US2016368952A1PendingUtilityA1
Proteins and nucleic acids useful in vaccines targeting staphylococcus aureus
Est. expiryDec 3, 2033(~7.4 yrs left)· nominal 20-yr term from priority
C07K 14/31G01N 2500/04G01N 2333/31C07K 16/1271G01N 33/56938A61K 2039/55505C12Q 1/689A61K 39/085
62
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Claims
Abstract
The present invention relates to proteins and nucleic acids derived from Staphylococcus aureus as well as therapeutic and diagnostic uses of the proteins and nucleic acids.
Claims
exact text as granted — not AI-modified1 . A polypeptide comprising
a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 5, 14, 6-16 and 49, or b) an amino acid sequence consisting of at least or exactly or at most 5 contiguous amino acid residues from any one of SEQ ID NOs: 5, 1-4, 6-16 and 49, or c) 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: 5, 1-4, 6-16 and 49, 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.
2 . The polypeptide according to claim 1 , wherein the at least or exactly or at most 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, and at least or exactly or at most 35 contiguous amino acid residues.
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 or exactly or at most 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, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 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, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135 and 136 in any one of SEQ ID NOs: 1-16 and 49.
6 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189 in any on of SEQ ID NOs: 2-16 and 49.
7 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204 and 205 in any one of SEQ ID NOs: 3-16 and 49.
8 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 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, 233, 234, 235, 236, 237 and 238 in any one of SEQ ID NOs: 4-16 and 49.
9 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 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, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322 and 323 in any one of SEQ ID NOs: 5-16 and 49.
10 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 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 and 353 in any one of SEQ ID NOs: 6-16 and 49.
11 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 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, 392, 393, 394 and 395 in any one of SEQ ID NOs: 7-16 and 49.
12 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, and 408 in any one of SEQ ID NOs: 8-16 and 49.
13 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 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 and 491 in any one of SEQ ID NOs: 8-16.
14 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502 and 503 in any one of SEQ ID NOs: 9-16.
15 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 504 and 505 in any one of SEQ ID NOs: 10-16.
16 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 506, 507, 508, 509, 510 and 511 in any one of SEQ ID NOs: 11-16.
17 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 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, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560 and 561 in any one of SEQ ID NOs: 12-16.
18 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 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 and 615 in any one of SEQ ID NOs: 13-16.
19 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 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, 671, 672, 673, 674, 675, 676 and 677 in any one of SEQ ID NOs: 14-16.
20 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 678, 679, 680, 681, 682, 683, 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, 799, 800, 801 and 802 in any one of SEQ ID NOs: 15-16.
21 . The polypeptide according to any one of claims 1 - 4 , wherein the at least or exactly or at most 5 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 803 and 804 in SEQ ID NOs: 16.
22 . A polypeptide comprising
a) the amino acid sequence SEQ ID NO: 5, or b) an amino acid sequence consisting of at least or exactly or at most 5 contiguous amino acid residues from one SEQ ID NO: 5, or c) 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 SEQ ID NOs: 5 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.
23 . The polypeptide according to claim 21 , which is as defined in any one of claims 2 - 9 .
24 . The polypeptide according to any one of the preceding claims, which is fused or conjugated to an immunogenic carrier molecule.
25 . The polypeptide according to claim 24 , 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.
26 . 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.
27 . The polypeptide according to claim 26 , which is capable of inducing, in the mammal, a protective adaptive immune response against infection with S. aureus.
28 . The polypeptide according to claim 26 or 27 , which induces a humoral and/or a cellular immune response.
29 . 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: 17-48, 50, and 51. iii) a nucleotide sequence consisting of at least or exactly or at most 10 consecutive nucleotides in the amino acid encoding part of any one of SEQ ID NOs: 17-48, 50, and 51, 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).
30 . The nucleic acid fragment according to claim 29 , which is a DNA or an RNA fragment.
