Vaccines targeting Pseufomonas aeruginosa
First Claim
Patent Images
1. A polypeptide comprisinga) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs:
- 11, 1-10, and 12-14, orb) an amino acid sequence consisting of at least or exactly 5 contiguous amino acid residues from any one of SEQ ID NOs;
11, 1-10, and 12-14, orc) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of a),d) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of b), ore) an assembly of amino acids derived from any one of SEQ ID NOs;
11, 1-10, and 12-14 which has essentially the same 3D conformation as in the protein from which said assembly is derived so as to constitute a B-cell epitope,said polypeptide being antigenic in a mammal.
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Accused Products
Abstract
Disclosed are immunogenic proteins from Pseudomonas aeruginosa as well as nucleic acids, vectors and transformed cells useful for expression of the proteins. Also disclosed are methods for prophylaxis of infection with Pseudomonas aeruginosa using the proteins, nucleic acids, vectors or transformed cell.
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Citations
75 Claims
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1. A polypeptide comprising
a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: - 11, 1-10, and 12-14, or
b) an amino acid sequence consisting of at least or exactly 5 contiguous amino acid residues from any one of SEQ ID NOs;
11, 1-10, and 12-14, orc) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of a), d) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of b), or e) an assembly of amino acids derived from any one of SEQ ID NOs;
11, 1-10, and 12-14 which has essentially the same 3D conformation as in the protein from which said assembly is derived so as to constitute a B-cell epitope,said polypeptide being antigenic in a mammal. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75)
-
2. The polypeptide according to claim 1, wherein the at least or exactly 5 contiguous amino acids are at least or exactly or at most 6, such as at least or exactly or at most 7, at least or exactly or at most 8, at least or exactly or at most 9, at least or exactly or at most 10, at least or exactly or at most 11, at least or exactly or at most 12, at least or exactly or at most 13, at least or exactly or at most 14, at least or exactly or at most 15, at least or exactly or at most 16, at least or exactly or at most 17, at least or exactly or at most 18, at least or exactly or at most 19, at least or exactly or at most 20, at least or exactly or at most 21, at least or exactly or at most 22, at least or exactly or at most 23, at least or exactly or at most 24, at least or exactly or at most 25, at least or exactly or at most 26, at least or exactly or at most 27 at least or exactly or at most 28, at least or exactly or at most 29, at least or exactly or at most 30, at least or exactly or at most 31, at least or exactly or at most 32, at least or exactly or at most 33, at least or exactly or at most 34, at least or exactly or at most 35, at least or exactly or at most 36, at least or exactly or at most 37, at least or exactly or at most 38, at least or exactly or at most 39, at least or exactly or at most 40, at least or exactly or at most 41, at least or exactly or at most 42, at least or exactly or at most 43, at least or exactly or at most 44, at least or exactly or at most 45, at least or exactly or at most 46, at least or exactly or at most 47, at least or exactly or at most 48, at least or exactly or at most 49, at least or exactly or at most 50, at least or exactly or at most 51, at least or exactly or at most 52, at least or exactly or at most 53, at least or exactly or at most 54, at least or exactly or at most 55, at least or exactly or at most 56, at least or exactly or at most 57, at least or exactly or at most 58, at least or exactly or at most 59, at least or exactly or at most 60, at least or exactly or at most 61, at least or exactly or at most 62, at least or exactly or at most 63, at least or exactly or at most 64, at least or exactly or at most 65, at least or exactly or at most 66, at least or exactly or at most 67, at least or exactly or at most 68, at least or exactly or at most 69, at least or exactly or at most 70, at least or exactly or at most 71, at least or exactly or at most 72, at least or exactly or at most 73, at least or exactly or at most 74, at least or exactly or at most 75, at least or exactly or at most 76, at least or exactly or at most 77, at least or exactly or at most 78, at least or exactly or at most 79, at least or