KR20090088936A - 사람 델타 유사 리간드 4에 대한 사람 항체 - Google Patents
사람 델타 유사 리간드 4에 대한 사람 항체 Download PDFInfo
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- KR20090088936A KR20090088936A KR1020097013986A KR20097013986A KR20090088936A KR 20090088936 A KR20090088936 A KR 20090088936A KR 1020097013986 A KR1020097013986 A KR 1020097013986A KR 20097013986 A KR20097013986 A KR 20097013986A KR 20090088936 A KR20090088936 A KR 20090088936A
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- ser
- gly
- thr
- tyr
- leu
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Abstract
본 발명은 사람 델타-유사 리간드 4 (hDll4)에 특이적으로 결합하며, 노치 수용체에 대한 hDll4 결합을 차단하는 분리된 사람 항체 또는 사람 항체의 단편에 관한 것이다. 사람 항-hDll4 항체 또는 항체 단편은 표면 플라즈몬 공명에 의해서 측정한 바에 의하면 500 pM 이하의 친화도로 hDll4에 결합한다.
사람 델타-유사 리간드 4, hDll4, 항-hDll4 항체, 표면 플라즈몬 공명, Dll4-매개된 질병
Description
노치-신호전달 경로 (Notch-signaling pathway)는 분화, 증식 및 항상성과 같은 다수의 생물학적 과정을 위해서 광범위한 진핵생물에 의해 사용되는 세포간 소통 (cell-to-cell communication)을 위한 시스템이다. 델타 유사 (delta like) 4 (Dl4) 또는 델타-유사 리간드 4 (Dll4) (이하에서는 "Dll4")는 혈관 내피에 의한 고도로 선택적인 발현을 나타내는 노치 리간드의 델타 집단의 구성원이다 (Shutter et al. (2000) Genes Develop. 14:1313-1318). Dll4는 노치 1 및 노치 4를 포함한 노치 수용체에 대한 리간드이다. 사람 Dll4에 대한 핵산 및 아미노산 서열은 각각 서열번호 1-2에 나타내었다.
사람 치료제로서 유용한 항체를 생산하는 방법은 키메릭 항체 및 사람화된 항체의 생성을 포함한다 (참조: 예를 들어, U.S. 6,949,245). 예를 들어, 사람 항체를 생산할 수 있는 비사람 유전자이식 마우스를 생성시키는 방법을 기술한 WO 94/02602 (Abgenix) 및 U.S. 6,596,541 (Regeneron Pharmaceuticals)을 참조한다.
일본 특허출원 제2003/047470A2호 (Asahi Kasei Kogyo)는 사람 노치 리간드 단백질의 세포외 부분에 대한 항체를 기술하였다.
발명의 개요
첫 번째 관점에서, 본 발명은 사람 델타-유사 리간드 4 (hDll4)에 특이적으로 결합하는 사람 항체, 바람직하게는 재조합 사람 항체를 제공한다. 이들 항체는 높은 친화도로 hDll4에 결합하고 Dll4 활성을 중화시키는 능력을 특징으로 한다. 본 발명의 항체는 이의 노치 수용체(들)에 대한 Dll4 결합을 차단할 수 있으며, 따라서 Dll4에 의한 신호전달을 억제한다. 항체는 전체-길이일 수 있거나 (예를 들어, IgG1 또는 IgG4 항체), 단지 항원-결합 부분만을 포함할 수 있거나 (예를 들어, Fab, F(ab')2 또는 scFv 단편), 기능성을 발휘하도록, 예를 들어, 잔류하는 효과기 기능 (effector function)을 제거하도록 변형될 수 있다 (잔류하는 효과기 기능을 제거하는 Glu (Reddy et al. (2000) J. Immunol. 164:1925-1933)).
한가지 구체예에서, 본 발명의 항체는 서열번호 4, 20, 36, 52, 68, 84, 100, 116, 132, 148, 164, 180, 196, 212, 228, 244, 260, 276, 292, 308, 324, 340, 356, 372, 397, 413, 429, 445, 461, 477, 493, 509, 525, 541, 557, 573, 589, 605, 621, 637, 653, 669, 685, 701, 717, 733, 749, 765, 781, 797, 813, 893, 897, 901, 905, 909, 913, 917, 921, 925, 935, 939, 943 및 947 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 중쇄 가변 영역 (HCVR)을 포함한다. 바람직한 구체예에서, HCVR은 서열번호 429 또는 901의 아미노산 서열이다.
한가지 구체예에서, 본 발명의 항체는 서열번호 12, 28, 44, 60, 76, 92, 108, 124, 140, 156, 172, 188, 204, 220, 236, 252, 268, 284, 300, 316, 332, 348, 364, 380, 405, 421, 437, 453, 469, 485, 501, 517, 533, 549, 565, 581, 597, 613, 629, 645, 661, 677, 693, 709, 725, 741, 757, 773, 789, 805, 821, 895, 899, 903, 907, 911, 915, 919, 923, 927, 937, 941, 945 및 949 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 경쇄 가변 영역 (LCVR)을 포함한다. 바람직한 구체예에서, LCVR은 서열번호 437 또는 903의 아미노산 서열이다.
한가지 구체예에서, 본 발명의 항체는 서열번호 4, 20, 36, 52, 68, 84, 100, 116, 132, 148, 164, 180, 196, 212, 228, 244, 260, 276, 292, 308, 324, 340, 356, 372, 397, 413, 429, 445, 461, 477, 493, 509, 525, 541, 557, 573, 589, 605, 621, 637, 653, 669, 685, 701, 717, 733, 749, 765, 781, 797, 813, 893, 897, 901, 905, 909, 913, 917, 921, 925, 935, 939, 943 및 947 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 HCVR, 및 서열번호 12, 28, 44, 60, 76, 92, 108, 124, 140, 156, 172, 188, 204, 220, 236, 252, 268, 284, 300, 316, 332, 348, 364, 380, 405, 421, 437, 453, 469, 485, 501, 517, 533, 549, 565, 581, 597, 613, 629, 645, 661, 677, 693, 709, 725, 741, 757, 773, 789, 805, 821, 895, 899, 903, 907, 911, 915, 919, 923, 927, 937, 941, 945 및 949 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로 선택된 LCVR을 포함한다. 바람직한 구체예에서, HCVR/LCVR은 아미노산 서열 쌍 서열번호 429/437또는 901/903이다.
한가지 구체예에서, 본 발명은 서열번호 6, 22, 38, 54, 70, 86, 102, 118, 134, 150, 166, 182, 198, 214, 230, 246, 262, 278 294, 310, 326, 342, 358, 374, 399, 415, 431, 447, 463, 479, 495, 511, 527, 543, 559, 575, 591, 607, 623, 639, 655, 671, 687, 703, 711119, 735, 751, 767, 783, 799, 815, 831, 847, 863 및 879, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 중쇄 상보성 결정 영역 1 (CDR1)을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 8, 24, 40, 56, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, 328, 344, 360, 376, 401, 417, 433, 449, 465, 481, 497, 513, 529, 545, 561, 577, 593, 609, 625, 641, 657, 673, 689, 705, 721, 737, 753, 769, 785, 801, 817, 833, 849, 865 및 881, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 중쇄 CDR2를 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 186, 202, 218, 234, 250, 266, 282, 298, 314, 330, 346, 362, 378, 403, 419, 435, 451, 467, 483, 499, 515, 531, 547, 563, 579, 595, 611, 627, 643, 659, 675, 691, 707, 723, 739, 755, 771, 787, 803, 819, 835, 851, 867 및 883, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 중쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 6, 22, 38, 54, 70, 86, 102, 118, 134, 150, 166, 182, 198, 214, 230, 246, 262, 278 294, 310, 326, 342, 358, 374, 399, 415, 431, 447, 463, 479, 495, 511, 527, 543, 559, 575, 591, 607, 623, 639, 655, 671, 687, 703, 711119, 735, 751, 767, 783, 799, 815, 831, 847, 863 및 879, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 중쇄 CDR1; 서열번호 8, 24, 40, 56, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, 328, 344, 360, 376, 401, 417, 433, 449, 465, 481, 497, 513, 529, 545, 561, 577, 593, 609, 625, 641, 657, 673, 689, 705, 721, 737, 753, 769, 785, 801, 817, 833, 849, 865 및 881, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 중쇄 CDR2; 및 서열번호 10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 186, 202, 218, 234, 250, 266, 282, 298, 314, 330, 346, 362, 378, 403, 419, 435, 451, 467, 483, 499, 515, 531, 547, 563, 579, 595, 611, 627, 643, 659, 675, 691, 707, 723, 739, 755, 771, 787, 803, 819, 835, 851, 867 및 883, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 중쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다. 바람직한 구체예에서, 항체 또는 항체 단편은 서열번호 431/433/435; 374/376/378; 783/785/787; 및 799/801/803으로 이루어진 그룹으로부터 선택된 중쇄 CDR1, CDR2 및 CDR3을 포함한다.
한가지 구체예에서, 본 발명은 서열번호 14, 30, 46, 62, 78, 94, 110, 126, 142, 158, 174, 190, 206, 222, 238, 254, 270, 286, 302, 318, 334, 350, 366, 382, 407, 423, 439, 455, 471, 487, 503, 519, 535, 551, 567, 583, 599, 615, 631, 647, 663, 679, 695, 711, 727, 743, 759, 775, 791, 807, 823, 839, 855, 871 및 887, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 경쇄 CDR1을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 16, 32, 48, 64, 80, 96, 112, 128, 144, 160, 176, 192, 208, 224, 240, 256, 272, 288, 304, 320, 336, 352, 368, 384, 409. 425, 441, 457, 473, 489, 505, 521, 537, 553, 569, 585, 601, 617, 633, 649, 665, 681, 697, 713, 729, 745, 761, 777, 793, 809, 825, 841, 857, 873 및 889, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 경쇄 CDR2를 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 18, 34, 50, 66, 82, 98, 11, 130, 146, 162, 178, 194, 210, 226, 242, 258, 274, 290, 306, 322, 338, 354, 370, 386, 411, 427, 443, 459, 475, 491, 507, 523, 539, 555, 571, 587, 603, 619, 635, 651, 667, 683, 699, 715, 731, 747, 763, 779, 795, 811, 827, 843, 859, 875 및 891, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 경쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 14, 30, 46, 62, 78, 94, 110, 126, 142, 158, 174, 190, 206, 222, 238, 254, 270, 286, 302, 318, 334, 350, 366, 382, 407, 423, 439, 455, 471, 487, 503, 519, 535, 551, 567, 583, 599, 615, 631, 647, 663, 679, 695, 711, 727, 743, 759, 775, 791, 807, 823, 839, 855, 871 및 887, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 경쇄 CDR1; 서열번호 16, 32, 48, 64, 80, 96, 112, 128, 144, 160, 176, 192, 208, 224, 240, 256, 272, 288, 304, 320, 336, 352, 368, 384, 409. 425, 441, 457, 473, 489, 505, 521, 537, 553, 569, 585, 601, 617, 633, 649, 665, 681, 697, 713, 729, 745, 761, 777, 793, 809, 825, 841, 857, 873 및 889, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 경쇄 CDR2; 및 서열번호 18, 34, 50, 66, 82, 98, 11, 130, 146, 162, 178, 194, 210, 226, 242, 258, 274, 290, 306, 322, 338, 354, 370, 386, 411, 427, 443, 459, 475, 491, 507, 523, 539, 555, 571, 587, 603, 619, 635, 651, 667, 683, 699, 715, 731, 747, 763, 779, 795, 811, 827, 843, 859, 875 및 891, 또는 이의 실질적으로 동일한 서열로 이루어진 그룹으로부터 선택된 경쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다. 바람직한 구체예에서, 항체 또는 항체 단편은 서열번호 439/441/443; 382/384/386; 791/793/795; 및 807/809/811로 이루어진 그룹으로부터 선택된 경쇄 CDR1, CDR2 및 CDR3을 포함한다.
두 번째 관점에서, 본 발명은 본 발명의 항체 또는 항원-결합 부분을 암호화하는 핵산 분자를 제공한다. 본 발명의 항체-암호화 핵산을 보유하는 재조합 발현 벡터, 및 이러한 벡터가 도입된 숙주 세포도 또한, 본 발명의 숙주 세포를 배양함으로써 본 발명의 항체를 제조하는 방법과 마찬가지로 본 발명에 포함된다.
한가지 구체예에서, 본 발명의 항체는 서열번호 3, 19, 35, 51, 67, 83, 99, 115, 131, 147, 163, 179, 195, 211, 227, 243, 259, 275, 291, 307, 323, 339, 355, 371, 396, 412, 428, 444, 460, 476, 492, 508, 524, 540, 556, 572, 588, 604, 620, 636, 652, 668, 684, 700, 716, 732, 748, 764, 780, 796, 812, 892, 896, 900, 904, 908, 912, 916, 920, 924, 934, 938, 942 및 946 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 HCVR을 포함한다.
한가지 구체예에서, 본 발명의 항체는 서열번호 11, 27, 43, 59, 75, 91, 107, 123, 139, 155, 171, 187, 203, 219, 235, 251, 267, 283, 299, 315, 331, 347, 363, 379, 404, 420, 436, 452, 468, 484, 500, 516, 532, 548, 564, 580, 596, 612, 628, 644, 660, 676, 692, 708, 724, 740, 756, 772, 788, 804, 820, 894, 898, 902, 906, 910, 914, 918, 922, 926, 936, 940, 944 및 948 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 LCVR을 포함한다.
한가지 구체예에서, 본 발명의 항체는 서열번호 3, 19, 35, 51, 67, 83, 99, 115, 131, 147, 163, 179, 195, 211, 227, 243, 259, 275, 291, 307, 323, 339, 355, 371, 396, 412, 428, 444, 460, 476, 492, 508, 524, 540, 556, 572, 588, 604, 620, 636, 652, 668, 684, 700, 716, 732, 748, 764, 780, 796, 812, 892, 896, 900, 904, 908, 912, 916, 920, 924, 934, 938, 942 및 946 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 HCVR, 및 서열번호 11, 27, 43, 59, 75, 91, 107, 123, 139, 155, 171, 187, 203, 219, 235, 251, 267, 283, 299, 315, 331, 347, 363, 379, 404, 420, 436, 452, 468, 484, 500, 516, 532, 548, 564, 580, 596, 612, 628, 644, 660, 676, 692, 708, 724, 740, 756, 772, 788, 804, 820, 894, 898, 902, 906, 910, 914, 918, 922, 926, 936, 940, 944 및 948 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 LCVR을 포함한다.
한가지 구체예에서, 본 발명은 서열번호 5, 21, 37, 53, 69, 85, 101, 117, 133, 149, 165, 181, 197, 213, 229, 245, 261, 277, 293, 309, 325, 341, 357, 373, 398, 414, 430, 446, 462, 478, 494, 510, 526, 542, 558, 574, 590, 606, 622, 638, 654, 670, 686, 702, 718, 734, 750, 766, 782, 798, 814, 830, 846, 862 및 878, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 중쇄 CDR1을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 7, 23, 39, 55, 71, 87, 103, 119, 135, 151, 167, 183, 100, 215, 231, 247, 263, 279, 295, 311, 327, 343, 359, 375, 400, 416, 432, 448, 464, 480, 496, 512, 528, 544, 560, 576, 592, 608, 624, 640, 656, 672, 688, 704, 720, 736, 752, 768, 784, 800, 816, 832, 848, 864 및 880, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 중쇄 CDR2를 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 9, 25, 41, 57, 73, 89, 105, 121, 137, 153, 169, 185, 201, 217, 233, 249, 265, 281, 297, 313, 329, 345, 361, 377, 402, 418, 434, 450, 466, 482, 498, 514, 530, 546, 562, 578, 594, 610, 626, 642, 658, 674, 690, 706, 722, 738, 754, 770, 786, 802, 818, 834, 850, 866 및 882, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 중쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 5, 21, 37, 53, 69, 85, 101, 117, 133, 149, 165, 181, 197, 213, 229, 245, 261, 277, 293, 309, 325, 341, 357, 373, 398, 414, 430, 446, 462, 478, 494, 510, 526, 542, 558, 574, 590, 606, 622, 638, 654, 670, 686, 702, 718, 734, 750, 766, 782, 798, 814, 830, 846, 862 및 878, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 중쇄 CDR1; 서열번호 7, 23, 39, 55, 71, 87, 103, 119, 135, 151, 167, 183, 100, 215, 231, 247, 263, 279, 295, 311, 327, 343, 359, 375, 400, 416, 432, 448, 464, 480, 496, 512, 528, 544, 560, 576, 592, 608, 624, 640, 656, 672, 688, 704, 720, 736, 752, 768, 784, 800, 816, 832, 848, 864 및 880, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 중쇄 CDR2; 및 서열번호 9, 25, 41, 57, 73, 89, 105, 121, 137, 153, 169, 185, 201, 217, 233, 249, 265, 281, 297, 313, 329, 345, 361, 377, 402, 418, 434, 450, 466, 482, 498, 514, 530, 546, 562, 578, 594, 610, 626, 642, 658, 674, 690, 706, 722, 738, 754, 770, 786, 802, 818, 834, 850, 866 및 882, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 중쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다. 바람직한 구체예에서, 항체 또는 항체 단편은 서열번호 430/432/434; 373/375/377; 782/784/786; 및 798/800/802로 이루어진 그룹으로부터 선택된 핵산 서열에 의해서 암호화된 중쇄 CDR1, CDR2 및 CDR3을 포함한다.
한가지 구체예에서, 본 발명은 서열번호 13, 29, 45, 61, 77, 93, 109, 125, 141, 157, 173, 189, 205, 221, 237, 253, 269, 285, 301, 317, 333, 349, 365, 381, 406, 422, 438, 454, 470, 486, 502, 518, 534, 550, 566, 582, 598, 614, 630, 646, 662, 678, 694, 710, 726, 742, 758, 774, 790, 806, 822, 838, 854, 870 및 886, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 경쇄 CDR1을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 15, 31, 47, 63, 79, 95, 111, 127, 143, 159, 175, 191, 207, 223, 239, 255, 271, 287, 303, 319, 335, 351, 367, 383, 408, 424, 440, 456, 472, 488, 504, 520, 536, 552, 568, 584, 600, 616, 632, 648, 664, 680, 696, 712, 728, 744, 760, 776, 792, 808, 824, 840, 856, 872 및 888, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 경쇄 CDR2를 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 17, 33, 49, 65, 81, 97, 113, 129, 145, 161, 177, 193, 209, 225, 241, 257, 273, 289, 305, 321, 337, 353, 369, 385, 410, 426, 442, 458, 474, 490, 506, 522, 538, 554, 570, 586, 602, 618, 634, 650, 666, 682, 698, 714, 730, 746, 762, 778, 794, 810, 826, 842, 858, 874 및 890, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 경쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다.
한가지 구체예에서, 본 발명은 서열번호 13, 29, 45, 61, 77, 93, 109, 125, 141, 157, 173, 189, 205, 221, 237, 253, 269, 285, 301, 317, 333, 349, 365, 381, 406, 422, 438, 454, 470, 486, 502, 518, 534, 550, 566, 582, 598, 614, 630, 646, 662, 678, 694, 710, 726, 742, 758, 774, 790, 806, 822, 838, 854, 870 및 886, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 경쇄 CDR1; 서열번호 15, 31, 47, 63, 79, 95, 111, 127, 143, 159, 175, 191, 207, 223, 239, 255, 271, 287, 303, 319, 335, 351, 367, 383, 408, 424, 440, 456, 472, 488, 504, 520, 536, 552, 568, 584, 600, 616, 632, 648, 664, 680, 696, 712, 728, 744, 760, 776, 792, 808, 824, 840, 856, 872 및 888, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 경쇄 CDR2; 및 서열번호 17, 33, 49, 65, 81, 97, 113, 129, 145, 161, 177, 193, 209, 225, 241, 257, 273, 289, 305, 321, 337, 353, 369, 385, 410, 426, 442, 458, 474, 490, 506, 522, 538, 554, 570, 586, 602, 618, 634, 650, 666, 682, 698, 714, 730, 746, 762, 778, 794, 810, 826, 842, 858, 874 및 890, 또는 적어도 95% 상동성을 갖는 이의 실질적으로 유사한 서열로 이루어진 그룹으로부터 선택된 뉴클레오타이드 서열에 의해서 암호화된 경쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다. 바람직한 구체예에서, 항체 또는 항체 단편은 서열번호 438/440/442; 381/383/385; 790/792/794; 및 806/808/810으로 이루어진 그룹으로부터 선택된 핵산 서열에 의해서 암호화된 경쇄 CDR1, CDR2 및 CDR3을 포함한다.
세 번째 관점에서, 본 발명은 hDll4에 특이적으로 결합하며, (a) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 928) (여기에서, X1은 Gly이고; X2는 Phe 또는 Tyr이며; X3은 Thr이고; X4는 Phe이며; X5는 Ser, Thr 또는 Asn이고; X6은 Ser, Asn 또는 Tyr이며; X7은 Tyr 또는 Phe이고; X8은 Gly 또는 Ala이다)의 아미노산 서열을 포함하는 중쇄 CDR1 영역; (b) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 929) (여기에서, X1은 Ile 또는 Leu이며; X2는 Trp 또는 Ser이고; X3은 Tyr, Ala 또는 Gly이며; X4는 Asp, Ser 또는 Tyr이고; X5는 Gly 또는 Asp이며; X6은 Ser, Gly, Thr 또는 Val이고; X7은 Asn 또는 Asp이며; X8은 Lys 또는 Arg이다)의 아 미노산 서열을 포함하는 중쇄 CDR2 영역; (c) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 - X10 - X11 - X12 - X13 - X14 - X15 - X16 (서열번호 930) (여기에서, X1은 Ala 또는 Ser이고; X2는 Arg 또는 Lys이며; X3은 Asp 또는 Tyr이고; X4는 Ser, Gly 또는 His이며; X5는 Asp, Ala 또는 Trp이고; X6은 Asn 또는 Phe이며; X7은 Tyr, Arg 또는 Lys이고; X8은 His 또는 Ser이며; X9는 Gly 또는 Trp이고; X10은 Tyr 또는 Phe이며; X11은 Glu 또는 Asp이고; X12는 Gly, His 또는 Pro이며; X13은 Tyr 또는 Trp이거나 존재하지 않고; X14는 Phe이거나 존재하지 않으며; X15는 Asp이거나 존재하지 않으며; X16은 Pro이거나 존재하지 않는다)의 아미노산 서열을 포함하는 중쇄 CDR3 영역으로 이루어진 그룹으로부터 선택된 CDR 1, 2 및 3을 포함하는 분리된 항체 또는 항체 단편을 특징으로 한다.
바람직한 구체예에서, 항체 또는 항체 단편은 (a) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 928) (여기에서, X1은 Gly이고; X2는 Phe이며; X3은 Thr이고; X4는 Phe이며; X5는 Ser 또는 Asn이고; X6은 Ser 또는 Asn이며; X7은 Tyr 또는 Phe이고; X8은 Gly 또는 Ala이다)의 아미노산 서열을 포함하는 중쇄 CDR1 영역; (b) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 929) (여기에서, X1 은 Ile 또는 Leu이고; X2는 Trp 또는 Ser이며; X3은 Tyr 또는 Gly이고; X4는 Asp 또는 Ser이며; X5는 Gly이고; X6은 Ser, Thr 또는 Val이며; X7은 Asn 또는 Asp이고; X8은 Lys 또는 Arg이다)의 아미노산 서열을 포함하는 중쇄 CDR2 영역; (c) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 - X10 - X11 - X12 - X13 - X14 - X15 - X16 (서열번호 930) (여기에서, X1은 Ala 또는 Ser이고; X2는 Arg 또는 Lys이며; X3은 Asp이고; X4는 Gly 또는 His이며; X5는 Asp 또는 Ala이고; X6은 Phe이며; X7은 Tyr 또는 Arg이고; X8은 Ser이며; X9는 Gly이고; X10은 Tyr이며; X11은 Glu이고; X12는 Gly 또는 His이며; X13은 Tyr 또는 Trp이고; X14는 Phe이거나 존재하지 않으며; X15는 Asp이거나 존재하지 않고; X16은 Pro이거나 존재하지 않는다)의 아미노산 서열을 포함하는 중쇄 CDR3 영역으로 이루어진 그룹으로부터 선택된 중쇄 CDR 1, 2 및 3을 포함한다.
추가의 구체예에서, 분리된 항체 또는 항체 단편은 (d) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 (서열번호 931) (여기에서, X1은 Gln이고; X2는 Ser이며; X3은 Val이고; X4는 Arg, Ser 또는 Thr이며; X5는 Ser 또는 Gly이고; X6은 Ser 또는 Tyr이며; X7은 Tyr이거나 존재하지 않는다)의 아미노산 서열을 포함하는 경쇄 CDR1 영 역; (e) 화학식 X1 - X2 - X3 (서열번호 932) (여기에서, X1은 Gly 또는 Asp이고; X2는 Ala 또는 Thr이며; X3은 Ser이다)의 아미노산 서열을 포함하는 경쇄 CDR2 영역; 및 (f) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 (서열번호 933) (여기에서, X1은 Gln이고; X2는 Gln 또는 His이며; X3은 Tyr, Arg 또는 Ser이고; X4는 Gly, Ser 또는 Ala이며; X5는 Ser, Asn 또는 Phe이고; X6은 Trp 또는 Ser이며; X7은 Pro이고; X8은 Trp, Pro 또는 Arg이며; X9는 Thr이다)의 아미노산 서열을 포함하는 경쇄 CDR3 영역을 추가로 포함한다.
바람직한 구체예에서, 분리된 항체 또는 항체 단편은 (d) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 (서열번호 931) (여기에서, X1은 Gln이고; X2는 Ser이며; X3은 Val이고; X4는 Arg 또는 Ser이며; X5는 Ser이고; X6은 Ser 또는 Tyr이며; X7은 Tyr이거나 존재하지 않는다)의 아미노산 서열을 포함하는 경쇄 CDR1 영역; (e) 화학식 X1 - X2 - X3 (서열번호 932) (여기에서, X1은 Gly 또는 Asp이고; X2는 Ala 또는 Thr이며; X3은 Ser이다)의 아미노산 서열을 포함하는 경쇄 CDR2 영역; 및 (f) 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 (서열번호 933) (여기에서, X1은 Gln이고; X2는 Gln 또는 His이며; X3은 Tyr 또는 Arg이고; X4는 Gly 또는 Ser이며; X5는 Ser 또는 Asn이고; X6은 Trp 또는 Ser이며; X7은 Pro이고; X8은 Pro 또는 Arg이며; X9는 Thr이다)의 아미노산 서열을 포함하는 경쇄 CDR3 영역을 추가로 포함한다.
네 번째 관점에서, 본 발명은 시험관내 시험 또는 ELISA-기반 Dll4 차단시험 (이하에 기술함)에서 측정한 바에 의하면 약 10 nM 미만의 IC50으로 hDll4에 결합하는 완전한 사람 항체 또는 항체 단편을 특징으로 한다. 바람직한 구체예에서, 본 발명의 항체는 약 500 pM 이하의 IC50을 나타낸다. 더 더욱 바람직한 구체예에서, 본 발명의 항체는 약 100 pM 이하의 IC50을 나타낸다.
한가지 구체예에서, 본 발명은 사람 Dll4에 특이적으로 결합하여 이를 억제시키고, hDll4-Fc를 사용한 노치-유도성 루시퍼라제 생물검정법 (bioassay)에 의해서 측정한 바에 의하면 약 150 pM, 100 pM, 75 pM 또는 50 pM 이하의 IC50을 나타내는 완전한 사람 모노클로날 항체를 제공한다. 이하의 실험항목에서 나타낸 바와 같이, 본 발명의 항-hDll4 항체는 hDll1 및 hDll3과 같은 밀접하게 관련된 델타 단백질과 교차-반응하지 않는다.
한가지 구체예에서, 본 발명은 예를 들어, 이량체 hDll4를 사용한 표면 플라즈몬 공명 (BIACORE™)에 의해서 측정한 바에 의하면 약 500 pM 미만, 바람직하게는 약 300 pM 미만, 더 더욱 바람직하게는 약 100 pM 미만, 약 50 pM 미만, 약 10 pM 미만의 KD로 hDll4에 결합하는 분리된 사람 항체 또는 이의 항원-결합 부분을 제공한다 (표 2).
본 발명은 변형된 글리코실화 패턴을 갖는 항-hDll4 항체를 포함한다. 일부의 적용 시에, 바람직하지 않은 글리코실화 부위를 제거하는 변형이 유용할 수 있거나, 또는 예를 들어, 항체 의존적 세포성 세포독성 (ADCC) 기능을 증가시키기 위하여 올리고사카라이드 쇄 상에 존재하는 푸코즈 부위가 결여된 항체가 사용될 수도 있다 (참조: Shield et al. (2002) JBC 277:26733). 그 밖의 다른 적용 시에는, 보체 의존적 세포독성 (CDC)을 변형시키기 위해서 갈락토실화의 변형이 이루어질 수 있다.
본 발명은 hDll4의 특이적 에피토프 (epitope)에 결합하며, hDll4의 생물학적 활성을 차단할 수 있는 항-hDll4 항체를 포함한다. Dll4의 세포외 도메인은 N-말단 도메인, 델타/세레이트/라그 (Delta/Serrate/Lag)-2 (DSL) 도메인, 및 8개의 상피성장인자 (EGF)-유사 반복부 (repeat)의 탠덤 (tandem)으로 구성된다. 일반적으로, EGF 도메인은 hDll4 (서열번호 2)의 대략 아미노산 잔기 218-251 (도메인 1), 252-282 (도메인 2), 284-322 (도메인 3), 324-360 (도메인 4), 및 362-400 (도메인 5)에서 나타나며, DSL 도메인은 대략 아미노산 잔기 173-217에서, N-말단 도메인은 대략 아미노산 잔기 27-172에서 나타나는 것으로 인식된다.
한가지 구체예에서, 본 발명의 차단 항체는 서열번호 2의 아미노산 잔기 27 내지 524 내에서 결합한다. 더욱 특정한 구체예에서, 본 발명의 차단 항체는 서열번호 2의 N-말단-DSL 도메인 27-217 내에서 에피토프에 결합하며; 더 더욱 특정한 구체예에서, 차단 항체는 대략 아미노산 잔기 27-172 (N-말단 영역) 또는 173-217 (DSL 도메인) 내에서 에피토프에 결합한다. 또 다른 구체예에서, 본 발명의 차단 항체는 대략 서열번호 2의 아미노산 잔기 252-282 내에서 EGF-2 에피토프에 결합한다.
다섯 번째 관점에서, 본 발명은 재조합 사람 항-사람 Dll4 항체 및 허용되는 담체를 포함하는 조성물을 특징으로 한다. 추가로, 본 발명에는 본 발명의 사람 항-hDll4 항체를 암호화하는 핵산 분자를 함유하는 벡터 및 벡터를 포함하는 숙주 세포뿐만 아니라, 본 발명의 항-hDll4 항체 또는 항체 단편을 암호화하는 핵산을 포함하는 숙주 세포를 단백질의 생산을 허용하는 조건 하에서 성장시키고, 이렇게 생산된 단백질을 회수하는 단계를 포함하여 이들 신규 항체를 생산하는 방법이 포함된다.
여섯 번째 관점에서, 본 발명은 본 발명의 항체 또는 이의 항원-결합 부분을 사용하여 hDll4 활성을 억제하는 방법을 특징으로 한다. 한가지 구체예에서, 이 방법은 hDll4가 노치 수용체, 예를 들어, 노치-1에 결합하는 것이 억제되도록 hDll4를 본 발명의 항체 또는 이의 항원-결합 부분과 접촉시키는 것을 포함한다. 또 다른 구체예에서, 이 방법은 Dll4 활성을 억제함으로써 개선되는 장애를 앓고 있는 사람 대상체에게 본 발명의 항체 또는 항체 단편을 투여하는 것을 포함한다. 치료되는 장애는 Dll4 활성을 제거, 억제 또는 감소시킴으로써 호전, 개선, 억제 또는 예방되는 질병 또는 상태, 예를 들어, 종양 혈관형성 및 암과 연관된 병리학적 혈관신생, 면역결핍성 질병, 이식 거부반응, 또는 염증; 및 예를 들어, 프리온 (prion) 질병과 연관된 신경변성 상태이다. 본 발명은 또한, 사람에서 Dll4-매개된 질병 또는 장애를 약화시키거나 억제하는데 사용하기 위한 약제를 제조하는데 있어서의, 상술한 바와 같은 항체 또는 항체의 항원-결합 단편의 용도를 제공한다.
그 밖의 다른 목적 및 이점은 이하의 상세한 설명을 검토하면 명백해질 것이다.
본 발명의 방법을 설명하기에 앞서서, 본 발명은 특정한 방법 및 기술된 실험조건으로 제한되지는 않는 것으로 이해되어야 하는데, 이는 이러한 방법 및 조건은 변화할 수 있기 때문이다. 또한, 본 발명의 범위는 단지 첨부된 특허청구범위에 의해서만 제한되기 때문에, 여기에서 사용된 용어는 단지 특정한 구체예를 기술하기 위한 것이며, 제한하고자 하는 것은 아님을 이해하여야 한다.
본 명세서 및 첨부된 특허청구범위에서 사용된 단수 형태 "하나" 및 "상기"는 문맥이 분명하게 다른 식으로 지시하지 않는 한은 복수에 대한 언급을 포함한다. 따라서, 예를 들어, "방법"에 대한 언급은 여기에 기술되고/되거나 본 명세서를 읽으면 본 기술분야에서 숙련된 전문가에게 명백할 수 있는 하나 이상의 방법 및/또는 단계를 포함한다.
다른 식으로 정의되지 않는 한, 본 명세서에서 사용된 모든 기술적 및 과학적 용어들은 본 발명이 속하는 기술분야에서 통상적으로 숙련된 전문가에 의해서 일반적으로 이해되는 것과 같은 의미를 갖는다. 본 명세서에 기술된 것과 유사하거나 동등한 어떠한 방법 및 물질이라도 본 발명을 실시하거나 시험하는데 사용될 수 있지만, 이하에 바람직한 방법 및 물질이 기술된다.
