KR20090088865A - 사람 ｉｌ-4 수용체에 대한 고친화성 사람 항체 - Google Patents
사람 ｉｌ-4 수용체에 대한 고친화성 사람 항체 Download PDFInfo
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- KR20090088865A KR20090088865A KR1020097008844A KR20097008844A KR20090088865A KR 20090088865 A KR20090088865 A KR 20090088865A KR 1020097008844 A KR1020097008844 A KR 1020097008844A KR 20097008844 A KR20097008844 A KR 20097008844A KR 20090088865 A KR20090088865 A KR 20090088865A
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Abstract
본 발명은 표면 플라스몬 공명에 의한 측정시 200pM 미만의 친화성 상수(KD)로 사람 인터루킨-4 수용체 알파(hIL-4Rα)에 결합하는 분리된 사람 항체 또는 이의 항체 단편에 관한 것이다.
사람 인터루킨-4 수용체, hIL-4R, 항-hIL-4R 항체, 표면 플라스몬 공명, IL-4-매개된 질환
Description
인터루킨-4 (IL-4, 또한 B 세포 자극 인자 또는 BSF-1으로서 공지됨)는 본래에 표면 면역글로불린에 대해 지시된 저농도의 항체에 반응하여 B 세포의 증식을 자극하는 능력을 특징으로 한다. IL-4는 광범위한 생물학적 활성을 갖는 것으로 밝혀졌고 이의 활성은 T 세포, 비만 세포, 과립구, 거대핵세포 및 적혈구의 성장 자극을 포함한다. IL-4는 휴지기 B 세포에서 클래스 II 주요 조직적합성 복합체 분자의 발현을 유도하고 자극된 B 세포에 의한 IgE 및 IgG1 이소타입의 분비를 증진시킨다.
IL-4의 생물학적 활성은 IL-4에 대한 특이적 세포 표면 수용체에 의해 매개된다. 사람 IL-4 수용체 알파 (hIL-4R) (서열번호 1)는 예를 들어, 미국 특허 제 5,599,905호, 제5,767,065호 및 제5,840,869호에 기재되어 있다. hIL-4R에 대한 항체는 미국 특허 제5,717,072호에 기재되어 있다.
IL-4의 생물학적 활성은 IL-4에 대한 특이적 세포 표면 수용체에 의해 매개된다. 사람 IL-4 수용체 알파 (hIL-4R) (서열번호 1)은 예를 들어, 미국 특허 제5,599,905호, 제5,767,065호 및 제5,840,869호 기재되어 있다. hIL-4R에 대한 항 체는 미국 특허 제5,717,072호 및 제7,186,809호에 기재되어 있다.
사람 치료제로서 유용한 항체를 제조하는 방법은 키메라 항체 및 사람화된 항체의 생성을 포함한다[문헌참조: 예를 들어, 미국 특허 제 6,949,245호]. 예를 들어, 사람 항체를 생산할 수 있는 비-사람 유전자도입 마우스를 제조하는 방법을 기재하고 있는 문헌[WO 94/02602 (Abgenix) 및 미국 특허 제6,596,541호 (Regeneron Pharmaceuticals) (이들 공보 둘다는 본원에 참조로서 인용된다)]을 참조한다.
hIL-4R에 대한 항체를 사용하는 방법은 미국 특허 제 5,714,146호; 제5,985,280호 및 제6,716,587호에 기재되어 있다.
발명의 간단한 요약
제1 측면에서, 본 발명은 사람 인터루킨-4 수용체(hIL-4R)에 특이적으로 결합하는 사람 항체, 바람직하게는 재조합 사람 항체를 제공한다. 사람 항체는 고친화성으로 hIL-4R에 결합한다는 것과 hIL-4 활성을 중화시키는 능력을 특징으로 한다. 구체적 양태에서, 사람 항체는 hIL-13/hIL-13R1 복합체의 hIL-4R로의 결합을 차단할 수 있어 hIL-13에 의한 시그날 전달을 억제할 수 있다. 당해 항체는 전장(예를 들어, IgG1 또는 IgG4 항체)일 수 있거나 단지 항원 결합부(예를 들어, Fab, F(ab')2 또는 scFv 단편)를 포함할 수 있고, 기능성을 나타내도록, 예를 들어, 잔류 효과기 기능을 제거하도록 변형될 수 있다 (Reddy et al. (2000) J. Immunol. 164:1925-1933).
하나의 양태에서, 본 발명은 hIL-4R (서열번호 1)에 특이적으로 결합하는 항체 또는 이의 항원 결합 단편을 제공하고 표면 플라스몬 공명에 의한 측정시 KD는 약 200pM 이하이다. 보다 구체적인 양태에서, 항체 또는 이의 항원 결합부는 약 150pM 미만 또는 약 50pM 미만, 또는 약 20pM 미만의 KD를 나타낸다. 다양한 양태에서, 항체 또는 항원 결합 단편은 STAT6 루시퍼라제 생물분석에 의한 측정시 약 200pM 이하의 IC50으로 hIL-4 활성을 차단한다. 보다 구체적 양태에서, 항체 또는 항원 결합 단편은 루시퍼라제 생물분석에 의한 측정시 약 150 pM 이하, 또는 약 100 pM 이하, 또는 약 50 pM 이하의 IC50을 나타낸다. 다양한 양태에서, 항체 또는 항원 결합 단편은 STAT6 루시퍼라제 생물분석에 의한 측정시 약 100 pM 이하의 IC50으로 hIL-13 활성을 차단한다. 보다 구체적인 양태에서, 당해 항체 또는 항원 결합 단편은 약 75 pM 이하, 또는 약 50 pM 이하, 또는 심지어 약 20 pM 이하의 IC50을 나타낸다.
제2 측면에서, 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, 387, 391, 395, 399, 403, 407, 411, 415, 419, 423, 427, 431, 435, 439, 443, 447, 451, 455, 459, 463, 467, 471, 475, 479, 483, 487, 491, 495, 499, 503, 507, 511, 515, 519, 523, 527, 531, 535, 539, 543, 547, 551, 555, 559, 563, 567, 571, 575, 579 및 581로 이루어진 그룹으로부터 선택되는 중쇄 가변 영 역(HCVR) 또는 이의 실질적으로 유사한 서열을 포함한다.
제3 측면에서, 본 발명의 항체는 서열번호 11, 27, 43, 59, 75, 91, 107, 123, 130, 155, 171, 187, 203, 219, 235, 251, 267, 283, 299, 315, 331, 347, 363, 379, 389, 393, 397, 401, 405, 409, 413, 417, 421, 425, 429, 433, 437, 441, 445, 449, 453, 457, 461, 465, 469, 473, 477, 481, 485, 489, 493, 497, 501, 505, 509, 513, 517, 521, 625, 529, 533, 537, 541, 545, 549, 553, 557, 561, 565, 569, 573 및 577로 이루어진 그룹으로부터 선택되는 경쇄 가변 영역(LCVR) 또는 이의 실질적으로 유사한 서열을 포함한다.
하나의 양태에서, 본 발명의 항체 또는 항체 단편은 서열번호 3/11, 19/27, 35/43, 51/59, 67/75, 83/91, 99/107, 115/123, 131/139, 147/155, 163/171, 179/187, 195/203, 211/219, 227/235, 243/251, 259/267, 275/283, 291/299, 307/315, 323/331, 339/347, 355/363, 371/379, 387/389, 391/393, 395/397, 399/401, 403/405, 407/409, 411/413, 415/417, 419/421, 423/425, 427/429, 431/433, 435/437, 439/441, 443/445, 447/449, 451/453, 455/457, 459/461, 463/465, 467/469, 471/473, 475/477, 479/481, 483/485, 487/489, 491/493, 495/497, 499/501, 503/505, 507/509, 511/513, 515/517, 519/521, 523/525, 527/529, 531/533, 535/537, 539/541, 543/545, 547/549, 551.553, 555/557, 559/561, 563/565, 567/569, 571/573, 575/577, 579/59 및 581/59로 이루어진 그룹으로부터 선택되는 HCVR 및 LCVR (HCVR/LCVR)을 포함한다. 바람직한 양태에서, 항체 또는 항체 단편은 서열번호 51/59, 259/267, 275/283, 291/299, 579/59 또는 581/59로부터 선택되는 HCVR/LCVR을 포함한다.
제4 측면에서, 본 발명은 HCVR을 암호화하는 핵산 분자를 제공하고, 이때 당해 핵산 분자는 서열번호 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 194, 210, 226, 242, 258, 274, 290, 306, 322, 338, 354, 370, 386, 390, 394, 398, 402, 406, 410, 414, 418, 422, 426, 430, 434, 438, 442, 446, 450, 454, 458, 462, 466, 470, 474, 478, 482, 486, 490, 494, 498, 502, 506, 510, 514, 518, 522, 526, 530, 534, 538, 542, 546, 550, 554, 558, 562, 566, 570, 574, 578 및 580으로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 동일한 서열이다.
제5 측면에서, 본 발명은 LCVR을 암호화하는 핵산 분자를 제공하고, 이때 핵산 분자는 서열번호 10, 26, 42, 58, 74, 90, 106, 122, 129, 154, 170, 186, 202, 218, 234, 250, 266, 282, 298, 314, 330, 346, 362, 378, 388, 392, 396, 400, 404, 408, 412, 416, 420, 424, 428, 432, 436, 440, 444, 448, 452, 456, 460, 464, 468, 472, 476, 480, 484, 488, 492, 496, 500, 504, 508, 512, 516, 520, 524, 528, 532, 536, 540, 544, 548, 552, 556, 560, 564, 568, 572 및 576으로 이루어진 그룹으로부터 선택되는 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 동일한 서열이다.
하나의 양태에서, 본 발명의 항체는 서열번호 2/10, 18/26, 34/42, 50/58, 66/74, 82/90, 98/106, 114/122, 130/138, 146/154, 162/170, 178/186, 194/202, 210/218, 226/234, 242/250, 258/266, 274/282, 290/298, 306/314, 322/330, 338/346, 354/362, 370/378, 386/388, 390/392, 394/396, 398/400, 402/404, 406/408, 410/412, 414/416, 418/420, 422/424, 426/428, 430/432, 434/436, 438/440, 442/444, 446/448, 450/452, 454/456, 458/460, 462/464, 466/468, 470/472, 474/476, 478/480, 482/484, 486/488, 490/492, 494/496, 498/500, 502/504, 506/508, 510/512, 514/516, 518/520, 522/524, 526/528, 530/532, 534/536, 538/540, 542/544, 546/548, 550/552, 554/556, 558/560, 562/564, 566/568, 570/572, 574/576, 578/59 및 580/59로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 쌍에 의해 암호화된 HCVR 및 LCVR을 포함한다. 바람직한 양태에서, 당해 항체 또는 항체 단편은 서열번호 50/58, 258/266, 274/282, 290/298, 578/58 또는 580/58로부터 선택되는 뉴클레오타이드 서열에 의해 암호화된 HCVR/LCVR을 포함한다.
제6 측면에서, 본 발명은 3개의 중쇄 및 3개의 경쇄 상보성 결정 영역(CDR)을 포함하는, hIL-4R과 특이적으로 결합하는 항체 또는 항체의 항원 결합 단편을 특징으로 하고,
이때, 중쇄 CDR1은 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 582)의 아미노산 서열을 포함하고, 여기서 X1 = Gly; X2 = Tyr 또는 Phe; X3 = Thr 또는 I; X4 = Phe; X5 = Asn 또는 Arg; X6 =Ser; X7 = Tyr; 및 X8 = Gly이고;
중쇄 CDR2는 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 583)의 아미노산 서열을 포함하고, 여기서 X1 = Ile, X2 = Ser 또는 Arg, X3 = Thr 또는 Tyr, X4= Tyr 또는 Asp, X5 = Asn 또는 Gly, X6 = Gly 또는 Ser, X7 = Lys 또는 Asn, 및 X8 = Thr이고;
중쇄 CDR3은 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 - X10 - X11 - X12 - X13 - X14 - X15 - X16 - X17 - X18 - X19 - X20 - X21 (서열번호 584)의 아미노산 서열을 포함하고, 여기서, X1 = Ala 또는 Val, X2 = Arg 또는 Lys, X3 = Asp 또는 Glu, X4 = Gly 또는 Glu, X5 = Ala 또는 Arg, X6 = Arg 또는 Ser, X7 = Ile 또는 Gly, X8 = Val 또는 Ser, X9 = Val 또는 Trp, X10 = Ala 또는 Phe, X11 = Gly 또는 Asp, X12 = Thr 또는 Pro, X13 = Thr 또는 부재, X14 = Pro 또는 부재, X15 = Tyr 또는 부재, X16 = Tyr 또는 부재, X17 = Tyr 또는 부재, X18 = Gly 또는 부재, X19 = Met 또는 부재, X20 = Asp 또는 부재, 및 X21 = Val 또는 부재이고;
경쇄 CDR1은 화학식 X1 - X2 - X3 - X4 - X5 - X6 (서열번호 585)의 아미노산 서열을 포함하고, 여기서, X1 = Gln, X2 = Asp 또는 Ala, X3 = Ile, X4 = Ser 또는 Asn, X5 = Asn 또는 Ile, 및 X6 = Trp 또는 Phe이고;
경쇄 CDR2는 화학식 X1 X2 X3 (서열번호 586)의 아미노산 서열을 포함하고, 여기서, X1 = Ala 또는 Val, X2 = Ala 또는 Thr, 및 X3 = Ser이고;
경쇄 CDR3은 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 (서열번호 587)의 아미노산 서열을 포함하고, 여기서, X1 = Gln, X2 = Gln, X3 = Ala 또는 Tyr, X4 = Asn, X5 = Ser, X6 = Phe 또는 His, X7 = Pro, X8 = Ile 또는 Trp, 및 X9 = Thr이다.
제7 측면에서, 본 발명은 중쇄 CDR3 및 경쇄 CDR3을 포함하는 항체 또는 항원 결합 단편을 제공하고, 여기서, 중쇄 CDR3 도메인은 서열번호 9, 25, 41, 57, 73, 89, 105, 121, 137, 153, 169, 185, 201, 217, 233, 249, 265, 281, 297, 313, 329, 345, 361 및 377로 이루어진 그룹으로부터 선택되고; 경쇄 CDR3 도메인은 서열번호 17, 33, 49, 65, 81, 97, 113, 129, 145, 161, 177, 193, 209, 225, 241, 257, 273, 289, 305, 321, 337, 353, 369 및 385로 이루어진 그룹으로부터 선택된다. 바람직한 양태에서, 중쇄 및 경쇄 CDR3은 서열쌍, 서열번호 57과 65; 265와 273; 281과 289; 및 297과 305로부터 선택된다.
추가의 양태에서, 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 및 373으로 이루어진 그룹으로부터 선택되는 중쇄 CDR1 도메인 또는 이와 실질적으로 유사한 서열; 서열번호 7, 23, 39, 55, 71, 87, 103, 119, 135, 151, 167, 183, 199, 215, 231, 247, 263, 279, 295, 311, 327, 343, 359 및 375로 이루어진 그룹으로부터 선택되는 중쇄 CDR2 도메인 또는 이와 실질적으로 유사한 서열; 서열번호 9, 25, 41, 57, 73, 89, 105, 121, 137, 153, 169, 185, 201, 217, 233, 249, 265, 281, 297, 313, 329, 345, 361 및 377로 이루어진 그룹으로부터 선택되는 중쇄 CDR3 도메인 또는 이와 실질적으로 유사한 서열; 서열번호 13, 29, 45, 61, 77, 93, 109, 125, 141, 157, 173, 189, 205, 221, 237, 253, 269, 285, 301, 317, 333, 349, 365 및 381로 이루어진 그룹으로부터 선택되는 경쇄 CDR1 도메인 또는 이와 실질적으로 유사한 서열; 서열번호 15, 31, 47, 63, 79, 95, 111, 127, 143, 159, 175, 191, 207, 223, 239, 255, 271, 287, 303, 319, 335, 351, 367 및 383으로 이루어진 그룹으로부터 선택되는 경쇄 CDR2 또는 이와 실질적으로 유사한 서열; 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 및 385로 이루어진 그룹으로부터 선택되는 경쇄 CDR3 도메인 또는 이와 실질적으로 유사한 서열을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다. 바람직한 양태에서, 당해 항체 또는 항원 결합 단편은 중쇄 CDR 서열번호 53, 55, 57 및 경쇄 CDR 서열번호 61, 63, 65; 중쇄 CDR 서열번호 261, 263, 265 및 경쇄 CDR 서열번호 269, 271, 273; 중쇄 CDR 서열번호 277, 279, 281 및 경쇄 CDR 서열번호 285, 287, 289; 및 중쇄 CDR 서열번호293, 295, 297 및 경쇄 CDR 서열번호 301, 303, 305를 포함한다.
제8 측면에서, 본 발명은 HCVR로부터의 3개의 CDR 및 LCVR로부터의 3개의 CDR을 포함하는 항체 또는 항원 결합 단편을 제공하고, 여기서, HCVR/LCVR은 51/59, 579/59, 581/59, 259/267, 275/283 및 291/299로 이루어진 그룹으로부터 선택된다.
하나의 양태에서, 본 발명은 중쇄 및 경쇄 CDR3을 포함하는 사람 항체 또는 항체 단편을 특징으로 하고, 중쇄 CDR3은 서열번호 8, 24, 40, 56, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, 328, 344, 360 및 376으로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열에 의해 암호화되고; 경쇄 CDR3은 서열번호 16, 32, 48, 64, 80, 96, 112, 128, 144, 160, 176, 192, 208, 224, 240, 256, 272, 288, 304, 320, 336, 352, 368 및 384로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열에 의해 암호화된다.
추가의 양태에서, 본 발명은 서열번호 4, 20, 36, 52, 68, 84, 100, 116, 132, 148, 164, 180, 196, 212, 228, 244, 260, 276, 292, 308, 324, 340, 356 및 372로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 동일한 서열에 의해 암호화된 중쇄 CDR1 도메인; 서열번호 6, 22, 38, 54, 70, 86, 102, 118, 134, 150, 166, 182, 198, 214, 230, 246, 262, 278, 294, 310, 326, 342, 358 및 374로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 동일한 서열에 의해 암호화된 중쇄 CDR2 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 및 376으로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 유사한 서열에 의해 암호화된 중쇄 CDR3 도메인; 서 열번호 12, 28, 44, 60, 76, 92, 108, 124, 140, 156, 172, 188, 204, 220, 236, 252, 268, 284, 300, 316, 332, 348, 364 및 380으로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 유사한 서열에 의해 암호화된 경쇄 CDR1 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 및 382로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 유사한 서열에 의해 암호화된 경쇄 CDR2 도메인; 및 서열번호 16, 32, 48, 64, 80, 96, 112, 128, 144, 160, 176, 192, 208, 224, 240, 256, 272, 288, 304, 320, 336, 352, 368 및 384로 이루어진 그룹으로부터 선택되는 뉴클레오타이드 서열 또는 이와 95% 이상의 상동성을 갖는 실질적으로 유사한 서열에 의해 암호화된 경쇄 CDR3 도메인을 포함하는 사람 항체 또는 항체 단편을 특징으로 한다. 바람직한 양태에서, 당해 항체 및 항원 결합 단편은 뉴클레오타이드 서열 서열번호 52, 54, 56에 의해 암호화된 중쇄 CDR 및 뉴클레오타이드 서열 서열번호 60, 62, 64에 의해 암호화된 경쇄 CDR; 뉴클레오타이드 서열 서열번호 260, 262, 264에 의해 암호화된 중쇄 CDR 및 뉴클레오타이드 서열 서열번호 268, 270, 272에 의해 암호화된 경쇄 CDR; 뉴클레오타이드 서열 서열번호 276, 278, 280에 의해 암호화된 중쇄 CDR 및 뉴클레오타이드 서열 서열번호 284, 286, 288에 의해 암호화된 경쇄 CDR; 및 뉴클레오타이드 서열 서열번호 292, 294, 296에 의해 암호화된 중쇄 CDR 및 뉴클레오타이드 서열 서열번호 300, 302, 304에 의해 암호화된 경쇄 CDR을 포함한다.