exactly or at most 80, at least or exactly or at most 81, at least or exactly or at most 82, at least or exactly or at most 83, at least or exactly or at most 84, at least or exactly or at most 85, at least or exactly or at most 86, at least or exactly or at most 87, at least or exactly or at most 88, at least or exactly or at most 89, at least or exactly or at most 90, at least or exactly or at most 91, at least or exactly or at most 92, at least or exactly or at most 93, at least or exactly or at most 94, at least or exactly or at most 95, at least or exactly or at most 96, at least or exactly or at most 97, at least or exactly or at most 98, at least or exactly or at most 99, at least or exactly or at most 100, at least or exactly or at most 101, at least or exactly or at most 102, at least or exactly or at most 103, at least or exactly or at most 104, at least or exactly or at most 105, at least or exactly or at most 106, at least or exactly or at most 107, at least or exactly or at most 108, at least or exactly or at most 109, at least or exactly or at most 110, at least or exactly or at most 111, at least or exactly or at most 112, at least or exactly or at most 113, at least or exactly or at most 114, at least or exactly or at most 115, at least or exactly or at most 116, at least or exactly or at most 117, at least or exactly or at most 118, at least or exactly or at most 119, at least or exactly or at most 120, at least or exactly or at most 121, at least or exactly or at most 122, at least or exactly or at most 123, at least or exactly or at most 124, at least or exactly or at most 125, at least or exactly or at most 126, at least or exactly or at most 127, at least or exactly or at most 128, at least or exactly or at most 129, at least or exactly or at most 130, at least or exactly or at most 131, at least or exactly or at most 132, at least or exactly or at most 133, and at least or exactly or at most 134 contiguous amino acid residues.
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3. The polypeptide according to claim 1 or 2, wherein the sequence identity with the amino acid sequence of a) is at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99%.
-
4. The polypeptide according to claim 1 or 2, wherein the sequence identity with the amino acid sequence of b) is at least 60%, such as at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99%.
-
5. The polypeptide according to any one of the preceding claims, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, and 131 in any one of SEQ ID NOs:
- 1-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 1-14,
-
6. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 132, 133, and 134 in any on of SEQ ID NOs:
- 2-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 2-14,
-
7. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 135, 136, and 137 in any one of SEQ ID NOs:
- 3-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 3-14,
-
8. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 138, 139, 140, 141, 142, 143, 144, 145, and 146 in any one of SEQ ID NOs:
- 4-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 4-14,
-
9. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, and 233 in any one of SEQ ID NOs:
- 5-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 5-14,
-
10. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, and 392 in any one of SEQ ID NOs:
- 6-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 6-14,
-
11. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, and 539 in any one of SEQ ID NOs:
- 7-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 7-14,
-
12. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, and 635 in any one of SEQ ID NOs:
- 8-14, with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 8-14, with the proviso that the selected amino acid residue satisfies the formula N≤
-
13. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, and 671 in any one of SEQ ID NOs:
- 9-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 9-14,
-
14. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 672, 673, 674, 675, 676, 677, and 678 in any one of SEQ ID NOs:
- 10-14, with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 10-14, with the proviso that the selected amino acid residue satisfies the formula N≤
-
15. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 679, 680, 681, 682, and 683 in any one of SEQ ID NOs:
- 11-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 11-14,
-
16. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, and 799 in any one of SEQ ID NOs:
- 12-14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 12-14,
-
17. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026, 1027, 1028, 1029, 1030, 1031, 1032, 1033, 1034, 1035, 1036, 1037, 1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048, 1049, 1050, 1051, 1052, 1053, 1054, 1055, 1056, 1057, 1058, 1059, 1060, 1061, 1062, 1063, 1064, 1065, 1066, 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1077, 1078, 1079, 1080, 1081, 1082, 1083, 1084, 1085, 1086, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106, 1107, 1108, 1109, 1110, 1111, 1112, 1113, 1114, 1115, 1116, 1117, 1118, 1119, 1120, 1121, 1122, 1123, 1124, 1125, 1126, 1127, 1128, 1129, 1130, 1131, 1132, 1133, 1134, 1135, 1136, 1137, 1138, 1139, 1140, 1141, 1142, 1143, 1144, 1145, 1146, 1147, 1148, 1149, 1150, 1151, 1152, 1153, 1154, 1155, 1156, 1157, and 1158 in SEQ ID NO:
- 13 or 14, with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 13 or 14, with the proviso that the selected amino acid residue satisfies the formula N≤
-
18. The polypeptide according to any one of claims 1-4, wherein the at least 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, 1168, 1169, 1170, 1171, 1172, 1173, 1174, 1175, 1176, 1177, 1178, 1179, 1180, 1181, 1182, 1183, 1184, 1185, 1186, 1187, 1188, 1189, 1190, 1191, 1192, 1193, 1194, 1195, 1196, 1197, 1198, 1199, 1200, 1201, 1202, 1203, 1204, 1205, 1206, 1207, 1208, 1209, 1210, 1211, 1212, 1213, 1214, 1215, 1216, 1217, 1218, 1219, 1220, 1221, 1222, 1223, 1224, 1225, 1226, 1227, 1228, 1229, 1230, 1231, 1232, 1233, 1234, 1235, 1236, 1237, 1238, 1239, 1240, 1241, 1242, 1243, 1244, 1245, 1246, 1247, 1248, 1249, 1250, 1251, 1252, 1253, 1254, 1255, 1256, 1257, 1258, 1259, 1260, 1261, 1262, 1263, 1264, 1265, 1266, 1267, 1268, 1269, 1270, 1271, 1272, 1273, 1274, 1275, 1276, 1277, 1278, 1279, 1280, 1281, 1282, 1283, 1284, 1285, 1286, 1287, 1288, 1289, 1290, 1291, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308, 1309, 1310, 1311, 1312, 1313, 1314, 1315, 1316, 1317, 1318, 1319, 1320, 1321, 1322, 1323, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332, 1333, 1334, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343, 1344, 1345, 1346, 1347, 1348, 1349, 1350, 1351, 1352, 1353, 1354, 1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1388, 1389, 1390, 1391, 1392, 1393, 1394, 1395, 1396, 1397, 1398, 1399, 1400, 1401, 1402, 1403, 1404, 1405, 1406, 1407, 1408, 1409, 1410, 1411, 1412, and 1413 in SEQ ID NO:
- 14,
with the proviso that the selected amino acid residue satisfies the formula N≤
L−
n+1, where N is the number of the selected residue, L is the number of amino acid residues in the sequence from which the residue is selected, and n is the number of consecutive amino acid residues.
- 14,
-
19. The polypeptide according to any one of the preceding claims, which is fused or conjugated to an immunogenic carrier molecule, and/or which is fused to at least one polypeptide according to any one of the preceding claims, optionally via a linker such as the polypeptide with SEQ ID NO:
- 43.
-
20. The polypeptide according to claim 19, wherein the immunogenic carrier molecule is a polypeptide that induces T-helper lymphocyte responses in a majority of humans, such as immunogenic carrier proteins selected from the group consisting of keyhole limpet hemocyanin or a fragment thereof, tetanus toxoid or a fragment thereof, diphtheria toxoid or a fragment thereof.
-
21. The polypeptide according to any one of the preceding claims, which is capable of inducing an adaptive immune response against the polypeptide in a mammal, in particular in a human being.
-
22. The polypeptide according to claim 21, which is capable of inducing, in the mammal, a protective adaptive immune response against infection with Pseudomonas aeruginosa.
-
23. The polypeptide according to claim 21 or 22, which induces a humoral and/or a cellular immune response.
-
24. An isolated nucleic acid fragment, which comprises
i) a nucleotide sequence encoding a polypeptide according to any one of the preceding claims, or ii) a nucleotide sequence consisting of the amino acid encoding part of any one of SEQ ID NOs: - 15-42.
iii) a nucleotide sequence consisting of at least 10 consecutive nucleotides in the amino acid encoding part of any one of SEQ ID NOs;
15-42,iv) a nucleotide sequence having a sequence identity of at least 60% with the nucleotide sequence in i) or ii), v) a nucleotide sequence having a sequence identity of at least 60% with the nucleotide sequence in iii), vi) a nucleotide sequence complementary to the nucleotide sequence in i)-v), or vii) a nucleotide sequence which hybridizes under stringent conditions with the nucleotide sequence in i)-vi).