정의
"델타-유사 리간드4", "Dll4", "hDll4"는 서열번호 1의 핵산 서열에 의해서 암호화된 단백질 및 서열번호 2의 아미노산 서열을 갖는 단백질을 나타내기 위해서 상호 교환하여 사용된다.
본 명세서에서 사용된 용어 "항체"는 디설파이드 결합에 의해서 서로 연결된 두 개의 중쇄 (H) 및 두 개의 경쇄 (L)인 4개의 폴리펩타이드 쇄를 포함하는 면역글로불린 분자를 나타내고자 하는 것이다. 각각의 중쇄는 중쇄 가변 영역 (여기에서는 HCVR 또는 VH로 약칭함) 및 중쇄 불변 영역을 포함한다. 중쇄 불변 영역은 3개의 영역 CH1, CH2 및 CH3을 포함한다. 각각의 경쇄는 경쇄 가변 영역 (여기에서는 LCVR 또는 VL로 약칭함) 및 경쇄 불변 영역을 포함한다. 경쇄 불변 영역은 한 개의 도메인 CL을 포함한다. VH 및 VL 부분은 골격 영역 (FR)이라 불리는 더 보존된 부분이 산재된, 상보성 결정 영역 (CDR)이라 불리는 고가변성의 영역으로 더 세분될 수 있다. 각각의 VH 및 VL은 다음의 순서로 아미노-말단으로부터 카복시-말단 쪽으로 배열된 3개의 CDR 및 4개의 FR로 구성된다: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
용어 "고친화도" 항체는 표면 플라즈몬 공명, 예를 들어, 비아코어 (BIACORE™), 또는 용액-친화도 ELISA에 의해서 측정한 바에 의하면 적어도 10-8 M; 바람직하게는 10-9 M; 더 더욱 바람직하게는 10-10 M의 hDll4에 대한 결합 친화도를 갖는 항체를 나타내는 것이다.
용어 "슬로우 오프 속도 (slow off rate)" 또는 "Koff"는 표면 플라즈몬 공명, 예를 들어, 비아코어 (BIACORE™)에 의해서 측정한 바에 의하면 1 x 10-3 s-1 이하, 바람직하게는 1 x 10-4 s-1 이하의 속도 상수 (rate constant)로 hDll4로부터 해리하는 항체를 의미한다.
"중화" 또는 "차단" 항체는 Dll4에 대한 이의 결합이 Dll4의 생물학적 활성의 억제를 야기하는 항체를 나타내고자 하는 것이다. 이러한 Dll4의 생물학적 활성의 억제는 Dll4 생물학적 활성의 하나 이상의 지표 (indicator)를 측정함으로써 평가될 수 있다. 이들 Dll4 생물학적 활성의 지표는 본 기술분야에서 공지된 하나 이상의 몇 가지 표준 시험관내 또는 생체내 시험방법에 의해서 평가될 수 있다 (이하의 실시예 참조). 바람직하게는, Dll4 활성을 중화시키는 항체의 능력은 노치 수용체에 대한 Dll4 결합의 억제에 의해서 평가된다.
본 명세서에서 사용된 용어, 항체의 "항원-결합 부분" (또는 간단하게 "항체 부분" 또는 "항체 단편")은 항원 (예를 들어, hDll4)에 특이적으로 결합하는 능력을 보유하는 항체의 하나 이상의 단편을 나타낸다. 항체의 항원-결합 기능은 전체-길이 항체의 단편에 의해서 수행될 수 있는 것으로 나타났다. 용어 항체의 "항원-결합 부분"에 포함된 결합 단편의 예로는 (i) VL, VH, CL 및 CH1 도메인으로 구성된 일가 단편인 Fab 단편; (ii) 경첩 영역 (hinge region)에서 디설파이드 브릿지에 의해서 연결된 두 개의 Fab 단편을 포함하는 2가 단편인 F(ab')2 단편; (iii) VH 및 CH1 도메인으로 구성된 Fd 단편; (iv) 항체의 단일 팔 (arm)의 VL 및 VH 영역으로 구성된 Fv 단편; (v) VH 영역으로 구성된 dAb 단편 (Ward et al. (1989) Nature 241:544-546); 및 (vi) 분리된 CDR이 포함된다. 또한, Fv 단편의 두 개의 도메인인 VL 및 VH는 별도의 유전자에 의해서 암호화되지만, 이들은 재조합 방법을 사용하여, 이들을 VL 및 VH 부분이 짝을 이루어서 일가 분자를 형성한 단일 단백질 쇄로 만들 수 있는 합성 링커에 의해서 결합될 수 있다 [단일쇄 Fv (scFv)로 공지됨; 참조: 예를 들어, Bird et al. (1988) Science 242:423-426; 및 Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883]. 이러한 단일쇄 항체도 또한, 용어 항체의 "항원-결합 부분"에 포함시키고자 한다. 디아바디 (diabody)와 같은 단일쇄 항체의 다른 형태로 또한 포함된다. 디아바디는 VH 및 VL 영역이 단일 폴리펩타이드 쇄 상에서, 그러나 너무 짧아서 동일한 쇄 상의 두 개의 도메인 사이에서 짝을 이루도록 하지 못하는 링커를 사용하여 발현됨으로써 도메인들이 강제적으로 또 다른 쇄의 상보적 영역과 짝을 이루도록 하여 두 개의 항원 결합 부위를 발생시키는 2가의 이중 특이성 (bispecific) 항체이다 (참조: 예를 들어, Holliger et al. (1993) Proc. Natl. Acad Sci. USA 90:6444-6448; Poljak et al. (1994) Structure 2:1121-1123).
또한, 항체 또는 이의 항원-결합 부분은 하나 이상의 다른 단백질 또는 펩타이드와 항체 또는 항체 부분과의 공유적 또는 비공유적 회합에 의해서 형성된 더 큰 면역부착 (immunoadhesion) 분자의 일부분일 수도 있다. 이러한 면역부착 분자의 예는 4량체 scFv 분자를 제조하기 위한 스트렙타비딘 코어 영역의 사용 (Kipriyanov et al. (1995) Human Antibodies and Hybridomas 6:93-101), 및 2가의 비오티닐화된 scFv 분자를 제조하기 위한 시스테인 잔기, 마커 (marker) 펩타이드 및 C-말단 폴리히스티딘 태그 (tag)의 사용 (Kipriyanov et al. (1994) Mol. Immunol. 31:1047-1058)을 포함한다. Fab 및 F(ab')2 단편과 같은 항체 부분은 전체 항체로부터, 각각 전체 항체의 파파인 또는 펩신 분해와 같은 통상적인 기술을 사용하여 제조할 수 있다. 또한, 항체, 항체 부분 및 면역부착 분자는 본 명세서에 기술된 바와 같은 표준 재조합 DNA 기술을 사용하여 수득할 수 있다.
본 명세서에서 사용된 용어 "사람 항체"는 사람 배선 (germline) 면역글로불린 서열로부터 유도된 가변 및 불변 영역을 갖는 항체를 포함하고자 하는 것이다. 본 발명의 사람 항체는 예를 들어, CDR, 특히 CDR3에서 사람 배선 면역글로불린 서열에 의해 암호화되지 않은 아미노산 잔기 (예를 들어, 시험관내에서의 랜덤 또는 부위-특이적 돌연변이유발에 의해서, 또는 생체내에서의 체세포 돌연변이에 의해서 도입된 돌연변이)를 포함할 수 있다. 그러나, 본 명세서에서 사용된 용어 "사람 항체"는 마우스와 같은 또 다른 포유동물 종의 배선으로부터 유도된 CDR 서열이 사람 골격구조 서열 상에 이식된 항체는 포함하지 않는다.
본 명세서에서 사용된 용어 "재조합 사람 항체"는 숙주 세포 내에 형질감염된 재조합 발현 벡터를 사용하여 발현된 항체 (이하에 더 기술됨), 재조합, 조합적 사람 항체 라이브러리로부터 분리된 항체 (이하에 더 기술됨), 사람 면역글로불린 유전자에 대해 유전자 이식된 동물 (예를 들어, 마우스)로부터 분리된 항체 (참조: 예를 들어, Taylor et al. (1992) Nucl. Acids Res. 20:6287-6295), 또는 다른 DNA 서열에 대한 사람 면역글로불린 유전자 서열의 스플라이싱 (splicing)을 수반하는 다른 수단에 의해서 제조, 발현, 발생 또는 분리된 항체와 같이 재조합 수단에 의해서 제조, 발현, 발생 또는 분리된 모든 사람 항체를 포함하고자 하는 것이다. 이러한 재조합 사람 항체는 사람 배선 면역글로불린 서열로부터 유도된 가변 및 불변 영역을 갖는다. 그러나, 특정 구체예에서, 이러한 재조합 사람 항체는 시험관내 돌연변이유발 (또는, 사람 Ig 서열에 대한 유전자이식 동물이 사용되는 경우에는, 생체내 체세포 돌연변이유발)에 적용되며, 따라서 재조합 항체의 VH 및 VL 부분의 아미노산 서열은 사람 배선 VH 및 VL 서열로부터 유도되고 이에 관련되지만, 생체내의 사람 항체 배선 레퍼토리 내에 자연적으로 존재하지 않을 수 있는 서열이다.
본 명세서에서 사용된 "재조합 사람 항체"는 상이한 항원 특이성을 갖는 다른 항체를 실질적으로 갖지 않는 항체를 나타내는 것이다 (예를 들어, hDll4에 특이적으로 결합하는 분리된 항체는 hDll4 이외의 다른 항원에 특이적으로 결합하는 항체를 실질적으로 갖지 않는다). 그러나, hDll4에 특이적으로 결합하는 분리된 항체는 다른 종으로부터 유래한 hDll4 분자와 같은 다른 항원에 대해서 교차-반응성을 가질 수 있다. 더구나, 분리된 항체는 다른 세포성 물질 및/또는 화학물질을 실질적으로 갖지 않을 수 있다.
본 명세서에서 사용된 용어 "표면 플라즈몬 공명"은 예를 들어, 비아코어 (BIACORE™) 시스템 (Pharmacia Biosensor AB, Uppsala, Sweden and Piscataway, N.J.)을 사용하여 바이오센서 매트릭스 내에서 단백질 농도의 변화를 검출함으로써 실시간 생물특이적 (biospecific) 상호작용을 분석할 수 있도록 하는 광학적 현상을 의미한다.
본 명세서에서 사용된 용어 "KD"는 특정의 항체-항원 상호작용의 해리상수를 나타내는 것이다.
용어 "에피토프"는 면역글로불린 또는 T-세포 수용체에 대해 특이적으로 결합할 수 있는 모든 결정인자 (determinant), 바람직하게는 폴리펩타이드 결정인자를 포함한다. 특정의 구체예에서, 에피토프 결정인자는 아미노산과 같은 분자의 화학적 활성 표면 그룹, 당 측쇄, 포스포릴 그룹, 또는 설포닐 그룹을 포함하며, 특정의 구체예에서는 특이적인 삼차원 구조적 특징 및/또는 특이적인 전하 특징을 가질 수 있다. 에피토프는 항체에 의해서 결합되는 항원의 영역이다. 특정의 구체예에서, 항체는 단백질 및/또는 거대분자의 복잡한 혼합물 내에서 이의 표적 항원을 선택적으로 인식하는 경우에 항원에 특이적으로 결합한다고 말한다. 바람직한 구체예에서, 항체는 평형 해리상수가 10-8 M 이하인 경우, 더욱 바람직하게는 평형 해리상수가 10-9 M 이하인 경우, 가장 바람직하게는 해리상수가 10-10 M 이하인 경우에 항원에 특이적으로 결합한다고 말한다.
단백질 또는 폴리펩타이드는 샘플의 적어도 약 60 내지 75%가 폴리펩타이드의 단일 종을 나타내는 경우에 "실질적으로 순수한", "실질적으로 균질한" 또는 "실질적으로 정제된" 것이다. 폴리펩타이드 또는 단백질은 단량체이거나 다량체일 수 있다. 실질적으로 순수한 폴리펩타이드 또는 단백질은 일반적으로 단백질 샘플의 약 50%, 60, 70%, 80% 또는 90% W/W, 더욱 통상적으로는 약 95%를 구성할 수 있으며, 바람직하게는 99% 이상 순수할 수 있다. 단백질 순도 또는 균일성은 단백질 샘플의 폴리아크릴아미드 겔 전기영동과 같은 본 기술분야에서 잘 알려진 다수의 수단에 이어서, 본 기술분야에서 잘 알려진 염료로 겔을 염색하여 단일 폴리펩타이드 밴드를 가시화시킴으로써 표시될 수 있다. 특정의 목적을 위해서, 더 고도의 분해능은 HPLC 또는 정제를 위해서 본 기술분야에서 잘 알려진 다른 수단을 사용함으로써 제공될 수 있다.
본 명세서에서 사용된 용어 "폴리펩타이드 유사체 또는 변이체"는 아미노산 서열의 일부분과 실질적인 동일성을 갖는 적어도 25개 아미노산의 절편으로 이루어지며, 다음의 특성 중의 적어도 하나를 갖는 폴리펩타이드를 나타낸다: (1) 적합한 결합조건 하에서 hDll4에 대한 특이적 결합, 또는 (2) 노치 수용체에 대한 Dll4 결합을 차단하는 능력. 일반적으로, 폴리펩타이드 유사체 또는 변이체는 천연적으로-존재하는 서열에 관해서 보존적 아미노산 치환 (또는 삽입 또는 결실)을 포함한다. 유사체는 일반적으로 적어도 20개 아미노산 길이, 바람직하게는 적어도 50, 60, 70, 80, 90, 100, 150 또는 200개 아미노산 길이 또는 그 이상이며, 흔히는 전체-길이의 천연적으로-존재하는 폴리펩타이드만큼 길 수 있다.
바람직한 아미노산 치환은 (1) 단백질 분해에 대한 민감성을 감소시키고, (2) 산화반응에 대한 민감성을 감소시키며, (3) 단백질 복합체를 형성하기 위한 결합 친화도를 변화시키고, (4) 결합 친화도를 변화시키며, (4) 이러한 유사체의 다른 물리화학적 또는 기능적 특정을 부여하거나 변형시키는 것이다. 유사체는 천연적으로-존재하는 펩타이드 서열 이외의 다른 서열의 다양한 돌연변이를 포함할 수 있다. 예를 들어, 단일 또는 다수의 아미노산 치환 (바람직하게는 보존적 아미노산 치환)은 천연적으로-존재하는 서열에서 (바람직하게는 분자간 접촉을 형성하는 영역(들) 외부의 폴리펩타이드 부분에서) 이루어질 수 있다. 보존적 아미노산 치환은 모 서열의 구조적 특징을 실질적으로 변화시키지 않아야 한다 (예를 들어, 아미노산의 치환은 모 서열에서 나타나는 나선 (helix)을 파괴하거나, 모 서열을 특정화하는 다른 유형의 이차 구조를 붕괴시키지 않아야 한다). 본 기술분야에서 인지된 폴리펩타이드 이차 및 삼차 구조의 예는 문헌 [Proteins, Structures and Molecular Principles (Creighton 1984 W. H. Freeman and Company, New York); Introduction to Protein Structure (Branden & Tooze, eds., 1991, Garland Publishing, NY); 및 Thornton et al. 1991 Nature 354:105]에 기술되어 있다.
비-펩타이드 유사체는 약제학적 산업에서 주형 (template) 펩타이드의 특성과 유사한 특성을 갖는 약물로서 통상적으로 사용된다. 이러한 유형의 비-펩타이드 화합물은 "펩타이드 모방체" 또는 "펩티도미메틱스 (peptidomimetics)"라 불린다 [참조: 예를 들어, Fauchere (1986) J. Adv. Drug Res. 15:29; 및 Evans et al. (1987) J. Med. Chem. 30:1229]. 동일한 유형의 D-아미노산에 의한 공통 서열 (consensus sequence)의 하나 이상의 아미노산의 체계적 치환 (예를 들어, L-리신 대신에 D-리신)을 사용하여 더 안정한 펩타이드를 생성시킬 수도 있다. 또한, 공통 서열 또는 실질적으로 동일한 공통 서열 변이를 포함하는 속박된 (constrained) 펩타이드는 본 기술분야에서 공지된 방법 (Rizo et al. (1992) Ann. Rev. Biochem. 61:387)에 의해서, 예를 들어, 펩타이드를 폐환시키는 분자내 디설파이드 브릿지를 형성할 수 있는 내부 시스테인 잔기를 첨가함으로써 생성될 수 있다.
핵산 서열의 문맥에서 용어 "서열 동일성 퍼센트"는 최대로 상응하도록 정렬하는 경우에 동일한 두 개의 서열 내의 잔기를 나타내는 것이다. 서열 동일성 비교의 길이는 적어도 약 9개 또는 그 이상의 뉴클레오타이드, 통상적으로는 적어도 약 18개의 뉴클레오타이드, 더욱 통상적으로는 적어도 약 24개의 뉴클레오타이드, 일반적으로 적어도 약 28개의 뉴클레오타이드, 더욱 일반적으로 적어도 약 32개의 뉴클레오타이드, 바람직하게는 적어도 약 36, 48개 또는 그 이상의 뉴클레오타이드의 범위에 걸칠 수 있다. 여기에는 뉴클레오타이드 서열 동일성을 측정하기 위해서 사용될 수 있는 본 기술분야에서 공지된 다수의 상이한 알고리즘이 있다. 예를 들어, 폴리뉴클레오타이드 서열은 예를 들어, 프로그램 FASTA2 및 FASTA3을 포함하며, 의문(query) 서열과 탐색(search) 서열 사이에서 최적 중복 부분의 정렬 및 서열 동일성 퍼센트를 제공하는, 위스콘신 패키지 버전 10.0 (Wisconsin Package Version 10.0, Genetics Computer Group (GCG), Madison, Wis.)의 프로그램인 FASTA, FASTA, Gap 또는 Bestfit를 사용하여 비교할 수 있다 (Pearson (1990) Methods Enzymol. 183:63-98; 및 (2000) Methods Mol. Biol. 132:185-219). 다른 식으로 명시되지 않는 한, 특정한 프로그램 또는 알고리즘을 위한 디폴트 (default) 파라메터가 사용될 수 있다. 예를 들어, 핵산 서열들 사이의 서열 동일성 퍼센트는 이의 디폴트 파라메터 (스코어링 매트릭스 (scoring matrix)를 위한 워드 (word) 크기 6 및 NOPAM 인자)를 갖는 FASTA를 사용하거나, GCG 버전 6.1에서 제공된 것과 같은 이의 디폴트 파라메터를 갖는 Gap을 사용하여 측정될 수 있다.
핵산 서열에 대한 언급은 다른 식으로 명시되지 않는 한, 이의 상보체 (complement)를 포함한다. 따라서, 특정한 서열을 갖는 핵산 분자에 대한 언급은 이의 상보체 서열을 갖는 이의 상보적 스트랜드를 포함하는 것으로 이해되어야 한다. 일반적으로, 본 기술분야에서 용어 "서열 동일성 퍼센트", "서열 유사성 퍼센트" 및 "서열 상동성 퍼센트"는 상호 교환하여 사용된다. 본 출원에서, 이들 용어는 핵산 서열에 관해서 동일한 의미를 갖는다.
핵산 또는 이의 단편을 언급하는 경우에, 용어 "실질적인 유사성" 또는 "실질적인 서열 유사성"은 적절한 뉴클레오타이드 삽입 또는 결실을 가지고 다른 핵산 (또는 이의 상보적 스트랜드)와 함께 최적으로 정렬되는 경우에, 상기 거론한 것으로서 FASTA, BLAST 또는 Gap과 같은 서열 동일성의 잘 알려진 어떤 알고리즘에 의해서나 측정한 바에 의하면 뉴클레오타이드 염기의 적어도 약 90%, 바람직하게는 적어도 약 95%, 더욱 바람직하게는 적어도 약 96%, 97%, 98% 또는 99%에서 뉴클레오타이드 서열 동일성이 있는 것을 시사한다.
폴리펩타이드에 대해서 적용되는 용어 "실질적인 동일성" 또는 "실질적으로 동일한"은 예를 들어, 디폴트 갭 (default gap) 가중치를 사용하는 프로그램 GAP 또는 BESTFIT에 의해서 최적으로 정렬되는 경우에, 두 개의 펩타이드 서열이 적어도 80% 서열 동일성, 바람직하게는 적어도 90% 또는 95% 서열 동일성, 더 더욱 바람직하게는 적어도 98% 또는 99% 서열 동일성을 공유하는 것을 의미하다. 바람직하게는, 동일하지 않은 잔기 위치는 보존적 아미노산 치환에 의해서 상이하다. "보존적 아미노산 치환"은 아미노산 잔기가 유사한 화학적 특성 (예를 들어, 전하 또는 소수성)을 갖는 측쇄 (R 그룹)를 갖는 또 다른 아미노산 잔기에 의해서 치환된 것이다. 일반적으로, 보존적 아미노산 치환은 단백질의 기능적 특성을 실질적으로 변화시키지 않을 것이다. 2개 이상의 아미노산 서열이 보존적 치환에 의해서 서로 상이한 경우에, 서열 동일성 퍼센트 또는 유사성의 정도는 치환의 보존적 성질을 교정하여 상향 조정될 수 있다. 이러한 조정을 이루기 위한 방법은 본 기술분야에서 숙련된 전문가에게 잘 알려져 있다 (참조: 예를 들어, Pearson (1994) Methods Mol. Biol. 24: 307-331). 유사한 화학적 특성을 갖는 측쇄를 갖는 아미노산의 그룹의 예로는 (1) 지방족 측쇄: 글리신, 알라닌, 발린, 로이신 및 이소로이신; (2) 지방족-하이드록실 측쇄: 세린 및 트레오닌; (3) 아미드-함유 측쇄: 아스파라긴 및 글루타민; (4) 방향족 측쇄: 페닐알라닌, 타이로신 및 트리프토판; (5) 염기성 측쇄: 리신, 아르기닌 및 히스티딘; 및 (6) 황-함유 측쇄인 시스테인 및 메티오닌이 포함된다. 바람직한 보존적 아미노산 치환 그룹은 발린-로이신-이소로이신, 페닐알라닌-타이로신, 리신-아르기닌, 알라닌-발린, 글루타메이트-아스파르테이트 및 아스파라긴-글루타민이다. 대신으로, 보존적 치환은 문헌 (Gonnet et al. (1992) Science 256: 1443 45)에 기술된 PAM250 로그-우도 (log-likelihood) 매트릭스에서 양의 값을 갖는 어떤 변화라도 된다. "중등도의 보존적" 치환은 PAM250 로그-우도 매트릭스에서 비음 (nonnegative)의 값을 갖는 어떤 변화라도 된다.
서열 동일성으로도 또한 불리는 폴리펩타이드에 대한 서열 유사성은 일반적으로, 서열 분석 소프트웨어를 사용하여 측정된다. 단백질 분석 소프트웨어는 보존적 아미노산 치환을 포함한 다양한 치환, 결실 및 그 밖의 다른 변형에 대해서 지정된 유사성의 척도를 사용하여 유사한 서열을 대응시킨다. 예를 들어, GCG는 상이한 종의 유기체로부터의 상동성 폴리펩타이드와 같은 밀접하게 연관된 폴리펩타이드 사이, 또는 야생형 단백질과 이의 뮤테인 사이의 서열 상동성 또는 서열 동일성을 측정하기 위한 디폴트 파라메터와 함께 사용될 수 있는 "gap" 및 "Bestfit"과 같은 프로그램을 함유한다 (참조: 예를 들어, GCG Version 6.1). 폴리펩타이드 서열은 또한, 디폴트 또는 추천된 파라메터, GCG 버전 6.1의 프로그램을 이용하는 FASTA를 사용하여 비교될 수도 있다. FASTA (예를 들어, FASTA2 및 FASTA3)는 의문의 서열과 탐색 서열 사이의 최대 중복이 있는 부분의 정렬 및 서열 동일성 퍼센트를 제공한다 (Pearson (2000) supra). 발명한 서열을 다양한 유기체로부터의 다수의 서열을 함유하는 데이터베이스와 비교하는 경우에 바람직한 또 다른 알고리즘은 디폴트 파라메터를 사용하는 컴퓨터 프로그램 BLAST, 특히 blastp 또는 tblastn이다 (참조: 예를 들어, Altschul et al. (1990) J. Mol. Biol. 215:403-410 및 Altschul et al. (1997) Nucleic Acids Res. 25:3389-402).
상동성을 위해서 비교되는 폴리펩타이드 서열의 길이는 일반적으로, 적어도 약 16개의 아미노산 잔기, 통상적으로는 적어도 약 20개의 잔기, 더욱 통상적으로는 적어도 약 24개의 잔기, 전형적으로는 적어도 약 28개의 잔기, 바람직하게는 약 35개 이상의 잔기일 수 있다. 다수의 다양한 유기체로부터의 서열을 함유하는 데이터베이스를 탐색하는 경우에, 이것은 아미노산 서열을 비교하는데 바람직하다.
사람 항체의 제조
사람 항체를 생성시키는 방법은 예를 들어, 벨록이뮨 (VELOCIMMUNE™; Regeneron Pharmaceuticals), 제노마우스 (XENOMOUSE™) 기술 (Abgenix), "미니로커스(minilocus)" 방법, 및 파지 디스플레이 (phage display)를 포함한다. 벨록이뮨 (VELOCIMMUNE™) 기술 (US 6,596,541)은 선택 항원에 대한 고특이성의 완전 사람 항체를 생성시키는 방법을 포함한다. 이 기술은 마우스가 항원성 자극에 대한 반응으로 사람 가변 영역 및 마우스 불변 영역을 포함하는 항체를 생산하도록 내인성 마우스 불변 영역의 유전자좌에 작동가능하게 연결된 사람 중쇄 및 경쇄 가변 영역을 포함하는 게놈을 갖는 유전자이식 마우스를 생성시키는 것을 수반한다. 항체의 중쇄 및 경쇄의 가변 영역을 암호화하는 DNA를 분리시키고, 사람 중쇄 및 경쇄 불변 영역을 암호화하는 DNA에 작동가능하게 연결시킨다. 그 후, DNA를 완전 사람 항체를 발현할 수 있는 세포에서 발현시킨다. 특정한 구체예에서, 세포는 CHO 세포이다.
제노마우스 (XENOMOUSE™) 기술 (Green et al. (1994) Nature Genetics 7:13-21)은 중쇄 및 카파 (kappa) 경쇄 유전자좌 둘 다로부터 유래한 사람 가변 및 불변 영역 둘 다를 갖는 마우스를 생성시킨다. 대용 방법에서, 다른 경우는 외인성 Ig 유전자좌가 Ig 유전자좌로부터의 개개 유전자의 삽입을 통해서 모방된 '미니로커스' 방법을 이용하였다 (참조: 예를 들어, U.S. 5,545,807). 가변 영역을 암호화하는 DNA는 사람 중쇄 및 경쇄 불변 영역을 암호화하는 DNA에 작동가능하게 연결되거나 연결됨이 없이 분리될 수 있다.
사람 공여체로부터의 분리를 포함하여, 사람 항체를 생성시키는 그 밖의 다른 방법은 공지되어 있다 (참조: 예를 들어, U.S. 6,787,637).
항체는 보체의 고정화 및 CDC에 대한 참여를 통해서 세포를 사멸시키는 것보다는 리간드-수용체 상호작용을 차단하거나 수용체 성분 상호작용을 억제하는데 치료학적으로 유용할 수 있다. 항체의 불변 영역은 보체를 고정하고, CDC 또는 항체-의존적 세포독성 (ADCC)을 통한 직접적 세포 사멸에 참여하는 항체의 능력에 중요하다. 따라서, 항체의 이소타입 (isotype)은 항체가 보체를 고정시키는데 대해 바람직한지 여부를 기준으로 하여 선택될 수 있다.
사람 면역글로불린은 경첩 이질성 (hinge heterogeneity)과 연관된 두 가지 형태로 존재할 수 있다. 한 가지 형태에서, 면역글로불린 분자는 약 150-160 kDa의 안정한 4쇄 구조를 포함하는데, 여기에서 이량체는 쇄간 (interchain) 중쇄 디설파이드 결합에 의해서 함께 유지된다. 두 번째 형태에서, 이량체는 중쇄간 디설파이드 결합을 통해서 연결되지 않고, 단일 경쇄 및 중쇄로 구성된 약 75-80 kDa의 분자가 형성된다. 이들 형태는 친화도 정제 후에 조차도 분리시키기 어렵다.
다양한, 온전한 IgG 이소타입에서 두 번째 형태의 출현 빈도는 항체의 경첩 영역 이소타입과 연관된 구조적 차이에 기인하지만, 이것으로 제한되지는 않는다. 실제로, 사람 IgG4 경첩의 경첩 영역에서 단일 아미노산 치환은 두 번째 형태의 출현을 사람 IgG1 경첩을 사용하여 일반적으로 관찰되는 수준까지 현저하게 감소시킬 수 있다 (Angal et al. (1993) Molecular Immunology 30: 105). 본 발명은 예를 들어, 생산시에 수율을 개선시키거나 효과기 기능을 변조시키는데 바람직할 수 있는 경첩, CH2 또는 CH3 부분에서의 하나 이상의 돌연변이를 갖는 항체를 포함한다.
본 발명의 항체는 바람직하게는, 벨록이뮨 (VELOCIMMUNE™)기술을 사용하여 제조된다. 내인성 면역글로불린 중쇄 및 경쇄 가변 영역이 상응하는 사람 가변 영역으로 치환된 유전자이식 마우스를 관심이 있는 항원으로 공격하고, 항체를 발현한 마우스로부터 림프세포 (예를 들어, B-세포)를 회수한다. 림프세포를 골수-유형 세포주와 융합시켜 불멸하는 하이브리도마 세포주를 제조할 수 있으며, 이러한 하이브리도마 세포주를 스크리닝하고, 관심이 있는 항원에 대해 특이적인 항체를 생산하는 하이브리도마 세포주를 확인하여 선택한다. 중쇄 및 경쇄의 가변 영역을 암호화하는 DNA를 분리시키고, 중쇄 및 경쇄의 바람직한 이소타입 불변 영역에 연결시킬 수 있다. 이러한 항체 단백질은 CHO 세포와 같은 세포에서 생산될 수 있다. 대신으로, 항원-특이적 키메릭 항체를 암호화하는 DNA를 항원-특이적 림프구로부터 직접 분리시킬 수도 있다. 다양한 구체예에서, 유전자이식 마우스는 12개의 기능적 사람 가변 중쇄 유전자 및 11개의 기능적 사람 가변 카파 경쇄 유전자; 25 내지 30개의 사람 가변 중쇄 유전자 및 18 내지 20개의 사람 가변 카파 경쇄 유전자; 43 내지 48개의 사람 가변 중쇄 유전자 및 20 내지 22개의 사람 가변 카파 경쇄 유전자; 또는 약 80개의 사람 가변 중쇄 유전자 및 약 40개의 사람 가변 카파 경쇄 유전자를 포함한다.
일반적으로, 본 발명의 항체는 고체상 위에 고정화되거나 용액 상태인 항원에 대한 결합에 의해 측정되는 경우에, 일반적으로 약 10-9 내지 약 10-11 M의 KD를 갖는 매우 높은 친화도를 갖는다. 마우스 불변 영역을 원하는 사람 불변 영역으로 치환시켜 본 발명의 완전한 사람 항체, 예를 들어, 야생형 또는 변형된 IgG1 또는 IgG4 (예를 들어, 서열번호 950, 951, 또는 952)를 생성시킨다. 선택된 불변 영역은 특정한 용도에 따라 달라질 수 있지만, 고친화도 항원-결합 및 표적 특이성 특징은 가변 영역에 존재한다.
암, 감염성 질병, 자가면역, 면역결핍, 이식, 염증, 상해 및 퇴행성 상태는 면역 시스템을 변조시킴으로써 치료될 수 있다. 자가면역 또는 염증과 같이 면역 시스템의 부적절한 기능 또는 활성항진 (hyperactivity)에 기인한 질병의 경우는 면역세포 기능을 억제하거나 면역세포 수를 감소시킴으로써 개선될 수 있다. 이것은 T, B 또는 NK 세포, 호중구, 대식세포, 항원 제시 세포, 비만 세포 또는 그 밖의 다른 세포 유형과 같이 질병 과정에 결정적인 면역세포 집단에 대한 양성 신호 (positive signal)의 봉쇄 또는 음성 신호의 자극에 의해서 이루어질 수 있다. 과잉활성 (overactivity)은 또한, 아폽토시스의 자극, 항체 또는 항체-약물 접합체의 고갈과 함께 특이적 표면 수용체의 표적화, 또는 면역세포계 또는 특이적 세포 유형의 분화의 봉쇄 또는 변화에 의한 다양한 면역세포 집단의 제거를 통해서 억제될 수도 있다. 비효율적이거나 감소된 면역 기능은 암, 감염성 질병 및 그 밖의 다른 면역결핍과 같은 장애를 야기하거나 악화시킬 수 있다. 면역 시스템의 활성저하는 교차결합성 또는 아고니스트 항체에 의한 양성 신호의 자극 또는 음성 신호의 봉쇄에 의해 면역세포를 활성화시킴으로써 개선될 수 있다. 면역세포 집단은 면역세포계의 일부 또는 전부의 발현의 자극, 아폽토시스의 방지, 또는 억제성 신호의 제거에 의해서 증가될 수 있다. 특정의 적용 시에, 본 발명의 항체는 예를 들어, 암, 면역결핍, 이식 거부반응 또는 염증과 같은 상태 또는 질병의 치료, 억제 또는 개선에 유용하다.