본 발명은 변형된 글리코실화 패턴을 갖는 항-hIL-4R 항체를 포함한다. 몇몇 적용에서, 바람직하지 않은 글리코실화 부위를 제거하기 위한 변형이 유용할 수 있거나 예를 들어, 항체 의존성 세포성 세포독성 (ADCC) 기능을 증가시키기 위해 항체는 올리고사카라이드 쇄상에 존재하는 푸코스 잔기가 부재이다 (문헌참조: Shield et al. (2002) JBC 277:26733). 다른 적용에서, 갈락토실화는 보체 의존성 세포독성(CDC)을 변형시키기 위해 변형될 수 있다.
제9 측면에서, 본 발명은 본 발명의 핵산 분자를 함유하는 재조합 발현 벡터, 및 당해 벡터가 포함된 숙주 세포를 제공하고, 본 발명의 숙주 세포를 배양함에 의해 수득되는 본 발명의 항체 또는 항원 결합 단편을 제조하는 방법에 관한 것이다. 당해 숙주 세포는 원핵 또는 진핵 세포일 수 있고 바람직하게 숙주 세포는 이.콜라이(E. coli) 또는 포유동물 세포, 예를 들어, CHO 세포이다.
제10 측면에서, 본 발명은 hIL-4R에 특이적으로 결합하는 재조합 사람 항체 및 허용되는 담체를 포함하는 조성물을 특징으로 한다.
제11 측면에서, 본 발명은 본 발명의 항체 또는 이의 항원 결합부를 사용하여 hIL-4 활성을 억제하기 위한 방법을 특징으로 한다. 구체적 양태에서, 본 발명의 항체는 또한 hIL-13/hIL-13R1 복합체의 hIL-4R로의 결합을 차단한다. 제1 양태에서, 당해 방법은 hIL-4R과 본 발명의 항체 또는 이의 항원 결합부를 접촉시킴을 포함하고 이로써 hIL-4 또는 hIL-4/hIL-13 활성이 억제된다. 또 다른 양태에서, 당해 방법은 hIL-4 또는 hIL-4/hIL-13 활성 억제에 의해 호전되는 장애를 앓는 사람 피검체에 본 발명의 항체 또는 이의 항원 결합부를 투여함을 포함한다. 당해 치료되는 장애는 hIL-4 또는 hIL-4/hIL-13 활성의 제거, 억제 또는 감소에 의해 개선되거나 호전되거나 억제되거나 예방되는 임의의 질환 또는 상태이다.
본 발명은 추가로 사람에서 IL-4 매개된 질환 또는 장애를 약화시키거나 억제시키는데 사용하기 위한 약제를 제조하는데 있어서 제1항 내지 제9항 중 어느 한 항에 따른 항체 또는 항체의 항원 결합 단편의 용도를 포함한다.
본 발명의 항체 또는 항체 단편에 의해 치료되는 IL-4-매개되거나 관련된 장애는 예를 들어, 관절염(패혈성 관절염을 포함), 포진, 만성 특발성 두드러기, 경피증, 비대성 반흔, 위플(Whipple) 질환, 양성 전립선 비대증, 폐 장애, 예를 들어, 약하거나, 중등증 또는 중증 천식, 염증 장애, 예를 들어, 염증성 장 질환, 알레르기 반응, 가와사키 질환, 겸상 세포 질환, 처그-스트라우스 증후군, 그레이브스병, 자간전증, 쇼그렌 증후군, 자가면역 림프증식성 증후군, 자가면역 용혈 빈혈증, 바레트 식도, 자가면역 포도막염, 결핵 및 신장증을 포함한다.
다른 목적 및 잇점은 계속되는 상세한 설명의 검토로부터 명백해질 것이다.
도 1(A-C). OCTET™-기반 순차 결합 분석으로 생성된 항체 결합 프로파일 평가. 도 1(A)는 결합된 항원에 노출된 제1 항체가 대조군 항체인 경우 얻어진 결과를 보여주는 막대 그래프이다. 도 1(B)는 결합된 항원에 노출된 제1 항체가 VAB16F3-1인 경우이다. 도 1(C)는 결합된 항원에 노출된 제1 항체가 VAK5H4-4인 경우이다. 제2 항체: 1=대조군; 2=VX4E7-9; 3=VX3F7-6; 4=VAB16G-1; 5=VAB16F3-1; 6=VAB15C8-17; 7=VAB11G8-1; 8=VAB10C1-5; 9=VAB10G8-19; 10=VAB8G10-1; 11=VAB7B9-3; 12=VAB6C10-14; 13=VAB5C5-11; 14=VAB3B4-10; 15=VAB4D5-3; 16=VAB1H1-2; 17=VAK5H4-4; 18=VAK7G8-5; 19=VAK8G11-13; 20=VAK9C6-11; 21=VAK10G6-7; 22=VAK11D4-1; 23=VAK12B11-9 및 24=VAK10G12-5. 흰 막대는 제1 항체의 결합 수준을 보여주고 검은 막대는 제2 항체에 의한 추가의 결합을 보여준다.
본 발명의 방법을 기술하기 전에, 본 발명은 특정 방법 및 기재된 실험적 조건에 제한되지 않고 당해 방법 및 조건은 다양할 수 있는 것으로 이해되어야만 한다. 또한 본원에 사용된 용어는 단지 특정 양태를 기술할 목적을 위한 것이지 제한하기 위한 것이 아닌 것으로 이해되어야만 하고, 본 발명의 범위는 단지 첨부된 특허청구범위에 의해서만 제한된다.
달리 정의되지 않는다면, 본원에 사용되는 모든 기술적 및 과학적 용어는 본 발명이 속하는 분야의 숙련자에 의해 일반적으로 이해되는 바와 동일한 의미를 갖는다. 본원에 기재된 것들과 유사하거나 동일한 임의의 방법 및 물질이 본 발명의 수행 또는 시험에 사용될 수 있지만 바람직한 방법 및 물질이 이하에 기재된다.
정의
본원에 사용된 용어 "사람 IL4R(hIL-4R)"은 인터루킨-4 (IL-4)에 특이적으로 결합하는 사람 사이토카인 수용체, IL-4R (서열번호 1)를 말한다. 당해 용어 "사람 인터루킨-13" (hIL-13)은 IL-13 수용체에 특이적으로 결합하는 사이토카인을 말하고 "hIL-13/hIL-13R1 복합체"는 hIL-4 수용체에 결합하여 생물학적 활성을 개시하는 hIL-13R1 복합체에 결합하는 hIL-13에 의해 형성된 복합체를 말한다.
본원에 사용된 용어 "항체"는 디설파이드 결합에 의해 서로 연결된 4개의 폴리펩타이드 쇄, 2개의 중(H) 쇄 및 2개의 경(L) 쇄를 포함하는 면역글로불린 분자를 말한다. 각각의 중쇄는 중쇄 가변 영역(본원에서 HCVR 또는 VH로서 약칭됨) 및 중쇄 불변 영역을 포함한다. 중쇄 불변 영역은 3개의 도메인, CH1, CH2 및 CH3을 포함한다. 각각의 경쇄는 경쇄 가변 영역(본원에서 LCVR 또는 VL로서 약칭됨) 및 경쇄 불변 영역을 포함한다. 경쇄 불변 영역은 하나의 도메인 (CL1)을 포함한다. VH 및 VL 영역은 추가로 상보성 결정 영역(CDR)으로 호칭되는 초가변영역으로 세분되고, 여기에는 골격 영역(FR)으로 호칭되는 보다 보존된 영역이 산재되어 있다. 각각의 VH 및 VL은 3개의 CDR 및 4개의 FR로 구성되고 하기의 순서로 아미노 말단에서 카복시 말단으로 배열되어 있다: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
본원에 사용된 항체의 "항원 결합부" (또는 간단히 "항체 부분" 또는 항체 단편")라는 용어는 항원(예를 들어, hIL-4R)에 특이적으로 결합하는 능력을 보유한 항체의 하나 이상의 단편을 말한다. 항체의 항원 결합 기능은 전장 항체의 단편에 의해 수행될 수 있는 것으로 밝혀졌다. 항체의 "항원 결합부"라는 용어에 포함되는 결합 단편의 예는 (i) VL, VH, CL1 및 CH1 도메인으로 이루어진 1가 단편인 Fab 단편; (ii) 힌지 영역에서 디설파이드 브릿지에 의해 연결된 2개의 F(ab)' 단편을 포함하는 2가 단편인 F(ab')2 단편; (iii) VH 및 CH1 도메인으로 이루어진 Fd 단편; (iv) 항체의 단일 암의 VL 및 VH 도메인으로 이루어진 Fv 단편, (v) VH 도메인으로 이루어진 dAb 단편 (문헌참조:Ward et al. (1989) Nature 241:544-546); 및 (vi) 분리된 상보성 결정 영역(CDR)을 포함한다. 또한 Fv 단편인 VL 및 VH의 2개의 도메인이 별개의 유전자들에 의해 암호화되어 있어도 이들은 재조합 방법을 사용하여 합성 링커에 의해 연결됨으로써 이들은 VL 및 VH 영역이 쌍을 이루어 1가 분자를 형성하는 단일 연속 쇄(단일 쇄 Fv(scFv)로서 공지됨: 문헌참조: Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883)로서 제조될 수 있다. 당해 단일 쇄 항체는 또한 항체의 "항원 결합부"라는 용어에 포함되는 것으로 의도된다. 디아바디(diabody)와 같은 또 다른 형태의 단일 쇄 항체가 또한 포함된다[문헌참조: Holliger et al. (1993) Proc. Natl. Acad Sci. USA 90:6444-6448)].
본원에 사용된 "중화" 또는 "차단" 항체는 hIL-4R에 결합하여 hIL-4 및/또는 hIL-12의 생물학적 활성을 억제시키는 항체를 말하는 것으로 의도된다. 이러한 hIL-4 및/또는 IL-13의 생물학적 활성의 억제는 당업계에 공지된 hIL-4 및/또는 hIL-13 생물학적 활성에 대한 하나 이상의 지표(indicator), 예를 들어, hIL-4 및/또는 IL-13 유도된 세포 활성화 및 hIL-4의 hIL-4R로의 결합을 측정함에 의해 평가될 수 있다(하기 실시예 참조).
"CDR" 또는 상보성 결정 영역은 "골격 영역"(FR)으로 호칭되는, 보다 보존된 영역내에 산재되어 있는 초가변 영역이다. 본 발명의 항-hIL-4R 항체 또는 단편의 상이한 양태에서, FR은 사람 생식선 서열과 동일할 수 있거나 천연적으로 또는 인공적으로 변형될 수 있다.
본원에 사용된 용어 "표면 플라스몬 공명"은 예를 들어, BIAcoreTM 시스템 (Pharmacia Biosensor AB)을 사용하여, 바이오센서 매트릭스내 단백질 농도를 검출하여 실시간 상호작용에 대한 분석을 가능하게 하는 광학 현상을 말한다.
용어 "에피토프"는 파라토프(paratope)로서 공지된 항체 분자의 가변 영역내에서 특정 항원 결합과 상호작용하는 항원성 결정인자이다. 단일 항원은 하나 이상의 에피토프를 가질 수 있다. 에피토프는 입체적이거나 선형일 수 있다. 입체적 에피토프는 선형 폴리펩타이드 쇄의 상이한 절편으로부터의 공간적으로 인접한 아미노산에 의해 생성된다. 선형 에피토프는 폴리펩타이드 쇄내 인접한 아미노산에 의해 생성되는 에피토프이다. 특정 상황에서, 에피토프는 항원상의 사카라이드 잔기, 포스포릴 그룹 또는 설포닐 그룹을 포함할 수 있다.
핵산 또는 이의 단편을 언급하는 경우, 용어 "실질적인 동일성" 또는 "실질적으로 동일한"은 적당한 뉴클레오타이드 삽입체 또는 결실체와 또 다른 핵산(또는 이의 상보적 쇄)과 최적으로 정렬되는 경우 서열 동일성에 대해 널리 공지된 알고리듬(예를 들어, 하기에 논의된 FASTA, BLAST 또는 Gap)에 의한 측정시 약 95% 이상 및 보다 바람직하게는 약 96%, 97%, 98% 또는 99% 이상의 뉴클레오타이드 염기에서 뉴클레오타이드 서열 동일성이 있음을 나타낸다.
폴리펩타이드에 적용되는 용어 "실질적인 유사성" 또는 "실질적으로 유사한"은 2개의 펩타이드 서열이, 예를 들어, 디폴트 갭 중량을 사용하는 프로그램 GAP 또는 BESTFIT에 의해 최적으로 정렬되는 경우, 95% 이상의 서열 동일성, 보다 더 바람직하게는 98% 이상 또는 99% 이상의 서열 동일성을 공유함을 의미한다. 바람직하게, 동일하지 않은 잔기 위치는 보존적 아미노산 치환에 의해 상이하다. "보존적 아미노산 치환"은 아미노산 잔기가 유사한 화학적 성질(예를 들어, 전하 또는 소수성)을 갖는 측쇄(R 그룹)를 갖는 또 다른 아미노산 잔기에 의해 치환된 것이다. 일반적으로, 보존적 아미노산 치환은 실질적으로 단백질의 기능적 성질을 변화시키지 않는다. 2개 이상의 아미노산 서열이 보존적 치환에 의해 서로 차이가 있는 경우, % 서열 동일성 또는 유사성 정도는 치환의 보존적 성질을 보정하기 위해 상향 조정될 수 있다. 당해 조정을 수행하는 수단은 당업자에게 널리 공지되어 있다[문헌참조: Pearson (1994) Methods Mol. Biol. 24: 307-331]. 화학적 성질이 유사한 측쇄를 갖는 아미노산 그룹의 예는 (1) 지방족 측쇄: 글라이신, 알라닌, 발린, 류신 및 이소류신; (2) 지방족-하이드록실 측쇄: 세린 및 트레오닌; (3) 아미드 함유 측쇄: 아스파라긴 및 글루타민; (4) 방향족 측쇄: 페닐알라닌, 타이로신, 및 트립토판; (5) 염기성 측쇄: 라이신, 아르기닌, 및 히스티딘; (6) 산성 측쇄: 아스파르테이트 및 글루타메이트, 및 (7) 황 함유 측쇄: 시스테인 및 메티오닌을 포함한다. 바람직한 보존적 아미노산 치환 그룹은 다음과 같다: 발린-류신-이소류신, 페닐알라닌-타이로신, 라이신-아르기닌, 알라닌-발린, 글루타메이트-아스파르테이트, 및 아스파라긴-글루타민. 또는, 보존적 대체는 문헌[참조: Gonnet et al. (1992) Science 256: 1443 45]에 기재된 PAM250 로그-가능성 매트릭스에서 양의 값을 갖는 임의의 변화이다. "중간정도의 보존적" 대체는 PAM250 로그-가능성 매트릭스에서 비음성 값을 갖는 임의의 변화이다.
폴리펩타이드에 대한 서열 유사성은 또한 서열 동일성으로서 언급되기도 하고 일반적으로 서열 분석 소프트웨어를 사용하여 측정된다. 단백질 분석 소프트웨어는 보존적 아미노산 치환을 포함하는, 다양한 치환, 결실 및 기타 변형에 할당된 유사성 측정을 사용하여 유사한 서열을 일치시킨다. 예를 들어, GCG 소프트웨어는 밀접하게 관련된 폴리펩타이드, 예를 들어, 유기체의 상이한 종으로부터의 상동성 폴리펩타이드간의, 또는 야생형 단백질과 이의 뮤테인간의 서열 상동성 또는 서열 동일성을 측정하기 위한 디폴트 파라미터와 함께 사용될 수 있는 Gap 및 Bestfit과 같은 프로그램을 포함한다[문헌참조: GCG Version 6.1]. 폴리펩타이드 서열은 또한 디폴트 또는 추천된 파라미터를 사용하는 FASTA를 사용하거나 GCG 버전 6.1의 프로그램을 사용하여 비교할 수 있다. FASTA (예를 들어, FASTA2 및 FASTA3)는 미지의 서열과 탐색 서열간의 최대의 오버랩 영역에 대한 정렬 및 % 서열 동일성을 제공한다 (Pearson (2000) supra). 본 발명의 서열을, 상이한 유기체로부터의 다수의 서열을 포함하는 데이터베이스와 비교하는 경우 또 다른 바람직한 알고리듬은 디폴트 파라미터를 사용하는 컴퓨터 프로그램 BLAST, 특히 BLASTP 또는 TBLASTN이다[문헌참조: Altschul et al. (1990) J. Mol. Biol. 215:403-410 및 Altschul et al. (1997) Nucleic Acids Res. 25:3389-402].
사람 항체의 제조
사람 항체를 제조하는 방법은 예를 들어 VelocImmune™(Regeneron Pharmaceuticals), XenoMouse™ 기술 (Green et al. (1994) Nature Genetics 7:13-21; Abgenix), "미니로커스(minilocus)" 방법, 및 파지 디스플레이 (및 예를 들어, US 5,545,807, US 6,787,637 참조)를 포함한다. VelocImmune™ 기술 (US 6, 596,541)은 선택 항원에 대한 고특이성의 완전한 사람 항체를 제조하는 방법을 포함한다.
설치류는 당업계에 공지된 임의의 방법에 의해 면역화될 수 있다 (문헌참조: 예를 들어, Harlow and Lane (1988) supra; Malik and Lillehoj (1994) Antibody techniques, Academic Press, CA). 바람직한 양태에서, hIL-4R 항원은 사람 Ig 중쇄 가변 영역 및 카파 경쇄 가변 영역 (VelocImmune, Regeneron Pharmaceuticals, Inc.; US 6,596,541) 둘다를 암호화하는 DNA 좌를 포함하는 마우스에게 면역 반응을 자극하기 위한 애주번트, 예를 들어, 완전 및 불완전 프로인트 애주번트, MPL+TDM 애주번트 시스템 (Sigma), 또는 RIBI (무라밀 디펩타이드) (문헌참조: O'Hagan (2000) Vaccine Adjuvant, Human Press, NJ)와 함께 직접 투여된다. 애주번트는 항원을 국소 저장소에 격리시켜 폴리펩타이드의 신속한 분산을 방지할 수있고 숙주 면역 반응을 자극할 수 있는 인자를 함유할 수 있다. VelocImmune™ 기술은 내인성 마우스 불변 영역 좌에 작동가능하게 연결된 사람 중쇄 및 경쇄 가변 영역을 포함하는 게놈을 가져 항원 자극에 반응하여 사람 가변 영역 및 마우스 불변 영역을 포함하는 항체를 생산하는 유전자도입 마우스를 생성시킴을 포함한다. 항체의 중쇄 및 경쇄의 가변 영역을 암호화하는 DNA는 분리되고 사람 중쇄 및 경쇄 영역을 암호화하는 DNA에 작동가능하게 연결된다. 이어서 DNA는 완전한 사람 항체를 발현할 수 있는 세포에서 발현된다. 특정 양태에서, 세포는 CHO 세포이다.