- 15-42.
-
25. The nucleic acid fragment according to claim 24, which is a DNA or an RNA fragment.
-
26. The nucleic acid fragment according to claim 24 or 25, wherein the nucleotide sequence consists of at least 11, such as at least 12, at least 13, at least 14, at least 15, at least 16, at least 17 at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83, at least 84, at least 85, at least 86, at least 87, at least 88, at least 89, at least 90, at least 91, at least 92, at least 93, at least 94, at least 95, at least 96, at least 97, at least 98, at least 99, at least 100, at least 101, at least 102, at least 103, at least 104, at least 105, at least 106, at least 107, at least 108, at least 109, at least 110, at least 111, at least 112, at least 113, at least 114, at least 115, at least 116, at least 117, at least 118, at least 119, at least 120, at least 121, at least 122, at least 123, at least 124, at least 125, at least 126, at least 127, at least 128, at least 129, at least 130, at least 131, at least 132, at least 133, at least 134, at least 135, at least 136, at least 137, at least 138, at least 139, at least 140, at least 141, at least 142, at least 143, at least 144, at least 145, at least 146, at least 147, at least 148, at least 149, at least 150, at least 151, at least 152, at least 153, at least 154, at least 155, at least 156, at least 157, at least 158, at least 159, at least 160, at least 171, at least 172, at least 173, at least 174, at least 175, at least 176, at least 177, at least 178, at least 179, at least 180, at least 181, at least 182, at least 183, at least 184, at least 185, at least 186, at least 187, at least 188, at least 189, at least 190, at least 191, at least 192, at least 193, at least 194, at least 195, at least 196, at least 197, at least 198, at least 199, at least 200 and at least 201 consecutive nucleotides in the amino acid encoding part of any one of SEQ ID NOs:
- 15-42.
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27. The nucleic acid fragment according to any one of claims 24-26, wherein the sequence identity with the nucleotide sequence in i) or ii) is at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99%.
-
28. The nucleic acid fragment according to any one of claims 24-27, wherein the sequence identity with the nucleotide sequence in iii) is at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99%.
-
29. A vector comprising the nucleic acid according to any one of claims 24-28, such as a cloning vector or an expression vector.
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30. The vector according to claim 29, which comprises in operable linkage and in the 5′
- -3′
direction, an expression control region comprising an enhancer/promoter for driving expression of the nucleic acid fragment defined in claim 24-i), optionally a signal peptide coding sequence, a nucleotide sequence defined in claim 24-i), and optionally a terminator.
- -3′
-
31. The vector according to claim 29 or 30, wherein the expression control region drives expression in prokaryotic cell such as a bacterium, e.g. in E coli.
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32. The vector according to claim any one of claims 29-31, which is capable of autonomous replication.
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33. The vector according to any one of claims 29-32, which is capable of being integrated into the genome of a host cell.
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34. The vector according to any one of claims 29-32, which is incapable of being integrated into the genome of a mammalian host cell.
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35. The vector according to any one of claims 29-34, which is selected from the group consisting of a virus, such as a attenuated virus, a bacteriophage, a plasmid, a minichromosome, and a cosmid.
-
36. A cell which is transformed so as to carry the vector according to any one of claims 29-35.
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37. The transformed cell according to claim 36, which is capable of replicating the nucleic acid fragment defined in claim 24-i).
-
38. The transformed cell according to claim 36 or 37, which is capable of expressing the nucleic acid fragment defined in claim 24-i).
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39. The transformed cell according to any one of claims 36-38, which is selected from a prokaryotic cell and a eukaryotic cell.
-
40. The transformed cell according to any one of claims 36-39, which is a bacterial cell selected from the group consisting of Escherichia (such as E. coli), Bacillus (e.g. Bacillus subtilis), Salmonella, and Mycobacterium, preferably non-pathogenic, e.g. M. bovis BCG.
