KR20230121831A - 인테그린 알파 11 베타 1에 대한 항체 - Google Patents
인테그린 알파 11 베타 1에 대한 항체 Download PDFInfo
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- KR20230121831A KR20230121831A KR1020237023939A KR20237023939A KR20230121831A KR 20230121831 A KR20230121831 A KR 20230121831A KR 1020237023939 A KR1020237023939 A KR 1020237023939A KR 20237023939 A KR20237023939 A KR 20237023939A KR 20230121831 A KR20230121831 A KR 20230121831A
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Abstract
본 개시내용은 인테그린 알파 11 베타 1(α11β1)에 특이적으로 결합하는 항체, 및 이러한 항체의 제조 방법 및 사용 방법을 포함한다.
Description
관련 출원의 교차 참조
본 출원은 2020년 12월 18일자로 출원된 미국 임시 출원 제63/127,849호 및 2021년 6월 23일자로 출원된 미국 임시 출원 제63/213,973호의 우선권의 이익을 주장하며, 이들은 모든 목적을 위해 그 전체가 본원에 원용되어 포함된다.
서열 목록
본 출원은 ASCII 서식으로 전자적으로 제출된 서열 목록을 포함하며, 이는 그 전체가 본원에 원용되어 포함된다. 2021년 11월 19일자로 생성된 상기 ASCII 사본은 파일명이 2010403_0592_SL.txt이며 크기가 440,570 바이트이다.
섬유증은 일반적으로 염증이나 조직 손상의 결과로 신체의 많은 조직에서 나타나는 흉터 과정이다. 세포외 기질의 생성 증가는 장기 부전 및 종종 사망을 초래한다. 섬유증과 관련된 질환은 선진국에서 전체 사망의 대략 45%를 차지한다(문헌[Wynn, T. A., 2008, J Pathol. 214:199-210]). 이러한 질환 중 하나는 전신성 경화증(SSc)이다. SSc는 만성 진행 과정과 환자 간 변동성이 높은 복잡한 자가 면역 질환이다. 이는 염증, 혈관 기능 장애 및 섬유증을 특징으로 한다. 피부와 내장 기관의 섬유화는 비가역적 흉터와 궁극적으로 장기 부전을 초래하여 높은 사망률을 초래한다. 현재 질환 수정 가능성이 있는 승인된 표적 치료법은 없다.
본 개시내용은 유형 I 콜라겐 수용체 인테그린 알파 11 베타 1(α11β1)에 대한 신규한 기능 차단 항체를 제공한다. 본 개시내용은 또한 섬유증 장애 및/또는 암을 치료하기 위한 이러한 항체의 용도를 제공한다.
일 양태에서, 본 개시내용은 SEQ ID NO: 103-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다. 또 다른 양태에서, 본 개시내용은 SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443 중 어느 하나에 포함된 CDR 서열을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다. 또 다른 양태에서 본 개시내용은 SEQ ID NO: 103-206, 또는 413-435 중 어느 하나에 포함된 CDR1, CDR2 및 CDR3을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114, 207-311 및 312-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114, 207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443 중 어느 하나에 포함된 CDR 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114 또는 413-434 중 어느 하나에 포함된 하나 이상의 CDR 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114, 또는 413-434 중 어느 하나에 포함된 CDR1, CDR2 및 CDR3을 포함한다.
일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 단일클론 항체 또는 이의 항원 결합 단편이다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 인간화된 항체 또는 이의 항원 결합 단편이다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 인간 α11β1 발현 세포에서 α11β1과 콜라겐의 상호작용을 감소시킨다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 본원에 설명된 항체 또는 이의 항원 결합 단편과 경쟁한다.
또 다른 양태에서, 본 개시내용은 본원에 기재된 항체 또는 이의 항원 결합 단편을 코딩하는 핵산 서열을 포함하는 핵산을 제공한다. 일부 실시형태에서, 핵산 서열은 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 서열을 포함한다.
또 다른 양태에서, 본 개시내용은 본원에 기재된 핵산을 포함하는 벡터를 제공한다.
또 다른 양태에서, 본 개시내용은 본원에 기재된 핵산 또는 본원에 기재된 벡터를 포함하는 숙주 세포를 제공한다.
또 다른 양태에서, 본 개시내용은 항체 또는 이의 항원 결합 단편의 발현에 적합한 조건 하에 본원에 기재된 숙주 세포를 배양하는 것을 포함하는, 항체 또는 이의 항원 결합 단편을 생산하는 방법을 제공한다.
또 다른 양태에서, 본 개시내용은 만성 신장 질환을 앓거나 만성 신장 질환의 위험이 있는 대상체를 치료하는 방법을 제공하며, 상기 방법은 대상체에게 치료적 유효량의 본원에 기재된 항체 또는 이의 항원 결합 단편을 투여하는 것을 포함한다. 일부 실시형태에서, 만성 신장 질환은 원발성 사구체 질환(IgA 신병증 및 국소 분절성 사구체 경화증을 포함하나 이에 제한되지 않음), 속발성 사구체 질환(루푸스 신염을 포함하나 이에 제한되지 않음), 혈전성 미세혈관병증, 세뇨관간질 질환(폐쇄성 요로병증을 포함하나 이에 제한되지 않음), 당뇨병성 신병증, 고혈압 신병증, 허혈성 신병증, CKD의 심신 증후군, 사구체의 유전성 장애(알포트 증후군을 포함하나 이에 제한되지 않음), 신장의 낭성 질환(다낭성 신장 질환을 포함하나 이에 제한되지 않음), 또는 세뇨관의 유전성 장애이거나 이를 포함한다. 일부 실시형태에서, 치료적 유효량의 항체 또는 이의 항원 결합 단편을 투여하는 것은 측정된 마커, 징후 및/또는 증상을 대조군에 비해 적어도 약 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% 또는 90% 감소시킨다. 일부 실시형태에서, 대조군은 항체 투여 전에 대상체에서 측정된 마커, 징후 및/또는 증상의 수준을 포함한다. 일부 실시형태에서, 대조군은 신장 관련 장애를 앓고 있는 대상체에서 측정된 마커, 징후 및/또는 증상의 수준을 포함한다. 일부 실시형태에서, 대조군은 신장 관련 장애를 앓고 있는 대상체 집단에서 측정된 마커, 징후 및/또는 증상의 평균 수준을 포함한다. 일부 실시형태에서, 측정된 마커, 징후 및/또는 증상은 COL1A1, 피브로넥틴, PAI-1, IL-11, CXCL1, MCP-1, IL-6, TIMP-1, 히알루론산, TGFβ, CTGF, PDGF, MMP9, 또는 이들의 조합이거나 이를 포함한다.
본원에 기술된 본 교시는 첨부된 도면과 함께 읽을 때 다양한 예시적인 실시형태의 다음 설명으로부터 더 완전히 이해될 것이다. 아래에 설명된 도면은 단지 설명을 위한 것이며 어떠한 방식으로든 본 교시의 범위를 제한하려는 의도가 아님을 이해해야 한다.
도 1은 인테그린 구조의 표현을 도시한다. 패널은 콜라겐 결합 인테그린의 구조와 세포 표면에 존재할 수 있는 세 가지 다른 배좌(conformation)의 인테그린을 보여준다.
도 2a는 인간 α11β1에 대한 예시적인 마우스 단일클론 항체의 결합에 대한 ELISA 분석을 보여주는 차트를 도시한다.
도 2b는 마우스 α11β1에 대한 마우스 단일클론 항체의 결합에 대한 예시적인 ELISA 분석을 보여주는 차트를 도시한다.
도 3a는 인간 α11β1 I 도메인에 대한 예시적인 래트 단일클론 항체의 결합에 대한 ELISA 분석을 예시하는 그래프를 도시한다.
도 3b는 인간 α11β1 I 도메인에 대한 예시적인 마우스 단일클론 항체의 결합에 대한 ELISA 분석을 예시하는 그래프를 도시한다.
도 4a는 인간 α11β1을 발현하는 CHO-K1 세포에 대한 예시적인 래트 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 4b는 인간 α11β를 발현하는 CHO-K1 세포에 대한 예시적인 마우스 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 5는 인간 폐 섬유모세포(HPF) 및 근섬유모세포(MF)에 대한 예시적인 마우스 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 6a는 인간 α11을 발현하는 CHO-K1 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 래트 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 6b는 인간 α11을 발현하는 CHO-K1 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 토끼 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 6c는 인간 α11을 발현하는 CHO-K1 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 마우스 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 7a는 αSMA 상향조절의 퍼센트 억제에 의해 측정된 바와 같이 섬유모세포에서 근섬유모세포로의 전이(FMT)를 억제하는 예시적인 래트 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 7b는 αSMA 상향조절의 퍼센트 억제에 의해 측정된 바와 같이 섬유모세포에서 근섬유모세포로의 전이(FMT)를 억제하는 예시적인 토끼 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 7c는 αSMA 상향조절의 퍼센트 억제에 의해 측정된 바와 같이 섬유모세포에서 근섬유모세포로의 전이(FMT)를 억제하는 예시적인 마우스 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 8은 CHO-K1 인간 α11-매개 래트 꼬리 유형 I 콜라겐 겔 수축을 억제하는 예시적인 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 9는 표면 플라즈몬 공명(SPR)을 통한 인간 α11β1에 대한 예시적인 단일클론 항체의 친화도를 나타내는 그래프를 도시한다.
도 10a 및 도 10b는 표면 플라즈몬 공명(SPR)을 통한 인간 α11β1에 대한 예시적인 단일클론 항체의 친화도를 나타내는 그래프를 도시한다.
도 11a 및 도 11b는 CHO 세포 표면에서 발현된 α11β1에 대한 선택된 토끼, 래트, 마우스 및 인간 단일클론 항체의 결합 능력을 보여주는 그래프를 도시한다.
도 12는 인간 폐 섬유모세포(HPF) 및 근섬유모세포(MF)에 대한 예시적인 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 13은 인간 근섬유모세포(MF)에 대한 예시적인 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프 및 표를 도시한다.
도 14는 CHO 세포 표면에서 발현된 α11β1에 대해 선택된 단일클론 항체의 결합 능력을 나타내는 그래프를 도시한다.
도 15a 및 도 15b는 인간 α11을 발현하는 CHO 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 16은 SCID 마우스에서 이종이식편 성장에 대한 예시적인 단일클론 항체의 효과를 예시하는 그래프를 도시한다.
도 17a, 도 17b 및 도 17c는 정밀 절단 간 절편(PCLS)의 용해성 섬유화 촉진 마커에 대한 예시적인 단일클론 항체의 효과를 설명한다.
도 18a, 도 18b 및 도 18c는 정밀 절단 신장 절편(PCKS)의 용해성 섬유화 촉진 마커 Col1a1에 대한 예시적인 단일클론 항체의 효과를 예시한다.
도 1은 인테그린 구조의 표현을 도시한다. 패널은 콜라겐 결합 인테그린의 구조와 세포 표면에 존재할 수 있는 세 가지 다른 배좌(conformation)의 인테그린을 보여준다.
도 2a는 인간 α11β1에 대한 예시적인 마우스 단일클론 항체의 결합에 대한 ELISA 분석을 보여주는 차트를 도시한다.
도 2b는 마우스 α11β1에 대한 마우스 단일클론 항체의 결합에 대한 예시적인 ELISA 분석을 보여주는 차트를 도시한다.
도 3a는 인간 α11β1 I 도메인에 대한 예시적인 래트 단일클론 항체의 결합에 대한 ELISA 분석을 예시하는 그래프를 도시한다.
도 3b는 인간 α11β1 I 도메인에 대한 예시적인 마우스 단일클론 항체의 결합에 대한 ELISA 분석을 예시하는 그래프를 도시한다.
도 4a는 인간 α11β1을 발현하는 CHO-K1 세포에 대한 예시적인 래트 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 4b는 인간 α11β를 발현하는 CHO-K1 세포에 대한 예시적인 마우스 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 5는 인간 폐 섬유모세포(HPF) 및 근섬유모세포(MF)에 대한 예시적인 마우스 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 6a는 인간 α11을 발현하는 CHO-K1 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 래트 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 6b는 인간 α11을 발현하는 CHO-K1 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 토끼 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 6c는 인간 α11을 발현하는 CHO-K1 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 마우스 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 7a는 αSMA 상향조절의 퍼센트 억제에 의해 측정된 바와 같이 섬유모세포에서 근섬유모세포로의 전이(FMT)를 억제하는 예시적인 래트 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 7b는 αSMA 상향조절의 퍼센트 억제에 의해 측정된 바와 같이 섬유모세포에서 근섬유모세포로의 전이(FMT)를 억제하는 예시적인 토끼 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 7c는 αSMA 상향조절의 퍼센트 억제에 의해 측정된 바와 같이 섬유모세포에서 근섬유모세포로의 전이(FMT)를 억제하는 예시적인 마우스 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 8은 CHO-K1 인간 α11-매개 래트 꼬리 유형 I 콜라겐 겔 수축을 억제하는 예시적인 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 9는 표면 플라즈몬 공명(SPR)을 통한 인간 α11β1에 대한 예시적인 단일클론 항체의 친화도를 나타내는 그래프를 도시한다.
도 10a 및 도 10b는 표면 플라즈몬 공명(SPR)을 통한 인간 α11β1에 대한 예시적인 단일클론 항체의 친화도를 나타내는 그래프를 도시한다.
도 11a 및 도 11b는 CHO 세포 표면에서 발현된 α11β1에 대한 선택된 토끼, 래트, 마우스 및 인간 단일클론 항체의 결합 능력을 보여주는 그래프를 도시한다.
도 12는 인간 폐 섬유모세포(HPF) 및 근섬유모세포(MF)에 대한 예시적인 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프를 도시한다.
도 13은 인간 근섬유모세포(MF)에 대한 예시적인 단일클론 항체의 결합의 FACS 분석을 예시하는 그래프 및 표를 도시한다.
도 14는 CHO 세포 표면에서 발현된 α11β1에 대해 선택된 단일클론 항체의 결합 능력을 나타내는 그래프를 도시한다.
도 15a 및 도 15b는 인간 α11을 발현하는 CHO 세포의 래트 꼬리 유형 I 콜라겐에 대한 부착을 억제하는 예시적인 단일클론 항체의 능력을 예시하는 그래프를 도시한다.
도 16은 SCID 마우스에서 이종이식편 성장에 대한 예시적인 단일클론 항체의 효과를 예시하는 그래프를 도시한다.
도 17a, 도 17b 및 도 17c는 정밀 절단 간 절편(PCLS)의 용해성 섬유화 촉진 마커에 대한 예시적인 단일클론 항체의 효과를 설명한다.
도 18a, 도 18b 및 도 18c는 정밀 절단 신장 절편(PCKS)의 용해성 섬유화 촉진 마커 Col1a1에 대한 예시적인 단일클론 항체의 효과를 예시한다.
본 개시내용은 부분적으로 α11β1에 선택적으로 결합하는 신규 항체의 발견에 기초한다. 본 개시내용은 또한 상기 항체를 코딩하는 핵산 및 섬유증 성분을 포함하는 섬유증 및 질환의 치료에 사용하는 방법에 관한 것이다.
섬유증 및 질환
섬유증은 일반적으로 염증이나 조직 손상의 결과로 신체의 많은 조직에서 나타나는 흉터 과정이다. 세포외 기질의 생성 증가는 장기 부전 및 종종 사망을 초래한다. 섬유증과 관련된 질환은 선진국에서 전체 사망의 대략 45%를 차지한다(문헌[Wynn, T. A., 2008, J Pathol. 214:199-210]). 이러한 질환 중 하나는 전신성 경화증(SSc)이다. SSc는 만성 진행 과정과 환자 간 변동성이 높은 복잡한 자가 면역 질환이다. 이는 염증, 혈관 기능 장애 및 섬유증을 특징으로 한다. 피부와 내장 기관의 섬유화는 비가역적 흉터와 궁극적으로 장기 부전을 초래하여 높은 사망률을 초래한다. 현재 질환 수정 가능성이 있는 승인된 표적 치료법은 없다.
조직 복구(및 섬유증)를 위한 세포외 기질(ECM) 생산을 담당하는 세포는 근섬유모세포(MF)라고 하는 특수 유형의 섬유모세포이다. 섬유증의 메커니즘이 광범위하게 연구되었지만 이 복잡한 과정은 잘 이해되지 않았다. 섬유증의 가장 중요한 동인에 초점을 맞추기 위해 공개된 환자 파생 데이터세트(SSc 환자 데이터 및 정상 대조군)를 인하우스(in-house) 파생된 신규한 데이터 분석 방법론을 사용하여 조사했다. 이 분석은 유형 I 콜라겐 결합 인테그린 알파 11 베타 1(α11β1)이 섬유증 조절을 위한 최고의 표적 중 하나로 식별되도록 한다.
현재까지 섬유증에 대한 진정한 질환 수정 치료제는 없다. 특발성 폐 섬유증(IPF)에 대해 승인된 두 가지 치료법인 닌테다닙과 피르페니돈은 불량하게 작동하고 질환을 수정하지 않으며, 현재까지 전신성 경화증(SSc)에 대해 승인된 치료법이 없다. 일부 실시형태에서, 섬유성 장애는 특발성 폐 섬유증(IPF), 만성 신장 질환, 당뇨병성 심근병증, 원발성 경화성 담관염(PSC), 원발성 담즙성 간경변증(PBC), 비알코올성 지방간 질환(NAFLD/NASH), 크론병, 궤양성 대장염 또는 전신성 경화증(SSc)이거나 이를 포함한다. 일부 실시형태에서, 섬유증 장애는 심방 섬유증, 심내막 섬유증, 관절 섬유증, 종격동 섬유증, 골수 섬유증, 진행성 거대 섬유증, 후복막 섬유증 또는 골격근 섬유증이거나 이를 포함한다.
종양 미세 환경의 임상적 특징 중 하나는 종양과 간질 사이의 상호 작용이며, 이는 주로 ECM 구성 요소 및 성장 인자와 상호 작용하는 다양한 인테그린에 의존한다. 이러한 상호 작용은 종양 생존, 진행 및 궁극적으로 전이에 영향을 미칠 수 있다. α11β1은 전이성 종양의 암 관련 섬유모세포(CAF)에서 과발현되는 것으로 보고되었으며, 그 발현은 환자의 공격적인 종양과 관련이 있다. 예를 들어, 인테그린 α11은 대부분의 두경부 편평 세포 암종(HNSCC)의 간질에서 과발현되었고 알파 평활근 액틴 발현과 양의 상관관계가 있었다(문헌[Parajuli et al., J. Oral Pathol. Med. 46:267-275 (2017)]). 인테그린 α11은 또한 췌관 선암종(PDAC) 간질에서 CAF에 의해 과발현되었다(문헌[Schnittert et al., FASEB J. 33:6609-6621 (2019)]). 또한, 종양 기질에서 인테그린 α11β1 과발현은 종양 성장 및 비소세포 폐암(NSCLC)의 전이 가능성과 관련이 있고, ITGA11(인간에서 인테그린 알파-11을 코딩하는 유전자)의 높은 발현은 모든 NSCLC 환자에서 더 낮은 무재발 생존율과 관련이 있었다; 동일한 연구에서 폐암 세포주에서 α11 과발현이 이동 및 침입을 증가시키는 것으로 나타났다(문헌[Ando et al., Cancer Sci. 111:200-208 (2020)]).
인테그린
인테그린은 유형 I 막관통 이종이량체 당단백질 수용체의 큰 계열이며 세포 부착에 대한 주요 수용체로 작용한다. 수용체의 인테그린 계열은 세포 부착, 이동, 증식, 분화 및 세포사멸을 조절하는 신호 전달 경로를 조절하는 데 중요한 역할을 한다. 18개의 α 및 8개의 β 서브유닛이 결합되어 24개의 인테그린 헤테로이량체를 형성한다. 각각의 인테그린 수용체는 2개의 비공유결합 서브유닛인 α와 β를 포함한다. 인테그린 α1β1, α2β1, α10β1 및 α11β1은 주요 콜라겐 수용체이다. α 및 β 서브유닛은 세포골격 상호작용을 매개하는 크고 모듈화된 세포외 도메인, 단일 막관통 나선 및 짧은 세포질 영역을 갖는 막관통 단백질이다. 인테그린의 세포외 도메인은 일반적으로 크며 대략 80 내지 150 kDa 구조이다. 세포 외 도메인은 두 개의 다리에 연결된 헤드피스를 포함하는 것으로 볼 수 있다(콜라겐 결합 인테그린의 구조에 대해서는 도 1 참조). 콜라겐 결합 인테그린은 리간드 결합 부위 역할을 하는 I 도메인을 함유한다. αI-도메인은 2가 금속 양이온(Mg2+)에 결합하고 리간드 결합에서 중요한 역할을 하는 보존된 "금속 이온 의존 접착 부위"(MIDAS)를 함유한다.
인테그린은 세 가지 다른 배좌로 존재할 수 있다: 1) 리간드 결합 부위를 함유하는 헤드 피스가 멤브레인 쪽으로 향하는 휴지, 낮은 친화도 상태(구부러진 배좌, 도 1, 패널 A); 2) 인테그린이 확장되지만 헤드 피스가 '닫힌' 상태로 유지되는 확장된 중간 친화도 상태(도 1, 패널 B) 및 3) 인테그린이 완전히 활성화되어 리간드에 쉽게 결합하는 확장된 높은 친화도 상태. 상이한 인테그린 상태의 복잡성은 인테그린 기능을 억제하는 알로스테릭 및 리간드 차단 방법 모두를 허용한다. 도 1에서 별표로 표시된 것처럼 인테그린의 기능을 차단하는 알로스테릭 방법 중 하나는 인테그린이, 확장된 중간적 배좌에서 완전히 확장된 배좌에 도달하는 것을 방지하는 단일클론 항체를 생성하는 것이다. 또 다른 알로스테릭 옵션은 구부러진/비활성 배좌로 인테그린을 결합하고 다른 두 상태 중 하나로 확장되지 않도록 하는 것이다. 인테그린 기능을 억제하는 비-알로스테릭 방법은 I 도메인에 결합하여 인테그린이 콜라겐에 부착되는 것을 방지하는 것이다. 리간드 결합 부위에 대한 결합은 인테그린 기능의 재조합 활성제를 생성할 위험이 직접 있다.
세포 표면 수용체로서 인테그린은 주변 매트릭스의 강성을 감지하여 세포가 섬유성 표현형을 영구화할 수 있는 결합 조직을 더 생산하고 개조하도록 촉발한다. 많은 인테그린이 섬유증에서 과발현되지만 어떤 알파 소단위가 섬유증이 발생하기에 충분한지는 명확하지 않다. α11β1 인테그린은 섬유모세포 및 근섬유모세포(즉, 말단 흉터 생성 세포)의 하위 집합에서 특이적으로 발현된다. 최근 문헌은 α11β1이 심장 조직, 간, 폐 및 신장에서 섬유화 표현형의 주요 동인 중 하나라는 강력한 증거를 제공했다(문헌[Romaine, A. et. al. Overexpression of integrin alpha 11 induces cardiac fibrosis in mice. Acta Physiol Feb 2018, 222(2)]; 문헌[Bansal, R. et.al. Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases. Exp Mol Med. 2017 Nov 17:49(11)]). α11β1 기능을 차단하면 근섬유모세포 분화 및 세포외 기질 침착(즉, 흉터 형성의 주요 사건)을 억제할 수 있고 α11β1 기능을 차단하면 섬유화 미세 환경을 근본적으로 변화시키고 섬유화 구성 요소가 있는 모든 질환의 질환 진행을 수정할 수 있는 섬유화의 국부적, 손상 특이적 감쇠 메커니즘을 제공할 수 있다.
일부 실시형태에서, 본 개시내용의 항-α11β1 항체 또는 이의 항원 결합 단편은 인간 α11β1 발현 세포에서 α11β1과 콜라겐의 상호작용을 감소시킨다. 일부 실시형태에서, 인간 α11β1을 발현하는 세포에서 α11β1과 콜라겐의 상호작용을 감소시키는 것은 항-α11β1 항체 또는 이의 항원 결합 단편을 포함하며, 휴지기의 낮은 친화도 상태(구부러진 배좌)에 있는 α11β1과 상호작용한다. 일부 실시형태에서, 인간 α11β1 발현 세포에서 α11β1과 콜라겐의 상호작용을 감소시키는 것은 연장된 중간 친화도 상태에 있는 α11β1과 상호작용하는 항-α11β1 항체 또는 이의 항원 결합 단편을 포함한다. 일부 실시형태에서, 인간 α11β1 발현 세포에서 α11β1과 콜라겐의 상호작용을 감소시키는 것은 확장된 높은 친화도 상태에 있는 α11β1과 상호작용하는 항-α11β1 항체 또는 이의 항원 결합 단편을 포함한다.
항체
용어 "항체"는 본원에서 가장 넓은 의미로 사용되며 단일클론 항체, 폴리클론 항체, 다중특이적 항체(예를 들어, 이중특이적 항체) 및/또는 항체 단편(바람직하게는 원하는 항원 결합 활성을 나타내는 단편)을 포함하나 이에 제한되지 않는 다양한 항체 구조를 포함한다. 본원에 기술된 항체는 면역글로불린, 중쇄 항체, 경쇄 항체, LRR 기반 항체 또는 항체 유사 특성을 가진 기타 단백질 스캐폴드, 뿐만 아니라 예를 들어, Fab, Fab', Fab'2, Fab2, Fab3, F(ab')2, Fd, Fv, Feb, scFv, SMIP, 항체, 디아바디, 트리아바디, 테트라바디, 미니바디, 맥시바디, 탄답, DVD, BiTe, TandAb, 등을 포함하는 당업계에 알려진 다른 면역학적 결합 모이어티, 또는 이들의 임의의 조합일 수 있다. 상이한 부류의 항체의 서브유닛 구조 및 3차원 구성은 당업계에 알려져 있다.
"단일클론 항체" 또는 "mAb"는 실질적으로 동종인 항체 집단으로부터 수득한 항체를 지칭하며, 즉 집단을 구성하는 개별 항체는 동일하고/동일하거나 가능한 변이체 항체를 제외하고는 동일한 에피토프에 결합하며(예를 들어, 자연적으로 발생하는 돌연변이를 함유하거나 단일클론 항체 제제의 생산 중에 발생), 이러한 변이체는 일반적으로 소량으로 존재한다. 전형적으로 상이한 결정인자(에피토프)에 대한 상이한 항체를 포함하는 폴리클론 항체 제제와 대조적으로, 단일클론 항체 제제의 각각의 단일클론 항체는 항원 상의 단일 결정인자에 대한 것이다.
"항원-결합 단편"은 무손상 항체가 결합하는 항원에 결합하는 무손상 항체의 일부를 지칭한다. 항체의 항원 결합 단편은 복합체를 형성하기 위해 항원에 특이적으로 결합하는 임의의 자연 발생적, 효소적으로 수득 가능한, 합성 또는 유전적으로 조작된 폴리펩티드 또는 당단백질을 포함한다. 예시적인 항체 단편은 다음을 포함하나 이에 제한되지 않는다: Fv, Fab, Fab', Fab'-SH, F(ab')2; 디아바디; 선형 항체; 단쇄 항체 분자(예를 들어 scFv 또는 VHH 또는 VH 또는 VL 도메인만); 및 항체 단편으로부터 형성된 다중특이적 항체. 일부 실시형태에서, 본원에 기재된 항체의 항원 결합 단편은 scFv이다. 전체 항체 분자와 마찬가지로 항원 결합 단편은 단일특이적 또는 다중특이적(예를 들어, 이중특이적)일 수 있다. 항체의 다중특이적 항원 결합 단편은 적어도 2개의 상이한 가변 도메인을 포함할 수 있고, 여기서 각각의 가변 도메인은 별도의 항원 또는 동일한 항원의 상이한 에피토프에 특이적으로 결합할 수 있다.
"다중특이적 항체"는 적어도 2개의 상이한 항원을 인식하고 특이적으로 결합하는 적어도 2개의 상이한 항원 결합 도메인을 포함하는 항체를 지칭한다. "이중특이적 항체"는 다중특이적 항체의 일종으로서 적어도 2개의 상이한 항원을 인식하고 특이적으로 결합하는 2개의 상이한 항원 결합 도메인을 포함하는 항체를 지칭한다.
"상이한 항원"은 상이한 그리고/또는 별개의 단백질, 폴리펩티드 또는 분자; 뿐만 아니라 상이한 그리고/또는 별개의 에피토프(이 에피토프는 하나의 단백질, 폴리펩티드 또는 다른 분자 내에 포함될 수 있음)를 지칭할 수 있다.
용어 "에피토프"는 파라토프로 알려진 항체 분자의 가변 영역에서 특정 항원 결합 부위와 상호 작용하는 항원 결정자를 지칭한다. 단일 항원은 하나 초과의 에피토프를 가질 수 있다. 따라서, 상이한 항체는 항원의 상이한 영역에 결합할 수 있고 상이한 생물학적 효과를 가질 수 있다. 용어 "에피토프"는 또한 B 세포 및/또는 T 세포가 반응하는 항원 부위를 지칭한다. 이는 또한 항체에 의해 결합되는 항원의 영역을 지칭한다. 에피토프는 구조적 또는 기능적이라고 정의될 수 있다. 기능적 에피토프는 일반적으로 구조적 에피토프의 하위 집합이며 상호 작용의 친화도에 직접적으로 기여하는 잔기를 가지고 있다. 에피토프는 또한 배좌적(conformational)일 수 있으며, 즉, 비선형 아미노산으로 구성된다. 특정 실시형태에서, 에피토프는 아미노산, 당 측쇄, 포스포릴 기 또는 술포닐 기와 같은 분자의 화학적 활성 표면 그룹화인 결정자를 포함할 수 있고, 특정 실시형태에서, 특정 3차원 구조적 특성 및/또는 특정 전하 특성을 가질 수 있다.
본원에서 사용되는 "선택적 결합", "선택적으로 결합하다" "특이적 결합" 또는 "특이적으로 결합하다"는, 항원 결합 모이어티 및 항원 표적과 관련하여, 항원 결합 모이어티가, 항원 표적이 아닌 실체에 말고 항원 표적에 우선적으로 회합되는 것을 지칭한다. 항원 결합 모이어티와 비표적 사이에는 어느 정도의 비특이적 결합이 발생할 수 있다. 일부 실시형태에서, 항원 결합 모이어티와 항원 표적 사이의 결합이 항원 결합 모이어티와 비-표적의 결합과 비교하여 2배 초과, 5배 초과, 10배 초과, 또는 100배 초과인 경우 항원 결합 모이어티는 항원 표적에 선택적으로 결합한다. 일부 실시형태에서, 항원 결합 모이어티는 결합 친화도가 약 10-5 M 미만, 약 10-6 M 미만, 약 10-7 M 미만, 약 10-8 M 미만, 또는 약 10-9 M 미만인 경우 항원 표적에 선택적으로 결합한다.
일부 실시형태에서, 항원에 결합하기 위해 종종 교차 경쟁할 동일한 에피토프 또는 중복 에피토프에 선택적으로 결합하는 항체 또는 이의 단편. 따라서, 일부 실시형태에서, 본 개시내용은 본원에 개시된 바와 같은 예시적인 항체 또는 이의 단편과 교차 경쟁하는 항체 또는 이의 단편을 제공한다. 일부 실시형태에서, "교차 경쟁하다", "경쟁하다", "교차 경쟁" 또는 "경쟁"은 항체 또는 이의 단편이 표적 상의 동일한 에피토프 또는 결합 부위에 대해 경쟁한다는 것을 의미한다. 이러한 경쟁은 참조 항체 또는 이의 단편이 시험 항체 또는 이의 단편의 특이적 결합을 방지하거나 억제하는 분석법에 의해 결정될 수 있으며, 그 역도 마찬가지이다. 시험 분자가 결합을 위해 참조 분자와 경쟁하는지 여부를 결정하기 위해 다양한 유형의 경쟁적 결합 검정을 사용할 수 있다. 사용할 수 있는 검정의 예는 고체 상 직접 또는 간접 방사면역검정(RIA), 고체 상 직접 또는 간접 효소 면역검정(EIA), 샌드위치 경쟁 검정(예를 들어, 문헌[Stahli et al. (1983) Methods in Enzymology 9:242-253] 참조), 고체 상 직접 비오틴-아비딘 EIA(예를 들어, 문헌[Kirkland et al., (1986) J. Immunol. 137:3614-9] 참조), 고체 상 직접 표지 검정, 고체 상 직접 표지 샌드위치 검정, Luminex(문헌[Jia et al. "A novel method of Multiplexed Competitive Antibody Binning for the characterization of monoclonal antibodies" J. Immunological Methods (2004) 288, 91-98]) 및 표면 플라즈몬 공명(문헌[Song et al. "Epitope Mapping of Ibalizumab, a Humanized Anti-CD4 Monoclonal Antibody with Anti-HIV-1 Activity in Infected Patients" J. Virol. (2010) 84, 6935-42])을 포함한다. 일반적으로 경쟁 항체 또는 이의 단편이 과잉으로 존재하는 경우 참조 항체 또는 이의 단편이 공통 항원에 결합하는 것을 적어도 50%, 55%, 60%, 65%, 70% 또는 75% 억제할 것이다. 일부 경우에, 결합은 적어도 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% 또는 그 이상 억제된다.
항체는 4개의 폴리펩티드 사슬, 예를 들어 2개의 중쇄(H) 및 2개의 경쇄(L)의 면역글로불린 분자일 수 있다. 일부 실시형태에서, 경쇄는 람다 경쇄이다. 일부 실시형태에서, 경쇄는 카파 경쇄이다. 중쇄는 중쇄 가변 도메인 및 중쇄 불변 도메인을 포함할 수 있다. 중쇄 불변 도메인은 CH1, 힌지, CH2, CH3 및 일부 경우 CH4 영역을 포함할 수 있다. 경쇄는 경쇄 가변 도메인 및 경쇄 불변 도메인을 포함할 수 있다. 경쇄 불변 도메인은 CL을 포함할 수 있다.
중쇄의 중쇄 가변 도메인 및 경쇄의 경쇄 가변 도메인은 일반적으로 상보성 결정 영역(CDR)이라고 하는 가변성 영역으로 더 세분될 수 있으며, 프레임워크 영역(FR)이라고 하는 보다 보존된 영역이 산재되어 있다. 이러한 중쇄 및 경쇄 가변 도메인은 각각 다음 순서로 아미노-말단에서 카르복실-말단까지 배열된 3개의 CDR 및 4개의 프레임워크 영역을 포함할 수 있다: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4(이 중 하나 이상은 본원에 기술된 바와 같이 조작될 수 있음). 중쇄의 CDR은 각각 "CDRH1", "CDRH2" 및 "CDRH3"로 지정되고, 경쇄의 CDR은 "CDRL1", "CDRL2" 및 "CDRL3"으로 지정된다.
항체에는 5가지 주요 부류가 있다: IgA, IgD, IgE, IgG 및 IgM, 그리고 이들 중 일부는 예를 들어 IgG1, IgG2, IgG3, IgG4, IgA1 및 IgA2와 같은 하위부류(이소형)로 더 나눌 수 있다. 상이한 클래스의 면역글로불린에 해당하는 중쇄 불변 도메인을 각각 α, δ, ε, γ 및 μ라고 한다.
예시적인 항체
본 개시내용은 본원에 기재된 다양한 중쇄 및 경쇄를 포함할 수 있는 항체를 제공한다. 일부 실시형태에서, 항체는 2개의 중쇄 및 경쇄를 포함한다. 일부 실시형태에서, 본 개시내용은 본원에 개시된 바와 같은 적어도 하나의 중쇄 및/또는 경쇄, 본원에 개시된 바와 같은 적어도 하나의 중쇄 프레임워크 도메인 및/또는 경쇄 프레임워크 도메인, 본원에 개시된 바와 같은 적어도 하나의 중쇄 CDR 도메인 및/또는 경쇄 CDR 도메인, 및/도는 본원에 개시된 바와 같은 임의의 중쇄 불변 도메인 및/또는 경쇄 불변 도메인을 포함하는 항체를 포함한다.
일부 실시형태에서, 본원에 개시된 항체는 동종이량체 단일클론 항체이다. 일부 실시형태에서, 본원에 개시된 항체는 이종이량체 항체이다. 일부 실시형태에서, 항체는 예를 들어 전형적인 항체 또는 디아바디, 트리아바디, 테트라바디, 미니바디, 맥시바디, 탄답, DVD, BiTe, scFv, TandAb scFv, Fab, Fab2, Fab3, F(ab')2, 등, 또는 이들의 조합이다.
본 개시내용은 특히 항-인테그린 알파 11 베타 1(α11β1) 항체 또는 이의 항원 결합 단편을 제공한다. 일부 실시형태에서, α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-435 중 어느 하나에 포함된 CDR 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-206, 또는 413-443 중 어느 하나에 포함된 CDR1, CDR2 및 CDR3을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114, 207-311 및 312-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114, 207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443 중 어느 하나에 포함된 CDR 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114 또는 413-434 중 어느 하나에 포함된 하나 이상의 CDR 서열을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 103-114, 또는 413-434 중 어느 하나에 포함된 CDR1, CDR2 및 CDR3을 포함한다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 단일클론 항체 또는 이의 항원 결합 단편이다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 인간화된 항체 또는 이의 항원 결합 단편이다. 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 인간 α11β1 발현 세포에서 α11β1과 콜라겐의 상호작용을 감소시킨다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 103-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함하는 항체 또는 이의 항원 결합 단편과 경쟁하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 103-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함하는 항체 또는 이의 항원 결합 단편과 경쟁하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다.
일부 실시형태에서, 본 개시내용은 본원에 제공된 중쇄와 본원에 제공된 경쇄를 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다. 일부 실시형태에서, 본 개시내용은 본원에 제공된 중쇄 가변 도메인과 본원에 제공된 경쇄 가변 영역을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다. 일부 실시형태에서, 본 개시내용은 중쇄 가변 도메인과 경쇄 가변 도메인의 특정 조합을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공한다. 예를 들어, 일부 실시형태에서, 항-α11β1 항체 또는 이의 항원 결합 단편은 표 1에서 선택된 중쇄 가변 도메인과 경쇄 가변 도메인의 조합을 포함한다.
[표 1]
일부 실시형태에서, 본 개시내용은 항-α11β1 항체 또는 이의 항원 결합 단편에 비해 1 내지 30개(예를 들어, 1, 2, 3, 4, 5, 10 또는 그 이상)의 추가, 결실 또는 치환을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공하며, 항-α11β1 항체는 SEQ ID NO: 103-158, 413, 414 및 421-434로 이루어진 군으로부터 선택된 아미노산 서열을 포함하며, 예를 들어 항체 또는 단편은 α11β1에 선택적으로 결합한다. 일부 실시형태에서, 본 개시내용은 항-α11β1 항체 또는 이의 항원 결합 단편에 비해 1 내지 30개의 추가, 결실 또는 치환을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공하며, 항-α11β1 항체는 SEQ ID NO: 103-114, 413, 414 및 421-434로 이루어진 군으로부터 선택된 아미노산 서열을 포함하며, 예를 들어 항체 또는 단편은 α11β1에 선택적으로 결합한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 103-158, 413, 414 및 421-434로 이루어진 군으로부터 선택된 아미노산 서열과 적어도 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 서열 동일성을 갖는 아미노산 서열을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공하고, 예를 들어 항체 또는 단편은 α11β1에 선택적으로 결합한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 103-114, 413, 414 및 421-434로 이루어진 군으로부터 선택된 아미노산 서열과 적어도 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 동일성을 갖는 아미노산 서열을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공하고, 예를 들어 항체 또는 단편은 α11β1에 선택적으로 결합한다.
일부 실시형태에서, 본 개시내용은 항-α11β1 항체 또는 이의 항원 결합 단편에 비해 1 내지 90개(예를 들어, 1 내지 50, 예를 들어, 적어도 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 또는 그 이상)의 추가, 결실 또는 치환을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공하며, 항-α11β1 항체 또는 이의 항원 결합 단편은 SEQ ID NO: 159-206 및 415-420으로 이루어진 군으로부터 선택된 아미노산 서열을 포함하며, 예를 들어 항체 또는 단편은 α11β1에 선택적으로 결합한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 159-206 및 415-420으로 이루어진 군으로부터 선택된 아미노산 서열과 적어도 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 동일성을 갖는 아미노산 서열을 포함하는 항-α11β1 항체 또는 이의 항원 결합 단편을 제공하고, 예를 들어 항체 또는 단편은 α11β1에 선택적으로 결합한다.
일부 실시형태에서, 본 개시내용은 α11β1에 선택적으로 결합하는 항체 또는 이의 단편을 제공하며, 여기서 항체 또는 단편은 본원에 제공된 예시적인 서열 목록에 묘사된 하나 이상의 CDR 서열을 포함한다. 예를 들어, 일부 실시형태에서, 항체 또는 이의 단편은 SEQ ID NO: 103-114로부터의 하나 이상의 CDR을 포함한다. 일부 실시형태에서, 본 개시내용은 α11β1에 선택적으로 결합하는 항체 또는 이의 단편을 제공하며, 여기서 항체 또는 단편은 SEQ ID NO: 103-114의 하나 이상의 CDR과 적어도 95%, 96%, 97%, 98%, 또는 99% 동일한 아미노산 서열을 포함한다. 일부 실시형태에서, 항체 또는 단편은 SEQ ID NO: 103-114 중 하나와 적어도 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 동일성을 갖는 아미노산 서열을 포함하고, 여기서 항체는 SEQ ID NO: 103-114중 하나에 기재된 하나 이상의 CDR을 포함한다. 예를 들어, 항체 또는 단편은 SEQ ID NO: 103과 적어도 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 동일성을 갖는 아미노산 서열을 포함하고, 여기서 항체는 SEQ ID NO:103에 나타낸 하나 이상의 CDR(예를 들어, 1, 2 또는 3개의 CDR)을 포함한다.