에피토프
지도작성 (
mapping
) 및 관련된 기술
특정한 에피토프에 결합하는 항체 (예를 들어, 이의 고친화도 수용체에 대한 IgE의 결합을 차단하는 것)에 대해서 스크리닝하기 위해서, 문헌 [Harlow and Lane (1990) supra]에 기술된 것과 같은 일상적인 교차-차단시험 (cross-blocking assay)이 수행될 수 있다. 다른 방법으로는 알라닌 스캐닝 (scanning) 돌연변이체, 펩타이드 블럿 (blot) (Reineke (2004) Methods Mol Biol 248:443-63), 또는 펩타이드 절단 분석이 포함된다. 또한, 에피토프 절제, 에피토프 추출 및 항원의 화학적 변형과 같은 방법이 이용될 수 있다 (Tomer (2000) Protein Science 9:487-496).
용어 "에피토프"는 B 및/또는 T 세포가 반응하는 항원 상의 부위를 의미한다. B-세포 에피토프는 연속적 아미노산 또는 단백질의 삼차 접힘 (tertiary folding)에 의해서 병렬된 비연속적 아미노산 둘 다로부터 형성될 수 있다. 연속적 아미노산으로부터 형성된 에피토프는 일반적으로, 변성 용매에 대한 노출 시에 유지되는 반면에, 삼차 접힘에 의해서 형성된 에피토프는 일반적으로 변성 용매로 처리하면 상실된다. 에피토프는 일반적으로, 독특한 공간적 구조 내에 적어도 3개, 더욱 통상적으로는 적어도 5개 또는 8-10개의 아미노산을 포함한다.
항원 구조-기반 항체 프로파일링 (ASAP)으로 또한 알려져 있는 변형-보조된 프로파일링 (Modification-Assisted Profiling; MAP)은 화학적으로 또는 효소적으로 변형된 항원 표면에 대한 각각의 항체의 결합 프로필의 유사성에 따라 동일한 항원에 대해 유도된 다수의 모노클로날 항체 (mAb)를 분류하는 방법이다 (US 특허공개 제 2004/0101920 호). 각각의 카테고리는 또 다른 카테고리로 표현되는 에피토프와 명백히 상이하거나, 부분적으로 중복되는 독특한 에피토프를 나타낼 수 있다. 이 기술은 특정화가 유전적으로 전혀 다른 항체에 집중될 수 있도록 유전적으로 동일한 항체를 빨리 여과할 수 있도록 허용한다. 하이브리도마 스크리닝에 적용되는 경우에, MAP는 원하는 특징을 갖는 mAb를 생산하는 희귀한 하이브리도마 클론의 확인을 용이하게 할 수 있다. MAP를 사용하여 본 발명의 hDll4 항체를 상이한 에피토프에 결합하는 항체의 그룹으로 구분할 수 있다.
고정화된 항원의 구조를 변화시키는데 유용한 성분은 예를 들어, 단백분해성 효소와 같은 효소, 예를 들어, 트립신, 엔도프로테이나제 Glu-C, 엔도프로테이나제 Asp-N, 키모트립신 등이다. 고정화된 항원의 구조를 변화시키는데 유용한 성분은 또한, 석신이미딜 에스테르 및 이들의 유도체, 일급 아민-함유 화합물, 하이드라진 및 카보하이드라진, 유리 아미노산 등과 같은 화학제일 수도 있다.
항원 단백질은 바이오센서 칩 (biosensor chip) 표면 또는 폴리스티렌 비드 상에 고정화될 수 있다. 후자는 예를 들어, 멀티플렉스 루미넥스 검출시험 (multiplex LUMINEX™ detection assay; Luminex Corp., Austin, TX)과 같은 시험방법에 의해서 처리될 수 있다. 100개까지의 다양한 유형의 비드를 사용하여 멀티플렉스 분석을 통제하는 루미넥스 (LUMINEX™)의 능력 때문에, 루미넥스는 다양한 변형에 의해 거의 무제한적인 항원 표면을 제공함으로써 바이오센서 시험방법에 비해 항체 에피토프 프로파일링에 있어서의 개선된 해결책을 제공한다.
치료학적 투여 및 제형
본 발명에 따르는 치료제의 투여는 개선된 수송, 송달, 내성 등을 제공하기 위해서 제제에 혼입되는 적합한 담체, 부형제 및 그 밖의 다른 성분과 함께 이루어질 수 있다. 다수의 적절한 제제는 모든 약화학자에게 공지된 규격서 (formulary) [Remington's Pharmaceutical Sciences (15th ed, Mack Publishing Company, Easton, PA)]에서 볼 수 있다. 이들 제제에는 예를 들어, 분말, 페이스트, 연고, 젤리, 왁스, 오일, 지질, 지질 (양이온성 또는 음이온성) 함유 소포체 (vesicle) (예를 들어, LIPOFECTIN™, DNA 접합체, 무수 흡수 페이스트, 수중유 및 유중수 에멀전, 에멀전 카보왁스 (다양한 분자량의 폴리에틸렌 글리콜), 반고체 겔, 및 카보왁스를 함유하는 반고체 혼합물이 포함된다. 전술한 혼합물 중의 어떤 것이라도 본 발명에 따르는 처리 및 치료에 적절할 수 있지만, 단 제제 내의 활성성분은 제제화에 의해서 불활성화되지 않아야 하고, 제제는 생리적으로 상용성이고, 투여의 경로에 대해 견딜 수 있어야 한다. 약화학자에게 잘 알려진 부형제 및 담체와 관련된 추가의 정보에 대해서는 문헌 (Powell et al. "Compendium of excipients for parenteral formulations" PDA (1998) J Pharm Sci Technol. 52:238-311) 및 이 문헌에서 인용된 것을 또한 참고로 한다.
실시예
1. 사람
Dll4
에 대한 사람 항체의 생성.
마우스는 본 기술분야에서 공지된 어떤 방법에 의해서나 면역시킬 수 있다 (참조: 예를 들어, Harlow and Lane supra). 한가지 구체예에서는, hDll4 항원을 면역반응을 자극하는 보조제와 함께, 사람 Ig 중쇄 가변 영역 및 카파 경쇄 가변 영역을 암호화하는 DNA 좌를 포함하는 벨록이뮨 (VELOCIMMUNE™) 마우스에게 직접 투여한다. 이러한 보조제에는 완전 및 불완전 프로인트 보조제 (Freund's adjuvant), MPL+TDM 보조제 시스템 (Sigma), 또는 RIBI (뮤라밀 디펩타이드)가 포함된다 (참조: O'Hagan 2000 Vaccine Adjuvant, by Human Press, Totawa, NJ). 항체 면역반응은 표준 항원 특이적 면역검정방법에 의해서 모니터된다. 원하는 면역반응을 달성하면, 항체-발현 B 세포를 수거하고, 그들의 생존도를 보존하기 위해서 마우스 골수종 세포와 융합시켜 하이브리도마 세포주를 형성시켰다. 이러한 하이브리도마 세포주를 이하에 기술하는 바와 같은 시험방법을 사용하여 스크리닝하고 선택하여 항원-특이적 항체를 생산하는 세포주를 확인한다.
대신으로, 항원-특이적 하이브리도마 세포는 유동 세포분석법 (flow cytometry)에 의해서 분리될 수 있다. 간략하여, 골수종 세포와 융합시킨 후에 모아진 하이브리도마 세포를 HAT 배지 내에서 10일 동안 성장시켰다. 그 후, 세포를 수거하고, 2 mg/ml의 비오틴-표지된 Dll4로 1시간 동안 염색하고, 이어서 피코에리트린-스트렙타비딘을 첨가하였다. 형광-표지된 세포를 유동 세포분석법에 의해서 분류하고 (하이브리도마 성장배지를 함유하는 96웰 플레이트 내에 웰 당 단일 세포), 8-10일 동안 배양하고, 조건화된 배지 (conditioned media)를 이하에 기술하는 바와 같은 기능적으로 바람직한 모노클로날 항체의 존재에 관하여 스크리닝하였다.
비장세포의 직접 분리에 의해서 생성된 항- hDll4 항체. 항원-특이적 항체는 또한, 미국 특허 공개 제 2007/0280945A1 호에 기술된 바와 같이, 골수종 세포에 융합시키지 않고 항원-면역화된 B 세포로부터 직접 분리될 수도 있다. 적합한 재조합 항체-발현 CHO 세포주는 분리된 적절한 재조합체로부터 확립되었다.
실시예
2. 항원 결합 친화도 측정.
상술한 바와 같이 선택된 항체에 대한 항원 결합에 관한 평형 해리상수 (KD 값)는 실시간 바이오센서 표면 플라즈몬 공명 시험 (BIACORE™ 2000)에서의 표면 속도론에 의해 결정되었다. 항체를 비아코어 칩 (BIACORE™ chip)에 대한 직접적인 화학적 커플링을 통해서 생성된 염소 항-마우스 IgG 폴리클로날 항체 표면 상에 포착시켜 포착된 (captured) 항체 표면을 형성시켰다. 다양한 농도의 단량체 hDll4 또는 이량체 hDll4-hFc를 포착된 항체 표면 상에 주입하고, 항원-항체 결합 및 해리를 실시간으로 모니터하였다. 속도론적 분석을 수행하여 KD, 해리속도 상 수, 및 항원/항체 복합체 해리의 반감기를 계산하였다 (표 1). 유사한 방법을 적용하여 사람 IgG 불변 도메인을 함유하도록 변형된 단일 B 세포-유도된 모노클로날 항체를 측정하였다. 항체를 비아코어 (BIACORE™) 칩 상에 고정화된 염소 항-hFc 폴리클로날 항체 시약 (Jackson Immuno Research Lab)에 의해서 나타내고, 이량체 Dll4-mFc 또는 단량체 Dll4 단백질에 노출시켰다 (표 2).
항체-항원 결합 친화도는 또한, ELISA-기반 용액 경쟁시험을 사용하여 평가되었다. 간략하면, 96-웰 미세역가 플레이트 상에서 항체 (정제된 단백질 또는 조건화된 배지 중의 항체)를 항체의 일정한 농도에 따라 0 내지 10 ㎍/ml 범위의 항원 단백질 (단량체 또는 이량체)의 계열 희석액과 예비혼합시켰다. 항원과 항체를 2시간 항온처리한 후에, 유리 항체의 측정을 위해서 용액을 항원으로 미리 코팅된 미세역가 플레이트 (MAXISORB™ VWR, West Chester, PA)에 옮겼다. 플레이트를 4oC에서 밤새 PBS 용액 중의 1 ㎍/ml hDll4-hFc 단백질로 코팅하고, 비특이적 결합부위는 BSA로 2시간 동안 차단시켰다. 옮긴 다음에 1시간 항온처리한 후에, 플레이트를 세척하고, 플레이트-결합된 항체를 HRP-접합된 염소 항-마우스 IgG 폴리클로날 항체 시약 (Jackson Immuno Laboratory)으로 검출하고, 비색용 기질 (OPTEIATM; BD Biosciences Pharmingen, San Diego, CA)을 사용하여 발색시켰다. 효소반응을 1 M 인산에 의해서 중지시키고, 450 nm에서 흡광도를 기록하고, 데이터는 S-자형 용량-반응 모델 (sigmoidal dose-response model)을 사용하여 분석하였으며, IC50값을 보고하였다 (표 1).
실시예
3.
Dll4
및
노치
상호작용의 억제.
노치에 대한 Dll4 결합을 차단하는 항체의 능력은 ELISA-기반 면역검정방법에 의해서 평가하였다. 간략하면, 노치-hFc 재조합 단백질을 4℃에서 밤새 PBS 완충액 중의 96-웰 플레이트 상에 1 mg/ml로 코팅하고, 비특이적 결합부위는 BSA로 차단시켰다. 이 플레이트를 사용하여 항체 적정 샘플 용액으로부터 유리 비오틴-Dll4-hFc를 측정하였다. 항체 적정 샘플을 만들기 위해서, 25 pM의 비오틴-Dll4-hFc의 일정량을, 조 하이브리도마 조건 배지 내의 또는 정제된 항체 단백질로서, 계열 희석액 중의 0 내지 약 50 nM 범위의 다양한 양의 항체와 미리 혼합시키고, 이어서 실온에서 2시간 항온처리하여 항체-항원 결합이 평형에 도달하도록 하였다. 그 후, 평형화된 샘플 용액을 유리 비오틴-Dll4-hFc의 측정을 위해서 노치-hFc 코팅된 플레이트에 옮겼다. 1시간 결합시킨 후에, 플레이트를 세척하고, 결합된 비오틴-Dll4-hFc를 HRP 접합된 스트렙타비딘 (Poly HRP streptavidin, Pierce Endogen)을 사용하여 검출하고, TMB 기질 (BD Pharmigen)을 사용하여 발색시켰다. 데이터는 그래프패드 프리즘 (GraphPad Prism) 소프트웨어를 사용하여 분석하고, IC50 값은 플레이트-코팅된 노치-Fc에 결합된 비오틴-Dll4-hFc의 50% 감소를 달성하는데 필요한 항체의 양으로 결정되었다 (표 3) (*조건화된 배지).
노치에 대한 Dll4 결합을 차단하는, 선택된 정제된 항-hDll4 항체의 능력은 또한, 25 pM의 비오틴-Dll4-hFc를 30 pM의 비오틴-Dll4-hFc로 대체시키고, 항체-항원 항온처리 기간을 2시간에서 1시간으로 감소시킴으로써 변형된, 상술한 ELISA-기반 면역검정법에 의해서 평가되었다. 편의를 위해서, 항체 318518-01A10-D8은 "REGN281" (HCVR/LCVR 서열번호 429/437 및 hIgG1 서열번호 950)로 다시 이름을 붙였다. 시험한 유도된 항체에는 REGN421 (HCVR/LCVR 서열번호 901/903, hIgG1 서열번호 950); 및 REGN422 (변형된 hIgG4 서열번호 952와 함께 HCVR/LCVR 서열번호 901/903)가 포함되었다. 결과는 표 4에 나타내었다.
Dll4 매개된 세포 기능을 중화시키는 항체의 능력은 또한, Dll4 발현 사람 제대정맥 내피세포 (HUVEC)를 사용하여 시험관내에서 시험하였다. 유도된 항체에 의한 HUVEC 내에서의 노치 매개된 hHes1 및 EphB2 유전자 발현의 억제는 다음과 같이 모니터하였다: 낮은 계대 (low passage)의 HUVEC을 MCDB-131 배지 (Vec Technologies) 내에서 배양하였다. 분석하기 하루 전에, HUVEC 세포를 1 ml 총 배지 용적 중의 24-웰 플레이트 내에 2 x 105 세포/웰의 밀도로 접종하였다. 시험 항체 또는 그 밖의 다른 억제제를 개개 샘플 웰에 삼중으로 직접 첨가하고, 이어서 37℃에서 5시간 배양하였다. 배양기간의 종료 시에, 배지를 제거하고, 전체 RNA는 키아졸 (QIAZOL™) 및 알엔이지 (RNEASY™) 지질 조직 키트 (Qiagen)를 사용하여 분리하였다. mRNA 수준 정량화는 PCR 및 형광성 (fluorogenic) 5' 뉴클레아제 시험방법 (TAQMAN® assay, Appied Biosystems)을 사용함으로써 수행되었다. 각각의 샘플에 대해, cDNA는 1-2 mg의 전체 RNA로부터 합성되었다. 동등한 양의 출발 RNA로부터 생성된 cDNA (일반적으로 25 ng)를 아비 프리즘 (ABI PRISM™) 광학반응 플레이트 상에 삼중으로 로딩시켰다. 각각의 RNA 샘플에 대해서, 신호에 대한 어떤 잠재적 게놈 DNA의 기여라도 공제하도록 어떠한 역전사효소도 첨가하지 않은 "no RT" 대조군도 또한 적용하였다. 2x 매스터믹스 (Mastermix) (TAQMAN® 2x PCR Mastermix; ABI)를 1x의 최종 농도로 각각의 반응에 첨가하였다. 추가로, 관심이 있는 유전자에 대한 타크만 (TAQMAN®) 프로브 및 프라이머를 각각의 반응에 첨가하였다. 각각의 프라이머는 900 nM의 최종 농도로 사용하였으며, 프로브는 200 nM의 최종 농도로 첨가하였다. 사람 게놈 DNA가 표준물로 사용되었다. 시험은 ABI 7900HT 기구 상에서 표준 타크만 (TAQMAN®) 조건 하에 수행되었다. Hes1 및 EphrinB2의 수준을 측정하고, 내인성 대조 유전자 (사이클로필린)에 대해 표준화시켰다 (표 5). 프로브 및 프라이머: 사람 Hes1 프로브 (서열번호 387); Oligos: hHes1-869F (서열번호 388); hHes1-940R (서열번호 389), 사람 ephrinB2 프로브: hEphB2-773T (서열번호 390); Oligos: hEphB2-752F (서열번호 391) hEphB2-812R (서열번호 392); 사람 사이클로필린: 프로브: h사이클로필린-343T (서열번호 393); Oligos: h사이클로필린-323F (서열번호 394); h사이클로필린-389R (서열번호 395).
HUVEC 증식시험. 사람 제대정맥 내피세포 (HUVEC)의 Dll4 매개된 성장 억제를 차단하는 항체의 능력은 시험관내 세포 증식시험에서 시험하였다. 낮은 계대의 HUVEC 세포를 수득하고, MCDB-131 배지 (Vec Technologies) 중에서 배양하였다. 분석하기 하루 전에, 12-웰 조직 배양 플레이트를 4℃에서 밤새 PBS 중의 hDll4-hFc (0.2 ㎍/ml; 0.5 ml PBS/웰)로 코팅하였다. 플레이트를 PBS로 1회 세척하고, HUVEC 세포를 1.0 ml 총 배지 용적 중에 4x103 세포/웰의 밀도로 접종하였다. 세포를 첨가한 직후에, 항-hDll4 항체를 일정한 범위의 농도에 걸쳐서 0.5 ml 총 용적으로 첨가하여 억제곡선을 생성시켰다. 세포를 37℃에서 96시간 동안 성장시켰다. 세포 수는 CCK-8 시약 (Dojindo)을 사용하여 정량하였다. 모든 시험은 삼중으로 수행되었다. (표 6, NB, 차단 없음).
노치 -유도성 루시퍼라제 시험. 생물검정을 개발하여 구성적으로 사람 노치 1을 발현하며, 노치-반응성 프로모터 구동 루시퍼라제를 함유하는 조작된 HEK293 세포주 (ATCC)를 사용하여, 시험관내에서 Dll4-매개된 세포 기능을 중화시키는 선택된 정제된 항체의 능력을 측정하였다. 노치-유도성 루시퍼라제 활성의 억제는 다음과 같이 측정되었다: 시험하기 하루 전에, 불투명한 96웰 조직 배양 플레이트의 각각의 웰을 4℃에서 밤새 PBS 중의 1 nM 또는 1.5 nM hDll4-hFc 100 ㎕로 코팅하였다. 세포를 배지 중에서 코팅된 플레이트 상에 2 x104 세포/웰로 접종하였다. 세포 배지 내에서 2 nM로부터 출발한 계열 희석액 중의 정제된 항체 단백질을 37℃에서 24시간 동안 세포와 함께 항온처리하였다. 루시퍼라제 활성은 동등한 웰 용적의 스테디-글로 (STEADY-GLO®) 기질 (Promega)을 첨가함으로써 측정되었다 (표 7).
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4.
노치1
절단의 억제
노치 1 절단을 억제하는 선택된 항-hDll4 항체의 능력은 SDS-Page/웨스턴 블럿팅 (Western blotting)에 의해서 전체 절단된 노치1 단백질을 검사함으로써 시험하였다. 낮은 계대의 HUVEC 세포를 상술한 바와 같이 배양하였다. 분석하기 하루 전에, 6-웰 플레이트를 밤새 4℃에서 PBS 중의 hDll4-hFc로 코팅하였다 (0.2 ㎍/ml; 1.0 ml PBS/웰). 플레이트를 PBS로 1회 세척하고, HUVEC 세포를 2.0 ml 총 배지 용적 중에서 7.5 x105 세포/웰로 접종하였다. 세포 접종한 직후에, 항-hDll4 항체를 각각의 웰에 10 nM의 최종 농도로 첨가하였다. 세포를 37℃에서 24시간 동안 성장시킨 후에, 전체 세포 추출물을 제조하여 SDS-PAGE로 분석하였다. 절단된 노치1의 수준은 항-절단된 노치 1 (Val1744) 항체 (세포 신호전달) 및 표준 웨스턴 블럿팅 기술을 사용하여 측정하였다. 항-hDll4 항체는 플레이트 코팅된 hDll4-hFc에 의해서 유도된 노치1 절단을 완전히 차단할 수 있었다 (데이터는 나타내지 않음).
실시예
5.
ADCC
및
CDC
시험방법
두 개의 시험 항체 (REGN421, REGN422)에 의해서 유도된 항체-의존적 세포-매개된 세포독성 (ADCC)은 다양한 hDll4 발현 수준을 갖는 8개의 표적 세포주의 패널을 사용하여 평가하였다. 8개의 표적 세포주는 (1) HUVEC; (2) 24시간 동안 10 nM VEGF로 자극된 HUVEC; (3) Colo205; (4) eGFP 발현성인 조작된 C6 랫트 신경교종 세포; (5) hDll4 발현성인 조작된 C6 랫트 신경교종 세포; (6) eGFP 발현성인 조작된 HT1080 세포; (7) hDll4 발현성인 조작된 HT1080 세포; 및 (8) HT29였다. 사람 Dll4 또는 eGFP는 레트로바이러스 형질감염을 통해서 C6 세포 또는 HT1080 게놈 내에 통합시켰다. 간략하면, 각각의 표적 세포주로부터의 세포 (50 ㎕ 중의 10,000 세포/웰)를 우선, 동등한 용적의 계열 희석된 REGN421 또는 REGN422와 혼합시켜 0.169 pM 내지 10 nM 범위의 최종 항체 농도를 제공하고, 96-웰 플레이트 체제에서 10분 동안 실온에서 항온처리하였다 (대조군 = 항체가 없는 웰). 별도로, 사람 말초혈액 단핵세포 (PBMC, 효과기 세포)를 통상적인 피콜-하이파크 (Ficoll-Hypaque) 구배 원심분리 농축 절차에 따라 제조하였다. 약 300,000 PBMC를 항체와 표적세포의 각각의 혼합물에 첨가하여 약 30:1의 효과기 세포 대 표적세포의 최종 비를 제공하였다. 그 후, 96-웰 플레이트를 37℃, 5% CO2 하에서 4시간 동안 항온처리하고, 이어서 250 x g으로 원심분리시켰다. 상청액을 수거하고, 사이토톡스 (CYTOTOX) 96® 비-방사성 세포독성 시험 시스템 (Promega)을 사용하여 락테이트 데하이드로게나제 (LDH) 활성에 대해서 시험하였다. 결과는 표 8에 나타내었다. REGN421-유도된 용량 의존적 세포 용해는 단지, (면역침강/웨스턴 블럿 및 유동 세포분석법에 의해서 측정한 바에 의하면) 모든 세포주 중에서 최고의 hDll4 발현을 나타내는, hDll4 발현 C6 세포 (col. 5)에서만 관찰되었다. C6-hDll4 세포주에서 최대 세포 세포독성은 20% 내지 60%의 범위였다. REGN421-유도된 세포 용해는 나머지 7가지의 표적 세포주에서는 관찰되지 않았다. REGN422는 어떤 표적 세포주에서도 세포 용해를 유도하지 않았다.
REGN421에 의해서 유도된 보체-의존적 세포독성 (CDC)은 상술한 세포주의 동일 패널을 사용하여 평가되었다. 간략하면, 각각의 표적 세포주로부터의 세포 (50 ㎕ 중의 50,000 세포/웰)를 우선 동등한 용적의 계열 희석된 REGN421과 혼합시켜 0.169 pM 내지 10 nM 범위의 최종 항체 농도를 제공하고, 96-웰 플레이트 체제에서 10분 동안 실온에서 항온처리하였다. 보체 성분을 갖는 정상 사람 혈청 (Quidel Corp., San Diego, CA)을 각각의 웰에 첨가하여 5%의 최종 혈청 농도를 제공하였다. 그 후, 플레이트를 37℃, 5% CO2 하에서 2시간 동안 항온처리하고, 이어서 셀타이터-블루 (CELLTITER-BLUE®) 시약 (Promega)을 첨가하였다 (대조군 = 항체가 없는 웰 및 항체는 있지만 혈청은 없는 웰). 플레이트를 밤새 항온처리하고, 세포 생존 (CDC 수준)을 시험하였다. 양성 대조군으로서, 다우디 (Daudi) 세포를 리툭시마브(rituximab)로 처리하였다. REGN421은 시험한 어떤 표적 세포주에 대해서도 CDC를 나타내지 않았다 (데이터는 나타내지 않음).
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6.
에피토프
지도작성 및 특이성.
에피토프 결합 특이성을 측정하기 위해서, 특정한 사람 Dll4 영역을 다음과 같이 마우스 Dll4 단백질 내로 치환시킨 일련의 7개의 키메릭 Dll4 단백질을 생성시켰다: #1은 사람 N-말단 및 DSL 도메인을 함유하며 (S27-Q218); #2는 사람 N-말단, DSL 및 EGF-1 도메인을 함유하고 (S27-N252); #3은 사람 N-말단, DSL, EGF-1 및 EGF-2 도메인을 함유하며 (S27-Q283); #4는 사람 N-말단, DSL, EGF-1, EGF-2, EGF-3, EGF-4 및 EGF-5를 함유하고; #5는 사람 N-말단 도메인을 함유하며 (S27-R172); #6은 사람 DSL 도메인을 함유하고 (V173-Q218); #7은 사람 EGF-2 도메인을 함유하였다 (E252-D282). 키메릭 단백질을 마우스 IgG2a-Fc 단편에 융합시키고, CHO-K1 세포 내에서 발현시켰다. 조건화된 배지를 수거하고, 단백질 발현을 웨스턴 블럿에 의해서 확인하였다.
hDll4, mDll4, 및 키메릭 단백질 #1, #2, #3, 및 #4에 대한 시험 항체의 결합 특이성은 다음과 같이 시험하였다: 정제된 항체 22G12, VAW3A7-2, 및 15E10을 CM5 칩 상의 5000 내지 6000 RU 사이에서 아민 커플링시켰다. 키메릭 Dll4 단백질, hDll4-mFc, 및 mDll4-mFc를 함유하는 CHO K1 세포로부터의 조건화된 배지를 연속적으로 주입하고, 이어서 항체-커플링된 표면에 걸쳐서 표면 재생시켰다. 블랭크 (blank) 아민 커플링된 플로우셀 (flowcell) 표면을 조건화된 배지의 비특이적 결합에 대한 대조군으로 사용하였다. 결과는 표 9에 요약하였다. 22G12는 hDll4의 S27-Q218 사이의 에피토프에 결합하고; VAW3A7-2는 hDll4의 Q283-E400 사이의 에피토프에 결합하며; 15E10은 hDll4의 E252-D282 사이의 에피토프에 결합했다.
(상술한) hDll4, mDll4 및 키메릭 단백질에 대한 정제된 시험 mAb의 결합 특이성을 측정하였다 (REGN279 = 314266-6F12-B7; REGN287 = 318518-1G04-F3; REGN289 = 318518-1H08-E9; REGN290 = 318518-2A07-B3; REGN306 = 318518-3F06-A3). 간략하면, 각각의 Dll4 단백질을 염소 항-마우스 IgG 항체 표면 상에 포착시키고 (70-130 RU), 이어서 시험 mAb를 100 ㎍/ml의 농도로 주입하였다. mDll4-mFc를 결합시킨 항체가 양성 대조군으로 사용되었다 (양성 대조군= 6C10). 결과 (표 10)는, REGN279가 hDll4의 S27-Q218 사이의 에피토프에 결합하고; REGN287은 hDll4의 Q283-E400 사이에서 결합하며; REGN289, REGN290 및 REGN306은 hDll4의 S27-E400 사이에서 결합하였음을 보여준다.
추가의 에피토프 결합 특이성 측정은 이하의 정제된 시험 항체를 사용하여 상술한 바와 같이 수행되었다: REGN281 = 318518-1A10-D8; REGN305 = 318518-3F04-A6; REGN309 = 318518-14A07-C4; REGN310 = 318518-14D08-G1; REGN421, 및 REGN422. 간략하면, 각각의 Dll4 단백질을 염소 항-마우스 IgG 항체 표면 상에 포착시키고 (240-470 RU), 이어서 시험 항체를 100 ㎍/ml의 농도로 주입하였다 (표 11).
웨스턴 블럿 분석. 키메릭, 마우스 및 사람 Dll4에 대한 선택된 항체의 결합 특이성은 웨스턴 블럿에 의해서 측정되었다. 간략하면, hDll4-mFc (레인당 200 ng), mDll4-mFc (레인당 200 ng), 및 키메릭 단백질 #1 - #7 (대략 레인당 150 ng)를 비-환원성 샘플 완충액을 사용하여 이중 SDS-PAGE 겔 상에서 전기영동하였다. 그 후, 각각의 겔을 PVDF 막에 옮겼다. 블럿을 우선 0.2 ㎍/ml의 REGN421에 노출시킨 다음에, HRP-접합된 항-hIgG 항체 (Pierce)에 노출시켰다. 대조 블럿은 HRP-접합된 항-mFc 항체 (Pierce)에 노출시켰다. 결과: REGN421은 hDll4-mFc 및 사람 N-말단 도메인 (#5), 사람 DSL 도메인 (#6), 또는 둘 다 (#1, #2, #3, 및 #4)를 함유하는 키메릭 단백질을 인식하였다. REGN421은 사람 EGF-2 도메인을 함유하는 키메릭 단백질 (#7)을 인식하지 않았다.
프로테아제 분해 분석 . REGN281과 hDll4 사이의 결합은 추가로, 보호적 프로테아제 분해, 및 HPLC1100 (Agilent) 및 LCQ 클래시컬 이온 트랩 (Classical Ion Trap) 질량분석계 (Thermo)를 사용한 액체 크로마토그라피/질량 분석법 (LC/MS)에 의해서 평가되었다. 간략하면, 1:5 몰 비의 hDll4 및 REGN281의 혼합물, 또는 hDll4 단독을 25℃ (GluC 프로테아제의 경우) 또는 37℃ (트립신의 경우)에서 밤새 프로테아제와 함께 항온처리하였다. 그 후, 생성된 단백분해성 분해 혼합물 각각을 LC/MS에 적용하였다. REGN281의 존재 하에서 수행된 단백분해적 분해물에서 감소되거나 소실되는 것으로서, REGN281의 부재 하에서 수행된 단백분해적 분해물에 존재하는 독특한 펩타이드 피크는 hDll4에 대한 REGN281의 결합에 의해서 프로테아제 분해로부터 보호된 hDll4 상의 잠재적 REGN281 결합부위를 시사한다. 펩타이드의 관찰된 질량, 예상된 질량, 및 N-말단 서열은 표 12에 나타내었다.
실시예
7. 사람 및 원숭이
Dll4
에 대한 정제된 항체의 결합 친화도.
hDll4, 마카카 팍시큘라리스 (M. facscicularis) Dll4 (mfDll4, 서열번호 956), 및 마카카 뮬라타 (M. mulatta) Dll4 (mmDll4, 서열번호 957) 단량체에 대한 선택된 정제된 항체의 결합 친화도는 비아코어 (BIACORE™) 2000 & 3000을 사용하여 측정하였다. 비아코어 (BIACORE™) 칩 상에 고정화된 염소 항-hFc 폴리클로날 항체 시약을 사용하여 REGN281, REGN421, 및 REGN422를 나타내었다. 다양한 농도의 각각의 단백질 hDll4 (12.5 nM 내지 100 nM), mfDll4 (3.13 nM 내지 100 nM), 또는 mmDll4 (12.5 nM 내지 100 nM)을 피분석물로 사용하였으며, 항체 표면 상에 주입하였다. 항원-항체 결합 및 결합된 복합체의 해리는 실시간으로 모니터하였다 (표 13).
hDll4 및 mmDll4 이량체에 대한 항-hDll4 항체의 결합 친화도는 또한, 피분석물로서 hDll4를 hDll4-mFc (3.13 nM 내지 100 nM)로, 또는 mmDll4를 mmDll4-mFc (0.78 nM 내지 25 nM)로 대체시키는 것을 제외하고는 비아코어 (BIACORETM) 2000 및 상술한 방법을 사용하여 측정되었다 (표 14).
실시예
8. 항체와
hDll1
,
hDll3
,
mDll4
, 또는
mfDll4
의 교차-반응성.
사람 델타-유사 리간드 1 (서열번호 953) 및 사람 델타-유사 리간드 3 (서열번호 954) 단백질에 대한 항체의 교차-반응성을 측정하였다. REGN281, REGN421 및 REGN422는 비아코어 (BIACORE™) 칩 상에 고정화된 염소 항-사람 카파 (hK) 폴리클로날 항체 시약 (Southern Biotech)에 의해서 나타내었으며, 100 ㎍/ml의 hDll4-hFc 또는 hDll1-hFc 단백질이 항체 표면 상에 주입된 피분석물로서 사용되었다. 3가지 항-hDll4 항체 모두는 단지 hDll4-hFc에만 결합하였지만, hDll1-hFc에는 결합하지 않았다.
대용 비아코어 (BIACORE™) 체제를 사용하여 항-hDll4 항체와 hDll1-hFc 또는 hDll3-hFc 사이의 교차-반응성을 평가하였다. 간략하면, 리간드 hDll4-hFc, hDll1-hFc, 및 hDll3-hFc는 각각, 약 8,000 내지 10,000의 RU 범위에서 아민 커플링을 통해 CM-5 칩에 공유적으로 연결되었다. 300 ㎍/ml의 REGN421을 각각의 칩의 표면 상에 주입하였다. REGN421는 단지 hDll4-hFc에 결합하였으며; hDll1-hFc 또는 hDll3-hFc에 대해서는 결합이 관찰되지 않았다. 동일한 결과는 REGN421 대신에 REGN422에 대해서 관찰되었다.