-
41. The transformed cell according to any one of claims 36-40, which is stably transformed by having the nucleic acid defined in claim 24-i) stably integrated into its genome.
-
42. The transformed cell according to any one of claims 36-41, which secretes or carries on its surface the polypeptide according to any one of claims 1-23.
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43. The transformed cell according to claim 42, wherein the cell is a bacterium and secretion is into the periplasmic space.
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44. A cell line derived from a transformed cell according to any one of claims 36-43.
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45. A pharmaceutical composition comprising a polypeptide according to any one of claims 1-19, a nucleic acid fragment according to any one of claims 24-28, a vector according to any one of claims 29-35, or a cell according to any one of claims 36-43, and a pharmaceutically acceptable carrier, vehicle or diluent.
-
46. The pharmaceutical composition according to claim 45, which further comprises an immunological adjuvant.
-
47. The pharmaceutical composition according to claim 46, wherein the adjuvant is an aluminium based adjuvant.
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48. A method for inducing immunity in an animal by administering at least once an immunogenically effective amount of a polypeptide according to any one of claims 1-23, a nucleic acid fragment according to any one of claims 24-28, a vector according to any one of claims 29-35, a cell according to any one of claims 36-43, or a pharmaceutical composition according to any one of claims 45-47 so as to induce adaptive immunity against Pseudomonas aeruginosa in the animal.
-
49. The method according to claim 48, wherein, when the polypeptide according to any one of claim 1-23 or a composition comprising said polypeptide is administered, the animal receives between 0.5 and 5,000 μ
- g of the polypeptide according to any one of claims 1-23 per administration.
-
50. The method according to claim 48 or 49, wherein the animal receives a priming administration and one or more booster administrations.
-
51. The method according to any one of claims 48-50, wherein the animal is a human being.
-
52. The method according to any one of claims 48-51, wherein the administration is for the purpose of inducing protective immunity against Pseudomonas aeruginosa.
-
53. The method according to claim 52, wherein the protective immunity is effective in reducing the risk of attracting infection with Pseudomonas aeruginosa or is effective in treating or ameliorating infection with Pseudomonas aeruginosa.
-
54. The method according to any one of claims 48-51, wherein the administration is for the purpose of inducing antibodies specific for Pseudomonas aeruginosa and wherein said antibodies or B-lymphocytes producing said antibodies are subsequently recovered from the animal.
-
55. The method according to any one of claims 48-51, wherein the administration is for the purpose of inducing antibodies specific for Pseudomonas aeruginosa and wherein B-lymphocytes producing said antibodies are subsequently recovered from the animal and used for preparation of monoclonal antibodies.
-
56. A polyclonal antibody in which the antibodies specifically bind to at least one polypeptide according to any one of claims 1-23, and which is essentially free from antibodies binding specifically to other Pseudomonas aeruginosa polypeptides.
-
57. An isolated monoclonal antibody or antibody analogue which binds specifically to a polypeptide according to any one of claims 1-23.
-
58. The isolated monoclonal antibody or antibody analogue according to claim 57, which is a monoclonal antibody selected from a multi-domain antibody such as a murine antibody, a chimeric antibody such as a humanized antibody, a fully human antibody, and single-domain antibody of a llama or a camel, or which is an antibody analogue selected from a fragment of an antibody such as an Fab or an F(ab′
- )2, and an scFV.
-
59. A pharmaceutical composition comprising an antibody according to any one of claims 56-58 and a pharmaceutically acceptable carrier, vehicle or diluent.
-
60. A method for prophylaxis, treatment or amelioration of infection with Pseudomonas aeruginosa, comprising administering a therapeutically effective amount of an antibody according to any one of claims 56-58 or a pharmaceutical composition according to claim 59 to an individual in need thereof.
-
61. A method for determining, quantitatively or qualitatively, the presence of Pseudomonas aeruginosa, in a sample, the method comprising contacting the sample with an antibody according to any one of claims 56-58 and detecting the presence of antibody bound to material in the sample.