31 . The nucleic acid fragment according to claim 29 or 30 , wherein the nucleotide sequence consists of at least or exactly or at most 11, such as 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, at least or exactly or at most 134, at least or exactly or at most 135, at least or exactly or at most 136, at least or exactly or at most 137, at least or exactly or at most 138, at least or exactly or at most 139, at least or exactly or at most 140, at least or exactly or at most 141, at least or exactly or at most 142, at least or exactly or at most 143, at least or exactly or at most 144, at least or exactly or at most 145, at least or exactly or at most 146, at least or exactly or at most 147, at least or exactly or at most 148, at least or exactly or at most 149, at least or exactly or at most 150, at least or exactly or at most 151, at least or exactly or at most 152, at least or exactly or at most 153, at least or exactly or at most 154, at least or exactly or at most 155, at least or exactly or at most 156, at least or exactly or at most 157, at least or exactly or at most 158, at least or exactly or at most 159, at least or exactly or at most 160, at least or exactly or at most 171, at least or exactly or at most 172, at least or exactly or at most 173, at least or exactly or at most 174, at least or exactly or at most 175, at least or exactly or at most 176, at least or exactly or at most 177, at least or exactly or at most 178, at least or exactly or at most 179, at least or exactly or at most 180, at least or exactly or at most 181, at least or exactly or at most 182, at least or exactly or at most 183, at least or exactly or at most 184, at least or exactly or at most 185, at least or exactly or at most 186, at least or exactly or at most 187, at least or exactly or at most 188, at least or exactly or at most 189, at least or exactly or at most 190, at least or exactly or at most 191, at least or exactly or at most 192, at least or exactly or at most 193, at least or exactly or at most 194, at least or exactly or at most 195, at least or exactly or at most 196, at least or exactly or at most 197, at least or exactly or at most 198, at least or exactly or at most 199, at least or exactly or at most 200, at least or exactly or at most 201, at least or exactly or at most 202, at least or exactly or at most 203, at least or exactly or at most 204, at least or exactly or at most 205, at least or exactly or at most 206, at least or exactly or at most 207, at least or exactly or at most 208, at least or exactly or at most 209, at least or exactly or at most 210, at least or exactly or at most 211, at least or exactly or at most 212, at least or exactly or at most 213, at least or exactly or at most 214, at least or exactly or at most 215, at least or exactly or at most 216, at least or exactly or at most 217, at least or exactly or at most 218, at least or exactly or at most 219, at least or exactly or at most 220, at least or exactly or at most 221, at least or exactly or at most 222, at least or exactly or at most 223, at least or exactly or at most 224, at least or exactly or at most 225, at least or exactly or at most 226, at least or exactly or at most 227, at least or exactly or at most 228, at least or exactly or at most 229, at least or exactly or at most 230, at least or exactly or at most 231, at least or exactly or at most 232, at least or exactly or at most 233, at least or exactly or at most 234, at least or exactly or at most 235, at least or exactly or at most 236, at least or exactly or at most 237, at least or exactly or at most 238, at least or exactly or at most 239, at least or exactly or at most 240, at least or exactly or at most 241, at least or exactly or at most 242, at least or exactly or at most 243, at least or exactly or at most 244, at least or exactly or at most 245, at least or exactly or at most 246, at least or exactly or at most 247, at least or exactly or at most 248, at least or exactly or at most 249, at least or exactly or at most 250, at least or exactly or at most 251, at least or exactly or at most 252, at least or exactly or at most 253, at least or exactly or at most 254, at least or exactly or at most 255, at least or exactly or at most 256, at least or exactly or at most 257, at least or exactly or at most 258, at least or exactly or at most 259, at least or exactly or at most 260, at least or exactly or at most 271, at least or exactly or at most 272, at least or exactly or at most 273, at least or exactly or at most 274, at least or exactly or at most 275, at least or exactly or at most 276, at least or exactly or at most 277, at least or exactly or at most 278, at least or exactly or at most 279, at least or exactly or at most 280, at least or exactly or at most 281, at least or exactly or at most 282, at least or exactly or at most 283, at least or exactly or at most 284, at least or exactly or at most 285, at least or exactly or at most 286, at least or exactly or