, 409, 603, 797, 991, 1185; AIP-133650 SEQ ID NOS: 216, 410, 604, 798, 992, 1186; AIP-190915 SEQ ID NOS: 217, 411, 605, 799, 993, 1187; AIP-167400 SEQ ID NOS: 219, 413, 607, 801, 995, 1189; AIP-109729 SEQ ID NOS: 220, 414, 608, 802, 996, 1190; AIP-151709 SEQ ID NOS: 221, 415, 609, 803, 997, 1191; AIP-136628 SEQ ID NOS: 226, 420, 614, 808, 1002, 1196; AIP-101601 SEQ ID NOS: 230, 424, 618, 812, 1006, 1200; AIP-146871 SEQ ID NOS: 232, 426, 620, 814, 1008, 1202; AIP-170053 SEQ ID NOS: 233, 427, 621, 815, 1009, 1203; AIP-199483 SEQ ID NOS: 234, 428, 622, 816, 1010, 1204; AIP-162041 SEQ ID NOS: 236, 430, 624, 818, 1012, 1206; AIP-180675 SEQ ID NOS: 1, 9, 43, 48, 59, 68; AIP-183133 SEQ ID NOS: 238, 432, 626, 820, 1014, 1208; AIP-191470 SEQ ID NOS: 239, 433, 627, 821, 1015, 1209; AIP-151167 SEQ ID NOS: 240, 434, 628, 822, 1016, 1210; AIP-106633 SEQ ID NOS: 241, 435, 629, 823, 1017, 1211; AIP-102624 SEQ ID NOS: 242, 436, 630, 824, 1018, 1212; AIP-109484 SEQ ID NOS: 243, 437, 631, 825, 1019, 1213; AIP-126080 SEQ ID NOS: 1, 9, 44, 48, 59, 68; AIP-161571 SEQ ID NOS: 1, 9, 45, 48, 59, 68; AIP-163039 SEQ ID NOS: 251, 445, 639, 833, 1027, 1221; AIP-101235 SEQ ID NOS: 1, 9, 20, 48, 59, 68; AIP-182061 SEQ ID NOS: 253, 447, 641, 835, 1029, 1223; AIP-181246 SEQ ID NOS: 1, 9, 46, 48, 59, 68; AIP-192216 SEQ ID NOS: 1, 9, 47, 48, 59, 68; AIP-171912 SEQ ID NOS: 255, 449, 643, 837, 1031, 1225; AIP-172872 SEQ ID NOS: 1, 18, 21, 48, 65, 75; AIP-167833 SEQ ID NOS: 256, 450, 644, 838, 1032, 1226; AIP-190051 SEQ ID NOS: 8, 9, 21, 58, 59, 72; AIP-145518 SEQ ID NOS: 257, 451, 645, 839, 1033, 1227; AIP-167533 SEQ ID NOS: 1, 19, 21, 48, 59, 68; AIP-112580 SEQ ID NOS: 1, 9, 27, 48, 59, 68; AIP-143155 SEQ ID NOS: 258, 452, 646, 840, 1034, 1228; AIP-119664 SEQ ID NOS: 259, 453, 647, 841, 1035, 1229; AIP-190526 SEQ ID NOS: 260, 454, 648, 842, 1036, 1230; AIP-114403 SEQ ID NOS: 261, 455, 649, 843, 1037, 1231; AIP-156760 SEQ ID NOS: 262, 456, 650, 844, 1038, 1232; AIP-103803 SEQ ID NOS: 263, 457, 651, 845, 1039, 1233; AIP-195588 SEQ ID NOS: 265, 459, 653, 847, 1041, 1235; AIP-145722 SEQ ID NOS: 266, 460, 654, 848, 1042, 1236; AIP-178251 SEQ ID NOS: 267, 461, 655, 849, 1043, 1237; AIP-116142 SEQ ID NOS: 268, 462, 656, 850, 1044, 1238; AIP-183350 SEQ ID NOS: 269, 463, 657, 851, 1045, 1239; AIP-127108 SEQ ID NOS: 270, 464, 658, 852, 1046, 1240; AIP-128147 SEQ ID NOS: 271, 465, 659, 853, 1047, 1241; AIP-109510 SEQ ID NOS: 272, 466, 660, 854, 1048, 1241; AIP-104086 SEQ ID NOS: 273, 467, 661, 855, 1049, 1243; AIP-143132 SEQ ID NOS: 274, 468, 662, 856, 1050, 1244; AIP-170105 SEQ ID NOS: 1, 9, 21, 56, 59, 68; AIP-169636 SEQ ID NOS: 275; 469, 663, 857, 1051, 1245; AIP-152243 SEQ ID NOS: 276, 470, 664, 858, 1052, 1246; AIP-138776 SEQ ID NOS: 277, 471, 665, 859, 1053, 1247; AIP-103817 SEQ ID NOS: 278, 472, 666, 860, 1054, 1248; AIP-130491 SEQ ID NOS: 279, 473, 667, 861, 1055, 1249; AIP-188155 SEQ ID NOS: 280, 474, 668, 862, 1056, 1250; AIP-167246 SEQ ID NOS: 281, 475, 669, 863, 1057, 1251; AIP-106139 SEQ ID NOS: 282, 476, 670, 864, 1058, 1252; AIP-198351 SEQ ID NOS: 283, 477, 671, 865, 1059, 1253; AIP-159326 SEQ ID NOS: 284, 478, 672, 866, 1060, 1254; AIP-192275 SEQ ID NOS: 285, 479, 673, 867, 1061, 1255; AIP-190761 SEQ ID NOS: 286, 480, 674, 868, 1062, 1256; AIP-166832 SEQ ID NOS: 287, 481, 675, 869, 1063, 1257; AIP-148062 SEQ ID NOS: 288, 482, 676, 870, 1064, 1258; AIP-129145 SEQ ID NOS: 289, 483, 677, 871, 1065, 1259; AIP-111240 SEQ ID NOS: 290, 484, 678, 872, 1066, 1260; AIP-153888 SEQ ID NOS: 292, 486, 680, 874, 1068, 1262; AIP-130915 SEQ ID NOS: 293, 487, 681, 875, 1069, 1263; AIP-109048 SEQ ID NOS: 294, 488, 682, 876, 1070, 1264; AIP-170569 SEQ ID NOS: 295, 489, 683, 877, 1071, 1265; AIP-154873 SEQ ID NOS: 296, 490, 684, 878, 1072, 1266; AIP-159037 SEQ ID NOS: 297, 491, 685, 879, 1073, 1267; AIP-186826 SEQ ID NOS: 298, 492, 686, 880, 1074, 1268; AIP-156514 SEQ ID NOS: 299, 493, 687, 881, 1075, 1269; AIP-157122 SEQ ID NOS: 300, 494, 688, 882, 1076, 1270; AIP-173276 SEQ ID NOS: 301, 495, 689, 883, 1077, 1271; AIP-150485 SEQ ID NOS: 302, 496, 690, 884, 1078, 1272; AIP-166847 SEQ ID NOS: 304, 498, 692, 886, 1080, 1274; AIP-124013 SEQ ID NOS: 305, 499, 693, 887, 1081, 1275; AIP-126285 SEQ ID NOS: 306, 500, 694, 888, 1082, 1276 AIP-168605 SEQ ID NOS: 1, 9, 21, 57, 59, 74; AIP-190274 SEQ ID NOS: 307, 501, 695, 889, 1083, 1277; AIP-136060 SEQ ID NOS: 1, 9, 21, 48, 67, 68; AIP-180422 SEQ ID NOS: 310, 504, 698, 892, 1086, 1280; AIP-166722 SEQ ID NOS: 311, 505, 699, 893, 1087, 1281; AIP-127782 SEQ ID NOS: 1, 504, 21, 48, 59, 68; AIP-189473 SEQ ID NOS: 1, 9, 22, 48, 59, 68; AIP-192571 SEQ ID NOS: 1, 9, 23, 48, 59, 68; AIP-112328 SEQ ID NOS: 322, 516, 710, 904, 1098, 1292; AIP-125258 SEQ ID NOS: 1, 9, 24, 48, 59, 68; AIP-150199 SEQ ID NOS: 1, 9, 25, 48, 59, 68; AIP-125062 SEQ ID NOS: 324, 518, 712, 906, 1100, 1294; AIP-177193 SEQ ID NOS: 331, 525, 719, 913, 1107, 1301; AIP-115388 SEQ ID NOS: 1, 9, 26, 48, 59, 68; AIP-107759 SEQ ID NOS: 338, 532, 726, 920, 1114, 1308; AIP-170221 SEQ ID NOS: 355, 549, 743, 937, 1131, 1325; AIP-143369 SEQ ID NOS: 2, 10, 21, 49, 60, 68; AIP-189475 SEQ ID NOS: 357, 551, 745, 939, 1133, 1327; AIP-102833 SEQ ID NOS: 358, 552, 746, 940, 1134, 1328; AIP-157045 SEQ ID NOS: 3, 11, 21, 50, 61, 69; AIP-175775 SEQ ID NOS: 4, 9, 27, 51, 62, 70; AIP-154181 SEQ ID NOS: 5, 12, 28, 52, 63, 71; AIP-125984 SEQ ID NOS: 6, 13, 21, 53, 64, 76; AIP-160829 SEQ ID NOS: 7, 14, 29, 52, 65, 69; AIP-184744 SEQ ID NOS: 4, 15, 30, 54, 62, 71; AIP-128136 SEQ ID NOS: 1, 12, 31, 55, 66, 72; AIP-181273 SEQ ID NOS: 1, 9, 32, 56, 59, 72; AIP-153125 SEQ ID NOS: 1, 12, 33, 50, 66, 68; or AIP-131972 SEQ ID NOS: 362, 556, 750, 944, 1138, 1332.