항체는 보체의 고정화(보체-의존성 세포독성)(CDC) 및 항체-의존성 세포-매개 세포독성(ADCC)에의 참여를 통해 세포를 사멸시킴에 의해서 보다는 리간드-수용체 상호작용을 억제하거나 수용체 성분 상호작용을 억제하는데 있어서 치료학적으로 유용할 수 있다. 항체의 불변 영역은 보체를 고정하고 세포-의존성 세포독성을 매개하는 항체의 능력에서 중요하다. 따라서, 항체의 이소타입은 항체가 세포독성을 매개하는데 바람직할 수 있는지의 여부를 기초로 선택될 수 있다.
사람 면역글로불린은 2가지 형태로 존재할 수 있고 이들은 힌지 이질성과 연관되어 있다. 하나의 형태에서, 면역글로불린 분자는 대략 150-160kDa의 안정한 4-쇄 작제물을 포함하고 이때 이량체는 함께 쇄간 중쇄 디설파이드 결합에 의해 유지된다. 2번째 형태에서, 이량체는 쇄간 디설파이드 결합을 통해 연결되어 있지 않고 약 75 내지 80kDa의 분자는 공유 결합된 경쇄 및 중쇄(절반-항체)로 이루어져 있다. 이들 형태는 심지어 친화성 정제후에도 분리하기가 극히 어렵다. 다양한 온전한 IgG 이소타입에서 제2 형태의 출현 빈도는 이에 제한되지는 않지만 항체의 힌지 영역 이소타입과 관련된 구조적 차이때문이다. 사실, 사람 IgG4 힌지의 힌지 영역에서 단일 아미노산 치환은 제2 형태의 출현을 일반적으로 사람 IgG1 힌지를 사용하여 관찰된 수준으로 상당히 감소시킬 수 있다(문헌참조:Angal et al. (1993) Molecular Immunology 30: 105). 본 발명은 예를 들어 제법에서 목적하는 항체 형태의 수율을 개선하기 위해 요구될 수 있는 힌지, CH2 또는 CH3 영역에서의 하나 이상의 돌연변이를 갖는 항체를 포함한다.
본 발명의 항체는 바람직하게 VelocImmune™ 기술을 사용하여 제조된다. 내인성 면역글로불린 중쇄 및 경쇄 가변 영역이 상응하는 사람 가변 영역으로 대체된 유전자도입 마우스에 목적하는 항원을 챌린지하고 림프구 세포(예를 들어 B-세포)는 항체를 발현하는 마우스로부터 회수한다. 림프구 세포는 골수종 세포주와 융합시켜 불멸의 하이브리도마 세포주를 생성할 수 있고 당해 하이브리도마 세포주를 스크리닝하고 선별하여 목적하는 항원에 특이적인 항체를 생산하는 하이브리도마 세포주를 동정할 수 있다. 중쇄 및 경쇄의 가변 영역을 암호화하는 DNA는 분리하고 중쇄 및 경쇄의 목적하는 이소타입 불변 영역에 연결할 수 있다. 당해 항체 단백질은 CHO 세포와 같은 세포에서 제조될 수 있다. 또는, 항원-특이적 키메라 항체 또는 경쇄 및 중쇄의 가변 영역을 암호화하는 DNA는 항원-특이적 림프구로부터 직접 분리할 수 있다.
하나의 양태에서, 유전자도입 마우스는 18개 이하의 기능성 사람 가변 중쇄 유전자 및 12개 이하의 기능성 사람 가변 카파 경쇄 유전자를 포함한다. 또 다른 양태에서, 유전자도입 마우스는 39개 이하의 사람 가변 중쇄 유전자 및 30개 이하의 사람 가변 카파 경쇄 유전자를 포함한다. 또 다른 양태에서, 유전자도입 마우스는 80개 이하의 사람 가변 중쇄 유전자 및 40개 이하의 사람 가변 카파 경쇄 유전자를 포함한다.
일반적으로, 본 발명의 항체는 매우 높은 친화성을 갖고 일반적으로 고체상에 고정화된 항원과의 결합에 의한 측정 또는 용액중에서 측정시 KD가 약 10-9 내지 약 10-12 M이다.
처음에는, 사람 가변 영역 및 마우스 불변 영역을 갖는 고친화성 키메라 항체를 분리한다. 하기에 논의되는 바와 같이, 항체는 특성 분석되고 hIL-4R에 대한 결합 친화성, hIL-4의 hIL-4R로의 결합을 차단하는 능력 및/또는 사람 단백질에 대한 선택성을 포함하는 목적하는 특성에 대해 선택된다. 마우스 불변 영역은 목적하는 사람 불변 영역으로 대체하여 본 발명의 완전한 사람 항체, 예를 들어, 야생형 또는 변형된 IgG4 또는 IgG1(예를 들어, 서열번호 588, 589, 590)을 제조한다. 선택된 불변 영역이 특정 용도에 따라 다양할 수 있지만, 고친화성 항원 결합 및 표적 특이성 특성은 가변 영역에 존재한다.
에피토프
맵핑
및 관련 기술
특정 에피토프에 결합하는 항체를 스크리닝하기 위해, 문헌[참조: Antibodies: A Laboratory Manual 1988 Cold Spring Harbor Laboratory, Harlow and Lane, eds]에 기재된 바와 같은 통상적인 교차-차단 분석을 수행할 수 있다. 기타 방법은 알라닌 스캐닝 돌연변이, 펩타이드 블롯((Reineke (2004) Methods Mol Biol 248:443-63), 또는 펩타이드 절단 분석을 포함한다. 추가로, 에피토프 절단, 에피토프 추출 및 항원의 화학적 변형과 같은 방법이 사용될 수 있다 (Tomer (2000) Protein Science: 9:487-496).
또한 항원 구조-기반 항체 프로파일링(ASAP)으로서 공지된 변형-보조된 프로파일링(MAP)은 화학적으로 또는 효소적으로 변형된 항원 표면에 대한 각각 항체의 결합의 프로파일의 유사성에 따라 동일한 항원에 대해 지시된 대다수의 모노클로날 항체(mAb)를 분류하는 방법이다 (미국 특허원 공보 제2004/0101920호). 각각의 카테고리는 또 다른 카테고리로 표현되는 에피토프와 명백히 상이하거나 일부가 오버래핑되는 독특한 에피토프를 반영할 수 있다. 당해 기술은 유전적으로 동일한 항체의 신속한 필터링을 허용하여 특성 분석이 유전적으로 독특한 항체에 집중될 수 있다. 하이브리도마 스크리닝에 적용되는 경우, MAP는 목적하는 특성을 갖는 희귀 하이브리도마 클론의 동정을 용이하게 할 수 있다. MAP를 사용하여 본 발명의 hIL-4R 항체를 상이한 에피토프와 결합하는 항체 그룹으로 분류할 수 있다.
고정화된 항원의 구조를 변화시키는데 유용한 제제는 효소, 예를 들어, 단백질분해 효소 및 화학적 제제이다. 항원 단백질은 바이오센서 칩 표면 또는 폴리스티렌 비드상에 고정화될 수 있다. 후자는 예를 들어, 멀티플렉스 Luminex™ 검출 분석 (Luminex Corp., TX)과 같은 분석으로 처리할 수 있다. 100개 이하의 상이한 유형의 비드와 함께 멀티플렉스 분석을 취급하는 Luminex의 능력 때문에, Luminex는 다양하게 변형된 거의 무제한의 항원 표면을 제공하여 바이오센서 분석에 있어서 항체 에피토프 프로파일링의 해상능을 개선시킨다.
치료학적 투여 및 제형
본 발명에 따른 치료제의 투여는 적합한 담체, 부형제, 및 제형중에 혼입되어 개선된 이동, 전달 및 내성등을 제공하는 기타 제제와 함께 달성할 수 있다. 다수의 적당한 제형은 모든 약제학적 화학자에게 공지된 제형에서 발견될 수 있다 (문헌참조: Remington: The Science and Practice of Pharmacy, 2003, 20th ed, Lippincott Williams & Wilkins). 이들 제형은 예를 들어, 산제, 페이스트, 연고, 젤리, 왁스, 오일, 지질(양이온성 또는 음이온성) 함유 소포(예를 들어, LIPOFECTIN), DNA 접합체, 무수 흡수 페이스트, 수중유 및 유중수 에멀젼, 에멀젼 카보왁스 (다양한 분자량의 폴리에틸렌 글리콜), 반고체 겔, 및 카보왁스 함유 반고체 혼합물을 포함한다. 이전의 임의의 혼합물은 본 발명에 따른 처리 및 치료에 적당할 수 있지만, 단, 제형중의 활성 성분은 제형에 의해 불활성화되지 않아야 하고 당해 제형은 투여 경로와 생리학적으로 적합하고 허용가능해야만 한다[문헌참조: Powell et al. "Compendium of excipients for parenteral formulations" PDA (1998) J Pharm Sci Technol. 52:238-311 및 약화학자에게 잘 알려진 부형제 및 담체와 관련된 추가의 정보에 대한 이 문헌에서의 인용문헌].
본 발명의 치료학적 분자는 예를 들어, 비경구적으로, 국소적으로 또는 흡입에 의해 적응증에 대한 적당한 방식으로 환자에게 투여될 수 있다. 주사되는 경우, 길항제는 예를 들어, 관절내, 정맥내, 근육내, 병변내, 복강내 또는 피하 경로, 일시 주사 또는 연속 주입에 의해 투여될 수 있다. 경피 전달 및 임플란트로부터의 서방출과 같이 질환 또는 손상 부위에서의 국소 투여가 고려된다. 흡입에 의한 전달은 예를 들어, 비강 또는 경우 흡입, 분무기의 사용, 에어로졸 형태의 길항제 흡입 등을 포함한다. 기타 또 다른 방법은 점안제, 환제, 시럽, 로젠지 또는 츄잉검을 포함하는 경구 제제; 및 로션, 겔, 스프레이 및 연고와 같은 국소 제제를 포함한다.
특정 투여 용량 및 횟수는 투여 경로, 치료될 질환의 특성 및 중중도, 증상이 급성 또는 만성인지의 여부 및 환자의 크기 및 일반적 상태와 같은 인자에 따라 다양할 수 있다. 적당한 용량은 당업계에서, 예를 들어, 용량 상승 연구를 포함할 수 있는 임상적 시험에서 공지된 과정에 의해 결정될 수 있다. 본 발명의 치료학적 분자는 1회 또는 반복적으로 투여될 수 있다. 특정 양태에서, 항체 또는 항체 단편은 적어도 1개월 이상의 기간, 예를 들어, 1개월, 2개월 또는 3개월 동안 또는 심지어 무기한적으로 투여된다. 만성 증상을 치료하기 위해, 장기 치료가 일반적으로 가장 효과적이다. 그러나, 급성 증상을 치료하기 위해, 보다 짧은 기간, 예를 들어, 1주 내지 6주 동안의 투여가 충분할 수 있다. 일반적으로, 치료제는 환자가 선택된 지표 또는 지표들에 대해 기준선에 비해서 의학적으로 관련된 차도를 보일때까지 투여된다. IL-4 수준은 본 발명의 치료학적 분자의 치료 동안에 및/또는 치료 후에 모니터될 수 있다. IL-4 혈청 수준을 측정하는 방법은 예를 들어, ELISA 등에 의한 것으로 당업계에 공지되어 있다.
치료학적 용도 및 병용 치료
본 발명의 항체 및 항체 단편은 IL-4 활성을 감소시킴에 의해 개선되거나 억제되거나 완화되는 질환 및 장애를 치료하기 위해 유용하다. 이들 장애는 비정상적이거나 과발현의 IL-4를 특징으로 하거나 IL-4 생산에 대한 비정상적인 숙주 반응을 특징으로 하는 장애들을 포함한다. IL-4 관련 장애는 본 발명의 항체 또는 항체 단편에 의해 치료되고 예를 들어, 관절염(패혈성 관절염을 포함), 포진, 만성 특발성 두드러기, 경피증, 비대성 반흔, 위플(Whipple) 질환, 양성 전립선 비대증, 경증, 중등증 또는 중증 천식과 같은 폐 장애, 염증 장애, 예를 들어, 염증성 장 질환, 알레르기 반응, 가와사키 질환, 겸상 세포 질환, 처그-스트라우스 증후군, 그레이브스병, 자간전증, 쇼그렌 증후군, 자가면역 림프증식성 증후군, 자가면역 용혈 빈혈증, 바레트 식도, 자가면역 포도막염, 결핵, 아토피성 피부염, 궤양성 장염, 섬유증 및 신장증을 포함한다(문헌참조: U.S. 7,186,809).
본 발명은 병용 치료를 포함하고 이때 항-IL-4R 항체 또는 항체 단편은 제2 치료제와 병용 투여된다. 공동 투여 및 병용 치료는 동시 투여에 제한되지 않고 항-IL-4R 항체 또는 항체 단편이 하나 이상의 다른 치료제가 환자에게 투여됨을 포함하는 치료 과정동안에서 1회 이상 투여되는 치료 방법을 포함한다. 제2 치료제는 또 다른 IL-4 길항제, 예를들어, 또 다른 항체/항체 단편, 또는 가용성 사이토카인 수용체, IgE 길항제, 항-천식 의약(코르티코스테로이드, 비스테로이드성 제제, 베타 효능제, 류코트리엔 길항제, 크산틴, 플루티카손, 살메테롤, 알부테롤)일 수 있고 이들은 흡입 또는 기타 적당한 수단에 의해 전달될 수 있다. 특정 양태에서, 본 발명의 항-IL-4R 항체 또는 항체 단편은 IL-1 길항제, 예를 들어, 릴로나셉트 또는 IL-13 길항제와 함께 투여될 수 있다. 제2 제제는 알레르기 염증 질환, 예를 들어, 천식 및 알레르기와 같은 장애를 치료하기 위해 하나 이상의 류코트리엔 수용체 길항제를 포함할 수 있다. 류코트리엔 수용체 길항제의 예는 몬텔루카스트, 프란루카스트 및 자피를루카스트를 포함하지만 이에 제한되지 않는다. 제2 제제는 하나 이상의 TNF(에타너셉트, ENBREL), IL-9, IL-5 또는 IL-17 길항제와 같은 사이토카인 억제제를 포함할 수 있다.
하기의 실시예는 당업자에게 본 발명의 방법 및 조성물이 어떻게 제조되고 사용되는지에 대해 완전한 공개 및 설명을 제공하기 위해 제시된 것이고 발명자가 그들의 발명으로서 여기는 것의 범위를 제한하고자 하는 것은 아니다. 사용되는 수치(예를 들어, 양, 온도 등)와 관련하여 정확성을 확실히 하기 위해 노력했지만 일부 실험적 오차 및 편차도 고려되어야 한다. 달리 지시되지 않는 경우, 부는 중량부이고 분자량은 평균 분자량이며 온도는 섭씨 온도이고 압력은 대기압 또는 거의 대기압이다.
실시예
1. 사람
IL
-4 수용체에 대한 사람 항체의 생성.
사람 Ig 중쇄 가변 영역 및 카파 경쇄 가변 영역 (VelocImmune, Regeneron Pharmaceuticals, Inc.; US Patent No. 6,596,541) 둘다를 암호화하는 DNA 좌를 포함하는 마우스를 사람 IL-4R (hIL-4R, 서열번호 1)로 면역화시켰다. hIL-4R은 애주번트 중의 정제된 항원을 직접 주사하거나 hIL-4R 유전자를 포함하고 숙주의 세포 단백질 발현 기구를 사용하여 hIL-4R을 발현함으로써 생체내에서 항원 폴리펩타이드를 생산하는 DNA 플라스미드내에 hIL-4R의 DNA 서열을 제공함에 간접적으로 투여하였다. 이어서 최적의 면역 반응을 수득하기 위해, 3 또는 4주 마다 동물을 부스트하였고 항-항원 반응의 진행을 평가하기 위해 각 부스트 후 10개의 혈액을 채취하였다.
마우스가 최대 면역 반응을 달성하는 경우, 항체-발현 B 세포를 수거하고 마우스 골수종 세포와 융합시켜 하이브리도마를 제조하였다. 기능적으로 목적하는 모노클로날 항체는 특이성, 항원-결합 친화성 및 hIL-4의 hIL-4R로의 결합 차단 효능에 대해 하이브리도마 또는 형질감염된 세포의 조건화된 배지를 스크리닝함에 의해 선택하였다(하기에 기재됨).
목적하는 항원 결합 친화성, 효능 및/또는 hIL-4의 hIL-4R로의 결합 차단 능력을 보여주는 선택된 항체는 다음을 포함한다: (HCVR/LCVR): VX 4E7-9 (서열번호 3/11; 387/389; 391/393); VX 3F7-6 (서열번호 19/27; 395/397; 399/401); VAB 16G1-1 (서열번호 35/43; 403/405; 407/409); VAB 16F3-1 (서열번호 51/59, 411/413, 415/417, 579/59 및 581/59); VAB 15C8-17 (서열번호 67/75, 419/421, 423/425); VAB 13A1-6 (서열번호 83/91, 427/429, 431/433); VAB 11G8-1 (서열번호 99/107, 435/437, 439/441); VAB 10G8-19 (서열번호 115/123, 443/445, 447/449); VAB 10C1-5 (서열번호 131/139, 451/453, 455/457); VAB 8G10-1 (서열번호 147/155, 459/461, 463/465); VAB 7B9-3 (서열번호 163/171, 467/469, 471/473); VAB 6C10-14 (서열번호 179/187, 475/477, 479/481); VAB 5C5-11 (서열번호 195/203, 483/485, 487/489); VAB 3B4-10 (서열번호 211/219, 491/493, 495/497); VAB 4D5-3 (서열번호 227/235, 499/501, 503/505); VAB 1H1-2 (서열번호 243/251, 507/509, 511/513); VAK5H4-4 (서열번호 259/267, 515/517, 519/521); VAK7G8-5 (서열번호 275/283, 523/525, 527/529); VAK8G11-13 (서열번호 291/299, 531/533, 535/537); VAK9C6-11 (서열번호 307/315, 539/541, 543/545); VAK10G6-7 (서열번호 323/331, 547/549, 551/553); VAK11D4-1 (서열번호 339/347, 555/557, 559/561); VAK12B11-9 (서열번호 355/363, 563/565, 567/569); 및 VAK10G12-5 (서열번호 371/379, 571/573, 575/577).
실시예
2. 항원 결합 친화성 측정
hIL-4R과 관련하여 선택된 항체의 결합 친화성 (KD)은 실시간 바이오센서 표면 플라스몬 공명 분석 (BIAcore 2000)을 사용하여 측정하였다. 간략히 설명하면, 항체를 GAM IgG의 BIAcore 칩으로의 직접적인 화학적 커플링을 통해 제조된 염소 항-마우스(GAM) IgG 폴리클로날 항체 표면상에 포획하여 포획된 항체 표면을 형성하였다. 다양한 농도(12.5nM 내지 0.625 nM 범위)의 단량체 hIL-4R(R&D 시스템) 또는 이량체 hIL-4R-hFc를 포획된 항체 표면에 대해 주사하였다. 항원의 항체로의 결합 및 결합된 복합체의 해리는 실시간으로 모니터하였다. 평형 해리 상수 (KD) 및 해리속도 상수는 BIA 평가 소프트웨어를 사용한 속도론적 분석을 수행하여 확인하였다. BIA 평가 소프트웨어를 또한 사용하여 항원/항체 복합체 해리의 반감기(T1 /2)를 계산하였다. 당해 결과는 표 1에 나타낸다. 대조군: 완전한 사람 항-IL-4R 항체 (미국 특허 제7,186, 809호; 서열번호 10 및 12). 속도론적 분석 결과는 선택된 항체가 1nM 미만의 KD로 이량체 수용체에 결합할 수 있는 고친화성 항체를 포함함을 밝혔다. 항-hIL-4R 항체의 마우스 또는 원숭이 (Macaca fascicularis) IL-4R에 대한 결합 친화성을 또한 시험하였다. 선택된 항체는 (1) 마우스 IL-4R과 교차 반응하지 않았고; (2) 원숭이 IL-4R에 결합하는데 실패하거나 매우 낮은 친화성으로 원숭이 IL-4R에 결합하였다.