at most 287, at least or exactly or at most 288, at least or exactly or at most 289, at least or exactly or at most 290, at least or exactly or at most 291, at least or exactly or at most 292, at least or exactly or at most 293, at least or exactly or at most 294, at least or exactly or at most 295, at least or exactly or at most 296, at least or exactly or at most 297, at least or exactly or at most 298, at least or exactly or at most 299, at least or exactly or at most 300, at least or exactly or at most 301, at least or exactly or at most 302, at least or exactly or at most 303, at least or exactly or at most 304, at least or exactly or at most 305, at least or exactly or at most 306, at least or exactly or at most 307, at least or exactly or at most 308, at least or exactly or at most 309, at least or exactly or at most 310, at least or exactly or at most 311, at least or exactly or at most 312, at least or exactly or at most 313, at least or exactly or at most 314, at least or exactly or at most 315, at least or exactly or at most 316, at least or exactly or at most 317, at least or exactly or at most 318, at least or exactly or at most 319, at least or exactly or at most 320, at least or exactly or at most 321, at least or exactly or at most 322, at least or exactly or at most 323, at least or exactly or at most 324, at least or exactly or at most 325, at least or exactly or at most 326, at least or exactly or at most 327, at least or exactly or at most 328, at least or exactly or at most 329, at least or exactly or at most 330, at least or exactly or at most 331, at least or exactly or at most 332, at least or exactly or at most 333, at least or exactly or at most 334, at least or exactly or at most 335, at least or exactly or at most 336, at least or exactly or at most 337, at least or exactly or at most 338, at least or exactly or at most 339, at least or exactly or at most 340, at least or exactly or at most 341, at least or exactly or at most 342, at least or exactly or at most 343, at least or exactly or at most 344, at least or exactly or at most 345, at least or exactly or at most 346, at least or exactly or at most 347, at least or exactly or at most 348, at least or exactly or at most 349, at least or exactly or at most 350, at least or exactly or at most 351, at least or exactly or at most 352, at least or exactly or at most 353, at least or exactly or at most 354, at least or exactly or at most 355, at least or exactly or at most 356, at least or exactly or at most 357, at least or exactly or at most 358, at least or exactly or at most 359, at least or exactly or at most 360, at least or exactly or at most 361, at least or exactly or at most 362, at least or exactly or at most 363, at least or exactly or at most 364, at least or exactly or at most 365, at least or exactly or at most 366, at least or exactly or at most 367, at least or exactly or at most 368, at least or exactly or at most 369, at least or exactly or at most 370, at least or exactly or at most 371, at least or exactly or at most 372, at least or exactly or at most 373, at least or exactly or at most 374, at least or exactly or at most 375, at least or exactly or at most 376, at least or exactly or at most 377, at least or exactly or at most 378, at least or exactly or at most 379, at least or exactly or at most 380, at least or exactly or at most 381, at least or exactly or at most 382, at least or exactly or at most 383, at least or exactly or at most 384, at least or exactly or at most 385, at least or exactly or at most 386, at least or exactly or at most 387, at least or exactly or at most 388, at least or exactly or at most 389, at least or exactly or at most 390, at least or exactly or at most 391, at least or exactly or at most 392, at least or exactly or at most 393, at least or exactly or at most 394, at least or exactly or at most 395, at least or exactly or at most 396, at least or exactly or at most 397, at least or exactly or at most 398, at least or exactly or at most 399, at least or exactly or at most 400, at least or exactly or at most 401, at least or exactly or at most 402, at least or exactly or at most 403, at least or exactly or at most 404, at least or exactly or at most 405, at least or exactly or at most 406, at least or exactly or at most 407, at least or exactly or at most 408, at least or exactly or at most 409, at least or exactly or at most 410, at least or exactly or at most 411, at least or exactly or at most 412, at least or exactly or at most 413, at least or exactly or at most 414, at least or exactly or at most 415, at least or exactly or at most 416, at least or exactly or at most 417, at least or exactly or at most 418, at least or exactly or at most 419, at least or exactly or at most 420, at least or exactly or at most 421, at least or exactly or at most 422, and at least or exactly or at most 423 consecutive nucleotides in the amino acid encoding part of any one of SEQ ID NOs: 17-48, 50, and 51.