일부 실시형태에서, 본 개시내용은 α11β1에 선택적으로 결합하는 항체 또는 이의 단편을 제공하며, 여기서 항체 또는 단편은 본원에 제공된 예시적인 서열 목록에 묘사된 하나 이상의 CDR 서열을 포함한다. 예를 들어, 일부 실시형태에서, 항체 또는 이의 단편은 SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443으로부터의 하나 이상의 CDR을 포함한다. 일부 실시형태에서, 본 개시내용은 α11β1에 선택적으로 결합하는 항체 또는 이의 단편을 제공하며, 여기서 항체 또는 단편은 SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443의 하나 이상의 CDR과 적어도 95%, 96%, 97%, 98% 또는 99% 동일한 아미노산 서열을 포함한다. 일부 실시형태에서, 항체 또는 단편은 SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443 중 하나와 적어도 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 동일성을 갖는 아미노산 서열을 포함하며, 여기서 항체는 SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443 중 하나에 기재된 하나 이상의 CDR을 포함한다. 예를 들어, 항체 또는 단편은 SEQ ID NO: 103과 적어도 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 동일성을 갖는 아미노산 서열을 포함하고, 여기서 항체는 SEQ ID NO:103에 나타낸 하나 이상의 CDR(예를 들어, 1, 2 또는 3개의 CDR)을 포함한다.
본 개시내용은 특히 항-α11β1 항체 또는 이의 항원 결합 단편의 제조 방법을 제공한다. 항체의 제조 방법은 당업계에 알려져 있다. 일부 실시형태에서, 본 개시내용은 항체 또는 이의 항원 결합 단편의 발현에 적합한 조건 하에서 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 핵산 서열을 포함하는 핵산을 포함하는 숙주 세포를 배양하는 것을 포함하는 항체 또는 이의 항원-결합 단편을 생산하는 방법을 제공한다.
예시적인 뉴클레오티드 서열
본 개시내용은 하나 이상의 중쇄, 중쇄 가변 도메인, 중쇄 프레임워크 영역, 중쇄 CDR, 중쇄 불변 도메인, 경쇄, 경쇄 가변 도메인, 경쇄 프레임워크 영역, 경쇄 CDR, 경쇄 불변 도메인, 또는 기타 면역글로불린 유사 서열, 항체, 또는 본원에 개시된 결합 분자를 코딩하는 뉴클레오티드 서열을 포함한다. 일부 실시형태에서, 이러한 뉴클레오티드 서열은 벡터에 존재할 수 있다. 일부 실시형태에서, 이러한 뉴클레오티드는 세포, 예를 들어, 치료를 필요로 하는 대상체의 세포 또는 항체 생산을 위한 세포, 예를 들어, 항체 생산을 위한 포유류 세포의 게놈에 존재할 수 있다.
일부 실시형태에서, 본 개시내용은 SEQ ID NO: 103-206으로 이루어진 군으로부터 선택된 아미노산 서열을 포함하는, 항체 또는 이의 항원 결합 단편을 코딩하는 핵산 서열을 포함하는 핵산을 제공한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 103-114로 이루어진 군으로부터 선택된 아미노산 서열을 포함하는, 항체 또는 이의 항원 결합 단편을 코딩하는 핵산 서열을 포함하는 핵산을 제공한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 핵산 서열을 포함하는 핵산을 제공한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 핵산 서열을 포함하는 핵산을 포함하는 벡터를 제공한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 핵산 서열을 포함하는 핵산을 포함하는 숙주 세포를 제공한다. 일부 실시형태에서, 본 개시내용은 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 핵산 서열을 포함하는 핵산을 포함하는 벡터를 제공한다.
일부 실시형태에서, 본 개시내용은 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 핵산 서열과 적어도 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 서열 동일성을 갖는 핵산 서열을 포함하는 핵산을 제공한다.
항체와 α11β1의 상호작용 측정
α11β1에 대한 본원에 기술된 항체의 결합 특성은 당업계에 알려진 방법, 예를 들어 다음 방법 중 하나에 의해 측정될 수 있다: BIACORE 분석, 효소 연관 면역흡착 검정(ELISA), x-선 결정학, 서열 분석 및 스캐닝 돌연변이유발. 항체와 α11β1의 결합 상호작용은 표면 플라즈몬 공명(SPR)을 사용하여 분석될 수 있다. SPR 또는 생체분자 상호작용 분석(BIA)은 상호작용 물질을 표지하지 않고 실시간으로 바이오 특이적 상호작용을 검출한다. BIA 칩의 결합 표면(결합 이벤트를 나타냄)에서 질량의 변화는 표면 근처에서 빛의 굴절률의 변경을 초래한다. 굴절률의 변화는 생물학적 분자 사이의 실시간 반응의 표시로 측정되는 검출 가능한 신호를 생성한다. SPR을 사용하는 방법은 예를 들어 미국 특허 제5,641,640호; 문헌[Raether (1988) Surface Plasmons Springer Verlag]; 문헌[Sjolander and Urbaniczky (1991) Anal. Chem. 63:2338-2345]; 문헌[Szabo et al. (1995) Curr. Opin. Struct. Biol. 5:699-705] 및 BIAcore International AB(스웨덴 웁살라 소재)에서 제공하는 온라인 리소스에 기재되어 있다. 추가로, Sapidyne Instruments(Boise, Id.)로부터 입수 가능한 KinExA®(Kinetic Exclusion Assay) 검정도 사용할 수 있다.
SPR의 정보는 α11β1에 대한 항체 결합에 대한 평형 해리 상수(KD) 및 동역학 파라미터(Kon 및 Koff 포함)의 정확하고 정량적인 측정을 제공하는 데 사용될 수 있다. 이러한 데이터는 다른 분자를 비교하는 데 사용될 수 있다. SPR의 정보는 구조 활동 관계(SAR)를 개발하는 데에도 사용될 수 있다. 특정 결합 파라미터, 예를 들어 높은 친화도와 상관관계가 있는 소정의 위치의 변이체 아미노산을 확인할 수 있다.
특정 실시형태에서, 본원에 기술된 항체는 α11β1 결합에 대해 높은 친화도를 나타낸다. 다양한 실시형태에서, α11β1에 대해 본원에 기재된 바와 같은 항체의 KD는 약 10-4, 10-5, 10-6, 10-7, 10-8, 10-9, 10-10, 10-11, 10-12, 10-13, 10-14, 또는 10-15 M 미만이다. 특정 경우, α11β1에 대한 본원에 기재된 바와 같은 항체의 KD는 0.001 내지 1 nM, 예를 들어, 0.001 nM, 0.005 nM, 0.01 nM, 0.05 nM, 0.1 nM, 0.5 nM, 또는 1 nM이다.
치료 방법
일부 실시형태에서 본원에 설명된 하나 이상의 항-α11β1 항체는 본원에 설명된 하나 이상의 장애, 예를 들어 하나 이상의 섬유성 장애 및/또는 하나 이상의 암을 치료하는 방법에 사용된다. 일부 실시형태에서, 방법은 본원에 기술된 항체 또는 이의 항원 결합 단편의 치료적 유효량을 이를 필요로 하는 대상체에게 투여하는 것을 포함한다. 일부 실시형태에서, 섬유성 장애는 특발성 폐 섬유증(IPF), 만성 신장 질환, 당뇨병성 심근병증, 원발성 경화성 담관염(PSC), 원발성 담즙성 간경변증(PBC), 비알코올성 지방간 질환(NAFLD/NASH), 크론병, 궤양성 대장염 또는 전신성 경화증이거나 이를 포함한다.
일부 실시형태에서, 섬유증 장애는 심방 섬유증, 심내막 섬유증, 관절 섬유증, 종격동 섬유증, 골수 섬유증, 진행성 거대 섬유증, 후복막 섬유증 또는 골격근 섬유증이거나 이를 포함한다.
일부 실시형태에서, 본원에 기술된 하나 이상의 항-α11β1 항체는 다음 중 하나 이상과 같은 암 치료 방법에 사용된다: 두경부 편평 세포 암종, 췌관 선암종, 비소세포 폐암, 부신피질 암종, 급성 골수성 백혈병, 방광 요로상피암종, 침윤성 유방 암종, 자궁경부 편평 세포 암종, 담관암종, 결장직장 선암종, 미만성 거대 B 세포 림프종, 식도 선암종, 다형성 교모세포종, 간 간세포 암종, 폐 선암종, 폐 편평 세포 암종, 피부 흑색종, 중피종, 난소 장액성 낭선암종, 갈색세포종 및 부신경절종, 전립선 선암종, 육종, 위 선암종, 고환 생식 세포 종양, 흉선종, 갑상선 암종, 자궁체 자궁내막 암종, 자궁 암육종, 포도막 흑색종, 신장 투명 세포 암종, 신장 발색단 및 신장 유두 세포 암종.
일부 실시형태에서 본원에 설명된 하나 이상의 항-α11β1 항체는 만성 신장 질환(CKD), 예를 들어 섬유증과 관련된 CKD를 갖거나 가질 위험이 있는 대상체를 치료하는 데 사용된다. CKD는 당업계에 알려져 있다(예를 들어, 문헌[Brenner, Barry M. (ed) Brenner & Rector's The Kidney, 11th edition 2019] 참조). CKD는 예를 들어 원발성 사구체 질환(IgA 신병증 및 국소 분절성 사구체 경화증을 포함하나 이에 제한되지 않음), 속발성 사구체 질환(루푸스 신염을 포함하나 이에 제한되지 않음), 혈전성 미세혈관병증, 세뇨관간질 질환(폐쇄성 요로병증을 포함하나 이에 제한되지 않음), 당뇨병성 신병증, 고혈압 신병증, 허혈성 신병증, CKD의 심신 증후군, 사구체의 유전성 장애(알포트 증후군을 포함하나 이에 제한되지 않음), 신장의 낭성 질환(다낭성 신장 질환을 포함하나 이에 제한되지 않음), 및 세뇨관의 유전성 장애를 포함한다(문헌[Brenner, Barry M. (ed) Brenner & Rector's The Kidney, 11th edition 2019]).
일부 실시형태에서, 본원에 설명된 항-α11β1 항체는 대상체에게 투여 시 본원에 설명된 신장 관련 장애의 하나 이상의 마커, 징후 및/또는 증상을 감소시킨다. 신장 관련 질환의 마커, 징후 및/또는 증상에는 예를 들어 COL1A1, IL-6, TIMP-1, 히알루론산, TGFβ, CTGF, PDGF 및 MMP9가 포함된다. 일부 실시형태에서, 대상체에게 투여시, 항-α11β1 항체는 대조군에 비해 측정된 마커, 징후 및/또는 증상을 적어도 약 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% 또는 90% 감소시킬 수 있다(예를 들어, 항체 투여 전 대상체에서 측정된 마커, 징후 및/또는 증상의 수준, 신장 관련 장애를 앓고 있는 대상체에서 측정된 마커, 징후 및/또는 증상의 수준, 및/또는 신장 관련 장애를 앓고 있는 대상체 집단에서 측정된 마커, 징후 및/또는 증상의 평균 수준).
일부 실시형태에서, 본원에 기술된 항-α11β1 항체는 신장 관련 장애 모델(예를 들어, 인간 정밀 절단 신장 절편(PCKS), ReninAAV Unx db/db 마우스 모델, 또는 5/6 Nephrectomy 모델)에서 측정 시 COL1A1, IL-6, TIMP-1, 히알루론산, TGFβ, CTGF, PDGF, MMP9 또는 이들의 조합의 수준을 대조군에 비해 적어도 약 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% 또는 90% 감소시킨다. 일부 실시형태에서, 신장 관련 장애의 마커, 징후 및/또는 증상은 단백질 수준, RNA 수준, DNA 수준 또는 이들의 조합을 측정함으로써 결정될 수 있다. 일부 실시형태에서, 신장 관련 장애의 마커, 징후 및/또는 증상은 ELISA, PCR, RNAseq, 생화학적 검정(예를 들어, 세포 과정(예를 들어, 아폽토시스, 세포 신호) 또는 대사 반응을 검출하고 정량화하기 위한 분석 절차), 세포학, 면역조직화학 또는 이들의 조합을 사용하여 결정될 수 있다.
일부 실시형태에서, 신장 관련 장애의 마커, 징후 및/또는 증상은 대상체로부터의 생물학적 샘플을 시험함으로써 결정될 수 있다. 적합한 생물학적 샘플의 예에는 혈청, 혈장, 뇌척수액, 소변, 순환 혈액 세포(예를 들어, 말초 혈액 단핵 세포) 및 생검 시편이 포함되나 이에 제한되지 않는다. 일부 실시형태에서, 샘플은 세포 또는 조직을 포함한다. 일부 실시형태에서, 제공된 방법은 세포를 용해하거나 조직 생검을 수행하는 단계를 추가로 포함하고 하나 이상의 마커는 하나 이상의 세포내 마커를 포함한다. 본 개시내용에 적합한 생물학적 샘플은 대상체로부터 수집된 신선 또는 냉동 샘플, 또는 알려진 진단, 치료 및/또는 결과 이력이 있는 보관 샘플일 수 있다. 생물학적 샘플은 임의의 침습적 또는 비침습적 수단, 예를 들어 대상체로부터 CSF 또는 혈액을 채취하거나 미세 바늘 흡인 또는 바늘 생검을 사용하거나 외과적 생검을 통해 수집할 수 있다. 일부 실시형태에서, 생물학적 샘플은 샘플의 제한된 처리 없이 또는 제한된 처리와 함께 사용될 수 있다.
조합 요법
일부 실시형태에서, 본원에 기술된 항-α11β1 항체는 화학요법제 또는 종양용해 치료제와 같은 하나 이상의 추가 치료제와 조합으로 투여된다. 본원에서 사용되는 "조합 요법"은 2개 이상의 상이한 약제가 중첩 레지먼으로 투여되어 대상체가 두 약제에 동시에 노출되는 상황을 지칭한다. 조합 요법에 사용되는 경우 두 가지 이상의 다른 약제를 동시에 또는 별도로 투여할 수 있다. 조합 투여는 동일한 투여 형태의 2개 이상의 제제의 동시 투여, 개별 투여 형태의 동시 투여 및 개별 투여를 포함할 수 있다. 즉, 2개 이상의 제제를 동일한 투여 형태로 함께 제형화되고 동시에 투여될 수 있다. 대안적으로, 2개 이상의 제제가 동시에 투여될 수 있으며, 여기서 제제는 별도의 제형으로 존재한다. 또 다른 대안에서, 제1 제제를 투여한 후 하나 이상의 추가 제제를 투여할 수 있다. 별도의 투여 프로토콜에서, 2개 이상의 제제는 몇 분 간격으로, 또는 몇 시간 간격으로, 또는 며칠 간격으로 투여될 수 있다.
본원에서 사용되는 용어 "화학요법제" 또는 "종양용해 치료제"(예를 들어, 항암 약물, 예를 들어, 항암 요법, 예를 들어, 면역 세포 요법)는 하나 이상의 아폽토시스 유도제, 세포증식억제제 및/또는 세포독성제, 및/또는 호르몬제를 지칭하는 당업계에서 이해되는 의미를 갖고, 예를 들어, 특히 바람직하지 않은 세포 증식과 관련된 하나 이상의 질환, 장애 또는 병태를 치료하는 데 사용되는 그리고/또는 사용이 권장되는 제제를 포함한다. 일부 실시형태에서, 화학요법제 및/또는 종양용해 치료제는 하기이거나 하기를 포함할 수 있다: 백금 화합물(예를 들어, 시스플라틴, 카르보플라틴 및 옥살리플라틴), 알킬화제(예를 들어, 사이클로포스파미드, 이포스파미드, 클로람부실, 질소 머스타드, 티오테파, 멜팔란, 부술판, 프로카르바진, 스트렙토조신, 테모졸로미드, 다카르바진 및 벤다무스틴), 항종양 항생제(예를 들어, 다우노루비신, 독소루비신, 이다루비신, 에피루비신, 미톡산트론, 블레오마이신, 마이토마이신 C, 플리카마이신 및 닥티노마이신), 탁산(예를 들어, 파클리탁셀 및 도세탁셀), 항대사제(예를 들어, 5-플루오로우라실, 시타라빈, 프레메트렉세드, 티오구아닌, 플록수리딘, 카페시타빈 및 메토트렉세이트), 뉴클레오시드 유사체(예를 들어, 플루다라빈, 클로파라빈, 클라드리빈, 펜토스타틴 및 넬라라빈), 토포이소머라제 억제제(예를 들어, 토포테칸 및 이리노테칸), 저메틸화제(예를 들어, 아자시티딘 및 데시타빈), 프로테오좀 억제제(예를 들어, 보르테조밉), 에피포도필로톡신(예를 들어, 에토포사이드 및 테니포사이드), DNA 합성 억제제(예를 들어, 하이드록시우레아), 빈카 알칼로이드(예를 들어, 비크리스틴, 빈데신, 비노렐빈 및 빈블라스틴), 티로신 키나제 억제제(예를 들어, 이마티닙, 다사티닙, 닐로티닙, 소라페닙 및 수니티닙), 니트로소우레아(예를 들어, 카르무스틴, 포테무스틴 및 로무스틴), 헥사메틸멜라민, 미토탄, 혈관신생 억제제(예를 들어, 탈리도마이드 및 레날리도마이드), 스테로이드(예를 들어, 프레드니손, 덱사메타손 및 프레드니솔론), 호르몬 제제(예를 들어, 타목시펜, 랄록시펜, 류프로라이드, 비칼루아트미드, 그라니세트론 및 플루타미드), 아로마타제 억제제(예를 들어, 레트로졸 및 아나스트로졸), 삼산화비소, 트레티노인, 비선택적 사이클로옥시게나제 억제제(예를 들어, 비스테로이드성 항염증제, 살리실레이트, 아스피린, 피록시캄, 이부프로펜, 인도메타신, 나프로신, 디클로페낙, 톨메틴, 케토프로펜, 나부메톤 및 옥사프로진), 선택적 사이클로옥시게나제-2(COX-2) 억제제, 또는 이들의 조합.
특정 실시형태에서, 항암 치료를 위한 화학요법제 및/또는 종양용해 치료제는 하기를 포함한다: 생물학적 제제, 예컨대 종양 침윤 림프구, CAR T 세포, 항체, 항원, 치료 백신(예를 들어, 환자 자신의 종양 세포 또는 특정 종양에 의해 생성되는 항원과 같은 기타 물질로 만들어짐), 면역 조절제(예를 들어, 사이토카인, 예를 들어 면역 조절 약물 또는 생물학적 반응 조절제), 체크포인트 억제제 또는 기타 면역 제제. 특정 실시형태에서, 면역제에는 면역글로빈, 면역자극제(예를 들어, 박테리아 백신, 콜로니 자극 인자, 인터페론, 인터루킨, 치료 백신, 백신 배합물, 바이러스 백신) 및/또는 면역억제제(예를 들어, 칼시뉴린 억제제, 인터루킨 억제제, TNF 알파 억제제)가 포함된다. 특정 실시형태에서, 호르몬제는 항안드로겐 요법용 제제(예를 들어, 케토코나졸, 아비라테론, TAK-700, TOK-OO1, 비칼루타미드, 닐루타미드, 플루타미드, 엔잘루타미드, ARN-509)를 포함한다.
추가적인 화학요법제 및/또는 종양용해 치료제에는 다음이 포함된다: 면역 체크포인트 치료제(예를 들어, 펨브롤리주맙, 니볼루맙, 이필리무맙, 아테졸리주맙, 아벨루맙, 더발루맙, 트레멜리무맙 또는 세미플리맙), 다른 단일클론 항체(예를 들어, 리툭시맙, 세툭시맙, 파네투무맙, 토시투모맙, 트라스투주맙, 알렘투주맙, 겜투주맙 오조가미신, 베바시주맙, 카투막소맙, 데노수맙, 오비누투주맙, 오파투무맙, 라무시루맙, 페르투주맙, 니모투주맙, 람브롤리주맙, 피딜리주맙, 실툭시맙, BMS-936559, RG7446/MPDL3280A, MEDI4736), 항체-약물 접합체(예를 들어, 브렌툭시맙 베도틴(ADCETRIS®, Seattle Genetics); 아도-트라스투주맙 엠탄신(KADCYLA®, Roche); 젬투주맙 오조가미신(Wyeth); CMC-544; SAR3419; CDX-011; PSMA-ADC; BT-062; 및 IMGN901(예를 들어, 문헌[Sassoon et al., Methods Mol. Biol. 1045:1-27 (2013)]; 문헌[Bouchard et al., Bioorganic Med. Chem. Lett. 24: 5357-5363 (2014)] 참조), 또는 이들의 임의의 조합.
일부 실시형태에서, 항-α11β1 항체와 추가 치료제의 조합 투여는 항-α11β1 항체 또는 추가 치료제 단독에 의해 생성된 것보다 더 큰 정도로 암을 개선시킨다. 조합 효과와 각 제제 단독 효과의 차이는 통계적으로 유의미한 차이가 될 수 있다. 일부 실시형태에서, 조합된 효과는 시너지 효과일 수 있다. 일부 실시형태에서, 항-α11β1 항체와 추가 치료제의 조합 투여는 표준 투약 레지먼, 예를 들어, 추가 치료제에 대해 승인된 투약 레지먼과 비교하여 감소된 용량, 감소된 횟수 및/또는 감소된 투여 빈도로 추가 치료제의 투여를 가능하게 한다.
일부 실시형태에서, 본원에 기재된 치료 방법은 의학적 병태의 다른 치료가 실패했거나 다른 수단을 통한 치료에서 덜 성공적이었던 대상체에서 수행된다. 추가로, 본원에 기재된 치료 방법은 의학적 병태의 하나 이상의 추가 치료와 함께 수행될 수 있다. 예를 들어, 방법은 본원에 설명된 항-α11β1 항체 또는 이의 조성물의 투여 이전에, 실질적으로 동시에 또는 이후에 암 레지먼, 예를 들어 비골수억제 화학요법, 수술, 호르몬 요법 및/또는 방사선을 투여하는 것을 포함할 수 있다.
제형 및 투여
다양한 실시형태에서, 본원에 기재된 항체는 약학 조성물에 혼입될 수 있다. 이러한 약학 조성물은 예를 들어 질환, 예를 들어 섬유성 장애의 예방 및/또는 치료에 유용할 수 있다. 약학 조성물은 당업자에게 알려진 방법에 의해 제형화될 수 있다(문헌 [Remington's Pharmaceutical Sciences, 17th edition, ed. Alfonso R. Gennaro, Mack Publishing Company, Easton, Pa. (1985)]에 기술된 것과 같음).
일부 실시형태에서, 약학 조성물은 약학적으로 허용되는 담체 또는 부형제를 포함하도록 제형화될 수 있다. 약학적으로 허용되는 담체의 예에는 생리학적으로 적합한 모든 용매, 분산 매질, 코팅제, 항균제 및 항진균제, 등장제 및 흡수 지연제 등이 포함되나 이에 제한되지 않는다. 본 발명의 조성물은 약학적으로 허용되는 염, 예를 들어 산 부가 염 또는 염기 부가 염을 포함할 수 있다.
일부 실시형태에서, 본원에 기술된 바와 같은 항체를 포함하는 조성물, 예를 들어 멸균 주사용 제형은 비히클로서 주사용 증류수를 사용하는 통상적인 약학적 관행에 따라 제형화될 수 있다. 예를 들어, 글루코오스 및 다른 보충물, 예컨대 D-소르비톨, D-만노오스, D-만니톨, 및 염화나트륨을 함유하는 등장성 용액 또는 생리 식염수가, 선택적으로 적합한 가용화제, 예를 들어 알코올, 예컨대 에탄올 및/또는 폴리알코올, 예컨대 프로필렌 글리콜 또는 폴리에틸렌 글리콜, 및/또는 비이온성 계면활성제, 예컨대 Polysorbate 80™ 또는 HCO-50과 조합하여, 주사용 수용액으로서 사용될 수 있다.
본원에 개시된 바와 같이, 약학 조성물은 당업계에 알려진 임의의 형태일 수 있다. 이러한 형태는 예를 들어 액체 용액(예를 들어, 주사 및 주입 용액), 분산액 또는 현탁액, 정제, 알약, 분말, 리포좀 및 좌약과 같은 액체, 반고체 및 고체 투여 형태를 포함한다.
임의의 특정 형태의 선택 또는 사용은 의도된 투여 방식 및 치료적 적용에 부분적으로 의존할 수 있다. 예를 들어, 전신 전달 또는 국소 전달을 위한 조성물을 함유하는 조성물은 주사가능 또는 주입가능 용액의 형태일 수 있다. 따라서, 조성물은 비경구 방식(예를 들어, 정맥내, 피하, 복강내 또는 근육내 주사)에 의한 투여를 위해 제형화될 수 있다. 본원에서 사용되는 비경구 투여는 일반적으로 주사에 의한 경장 및 국소 투여 이외의 투여 방식을 지칭하고, 비제한적으로, 정맥내, 비강내, 안구내, 폐, 근육내, 동맥내, 척수강내, 낭내, 안와내, 심장내, 피내, 폐내, 복강내, 기관내, 피하, 피하, 관절내, 낭하, 지주막하, 척수내, 경막외, 뇌내, 두개내, 경동맥 및 흉골내 주사 및 주입을 포함한다. 일부 실시형태에서, 조성물은 신장을 표적으로 할 수 있다. 일부 실시형태에서, 조성물은 신장 세포를 표적으로 할 수 있다.
투여 경로는 비경구 투여, 예를 들어 주사 투여, 경비 투여, 경폐 투여 또는 경피 투여일 수 있다. 투여는 정맥내 주사, 근육내 주사, 복강내 주사 또는 피하 주사에 의해 전신적 또는 국소적일 수 있다. 일부 실시형태에서, 투여 경로는 투석이거나 투석을 포함한다. 일부 실시형태에서, 투여 경로는 혈액투석이거나 혈액투석을 포함한다. 일부 실시형태에서, 투여 경로는 복막 투석이거나 복막 투석을 포함한다.
일부 실시형태에서, 본 발명의 약학 조성물은 용액, 마이크로에멀젼, 분산액, 리포좀, 또는 고농도에서 안정한 저장에 적합한 다른 정돈된 구조로 제형화될 수 있다. 멸균 주사액은 필요에 따라 상기 열거된 성분 중 하나 또는 조합과 함께 적절한 용매에 필요한 양으로 본원에 기술된 조성물을 혼입한 다음 필터 멸균하여 제조될 수 있다. 일반적으로, 분산액은 기본 분산 매질 및 상기 열거된 것들로부터 필요한 다른 성분을 함유하는 멸균 비히클에 본원에 기술된 조성물을 혼입함으로써 제조된다. 멸균 주사 용액의 제조를 위한 멸균 분말의 경우, 제조 방법은 진공 건조 및 동결 건조를 포함하여 이전에 멸균 여과된 용액으로부터 본원에 기술된 조성물의 분말과 임의의 추가의 원하는 성분(하기 참조)을 생성한다. 용액의 적절한 유동성은 예를 들어 레시틴과 같은 코팅의 사용, 분산의 경우 필요한 입자 크기의 유지 및 계면활성제의 사용에 의해 유지될 수 있다. 주사용 조성물의 장기적인 흡수는 흡수를 지연시키는 시약, 예를 들어 모노스테아레이트 염 및 젤라틴을 조성물에 포함시킴으로써 야기될 수 있다.
약학 조성물은 물 또는 다른 약학적으로 허용되는 액체 중 멸균 용액 또는 현탁액을 포함하는 주사가능한 제형의 형태로 비경구 투여될 수 있다. 예를 들어, 약학 조성물은 치료 분자를 약학적으로 허용되는 비히클 또는 매질, 예컨대 멸균수 및 생리 식염수, 식물성 오일, 유화제, 현탁화제, 계면활성제, 안정제, 향미부여 부형제, 희석제, 비히클, 보존제, 결합제와 적합하게 배합한 후, 일반적으로 허용되는 약학적 실무에서 필요로 하는 단위 용량 형태로 혼합함으로써 제형화될 수 있다. 약학 제제 내에 포함되는 활성 성분의 양은 지정된 범위 내의 적합한 용량이 제공되도록 하는 양이다. 유성 액체의 비제한적인 예에는 참깨유 및 대두유가 포함되며, 이것은 가용화제로서의 벤질 벤조에이트 또는 벤질 알코올과 조합될 수 있다. 포함될 수 있는 다른 품목은 완충제, 예컨대 인산염 완충제, 또는 아세트산나트륨 완충제, 진정제(soothing agent), 예컨대 프로카인 하이드로클로라이드, 안정제, 예컨대 벤질 알코올 또는 페놀, 및 산화방지제이다. 제형화된 주사액은 적합한 앰풀로 패키징될 수 있다.
다양한 실시형태에서, 피하 투여는 장치, 예컨대 주사기, 미리 채워진 주사기, 자동 주사기(예를 들어, 일회용 또는 재사용 가능), 펜 주사기, 패치 주사기, 착용형 주사기, 피하 주입 세트가 있는 이동식 주사기 주입 펌프 또는 피하 주사용 항체 약물과 조합하기 위한 기타 장치에 의해 달성될 수 있다.
본 개시내용의 주입 시스템은 미국 특허 제5,308,341호에 기재된 바와 같은 전달 펜을 사용할 수 있다. 당뇨병 환자에게 인슐린을 자가 전달하기 위해 가장 일반적으로 사용되는 펜 장치는 당업계에 잘 알려져 있다. 이러한 장치는 적어도 하나의 주사 바늘(예를 들어, 길이가 약 5 내지 8 mm인 31 게이지 바늘)을 포함할 수 있고, 일반적으로 치료 용액의 하나 이상의 치료 단위 용량으로 미리 채워져 있고, 가능한 한 적은 통증으로 대상체에게 용액을 신속하게 전달하는 데 유용하다. 하나의 약물 전달 펜은 치료제 또는 다른 약물의 바이알이 수용될 수 있는 바이알 홀더를 포함한다. 펜은 완전히 기계적인 장치이거나 전자 회로와 결합되어 사용자에게 주입되는 약물의 투여량을 정확하게 설정 및/또는 표시할 수 있다. 예를 들어, 미국 특허 제6,192,891호를 참조한다. 일부 실시형태에서, 펜 장치의 바늘은 일회용이고 키트는 하나 이상의 일회용 대체 바늘을 포함한다. 본 특징 조성물 중 임의의 하나의 전달에 적합한 펜 장치는 또한 예를 들어 미국 특허 제6,277,099호; 제6,200,296호; 및 제6,146,361호에 기재되어 있으며, 이들 각각의 개시내용은 그 전체가 본원에 원용되어 포함된다. 미세바늘 기반 펜 장치는 예를 들어 미국 특허 제7,556,615호에 기재되어 있으며, 이의 개시내용은 그 전체가 본원에 원용되어 포함된다. Scandinavian Health Ltd에서 제조한 정밀 펜 주입기(PPI) 장치 MOLLY™도 참조한다.
일부 실시형태에서, 본원에 기재된 조성물은 국소 투여에 의해 대상체에게 치료적으로 전달될 수 있다. 본원에서 사용되는 "국소 투여" 또는 "국소 전달"은 혈관계를 통해 의도된 표적 조직 또는 부위로 조성물 또는 제제의 수송에 의존하지 않는 전달을 지칭할 수 있다. 예를 들어, 조성물은 조성물 또는 제제의 주사 또는 이식에 의해 또는 조성물 또는 제제를 함유하는 장치의 주사 또는 이식에 의해 전달될 수 있다. 특정 실시형태에서, 표적 조직 또는 부위 부근에서의 국소 투여 후, 조성물 또는 제제, 또는 이의 하나 이상의 성분은 투여 부위가 아닌 의도된 표적 조직 또는 부위로 확산될 수 있다.
일부 실시형태에서, 조성물은 0℃ 미만의 온도(예를 들어, -20℃ 또는 -80℃)에서 보관하기 위해 제형화될 수 있다. 일부 실시형태에서, 조성물은 2 내지 8℃(예를 들어, 4℃)에서 최대 2년(예를 들어, 1개월, 2개월, 3개월, 4개월, 5개월, 6개월, 7개월, 8개월, 9개월, 10개월, 11개월, 1년, 11/2년 또는 2년) 동안 저장을 위해 제형화될 수 있다. 따라서, 일부 실시형태에서, 본원에 기재된 조성물은 2 내지 8℃(예를 들어, 4℃)에서 적어도 1년 동안 저장시 안정하다.
일부 실시형태에서, 약학 조성물은 용액으로 제형화될 수 있다. 일부 실시형태에서, 조성물은 예를 들어 2 내지 8℃(예를 들어, 4℃)에서 저장하기에 적합한 농도의 완충 용액으로서 제형화될 수 있다.
본원에 기재된 하나 이상의 항체를 포함하는 조성물은 면역리포좀 조성물로 제형화될 수 있다. 이러한 제형은 당업계에 공지된 방법에 의해 제조될 수 있다. 향상된 순환 시간을 갖는 리포좀은 예를 들어 미국 특허 제5,013,556호에 개시되어 있다.
특정 실시형태에서, 조성물은 이식물 및 마이크로캡슐화 전달 시스템을 포함하는 제어 방출 제형과 같은, 빠른 방출에 대해 화합물을 보호할 담체와 함께 제형화될 수 있다. 생분해성 생체적합성 중합체, 예를 들어 에틸렌 비닐 아세테이트, 폴리무수물, 폴리글리콜산, 콜라겐, 폴리오르토에스테르 및 폴리락트산이 사용될 수 있다. 이러한 제형의 제조를 위한 많은 방법이 당업계에 알려져 있다. 예를 들어, 문헌[J. R. Robinson (1978) "Sustained and Controlled Release Drug Delivery Systems," Marcel Dekker, Inc., New York] 참조.
일부 실시형태에서, 본원에 기재된 바와 같은 항체의 투여는 항체를 코딩하는 핵산을 대상체에게 투여함으로써 달성된다. 본원에 기재된 치료용 항체를 코딩하는 핵산은 세포 내에서 항체를 발현하고 생산하는 데 사용될 수 있는 핵산을 전달하기 위해 유전자 치료 프로토콜의 일부로 사용되는 유전자 작제물에 혼입될 수 있다. 이러한 성분의 발현 작제물은 임의의 치료학적으로 효과적인 담체로 예를 들어 성분 유전자를 생체내 세포에 효과적으로 전달할 수 있는 임의의 제형 또는 조성물로 투여될 수 있다. 접근법에는 재조합 레트로바이러스, 아데노바이러스, 아데노 관련 바이러스, 렌티바이러스 및 단순 헤르페스 바이러스-1(HSV-1) 또는 재조합 박테리아 또는 진핵 플라스미드를 포함하는 바이러스 벡터에 대상체 유전자를 삽입하는 것이 포함된다. 바이러스 벡터는 세포를 직접 형질 감염시킬 수 있다; 플라스미드 DNA는 예를 들어 양이온성 리포좀(리포펙틴) 또는 유도체화된 폴리라이신 접합체, 그라미시딘 S, 인공 바이러스 외피 또는 기타 이러한 세포내 담체의 도움으로 전달될 수 있으며, 유전자 작제물의 직접 주입 또는 CaPO4 침전을 통해 전달될 수 있다(예를 들어, 국제공개 WO04/060407호 참조). 적합한 레트로바이러스의 예는 당업자에게 알려진 pLJ, pZIP, pWE 및 pEM을 포함한다(예를 들어, 문헌[Eglitis et al. (1985) Science 230:1395-1398]; 문헌[Danos and Mulligan (1988) Proc Natl Acad Sci USA 85:6460-6464]; 문헌[Wilson et al. (1988) Proc Natl Acad Sci USA 85:3014-3018]; 문헌[Armentano et al. (1990) Proc Natl Acad Sci USA 87:6141-6145]; 문헌[Huber et al. (1991) Proc Natl Acad Sci USA 88:8039-8043]; 문헌[Ferry et al. (1991) Proc Natl Acad Sci USA 88:8377-8381]; 문헌[Chowdhury et al. (1991) Science 254:1802-1805]; 문헌[van Beusechem et al. (1992) Proc Natl Acad Sci USA 89:7640-7644]; 문헌[Kay et al. (1992) Human Gene Therapy 3:641-647]; 문헌[Dai et al. (1992) Proc Natl Acad Sci USA 89:10892-10895]; 문헌[Hwu et al. (1993) J Immunol 150:4104-4115]; 미국 특허 제4,868,116호 및 제4,980,286호; 및 PCT 국제공개 WO89/07136호, WO89/02468호, WO89/05345호, 및 WO92/07573호 참조). 또 다른 바이러스 유전자 전달 시스템은 아데노바이러스 유래 벡터를 활용한다(예를 들어, 문헌[Berkner et al. (1988) BioTechniques 6:616]; 문헌[Rosenfeld et al. (1991) Science 252:431-434]; 및 문헌[Rosenfeld et al. (1992) Cell 68:143-155] 참조). 아데노바이러스 균주 Ad 유형 5 dl324 또는 아데노바이러스의 다른 균주(예를 들어, Ad2, Ad3, Ad7 등)로부터 유도된 적합한 아데노바이러스 벡터는 당업자에게 알려져 있다. 대상체 유전자의 전달에 유용한 또 다른 바이러스 벡터 시스템은 아데노 관련 바이러스(AAV)이다. 예를 들어, 문헌[Flotte et al. (1992) Am J Respir Cell Mol Biol 7:349-356]; 문헌[Samulski et al. (1989) J Virol 63:3822-3828]; 및 문헌[McLaughlin et al. (1989) J Virol 62:1963-1973] 참조.
일부 실시형태에서, 본원에 제공된 조성물은 단위 투여 형태로 존재하며, 이 단위 투여 형태는 자가 투여에 적합할 수 있다. 이러한 단위 투여 형태는 용기, 전형적으로 예를 들어 바이알, 카트리지, 사전충전된 주사기 또는 일회용 펜 내에 제공될 수 있다. 미국 특허 제6,302,855호에 기재된 투여기 장치(doser device)와 같은 투여기는 예를 들어 본원에 기재된 주입 시스템과 함께 사용될 수도 있다.
대상체의 장애를 치료하거나 예방할 수 있는 본원에 기재된 조성물의 적합한 용량은 예를 들어 연령, 성별, 치료 대상체의 체중 및 사용되는 특정 억제제 화합물을 포함하는 다양한 요인에 따라 달라질 수 있다. 예를 들어, 본원에 기재된 바와 같은 항체를 포함하는 하나의 조성물의 상이한 용량은 그 항체의 상이한 제형의 용량과 비교하여 섬유성 장애를 갖는 대상체를 치료하는 데 필요할 수 있다. 대상체에게 투여되는 용량에 영향을 미치는 다른 요인에는 예를 들어 장애의 유형 또는 중증도가 포함된다. 다른 요인은 예를 들어 대상체에 동시에 또는 이전에 영향을 미친 다른 의학적 장애, 대상체의 일반적인 건강, 대상체의 유전적 소인, 식이, 투여 시간, 배설 속도, 약물 조합, 및 대상체에게 투여되는 임의의 다른 추가적인 치료제를 포함할 수 있다. 또한 임의의 특정 대상체에 대한 특정 투여량 및 치료 레지먼은 치료하는 의사의 판단에 따라 또한 조정될 수 있음을 이해해야 한다.
본원에 기재된 조성물은 고정 용량으로 또는 킬로그램당 밀리그램(mg/kg) 용량으로 투여될 수 있다. 일부 실시형태에서, 용량은 또한 조성물 내의 항원-결합 분자 중 하나 이상에 대한 항체 또는 다른 숙주 면역 반응의 생성을 감소시키거나 회피하도록 선택될 수 있다. 본원에 기재된 조성물과 같은 항체의 예시적인 투여량은 예를 들어 0.0001 내지 100 mg/kg, 0.01 내지 5 mg/kg, 1 내지 1000 mg/kg, 1 내지 100 mg/kg, 0.5 내지 50 mg/kg, 0.1 내지 100 mg/kg, 0.5 내지 25 mg/kg, 1 내지 20 mg/kg, 및 1 내지 10 mg/kg의 대상체 체중을 포함한다. 예를 들어 투여량은 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 3.0 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 10 mg/kg, 또는 20 mg/kg 체중, 또는 1 내지 20 mg/kg 체중 범위 내일 수 있다. 예시적인 치료 요법은 1주에 1회, 2주에 1회, 3주에 1회, 4주에 1회, 1개월에 1회, 3개월에 1회 또는 3 내지 6개월에 1회 투여, 또는 처음에는 짧은 투여 간격으로(예컨대 1주에 1회 내지 3주에 1회), 그리고 이후에는 연장된 간격으로(예컨대 1개월에 1회 내지 3 내지 6개월에 1회) 투여하는 것을 수반한다.
약학 용액은 본원에 기술된 조성물의 치료적 유효량을 포함할 수 있다. 이러한 유효량은 부분적으로는 투여된 조성물의 효과, 또는 조성물과 하나 이상의 추가 활성제의 조합 효과(하나 초과의 제제가 사용되는 경우)에 기초하여 당업자에 의해 용이하게 결정될 수 있다. 본원에 기술된 조성물의 치료적 유효량은 또한 다음과 같은 요인에 따라 달라질 수 있다: 개인의 질환 상태, 연령, 성별 및 체중, 및 개인에서 원하는 반응을 유도하는 조성물(및 하나 이상의 추가 활성제)의 능력, 예를 들어, 적어도 하나의 병태 파라미터의 개선, 예를 들어, 섬유성 장애의 적어도 하나의 증상의 개선. 예를 들어, 본원에 기술된 조성물의 치료적 유효량은 특정 장애, 및/또는 당업계에 알려지거나 본원에 기술된 특정 장애의 증상 중 임의의 하나를 억제(그 중증도를 감소시키거나 발생을 제거) 및/또는 예방할 수 있다. 치료적 유효량은 또한 조성물의 임의의 독성 또는 해로운 효과가 치료적으로 유익한 효과보다 더 중요한 양이다.
본원에 기재된 임의의 조성물의 적합한 인간 용량은 예를 들어 I상 용량 증량 연구에서 추가로 평가될 수 있다. 예를 들어, 문헌[van Gurp et al. (2008) Am J Transplantation 8(8):1711-1718]; 문헌[Hanouska et al. (2007) Clin Cancer Res 13(2, part 1):523-531]; 및 문헌[Hetherington et al. (2006) Antimicrobial Agents and Chemotherapy 50(10): 3499-3500] 참조.