항체-항원 결합 친화성은 또한 ELISA-기본 용액 경쟁 분석을 사용하여 평가하였다. 간략히 설명하면, 항체 (1 또는 3.3 ng/ml의 정제된 단백질)를 0 내지 10㎍/ml 범위의 연속 희석된 항원 단백질(단량체 또는 이량체)와 예비 혼합하였다. 항체 및 항원 혼합물 용액을 이어서 실온에서 2시간 내지 4시간 동안 항온처리하여 결합 평형에 도달하도록 하였다. 혼합물 중의 유리된 항체를 이어서 정량적 샌드위치 ELISA를 사용하여 측정하였다. 간략히 설명하면, 96-웰 Maxisorp™ 플레이트 (VWR, West Chester, PA)를 4℃에서 밤새 PBS 중의 2㎍/ml hIL-4R-hFc 단백질로 코팅함에 이어서 BSA를 사용하여 비특이적 결합을 차단하였다. 항체 항원 혼합물 용액을 이어서 코팅된 Maxisorb 플레이트에 전달함에 이어서 1시간 항온처리하였다. 이어서 당해 플레이트를 세척 완충액으로 세척하고 플레이트-결합된 항체를 HRP-접합된 염소 항-마우스 IgG 폴리클로날 항체 시약 (Jackson ImmunoResearch) 또는 대조군 항체용 HRP-접합된 염소 항-사람 IgG 폴리클로날 항체 시약 (Jackson ImmunoResearch)으로 검출하고 BD OptEIATM (BD Biosciences Pharmingen, San Diego, CA)와 같은 비색계 기질을 사용하여 발색시켰다. 1M 인산 또는 황산으로 반응을 종료한 후에, 450nm에서의 흡광도를 기록하고 데이터를 GraphPad™ Prism 소프트웨어를 사용하여 분석하였다. 용액 중의 항원 농도에 대한 시그날의 의존성은 4개의 파라미터 적합 분석을 사용하여 분석으로 분석하였고 용액 중의 항원 부재하에 항체 샘플로부터 시그날의 50%를 감소시키는데 요구되는 항원 농도인 IC50으로서 보고하였다. IC50은 상기된 바와 같이 측정하고 표 2에 요약하였다. 바람직한 양태에서, 본 발명의 항체 또는 항체 단편은 ELISA 용액 경쟁 분석에 의한 측정시 이량체 hIL-4R에 대해 약 20pM 이하의 IC50을 나타내고 단량체 hIL-4R에 대해 약 150pM 이하 또는 약 100pM 이하의 IC50을 나타낸다.
실시예
3.
hIL
-4와
hIL
-4R 상호작용의 억제
선택된 항체가 hIL-4의 hIL-4R로의 결합을 차단하는 능력은 BIAcoreTM hIL-4 차단 분석으로 스크리닝하였고 효능은 하기에 기재된 바와 같이 정량적 hIL-4 차단 면역분석으로 측정하였다. 결과는 표 3에 요약한다.
항체가 hIL-4의 hIL-4R로의 결합을 차단하는 능력은 표면 플라스몬 공명을 사용하여 측정하였다. 정제된 hIL-4R-hFc 분자는 CM-5 상에 고정화된 염소 항-사람 IgG 폴리클로날 항체에 의해 260RU의 밀도로 포획하여 수용체-코팅된 표면을 제조하였다. 사람 IL-4 (50nM에서 0.25 ml)는 이어서 수용체-코팅된 표면상에 주사하고 결합된 hIL-4의 양을 기록하였다(hIL-4의 첫번째 주사). 이어서 결합된 hIL-4를 3M MgCl2의 펄스에 이어서 조건화 완충액으로 제거하였다. 이어서 정제된 항-hIL4R 항체를 수용체 표면상에 주사하고 동일한 농도로 hIL-4를 두번째 주사하였다(hIL-4의 두번째 주사). 예비형성된 항체 및 수용체 복합체로부터 비롯된 hIL-4 결합의 % 감소는 표 3에 보고한다.
hIL-4의 hIL-4R로의 결합하는 차단하는 능력을 추가로 평가하기 위해 정량적 면역분석을 수행하였다. 간략히 설명하면, 25pM hIL-4R-Fc의 용액은 약 50 nM 내지 0 nM 범위로 연속 희석된 항체 단백질과 예비 혼합하였다. 유리된 hIL-4R-Fc (어떠한 항체도 결합되어 있지 않음)의 농도는 hIL-4R-특이적 샌드위치 ELISA를 사용하여 측정하였다. hIL-4R에 대한 검출 플레이트는 비오티닐화된 hIL-4 (0.5㎍/ml)를 스트렙타비딘-코팅된 96-웰 플레이트상에 결합시켜 제조하였다. 예비 결합된 항체-항원 샘플을 hIL-4-코팅된 검출 플레이트에 옮겼다. 실온에서 1시간 항온처리 후 검출 플레이트를 세척하고 플레이트-결합된 hIL-4R-hFc를 HRP 접합된 염소 항-hFc 를 사용하여 검출하고 예를 들어, BD OptEIATM (BD Biosciences Pharmingen, San Diego, CA)와 같은 비색 기질을 사용하여 발색시켰다. 반응을 1M 인산 또는 황산으로 종료하였고 450nm의 흡광도를 기록하고 데이터를 GraphPad™ Prism 소프트웨어를 사용하여 분석하였다. IC50은 플레이트 결합된 hIL-4에 대해 검출가능한 IL-4R-hFc를 50% 감소시키는데 요구되는 항체의 양으로서 측정하였다. 바람직한 양태에서, 본 발명의 항체 또는 항체 단편은 25pM hIL-4R을 차단하는데 있어서, ELISA 로 측정시 약 50 pM 미만 또는 약 40 pM 미만, 또는 약 30pM 미만 또는 약 20pM 미만의 IC50을 나타낸다.
실시예
4.
시험관내
hIL
-4의 생물학적 효과의 중화
IL-4-매개된 시그날 전달 경로는 문헌에 널리 보고되었다(예를 들어, 문헌 참조: Hebenstreit et al. 2006 Cytokine Growth Factor Rev.17(3):173-88, 2006). IL-4는 2개의 수용체 복합체, I형 및 II형을 자극할 수 있다. I형 수용체 복합체는 IL-4가 IL-4R에 결합함에 이어서 공통의 감마 쇄와 이종이량체화함에 의해 형성된다. 또는, IL4/IL4R 복합체는 IL-13 수용체 1과 이종이량체화하여 II형 수용체 복합체를 형성할 수 있다. I형 및 II형 복합체 둘다는 주로 STAT6을 통해 신호를 전달한다. 따라서, STAT6를 통한 시그날 전달을 차단하는 선택된 항체의 능력은 하기된 바와 같이 평가하였다.
hIL-4 및 hIL-13에 대해 고민감성의 세포주를 확립하였다. HEK293 세포는 사람 STAT6 및 STAT6 루시퍼라제 리포터 플라스미드로 안정하게 형질감염시키고 성장 배지(DMEM, 10% FBS, L-글루타민, 페니실린, 스트렙토마이신)에 유지시켰다. 강한 IL-4 수용체-매개된 반응은 10pM hIL-4가 STAT6-형질감염된 HEK293 세포의 성장 배지에 첨가되는 경우 달성되었다. hIL-4 반응의 생분석을 위해, 세포를 분석 배지 (Optimem I (Gibco) + 0.1% FBS)에서 1회 세척하고 80㎕의 분석 배지에 1 x 104 세포/웰 (96 웰 플레이트)로 분주하였다. 정제된 항체는 분석 배지에 연속으로 희석(최종 농도 범위는 20nM 내지 0)하고 각각의 시험 항체 10㎕는 10㎕의 hIL-4(10 pM의 일정한 최종 농도)와 함께 세포에 첨가하였다. 이어서 세포는 6시간 동안 37℃, 5% CO2에서 항온배양하였다. 세포 반응 정도는 루시퍼라제 분석법(Promega Biotech)에서 측정하였다. 당해 결과는 표 4에 나타낸다.
시험관내 IL-4-의존성 생물학적 활성 억제는 또한 사람 적아세포주, TF1 또는 변형된 Il-13Rα 과발현 TF1 세포주(TF1/A12)를 사용하여 확인하였다. 당해 생분석에서, 20,000개의 세포를 10% FBS, 2mM L-글루타민, 페니실린 및 스트렙토마이신을 함유하는 RPMI 1640 배지에서 96-웰 플레이트의 각각의 웰에 접종하였다. 0 내지 50nM(최종 농도) 범위의 25㎕의 정제된 항체를 25㎕의 hIL-4 재조합 단백질과 함께 첨가하여 세포주 TF1에 대해서는 50pM 또는 세포주 TF1/A12에 대해서는 20pM의 최종 농도가 되게 하였다. 이어서 세포를 37℃에서 3일 동안 성장하도록 하고 최종 세포 수는 CCK8 키트(Dojindo, Japan)를 사용하여 측정하였다. TF-1 세포 성장을 차단하는 항체의 능력은 세포 증식을 50% 감소시키는데 요구되는 항체의 농도로서 표 4에 나타낸다.
실시예
5.
시험관내
hIL
-13의 생물학적 효과의 중화
IL-4R은 IL-13/IL-13R 복합체에의 결합을 통한 IL-13 활성의 조절제인 것으로 나타났기 때문에, 선택된 항체는 상기된 HEK293 STAT6 루시퍼라제 분석에서 10pM IL-4이 40pM hIL-13으로 대체된 변법으로 IL-13 활성을 차단하는 능력에 대해 시험하였다. 당해 항체는 또한 0 내지 50nM 항체의 존재 하에서 150pM의 hIL-13이 상기된 TF-1 세포주 분석에서 hIL-13 활성을 차단하는 효능에 대해 평가하였다. 결과는 표 5에 나타낸다.
실시예
6. 항체 결합 프로파일 평가
항체 결합 프로파일은 항체(이의 항원에 결합된)가 후속적으로 동일한 항원에 결합하는 상이한 항체 패널의 능력에 대해 나타낼 수 있는 효과를 측정함으로써 확립될 수 있다. 예를 들어, 항원은 지지체상에 고정화되어 항원-코팅된 표면을 형성할 수 있고 항원-코팅된 표면은 항체로 포화될 수 있고 이어서 항체-포화된 항원-코팅된 표면은 다른 항체 페널에 노출될 수 있다. 다른 항체 패널이 항체-포화된 항원 표면에 결합하는 정도는 항체 결합 프로파일을 제공한다. OCTETTM-기본 순차 결합 분석을 사용하여 항체 결합 프로파일을 생성하였다. 간략히 설명하면, 24개의 스트렙타비딘 고 결합성 FA 바이오센서(ForteBio, Inc., Menlo Park, CA) 그룹은 먼저 30℃에서 10분 동안 2㎍/ml에서 항원인 비오틴-hIL-4R-hFc와 항온처리하여 포화시키고 결합된 항원 양은 파장 전환에 의해 직접 측정되는, 결합 단백질로 인한 생물학적 층의 두께(nm)의 변화로서 측정하였다. 비오틴-hIL-4R-hFc-결합된 바이오센서를 이어서 제1 항체(대조군 항체)와 30℃에서 15분 동안 50㎍/ml에서 항온처리하여 포화시키고 결합된 대조군 항체의 양은 생물학적 층의 두께(nm)의 변화로서 측정하였다. 각각의 대조군 항체-결합된 센서는 이어서 24개의 상이한 항-hIL-4R 항체(제2 항체)의 패널 중 하나와 30℃에서 15분 동안 50㎍/ml에서 항온처리하였고 결합된 제2 항체의 양은 생물학적 층의 두께 변화로서 측정하였다. 동일한 분석을, 제1 항체로서 VAB16F3-1 또는 VAK5H4-4 항-hIL-4R 항체를 사용하여 반복하였다. 당해 결과는 도 1A 내지 C에 나타낸다.
선택된 항-hIL-4R 항체는 또한 웨스턴 블롯으로 평가하였다(데이터는 나타내지 않음). 간략히 설명하면, hIL-4R 단량체(레인당 200 ng) 및 mfIL-4R His-태그화된 단량체(레인당 200 ng)를, 환원성 및 비-환원성 샘플 완충액 둘다를 사용하여 SDS-PAGE 겔상에 전기영동시켰다. 4개의 별개의 겔을 각각 PVDF 막으로 옮기고 각각의 막을 2차 항체로서 HRP-접합된 염소 항-mIgG 또는 항-hIgG(Pierce)와 함께 4개의 1차 항체 항-His mAb (Qiagen), VAB 16F3-1, VAK 5H4-4 또는 대조군 항-hIL-4R 항체 중 하나에 노출시켰다. 모든 3개의 항-hIL-4R 항체는 비-환원된 형태의 hIL-4R을 인식하였다. 단지 VAB 16F3-1 및 VAK 5H4-4만이 환원된 형태의 hIL-4R을 검출하였다. 항-hIL-4R 항체 중 어느 것도 원숭이 IL-4R을 검출하지 못했다.
<110> Regeneron Pharmaceuticals, Inc.
<120> High affinity human antibodies to human IL-4 receptor
<130> 6030A-WO
<150> US 60/848,694
<151> 2006-10-02
<150> US 60/957,738
<151> 2007-08-24
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<223> Synthetic
<400> 19
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 Ser Phe
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 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Pro Gly Arg Thr Met Val Arg Gly Gly Ile Arg 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> 20
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 20
ggattcacct ttagttcctt ctgg 24
<210> 21
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 21
Gly Phe Thr Phe Ser Ser Phe Trp
1 5
<210> 22
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 22
ataaagcaag atggaagtga gaaa 24
<210> 23
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 23
Ile Lys Gln Asp Gly Ser Glu Lys
1 5
<210> 24
<211> 63
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 24
gcgagagatc ccgggcgaac tatggttcgg ggaggtataa gatattacta tggtatggac 60
gtc 63
<210> 25
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 25
Ala Arg Asp Pro Gly Arg Thr Met Val Arg Gly Gly Ile Arg Tyr Tyr
1 5 10 15
Tyr Gly Met Asp Val
20
<210> 26
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 26
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcagttgtc gggcgagtca gggtgttagt agctggttag cctggtatca gcagaaacca 120
gggaacgccc ctaagctcct gatctctgct gcatccagta tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtcaacag gctaacagtt tccctctcac tttcggcgga 300
gggaccaagg tggagatcaa a 321
<210> 27
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 27
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Gly Val Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Asn Ala Pro Lys Leu Leu Ile
35 40 45
Ser Ala Ala Ser Ser Ile 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 Gln Gln Ala Asn Ser Phe Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 28
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 28
cagggtgtta gtagctgg 18
<210> 29
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 29
Gln Gly Val Ser Ser Trp
1 5
<210> 30
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 30
gctgcatcc 9
<210> 31
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 31
Ala Ala Ser
1
<210> 32
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 32
caacaggcta acagtttccc tctcact 27
<210> 33
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 33
Gln Gln Ala Asn Ser Phe Pro Leu Thr
1 5
<210> 34
<211> 366
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 34
gaggtgaagt tggcggagtc tgggggaggc ttggtccagc cgggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttagt agccattgga tgaactgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtggccaac ataaagcaag atggaagtga taaatactat 180
gtggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactctat 240
ctgcaattga acagcctgat agccgaggac acggctgtgt attactgtgc gagagatcgg 300
ggggttagac cacctcgtgg ggcttttgat atctggggcc aagggacaat ggtcaccgtc 360
tcttca 366
<210> 35
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 35
Glu Val Lys Leu Ala 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 Ser His
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 Lys Gln Asp Gly Ser Asp Lys Tyr Tyr Val 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 Leu Asn Ser Leu Ile Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Val Arg Pro Pro Arg Gly Ala Phe Asp Ile Trp
100 105 110
Gly Gln Gly Thr Met Val Thr Val Ser Ser
115 120
<210> 36
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 36
ggattcacct ttagtagcca ttgg 24
<210> 37
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 37
Gly Phe Thr Phe Ser Ser His Trp
1 5
<210> 38
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 38
ataaagcaag atggaagtga taaa 24
<210> 39
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 39
Ile Lys Gln Asp Gly Ser Asp Lys
1 5
<210> 40
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 40
gcgagagatc ggggggttag accacctcgt ggggcttttg atatc 45
<210> 41
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 41
Ala Arg Asp Arg Gly Val Arg Pro Pro Arg Gly Ala Phe Asp Ile
1 5 10 15
<210> 42
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 42
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca gggtatcagc agctggttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt ttcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttactt ttgtcaacag gctaacagtt tccctctcac tttcggcgga 300
gggaccacgg tggagatcaa a 321
<210> 43
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 43
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly 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 Ala Ala Ser Ser Phe 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 Phe Cys Gln Gln Ala Asn Ser Phe Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Thr Val Glu Ile Lys
100 105
<210> 44
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 44
cagggtatca gcagctgg 18
<210> 45
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 45
Gln Gly Ile Ser Ser Trp
1 5
<210> 46
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 46
gctgcatcc 9
<210> 47
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 47
Ala Ala Ser
1
<210> 48
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 48
caacaggcta acagtttccc tctcact 27
<210> 49
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 49
Gln Gln Ala Asn Ser Phe Pro Leu Thr
1 5
<210> 50
<211> 384
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 50
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttaat agttatggaa tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagaactt acaatggtaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagatgag 300
gcccgtatag tagtggctgg tacaactcct tactactacg gtatggacgt ctggggccaa 360
gggaccacgg tcaccgtctc ctca 384
<210> 51
<211> 128
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 51
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 Asn Ser 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 Arg Thr Tyr Asn 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 Asp Glu Ala Arg Ile Val Val Ala Gly Thr Thr Pro 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> 52
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 52
ggttacacct ttaatagtta tgga 24
<210> 53
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 53
Gly Tyr Thr Phe Asn Ser Tyr Gly
1 5
<210> 54
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 54
atcagaactt acaatggtaa caca 24
<210> 55
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 55
Ile Arg Thr Tyr Asn Gly Asn Thr
1 5
<210> 56
<211> 63
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 56
gcgagagatg aggcccgtat agtagtggct ggtacaactc cttactacta cggtatggac 60
gtc 63
<210> 57
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 57
Ala Arg Asp Glu Ala Arg Ile Val Val Ala Gly Thr Thr Pro Tyr Tyr
1 5 10 15
Tyr Gly Met Asp Val
20
<210> 58
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 58
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtgggaga cagagtcacc 60
atcacttgtc gggcgagtca ggatattagt atttggttag cctggtatca gcagagtcca 120
gggaaagccc ctaaactcct gatcaatgtt gcatcccgtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcaacag tctgcagcct 240
gaagattttg taacttacta ttgtcaacag gctaacagtt tcccgatcac cttcggccaa 300
gggacacgac tggcgaccaa a 321
<210> 59
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 59
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ile Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Ser Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Asn Val Ala Ser Arg 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 Asn Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Val Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ile
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Ala Thr Lys
100 105
<210> 60
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 60
caggatatta gtatttgg 18
<210> 61
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 61
Gln Asp Ile Ser Ile Trp
1 5
<210> 62
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 62
gttgcatcc 9
<210> 63
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 63
Val Ala Ser
1
<210> 64
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 64
caacaggcta acagtttccc gatcacc 27
<210> 65
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 65
Gln Gln Ala Asn Ser Phe Pro Ile Thr
1 5
<210> 66
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 66
caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggagggtc cctgagactc 60
tcctgtgcag tttctggatt cacaatcagt gaccactaca tgagctggat ccgccaggct 120
ccagggaagg ggctggagtg gatttcatac attagtagta gtggtagtaa aatatactac 180
gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgttt 240
ctgcaaatga acagcctgag agccgaggac acggccgttt attactgtgc gagaacacga 300
cagctcgtgg gggactactg gggccaggga accctggtca ccgtctcctc a 351
<210> 67
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 67
Gln 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 Val Ser Gly Phe Thr Ile Ser Asp His
20 25 30
Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Ser Tyr Ile Ser Ser Ser Gly Ser Lys Ile Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 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 Thr Arg Gln Leu Val Gly Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 68
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 68
ggattcacaa tcagtgacca ctac 24
<210> 69
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 69
Gly Phe Thr Ile Ser Asp His Tyr
1 5
<210> 70
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 70
attagtagta gtggtagtaa aata 24
<210> 71
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 71
Ile Ser Ser Ser Gly Ser Lys Ile
1 5
<210> 72
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 72
gcgagaacac gacagctcgt gggggactac 30
<210> 73
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 73
Ala Arg Thr Arg Gln Leu Val Gly Asp Tyr
1 5 10
<210> 74
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 74
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctttgct gcatccactt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaacag cttaatagtt acccgctcac tttcggcgga 300
gggaccaagg tggagatcag a 321
<210> 75
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 75
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
Phe Ala Ala Ser Thr 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 Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Arg
100 105
<210> 76
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 76
cagggcatta gcagttat 18
<210> 77
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 77
Gln Gly Ile Ser Ser Tyr
1 5
<210> 78
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 78
gctgcatcc 9
<210> 79
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 79
Ala Ala Ser
1
<210> 80
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 80
caacagctta atagttaccc gctcact 27
<210> 81
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 81
Gln Gln Leu Asn Ser Tyr Pro Leu Thr
1 5
<210> 82
<211> 372
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 82
gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttgat aattatgcca tgcactgggt ccggcaagct 120
ccagggaagg gcctggagtg ggtctcaggt attaggtgga atagtggtag cataggctat 180
gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240
ctgcaaatga atagtctgag agctgaggac acggccttgt attactgtgc aaaagaaggt 300
ggatatagtg gctaccgccc cggacccttc tttgactact ggggccaggg aaccctggtc 360
accgtctcct cc 372
<210> 83
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 83
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asn Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Gly Ile Arg 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 Glu Gly Gly Tyr Ser Gly Tyr Arg Pro Gly Pro Phe Phe Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 84
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 84
ggattcacct ttgataatta tgcc 24
<210> 85
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 85
Gly Phe Thr Phe Asp Asn Tyr Ala
1 5
<210> 86
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 86
attaggtgga atagtggtag cata 24
<210> 87
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 87
Ile Arg Trp Asn Ser Gly Ser Ile
1 5
<210> 88
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 88
gcaaaagaag gtggatatag tggctaccgc cccggaccct tctttgacta c 51
<210> 89
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 89
Ala Lys Glu Gly Gly Tyr Ser Gly Tyr Arg Pro Gly Pro Phe Phe Asp
1 5 10 15
Tyr
<210> 90
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 90
gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttaac tacaacttag cctggtacca gcataaacct 120
ggccaggctc ccaggctcct catctatggt gcatccacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggccgctcac tttcggcgga 300
gggaccaagg tggagatcaa a 321
<210> 91
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 91
Glu 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 Ser Val Asn Tyr Asn
20 25 30
Leu Ala Trp Tyr Gln His Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly 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 Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 92
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 92
cagagtgtta actacaac 18
<210> 93
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 93
Gln Ser Val Asn Tyr Asn
1 5
<210> 94
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 94
ggtgcatcc 9
<210> 95
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 95
Gly Ala Ser
1
<210> 96
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 96
cagcagtata ataactggcc gctcact 27
<210> 97
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 97
Gln Gln Tyr Asn Asn Trp Pro Leu Thr
1 5
<210> 98
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 98
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtca cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctcag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactcctg gggccaggga accctggtca ccgtctcctc a 351
<210> 99
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 99
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 Asn 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 Val Tyr Asn Gly His 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 Gly Ser Gly Tyr Asp Phe Asp Ser Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 100
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 100
ggttacacct ttaccaacta tggt 24
<210> 101
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 101
Gly Tyr Thr Phe Thr Asn Tyr Gly
1 5
<210> 102
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 102
atcagcgttt acaatggtca caca 24
<210> 103
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 103
Ile Ser Val Tyr Asn Gly His Thr
1 5
<210> 104
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 104
gcgagaggga gtggctacga ttttgactcc 30
<210> 105
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 105
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Ser
1 5 10
<210> 106
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 106
gccatccaga tgacccagtc ttcatcctcc ctgtctgcat ctgttggaga cagagtcacc 60
atcacttgcc gggcaagtca ggccattaga aatgctttag gctggtatca gcagaaaccg 120
gggaaagccc ctaaggtcct gatctatgct gcatccagtt tacaaagtgg catcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacgatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa a 321
<210> 107
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 107
Ala Ile Gln Met Thr Gln Ser Ser Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ala Ile Arg Asn Ala
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val 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 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 Asp Tyr Asp Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 108
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 108
caggccatta gaaatgct 18
<210> 109
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 109
Gln Ala Ile Arg Asn Ala
1 5
<210> 110
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 110
gctgcatcc 9
<210> 111
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 111
Ala Ala Ser
1
<210> 112
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 112
ctacaagatt acgattaccc gtacact 27
<210> 113
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 113
Leu Gln Asp Tyr Asp Tyr Pro Tyr Thr
1 5
<210> 114
<211> 348
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 114
caggtgcagc tggtacagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctagata caccttcacc agttatgata tcaactgggt gcgacaggcc 120
actggacaag ggcttgagtg gatgggatgg atgaacccaa acagtggtaa cacaggctat 180
gcacagaagt tccagggcag agtcaccatg accaggaaca cctccacaag cacagcctac 240
atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagtacga 300
cgcttttttg actactgggg ccagggaacc ctggtcaccg tctcctca 348
<210> 115
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 115
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 Arg 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 Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asn Thr Ser Thr 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 Val Arg Arg Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 116
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 116
agatacacct tcaccagtta tgat 24
<210> 117
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 117
Arg Tyr Thr Phe Thr Ser Tyr Asp
1 5
<210> 118
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 118
atgaacccaa acagtggtaa caca 24
<210> 119
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 119
Met Asn Pro Asn Ser Gly Asn Thr
1 5
<210> 120
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 120
gcgagagtac gacgcttttt tgactac 27
<210> 121
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 121
Ala Arg Val Arg Arg Phe Phe Asp Tyr
1 5
<210> 122
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 122
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgct gggccagtca gggcattatc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccactt tgcacagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaccag cttaaaagtt acccgatcac cttcggccaa 300
gggacacgac tggagattaa a 321
<210> 123
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 123
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 Ile 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 Thr Leu His 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 His Gln Leu Lys Ser Tyr Pro Ile
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 124
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 124
cagggcatta tcagttat 18
<210> 125
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 125
Gln Gly Ile Ile Ser Tyr
1 5
<210> 126
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 126
gctgcatcc 9
<210> 127
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 127
Ala Ala Ser
1
<210> 128
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 128
caccagctta aaagttaccc gatcacc 27
<210> 129
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 129
His Gln Leu Lys Ser Tyr Pro Ile Thr
1 5
<210> 130
<211> 348
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 130
caggtgcagt tggtggagac tgggggagac ttggtcaggc ctggagggtc cctgagactc 60
tcctgtacag cctctggatt caccctcagt gactactaca tgagctggat ccgtcaggct 120
ccagggaagg ggctggagtg ggtttcatac attaggagaa gtggtaatac catatactac 180
gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gagagggggg 300
gactgggcgg acgtctgggg ccaagggacc acggtcaccg tctcctca 348
<210> 131
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 131
Gln Val Gln Leu Val Glu Thr Gly Gly Asp Leu Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Leu Ser Asp Tyr
20 25 30
Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Tyr Ile Arg Arg Ser Gly Asn Thr Ile Tyr 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Gly Asp Trp Ala Asp Val Trp Gly Gln Gly Thr Thr Val
100 105 110
Thr Val Ser Ser
115
<210> 132
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 132
ggattcaccc tcagtgacta ctac 24
<210> 133
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 133
Gly Phe Thr Leu Ser Asp Tyr Tyr
1 5
<210> 134
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 134
attaggagaa gtggtaatac cata 24
<210> 135
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 135
Ile Arg Arg Ser Gly Asn Thr Ile
1 5
<210> 136
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 136
gcgagagggg gggactgggc ggacgtc 27
<210> 137
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 137
Ala Arg Gly Gly Asp Trp Ala Asp Val
1 5
<210> 138
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 138
gacatccaga tgacccagtc tccatcctca ctgtctgcct ctgtgggaga cagagtcacc 60
atcacttgtc gggcgagtca gggcattagc atttatttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct gcatccagtt tgcaacgtgg ggtcccatca 180
aagttcagcg gcagtggatc tgggacagat ttcactctca ccatcagtag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtt acccgtacac ttttggccag 300
gggaccaaac tggaaatcaa a 321
<210> 139
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 139
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 Ser Ile Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Arg Gly Val Pro Ser Lys 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 Gln Gln Tyr Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 140