32 . The nucleic acid fragment according to any one of claims 29 - 31 , 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%.
33 . The nucleic acid fragment according to any one of claims 29 - 31 , 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%.
34 . A vector comprising the nucleic acid according to any one of claims 29 - 33 , such as a cloning vector or an expression vector.
35 . The vector according to claim 34 , 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 29 -i), optionally a signal peptide coding sequence, a nucleotide sequence defined in claim 29 -i), and optionally a terminator.
36 . The vector according to claim 34 or 35 , wherein the expression control region drives expression in prokaryotic cell such as a bacterium, e.g. in E coli.
37 . The vector according to claim any one of claims 34 - 36 , which is capable of autonomous replication.
38 . The vector according to any one of claims 34 - 37 , which is capable of being integrated into the genome of a host cell.
39 . The vector according to any one of claims 34 - 38 , which is incapable of being integrated into the genome of a mammalian host cell.
40 . The vector according to any one of claims 34 - 39 , which is selected from the group consisting of a virus, such as a attenuated virus, a bacteriophage, a plasmid, a minichromosome, and a cosmid.
41 . A cell which is transformed so as to carry the vector according to any one of claims 34 - 40 .
42 . The transformed cell according to claim 41 , which is capable of replicating the nucleic acid fragment defined in claim 29 -i).
43 . The transformed cell according to claim 42 , which is capable of expressing the nucleic acid fragment defined in claim 29 -i).
44 . The transformed cell according to any one of claims 41 - 43 , which is selected from a prokaryotic cell and a eukaryotic cell.
45 . The transformed cell according to any one of claims 41 - 43 , 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.
46 . The transformed cell according to any one of claims 41 - 45 , which is stably transformed by having the nucleic acid defined in claim 29 -i) stably integrated into its genome.
47 . The transformed cell according to any one of claims 41 - 46 , which secretes or carries on its surface the polypeptide according to any one of claims 1 - 28 .
48 . The transformed cell according to claim 47 , wherein the cell is a bacterium and secretion is into the periplasmic space.
49 . A cell line derived from a transformed cell according to any one of claims 41 - 48 .
50 . A pharmaceutical composition comprising a polypeptide according to any one of claims 1 - 28 , a nucleic acid fragment according to any one of claims 29 - 33 , a vector according to any one of claims 34 - 40 , or a cell according to any one of claims 41 - 48 , and a pharmaceutically acceptable carrier, vehicle or diluent.
51 . The pharmaceutical composition according to claim 50 , which further comprises an immunological adjuvant.
52 . The pharmaceutical composition according to claim 51 , wherein the adjuvant is an aluminium based adjuvant.
53 . 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 - 28 , a nucleic acid fragment according to any one of claims 29 - 33 , a vector according to any one of claims 34 - 340 , a cell according to any one of claims 41 - 48 , or a pharmaceutical composition according to any one of claims 50 - 52 so as to induce adaptive immunity against S. aureus in the animal.
54 . The method according to claim 53 , wherein, when the polypeptide according to any one of claim 1 - 28 or a composition comprising said polypeptide is administered, the animal receives between 0.5 and 5,000 μg of the polypeptide according to any one of claims 1 - 28 per administration.
55 . The method according to claim 53 or 54 , wherein the animal receives a priming administration and one or more booster administrations.
56 . The method according to any one of claims 53 - 55 , wherein the animal is a human being.
57 . The method according to any one of claims 53 - 56 , wherein the administration is for the purpose of inducing protective immunity against S. aureus.
58 . The method according to claim 57 , wherein the protective immunity is effective in reducing the risk of attracting infection with S. aureus or is effective in treating or ameliorating infection with S. aureus.
59 . The method according to any one of claims 53 - 55 , wherein the administration is for the purpose of inducing antibodies specific for S. aureus and wherein said antibodies or B-lymphocytes producing said antibodies are subsequently recovered from the animal.
60 . The method according to any one of claims 53 - 55 , wherein the administration is for the purpose of inducing antibodies specific for S. aureus and wherein B-lymphocytes producing said antibodies are subsequently recovered from the animal and used for preparation of monoclonal antibodies.