OCTETTM-기반 결합시험을 사용하여 선택된 정제된 항-hDll4 항체와 hDll4-hFc, hDll3-hFc, hDll1-hFc, mfDll4-mmh, 또는 mDll4-mFc 사이의 결합을 측정하였다. 간략하면, 스트렙타비딘 고결합성 FA 바이오센서 (ForteBio, Inc., Menlo Park, CA)를 우선, 30℃에서 10분 동안, 5 ㎍/ml의 비오틴-항-hK와 함께 포화에 도달하도록 항온처리하였다. 그 후, 비오틴-항-hK-결합된 바이오센서를 30℃에서 10 분 동안, 20 ㎍/ml의 항체 REGN281, REGN421 또는 REGN422와 함께 포화에 도달하도록 항온처리하였다. 그 후, 항체-결합된 바이오센서를 200 nM의 hDll4-hFc 또는 hDll3-hFc, hDll1-hFc, 또는 mDll4-mFc, 또는 100 nM의 mfDll4-mmh와 함께 30℃에서 10분 동안 항온처리하였다. 각각의 배양 후에 생물학적 층의 두께에 있어서의 변화를 측정하였다. 사람 Dll4-hFc 및 mfDll4-mmh는 항-hDll4 항체-결합된 바이오센서에 결합하였으며, 그 반면에 hDll3-hFc, hDll1-hFc, 및 mDll4-mFc는 항-hDll4 항체-결합된 바이오센서에 결합하지 않았다.
실시예
9. 종양 성장에 대한 항-
hDll4
항체의 효과.
종양 성장에 대한 REGN421의 효과는 사람화된 Dll4 단백질을 발현하는 중증 복합 면역결핍 (SCID) 마우스 (SCIDxhDll4)에 이식된 종양에 대해서 평가하였다. 간략하면, 사람화된 Dll4 마우스는 마우스 Dll4 유전자의 전체 세포외 도메인을 배아줄기 (ES) 세포 내의 사람 Dll4 유전자의 상응하는 세포외 부분 (7kb)으로 치환시킴으로써 만들었다. 동형접합성 hDll4 마우스를 생성시키고, SCID 배경으로 번식시켰다. 그 후, 각각의 마우스를 2.5 x 106 사람 HT1080 종양세포로 피하 (SC) 이식하였다. 종양이 마우스에 정착한 후에 (이식한지 18일 후에 약 100-150 mm3), 마우스를 측정하고, hFc, hDll4-Fc 또는 REGN421로 처리하였다. 총 7마리의 마우스를 3 그룹으로 나누었다. 제1 그룹 (n=3)은 25 mg/kg의 hFc로 피하 처리하였으며; 제2 그룹 (n=1)은 25 mg/kg의 hDll4-Fc로 처리하였고; 제3 그룹 (n=3)은 10 mg/kg의 REGN421로 처리하였다. 처리는 제18일에 시작하여 매 48시간 마다 반복하였다. 생체내 종양 측정치는 처음 처리하기 3일 전 (제15일), 각각의 처리와 같은 날 (제18, 20 및 22일), 및 제25일에 수득되었다. 종양 크기는 수학식 l x w2/2를 사용하여 계산되었다. 결과는 표 15에 나타내었다. 제25일에, 마우스를 안락사시키고, 각각의 종양을 분리하여 생체외에서 측정하고 계산하였다 (길이 x 폭 x 깊이) (표 16).
또한, 내인성 mDll4를 발현하는 SCID 마우스의 그룹 (n=2)을 종양 세포로 이식하고, 동일한 투약 스케줄에 따라서 hDll4-Fc (25 mg/kg)로 처리하였다.
<110> Regeneron Pharmaceuticals, Inc.
<120> Human antibodies to human delta like ligand 4
<130> 6040A-WO
<150> US 60/874,922
<151> 2006-12-14
<150> US 60/916,415
<151> 2007-05-07
<150> US 60/985,323
<151> 2007-11-05
<160> 957
<170> KopatentIn 1.71
<210> 1
<211> 2058
<212> DNA
<213> Homo sapiens
<400> 1
atggcggcag cgtcccggag cgcctctggc tgggcgctac tgctgctggt ggcactttgg 60
cagcagcgcg cggccggctc cggcgtcttc cagctgcagc tgcaggagtt catcaacgag 120
cgcggcgtac tggccagtgg gcggccttgc gagcccggct gccggacttt cttccgcgtc 180
tgccttaagc acttccaggc ggtcgtctcg cccggaccct gcaccttcgg gaccgtctcc 240
acgccggtat tgggcaccaa ctccttcgct gtccgggacg acagtagcgg cggggggcgc 300
aaccctctcc aactgccctt caatttcacc tggccgggta ccttctcgct catcatcgaa 360
gcttggcacg cgccaggaga cgacctgcgg ccagaggcct tgccaccaga tgcactcatc 420
agcaagatcg ccatccaggg ctccctagct gtgggtcaga actggttatt ggatgagcaa 480
accagcaccc tcacaaggct gcgctactct taccgggtca tctgcagtga caactactat 540
ggagacaact gctcccgcct gtgcaagaag cgcaatgacc acttcggcca ctatgtgtgc 600
cagccagatg gcaacttgtc ctgcctgccc ggttggactg gggaatattg ccaacagcct 660
atctgtcttt cgggctgtca tgaacagaat ggctactgca gcaagccagc agagtgcctc 720
tgccgcccag gctggcaggg ccggctgtgt aacgaatgca tcccccacaa tggctgtcgc 780
cacggcacct gcagcactcc ctggcaatgt acttgtgatg agggctgggg aggcctgttt 840
tgtgaccaag atctcaacta ctgcacccac cactccccat gcaagaatgg ggcaacgtgc 900
tccaacagtg ggcagcgaag ctacacctgc acctgtcgcc caggctacac tggtgtggac 960
tgtgagctgg agctcagcga gtgtgacagc aacccctgtc gcaatggagg cagctgtaag 1020
gaccaggagg atggctacca ctgcctgtgt cctccgggct actatggcct gcattgtgaa 1080
cacagcacct tgagctgcgc cgactccccc tgcttcaatg ggggctcctg ccgggagcgc 1140
aaccaggggg ccaactatgc ttgtgaatgt ccccccaact tcaccggctc caactgcgag 1200
aagaaagtgg acaggtgcac cagcaacccc tgtgccaacg ggggacagtg cctgaaccga 1260
ggtccaagcc gcatgtgccg ctgccgtcct ggattcacgg gcacctactg tgaactccac 1320
gtcagcgact gtgcccgtaa cccttgcgcc cacggtggca cttgccatga cctggagaat 1380
gggctcatgt gcacctgccc tgccggcttc tctggccgac gctgtgaggt gcggacatcc 1440
atcgatgcct gtgcctcgag tccctgcttc aacagggcca cctgctacac cgacctctcc 1500
acagacacct ttgtgtgcaa ctgcccttat ggctttgtgg gcagccgctg cgagttcccc 1560
gtgggcttgc cgcccagctt cccctgggtg gccgtctcgc tgggtgtggg gctggcagtg 1620
ctgctggtac tgctgggcat ggtggcagtg gctgtgcggc agctgcggct tcgacggccg 1680
gacgacggca gcagggaagc catgaacaac ttgtcggact tccagaagga caacctgatt 1740
cctgccgccc agcttaaaaa cacaaaccag aagaaggagc tggaagtgga ctgtggcctg 1800
gacaagtcca actgtggcaa acagcaaaac cacacattgg actataatct ggccccaggg 1860
cccctggggc gggggaccat gccaggaaag tttccccaca gtgacaagag cttaggagag 1920
aaggcgccac tgcggttaca cagtgaaaag ccagagtgtc ggatatcagc gatatgctcc 1980
cccagggact ccatgtacca gtctgtgtgt ttgatatcag aggagaggaa tgaatgtgtc 2040
attgccacgg aggtataa 2058
<210> 2
<211> 685
<212> PRT
<213> Homo sapiens
<400> 2
Met Ala Ala Ala Ser Arg Ser Ala Ser Gly Trp Ala Leu Leu Leu Leu
1 5 10 15
Val Ala Leu Trp Gln Gln Arg Ala Ala Gly Ser Gly Val Phe Gln Leu
20 25 30
Gln Leu Gln Glu Phe Ile Asn Glu Arg Gly Val Leu Ala Ser Gly Arg
35 40 45
Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe Arg Val Cys Leu Lys His
50 55 60
Phe Gln Ala Val Val Ser Pro Gly Pro Cys Thr Phe Gly Thr Val Ser
65 70 75 80
Thr Pro Val Leu Gly Thr Asn Ser Phe Ala Val Arg Asp Asp Ser Ser
85 90 95
Gly Gly Gly Arg Asn Pro Leu Gln Leu Pro Phe Asn Phe Thr Trp Pro
100 105 110
Gly Thr Phe Ser Leu Ile Ile Glu Ala Trp His Ala Pro Gly Asp Asp
115 120 125
Leu Arg Pro Glu Ala Leu Pro Pro Asp Ala Leu Ile Ser Lys Ile Ala
130 135 140
Ile Gln Gly Ser Leu Ala Val Gly Gln Asn Trp Leu Leu Asp Glu Gln
145 150 155 160
Thr Ser Thr Leu Thr Arg Leu Arg Tyr Ser Tyr Arg Val Ile Cys Ser
165 170 175
Asp Asn Tyr Tyr Gly Asp Asn Cys Ser Arg Leu Cys Lys Lys Arg Asn
180 185 190
Asp His Phe Gly His Tyr Val Cys Gln Pro Asp Gly Asn Leu Ser Cys
195 200 205
Leu Pro Gly Trp Thr Gly Glu Tyr Cys Gln Gln Pro Ile Cys Leu Ser
210 215 220
Gly Cys His Glu Gln Asn Gly Tyr Cys Ser Lys Pro Ala Glu Cys Leu
225 230 235 240
Cys Arg Pro Gly Trp Gln Gly Arg Leu Cys Asn Glu Cys Ile Pro His
245 250 255
Asn Gly Cys Arg His Gly Thr Cys Ser Thr Pro Trp Gln Cys Thr Cys
260 265 270
Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp Gln Asp Leu Asn Tyr Cys
275 280 285
Thr His His Ser Pro Cys Lys Asn Gly Ala Thr Cys Ser Asn Ser Gly
290 295 300
Gln Arg Ser Tyr Thr Cys Thr Cys Arg Pro Gly Tyr Thr Gly Val Asp
305 310 315 320
Cys Glu Leu Glu Leu Ser Glu Cys Asp Ser Asn Pro Cys Arg Asn Gly
325 330 335
Gly Ser Cys Lys Asp Gln Glu Asp Gly Tyr His Cys Leu Cys Pro Pro
340 345 350
Gly Tyr Tyr Gly Leu His Cys Glu His Ser Thr Leu Ser Cys Ala Asp
355 360 365
Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg Glu Arg Asn Gln Gly Ala
370 375 380
Asn Tyr Ala Cys Glu Cys Pro Pro Asn Phe Thr Gly Ser Asn Cys Glu
385 390 395 400
Lys Lys Val Asp Arg Cys Thr Ser Asn Pro Cys Ala Asn Gly Gly Gln
405 410 415
Cys Leu Asn Arg Gly Pro Ser Arg Met Cys Arg Cys Arg Pro Gly Phe
420 425 430
Thr Gly Thr Tyr Cys Glu Leu His Val Ser Asp Cys Ala Arg Asn Pro
435 440 445
Cys Ala His Gly Gly Thr Cys His Asp Leu Glu Asn Gly Leu Met Cys
450 455 460
Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg Cys Glu Val Arg Thr Ser
465 470 475 480
Ile Asp Ala Cys Ala Ser Ser Pro Cys Phe Asn Arg Ala Thr Cys Tyr
485 490 495
Thr Asp Leu Ser Thr Asp Thr Phe Val Cys Asn Cys Pro Tyr Gly Phe
500 505 510
Val Gly Ser Arg Cys Glu Phe Pro Val Gly Leu Pro Pro Ser Phe Pro
515 520 525
Trp Val Ala Val Ser Leu Gly Val Gly Leu Ala Val Leu Leu Val Leu
530 535 540
Leu Gly Met Val Ala Val Ala Val Arg Gln Leu Arg Leu Arg Arg Pro
545 550 555 560
Asp Asp Gly Ser Arg Glu Ala Met Asn Asn Leu Ser Asp Phe Gln Lys
565 570 575
Asp Asn Leu Ile Pro Ala Ala Gln Leu Lys Asn Thr Asn Gln Lys Lys
580 585 590
Glu Leu Glu Val Asp Cys Gly Leu Asp Lys Ser Asn Cys Gly Lys Gln
595 600 605
Gln Asn His Thr Leu Asp Tyr Asn Leu Ala Pro Gly Pro Leu Gly Arg
610 615 620
Gly Thr Met Pro Gly Lys Phe Pro His Ser Asp Lys Ser Leu Gly Glu
625 630 635 640
Lys Ala Pro Leu Arg Leu His Ser Glu Lys Pro Glu Cys Arg Ile Ser
645 650 655
Ala Ile Cys Ser Pro Arg Asp Ser Met Tyr Gln Ser Val Cys Leu Ile
660 665 670
Ser Glu Glu Arg Asn Glu Cys Val Ile Ala Thr Glu Val
675 680 685
<210> 3
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 3
gaggtgcaac tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttagt acctattgga tgaactgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtggccaac ataaaccaag atggaagtga gaaatactat 180
gtggactctg tgaagggccg aatcaccatc tccagagaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agtcgaggac acggctgtat attactgtgc gagaaaatgg 300
aacaactgga acccggagga gaactggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 4
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 4
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Asn Ile Asn Gln Asp Gly Ser Glu Lys Tyr Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Ile Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Lys Trp Asn Asn Trp Asn Pro Glu Glu Asn Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 5
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 5
ggattcacct ttagtaccta ttgg 24
<210> 6
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 6
Gly Phe Thr Phe Ser Thr Tyr Trp
1 5
<210> 7
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 7
ataaaccaag atggaagtga gaaa 24
<210> 8
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 8
Ile Asn Gln Asp Gly Ser Glu Lys
1 5
<210> 9
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 9
gcgagaaaat ggaacaactg gaacccggag gagaac 36
<210> 10
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 10
Ala Arg Lys Trp Asn Asn Trp Asn Pro Glu Glu Asn
1 5 10
<210> 11
<211> 337
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 11
gatattgtga tgactcagtc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60
atctcctgca ggtctagtca gagcctcctg cataatagtg gatacaactt tttggattgg 120
tacctgcaga agccagggca gtctccacaa ctcctgatct atttgcgttc taatcgggcc 180
tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaagatc 240
agaagagtgg aggctgagga tgttgggatt tattactgca tgcaagctct acacactcct 300
tacacttttg gccaggggac caaggtggag atcaaac 337
<210> 12
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 12
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Asn
20 25 30
Ser Gly Tyr Asn Phe Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Leu Arg Ser Asn Arg Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Arg Arg Val Glu Ala Glu Asp Val Gly Ile Tyr Tyr Cys Met Gln Ala
85 90 95
Leu His Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 13
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 13
cagagcctcc tgcataatag tggatacaac ttt 33
<210> 14
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 14
Gln Ser Leu Leu His Asn Ser Gly Tyr Asn Phe
1 5 10
<210> 15
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 15
ttgcgttct 9
<210> 16
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 16
Leu Arg Ser
1
<210> 17
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 17
atgcaagctc tacacactcc ttacact 27
<210> 18
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 18
Met Gln Ala Leu His Thr Pro Tyr Thr
1 5
<210> 19
<211> 376
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 19
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgtag cctctggatt cacctttagt agctattgga tgacctgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtggccaac ataaaacaag atggaagtga gaaatactat 180
gtggactctg tgaagggccg attcaccgtc tccagagaca acgccaagaa ctcagtgtat 240
ctgcaaatga gcagcctgag agccgaggac acggctgtgt attactgtgc gagagattgg 300
aactatggcc ccgattacta ctactaccac ggtttggacg tctggggcca agggaccacg 360
gtcaccgtct cctcag 376
<210> 20
<211> 125
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 20
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Trp Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Asn Ile Lys Gln Asp Gly Ser Glu Lys Tyr Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Val Ser Arg Asp Asn Ala Lys Asn Ser Val Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Trp Asn Tyr Gly Pro Asp Tyr Tyr Tyr Tyr His Gly Leu
100 105 110
Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<210> 21
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 21
ggattcacct ttagtagcta ttgg 24
<210> 22
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 22
Gly Phe Thr Phe Ser Ser Tyr Trp
1 5
<210> 23
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 23
ataaaacaag atggaagtga gaaa 24
<210> 24
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 24
Ile Lys Gln Asp Gly Ser Glu Lys
1 5
<210> 25
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 25
gcgagagatt ggaactatgg ccccgattac tactactacc acggtttgga cgtc 54
<210> 26
<211> 18
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 26
Ala Arg Asp Trp Asn Tyr Gly Pro Asp Tyr Tyr Tyr Tyr His Gly Leu
1 5 10 15
Asp Val
<210> 27
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 27
gacctccaga tgacccagtc tccgtcctcc ctgtctgtat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtttca gcagaaacca 120
gggaaagccc ctaagcgcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgctgcct 240
gaagattttg caacttatta ctgtctacag cataatactt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 28
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 28
Asp Leu Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp
20 25 30
Leu Gly Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Leu Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln His Asn Thr Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 29
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 29
cagggcatta gaaatgat 18
<210> 30
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 30
Gln Gly Ile Arg Asn Asp
1 5
<210> 31
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 31
gctgcatcc 9
<210> 32
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 32
Ala Ala Ser
1
<210> 33
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 33
ctacagcata atacttaccc gtacact 27
<210> 34
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 34
Leu Gln His Asn Thr Tyr Pro Tyr Thr
1 5
<210> 35
<211> 361
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 35
caggggcagt tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgaag catctggatt cagtttcaga agttatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg gatggcagtt atttggtacg atggcagtaa gacatactat 180
acagagtccg tgacgggccg attcaccatc tccagagaca attccaagaa cacgctatat 240
ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gagcggtttt 300
tcagtgcctg ccacgatcct tgacaactgg ggccagggaa ccctggtctc cgtctcctca 360
g 361
<210> 36
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 36
Gln Gly Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe Ser Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Met
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Thr Tyr Tyr Thr Glu Ser Val
50 55 60
Thr Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ser Gly Phe Ser Val Pro Ala Thr Ile Leu Asp Asn Trp Gly Gln
100 105 110
Gly Thr Leu Val Ser Val Ser Ser
115 120
<210> 37
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 37
ggattcagtt tcagaagtta tggc 24
<210> 38
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 38
Gly Phe Ser Phe Arg Ser Tyr Gly
1 5
<210> 39
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 39
atttggtacg atggcagtaa gaca 24
<210> 40
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 40
Ile Trp Tyr Asp Gly Ser Lys Thr
1 5
<210> 41
<211> 39
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 41
gcgagcggtt tttcagtgcc tgccacgatc cttgacaac 39
<210> 42
<211> 13
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 42
Ala Ser Gly Phe Ser Val Pro Ala Thr Ile Leu Asp Asn
1 5 10
<210> 43
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 43
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtttca gcagaaacca 120
gggaaagccc ctaaccgcct gatctatgga gcatccagtt tggaaggtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca caatcagcag cctgcagcca 240
gaagattttg caacttatta ctgtctacag cataattctt acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 44
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 44
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp
20 25 30
Leu Gly Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Asn Arg Leu Ile
35 40 45
Tyr Gly Ala Ser Ser Leu Glu Gly Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln His Asn Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 45
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 45
cagggcatta gaaatgat 18
<210> 46
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 46
Gln Gly Ile Arg Asn Asp
1 5
<210> 47
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 47
ggagcatcc 9
<210> 48
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 48
Gly Ala Ser
1
<210> 49
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 49
ctacagcata attcttaccc gtggacg 27
<210> 50
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 50
Leu Gln His Asn Ser Tyr Pro Trp Thr
1 5
<210> 51
<211> 367
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 51
caggtgcagc tggtggagtc tgggggaggc gtagtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cgtctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatggtatg atggaaataa taaatactat 180
atagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagaccgt 300
ggatatagtg gctacgaggg atacttcgat ctctggggcc gtggcaccct ggtcactgtc 360
tcctcag 367
<210> 52
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 52
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Asn Asn Lys Tyr Tyr Ile Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Tyr Ser Gly Tyr Glu Gly Tyr Phe Asp Leu Trp
100 105 110
Gly Arg Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 53
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 53
ggattcacct tcagtagcta tggc 24
<210> 54
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 54
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 55
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 55
atatggtatg atggaaataa taaa 24
<210> 56
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 56
Ile Trp Tyr Asp Gly Asn Asn Lys
1 5
<210> 57
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 57
gcgagagacc gtggatatag tggctacgag ggatacttcg atctc 45
<210> 58
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 58
Ala Arg Asp Arg Gly Tyr Ser Gly Tyr Glu Gly Tyr Phe Asp Leu
1 5 10 15
<210> 59
<211> 337
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 59
gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60
ctcaactgta agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct 120
tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atctacccgg 180
gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240
atcagcagcc tgcaggctga agatgtggca gtttatttct gtcagcaata ttatactact 300
tggacgttcg gccaagggac caaggtggaa atcaaac 337
<210> 60
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 60
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Leu Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Phe Cys Gln Gln
85 90 95
Tyr Tyr Thr Thr Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 61
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 61
cagagtgttt tatacagctc caacaataag aactac 36
<210> 62
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 62
Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr
1 5 10
<210> 63
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 63
tgggcatct 9
<210> 64
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 64
Trp Ala Ser
1
<210> 65
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 65
cagcaatatt atactacttg gacg 24
<210> 66
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 66
Gln Gln Tyr Tyr Thr Thr Trp Thr
1 5
<210> 67
<211> 385
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 67
caggtgcagt tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctgcatc caccttcagt aggcatggca tgcactgggt ccgccaggct 120
ccaggcaagg gactggagtg ggtggcagtt atatcatatg atggaaataa taaatactat 180
gtagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga atagcctgag aactgacgac acggctgtgt attattgttc gaaagagtta 300
gtaggtatta ctggaaacct ggtctactac tactactacg gaatggacgt ctggggccaa 360
gggaccacgg tcaccgtctc ctcag 385
<210> 68
<211> 128
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 68
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Ala Ser Thr Phe Ser Arg His
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Thr Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Lys Glu Leu Val Gly Ile Thr Gly Asn Leu Val Tyr Tyr Tyr Tyr
100 105 110
Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<210> 69
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 69
gcatccacct tcagtaggca tggc 24
<210> 70
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 70
Ala Ser Thr Phe Ser Arg His Gly
1 5
<210> 71
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 71
atatcatatg atggaaataa taaa 24
<210> 72
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 72
Ile Ser Tyr Asp Gly Asn Asn Lys
1 5
<210> 73
<211> 63
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 73
tcgaaagagt tagtaggtat tactggaaac ctggtctact actactacta cggaatggac 60
gtc 63
<210> 74
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 74
Ser Lys Glu Leu Val Gly Ile Thr Gly Asn Leu Val Tyr Tyr Tyr Tyr
1 5 10 15
Tyr Gly Met Asp Val
20
<210> 75
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 75
gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gactattaac agcagctact taggctggta ccagcagaaa 120
cctggccagg ctcccagact cctcatctat ggtgcatcca acagggccac tggcatccca 180
gacagtttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcaa cattataaca actcacctta cacttttggc 300
caggggacca agctggagat caaac 325
<210> 76
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 76
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Ile Asn Ser Ser
20 25 30
Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Asn Arg Ala Thr Gly Ile Pro Asp Ser Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Asn Asn Ser Pro
85 90 95
Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 77
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 77
cagactatta acagcagcta c 21
<210> 78
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 78
Gln Thr Ile Asn Ser Ser Tyr
1 5
<210> 79
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 79
ggtgcatcc 9
<210> 80
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 80
Gly Ala Ser
1
<210> 81
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 81
caacattata acaactcacc ttacact 27
<210> 82
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 82
Gln His Tyr Asn Asn Ser Pro Tyr Thr
1 5
<210> 83
<211> 361
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 83
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccataagc agtggtggtt actactggag ctggatccgc 120
cactacccag ggaagggcct ggagtggatt ggctacgtcc attacagtgg gaacacccac 180
tacaatacgt ccctcaagag gcgacttacc atatcaatag acacgtctaa gagccaattc 240
tccctggatc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagcc 300
ccccgtggat accattactt tgcctactgg ggccagggaa ccctggtcac cgtctcctca 360
g 361
<210> 84
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 84
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg His Tyr Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Val His Tyr Ser Gly Asn Thr His Tyr Asn Thr Ser
50 55 60
Leu Lys Arg Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Ser Gln Phe
65 70 75 80
Ser Leu Asp Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 85
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 85
ggtggctcca taagcagtgg tggttactac 30
<210> 86
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 86
Gly Gly Ser Ile Ser Ser Gly Gly Tyr Tyr
1 5 10
<210> 87
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 87
gtccattaca gtgggaacac c 21
<210> 88
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 88
Val His Tyr Ser Gly Asn Thr
1 5
<210> 89
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 89
gcgagagccc cccgtggata ccattacttt gcctac 36
<210> 90
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 90
Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr
1 5 10
<210> 91
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 91
gaaattgggt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtattagc agcaggtact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatcttt ggtgcatcca gcagggccac tggcatacca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct cactttcggc 300
ggagggacca aggtggagat caaac 325
<210> 92
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 92
Glu Ile Gly Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Arg
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 93
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 93
cagagtatta gcagcaggta c 21
<210> 94
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 94
Gln Ser Ile Ser Ser Arg Tyr
1 5
<210> 95
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 95
ggtgcatcc 9
<210> 96
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 96
Gly Ala Ser
1
<210> 97
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 97
cagcagtatg gtagctcacc gctcact 27
<210> 98
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 98
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<210> 99
<211> 361
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 99
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtagtggtt actactggag ttggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacgtcc attacagtgg gaacacccac 180
tacagcccgt ccctcaagag tcgacttacc atatcagttg acacgtctaa gaaccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagcc 300
ccccgtggat accattactt tgcctactgg ggccagggaa ccctggtcac cgtctcctca 360
g 361
<210> 100
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 100
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Val His Tyr Ser Gly Asn Thr His Tyr Ser Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 101
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 101
ggtggctcca tcagcagtag tggttactac 30
<210> 102
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 102
Gly Gly Ser Ile Ser Ser Ser Gly Tyr Tyr
1 5 10
<210> 103
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 103
gtccattaca gtgggaacac c 21
<210> 104
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 104
Val His Tyr Ser Gly Asn Thr
1 5
<210> 105
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 105
gcgagagccc cccgtggata ccattacttt gcctac 36
<210> 106
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 106
Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr
1 5 10
<210> 107
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 107
aaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga gagagccacc 60
ctctcctgca gggccagtca gagtattagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatcttt ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggcca gacttcactc tcaccattag gagactggag 240
cctgaagatt ttgcggtgta ttactgtcag cagtatggta gttcaccgct cactttcggc 300
ggagggacca aggtggagat caaac 325
<210> 108
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 108
Lys Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Pro Asp Phe Thr Leu Thr Ile Arg Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 109
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 109
cagagtatta gcagcagcta c 21
<210> 110
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 110
Gln Ser Ile Ser Ser Ser Tyr
1 5
<210> 111
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 111
ggtgcatcc 9
<210> 112
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 112
Gly Ala Ser
1
<210> 113
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 113
cagcagtatg gtagttcacc gctcact 27
<210> 114
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 114
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<210> 115
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 115
caggttcagt tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta caccttttcc acctatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acgacaataa cgcggactat 180
gcacagaact tccaggccag agtcaccatg accacagaca catccacgac cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gaggtatagc 300
tggaactttc actggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 116
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 116
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Thr Tyr
20 25 30
Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Asp Asn Asn Ala Asp Tyr Ala Gln Asn Phe
50 55 60
Gln Ala Arg Val Thr Met Thr Thr Asp Thr Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Ser Trp Asn Phe His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 117
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 117
ggttacacct tttccaccta tggt 24
<210> 118
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 118
Gly Tyr Thr Phe Ser Thr Tyr Gly
1 5
<210> 119
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 119
atcagcgctt acgacaataa cgcg 24
<210> 120
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 120
Ile Ser Ala Tyr Asp Asn Asn Ala
1 5
<210> 121
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 121
gcgaggtata gctggaactt tcactggttc gacccc 36
<210> 122
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 122
Ala Arg Tyr Ser Trp Asn Phe His Trp Phe Asp Pro
1 5 10
<210> 123
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 123
gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agtacctact tagcctggta ccagcagcaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatggta actcaccgtg gacgttcggc 300
caagggacca aggtggaaat caaac 325
<210> 124
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 124
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Gln Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Asn Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 125
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 125
cagagtgtta gcagtaccta c 21
<210> 126
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 126
Gln Ser Val Ser Ser Thr Tyr
1 5
<210> 127
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 127
ggtgcatcc 9
<210> 128
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 128
Gly Ala Ser
1
<210> 129
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 129
cagcagtatg gtaactcacc gtggacg 27
<210> 130
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 130
Gln Gln Tyr Gly Asn Ser Pro Trp Thr
1 5
<210> 131
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 131
caggttcacc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaggg cttctggtta cacctttacc aactatggta tcacctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acagtggtaa cacagactat 180
gcacagaagt tccaggccag aatcaccatg accacagaca catccacgac cacagcctac 240
atggaactga ggagcctgac atctgacgac acggccgtgt attactgtgc gaggtatagc 300
tggaactttc actggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 132
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 132
Gln Val His Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Arg Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Ser Gly Asn Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Ala Arg Ile Thr Met Thr Thr Asp Thr Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Ser Trp Asn Phe His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 133
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 133
ggttacacct ttaccaacta tggt 24
<210> 134
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 134
Gly Tyr Thr Phe Thr Asn Tyr Gly
1 5
<210> 135
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 135
atcagcgctt acagtggtaa caca 24
<210> 136
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 136
Ile Ser Ala Tyr Ser Gly Asn Thr
1 5
<210> 137
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 137
gcgaggtata gctggaactt tcactggttc gacccc 36
<210> 138
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 138
Ala Arg Tyr Ser Trp Asn Phe His Trp Phe Asp Pro
1 5 10
<210> 139
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 139
gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga cagagtcacc 60
ctctcctgca gggccagtca gagtgttagt agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagtctggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtgtggtg gctcaccgtg gacgttcggc 300
caagggacca gggtggagat caaac 325
<210> 140
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Asp Arg Val Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Cys Gly Gly Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Arg Val Glu Ile Lys
100 105
<210> 141
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 141
cagagtgtta gtagcagcta c 21
<210> 142
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 142
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 143
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 143
ggtgcatcc 9
<210> 144
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 144
Gly Ala Ser
1
<210> 145
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 145
cagcagtgtg gtggctcacc gtggacg 27
<210> 146
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 146
Gln Gln Cys Gly Gly Ser Pro Trp Thr
1 5
<210> 147
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 147
caggttcaac tggtgcagtc tgggcctgag gtgaagaagc ctggggcctc agtgaaggtc 60
gcctgcaagg cttctggtta cacctttacc cactatggtt tcacctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acagtggtca tacagactat 180
gcacggaagt tccaggccag agtcaccatg accacagaca cattcacgac cacagcctac 240
atggaactga ggagcctgag atctgacgac acggccgttt attactgtgc gagttatagc 300
tggaactttc actggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 148
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 148
Gln Val Gln Leu Val Gln Ser Gly Pro Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ala Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr
20 25 30
Gly Phe Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Ser Gly His Thr Asp Tyr Ala Arg Lys Phe
50 55 60
Gln Ala Arg Val Thr Met Thr Thr Asp Thr Phe Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ser Tyr Ser Trp Asn Phe His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 149
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 149
ggttacacct ttacccacta tggt 24
<210> 150
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 150
Gly Tyr Thr Phe Thr His Tyr Gly
1 5
<210> 151
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 151
atcagcgctt acagtggtca taca 24
<210> 152
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 152
Ile Ser Ala Tyr Ser Gly His Thr
1 5
<210> 153
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 153
gcgagttata gctggaactt tcactggttc gacccc 36
<210> 154
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 154
Ala Ser Tyr Ser Trp Asn Phe His Trp Phe Asp Pro
1 5 10
<210> 155
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 155
caaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagt accacctact tagcctggta ccagcagaaa 120
cctggccagg ctcccagtct cctcatctat ggtacatcca ccagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggact gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtgtggtg gctcaccgtg gacgttcggc 300
caagggacca aggtgaaaat caaac 325
<210> 156
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 156
Gln Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Thr Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Ser Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Cys Gly Gly Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Val Lys Ile Lys
100 105
<210> 157
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 157
cagagtgtta gtaccaccta c 21
<210> 158
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 158
Gln Ser Val Ser Thr Thr Tyr
1 5
<210> 159
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 159
ggtacatcc 9
<210> 160
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 160
Gly Thr Ser
1
<210> 161
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 161
cagcagtgtg gtggctcacc gtggacg 27
<210> 162
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 162
Gln Gln Cys Gly Gly Ser Pro Trp Thr
1 5
<210> 163
<211> 367
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 163
caggtgcagt tggtgcagtc tggggctgag gtgaagaagc ctggggccgc tgtgaaggtc 60
tcctgcaagg cttctggata cacgttcacc agttatgata tcaactgggt gcgacaggcc 120
actggacaag ggcttgagtg gatgggatgg ataaacccta acagtggtaa cacaggctat 180
gcacagaagt ttcagggcag agtcaccttg accaggaaca cctccataag cacagcctac 240
atggaactga gcagcctgag atctgaggac acggccgttt attactgtgc gagagaggga 300
tattgtggtg gtgattgcta tgcttttgat atctggggcc aagggacaat ggtcaccgtc 360
tcttcag 367
<210> 164
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 164
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ala Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asp Ile Asn Trp Val Arg Gln Ala Thr Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Arg Asn Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Tyr Cys Gly Gly Asp Cys Tyr Ala Phe Asp Ile Trp
100 105 110
Gly Gln Gly Thr Met Val Thr Val Ser Ser
115 120
<210> 165
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 165
ggatacacgt tcaccagtta tgat 24
<210> 166
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 166
Gly Tyr Thr Phe Thr Ser Tyr Asp
1 5
<210> 167
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 167
ataaacccta acagtggtaa caca 24
<210> 168
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 168
Ile Asn Pro Asn Ser Gly Asn Thr
1 5
<210> 169
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 169
gcgagagagg gatattgtgg tggtgattgc tatgcttttg atatc 45
<210> 170
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 170
Ala Arg Glu Gly Tyr Cys Gly Gly Asp Cys Tyr Ala Phe Asp Ile
1 5 10 15
<210> 171
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 171
gaaattgtgt tgacacaatc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatcttt ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct cactttcggc 300
ggagggacca aggtggagat caaac 325
<210> 172
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 172
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 173
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 173
cagagtgtta gcagcagcta c 21
<210> 174
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 174
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 175
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 175
ggtgcatcc 9
<210> 176
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 176
Gly Ala Ser
1
<210> 177
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 177
cagcagtatg gtagctcacc gctcact 27
<210> 178
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 178
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<210> 179
<211> 361
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 179
cagctgcagc tgcaggagtc gggcccagga ctggtgaagc cttcggagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtagtagtt actactgggg ctggatccgc 120
cagcccccag ggaaggggct ggagtggatt gggagtatct attatagtgg gagcacctac 180
tacaacccgt ccctcaagag tcgagtcacc atatccgtag acacgtccaa gaaccagttc 240
tccctgaagc tgagctctgt gaccgccgca gacacggctg tgtattactg tgcggcaaac 300
tgggacgacg ccttcttctt tgactactgg ggccagggaa ccctggtcac cgtctcctca 360
g 361
<210> 180
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 180
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Ala Asn Trp Asp Asp Ala Phe Phe Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 181
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 181
ggtggctcca tcagcagtag tagttactac 30
<210> 182
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 182
Gly Gly Ser Ile Ser Ser Ser Ser Tyr Tyr
1 5 10
<210> 183
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 183
atctattata gtgggagcac c 21
<210> 184
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 184
Ile Tyr Tyr Ser Gly Ser Thr
1 5
<210> 185
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 185
gcggcaaact gggacgacgc cttcttcttt gactac 36
<210> 186
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 186
Ala Ala Asn Trp Asp Asp Ala Phe Phe Phe Asp Tyr
1 5 10
<210> 187
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 187
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag tataatagtt attcgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 188