9 . A method of treating a cancer patient having a tumor that comprises an extracellular RNA-protein complex, the method comprising administering to the patient an antibody that binds to tissue from the tumor, wherein the antibody comprises:
(a) a heavy chain variable region comprising:
(i) an HCDR1 having the sequence GF(T/V)(F/Y)(S/A)X 6 AWM(S/T) (SEQ ID NO:1728), wherein X 6 is K, A, or M;
(ii) an HCDR2 having the sequence of RIK(S/A)X 5 X 6 (D/E)(G/A)X 9 X 10 T(D/E)YAA(P/S)VKG (SEQ ID NO:1729), wherein X 5 is V, N, A, or T; X 6 is T, Q, S, D, or H; X 9 is E, H, K, or G; and X 10 is T, Q, or I; and
(iii) an HCDR3 having the sequence of (I/T)(S/T)SFCC(H/R)(G/S)X 9 X 10 CPSX 14 (D/E)TS(F/Y)CX 20 (G/N)X 22 X 23 X 24 X 25 (F/Y)Y(F/Y)(M/V)(D/N)X 31 (SEQ ID NO:1730), wherein X 9 is A, G, K, or N; X 10 is N, Q, R, or S; X 14 is H, R, or S; X 20 is A, G, or N; X 22 is Q, S, or Y; X 23 is D, F, N, or Y; X 24 is A, K, N, P, or S; X 25 is D, Q, R, or S; and X 31 is I, P, or V; and
(b) a light chain variable region comprising:
(i) an LCDR1 having the sequence of SG(S/A)X 4 (S/T)(N/D)IGSSX 11 VX 13 (SEQ ID NO:1731), wherein X 4 is S, P, or K; X 11 is S, Y, or T; and X 13 is S, Y, or T;
(ii) an LCDR2 having the sequence of (K/M)(N/D)X 3 X 4 R(P/A)X 7 , wherein X 3 is S, N or T; X 4 is L, Q, or A; X 7 is Q, S, Y, or L; and
(iii) an LCDR3 having the sequence of (S/A)(T/S)W(D/N)X 5 X 6 (L/N)X 8 (V/I)R(V/I), wherein X 5 is E, D or N; X 6 is S, A, or Q; and X 8 is N, S or T.
10 . The method of claim 9 , wherein:
the HCDR1 has a sequence GFTFSKAWMS (SEQ ID NO:1), GFTFSAAWMS (SEQ ID NO:4), or GFTFSKAWMT (SEQ ID NO:8); the HCDR2 has a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9) or RIKSTSDGETTDYAAPVKG (SEQ ID NO:15); the HCDR3 has a sequence TSSFCCRGGSCPSSDTSYCGGQYKSYYFMDV (SEQ ID NO:32), TSSFCCRSGSCPSSDTSYCNGQYKSYYYMDV (SEQ ID NO:20), TSSFCCRGNQCPSSDTSYCGGQYPSYYYMDP (SEQ ID NO:23), ISSFCCRGGSCPSRDTSYCGGQYKSYYFMDV (SEQ ID NO:30), ISSFCCRGNSCPSSDTSYCNGQYKSYYYMDV (SEQ ID NO:27), TSSFCCRGGSCPSHDTSYCGGQYKSYYYMDV (SEQ ID NO:21), or TSSFCCRGGSCPSHDTSFCGGQDKRYYYMDV (SEQ ID NO:34); the LCDR1 has a sequence SGSSSNIGSSSVY (SEQ ID NO:56), SGSSSNIGSSSVS (SEQ ID NO:48), SGSSTNIGSSSVS (SEQ ID NO:54), or SGSKSNIGSSSVS (SEQ ID NO:51); the LCDR2 has a sequence KNNQRPS (SEQ ID NO:59) or KDNQRPS (SEQ ID NO:62); and the LCDR3 has a sequence STWDDALSVRV (SEQ ID NO:72), STWDDSLSVRV (SEQ ID NO:68), SSWDDSNSVRI (SEQ ID NO:71), or ATWDNSLSIRV (SEQ ID NO:70).