조성물의 독성 및 치료 효능은 세포 배양물 또는 실험 동물(예를 들어, 본원에 기재된 임의의 섬유성 장애의 동물 모델)에서 알려진 약학적 절차에 의해 결정될 수 있다. 이러한 절차는 예를 들어 LD50(집단의 50%에 치명적인 용량) 및 ED50(집단의 50%에서 치료적으로 효과적인 용량)을 결정하는 데 사용될 수 있다. 독성 효과와 치료 효과 사이의 용량 비는 치료 지수이며 LD50/ED50 비로 표현될 수 있다. 높은 치료 지수를 나타내는 본원에 기재된 조성물이 바람직하다. 독성 부작용을 나타내는 조성물이 사용될 수 있지만, 영향을 받는 조직 부위에 이러한 화합물을 표적으로 하고 정상 세포에 대한 잠재적인 손상을 최소화하여 부작용을 감소시키는 전달 시스템을 설계하는 데 주의를 기울여야 한다.
당업자는 세포 배양 검정 및 동물 연구로부터 얻은 데이터가 인간에게 사용하기 위한 투여량 범위를 공식화하는 데 사용될 수 있음을 이해할 것이다. 본원에 기재된 조성물의 적절한 투여량은 일반적으로 독성이 거의 또는 전혀 없는 ED50을 포함하는 조성물의 순환 농도 범위 내에 있다. 투여량은 사용된 투여 형태 및 사용된 투여 경로에 따라 이 범위 내에서 변할 수 있다. 본원에 기술된 조성물의 경우, 치료 유효 용량은 초기에 세포 배양 검정으로부터 추정될 수 있다. 세포 배양에서 결정된 바와 같은 IC50(즉, 증상의 절반-최대 억제를 달성하는 항체의 농도)을 포함하는 순환 혈장 농도 범위를 달성하기 위해, 동물 모델에서 용량이 조제될 수 있다. 이러한 정보는 인간의 유용한 용량을 보다 정확하게 결정하는 데 사용될 수 있다. 혈장 내 수준은 예를 들어 고성능 액체 크로마토그래피로 측정될 수 있다. 일부 실시형태에서, 예를 들어 국소 투여(예를 들어, 눈 또는 관절)가 요구되는 경우, 세포 배양 또는 동물 모델링을 사용하여 국소 부위 내에서 치료 유효 농도를 달성하는 데 필요한 용량을 결정할 수 있다.
본원에 언급된 모든 간행물, 특허 출원, 특허, 및 다른 참고문헌은 그 전체가 원용되어 포함된다. 또한, 재료, 방법, 및 실시예는 단지 예시적인 것이며, 제한하고자 하는 것이 아니다. 달리 정의되지 않는 한, 본원에 사용되는 모든 기술 과학 용어는 당업자가 통상적으로 이해하는 것과 동일한 의미를 갖는다. 본원에서 기술되는 것과 유사하거나 동등한 방법 및 재료가 본 발명의 실시 또는 시험에 사용될 수 있지만, 바람직한 방법 및 재료가 본원에 기술된다.
본 개시내용은 하기 실시예에 의해 추가로 예시된다. 실시예는 단지 예시적인 목적을 위해 제공된다. 이들은 어떠한 방식으로든 본 개시내용의 범주 또는 내용을 제한하는 것으로 해석되어서는 안 된다.
실시예
방법
α11β1에 대한 신규 항체의 생성
래트 면역화
Wistar 래트는 재조합 인간 α11β1 단백질로 면역화되었다. 효소 면역 분석법(ELISA)을 사용하여 표적 인간 및 마우스 단백질에 대한 면역 반응을 시험했다. 그 후, 양호한 면역 반응을 생성하는 동물과 함께 세포 융합(전기 융합에 의한)을 수행하였다. 모든 융합 세포를 96-웰 플레이트에 플레이팅하고 상청액을 가용성 인간 및 마우스 α11β1에 대해 ELISA로 스크리닝하였다. 양성 클론은 인간 α1β1, α2β1 및 α10β1에 대해 카운터-스크리닝되었다. 인간 및 마우스 α11β1에 특이적으로 결합하고 α1β1, α2β1 및 α10β1에는 결합하지 않는 클론을 선택하고, 서브클로닝하고, 확장하고, 동결보존하였다. 그런 다음 선택된 클론으로부터 정제된 항체를 생성하고 각각의 정제된 항체로부터 중쇄 및 경쇄 가변 도메인 서열을 수득하였다.
토끼 면역화
토끼는 세포 기반 단일클론 항체 플랫폼을 사용하여 면역화되었다. 두 마리의 토끼는 재조합 인간 α11β1 단백질로 면역화되었다. β1 특이적 B 세포 클론의 수를 줄이기 위해 면역화된 토끼의 비장 세포를 분류하고 인간 β1에 대해 선택했다. 그런 다음 분류된 비장 세포를 대략 1주 동안 배양하고 배양 상청액을 인간 α11β1에 대한 결합에 대해 스크리닝했다. 최고의 결과를 시퀀싱한 후 토끼 항체를 HEK 세포 시스템을 사용하여 재조합 방식으로 생산했다.
마우스 면역화
5가지 다른 변종의 마우스 10마리를 인간 α11β1, 마우스 α11β1 및 내성 파괴 단백질의 적절한 혼합물로 면역화했다. 인간 및 마우스 α11β1의 혼합물에 대해 ELISA로 혈장 역가를 평가하였다. 슬와, 사타구니 및 장골 림프절을 수집했다. ELISA-양성 항-인간/마우스 α11β1 하이브리도마를 확장하고 인간 및 마우스 α11β1, 대조군 HIS 단백질에 대한 2차 스크리닝을 수행하고, 인간 α11β1, α2β1 및 α10β1에 대해 카운터-스크리닝을 수행하였다. 상청액 IgG 농도는 기능적 스크리닝에 충분했다. 모든 기준을 만족하는 선택된 하이브리도마를 클로닝하고 클로날 하이브리도마를 인간 및 마우스 α11β1에 대해 ELISA로 확인한 후 규모를 확대하고 IgG를 정제하였다. 그 다음 선택된 하이브리도마의 중쇄 및 경쇄 가변 영역을 시퀀싱하였다.
파지 라이브러리 디스플레이
완전 인간 항-α11β1 항체 생성을 위해 파지 라이브러리 디스플레이를 사용했다. 완전 인간 항-α11β1 항체는 파지(파지 디스플레이 라이브러리)에 표시된 단일 사슬 단편 가변(scFv) 항원 결합 단편을 사용하여 발견되었다. 정제된 인간 및 마우스 α11β1 항원과 α10β1에 대한 선택 해제에 대해 3라운드의 선택을 수행하여 α11 서브유닛 특이적 항체를 풍부하게 했다. 이어서, 최적 집단을 박테리아 가용성 발현 벡터에 서브클로닝하고, 재조합 항체 발현을 유도하고, 상청액을 ELISA 검정을 통해 결합에 대해 스크리닝하였다. 적절한 결합 프로파일을 가진 항체를 시퀀싱한 후 scFv에서 IgG로 전환했다.
ELISA
0.25 μg/mL의 표적 항원(재조합 인간 또는 마우스 α11β1)을 4℃에서 밤새 96-웰 플레이트에 플레이팅했다. 플레이트를 실온에서 세척하고(0.1% Tween-20을 함유한 PBS), 1시간 동안 차단하고(2% BSA 및 0.05% Tween-20을 함유한 PBS) 실온에서 1시간 동안 일정 범위의 항체 농도로 인큐베이션하였다. 이어서, 플레이트를 세척하고 1:1000 희석 완충액에서 비오티닐화된 항-토끼/마우스/인간 IgG와 함께 인큐베이션하고 실온에서 1시간 동안 인큐베이션하였다. 플레이트를 세척한 후, 스트렙타비딘 HRP를 희석 완충액에 1:200으로 첨가하고 실온에서 1시간 동안 인큐베이션했다. Ultra TMB ELISA 기질 용액을 첨가하고 플레이트를 플레이트 쉐이커에서 5분 동안 인큐베이션했다. 정지 용액을 각 웰에 첨가하여 반응을 정지시키고 플레이트를 450 nm에서 판독하였다.
FACS
CHO-K1에 결합하는 항체
200,000개의 세포(야생형 CHO-K1 세포 또는 인간 α11을 발현하는 CHO-K1 세포)를 FACS 완충액에서 원하는 농도로 각 항체와 함께 4℃에서 30분 동안 인큐베이션했다. 그런 다음 세포를 FACS 완충액으로 세척하고 1:100으로 희석한 2차 항체와 함께 4℃에서 30분 동안 인큐베이션했다. 이어서 세포를 세척하고 실온에서 20분 동안 PBS 중 1% PFA로 고정시켰다; 다시 세척하고 FACS 완충액에서 세포계산기에서 판독한다.
HPF/MF에 결합하는 항체
인간 폐 섬유모세포(ScienCell)는 T-150 플라스크에서 80% 융합될 때까지 완전한 섬유모세포 성장 배지(ScienCell)에서 배양되었다. 아큐타제를 사용하여 세포를 세척하고 수확했다. 세포를 완전한 FGF에서 7,500개 세포/cm2로 T-150 플라스크에 시딩하고 72시간 동안 배양하였다. 이어서 세포를 세척하고 혈청 감소 배지에서 24시간 동안 기아 상태로 하였다. 기아 후, 세포를 TGFβ-1(R&D Systems)로 72시간 동안 처리하였다. 아큐타제를 사용하여 세포를 수확하고 96-웰 원추형 바닥 플레이트에 시딩했다. 열 불활성화 태아 소 혈청(Gibco)으로 세포를 4℃에서 30분 동안 차단했다. 그런 다음 세포를 각 도면에 설명된 용량의 항-α11 항체와 함께 4℃에서 30분 동안 인큐베이션했다. 인간 항-α11 항체(Creative BioLabs)가 양성 대조군과 적절한 IgG 이소타입 음성 대조군으로 포함되었다. 세포를 두 번 세척하고 시험 중인 항-α11 항체의 IgG 클래스에 특이적인 PE 접합 2차 항체와 함께 4℃에서 30분 동안 인큐베이션했다. 세포를 2회 세척하고 1% PFA에서 30분 동안 고정시켰다. 각 항체의 FACS Verse(Benton Dickson) 결합에서 세포를 획득했다. 단일 세포를 게이팅하고 각 샘플에 대한 PE 채널의 기하학적 평균 형광 강도(gMFI)를 결정하여 데이터를 분석했다.
표면 플라즈몬 공명(SPR)
인간 α11β1에 대한 항체의 친화도는 표면 플라즈몬 공명 분석(SPR)으로 측정했다. Biacore T200 기기를 사용하여 pH 7.6 및 25℃에서 친화도를 측정했다. 항-HIS 항체는 EDC/NHS 공유 부착을 사용하여 SPR 센서 표면에 고정되었다. HIS 태그가 부착된 인간 α11β1을 센서 표면에 포획하고 단일 사이클 동역학 분석을 사용했다. 증가하는 농도의 시험 항체가 센서 결합 α11β1에 연속적으로 주입되었다. 해리를 1000초 동안 모니터링하였다. 항-HIS 항체만 있는 센서 표면과 일련의 블랭크 주입을 사용하여 데이터를 이중 참조로 감산한다. 1:1 Langmuir 모델을 데이터에 피팅하여 동역학 결합 상수 및 해리 상수를 추정했다. 상호작용의 친화도(평형 해리 상수)는 동역학 해리 상수를 동역학 결합 상수로 나누어 계산하였다. 주입 사이클들 사이에 pH 1.5에서 10 mM 글리신을 주입하여 α11β1과 결합된 항체를 제거했다.
세포 부착 억제
0.6 x 106개 세포/mL를 농도 범위에서 각 항체와 함께 37℃에서 20분 동안 인큐베이션했다. 실온에서 밤새 100 ng/mL 유형 I 콜라겐 또는 PBS로 코팅된 E-Plate VIEW 96 PET 플레이트를 실온에서 3% BSA에서 1 하우스 차단했다. 플레이트를 PBS로 세척한 후, 세포 및 항체 혼합물을 웰에 첨가하고 플레이트를 xCelligence 기계에 넣었다. 세포 부착은 6시간에 걸쳐 기록되었다. 최대 세포 부착 시점을 대조군과 비교하기 위해 사용하였다.
섬유모세포에서 근섬유모세포로의 전환(FMT)
인간 폐 섬유모세포(ScienCell)는 80% 융합될 때까지 완전 섬유모세포 성장 배지(ScienCell)에서 배양되었다. 아큐타제를 사용하여 세포를 세척하고 수확했다. 세포를 완전한 섬유모세포 성장 배지에서 20,000개 세포/웰로 조직 배양 처리된 96웰 플레이트에 시딩하였다. 24시간 후, 세포를 세척하고 추가 24시간 동안 혈청 감소 배지에서 기아 상태로 하였다. 기아 후, 세포를 항-α11 항체 유무에 관계없이 TGFβ-1(R&D Systems)로 처리하였다. 폴리클론 토끼 항-인간 α11 항체를 양성 대조군으로 사용했다. 적절한 IgG 이소타입 대조군도 포함되었다. 48시간 후, 세포를 수확, 고정, 투과화하고 AlexaFluor488 표지된 항-αSMA(α-평활근 액틴)(Invitrogen)로 염색했다. FACS Verse(Benton Dickson)에서 세포를 획득하여 αSMA의 발현 수준을 결정했다. 단일 세포를 게이팅하고 각 샘플에 대한 FITC 채널의 기하학적 평균 형광 강도(gMFI)를 결정하여 데이터를 분석했다. 각 샘플에 대한 gMFI는 처리되지 않은 대조군에 대해 정규화되었고 억제 %로 표시되었다.
콜라겐 겔 수축 검정
24-웰 플레이트를 PBS 중 2% BSA로 37℃에서 밤새 차단하였다. 다음날, 플레이트를 검정에 사용하기 전에 PBS로 3회 세척하였다. α11을 발현하는 인간 CHO 세포주를 수확하고 ExpiCHO 발현 배지(Gibco™ Cat# A2910002)에 1.25x106으로 재현탁했다. 콜라겐 겔 용액은 3 mg/mL 스톡 콜라겐 유형 I(Gibco™ Collagen I Rat Protein, Tail Cat# A1048301)을 CHO 세포를 함유하는 배지에서 1 mg/mL로 희석하여 제조했다. 용액에 수산화나트륨을 첨가하여 pH를 중화시키고 콜라겐 용액 400 μL를 24-웰 플레이트의 각 웰에 첨가하였다. 항체가 콜라겐 겔 용액에 포함된 웰의 경우, CHO 세포를 2.5x106으로 제조하고 항체를 ExpiCHO 배지에서 2x 최종 농도로 제조했다. 그런 다음 스톡 콜라겐 유형 1을 첨가하기 전에 세포와 항체를 1:1로 결합했다. 겔을 37℃에서 60분 동안 중합시켰다. ExpiCHO 배지에 항체를 첨가한 다음 중합 겔(400 μL/웰) 위에 층을 이루었다. 겔 수축을 정량화하기 전에 겔을 37℃에서 6일 동안 인큐베이션했다. Image J를 사용하여 각 웰의 이미지를 분석하고 겔 수축을 초기 겔 면적의 백분율로 결정했다.
종양 이종이식 모델
56마리의 암컷 C.B-17 SCID 마우스에 옆구리 피하로 A549 세포(5x106 세포/마우스)를 접종하였다. 종양 부피가 약 100 mm3에 도달하면 동물을 무작위로 각각 8마리씩 7개 그룹으로 랜덤화하였다. 그런 다음 마우스를 이소형 대조군 또는 신규 mAb 79E3E3, 16E10 및 9G04(2 및 20 mg/kg)로 총 7회 용량 동안 3일마다 복강내로 처리하거나 총 6회 용량 동안 4일마다 10 mg/kg의 도세탁셀로 처리했다. 정의된 다음 조건 중 임의의 것이 관찰될 때까지 두 측정 사이에 2 내지 3일의 간격을 두고 종양 부피 및 체중을 일주일에 두 번 기록했다: 20% 이상의 체중 손실; 섭식, 음수 및 이동과 같은 정상적인 생리 기능을 억제하는 종양; 궤양성 종양; 2000 mm3 초과의 종양 크기 및 쇠약, 마비, 발작 및 출혈의 임상적 관찰.
정밀 절단 간 절편(PCLS)
정밀 절단 간 절편(PCLS)은 절제된 간 조직으로부터 제조되었고 실험이 시작되기 전에 절단 후 스트레스 기간이 경과하도록 24시간 동안 휴식을 취했다. PCLS는 100 μg/mL 대조군 항체(그룹 2 및 3 - 마우스 IgG2a 또는 토끼 IgG) 또는 TGF-β1(3 ng/mL) 및 PDGF-ββ의 조합과 함께 외인성 챌린지(그룹 1) 없이 배양되었다(50 ng/mL)(그룹 2-10). PCLS는 그룹 5 내지 10에서 2 단계 증량 용량(10 및 100 μg/mL)으로 양성 대조군 또는 신규 억제제(16E10, 79E3E3 및 9G05)로서 10 μM Alk5i(그룹 4)의 존재 또는 부재 하에 배양되었다. 10개 그룹 각각에는 단일 인간 간으로부터 제조된 n=6 인간 PCLS가 포함되었다. 모든 자극 및 화합물을 포함하는 PCLS 배양 배지를 24시간 간격으로 리프레쉬하고 수확했다. 세포 배양 상청액(n=2/3 쌍을 이룬 웰)을 24시간마다 수집하고 용해성 출력의 정량화를 위해 급속 동결했다. 모든 PCLS는 96시간에 수확되었다.
간 손상 마커(젖산 탈수소효소(LDH) 및 아스파르테이트 트랜스아미나제(AST)) 및 간세포 기능/생존율(알부민)의 조직 배양 수준을 모든 시점에서 모든 PCLS에서 정량화했다. 알부민 분비는 PCLS 무결성 및 기능의 마커로서 ELISA에 의해 정량화되었다. R&D Duoset ELISA 키트를 사용하여 세포 배양 상청액에서 콜라겐 1a1, IL-6, 히알루론산 및 Timp-1의 수준을 정량화했다.
PCLS에서 전체 RNA 추출을 모든 샘플에서 수행했다. RNeasy 미니 키트(Qiagen)를 RNA 추출에 사용했다. RNA를 cDNA로 역전사하고 qPCR에 사용하여 Col1a1, αSMA, TIMP-1, TGF-β1, IL-6 및 β-액틴/GAPDH의 전사 수준을 측정했다.
정밀 절단 신장 절편(PCKS)
PCKS는 이식된 섬유성 인간 신장 조직으로부터 제조되었고 실험이 시작되기 전에 절단 후 스트레스 기간이 경과하도록 24시간 동안 휴식을 취했다. PCKS는 Alk5i(10 μM, 양성 대조군)의 존재 또는 부재 하에 TGF-β1(3 ng/mL) 및 PDGFββ(50 ng/mL)와 함께 배양되었고, 항-α11β1 항체를 세 가지 용량(1, 10 및 50 μg/mL)에 걸쳐 테스트하거나 단일 고용량에서 IgG 대조군 항체가 있는 상태에서 시험한다. PCKS 배양 배지는 총 3개의 시점에서 24시간마다 수확되었다. R&D Duoset ELISA 키트를 사용하여 조직 배양 상청액에서 콜라겐 유형 I α1(col1a1)의 수준을 정량화했다. 통계는 이원 ANOVA와 그 후의 Dunnett의 다중 비교 시험을 사용하여 수행되었다.
실시예 1. α11β1에 대한 신규 단일클론 항체 생성 및 결합 친화도 결정
항체 발견은 재조합 인간 α11β1로 래트와 토끼를 면역화하고 마우스를 인간과 마우스 α11β1 모두로 면역화함으로써 수행되었다. 51개의 신규 항-인간 α11β1 단일클론 항체가 생성되었다(토끼 24개, 래트 7개 및 마우스 20개). 마우스 및 래트 항체에 대해 중쇄 및 경쇄 가변 영역 서열을 결정한 반면, 토끼 항체에 대해 전체 중쇄 및 경쇄 서열을 결정하였다.
재조합 인간 α11β1에 대한 선택된 마우스 단일클론 항체의 예시적인 결합을 보여주는 ELISA 결과가 도 2a에 나와 있다. 도 2b에 표시된 것처럼 3개의 mAbs도 마우스 α11β1에 결합했다.
관심있는 항체가 α11β1의 I 도메인에 결합하는지 여부를 결정하기 위해 데이터도 수집했다. 인하우스 생성된 α11β1의 I 도메인이 사용되었다. 래트 클론 79E3E3, 8H8E9 및 6E5C11은 ELISA에 의해 결정된 바와 같이 각각 높은, 중간 및 낮은 결합을 나타내었다. 마우스 항체 10-F23, 10-L15, 7-O8, 6-A12, 9-G05 및 9-E16 및 토끼 항체 7-H12 및 2-D3도 인하우스 생성된 α11β1 I 도메인에 대한 결합에 대해 시험되었다. 도 3a 및 도 3b는 예시적인 mAb로부터의 결합 데이터를 예시하는 그래프를 보여준다.
α11β1은 콜라겐 수용체 계열에 속하며 상대적으로 상동성이 높다. 따라서, 본 발명의 신규 항체를 α1β1, α2β1 및/또는 α10β1에 대해 카운터-스크리닝하였다. 표 2는 다른 수용체에 대한 교차 반응성 결과를 포함한다.
[표 2]
인테그린은 크기가 크고, 막관통 수용체는 서로 다른 배좌적 형상으로 존재하기 때문에, 신규 항체가 세포 발현 α11β1에도 결합하는지 확인하기 위해 실험을 수행했다. 높은 수준의 β1 소단위를 내생적으로 발현하는 CHO-K1 세포주는 인간 α11(CHO-K1 hu α11)을 안정적으로 발현하도록 조작되었다.
도 4a 및 도 4b는 인간 α11β1(ELISA에 의해 시험됨)에 결합하고 또한 CHO-K1 세포의 표면에서 발현된 α11β1에 대한 결합 능력을 입증한 선택된 래트 및 마우스 mAb를 보여준다. 도 11a 및 도 11b는 CHO 세포 표면에서 발현된 α11β1에 대한 결합 능력을 입증한 선택된 토끼, 래트, 마우스 및 인간 mAb를 보여준다. 추가로, 도 14는 CHO 세포 표면에서 발현된 α11β1에 대한 결합 능력을 입증한 선택된 완전 인간 mAb를 보여준다. 그러나, 표 1에 나타낸 바와 같이, ELISA에 의해 α11β1에 결합하는 것으로 나타났으나 세포-발현 α11β1에는 결합하지 않는 몇몇 mAb가 있었다.
결합 EC50은 CHO-K1 hu α11β1 세포로 수행된 형광 활성 세포 분류(FACS) 데이터를 사용하여 추정되었다. 결과를 표 3에 나타내었다. 시험된 6개의 mAb 중 4개는 낮은 나노몰 범위(8-P20, 8-G15, 8-J17, 8-l14)에서 EC50 결과를 가졌고, 나머지 2개의 mAb는 강력하지 않았다(9-G05 및 9-E16; 둘 모두 I 도메인 바인더).
[표 3]
도 9에 도시된 바와 같이, 항체 16E10, 79E3E3, 9G05 및 1994_01_C07이 표면 플라즈몬 공명(SPR)을 통해 인간 α11β1에 대한 친화도를 시험했을 때, 이들은 각각 48 pM, 10 pM, 2.85 nM 및 0.77 nM의 KD를 나타냈다. 흥미롭게도 16E10 및 1994_01_C07은 α11β1의 I 도메인 또는 헤드피스 도메인에 결합하지 않으며, 이는 둘 다 리간드 결합 도메인에 결합하지 않지만 여전히 α11β1 기능을 억제함으로써 알로스테릭 억제제로 작용할 수 있음을 나타낸다. 9G05 및 79E3E3은 I 도메인(리간드 결합 도메인)에 결합하므로 리간드 결합 부위를 직접 억제할 수 있다. SPR로 측정한 α11β1 헤드피스 및 α11β1 I 도메인에 대한 항체의 결합 친화도는 각각 도 10a 및 도 10b에 나와 있다.
생리학적으로 관련된 일차 인간 세포 유형에 대한 결합도 시험되었다. 인간 폐 섬유모세포(HPF) 및 TGFβ 처리를 사용하여 섬유모세포에서 근섬유모세포로의 전이(FMT)를 유도하여 근섬유모세포(MF)를 발생시켰다. HPF는 α11β1을 발현하지 않지만 MF는 α11β1의 상당한 발현을 보인다. 추가로 HPF는 다른 콜라겐 결합 수용체인 α1β1 및 α2β1을 발현하는데, 이는 HPF가 관심 있는 항체의 교차 반응성을 시험할 수 있음을 의미한다. 선택된 mAb는 HPF 및 MF에 대한 결합에 대해 평가되었고, 도 5, 도 12 및 도 13에 도시된 바와 같이, 시험된 항체가 HPF에 결합하지 않으면서 MF에 강력하게 결합하는 것이 분명하며, 단, 오프-타겟 결합을 나타내는 일부 HPF 결합을 나타낸 9-E16은 예외이다.
실시예 2. α11β1에 대한 신규 단일클론 항체의 생물학적 활성
근섬유모세포는 섬유화 기질 분비를 담당하므로 MF 축적을 차단 및/또는 감소시키는 것은 섬유증을 치료 및/또는 예방하기 위한 중요한 단계이다. 이는 항-α11β1 항체를 사용하여 섬유모세포에서 근섬유모세포로의 전이를 억제함으로써 달성할 수 있다. 수용체 차단 리간드 결합의 전형적인 기능적 억제제는 α11β1과 유형 I 콜라겐의 결합을 방지하는 것이 항-α11β1 항체의 바람직한 특징이지만 치료 효능에는 필요하지 않을 수 있다. 다른 많은 수용체와 달리 인테그린은 "외부에서"(표준, 리간드 매개) 신호와 "내부에서" 신호를 모두 수행할 수 있다. 따라서, 항체가 내부 신호 및 FMT를 방지하는 방식으로 α11β1의 구조에 영향을 주는 방식으로 α11β1에 결합할 수 있지만 α11β1이 유형 I 콜라겐에 결합하는 능력에는 영향을 미치지 않는다. 이러한 이유로 리간드 결합을 차단하는 mAb와 차단하지 않는 mAb가 모두 이 연구에 포함되었다.
CHO-K1 hu α11 세포주를 사용하여 유형 I 콜라겐에 대한 α11β1 매개 결합을 차단하는 mAb의 능력을 평가했다. 도 6a에 나타낸 바와 같이, 시험된 3개의 래트 mAb 중 2개는 유형 I 콜라겐 코팅 플레이트에 대한 CHO-K1 hu α11 세포의 부착을 상당히 억제했다. "미처리" 조건에서, 세포는 유형 I 콜라겐에 플레이팅되었지만 항체는 첨가되지 않았고 "비코팅" 조건에서 세포는 유형 I 콜라겐을 함유하지 않는 BSA-코팅된 웰에 시딩되었다. 통계는 일원 ANOVA와 그 후의 Dunnett의 다중 비교 시험을 사용하여 수행되었다. I-도메인 결합제인 79E3E3은 9.4 nM의 IC50으로 세포 부착을 차단할 수 있었다. 그러나, 40G10H11은 세포 부착을 강력하게 억제했지만 다른 콜라겐 수용체(α1β1, α2β1 및 α10β1)와 교차 반응하지만 I-도메인 바인더인 것으로 밝혀지지 않았다. 24E4G6은 I-도메인에 결합하지도 않았고 콜라겐에 대한 세포 부착을 억제하지도 않았다. 토끼 mAb를 시험했을 때 9개의 mAb 중 8개가 강력하게 그리고 상당히 세포 부착을 억제했으며 이러한 mAb 중 어느 것도 I-도메인 결합제로 밝혀지지 않았다(도 6b). 따라서, 이러한 mAb는 인테그린을 낮은 또는 중간 친화도 상태로 유지하는 α11β1 도메인에 결합할 수 있다. 도 6c는 선택된 마우스 mAb의 활동을 보여준다. 6개 mAb 중 3개는 세포 부착을 상당히 차단했고, 그 mAb 중 2개는 I-도메인 결합제(9-G05 및 9-E16)인 것으로 밝혀졌다. 그러나, 8-G15는 세포 부착의 강력한 차단제이지만 I-도메인에 결합하는 것으로 밝혀지지 않았다. 8-P20, 8-J17 및 8-I14는 유형 I 콜라겐에 대한 세포 부착을 차단하지 않았다. 9종의 인간 mAb에 대해서도 인간 CHO-α11 세포가 유형 I 콜라겐에 결합하는 것을 억제하는 능력에 대해 시험했다. 도 15a 및 도 15b에 나타낸 바와 같이, 모든 인간 Ab는 대조군에 비해 세포 부착을 억제하였으며, 1994-01-C07은 3.3 nM의 IC50을 가졌다. 이러한 데이터에 의해 설명된 바와 같이(그리고 표 1에 요약됨), 일부 항-α11β1 mAb는 ELISA 및 FACS로 시험했을 때 인간 α11β1에 강력하게 결합하는 것으로 밝혀졌지만 모든 항체가 리간드 상호작용을 차단할 수 있는 것은 아니다. 또한, I-도메인(α11β1의 리간드 결합 도메인)에 대한 결합은 α11β1과 유형 I 콜라겐의 상호작용을 차단하는 데 필요하지 않은 것으로 밝혀졌다.
위에서 설명한 결합 능력 외에도 항-α11β1 항체가 섬유모세포에서 근섬유모세포로의 전이(FMT)를 억제하는 것이 중요하다. 근섬유모세포는 서로 다른 활성화 상태에 존재하는 이질적인 세포 집단이며, 콜라겐 세포외 기질(ECM)을 생성하고 수축시키는 주요 기능을 가지고 있음이 이제 인정된다. FMT는 복구 중인 조직의 변화하는 기계적 환경에 의해 제어되는 다단계 이벤트이다. TGFβ는 이 과정을 강화하는 강력한 인자 중 하나이며 알파 평활근 액틴(αSMA)은 섬유모세포가 근섬유모세포로 변이를 겪을 때 과발현되는 주요 마커 중 하나이다. αSMA의 존재는 섬유모세포 수축을 강화하고 세포내 피드백 루프를 통해 근섬유모세포 활성화를 안내한다. αSMA는 근섬유모세포의 주요 분자 마커이기 때문에 TGFβ 유도 FMT에서 αSMA 발현을 억제하는 신규 항-α11β1 mAb의 능력을 시험했다.
도 7a에 나타낸 바와 같이, 2개의 래트 mAb(40G10H11 및 24E4G6)는 대조군과 비교하여 αSMA 발현을 상당히 억제했지만, 어느 항체도 I-도메인 바인더는 아닌 것으로 밝혀졌다. 통계는 일원 ANOVA와 그 후의 Dunnett의 다중 비교 시험을 사용하여 수행되었다. 또한, 40G10H11만이 유형 I 콜라겐에 대한 세포 부착을 억제했다. 흥미롭게도, 79E3E3 mAb는 I-도메인 바인더인 것으로 밝혀졌으며 콜라겐에 대한 세포 부착을 강력하게 억제했지만 αSMA 발현(근섬유모세포 생성을 위한 대용물)을 감소시키지는 못했다. 도 7b에 나타낸 바와 같이, 2개의 토끼 mAb는 대조군과 비교하여 αSMA 발현을 상당히 억제했지만, 어느 항체도 I-도메인 바인더는 아닌 것으로 밝혀졌다. 16E10은 리간드 결합과 FMT(αSMA 상향 조절의 억제 %)를 모두 억제하는 것으로 밝혀졌지만, 16G7은 FMT를 억제하는 것으로 밝혀졌지만 콜라겐에 대한 세포 부착에는 영향을 미치지 않았다. 마지막으로, 도 7c에 나타낸 바와 같이, 6개의 시험된 마우스 mAb 중 5개가 대조군에 비해 αSMA 발현을 상당히 억제하였다. 세 가지 FMT 억제제(9-G05, 8-G15, 9-E16)도 콜라겐에 대한 세포 부착을 감소시키는 것으로 밝혀졌으며 그 중 두 가지(9-G05, 9-E16)도 I 도메인에 결합했다. 마우스 항체 8-J17 및 8-I14는 FMT만 억제하고 리간드 결합에 영향을 미쳤다.
실시예 3. 콜라겐 겔의 세포 매개 수축을 억제하는 선택된 항체의 능력
CD 콜라겐 I 겔의 세포 매개 수축은 이전에 α11β1 매개인 것으로 밝혀진 과정이며, 보다 최근의 연구에서는 α11β1 매개 다운스트림 신호가 겔 수축이 발생하는 데 필수불가결한 것으로 나타났다. 선택된 예시적인 항체는 세포-매개된 3D 겔 수축을 억제하는 능력에 대해 시험되었는데, 이는 이러한 능력이 예시적인 항체의 기능성에 직접적으로 연결되기 때문이다.
도 8에서 볼 수 있는 바와 같이, 래트 79E3E3, 마우스 9E16, 9G05 및 8I14, 토끼 16E10 및 인간 1994_01_C07, 2004_04_B03, 2004_04_C12 및 1994_01_D12 항체는 모두 CHO-hu α11 매개 콜라겐 겔 수축을 억제했다. 주목할 점은 UT(미처리) 조건에서 볼 수 있듯이 CHO-hu α11 세포는 TGFβ를 첨가하지 않고도 콜라겐 겔을 수축시킬 수 있다는 것이다. 미처리 조건에서, 세포는 콜라겐 겔에 포매되었지만 항체는 첨가되지 않았다. 통계는 일원 ANOVA와 그 후의 Dunnett의 다중 비교 시험을 사용하여 수행되었다; 각각의 처리 조건을 미처리 조건과 비교하였다. 별표는 통계적 유의성을 나타내고 "ns"는 차이가 통계적으로 유의하지 않음을 나타낸다.
실시예 4. 종양 이종이식편 성장에 대한 선택된 항체의 효과 평가
이전 연구에서는 α11 녹아웃 SCID 마우스에서 A549 세포 이종이식편의 성장이 야생형 마우스에 비해 상당히 방해되는 것으로 나타났다. 이 예에서는 mAb로 α11β1 기능을 억제하면 이종이식 성장이 억제되는지 확인하기 위한 연구가 수행되었다. 도 16 및 표 4에서 볼 수 있듯이 마우스 CAF에서 α11β1을 차단하면 SCID 마우스에서 이종이식 성장이 지연되었다. 구체적으로, 마우스 α11β1과 교차 반응하는 이펙터가 없는 mAb인 79E3E3은 이소형 대조군과 비교하여 종양 성장을 상당히 억제한 반면, 마우스 α11β1에 결합하지 않는 mAb인 16E10은 종양 성장의 상당한 억제를 나타내지 않았다. 종양 발현 α11β1의 억제는 16E10이 어떠한 효과도 나타내지 않았기 때문에 종양 성장에 영향을 미치지 않았다.
[표 4]
실시예 5. 인간 정밀 절단 간 절편(PCLS)에 대한 항-α11β1 항체의 효과
인간 간 조직의 정밀 절단 간 절편(PCLS)은 조직 구조를 생리학적 및 구조적으로 대표하고 인간 PCLS에서 치료 표적을 시험하면 임상 상황에 대한 효과 및 관련성을 평가할 수 있어 생체내 설치류 모델 및 시험관내 2D 세포 배양 방법의 한계를 극복할 수 있다. 조직 생물 반응기 기술은 시험관내에서 적어도 6일 동안 인간 간 조직에서 PCLS의 생존력과 기능을 유지한다.
도 17a 내지 도 17c에 나타낸 바와 같이, 시험된 모든 항-α11-β1 항체는 용량 의존적 방식으로 또는 시험된 최고 용량에서 용해성 섬유화 촉진 마커(COL1A1, 히알루론산 및 TIMP1)의 부분 억제를 제공했다. 어떤 항체로 치료한 후에도 독성이 관찰되지 않았다(즉, ALT, AST 또는 알부민의 상승 없음, 데이터는 표시되지 않음).
실시예 6. 인간 정밀 절단 신장 절편(PCKS)에 대한 항-α11β1 항체의 효과
인간 정밀 절단 신장 절편(PCKS)은 중간 정도의 섬유증이 있는 인간 신장 조직으로부터 제조된다. 24시간 동안의 휴지 후, PCKS는 신규 항-α11β1 단일클론 항체와 함께 상이한 용량과 시간에 따라 배양된다. 각 시점에서 PCKS 배양 배지를 수집한다. 수확 시점에서 배양 배지를 수집한 후 각 조직 절편에서 RNA를 추출한다. 섬유화 촉진 매개체의 범위는 분비 단백질(COL1A1, 피브로넥틴, PAI-1, IL-11, CXCL1, MCP-1, IL-6, TIMP-1, 히알루론산, TGFβ, CTGF, PDGF 및 MMP9를 포함하지만 제한되지 않음)로서 배양 배지에서 측정되며 또한 전사 수준(COL1A1, IL-6, TIMP-1, 히알루론산, TGFβ, CTGF, aSMA 및 ITGA11을 포함하지만 이에 제한되지 않음)에서도 측정된다.
상기 방법에 설명된 바와 같이, PCKS는 이식된 섬유성 인간 신장 조직으로부터 제조되었고 실험이 시작되기 전에 절단 후 스트레스 기간이 경과하도록 24시간 동안 휴식을 취했다. PCKS는 Alk5i(10 μM, 양성 대조군)의 존재 또는 부재 하에 TGF-β1(3 ng/mL) 및 PDGFββ(50 ng/mL)와 함께 배양되었고, 항-α11β1 항체를 세 가지 용량(1, 10 및 50 μg/mL)에 걸쳐 테스트하거나 단일 고용량에서 IgG 대조군 항체가 있는 상태에서 시험한다. PCKS 배양 배지는 총 3개의 시점에서 24시간마다 수확되었다. R&D Duoset ELISA 키트를 사용하여 조직 배양 상청액에서 콜라겐 유형 I α1(col1a1)의 수준을 정량화했다. 통계는 이원 ANOVA와 그 후의 Dunnett의 다중 비교 시험을 사용하여 수행되었다.
도 18a 내지 도 18c에 나타난 바와 같이, 각 항-α11-β1 항체에 대해 적어도 한 시점에서 적어도 한 번 용량은 col1a1 분비의 상당한 억제를 제공했다. 시험된 각 용량에서 72시간 및 96시간 시점에서 1994_01_C07 신규 mAb에 의해 col1a1 분비가 상당히 억제되었다. 이것은 콜라겐 유형 I 침착이 섬유 조직의 주요한 문제원인이기 때문에 중요한 발견이다.
실시예 7. 생체내 신장 섬유증 모델에 대한 항-α11β1 항체의 효과
두 가지 다른 신장 섬유증 모델, 즉 5/6 신장 절제술 모델과 ReninAAV Unx db/db 마우스 모델이 사용된다. 이 두 모델은 측정 가능한 감소된 신장 기능을 가진 상당한 신장 섬유증을 특징으로 한다. 이러한 모델에서 항-α11β1 mAb를 테스트하고 신장 형태(섬유증) 및 신장 기능(GFR 및 알부민뇨)에 미치는 영향을 측정한다.