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 188
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 189
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 189
cagagtatta gtagctgg 18
<210> 190
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 190
Gln Ser Ile Ser Ser Trp
1 5
<210> 191
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 191
aaggcgtct 9
<210> 192
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 192
Lys Ala Ser
1
<210> 193
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 193
caacagtata atagttattc gtacact 27
<210> 194
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 194
Gln Gln Tyr Asn Ser Tyr Ser Tyr Thr
1 5
<210> 195
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 195
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggata caccttcacc ggctactata ttcactgggt acgacaggcc 120
cctggacaag gccttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180
gcacagaagt ttcagggcag ggtcaccatg accagggaca cgtccatcac cacagcctac 240
atggagctga gcaggctgat atctgacgac acggccgtgt attactgtgc gagaggaccc 300
tgggatttct ttgactactg gggccaggga accctggtca ccgtctcctc ag 352
<210> 196
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 196
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Ile Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Pro Trp Asp Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 197
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 197
ggatacacct tcaccggcta ctat 24
<210> 198
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 198
Gly Tyr Thr Phe Thr Gly Tyr Tyr
1 5
<210> 199
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 199
atcaacccta acagtggtgg caca 24
<210> 200
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 200
Ile Asn Pro Asn Ser Gly Gly Thr
1 5
<210> 201
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 201
gcgagaggac cctgggattt ctttgactac 30
<210> 202
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 202
Ala Arg Gly Pro Trp Asp Phe Phe Asp Tyr
1 5 10
<210> 203
<211> 340
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 203
gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60
atcaactgca agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct 120
tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atctacccgg 180
gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240
atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtact 300
ccgtacactt ttggccaggg gaccaagctg gagatcaaac 340
<210> 204
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 204
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
100 105 110
Lys
<210> 205
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 205
cagagtgttt tatacagctc caacaataag aactac 36
<210> 206
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 206
Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr
1 5 10
<210> 207
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 207
tgggcatct 9
<210> 208
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 208
Trp Ala Ser
1
<210> 209
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 209
cagcaatatt atagtactcc gtacact 27
<210> 210
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 210
Gln Gln Tyr Tyr Ser Thr Pro Tyr Thr
1 5
<210> 211
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 211
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggata caccttcacc ggctactata ttcactgggt acgacaggcc 120
cctggacaag gccttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180
gcacagaagt ttcagggcag ggtcaccatg accagggaca cgtccatcag cacagcctac 240
atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagaggaccc 300
tgggatttct ttgactactg gggccaggga accctggtca ccgtctcctc ag 352
<210> 212
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 212
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Pro Trp Asp Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 213
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 213
ggatacacct tcaccggcta ctat 24
<210> 214
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 214
Gly Tyr Thr Phe Thr Gly Tyr Tyr
1 5
<210> 215
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 215
atcaacccta acagtggtgg caca 24
<210> 216
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 216
Ile Asn Pro Asn Ser Gly Gly Thr
1 5
<210> 217
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 217
gcgagaggac cctgggattt ctttgactac 30
<210> 218
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 218
Ala Arg Gly Pro Trp Asp Phe Phe Asp Tyr
1 5 10
<210> 219
<211> 340
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 219
gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60
atcaactgca agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct 120
tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atctacccgg 180
gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240
atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtact 300
ccgtacactt ttggccaggg gaccaagctg gagatcaaac 340
<210> 220
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 220
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
100 105 110
Lys
<210> 221
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 221
cagagtgttt tatacagctc caacaataag aactac 36
<210> 222
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 222
Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr
1 5 10
<210> 223
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 223
tgggcatct 9
<210> 224
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 224
Trp Ala Ser
1
<210> 225
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 225
cagcaatatt atagtactcc gtacact 27
<210> 226
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 226
Gln Gln Tyr Tyr Ser Thr Pro Tyr Thr
1 5
<210> 227
<211> 361
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 227
caggtgcagt tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcggc agtggtggtt actactggag ctggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacgtcc attacagtgg gaacacccac 180
tacaacccgt ccctcaagag tcgactttcc atatcaatag acacgtctaa gatccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagcc 300
ccccgtggat accattactt tgcctactgg ggccagggaa ccctggtcac cgtctcctca 360
g 361
<210> 228
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 228
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Gly Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Val His Tyr Ser Gly Asn Thr His Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Ser Ile Ser Ile Asp Thr Ser Lys Ile Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 229
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 229
ggtggctcca tcggcagtgg tggttactac 30
<210> 230
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 230
Gly Gly Ser Ile Gly Ser Gly Gly Tyr Tyr
1 5 10
<210> 231
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 231
gtccattaca gtgggaacac c 21
<210> 232
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 232
Val His Tyr Ser Gly Asn Thr
1 5
<210> 233
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 233
gcgagagccc cccgtggata ccattacttt gcctac 36
<210> 234
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 234
Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr
1 5 10
<210> 235
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 235
gaaattgtgt tgacacaatc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatcttt ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct cactttcggc 300
ggagggacca aggtggagat caaac 325
<210> 236
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 236
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 237
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 237
cagagtgtta gcagcagcta c 21
<210> 238
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 238
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 239
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 239
ggtgcatcc 9
<210> 240
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 240
Gly Ala Ser
1
<210> 241
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 241
cagcagtatg gtagctcacc gctcact 27
<210> 242
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 242
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<210> 243
<211> 361
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 243
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggag ctggatccgc 120
cagtacccag ggaagggcct ggagtggatt ggttacgtcc attacagtgg gagcacccac 180
tacaacccgt ccctcaagag tcgacttacc atatcaatag acacgtctaa gagccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagcc 300
ccccgtggat accattactt tgcctactgg ggccagggaa ccctggtcac cgtctcctca 360
g 361
<210> 244
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 244
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln Tyr Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Val His Tyr Ser Gly Ser Thr His Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Ser Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 245
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 245
ggtggctcca tcagcagtgg tggttactac 30
<210> 246
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 246
Gly Gly Ser Ile Ser Ser Gly Gly Tyr Tyr
1 5 10
<210> 247
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 247
gtccattaca gtgggagcac c 21
<210> 248
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 248
Val His Tyr Ser Gly Ser Thr
1 5
<210> 249
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 249
gcgagagccc cccgtggata ccattacttt gcctac 36
<210> 250
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 250
Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr
1 5 10
<210> 251
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 251
gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcaggtact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatcttt ggtgcatcca gcagggccac tggcatacca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct cactttcggc 300
ggagggacca aggtggagat caaac 325
<210> 252
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 252
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Arg
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 253
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 253
cagagtgtta gcagcaggta c 21
<210> 254
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 254
Gln Ser Val Ser Ser Arg Tyr
1 5
<210> 255
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 255
ggtgcatcc 9
<210> 256
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 256
Gly Ala Ser
1
<210> 257
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 257
cagcagtatg gtagctcacc gctcact 27
<210> 258
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 258
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<210> 259
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 259
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggag ctggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacatct attacagtgg gagcacctac 180
tacaacccgt ccctcaagag tcgaattatc atatcagtag acacgtctaa gaaccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagaa 300
ggggctatgg tttttgacta ctggggccag ggaaccctgg tcaccgtctc ctcag 355
<210> 260
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 260
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Ile Ile Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Glu Gly Ala Met Val Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 261
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 261
ggtggctcca tcagcagtgg tggttactac 30
<210> 262
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 262
Gly Gly Ser Ile Ser Ser Gly Gly Tyr Tyr
1 5 10
<210> 263
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 263
atctattaca gtgggagcac c 21
<210> 264
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 264
Ile Tyr Tyr Ser Gly Ser Thr
1 5
<210> 265
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 265
gcgagagaag gggctatggt ttttgactac 30
<210> 266
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 266
Ala Arg Glu Gly Ala Met Val Phe Asp Tyr
1 5 10
<210> 267
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 267
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaaactcct gatttatgct gcatccgctt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaacag cttaatagtt acccgttcac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 268
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 268
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 269
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 269
cagggcatta gcagttat 18
<210> 270
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 270
Gln Gly Ile Ser Ser Tyr
1 5
<210> 271
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 271
gctgcatcc 9
<210> 272
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 272
Ala Ala Ser
1
<210> 273
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 273
caacagctta atagttaccc gttcact 27
<210> 274
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 274
Gln Gln Leu Asn Ser Tyr Pro Phe Thr
1 5
<210> 275
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 275
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggag ctggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacatct attacagtgg gagcacctac 180
tacaacccgt ccctcaagag tcgaattatc atatcagtag acacgtctaa gaaccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagaa 300
ggggctatgg tttttgacta ctggggccag ggaaccctgg tcaccgtctc ctcag 355
<210> 276
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 276
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Ile Ile Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Glu Gly Ala Met Val Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 277
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 277
ggtggctcca tcagcagtgg tggttactac 30
<210> 278
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 278
Gly Gly Ser Ile Ser Ser Gly Gly Tyr Tyr
1 5 10
<210> 279
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 279
atctattaca gtgggagcac c 21
<210> 280
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 280
Ile Tyr Tyr Ser Gly Ser Thr
1 5
<210> 281
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 281
gcgagagaag gggctatggt ttttgactac 30
<210> 282
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 282
Ala Arg Glu Gly Ala Met Val Phe Asp Tyr
1 5 10
<210> 283
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 283
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaaactcct gatttatgct gcatccgctt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaacag cttaatagtt acccgttcac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 284
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 284
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 285
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 285
cagggcatta gcagttat 18
<210> 286
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 286
Gln Gly Ile Ser Ser Tyr
1 5
<210> 287
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 287
gctgcatcc 9
<210> 288
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 288
Ala Ala Ser
1
<210> 289
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 289
caacagctta atagttaccc gttcact 27
<210> 290
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 290
Gln Gln Leu Asn Ser Tyr Pro Phe Thr
1 5
<210> 291
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 291
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggac ctggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacatct attacagtgg gagcacctac 180
tacaacccgt ccctcaagag tcgagttatc atatcagtag acacgtctaa gaaccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagaa 300
ggggctatgg tttttgacta ctggggccag ggaaccctgg tcaccgtctc ctcag 355
<210> 292
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 292
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Ile Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Glu Gly Ala Met Val Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 293
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 293
ggtggctcca tcagcagtgg tggttactac 30
<210> 294
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 294
Gly Gly Ser Ile Ser Ser Gly Gly Tyr Tyr
1 5 10
<210> 295
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 295
atctattaca gtgggagcac c 21
<210> 296
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 296
Ile Tyr Tyr Ser Gly Ser Thr
1 5
<210> 297
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 297
gcgagagaag gggctatggt ttttgactac 30
<210> 298
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 298
Ala Arg Glu Gly Ala Met Val Phe Asp Tyr
1 5 10
<210> 299
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 299
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccgctt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaacag cttaatagtt acccgttcac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 300
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 300
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 301
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 301
cagggcatta gcagttat 18
<210> 302
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 302
Gln Gly Ile Ser Ser Tyr
1 5
<210> 303
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 303
gctgcatcc 9
<210> 304
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 304
Ala Ala Ser
1
<210> 305
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 305
caacagctta atagttaccc gttcact 27
<210> 306
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 306
Gln Gln Leu Asn Ser Tyr Pro Phe Thr
1 5
<210> 307
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 307
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggac ctggatccgc 120
cagtacccag ggaagggcct ggagtggatt gggtacatct attacagtgg gagcacctac 180
tacaacccgt ccctcaagag tcgagttatc atatcagtag acacgtctaa gaaccagttc 240
tccctgaggc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagaa 300
ggggctatgg tttttgacta ctggggccag ggaaccctgg tcaccgtctc ctcag 355
<210> 308
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 308
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Thr Trp Ile Arg Gln Tyr Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Ile Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Glu Gly Ala Met Val Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 309
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 309
ggtggctcca tcagcagtgg tggttactac 30
<210> 310
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 310
Gly Gly Ser Ile Ser Ser Gly Gly Tyr Tyr
1 5 10
<210> 311
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 311
atctattaca gtgggagcac c 21
<210> 312
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 312
Ile Tyr Tyr Ser Gly Ser Thr
1 5
<210> 313
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 313
gcgagagaag gggctatggt ttttgactac 30
<210> 314
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 314
Ala Arg Glu Gly Ala Met Val Phe Asp Tyr
1 5 10
<210> 315
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 315
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccgctt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaacag cttaatagtt acccgttcac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 316
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 316
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 317
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 317
cagggcatta gcagttat 18
<210> 318
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 318
Gln Gly Ile Ser Ser Tyr
1 5
<210> 319
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 319
gctgcatcc 9
<210> 320
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 320
Ala Ala Ser
1
<210> 321
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 321
caacagctta atagttaccc gttcact 27
<210> 322
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 322
Gln Gln Leu Asn Ser Tyr Pro Phe Thr
1 5
<210> 323
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 323
caggttcacc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaggg cttctggtta cacctttacc aactatggta tcacctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgcta acagtggtaa cacagactct 180
gcacagaagt tccaggccag agtcaccatg accacagaca catccacgac cacagcctac 240
atggaactga ggagcctgag atctgacgac acggccgtgt attattgtgc gacgtatagt 300
tggaactttc actggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 324
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 324
Gln Val His Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Arg Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Asn Ser Gly Asn Thr Asp Ser Ala Gln Lys Phe
50 55 60
Gln Ala Arg Val Thr Met Thr Thr Asp Thr Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Tyr Ser Trp Asn Phe His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 325
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 325
ggttacacct ttaccaacta tggt 24
<210> 326
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 326
Gly Tyr Thr Phe Thr Asn Tyr Gly
1 5
<210> 327
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 327
atcagcgcta acagtggtaa caca 24
<210> 328
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 328
Ile Ser Ala Asn Ser Gly Asn Thr
1 5
<210> 329
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 329
gcgacgtata gttggaactt tcactggttc gacccc 36
<210> 330
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 330
Ala Thr Tyr Ser Trp Asn Phe His Trp Phe Asp Pro
1 5 10
<210> 331
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 331
gaaattgtgt tgacgcagtc tccaggcact ctgtctttgt ctccagggga aagagtcacc 60
ctctcctgca gggccagtca gagtgtcagt accaactact taacctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcattc tcaccatcag aagtctggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtgtggtg gctcaccgtg gacgttcggc 300
caagggacca gggtggaaat caaac 325
<210> 332
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 332
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Val Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Thr Asn
20 25 30
Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Arg Ser Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Cys Gly Gly Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Arg Val Glu Ile Lys
100 105
<210> 333
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 333
cagagtgtca gtaccaacta c 21
<210> 334
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 334
Gln Ser Val Ser Thr Asn Tyr
1 5
<210> 335
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 335
ggtgcatcc 9
<210> 336
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 336
Gly Ala Ser
1
<210> 337
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 337
cagcagtgtg gtggctcacc gtggacg 27
<210> 338
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 338
Gln Gln Cys Gly Gly Ser Pro Trp Thr
1 5
<210> 339
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 339
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc tctgagactc 60
tcctgtgcag cgtctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg gactggagtg ggtggcagtt atatggtatg atggaagtaa taaatattat 180
ggagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggctgtat attactgtgc gagagatgga 300
gtagacggtg cttttgatat ttggggccaa gggacaacgg tcaccgtctc ttcag 355
<210> 340
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 340
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Gly Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Val Asp Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 341
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 341
ggattcacct tcagtagcta tggc 24
<210> 342
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 342
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 343
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 343
atatggtatg atggaagtaa taaa 24
<210> 344
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 344
Ile Trp Tyr Asp Gly Ser Asn Lys
1 5
<210> 345
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 345
gcgagagatg gagtagacgg tgcttttgat att 33
<210> 346
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 346
Ala Arg Asp Gly Val Asp Gly Ala Phe Asp Ile
1 5 10
<210> 347
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 347
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggacattaga aatgatttag gctggtatca gcagaaacca 120
gggaaagccc ctaaactcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag actgcagcct 240
gaagattttg caacttatta ctgtcaacaa gattacaatt acctgtatac ttttggccag 300
gggaccaacc tggagatcaa ac 322
<210> 348
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 348
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Arg Asn Asp
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Tyr Asn Tyr Leu Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Asn Leu Glu Ile Lys
100 105
<210> 349
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 349
caggacatta gaaatgat 18
<210> 350
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 350
Gln Asp Ile Arg Asn Asp
1 5
<210> 351
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 351
gctgcatcc 9
<210> 352
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 352
Ala Ala Ser
1
<210> 353
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 353
caacaagatt acaattacct gtatact 27
<210> 354
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 354
Gln Gln Asp Tyr Asn Tyr Leu Tyr Thr
1 5
<210> 355
<211> 364
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 355
gaggtgcagt tggtggagtc ggggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgaag cctctggatt cacctttgat aactattata tgacctgggt ccgccagact 120
ccagggaagg ggctggagtg ggtggccaac ataaaggaag atggaaatga tagatactat 180
gtggactctg tgaagggccg cttcaccatc tccagagaca acgccaagca gtcactgttt 240
ctacaaatga acagtctgag agccgaggac acggctgttt attactgtgc gagagaattt 300
tggagtggcc ctcactacgg tttggacgtc tggggccaag ggaccacggt caccgtctcc 360
tcag 364
<210> 356
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 356
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe Thr Phe Asp Asn Tyr
20 25 30
Tyr Met Thr Trp Val Arg Gln Thr Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Asn Ile Lys Glu Asp Gly Asn Asp Arg Tyr Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Gln Ser Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Phe Trp Ser Gly Pro His Tyr Gly Leu Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 357
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 357
ggattcacct ttgataacta ttat 24
<210> 358
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 358
Gly Phe Thr Phe Asp Asn Tyr Tyr
1 5
<210> 359
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 359
ataaaggaag atggaaatga taga 24
<210> 360
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 360
Ile Lys Glu Asp Gly Asn Asp Arg
1 5
<210> 361
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 361
gcgagagaat tttggagtgg ccctcactac ggtttggacg tc 42
<210> 362
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 362
Ala Arg Glu Phe Trp Ser Gly Pro His Tyr Gly Leu Asp Val
1 5 10
<210> 363
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 363
gccctccaga tgacccagtc tccatcctcc ctgtctgcac ctgtaggcga cagagtcacc 60
atcacttgcc gggcaagtca ggacgttaga aataatttag gctggtatca gcagaaacca 120
gggaatgccc ctaaattcct gatctatgct gcatccagtt tacaaagtgg aatcccatca 180
aggttcagcg gcagtggatc tggctcagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacaatt accctccgac gttcggccag 300
gggaccaagg tggaaatcaa gc 322
<210> 364
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 364
Ala Leu Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Pro Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Arg Asn Asn
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Asn Ala Pro Lys Phe Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Ser Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Pro
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 365
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 365
caggacgtta gaaataat 18
<210> 366
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 366
Gln Asp Val Arg Asn Asn
1 5
<210> 367
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 367
gctgcatcc 9
<210> 368
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 368
Ala Ala Ser
1
<210> 369
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 369
ctacaagatt acaattaccc tccgacg 27
<210> 370
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 370
Leu Gln Asp Tyr Asn Tyr Pro Pro Thr
1 5
<210> 371
<211> 370
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 371
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cgtctggatt caccttcagt agttatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt ttatggtatg atggaagtaa taaaaactat 180
gtagactccg tgaagggccg attcaccatc tcaagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatcac 300
gattttagga gtggttatga ggggtggttc gacccctggg gccagggaac cttggtcacc 360
gtctcctcag 370
<210> 372
<211> 123
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 372
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Leu Trp Tyr Asp Gly Ser Asn Lys Asn Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 373
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 373
ggattcacct tcagtagtta tggc 24
<210> 374
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 374
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 375
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 375
ttatggtatg atggaagtaa taaa 24
<210> 376
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 376
Leu Trp Tyr Asp Gly Ser Asn Lys
1 5
<210> 377
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 377
gcgagagatc acgattttag gagtggttat gaggggtggt tcgacccc 48
<210> 378
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 378
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
1 5 10 15
<210> 379
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 379
gaaattgtgt tgacacagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttcgc agctacttag cctggtacca acagaaacct 120
ggccaggctc ccaggctcct catctatgat gcatccaaca gggccactgg catcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag cctagagcct 240
gaagattttg cagtttatta ctgtcagcac cgtagcaact ggcctcccac tttcggcgga 300
gggaccgagg tggaggtcag ac 322
<210> 380
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 380
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gly Gly Thr Glu Val Glu Val Arg
100 105
<210> 381
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 381
cagagtgttc gcagctac 18
<210> 382
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 382
Gln Ser Val Arg Ser Tyr
1 5
<210> 383
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 383
gatgcatcc 9
<210> 384
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 384
Asp Ala Ser
1
<210> 385
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 385
cagcaccgta gcaactggcc tcccact 27
<210> 386
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 386
Gln His Arg Ser Asn Trp Pro Pro Thr
1 5
<210> 387
<211> 16
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 387
taccggctcc cgatgg 16
<210> 388
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 388
ggcggctaag gtgtttgga 19
<210> 389
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 389
ttgggaatga ggaaagcaaa ct 22
<210> 390
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 390
ctgaagtacc ggaggaga 18
<210> 391
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 391
atcacgctgg tggtcctctt 20
<210> 392
<211> 16
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 392
gctgcggcga gtgctt 16
<210> 393
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 393
tggcaaatgc tggacccaac aca 23
<210> 394
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 394
gggtcctggc atcttgtcc 19
<210> 395
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 395
gcagatgaaa aactgggaac ca 22
<210> 396
<211> 372
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 396
caggtgcagc tggtgcagtc aggtccagga ctggtgaagc cctcgcagaa cctctcactc 60
acctgtgcca tctccggaga cagtgtctct agtgatagtg ctgcttggaa ctggatcagg 120
cagtccccat cgagaggcct tgagtggctg ggaaggacat actacaggtc caagtggtat 180
aatgattatg cagtatctgt gaaaagtcga ataaccttca acccagatac atccaagaac 240
cacatctccc tgcagctgaa ctctgtgact cccgaggaca cggctatcta ttactgtgca 300
agagaggggg ataattggaa ttacggctgg ctcgacccct ggggccaggg aaccacggtc 360
accgtctcct ca 372
<210> 397
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 397
Gln Val Gln Leu Val Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Asn Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asp
20 25 30
Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu
35 40 45
Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Asn Asp Tyr Ala
50 55 60
Val Ser Val Lys Ser Arg Ile Thr Phe Asn Pro Asp Thr Ser Lys Asn
65 70 75 80
His Ile Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Ile
85 90 95
Tyr Tyr Cys Ala Arg Glu Gly Asp Asn Trp Asn Tyr Gly Trp Leu Asp
100 105 110
Pro Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 398
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 398
ggagacagtg tctctagtga tagtgctgct 30
<210> 399
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 399
Gly Asp Ser Val Ser Ser Asp Ser Ala Ala
1 5 10
<210> 400
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 400
acatactaca ggtccaagtg gtataat 27
<210> 401
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 401
Thr Tyr Tyr Arg Ser Lys Trp Tyr Asn
1 5
<210> 402
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 402
gcaagagagg gggataattg gaattacggc tggctcgacc cc 42
<210> 403
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 403
Ala Arg Glu Gly Asp Asn Trp Asn Tyr Gly Trp Leu Asp Pro
1 5 10
<210> 404
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 404
gacatccagt tgacccagtc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60
atctcctgca ggtctagtca gagcctcctt cttagtaatg gatacaacta tttggattgg 120
tacctgcaga agccagggca gtctccacaa ctcctgatct atttggtttc tagtcgggcc 180
tccggggtcc ctgacaggtt cagtggcagt ggatccggca cagattttac actgaaaatc 240
agcagagtgg aggctgagga ttttggaatt tattattgta tgcaagctct acaaactccg 300
tacacttttg gccgggggac caaggtggaa atcaaa 336
<210> 405
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 405
Asp Ile Gln Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu Leu Ser
20 25 30
Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Leu Val Ser Ser Arg Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Phe Gly Ile Tyr Tyr Cys Met Gln Ala
85 90 95
Leu Gln Thr Pro Tyr Thr Phe Gly Arg Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 406
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 406
cagagcctcc ttcttagtaa tggatacaac tat 33
<210> 407
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 407
Gln Ser Leu Leu Leu Ser Asn Gly Tyr Asn Tyr
1 5 10
<210> 408
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 408
ttggtttct 9
<210> 409
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 409
Leu Val Ser
1
<210> 410
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 410
atgcaagctc tacaaactcc gtacact 27
<210> 411
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 411
Met Gln Ala Leu Gln Thr Pro Tyr Thr
1 5
<210> 412
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 412
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccgtcagc agtggtaatt actactggag ctgggtccgc 120
caacacccag ggaagggcct ggagtggttt ggttacatca aaaacagtgg gggcacctac 180
tacaacccgt ccctcaagag tcgaattacc atatcagtag acacgtctaa gaaccacttc 240
tccctgaggc tgagctctat gacggccgcg gacacggccg tgtattactg tgcgagagct 300
ggttcgggga gtcactactt tgactactgg ggccagggaa ccctggtcac cgtctcctca 360
<210> 413
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 413
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asn Tyr Tyr Trp Ser Trp Val Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Phe Gly Tyr Ile Lys Asn Ser Gly Gly Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Ile Thr Ile Ser Val Asp Thr Ser Lys Asn His Phe
65 70 75 80
Ser Leu Arg Leu Ser Ser Met Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Gly Ser Gly Ser His Tyr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 414
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 414
ggtggctccg tcagcagtgg taattactac 30
<210> 415
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 415
Gly Gly Ser Val Ser Ser Gly Asn Tyr Tyr
1 5 10
<210> 416
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 416
atcaaaaaca gtgggggcac c 21
<210> 417
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 417
Ile Lys Asn Ser Gly Gly Thr
1 5
<210> 418
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 418
gcgagagctg gttcggggag tcactacttt gactac 36
<210> 419
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 419
Ala Arg Ala Gly Ser Gly Ser His Tyr Phe Asp Tyr
1 5 10
<210> 420
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 420
gacatccagt tgacccagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcaactact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt gtgcagtgta ttactgtcag cagtacggtt actcaccgat caccttcggc 300
caagggacca agctggagat caaa 324
<210> 421
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 421
Asp Ile Gln Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Cys Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Tyr Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 422
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 422
cagagtgtta gcagcaacta c 21
<210> 423
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 423
Gln Ser Val Ser Ser Asn Tyr
1 5
<210> 424
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 424
ggtgcatcc 9
<210> 425
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 425
Gly Ala Ser
1
<210> 426
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 426
cagcagtacg gttactcacc gatcacc 27
<210> 427
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 427
Gln Gln Tyr Gly Tyr Ser Pro Ile Thr
1 5
<210> 428
<211> 369
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 428
gaggtgcagc tggtgcagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cgtctggatt caccttcagt agttatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtgtcattt ttatggtatg atggaactaa taaaaactat 180
gtagagtccg tgaagggccg attcaccatc tcaagagaca attccaagaa tatgctgtat 240
ctggaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatcac 300
gattttagga gtggttatga ggggtggttc gacccctggg gccagggaac cctggtcacc 360
gtctcctca 369
<210> 429
<211> 123
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 429
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Phe Leu Trp Tyr Asp Gly Thr Asn Lys Asn Tyr Val Glu Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Met Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 430
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 430
ggattcacct tcagtagtta tggc 24
<210> 431
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 431
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 432
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 432
ttatggtatg atggaactaa taaa 24
<210> 433
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 433
Leu Trp Tyr Asp Gly Thr Asn Lys
1 5
<210> 434
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 434
gcgagagatc acgattttag gagtggttat gaggggtggt tcgacccc 48
<210> 435
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 435
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
1 5 10 15
<210> 436
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 436
gaaatagtga tgacacagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agctacttag cctggtacca acagaaacct 120
ggccaggctc ccaggctcct catctatgat gcatccaaca gggccactgg catcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag cctagagcct 240
gaagattttg cagtttatta ctgtcaacac cgtagcaact ggcctcccac tttcggcgga 300
gggaccaagg tggaaatcaa a 321
<210> 437
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 437