11 . The method of claim 10 , wherein the heavy chain variable region has a sequence having at least 90% identity to the sequence of any one of
(SEQ ID NO: 92)
EVQLVESGGALVKPGGSLRLSCAASGFTFSKAWMSWVRQAPGKGLEWVGR
IKSVTDGETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCTS
SFCCRGGSCPSSDTSYCGGQYKSYYFMDVWGKGTTVTVSS,
(SEQ ID NO: 77)
EVQLVESGGALVKPGGSLRLSCAASGFTFSKAWMSWVRQAPGKGLEWVGR
IKSVTDGETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCTS
SFCCRSGSCPSSDTSYCNGQYKSYYYMDVWGKGTTVTVSS,
(SEQ ID NO: 80)
EVQLVESGGALVKPGGSLRLSCAASGFTFSKAWMSWVRQAPGKGLEWVGR
IKSVTDGETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCTS
SFCCRGNQCPSSDTSYCGGQYPSYYYMDPWGKGTTVTVSS,
(SEQ ID NO: 90)
EVQLVESGGALVKPGGSLRLSCAASGFTFSAAWMSWVRQAPGKGLEWVGR
IKSTSDGETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCIS
SFCCRGGSCPSRDTSYCGGQYKSYYFMDVWGKGTTVTVSS,
(SEQ ID NO: 86)
EVQLVESGGALVKPGGSLRLSCAASGFTFSAAWMSWVRQAPGKGLEWVGR
IKSVTDGETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCIS
SFCCRGNSCPSSDTSYCNGQYKSYYYMDVWGKGTTVTVSS,
(SEQ ID NO: 94)
EVQLVESGGALVKPGGSLRLSCAASGFTFSKAWMSWVRQAPGKGLEWVGR
IKSVTDGETTDYAAPVKGRFTISRDDSKSTLYLQMNSLKTEDTAVYYCTS
SFCCRGGSCPSHDTSYCGGQYKSYYYMDVWGKGTTVTVSS,
and
(SEQ ID NO: 95)
EVQLVESGGALVKPGGSLRLSCAASGFTFSKAWMTWVRQAPGKGLEWVGR
IKSVTDGETTDYAAPVKGRFTISRDDSKSVLYLQMSSLKTEDTAVYFCTS
SFCCRGGSCPSHDTSFCGGQDKRYYYMDVWGKGTTVTVSS.
12 . The method of claim 10 , wherein the light chain variable region has a sequence having at least 90% identity to the sequence of any one of
(SEQ ID NO: 138)
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSSSVYWYQQLPGTAPKWYKN
NQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSTWDDALSVRVFG
GGTKLTVL,
(SEQ ID NO: 140)
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSSSVSWYQQLPGTAPKLLIY
KNNQRPSGVPD,
(SEQ ID NO: 136)
RFSGSKSGTSASLAISGLRSEDEADYYCSTWDDSLSVRVFGGGTKLTVL,
QSVLTQPPSASGTPGQRVTISCSGSSTNIGSSSVSWYQQLPGTAPKLLIY
KDNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSSWDDSNSVRI
FGGGTKLTVL,
(SEQ ID NO: 132)
QSVLTQPPSASGTPGQRVTISCSGSKSNIGSSSVSWYQQLPGTAPKLLIY
KDNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCATWDNSLSIRV
FGGGTKLTVL,
and
(SEQ ID NO: 141)
QSVLTQAPSASETPGQRVIISCSGSSSNIGSSSVSWYQQLPGTAPKLLIY
KNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSTWDDSLSVRV
FGGGTKLTVL.
13 . The method of claim 10 , wherein:
the HCDR1 has a sequence GFTFSKAWMS (SEQ ID NO:1); the HCDR2 has a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9); the HCDR3 has a sequence TSSFCCRGGSCPSSDTSYCGGQYKSYYFMDV (SEQ ID NO:32); the LCDR1 has a sequence SGSSSNIGSSSVY (SEQ ID NO:56); the LCDR2 has a sequence KNNQRPS (SEQ ID NO:59); and the LCDR3 has a sequence STWDDALSVRV (SEQ ID NO:72).