-
62. A method for determining, quantitatively or qualitatively, the presence of antibodies specific for Pseudomonas aeruginosa, in a sample, the method comprising contacting the sample with a polypeptide according to any one of claims 1-23 and detecting the presence of antibody said polypeptide.
-
63. A method for determining, quantitatively or qualitatively, the presence of a nucleic acid characteristic of Pseudomonas aeruginosa in a sample, the method comprising contacting the sample with a nucleic acid fragment according to any one of claims 24-28 and detecting the presence of nucleic acid in the sample that hybridized to said nucleic acid fragment.
-
64. The method according to claim 63, which includes at least one step of molecular amplification of the nucleic acid which is to be detected in the sample, for instance a step of PCR amplification.
-
65. A method for the preparation of the polypeptide according to any one of claims 1-23, comprising
culturing a transformed cell according to claim 38 and any one of claims 39-43 insofar as these depend on claim 39 under conditions that facilitate that the transformed cell expresses the nucleic acid fragment according to claim 24-i) and any one of claims 25-28 Insofar as these depend on claim 24-i) and subsequently recovering said polypeptide, or preparing said polypeptide by means of solid or liquid phase peptide synthesis. -
66. A method for determining whether a substance, such as an antibody, is potentially useful for treating infection with Pseudomonas aeruginosa, the method comprising contacting the polypeptide according to any one of claims 1-23 with the substance and subsequently establishing whether the substance has at least one of the following characteristics:
-
1) the ability to bind specifically to said polypeptide, 2) the ability to competed with said polypeptide for specific binding to a ligand/receptor, 3) the ability to specifically inactivate said polypeptide.
-
-
67. A method for determining whether a substance, such as a nucleic acid, is potentially useful for treating infection with Pseudomonas aeruginosa, the method comprising contacting the substance with the nucleic acid fragment of any one of claims 24-28 and subsequently establishing whether the substance has either the ability tobind specifically to the nucleic acid fragment, orbind specifically to a nucleic acid that hybridizes specifically with the nucleic acid fragment.
-
68. The polypeptide according to any one of claims 1-23 for use as a pharmaceutical.
-
69. The polypeptide according to any one of claims 1-23 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with Pseudomonas aeruginosa.
-
70. The nucleic acid fragment according to any one of claims 24-28 or the vector according to any one of claims 29-35 for use as a pharmaceutical.
-
71. The nucleic acid fragment according to any one of claims 24-28 or the vector according to any one of claims 29-35 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with Pseudomonas aeruginosa.
-
72. The cell according to any one of claims 36-43 for use as a pharmaceutical.
-
73. The cell according to any one of claims 36-43 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with Pseudomonas aeruginosa.
-
74. The antibody, antibody fragment or antibody analogue according to any one of claims 56-58 for use as a pharmaceutical.
-
75. The antibody, antibody fragment or antibody analogue according to any one of claims 56-58 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with Pseudomonas aeruginosa.