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 438
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 438
cagagtgtta gcagctac 18
<210> 439
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 439
Gln Ser Val Ser Ser Tyr
1 5
<210> 440
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 440
gatgcatcc 9
<210> 441
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 441
Asp Ala Ser
1
<210> 442
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 442
caacaccgta gcaactggcc tcccact 27
<210> 443
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 443
Gln His Arg Ser Asn Trp Pro Pro Thr
1 5
<210> 444
<211> 366
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 444
caggtacagc tgcagcagtc gggtccagga ctgctgaaac cttcacagac cctgtccctc 60
acctgctctg tctctggtgg ctccatcagc agtggtaatt actactggac ctggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacatca agaacagtgg aagcgcctac 180
tacaatccgt ccctcaagag tcgacttacc atgtcaatag acacgtctca gaaccacttc 240
tccttgattt tgacttctgt gactgccgcg gacacggcct tatattactg tgcgagagat 300
gaaaatatag cagttcgtca tgcttttgat atctggggcc aagggacatc ggtcaccgtc 360
tcctca 366
<210> 445
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 445
Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Leu Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Asn Tyr Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Asn Ser Gly Ser Ala Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Met Ser Ile Asp Thr Ser Gln Asn His Phe
65 70 75 80
Ser Leu Ile Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Leu Tyr Tyr
85 90 95
Cys Ala Arg Asp Glu Asn Ile Ala Val Arg His Ala Phe Asp Ile Trp
100 105 110
Gly Gln Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 446
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 446
ggtggctcca tcagcagtgg taattactac 30
<210> 447
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 447
Gly Gly Ser Ile Ser Ser Gly Asn Tyr Tyr
1 5 10
<210> 448
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 448
atcaagaaca gtggaagcgc c 21
<210> 449
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 449
Ile Lys Asn Ser Gly Ser Ala
1 5
<210> 450
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 450
gcgagagatg aaaatatagc agttcgtcat gcttttgata tc 42
<210> 451
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 451
Ala Arg Asp Glu Asn Ile Ala Val Arg His Ala Phe Asp Ile
1 5 10
<210> 452
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 452
gaaatagtgt tgacacagtc tccaggcgcc ctgtctttgt ctccaggaga aagagccacc 60
ctctcctgta gggccagtcg gactgttagc agcagctact tagcctggta ccaacagaaa 120
cctggccagg ctcccaggct cctcatctat ggtacatcca gccgggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcac cagactggag 240
cctgaagatt ttgcaatata ttactgtcag cagtctggtt actcacctct cactttcggc 300
ggagggacca aggtggaaat caaa 324
<210> 453
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 453
Glu Ile Val Leu Thr Gln Ser Pro Gly Ala Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Arg Thr Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Thr Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Ile Tyr Tyr Cys Gln Gln Ser Gly Tyr Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 454
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 454
cggactgtta gcagcagcta c 21
<210> 455
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 455
Arg Thr Val Ser Ser Ser Tyr
1 5
<210> 456
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 456
ggtacatcc 9
<210> 457
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 457
Gly Thr Ser
1
<210> 458
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 458
cagcagtctg gttactcacc tctcact 27
<210> 459
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 459
Gln Gln Ser Gly Tyr Ser Pro Leu Thr
1 5
<210> 460
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 460
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctgatga ctccatcaac aatgttgaat cctactggac ctggatccgc 120
caacacccag ggaagggcct ggagtggatt ggatacatca aatacactgg gggcatccac 180
tataacccgt ccctcaagag tcgactcgcc atatcagtgg acacgtcaaa gaaccagttc 240
tccctgaaaa tgaactctgt gactgccgcg gacacggcca aatattactg tgcgagagca 300
cgtggaagtc atacttttga tgtctggggc caggggacaa cggtcaccgt ctcctca 357
<210> 461
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 461
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Asp Ser Ile Asn Asn Val
20 25 30
Glu Ser Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Tyr Thr Gly Gly Ile His Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Ala Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Met Asn Ser Val Thr Ala Ala Asp Thr Ala Lys Tyr Tyr
85 90 95
Cys Ala Arg Ala Arg Gly Ser His Thr Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Thr Val Thr Val Ser Ser
115
<210> 462
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 462
gatgactcca tcaacaatgt tgaatcctac 30
<210> 463
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 463
Asp Asp Ser Ile Asn Asn Val Glu Ser Tyr
1 5 10
<210> 464
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 464
atcaaataca ctgggggcat c 21
<210> 465
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 465
Ile Lys Tyr Thr Gly Gly Ile
1 5
<210> 466
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 466
gcgagagcac gtggaagtca tacttttgat gtc 33
<210> 467
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 467
Ala Arg Ala Arg Gly Ser His Thr Phe Asp Val
1 5 10
<210> 468
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 468
gccatccggt tgacccagtc tccaggcacc ctgtcttggt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agtaactact tagcctggta ccagcagaaa 120
cctggccagg ctccccgact cctcatttat ggtgcatcca gcagggtcgc tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcactgta ttattgtcag caatatagta ggtcaccgat caccttcggc 300
caagggacca agctggagat caaa 324
<210> 469
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 469
Ala Ile Arg Leu Thr Gln Ser Pro Gly Thr Leu Ser Trp Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Val Ala Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Leu Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 470
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 470
cagagtgtta gcagtaacta c 21
<210> 471
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 471
Gln Ser Val Ser Ser Asn Tyr
1 5
<210> 472
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 472
ggtgcatcc 9
<210> 473
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 473
Gly Ala Ser
1
<210> 474
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 474
cagcaatata gtaggtcacc gatcacc 27
<210> 475
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 475
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 476
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 476
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcaac agtgttactt actactggac ctggatccgc 120
cagcacccag ggaggggcct agagtggatt gggtacatca aattcagtgg gagcacctac 180
tacaacccgt ccctcaaggg tcgagtcacc atatcagtgg acacgtctaa gaaccaattc 240
tcccttaaaa ttaactctgt gactgccgcg gacacggccg tgttttactg tgcgagagct 300
tctggaagtc atacttttga tatctggggc caagggacaa tggtcaccgt ctcctca 357
<210> 477
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 477
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Asn Ser Val
20 25 30
Thr Tyr Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Arg Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Phe Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Gly Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Ile Asn Ser Val Thr Ala Ala Asp Thr Ala Val Phe Tyr
85 90 95
Cys Ala Arg Ala Ser Gly Ser His Thr Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 478
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 478
ggtggctcca tcaacagtgt tacttactac 30
<210> 479
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 479
Gly Gly Ser Ile Asn Ser Val Thr Tyr Tyr
1 5 10
<210> 480
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 480
atcaaattca gtgggagcac c 21
<210> 481
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 481
Ile Lys Phe Ser Gly Ser Thr
1 5
<210> 482
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 482
gcgagagctt ctggaagtca tacttttgat atc 33
<210> 483
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 483
Ala Arg Ala Ser Gly Ser His Thr Phe Asp Ile
1 5 10
<210> 484
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 484
gccatccgga tgacccagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgct gggccagtca gagtattagc ggctattttg cctggtatca acagaaacct 120
ggccaggctc ccaggctcct catctatgat acatcctaca gggccactga cgtcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcaacaa cctagagcct 240
gaagattttg cagtttatta ctgtcagcag cgtagcgact ggccgctcag cttcggcgga 300
gggaccaaac tggagatcaa a 321
<210> 485
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 485
Ala Ile Arg Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Trp Ala Ser Gln Ser Ile Ser Gly Tyr
20 25 30
Phe Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Tyr Arg Ala Thr Asp Val Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Asn Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asp Trp Pro Leu
85 90 95
Ser Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 486
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 486
cagagtatta gcggctat 18
<210> 487
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 487
Gln Ser Ile Ser Gly Tyr
1 5
<210> 488
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 488
gatacatcc 9
<210> 489
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 489
Asp Thr Ser
1
<210> 490
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 490
cagcagcgta gcgactggcc gctcagc 27
<210> 491
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 491
Gln Gln Arg Ser Asp Trp Pro Leu Ser
1 5
<210> 492
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 492
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcaac agtgttactt actactggac ctggatccgc 120
cagcacccag ggaggggcct agagtggatt gggtacatca aattcagtgg gagcacctac 180
tacaacccgt ccctcaaggg tcgagtcacc atatcagtgg acacgtctaa gaaccaattc 240
tcccttaaaa ttaactctgt gactgccgcg gacacggccg tgttttactg tgcgagagct 300
tctggaagtc atacttttga tatctggggc caagggacaa tggtcaccgt ctcctca 357
<210> 493
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 493
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Asn Ser Val
20 25 30
Thr Tyr Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Arg Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Phe Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Gly Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Ile Asn Ser Val Thr Ala Ala Asp Thr Ala Val Phe Tyr
85 90 95
Cys Ala Arg Ala Ser Gly Ser His Thr Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 494
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 494
ggtggctcca tcaacagtgt tacttactac 30
<210> 495
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 495
Gly Gly Ser Ile Asn Ser Val Thr Tyr Tyr
1 5 10
<210> 496
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 496
atcaaattca gtgggagcac c 21
<210> 497
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 497
Ile Lys Phe Ser Gly Ser Thr
1 5
<210> 498
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 498
gcgagagctt ctggaagtca tacttttgat atc 33
<210> 499
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 499
Ala Arg Ala Ser Gly Ser His Thr Phe Asp Ile
1 5 10
<210> 500
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 500
gatattgtga tgacccagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc aacagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctct ggtgcgtcca gcagggtcac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttggaatgta ttactgtcag cagtatagta ggtcaccgat caccttcggc 300
caagggacca aggtggaaat caaa 324
<210> 501
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 501
Asp Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Asn Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Val Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Gly Met Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 502
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 502
cagagtgtta gcaacagcta c 21
<210> 503
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 503
Gln Ser Val Ser Asn Ser Tyr
1 5
<210> 504
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 504
ggtgcgtcc 9
<210> 505
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 505
Gly Ala Ser
1
<210> 506
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 506
cagcagtata gtaggtcacc gatcacc 27
<210> 507
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 507
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 508
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 508
gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta ctcctttacc agctttggtt tcagctgggt gcgacaggcc 120
cctggacaag gacttgagtg gctgggatgg atcagcgctt acagtggtga cacagactat 180
gcacagaagt tccagggcag agtcaccctg accactgaca catccacgac cactgcctac 240
atggagctga ggagcctgag atctgacgac acggccgtct attactgtgc gcgatataac 300
tggaacctcc actggttcga cccctggggc cagggaaccc tggtcaccgt ctcctca 357
<210> 509
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 509
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Ser Phe
20 25 30
Gly Phe Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Leu
35 40 45
Gly Trp Ile Ser Ala Tyr Ser Gly Asp Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Thr Asp Thr Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Asn Trp Asn Leu His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 510
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 510
ggttactcct ttaccagctt tggt 24
<210> 511
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 511
Gly Tyr Ser Phe Thr Ser Phe Gly
1 5
<210> 512
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 512
atcagcgctt acagtggtga caca 24
<210> 513
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 513
Ile Ser Ala Tyr Ser Gly Asp Thr
1 5
<210> 514
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 514
gcgcgatata actggaacct ccactggttc gacccc 36
<210> 515
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 515
Ala Arg Tyr Asn Trp Asn Leu His Trp Phe Asp Pro
1 5 10
<210> 516
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 516
gacatccgga tgacccagtc tccaggcatc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gaatattaaa agcaactact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatcttt ggtacatcca acagggccac tgccatttca 180
gacaggttca gtggcagtgg gtctgggaca gacttccttt tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatggta actcaccgtg gacgttcggc 300
caagggacca aagtggatat caaa 324
<210> 517
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 517
Asp Ile Arg Met Thr Gln Ser Pro Gly Ile Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asn Ile Lys Ser Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Phe Gly Thr Ser Asn Arg Ala Thr Ala Ile Ser Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Leu Phe Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Asn Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys
100 105
<210> 518
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 518
cagaatatta aaagcaacta c 21
<210> 519
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 519
Gln Asn Ile Lys Ser Asn Tyr
1 5
<210> 520
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 520
ggtacatcc 9
<210> 521
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 521
Gly Thr Ser
1
<210> 522
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 522
cagcagtatg gtaactcacc gtggacg 27
<210> 523
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 523
Gln Gln Tyr Gly Asn Ser Pro Trp Thr
1 5
<210> 524
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 524
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctgatgg ctccatcaac agtgttgaat cctactggac ctggatccgc 120
cagcacccag ggaagggcct ggagtggatt ggatacatca aatacactgg gggcatccac 180
tataacccgt ccctcaagag tcgacttgcc atatcagtgg acacgtcaaa gaaccagttc 240
tccctgaaaa tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagca 300
cgtggaagtc atacttttga tgtctggggc caggggacaa tggtcaccgt ctcttca 357
<210> 525
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 525
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Ile Asn Ser Val
20 25 30
Glu Ser Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Tyr Thr Gly Gly Ile His Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Ala Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Met Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Arg Gly Ser His Thr Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 526
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 526
gatggctcca tcaacagtgt tgaatcctac 30
<210> 527
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 527
Asp Gly Ser Ile Asn Ser Val Glu Ser Tyr
1 5 10
<210> 528
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 528
atcaaataca ctgggggcat c 21
<210> 529
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 529
Ile Lys Tyr Thr Gly Gly Ile
1 5
<210> 530
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 530
gcgagagcac gtggaagtca tacttttgat gtc 33
<210> 531
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 531
Ala Arg Ala Arg Gly Ser His Thr Phe Asp Val
1 5 10
<210> 532
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 532
gaaattgtgc tgactcagtc tccaggcacc ctgtcttggt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtattagc agtaactact tagcctggta ccagcagaaa 120
cctggccagg ctcccagact cctcatttat ggtgcatcca gcagggtcac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcactgta ttattgtcag cagtatagta ggtcaccgat caccttcggc 300
caagggacca aagtggatat caaa 324
<210> 533
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 533
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Trp Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Val Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Leu Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys
100 105
<210> 534
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 534
cagagtatta gcagtaacta c 21
<210> 535
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 535
Gln Ser Ile Ser Ser Asn Tyr
1 5
<210> 536
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 536
ggtgcatcc 9
<210> 537
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 537
Gly Ala Ser
1
<210> 538
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 538
cagcagtata gtaggtcacc gatcacc 27
<210> 539
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 539
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 540
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 540
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccgtcagc agtggtaatt actactggag ctggatccgc 120
cagcacccag ggaagggcct ggagtggttt gggtacatca aaaacagtgg gggcacctac 180
tacaacccgt ccctcaagag tcgaattacc atatcagtag acacgtctaa gaaccacttc 240
tccctgaggc tgagctctat gacggccgcg gacacggccg tgtattactg tgcgagagct 300
ggttcgggga gtcactactt tgactactgg ggccagggaa ccctggtcac cgtctcctca 360
<210> 541
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 541
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asn Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Phe Gly Tyr Ile Lys Asn Ser Gly Gly Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Ile Thr Ile Ser Val Asp Thr Ser Lys Asn His Phe
65 70 75 80
Ser Leu Arg Leu Ser Ser Met Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Gly Ser Gly Ser His Tyr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 542
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 542
ggtggctccg tcagcagtgg taattactac 30
<210> 543
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 543
Gly Gly Ser Val Ser Ser Gly Asn Tyr Tyr
1 5 10
<210> 544
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 544
atcaaaaaca gtgggggcac c 21
<210> 545
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 545
Ile Lys Asn Ser Gly Gly Thr
1 5
<210> 546
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 546
gcgagagctg gttcggggag tcactacttt gactac 36
<210> 547
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 547
Ala Arg Ala Gly Ser Gly Ser His Tyr Phe Asp Tyr
1 5 10
<210> 548
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 548
gaaacgacac tcacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggctca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt gtgcagtgta ttactgtcag cagtatggtt actcaccgat caccttcggc 300
caagggacca aggtggaaat caaa 324
<210> 549
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 549
Glu Thr Thr Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Leu Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Cys Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Tyr Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 550
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 550
cagagtgtta gcagcagcta c 21
<210> 551
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 551
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 552
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 552
ggtgcatcc 9
<210> 553
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 553
Gly Ala Ser
1
<210> 554
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 554
cagcagtatg gttactcacc gatcacc 27
<210> 555
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 555
Gln Gln Tyr Gly Tyr Ser Pro Ile Thr
1 5
<210> 556
<211> 369
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 556
gaagtgcagc tggtgcagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtacag cgtctggatt caccttcagt agctatgcca tgtactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatggtatg atggaagtaa taaaaactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacactgtat 240
ctgcaagtga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatcac 300
gattttttga gtggttatga ggggtggttc gacccctggg gccagggaac cctggtcacc 360
gtctcctca 369
<210> 557
<211> 123
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 557
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Asn Lys Asn Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Val Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp His Asp Phe Leu Ser Gly Tyr Glu Gly Trp Phe Asp Pro
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 558
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 558
ggattcacct tcagtagcta tgcc 24
<210> 559
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 559
Gly Phe Thr Phe Ser Ser Tyr Ala
1 5
<210> 560
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 560
atatggtatg atggaagtaa taaa 24
<210> 561
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 561
Ile Trp Tyr Asp Gly Ser Asn Lys
1 5
<210> 562
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 562
gcgagagatc acgatttttt gagtggttat gaggggtggt tcgacccc 48
<210> 563
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 563
Ala Arg Asp His Asp Phe Leu Ser Gly Tyr Glu Gly Trp Phe Asp Pro
1 5 10 15
<210> 564
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 564
gaaattgtgc tgactcagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagt agctacttag cctggtacca acagaaacct 120
ggccaggctc ccaggctcct catctatgat gcatccaaca gggccactgg catcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagtag cctagagcct 240
gaagattttg cagtttatta ctgtcagcaa cgtagcaact ggcctcccac tttcggcgga 300
gggaccaaag tggatatcaa a 321
<210> 565
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 565
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys
100 105
<210> 566
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 566
cagagtgtta gtagctac 18
<210> 567
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 567
Gln Ser Val Ser Ser Tyr
1 5
<210> 568
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 568
gatgcatcc 9
<210> 569
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 569
Asp Ala Ser
1
<210> 570
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 570
cagcaacgta gcaactggcc tcccact 27
<210> 571
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 571
Gln Gln Arg Ser Asn Trp Pro Pro Thr
1 5
<210> 572
<211> 375
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 572
gaggtgcagc tggtgcagtc tggagctgaa gtgaagaacc ctggggcctc agttagggtc 60
tcctgcaagg cttctggtta cacctttacc acctatggta tcacctgggt gcgacagggc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt tcaatggtga cacaaacttt 180
gcacagaacc tccagaacag agtcaccctg accacagaca catccactag cacagcctat 240
atggaactga ggagcctgag atctgacgac acggccgttt attactgtgc gagaggggga 300
ggagctcgtc cggggaactt cttcttctac ggtatggacg tctggggcca ggggaccacg 360
gtcaccgtct cctca 375
<210> 573
<211> 125
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 573
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Asn Pro Gly Ala
1 5 10 15
Ser Val Arg Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr
20 25 30
Gly Ile Thr Trp Val Arg Gln Gly Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Phe Asn Gly Asp Thr Asn Phe Ala Gln Asn Leu
50 55 60
Gln Asn Arg Val Thr Leu Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Gly Gly Ala Arg Pro Gly Asn Phe Phe Phe Tyr Gly Met
100 105 110
Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<210> 574
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 574
ggttacacct ttaccaccta tggt 24
<210> 575
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 575
Gly Tyr Thr Phe Thr Thr Tyr Gly
1 5
<210> 576
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 576
atcagcgctt tcaatggtga caca 24
<210> 577
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 577
Ile Ser Ala Phe Asn Gly Asp Thr
1 5
<210> 578
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 578
gcgagagggg gaggagctcg tccggggaac ttcttcttct acggtatgga cgtc 54
<210> 579
<211> 18
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 579
Ala Arg Gly Gly Gly Ala Arg Pro Gly Asn Phe Phe Phe Tyr Gly Met
1 5 10 15
Asp Val
<210> 580
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 580
gatgttgtga tgactcagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgta gggccagtca gagttttgcc agctacttag cctggtacca acagaaacct 120
ggccaggctc ccaggctcct catctatgat acctcctaca gggccactgg cgtcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca acatcagcaa cctggagcct 240
gaagattttg cagtttatta ctgtcagcaa cgtggcaact ggccgctcac tttcggcgga 300
gggaccaagg tggaaatcaa a 321
<210> 581
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 581
Asp Val Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Phe Ala Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Tyr Arg Ala Thr Gly Val Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile Ser Asn Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Gly Asn Trp Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 582
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 582
cagagttttg ccagctac 18
<210> 583
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 583
Gln Ser Phe Ala Ser Tyr
1 5
<210> 584
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 584
gatacctcc 9
<210> 585
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 585
Asp Thr Ser
1
<210> 586
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 586
cagcaacgtg gcaactggcc gctcact 27
<210> 587
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 587
Gln Gln Arg Gly Asn Trp Pro Leu Thr
1 5
<210> 588
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 588
caggtgcagc tggtgcagtc tggaactgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttagc tacaatggtg tcacttgggt acgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acgatggtaa cacagactat 180
gcacagaagt tccaagacag aatcaccatg accacagaca catccacgag tacagcctac 240
atggaactga ggagccttag atctgacgac acggccgtct attactgtgc gaggtatagt 300
tggaacaacc actggttcga cccctggggc cagggaaccc tggtcaccgt ctcctca 357
<210> 589
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 589
Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Tyr Asn
20 25 30
Gly Val Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Asp Gly Asn Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Asp Arg Ile Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Ser Trp Asn Asn His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 590
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 590
ggttacacct ttagctacaa tggt 24
<210> 591
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 591
Gly Tyr Thr Phe Ser Tyr Asn Gly
1 5
<210> 592
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 592
atcagcgctt acgatggtaa caca 24
<210> 593
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 593
Ile Ser Ala Tyr Asp Gly Asn Thr
1 5
<210> 594
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 594
gcgaggtata gttggaacaa ccactggttc gacccc 36
<210> 595
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 595
Ala Arg Tyr Ser Trp Asn Asn His Trp Phe Asp Pro
1 5 10
<210> 596
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 596
gatattgtga tgactcagtc tccaggcacc ctgtctttgt ctccaggaga cggggccacc 60
ctctcctgca gggccagtca gagtgtttcc ggcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatttat ggtgcatcca acagggccac tggcatccca 180
gacaggttca ctggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta tttctgtcag cagagtgctt tctcaccgtg gacgttcggc 300
caagggacca agctggagat caaa 324
<210> 597
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 597
Asp Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Asp Gly Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Gly Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Thr
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Ser Ala Phe Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 598
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 598
cagagtgttt ccggcagcta c 21
<210> 599
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 599
Gln Ser Val Ser Gly Ser Tyr
1 5
<210> 600
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 600
ggtgcatcc 9
<210> 601
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 601
Gly Ala Ser
1
<210> 602
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 602
cagcagagtg ctttctcacc gtggacg 27
<210> 603
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 603
Gln Gln Ser Ala Phe Ser Pro Trp Thr
1 5
<210> 604
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 604
gaagtgcagc tggtgcagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt atgtacgaca tgcactgggt ccgccaaact 120
ataggaaaag gtctggagtg ggtctcagca attggtactg ctggtgacac atactatcca 180
ggctccgtga agggccgatt caccatctcc agagaaaatg ccaagaactc cttgtttctt 240
caaatgaaca gcctgagagc cggggacacg gctgtttatt actgtgtaag atccgggact 300
acagagtggt tcgacccctg gggccaggga accccggtca ctgtctcctc a 351
<210> 605
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 605
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Met Tyr
20 25 30
Asp Met His Trp Val Arg Gln Thr Ile Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Gly Thr Ala Gly Asp Thr Tyr Tyr Pro Gly Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Glu Asn Ala Lys Asn Ser Leu Phe Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Gly Asp Thr Ala Val Tyr Tyr Cys Val
85 90 95
Arg Ser Gly Thr Thr Glu Trp Phe Asp Pro Trp Gly Gln Gly Thr Pro
100 105 110
Val Thr Val Ser Ser
115
<210> 606
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 606
ggattcacct tcagtatgta cgac 24
<210> 607
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 607
Gly Phe Thr Phe Ser Met Tyr Asp
1 5
<210> 608
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 608
attggtactg ctggtgacac a 21
<210> 609
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 609
Ile Gly Thr Ala Gly Asp Thr
1 5
<210> 610
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 610
gtaagatccg ggactacaga gtggttcgac ccc 33
<210> 611
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 611
Val Arg Ser Gly Thr Thr Glu Trp Phe Asp Pro
1 5 10
<210> 612
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 612
gacatccggt tgacccagtc tccatcttcc gtgtctgcat ctgtgggaga cagagtcacc 60
atcacttgtc ggacgagtca gggtattagt agctggttag cctggtatca gcagaaacca 120
ggaaaagccc ctaacctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtctacag gctaacagtt tcccgtacac ttttggccag 300
gggaccaagg tggagatcaa a 321
<210> 613
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 613
Asp Ile Arg Leu Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Thr Ser Gln Gly Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Ala Asn Ser Phe Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 614
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 614
cagggtatta gtagctgg 18
<210> 615
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 615
Gln Gly Ile Ser Ser Trp
1 5
<210> 616
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 616
gctgcatcc 9
<210> 617
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 617
Ala Ala Ser
1
<210> 618
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 618
ctacaggcta acagtttccc gtacact 27
<210> 619
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 619
Leu Gln Ala Asn Ser Phe Pro Tyr Thr
1 5
<210> 620
<211> 369
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 620
caggtccagc tggtgcagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cgtctggatt caccttcagt agttatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt ttatggtatg atggaagtaa taaaaactat 180
gtagactccg tgaagggccg attcaccatc tcaagagaca attccaagaa cacgctttat 240
ctgcaaatga acagcctgag agccgaggac acggctgtgt attattgtgc gagagatcat 300
gattttagga gtggttatga ggggtggttc gacccctggg gccagggaac cctggtcacc 360
gtctcctca 369
<210> 621
<211> 123
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 621
Gln Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Leu Trp Tyr Asp Gly Ser Asn Lys Asn Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 622
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 622
ggattcacct tcagtagtta tggc 24
<210> 623
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 623
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 624
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 624
ttatggtatg atggaagtaa taaa 24
<210> 625
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 625
Leu Trp Tyr Asp Gly Ser Asn Lys
1 5
<210> 626
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 626
gcgagagatc atgattttag gagtggttat gaggggtggt tcgacccc 48
<210> 627
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 627
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
1 5 10 15
<210> 628
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 628
gaaattgtgc tgacgcagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttcgc agctacttag cctggtacca acagaaacct 120
ggccaggctc ccaggctcct catctatgat gcatccaaca gggccactgg catcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag cctagagcct 240
gaagattttg cagtttatta ctgtcaacac cgtagcaact ggcctcccac tttcggcgga 300
gggaccaagg tggaaatcaa a 321
<210> 629
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 629
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 630
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 630
cagagtgttc gcagctac 18
<210> 631
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 631
Gln Ser Val Arg Ser Tyr
1 5
<210> 632
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 632
gatgcatcc 9
<210> 633
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 633
Asp Ala Ser
1
<210> 634
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 634
caacaccgta gcaactggcc tcccact 27
<210> 635
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 635
Gln His Arg Ser Asn Trp Pro Pro Thr
1 5
<210> 636
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 636
caggtcacct tgaaggagtc gggcccagga ctggtgaagt cttcggagac cctgtccctc 60
acttgcactg tctctactgg ctccatcagc agtagtagtt actactgggc ctggatccgc 120
cagcccccag ggaagggact ggagtggatt gggagtatct attatagtgg gagtaaattc 180
tacagcccgt ccctcaagag tcgagtcacc atatacgttg acacgtccaa gaatcagttc 240
tccctgcaac tgagctcggt gaccgccgca gacacggctg tatattactg tgcgagacag 300
gtcggtgcaa tctttgacta ctggggccag ggaaccctgg tcaccgtctc ctca 354
<210> 637
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 637
Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Leu Val Lys Ser Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Thr Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ala Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Lys Phe Tyr Ser Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Tyr Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Gln Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Gln Val Gly Ala Ile Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 638
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 638
actggctcca tcagcagtag tagttactac 30
<210> 639
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 639
Thr Gly Ser Ile Ser Ser Ser Ser Tyr Tyr
1 5 10
<210> 640
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 640
atctattata gtgggagtaa a 21
<210> 641
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 641
Ile Tyr Tyr Ser Gly Ser Lys
1 5
<210> 642
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 642
gcgagacagg tcggtgcaat ctttgactac 30
<210> 643
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 643
Ala Arg Gln Val Gly Ala Ile Phe Asp Tyr
1 5 10
<210> 644
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 644
gccatccggt tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atctcttgcc gggccagtca gagtattagt agttggttgg cctggtatca gcacaaacca 120
gggaaagccc ctaaactcct gctctataag gcgtctagtt tagaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagag ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag tataatagtt attctcggac gttcggccaa 300
gggaccaagg tggagatcaa a 321
<210> 645
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 645
Ala Ile Arg Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln His Lys Pro Gly Lys Ala Pro Lys Leu Leu Leu
35 40 45
Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Arg
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 646
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 646
cagagtatta gtagttgg 18
<210> 647
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 647
Gln Ser Ile Ser Ser Trp
1 5
<210> 648
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 648
aaggcgtct 9
<210> 649
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 649
Lys Ala Ser
1
<210> 650
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 650
caacagtata atagttattc tcggacg 27
<210> 651
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 651
Gln Gln Tyr Asn Ser Tyr Ser Arg Thr
1 5
<210> 652
<211> 372
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 652
gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cctctggtta cacctttaac atctatggta tcagctgggt acgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acaatggtaa cacaaactat 180
gcacagaaac tccagggcag agtcaccatg accacagaaa catccacgac cacagcctac 240
atggagttga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagattct 300
gattggggaa ctccctacca ctactacggt atggacgtct ggggccaagg gaccacggtc 360
accgtctcct ca 372
<210> 653
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 653
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Asn Ile Tyr
20 25 30
Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Glu Thr Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ser Asp Trp Gly Thr Pro Tyr His Tyr Tyr Gly Met Asp
100 105 110
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 654
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 654
ggttacacct ttaacatcta tggt 24
<210> 655
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 655
Gly Tyr Thr Phe Asn Ile Tyr Gly
1 5
<210> 656
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 656
atcagcgctt acaatggtaa caca 24
<210> 657
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 657
Ile Ser Ala Tyr Asn Gly Asn Thr
1 5
<210> 658
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 658