14 . The method of claim 10 , wherein:
the HCDR1 has a sequence GFTFSKAWMS (SEQ ID NO:1); the HCDR2 has a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9); the HCDR3 has a sequence of TSSFCCRSGSCPSSDTSYCNGQYKSYYYMDV (SEQ ID NO:20); the LCDR1 has a sequence SGSSSNIGSSSVS (SEQ ID NO:48); the LCDR2 has a sequence KNNQRPS (SEQ ID NO:59); and the LCDR3 has a sequence STWDDSLSVRV (SEQ ID NO:68).
15 . The method of claim 10 , wherein:
the HCDR1 has a sequence GFTFSKAWMS (SEQ ID NO:1); the HCDR2 has a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9); the HCDR3 has a sequence TSSFCCRGNQCPSSDTSYCGGQYPSYYYMDP (SEQ ID NO:23); the LCDR1 has a sequence SGSSSNIGSSSVS (SEQ ID NO:48); the LCDR2 has a sequence KNNQRPS (SEQ ID NO:59); and the LCDR3 has a sequence STWDDSLSVRV (SEQ ID NO:68).
16 . The method of claim 10 , wherein:
the HCDR1 has a sequence GFTFSAAWMS (SEQ ID NO:4); the HCDR2 has a sequence RIKSTSDGETTDYAAPVKG (SEQ ID NO:15); the HCDR3 has a sequence ISSFCCRGGSCPSRDTSYCGGQYKSYYFMDV (SEQ ID NO:30); the LCDR1 has a sequence SGSSTNIGSSSVS (SEQ ID NO:54); the LCDR2 has a sequence KDNQRPS (SEQ ID NO:62); and the LCDR3 has a sequence SSWDDSNSVRI (SEQ ID NO:71).
17 . The method of claim 10 , wherein:
the HCDR1 has a sequence GFTFSAAWMS (SEQ ID NO:4); the HCDR2 has a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9); the HCDR3 has a sequence ISSFCCRGNSCPSSDTSYCNGQYKSYYYMDV (SEQ ID NO:27); the LCDR1 has a sequence SGSKSNIGSSSVS (SEQ ID NO:51); the LCDR2 has a sequence KDNQRPS (SEQ ID NO:62); and the LCDR3 has a sequence ATWDNSLSIRV (SEQ ID NO:70).
18 . The method of claim 10 , wherein:
the HCDR1 has a sequence GFTFSKAWMT (SEQ ID NO:8); the HCDR2 has a sequence RIKSVTDGETTDYAAPVKG (SEQ ID NO:9); the HCDR3 has a sequence TSSFCCRGGSCPSHDTSFCGGQDKRYYYMDV (SEQ ID NO:34); the LCDR1 has a sequence SGSSSNIGSSSVS (SEQ ID NO:48); the LCDR2 has a sequence KNNQRPS (SEQ ID NO:59); and the LCDR3 has a sequence STWDDSLSVRV (SEQ ID NO:68).
19 . The method of claim 1 , wherein the cancer is lung cancer, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, kidney cancer, ovarian cancer, melanoma, uterine cancer, liver cancer, bladder cancer, or testicular cancer.
20 . The method of claim 19 , wherein the cancer is non-small cell lung cancer, triple negative breast cancer, colorectal cancer, ovarian cancer or melanoma.
21 . The method of claim 1 , wherein the antibody is administered intravenously.
22 . The method of claim 1 , further comprising administering chemotherapy and/or radiation therapy.
23 . The method of claim 1 , further comprising administering an agent that targets an immunological checkpoint antigen.
24 . The method of claim 23 , wherein the agent is a monoclonal antibody.
25 . The method of claim 24 , wherein the monoclonal antibody blocks PD-1 ligand binding to PD-1.
26 . The method of claim 25 , wherein the monoclonal antibody is an anti-PD-1 antibody.
27 . The method of claim 9 , wherein the cancer is lung cancer, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, kidney cancer, ovarian cancer, melanoma, uterine cancer, liver cancer, bladder cancer, or testicular cancer.
28 . The method of claim 27 , wherein the cancer is non-small cell lung cancer, triple negative breast cancer, colorectal cancer, ovarian cancer or melanoma.
29 . The method of claim 9 , wherein the antibody is administered intravenously.
30 . The method of claim 9 , further comprising administering chemotherapy and/or radiation therapy.
31 . The method of claim 9 , further comprising administering an agent that targets an immunological checkpoint antigen.
32 . The method of claim 31 , wherein the agent is a monoclonal antibody.
33 . The method of claim 32 , wherein the monoclonal antibody blocks PD-1 ligand binding to PD-1.
34 . The method of claim 33 , wherein the monoclonal antibody is an anti-PD-1 antibody.Join the waitlist — get patent alerts
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