-
2. The polypeptide according to claim 1, wherein the at least or exactly 5 contiguous amino acids are at least or exactly or at most 6, such as at least or exactly or at most 7, at least or exactly or at most 8, at least or exactly or at most 9, at least or exactly or at most 10, at least or exactly or at most 11, at least or exactly or at most 12, at least or exactly or at most 13, at least or exactly or at most 14, at least or exactly or at most 15, at least or exactly or at most 16, at least or exactly or at most 17, at least or exactly or at most 18, at least or exactly or at most 19, at least or exactly or at most 20, at least or exactly or at most 21, at least or exactly or at most 22, at least or exactly or at most 23, at least or exactly or at most 24, at least or exactly or at most 25, at least or exactly or at most 26, at least or exactly or at most 27 at least or exactly or at most 28, at least or exactly or at most 29, at least or exactly or at most 30, at least or exactly or at most 31, at least or exactly or at most 32, at least or exactly or at most 33, at least or exactly or at most 34, at least or exactly or at most 35, at least or exactly or at most 36, at least or exactly or at most 37, at least or exactly or at most 38, at least or exactly or at most 39, at least or exactly or at most 40, at least or exactly or at most 41, at least or exactly or at most 42, at least or exactly or at most 43, at least or exactly or at most 44, at least or exactly or at most 45, at least or exactly or at most 46, at least or exactly or at most 47, at least or exactly or at most 48, at least or exactly or at most 49, at least or exactly or at most 50, at least or exactly or at most 51, at least or exactly or at most 52, at least or exactly or at most 53, at least or exactly or at most 54, at least or exactly or at most 55, at least or exactly or at most 56, at least or exactly or at most 57, at least or exactly or at most 58, at least or exactly or at most 59, at least or exactly or at most 60, at least or exactly or at most 61, at least or exactly or at most 62, at least or exactly or at most 63, at least or exactly or at most 64, at least or exactly or at most 65, at least or exactly or at most 66, at least or exactly or at most 67, at least or exactly or at most 68, at least or exactly or at most 69, at least or exactly or at most 70, at least or exactly or at most 71, at least or exactly or at most 72, at least or exactly or at most 73, at least or exactly or at most 74, at least or exactly or at most 75, at least or exactly or at most 76, at least or exactly or at most 77, at least or exactly or at most 78, at least or exactly or at most 79, at least or exactly or at most 80, at least or exactly or at most 81, at least or exactly or at most 82, at least or exactly or at most 83, at least or exactly or at most 84, at least or exactly or at most 85, at least or exactly or at most 86, at least or exactly or at most 87, at least or exactly or at most 88, at least or exactly or at most 89, at least or exactly or at most 90, at least or exactly or at most 91, at least or exactly or at most 92, at least or exactly or at most 93, at least or exactly or at most 94, at least or exactly or at most 95, at least or exactly or at most 96, at least or exactly or at most 97, at least or exactly or at most 98, at least or exactly or at most 99, at least or exactly or at most 100, at least or exactly or at most 101, at least or exactly or at most 102, at least or exactly or at most 103, at least or exactly or at most 104, at least or exactly or at most 105, at least or exactly or at most 106, at least or exactly or at most 107, at least or exactly or at most 108, at least or exactly or at most 109, at least or exactly or at most 110, at least or exactly or at most 111, at least or exactly or at most 112, at least or exactly or at most 113, at least or exactly or at most 114, at least or exactly or at most 115, at least or exactly or at most 116, at least or exactly or at most 117, at least or exactly or at most 118, at least or exactly or at most 119, at least or exactly or at most 120, at least or exactly or at most 121, at least or exactly or at most 122, at least or exactly or at most 123, at least or exactly or at most 124, at least or exactly or at most 125, at least or exactly or at most 126, at least or exactly or at most 127, at least or exactly or at most 128, at least or exactly or at most 129, at least or exactly or at most 130, at least or exactly or at most 131, at least or exactly or at most 132, at least or exactly or at most 133, and at least or exactly or at most 134 contiguous amino acid residues.
- 11, 1-10, and 12-14, or
Specification
- Resources
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Current AssigneeEvaxion Biotech A/S
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Original AssigneeEvaxion Biotech ApS
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InventorsMoller, Niels Iversen, Mattsson, Andreas Holm
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current
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CPC Class CodesA61K 2039/505 comprising antibodiesA61K 2039/55505 Inorganic adjuvantsA61K 2039/6037 Bacterial toxins, e.g. diph...A61K 2039/6081 Albumin; Keyhole limpet hae...A61K 2039/627 characterised by the linkerA61K 38/164 from bacteriaA61K 39/104 Pseudomonadales, e.g. Pseud...A61P 31/04 Antibacterial agentsC07K 14/21 from Pseudomonadaceae (F)C07K 14/33 from Clostridium (G)C07K 14/34 from Corynebacterium (G)C07K 14/43504 from invertebratesC07K 16/1214 from Pseudomonadaceae (F)C12N 1/20 Bacteria; Culture media the...C12Q 1/68 involving nucleic acidsC12Q 1/6844 Nucleic acid amplification ...C12Q 1/689 for bacteriaG01N 33/56911 BacteriaY02A 50/30 Against vector-borne diseas...