gcgagagatt ctgattgggg aactccctac cactactacg gtatggacgt c 51
<210> 659
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 659
Ala Arg Asp Ser Asp Trp Gly Thr Pro Tyr His Tyr Tyr Gly Met Asp
1 5 10 15
Val
<210> 660
<211> 339
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 660
gatattgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60
atcaactgca agtccagcca gaatatttta tacacctcca acaataagaa ctacttagct 120
tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atttacccgg 180
aaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240
atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttataatact 300
cctcggacgt tcggccaagg gaccaaagtg gatatcaaa 339
<210> 661
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 661
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Asn Ile Leu Tyr Thr
20 25 30
Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Phe Thr Arg Lys Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Asn Thr Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Asp Ile
100 105 110
Lys
<210> 662
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 662
cagaatattt tatacacctc caacaataag aactac 36
<210> 663
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 663
Gln Asn Ile Leu Tyr Thr Ser Asn Asn Lys Asn Tyr
1 5 10
<210> 664
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 664
tgggcattt 9
<210> 665
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 665
Trp Ala Phe
1
<210> 666
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 666
cagcaatatt ataatactcc tcggacg 27
<210> 667
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 667
Gln Gln Tyr Tyr Asn Thr Pro Arg Thr
1 5
<210> 668
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 668
cagatcacct tgaaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctgatgg ctccatcaac agtggtggtt cctactggag ctggatccgc 120
cagcacccgg ggaagggcct ggagtggatt gggtacatca aatacagtgg gggcgtccac 180
tataacccgt ccctcaagag tcgaatcacc atatcagtgg acacgtctaa gaaccatttc 240
tccctgaaaa tgacctctgt gactgccgcg gacacggccg tgtatttctg tgcgagagca 300
cctggaagtc acacttttga tatctggggc caggggacaa tggtcaccgt ctcttca 357
<210> 669
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 669
Gln Ile Thr Leu Lys Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Ile Asn Ser Gly
20 25 30
Gly Ser Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Tyr Ser Gly Gly Val His Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Ile Thr Ile Ser Val Asp Thr Ser Lys Asn His Phe
65 70 75 80
Ser Leu Lys Met Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Phe
85 90 95
Cys Ala Arg Ala Pro Gly Ser His Thr Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 670
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 670
gatggctcca tcaacagtgg tggttcctac 30
<210> 671
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 671
Asp Gly Ser Ile Asn Ser Gly Gly Ser Tyr
1 5 10
<210> 672
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 672
atcaaataca gtgggggcgt c 21
<210> 673
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 673
Ile Lys Tyr Ser Gly Gly Val
1 5
<210> 674
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 674
gcgagagcac ctggaagtca cacttttgat atc 33
<210> 675
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 675
Ala Arg Ala Pro Gly Ser His Thr Phe Asp Ile
1 5 10
<210> 676
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 676
gatattgtga tgactcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc aacaactact tagcctggta ccagcagaaa 120
cctggccagg ctcccagact cctcatctat ggtacatcca atagggtcag tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgaactata ttattgtcag cagtatagta ggtcaccgat caccttcggc 300
caagggacac gactggagat taaa 324
<210> 677
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 677
Asp Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Asn Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Arg Val Ser Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Glu Leu Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 678
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 678
cagagtgtta gcaacaacta c 21
<210> 679
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 679
Gln Ser Val Ser Asn Asn Tyr
1 5
<210> 680
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 680
ggtacatcc 9
<210> 681
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 681
Gly Thr Ser
1
<210> 682
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 682
cagcagtata gtaggtcacc gatcacc 27
<210> 683
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 683
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 684
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 684
gaggtgcagc tggtgcagtc tgggggaggc ttggtacaac ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttaac aactttgcca tgacctgggt ccgccaggct 120
ccagggaagg gcctggagtg ggtctcaact attagtggta gtggcgttga cacatactgc 180
gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gaaagatggc 300
gccttctata gtggctacga acactactgg ggccagggaa caatggtcac cgtctcctca 360
<210> 685
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 685
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Asn Phe
20 25 30
Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Thr Ile Ser Gly Ser Gly Val Asp Thr Tyr Cys Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr Trp Gly Gln
100 105 110
Gly Thr Met Val Thr Val Ser Ser
115 120
<210> 686
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 686
ggattcacct ttaacaactt tgcc 24
<210> 687
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 687
Gly Phe Thr Phe Asn Asn Phe Ala
1 5
<210> 688
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 688
attagtggta gtggcgttga caca 24
<210> 689
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 689
Ile Ser Gly Ser Gly Val Asp Thr
1 5
<210> 690
<211> 39
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 690
gcgaaagatg gcgccttcta tagtggctac gaacactac 39
<210> 691
<211> 13
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 691
Ala Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr
1 5 10
<210> 692
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 692
gaaacgacac tcacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtacatcca acagggcctc tggcatccca 180
gacaggctca ttggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
tctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcg gacgttcggc 300
caagggacca aagtggatat caaa 324
<210> 693
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 693
Glu Thr Thr Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Arg Ala Ser Gly Ile Pro Asp Arg Leu Ile
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys
100 105
<210> 694
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 694
cagagtgtta gcagcagcta c 21
<210> 695
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 695
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 696
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 696
ggtacatcc 9
<210> 697
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 697
Gly Thr Ser
1
<210> 698
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 698
cagcagtatg gtagctcacc tcggacg 27
<210> 699
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 699
Gln Gln Tyr Gly Ser Ser Pro Arg Thr
1 5
<210> 700
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 700
gaggtgcagc tggtgcagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cgtctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatggtatg atggaagtaa taaatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa catgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc ggcttacgat 300
attttgattg gttattcccc ggttgactac tggggccagg gaaccctggt caccgtctcc 360
tca 363
<210> 701
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 701
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Met Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Tyr Asp Ile Leu Ile Gly Tyr Ser Pro Val Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 702
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 702
ggattcacct tcagtagcta tggc 24
<210> 703
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 703
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 704
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 704
atatggtatg atggaagtaa taaa 24
<210> 705
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 705
Ile Trp Tyr Asp Gly Ser Asn Lys
1 5
<210> 706
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 706
gcggcttacg atattttgat tggttattcc ccggttgact ac 42
<210> 707
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 707
Ala Ala Tyr Asp Ile Leu Ile Gly Tyr Ser Pro Val Asp Tyr
1 5 10
<210> 708
<211> 318
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 708
gatattgtga tgacccagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gactgttagt agcaacttag cctggttcca gcagaaacct 120
ggccaggctc ccagactcct catctatgat gcatccacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacagaa ttcactctca ccatcagcag cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggtacacttt tggccagggg 300
accaagctgg agatcaaa 318
<210> 709
<211> 106
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 709
Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Asn
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asn Asn Trp Tyr Thr
85 90 95
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 710
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 710
cagactgtta gtagcaac 18
<210> 711
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 711
Gln Thr Val Ser Ser Asn
1 5
<210> 712
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 712
gatgcatcc 9
<210> 713
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 713
Asp Ala Ser
1
<210> 714
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 714
cagcagtata ataactggta cact 24
<210> 715
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 715
Gln Gln Tyr Asn Asn Trp Tyr Thr
1 5
<210> 716
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 716
gaggtgcagc tggtgcagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccattacc agtggtggtt actactggac ctggatccgc 120
cagcacccag ggaagggcct ggaatggatt ggatacatca aatttagtgg gaacacctac 180
tacaacccgt ccctcaggag tcgagtcacc atatcacttg acacgtctaa gaatcagttc 240
tccctgaata tgacctctgt gactgccgcg gacacggccg tgtattattg tgcgagagca 300
cctggaagtc ataactttga catctggggc caagggacaa tggtcaccgt ctcttca 357
<210> 717
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 717
Glu Val Gln Leu Val Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Thr Ser Gly
20 25 30
Gly Tyr Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Phe Ser Gly Asn Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Arg Ser Arg Val Thr Ile Ser Leu Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Asn Met Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Gly Ser His Asn Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 718
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 718
ggtggctcca ttaccagtgg tggttactac 30
<210> 719
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 719
Gly Gly Ser Ile Thr Ser Gly Gly Tyr Tyr
1 5 10
<210> 720
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 720
atcaaattta gtgggaacac c 21
<210> 721
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 721
Ile Lys Phe Ser Gly Asn Thr
1 5
<210> 722
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 722
gcgagagcac ctggaagtca taactttgac atc 33
<210> 723
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 723
Ala Arg Ala Pro Gly Ser His Asn Phe Asp Ile
1 5 10
<210> 724
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 724
gccatccggt tgacccagtc tccagacacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtgt gagtattagt aataactatt tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag aagactggag 240
tctgcagatt ttgcaccgta ttactgtcag caatatagta ggtcaccgat caccttcggc 300
caagggacac gactggagat taaa 324
<210> 725
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 725
Ala Ile Arg Leu Thr Gln Ser Pro Asp Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Val Ser Ile Ser Asn Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Arg Leu Glu
65 70 75 80
Ser Ala Asp Phe Ala Pro Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 726
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 726
gtgagtatta gtaataacta t 21
<210> 727
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 727
Val Ser Ile Ser Asn Asn Tyr
1 5
<210> 728
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 728
ggtgcatcc 9
<210> 729
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 729
Gly Ala Ser
1
<210> 730
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 730
cagcaatata gtaggtcacc gatcacc 27
<210> 731
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 731
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 732
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 732
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcaac agtgttactt actactggac ctggatccgc 120
cagcacccag ggaggggcct agagtggatt gggtacatca aattcagtgg gagcacctac 180
tacaacccgt ccctcaaggg tcgagtcacc atatcagtgg acacgtctaa gaaccaattc 240
tcccttaaaa ttaactctgt gactgccgcg gacacggccg tgttttactg tgcgagagct 300
tctggaagtc atacttttga tatctggggc caagggacaa tggtcaccgt ctcctca 357
<210> 733
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 733
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Asn Ser Val
20 25 30
Thr Tyr Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Arg Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Phe Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Gly Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Ile Asn Ser Val Thr Ala Ala Asp Thr Ala Val Phe Tyr
85 90 95
Cys Ala Arg Ala Ser Gly Ser His Thr Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 734
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 734
ggtggctcca tcaacagtgt tacttactac 30
<210> 735
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 735
Gly Gly Ser Ile Asn Ser Val Thr Tyr Tyr
1 5 10
<210> 736
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 736
atcaaattca gtgggagcac c 21
<210> 737
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 737
Ile Lys Phe Ser Gly Ser Thr
1 5
<210> 738
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 738
gcgagagctt ctggaagtca tacttttgat atc 33
<210> 739
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 739
Ala Arg Ala Ser Gly Ser His Thr Phe Asp Ile
1 5 10
<210> 740
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 740
gaaacgacac tcacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc aacagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctct ggtgcgtcca gcagggtcac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttggaatgta ttactgtcag cagtatagta ggtcaccgat caccttcggc 300
caagggacca agctggagat caaa 324
<210> 741
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 741
Glu Thr Thr Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Asn Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Val Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Gly Met Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 742
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 742
cagagtgtta gcaacagcta c 21
<210> 743
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 743
Gln Ser Val Ser Asn Ser Tyr
1 5
<210> 744
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 744
ggtgcgtcc 9
<210> 745
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 745
Gly Ala Ser
1
<210> 746
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 746
cagcagtata gtaggtcacc gatcacc 27
<210> 747
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 747
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 748
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 748
gaggtgcagc tggtgcagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgcag cctctggagt caccttggat gattatgcca tgcactgggt ccggcaagct 120
ccagggaagg gcctggagtg ggtctcaagt attagttgga atagtggtag tataggctat 180
gcggactctg tgaagggccg cttcaccatc tccagagaca acgccaagaa ctccctgtat 240
ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagatggg 300
tggaacccgt actactttga ctattggggc cagggaataa cggtcaccgt ctcctca 357
<210> 749
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 749
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Leu Asp Asp Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ser Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Lys Asp Gly Trp Asn Pro Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Ile Thr Val Thr Val Ser Ser
115
<210> 750
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 750
ggagtcacct tggatgatta tgcc 24
<210> 751
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 751
Gly Val Thr Leu Asp Asp Tyr Ala
1 5
<210> 752
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 752
attagttgga atagtggtag tata 24
<210> 753
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 753
Ile Ser Trp Asn Ser Gly Ser Ile
1 5
<210> 754
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 754
gcaaaagatg ggtggaaccc gtactacttt gactat 36
<210> 755
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 755
Ala Lys Asp Gly Trp Asn Pro Tyr Tyr Phe Asp Tyr
1 5 10
<210> 756
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 756
gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga agtgatttag gctggtatca gcagaaacca 120
gggaaagccc ctaagcgcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacag cataatagtt accctctcac tttcggcgga 300
gggaccaagg tggaaatcaa a 321
<210> 757
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 757
Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser Asp
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln His Asn Ser Tyr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 758
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 758
cagggcatta gaagtgat 18
<210> 759
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 759
Gln Gly Ile Arg Ser Asp
1 5
<210> 760
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 760
gctgcatcc 9
<210> 761
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 761
Ala Ala Ser
1
<210> 762
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 762
ctacagcata atagttaccc tctcact 27
<210> 763
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 763
Leu Gln His Asn Ser Tyr Pro Leu Thr
1 5
<210> 764
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 764
cagatcacct tgaaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcgccg tctctggtga ctccttcagc agtggtaatt actactggag ctggatccgc 120
caacacccag ggaagggcct ggagtggatt gggtacatca agtacactgg gagcacctac 180
tacaacccgt ccctcaagag tcgagttatt atattagtag acacgtctaa gacccagttc 240
tccctgaagc tgagctctgt gaatgccgcg gacacggccg tgtattactg tgcgagagca 300
cctggaactc atgcttttga tgtttggggc caagggacaa tggtcaccgt ctcctca 357
<210> 765
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 765
Gln Ile Thr Leu Lys Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Asp Ser Phe Ser Ser Gly
20 25 30
Asn Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Tyr Thr Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Ile Ile Leu Val Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Asn Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Gly Thr His Ala Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 766
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 766
ggtgactcct tcagcagtgg taattactac 30
<210> 767
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 767
Gly Asp Ser Phe Ser Ser Gly Asn Tyr Tyr
1 5 10
<210> 768
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 768
atcaagtaca ctgggagcac c 21
<210> 769
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 769
Ile Lys Tyr Thr Gly Ser Thr
1 5
<210> 770
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 770
gcgagagcac ctggaactca tgcttttgat gtt 33
<210> 771
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 771
Ala Arg Ala Pro Gly Thr His Ala Phe Asp Val
1 5 10
<210> 772
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 772
gaaacgacac tcacgcagtc tccaggcacc ctgtctttgt ttccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agtagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgtgaca gactccactc tcaccatcag cagcctggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatagta ggtcaccgat caccttcggc 300
caagggacca agctggagat caaa 324
<210> 773
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 773
Glu Thr Thr Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Phe Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Val Thr Asp Ser Thr Leu Thr Ile Ser Ser Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 774
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 774
cagagtgtta gcagtagcta c 21
<210> 775
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 775
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 776
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 776
ggtgcatcc 9
<210> 777
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 777
Gly Ala Ser
1
<210> 778
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 778
cagcagtata gtaggtcacc gatcacc 27
<210> 779
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 779
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 780
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 780
gaagtgcagc tggtgcagtc tgggggagcc ttggtacaac ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttaac aactttgcca tgacctgggt ccgccaggct 120
ccagggaagg gcctggagtg ggtctcaact attagtggta gtggcgttga cacatactgc 180
gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgttc gaaagatggc 300
gccttctata gtggctacga acactactgg ggccagggaa ccacggtcac cgtctcctca 360
<210> 781
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 781
Glu Val Gln Leu Val Gln Ser Gly Gly Ala Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Asn Phe
20 25 30
Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Thr Ile Ser Gly Ser Gly Val Asp Thr Tyr Cys Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 782
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 782
ggattcacct ttaacaactt tgcc 24
<210> 783
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 783
Gly Phe Thr Phe Asn Asn Phe Ala
1 5
<210> 784
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 784
attagtggta gtggcgttga caca 24
<210> 785
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 785
Ile Ser Gly Ser Gly Val Asp Thr
1 5
<210> 786
<211> 39
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 786
tcgaaagatg gcgccttcta tagtggctac gaacactac 39
<210> 787
<211> 13
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 787
Ser Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr
1 5 10
<210> 788
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 788
gaaacgacac tcacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtacatcca acagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
tctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcg gacgttcggc 300
caagggacca aggtggagat caaa 324
<210> 789
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 789
Glu Thr Thr Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 790
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 790
cagagtgtta gcagcagcta c 21
<210> 791
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 791
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 792
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 792
ggtacatcc 9
<210> 793
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 793
Gly Thr Ser
1
<210> 794
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 794
cagcagtatg gtagctcacc tcggacg 27
<210> 795
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 795
Gln Gln Tyr Gly Ser Ser Pro Arg Thr
1 5
<210> 796
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 796
gaagtgcagc tggtgcagtc tggacctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc tactatggta tcagttggat acgacagacc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acgatggtaa cacagactat 180
gcacagaagt tccaagacag aatcaccatg accacagaca catcctcgac cacagcctac 240
atggaactga ggagcctgag atctgacgac acggccgtct attactgtgc gaggtatagt 300
tggaacaagc actggttcga cccctggggc cagggaacca tggtcaccgt ctcttca 357
<210> 797
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 797
Glu Val Gln Leu Val Gln Ser Gly Pro Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Tyr Tyr
20 25 30
Gly Ile Ser Trp Ile Arg Gln Thr Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Asp Gly Asn Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Asp Arg Ile Thr Met Thr Thr Asp Thr Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Ser Trp Asn Lys His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 798
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 798
ggttacacct ttacctacta tggt 24
<210> 799
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 799
Gly Tyr Thr Phe Thr Tyr Tyr Gly
1 5
<210> 800
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 800
atcagcgctt acgatggtaa caca 24
<210> 801
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 801
Ile Ser Ala Tyr Asp Gly Asn Thr
1 5
<210> 802
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 802
gcgaggtata gttggaacaa gcactggttc gacccc 36
<210> 803
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 803
Ala Arg Tyr Ser Trp Asn Lys His Trp Phe Asp Pro
1 5 10
<210> 804
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 804
gaaattgtga tgacacagtc tccaggcacc ctgtctttgt ctccagggga cagagccacc 60
ctctcctgca gggccagtca gagtgttacc ggcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccagact cctcatctat ggtgcatcca acagggccac tggcatccca 180
gacaggttca ctggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta tttctgtcaa cagtctgctt tctcaccgtg gacgttcggc 300
caggggacca aggtggaaat caaa 324
<210> 805
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 805
Glu Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Asp Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Gly Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Thr
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Ser Ala Phe Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 806
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 806
cagagtgtta ccggcagcta c 21
<210> 807
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 807
Gln Ser Val Thr Gly Ser Tyr
1 5
<210> 808
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 808
ggtgcatcc 9
<210> 809
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 809
Gly Ala Ser
1
<210> 810
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 810
caacagtctg ctttctcacc gtggacg 27
<210> 811
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 811
Gln Gln Ser Ala Phe Ser Pro Trp Thr
1 5
<210> 812
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 812
gaggtgcagc tggtgcagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgcag cctctggagt caccttggat gattatgcca tgcactgggt ccggcaagct 120
ccagggaagg gcctggagtg ggtctcaagt attagttgga atagtggtag tataggctat 180
gcggactctg tgaagggccg cttcaccatc tccagagaca acgccaagaa ctccctgtat 240
ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagatggg 300
tggaacccgt actactttga ctattggggc cagggaatac cggtcaccgt ctcctca 357
<210> 813
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 813
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Leu Asp Asp Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ser Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Lys Asp Gly Trp Asn Pro Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Ile Pro Val Thr Val Ser Ser
115
<210> 814
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 814
ggagtcacct tggatgatta tgcc 24
<210> 815
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 815
Gly Val Thr Leu Asp Asp Tyr Ala
1 5
<210> 816
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 816
attagttgga atagtggtag tata 24
<210> 817
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 817
Ile Ser Trp Asn Ser Gly Ser Ile
1 5
<210> 818
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 818
gcaaaagatg ggtggaaccc gtactacttt gactat 36
<210> 819
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 819
Ala Lys Asp Gly Trp Asn Pro Tyr Tyr Phe Asp Tyr
1 5 10
<210> 820
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 820
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga agtgatttag gctggtatca gcagaaacca 120
gggaaagccc ctaagcgcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacctatta ctgtctacag cataatagtt accctctcac tttcggcgga 300
gggaccaagc tggagatcaa a 321
<210> 821
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 821
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser Asp
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln His Asn Ser Tyr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 822
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 822
cagggcatta gaagtgat 18
<210> 823
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 823
Gln Gly Ile Arg Ser Asp
1 5
<210> 824
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 824
gctgcatcc 9
<210> 825
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 825
Ala Ala Ser
1
<210> 826
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 826
ctacagcata atagttaccc tctcact 27
<210> 827
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 827
Leu Gln His Asn Ser Tyr Pro Leu Thr
1 5
<210> 828
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 828
caggtacagc tgcagcagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcgctg tctctggtga ctccttcagc agtggtaatt actactggag ctggatccgc 120
caacacccag ggaagggcct ggagtggatt gggtacatca agtacactgg gagcacctac 180
tacaacccgt ccctcaagag tcgagttacc atattagtag acacgtctaa gacccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagca 300
cctggaactc atgtttttga tgtctggggc caagggacaa tggtcaccgt ctcttca 357
<210> 829
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 829
Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Asp Ser Phe Ser Ser Gly
20 25 30
Asn Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Tyr Thr Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Leu Val Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Gly Thr His Val Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 830
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 830
ggtgactcct tcagcagtgg taattactac 30
<210> 831
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 831
Gly Asp Ser Phe Ser Ser Gly Asn Tyr Tyr
1 5 10
<210> 832
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 832
atcaagtaca ctgggagcac c 21
<210> 833
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 833
Lys Tyr Thr Gly Ser Thr
1 5
<210> 834
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 834
gcgagagcac ctggaactca tgtttttgat gtc 33
<210> 835
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 835
Ala Arg Ala Pro Gly Thr His Val Phe Asp Val
1 5 10
<210> 836
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 836
gacatccagt tgacccagtc tccaggcacc ctgtctttgc ttccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agtagctatt tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgtgaca gacttcactc tcaccatcag cagcctggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatagta ggtcaccgat caccttcggc 300
caagggacca aggtggagat caaa 324
<210> 837
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 837
Asp Ile Gln Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Leu Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Val Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 838
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 838
cagagtgtta gcagtagcta t 21
<210> 839
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 839
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 840
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 840
ggtgcatcc 9
<210> 841
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 841
Gly Ala Ser
1
<210> 842
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 842
cagcagtata gtaggtcacc gatcacc 27
<210> 843
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 843
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 844
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 844
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggag ttggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacatcc attatagtgg gaacacccac 180
tacaatccga ccctcaagag tcgaattacc atatcagtag acacgtctaa gaaccagttc 240
tcccttgagg tgaactctgt gactgccgcg gacacggccg tatactactg tgcgaggaat 300
atggttcggg gagttcactg gttcgacccc tggggccagg gaaccacggt caccgtctcc 360
tca 363
<210> 845
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 845
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile His Tyr Ser Gly Asn Thr His Tyr Asn Pro Thr
50 55 60
Leu Lys Ser Arg Ile Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Glu Val Asn Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Asn Met Val Arg Gly Val His Trp Phe Asp Pro Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 846
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 846
ggtggctcca tcagcagtgg tggttactac 30
<210> 847
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 847
Gly Gly Ser Ile Ser Ser Gly Gly Tyr Tyr
1 5 10
<210> 848
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 848
atccattata gtgggaacac c 21
<210> 849
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 849
Ile His Tyr Ser Gly Asn Thr
1 5
<210> 850
<211> 39
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 850
gcgaggaata tggttcgggg agttcactgg ttcgacccc 39
<210> 851
<211> 13
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 851
Ala Arg Asn Met Val Arg Gly Val His Trp Phe Asp Pro
1 5 10
<210> 852
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 852
gaaatagtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga gagagccacc 60
ctcttctgtt gggccagtcg gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctct ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtata tttctgtcaa cagtatagta gttcaccgct cactttcggc 300
ggagggacca agctggagat caaa 324
<210> 853
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 853
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Phe Cys Trp Ala Ser Arg Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Tyr Ser Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 854
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 854
cggagtgtta gcagcagcta c 21
<210> 855
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 855
Arg Ser Val Ser Ser Ser Tyr
1 5
<210> 856
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 856
ggtgcatcc 9
<210> 857
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 857
Gly Ala Ser
1
<210> 858
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 858
caacagtata gtagttcacc gctcact 27
<210> 859
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 859
Gln Gln Tyr Ser Ser Ser Pro Leu Thr
1 5
<210> 860
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 860
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctagtga ctccatcagc agtggtaata actactggac ctggatccgc 120
cagcacccag ggaggggcct ggagtggatt gggtacatca aatacactgg gagcgcccac 180
tacaacccgt ccctcaagag tcgagtcacc atgtcagtag acacgtctaa gaatcagttc 240
tccctgaaaa tgacctctgt gactgacgcg gacacggccg tgtattattg tgcgagggca 300
cctggaagcc attcttttga tatatggggc cgagggacaa tggtcaccgt ctcctca 357
<210> 861
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 861
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Ser Asp Ser Ile Ser Ser Gly
20 25 30
Asn Asn Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Arg Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Tyr Thr Gly Ser Ala His Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Met Thr Ser Val Thr Asp Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Gly Ser His Ser Phe Asp Ile Trp Gly Arg Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 862
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 862
agtgactcca tcagcagtgg taataactac 30
<210> 863
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 863
Ser Asp Ser Ile Ser Ser Gly Asn Asn Tyr
1 5 10
<210> 864
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 864
atcaaataca ctgggagcgc c 21
<210> 865
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 865
Ile Lys Tyr Thr Gly Ser Ala
1 5
<210> 866
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 866
gcgagggcac ctggaagcca ttcttttgat ata 33
<210> 867
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 867
Ala Arg Ala Pro Gly Ser His Ser Phe Asp Ile
1 5 10
<210> 868
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 868
gatgttgtga tgacccagtc tccaggcacc ctgtttttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaacatcag cagactggag 240
cctgaagatt ttgcactgta ttactgtcag cagtatagta ggtcaccgat caccttcggc 300
caagggacac gactggagat taaa 324
<210> 869
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 869
Asp Val Val Met Thr Gln Ser Pro Gly Thr Leu Phe Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Leu Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 870
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 870
cagagtgtta gcagcagcta c 21
<210> 871
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 871
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 872
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 872
ggtgcatcc 9
<210> 873
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 873
Gly Ala Ser
1
<210> 874
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 874
cagcagtata gtaggtcacc gatcacc 27
<210> 875
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 875
Gln Gln Tyr Ser Arg Ser Pro Ile Thr
1 5
<210> 876
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 876
caggtgcagc tggtgcagtc tgggggaggc ttggtacaac ctggggggtc cctaagactc 60
tcctgtgcag cctctggatt cacctctaac aactttgcca tgacctgggt ccgccaggct 120
ccagggaagg gcctggagtg ggtctcaact attagtggta gtggcgttga cacatactgc 180
gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacactgtat 240
ctgcaaatga acagcctgag agtcgaggac acggccgtat attactgtgc taaagatggc 300
gccttctata gtggctacga acactactgg ggccagggaa ccctggtcac cgtctcctca 360
<210> 877
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 877
Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ser Asn Asn Phe
20 25 30
Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Thr Ile Ser Gly Ser Gly Val Asp Thr Tyr Cys Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 878
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 878
ggattcacct ctaacaactt tgcc 24
<210> 879
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 879
Gly Phe Thr Ser Asn Asn Phe Ala
1 5
<210> 880
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 880
attagtggta gtggcgttga caca 24
<210> 881
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 881
Ile Ser Gly Ser Gly Val Asp Thr
1 5
<210> 882
<211> 39
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 882
gctaaagatg gcgccttcta tagtggctac gaacactac 39
<210> 883
<211> 13
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 883
Ala Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr
1 5 10
<210> 884
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 884
gatgttgtga tgacccagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtacatcca acagggcctc tggcatccca 180
gacaagttca ttggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
tctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcg gacgttcggc 300
caagggacca aagtggatat caaa 324
<210> 885
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 885
Asp Val Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Arg Ala Ser Gly Ile Pro Asp Lys Phe Ile
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys
100 105
<210> 886
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 886
cagagtgtta gcagcagcta c 21
<210> 887
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 887
Gln Ser Val Ser Ser Ser Tyr
1 5
<210> 888