예시적인 서열
항-α11β1 단일클론 항체의 DNA 서열
래트 mAb 서열
신호 서열-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4
79E3E3 중쇄 가변 영역
신호 서열-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4
ATGGATTGGTTGTGGAACTTGCTATTCCTGATGGTAGTTGCCCAAAGTGCTCAAGCACAGATCCAGTTGGTACAGTCTGGACCTGAAGTAAAGAAGCCTGGAGAGTCAGTGAAGATCTCCTGCAAGGCCTCTGGGTATACCTTCACAGACTATGCAATGAACTGGGTGAAACAGGCTCCAGGAAATGGCCTGAAGTGGATGGGCTGGATCAACACCCAAACTGGAAAGCCAACATATGCGGATGATTTCAAACAACGGTTTGTCTTCTCTTTGGAAACTTCTGCCAGAACTACATATTTGCAGATCAACAACCTCAATATTGAAGACACAGCTACATATTTCTGTACGAGATTGGGTACAGGTAATACGAAGGGGTTTGCTTACTGGGGCCAAGGCACTCTGGTCACTGTCTCTTCA (SEQ ID NO: 1)
79E3E3 경쇄 가변 영역
ATGGAATCACAGACGCATGTCCTCATTTCCCTTCTGCTCTGTGTATCAGGTACCTGTGGGGACATTTTGATAAACCAGTCTCCAGCCTCTCTGACTGTGTCAGCAGGAGAGAGGGTCACTATGAGCTGCAAGTCCAGTCAGAGTCTTCTATACAGTGAAAACAACCAGGACTATTTGGCTTGGTACCAGCAGAAACCAGGACAGTTTCCTAAATTGCTTATCTATGGGGCATCCAACCGGCACACTGGGGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGACTTCACTCTGACCATCAGCAGTGTGCAGGCTGAAGACCTGGCTGATTATTATTGTGAGCAGACCTACAGATATCCATTCACGTTCGGCTCAGGGACGAAGTTGGAAATAAAA (SEQ ID NO: 2)
24E4G6 중쇄 가변 영역
ATGGAGTTGGAATTGAGCTTAATTTTTATTTTTTCTCTTTTAAAAGATGTCCAGTGTGAAGTACAGCTGGTGGAGTCTGGAGGAAGCTTGGTTCAACCTGGGGGTTCTCTGAAACTCTCCTGTGTAGCCTCAGGATACACTTTCAGTAACTACTGGATGGACTGGGTTCGGCAGTCTCCTGGAAAGTCCCTGGAATGGATTGGAGAGATTAACACGGATGGCAGAAGGACCAACTATGCACCATCCATAAAGGATCGATTCACAATCTCCAGAGACAATGCCAAGAGCACCCTGTATCTGCAGATGAGCAATGTGAAATCAGATGACACAGCCATTTATTACTGTACCATACTACGGGTATACCCCCACTACTTTGATTACTGGGGCCAAGGAGTCATGGTCACAGTCTCCTCA (SEQ ID NO: 3)
24E4G6 경쇄 가변 영역
ATGATGAGTCCTGCCCAGTTCCTGTTTCTGCTAATGCTCTGGATCCAGGAAGCCCGCGGAGATGTTGTGATGACCCAGACACCACCGTCTTTGTCGGTTGCCATTGGACAATCAGTCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCGTATATAGTGATGGAGAGACATATTTGCATTGGTTTTTACAGAGTCCTGGCAGGTCTCCGAAGCGCCTAATTTATCACGTGTCTAATCTGGGCTCTGGAGTCCCTGACAGGTTCAGTGGCACTGGATCACTGACAGATTTTACACTTAGAATCAGCAGAGTGGAGGCTGAGGATTTGGGAGTTTATTACTGCGCGCAAACTACACATTTTCCTCCCACGTTTGGAGCTGGGACCAAGCTGGAACTGAAA (SEQ ID NO: 4)
8H8E9 중쇄 가변 영역
ATGGCTGTCCTGGTGCTGTTGCTCTGCCTGGTGACATTTCCAAGCTGTGCCCTGTCCCAGGTGCAGTTGAAGGAGTCAGGACCTGGTCTGGTGCAGCCCTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGGTTCTCATTAACCAGCAATAGTGTTAGCTGGGTTCGCCAGGCTCCGGGAAAGGGTCTGGAGTGGATGGGAGCAATATGGAGTGGTGGAAGCACAGATTATAATTCAGCTCTCAAATCCCGACTGAGCATCAGCAGGGACACCTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTGCAAACTGAAGACACAGCCATTTACTTCTGTACCAGATCTCACTGGGAGCCCTTTGATTACTGGGGCCAAGGAGTCATGGTCACAGTCTCCTCA (SEQ ID NO: 5)
8H8E9 경쇄 가변 영역
ATGGAATCACAAACTCAGGCCCTCATATCCCTGCTGCTCTGGGTATATGGTACCTGTGGGGACATTGTGATGACCCAGTCTCCATTCTCCCTGGCTGTGTCAGAAGGAGAGATGGTCACTATAAACTGCAAGTCCAGTCAGGGTCTTTTATCCAGTGGAAACCAAAAGAACTACTTGGCCTGGTACCAGCAGAGACCAGGGCAGTCTCCTAAACTACTGATCTACTATGCATCCACTAGGCAATCAGGGGTCCCTGATCGCTTCATAGGCGGTGGATCTGGGACAGACTTCACTCTGACCATCAGCGATGTGCAGGCTGAAGACCTGGCAGATTATTACTGCCTGCAGCATTACAGCTATCCTCCCACGTTCGGTTCTGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 6)
6E5C11 중쇄 가변 영역
ATGGCTGTCCTGGTGCTGTTGCTCTGCCTGGTGACATTTCCAAGCTGTGCCCTGTCCCAGGTGCAGCTGAGGGAGTCAGGACCTGGTCTGGTGCAGCCCTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGGTTCTCATTGACCAGCAATAGTGTGACCTGGGTTCGCCAGCCTCCGGGAAAGGGTCTGGAGTGGATGGGAGCGATATGGAGTGATGGAAGCACAGATTATAATTCAACTCTCAAATCCCGACTGAGCATCAGTAGGGACACCTCCAAGAGCCAAGTTTTCTTAAAAATGAGCAGTCTGCAAACTGAAGACACAGCCATTTACTTCTGTACCAGATCCCACTGGGAGCCCTTTGATTACTGGGGCCAAGGAGTCATGGTCACAGTCTCCTCA (SEQ ID NO: 7)
6E5C11 경쇄 가변 영역
ATGGAATCACAAACTCAGGCCCTCATATCCCTGCTGCTCTGGGTATATGGTACCTGTGGGGACATTGTGATGACCCAGTCTCCACTCTCCCTGGCTGTGTCAGAAGGAGAGACGGTCACTATGAACTGCAAGTCCAGTCAGAGTCTTTTTTCCAGTGGAAATCAAAAGAACTACTTGGCCTGGTACCAGCAGAAACCAGGGCAGTCTCCTAAACTACTGATCTACTATGCATCCACTAGGCAATCAGGGGTCCCTGATCGCTTCATAGGCAGTGGATCTGGGACAGACTTCACTCTGACCATCAGCGATGTGCAGACTGAAGACCTGGCAGATTATTACTGCCTGCAGCATTACAACTATCCTCCCACGTTCGGTTCTGGGACCAAGCTGGAGA (SEQ ID NO: 8)
7D8B10 중쇄 가변 영역
ATGGACTTGCGACTGACTTATGTCTTTATTGTTGCTATTTTAAAAGGTGTCTTGTGTGAGGTGAAACTGGAGGAATCTGGGGGAGGTTTGGTGCAACCTGGAATGTCCGTGAAACTCTCTTGTGCAACCTCTGGATTCATTTTCAGTGACTACTGGATGGAATGGGTCCGCCAGGCTCCAGGGAAGGGGCTAGAATGGGTAGCCGAAATTAGAAACAAAGCTAATAATTATGCAACATACTATGGGAAGTCTATGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGTATAGTCTACCTACAAGTGAACAGCATAAGATCTGAAGATACTGCTATTTATTACTGTGCACCGAATTTTGATTACTGGGGCCAAGGAGTCATGGTCACGGTCTCCTCA (SEQ ID NO: 9)
7D8B10 경쇄 가변 영역
ATGAGTCCTGTCCAGTCCCTGTTTTTGCTATTGCTTTGGATTCTGGGAACCCATGGTGATGTTGTGCTGACCCAGACTCCACCCACTTTATCGGCTACCATTGGACAATCAGTCTCTATCTCTTGCAGGTCAAGTCAGAGTCTCTTACATAGTACTGGAAACACCTATTTAAATTGGTTGCTACAGAGGCCAGGCCAACCTCCGCAACTTCTAATTTATTTGGTTTCCAGACTGGAATCTGGGGTCCCCAACAGGTTCAGTGCCAGTGGGTCAGGAACTGATTTCACACTCAAAATCAGTGGAATAGAGGCTGAGGATTTGGGGGTTTATTACTGCGTGCAAAGTTCCCATACTCCGTACACGTTTGGGACTGGGACCAAGCTGGAACTGAAA (SEQ ID NO: 10)
18E10F10 중쇄 가변 영역
ATGGACATCAGGCTCAGCTTGGTTTTCCTTGTCCTTTTTATGAAAGGTGTCCAGTGTGAGGTGCAGTTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAAGGTCCCTGAAACTCTCCTGTGCAGCCTCACGATTCACTTTTAGTGACTATAACATGGCCTGGGTCCGCCAGGCTCCAAAGAAGGGTCTGGAGTGGGTCGCAACCATTTATCATGATGATAGTGGTTCTTACTATCGAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAAATAATGCAAAAAGCACTCTGTACCTGCAGATGGACAGTCTGAGGTCTGAGGACATGGCCACTTATTACTGTGCAAGACATAACAATGGCTTTGATTACTGGGGCCAAGGAGTCATGGTCACAGTCGCCTCA (SEQ ID NO: 11)
18E10F10 경쇄 가변 영역
ATGAAGTGGCCTGTTAGGCTGTTGGTGCTGTTCTTCTGGATTCCTGCTTCCGGGGGTGATGTTGTGATGACACAAACTCCAGTCTCCCTGCCTGTCCGCCTTGGAGGTCAAGCCTCTATCTCTTGCCGGTCAAGTCAGAGCCTGGTACACAGTAATGGAAACACCTACTTGCATTGGTACCTACAGAAGCCAGGCCAGTCTCCACAGCTCCTCATCAATCGGGTTTCCAACAGATTTTCTGGGGTGCCAGACAGGTTCAGTGGCAGTGGGTCAGGGACAGATTTCACCCTCAAGATCAACAGAGTAGAGCCTGAGGACTTGGGAGATTATTACTGCTTACAAAGTACACATTTTCCACTCACGTTCGGTTCTGGGACCAAGCTGGAGACCAAA (SEQ ID NO: 12)
40G10H11 중쇄 가변 영역
ATGGACATCAGGCTCAGCTTGGGTTTCCTTGTCCTTTTCATAAAAGGTGACCAGTGTGCGGTGCAACTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAAGGTCCCTGAAACTCTCCTGTGCAGCCTCAAGAATCACTTTCACTGACTATTACATGGCCTGGGTCCGCCAGGCTCCAACGAAGGGTCTGGAGTGGGTCGCAACCATTAGTTCTGATGGTGGTGACACTTTCTATCGAGACTCCGTGAAGGGCCGATTTACTATCTCCAGAGACAATGCAAAAAGCACCCTATATTTGCAAATGGTCAGTCTGAGGTCTGAGGACACGGCCACTTATTACTGTTCAACAGATCGGGGAGCTCAGTTTGGTTACTGGGGCCAAGGCACTCTGGTCACTGTCTCTTCA (SEQ ID NO: 13)
40G10H11 경쇄 가변 영역
ATGGCTCCAGTCCAGCTCTTAGGGCTGCTGCTGATTTGGCTCCCAGCCATGAGATGTGACATCCAGATGACCCAGTCTCCTTCATTCCTGTCTGCATCTGTGGGAGACAGAGTCTCTATCAACTGCAAAGCAAGTCAGAATGTTCACGAGAACCTAAACTGGTATCAGCAAAAGCTTGGAGAAGCTCCCAAACGCCTGATATATAATACAAACAATTTGCAAACAGGCATCCCATCAAGGTTCAGTGGCAGTGGATCTGGTGCAGATTACACACTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCCACATATTTCTGTTTGCAGCATAATGCTTTTCCGTACACGTTTGGACCTGGGACGAAGCTGGAACTGAAA (SEQ ID NO: 14)
마우스 mAb 서열
9-G05 중쇄 가변 영역
GAGGTCCAGCTGCAACAGTCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATACCCTGCAAGGCTTCTGGATACACATTCCCTGACTACAACATGGACTGGGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTGGATTGGATATATTAATCCTGACAATGGTGGTACTATCTACAACCAGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAGTCCTCCAGCACAGCCTACATGGAGCTCCGCAGCCTGACATCTGAGGACACTGCAGTCTATTACTGTGCAAGATTAGACAGCTCAGGCTACGGTTACTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA (SEQ ID NO: 15)
9-G05 경쇄 가변 영역
GACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCATCTCCTGCAGAGCCAGCGAAAGTGTTGATAATTATGGCATTAGTTTTATGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCGTGCATCCAACCTAGACTCTGAGATCCCTGCCAGGTTCAGTGGCAGTGGGTCTAGGACAGACTTCACCCTCACCATTGATCCTGTGGAGACTGATGATGTTGCAACCTATTACTGTCAGCAAAGTTATAAGGATCCTCGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (SEQ ID NO: 16)
8-P20 중쇄 가변 영역
AAAGTGATGCTGGTGGAGTCTGGGGGAGCCTTAGTGAAGCCTGGAGGGTCCCTGAAACTCTCCTGTGTAGCCTCTGGATTCACTTTCAGTAACTATGCCATGTCTTGGGTTCGCCAGACTCCAGAGAAGAGGCTGGAGTGGGTCGCAACCATTAGTAGTGGTGGTTATTACACTTACTATCCAGACAGTGTGAAGGGTCGATTCACCATCTCCAGAGACAATGCCAGGAACACCCTGTTCCTGCAAATGAGCAGTCTGAGGTCTGAGGACACGGCCATGTTTTACTGTGCAAGAGAGGATGATTACGGAAGATATTCCTATACTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA (SEQ ID NO: 17)
8-P20 경쇄 가변 영역
GATGTTGTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGTCTCCATCTCTTGCAGATGTAGTCAGAGCCTTGTACACAGTAATGGAAACACCTATTTACATTGGTACCTGCAGAAGCCAGGCCAGTCTCCACAGCTCCTGATCTACAAAATTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGCTCTCAAAGTACACATGTTCCGTACACGTTCGGAGGGGGGACCGAGCTGGAAATAAAA (SEQ ID NO: 18)
8-G15 중쇄 가변 영역
GAGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGTAAAGCCTGGGGCTTCAGTGAGGATATCCTGCAAGGCTTCTGGATACACATTCACTGACTACTACATACACTGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAATGCATTGGAGAGATTTATCCTGGAACTGATAATACTTACTACAGTAAAAAATTCAGGGGCAAGGCCACACTGACTGCAGACAAATCCTCCGACACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTTCTGTGCAAGAGGAGACTACTATAGGGGGTACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 19)
8-G15 경쇄 가변 영역
GATGTTGTGATGACTCAGACCTCACTCACTTTGTCGGTTACCATTGGACAACCAGCCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTACATAGTAATGGAAAGACATATTTGAATTGGTTATTACAGAGGCCAGGCCAGTCTCCAAAGTTCCTAATCTATCTGGTGTCTAAACTGGAATCTGGAGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTGAAAATCAGCAGAGTGGAGGCTGAGGATTTGGGGGTTTATTACTGCTTGCAATCTACACATTTTCCTTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (SEQ ID NO: 20)
8-I14 중쇄 가변 영역
GAGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGTAAAGCCTGGGGCTTCAGTGAAGAAATCCTGCAAGGCTTCTGGATACACATTCACTGACTACTACATGCACTGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAGTGGATTGGAAAGATTTATCCTGGAAGTGGTAATACTCACTACAATGAGAAGTTCAAGGGCAAGGCCACACTGACTGCAGACAAATCCTCCAGCACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTTCTGTGCAACCAATTACTACGGCTACAGGGCAATGAACTATTGGGGTCAAGGATCCTCAGTCACCGTCTCCTCA (SEQ ID NO: 21)
8-I14 경쇄 가변 영역
GACATCCATTTGACCCAGTCTCCATCCTCCTTATCTGCCTCTCTGGGAGAAAGAATCAGTCTCACTTGCCGGGCAAGTCAGGACATTTATATTAGCTTAAACTGGTTTCAGCAGAAACCAGATGGAACTATTAAACTCCTGATCTACGGCACATCCAGTTTAGATTCTGGTGTCCCCAAAAGGTTCAGTGGCAGTAGGTCTGGGTCAGATTATTCTCTCACCATCAGCAGCCTTGAGTCTGAAGATTTTGCAGACTATTACTGTCTACAATATGCTAGTTCTCCGTACACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 22)
9-E16 중쇄 가변 영역
GAGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGTAAAGCCTGGGGCTTCAGTGAAGATATCCTGCAAGGCTTCTGGATACACATTCACTGACTACTACATGCACTGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAGTGGATTGGAGAGATTTATCCTGGAAGTGGTAATCCTTACTACAATGAGAAGTTCAAGGGCAAGGCCACACTGACTGCAGACAAATCATCCAGCTCAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTTCTGTGCAAGAACCTCCTACGGTAGAGTAGGGACAGGGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA (SEQ ID NO: 23)
9-E16 경쇄 가변 영역
AATTTTGTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAGCCTTCTACACAGTAACGGAAACACCTATTTACATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAACAGAGTGGAGACTGAGGATCTGGGAATTTATTTCTGCTCTCAAAGTTCACATGTTCCCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAA (SEQ ID NO: 24)
8-J17 중쇄 가변 영역
CAGGTCCAGCTGCAGCAGTCTGGGGCTGAACTGGCAAAACCTGGGGCCTCAGTGAAGATGTCCTGCAAGGCTTCTGGCTACACCTTTACTAACTACTGGATGCACTGGGTAAAACAGAGGCCTGGACAGGGTCTGGAATGGATTGGATACATTAATCCTAACAATGGTTATACTGAGTACAATCAGCGATTCAAGGACAAGGCCACATTGACTGCAGACAGATCCTCCACCACAGCCTACATGCAACTAAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGATCCGATATCATTACGACAGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 25)
8-J17 경쇄 가변 영역
GATGTTGTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAGCCTTGTATATAGTAATGGAAATACCTATTTACATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATAAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGCTCTCAAAGTACACATGTTCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (SEQ ID NO: 26)
6-O12 중쇄 가변 영역
GAAGTGAAGCTTGAGGAGTCTGGAGGAGGCTTGGTGCAACCTGGAGGATCCATGAAACTCTCTTGTGCTGCCTCTGGATTCACTTTTAGTGACGCCTGGATGGACTGGGTCCGCCAGTCTCCAGAGGCGGGGCTTGAGTGGGTTGCTGAAATTAGAAACAAAGCTCATAATCCTGCAACATACTATGCTGAGTCTGTGAAAGGGAGATTCACCATCTCAAGAGATGATTCCAAAAGTAGTGTCTACCTGCAAATGAACAGCTTAAGAGCTGAAGACACTGGCATTTATTACTGTACCTTAGTAGCCCCTGATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA (SEQ ID NO: 27)
6-O12 경쇄 가변 영역
GACATTGTGATGTCACTGTCTCCATCCTCCCTAGCTGTGTCAGTTGGAGAGAAGGTTACTATGAGCTGCAAGTCCAGTCAGAGCCTTTTATATAGTCGCAATCAAAAGAACTACTTGGCCTGGTACCAGCAGAAACCAGGGCAGTCTCCTAAACTGCTGATTTACTGGGCATCCACTAGGGCATCTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTGTGAAGGCTGAAGACCTGGCAGTTTATTACTGTCAGCAATATTATAGCTATCCGTACACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 28)
10-L15 중쇄 가변 영역
CAGGTCCAACTGCAGCAGTCTGGGCCTGAGCTGGTGAGGCCTGGGGCTTCAGTGAAGATGTCCTGCAAGGCTTCAGGCTATACCTTCACCAGCTACTGGATGCACTGGGTGAAACAGAGGCCTGGACAAGGCCTTGAGTGGATTGGCATGATTGATCCTTCCAATAGTGAAACTTGGTTAAATCAGAAGTTCAAGGACAAGGCCACATTGAATGTAGACAAATCCTCCAACACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGATATGATGGTTACTACGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 29)
10-L15 경쇄 가변 영역
AACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCATATCCTGCAGAGCCAGTGAAAGTGTTGATAGTTATGGCAATAGTTTTATGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTTGCATCCAACGTAGAATCTGGGGTCCCTGCCAGGTTCAGTGGCAGTGGGTCTAGGACAGACTTCACCCTCACCATTGATCCTGTGGAGGCTGATGATGCTGCAACCTATTACTGTCAGCAAAATAATGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (SEQ ID NO: 30)
7-H14 중쇄 가변 영역
CAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTGGTGAGGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGCCTTCTGGCTACACCTTCACCAGCTACTGGATGAACTGGGTGAAGCAGAGGCCTGGACAAGGCCTTGAATGGATTGGTATGATTGATCCTTCAGACAGTGAAACTCACTACAATCAAATGTTCAAGGACAAGGCCACATTGACTGTTGACAAATCCTCCAACACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTACTGTGCGCAGATCTACTATGCTTACGACAAGGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA (SEQ ID NO: 31)
7-H14 경쇄 가변 영역
GACATTGTGATGTCACAGTCTCCATCCTCCCTAGCTGTGTCAGTTGGAGAGAAGGTTACTATGAGCTGCAAGTCCAGTCAGAGCCTTTTATATAGTAGCCATCAAAAGAACTACTTGGCCTGGTACCAGCAGAAACCAGGGCAGTCTCCTAAACTGCTGATTTACTGGGCATCCACTAGGGAATCTGGGGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTTCAGTCTCACCATCAGCAGTGTGAAGGCTGAAGACCTGGCAGTTTATTACTGTCAGGAATATTATAGCTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (SEQ ID NO: 32)
6-B21 중쇄 가변 영역
GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATATCCTGTAAGGCTTCTGGATACACGTTCACTGACTACTACATGAACTGGGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTGGATTGGAGATATTAATCCTCACAATGGTGGTACTAGCTTCATCCAGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAGTCCTCCAGCACAGCCTACATGGAGCTCCGCAGCCTGACATCTGAGGACTCTGCAGTCTATTATTGTGCCCCTCTGGGACGAAAGGAGGGGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA (SEQ ID NO: 33)
6-B21 경쇄 가변 영역
GACACTGTGCTGACACAGTCTCCTGCTTCCTTAGTTGTATCTCTGGGGCAGAGGGCCACCATCTCATGCAGGGCCAGCAAAAGTGTCAGTACATCTGGCTATAGTTATATGCACTGGTACCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTTGCATCCAACCTAGAATCTGGGGTCCCTGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGCCTTCACCCTCAACATCCATCCTGTGGAGGAGGAGGATGCTGCAACCTATTACTGTCAGCACAGTAGGGAGCTTCCGTACACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 34)
10-F23 중쇄 가변 영역
CAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTTTGCTATGGGTGTAGGCTGGATTCGTCAGCCTTCAGGGAAGGGTCTGGAGTGGCTGGCACACATTTGGTGGGATGATGATAAGTACTATAACCCAGCCCTGAAGAGCCGGCTCACAATCTCCAAGGATACCTCCAAAAACCATGTATTCCTCAAGATCGCCAATGTGGACACTGCAGATACTGCCACATACTACTGTGCTCGAATGCCGCTAACTTTCTACTTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 35)
10-F23 경쇄 가변 영역
GATGTTTTGCTGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAGCATTGTACATAGTAATGGACACACCTATTTAGAATGGTACCTGCAGAAACCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCGTTCACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 36)
6-A12 중쇄 가변 영역
CAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGAACTTTTGCTATGGGTGTAGGCTGGATTCGTCAGCCTTCAGGGAAGGGTCTGGAGTGGCTGGCACACATTTGGTGGGATGATGATAAGTACTATAACCCAGCCCTGAAGAGCCGGCTCACAATCTCCAAGGATACCTCCAAAAACCAGGTATTCCTCAAGATCGCCAATGTGGACACTGCAGATACTGCCACATACTACTGTGCTCGAATGCCGCTAACTTTCTACTTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 37)
6-A12 경쇄 가변 영역
GATGTTTTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGTAGATCTAGTCAGAGCATTGTACATAGTAATGGAAACACCTATTTAGAATGGTACCTGCAGAAACCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTCCACCCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCGTTCACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 38)
6-M8 중쇄 가변 영역
CAGGTCCAACTGCAGCAGCCTGGGGCTGAACTTGTGATGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAACTACTGGATGCACTGGGTGAAACAGAGGCCTGGACAAGGCCTTGAGTGGATCGGAGAGATTGATCCTTCTGATAGTTATACTAACTACAATCAAAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTACTGTACAAGACAGGGTAGTACCTACGCGTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA (SEQ ID NO: 39)
6-M8 경쇄 가변 영역
GATATTGTGATGACGCAGGCTGCATTCTCCAATCCAGTCACTCTTGGAACATCAGCTTCCATCTCCTGCAGGTCTAGTAAGAGTCTCCTACATAGTAATGGCATCACTTATTTGTATTGGTATCTGCAGAAGCCAGGCCAGTCTCCTCAGCTCCTGATTTATCAGATGTCCAACCTTGCCTCAGGAGTCCCAGACAGGTTCAGTAGCAGTGGGTCAGGAACTGATTTCACACTGAGAATCAGCAGAGTGGAGGCTGAGGATGTGGGTGTTTATTACTGTGCTCAAAATCTAGAACTTCCTCCGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (SEQ ID NO: 40)
2-A3 중쇄 가변 영역
GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATGTCCTGTAAGGCTTCTGGATACACATTCACTGACTACTACATGATGTGGGTGAAGCAGAGTCATGGAAAGAGCCTTGAGTGGATTGGAGATATTAATCCTTACAATGGTGGTTCTAGCTACAACCCGAAGTTCAAGGGCAGGGCCACATTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCAGCTCAACAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGAGGGACTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA (SEQ ID NO: 41)
2-A3 경쇄 가변 영역
GATGTTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACCAGCCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTAGATAGTGCTGGAAAGACATATTTGAATTGGTTGTTACAGAGGCCAGGCCAGTCTCCAAAGCGCCTAATGTATCTGGTGTCTAAACTGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGCGGATCAGGGACAGATTTCACACTGAAAATCAGCAGAGTGGAGGCTGAGGATTTGGGAGTTTATTATTGCTGGCAAGGTACACATTTTCCGTACACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 42)
6-O17 중쇄 가변 영역
CAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTTGTGAAGCCTGGGGCTTCAGTGAAGTTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATGCACTGGATAAAGCAGAGACCTGGACAAGGCCTTGAGTGGATTGGAGAGATTAACCCTAGCAATGGTGGTTCTAACTACAATGAGAAGTTCAAGAGCAAGGCCACACTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCAACTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATCACTGTAAAAGCAGAGGCTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 43)
6-O17 경쇄 가변 영역
GATGTTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACCAGCCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTAGATAGTTATGGAAAGACATATTTGAATTGGTTGTTACAGCGGCCAGGCCAGTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAATTGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGTGGATCAGGGACAGATTTCACACTGAAAATCAGCAGAGTGGAGGCTGAGGATTTGGGAATTTATTATTGCTGGCAAGGTACACATTTTCCTCACACGTTCGGCTCGGGGACAAAGTTGGAAATAAAA (SEQ ID NO: 44)
3-G5 중쇄 가변 영역
CAGGTTCAGCTGCAGCAGTCTGGAGCTGAGCTGGCGAGGCCTGGGGCTTCAGTGAAACTGTCCTGCAAGGCTTCTGGCTACACCTTCACAAGCTATGGTATAAGCTGGGTGAAACAGAGAACTGGACAGGGCCTTGAGTGGATTGGAGAGATTTTTCCTAGAAGTAGTAATACTTACTATAATGAGAAGTTCAAGGGCAAGGCCACACTGACTGCAGACAAGTCCTCCAGCACAGTGTACATGGAGTTCCGCAGCCTGACATCTGAGGACTCTGCGGTCTATTTCTGTGCAAGAGAGGGGGGCCTGGCCTGGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA (SEQ ID NO: 45)
3-G5 경쇄 가변 영역
GATGTTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACCAGCTTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTATATACTAATGGAAACACCTATTTGAATTGGTTATTACAGAGGCCAGGCCAGTCTCCAAAACGCCTAATCTATCTGGTGTCTAAATTGGACTCTGGAATCCCTGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTGAGAATCAGCAGAGTGGAGGCTGAGGATTTGGGAGTTTATTACTGCTTGCAGAGTACACATTTTCCATTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAAA (SEQ ID NO: 46)
6-A15 중쇄 가변 영역
GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATGTCCTGTAAGGCTTCTGGATACACAATCACTGACTACTACATGATGTGGTTGAAGCAGAGTCATGGAAAGAGCCTTGAATGGATTGGAGATATTAATCCTTACACTGGTGGTACTAGCTACAACCAGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAATCCTCCAGCACAGCCTACCTGCAGCTCCACAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGAGGGGCCTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 47)
6-A15 경쇄 가변 영역
GATGTTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACCAGCCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTAGATAGTGATGGAAAGACATATTTGAATTGGTTGTTACAGAGGCCAGGCCAGTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAACTGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGTGGATCAGGGACAGATTTCACACTGAAAATCAGCAGAGTGGAGGCTGAGGATTTGGGAGTTTATTATTGCTGGCAAGGTACACATTTTCCGTACACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 48)
10-K10 중쇄 가변 영역
GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATGTCCTGTAAGGCTTCTGGATACACAATCACTGACTACTACATGATGTGGTTGAAGCAGAGTCATGGAAAGAGCCTTGAATGGATTGGAGATATTAATCCTTACACTGGTGGTACTAGCTACAACCAGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCAGCTCAACAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGAGGGGCCTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 49)
10-K10 경쇄 가변 영역
GATGTTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACCAGCCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTAGATAGTGATGGAAAGACATATTTGAATTGGTTGTTACAGAGGCCAGGCCAGTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAACTGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGTGGATCAGGGACAGATTTCACACTGAAAATCAGCAGAGTGGAGGCTGAGGATTTGGGAGTTTATTATTGCTGGCAAGGTACACATTTTCCGTACACGTTCGGAGGGGGGACCAAGCTGGAAATAAAA (SEQ ID NO: 50)
6-P20 중쇄 가변 영역
GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATATCCTGTAAGGCTTCTGGATACACGTTCACTGACTACTACATGAACTGGGTGAAGCAGAGCCATGGCAGGAGCCTTGAGTTGATTGGAGATATTAATCCTAACAATGGTGGTTCTAACTTCAACCAGAAGTTCAGGGGCAAGGCCACATTGACTGTAGACAAGTCCTCCAGCACAGCCTATATGGAGCTCCGCAGCCTGACATCTGAGGACTCTGCAATCTATTACTGTGCAAGAATGGGTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA (SEQ ID NO: 51)
6-P20 경쇄 가변 영역
GATGTTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACCAGCCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTACATAGTGATGGAAAGACATATTTGAATTGGATGTTCCAGAGGCCAGGCCAGTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAACTGGACTCTGGAGTCCCTTACAGGTTCACTGGCGGTGGATCAGGGACAGATTTCACACTGCAAATCAGCAGAGTGGAGACTGAGGATTTGGGAGTTTATTATTGCTGGCAAGGTACACATTTTCCTCGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (SEQ ID NO: 52)
7-O8 중쇄 가변 영역
GAGGTCCAGCTGCAGCAGTCTGGACCTGAACTGGTCAAGCCTGGGGCTTCAGTGAAGATGTCCTGCAAGGCTTCTGGATACACATTCACTGACTACTACATACACTGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAGTACATTGGAGAGATTTATCCTGGAAGTGGTAATACTTACTACAATGGGAAGTTCAGGGGCAAGGCCACACTGACTGCAGACAAGTCCTCCAGCACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTTCTGTGGTAGTGGCTACTTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA (SEQ ID NO: 53)
7-O8 경쇄 가변 영역
GATGTTGTGATGACCCAGACTCCACTCACTTTGTCTGTTACCATTGGACAGCCAGCTTCCATTTCTTGCAAGTCAAGTCAGAGCCTCTTATATAGTAATGGAAAAACCTATTTGAATTGGTTATTACAGAGTCCAGGCCAGTCTCCAAAGCTCCTAATCTATCTGGTGTCTAAACTGGAATCTGGAGTCCCTGACAGATTCAGTGGCAGTGGATCAGGGACAGATTTTACACTGAAACTCAGCAGAGTGGAGGCTGAGGATTTGGGAGTATATTACTGCGTGCAAGGTACACATTTCCCATTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAAA (SEQ ID NO: 54)
토끼 mAb 서열
A11B1_16G7 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGTTCAAAGGTGTCCAGTGTCAGGAGCAACTGGTGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCTTCAATAAGAATTATTGGATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATGCATTTATAATGGTGATGGCAACACATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGGACACGGCCATCTATTTCTGTGCGAGACTACTTAATATGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGG GTAAATAG (SEQ ID NO: 55)
A11B1_16G7 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTCTGGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTGAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATACTGCAGCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGTGGCGTGCAGTGTGACGATGCTGCCACTTACTACTGTCAAAGCTATTATTTTACTAGTGTTAGTAGTTATGGCAATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 56)
A11B1_16E10 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCAGAGTCTCTGGATTCTCCTTCAGTAGCAGTTATTATATGTGTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATGGATCGCATGTATTGGTACTACTCGTGGTAGCACTTACTACGCGACCTGGGCGAAAGGCCGATTCACCATTTCTAAAATCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTGACAGACGCGGACACGGCCACCTATTTCTGTGCGAGAGATGCTACTGGTTATAGGATTAACACGATTGGCCTCTATTTTAATTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 57)
A11B1_16E10 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGCGTTCGAATTGACCCAGACTCCATCCTCCGTGGAGGCTGCTGTGGGAGGCACGCCCACCATCAAGTGCCAGGCCAGTCAGACCATTTACAGTTACTTATCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGAAGCGTCCAAACTGGCCTCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACAGACTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAAAGCTATCATGGTACTGCTAGTACTGAATATAATACTTTCGGCGGGGGGACCGAGGTGGTGGTCAGAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 58)
A11B1_15G10 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGCAGCAGCTGGTGGAGTCCGGGGGAGGCCTGGTCAAGCCTGGGGCAGCCCTGACATTCACCTGCACAGCCTCTGGATTCTCCTTCAGTGGCAATTATTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGTTGGAGTGGATCGCGTGCATTGGTACTATTACTAGTAGGACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATTTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACGTATTTCTGTGCGAGAGGTGCGGTTGTTAGTAGTGGTAATGCTCCCTACTACTTTACCTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 59)
A11B1_15G10 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGCATTCGAATTGACGCAGACTCCATCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTAGTTACTTATCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGGAATCTGGGGTCCCATCGCGGTTTAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTTCTGTCAAAGCTATTATGGTGTTACTTTTAGTGGTTTTGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 60)
A11B1_14H1 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCAAAGCCTCTGGAATCGACTTCAATAACTATTGGATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTTATGTTGGAATTACCGGCCGCACATGGTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAGGCCTCGAGCACGGTGGATCTGAAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGGAATGGTGATGGTGGTATTTATGCTCTTAACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 61)
A11B1_14H1 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCACATTTGCACAAGTGCTGACCCAGACTGCATCGTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAGTTGCCAGTCCAGTCAGAGTGTTTATAATAATAATTGGTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGACATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTGCAGGCGGTTATAGTGGTAATATTTACGTAAATGATTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 62)
A11B1_13G4 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTCTCCTTCAGTAATACCTACTGGGCATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATGAATCCTGCTAGTAGTGGTAGCTCTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCACATGCCCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAAATGGGATACTGCTTTCGATGTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 63)
A11B1_13G4 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGCCGATGTTGTGATGACCCAGACTCCATCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCCAATCTGGAGTCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTGCCACTTACTACTGTCAAAACTATTATGCTATTGATACTTATGGTCATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 64)
A11B1_13C3 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCTTTAGTAGCAACTATCACATCTGCTGGGTCCGCCAGGCTCCAGGAAAGGGGCTGGAGTTGATCGCATGCATTTATGTTGGTGATGGCAGCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAATCCTCGTCGACCACGGTAGCTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGGGAGAATGTTTAACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 65)
A11B1_13C3 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCATATGTGACCCTGTGCTGACCCAGACTCCATCCTCCGTGTCTGCGGCTGTGGGAGTCACAGTCACCATCAACTGCCAGTCCAGTCCGAGTGTTTATAGTAACTACTTATCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTCATCTATCTGGCATCTACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACGTGCAGTGTGACGATGCTGCCACTTACTACTGTGCAGGCACTTATAGTGGTAATATTTGGTCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 66)
A11B1_12F2 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGCAGCAGCTGGTGGAGTCCGGGGGAGGCCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCTTCAGTAGCGGCTATCACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCTTTGGTGTTTATACTGGTACCACTACCTACGCGAGCTGGGCGAAAGGTCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTAACAGTCGCGGACACGGCCACCTATTTCTGTGCGAGAATCAGTGCTGAAAATGGTGGGGACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 67)
A11B1_12F2 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGCAACTACTTTTCTTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCGTCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATTCTGCCACTTACTACTGTCAGTGCACTTATGGTAGTAGTAGTACTGGTTTTGGTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCCCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 68)
A11B1_11D10 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCATGGCCTCTGGAATCGACTTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAGTATATCGGATACATTGATACTGGTGATGATAACACATACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGGACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTGGGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 69)
A11B1_11D10 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGACTCCTACTGCTCTGGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTAGTTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTACAGGGCATCCACTCTAAAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTATTATTGTCAAGCGTATTATCTTAGTAGTAGTATCAGTTATGGTAATACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 70)
A11B1_10F9 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCGTCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCCTCAGTAGCGGGTATGGCATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAGTGGATCGGATACACTGATACTGCTACTGGTACCATTCACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATGGACCTCTGGGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 71)
A11B1_10F9 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTCTGGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGACATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTATTGTCAAAGCTATGCTTATAGTAGTAGTAGCAGTTATGGTAATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 72)
A11B1_7H12 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGGCTCTGGAATCGACTTCAGTAGCAGCTACTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATCGATGGTAGTGATGGTAACACTTACTACGCGAGCTGGGCGAGAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGGCCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTACGAGAGATCTCAGGTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 73)
A11B1_7H12 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGCTGACATTGTGCTGACCCAGACTCCAGCCTCGGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAACTGCCAGGCCAGTCAGAATGTTTATAGTAACAATGCCTTAGCCTGGCATCAGCAGAAACCAGGGCAGCGTCCCAACCTCCTGATCTACAAGGCTTCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTTACTCTCACCATCAGCGACGTGCAGTGTGACGATGCTGCCACTTACTACTGTCTAGGCGAATTTAGTTGTAGTAGTGGTGATTGTTTTGTTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 74)
A11B1_7G12 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCATGGCCTCTGGAATCGACTTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAGTATATCGGATACATTGATACTGGTGATGATAACACATACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGGACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTGGGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 75)
A11B1_7G12 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGACTCCTACTGCTCTGGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTAGTTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTACAGGGCATCCACTCTAAAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTATTATTGTCAAGCGTATTATCTTAGTAGTAGTATCAGTTATGGTAATACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 76)
A11B1_6G4 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGCAGCAGCTGGAGGAGTCCGGGGGAGGCCTGGTCAAGCCTGGAGGAACCCTGACACTCACCTGCAAAGCCTCTGGAGTCGCCCTCAATCCCTACTACTATATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCGTGGATGCTGATAGTAGTGGTAGCACTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGAAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGAATCGGTTGACTATAGTTCTGTTGGTATTGGCTATGTACATGGTACGGATGGCTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 77)
A11B1_6G4 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGCCGACATCGTGGTGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGCAACTACTTTTCTTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCGTCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAATGCACTTACGGTAGAAGTAATAGTAATTTTTTTTATGGTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 78)
A11B1_6F9 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCCGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCCTCCCTGACACTCACCTGCACAGCCTCTGGATCCTCCTTCAGTAGTACCTACTGGAACTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTAATGCTGGTAGTGGTACCACTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCGTCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTACGAGAGATAGTGATGGTCGTTTTAGTAGTGGCTACTATTTTAACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 79)
A11B1_6F9 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTGCATCCCCTGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGTCAGTCCAGTCAGAGTGTTTATGATAACAACTGGTTAGCCTGGTATCAGCAAAAACCAGGGCAGCCTCCCAAACTCTTGATCGACGATGCATCCAAATTGACATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACGCAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTGCCACTTACTACTGTCAAGGCGCTTATTATAGTAGTGGTTGGTACTGGGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 80)