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 140
cagggcatta gcatttat 18
<210> 141
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 141
Gln Gly Ile Ser Ile Tyr
1 5
<210> 142
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 142
gctgcatcc 9
<210> 143
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 143
Ala Ala Ser
1
<210> 144
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 144
caacagtata atagttaccc gtacact 27
<210> 145
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 145
Gln Gln Tyr Asn Ser Tyr Pro Tyr Thr
1 5
<210> 146
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 146
caggttcagc tggtgcagtc tggacctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa cataaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggacctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaggga accctggtca ccgtctcctc a 351
<210> 147
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 147
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 Asn 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 Val Tyr Asn Gly Asn Ile 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 Asp Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 148
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 148
ggttacacct ttaccaacta tggt 24
<210> 149
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 149
Gly Tyr Thr Phe Thr Asn Tyr Gly
1 5
<210> 150
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 150
atcagcgttt acaatggtaa cata 24
<210> 151
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 151
Ile Ser Val Tyr Asn Gly Asn Ile
1 5
<210> 152
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 152
gcgagaggga gtggctacga ttttgactac 30
<210> 153
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 153
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr
1 5 10
<210> 154
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 154
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgttggaga cagagtcacc 60
atcacttgcc gggcaagtca ggacattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtgcttc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg cagcttatta ctgtctacaa gattacaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa a 321
<210> 155
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 155
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 Ala
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 Ala Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Ala Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 156
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 156
caggacatta gaaatgct 18
<210> 157
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 157
Gln Asp Ile Arg Asn Ala
1 5
<210> 158
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 158
gctgcatcc 9
<210> 159
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 159
Ala Ala Ser
1
<210> 160
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 160
ctacaagatt acaattaccc gtacact 27
<210> 161
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 161
Leu Gln Asp Tyr Asn Tyr Pro Tyr Thr
1 5
<210> 162
<211> 366
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 162
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg attctgctta cacctttaat agatatggta tcagctgggt gcgacaggcc 120
cctggacaag gccttgagtg gatgggatgg atcagcgctt acactggtaa cacagtctat 180
gcacagaagc tccagggcag agtcaccatg accacagaca attccacgag cacagcttac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagataag 300
tcgatttttg gagtggttag agggtttgac tactggggcc agggaaccct ggtcaccgtc 360
tcctca 366
<210> 163
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 163
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 Asp Ser Ala Tyr Thr Phe Asn Arg 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 Thr Gly Asn Thr Val Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Asn 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 Asp Lys Ser Ile Phe Gly Val Val Arg Gly Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 164
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 164
gcttacacct ttaatagata tggt 24
<210> 165
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 165
Ala Tyr Thr Phe Asn Arg Tyr Gly
1 5
<210> 166
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 166
atcagcgctt acactggtaa caca 24
<210> 167
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 167
Ile Ser Ala Tyr Thr Gly Asn Thr
1 5
<210> 168
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 168
gcgagagata agtcgatttt tggagtggtt agagggtttg actac 45
<210> 169
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 169
Ala Arg Asp Lys Ser Ile Phe Gly Val Val Arg Gly Phe Asp Tyr
1 5 10 15
<210> 170
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 170
gaaatagtga tgacgcagtc tccagtcacc ctgtctctgt ctccagggga aagagccacc 60
ctcccctgca gggccagtca gagtgttagc agcagcttag cctggtacca gcagaaagct 120
ggccagtctc ccaggctcct catctatggt gcatctacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacggag ttcactctca ccatcagcaa cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggcctctcac tttcggcgga 300
gggaccaagg tggagatcaa a 321
<210> 171
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 171
Glu Ile Val Met Thr Gln Ser Pro Val Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Pro Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Ala Gly Gln Ser Pro Arg Leu Leu Ile
35 40 45
Tyr Gly 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 Asn Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asn Asn Trp Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 172
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 172
cagagtgtta gcagcagc 18
<210> 173
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 173
Gln Ser Val Ser Ser Ser
1 5
<210> 174
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 174
ggtgcatct 9
<210> 175
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 175
Gly Ala Ser
1
<210> 176
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 176
cagcagtata ataactggcc tctcact 27
<210> 177
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 177
Gln Gln Tyr Asn Asn Trp Pro Leu Thr
1 5
<210> 178
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 178
caggttcagc tggtgcagtc tggagctgaa gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggcc tcacttgggt gcgacaggcc 120
ccgggacgag gtcttgagtg gatgggatgg atcagtgttt acaatggcaa cacaaactat 180
gcacagacgc tcaagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggaactga agagcctgag atctgacgac acggccgttt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaggga accctggtca ccgtctcctc a 351
<210> 179
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 179
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 Asn Tyr
20 25 30
Gly Leu Thr Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Val Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Thr Leu
50 55 60
Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 180
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 180
ggttacacct ttaccaacta tggc 24
<210> 181
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 181
Gly Tyr Thr Phe Thr Asn Tyr Gly
1 5
<210> 182
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 182
atcagtgttt acaatggcaa caca 24
<210> 183
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 183
Ile Ser Val Tyr Asn Gly Asn Thr
1 5
<210> 184
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 184
gcgagaggga gtggctacga ttttgactac 30
<210> 185
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 185
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr
1 5 10
<210> 186
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 186
gccatccaga tgacccagtc tccttcctcc ctgtctgcat ctgttggaga cagagtcgcc 60
atcacttgcc gggcaagtca ggacattaga aatgatttag gctggtatca gcagaaacca 120
gggaaagccc ctaagcttct gatccatact gcttccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcaa cctgcagcct 240
gaagattttg ccacttatta ctgtctccaa gataatagtt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa t 321
<210> 187
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 187
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Ala 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
His Thr 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 Asn Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Asn
100 105
<210> 188
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 188
caggacatta gaaatgat 18
<210> 189
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 189
Gln Asp Ile Arg Asn Asp
1 5
<210> 190
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 190
actgcttcc 9
<210> 191
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 191
Thr Ala Ser
1
<210> 192
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 192
ctccaagata atagttaccc gtacact 27
<210> 193
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 193
Leu Gln Asp Asn Ser Tyr Pro Tyr Thr
1 5
<210> 194
<211> 348
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 194
caggtgcaac tggtgcagtc tggggctgag gtgcagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggata caccttcacc ggccagtata ttcactgggt tcgacaggcc 120
cctggacaag gacttgagtg gatgggatgg atcaacccta acagtggtgg cacaaacttt 180
gcacagaagt ttcaggacag ggtcaccatg accagggaca cgtccatcgg cacagtatac 240
atggaactga ggaggctgac atctgacgac acggccgtat tttattgtgt gagagaaaag 300
agaggttttg atatctgggg ccaagggaca atggtcaccg tttcttca 348
<210> 195
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 195
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Gln Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Gln
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 Phe Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Gly Thr Val Tyr
65 70 75 80
Met Glu Leu Arg Arg Leu Thr Ser Asp Asp Thr Ala Val Phe Tyr Cys
85 90 95
Val Arg Glu Lys Arg Gly Phe Asp Ile Trp Gly Gln Gly Thr Met Val
100 105 110
Thr Val Ser Ser
115
<210> 196
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 196
ggatacacct tcaccggcca gtat 24
<210> 197
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 197
Gly Tyr Thr Phe Thr Gly Gln Tyr
1 5
<210> 198
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 198
atcaacccta acagtggtgg caca 24
<210> 199
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 199
Ile Asn Pro Asn Ser Gly Gly Thr
1 5
<210> 200
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 200
gtgagagaaa agagaggttt tgatatc 27
<210> 201
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 201
Val Arg Glu Lys Arg Gly Phe Asp Ile
1 5
<210> 202
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 202
gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcaacttag cctggtacca gcagaaacct 120
ggccaggctc ccaggctcct catctatggt gcatccacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggccattcac tttcggccct 300
gggaccaaag tggatatcaa a 321
<210> 203
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 203
Glu 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 Ser Val Ser Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly 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 Pro Phe
85 90 95
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
100 105
<210> 204
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 204
cagagtgtta gcagcaac 18
<210> 205
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 205
Gln Ser Val Ser Ser Asn
1 5
<210> 206
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 206
ggtgcatcc 9
<210> 207
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 207
Gly Ala Ser
1
<210> 208
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 208
cagcagtata ataactggcc attcact 27
<210> 209
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 209
Gln Gln Tyr Asn Asn Trp Pro Phe Thr
1 5
<210> 210
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 210
caggttcatc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcggctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtattt acaatggtaa cacaaattat 180
gcacagaggc tccagggcag agtcaccatg accacagaca catccacgag cacagccttc 240
atggacctga ggagcctgaa atctgacgac acggccgttt attactgtgc gagaggtagt 300
ggctacaatt tcgaccactg gggccaggga accctggtca ccgtctcctc c 351
<210> 211
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 211
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 Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Gly Ile Gly Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ile Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Arg Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Phe
65 70 75 80
Met Asp Leu Arg Ser Leu Lys Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asn Phe Asp His Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 212
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 212
ggttacacct ttaccaacta tggt 24
<210> 213
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 213
Gly Tyr Thr Phe Thr Asn Tyr Gly
1 5
<210> 214
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 214
atcagtattt acaatggtaa caca 24
<210> 215
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 215
Ile Ser Ile Tyr Asn Gly Asn Thr
1 5
<210> 216
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 216
gcgagaggta gtggctacaa tttcgaccac 30
<210> 217
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 217
Ala Arg Gly Ser Gly Tyr Asn Phe Asp His
1 5 10
<210> 218
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 218
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtatca gcagataccg 120
gggaaagccc ctaaactcct gatctatgct gcatccagtt tacaaagtgg ggtcccgtca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcaa cctgcagcct 240
gaagattttg cagtttattt ctgtctacaa gataacactt atccgtacac ttttggccag 300
gggaccaatc tggagagcaa a 321
<210> 219
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 219
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 Gly Ile Arg Asn Asp
20 25 30
Leu Gly Trp Tyr Gln Gln Ile 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 Asn Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Phe Cys Leu Gln Asp Asn Thr Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Asn Leu Glu Ser Lys
100 105
<210> 220
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 220
cagggcatta gaaatgat 18
<210> 221
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 221
Gln Gly Ile Arg Asn Asp
1 5
<210> 222
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 222
gctgcatcc 9
<210> 223
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 223
Ala Ala Ser
1
<210> 224
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 224
ctacaagata acacttatcc gtacact 27
<210> 225
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 225
Leu Gln Asp Asn Thr Tyr Pro Tyr Thr
1 5
<210> 226
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 226
caggttcagt tggtgcagtc tggacctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagttgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa aacaaactat 180
gcacagaagt tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggacctga ggagcctgag atctgacgac acggccgtat attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaggga accctggtca ccgtctcctc a 351
<210> 227
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 227
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 Asn 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 Val Tyr Asn Gly Lys Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 228
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 228
ggttacacct ttaccaacta tggt 24
<210> 229
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 229
Gly Tyr Thr Phe Thr Asn Tyr Gly
1 5
<210> 230
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 230
atcagcgttt acaatggtaa aaca 24
<210> 231
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 231
Ile Ser Val Tyr Asn Gly Lys Thr
1 5
<210> 232
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 232
gcgagaggga gtggctacga ttttgactac 30
<210> 233
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 233
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr
1 5 10
<210> 234
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 234
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctttgct tcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatccgcag cctgcagcct 240
gaagattttg cagcttatta ctgtctacaa gattataatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa a 321
<210> 235
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 235
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 Gly Ile Arg Asn Ala
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Phe Ala Ser 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 Arg Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Ala Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 236
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 236
cagggcatta gaaatgct 18
<210> 237
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 237
Gln Gly Ile Arg Asn Ala
1 5
<210> 238
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 238
gcttcatcc 9
<210> 239
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 239
Ala Ser Ser
1
<210> 240
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 240
ctacaagatt ataattaccc gtacact 27
<210> 241
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 241
Leu Gln Asp Tyr Asn Tyr Pro Tyr Thr
1 5
<210> 242
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 242
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtgttt acaatggtaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggacctga ggagcctgag atctgacgac gcggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaggga accctggtca ccgtctcctc a 351
<210> 243
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 243
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 Ser 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 Val Tyr Asn 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 Asp Leu Arg Ser Leu Arg Ser Asp Asp Ala Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 244
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 244
ggttacacct ttaccagcta tggt 24
<210> 245
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 245
Gly Tyr Thr Phe Thr Ser Tyr Gly
1 5
<210> 246
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 246
atcagtgttt acaatggtaa caca 24
<210> 247
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 247
Ile Ser Val Tyr Asn Gly Asn Thr
1 5
<210> 248
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 248
gcgagaggga gtggctacga ttttgactac 30
<210> 249
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 249
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr
1 5 10
<210> 250
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 250
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaaactcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggtacagat ttcactctca ccatcagcag cctgcagtct 240
gaagattttg caacttatta ctgtctacaa gattacaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa a 321
<210> 251
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 251
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 Gly Ile Arg Asn Ala
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 Ser Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 252
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 252
cagggcatta gaaatgct 18
<210> 253
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 253
Gln Gly Ile Arg Asn Ala
1 5
<210> 254
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 254
gctgcatcc 9
<210> 255
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 255
Ala Ala Ser
1
<210> 256
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 256
ctacaagatt acaattaccc gtacact 27
<210> 257
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 257
Leu Gln Asp Tyr Asn Tyr Pro Tyr Thr
1 5
<210> 258
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 258
caggtgcgac tggtggagtc tgggggaggc gtggtccagc ctggagggtc cctgagactc 60
tcctgtgtag cctctggatt caccttcaga agctatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtt atatcatatg atggcagtaa aacattctac 180
gtagattccg tgaaggtccg attcaccatc tccagagaca attccaagaa cacgctttat 240
ttggaaatga acagcctgag agttgacgac acggctgtgt atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcgccgt ctcctca 357
<210> 259
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 259
Gln Val Arg Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Ala Val Ser Ser
115
<210> 260
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 260
ggattcacct tcagaagcta tggc 24
<210> 261
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 261
Gly Phe Thr Phe Arg Ser Tyr Gly
1 5
<210> 262
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 262
atatcatatg atggcagtaa aaca 24
<210> 263
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 263
Ile Ser Tyr Asp Gly Ser Lys Thr
1 5
<210> 264
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 264
gtgaaagaag gaagaagtgg gagttggttc gacccc 36
<210> 265
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 265
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro
1 5 10
<210> 266
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 266
gacatccaga tgacccagtc tccatcctca ctgtctgcgt ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaaaccc ctaactccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg ccggtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa a 321
<210> 267
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 267
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Asn Ser Leu Ile
35 40 45
Phe Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Ala
50 55 60
Gly 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 268
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 268
caggccatta acaatttt 18
<210> 269
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 269
Gln Ala Ile Asn Asn Phe
1 5
<210> 270
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 270
gctacatcc 9
<210> 271
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 271
Ala Thr Ser
1
<210> 272
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 272
cagcagtata atagtcaccc gtggacg 27
<210> 273
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 273
Gln Gln Tyr Asn Ser His Pro Trp Thr
1 5
<210> 274
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 274
caggtgcgac tggtggagtc tgggggaggc gtggtccagc ctggagggtc cctgagactc 60
tcctgtactg cctctggatt catcttcaga agttatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtc atatcatatg atggcagtaa aacattctac 180
gtagattccg tgaaggtccg attcaccatc tccagagaca actccaagaa cacgctttat 240
ttggagatga acagcctgag agttgacgac acggctgtat atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcgccgt ctcctca 357
<210> 275
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 275
Gln Val Arg Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ile Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Ala Val Ser Ser
115
<210> 276
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 276
ggattcatct tcagaagtta tggc 24
<210> 277
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 277
Gly Phe Ile Phe Arg Ser Tyr Gly
1 5
<210> 278
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 278
atatcatatg atggcagtaa aaca 24
<210> 279
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 279
Ile Ser Tyr Asp Gly Ser Lys Thr
1 5
<210> 280
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 280
gtgaaagaag gaagaagtgg gagttggttc gacccc 36
<210> 281
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 281
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro
1 5 10
<210> 282
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 282
gacatccaca tgacccagtc tccatcctca ctgtctgcgt ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcag a 321
<210> 283
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 283
Asp Ile His 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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Arg
100 105
<210> 284
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 284
caggccatta acaatttt 18
<210> 285
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 285
Gln Ala Ile Asn Asn Phe
1 5
<210> 286
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 286
gctacatcc 9
<210> 287
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 287
Ala Thr Ser
1
<210> 288
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 288
caacagtata atagtcaccc gtggacg 27
<210> 289
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 289
Gln Gln Tyr Asn Ser His Pro Trp Thr
1 5
<210> 290
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 290
caggtgcgac tggtggagtc tgggggaggc gtggtccagc ctggagggtc cctgagactc 60
tcctgtgctg cctctggatt catcttcaga agctatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtc atatcatatg atggcagtaa aacattctac 180
gtagattccg tgaaggtccg attcaccata tccagagaca actccaagaa cacgctttat 240
ttggaaatga acagcctgag agttgacgac acggctgtat atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcgccgt ctcctca 357
<210> 291
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 291
Gln Val Arg Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ile Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Ala Val Ser Ser
115
<210> 292
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 292
ggattcatct tcagaagcta tggc 24
<210> 293
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 293
Gly Phe Ile Phe Arg Ser Tyr Gly
1 5
<210> 294
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 294
atatcatatg atggcagtaa aaca 24
<210> 295
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 295
Ile Ser Tyr Asp Gly Ser Lys Thr
1 5
<210> 296
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 296
gtgaaagaag gaagaagtgg gagttggttc gacccc 36
<210> 297
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 297
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro
1 5 10
<210> 298
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 298
gacatccaca tgacccagtc tccatcctca ctgtctgcgt ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa a 321
<210> 299
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 299
Asp Ile His 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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 300
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 300
caggccatta acaatttt 18
<210> 301
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 301
Gln Ala Ile Asn Asn Phe
1 5
<210> 302
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 302
gctacatcc 9
<210> 303
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 303
Ala Thr Ser
1
<210> 304
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 304
caacagtata atagtcaccc gtggacg 27
<210> 305
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 305
Gln Gln Tyr Asn Ser His Pro Trp Thr
1 5
<210> 306
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 306