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 888
ggtacatcc 9
<210> 889
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 889
Gly Thr Ser
1
<210> 890
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 890
cagcagtatg gtagctcacc tcggacg 27
<210> 891
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 891
Gln Gln Tyr Gly Ser Ser Pro Arg Thr
1 5
<210> 892
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 892
caggtgcagc tgcaggagtc cggccccggc ctggtgaagc cctcccagac cctgtccctg 60
acctgcaccg tgtccggcgg ctccatcggc tccggcggct actactggtc ctggatccgg 120
cagcaccccg gcaagggcct ggagtggatc ggctacgtgc actactccgg caacacctac 180
tacaacccct ccctgaagtc ccgggtgacc atctccgtgg acacctccaa gaaccagttc 240
tccctgaagc tgtcctccgt gaccgccgcc gacaccgccg tgtactactg cgcccgggcc 300
ccccggggct accactactt cgcctactgg ggccagggca ccctggtgac cgtgtcctcc 360
<210> 893
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 893
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Gly Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Val His Tyr Ser Gly Asn Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 894
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 894
gagatcgtgc tgacccagtc ccccggcacc ctgtccctgt cccccggcga gcgggccacc 60
ctgtcctgcc gggcctccca gtccgtgtcc tcctcctacc tggcctggta ccagcagaag 120
cccggccagg ccccccggct gctgatctac ggcgcctcct cccgggccac cggcatcccc 180
gaccggttct ccggctccgg ctccggcacc gacttcaccc tgaccatctc ccggctggag 240
cccgaggact tcgccgtgta ctactgccag cagtacggct cctcccccct gaccttcggc 300
ggcggcacca aggtggagat caag 324
<210> 895
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 895
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 896
<211> 369
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 896
caggtgcagc tggtggagtc cggcggcggc gtggtgcagc ccggccggtc cctgcggctg 60
tcctgcgccg cctccggctt caccttctcc tcctacggca tgcactgggt gcggcaggcc 120
cccggcaagg gcctggagtg ggtggccgtg ctgtggtacg acggcaccaa caagtactac 180
gccgactccg tgaagggccg gttcaccatc tcccgggaca actccaagaa caccctgtac 240
ctgcagatga actccctgcg ggccgaggac accgccgtgt actactgcgc ccgggaccac 300
gacttccggt ccggctacga gggctggttc gacccctggg gccagggcac cctggtgacc 360
gtgtcctcc 369
<210> 897
<211> 123
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 897
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Leu Trp Tyr Asp Gly Thr Asn Lys Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 898
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 898
gagatcgtgc tgacccagtc ccccgccacc ctgtccctgt cccccggcga gcgggccacc 60
ctgtcctgcc gggcctccca gtccgtgtcc tcctacctgg cctggtacca gcagaagccc 120
ggccaggccc cccggctgct gatctacgac gcctccaacc gggccaccgg catccccgcc 180
cggttctccg gctccggctc cggcaccgac ttcaccctga ccatctcctc cctggagccc 240
gaggacttcg ccgtgtacta ctgccagcac cggtccaact ggccccccac cttcggcggc 300
ggcaccaagg tggagatcaa g 321
<210> 899
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 899
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 900
<211> 369
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 900
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cgtctggatt caccttcagt agttatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtgtcattt ttatggtatg atggaactaa taaaaactat 180
gtagagtccg tgaagggccg attcaccatc tcaagagaca attccaagaa tatgctgtat 240
ctggaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatcac 300
gattttagga gtggttatga ggggtggttc gacccctggg gccagggaac cctggtcacc 360
gtctcctca 369
<210> 901
<211> 123
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 901
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Phe Leu Trp Tyr Asp Gly Thr Asn Lys Asn Tyr Val Glu Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Met Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp His Asp Phe Arg Ser Gly Tyr Glu Gly Trp Phe Asp Pro
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 902
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 902
gaaatagtgt tgacacagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agctacttag cctggtacca acagaaacct 120
ggccaggctc ccaggctcct catctatgat gcatccaaca gggccactgg catcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag cctagagcct 240
gaagattttg cagtttatta ctgtcaacac cgtagcaact ggcctcccac tttcggcgga 300
gggaccaagg tggaaatcaa a 321
<210> 903
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 903
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 904
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 904
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggag ttggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacatcc attatagtgg gaacacccac 180
tacaatccga ccctcaagag tcgaattacc atatcagtag acacgtctaa gaaccagttc 240
tcccttgagg tgaactctgt gactgccgcg gacacggccg tatactactg tgcgaggaat 300
atggttcggg gagttcactg gttcgacccc tggggccagg gaaccacggt caccgtctcc 360
tca 363
<210> 905
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 905
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile His Tyr Ser Gly Asn Thr His Tyr Asn Pro Thr
50 55 60
Leu Lys Ser Arg Ile Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Glu Val Asn Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Asn Met Val Arg Gly Val His Trp Phe Asp Pro Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 906
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 906
gaaatagtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga gagagccacc 60
ctcttctgtt gggccagtcg gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctct ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtata tttctgtcaa cagtatagta gttcaccgct cactttcggc 300
ggagggacca agctggagat caaa 324
<210> 907
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 907
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Phe Cys Trp Ala Ser Arg Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Tyr Ser Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 908
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 908
caggtgcagc tgcaggagtc cggccccggc ctggtgaagc cctcccagac cctgtccctg 60
acctgcaccg tgtccggcgg ctccatctcc tccggcggct actactggtc ctggatccgg 120
cagcaccccg gcaagggcct ggagtggatc ggctacatcc actactccgg caacacctac 180
tacaacccct ccctgaagtc ccgggtgacc atctccgtgg acacctccaa gaaccagttc 240
tccctgaagc tgtcctccgt gaccgccgcc gacaccgccg tgtactactg cgcccggaac 300
atggtgcggg gcgtgcactg gttcgacccc tggggccagg gcaccctggt gaccgtgtcc 360
tcc 363
<210> 909
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 909
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile His Tyr Ser Gly Asn Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Asn Met Val Arg Gly Val His Trp Phe Asp Pro Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 910
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 910
gagatcgtgc tgacccagtc ccccggcacc ctgtccctgt cccccggcga gcgggccacc 60
ctgtcctgcc gggcctcccg gtccgtgtcc tcctcctacc tggcctggta ccagcagaag 120
cccggccagg ccccccggct gctgatctac ggcgcctcct cccgggccac cggcatcccc 180
gaccggttct ccggctccgg ctccggcacc gacttcaccc tgaccatctc ccggctggag 240
cccgaggact tcgccgtgta ctactgccag cagtactcct cctcccccct gaccttcggc 300
ggcggcacca aggtggagat caag 324
<210> 911
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 911
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Arg Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Ser Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 912
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 912
caggtgcagc tgcaggagtc gggcctagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcagc agtggtggtt actactggag ttggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacatcc attatagtgg gaacacccac 180
tacaatccga ccctcaagag tcgaattacc atatcagtag acacgtctaa gaaccagttc 240
tcccttgagg tgaactctgt gactgccgcg gacacggccg tatactactg tgcgaggaat 300
atggttcggg gagttcactg gttcgacccc tggggccagg gaaccctggt caccgtctcc 360
tca 363
<210> 913
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 913
Gln Val Gln Leu Gln Glu Ser Gly Leu Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile His Tyr Ser Gly Asn Thr His Tyr Asn Pro Thr
50 55 60
Leu Lys Ser Arg Ile Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Glu Val Asn Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Asn Met Val Arg Gly Val His Trp Phe Asp Pro Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 914
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 914
gaaatagtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga gagagccacc 60
ctcttctgtt gggccagtcg gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctct ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtata tttctgtcaa cagtatagta gttcaccgct cactttcggc 300
ggagggacca aggtggaaat caaa 324
<210> 915
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 915
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Phe Cys Trp Ala Ser Arg Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Tyr Ser Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 916
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 916
caggtgcagc tgcaggagtc cggccccggc ctggtgaagc cctcccagac cctgtccctg 60
acctgcaccg tgtccggcgg ctccatcacc tccggcggct actactggtc ctggatccgg 120
cagcaccccg gcaagggcct ggagtggatc ggctacatca agttctccgg caacacctac 180
tacaacccct ccctgaagtc ccgggtgacc atctccgtgg acacctccaa gaaccagttc 240
tccctgaagc tgtcctccgt gaccgccgcc gacaccgccg tgtactactg cgcccgggcc 300
cccggctccc acaacttcga catctggggc cagggcacca tggtgaccgt gtcctcc 357
<210> 917
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 917
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Thr Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Phe Ser Gly Asn Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Gly Ser His Asn Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 918
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 918
gagatcgtgc tgacccagtc ccccggcacc ctgtccctgt cccccggcga gcgggccacc 60
ctgtcctgcc gggcctccgt gtccatctcc aacaactacc tggcctggta ccagcagaag 120
cccggccagg ccccccggct gctgatctac ggcgcctcct cccgggccac cggcatcccc 180
gaccggttct ccggctccgg ctccggcacc gacttcaccc tgaccatccg gcggctggag 240
cccgaggact tcgcccccta ctactgccag cagtactccc ggtcccccat caccttcggc 300
cagggcaccc ggctggagat caag 324
<210> 919
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 919
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Val Ser Ile Ser Asn Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Pro Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 920
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 920
gaggtgcagc tggtggagtc cggcggcggc ctggtgcagc ccggcggctc cctgcggctg 60
tcctgcgccg cctccggctt caccttcaac aacttcgcca tgtcctgggt gcggcaggcc 120
cccggcaagg gcctggagtg ggtgtccgcc atctccggct ccggcgtgga cacctactac 180
gccgactccg tgaagggccg gttcaccatc tcccgggaca actccaagaa caccctgtac 240
ctgcagatga actccctgcg ggccgaggac accgccgtgt actactgctc caaggacggc 300
gccttctact ccggctacga gcactactgg ggccagggca ccctggtgac cgtgtcctcc 360
<210> 921
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 921
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Asn Phe
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Val Asp Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 922
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 922
gagatcgtgc tgacccagtc ccccggcacc ctgtccctgt cccccggcga gcgggccacc 60
ctgtcctgcc gggcctccca gtccgtgtcc tcctcctacc tggcctggta ccagcagaag 120
cccggccagg ccccccggct gctgatctac ggcacctcct cccgggccac cggcatcccc 180
gaccggttct ccggctccgg ctccggcacc gacttcaccc tgaccatctc ccggctggag 240
cccgaggact tcgccgtgta ctactgccag cagtacggct cctccccccg gaccttcggc 300
cagggcacca aggtggagat caag 324
<210> 923
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 923
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 924
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 924
caggtgcagc tggtgcagtc cggcgccgag gtgaagaagc ccggcgcctc cgtgaaggtg 60
tcctgcaagg cctccggcta caccttcacc tactacggca tctcctgggt gcggcaggcc 120
cccggccagg gcctggagtg gatgggctgg atctccgcct acgacggcaa caccaactac 180
gcccagaagc tgcagggccg ggtgaccatg accaccgaca cctccacctc caccgcctac 240
atggagctgc ggtccctgcg gtccgacgac accgccgtgt actactgcgc ccggtactcc 300
tggaacaagc actggttcga cccctggggc cagggcaccc tggtgaccgt gtcctcc 357
<210> 925
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 925
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Tyr Tyr
20 25 30
Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Asp Gly Asn Thr Asn Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Ser Trp Asn Lys His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 926
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 926
gagatcgtgc tgacccagtc ccccggcacc ctgtccctgt cccccggcga gcgggccacc 60
ctgtcctgcc gggcctccca gtccgtgacc ggctcctacc tggcctggta ccagcagaag 120
cccggccagg ccccccggct gctgatctac ggcgcctcct cccgggccac cggcatcccc 180
gaccggttct ccggctccgg ctccggcacc gacttcaccc tgaccatctc ccggctggag 240
cccgaggact tcgccgtgta ctactgccag cagtccgcct tctccccctg gaccttcggc 300
cagggcacca aggtggagat caag 324
<210> 927
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 927
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Gly Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ala Phe Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 928
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(8)
<223> Xaa = Any amino acid or absent
<400> 928
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 929
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(8)
<223> Xaa = Any amino acid or absent
<400> 929
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 930
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(16)
<223> Xaa = Any amino acid or absent
<400> 930
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5 10 15
<210> 931
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(7)
<223> Xaa = Any amino acid or absent
<400> 931
Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 932
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(3)
<223> Xaa = Any amino acid or absent
<400> 932
Xaa Xaa Xaa
1
<210> 933
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(9)
<223> Xaa = Any amino acid or absent
<400> 933
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 934
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 934
caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccattacc agtggtggtt actactggac ctggatccgc 120
cagcacccag ggaagggcct ggaatggatt ggatacatca aatttagtgg gaacacctac 180
tacaacccgt ccctcaggag tcgagtcacc atatcacttg acacgtctaa gaatcagttc 240
tccctgaata tgacctctgt gactgccgcg gacacggccg tgtattattg tgcgagagca 300
cctggaagtc ataactttga catctggggc caagggacaa tggtcaccgt ctcttca 357
<210> 935
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 935
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Thr Ser Gly
20 25 30
Gly Tyr Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Lys Phe Ser Gly Asn Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Arg Ser Arg Val Thr Ile Ser Leu Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Asn Met Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Gly Ser His Asn Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser
115
<210> 936
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 936
gaaatcgtgt tgacccagtc tccagacacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtgt gagtattagt aataactatt tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag aagactggag 240
tctgcagatt ttgcaccgta ttactgtcag caatatagta ggtcaccgat caccttcggc 300
caagggacac gactggagat taaa 324
<210> 937
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 937
Glu Ile Val Leu Thr Gln Ser Pro Asp Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Val Ser Ile Ser Asn Asn
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Arg Leu Glu
65 70 75 80
Ser Ala Asp Phe Ala Pro Tyr Tyr Cys Gln Gln Tyr Ser Arg Ser Pro
85 90 95
Ile Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 938
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 938
gaagtgcagc tggtggagtc tgggggagcc ttggtacaac ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttaac aactttgcca tgacctgggt ccgccaggct 120
ccagggaagg gcctggagtg ggtctcaact attagtggta gtggcgttga cacatactgc 180
gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgttc gaaagatggc 300
gccttctata gtggctacga acactactgg ggccagggaa ccctggtcac cgtctcctca 360
<210> 939
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 939
Glu Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Asn Phe
20 25 30
Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Thr Ile Ser Gly Ser Gly Val Asp Thr Tyr Cys Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Lys Asp Gly Ala Phe Tyr Ser Gly Tyr Glu His Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 940
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 940
gaaattgtgc tcacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatctat ggtacatcca acagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
tctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcg gacgttcggc 300
caagggacca aggtggagat caaa 324
<210> 941
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 941
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 942
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 942
caggtgcagc tggtgcagtc tggacctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc tactatggta tcagttggat acgacagacc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acgatggtaa cacagactat 180
gcacagaagt tccaagacag aatcaccatg accacagaca catcctcgac cacagcctac 240
atggaactga ggagcctgag atctgacgac acggccgtct attactgtgc gaggtatagt 300
tggaacaagc actggttcga cccctggggc cagggaaccc tggtcaccgt ctcttca 357
<210> 943
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 943
Gln Val Gln Leu Val Gln Ser Gly Pro Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Tyr Tyr
20 25 30
Gly Ile Ser Trp Ile Arg Gln Thr Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ala Tyr Asp Gly Asn Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Asp Arg Ile Thr Met Thr Thr Asp Thr Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Ser Trp Asn Lys His Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 944
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 944
gaaattgtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga cagagccacc 60
ctctcctgca gggccagtca gagtgttacc ggcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccagact cctcatctat ggtgcatcca acagggccac tggcatccca 180
gacaggttca ctggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta tttctgtcaa cagtctgctt tctcaccgtg gacgttcggc 300
caggggacca aggtggaaat caaa 324
<210> 945
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 945
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Asp Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Gly Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Thr
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Ser Ala Phe Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 946
<211> 361
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 946
caggtgcagt tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60
acctgcactg tctctggtgg ctccatcggc agtggtggtt actactggag ctggatccgc 120
cagcacccag ggaagggcct ggagtggatt gggtacgtcc attacagtgg gaacacccac 180
tacaacccgt ccctcaagag tcgactttcc atatcaatag acacgtctaa gatccagttc 240
tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagagcc 300
ccccgtggat accattactt tgcctactgg ggccagggaa ccctggtcac cgtctcctca 360
g 361
<210> 947
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 947
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Gly Ser Gly
20 25 30
Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Val His Tyr Ser Gly Asn Thr His Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Ser Ile Ser Ile Asp Thr Ser Lys Ile Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Ala Pro Arg Gly Tyr His Tyr Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 948
<211> 325
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 948
gaaattgtgt tgacacaatc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120
cctggccagg ctcccaggct cctcatcttt ggtgcatcca gcagggccac tggcatccca 180
gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240
cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct cactttcggc 300
ggagggacca aggtggagat caaac 325
<210> 949
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 949
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 950
<211> 330
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 950
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
225 230 235 240
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 951
<211> 327
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 951
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
<210> 952
<211> 327
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 952
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
<210> 953
<211> 544
<212> PRT
<213> Homo sapiens
<400> 953
Met Gly Ser Arg Cys Ala Leu Ala Leu Ala Val Leu Ser Ala Leu Leu
1 5 10 15
Cys Gln Val Trp Ser Ser Gly Val Phe Glu Leu Lys Leu Gln Glu Phe
20 25 30
Val Asn Lys Lys Gly Leu Leu Gly Asn Arg Asn Cys Cys Arg Gly Gly
35 40 45
Ala Gly Pro Pro Pro Cys Ala Cys Arg Thr Phe Phe Arg Val Cys Leu
50 55 60
Lys His Tyr Gln Ala Ser Val Ser Pro Glu Pro Pro Cys Thr Tyr Gly
65 70 75 80
Ser Ala Val Thr Pro Val Leu Gly Val Asp Ser Phe Ser Leu Pro Asp
85 90 95
Gly Gly Gly Ala Asp Ser Ala Phe Ser Asn Pro Ile Arg Phe Pro Phe
100 105 110
Gly Phe Thr Trp Pro Gly Thr Phe Ser Leu Ile Ile Glu Ala Leu His
115 120 125
Thr Asp Ser Pro Asp Asp Leu Ala Thr Glu Asn Pro Glu Arg Leu Ile
130 135 140
Ser Arg Leu Ala Thr Gln Arg His Leu Thr Val Gly Glu Glu Trp Ser
145 150 155 160
Gln Asp Leu His Ser Ser Gly Arg Thr Asp Leu Lys Tyr Ser Tyr Arg
165 170 175
Phe Val Cys Asp Glu His Tyr Tyr Gly Glu Gly Cys Ser Val Phe Cys
180 185 190
Arg Pro Arg Asp Asp Ala Phe Gly His Phe Thr Cys Gly Glu Arg Gly
195 200 205
Glu Lys Val Cys Asn Pro Gly Trp Lys Gly Pro Tyr Cys Thr Glu Pro
210 215 220
Ile Cys Leu Pro Gly Cys Asp Glu Gln His Gly Phe Cys Asp Lys Pro
225 230 235 240
Gly Glu Cys Lys Cys Arg Val Gly Trp Gln Gly Arg Tyr Cys Asp Glu
245 250 255
Cys Ile Arg Tyr Pro Gly Cys Leu His Gly Thr Cys Gln Gln Pro Trp
260 265 270
Gln Cys Asn Cys Gln Glu Gly Trp Gly Gly Leu Phe Cys Asn Gln Asp
275 280 285
Leu Asn Tyr Cys Thr His His Lys Pro Cys Lys Asn Gly Ala Thr Cys
290 295 300
Thr Asn Thr Gly Gln Gly Ser Tyr Thr Cys Ser Cys Arg Pro Gly Tyr
305 310 315 320
Thr Gly Ala Thr Cys Glu Leu Gly Ile Asp Glu Cys Asp Pro Ser Pro
325 330 335
Cys Lys Asn Gly Gly Ser Cys Thr Asp Leu Glu Asn Ser Tyr Ser Cys
340 345 350
Thr Cys Pro Pro Gly Phe Tyr Gly Lys Ile Cys Glu Leu Ser Ala Met
355 360 365
Thr Cys Ala Asp Gly Pro Cys Phe Asn Gly Gly Arg Cys Ser Asp Ser
370 375 380
Pro Asp Gly Gly Tyr Ser Cys Arg Cys Pro Val Gly Tyr Ser Gly Phe
385 390 395 400
Asn Cys Glu Lys Lys Ile Asp Tyr Cys Ser Ser Ser Pro Cys Ser Asn
405 410 415
Gly Ala Lys Cys Val Asp Leu Gly Asp Ala Tyr Leu Cys Arg Cys Gln
420 425 430
Ala Gly Phe Ser Gly Arg His Cys Asp Asp Asn Val Asp Asp Cys Ala
435 440 445
Ser Ser Pro Cys Ala Asn Gly Gly Thr Cys Arg Asp Gly Val Asn Asp
450 455 460
Phe Ser Cys Thr Cys Pro Pro Gly Tyr Thr Gly Arg Asn Cys Ser Ala
465 470 475 480
Pro Val Ser Arg Cys Glu His Ala Pro Cys His Asn Gly Ala Thr Cys
485 490 495
His Glu Arg Gly His Arg Tyr Val Cys Glu Cys Ala Arg Gly Tyr Gly
500 505 510
Gly Pro Asn Cys Gln Phe Leu Leu Pro Glu Leu Pro Pro Gly Pro Ala
515 520 525
Val Val Asp Leu Thr Glu Lys Leu Glu Gly Gln Gly Gly Pro Phe Pro
530 535 540
<210> 954
<211> 490
<212> PRT
<213> Homo sapiens
<400> 954
Met Val Ser Pro Arg Met Ser Gly Leu Leu Ser Gln Thr Val Ile Leu
1 5 10 15
Ala Leu Ile Phe Leu Pro Gln Thr Arg Pro Ala Gly Val Phe Glu Leu
20 25 30
Gln Ile His Ser Phe Gly Pro Gly Pro Gly Pro Gly Ala Pro Arg Ser
35 40 45
Pro Cys Ser Ala Arg Leu Pro Cys Arg Leu Phe Phe Arg Val Cys Leu
50 55 60
Lys Pro Gly Leu Ser Glu Glu Ala Ala Glu Ser Pro Cys Ala Leu Gly
65 70 75 80
Ala Ala Leu Ser Ala Arg Gly Pro Val Tyr Thr Glu Gln Pro Gly Ala
85 90 95
Pro Ala Pro Asp Leu Pro Leu Pro Asp Gly Leu Leu Gln Val Pro Phe
100 105 110
Arg Asp Ala Trp Pro Gly Thr Phe Ser Phe Ile Ile Glu Thr Trp Arg
115 120 125
Glu Glu Leu Gly Asp Gln Ile Gly Gly Pro Ala Trp Ser Leu Leu Ala
130 135 140
Arg Val Ala Gly Arg Arg Arg Leu Ala Ala Gly Gly Pro Trp Ala Arg
145 150 155 160
Asp Ile Gln Arg Ala Gly Ala Trp Glu Leu Arg Phe Ser Tyr Arg Ala
165 170 175
Arg Cys Glu Pro Pro Ala Val Gly Thr Ala Cys Thr Arg Leu Cys Arg
180 185 190
Pro Arg Ser Ala Pro Ser Arg Cys Gly Pro Gly Leu Arg Pro Cys Ala
195 200 205
Pro Leu Glu Asp Glu Cys Glu Ala Pro Pro Val Cys Arg Ala Gly Cys
210 215 220
Ser Pro Glu His Gly Phe Cys Glu Gln Pro Gly Glu Cys Arg Cys Leu
225 230 235 240
Glu Gly Trp Thr Gly Pro Leu Cys Thr Val Pro Val Ser Thr Ser Ser
245 250 255
Cys Leu Ser Pro Arg Gly Pro Ser Ser Ala Thr Thr Gly Cys Leu Val
260 265 270
Pro Gly Pro Gly Pro Cys Asp Gly Asn Pro Cys Ala Asn Gly Gly Ser
275 280 285
Cys Ser Glu Thr Pro Arg Ser Phe Glu Cys Thr Cys Pro Arg Gly Phe
290 295 300
Tyr Gly Leu Arg Cys Glu Val Ser Gly Val Thr Cys Ala Asp Gly Pro
305 310 315 320
Cys Phe Asn Gly Gly Leu Cys Val Gly Gly Ala Asp Pro Asp Ser Ala
325 330 335
Tyr Ile Cys His Cys Pro Pro Gly Phe Gln Gly Ser Asn Cys Glu Lys
340 345 350
Arg Val Asp Arg Cys Ser Leu Gln Pro Cys Arg Asn Gly Gly Leu Cys
355 360 365
Leu Asp Leu Gly His Ala Leu Arg Cys Arg Cys Arg Ala Gly Phe Ala
370 375 380
Gly Pro Arg Cys Glu His Asp Leu Asp Asp Cys Ala Gly Arg Ala Cys
385 390 395 400
Ala Asn Gly Gly Thr Cys Val Glu Gly Gly Gly Ala His Arg Cys Ser
405 410 415
Cys Ala Leu Gly Phe Gly Gly Arg Asp Cys Arg Glu Arg Ala Asp Pro
420 425 430
Cys Ala Ala Arg Pro Cys Ala His Gly Gly Arg Cys Tyr Ala His Phe
435 440 445
Ser Gly Leu Val Cys Ala Cys Ala Pro Gly Tyr Met Gly Ala Arg Cys
450 455 460
Glu Phe Pro Val His Pro Asp Gly Ala Ser Ala Leu Pro Ala Ala Pro
465 470 475 480
Pro Gly Leu Arg Pro Gly Asp Pro Gln Arg
485 490
<210> 955
<211> 527
<212> PRT
<213> Mus musculus
<400> 955
Met Thr Pro Ala Ser Arg Ser Ala Cys Arg Trp Ala Leu Leu Leu Leu
1 5 10 15
Ala Val Leu Trp Pro Gln Gln Arg Ala Ala Gly Ser Gly Ile Phe Gln
20 25 30
Leu Arg Leu Gln Glu Phe Val Asn Gln Arg Gly Met Leu Ala Asn Gly
35 40 45
Gln Ser Cys Glu Pro Gly Cys Arg Thr Phe Phe Arg Ile Cys Leu Lys
50 55 60
His Phe Gln Ala Thr Phe Ser Glu Gly Pro Cys Thr Phe Gly Asn Val
65 70 75 80
Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Val Val Arg Asp Lys Asn
85 90 95
Ser Gly Ser Gly Arg Asn Pro Leu Gln Leu Pro Phe Asn Phe Thr Trp
100 105 110
Pro Gly Thr Phe Ser Leu Asn Ile Gln Ala Trp His Thr Pro Gly Asp
115 120 125
Asp Leu Arg Pro Glu Thr Ser Pro Gly Asn Ser Leu Ile Ser Gln Ile
130 135 140
Ile Ile Gln Gly Ser Leu Ala Val Gly Lys Ile Trp Arg Thr Asp Glu
145 150 155 160
Gln Asn Asp Thr Leu Thr Arg Leu Ser Tyr Ser Tyr Arg Val Ile Cys
165 170 175
Ser Asp Asn Tyr Tyr Gly Glu Ser Cys Ser Arg Leu Cys Lys Lys Arg
180 185 190
Asp Asp His Phe Gly His Tyr Glu Cys Gln Pro Asp Gly Ser Leu Ser
195 200 205
Cys Leu Pro Gly Trp Thr Gly Lys Tyr Cys Asp Gln Pro Ile Cys Leu
210 215 220
Ser Gly Cys His Glu Gln Asn Gly Tyr Cys Ser Lys Pro Asp Glu Cys
225 230 235 240
Ile Cys Arg Pro Gly Trp Gln Gly Arg Leu Cys Asn Glu Cys Ile Pro
245 250 255
His Asn Gly Cys Arg His Gly Thr Cys Ser Ile Pro Trp Gln Cys Ala
260 265 270
Cys Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp Gln Asp Leu Asn Tyr
275 280 285
Cys Thr His His Ser Pro Cys Lys Asn Gly Ser Thr Cys Ser Asn Ser
290 295 300
Gly Pro Lys Gly Tyr Thr Cys Thr Cys Leu Pro Gly Tyr Thr Gly Glu
305 310 315 320
His Cys Glu Leu Gly Leu Ser Lys Cys Ala Ser Asn Pro Cys Arg Asn
325 330 335
Gly Gly Ser Cys Lys Asp Gln Glu Asn Ser Tyr His Cys Leu Cys Pro
340 345 350
Pro Gly Tyr Tyr Gly Gln His Cys Glu His Ser Thr Leu Thr Cys Ala
355 360 365
Asp Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg Glu Arg Asn Gln Gly
370 375 380
Ser Ser Tyr Ala Cys Glu Cys Pro Pro Asn Phe Thr Gly Ser Asn Cys
385 390 395 400
Glu Lys Lys Val Asp Arg Cys Thr Ser Asn Pro Cys Ala Asn Gly Gly
405 410 415
Gln Cys Gln Asn Arg Gly Pro Ser Arg Thr Cys Arg Cys Arg Pro Gly
420 425 430
Phe Thr Gly Thr His Cys Glu Leu His Ile Ser Asp Cys Ala Arg Ser
435 440 445
Pro Cys Ala His Gly Gly Thr Cys His Asp Leu Glu Asn Gly Pro Val
450 455 460
Cys Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg Cys Glu Val Arg Ile
465 470 475 480
Thr His Asp Ala Cys Ala Ser Gly Pro Cys Phe Asn Gly Ala Thr Cys
485 490 495
Tyr Thr Gly Leu Ser Pro Asn Asn Phe Val Cys Asn Cys Pro Tyr Gly
500 505 510
Phe Val Gly Ser Arg Cys Glu Phe Pro Val Gly Leu Pro Pro Ser
515 520 525
<210> 956
<211> 498
<212> PRT
<213> Macaca fascicularis
<400> 956
Ser Gly Val Phe Gln Leu Gln Leu Gln Glu Phe Val Asn Glu Arg Gly
1 5 10 15
Val Leu Ala Ser Gly Arg Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe
20 25 30
Arg Val Cys Leu Lys His Phe Gln Ala Val Val Ser Pro Gly Pro Cys
35 40 45
Thr Phe Gly Ser Val Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Ala
50 55 60
Val Arg Asp Asp Ser Ser Gly Gly Gly Arg Asn Pro Leu Gln Leu Pro
65 70 75 80
Phe Asn Phe Thr Trp Pro Gly Thr Phe Ser Leu Ile Ile Glu Ala Trp
85 90 95
His Ala Pro Gly Asp Asp Leu Arg Pro Glu Ala Leu Pro Pro Asp Ala
100 105 110
Leu Ile Ser Lys Ile Ala Ile Gln Gly Ser Leu Ala Val Gly Gln Asn
115 120 125
Trp Leu Leu Asp Glu Gln Thr Ser Thr Leu Thr Arg Leu Arg Tyr Ser
130 135 140
Tyr Arg Val Ile Cys Ser Asp Asn Tyr Tyr Gly Asp Asn Cys Ser Arg
145 150 155 160
Leu Cys Lys Lys Arg Asn Asp His Phe Gly His Tyr Val Cys Gln Pro
165 170 175
Asp Gly Asn Leu Ser Cys Leu Pro Gly Trp Thr Gly Glu Tyr Cys Gln
180 185 190
Gln Pro Ile Cys Leu Ser Gly Cys His Glu Gln Asn Gly Tyr Cys Ser
195 200 205
Lys Pro Ala Glu Cys Leu Cys Arg Pro Gly Trp Gln Gly Arg Leu Cys
210 215 220
Asn Glu Cys Ile Pro His Asn Gly Cys Arg His Gly Thr Cys Ser Thr
225 230 235 240
Pro Trp Gln Cys Thr Cys Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp
245 250 255
Gln Asp Leu Asn Tyr Cys Thr His His Ser Pro Cys Lys Asn Gly Ala
260 265 270
Thr Cys Ser Asn Ser Gly Gln Arg Ser Tyr Thr Cys Thr Cys Arg Pro
275 280 285
Gly Tyr Thr Gly Val Asp Cys Glu Leu Glu Leu Ser Glu Cys Asp Ser
290 295 300
Asn Pro Cys Arg Asn Gly Gly Ser Cys Lys Asp Gln Glu Asp Gly Tyr
305 310 315 320
His Cys Leu Cys Pro Pro Gly Tyr Tyr Gly Leu His Cys Glu His Ser
325 330 335
Thr Leu Ser Cys Ala Asp Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg
340 345 350
Glu Arg Asn Gln Gly Ala Ser Tyr Ala Cys Glu Cys Pro Pro Asn Phe
355 360 365
Thr Gly Ser Asn Cys Glu Lys Lys Val Asp Arg Cys Thr Ser Asn Pro
370 375 380
Cys Ala Asn Gly Gly Gln Cys Leu Asn Arg Gly Pro Ser Arg Met Cys
385 390 395 400
Arg Cys Arg Pro Gly Phe Thr Gly Thr Tyr Cys Glu Arg His Val Ser
405 410 415
Asp Cys Ala Arg Asn Pro Cys Ala His Gly Gly Thr Cys His Asp Leu
420 425 430
Glu Ser Gly Leu Met Cys Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg
435 440 445
Cys Glu Val Arg Thr Ser Ile Asp Ala Cys Ala Ser Ser Pro Cys Phe
450 455 460
Asn Arg Ala Thr Cys Tyr Thr Asp Leu Ser Thr Asp Thr Phe Val Cys
465 470 475 480
Asn Cys Pro Tyr Gly Phe Val Gly Ser Arg Cys Glu Phe Pro Met Gly
485 490 495
Leu Pro
<210> 957
<211> 498
<212> PRT
<213> Macaca mulatta
<400> 957
Ser Gly Val Phe Gln Leu Gln Leu Gln Glu Phe Val Asn Glu Arg Gly
1 5 10 15
Val Leu Ala Ser Gly Arg Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe
20 25 30
Arg Val Cys Leu Lys His Phe Gln Ala Val Val Ser Pro Gly Pro Cys
35 40 45
Thr Phe Gly Ser Val Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Ala
50 55 60
Val Arg Asp Asp Ser Ser Gly Gly Gly Arg Asn Pro Leu Gln Leu Pro
65 70 75 80
Phe Asn Phe Thr Trp Pro Gly Thr Phe Ser Leu Ile Ile Glu Ala Trp
85 90 95
His Ala Pro Gly Asp Asp Leu Arg Pro Glu Ala Leu Pro Pro Asp Ala
100 105 110
Leu Ile Ser Lys Ile Ala Ile Gln Gly Ser Leu Ala Val Gly Gln Asn
115 120 125
Trp Leu Leu Asp Glu Gln Thr Ser Thr Leu Thr Arg Leu Arg Tyr Ser
130 135 140
Tyr Arg Val Ile Cys Ser Asp Asn Tyr Tyr Gly Asp Asn Cys Ser Arg
145 150 155 160
Leu Cys Lys Lys Arg Asn Asp His Phe Gly His Tyr Val Cys Gln Pro
165 170 175
Asp Gly Asn Leu Ser Cys Leu Pro Gly Trp Thr Gly Glu Tyr Cys Gln
180 185 190
Gln Pro Ile Cys Leu Ser Gly Cys His Glu Gln Asn Gly Tyr Cys Ser
195 200 205
Lys Pro Ala Glu Cys Leu Cys Arg Pro Gly Trp Gln Gly Arg Leu Cys
210 215 220
Asn Glu Cys Ile Pro His Asn Gly Cys Arg His Gly Thr Cys Ser Thr
225 230 235 240
Pro Trp Gln Cys Thr Cys Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp
245 250 255
Gln Asp Leu Asn Tyr Cys Thr His His Ser Pro Cys Lys Asn Gly Ala
260 265 270
Thr Cys Ser Asn Ser Gly Gln Arg Ser Tyr Thr Cys Thr Cys Arg Pro
275 280 285
Gly Tyr Thr Gly Val Asp Cys Glu Leu Glu Leu Ser Glu Cys Asp Ser
290 295 300
Asn Pro Cys Arg Asn Gly Gly Ser Cys Lys Asp Gln Glu Asp Gly Tyr
305 310 315 320
His Cys Leu Cys Pro Pro Gly Tyr Tyr Gly Leu His Cys Glu His Ser
325 330 335
Thr Leu Ser Cys Ala Asp Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg
340 345 350
Glu Arg Asn Gln Gly Ala Ser Tyr Ala Cys Glu Cys Pro Pro Asn Phe
355 360 365
Thr Gly Ser Asn Cys Glu Lys Lys Val Asp Arg Cys Thr Ser Asn Pro
370 375 380
Cys Ala Asn Gly Gly Gln Cys Leu Asn Arg Gly Pro Ser Arg Met Cys
385 390 395 400
Arg Cys Arg Pro Gly Phe Thr Gly Thr Tyr Cys Glu Arg His Val Ser
405 410 415
Asp Cys Ala Arg Asn Pro Cys Ala His Gly Gly Thr Cys His Asp Leu
420 425 430
Glu Ser Gly Leu Met Cys Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg
435 440 445
Cys Glu Val Arg Thr Ser Ile Asp Ala Cys Ala Ser Ser Pro Cys Phe
450 455 460
Asn Arg Ala Thr Cys Tyr Thr Asp Leu Ser Thr Asp Thr Phe Val Cys
465 470 475 480
Asn Cys Pro Tyr Gly Phe Val Gly Ser Arg Cys Glu Phe Pro Val Gly
485 490 495
Leu Pro
Claims (17)
- 표면 플라즈몬 공명에 의해서 측정한 바에 의하면 약 500 pM 이하의 친화도 상수 (KD)로 사람 델타-유사 리간드 4 (hDll4)에 특이적으로 결합하는 사람 항체 또는 항체 단편.
- 제1항에 있어서, KD가 약 400 pM 이하인 사람 항체 또는 항체 단편.
- 제1항 또는 제2항에 있어서, 서열번호 4, 20, 36, 52, 68, 84, 100, 116, 132, 148, 164, 180, 196, 212, 228, 244, 260, 276, 292, 308, 324, 340, 356, 372, 397, 413, 429, 445, 461, 477, 493, 509, 525, 541, 557, 573, 589, 605, 621, 637, 653, 669, 685, 701, 717, 733, 749, 765, 781, 797, 813, 893, 897, 901, 905, 909, 913, 917, 921, 925, 935, 939, 943 및 947로 이루어진 그룹으로부터 선택된 중쇄 가변 영역 (HCVR)을 포함하는 사람 항체 또는 항체 단편.
- 제3항에 있어서, 서열번호 12, 28, 44, 60, 76, 92, 108, 124, 140, 156, 172, 188, 204, 220, 236, 252, 268, 284, 300, 316, 332, 348, 364, 380, 405, 421, 437, 453, 469, 485, 501, 517, 533, 549, 565, 581, 597, 613, 629, 645, 661, 677, 693, 709, 725, 741, 757, 773, 789, 805, 821, 895, 899, 903, 907, 911, 915, 919, 923, 927, 937, 941, 945 및 949로 이루어진 그룹으로부터 선택된 경쇄 가변 영역 (LCVR)을 포함하는 사람 항체 또는 항체 단편.
- 제4항에 있어서, HCVR/LCVR이 서열번호 429/437 및 901/903으로 이루어진 그룹으로부터 선택되는 사람 항체 또는 항체 단편.
- 제5항에 있어서, 서열번호 950, 951 및 952로 이루어진 그룹으로부터 선택된 불변 영역을 추가로 포함하는 사람 항체 또는 항체 단편.
- 제1항 또는 제2항에 있어서, 중쇄 상보성 결정 영역 3 (CDR3) 및 경쇄 CDR3을 포함하며, 여기에서상기 중쇄 CDR3은 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 - X10 - X11 - X12 - X13 - X14 - X15 - X16 (서열번호 930) (여기에서, X1은 Ala 또는 Ser이고; X2는 Arg 또는 Lys이며; X3은 Asp이고; X4는 Gly 또는 His이며; X5는 Asp 또는 Ala이고; X6은 Phe이며; X7은 Tyr 또는 Arg이고; X8은 Ser이며; X9는 Gly이고; X10은 Tyr이며; X11은 Glu이고; X12는 Gly 또는 His이며; X13은 Tyr 또는 Trp이고; X14는 Phe이거나 존재하지 않으며; X15는 Asp이거나 존재하지 않고; X16은 Pro이거나 존재하지 않 는다)의 아미노산 서열을 포함하고;상기 경쇄 CDR3은 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 (서열번호 933) (여기에서, X1은 Gln이고; X2는 Gln 또는 His이며; X3은 Tyr 또는 Arg이고; X4는 Gly 또는 Ser이며; X5는 Ser 또는 Asn이고; X6은 Trp 또는 Ser이며; X7은 Pro이고; X8은 Pro 또는 Arg이며; X9는 Thr이다)의 아미노산 서열을 포함하는, 사람 항체 또는 항체 단편.
- 제7항에 있어서,화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 928) (여기에서, X1은 Gly이고; X2는 Phe이며; X3은 Thr이고; X4는 Phe이며; X5는 Ser 또는 Asn이고; X6은 Ser 또는 Asn이며; X7은 Tyr 또는 Phe이고; X8은 Gly 또는 Ala이다)의 아미노산 서열을 포함하는 중쇄 CDR1 영역;화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 929) (여기에서, X1은 Ile 또는 Leu이고; X2는 Trp 또는 Ser이며; X3은 Tyr 또는 Gly이고; X4는 Asp 또는 Ser이며; X5는 Gly이고; X6은 Ser, Thr 또는 Val이며; X7은 Asn 또는 Asp이고; X8은 Lys 또는 Arg이다)의 아미노산 서열을 포함하는 중쇄 CDR2 영역;화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 (서열번호 931) (여기에서, X1은 Gln이고; X2는 Ser이며; X3은 Val이고; X4는 Arg 또는 Ser이며; X5는 Ser이고; X6은 Ser 또는 Tyr이며; X7은 Tyr이거나 존재하지 않는다)의 아미노산 서열을 포함하는 경쇄 CDR1 영역; 및화학식 X1 - X2 - X3 (서열번호 932) (여기에서, X1은 Gly 또는 Asp이고; X2는 Ala 또는 Thr이며; X3은 Ser이다)의 아미노산 서열을 포함하는 경쇄 CDR2 영역을 추가로 포함하는 사람 항체 또는 항체 단편.
- 제1항 또는 제2항에 있어서,서열번호 10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 186, 202, 218, 234, 250, 266, 282, 298, 314, 330, 346, 362, 378, 403, 419, 435, 451, 467, 483, 499, 515, 531, 547, 563, 579, 595, 611, 627, 643, 659, 675, 691, 707, 723, 739, 755, 771, 787, 803, 819, 835, 851, 867 및 883으로 이루어진 그룹으로부터 선택된 중쇄 CDR3 도메인; 및서열번호 18, 34, 50, 66, 82, 98, 11, 130, 146, 162, 178, 194, 210, 226, 242, 258, 274, 290, 306, 322, 338, 354, 370, 386, 411, 427, 443, 459, 475, 491, 507, 523, 539, 555, 571, 587, 603, 619, 635, 651, 667, 683, 699, 715, 731, 747, 763, 779, 795, 811, 827, 843, 859, 875 및 891로 이루어진 그룹으로부 터 선택된 경쇄 CDR3 도메인을 포함하는 항체 또는 항체 단편.
- 제9항에 있어서,서열번호 6, 22, 38, 54, 70, 86, 102, 118, 134, 150, 166, 182, 198, 214, 230, 246, 262, 278 294, 310, 326, 342, 358, 374, 399, 415, 431, 447, 463, 479, 495, 511, 527, 543, 559, 575, 591, 607, 623, 639, 655, 671, 687, 703, 711119, 735, 751, 767, 783, 799, 815, 831, 847, 863 및 879로 이루어진 그룹으로부터 선택된 중쇄 CDR1 도메인;서열번호 8, 24, 40, 56, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, 328, 344, 360, 376, 401, 417, 433, 449, 465, 481, 497, 513, 529, 545, 561, 577, 593, 609, 625, 641, 657, 673, 689, 705, 721, 737, 753, 769, 785, 801, 817, 833, 849, 865 및 881로 이루어진 그룹으로부터 선택된 중쇄 CDR2 도메인;서열번호 14, 30, 46, 62, 78, 94, 110, 126, 142, 158, 174, 190, 206, 222, 238, 254, 270, 286, 302, 318, 334, 350, 366, 382, 407, 423, 439, 455, 471, 487, 503, 519, 535, 551, 567, 583, 599, 615, 631, 647, 663, 679, 695, 711, 727, 743, 759, 775, 791, 807, 823, 839, 855, 871 및 887로 이루어진 그룹으로부터 선택된 경쇄 CDR1 도메인; 및서열번호 16, 32, 48, 64, 80, 96, 112, 128, 144, 160, 176, 192, 208, 224, 240, 256, 272, 288, 304, 320, 336, 352, 368, 384, 409. 425, 441, 457, 473, 489, 505, 521, 537, 553, 569, 585, 601, 617, 633, 649, 665, 681, 697, 713, 729, 745, 761, 777, 793, 809, 825, 841, 857, 873 및 889로 이루어진 그룹으로부터 선택된 경쇄 CDR2 도메인을 추가로 포함하는 사람 항체 또는 항체 단편.
- 제1항 내지 제10항 중의 어느 한 항에 따르는 항체 또는 항원-결합 단편을 암호화하는, 분리된 핵산 분자.
- 제11항에 따르는 뉴클레오타이드 서열을 포함하는 벡터.
- 적합한 숙주 세포 내에 제12항에 따르는 벡터를 포함하는, 사람 Dll4에 특이적으로 결합하는 항체 또는 항체의 항원-결합 단편을 생산하기 위한 숙주-벡터 시스템.
- 제13항에 있어서, 숙주 세포가 이.콜라이 (E. coli) 또는 CHO 세포로부터 선택된 원핵 또는 진핵 세포인 숙주-벡터 시스템.
- 제13항 또는 제14항에 따르는 숙주-벡터 시스템의 세포를 항체 또는 이의 단편의 생산을 허용하는 조건 하에서 성장시키고, 이렇게 생산된 항체 또는 단편을 회수함을 포함하는, 항-사람 Dll4 항체 또는 이의 항원-결합 단편의 생산 방법.
- 사람에서 Dll4-매개된 질병 또는 장애를 약화시키거나 억제하기 위해서 사용하는 약제를 제조하는데 있어서의, 제1항 내지 제10항 중의 어느 한 항에 따르는 항체 또는 항체의 항원-결합 단편의 용도.
- 제16항에 있어서, Dll4-관련된 상태 또는 질병이 병리학적 혈관형성, 암, 면역결핍성 질병, 이식 거부반응 또는 염증인 용도.
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| PCT/US2007/025653 WO2008076379A2 (en) | 2006-12-14 | 2007-12-14 | Human antibodies to human delta like ligand 4 |
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| JO3183B1 (ar) * | 2010-01-29 | 2018-03-08 | Regeneron Pharma | طرق لمعالجة أمراض المناعة الذاتية مضادات dll4 |
| AR093445A1 (es) * | 2012-11-14 | 2015-06-10 | Regeneron Pharma | Metodos para tratar el cancer de ovario con antagonistas de dll4 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015005632A1 (ko) * | 2013-07-09 | 2015-01-15 | 한화케미칼 주식회사 | Dll4와 vegf에 특이적으로 결합하는 신규 이중표적 단백질 및 이의 용도 |
| US10184010B2 (en) | 2013-07-09 | 2019-01-22 | Ablbio | Dual-targeting protein binding specifically to DLL4 and VEGF and use thereof |
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