A11B1_6C7 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGCAGCAGCTGGAGGAGTCCGGGGGAGGCCTGGTCAAGCCTGGAGGAACCCTGACACTCACCTGCAAAGCCTCTGGAATCGACTTCAGTAGCTACTACTACATGTGTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTTGATCGTATGTATTTATACTAGTAGTGGTGGCACATGGTACGCGAGCTGGGTGAATGGCCGACTCACCATCTCCAGAAGCACCAGCCTAAACACGGTGGATCTGAAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCCAGAGGGGTTTATTCTGGTAGTAGTGATTATCCAACTCGGTTGGATCTCTGGGGCCAGGGCACCCTGGTCACCGTCTCCTTAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 81)
A11B1_6C7 경쇄
ATGGACACGAGCACCTCCACTGCGCTCCTGGGGCTCCTGCTGCTCTGGCTCACAGGTGCCAGATGTGCCATCGAGATGACCCAGTCTCCACCCTCCCTGTCTGCATCTGTGGGAGAAACTGTCAGGATTAGGTGCCTGGCCAGTGAGGACATTTACAGTGGTATATCCTGGTACCAACAGAAGCCAGAGAAACCTCCTACACTCCTGATCTCTGGTGCATCCAATTTAGAATCTGGGGTCCCACCACGGTTCAGTGGCGGTGGATCCGGGACAGATTACACCCTCACCATCGGCGGCGTGCAGGCTGAAGATGTTGCCACCTACTACTGTCTAGGCGGTTATAGTTTCAGTAGTACCGGTTTGACTTTTGGAGCTGGCACCAAGGTGGAAATCAAACGTGATCCAGTTGCGCCTTCTGTCCTCCTCTTCCCACCATCTAAGGAGGAGCTGACAACTGGAACAGCCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 82)
A11B1_6B6 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGCAACATCTGGTGGAGTCCGGGGGAGGCCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCTTCACTACCGGCTATCACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGTTTTGGTGTTTATACTAGTACCACTACCTACGCGAGCTGGGCGAAAGGTCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTAACAGTCGCGGACACGGCCACCTATTTCTGTGCGAGAATCAGTGCTGAAGATGGTGGGGACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 83)
A11B1_6B6 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCACGTGCCAGGCCAGTCAGAGCATTAGCAACTACTTTTCTTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCGTCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATTCTGCCACTTACGCCTGTCAGTGCACTTATGGTAGTAGTAGTACTGGTTTTGGTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 84)
A11B1_5F7 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCAAAGCCTCTGGATTCTCCTTCAGTAGTTACTTCTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGAGCGCATGCATCTATGGTGATAGTAGTGGTAGTAGTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGTTATGGTAGTAGTAGTTATTACTACTCTAATTTATGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 85)
A11B1_5F7 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCATATGTGACCCTGTGATGACCCAGACTCCATCTTCCACGTCTGCGGCTGTGGGAGGCACAGTCACCATCAGTTGCCAGTCCAGTCAGAGTGTTTATAATAACAACTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAACGCCTGATCTACGAATCATCCAAACTGGCATCTGGGGTCCCATCGCGGTTCAGAGGCAGTGGATCTGGGGCACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTCTAGGCGCATATTATACTACTCTTGATTTCGGCGGAGGGACCGAGGTGGTGGTCAGAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 86)
A11B1_5D7 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGGAGCAGTTGGTGGAGTCCGGGGGAGGCCTGGTCCAGCCTGAGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTCGACTTCAGTAGCAATGCAATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTTATAATGGTGATGGCAGCACATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCCAAGACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGGTCTCTCTAATTGGAATAGGGATAACTTATGGGGCCCTGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 87)
A11B1_5D7 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGCCACCATCAACTGCCAGGCCAGTCAGAGTCTTTATAGTCCCAAGAATTTAGCCTGGTATCAGCAGACACCAGGGCAGCCTCCCAAGCTCCTGATCTATTCTGCATCGAAACTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTGCAATTTACTACTGTCAAGGCGAATTTAGTTGTACTACTGCTGCTTGTTTTGCTTTTGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 88)
A11B1_5A7 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCTTTGGAGGAGTCCGGGGGAGGCCTGGTCCAGCCTGAGGGATCCCTGACACTCGCCTGCACAGCTTCGGGATTCTCCTTCAGTAGCTACTACTACATCTGCTGGGTCCGCCAGGCTCCAGGGACGGGGCTGGAGTGGATCGGATGCATTAATACTGGTAGTGATGACACTCACTACGCGAGCTGGTTGAAAGGCCGATTCACCTTCTCCAAGGCCTCGTCGACCACGTTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGATCATCTGGTAGTAGTGATGATGCTTATGATCTCTGGGGCCCAGGCACCCTGGTCACTGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 89)
A11B1_5A7 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGATGTTGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCGCAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTGGTAGTAATTTAGCCTGGTATCAGCACAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATTTTGCATCCAGCCTGGCATCTGGGGTCTCGTCGCGGTTCAAGGGCGGTAGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCACTGTACTTATTATCCTCTTAGTTATGTTACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 90)
A11B1_4E1 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGACATCCCTGACACTCTCCTGCACAGCCTCTGGATTCTCCTTCGGTAGCTATTATTATATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTGATGTTGGTAGTAGTGGTGACACATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATACTGCTGCTGGTGGTTTTGGTAATTTGGAATTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 91)
A11B1_4E1 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGCATTCGAATTGACCCAGACTCCATCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTTACAGCTACTTTTCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATTTACCAGGCATCCACTCTGGCTTCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAAAACAATTATGGTAGGGGTAGTGGTAGTTATTTTTTTGGTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 92)
A11B1_3H9 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCAAAGCCTCTGGAATCGACTTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAGTATATCGGATACATTGATACTGGTAGTGGTAGCACTTACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCATGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGGACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTGGGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 93)
A11B1_3H9 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGACTCCTACTGCTCTGGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTAGTTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGACTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTATTATTGTCATACCTATTATCTTAGTAGTAGTATCAGTTATGGTAATACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 94)
A11B1_3G2 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGAGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTCTCCTTCAGTAGCATCTACTGGATTTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCACTACTGTTGTCAAAAGTGGTAGAACTTACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGAATTTGTTGATGGTGGTGGTAGTAGTGGTAGGGACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 95)
A11B1_3G2 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCAGATGTGCCTATGATATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTAGGGACTTATCCTGGTATCAGCAGAAACCTGGACAGCCTCCCAAGCGCCTAATCTACAAGGCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAACAGGGTTATAGTAGTATTGATGTTGATAATGATTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 96)
A11B1_3B1 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGGCCTGGTCAAGCCTGAGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTCGACCTCAGTAGCGGCTATGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTTATGCTGATTATAGTGGTAGCACATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCCAGCAGCACCAGCCTAAACACGGTGGATCTGAAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCCAGAGGGGCTACTGGTAATGGTGGTTATGGATACTACTTTAACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 97)
A11B1_3B1 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTCTGGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACCATCAAGTGTCAGGCCAGTCAGAACATTAATAGCGGCTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAAGGCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAAACCTATTATTATAGTAGTAGTAGTAGTGATAATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 98)
A11B1_2D3 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCTTCTGGATTCTCCTTCAGTAGCAGTTATTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGTATTTATGGTGGTAGTAGTGGTAACATTGCCTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATATTCCTAGTGATGCTTTCACCTTAGACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 99)
A11B1_2D3 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAAGCACAGTCACCATCAATTGCCAGGCCAGTCAGAGTGTTTATAAAGACAACAATTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAAGGCTTCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGAAGATGCTGCCACTTACTACTGTCAAGGCGAATTCAGTTGTGGTAGTGCTGATTGTATTGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 100)
A11B1_2A7 중쇄
ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCAAAGGCTCTGGAATCGACTTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAGTATATCGGATACATTGATACTGGTTATGGTAGCACTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAGACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGGACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTGGGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG (SEQ ID NO: 101)
A11B1_2A7 경쇄
ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTGGCTCCCAGGTGCCACATTTGCAGCCGTGCTGACCCAGACTCCGGCTTCCACGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGTCAGTCCAGTCAGAGCGTGTATCGTAGCAACTGGTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGATGTATTTAATTTGGCATCTGGGGTCCCATCCCGGTTCAAGGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGCCGATGCTGCCACTTACTACTGTCAAGGCAGTTATTATAGTGGTAATTGGTACAGTGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG (SEQ ID NO: 102)
항-α11β1 단일클론 항체의 단백질 서열
래트 mAb 서열
신호 펩티드-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4
79E3E3 중쇄 가변 영역
MDWLWNLLFLMVVAQSAQAQIQLVQSGPEVKKPGESVKISCKASGYTFTDYAMNWVKQAPGNGLKWMGWINTQTGKPTYADDFKQRFVFSLETSARTTYLQINNLNIEDTATYFCTRLGTGNTKGFAYWGQGTLVTVSS (SEQ ID NO: 145)
79E3E3 경쇄 가변 영역
MESQTHVLISLLLCVSGTCGDILINQSPASLTVSAGERVTMSCKSSQSLLYSENNQDYLAWYQQKPGQFPKLLIYGASNRHTGVPDRFTGSGSGTDFTLTISSVQAEDLADYYCEQTYRYPFTFGSGTKLEIK (SEQ ID NO: 146)
24E4G6 중쇄 가변 영역
MELELSLIFIFSLLKDVQCEVQLVESGGSLVQPGGSLKLSCVASGYTFSNYWMDWVRQSPGKSLEWIGEINTDGRRTNYAPSIKDRFTISRDNAKSTLYLQMSNVKSDDTAIYYCTILRVYPHYFDYWGQGVMVTVSS (SEQ ID NO: 147)
24E4G6 경쇄 가변 영역
MMSPAQFLFLLMLWIQEARGDVVMTQTPPSLSVAIGQSVSISCKSSQSLVYSDGETYLHWFLQSPGRSPKRLIYHVSNLGSGVPDRFSGTGSLTDFTLRISRVEAEDLGVYYCAQTTHFPPTFGAGTKLELK (SEQ ID NO: 148)
8H8E9 중쇄 가변 영역
MAVLVLLLCLVTFPSCALSQVQLKESGPGLVQPSQTLSLTCTVSGFSLTSNSVSWVRQAPGKGLEWMGAIWSGGSTDYNSALKSRLSISRDTSKSQVFLKMNSLQTEDTAIYFCTRSHWEPFDYWGQGVMVTVSS (SEQ ID NO: 149)
8H8E9 경쇄 가변 영역
MESQTQALISLLLWVYGTCGDIVMTQSPFSLAVSEGEMVTINCKSSQGLLSSGNQKNYLAWYQQRPGQSPKLLIYYASTRQSGVPDRFIGGGSGTDFTLTISDVQAEDLADYYCLQHYSYPPTFGSGTKLEIK (SEQ ID NO: 150)
6E5C11 중쇄 가변 영역
MAVLVLLLCLVTFPSCALSQVQLRESGPGLVQPSQTLSLTCTVSGFSLTSNSVTWVRQPPGKGLEWMGAIWSDGSTDYNSTLKSRLSISRDTSKSQVFLKMSSLQTEDTAIYFCTRSHWEPFDYWGQGVMVTVSS (SEQ ID NO: 151)
6E5C11 경쇄 가변 영역
MESQTQALISLLLWVYGTCGDIVMTQSPLSLAVSEGETVTMNCKSSQSLFSSGNQKNYLAWYQQKPGQSPKLLIYYASTRQSGVPDRFIGSGSGTDFTLTISDVQTEDLADYYCLQHYNYPPTFGSGTKLEIK (SEQ ID NO: 152)
7D8B10 중쇄 가변 영역
MDLRLTYVFIVAILKGVLCEVKLEESGGGLVQPGMSVKLSCATSGFIFSDYWMEWVRQAPGKGLEWVAEIRNKANNYATYYGKSMKGRFTISRDDSKSIVYLQVNSIRSEDTAIYYCAPNFDYWGQGVMVTVSS (SEQ ID NO: 153)
7D8B10 경쇄 가변 영역
MSPVQSLFLLLLWILGTHGDVVLTQTPPTLSATIGQSVSISCRSSQSLLHSTGNTYLNWLLQRPGQPPQLLIYLVSRLESGVPNRFSASGSGTDFTLKISGIEAEDLGVYYCVQSSHTPYTFGTGTKLELK (SEQ ID NO: 154)
18E10F10 중쇄 가변 영역
MDIRLSLVFLVLFMKGVQCEVQLVESGGGLVQPGRSLKLSCAASRFTFSDYNMAWVRQAPKKGLEWVATIYHDDSGSYYRDSVKGRFTISRNNAKSTLYLQMDSLRSEDMATYYCARHNNGFDYWGQGVMVTVAS (SEQ ID NO: 155)
18E10F10 경쇄 가변 영역
MKWPVRLLVLFFWIPASGGDVVMTQTPVSLPVRLGGQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPQLLINRVSNRFSGVPDRFSGSGSGTDFTLKINRVEPEDLGDYYCLQSTHFPLTFGSGTKLETK (SEQ ID NO: 156)
40G10H11 중쇄 가변 영역
MDIRLSLGFLVLFIKGDQCAVQLVESGGGLVQPGRSLKLSCAASRITFTDYYMAWVRQAPTKGLEWVATISSDGGDTFYRDSVKGRFTISRDNAKSTLYLQMVSLRSEDTATYYCSTDRGAQFGYWGQGTLVTVSS (SEQ ID NO: 157)
40G10H11 경쇄 가변 영역
MAPVQLLGLLLIWLPAMRCDIQMTQSPSFLSASVGDRVSINCKASQNVHENLNWYQQKLGEAPKRLIYNTNNLQTGIPSRFSGSGSGADYTLTISSLQPEDFATYFCLQHNAFPYTFGPGTKLELK (SEQ ID NO: 158)
마우스 mAb 서열
FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4
9-G05 중쇄 가변 영역
EVQLQQSGPELVKPGASVKIPCKASGYTFPDYNMDWVKQSHGKSLEWIGYINPDNGGTIYNQKFKGKATLTVDKSSSTAYMELRSLTSEDTAVYYCARLDSSGYGYYAMDYWGQGTSVTVSS (SEQ ID NO: 103)
9-G05 경쇄 가변 영역
DIVLTQSPASLAVSLGQRATISCRASESVDNYGISFMHWYQQKPGQPPKLLIYRASNLDSEIPARFSGSGSRTDFTLTIDPVETDDVATYYCQQSYKDPRTFGGGTKLEIK (SEQ ID NO: 104)
8-P20 중쇄 가변 영역
KVMLVESGGALVKPGGSLKLSCVASGFTFSNYAMSWVRQTPEKRLEWVATISSGGYYTYYPDSVKGRFTISRDNARNTLFLQMSSLRSEDTAMFYCAREDDYGRYSYTMDYWGQGTSVTVSS (SEQ ID NO: 105)
8-P20 경쇄 가변 영역
DVVMTQTPLSLPVSLGDQVSISCRCSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKISNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPYTFGGGTELEIK (SEQ ID NO: 106)
8-G15 중쇄 가변 영역
EVQLQQSGPELVKPGASVRISCKASGYTFTDYYIHWVKQKPGQGLECIGEIYPGTDNTYYSKKFRGKATLTADKSSDTAYMQLSSLTSEDSAVYFCARGDYYRGYFDVWGAGTTVTVSS (SEQ ID NO: 107)
8-G15 경쇄 가변 영역
DVVMTQTSLTLSVTIGQPASISCKSSQSLLHSNGKTYLNWLLQRPGQSPKFLIYLVSKLESGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCLQSTHFPWTFGGGTKLEIK (SEQ ID NO: 108)
8-I14 중쇄 가변 영역
EVQLQQSGPELVKPGASVKKSCKASGYTFTDYYMHWVKQKPGQGLEWIGKIYPGSGNTHYNEKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCATNYYGYRAMNYWGQGSSVTVSS (SEQ ID NO: 109)
8-I14 경쇄 가변 영역
DIHLTQSPSSLSASLGERISLTCRASQDIYISLNWFQQKPDGTIKLLIYGTSSLDSGVPKRFSGSRSGSDYSLTISSLESEDFADYYCLQYASSPYTFGGGTKLEIK (SEQ ID NO: 110)
9-E16 중쇄 가변 영역
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMHWVKQKPGQGLEWIGEIYPGSGNPYYNEKFKGKATLTADKSSSSAYMQLSSLTSEDSAVYFCARTSYGRVGTGFAYWGQGTLVTVSA (SEQ ID NO: 111)
9-E16 경쇄 가변 영역
NFVMTQTPLSLPVSLGDQASISCRSSQSLLHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKINRVETEDLGIYFCSQSSHVPTFGAGTKLELK (SEQ ID NO: 112)
8-J17 중쇄 가변 영역
QVQLQQSGAELAKPGASVKMSCKASGYTFTNYWMHWVKQRPGQGLEWIGYINPNNGYTEYNQRFKDKATLTADRSSTTAYMQLSSLTSEDSAVYYCARSDIITTDYWGQGTTLTVSS (SEQ ID NO: 113)
8-J17 경쇄 가변 영역
DVVMTQTPLSLPVSLGDQASISCRSSQSLVYSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPWTFGGGTKLEIK (SEQ ID NO: 114)
9-B11 중쇄 가변 영역
QVQLQQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVQQRPGQGLEWIGVIDPSDSYTNYNQKFKGKATLTVDTSSSSAYMQLSSLTSEDSAVYYCARDDVAMDYWGQGTSVTVSS (SEQ ID NO: 115)
9-B11 경쇄 가변 영역
DIVVTQSPASLAVSLGQRATISCRASESVDSYGNSFIHWYQQKPGQPPKLLIYRASNLKSGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPYTFGGGTKLEIK (SEQ ID NO: 116)
SEQ ID NO: 117-144의 경우, CDR3 은 굵게 밑줄이 그어진 텍스트로 표시된다.
6-O12 중쇄 가변 영역
EVKLEESGGGLVQPGGSMKLSCAASGFTFSDAWMDWVRQSPEAGLEWVAEIRNKAHNPATYYAESVKGRFTISRDDSKSSVYLQMNSLRAEDTGIYY CTLVAPDAMDYW GQGTSVTVSS (SEQ ID NO: 117)
6-O12 경쇄 가변 영역
DIVMSLSPSSLAVSVGEKVTMSCKSSQSLLYSRNQKNYLAWYQQKPGQSPKLLIYWASTRASGVPDRFTGSGSGTDFTLTISSVKAEDLAVYY CQQYYSYPYTF GGGTKLEIK (SEQ ID NO: 118)
10-L15 중쇄 가변 영역
QVQLQQSGPELVRPGASVKMSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIDPSNSETWLNQKFKDKATLNVDKSSNTAYMQLSSLTSEDSAVYY CARYDGYYDYW GQGTTLTVSS (SEQ ID NO: 119)
10-L15 경쇄 가변 영역
NIVLTQSPASLAVSLGQRATISCRASESVDSYGNSFMHWYQQKPGQPPKLLIYLASNVESGVPARFSGSGSRTDFTLTIDPVEADDAATYY CQQNNEDPWTF GGGTKLEIK (SEQ ID NO: 120)
7-H14 중쇄 가변 영역
QVQLQQPGAELVRPGASVKLSCKPSGYTFTSYWMNWVKQRPGQGLEWIGMIDPSDSETHYNQMFKDKATLTVDKSSNTAYMQLSSLTSEDSAVYY CAQIYYAYDKAYW GQGTLVTVSA (SEQ ID NO: 121)
7-H14 경쇄 가변 영역
DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSSHQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFSLTISSVKAEDLAVYY CQEYYSWTF GGGTKLEIK (SEQ ID NO: 122)
6-B21 중쇄 가변 영역
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGKSLEWIGDINPHNGGTSFIQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYY CAPLGRKEGFAYW GQGTLVTVSA (SEQ ID NO: 123)
6-B21 경쇄 가변 영역
DTVLTQSPASLVVSLGQRATISCRASKSVSTSGYSYMHWYQQKPGQPPKLLIYLASNLESGVPARFSGSGSGTAFTLNIHPVEEEDAATYY CQHSRELPYTF GGGTKLEIK (SEQ ID NO: 124)
10-F23 중쇄 가변 영역
QVTLKESGPGILQPSQTLSLTCSFSGFSLSTFAMGVGWIRQPSGKGLEWLAHIWWDDDKYYNPALKSRLTISKDTSKNHVFLKIANVDTADTATYY CARMPLTFYFDYW GQGTTLTVSS (SEQ ID NO: 125)
10-F23 경쇄 가변 영역
DVLLTQTPLSLPVSLGDQASISCRSSQSIVHSNGHTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYY CFQGSHVPFTF GGGTKLEIK (SEQ ID NO: 126)
6-A12 중쇄 가변 영역
QVTLKESGPGILQPSQTLSLTCSFSGFSLRTFAMGVGWIRQPSGKGLEWLAHIWWDDDKYYNPALKSRLTISKDTSKNQVFLKIANVDTADTATYY CARMPLTFYFDYW GQGTTLTVSS (SEQ ID NO: 127)
6-A12 경쇄 가변 영역
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSTRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYY CFQGSHVPFTF GGGTKLEIK (SEQ ID NO: 128)
6-M8 중쇄 가변 영역
QVQLQQPGAELVMPGASVKLSCKASGYTFTNYWMHWVKQRPGQGLEWIGEIDPSDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYY CTRQGSTYAW GQGTSVTVSS (SEQ ID NO: 129)
6-M8 경쇄 가변 영역
DIVMTQAAFSNPVTLGTSASISCRSSKSLLHSNGITYLYWYLQKPGQSPQLLIYQMSNLASGVPDRFSSSGSGTDFTLRISRVEAEDVGVYY CAQNLELPPTF GGGTKLEIK (SEQ ID NO: 130)
2-A3 중쇄 가변 영역
EVQLQQSGPELVKPGASVKMSCKASGYTFTDYYMMWVKQSHGKSLEWIGDINPYNGGSSYNPKFKGRATLTVDKSSSTAYMQLNSLTSEDSAVYY CARGTYW GQGTLVTVSA (SEQ ID NO: 131)
2-A3 경쇄 가변 영역
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSAGKTYLNWLLQRPGQSPKRLMYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYY CWQGTHFPYTF GGGTKLEIK (SEQ ID NO: 132)
6-O17 중쇄 가변 영역
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWIKQRPGQGLEWIGEINPSNGGSNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYH CKSRGYW GQGTTLTVSS (SEQ ID NO: 133)
6-O17 경쇄 가변 영역
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSYGKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLGIYY CWQGTHFPHTF GSGTKLEIK (SEQ ID NO: 134)
3-G5 중쇄 가변 영역
QVQLQQSGAELARPGASVKLSCKASGYTFTSYGISWVKQRTGQGLEWIGEIFPRSSNTYYNEKFKGKATLTADKSSSTVYMEFRSLTSEDSAVYF CAREGGLAWFAYW GQGTLVTVSA (SEQ ID NO: 135)
3-G5 경쇄 가변 영역
DVVMTQTPLTLSVTIGQPASISCKSSQSLLYTNGNTYLNWLLQRPGQSPKRLIYLVSKLDSGIPDRFSGSGSGTDFTLRISRVEAEDLGVYY CLQSTHFPFTF GSGTKLEIK (SEQ ID NO: 136)
6-A15 중쇄 가변 영역
EVQLQQSGPELVKPGASVKMSCKASGYTITDYYMMWLKQSHGKSLEWIGDINPYTGGTSYNQKFKGKATLTVDKSSSTAYLQLHSLTSEDSAVYY CARGAYW GQGTTLTVSS (SEQ ID NO: 137)
6-A15 경쇄 가변 영역
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYY CWQGTHFPYTF GGGTKLEIK (SEQ ID NO: 138)
10-K10 중쇄 가변 영역
EVQLQQSGPELVKPGASVKMSCKASGYTITDYYMMWLKQSHGKSLEWIGDINPYTGGTSYNQKFKGKATLTVDKSSSTAYMQLNSLTSEDSAVYY CARGAYW GQGTTLTVSS (SEQ ID NO: 139)
10-K10 경쇄 가변 영역
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYY CWQGTHFPYTF GGGTKLEIK (SEQ ID NO: 140)
6-P20 중쇄 가변 영역
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGRSLELIGDINPNNGGSNFNQKFRGKATLTVDKSSSTAYMELRSLTSEDSAIYY CARMGYW GQGTLVTVSA (SEQ ID NO: 141)
6-P20 경쇄 가변 영역
DVVMTQTPLTLSVTIGQPASISCKSSQSLLHSDGKTYLNWMFQRPGQSPKRLIYLVSKLDSGVPYRFTGGGSGTDFTLQISRVETEDLGVYY CWQGTHFPRTF GGGTKLEIK (SEQ ID NO: 142)
7-O8 중쇄 가변 영역
EVQLQQSGPELVKPGASVKMSCKASGYTFTDYYIHWVKQKPGQGLEYIGEIYPGSGNTYYNGKFRGKATLTADKSSSTAYMQLSSLTSEDSAVYF CGSGYFDYW GQGTTLTVSS (SEQ ID NO: 143)
7-O8 경쇄 가변 영역
DVVMTQTPLTLSVTIGQPASISCKSSQSLLYSNGKTYLNWLLQSPGQSPKLLIYLVSKLESGVPDRFSGSGSGTDFTLKLSRVEAEDLGVYY CVQGTHFPFTF GSGTKLEIK (SEQ ID NO: 144)
토끼 mAb 서열
A11B1_16G7 중쇄
METGLRWLLLVAVFKGVQCQEQLVESGGDLVKPGASLTLTCTASGFSFNKNYWMCWVRQAPGKGLEWIGCIYNGDGNTYYASWVNGRFTISKTSSTTVTLQMTSLTVADTAIYFCARLLNMWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 159)
A11B1_16G7 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGGTVTIKCQASESIGNALAWYQQKPGQPPKLLIYTAATLASGVPSRFSGSGSGTEFTLTISGVQCDDAATYYCQSYYFTSVSSYGNAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 160)
A11B1_16E10 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCRVSGFSFSSSYYMCWVRQAPGKGLEWIACIGTTRGSTYYATWAKGRFTISKISSTTVTLQMTSLTDADTATYFCARDATGYRINTIGLYFNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 161)
A11B1_16E10 경쇄
MDTRAPTQLLGLLLLWLPGARCAFELTQTPSSVEAAVGGTPTIKCQASQTIYSYLSWYQQKPGQPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISDLECADAATYYCQSYHGTASTEYNTFGGGTEVVVRGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 162)
A11B1_15G10 중쇄
METGLRWLLLVAVLKGVQCQQQLVESGGGLVKPGAALTFTCTASGFSFSGNYWICWVRQAPGKGLEWIACIGTITSRTYYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARGAVVSSGNAPYYFTLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 163)
A11B1_15G10 경쇄
MDTRAPTQLLGLLLLWLPGARCAFELTQTPSSVEAAVGGTVTIKCQASQSISSYLSWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTEFTLTISDLECADAATYFCQSYYGVTFSGFAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 164)
A11B1_14H1 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCKASGIDFNNYWITWVRQAPGKGLEWIACIYVGITGRTWYANWAKGRFTISKASSTVDLKMTSLTAADTATYFCARNGDGGIYALNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 165)
A11B1_14H1 경쇄
MDTRAPTQLLGLLLLWLPGATFAQVLTQTASSVSAAVGGTVTISCQSSQSVYNNNWLAWYQQKPGQPPKLLIYRASTLTSGVPSRFKGSGSGTQFTLTISDLECDDAATYYCAGGYSGNIYVNDFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 166)
A11B1_13G4 중쇄
METGLRWLLLVAVLKGVQCQEQLEESGGDLVKPGGSLTLTCKASGFSFSNTYWACWVRQAPGKGLEWIACMNPASSGSSYYASWAKGRFTISKTSSTTVTLHMPSLTAADTATYFCAKWDTAFDVWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 167)
A11B1_13G4 경쇄
MDTRAPTQLLGLLLLWLPGARCADVVMTQTPSSVEAAVGGTVTIKCQASQSISSYLAWYQQKPGQPPKLLIYGASNLESGVPSRFKGSGSGTEYTLTISGVQCDDAATYYCQNYYAIDTYGHAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 168)
A11B1_13C3 중쇄
METGLRWLLLVAVLKGVQCQEQLEESGGDLVKPGASLTLTCTASGFSFSSNYHICWVRQAPGKGLELIACIYVGDGSTYYASWAKGRFTISKSSSTTVALQMTSLTAADTATYFCGRMFNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 169)
A11B1_13C3 경쇄
MDTRAPTQLLGLLLLWLPGAICDPVLTQTPSSVSAAVGVTVTINCQSSPSVYSNYLSWYQQKPGQPPKLLIYLASTLASGVPSRFKGSGSGTQFTLTISDVQCDDAATYYCAGTYSGNIWSFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 170)
A11B1_12F2 중쇄
METGLRWLLLVAVLKGVQCQQQLVESGGGLVKPGASLTLTCTASGFSFSSGYHMCWVRQAPGKGLEWIACFGVYTGTTTYASWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCARISAENGGDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 171)
A11B1_12F2 경쇄
MDTRAPTQLLGLLLLWLPGARCDVVMTQTPASVEAAVGGTVTIKCQASQSISNYFSWYQQKPGQPPKLLIYRASTLASGVPSRFSGSGSGTEFTLTISDLECADSATYYCQCTYGSSSTGFGFGGGTEVVVKGDPVAPTVPIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 172)
A11B1_11D10 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCMASGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGDDNTYYANWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCAKGGAIDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 173)
A11B1_11D10 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGGTVTIKCQASQSISSYLAWYQQKPGQRPKLLIYRASTLKSGVPSRFKGSGSGTEYTLTISDLECADAATYYCQAYYLSSSISYGNTFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 174)
A11B1_10F9 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCTASGFSLSSGYGMCWVRQAPGKGLEWIGYTDTATGTIHYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCAKGGAMDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 175)
A11B1_10F9 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGGTVTIKCQASQSISSYLAWYQQKPGQPPKLLIYRTSTLASGVPSRFKGSGSGTEYTLTISDLECADAATYYCQSYAYSSSSSYGNAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 176)
A11B1_7H12 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCTGSGIDFSSSYWICWVRQAPGKGLEWIACIDGSDGNTYYASWARGRFTISKTSSTTVTLQMASLTAADTATYFCTRDLRLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 177)
A11B1_7H12 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVLTQTPASVSAAVGGTVTINCQASQNVYSNNALAWHQQKPGQRPNLLIYKASTLASGVPSRFKGSGSGTQFTLTISDVQCDDAATYYCLGEFSCSSGDCFVFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 178)
A11B1_7G12 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCMASGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGDDNTYYANWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCAKGGAIDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 179)
A11B1_7G12 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGGTVTIKCQASQSISSYLAWYQQKPGQRPKLLIYRASTLKSGVPSRFKGSGSGTEYTLTISDLECADAATYYCQAYYLSSSISYGNTFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 180)
A11B1_6G4 중쇄
METGLRWLLLVAVLKGVQCQQQLEESGGGLVKPGGTLTLTCKASGVALNPYYYMCWVRQAPGKGLEWIACVDADSSGSTYYASWAKGRFTISKTSSTTVTLKMTSLTAADTATYFCARESVDYSSVGIGYVHGTDGLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 181)
A11B1_6G4 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVVTQTPSSVSAAVGGTVTIKCQASQSISNYFSWYQQKPGQPPKLLIYRASTLASGVPSRFKGSGSGTEFTLTISDLECADAATYYCQCTYGRSNSNFFYGFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 182)
A11B1_6F9 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCTASGSSFSSTYWNCWVRQAPGKGLEWIACINAGSGTTYYASWAKGRFTVSKTSSTTVTLQMTSLTAADTATYFCTRDSDGRFSSGYYFNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 183)
A11B1_6F9 경쇄
MDTRAPTQLLGLLLLWLPGATFAQVLTQTASPVSAAVGGTVTINCQSSQSVYDNNWLAWYQQKPGQPPKLLIDDASKLTSGVSSRFKGSGSGTQFTLTISGVQCDDAATYYCQGAYYSSGWYWAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 184)
A11B1_6C7 중쇄
METGLRWLLLVAVLKGVQCQQQLEESGGGLVKPGGTLTLTCKASGIDFSSYYYMCWVRQAPGKGLELIVCIYTSSGGTWYASWVNGRLTISRSTSLNTVDLKMTSLTAADTATYFCARGVYSGSSDYPTRLDLWGQGTLVTVSLGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 185)
A11B1_6C7 경쇄
MDTSTSTALLGLLLLWLTGARCAIEMTQSPPSLSASVGETVRIRCLASEDIYSGISWYQQKPEKPPTLLISGASNLESGVPPRFSGGGSGTDYTLTIGGVQAEDVATYYCLGGYSFSSTGLTFGAGTKVEIKRDPVAPSVLLFPPSKEELTTGTATIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 186)
A11B1_6B6 중쇄
METGLRWLLLVAVLKGVQCQQHLVESGGGLVKPGASLTLTCTASGFSFTTGYHMCWVRQAPGKGLEWIACFGVYTSTTTYASWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCARISAEDGGDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 187)
A11B1_6B6 경쇄
MDTRAPTQLLGLLLLWLPGARCDVVMTQTPASVEAAVGGTVTITCQASQSISNYFSWYQQKPGQPPKLLIYRASTLASGVPSRFSGSGSGTQFTLTISDLECADSATYACQCTYGSSSTGFGFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 188)
A11B1_5F7 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCKASGFSFSSYFWICWVRQAPGKGLEWSACIYGDSSGSSYYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCASYGSSSYYYSNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 189)
A11B1_5F7 경쇄
MDTRAPTQLLGLLLLWLPGAICDPVMTQTPSSTSAAVGGTVTISCQSSQSVYNNNYLAWYQQKPGQPPKRLIYESSKLASGVPSRFRGSGSGAQFTLTISDLECDDAATYYCLGAYYTTLDFGGGTEVVVRGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 190)
A11B1_5D7 중쇄
METGLRWLLLVAVLKGVQCQEQLVESGGGLVQPEGSLTLTCKASGFDFSSNAMCWVRQAPGKGLEWIACIYNGDGSTYYASWVNGRFTISKTSSTTVTLQMTSLTAADTATYFCARGLSNWNRDNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 191)
A11B1_5D7 경쇄
MDTRAPTQLLGLLLLWLPGATFAQVLTQTPSSVSAAVGGTATINCQASQSLYSPKNLAWYQQTPGQPPKLLIYSASKLASGVPSRFKGSGSGTQFTLTISGVQCDDAAIYYCQGEFSCTTAACFAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 192)
A11B1_5A7 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGGLVQPEGSLTLACTASGFSFSSYYYICWVRQAPGTGLEWIGCINTGSDDTHYASWLKGRFTFSKASSTTLTLQMTSLTAADTATYFCARSSGSSDDAYDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 193)
A11B1_5A7 경쇄
MDTRAPTQLLGLLLLWLPGARCDVVMTQTPASVSEPVGGAVTIKCQASQSIGSNLAWYQHKPGQPPKLLIYFASSLASGVSSRFKGGRSGTQFTLTISDLECADAATYYCHCTYYPLSYVTFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 194)
A11B1_4E1 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGTSLTLSCTASGFSFGSYYYMCWVRQAPGKGLEWIACIDVGSSGDTYYASWVNGRFTISKTSSTTVTLQMTSLTAADTATYFCARDDTAAGGFGNLELWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 195)
A11B1_4E1 경쇄
MDTRAPTQLLGLLLLWLPGARCAFELTQTPSSVSEPVGGTVTIKCQASQSIYSYFSWYQQKPGQPPKRLIYQASTLASGVPSRFKGSGSGTDFTLTISDLECADAATYYCQNNYGRGSGSYFFGFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 196)
A11B1_3H9 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCKASGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGSGSTYYANWAKGRFTISKTSSTMVTLQMTSLTVADTATYFCAKGGAIDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 197)
A11B1_3H9 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGGTVTIKCQASQSISSYLAWYQQKPGQRPKLLIYRASTLASGVPSRFKGSGSGTDYTLTISDLECADAATYYCHTYYLSSSISYGNTFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 198)
A11B1_3G2 중쇄
METGLRWLLLVAVLKGVQCQEQLEESGGDLVKPEGSLTLTCKASGFSFSSIYWICWVRQAPGKGLEWIACTTVVKSGRTYYANWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCAREFVDGGGSSGRDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 199)
A11B1_3G2 경쇄
MDTRAPTQLLGLLLLWLPGARCAYDMTQTPASVEAAVGGTVTIKCQASQSISRDLSWYQQKPGQPPKRLIYKASTLASGVPSRFKGSGSGTDFTLTISDLECADAATYYCQQGYSSIDVDNDFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 200)
A11B1_3B1 중쇄
METGLRWLLLVAVLKGVQCQEQLEESGGGLVKPEGSLTLTCKASGFDLSSGYDMCWVRQAPGKGLEWIACIYADYSGSTYYASWVNGRFTISSSTSLNTVDLKMTSLTAADTATYFCARGATGNGGYGYYFNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 201)
A11B1_3B1 경쇄
MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVSEPVGGTVTIKCQASQNINSGLAWYQQKPGQPPKLLIYKASTLASGVSSRFKGSGSGTEFTLTISDLECADAATYYCQTYYYSSSSSDNAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 202)
A11B1_2D3 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIYGGSSGNIAYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDIPSDAFTLDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 203)
A11B1_2D3 경쇄
MDTRAPTQLLGLLLLWLPGATFAQVLTQTPSSVSAAVGSTVTINCQASQSVYKDNNLAWYQQKPGQPPKLLIYKASTLASGVPSRFKGSGSGTQFTLTISGVQCEDAATYYCQGEFSCGSADCIAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 204)
A11B1_2A7 중쇄
METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTCKGSGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGYGSTYYASWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCAKGGAIDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK* (SEQ ID NO: 205)
A11B1_2A7 경쇄
MDTRAPTQLLGLLLLWLPGATFAAVLTQTPASTSAAVGGTVTINCQSSQSVYRSNWLAWYQQKPGQPPKLLIYDVFNLASGVPSRFKGSGSGTQFTLTISGVQCADAATYYCQGSYYSGNWYSAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC* (SEQ ID NO: 206)
인간 mAb 서열
중쇄 및 경쇄 가변 영역 서열
인간화 mAb 서열
인간화된 79E3E3 중쇄 가변 영역
QIQLVQSGAEVKKPGESLKISCKASGYTFTDYAIGWVRQMPGKGLEWMGIINTQTGKPKYSPSFQGQFIFSLDTSINTTYLQWSSLKASDTAIYFCTRLGTGNTKGFAYWGQGTTVTVSS (SEQ ID NO: 413)
인간화된 79E3E3 경쇄 가변 영역
DIQITQSPSSLSASLGDKVTITCRSSQSLLYSENNQDYLAWYQQKPGKAPKLLIYGASNLQSGVPSRFSGRGSGTDFTLTISSLQPEDFATYYCEQTYRYPFTFGPGTKVDIKR (SEQ ID NO: 414)
인간화된 9-G05 중쇄 VH_1
리더 서열 -VH-hIgG1CH-정지 코돈*
MGWSCIILFLVATATGVHS QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVRQAPGQRLEWMGYINPDNGGTIYNQKFKGRVTLTVDTSASTAYMELSSLRSEDTAVYYCARLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK* (SEQ ID NO: 415)
인간화된 9-G05 중쇄 VH_2
리더 서열 -VH-hIgG1CH-정지 코돈*
MGWSCIILFLVATATGVHS QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVRQAPGQRLEWIGYINPDNGGTIYNQKFKGRVTLTVDTSASTAYMELSSLRSEDTAVYYCARLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK* (SEQ ID NO: 416)
인간화된 9-G05 중쇄 VH_3
리더 서열 -VH-hIgG1CH-정지 코돈*
MGWSCIILFLVATATGVHS QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVRQAPGQRLEWMGYINPDNGGTIYNQKFKGRATLTVDTSASTAYMELSSLRSEDTAVYYCARLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK* (SEQ ID NO: 417)
인간화된 9-G05 중쇄 VH_4
리더 서열 -VH-hIgG1CH-정지 코돈*
MGWSCIILFLVATATGVHS QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVRQAPGQSLEWIGYINPDNGGTIYNQKFKGRATLTVDTSASTAYMELSSLRSEDTAVYYCARLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK* (SEQ ID NO: 418)
인간화된 9-G05 경쇄 VL_1
리더 서열 -VL-hIgKCL-정지 코돈*
MGWSCIILFLVATATGVHS DIVMTQSPDSLAVSLGERATINCRASESVDNYGISFMHWYQQKPGQPPKLLIYRASNLDSGVPDRFSGSGSGTDFTLTISSLQAEDVATYYCQQSYKDPRTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 419)
인간화된 9-G05 경쇄 VL_2
리더 서열 -VL-hIgKCL-정지 코돈*
MGWSCIILFLVATATGVHS DIVLTQSPASLAVSPGQRATITCRASESVDNYGISFMHWYQQKPGQPPKLLIYRASNLDSEVPARFSGSGSRTDFTLTINPVEANDTATYYCQQSYKDPRTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 420)
16E10 중쇄 가변 영역
QSLEESGGDLVKPGASLTLTCRVSGFSFSSSYYMCWVRQAPGKGLEWIACIGTTRGSTYYATWAKGRFTISKISSTTVTLQMTSLTDADTATYFCARDATGYRINTIGLYFNLWGPGTLVTVSS (SEQ ID NO: 421)
인간화된 16E10 중쇄 가변 영역 VH_1
QSLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTYYADSAKGRFTISKISKNTVYLQMTSLRAEDTAVYFCARDATGYRINTIGLYFNLWGPGTLVTVSS (SEQ ID NO: 422)
인간화된 16E10 중쇄 가변 영역 VH_2
EVQLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTYYADSAKGRFTISKDNSKNTVYLQMTSLRAEDTAVYFCARDATGYRINTIGLYFNLWGQGTLVTVSS (SEQ ID NO: 423)
인간화된 16E10 중쇄 가변 영역 VH_3
QSLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTYYADSAKGRFTISKESKNTVYLQMSSLRAEDTAVYFCARDATGYRINTIGLYFNLWGPGTLVTVSS (SEQ ID NO: 424)
인간화된 16E10 중쇄 가변 영역 VH_4
EVQLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTYYADSAKGRFTISKDNSKNTVYLQMSSLRAEDTAVYFCARDATGYRINTIGLYFNLWGQGTLVTVSS (SEQ ID NO: 425)
인간화된 16E10 중쇄 가변 영역 VH_5
QSLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTYYADSAKGRFTISKESKNTVYLQMSSLRAEDTAVYFCARDATGYRIQTIGLYFNLWGPGTLVTVSS (SEQ ID NO: 426)
인간화된 16E10 중쇄 가변 영역 VH_6
EVQLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTYYADSAKGRFTISKDNSKNTVYLQMSSLRAEDTAVYFCARDATGYRIQTIGLYFNLWGQGTLVTVSS (SEQ ID NO: 427)
16E10 경쇄 가변 영역
ELTQTPSSVEAAVGGTPTIKCQASQTIYSYLSWYQQKPGQPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISDLECADAATYYCQSYHGTASTEYNTFGGGTEVVVK (SEQ ID NO: 428)
인간화된 16E10 경쇄 가변 영역 VL_1
QLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQSYHGTASTEYNTFGGGTKVEIK (SEQ ID NO: 429)
인간화된 16E10 경쇄 가변 영역 VL_2
DIQLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQSYHGTASTEYNTFGGGTKVEIK (SEQ ID NO: 430)
인간화된 16E10 경쇄 가변 영역 VL_3
QLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYNTFGGGTKVEIK (SEQ ID NO: 431)
인간화된 16E10 경쇄 가변 영역 VL_4
DIQLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYNTFGGGTKVEIK (SEQ ID NO: 432)
인간화된 16E10 경쇄 가변 영역 VL_5
QLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYQTFGGGTKVEIK (SEQ ID NO: 433)
인간화된 16E10 경쇄 가변 영역 VL_6
DIQLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFSGSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYQTFGGGTKVEIK (SEQ ID NO: 434)
균등물
본 발명이 이의 상세한 설명과 함께 기재되었지만, 전술한 설명은 예시하고자 하는 것이고, 첨부된 청구범위의 범주에 의해 규정되는 본 발명의 범주를 제한하고자 하는 것이 아님이 이해되어야 한다. 다른 양태, 이점, 및 변형이 하기 청구범위의 범주 내에 있다.
SEQUENCE LISTING
<110> JANSSEN BIOTECH, INC.