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg gtctggagtg ggtgacagtt atatcatatg atggaagtat taaatattat 180
gtagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgttt 240
ctgcaaatga atagcctgcg agttgaggac acggctgtgt attactgtgc gaaggaaggt 300
aggaagtacg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc ctca 354
<210> 307
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 307
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
Thr Val Ile Ser Tyr Asp Gly Ser Ile 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 Phe
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 Glu Gly Arg Lys Tyr Gly Met Asp Val Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 308
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 308
ggattcacct tcagtagcta tggc 24
<210> 309
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 309
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 310
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 310
atatcatatg atggaagtat taaa 24
<210> 311
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 311
Ile Ser Tyr Asp Gly Ser Ile Lys
1 5
<210> 312
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 312
gcgaaggaag gtaggaagta cggtatggac gtc 33
<210> 313
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 313
Ala Lys Glu Gly Arg Lys Tyr Gly Met Asp Val
1 5 10
<210> 314
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 314
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gattattagt agcttattgg tctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag tatcatagtt acatgtacac ttttggccag 300
gggaccaagc tggagatcaa a 321
<210> 315
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 315
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 Ile Ile Ser Ser Leu
20 25 30
Leu Val 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 His Ser Tyr Met Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 316
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 316
cagattatta gtagctta 18
<210> 317
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 317
Gln Ile Ile Ser Ser Leu
1 5
<210> 318
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 318
aaggcgtct 9
<210> 319
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 319
Lys Ala Ser
1
<210> 320
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 320
caacagtatc atagttacat gtacact 27
<210> 321
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 321
Gln Gln Tyr His Ser Tyr Met Tyr Thr
1 5
<210> 322
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 322
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtacag cctctggatt caccttcagt agctttggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtt atatcatatg atggcagtaa aaaatactac 180
gcagactccg tgaaggtccg attcaccatc tccagagaca actccaagaa cacgctttat 240
ctgcaaatga acagcctgag agttgacgac acggctgtgt atttctgtgc gaaagaagga 300
agaactggga attggttcga cccctggggc caggggaccc tggtcgccgt ctcctca 357
<210> 323
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 323
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 Thr Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Lys Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Val 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 Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Ala Val Ser Ser
115
<210> 324
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 324
ggattcacct tcagtagctt tggc 24
<210> 325
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 325
Gly Phe Thr Phe Ser Ser Phe Gly
1 5
<210> 326
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 326
atatcatatg atggcagtaa aaaa 24
<210> 327
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 327
Ile Ser Tyr Asp Gly Ser Lys Lys
1 5
<210> 328
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 328
gcgaaagaag gaagaactgg gaattggttc gacccc 36
<210> 329
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 329
Ala Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro
1 5 10
<210> 330
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 330
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattatttag cctggtttca gcagaaacca 120
gggaaaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcactggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcag a 321
<210> 331
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 331
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 Ala Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Arg
100 105
<210> 332
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 332
caggccatta acaattat 18
<210> 333
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 333
Gln Ala Ile Asn Asn Tyr
1 5
<210> 334
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 334
gctacatcc 9
<210> 335
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 335
Ala Thr Ser
1
<210> 336
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 336
caacagtata atagtcaccc gtggacg 27
<210> 337
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 337
Gln Gln Tyr Asn Ser His Pro Trp Thr
1 5
<210> 338
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 338
caggtgcgac tggtggagtc tgggggaggc gtggtccagc ctggaaggtc cctgagactc 60
tcctgtgtag cctctggatt caccttcaga agttatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtc atatcatatg atggcagtca aacattctat 180
gtagattccg tgaaggtccg attcaccatc tccagagaca actccaacaa cacgctttat 240
ttggaaatga acagcctgag agttgacgac acggctgttt atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcgccgt ctcctca 357
<210> 339
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 339
Gln Val Arg Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Gln Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Ala Val Ser Ser
115
<210> 340
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 340
ggattcacct tcagaagtta tggc 24
<210> 341
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 341
Gly Phe Thr Phe Arg Ser Tyr Gly
1 5
<210> 342
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 342
atatcatatg atggcagtca aaca 24
<210> 343
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 343
Ile Ser Tyr Asp Gly Ser Gln Thr
1 5
<210> 344
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 344
gtgaaagaag gaagaagtgg gagttggttc gacccc 36
<210> 345
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 345
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro
1 5 10
<210> 346
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 346
gacatccaca tgacccagtc tccatcctca ctgtctgcgt ctgttggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaat aattatttag cctggtttca gcagaaacca 120
gggagaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa a 321
<210> 347
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 347
Asp Ile His 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 Ala Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Arg Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 348
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 348
caggccatta ataattat 18
<210> 349
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 349
Gln Ala Ile Asn Asn Tyr
1 5
<210> 350
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 350
gctacatcc 9
<210> 351
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 351
Ala Thr Ser
1
<210> 352
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 352
caacagtata atagtcaccc gtggacg 27
<210> 353
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 353
Gln Gln Tyr Asn Ser His Pro Trp Thr
1 5
<210> 354
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 354
caggtgcagt tggtggagtc agggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agttatgcca tgtactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtg atatcatatg atggaagtaa taaatactat 180
acagactccg tgaagggccg attcaccgtc tccagagaca attccaaaaa cacgctgttt 240
ctgcaaatga acagcctgag agctgaggac acggctctgt attactgtgc gaaagaaagt 300
tcttcgtacg gtttggacgt ctggggtcaa gggaccacgg tcaccgtctc ctca 354
<210> 355
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 355
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
Ala Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Thr Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Val Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
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 Glu Ser Ser Ser Tyr Gly Leu Asp Val Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 356
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 356
ggattcacct tcagtagtta tgcc 24
<210> 357
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 357
Gly Phe Thr Phe Ser Ser Tyr Ala
1 5
<210> 358
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 358
atatcatatg atggaagtaa taaa 24
<210> 359
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 359
Ile Ser Tyr Asp Gly Ser Asn Lys
1 5
<210> 360
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 360
gcgaaagaaa gttcttcgta cggtttggac gtc 33
<210> 361
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 361
Ala Lys Glu Ser Ser Ser Tyr Gly Leu Asp Val
1 5 10
<210> 362
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 362
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcgcc 60
atcacttgcc gggccagtca gagtattagt aactggttgg cctggtatca gcagaaacca 120
gggaaagccc ctaaactcct gatctctaag gcgtctagtt taaaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg cagcttatta ctgccaacag tataatagtt attcgtacac ttttggccag 300
gggaccaagc tggagataaa a 321
<210> 363
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 363
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Ala Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Ser Lys Ala Ser Ser Leu Lys 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 Ala 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> 364
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 364
cagagtatta gtaactgg 18
<210> 365
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 365
Gln Ser Ile Ser Asn Trp
1 5
<210> 366
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 366
aaggcgtct 9
<210> 367
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 367
Lys Ala Ser
1
<210> 368
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 368
caacagtata atagttattc gtacact 27
<210> 369
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 369
Gln Gln Tyr Asn Ser Tyr Ser Tyr Thr
1 5
<210> 370
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 370
caggtccaac tggtggagtc tgggggaggc gtggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtt ttatcatatg atggcagtaa agaattctac 180
gcagactccg tgaaggtccg attcaccgtc tccagagaca actccaagaa cacgctttat 240
ctgcaaatga gcagcctgag agttgaggac acggctatat atttctgtgc gaaagaagga 300
agaactggga attggttcga cccctggggc cagggaaccc tggtcgccgt ctcctca 357
<210> 371
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 371
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
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 Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Leu Ser Tyr Asp Gly Ser Lys Glu Phe Tyr Ala Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Val Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Val Glu Asp Thr Ala Ile Tyr Phe Cys
85 90 95
Ala Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Ala Val Ser Ser
115
<210> 372
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 372
ggattcacct tcagtagcta tggc 24
<210> 373
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 373
Gly Phe Thr Phe Ser Ser Tyr Gly
1 5
<210> 374
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 374
ttatcatatg atggcagtaa agaa 24
<210> 375
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 375
Leu Ser Tyr Asp Gly Ser Lys Glu
1 5
<210> 376
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 376
gcgaaagaag gaagaactgg gaattggttc gacccc 36
<210> 377
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 377
Ala Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro
1 5 10
<210> 378
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 378
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
ggtaaaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtgaatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa a 321
<210> 379
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 379
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Glu 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 380
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 380
caggccatta acaatttt 18
<210> 381
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 381
Gln Ala Ile Asn Asn Phe
1 5
<210> 382
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 382
gctacatcc 9
<210> 383
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 383
Ala Thr Ser
1
<210> 384
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 384
caacagtata atagtcaccc gtggacg 27
<210> 385
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 385
Gln Gln Tyr Asn Ser His Pro Trp Thr
1 5
<210> 386
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 386
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa aacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggtagt 300
ggctacgatt tggactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 387
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 387
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 Asn 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 Val Tyr Asn Gly Lys 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 Gly Ser Gly Tyr Asp Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 388
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 388
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gatttcaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 389
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 389
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 Gly Ile Arg Asn Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Phe Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 390
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 390
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa aacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgac cacagcctac 240
atggaaatga ggagcctgag atctgacgac acggccgttt attactgtgc gagaggtagt 300
ggctacgatt tggactactg gggccaggga accctggtca ccgtctcctc ag 352
<210> 391
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 391
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 Asn 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 Val Tyr Asn Gly Lys Thr Asn Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Met Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asp Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 392
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 392
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gatttcaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 393
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 393
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 Gly Ile Arg Asn Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Phe Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 394
<211> 385
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 394
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttagt tccttctgga tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtggccaac ataaagcaag atggaagtga gaaatactat 180
gtggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatccc 300
gggcgaacta tggttcgggg aggtataaga tattactatg gtatggacgt ctgggggcaa 360
gggaccacgg tcaccgtctc ctcag 385
<210> 395
<211> 128
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 395
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 Ser Phe
20 25 30
Trp Met Ser 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 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Pro Gly Arg Thr Met Val Arg Gly Gly Ile Arg 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> 396
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 396
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca gggtgttagt agctggttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtcaacag gctaacagtt tccctctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 397
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 397
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Val 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 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 Gln Gln Ala Asn Ser Phe Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 398
<211> 385
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 398
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttagt tccttctgga tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtggccaac ataaagcaag atggaagtga gaaatactat 180
gtggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatccc 300
gggcgaacta tggttcgggg aggtataaga tattactatg gtatggacgt ctgggggcaa 360
gggaccacgg tcaccgtctc ctcag 385
<210> 399
<211> 128
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 399
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 Ser Phe
20 25 30
Trp Met Ser 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 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Pro Gly Arg Thr Met Val Arg Gly Gly Ile Arg 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> 400
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 400
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca gggtgttagt agctggttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtcaacag gctaacagtt tccctctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 401
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 401
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Val 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 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 Gln Gln Ala Asn Ser Phe Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 402
<211> 367
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 402
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttagt agccattgga tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtggccaac ataaagcaag atggaagtga taaatactat 180
gtggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatcgg 300
ggggttagac cacctcgtgg ggcttttgat atctggggcc aagggacaat ggtcaccgtc 360
tcttcag 367
<210> 403
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 403
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 Ser His
20 25 30
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Asn Ile Lys Gln Asp Gly Ser Asp Lys Tyr Tyr Val 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Val Arg Pro Pro Arg Gly Ala Phe Asp Ile Trp
100 105 110
Gly Gln Gly Thr Met Val Thr Val Ser Ser
115 120
<210> 404
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 404
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca gggtatcagc agctggttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtcaacag gctaacagtt tccctctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 405
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 405
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly 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 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 Gln Gln Ala Asn Ser Phe Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 406
<211> 367
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 406
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc cgggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttagt agccattgga tgaactgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtggccaac ataaagcaag atggaagtga taaatactat 180
gtggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactctat 240
ctgcaattga acagcctgat agccgaggac acggctgtgt attactgtgc gagagatcgg 300
ggggttagac cacctcgtgg ggcttttgat atctggggcc aagggacaat ggtcaccgtc 360
tcttcag 367
<210> 407
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 407
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 Ser His
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 Lys Gln Asp Gly Ser Asp Lys Tyr Tyr Val 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 Leu Asn Ser Leu Ile Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Val Arg Pro Pro Arg Gly Ala Phe Asp Ile Trp
100 105 110
Gly Gln Gly Thr Met Val Thr Val Ser Ser
115 120
<210> 408
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 408
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca gggtatcagc agctggttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt ttcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttactt ttgtcaacag gctaacagtt tccctctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 409
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 409
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly 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 Ala Ala Ser Ser Phe 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 Phe Cys Gln Gln Ala Asn Ser Phe Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 410
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 410
gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120
ccagggaagg gcctggagtg ggtctcaggt cttagtcgga caagtgtcag tataggctat 180
gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240
ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaatggggg 300
acccgggggt attttgacta ctggggccaa ggaaccctgg tcaccgtctc ctcag 355
<210> 411
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 411
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 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 Gly Leu Ser Arg Thr Ser Val 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 Trp Gly Thr Arg Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 412
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 412
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggatattagt atttggttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgtt gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtcaacag gctaacagtt tcccgatcac cttcggccaa 300
gggacacgac tggagattaa ac 322
<210> 413
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 413
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ile Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Val 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 Gln Gln Ala Asn Ser Phe Pro Ile
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 414
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 414
gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgagg cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120
ccggggaagg gcctggaatg ggtctcaggt cttagtcgga caagtgtcag tataggctat 180
gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctttat 240
ttggaaatga acagtctgag acctgaggac acggccttat attactgtgc aaaatggggg 300
acccgggggt attttgacta ccggggccag ggaaccctgg tcaccgtctc ctcag 355
<210> 415
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 415
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe Thr Phe 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 Gly Leu Ser Arg Thr Ser Val 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 Glu Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Lys Trp Gly Thr Arg Gly Tyr Phe Asp Tyr Arg Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 416
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 416
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtgggaga cagagtcacc 60
atcacttgtc gggcgagtca ggatattagt atttggttag cctggtatca gcagagtcca 120
gggaaagccc ctaaactcct gatcaatgtt gcatcccgtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcaacag tctgcagcct 240
gaagattttg taacttacta ttgtcaacag gctaacagtt tcccgatcac cttcggccaa 300
gggacacgac tggagattaa ac 322
<210> 417
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 417
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ile Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Ser Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Asn Val Ala Ser Arg 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 Asn Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Val Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ile
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 418
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 418
caggtgcagc tggtggagtc tgggggaggc ttggtcaagc ctggagggtc cctgagactc 60
tcctgtgcag cctctggatt cacaatcagt gaccactaca tgagctggat ccgccaggct 120
ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtaa aatatactac 180
gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagaacacga 300
cagctcgtgg gggactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 419
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 419
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Ser Asp His
20 25 30
Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Tyr Ile Ser Ser Ser Gly Ser Lys Ile Tyr 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Arg Gln Leu Val Gly Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 420
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 420
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaacag cttaatagtt acccgctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 421
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 421
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 Arg 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 Thr 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 Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 422
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 422
caggtgcagc tggtggagtc tgggggaggc ttggtcaagc ctggagggtc cctgagactc 60
tcctgtgcag cctctggatt cacaatcagt gaccactaca tgagctggat ccgccaggct 120
ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtaa aatatactac 180
gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagaacacga 300
cagctcgtgg gggactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 423
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 423
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Ser Asp His
20 25 30
Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Tyr Ile Ser Ser Ser Gly Ser Lys Ile Tyr 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Arg Gln Leu Val Gly Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 424
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 424
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctttgct gcatccactt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaacag cttaatagtt acccgctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 425
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 425
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
Phe Ala Ala Ser Thr 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 Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 426
<211> 373
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 426
gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttgat aattatgcca tgcactgggt ccggcaagct 120
ccagggaagg gcctggagtg ggtctcaggt attaggtgga atagtggtag cataggctat 180
gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240
ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaaggt 300