61 . A polyclonal antibody in which the antibodies specifically bind to at least one polypeptide according to any one of claims 1 - 28 , and which is essentially free from antibodies binding specifically to other S. aureus polypeptides.
62 . An isolated monoclonal antibody or antibody analogue which binds specifically to a polypeptide according to any one of claims 1 - 28 .
63 . The isolated monoclonal antibody or antibody analogue according to claim 62 , 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.
64 . A pharmaceutical composition comprising an antibody according to any one of claims 61 - 63 and a pharmaceutically acceptable carrier, vehicle or diluent.
65 . A method for prophylaxis, treatment or amelioration of infection with S. aureus , in particular infection with multi-resistant S. aureus , comprising administering a therapeutically effective amount of an antibody according to any one of claims 61 - 63 or a pharmaceutical composition according to claim 63 to an individual in need thereof.
66 . A method for determining, quantitatively or qualitatively, the presence of S. aureus , in particular the presence of multi-resistant S. aureus , in a sample, the method comprising contacting the sample with an antibody according to any one of claims 61 - 63 and detecting the presence of antibody bound to material in the sample.
67 . A method for determining, quantitatively or qualitatively, the presence of antibodies specific for S. aureus , in particular the presence of antibodies specific for multi-resistant S. aureus , in a sample, the method comprising contacting the sample with a polypeptide according to any one of claims 1 - 28 and detecting the presence of antibody said polypeptide.
68 . A method for determining, quantitatively or qualitatively, the presence of a nucleic acid characteristic of S. aureus , in particular the presence of a nucleic acid characteristic of multi-resistant S. aureus , in a sample, the method comprising contacting the sample with a nucleic acid fragment according to any one of claims 29 - 33 and detecting the presence of nucleic acid in the sample that hybridized to said nucleic acid fragment.
69 . The method according to claim 68 , 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.
70 . A method for the preparation of the polypeptide according to any one of claims 1 - 28 , comprising
culturing a transformed cell according to claim 43 and any one of claims 44 - 48 , insofar as these depend on claim 43 under conditions that facilitate that the transformed cell expresses the nucleic acid fragment according to claim 29 -i) and any one of claims 30 - 33 insofar as these depend on claim 29 -i) and subsequently recovering said polypeptide, or preparing said polypeptide by means of solid or liquid phase peptide synthesis.
71 . A method for determining whether a substance, such as an antibody, is potentially useful for treating infection with S. aureus , the method comprising contacting the polypeptide according to any one of claims 1 - 28 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 compeed with said polypeptide for specific binding to a ligand/receptor,
3) the ability to specifically inactivate said polypeptide.
72 . A method for determining whether a substance, such as a nucleic acid, is potentially useful for treating infection with S. aureus , the method comprising contacting the substance with the nucleic acid fragment of any one of claims 29 - 33 and subsequently establishing whether the substance has either the ability to
1) bind specifically to the nucleic acid fragment, or
2) bind specifically to a nucleic acid that hybridizes specifically with the nucleic acid fragment.
73 . The polypeptide according to any one of claims 1 - 28 for use as a pharmaceutical.
74 . The polypeptide according to any one of claims 1 - 28 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with S. aureus.
75 . The nucleic acid fragment according to any one of claims 29 - 33 or the vector according to any one of claims 34 - 40 for use as a pharmaceutical.
76 . The nucleic acid fragment according to any one of claims 29 - 33 or the vector according to any one of claims 34 - 40 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with S. aureus.
77 . The cell according to any one of claims 41 - 48 for use as a pharmaceutical.
78 . The cell according to any one of claims 41 - 48 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with S. aureus.
79 . The antibody, antibody fragment or antibody analogue according to any one of claims 61 - 63 for use as a pharmaceutical.
80 . The antibody, antibody fragment or antibody analogue according to any one of claims 61 - 63 for use as a pharmaceutical in the treatment, prophylaxis or amelioration of infection with S. aureus.Join the waitlist — get patent alerts
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