<120> ANTIBODIES AGAINST INTEGRIN ALPHA 11 BETA 1
<130> MPI6002WOPCT1
<140>
<141>
<150> 63/213,973
<151> 2021-06-23
<150> 63/127,849
<151> 2020-12-18
<160> 443
<170> PatentIn version 3.5
<210> 1
<211> 417
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 1
atggattggt tgtggaactt gctattcctg atggtagttg cccaaagtgc tcaagcacag 60
atccagttgg tacagtctgg acctgaagta aagaagcctg gagagtcagt gaagatctcc 120
tgcaaggcct ctgggtatac cttcacagac tatgcaatga actgggtgaa acaggctcca 180
ggaaatggcc tgaagtggat gggctggatc aacacccaaa ctggaaagcc aacatatgcg 240
gatgatttca aacaacggtt tgtcttctct ttggaaactt ctgccagaac tacatatttg 300
cagatcaaca acctcaatat tgaagacaca gctacatatt tctgtacgag attgggtaca 360
ggtaatacga aggggtttgc ttactggggc caaggcactc tggtcactgt ctcttca 417
<210> 2
<211> 399
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 2
atggaatcac agacgcatgt cctcatttcc cttctgctct gtgtatcagg tacctgtggg 60
gacattttga taaaccagtc tccagcctct ctgactgtgt cagcaggaga gagggtcact 120
atgagctgca agtccagtca gagtcttcta tacagtgaaa acaaccagga ctatttggct 180
tggtaccagc agaaaccagg acagtttcct aaattgctta tctatggggc atccaaccgg 240
cacactgggg tccctgatcg cttcacaggc agtggatctg ggacagactt cactctgacc 300
atcagcagtg tgcaggctga agacctggct gattattatt gtgagcagac ctacagatat 360
ccattcacgt tcggctcagg gacgaagttg gaaataaaa 399
<210> 3
<211> 414
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 3
atggagttgg aattgagctt aatttttatt ttttctcttt taaaagatgt ccagtgtgaa 60
gtacagctgg tggagtctgg aggaagcttg gttcaacctg ggggttctct gaaactctcc 120
tgtgtagcct caggatacac tttcagtaac tactggatgg actgggttcg gcagtctcct 180
ggaaagtccc tggaatggat tggagagatt aacacggatg gcagaaggac caactatgca 240
ccatccataa aggatcgatt cacaatctcc agagacaatg ccaagagcac cctgtatctg 300
cagatgagca atgtgaaatc agatgacaca gccatttatt actgtaccat actacgggta 360
tacccccact actttgatta ctggggccaa ggagtcatgg tcacagtctc ctca 414
<210> 4
<211> 396
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 4
atgatgagtc ctgcccagtt cctgtttctg ctaatgctct ggatccagga agcccgcgga 60
gatgttgtga tgacccagac accaccgtct ttgtcggttg ccattggaca atcagtctcc 120
atctcttgca agtcaagtca gagcctcgta tatagtgatg gagagacata tttgcattgg 180
tttttacaga gtcctggcag gtctccgaag cgcctaattt atcacgtgtc taatctgggc 240
tctggagtcc ctgacaggtt cagtggcact ggatcactga cagattttac acttagaatc 300
agcagagtgg aggctgagga tttgggagtt tattactgcg cgcaaactac acattttcct 360
cccacgtttg gagctgggac caagctggaa ctgaaa 396
<210> 5
<211> 405
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 5
atggctgtcc tggtgctgtt gctctgcctg gtgacatttc caagctgtgc cctgtcccag 60
gtgcagttga aggagtcagg acctggtctg gtgcagccct cacagaccct gtccctcacc 120
tgcactgtct ctgggttctc attaaccagc aatagtgtta gctgggttcg ccaggctccg 180
ggaaagggtc tggagtggat gggagcaata tggagtggtg gaagcacaga ttataattca 240
gctctcaaat cccgactgag catcagcagg gacacctcca agagccaagt tttcttaaaa 300
atgaacagtc tgcaaactga agacacagcc atttacttct gtaccagatc tcactgggag 360
ccctttgatt actggggcca aggagtcatg gtcacagtct cctca 405
<210> 6
<211> 399
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 6
atggaatcac aaactcaggc cctcatatcc ctgctgctct gggtatatgg tacctgtggg 60
gacattgtga tgacccagtc tccattctcc ctggctgtgt cagaaggaga gatggtcact 120
ataaactgca agtccagtca gggtctttta tccagtggaa accaaaagaa ctacttggcc 180
tggtaccagc agagaccagg gcagtctcct aaactactga tctactatgc atccactagg 240
caatcagggg tccctgatcg cttcataggc ggtggatctg ggacagactt cactctgacc 300
atcagcgatg tgcaggctga agacctggca gattattact gcctgcagca ttacagctat 360
cctcccacgt tcggttctgg gaccaagctg gagatcaaa 399
<210> 7
<211> 405
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 7
atggctgtcc tggtgctgtt gctctgcctg gtgacatttc caagctgtgc cctgtcccag 60
gtgcagctga gggagtcagg acctggtctg gtgcagccct cacagaccct gtccctcacc 120
tgcactgtct ctgggttctc attgaccagc aatagtgtga cctgggttcg ccagcctccg 180
ggaaagggtc tggagtggat gggagcgata tggagtgatg gaagcacaga ttataattca 240
actctcaaat cccgactgag catcagtagg gacacctcca agagccaagt tttcttaaaa 300
atgagcagtc tgcaaactga agacacagcc atttacttct gtaccagatc ccactgggag 360
ccctttgatt actggggcca aggagtcatg gtcacagtct cctca 405
<210> 8
<211> 394
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 8
atggaatcac aaactcaggc cctcatatcc ctgctgctct gggtatatgg tacctgtggg 60
gacattgtga tgacccagtc tccactctcc ctggctgtgt cagaaggaga gacggtcact 120
atgaactgca agtccagtca gagtcttttt tccagtggaa atcaaaagaa ctacttggcc 180
tggtaccagc agaaaccagg gcagtctcct aaactactga tctactatgc atccactagg 240
caatcagggg tccctgatcg cttcataggc agtggatctg ggacagactt cactctgacc 300
atcagcgatg tgcagactga agacctggca gattattact gcctgcagca ttacaactat 360
cctcccacgt tcggttctgg gaccaagctg gaga 394
<210> 9
<211> 402
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 9
atggacttgc gactgactta tgtctttatt gttgctattt taaaaggtgt cttgtgtgag 60
gtgaaactgg aggaatctgg gggaggtttg gtgcaacctg gaatgtccgt gaaactctct 120
tgtgcaacct ctggattcat tttcagtgac tactggatgg aatgggtccg ccaggctcca 180
gggaaggggc tagaatgggt agccgaaatt agaaacaaag ctaataatta tgcaacatac 240
tatgggaagt ctatgaaagg cagattcacc atctcaagag atgattccaa aagtatagtc 300
tacctacaag tgaacagcat aagatctgaa gatactgcta tttattactg tgcaccgaat 360
tttgattact ggggccaagg agtcatggtc acggtctcct ca 402
<210> 10
<211> 393
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 10
atgagtcctg tccagtccct gtttttgcta ttgctttgga ttctgggaac ccatggtgat 60
gttgtgctga cccagactcc acccacttta tcggctacca ttggacaatc agtctctatc 120
tcttgcaggt caagtcagag tctcttacat agtactggaa acacctattt aaattggttg 180
ctacagaggc caggccaacc tccgcaactt ctaatttatt tggtttccag actggaatct 240
ggggtcccca acaggttcag tgccagtggg tcaggaactg atttcacact caaaatcagt 300
ggaatagagg ctgaggattt gggggtttat tactgcgtgc aaagttccca tactccgtac 360
acgtttggga ctgggaccaa gctggaactg aaa 393
<210> 11
<211> 405
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 11
atggacatca ggctcagctt ggttttcctt gtccttttta tgaaaggtgt ccagtgtgag 60
gtgcagttgg tggagtctgg gggaggctta gtgcagcctg gaaggtccct gaaactctcc 120
tgtgcagcct cacgattcac ttttagtgac tataacatgg cctgggtccg ccaggctcca 180
aagaagggtc tggagtgggt cgcaaccatt tatcatgatg atagtggttc ttactatcga 240
gactccgtga agggccgatt caccatctcc agaaataatg caaaaagcac tctgtacctg 300
cagatggaca gtctgaggtc tgaggacatg gccacttatt actgtgcaag acataacaat 360
ggctttgatt actggggcca aggagtcatg gtcacagtcg cctca 405
<210> 12
<211> 393
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 12
atgaagtggc ctgttaggct gttggtgctg ttcttctgga ttcctgcttc cgggggtgat 60
gttgtgatga cacaaactcc agtctccctg cctgtccgcc ttggaggtca agcctctatc 120
tcttgccggt caagtcagag cctggtacac agtaatggaa acacctactt gcattggtac 180
ctacagaagc caggccagtc tccacagctc ctcatcaatc gggtttccaa cagattttct 240
ggggtgccag acaggttcag tggcagtggg tcagggacag atttcaccct caagatcaac 300
agagtagagc ctgaggactt gggagattat tactgcttac aaagtacaca ttttccactc 360
acgttcggtt ctgggaccaa gctggagacc aaa 393
<210> 13
<211> 408
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 13
atggacatca ggctcagctt gggtttcctt gtccttttca taaaaggtga ccagtgtgcg 60
gtgcaactgg tggagtctgg gggaggctta gtgcagcctg gaaggtccct gaaactctcc 120
tgtgcagcct caagaatcac tttcactgac tattacatgg cctgggtccg ccaggctcca 180
acgaagggtc tggagtgggt cgcaaccatt agttctgatg gtggtgacac tttctatcga 240
gactccgtga agggccgatt tactatctcc agagacaatg caaaaagcac cctatatttg 300
caaatggtca gtctgaggtc tgaggacacg gccacttatt actgttcaac agatcgggga 360
gctcagtttg gttactgggg ccaaggcact ctggtcactg tctcttca 408
<210> 14
<211> 378
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 14
atggctccag tccagctctt agggctgctg ctgatttggc tcccagccat gagatgtgac 60
atccagatga cccagtctcc ttcattcctg tctgcatctg tgggagacag agtctctatc 120
aactgcaaag caagtcagaa tgttcacgag aacctaaact ggtatcagca aaagcttgga 180
gaagctccca aacgcctgat atataataca aacaatttgc aaacaggcat cccatcaagg 240
ttcagtggca gtggatctgg tgcagattac acactcacca tcagcagcct gcagcctgaa 300
gattttgcca catatttctg tttgcagcat aatgcttttc cgtacacgtt tggacctggg 360
acgaagctgg aactgaaa 378
<210> 15
<211> 366
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 15
gaggtccagc tgcaacagtc tggacctgag ctggtgaagc ctggggcttc agtgaagata 60
ccctgcaagg cttctggata cacattccct gactacaaca tggactgggt gaagcagagc 120
catggaaaga gccttgagtg gattggatat attaatcctg acaatggtgg tactatctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccag cacagcctac 240
atggagctcc gcagcctgac atctgaggac actgcagtct attactgtgc aagattagac 300
agctcaggct acggttacta tgctatggac tactggggtc aaggaacctc agtcaccgtc 360
tcctca 366
<210> 16
<211> 333
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 16
gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 60
atctcctgca gagccagcga aagtgttgat aattatggca ttagttttat gcactggtac 120
cagcagaaac caggacagcc acccaaactc ctcatctatc gtgcatccaa cctagactct 180
gagatccctg ccaggttcag tggcagtggg tctaggacag acttcaccct caccattgat 240
cctgtggaga ctgatgatgt tgcaacctat tactgtcagc aaagttataa ggatcctcgg 300
acgttcggtg gaggcaccaa gctggaaatc aaa 333
<210> 17
<211> 366
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 17
aaagtgatgc tggtggagtc tgggggagcc ttagtgaagc ctggagggtc cctgaaactc 60
tcctgtgtag cctctggatt cactttcagt aactatgcca tgtcttgggt tcgccagact 120
ccagagaaga ggctggagtg ggtcgcaacc attagtagtg gtggttatta cacttactat 180
ccagacagtg tgaagggtcg attcaccatc tccagagaca atgccaggaa caccctgttc 240
ctgcaaatga gcagtctgag gtctgaggac acggccatgt tttactgtgc aagagaggat 300
gattacggaa gatattccta tactatggac tactggggtc aaggaacctc agtcaccgtc 360
tcctca 366
<210> 18
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 18
gatgttgtga tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagtctcc 60
atctcttgca gatgtagtca gagccttgta cacagtaatg gaaacaccta tttacattgg 120
tacctgcaga agccaggcca gtctccacag ctcctgatct acaaaatttc caaccgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tctgggagtt tatttctgct ctcaaagtac acatgttccg 300
tacacgttcg gaggggggac cgagctggaa ataaaa 336
<210> 19
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 19
gaggtccagc tgcagcagtc tggacctgag ctggtaaagc ctggggcttc agtgaggata 60
tcctgcaagg cttctggata cacattcact gactactaca tacactgggt gaagcagaag 120
cctgggcagg gccttgaatg cattggagag atttatcctg gaactgataa tacttactac 180
agtaaaaaat tcaggggcaa ggccacactg actgcagaca aatcctccga cacagcctac 240
atgcagctca gcagcctgac atctgaggac tctgcagtct atttctgtgc aagaggagac 300
tactataggg ggtacttcga tgtctggggc gcagggacca cggtcaccgt ctcctca 357
<210> 20
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 20
gatgttgtga tgactcagac ctcactcact ttgtcggtta ccattggaca accagcctcc 60
atctcttgca agtcaagtca gagcctctta catagtaatg gaaagacata tttgaattgg 120
ttattacaga ggccaggcca gtctccaaag ttcctaatct atctggtgtc taaactggaa 180
tctggagtcc ctgacaggtt cagtggcagt ggatcaggga cagatttcac actgaaaatc 240
agcagagtgg aggctgagga tttgggggtt tattactgct tgcaatctac acattttcct 300
tggacgttcg gtggaggcac caagctggaa atcaaa 336
<210> 21
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 21
gaggtccagc tgcagcagtc tggacctgag ctggtaaagc ctggggcttc agtgaagaaa 60
tcctgcaagg cttctggata cacattcact gactactaca tgcactgggt gaagcagaag 120
cctgggcagg gccttgagtg gattggaaag atttatcctg gaagtggtaa tactcactac 180
aatgagaagt tcaagggcaa ggccacactg actgcagaca aatcctccag cacagcctac 240
atgcagctca gcagcctgac atctgaggac tctgcagtct atttctgtgc aaccaattac 300
tacggctaca gggcaatgaa ctattggggt caaggatcct cagtcaccgt ctcctca 357
<210> 22
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 22
gacatccatt tgacccagtc tccatcctcc ttatctgcct ctctgggaga aagaatcagt 60
ctcacttgcc gggcaagtca ggacatttat attagcttaa actggtttca gcagaaacca 120
gatggaacta ttaaactcct gatctacggc acatccagtt tagattctgg tgtccccaaa 180
aggttcagtg gcagtaggtc tgggtcagat tattctctca ccatcagcag ccttgagtct 240
gaagattttg cagactatta ctgtctacaa tatgctagtt ctccgtacac gttcggaggg 300
gggaccaagc tggaaataaa a 321
<210> 23
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 23
gaggtccagc tgcagcagtc tggacctgag ctggtaaagc ctggggcttc agtgaagata 60
tcctgcaagg cttctggata cacattcact gactactaca tgcactgggt gaagcagaag 120
cctgggcagg gccttgagtg gattggagag atttatcctg gaagtggtaa tccttactac 180
aatgagaagt tcaagggcaa ggccacactg actgcagaca aatcatccag ctcagcctac 240
atgcagctca gcagcctgac atctgaggac tctgcagtct atttctgtgc aagaacctcc 300
tacggtagag tagggacagg gtttgcttac tggggccaag ggactctggt cactgtctct 360
gca 363
<210> 24
<211> 333
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 24
aattttgtga tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagcctcc 60
atctcttgca gatctagtca gagccttcta cacagtaacg gaaacaccta tttacattgg 120
tacctgcaga agccaggcca gtctccaaag ctcctgatct acaaagtttc caaccgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
aacagagtgg agactgagga tctgggaatt tatttctgct ctcaaagttc acatgttccc 300
acgttcggtg ctgggaccaa gctggagctg aaa 333
<210> 25
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 25
caggtccagc tgcagcagtc tggggctgaa ctggcaaaac ctggggcctc agtgaagatg 60
tcctgcaagg cttctggcta cacctttact aactactgga tgcactgggt aaaacagagg 120
cctggacagg gtctggaatg gattggatac attaatccta acaatggtta tactgagtac 180
aatcagcgat tcaaggacaa ggccacattg actgcagaca gatcctccac cacagcctac 240
atgcaactaa gcagcctgac atctgaggac tctgcagtct attactgtgc aagatccgat 300
atcattacga cagactactg gggccaaggc accactctca cagtctcctc a 351
<210> 26
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 26
gatgttgtga tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagcctcc 60
atctcttgca gatctagtca gagccttgta tatagtaatg gaaataccta tttacattgg 120
tacctgcaga agccaggcca gtctccaaag ctcctgatct acaaagtttc caaccgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagata 240
agcagagtgg aggctgagga tctgggagtt tatttctgct ctcaaagtac acatgttccg 300
tggacgttcg gtggaggcac caagctggaa atcaaa 336
<210> 27
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 27
gaagtgaagc ttgaggagtc tggaggaggc ttggtgcaac ctggaggatc catgaaactc 60
tcttgtgctg cctctggatt cacttttagt gacgcctgga tggactgggt ccgccagtct 120
ccagaggcgg ggcttgagtg ggttgctgaa attagaaaca aagctcataa tcctgcaaca 180
tactatgctg agtctgtgaa agggagattc accatctcaa gagatgattc caaaagtagt 240
gtctacctgc aaatgaacag cttaagagct gaagacactg gcatttatta ctgtacctta 300
gtagcccctg atgctatgga ctactggggt caaggaacct cagtcaccgt ctcctca 357
<210> 28
<211> 339
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 28
gacattgtga tgtcactgtc tccatcctcc ctagctgtgt cagttggaga gaaggttact 60
atgagctgca agtccagtca gagcctttta tatagtcgca atcaaaagaa ctacttggcc 120
tggtaccagc agaaaccagg gcagtctcct aaactgctga tttactgggc atccactagg 180
gcatctggag tccctgatcg cttcacaggc agtggatctg ggacagattt cactctcacc 240
atcagcagtg tgaaggctga agacctggca gtttattact gtcagcaata ttatagctat 300
ccgtacacgt tcggaggggg gaccaagctg gaaataaaa 339
<210> 29
<211> 348
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 29
caggtccaac tgcagcagtc tgggcctgag ctggtgaggc ctggggcttc agtgaagatg 60
tcctgcaagg cttcaggcta taccttcacc agctactgga tgcactgggt gaaacagagg 120
cctggacaag gccttgagtg gattggcatg attgatcctt ccaatagtga aacttggtta 180
aatcagaagt tcaaggacaa ggccacattg aatgtagaca aatcctccaa cacagcctac 240
atgcagctca gcagcctgac atctgaggac tctgcagtct attactgtgc aagatatgat 300
ggttactacg actactgggg ccaaggcacc actctcacag tctcctca 348
<210> 30
<211> 333
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 30
aacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 60
atatcctgca gagccagtga aagtgttgat agttatggca atagttttat gcactggtac 120
cagcagaaac caggacagcc acccaaactc ctcatctatc ttgcatccaa cgtagaatct 180
ggggtccctg ccaggttcag tggcagtggg tctaggacag acttcaccct caccattgat 240
cctgtggagg ctgatgatgc tgcaacctat tactgtcagc aaaataatga ggatccgtgg 300
acgttcggtg gaggcaccaa gctggaaatc aaa 333
<210> 31
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 31
caggtccaac tgcagcagcc tggggctgag ctggtgaggc ctggggcttc agtgaagctg 60
tcctgcaagc cttctggcta caccttcacc agctactgga tgaactgggt gaagcagagg 120
cctggacaag gccttgaatg gattggtatg attgatcctt cagacagtga aactcactac 180
aatcaaatgt tcaaggacaa ggccacattg actgttgaca aatcctccaa cacagcctac 240
atgcagctca gcagcctgac atctgaggac tctgcggtct attactgtgc gcagatctac 300
tatgcttacg acaaggctta ctggggccaa gggactctgg tcactgtctc tgca 354
<210> 32
<211> 333
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 32
gacattgtga tgtcacagtc tccatcctcc ctagctgtgt cagttggaga gaaggttact 60
atgagctgca agtccagtca gagcctttta tatagtagcc atcaaaagaa ctacttggcc 120
tggtaccagc agaaaccagg gcagtctcct aaactgctga tttactgggc atccactagg 180
gaatctgggg tccctgatcg cttcacaggc agtggatctg ggacagattt cagtctcacc 240
atcagcagtg tgaaggctga agacctggca gtttattact gtcaggaata ttatagctgg 300
acgttcggtg gaggcaccaa gctggaaatc aaa 333
<210> 33
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 33
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctggggcttc agtgaagata 60
tcctgtaagg cttctggata cacgttcact gactactaca tgaactgggt gaagcagagc 120
catggaaaga gccttgagtg gattggagat attaatcctc acaatggtgg tactagcttc 180
atccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccag cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attattgtgc ccctctggga 300
cgaaaggagg ggtttgctta ctggggccaa gggactctgg tcactgtctc tgca 354
<210> 34
<211> 333
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 34
gacactgtgc tgacacagtc tcctgcttcc ttagttgtat ctctggggca gagggccacc 60
atctcatgca gggccagcaa aagtgtcagt acatctggct atagttatat gcactggtac 120
caacagaaac caggacagcc acccaaactc ctcatctatc ttgcatccaa cctagaatct 180
ggggtccctg ccaggttcag tggcagtggg tctgggacag ccttcaccct caacatccat 240
cctgtggagg aggaggatgc tgcaacctat tactgtcagc acagtaggga gcttccgtac 300
acgttcggag gggggaccaa gctggaaata aaa 333
<210> 35
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 35
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg 60
acttgttctt tctctgggtt ttcactgagc acttttgcta tgggtgtagg ctggattcgt 120
cagccttcag ggaagggtct ggagtggctg gcacacattt ggtgggatga tgataagtac 180
tataacccag ccctgaagag ccggctcaca atctccaagg atacctccaa aaaccatgta 240
ttcctcaaga tcgccaatgt ggacactgca gatactgcca catactactg tgctcgaatg 300
ccgctaactt tctactttga ctactggggc caaggcacca ctctcacagt ctcctca 357
<210> 36
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 36
gatgttttgc tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagcctcc 60
atctcttgca gatctagtca gagcattgta catagtaatg gacacaccta tttagaatgg 120
tacctgcaga aaccaggcca gtctccaaag ctcctgatct acaaagtttc caaccgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tctgggagtt tattactgct ttcaaggttc acatgttccg 300
ttcacgttcg gaggggggac caagctggaa ataaaa 336
<210> 37
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 37
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg 60
acttgttctt tctctgggtt ttcactgaga acttttgcta tgggtgtagg ctggattcgt 120
cagccttcag ggaagggtct ggagtggctg gcacacattt ggtgggatga tgataagtac 180
tataacccag ccctgaagag ccggctcaca atctccaagg atacctccaa aaaccaggta 240
ttcctcaaga tcgccaatgt ggacactgca gatactgcca catactactg tgctcgaatg 300
ccgctaactt tctactttga ctactggggc caaggcacca ctctcacagt ctcctca 357
<210> 38
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 38
gatgttttga tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagcctcc 60
atctcttgta gatctagtca gagcattgta catagtaatg gaaacaccta tttagaatgg 120
tacctgcaga aaccaggcca gtctccaaag ctcctgatct acaaagtttc cacccgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tctgggagtt tattactgct ttcaaggttc acatgttccg 300
ttcacgttcg gaggggggac caagctggaa ataaaa 336
<210> 39
<211> 345
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 39
caggtccaac tgcagcagcc tggggctgaa cttgtgatgc ctggggcttc agtgaagctg 60
tcctgcaagg cttctggcta caccttcacc aactactgga tgcactgggt gaaacagagg 120
cctggacaag gccttgagtg gatcggagag attgatcctt ctgatagtta tactaactac 180
aatcaaaagt tcaagggcaa ggccacattg actgtagaca aatcctccag cacagcctac 240
atgcagctca gcagcctgac atctgaggac tctgcggtct attactgtac aagacagggt 300
agtacctacg cgtggggtca aggaacctca gtcaccgtct cctca 345
<210> 40
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 40
gatattgtga tgacgcaggc tgcattctcc aatccagtca ctcttggaac atcagcttcc 60
atctcctgca ggtctagtaa gagtctccta catagtaatg gcatcactta tttgtattgg 120
tatctgcaga agccaggcca gtctcctcag ctcctgattt atcagatgtc caaccttgcc 180
tcaggagtcc cagacaggtt cagtagcagt gggtcaggaa ctgatttcac actgagaatc 240
agcagagtgg aggctgagga tgtgggtgtt tattactgtg ctcaaaatct agaacttcct 300
ccgacgttcg gtggaggcac caagctggaa atcaaa 336
<210> 41
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 41
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctggggcttc agtgaagatg 60
tcctgtaagg cttctggata cacattcact gactactaca tgatgtgggt gaagcagagt 120
catggaaaga gccttgagtg gattggagat attaatcctt acaatggtgg ttctagctac 180
aacccgaagt tcaagggcag ggccacattg actgtagaca aatcctccag cacagcctac 240
atgcagctca acagcctgac atctgaggac tctgcagtct attactgtgc aagagggact 300
tactggggcc aagggactct ggtcactgtc tctgca 336
<210> 42
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 42
gatgttgtga tgacccagac tccactcact ttgtcggtta ccattggaca accagcctcc 60
atctcttgca agtcaagtca gagcctctta gatagtgctg gaaagacata tttgaattgg 120
ttgttacaga ggccaggcca gtctccaaag cgcctaatgt atctggtgtc taaactggac 180
tctggagtcc ctgacaggtt cactggcagc ggatcaggga cagatttcac actgaaaatc 240
agcagagtgg aggctgagga tttgggagtt tattattgct ggcaaggtac acattttccg 300
tacacgttcg gaggggggac caagctggaa ataaaa 336
<210> 43
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 43
caggtccaac tgcagcagcc tggggctgag cttgtgaagc ctggggcttc agtgaagttg 60
tcctgcaagg cttctggcta caccttcacc agctactgga tgcactggat aaagcagaga 120
cctggacaag gccttgagtg gattggagag attaacccta gcaatggtgg ttctaactac 180
aatgagaagt tcaagagcaa ggccacactg actgtagaca aatcctccag cacagcctac 240
atgcaactca gcagcctgac atctgaggac tctgcggtct atcactgtaa aagcagaggc 300
tactggggcc aaggcaccac tctcacagtc tcctca 336
<210> 44
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 44
gatgttgtga tgacccagac tccactcact ttgtcggtta ccattggaca accagcctcc 60
atctcttgca agtcaagtca gagcctctta gatagttatg gaaagacata tttgaattgg 120
ttgttacagc ggccaggcca gtctccaaag cgcctaatct atctggtgtc taaattggac 180
tctggagtcc ctgacaggtt cactggcagt ggatcaggga cagatttcac actgaaaatc 240
agcagagtgg aggctgagga tttgggaatt tattattgct ggcaaggtac acattttcct 300
cacacgttcg gctcggggac aaagttggaa ataaaa 336
<210> 45
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 45
caggttcagc tgcagcagtc tggagctgag ctggcgaggc ctggggcttc agtgaaactg 60
tcctgcaagg cttctggcta caccttcaca agctatggta taagctgggt gaaacagaga 120
actggacagg gccttgagtg gattggagag atttttccta gaagtagtaa tacttactat 180
aatgagaagt tcaagggcaa ggccacactg actgcagaca agtcctccag cacagtgtac 240
atggagttcc gcagcctgac atctgaggac tctgcggtct atttctgtgc aagagagggg 300
ggcctggcct ggtttgctta ctggggccaa gggactctgg tcactgtctc tgca 354
<210> 46
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 46
gatgttgtga tgacccagac tccactcact ttgtcggtta ccattggaca accagcttcc 60
atctcttgca agtcaagtca gagcctctta tatactaatg gaaacaccta tttgaattgg 120
ttattacaga ggccaggcca gtctccaaaa cgcctaatct atctggtgtc taaattggac 180
tctggaatcc ctgacaggtt cagtggcagt ggatcaggga cagatttcac actgagaatc 240
agcagagtgg aggctgagga tttgggagtt tattactgct tgcagagtac acattttcca 300
ttcacgttcg gctcggggac aaagttggaa ataaaa 336
<210> 47
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 47
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctggggcttc agtgaagatg 60
tcctgtaagg cttctggata cacaatcact gactactaca tgatgtggtt gaagcagagt 120
catggaaaga gccttgaatg gattggagat attaatcctt acactggtgg tactagctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca aatcctccag cacagcctac 240
ctgcagctcc acagcctgac atctgaggac tctgcagtct attactgtgc aagaggggcc 300
tactggggcc aaggcaccac tctcacagtc tcctca 336
<210> 48
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 48
gatgttgtga tgacccagac tccactcact ttgtcggtta ccattggaca accagcctcc 60
atctcttgca agtcaagtca gagcctctta gatagtgatg gaaagacata tttgaattgg 120
ttgttacaga ggccaggcca gtctccaaag cgcctaatct atctggtgtc taaactggac 180
tctggagtcc ctgacaggtt cactggcagt ggatcaggga cagatttcac actgaaaatc 240
agcagagtgg aggctgagga tttgggagtt tattattgct ggcaaggtac acattttccg 300
tacacgttcg gaggggggac caagctggaa ataaaa 336
<210> 49
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 49
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctggggcttc agtgaagatg 60
tcctgtaagg cttctggata cacaatcact gactactaca tgatgtggtt gaagcagagt 120
catggaaaga gccttgaatg gattggagat attaatcctt acactggtgg tactagctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca aatcctccag cacagcctac 240
atgcagctca acagcctgac atctgaggac tctgcagtct attactgtgc aagaggggcc 300
tactggggcc aaggcaccac tctcacagtc tcctca 336
<210> 50
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 50
gatgttgtga tgacccagac tccactcact ttgtcggtta ccattggaca accagcctcc 60
atctcttgca agtcaagtca gagcctctta gatagtgatg gaaagacata tttgaattgg 120
ttgttacaga ggccaggcca gtctccaaag cgcctaatct atctggtgtc taaactggac 180
tctggagtcc ctgacaggtt cactggcagt ggatcaggga cagatttcac actgaaaatc 240
agcagagtgg aggctgagga tttgggagtt tattattgct ggcaaggtac acattttccg 300
tacacgttcg gaggggggac caagctggaa ataaaa 336
<210> 51
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 51
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctggggcttc agtgaagata 60
tcctgtaagg cttctggata cacgttcact gactactaca tgaactgggt gaagcagagc 120
catggcagga gccttgagtt gattggagat attaatccta acaatggtgg ttctaacttc 180
aaccagaagt tcaggggcaa ggccacattg actgtagaca agtcctccag cacagcctat 240
atggagctcc gcagcctgac atctgaggac tctgcaatct attactgtgc aagaatgggt 300
tactggggcc aagggactct ggtcactgtc tctgca 336
<210> 52
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 52
gatgttgtga tgacccagac tccactcact ttgtcggtta ccattggaca accagcctcc 60
atctcttgca agtcaagtca gagcctctta catagtgatg gaaagacata tttgaattgg 120
atgttccaga ggccaggcca gtctccaaag cgcctaatct atctggtgtc taaactggac 180
tctggagtcc cttacaggtt cactggcggt ggatcaggga cagatttcac actgcaaatc 240
agcagagtgg agactgagga tttgggagtt tattattgct ggcaaggtac acattttcct 300
cggacgttcg gtggaggcac caagctggaa atcaaa 336
<210> 53
<211> 342
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 53
gaggtccagc tgcagcagtc tggacctgaa ctggtcaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata cacattcact gactactaca tacactgggt gaagcagaag 120
cctgggcagg gccttgagta cattggagag atttatcctg gaagtggtaa tacttactac 180
aatgggaagt tcaggggcaa ggccacactg actgcagaca agtcctccag cacagcctac 240
atgcagctca gcagcctgac atctgaggac tctgcagtct atttctgtgg tagtggctac 300
tttgactact ggggccaagg caccactctc acagtctcct ca 342
<210> 54
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 54
gatgttgtga tgacccagac tccactcact ttgtctgtta ccattggaca gccagcttcc 60
atttcttgca agtcaagtca gagcctctta tatagtaatg gaaaaaccta tttgaattgg 120
ttattacaga gtccaggcca gtctccaaag ctcctaatct atctggtgtc taaactggaa 180
tctggagtcc ctgacagatt cagtggcagt ggatcaggga cagattttac actgaaactc 240
agcagagtgg aggctgagga tttgggagta tattactgcg tgcaaggtac acatttccca 300
ttcacgttcg gctcggggac aaagttggaa ataaaa 336
<210> 55
<211> 1368
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 55
atggagactg ggctgcgctg gcttctcctg gtcgctgtgt tcaaaggtgt ccagtgtcag 60
gagcaactgg tggagtccgg gggagacctg gtcaagcctg gggcatccct gacactcacc 120
tgcacagcct ctggattctc cttcaataag aattattgga tgtgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcggatgc atttataatg gtgatggcaa cacatactac 240
gcgagctggg tgaatggccg attcaccatc tccaaaacct cgtcgaccac ggtgactctg 300
caaatgacca gtctgacagt cgcggacacg gccatctatt tctgtgcgag actacttaat 360
atgtggggcc caggcaccct ggtcaccgtc tcctcagggc aacctaaggc tccatcagtc 420
ttcccactgg ccccctgctg cggggacaca cccagctcca cggtgaccct gggctgcctg 480
gtcaaaggct acctcccgga gccagtgacc gtgacctgga actcgggcac cctcaccaat 540
ggggtacgca ccttcccgtc cgtccggcag tcctcaggcc tctactcgct gagcagcgtg 600
gtgagcgtga cctcaagcag ccagcccgtc acctgcaacg tggcccaccc agccaccaac 660
accaaagtgg acaagaccgt tgcgccctcg acatgcagca agcccatgtg cccaccccct 720
gaactcccgg ggggaccgtc tgtcttcatc ttccccccaa aacccaagga caccctcatg 780
atctcacgca cccccgaggt cacatgcgtg gtggtggacg tgagccagga tgaccccgag 840
gtgcagttca catggtacat aaacaacgag caggtgcgca ccgcccggcc gccgctacgg 900
gagcagcagt tcaacagcac gatccgcgtg gtcagcaccc tccccatcgc gcaccaggac 960
tggctgaggg gcaaggagtt caagtgcaaa gtccacaaca aggcactccc ggcccccatc 1020
gagaaaacca tctccaaagc cagagggcag cccctggagc cgaaggtcta caccatgggc 1080
cctccccggg aggagctgag cagcaggtcg gtcagcctga cctgcatgat caacggcttc 1140
tacccttccg acatctcggt ggagtgggag aagaacggga aggcagagga caactacaag 1200
accacgccga ccgtgctgga cagcgacggc tcctacttcc tctacagcaa gctctcagtg 1260
cccacgagtg agtggcagcg gggcgacgtc ttcacctgct ccgtgatgca cgaggccttg 1320
cacaaccact acacgcagaa gtccatctcc cgctctccgg gtaaatag 1368
<210> 56
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 56
atggacacga gggcccccac tcagctgctg gggctcctac tgctctggct cccaggtgcc 60
agatgtgctg acattgtgat gacccagact ccagcctccg tggaggcagc tgtgggaggc 120
acagtcacca tcaagtgcca ggccagtgag agcattggca atgcattagc ctggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctatactg cagccactct ggcatctggg 240
gtcccatcgc ggttcagcgg cagtggatct gggacagagt tcactctcac catcagtggc 300
gtgcagtgtg acgatgctgc cacttactac tgtcaaagct attattttac tagtgttagt 360
agttatggca atgctttcgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 57
<211> 1401
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 57
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
agagtctctg gattctcctt cagtagcagt tattatatgt gttgggtccg ccaggctcca 180
gggaaggggc tggaatggat cgcatgtatt ggtactactc gtggtagcac ttactacgcg 240
acctgggcga aaggccgatt caccatttct aaaatctcgt cgaccacggt gactctacaa 300
atgaccagtc tgacagacgc ggacacggcc acctatttct gtgcgagaga tgctactggt 360
tataggatta acacgattgg cctctatttt aatttgtggg gcccaggcac cctggtcacc 420
gtctcctcag ggcaacctaa ggctccatca gtcttcccac tggccccctg ctgcggggac 480
acacccagct ccacggtgac cctgggctgc ctggtcaaag gctacctccc ggagccagtg 540
accgtgacct ggaactcggg caccctcacc aatggggtac gcaccttccc gtccgtccgg 600
cagtcctcag gcctctactc gctgagcagc gtggtgagcg tgacctcaag cagccagccc 660
gtcacctgca acgtggccca cccagccacc aacaccaaag tggacaagac cgttgcgccc 720
tcgacatgca gcaagcccat gtgcccaccc cctgaactcc cggggggacc gtctgtcttc 780
atcttccccc caaaacccaa ggacaccctc atgatctcac gcacccccga ggtcacatgc 840
gtggtggtgg acgtgagcca ggatgacccc gaggtgcagt tcacatggta cataaacaac 900
gagcaggtgc gcaccgcccg gccgccgcta cgggagcagc agttcaacag cacgatccgc 960
gtggtcagca ccctccccat cgcgcaccag gactggctga ggggcaagga gttcaagtgc 1020
aaagtccaca acaaggcact cccggccccc atcgagaaaa ccatctccaa agccagaggg 1080
cagcccctgg agccgaaggt ctacaccatg ggccctcccc gggaggagct gagcagcagg 1140
tcggtcagcc tgacctgcat gatcaacggc ttctaccctt ccgacatctc ggtggagtgg 1200
gagaagaacg ggaaggcaga ggacaactac aagaccacgc cgaccgtgct ggacagcgac 1260
ggctcctact tcctctacag caagctctca gtgcccacga gtgagtggca gcggggcgac 1320
gtcttcacct gctccgtgat gcacgaggcc ttgcacaacc actacacgca gaagtccatc 1380
tcccgctctc cgggtaaata g 1401
<210> 58
<211> 714
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 58
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcgt tcgaattgac ccagactcca tcctccgtgg aggctgctgt gggaggcacg 120
cccaccatca agtgccaggc cagtcagacc atttacagtt acttatcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tatgaagcgt ccaaactggc ctctggggtc 240
ccatcgcggt tcagcggcag tggatctggg acagactaca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caaagctatc atggtactgc tagtactgaa 360
tataatactt tcggcggggg gaccgaggtg gtggtcagag gtgatccagt tgcacctact 420
gtcctcatct tcccaccagc tgctgatcag gtggcaactg gaacagtcac catcgtgtgt 480
gtggcgaata aatactttcc cgatgtcacc gtcacctggg aggtggatgg caccacccaa 540
acaactggca tcgagaacag taaaacaccg cagaattctg cagattgtac ctacaacctc 600
agcagcactc tgacactgac cagcacacag tacaacagcc acaaagagta cacctgcaag 660
gtgacccagg gcacgacctc agtcgtccag agcttcaata ggggtgactg ttag 714
<210> 59
<211> 1401
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 59
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
cagcagctgg tggagtccgg gggaggcctg gtcaagcctg gggcagccct gacattcacc 120
tgcacagcct ctggattctc cttcagtggc aattattgga tatgctgggt ccgccaggct 180
ccagggaagg ggttggagtg gatcgcgtgc attggtacta ttactagtag gacatactac 240
gcgagctggg cgaaaggccg attcaccatt tccaaaacct cgtcgaccac ggtgactctg 300
caaatgacca gtctgacagc cgcggacacg gccacgtatt tctgtgcgag aggtgcggtt 360
gttagtagtg gtaatgctcc ctactacttt accttgtggg gcccaggcac cctggtcacc 420
gtctcctcag ggcaacctaa ggctccatca gtcttcccac tggccccctg ctgcggggac 480
acacccagct ccacggtgac cctgggctgc ctggtcaaag gctacctccc ggagccagtg 540
accgtgacct ggaactcggg caccctcacc aatggggtac gcaccttccc gtccgtccgg 600
cagtcctcag gcctctactc gctgagcagc gtggtgagcg tgacctcaag cagccagccc 660
gtcacctgca acgtggccca cccagccacc aacaccaaag tggacaagac cgttgcgccc 720
tcgacatgca gcaagcccat gtgcccaccc cctgaactcc cggggggacc gtctgtcttc 780
atcttccccc caaaacccaa ggacaccctc atgatctcac gcacccccga ggtcacatgc 840
gtggtggtgg acgtgagcca ggatgacccc gaggtgcagt tcacatggta cataaacaac 900
gagcaggtgc gcaccgcccg gccgccgcta cgggagcagc agttcaacag cacgatccgc 960
gtggtcagca ccctccccat cgcgcaccag gactggctga ggggcaagga gttcaagtgc 1020
aaagtccaca acaaggcact cccggccccc atcgagaaaa ccatctccaa agccagaggg 1080
cagcccctgg agccgaaggt ctacaccatg ggccctcccc gggaggagct gagcagcagg 1140
tcggtcagcc tgacctgcat gatcaacggc ttctaccctt ccgacatctc ggtggagtgg 1200
gagaagaacg ggaaggcaga ggacaactac aagaccacgc cgaccgtgct ggacagcgac 1260
ggctcctact tcctctacag caagctctca gtgcccacga gtgagtggca gcggggcgac 1320
gtcttcacct gctccgtgat gcacgaggcc ttgcacaacc actacacgca gaagtccatc 1380
tcccgctctc cgggtaaata g 1401
<210> 60
<211> 711
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 60
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcat tcgaattgac gcagactcca tcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagc attagtagtt acttatcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tacagggcat ccactctgga atctggggtc 240
ccatcgcggt ttaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttacttctgt caaagctatt atggtgttac ttttagtggt 360
tttgctttcg gcggagggac cgaggtggtg gtcaaaggtg atccagttgc acctactgtc 420
ctcatcttcc caccagctgc tgatcaggtg gcaactggaa cagtcaccat cgtgtgtgtg 480
gcgaataaat actttcccga tgtcaccgtc acctgggagg tggatggcac cacccaaaca 540
actggcatcg agaacagtaa aacaccgcag aattctgcag attgtaccta caacctcagc 600
agcactctga cactgaccag cacacagtac aacagccaca aagagtacac ctgcaaggtg 660
acccagggca cgacctcagt cgtccagagc ttcaataggg gtgactgtta g 711
<210> 61
<211> 1383
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 61
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
aaagcctctg gaatcgactt caataactat tggataacct gggtccgcca ggctccaggg 180
aaggggctgg agtggatcgc atgcatttat gttggaatta ccggccgcac atggtacgcg 240
aactgggcga aaggccgatt caccatctcc aaggcctcga gcacggtgga tctgaaaatg 300
accagtctga cagccgcgga cacggccacc tatttctgtg cgaggaatgg tgatggtggt 360
atttatgctc ttaacttgtg gggcccaggc accctggtca ccgtctcctc agggcaacct 420
aaggctccat cagtcttccc actggccccc tgctgcgggg acacacccag ctccacggtg 480
accctgggct gcctggtcaa aggctacctc ccggagccag tgaccgtgac ctggaactcg 540
ggcaccctca ccaatggggt acgcaccttc ccgtccgtcc ggcagtcctc aggcctctac 600
tcgctgagca gcgtggtgag cgtgacctca agcagccagc ccgtcacctg caacgtggcc 660
cacccagcca ccaacaccaa agtggacaag accgttgcgc cctcgacatg cagcaagccc 720
atgtgcccac cccctgaact cccgggggga ccgtctgtct tcatcttccc cccaaaaccc 780
aaggacaccc tcatgatctc acgcaccccc gaggtcacat gcgtggtggt ggacgtgagc 840
caggatgacc ccgaggtgca gttcacatgg tacataaaca acgagcaggt gcgcaccgcc 900
cggccgccgc tacgggagca gcagttcaac agcacgatcc gcgtggtcag caccctcccc 960
atcgcgcacc aggactggct gaggggcaag gagttcaagt gcaaagtcca caacaaggca 1020
ctcccggccc ccatcgagaa aaccatctcc aaagccagag ggcagcccct ggagccgaag 1080
gtctacacca tgggccctcc ccgggaggag ctgagcagca ggtcggtcag cctgacctgc 1140
atgatcaacg gcttctaccc ttccgacatc tcggtggagt gggagaagaa cgggaaggca 1200
gaggacaact acaagaccac gccgaccgtg ctggacagcg acggctccta cttcctctac 1260
agcaagctct cagtgcccac gagtgagtgg cagcggggcg acgtcttcac ctgctccgtg 1320
atgcacgagg ccttgcacaa ccactacacg cagaagtcca tctcccgctc tccgggtaaa 1380
tag 1383
<210> 62
<211> 717
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 62
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcac aagtgctgac ccagactgca tcgtccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca gttgccagtc cagtcagagt gtttataata ataattggtt agcctggtat 180
cagcagaaac cagggcagcc tcccaagctc ctgatctaca gggcatccac tctgacatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