ggatatagtg gctaccgccc cggacccttc tttgactact ggggccaagg aaccctggtc 360
accgtctcct cag 373
<210> 427
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 427
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asn Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Gly Ile Arg 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 Glu Gly Gly Tyr Ser Gly Tyr Arg Pro Gly Pro Phe Phe Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 428
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 428
gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttaac tacaacttag cctggtacca gcagaaacct 120
ggccaggctc ccaggctcct catctatggt gcatccacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggccgctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 429
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 429
Glu 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 Ser Val Asn Tyr Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly 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 Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 430
<211> 373
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 430
gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttgat aattatgcca tgcactgggt ccggcaagct 120
ccagggaagg gcctggagtg ggtctcaggt attaggtgga atagtggtag cataggctat 180
gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240
ctgcaaatga atagtctgag agctgaggac acggccttgt attactgtgc aaaagaaggt 300
ggatatagtg gctaccgccc cggacccttc tttgactact ggggccaggg aaccctggtc 360
accgtctcct cag 373
<210> 431
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 431
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asn Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Gly Ile Arg 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 Glu Gly Gly Tyr Ser Gly Tyr Arg Pro Gly Pro Phe Phe Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 432
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 432
gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttaac tacaacttag cctggtacca gcagaaacct 120
ggccaggctc ccaggctcct catctatggt gcatccacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggccgctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 433
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 433
Glu 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 Ser Val Asn Tyr Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly 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 Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 434
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 434
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtca cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactcctg gggccaagga accctggtca ccgtctcctc ag 352
<210> 435
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 435
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 Asn 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 Val Tyr Asn Gly His 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 Gly Ser Gly Tyr Asp Phe Asp Ser Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 436
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 436
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggccattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacgatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 437
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 437
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 Ala Ile Arg Asn Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asp Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 438
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 438
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtca cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactcctg gggccaagga accctggtca ccgtctcctc ag 352
<210> 439
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 439
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 Asn 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 Val Tyr Asn Gly His 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 Gly Ser Gly Tyr Asp Phe Asp Ser Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 440
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 440
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggccattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacgatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 441
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 441
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 Ala Ile Arg Asn Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asp Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 442
<211> 349
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 442
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctagata caccttcacc agttatgata tcaactgggt gcgacaggcc 120
actggacaag ggcttgagtg gatgggatgg atgaacccaa acagtggtaa cacaggctat 180
gcacagaagt tccagggcag agtcaccatg accaggaaca cctccataag cacagcctac 240
atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagtacga 300
cgcttttttg actactgggg ccaaggaacc ctggtcaccg tctcctcag 349
<210> 443
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 443
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 Arg 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 Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met 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 Val Arg Arg Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 444
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 444
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gggcattatc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaccag cttaaaagtt acccgatcac cttcggccaa 300
gggacacgac tggagattaa ac 322
<210> 445
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 445
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 Arg Ala Ser Gln Gly Ile Ile 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 Thr 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 His Gln Leu Lys Ser Tyr Pro Ile
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 446
<211> 349
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 446
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctagata caccttcacc agttatgata tcaactgggt gcgacaggcc 120
actggacaag ggcttgagtg gatgggatgg atgaacccaa acagtggtaa cacaggctat 180
gcacagaagt tccagggcag agtcaccatg accaggaaca cctccacaag cacagcctac 240
atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagtacga 300
cgcttttttg actactgggg ccagggaacc ctggtcaccg tctcctcag 349
<210> 447
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 447
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 Arg 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 Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asn Thr Ser Thr 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 Val Arg Arg Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 448
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 448
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gggcattatc agttatttag cctggtatca gcaaaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtcaccag cttaaaagtt acccgatcac cttcggccaa 300
gggacacgac tggagattaa ac 322
<210> 449
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 449
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 Arg Ala Ser Gln Gly Ile Ile 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 Thr 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 His Gln Leu Lys Ser Tyr Pro Ile
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 450
<211> 349
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 450
caggtgcagc tggtggagtc tgggggaggc ttggtcaagc ctggagggtc cctgagactc 60
tcctgtgcag cctctggatt caccctcagt gactactaca tgagctggat ccgccaggct 120
ccagggaagg ggctggagtg ggtttcatac attaggagaa gtggtaatac catatactac 180
gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagagggggg 300
gactgggcgg acgtctgggg gcaagggacc acggtcaccg tctcctcag 349
<210> 451
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 451
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Leu Ser Asp Tyr
20 25 30
Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Tyr Ile Arg Arg Ser Gly Asn Thr Ile Tyr 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Gly Asp Trp Ala Asp Val Trp Gly Gln Gly Thr Thr Val
100 105 110
Thr Val Ser Ser
115
<210> 452
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 452
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca gggcattagc atttatttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 453
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 453
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 Ser Ile Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser 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 Gln Gln Tyr Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 454
<211> 349
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 454
caggtgcagc tggtggagtc tgggggagac ttggtcaggc ctggagggtc cctgagactc 60
tcctgtacag cctctggatt caccctcagt gactactaca tgagctggat ccgtcaggct 120
ccagggaagg ggctggagtg ggtttcatac attaggagaa gtggtaatac catatactac 180
gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gagagggggg 300
gactgggcgg acgtctgggg ccaagggacc acggtcaccg tctcctcag 349
<210> 455
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 455
Gln Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Leu Ser Asp Tyr
20 25 30
Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Tyr Ile Arg Arg Ser Gly Asn Thr Ile Tyr 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Gly Asp Trp Ala Asp Val Trp Gly Gln Gly Thr Thr Val
100 105 110
Thr Val Ser Ser
115
<210> 456
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 456
gacatccaga tgacccagtc tccatcctca ctgtctgcct ctgtgggaga cagagtcacc 60
atcacttgtc gggcgagtca gggcattagc atttatttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct gcatccagtt tgcaacgtgg ggtcccatca 180
aagttcagcg gcagtggatc tgggacagat ttcactctca ccatcagtag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 457
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 457
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 Ser Ile Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Arg Gly Val Pro Ser Lys 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 Gln Gln Tyr Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 458
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 458
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa cataaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 459
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 459
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 Asn 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 Val Tyr Asn Gly Asn Ile 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 Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 460
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 460
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggacattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 461
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 461
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 Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 462
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 462
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa cataaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 463
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 463
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 Asn 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 Val Tyr Asn Gly Asn Ile 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 Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 464
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 464
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggacattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 465
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 465
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 Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 466
<211> 367
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 466
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctgctta cacctttaat agatatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acactggtaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagataag 300
tcgatttttg gagtggttag agggtttgac tactggggcc aaggaaccct ggtcaccgtc 360
tcctcag 367
<210> 467
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 467
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 Ala Tyr Thr Phe Asn Arg 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 Thr 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 Asp Lys Ser Ile Phe Gly Val Val Arg Gly Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 468
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 468
gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagcttag cctggtacca gcagaaacct 120
ggccaggctc ccaggctcct catctatggt gcatctacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggcctctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 469
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 469
Glu 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 Ser Val Ser Ser Ser
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly 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 Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 470
<211> 367
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 470
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctgctta cacctttaat agatatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgctt acactggtaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagataag 300
tcgatttttg gagtggttag agggtttgac tactggggcc aaggaaccct ggtcaccgtc 360
tcctcag 367
<210> 471
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 471
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 Ala Tyr Thr Phe Asn Arg 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 Thr 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 Asp Lys Ser Ile Phe Gly Val Val Arg Gly Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 472
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 472
gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagc agcagcttag cctggtacca gcagaaacct 120
ggccaggctc ccaggctcct catctatggt gcatctacca gggccactgg tatcccagcc 180
aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240
gaagattttg cagtttatta ctgtcagcag tataataact ggcctctcac tttcggcgga 300
gggaccaagg tggagatcaa ac 322
<210> 473
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 473
Glu 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 Ser Val Ser Ser Ser
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly 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 Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 474
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 474
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggca tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtgttt acaatggcaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 475
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 475
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 Asn 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 Val Tyr Asn 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 Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 476
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 476
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggacattaga aatgatttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatact gcttccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctccaa gataatagtt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 477
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 477
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 Thr 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 Asp Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 478
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 478
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggca tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtgttt acaatggcaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 479
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 479
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 Asn 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 Val Tyr Asn 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 Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 480
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 480
gccatccaga tgacccagtc tccttcctcc ctgtctgcat ctgttggaga cagagtcgcc 60
atcacttgcc gggcaagtca ggacattaga aatgatttag gctggtatca gcagaaacca 120
gggaaagccc ctaagcttct gatccatact gcttccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcaa cctgcagcct 240
gaagattttg ccacttatta ctgtctccaa gataatagtt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 481
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 481
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Ala 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
His Thr 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 Asn Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 482
<211> 349
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 482
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggata caccttcacc ggccagtata tgcactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180
gcacagaagt ttcagggcag ggtcaccatg accagggaca cgtccatcag cacagcctac 240
atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgt gagagaaaag 300
agaggttttg atatctgggg ccaagggaca atggtcaccg tctcttcag 349
<210> 483
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 483
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 Gln
20 25 30
Tyr Met 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
Val Arg Glu Lys Arg Gly Phe Asp Ile Trp Gly Gln Gly Thr Met Val
100 105 110
Thr Val Ser Ser
115
<210> 484
<211> 319
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 484
gaaattgtgt tgacacagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagg agctacttag cctggtacca acagaaacct 120
ggccaggctc ccaggctcct catctatgat gcatccaaca gggccactgg catcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag cctagagcct 240
gaagattttg cagtttatta ctgtcagcag cgtagcgact ggcctacttt cggccctggg 300
accaaagtgg atatcaaac 319
<210> 485
<211> 106
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 485
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 Gln Arg Ser Asp Trp Pro Thr
85 90 95
Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
100 105
<210> 486
<211> 349
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 486
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggata caccttcacc ggccagtata ttcactgggt tcgacaggcc 120
cctggacaag gacttgagtg gatgggatgg atcaacccta acagtggtgg cacaaacttt 180
gcacagaagt ttcaggacag ggtcaccatg accagggaca cgtccatcgg cacagtatac 240
atggaactga ggaggctgac atctgacgac acggccgtat tttattgtgt gagagaaaag 300
agaggttttg atatctgggg ccaagggaca atggtcaccg tttcttcag 349
<210> 487
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 487
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 Gln
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 Phe Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Gly Thr Val Tyr
65 70 75 80
Met Glu Leu Arg Arg Leu Thr Ser Asp Asp Thr Ala Val Phe Tyr Cys
85 90 95
Val Arg Glu Lys Arg Gly Phe Asp Ile Trp Gly Gln Gly Thr Met Val
100 105 110
Thr Val Ser Ser
115
<210> 488
<211> 319
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 488
gaaattgtgt tgacacagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gggccagtca gagtgttagg agctactttg cctggtacca acagaaacct 120
ggccaggctc ccagggtcct catctatgat gcatccatca gggccaccgg catcccagcc 180
aggttcagtg gcagtgggtc tgggacagac ttcagtctca ccattgacag cctagagcct 240
gaagattttg cagtttatta ctgtcagcag cgtagcgact ggcctacttt cggccctggg 300
accaaagtgg atatcaaac 319
<210> 489
<211> 106
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 489
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
Phe Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Val Leu Ile
35 40 45
Tyr Asp Ala Ser Ile Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr Ile Asp Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asp Trp Pro Thr
85 90 95
Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
100 105
<210> 490
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 490
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtattt acaatggtaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggtagt 300
ggctacaatt tcgaccactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 491
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 491
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 Asn 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 Ile Tyr Asn 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 Gly Ser Gly Tyr Asn Phe Asp His Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 492
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 492
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gataacactt atccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 493
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 493
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 Gly 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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Asn Thr Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 494
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 494
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcggctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtattt acaatggtaa cacaaattat 180
gcacagaggc tccagggcag agtcaccatg accacagaca catccacgag cacagccttc 240
atggacctga ggagcctgaa atctgacgac acggccgttt attactgtgc gagaggtagt 300
ggctacaatt tcgaccactg gggccaggga accctggtca ccgtctcctc ag 352
<210> 495
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 495
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 Asn Tyr
20 25 30
Gly Ile Gly Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Ile Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Arg Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Phe
65 70 75 80
Met Asp Leu Arg Ser Leu Lys Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asn Phe Asp His Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 496
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 496
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtatca gcagataccg 120
gggaaagccc ctaaactcct gatctatgct gcatccagtt tacaaagtgg ggtcccgtca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcaa cctgcagcct 240
gaagattttg cagtttattt ctgtctacaa gataacactt atccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 497
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 497
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 Gly Ile Arg Asn Asp
20 25 30
Leu Gly Trp Tyr Gln Gln Ile 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 Asn Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Phe Cys Leu Gln Asp Asn Thr Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 498
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 498
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa aacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 499
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 499
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 Asn 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 Val Tyr Asn Gly Lys 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 Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 500
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 500
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct tcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattataatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 501
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 501
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 Gly Ile Arg Asn Ala
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ser 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 Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 502
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 502
caggttcagc tggtgcagtc tggacctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc aactatggta tcagttgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagcgttt acaatggtaa aacaaactat 180
gcacagaagt tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggacctga ggagcctgag atctgacgac acggccgtat attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaggga accctggtca ccgtctcctc ag 352
<210> 503
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 503
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 Asn 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 Val Tyr Asn Gly Lys Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 504
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 504
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct tcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattataatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 505
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 505
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 Gly Ile Arg Asn Ala
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ser 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 Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 506
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 506
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtgttt acaatggtaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 507
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 507
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 Ser 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 Val Tyr Asn 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 Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 508
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 508
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 509
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 509
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 Gly Ile Arg Asn Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 510
<211> 352
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 510
caggttcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcagtgttt acaatggtaa cacaaactat 180
gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagggagt 300
ggctacgatt ttgactactg gggccaagga accctggtca ccgtctcctc ag 352
<210> 511
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 511
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 Ser 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 Val Tyr Asn 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 Gly Ser Gly Tyr Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 512
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 512
gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca gggcattaga aatgctttag gctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgtctacaa gattacaatt acccgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 513
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 513
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 Gly Ile Arg Asn Ala
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 Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 514
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 514
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcaga agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggcagtaa aacatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc caaggaaccc tggtcaccgt ctcctcag 358
<210> 515
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 515
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 Arg 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 Ser Tyr Asp Gly Ser Lys 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
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 516
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 516
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct acatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 517
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 517
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 518
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 518
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctggagggtc cctgagactc 60
tcctgtgtag cctctggatt caccttcaga agctatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtt atatcatatg atggcagtaa aacattctac 180
gtagattccg tgaaggtccg attcaccatc tccagagaca attccaagaa cacgctttat 240
ttggaaatga acagcctgag agttgacgac acggctgtgt atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcgccgt ctcctcag 358
<210> 519
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 519
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Ala Val Ser Ser
115
<210> 520
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 520
gacatccaga tgacccagtc tccatcctca ctgtctgcgt ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaaaccc ctaactccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg ccggtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 521
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 521
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Asn Ser Leu Ile
35 40 45
Phe Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Ala
50 55 60
Gly 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 522
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 522
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt catcttcaga agttatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggcagtaa aacatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc caaggaaccc tggtcaccgt ctcctcag 358
<210> 523
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 523
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 Ile Phe Arg 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 Ser Tyr Asp Gly Ser Lys 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
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 524
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 524
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct acatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 525
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 525
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 526
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 526
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctggagggtc cctgagactc 60
tcctgtactg cctctggatt catcttcaga agttatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtc atatcatatg atggcagtaa aacattctac 180
gtagattccg tgaaggtccg attcaccatc tccagagaca actccaagaa cacgctttat 240
ttggagatga acagcctgag agttgacgac acggctgtat atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 527
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 527
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ile Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 528
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 528
gacatccaga tgacccagtc tccatcctca ctgtctgcgt ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 529
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 529
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 530
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 530
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt catcttcaga agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggcagtaa aacatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc caaggaaccc tggtcaccgt ctcctcag 358
<210> 531
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 531
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 Ile Phe Arg 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 Ser Tyr Asp Gly Ser Lys 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
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 532
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 532
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct acatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 533
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 533
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 534
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 534
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctggagggtc cctgagactc 60
tcctgtgctg cctctggatt catcttcaga agctatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtc atatcatatg atggcagtaa aacattctac 180
gtagattccg tgaaggtccg attcaccata tccagagaca actccaagaa cacgctttat 240
ttggaaatga acagcctgag agttgacgac acggctgtat atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 535
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 535
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ile Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 536
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 536
gacatccaga tgacccagtc tccatcctca ctgtctgcgt ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 537
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 537
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 538
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 538
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtat taaatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gaaggaaggt 300
aggaagtacg gtatggacgt ctgggggcaa gggaccacgg tcaccgtctc ctcag 355
<210> 539
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 539
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 Ser Tyr Asp Gly Ser Ile 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 Lys Glu Gly Arg Lys Tyr Gly Met Asp Val Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 540
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 540
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gattattagt agcttattgg cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag tatcatagtt acatgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 541
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 541
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 Ile Ile Ser Ser Leu
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 His Ser Tyr Met Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 542
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 542
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtat taaatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gaaggaaggt 300
aggaagtacg gtatggacgt ctgggggcaa gggaccacgg tcaccgtctc ctcag 355
<210> 543
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 543
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 Ser Tyr Asp Gly Ser Ile 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 Lys Glu Gly Arg Lys Tyr Gly Met Asp Val Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 544
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 544
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gattattagt agcttattgg cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag tatcatagtt acatgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 545
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 545
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 Ile Ile Ser Ser Leu
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 His Ser Tyr Met Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 546
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 546
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agctttggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggcagtaa aaaatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gaaagaagga 300
agaactggga attggttcga cccctggggc caaggaaccc tggtcaccgt ctcctcag 358
<210> 547
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 547
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 Phe
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 Ser Lys 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 Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 548
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 548
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattatttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct acatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 549
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 549
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 Ala Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 550
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 550
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtacag cctctggatt caccttcagt agctttggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtt atatcatatg atggcagtaa aaaatactac 180
gcagactccg tgaaggtccg attcaccatc tccagagaca actccaagaa cacgctttat 240
ctgcaaatga acagcctgag agttgacgac acggctgtgt atttctgtgc gaaagaagga 300
agaactggga attggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 551
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 551
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 Thr Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Lys Lys Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Val 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 Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 552
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 552
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattatttag cctggtttca gcagaaacca 120
gggaaaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcactggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 553
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 553
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 Ala Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 554
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 554
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcaga agttatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggcagtca aacatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc caaggaaccc tggtcaccgt ctcctcag 358
<210> 555
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 555
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 Arg 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 Ser Tyr Asp Gly Ser Gln 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
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 556
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 556
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaat aattatttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct acatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 557
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 557
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 Ala Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 558
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 558
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctggaaggtc cctgagactc 60
tcctgtgtag cctctggatt caccttcaga agttatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtc atatcatatg atggcagtca aacattctat 180
gtagattccg tgaaggtccg attcaccatc tccagagaca actccaacaa cacgctttat 240
ttggaaatga acagcctgag agttgacgac acggctgttt atttctgtgt gaaagaagga 300
agaagtggga gttggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 559
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 559
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 Val Ala Ser Gly Phe Thr Phe Arg Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Gln Thr Phe Tyr Val Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn Thr Leu Tyr
65 70 75 80
Leu Glu Met Asn Ser Leu Arg Val Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Val Lys Glu Gly Arg Ser Gly Ser Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 560
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 560
gacatccaga tgacccagtc tccatcctca ctgtctgcgt ctgttggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaat aattatttag cctggtttca gcagaaacca 120
gggagaaccc ctaagtccct gatctttgct acatccagtt tacaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 561
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 561
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 Ala Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Arg Thr Pro Lys Ser Leu Ile
35 40 45
Phe Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 562
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 562
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agttatgcca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gaaagaaagt 300
tcttcgtacg gtttggacgt ctgggggcaa gggaccacgg tcaccgtctc ctcag 355
<210> 563
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 563
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
Ala 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 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 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 Glu Ser Ser Ser Tyr Gly Leu Asp Val Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 564
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 564
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggccagtca gagtattagt aactggttgg 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> 565
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 565
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 Asn 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> 566
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 566
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agttatgcca tgtactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtg atatcatatg atggaagtaa taaatactat 180
acagactccg tgaagggccg attcaccgtc tccagagaca attccaaaaa cacgctgttt 240
ctgcaaatga acagcctgag agctgaggac acggctctgt attactgtgc gaaagaaagt 300
tcttcgtacg gtttggacgt ctggggtcaa gggaccacgg tcaccgtctc ctcag 355
<210> 567
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 567
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
Ala Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Thr Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Val Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
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 Glu Ser Ser Ser Tyr Gly Leu Asp Val Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 568
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 568
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcgcc 60
atcacttgcc gggccagtca gagtattagt aactggttgg cctggtatca gcagaaacca 120
gggaaagccc ctaaactcct gatctctaag gcgtctagtt taaaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg cagcttatta ctgccaacag tataatagtt attcgtacac ttttggccag 300
gggaccaagc tggagatcaa ac 322
<210> 569
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 569
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Ala Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Ser Lys Ala Ser Ser Leu Lys 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 Ala 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> 570
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 570
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaagg ggctggagtg ggtggcagtt ttatcatatg atggcagtaa agaatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gaaagaagga 300
agaactggga attggttcga cccctggggc caaggaaccc tggtcaccgt ctcctcag 358
<210> 571
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 571
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 Ser Tyr Asp Gly Ser Lys Glu 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 Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 572
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 572
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct acatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 573
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 573
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 574
<211> 358
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 574
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120
ccaggcaggg gactggagtg ggtggcagtt ttatcatatg atggcagtaa agaattctac 180
gcagactccg tgaaggtccg attcaccgtc tccagagaca actccaagaa cacgctttat 240
ctgcaaatga gcagcctgag agttgaggac acggctatat atttctgtgc gaaagaagga 300
agaactggga attggttcga cccctggggc cagggaaccc tggtcaccgt ctcctcag 358
<210> 575
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 575
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
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 Arg Gly Leu Glu Trp Val
35 40 45
Ala Val Leu Ser Tyr Asp Gly Ser Lys Glu Phe Tyr Ala Asp Ser Val
50 55 60
Lys Val Arg Phe Thr Val Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Val Glu Asp Thr Ala Ile Tyr Phe Cys
85 90 95
Ala Lys Glu Gly Arg Thr Gly Asn Trp Phe Asp Pro Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 576
<211> 322
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 576
gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc gggcgagtca ggccattaac aattttttag cctggtttca gcagaaacca 120
gggaaagccc ctaagtccct gatctatgct acatccagtt tgcaaagtgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttatta ctgccaacag tataatagtc acccgtggac gttcggccaa 300
gggaccaagg tggaaatcaa ac 322
<210> 577
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 577
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 Ala Ile Asn Asn Phe
20 25 30
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Thr 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 Gln Gln Tyr Asn Ser His Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 578
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 578
gaagtgcacc tggtggaatc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgagg cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120
ccggggaagg gcctggaatg ggtctcaggt cttagtcgga caagtgtcag tataggctat 180
gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctttat 240
ttggaaatga acagtctgag acctgaggac acggccttat attactgtgc aaaatggggg 300
acccgggggt attttgacta ctggggccag ggaaccctgg tcaccgtctc ctcag 355
<210> 579
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 579
Glu Val His Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe Thr Phe 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 Gly Leu Ser Arg Thr Ser Val 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 Glu Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Lys Trp Gly Thr Arg Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 580
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 580
gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60
tcctgtgagg cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120
ccggggaagg gcctggaatg ggtctcaggt cttagtcgga caagtgtcag tataggctat 180
gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctttat 240
ttggaaatga acagtctgag acctgaggac acggccttat attactgtgc aaaatggggg 300
acccgggggt attttgacta ctggggccag ggaaccctgg tcaccgtctc ctcag 355
<210> 581
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 581
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe Thr Phe 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 Gly Leu Ser Arg Thr Ser Val 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 Glu Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Lys Trp Gly Thr Arg Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 582
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(8)
<223> Xaa = Any amino acid
<400> 582
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 583
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(8)
<223> Xaa = Any amino acid
<400> 583
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 584
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(21)
<223> Xaa = ANy amino acid
<400> 584
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5 10 15
Xaa Xaa Xaa Xaa Xaa
20
<210> 585
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(6)
<223> Xaa = Any amino acid
<400> 585
Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 586
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(3)
<223> Xaa = Any amino acid
<400> 586
Xaa Xaa Xaa
1
<210> 587
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<220>
<221> VARIANT
<222> (1)...(9)
<223> Xaa = Any amino acid
<400> 587
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5
<210> 588
<211> 330
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 588
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> 589
<211> 327
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 589
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> 590
<211> 327
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic
<400> 590
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
Claims (16)
- 표면 플라스몬 공명에 의한 측정시 약 200pM 이하, 바람직하게는 약 150pM 이하의 KD로 hIL-4R(서열번호 1)과 특이적으로 결합하는 항체 또는 이의 항원 결합 단편.
- 제1항에 있어서,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, 387, 391, 395, 399, 403, 407, 411, 415, 419, 423, 427, 431, 435, 439, 443, 447, 451, 455, 459, 463, 467, 471, 475, 479, 483, 487, 491, 495, 499, 503, 507, 511, 515, 519, 523, 527, 531, 535, 539, 543, 547, 551, 555, 559, 563, 567, 571, 575, 579 및 581로부터 선택되는 중쇄 가변 영역(HCVR); 및서열번호 11, 27, 43, 59, 75, 91, 107, 123, 130, 155, 171, 187, 203, 219, 235, 251, 267, 283, 299, 315, 331, 347, 363, 379, 389, 393, 397, 401, 405, 409, 413, 417, 421, 425, 429, 433, 437, 441, 445, 449, 453, 457, 461, 465, 469, 473, 477, 481, 485, 489, 493, 497, 501, 505, 509, 513, 517, 521, 625, 529, 533, 537, 541, 545, 549, 553, 557, 561, 565, 569, 573 및 577로부터 선택되는 경쇄 가변 영역(LCVR)을 포함하는, 항체 또는 이의 항원 결합 단편.
- 제1항 또는 제2항에 있어서, 서열번호 3/11, 19/27, 35/43, 51/59, 67/75, 83/91, 99/107, 115/123, 131/139, 147/155, 163/171, 179/187, 195/203, 211/219, 227/235, 243/251, 259/267, 275/283, 291/299, 307/315, 323/331, 339/347, 355/363, 371/379, 387/389, 391/393, 395/397, 399/401, 403/405, 407/409, 411/413, 415/417, 419/421, 423/425, 427/429, 431/433, 435/437, 439/441, 443/445, 447/449, 451/453, 455/457, 459/461, 463/465, 467/469, 471/473, 475/477, 479/481, 483/485, 487/489, 491/493, 495/497, 499/501, 503/505, 507/509, 511/513, 515/517, 519/521, 523/525, 527/529, 531/533, 535/537, 539/541, 543/545, 547/549, 551.553, 555/557, 559/561, 563/565, 567/569, 571/573, 575/577, 579/59 및 581/59로부터 선택되는 HCVR/LCVR 쌍을 포함하는, 항체 또는 이의 항원 결합 단편.
- 제3항에 있어서, 바람직하게 서열번호 51/59, 259/267, 275/283, 291/299, 579/59 또는 581/59로부터 선택되는 HCVR/LCVR을 포함하는, 항체 또는 이의 항원 결합 단편.
- 제1항에 있어서,중쇄 CDR1이 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 582)의 아미노산 서열을 포함하고, 여기서 X1 = Gly; X2 = Tyr 또는 Phe; X3 = Thr 또는 I; X4 = Phe; X5 = Asn 또는 Arg; X6 =Ser; X7 = Tyr; 및 X8 = Gly이고;중쇄 CDR2가 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 (서열번호 583)의 아미노산 서열을 포함하고, 여기서 X1 = Ile, X2 = Ser 또는 Arg, X3 = Thr 또는 Tyr, X4= Tyr 또는 Asp, X5 = Asn 또는 Gly, X6 = Gly 또는 Ser, X7 = Lys 또는 Asn, 및 X8 = Thr이고;중쇄 CDR3이 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 - X10 - X11 - X12 - X13 - X14 - X15 - X16 - X17 - X18 - X19 - X20 - X21 (서열번호 584)의 아미노산 서열을 포함하고, 여기서, X1 = Ala 또는 Val, X2 = Arg 또는 Lys, X3 = Asp 또는 Glu, X4 = Gly 또는 Glu, X5 = Ala 또는 Arg, X6 = Arg 또는 Ser, X7 = Ile 또는 Gly, X8 = Val 또는 Ser, X9 = Val 또는 Trp, X10 = Ala 또는 Phe, X11 = Gly 또는 Asp, X12 = Thr 또는 Pro, X13 = Thr 또는 부재, X14 = Pro 또는 부재, X15 = Tyr 또는 부재, X16 = Tyr 또는 부재, X17 = Tyr 또는 부재, X18 = Gly 또는 부재, X19 = Met 또는 부재, X20 = Asp 또는 부재, 및 X21 = Val 또는 부재이고;경쇄 CDR1이 화학식 X1 - X2 - X3 - X4 - X5 - X6 (서열번호 585)의 아미노산 서열을 포함하고, 여기서, X1 = Gln, X2 = Asp 또는 Ala, X3 = Ile, X4 = Ser 또는 Asn, X5 = Asn 또는 Ile, 및 X6 = Trp 또는 Phe이고;경쇄 CDR2가 화학식 X1 - X2 - X3 (서열번호 586)의 아미노산 서열을 포함하고, 여기서, X1 = Ala 또는 Val, X2 = Ala 또는 Thr, 및 X3 = Ser이고;경쇄 CDR3이 화학식 X1 - X2 - X3 - X4 - X5 - X6 - X7 - X8 - X9 (서열번호 587)의 아미노산 서열을 포함하고, 여기서, X1 = Gln, X2 = Gln, X3 = Ala 또는 Tyr, X4 = Asn, X5 = Ser, X6 = Phe 또는 His, X7 = Pro, X8 = Ile 또는 Trp, 및 X9 = Thr인, 항체 또는 이의 항원 결합 단편.
- 제1항에 있어서,서열번호 9, 25, 41, 57, 73, 89, 105, 121, 137, 153, 169, 185, 201, 217, 233, 249, 265, 281, 297, 313, 329, 345, 361 및 377로 이루어진 그룹으로부터 선택되는 중쇄 CDR3 도메인; 및서열번호 17, 33, 49, 65, 81, 97, 113, 129, 145, 161, 177, 193, 209, 225, 241, 257, 273, 289, 305, 321, 337, 353, 369 및 385로 이루어진 그룹으로부터 선택되는 경쇄 CDR3 도메인을 포함하는, 항체 또는 이의 항원 결합 단편.
- 제6항에 있어서,서열번호 5, 21, 37, 53, 69, 85, 101, 117, 133, 149, 165, 181, 197, 213, 229, 245, 261, 277, 293, 309, 325, 341, 357 및 373으로 이루어진 그룹으로부터 선택되는 중쇄 CDR1 도메인;서열번호 7, 23, 39, 55, 71, 87, 103, 119, 135, 151, 167, 183, 199, 215, 231, 247, 263, 279, 295, 311, 327, 343, 359 및 375로 이루어진 그룹으로부터 선택되는 중쇄 CDR2 도메인;서열번호 13, 29, 45, 61, 77, 93, 109, 125, 141, 157, 173, 189, 205, 221, 237, 253, 269, 285, 301, 317, 333, 349, 365 및 381로 이루어진 그룹으로부터 선택되는 경쇄 CDR1 도메인; 및서열번호 15, 31, 47, 63, 79, 95, 111, 127, 143, 159, 175, 191, 207, 223, 239, 255, 271, 287, 303, 319, 335, 351, 367 및 383으로 이루어진 그룹으로부터 선택되는 경쇄 CDR2 도메인을 추가로 포함하는, 항체 또는 이의 항원 결합 단편.
- 제1항에 있어서, HCVR/LCVR 서열이 51/59, 579/59, 581/59, 259/267, 275/283 및 291/299로 이루어진 그룹으로부터 선택되는, HCVR 및 LCVR 서열로부터의 CDR을 포함하는, 항체 또는 이의 항원 결합 단편.
- 제1항 내지 제8항 중 어느 한 항에 따른 항체 또는 이의 항원 결합 단편을 암호화하는 분리된 핵산 분자.
- 제9항에 따른 핵산 서열을 포함하는 벡터.
- 적합한 숙주 세포에서, 제10항에 따른 벡터를 포함하는, IL-4 수용체에 특이적으로 결합하는 항체 또는 항체의 항원 결합 단편을 제조하기 위한 숙주-벡터 시스템.
- 제11항에 있어서, 숙주 세포가 이.콜라이(E. coli) 또는 CHO 세포 중 하나로부터 선택되는 원핵 세포 또는 진핵 세포인, 숙주-벡터 시스템.
- 항체 또는 이의 단편의 제조를 허용하는 조건하에서, 제11항 또는 제12항에 따른 숙주-벡터 시스템의 세포를 성장시키고, 이로써 발현된 항체 또는 단편을 회수함을 포함하는, 항-IL-4R 항체 또는 이의 항원 결합 단편을 제조하는 방법.
- 사람에서 IL-4-매개된 질환 또는 장애를 약화시키거나 억제하는데 사용하기 위한 약제를 제조하는데 있어서의, 제1항 내지 제9항 중 어느 한 항에 따른 항체 또는 항체의 항원 결합 단편의 용도.
- 제1항 내지 제9항 중 어느 한 항에 따른 항체 또는 이의 항원 결합 단편을 투여함에 의해, 사람 인터루킨-4(hIL-4) 활성을 제거하거나 억제하거나 감소시킴으로써 개선되거나 완화되거나 억제되는 질환 또는 장애를 치료하는 방법.
- 제15항에 있어서, 질환 또는 장애가 관절염, 포진, 만성 특발성 두드러기, 경피증, 비대성 반흔, 위플(Whipple) 질환, 양성 전립선 비대증, 폐 장애, 염증성 장애, 알레르기 반응, 가와사키 질환, 겸상 세포 질환, 처그-스트라우스 증후군(Churg-Strauss syndrome), 그레이브스병(Grave's disease), 자간전증, 쇼그렌 증후군(Sjogren's syndrome), 자가면역 림프증식성 증후군, 자가면역 용혈 빈혈증, 바레트 식도, 자가면역 포도막염, 결핵 및 신장증으로부터 선택되는 방법.
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