gacctggagt gtgacgatgc tgccacttac tactgtgcag gcggttatag tggtaatatt 360
tacgtaaatg atttcggcgg agggaccgag gtggtggtca aaggtgatcc agttgcacct 420
actgtcctca tcttcccacc agctgctgat caggtggcaa ctggaacagt caccatcgtg 480
tgtgtggcga ataaatactt tcccgatgtc accgtcacct gggaggtgga tggcaccacc 540
caaacaactg gcatcgagaa cagtaaaaca ccgcagaatt ctgcagattg tacctacaac 600
ctcagcagca ctctgacact gaccagcaca cagtacaaca gccacaaaga gtacacctgc 660
aaggtgaccc agggcacgac ctcagtcgtc cagagcttca ataggggtga ctgttag 717
<210> 63
<211> 1380
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 63
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctgg aggagtccgg gggagacctg gtcaagcctg ggggatccct gacactcacc 120
tgcaaagcct ctggattctc cttcagtaat acctactggg catgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcgcatgc atgaatcctg ctagtagtgg tagctcttac 240
tacgcgagct gggcgaaagg ccgattcacc atctccaaaa cctcgtcgac cacggtgact 300
ctgcacatgc ccagtctgac agccgcggac acggccacct atttctgtgc gaaatgggat 360
actgctttcg atgtgtgggg cccaggcacc ctggtcaccg tctcctcagg gcaacctaag 420
gctccatcag tcttcccact ggccccctgc tgcggggaca cacccagctc cacggtgacc 480
ctgggctgcc tggtcaaagg ctacctcccg gagccagtga ccgtgacctg gaactcgggc 540
accctcacca atggggtacg caccttcccg tccgtccggc agtcctcagg cctctactcg 600
ctgagcagcg tggtgagcgt gacctcaagc agccagcccg tcacctgcaa cgtggcccac 660
ccagccacca acaccaaagt ggacaagacc gttgcgccct cgacatgcag caagcccatg 720
tgcccacccc ctgaactccc ggggggaccg tctgtcttca tcttcccccc aaaacccaag 780
gacaccctca tgatctcacg cacccccgag gtcacatgcg tggtggtgga cgtgagccag 840
gatgaccccg aggtgcagtt cacatggtac ataaacaacg agcaggtgcg caccgcccgg 900
ccgccgctac gggagcagca gttcaacagc acgatccgcg tggtcagcac cctccccatc 960
gcgcaccagg actggctgag gggcaaggag ttcaagtgca aagtccacaa caaggcactc 1020
ccggccccca tcgagaaaac catctccaaa gccagagggc agcccctgga gccgaaggtc 1080
tacaccatgg gccctccccg ggaggagctg agcagcaggt cggtcagcct gacctgcatg 1140
atcaacggct tctacccttc cgacatctcg gtggagtggg agaagaacgg gaaggcagag 1200
gacaactaca agaccacgcc gaccgtgctg gacagcgacg gctcctactt cctctacagc 1260
aagctctcag tgcccacgag tgagtggcag cggggcgacg tcttcacctg ctccgtgatg 1320
cacgaggcct tgcacaacca ctacacgcag aagtccatct cccgctctcc gggtaaatag 1380
<210> 64
<211> 714
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 64
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgccg atgttgtgat gacccagact ccatcctccg tggaggcagc tgtgggaggc 120
acagtcacca tcaagtgcca ggccagtcag agcattagta gctacttagc ctggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctatggtg catccaatct ggagtctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacagagt acactctcac catcagcggc 300
gtgcagtgtg acgatgctgc cacttactac tgtcaaaact attatgctat tgatacttat 360
ggtcatgctt tcggcggagg gaccgaggtg gtggtcaaag gtgatccagt tgcacctact 420
gtcctcatct tcccaccagc tgctgatcag gtggcaactg gaacagtcac catcgtgtgt 480
gtggcgaata aatactttcc cgatgtcacc gtcacctggg aggtggatgg caccacccaa 540
acaactggca tcgagaacag taaaacaccg cagaattctg cagattgtac ctacaacctc 600
agcagcactc tgacactgac cagcacacag tacaacagcc acaaagagta cacctgcaag 660
gtgacccagg gcacgacctc agtcgtccag agcttcaata ggggtgactg ttag 714
<210> 65
<211> 1368
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 65
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctgg aggagtccgg gggagacctg gtcaagcctg gggcatccct gacactcacc 120
tgcacagcct ctggattctc ctttagtagc aactatcaca tctgctgggt ccgccaggct 180
ccaggaaagg ggctggagtt gatcgcatgc atttatgttg gtgatggcag cacatactac 240
gcgagctggg cgaaaggccg attcaccatc tccaaatcct cgtcgaccac ggtagctctg 300
caaatgacca gtctgacagc cgcggacacg gccacctatt tctgtgggag aatgtttaac 360
ttgtggggcc caggcaccct ggtcaccgtc tcctcagggc aacctaaggc tccatcagtc 420
ttcccactgg ccccctgctg cggggacaca cccagctcca cggtgaccct gggctgcctg 480
gtcaaaggct acctcccgga gccagtgacc gtgacctgga actcgggcac cctcaccaat 540
ggggtacgca ccttcccgtc cgtccggcag tcctcaggcc tctactcgct gagcagcgtg 600
gtgagcgtga cctcaagcag ccagcccgtc acctgcaacg tggcccaccc agccaccaac 660
accaaagtgg acaagaccgt tgcgccctcg acatgcagca agcccatgtg cccaccccct 720
gaactcccgg ggggaccgtc tgtcttcatc ttccccccaa aacccaagga caccctcatg 780
atctcacgca cccccgaggt cacatgcgtg gtggtggacg tgagccagga tgaccccgag 840
gtgcagttca catggtacat aaacaacgag caggtgcgca ccgcccggcc gccgctacgg 900
gagcagcagt tcaacagcac gatccgcgtg gtcagcaccc tccccatcgc gcaccaggac 960
tggctgaggg gcaaggagtt caagtgcaaa gtccacaaca aggcactccc ggcccccatc 1020
gagaaaacca tctccaaagc cagagggcag cccctggagc cgaaggtcta caccatgggc 1080
cctccccggg aggagctgag cagcaggtcg gtcagcctga cctgcatgat caacggcttc 1140
tacccttccg acatctcggt ggagtgggag aagaacggga aggcagagga caactacaag 1200
accacgccga ccgtgctgga cagcgacggc tcctacttcc tctacagcaa gctctcagtg 1260
cccacgagtg agtggcagcg gggcgacgtc ttcacctgct ccgtgatgca cgaggccttg 1320
cacaaccact acacgcagaa gtccatctcc cgctctccgg gtaaatag 1368
<210> 66
<211> 708
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 66
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
atatgtgacc ctgtgctgac ccagactcca tcctccgtgt ctgcggctgt gggagtcaca 120
gtcaccatca actgccagtc cagtccgagt gtttatagta actacttatc ctggtatcag 180
cagaaaccag ggcagcctcc caagctcctc atctatctgg catctactct ggcatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacacagt tcactctcac catcagcgac 300
gtgcagtgtg acgatgctgc cacttactac tgtgcaggca cttatagtgg taatatttgg 360
tctttcggcg gagggaccga ggtggtggtc aaaggtgatc cagttgcacc tactgtcctc 420
atcttcccac cagctgctga tcaggtggca actggaacag tcaccatcgt gtgtgtggcg 480
aataaatact ttcccgatgt caccgtcacc tgggaggtgg atggcaccac ccaaacaact 540
ggcatcgaga acagtaaaac accgcagaat tctgcagatt gtacctacaa cctcagcagc 600
actctgacac tgaccagcac acagtacaac agccacaaag agtacacctg caaggtgacc 660
cagggcacga cctcagtcgt ccagagcttc aataggggtg actgttag 708
<210> 67
<211> 1383
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 67
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
cagcagctgg tggagtccgg gggaggcctg gtcaagcctg gggcatccct gacactcacc 120
tgcacagcct ctggattctc cttcagtagc ggctatcaca tgtgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcgcatgc tttggtgttt atactggtac cactacctac 240
gcgagctggg cgaaaggtcg attcaccatc tccaaaacct cgtcgaccac ggtgactcta 300
caaatgacca gtctaacagt cgcggacacg gccacctatt tctgtgcgag aatcagtgct 360
gaaaatggtg gggacttgtg gggcccaggc accctggtca ccgtctcctc agggcaacct 420
aaggctccat cagtcttccc actggccccc tgctgcgggg acacacccag ctccacggtg 480
accctgggct gcctggtcaa aggctacctc ccggagccag tgaccgtgac ctggaactcg 540
ggcaccctca ccaatggggt acgcaccttc ccgtccgtcc ggcagtcctc aggcctctac 600
tcgctgagca gcgtggtgag cgtgacctca agcagccagc ccgtcacctg caacgtggcc 660
cacccagcca ccaacaccaa agtggacaag accgttgcgc cctcgacatg cagcaagccc 720
atgtgcccac cccctgaact cccgggggga ccgtctgtct tcatcttccc cccaaaaccc 780
aaggacaccc tcatgatctc acgcaccccc gaggtcacat gcgtggtggt ggacgtgagc 840
caggatgacc ccgaggtgca gttcacatgg tacataaaca acgagcaggt gcgcaccgcc 900
cggccgccgc tacgggagca gcagttcaac agcacgatcc gcgtggtcag caccctcccc 960
atcgcgcacc aggactggct gaggggcaag gagttcaagt gcaaagtcca caacaaggca 1020
ctcccggccc ccatcgagaa aaccatctcc aaagccagag ggcagcccct ggagccgaag 1080
gtctacacca tgggccctcc ccgggaggag ctgagcagca ggtcggtcag cctgacctgc 1140
atgatcaacg gcttctaccc ttccgacatc tcggtggagt gggagaagaa cgggaaggca 1200
gaggacaact acaagaccac gccgaccgtg ctggacagcg acggctccta cttcctctac 1260
agcaagctct cagtgcccac gagtgagtgg cagcggggcg acgtcttcac ctgctccgtg 1320
atgcacgagg ccttgcacaa ccactacacg cagaagtcca tctcccgctc tccgggtaaa 1380
tag 1383
<210> 68
<211> 711
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 68
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagc attagcaact acttttcttg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tacagggcgt ccactctggc atctggggtc 240
ccatcgcggt tcagcggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg attctgccac ttactactgt cagtgcactt atggtagtag tagtactggt 360
tttggtttcg gcggagggac cgaggtggtg gtcaaaggtg atccagttgc acctactgtc 420
cccatcttcc caccagctgc tgatcaggtg gcaactggaa cagtcaccat cgtgtgtgtg 480
gcgaataaat actttcccga tgtcaccgtc acctgggagg tggatggcac cacccaaaca 540
actggcatcg agaacagtaa aacaccgcag aattctgcag attgtaccta caacctcagc 600
agcactctga cactgaccag cacacagtac aacagccaca aagagtacac ctgcaaggtg 660
acccagggca cgacctcagt cgtccagagc ttcaataggg gtgactgtta g 711
<210> 69
<211> 1371
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 69
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
atggcctctg gaatcgactt cagtagcggc tacggcatgt ggtgggtccg ccaggctcca 180
gggaagggac tggagtatat cggatacatt gatactggtg atgataacac atactacgcg 240
aactgggcga aaggccgatt caccatctcc aaaacctcgt cgaccacggt gactctgcaa 300
atgaccagtc tgacagtcgc ggacacggcc acctatttct gtgcgaaagg gggcgccata 360
gacctctggg gcccagggac cctcgtcacc gtctcttcag ggcaacctaa ggctccatca 420
gtcttcccac tggccccctg ctgcggggac acacccagct ccacggtgac cctgggctgc 480
ctggtcaaag gctacctccc ggagccagtg accgtgacct ggaactcggg caccctcacc 540
aatggggtac gcaccttccc gtccgtccgg cagtcctcag gcctctactc gctgagcagc 600
gtggtgagcg tgacctcaag cagccagccc gtcacctgca acgtggccca cccagccacc 660
aacaccaaag tggacaagac cgttgcgccc tcgacatgca gcaagcccat gtgcccaccc 720
cctgaactcc cggggggacc gtctgtcttc atcttccccc caaaacccaa ggacaccctc 780
atgatctcac gcacccccga ggtcacatgc gtggtggtgg acgtgagcca ggatgacccc 840
gaggtgcagt tcacatggta cataaacaac gagcaggtgc gcaccgcccg gccgccgcta 900
cgggagcagc agttcaacag cacgatccgc gtggtcagca ccctccccat cgcgcaccag 960
gactggctga ggggcaagga gttcaagtgc aaagtccaca acaaggcact cccggccccc 1020
atcgagaaaa ccatctccaa agccagaggg cagcccctgg agccgaaggt ctacaccatg 1080
ggccctcccc gggaggagct gagcagcagg tcggtcagcc tgacctgcat gatcaacggc 1140
ttctaccctt ccgacatctc ggtggagtgg gagaagaacg ggaaggcaga ggacaactac 1200
aagaccacgc cgaccgtgct ggacagcgac ggctcctact tcctctacag caagctctca 1260
gtgcccacga gtgagtggca gcggggcgac gtcttcacct gctccgtgat gcacgaggcc 1320
ttgcacaacc actacacgca gaagtccatc tcccgctctc cgggtaaata g 1371
<210> 70
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 70
atggacacga gggcccccac tcagctgctg ggactcctac tgctctggct cccaggtgcc 60
agatgtgctg acattgtgat gacccagact ccagcctccg tggaggcagc tgtgggaggc 120
acagtcacca tcaagtgcca ggccagtcag agcattagta gttacttagc ctggtatcag 180
cagaaaccag ggcagcgtcc caagctcctg atctacaggg catccactct aaaatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacagagt acactctcac catcagcgac 300
ctggagtgtg ccgatgctgc cacttattat tgtcaagcgt attatcttag tagtagtatc 360
agttatggta atactttcgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 71
<211> 1371
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 71
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg cgtccctgac actcacctgc 120
acagcctctg gattctccct cagtagcggg tatggcatgt gctgggtccg ccaggctcca 180
gggaagggac tggagtggat cggatacact gatactgcta ctggtaccat tcactacgcg 240
agctgggcga aaggccgatt caccatctcc aaaacctcgt cgaccacggt gactctgcaa 300
atgaccagtc tgacagccgc ggacacggcc acctatttct gtgcgaaagg gggcgccatg 360
gacctctggg gcccagggac cctcgtcacc gtctcttcag ggcaacctaa ggctccatca 420
gtcttcccac tggccccctg ctgcggggac acacccagct ccacggtgac cctgggctgc 480
ctggtcaaag gctacctccc ggagccagtg accgtgacct ggaactcggg caccctcacc 540
aatggggtac gcaccttccc gtccgtccgg cagtcctcag gcctctactc gctgagcagc 600
gtggtgagcg tgacctcaag cagccagccc gtcacctgca acgtggccca cccagccacc 660
aacaccaaag tggacaagac cgttgcgccc tcgacatgca gcaagcccat gtgcccaccc 720
cctgaactcc cggggggacc gtctgtcttc atcttccccc caaaacccaa ggacaccctc 780
atgatctcac gcacccccga ggtcacatgc gtggtggtgg acgtgagcca ggatgacccc 840
gaggtgcagt tcacatggta cataaacaac gagcaggtgc gcaccgcccg gccgccgcta 900
cgggagcagc agttcaacag cacgatccgc gtggtcagca ccctccccat cgcgcaccag 960
gactggctga ggggcaagga gttcaagtgc aaagtccaca acaaggcact cccggccccc 1020
atcgagaaaa ccatctccaa agccagaggg cagcccctgg agccgaaggt ctacaccatg 1080
ggccctcccc gggaggagct gagcagcagg tcggtcagcc tgacctgcat gatcaacggc 1140
ttctaccctt ccgacatctc ggtggagtgg gagaagaacg ggaaggcaga ggacaactac 1200
aagaccacgc cgaccgtgct ggacagcgac ggctcctact tcctctacag caagctctca 1260
gtgcccacga gtgagtggca gcggggcgac gtcttcacct gctccgtgat gcacgaggcc 1320
ttgcacaacc actacacgca gaagtccatc tcccgctctc cgggtaaata g 1371
<210> 72
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 72
atggacacga gggcccccac tcagctgctg gggctcctac tgctctggct cccaggtgcc 60
agatgtgctg acattgtgat gacccagact ccagcctccg tggaggcagc tgtgggaggc 120
acagtcacca tcaagtgcca ggccagtcag agcattagta gctacttagc ctggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctacagga catccactct ggcatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacagagt acactctcac catcagcgac 300
ctggagtgtg ccgatgctgc cacttactat tgtcaaagct atgcttatag tagtagtagc 360
agttatggta atgctttcgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 73
<211> 1365
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 73
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
acaggctctg gaatcgactt cagtagcagc tactggatat gctgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcatgcatc gatggtagtg atggtaacac ttactacgcg 240
agctgggcga gaggccgatt caccatctcc aaaacctcgt cgaccacggt gactctgcaa 300
atggccagtc tgacagccgc ggacacggcc acctatttct gtacgagaga tctcaggttg 360
tggggcccag gcaccctggt caccgtctcc tcagggcaac ctaaggctcc atcagtcttc 420
ccactggccc cctgctgcgg ggacacaccc agctccacgg tgaccctggg ctgcctggtc 480
aaaggctacc tcccggagcc agtgaccgtg acctggaact cgggcaccct caccaatggg 540
gtacgcacct tcccgtccgt ccggcagtcc tcaggcctct actcgctgag cagcgtggtg 600
agcgtgacct caagcagcca gcccgtcacc tgcaacgtgg cccacccagc caccaacacc 660
aaagtggaca agaccgttgc gccctcgaca tgcagcaagc ccatgtgccc accccctgaa 720
ctcccggggg gaccgtctgt cttcatcttc cccccaaaac ccaaggacac cctcatgatc 780
tcacgcaccc ccgaggtcac atgcgtggtg gtggacgtga gccaggatga ccccgaggtg 840
cagttcacat ggtacataaa caacgagcag gtgcgcaccg cccggccgcc gctacgggag 900
cagcagttca acagcacgat ccgcgtggtc agcaccctcc ccatcgcgca ccaggactgg 960
ctgaggggca aggagttcaa gtgcaaagtc cacaacaagg cactcccggc ccccatcgag 1020
aaaaccatct ccaaagccag agggcagccc ctggagccga aggtctacac catgggccct 1080
ccccgggagg agctgagcag caggtcggtc agcctgacct gcatgatcaa cggcttctac 1140
ccttccgaca tctcggtgga gtgggagaag aacgggaagg cagaggacaa ctacaagacc 1200
acgccgaccg tgctggacag cgacggctcc tacttcctct acagcaagct ctcagtgccc 1260
acgagtgagt ggcagcgggg cgacgtcttc acctgctccg tgatgcacga ggccttgcac 1320
aaccactaca cgcagaagtc catctcccgc tctccgggta aatag 1365
<210> 74
<211> 723
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 74
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgctg acattgtgct gacccagact ccagcctcgg tgtctgcagc tgtgggaggc 120
acagtcacca tcaactgcca ggccagtcag aatgtttata gtaacaatgc cttagcctgg 180
catcagcaga aaccagggca gcgtcccaac ctcctgatct acaaggcttc cactctggca 240
tctggggtcc catcgcggtt caaaggcagt ggatctggga cacagtttac tctcaccatc 300
agcgacgtgc agtgtgacga tgctgccact tactactgtc taggcgaatt tagttgtagt 360
agtggtgatt gttttgtttt cggcggaggg accgaggtgg tggtcaaagg tgatccagtt 420
gcacctactg tcctcatctt cccaccagct gctgatcagg tggcaactgg aacagtcacc 480
atcgtgtgtg tggcgaataa atactttccc gatgtcaccg tcacctggga ggtggatggc 540
accacccaaa caactggcat cgagaacagt aaaacaccgc agaattctgc agattgtacc 600
tacaacctca gcagcactct gacactgacc agcacacagt acaacagcca caaagagtac 660
acctgcaagg tgacccaggg cacgacctca gtcgtccaga gcttcaatag gggtgactgt 720
tag 723
<210> 75
<211> 1371
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 75
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
atggcctctg gaatcgactt cagtagcggc tacggcatgt ggtgggtccg ccaggctcca 180
gggaagggac tggagtatat cggatacatt gatactggtg atgataacac atactacgcg 240
aactgggcga aaggccgatt caccatctcc aaaacctcgt cgaccacggt gactctgcaa 300
atgaccagtc tgacagtcgc ggacacggcc acctatttct gtgcgaaagg gggcgccata 360
gacctctggg gcccagggac cctcgtcacc gtctcttcag ggcaacctaa ggctccatca 420
gtcttcccac tggccccctg ctgcggggac acacccagct ccacggtgac cctgggctgc 480
ctggtcaaag gctacctccc ggagccagtg accgtgacct ggaactcggg caccctcacc 540
aatggggtac gcaccttccc gtccgtccgg cagtcctcag gcctctactc gctgagcagc 600
gtggtgagcg tgacctcaag cagccagccc gtcacctgca acgtggccca cccagccacc 660
aacaccaaag tggacaagac cgttgcgccc tcgacatgca gcaagcccat gtgcccaccc 720
cctgaactcc cggggggacc gtctgtcttc atcttccccc caaaacccaa ggacaccctc 780
atgatctcac gcacccccga ggtcacatgc gtggtggtgg acgtgagcca ggatgacccc 840
gaggtgcagt tcacatggta cataaacaac gagcaggtgc gcaccgcccg gccgccgcta 900
cgggagcagc agttcaacag cacgatccgc gtggtcagca ccctccccat cgcgcaccag 960
gactggctga ggggcaagga gttcaagtgc aaagtccaca acaaggcact cccggccccc 1020
atcgagaaaa ccatctccaa agccagaggg cagcccctgg agccgaaggt ctacaccatg 1080
ggccctcccc gggaggagct gagcagcagg tcggtcagcc tgacctgcat gatcaacggc 1140
ttctaccctt ccgacatctc ggtggagtgg gagaagaacg ggaaggcaga ggacaactac 1200
aagaccacgc cgaccgtgct ggacagcgac ggctcctact tcctctacag caagctctca 1260
gtgcccacga gtgagtggca gcggggcgac gtcttcacct gctccgtgat gcacgaggcc 1320
ttgcacaacc actacacgca gaagtccatc tcccgctctc cgggtaaata g 1371
<210> 76
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 76
atggacacga gggcccccac tcagctgctg ggactcctac tgctctggct cccaggtgcc 60
agatgtgctg acattgtgat gacccagact ccagcctccg tggaggcagc tgtgggaggc 120
acagtcacca tcaagtgcca ggccagtcag agcattagta gttacttagc ctggtatcag 180
cagaaaccag ggcagcgtcc caagctcctg atctacaggg catccactct aaaatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacagagt acactctcac catcagcgac 300
ctggagtgtg ccgatgctgc cacttattat tgtcaagcgt attatcttag tagtagtatc 360
agttatggta atactttcgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 77
<211> 1416
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 77
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
cagcagctgg aggagtccgg gggaggcctg gtcaagcctg gaggaaccct gacactcacc 120
tgcaaagcct ctggagtcgc cctcaatccc tactactata tgtgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcgcatgc gtggatgctg atagtagtgg tagcacttac 240
tacgcgagct gggcgaaagg ccgattcacc atctccaaaa cctcgtcgac cacggtgact 300
ctgaaaatga ccagtctgac agccgcggac acggccacct atttctgtgc gagagaatcg 360
gttgactata gttctgttgg tattggctat gtacatggta cggatggctt gtggggccca 420
ggcaccctgg tcaccgtctc ctcagggcaa cctaaggctc catcagtctt cccactggcc 480
ccctgctgcg gggacacacc cagctccacg gtgaccctgg gctgcctggt caaaggctac 540
ctcccggagc cagtgaccgt gacctggaac tcgggcaccc tcaccaatgg ggtacgcacc 600
ttcccgtccg tccggcagtc ctcaggcctc tactcgctga gcagcgtggt gagcgtgacc 660
tcaagcagcc agcccgtcac ctgcaacgtg gcccacccag ccaccaacac caaagtggac 720
aagaccgttg cgccctcgac atgcagcaag cccatgtgcc caccccctga actcccgggg 780
ggaccgtctg tcttcatctt ccccccaaaa cccaaggaca ccctcatgat ctcacgcacc 840
cccgaggtca catgcgtggt ggtggacgtg agccaggatg accccgaggt gcagttcaca 900
tggtacataa acaacgagca ggtgcgcacc gcccggccgc cgctacggga gcagcagttc 960
aacagcacga tccgcgtggt cagcaccctc cccatcgcgc accaggactg gctgaggggc 1020
aaggagttca agtgcaaagt ccacaacaag gcactcccgg cccccatcga gaaaaccatc 1080
tccaaagcca gagggcagcc cctggagccg aaggtctaca ccatgggccc tccccgggag 1140
gagctgagca gcaggtcggt cagcctgacc tgcatgatca acggcttcta cccttccgac 1200
atctcggtgg agtgggagaa gaacgggaag gcagaggaca actacaagac cacgccgacc 1260
gtgctggaca gcgacggctc ctacttcctc tacagcaagc tctcagtgcc cacgagtgag 1320
tggcagcggg gcgacgtctt cacctgctcc gtgatgcacg aggccttgca caaccactac 1380
acgcagaagt ccatctcccg ctctccgggt aaatag 1416
<210> 78
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 78
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgccg acatcgtggt gacccagact ccatcctccg tgtctgcagc tgtgggaggc 120
acagtcacca tcaagtgcca ggccagtcag agcattagca actacttttc ttggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctacaggg cgtccactct ggcatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacagagt tcactctcac catcagcgac 300
ctggagtgtg ccgatgctgc cacttactac tgtcaatgca cttacggtag aagtaatagt 360
aatttttttt atggtttcgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 79
<211> 1395
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 79
atggagactg ggctgcgctg gcttctcctg gtcgccgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg cctccctgac actcacctgc 120
acagcctctg gatcctcctt cagtagtacc tactggaact gctgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcatgcatt aatgctggta gtggtaccac ttactacgcg 240
agctgggcga aaggccgatt caccgtctcc aaaacctcgt cgaccacggt gactctgcaa 300
atgaccagtc tgacagccgc ggacacggcc acctatttct gtacgagaga tagtgatggt 360
cgttttagta gtggctacta ttttaacttg tggggcccag gcaccctggt caccgtctcc 420
tcagggcaac ctaaggctcc atcagtcttc ccactggccc cctgctgcgg ggacacaccc 480
agctccacgg tgaccctggg ctgcctggtc aaaggctacc tcccggagcc agtgaccgtg 540
acctggaact cgggcaccct caccaatggg gtacgcacct tcccgtccgt ccggcagtcc 600
tcaggcctct actcgctgag cagcgtggtg agcgtgacct caagcagcca gcccgtcacc 660
tgcaacgtgg cccacccagc caccaacacc aaagtggaca agaccgttgc gccctcgaca 720
tgcagcaagc ccatgtgccc accccctgaa ctcccggggg gaccgtctgt cttcatcttc 780
cccccaaaac ccaaggacac cctcatgatc tcacgcaccc ccgaggtcac atgcgtggtg 840
gtggacgtga gccaggatga ccccgaggtg cagttcacat ggtacataaa caacgagcag 900
gtgcgcaccg cccggccgcc gctacgggag cagcagttca acagcacgat ccgcgtggtc 960
agcaccctcc ccatcgcgca ccaggactgg ctgaggggca aggagttcaa gtgcaaagtc 1020
cacaacaagg cactcccggc ccccatcgag aaaaccatct ccaaagccag agggcagccc 1080
ctggagccga aggtctacac catgggccct ccccgggagg agctgagcag caggtcggtc 1140
agcctgacct gcatgatcaa cggcttctac ccttccgaca tctcggtgga gtgggagaag 1200
aacgggaagg cagaggacaa ctacaagacc acgccgaccg tgctggacag cgacggctcc 1260
tacttcctct acagcaagct ctcagtgccc acgagtgagt ggcagcgggg cgacgtcttc 1320
acctgctccg tgatgcacga ggccttgcac aaccactaca cgcagaagtc catctcccgc 1380
tctccgggta aatag 1395
<210> 80
<211> 717
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 80
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccc aagtgctgac ccagactgca tcccctgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgtcagtc cagtcagagt gtttatgata acaactggtt agcctggtat 180
cagcaaaaac cagggcagcc tcccaaactc ttgatcgacg atgcatccaa attgacatct 240
ggggtctcat cgcggttcaa aggcagtgga tctgggacgc agttcactct caccatcagc 300
ggcgtgcagt gtgacgatgc tgccacttac tactgtcaag gcgcttatta tagtagtggt 360
tggtactggg ctttcggcgg agggaccgag gtggtggtca aaggtgatcc agttgcacct 420
actgtcctca tcttcccacc agctgctgat caggtggcaa ctggaacagt caccatcgtg 480
tgtgtggcga ataaatactt tcccgatgtc accgtcacct gggaggtgga tggcaccacc 540
caaacaactg gcatcgagaa cagtaaaaca ccgcagaatt ctgcagattg tacctacaac 600
ctcagcagca ctctgacact gaccagcaca cagtacaaca gccacaaaga gtacacctgc 660
aaggtgaccc agggcacgac ctcagtcgtc cagagcttca ataggggtga ctgttag 717
<210> 81
<211> 1404
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 81
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
cagcagctgg aggagtccgg gggaggcctg gtcaagcctg gaggaaccct gacactcacc 120
tgcaaagcct ctggaatcga cttcagtagc tactactaca tgtgttgggt ccgccaggct 180
ccagggaagg ggctggagtt gatcgtatgt atttatacta gtagtggtgg cacatggtac 240
gcgagctggg tgaatggccg actcaccatc tccagaagca ccagcctaaa cacggtggat 300
ctgaaaatga ccagtctgac agccgcggac acggccacct atttctgtgc cagaggggtt 360
tattctggta gtagtgatta tccaactcgg ttggatctct ggggccaggg caccctggtc 420
accgtctcct tagggcaacc taaggctcca tcagtcttcc cactggcccc ctgctgcggg 480
gacacaccca gctccacggt gaccctgggc tgcctggtca aaggctacct cccggagcca 540
gtgaccgtga cctggaactc gggcaccctc accaatgggg tacgcacctt cccgtccgtc 600
cggcagtcct caggcctcta ctcgctgagc agcgtggtga gcgtgacctc aagcagccag 660
cccgtcacct gcaacgtggc ccacccagcc accaacacca aagtggacaa gaccgttgcg 720
ccctcgacat gcagcaagcc catgtgccca ccccctgaac tcccgggggg accgtctgtc 780
ttcatcttcc ccccaaaacc caaggacacc ctcatgatct cacgcacccc cgaggtcaca 840
tgcgtggtgg tggacgtgag ccaggatgac cccgaggtgc agttcacatg gtacataaac 900
aacgagcagg tgcgcaccgc ccggccgccg ctacgggagc agcagttcaa cagcacgatc 960
cgcgtggtca gcaccctccc catcgcgcac caggactggc tgaggggcaa ggagttcaag 1020
tgcaaagtcc acaacaaggc actcccggcc cccatcgaga aaaccatctc caaagccaga 1080
gggcagcccc tggagccgaa ggtctacacc atgggccctc cccgggagga gctgagcagc 1140
aggtcggtca gcctgacctg catgatcaac ggcttctacc cttccgacat ctcggtggag 1200
tgggagaaga acgggaaggc agaggacaac tacaagacca cgccgaccgt gctggacagc 1260
gacggctcct acttcctcta cagcaagctc tcagtgccca cgagtgagtg gcagcggggc 1320
gacgtcttca cctgctccgt gatgcacgag gccttgcaca accactacac gcagaagtcc 1380
atctcccgct ctccgggtaa atag 1404
<210> 82
<211> 711
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 82
atggacacga gcacctccac tgcgctcctg gggctcctgc tgctctggct cacaggtgcc 60
agatgtgcca tcgagatgac ccagtctcca ccctccctgt ctgcatctgt gggagaaact 120
gtcaggatta ggtgcctggc cagtgaggac atttacagtg gtatatcctg gtaccaacag 180
aagccagaga aacctcctac actcctgatc tctggtgcat ccaatttaga atctggggtc 240
ccaccacggt tcagtggcgg tggatccggg acagattaca ccctcaccat cggcggcgtg 300
caggctgaag atgttgccac ctactactgt ctaggcggtt atagtttcag tagtaccggt 360
ttgacttttg gagctggcac caaggtggaa atcaaacgtg atccagttgc gccttctgtc 420
ctcctcttcc caccatctaa ggaggagctg acaactggaa cagccaccat cgtgtgtgtg 480
gcgaataaat actttcccga tgtcaccgtc acctgggagg tggatggcac cacccaaaca 540
actggcatcg agaacagtaa aacaccgcag aattctgcag attgtaccta caacctcagc 600
agcactctga cactgaccag cacacagtac aacagccaca aagagtacac ctgcaaggtg 660
acccagggca cgacctcagt cgtccagagc ttcaataggg gtgactgtta g 711
<210> 83
<211> 1383
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 83
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
caacatctgg tggagtccgg gggaggcctg gtcaagcctg gggcatccct gacactcacc 120
tgcacagcct ctggattctc cttcactacc ggctatcaca tgtgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcgcatgt tttggtgttt atactagtac cactacctac 240
gcgagctggg cgaaaggtcg attcaccatc tccaaaacct cgtcgaccac ggtgactcta 300
caaatgacca gtctaacagt cgcggacacg gccacctatt tctgtgcgag aatcagtgct 360
gaagatggtg gggacttgtg gggcccaggc accctggtca ccgtctcctc agggcaacct 420
aaggctccat cagtcttccc actggccccc tgctgcgggg acacacccag ctccacggtg 480
accctgggct gcctggtcaa aggctacctc ccggagccag tgaccgtgac ctggaactcg 540
ggcaccctca ccaatggggt acgcaccttc ccgtccgtcc ggcagtcctc aggcctctac 600
tcgctgagca gcgtggtgag cgtgacctca agcagccagc ccgtcacctg caacgtggcc 660
cacccagcca ccaacaccaa agtggacaag accgttgcgc cctcgacatg cagcaagccc 720
atgtgcccac cccctgaact cccgggggga ccgtctgtct tcatcttccc cccaaaaccc 780
aaggacaccc tcatgatctc acgcaccccc gaggtcacat gcgtggtggt ggacgtgagc 840
caggatgacc ccgaggtgca gttcacatgg tacataaaca acgagcaggt gcgcaccgcc 900
cggccgccgc tacgggagca gcagttcaac agcacgatcc gcgtggtcag caccctcccc 960
atcgcgcacc aggactggct gaggggcaag gagttcaagt gcaaagtcca caacaaggca 1020
ctcccggccc ccatcgagaa aaccatctcc aaagccagag ggcagcccct ggagccgaag 1080
gtctacacca tgggccctcc ccgggaggag ctgagcagca ggtcggtcag cctgacctgc 1140
atgatcaacg gcttctaccc ttccgacatc tcggtggagt gggagaagaa cgggaaggca 1200
gaggacaact acaagaccac gccgaccgtg ctggacagcg acggctccta cttcctctac 1260
agcaagctct cagtgcccac gagtgagtgg cagcggggcg acgtcttcac ctgctccgtg 1320
atgcacgagg ccttgcacaa ccactacacg cagaagtcca tctcccgctc tccgggtaaa 1380
tag 1383
<210> 84
<211> 711
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 84
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca cgtgccaggc cagtcagagc attagcaact acttttcttg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tacagggcgt ccactctggc atctggggtc 240
ccatcgcggt tcagcggcag tggatctggg acacagttca ctctcaccat cagcgacctg 300
gagtgtgccg attctgccac ttacgcctgt cagtgcactt atggtagtag tagtactggt 360
tttggtttcg gcggagggac cgaggtggtg gtcaaaggtg atccagttgc acctactgtc 420
ctcatcttcc caccagctgc tgatcaggtg gcaactggaa cagtcaccat cgtgtgtgtg 480
gcgaataaat actttcccga tgtcaccgtc acctgggagg tggatggcac cacccaaaca 540
actggcatcg agaacagtaa aacaccgcag aattctgcag attgtaccta caacctcagc 600
agcactctga cactgaccag cacacagtac aacagccaca aagagtacac ctgcaaggtg 660
acccagggca cgacctcagt cgtccagagc ttcaataggg gtgactgtta g 711
<210> 85
<211> 1389
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 85
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
aaagcctctg gattctcctt cagtagttac ttctggatat gctgggtccg ccaggctcca 180
gggaaggggc tggagtggag cgcatgcatc tatggtgata gtagtggtag tagttactac 240
gcgagctggg cgaaaggccg attcaccatc tccaaaacct cgtcgaccac ggtgactctg 300
caaatgacca gtctgacagc cgcggacacg gccacctatt tctgtgcgag ttatggtagt 360
agtagttatt actactctaa tttatggggc ccaggcaccc tggtcaccgt ctcctcaggg 420
caacctaagg ctccatcagt cttcccactg gccccctgct gcggggacac acccagctcc 480
acggtgaccc tgggctgcct ggtcaaaggc tacctcccgg agccagtgac cgtgacctgg 540
aactcgggca ccctcaccaa tggggtacgc accttcccgt ccgtccggca gtcctcaggc 600
ctctactcgc tgagcagcgt ggtgagcgtg acctcaagca gccagcccgt cacctgcaac 660
gtggcccacc cagccaccaa caccaaagtg gacaagaccg ttgcgccctc gacatgcagc 720
aagcccatgt gcccaccccc tgaactcccg gggggaccgt ctgtcttcat cttcccccca 780
aaacccaagg acaccctcat gatctcacgc acccccgagg tcacatgcgt ggtggtggac 840
gtgagccagg atgaccccga ggtgcagttc acatggtaca taaacaacga gcaggtgcgc 900
accgcccggc cgccgctacg ggagcagcag ttcaacagca cgatccgcgt ggtcagcacc 960
ctccccatcg cgcaccagga ctggctgagg ggcaaggagt tcaagtgcaa agtccacaac 1020
aaggcactcc cggcccccat cgagaaaacc atctccaaag ccagagggca gcccctggag 1080
ccgaaggtct acaccatggg ccctccccgg gaggagctga gcagcaggtc ggtcagcctg 1140
acctgcatga tcaacggctt ctacccttcc gacatctcgg tggagtggga gaagaacggg 1200
aaggcagagg acaactacaa gaccacgccg accgtgctgg acagcgacgg ctcctacttc 1260
ctctacagca agctctcagt gcccacgagt gagtggcagc ggggcgacgt cttcacctgc 1320
tccgtgatgc acgaggcctt gcacaaccac tacacgcaga agtccatctc ccgctctccg 1380
ggtaaatag 1389
<210> 86
<211> 708
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 86
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
atatgtgacc ctgtgatgac ccagactcca tcttccacgt ctgcggctgt gggaggcaca 120
gtcaccatca gttgccagtc cagtcagagt gtttataata acaactactt agcctggtat 180
cagcagaaac cagggcagcc tcccaaacgc ctgatctacg aatcatccaa actggcatct 240
ggggtcccat cgcggttcag aggcagtgga tctggggcac agttcactct caccatcagc 300
gacctggagt gtgacgatgc tgccacttac tactgtctag gcgcatatta tactactctt 360
gatttcggcg gagggaccga ggtggtggtc agaggtgatc cagttgcacc tactgtcctc 420
atcttcccac cagctgctga tcaggtggca actggaacag tcaccatcgt gtgtgtggcg 480
aataaatact ttcccgatgt caccgtcacc tgggaggtgg atggcaccac ccaaacaact 540
ggcatcgaga acagtaaaac accgcagaat tctgcagatt gtacctacaa cctcagcagc 600
actctgacac tgaccagcac acagtacaac agccacaaag agtacacctg caaggtgacc 660
cagggcacga cctcagtcgt ccagagcttc aataggggtg actgttag 708
<210> 87
<211> 1383
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 87
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagttgg tggagtccgg gggaggcctg gtccagcctg agggatccct gacactcacc 120
tgcaaagcct ctggattcga cttcagtagc aatgcaatgt gctgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcatgcatt tataatggtg atggcagcac atactacgcg 240
agctgggtga atggccgatt caccatctcc aagacctcgt cgaccacggt gactctgcaa 300
atgaccagtc tgacagccgc ggacacggcc acctatttct gtgcgagagg tctctctaat 360
tggaataggg ataacttatg gggccctggc accctggtca ccgtctcctc agggcaacct 420
aaggctccat cagtcttccc actggccccc tgctgcgggg acacacccag ctccacggtg 480
accctgggct gcctggtcaa aggctacctc ccggagccag tgaccgtgac ctggaactcg 540
ggcaccctca ccaatggggt acgcaccttc ccgtccgtcc ggcagtcctc aggcctctac 600
tcgctgagca gcgtggtgag cgtgacctca agcagccagc ccgtcacctg caacgtggcc 660
cacccagcca ccaacaccaa agtggacaag accgttgcgc cctcgacatg cagcaagccc 720
atgtgcccac cccctgaact cccgggggga ccgtctgtct tcatcttccc cccaaaaccc 780
aaggacaccc tcatgatctc acgcaccccc gaggtcacat gcgtggtggt ggacgtgagc 840
caggatgacc ccgaggtgca gttcacatgg tacataaaca acgagcaggt gcgcaccgcc 900
cggccgccgc tacgggagca gcagttcaac agcacgatcc gcgtggtcag caccctcccc 960
atcgcgcacc aggactggct gaggggcaag gagttcaagt gcaaagtcca caacaaggca 1020
ctcccggccc ccatcgagaa aaccatctcc aaagccagag ggcagcccct ggagccgaag 1080
gtctacacca tgggccctcc ccgggaggag ctgagcagca ggtcggtcag cctgacctgc 1140
atgatcaacg gcttctaccc ttccgacatc tcggtggagt gggagaagaa cgggaaggca 1200
gaggacaact acaagaccac gccgaccgtg ctggacagcg acggctccta cttcctctac 1260
agcaagctct cagtgcccac gagtgagtgg cagcggggcg acgtcttcac ctgctccgtg 1320
atgcacgagg ccttgcacaa ccactacacg cagaagtcca tctcccgctc tccgggtaaa 1380
tag 1383
<210> 88
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 88
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccc aagtgctgac ccagactcca tcctccgtgt ctgcagctgt gggaggcaca 120
gccaccatca actgccaggc cagtcagagt ctttatagtc ccaagaattt agcctggtat 180
cagcagacac cagggcagcc tcccaagctc ctgatctatt ctgcatcgaa actggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
ggcgtgcagt gtgacgatgc tgcaatttac tactgtcaag gcgaatttag ttgtactact 360
gctgcttgtt ttgcttttgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 89
<211> 1386
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 89
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tctttggagg agtccggggg aggcctggtc cagcctgagg gatccctgac actcgcctgc 120
acagcttcgg gattctcctt cagtagctac tactacatct gctgggtccg ccaggctcca 180
gggacggggc tggagtggat cggatgcatt aatactggta gtgatgacac tcactacgcg 240
agctggttga aaggccgatt caccttctcc aaggcctcgt cgaccacgtt gactctgcaa 300
atgaccagtc tgacagccgc ggacacggcc acctatttct gtgcgagatc atctggtagt 360
agtgatgatg cttatgatct ctggggccca ggcaccctgg tcactgtctc ctcagggcaa 420
cctaaggctc catcagtctt cccactggcc ccctgctgcg gggacacacc cagctccacg 480
gtgaccctgg gctgcctggt caaaggctac ctcccggagc cagtgaccgt gacctggaac 540
tcgggcaccc tcaccaatgg ggtacgcacc ttcccgtccg tccggcagtc ctcaggcctc 600
tactcgctga gcagcgtggt gagcgtgacc tcaagcagcc agcccgtcac ctgcaacgtg 660
gcccacccag ccaccaacac caaagtggac aagaccgttg cgccctcgac atgcagcaag 720
cccatgtgcc caccccctga actcccgggg ggaccgtctg tcttcatctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcacgcacc cccgaggtca catgcgtggt ggtggacgtg 840
agccaggatg accccgaggt gcagttcaca tggtacataa acaacgagca ggtgcgcacc 900
gcccggccgc cgctacggga gcagcagttc aacagcacga tccgcgtggt cagcaccctc 960
cccatcgcgc accaggactg gctgaggggc aaggagttca agtgcaaagt ccacaacaag 1020
gcactcccgg cccccatcga gaaaaccatc tccaaagcca gagggcagcc cctggagccg 1080
aaggtctaca ccatgggccc tccccgggag gagctgagca gcaggtcggt cagcctgacc 1140
tgcatgatca acggcttcta cccttccgac atctcggtgg agtgggagaa gaacgggaag 1200
gcagaggaca actacaagac cacgccgacc gtgctggaca gcgacggctc ctacttcctc 1260
tacagcaagc tctcagtgcc cacgagtgag tggcagcggg gcgacgtctt cacctgctcc 1320
gtgatgcacg aggccttgca caaccactac acgcagaagt ccatctcccg ctctccgggt 1380
aaatag 1386
<210> 90
<211> 708
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 90
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgt ctgaacctgt gggaggcgca 120
gtcaccatca agtgccaggc cagtcagagc attggtagta atttagcctg gtatcagcac 180
aaaccagggc agcctcccaa gctcctgatc tattttgcat ccagcctggc atctggggtc 240
tcgtcgcggt tcaagggcgg tagatctggg acacagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt cactgtactt attatcctct tagttatgtt 360
actttcggcg gagggaccga ggtggtggtc aaaggtgatc cagttgcacc tactgtcctc 420
atcttcccac cagctgctga tcaggtggca actggaacag tcaccatcgt gtgtgtggcg 480
aataaatact ttcccgatgt caccgtcacc tgggaggtgg atggcaccac ccaaacaact 540
ggcatcgaga acagtaaaac accgcagaat tctgcagatt gtacctacaa cctcagcagc 600
actctgacac tgaccagcac acagtacaac agccacaaag agtacacctg caaggtgacc 660
cagggcacga cctcagtcgt ccagagcttc aataggggtg actgttag 708
<210> 91
<211> 1395
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 91
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctggga catccctgac actctcctgc 120
acagcctctg gattctcctt cggtagctat tattatatgt gctgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcatgcatt gatgttggta gtagtggtga cacatactac 240
gcgagctggg tgaatggccg attcaccatc tccaaaacct cgtcgaccac ggtgactctg 300
caaatgacca gtctgacagc cgcggacacg gccacctatt tctgtgcgag agatgatact 360
gctgctggtg gttttggtaa tttggaattg tggggcccag gcaccctggt caccgtctcc 420
tcagggcaac ctaaggctcc atcagtcttc ccactggccc cctgctgcgg ggacacaccc 480
agctccacgg tgaccctggg ctgcctggtc aaaggctacc tcccggagcc agtgaccgtg 540
acctggaact cgggcaccct caccaatggg gtacgcacct tcccgtccgt ccggcagtcc 600
tcaggcctct actcgctgag cagcgtggtg agcgtgacct caagcagcca gcccgtcacc 660
tgcaacgtgg cccacccagc caccaacacc aaagtggaca agaccgttgc gccctcgaca 720
tgcagcaagc ccatgtgccc accccctgaa ctcccggggg gaccgtctgt cttcatcttc 780
cccccaaaac ccaaggacac cctcatgatc tcacgcaccc ccgaggtcac atgcgtggtg 840
gtggacgtga gccaggatga ccccgaggtg cagttcacat ggtacataaa caacgagcag 900
gtgcgcaccg cccggccgcc gctacgggag cagcagttca acagcacgat ccgcgtggtc 960
agcaccctcc ccatcgcgca ccaggactgg ctgaggggca aggagttcaa gtgcaaagtc 1020
cacaacaagg cactcccggc ccccatcgag aaaaccatct ccaaagccag agggcagccc 1080
ctggagccga aggtctacac catgggccct ccccgggagg agctgagcag caggtcggtc 1140
agcctgacct gcatgatcaa cggcttctac ccttccgaca tctcggtgga gtgggagaag 1200
aacgggaagg cagaggacaa ctacaagacc acgccgaccg tgctggacag cgacggctcc 1260
tacttcctct acagcaagct ctcagtgccc acgagtgagt ggcagcgggg cgacgtcttc 1320
acctgctccg tgatgcacga ggccttgcac aaccactaca cgcagaagtc catctcccgc 1380
tctccgggta aatag 1395
<210> 92
<211> 717
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 92
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcat tcgaattgac ccagactcca tcctccgtgt ctgaacctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagc atttacagct acttttcctg gtatcagcag 180
aaaccagggc agcctcccaa gcgcctgatt taccaggcat ccactctggc ttctggggtc 240
ccatcgcggt tcaaaggcag tggatctggg acagatttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caaaacaatt atggtagggg tagtggtagt 360
tatttttttg gtttcggcgg agggaccgag gtggtggtca aaggtgatcc agttgcacct 420
actgtcctca tcttcccacc agctgctgat caggtggcaa ctggaacagt caccatcgtg 480
tgtgtggcga ataaatactt tcccgatgtc accgtcacct gggaggtgga tggcaccacc 540
caaacaactg gcatcgagaa cagtaaaaca ccgcagaatt ctgcagattg tacctacaac 600
ctcagcagca ctctgacact gaccagcaca cagtacaaca gccacaaaga gtacacctgc 660
aaggtgaccc agggcacgac ctcagtcgtc cagagcttca ataggggtga ctgttag 717
<210> 93
<211> 1371
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 93
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
aaagcctctg gaatcgactt cagtagcggc tacggcatgt ggtgggtccg ccaggctcca 180
gggaagggac tggagtatat cggatacatt gatactggta gtggtagcac ttactacgcg 240
aactgggcga aaggccgatt caccatctcc aaaacctcgt cgaccatggt gactctgcaa 300
atgaccagtc tgacagtcgc ggacacggcc acctatttct gtgcgaaagg gggcgccata 360
gacctctggg gcccagggac cctcgtcacc gtctcttcag ggcaacctaa ggctccatca 420
gtcttcccac tggccccctg ctgcggggac acacccagct ccacggtgac cctgggctgc 480
ctggtcaaag gctacctccc ggagccagtg accgtgacct ggaactcggg caccctcacc 540
aatggggtac gcaccttccc gtccgtccgg cagtcctcag gcctctactc gctgagcagc 600
gtggtgagcg tgacctcaag cagccagccc gtcacctgca acgtggccca cccagccacc 660
aacaccaaag tggacaagac cgttgcgccc tcgacatgca gcaagcccat gtgcccaccc 720
cctgaactcc cggggggacc gtctgtcttc atcttccccc caaaacccaa ggacaccctc 780
atgatctcac gcacccccga ggtcacatgc gtggtggtgg acgtgagcca ggatgacccc 840
gaggtgcagt tcacatggta cataaacaac gagcaggtgc gcaccgcccg gccgccgcta 900
cgggagcagc agttcaacag cacgatccgc gtggtcagca ccctccccat cgcgcaccag 960
gactggctga ggggcaagga gttcaagtgc aaagtccaca acaaggcact cccggccccc 1020
atcgagaaaa ccatctccaa agccagaggg cagcccctgg agccgaaggt ctacaccatg 1080
ggccctcccc gggaggagct gagcagcagg tcggtcagcc tgacctgcat gatcaacggc 1140
ttctaccctt ccgacatctc ggtggagtgg gagaagaacg ggaaggcaga ggacaactac 1200
aagaccacgc cgaccgtgct ggacagcgac ggctcctact tcctctacag caagctctca 1260
gtgcccacga gtgagtggca gcggggcgac gtcttcacct gctccgtgat gcacgaggcc 1320
ttgcacaacc actacacgca gaagtccatc tcccgctctc cgggtaaata g 1371
<210> 94
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 94
atggacacga gggcccccac tcagctgctg ggactcctac tgctctggct cccaggtgcc 60
agatgtgctg acattgtgat gacccagact ccagcctccg tggaggcagc tgtgggaggc 120
acagtcacca tcaagtgcca ggccagtcag agcattagta gttacttagc ctggtatcag 180
cagaaaccag ggcagcgtcc caagctcctg atctacaggg catccactct ggcatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacagact acactctcac catcagcgac 300
ctggagtgtg ccgatgctgc cacttattat tgtcatacct attatcttag tagtagtatc 360
agttatggta atactttcgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 95
<211> 1398
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 95
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctgg aggagtccgg gggagacctg gtcaagcctg agggatccct gacactcacc 120
tgcaaagcct ctggattctc cttcagtagc atctactgga tttgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcgcatgc actactgttg tcaaaagtgg tagaacttac 240
tacgcgaact gggcgaaagg ccgattcacc atctccaaaa cctcgtcgac cacggtgact 300
ctgcaaatga ccagtctgac agccgcggac acggccacct atttctgtgc gagagaattt 360
gttgatggtg gtggtagtag tggtagggac ttgtggggcc caggcaccct ggtcaccgtc 420
tcctcagggc aacctaaggc tccatcagtc ttcccactgg ccccctgctg cggggacaca 480
cccagctcca cggtgaccct gggctgcctg gtcaaaggct acctcccgga gccagtgacc 540
gtgacctgga actcgggcac cctcaccaat ggggtacgca ccttcccgtc cgtccggcag 600
tcctcaggcc tctactcgct gagcagcgtg gtgagcgtga cctcaagcag ccagcccgtc 660
acctgcaacg tggcccaccc agccaccaac accaaagtgg acaagaccgt tgcgccctcg 720
acatgcagca agcccatgtg cccaccccct gaactcccgg ggggaccgtc tgtcttcatc 780
ttccccccaa aacccaagga caccctcatg atctcacgca cccccgaggt cacatgcgtg 840
gtggtggacg tgagccagga tgaccccgag gtgcagttca catggtacat aaacaacgag 900
caggtgcgca ccgcccggcc gccgctacgg gagcagcagt tcaacagcac gatccgcgtg 960
gtcagcaccc tccccatcgc gcaccaggac tggctgaggg gcaaggagtt caagtgcaaa 1020
gtccacaaca aggcactccc ggcccccatc gagaaaacca tctccaaagc cagagggcag 1080
cccctggagc cgaaggtcta caccatgggc cctccccggg aggagctgag cagcaggtcg 1140
gtcagcctga cctgcatgat caacggcttc tacccttccg acatctcggt ggagtgggag 1200
aagaacggga aggcagagga caactacaag accacgccga ccgtgctgga cagcgacggc 1260
tcctacttcc tctacagcaa gctctcagtg cccacgagtg agtggcagcg gggcgacgtc 1320
ttcacctgct ccgtgatgca cgaggccttg cacaaccact acacgcagaa gtccatctcc 1380
cgctctccgg gtaaatag 1398
<210> 96
<211> 711
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 96
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagc attagtaggg acttatcctg gtatcagcag 180
aaacctggac agcctcccaa gcgcctaatc tacaaggcat ccactctggc atctggggtc 240
ccatcgcggt tcaaaggcag tggatctggg acagatttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caacagggtt atagtagtat tgatgttgat 360
aatgatttcg gcggagggac cgaggtggtg gtcaaaggtg atccagttgc acctactgtc 420
ctcatcttcc caccagctgc tgatcaggtg gcaactggaa cagtcaccat cgtgtgtgtg 480
gcgaataaat actttcccga tgtcaccgtc acctgggagg tggatggcac cacccaaaca 540
actggcatcg agaacagtaa aacaccgcag aattctgcag attgtaccta caacctcagc 600
agcactctga cactgaccag cacacagtac aacagccaca aagagtacac ctgcaaggtg 660
acccagggca cgacctcagt cgtccagagc ttcaataggg gtgactgtta g 711
<210> 97
<211> 1404
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 97
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctgg aggagtccgg gggaggcctg gtcaagcctg agggatccct gacactcacc 120
tgcaaagcct ctggattcga cctcagtagc ggctatgaca tgtgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcgcatgc atttatgctg attatagtgg tagcacatac 240
tacgcgagct gggtgaatgg ccgattcacc atctccagca gcaccagcct aaacacggtg 300
gatctgaaaa tgaccagtct gacagccgcg gacacggcca cctatttctg tgccagaggg 360
gctactggta atggtggtta tggatactac tttaacttgt ggggcccagg caccctggtc 420
accgtctcct cagggcaacc taaggctcca tcagtcttcc cactggcccc ctgctgcggg 480
gacacaccca gctccacggt gaccctgggc tgcctggtca aaggctacct cccggagcca 540
gtgaccgtga cctggaactc gggcaccctc accaatgggg tacgcacctt cccgtccgtc 600
cggcagtcct caggcctcta ctcgctgagc agcgtggtga gcgtgacctc aagcagccag 660
cccgtcacct gcaacgtggc ccacccagcc accaacacca aagtggacaa gaccgttgcg 720
ccctcgacat gcagcaagcc catgtgccca ccccctgaac tcccgggggg accgtctgtc 780
ttcatcttcc ccccaaaacc caaggacacc ctcatgatct cacgcacccc cgaggtcaca 840
tgcgtggtgg tggacgtgag ccaggatgac cccgaggtgc agttcacatg gtacataaac 900
aacgagcagg tgcgcaccgc ccggccgccg ctacgggagc agcagttcaa cagcacgatc 960
cgcgtggtca gcaccctccc catcgcgcac caggactggc tgaggggcaa ggagttcaag 1020
tgcaaagtcc acaacaaggc actcccggcc cccatcgaga aaaccatctc caaagccaga 1080
gggcagcccc tggagccgaa ggtctacacc atgggccctc cccgggagga gctgagcagc 1140
aggtcggtca gcctgacctg catgatcaac ggcttctacc cttccgacat ctcggtggag 1200
tgggagaaga acgggaaggc agaggacaac tacaagacca cgccgaccgt gctggacagc 1260
gacggctcct acttcctcta cagcaagctc tcagtgccca cgagtgagtg gcagcggggc 1320
gacgtcttca cctgctccgt gatgcacgag gccttgcaca accactacac gcagaagtcc 1380
atctcccgct ctccgggtaa atag 1404
<210> 98
<211> 717
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 98
atggacacga gggcccccac tcagctgctg gggctcctac tgctctggct cccaggtgcc 60
agatgtgctg acattgtgat gacccagact ccagcctccg tgtctgaacc tgtgggaggc 120
acagtcacca tcaagtgtca ggccagtcag aacattaata gcggcttagc ctggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctacaagg catccactct ggcatctggg 240
gtctcatcgc ggttcaaagg cagtggatct gggacagaat tcactctcac catcagcgac 300
ctggagtgtg ccgatgctgc cacttactac tgtcaaacct attattatag tagtagtagt 360
agtgataatg ctttcggcgg agggaccgag gtggtggtca aaggtgatcc agttgcacct 420
actgtcctca tcttcccacc agctgctgat caggtggcaa ctggaacagt caccatcgtg 480
tgtgtggcga ataaatactt tcccgatgtc accgtcacct gggaggtgga tggcaccacc 540
caaacaactg gcatcgagaa cagtaaaaca ccgcagaatt ctgcagattg tacctacaac 600
ctcagcagca ctctgacact gaccagcaca cagtacaaca gccacaaaga gtacacctgc 660
aaggtgaccc agggcacgac ctcagtcgtc cagagcttca ataggggtga ctgttag 717
<210> 99
<211> 1389
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 99
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
acagcttctg gattctcctt cagtagcagt tattggatat gctgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcatgtatt tatggtggta gtagtggtaa cattgcctac 240
gcgagctggg cgaaaggccg attcaccatc tccaaaacct cgtcgaccac ggtgactcta 300
caaatgacca gtctgacagc cgcggacacg gccacctatt tctgtgcgag agatattcct 360
agtgatgctt tcaccttaga cttgtggggc ccaggcaccc tggtcaccgt ctcctcaggg 420
caacctaagg ctccatcagt cttcccactg gccccctgct gcggggacac acccagctcc 480
acggtgaccc tgggctgcct ggtcaaaggc tacctcccgg agccagtgac cgtgacctgg 540
aactcgggca ccctcaccaa tggggtacgc accttcccgt ccgtccggca gtcctcaggc 600
ctctactcgc tgagcagcgt ggtgagcgtg acctcaagca gccagcccgt cacctgcaac 660
gtggcccacc cagccaccaa caccaaagtg gacaagaccg ttgcgccctc gacatgcagc 720
aagcccatgt gcccaccccc tgaactcccg gggggaccgt ctgtcttcat cttcccccca 780
aaacccaagg acaccctcat gatctcacgc acccccgagg tcacatgcgt ggtggtggac 840
gtgagccagg atgaccccga ggtgcagttc acatggtaca taaacaacga gcaggtgcgc 900
accgcccggc cgccgctacg ggagcagcag ttcaacagca cgatccgcgt ggtcagcacc 960
ctccccatcg cgcaccagga ctggctgagg ggcaaggagt tcaagtgcaa agtccacaac 1020
aaggcactcc cggcccccat cgagaaaacc atctccaaag ccagagggca gcccctggag 1080
ccgaaggtct acaccatggg ccctccccgg gaggagctga gcagcaggtc ggtcagcctg 1140
acctgcatga tcaacggctt ctacccttcc gacatctcgg tggagtggga gaagaacggg 1200
aaggcagagg acaactacaa gaccacgccg accgtgctgg acagcgacgg ctcctacttc 1260
ctctacagca agctctcagt gcccacgagt gagtggcagc ggggcgacgt cttcacctgc 1320
tccgtgatgc acgaggcctt gcacaaccac tacacgcaga agtccatctc ccgctctccg 1380
ggtaaatag 1389
<210> 100
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 100
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccc aagtgctgac ccagactcca tcctccgtgt ctgcagctgt gggaagcaca 120
gtcaccatca attgccaggc cagtcagagt gtttataaag acaacaattt agcctggtat 180
cagcagaaac cagggcagcc tcccaagctc ctgatctaca aggcttccac tctggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
ggcgtgcagt gtgaagatgc tgccacttac tactgtcaag gcgaattcag ttgtggtagt 360
gctgattgta ttgctttcgg cggagggacc gaggtggtgg tcaaaggtga tccagttgca 420
cctactgtcc tcatcttccc accagctgct gatcaggtgg caactggaac agtcaccatc 480
gtgtgtgtgg cgaataaata ctttcccgat gtcaccgtca cctgggaggt ggatggcacc 540
acccaaacaa ctggcatcga gaacagtaaa acaccgcaga attctgcaga ttgtacctac 600
aacctcagca gcactctgac actgaccagc acacagtaca acagccacaa agagtacacc 660
tgcaaggtga cccagggcac gacctcagtc gtccagagct tcaatagggg tgactgttag 720
<210> 101
<211> 1371
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 101
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
aaaggctctg gaatcgactt cagtagcggc tacggcatgt ggtgggtccg ccaggctcca 180
gggaagggac tggagtatat cggatacatt gatactggtt atggtagcac ttactacgcg 240
agctgggcga aaggccgatt caccatctcc aagacctcgt cgaccacggt gactctgcaa 300
atgaccagtc tgacagtcgc ggacacggcc acctatttct gtgcgaaagg gggcgccata 360
gacctctggg gcccagggac cctcgtcacc gtctcttcag ggcaacctaa ggctccatca 420
gtcttcccac tggccccctg ctgcggggac acacccagct ccacggtgac cctgggctgc 480
ctggtcaaag gctacctccc ggagccagtg accgtgacct ggaactcggg caccctcacc 540
aatggggtac gcaccttccc gtccgtccgg cagtcctcag gcctctactc gctgagcagc 600
gtggtgagcg tgacctcaag cagccagccc gtcacctgca acgtggccca cccagccacc 660
aacaccaaag tggacaagac cgttgcgccc tcgacatgca gcaagcccat gtgcccaccc 720
cctgaactcc cggggggacc gtctgtcttc atcttccccc caaaacccaa ggacaccctc 780
atgatctcac gcacccccga ggtcacatgc gtggtggtgg acgtgagcca ggatgacccc 840
gaggtgcagt tcacatggta cataaacaac gagcaggtgc gcaccgcccg gccgccgcta 900
cgggagcagc agttcaacag cacgatccgc gtggtcagca ccctccccat cgcgcaccag 960
gactggctga ggggcaagga gttcaagtgc aaagtccaca acaaggcact cccggccccc 1020
atcgagaaaa ccatctccaa agccagaggg cagcccctgg agccgaaggt ctacaccatg 1080
ggccctcccc gggaggagct gagcagcagg tcggtcagcc tgacctgcat gatcaacggc 1140
ttctaccctt ccgacatctc ggtggagtgg gagaagaacg ggaaggcaga ggacaactac 1200
aagaccacgc cgaccgtgct ggacagcgac ggctcctact tcctctacag caagctctca 1260
gtgcccacga gtgagtggca gcggggcgac gtcttcacct gctccgtgat gcacgaggcc 1320
ttgcacaacc actacacgca gaagtccatc tcccgctctc cgggtaaata g 1371
<210> 102
<211> 717
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 102
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcag ccgtgctgac ccagactccg gcttccacgt ctgcagctgt gggaggcaca 120
gtcaccatca attgtcagtc cagtcagagc gtgtatcgta gcaactggtt agcctggtat 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatg atgtatttaa tttggcatct 240
ggggtcccat cccggttcaa gggcagtgga tctgggacac agttcactct caccatcagc 300
ggcgtgcagt gtgccgatgc tgccacttac tactgtcaag gcagttatta tagtggtaat 360
tggtacagtg ctttcggcgg agggaccgag gtggtggtca aaggtgatcc agttgcacct 420
actgtcctca tcttcccacc agctgctgat caggtggcaa ctggaacagt caccatcgtg 480
tgtgtggcga ataaatactt tcccgatgtc accgtcacct gggaggtgga tggcaccacc 540
caaacaactg gcatcgagaa cagtaaaaca ccgcagaatt ctgcagattg tacctacaac 600
ctcagcagca ctctgacact gaccagcaca cagtacaaca gccacaaaga gtacacctgc 660
aaggtgaccc agggcacgac ctcagtcgtc cagagcttca ataggggtga ctgttag 717
<210> 103
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 103
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Pro Cys Lys Ala Ser Gly Tyr Thr Phe Pro Asp Tyr
20 25 30
Asn Met Asp Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asp Asn Gly Gly Thr Ile Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Asp Ser Ser Gly Tyr Gly Tyr Tyr Ala Met Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 104
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 104
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Asn Tyr
20 25 30
Gly Ile Ser Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Asp Ser Glu Ile Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp
65 70 75 80
Pro Val Glu Thr Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr
85 90 95
Lys Asp Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 105
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 105
Lys Val Met Leu Val Glu Ser Gly Gly Ala Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val
35 40 45
Ala Thr Ile Ser Ser Gly Gly Tyr Tyr Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Phe Tyr Cys
85 90 95
Ala Arg Glu Asp Asp Tyr Gly Arg Tyr Ser Tyr Thr Met Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 106
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 106
Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Val Ser Ile Ser Cys Arg Cys Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Glu Leu Glu Ile Lys
100 105 110
<210> 107
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 107
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Arg Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Cys Ile
35 40 45
Gly Glu Ile Tyr Pro Gly Thr Asp Asn Thr Tyr Tyr Ser Lys Lys Phe
50 55 60
Arg Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Asp Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Gly Asp Tyr Tyr Arg Gly Tyr Phe Asp Val Trp Gly Ala Gly
100 105 110
Thr Thr Val Thr Val Ser Ser
115
<210> 108
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 108
Asp Val Val Met Thr Gln Thr Ser Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu His Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Phe Leu Ile Tyr Leu Val Ser Lys Leu Glu Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Leu Gln Ser
85 90 95
Thr His Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 109
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 109
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Lys Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Lys Ile Tyr Pro Gly Ser Gly Asn Thr His Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Thr Asn Tyr Tyr Gly Tyr Arg Ala Met Asn Tyr Trp Gly Gln Gly
100 105 110
Ser Ser Val Thr Val Ser Ser
115
<210> 110
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 110
Asp Ile His Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Ile Ser Leu Thr Cys Arg Ala Ser Gln Asp Ile Tyr Ile Ser
20 25 30
Leu Asn Trp Phe Gln Gln Lys Pro Asp Gly Thr Ile Lys Leu Leu Ile
35 40 45
Tyr Gly Thr Ser Ser Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Ser Asp Tyr Ser Leu Thr Ile Ser Ser Leu Glu Ser
65 70 75 80
Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala Ser Ser Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 111
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 111
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Tyr Pro Gly Ser Gly Asn Pro Tyr Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Ser Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Thr Ser Tyr Gly Arg Val Gly Thr Gly Phe Ala Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ala
115 120
<210> 112
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 112
Asn Phe Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Asn Arg Val Glu Thr Glu Asp Leu Gly Ile Tyr Phe Cys Ser Gln Ser
85 90 95
Ser His Val Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
100 105 110
<210> 113
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 113
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Tyr Thr Glu Tyr Asn Gln Arg Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Ala Asp Arg Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Asp Ile Ile Thr Thr Asp Tyr Trp Gly Gln Gly Thr Thr
100 105 110
Leu Thr Val Ser Ser
115
<210> 114
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 114
Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val Tyr Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 115
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 115
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Val Gln Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Val Ile Asp Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Ser Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Asp Val Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val
100 105 110
Thr Val Ser Ser
115
<210> 116
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 116
Asp Ile Val Val Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Ser Tyr
20 25 30
Gly Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Lys Ser Gly Ile Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asn
65 70 75 80
Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Ser Asn
85 90 95
Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 117
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 117
Glu Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Met Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ala
20 25 30
Trp Met Asp Trp Val Arg Gln Ser Pro Glu Ala Gly Leu Glu Trp Val
35 40 45
Ala Glu Ile Arg Asn Lys Ala His Asn Pro Ala Thr Tyr Tyr Ala Glu
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Ser Ser
65 70 75 80
Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Gly Ile Tyr
85 90 95
Tyr Cys Thr Leu Val Ala Pro Asp Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser
115
<210> 118
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 118
Asp Ile Val Met Ser Leu Ser Pro Ser Ser Leu Ala Val Ser Val Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Ala Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
100 105 110
Lys
<210> 119
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 119
Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asn Ser Glu Thr Trp Leu Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Asn Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Asp Gly Tyr Tyr Asp Tyr Trp Gly Gln Gly Thr Thr Leu
100 105 110
Thr Val Ser Ser
115
<210> 120
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 120
Asn Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Ser Tyr
20 25 30
Gly Asn Ser Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Leu Ala Ser Asn Val Glu Ser Gly Val Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp
65 70 75 80
Pro Val Glu Ala Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Asn Asn
85 90 95
Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 121
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 121
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Pro Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asp Ser Glu Thr His Tyr Asn Gln Met Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Gln Ile Tyr Tyr Ala Tyr Asp Lys Ala Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala
115
<210> 122
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 122
Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Ser His Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr
65 70 75 80
Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Glu
85 90 95
Tyr Tyr Ser Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 123
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 123
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro His Asn Gly Gly Thr Ser Phe Ile Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Pro Leu Gly Arg Lys Glu Gly Phe Ala Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala
115
<210> 124
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 124
Asp Thr Val Leu Thr Gln Ser Pro Ala Ser Leu Val Val Ser Leu Gly
1 5 10 15
Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys Ser Val Ser Thr Ser
20 25 30
Gly Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Ser Gly Val Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Asn Ile His
65 70 75 80
Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ser Arg
85 90 95
Glu Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 125
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 125
Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Phe
20 25 30
Ala Met Gly Val Gly Trp Ile Arg Gln Pro Ser Gly Lys Gly Leu Glu
35 40 45
Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Tyr Tyr Asn Pro Ala
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn His Val
65 70 75 80
Phe Leu Lys Ile Ala Asn Val Asp Thr Ala Asp Thr Ala Thr Tyr Tyr
85 90 95
Cys Ala Arg Met Pro Leu Thr Phe Tyr Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Thr Leu Thr Val Ser Ser
115
<210> 126
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 126
Asp Val Leu Leu Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly His Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 127
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 127
Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Arg Thr Phe
20 25 30
Ala Met Gly Val Gly Trp Ile Arg Gln Pro Ser Gly Lys Gly Leu Glu
35 40 45
Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Tyr Tyr Asn Pro Ala
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Val
65 70 75 80
Phe Leu Lys Ile Ala Asn Val Asp Thr Ala Asp Thr Ala Thr Tyr Tyr
85 90 95
Cys Ala Arg Met Pro Leu Thr Phe Tyr Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Thr Leu Thr Val Ser Ser
115
<210> 128
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 128
Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Thr Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 129
<211> 115
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 129
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Met Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asp Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Gln Gly Ser Thr Tyr Ala Trp Gly Gln Gly Thr Ser Val Thr
100 105 110
Val Ser Ser
115
<210> 130
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 130
Asp Ile Val Met Thr Gln Ala Ala Phe Ser Asn Pro Val Thr Leu Gly
1 5 10 15
Thr Ser Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Gln Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Ser Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn
85 90 95
Leu Glu Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 131
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 131
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Met Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Gly Gly Ser Ser Tyr Asn Pro Lys Phe
50 55 60
Lys Gly Arg Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala
100 105 110
<210> 132
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 132
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser
20 25 30
Ala Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Met Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Trp Gln Gly
85 90 95
Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 133
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 133
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Ser Asn Gly Gly Ser Asn Tyr Asn Glu Lys Phe
50 55 60
Lys Ser Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr His Cys
85 90 95
Lys Ser Arg Gly Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
100 105 110
<210> 134
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 134
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser
20 25 30
Tyr Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Ile Tyr Tyr Cys Trp Gln Gly
85 90 95
Thr His Phe Pro His Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 135
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 135
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Gly Ile Ser Trp Val Lys Gln Arg Thr Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Phe Pro Arg Ser Ser Asn Thr Tyr Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Val Tyr
65 70 75 80
Met Glu Phe Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Gly Gly Leu Ala Trp Phe Ala Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala
115
<210> 136
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 136
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Thr
20 25 30
Asn Gly Asn Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Ile Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Leu Gln Ser
85 90 95
Thr His Phe Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 137
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 137
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Ile Thr Asp Tyr
20 25 30
Tyr Met Met Trp Leu Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Tyr Thr Gly Gly Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Leu Gln Leu His Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ala Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
100 105 110
<210> 138
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 138
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser
20 25 30
Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Trp Gln Gly
85 90 95
Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 139
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 139
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Ile Thr Asp Tyr
20 25 30
Tyr Met Met Trp Leu Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Tyr Thr Gly Gly Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ala Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
100 105 110
<210> 140
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 140
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser
20 25 30
Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Trp Gln Gly
85 90 95
Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 141
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 141
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Arg Ser Leu Glu Leu Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Gly Ser Asn Phe Asn Gln Lys Phe
50 55 60
Arg Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys
85 90 95
Ala Arg Met Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala
100 105 110
<210> 142
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 142
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu His Ser
20 25 30
Asp Gly Lys Thr Tyr Leu Asn Trp Met Phe Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Tyr Arg Phe Thr Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Gln Ile
65 70 75 80
Ser Arg Val Glu Thr Glu Asp Leu Gly Val Tyr Tyr Cys Trp Gln Gly
85 90 95
Thr His Phe Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 143
<211> 114
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 143
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Tyr Ile
35 40 45
Gly Glu Ile Tyr Pro Gly Ser Gly Asn Thr Tyr Tyr Asn Gly Lys Phe
50 55 60
Arg Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Gly Ser Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val
100 105 110
Ser Ser
<210> 144
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 144
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Ser Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Leu Val Ser Lys Leu Glu Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Leu
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Val Gln Gly
85 90 95
Thr His Phe Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 145
<211> 139
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 145
Met Asp Trp Leu Trp Asn Leu Leu Phe Leu Met Val Val Ala Gln Ser
1 5 10 15
Ala Gln Ala Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Val Lys Lys
20 25 30
Pro Gly Glu Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Ala Met Asn Trp Val Lys Gln Ala Pro Gly Asn Gly Leu
50 55 60
Lys Trp Met Gly Trp Ile Asn Thr Gln Thr Gly Lys Pro Thr Tyr Ala
65 70 75 80
Asp Asp Phe Lys Gln Arg Phe Val Phe Ser Leu Glu Thr Ser Ala Arg
85 90 95
Thr Thr Tyr Leu Gln Ile Asn Asn Leu Asn Ile Glu Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Thr Arg Leu Gly Thr Gly Asn Thr Lys Gly Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 146
<211> 133
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 146
Met Glu Ser Gln Thr His Val Leu Ile Ser Leu Leu Leu Cys Val Ser
1 5 10 15
Gly Thr Cys Gly Asp Ile Leu Ile Asn Gln Ser Pro Ala Ser Leu Thr
20 25 30
Val Ser Ala Gly Glu Arg Val Thr Met Ser Cys Lys Ser Ser Gln Ser
35 40 45
Leu Leu Tyr Ser Glu Asn Asn Gln Asp Tyr Leu Ala Trp Tyr Gln Gln
50 55 60
Lys Pro Gly Gln Phe Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Arg
65 70 75 80
His Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp
85 90 95
Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Asp Tyr
100 105 110
Tyr Cys Glu Gln Thr Tyr Arg Tyr Pro Phe Thr Phe Gly Ser Gly Thr
115 120 125
Lys Leu Glu Ile Lys
130
<210> 147
<211> 138
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 147
Met Glu Leu Glu Leu Ser Leu Ile Phe Ile Phe Ser Leu Leu Lys Asp
1 5 10 15
Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Ser Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Lys Leu Ser Cys Val Ala Ser Gly Tyr Thr Phe
35 40 45
Ser Asn Tyr Trp Met Asp Trp Val Arg Gln Ser Pro Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Thr Asp Gly Arg Arg Thr Asn Tyr Ala
65 70 75 80
Pro Ser Ile Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser
85 90 95
Thr Leu Tyr Leu Gln Met Ser Asn Val Lys Ser Asp Asp Thr Ala Ile
100 105 110
Tyr Tyr Cys Thr Ile Leu Arg Val Tyr Pro His Tyr Phe Asp Tyr Trp
115 120 125
Gly Gln Gly Val Met Val Thr Val Ser Ser
130 135
<210> 148
<211> 132
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 148
Met Met Ser Pro Ala Gln Phe Leu Phe Leu Leu Met Leu Trp Ile Gln
1 5 10 15
Glu Ala Arg Gly Asp Val Val Met Thr Gln Thr Pro Pro Ser Leu Ser
20 25 30
Val Ala Ile Gly Gln Ser Val Ser Ile Ser Cys Lys Ser Ser Gln Ser
35 40 45
Leu Val Tyr Ser Asp Gly Glu Thr Tyr Leu His Trp Phe Leu Gln Ser
50 55 60
Pro Gly Arg Ser Pro Lys Arg Leu Ile Tyr His Val Ser Asn Leu Gly
65 70 75 80
Ser Gly Val Pro Asp Arg Phe Ser Gly Thr Gly Ser Leu Thr Asp Phe
85 90 95
Thr Leu Arg Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr
100 105 110
Cys Ala Gln Thr Thr His Phe Pro Pro Thr Phe Gly Ala Gly Thr Lys
115 120 125
Leu Glu Leu Lys
130
<210> 149
<211> 135
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 149
Met Ala Val Leu Val Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Ala Leu Ser Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Gln
20 25 30
Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu
35 40 45
Thr Ser Asn Ser Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Met Gly Ala Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Ser
65 70 75 80
Ala Leu Lys Ser Arg Leu Ser Ile Ser Arg Asp Thr Ser Lys Ser Gln
85 90 95
Val Phe Leu Lys Met Asn Ser Leu Gln Thr Glu Asp Thr Ala Ile Tyr
100 105 110
Phe Cys Thr Arg Ser His Trp Glu Pro Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Val Met Val Thr Val Ser Ser
130 135
<210> 150
<211> 133
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 150
Met Glu Ser Gln Thr Gln Ala Leu Ile Ser Leu Leu Leu Trp Val Tyr
1 5 10 15
Gly Thr Cys Gly Asp Ile Val Met Thr Gln Ser Pro Phe Ser Leu Ala
20 25 30
Val Ser Glu Gly Glu Met Val Thr Ile Asn Cys Lys Ser Ser Gln Gly
35 40 45
Leu Leu Ser Ser Gly Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln
50 55 60
Arg Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Arg
65 70 75 80
Gln Ser Gly Val Pro Asp Arg Phe Ile Gly Gly Gly Ser Gly Thr Asp
85 90 95
Phe Thr Leu Thr Ile Ser Asp Val Gln Ala Glu Asp Leu Ala Asp Tyr
100 105 110
Tyr Cys Leu Gln His Tyr Ser Tyr Pro Pro Thr Phe Gly Ser Gly Thr
115 120 125
Lys Leu Glu Ile Lys
130
<210> 151
<211> 135
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 151
Met Ala Val Leu Val Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Ala Leu Ser Gln Val Gln Leu Arg Glu Ser Gly Pro Gly Leu Val Gln
20 25 30
Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu
35 40 45
Thr Ser Asn Ser Val Thr Trp Val Arg Gln Pro Pro Gly Lys Gly Leu
50 55 60
Glu Trp Met Gly Ala Ile Trp Ser Asp Gly Ser Thr Asp Tyr Asn Ser
65 70 75 80
Thr Leu Lys Ser Arg Leu Ser Ile Ser Arg Asp Thr Ser Lys Ser Gln
85 90 95
Val Phe Leu Lys Met Ser Ser Leu Gln Thr Glu Asp Thr Ala Ile Tyr
100 105 110
Phe Cys Thr Arg Ser His Trp Glu Pro Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Val Met Val Thr Val Ser Ser
130 135
<210> 152
<211> 133
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 152
Met Glu Ser Gln Thr Gln Ala Leu Ile Ser Leu Leu Leu Trp Val Tyr
1 5 10 15
Gly Thr Cys Gly Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Ala
20 25 30
Val Ser Glu Gly Glu Thr Val Thr Met Asn Cys Lys Ser Ser Gln Ser
35 40 45
Leu Phe Ser Ser Gly Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln
50 55 60
Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Arg
65 70 75 80
Gln Ser Gly Val Pro Asp Arg Phe Ile Gly Ser Gly Ser Gly Thr Asp
85 90 95
Phe Thr Leu Thr Ile Ser Asp Val Gln Thr Glu Asp Leu Ala Asp Tyr
100 105 110
Tyr Cys Leu Gln His Tyr Asn Tyr Pro Pro Thr Phe Gly Ser Gly Thr
115 120 125
Lys Leu Glu Ile Lys
130
<210> 153
<211> 134
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 153
Met Asp Leu Arg Leu Thr Tyr Val Phe Ile Val Ala Ile Leu Lys Gly
1 5 10 15
Val Leu Cys Glu Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Met Ser Val Lys Leu Ser Cys Ala Thr Ser Gly Phe Ile Phe
35 40 45
Ser Asp Tyr Trp Met Glu Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Glu Ile Arg Asn Lys Ala Asn Asn Tyr Ala Thr Tyr
65 70 75 80
Tyr Gly Lys Ser Met Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser
85 90 95
Lys Ser Ile Val Tyr Leu Gln Val Asn Ser Ile Arg Ser Glu Asp Thr
100 105 110
Ala Ile Tyr Tyr Cys Ala Pro Asn Phe Asp Tyr Trp Gly Gln Gly Val
115 120 125
Met Val Thr Val Ser Ser
130
<210> 154
<211> 131
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 154
Met Ser Pro Val Gln Ser Leu Phe Leu Leu Leu Leu Trp Ile Leu Gly
1 5 10 15
Thr His Gly Asp Val Val Leu Thr Gln Thr Pro Pro Thr Leu Ser Ala
20 25 30
Thr Ile Gly Gln Ser Val Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu
35 40 45
Leu His Ser Thr Gly Asn Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro
50 55 60
Gly Gln Pro Pro Gln Leu Leu Ile Tyr Leu Val Ser Arg Leu Glu Ser
65 70 75 80
Gly Val Pro Asn Arg Phe Ser Ala Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Lys Ile Ser Gly Ile Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys
100 105 110
Val Gln Ser Ser His Thr Pro Tyr Thr Phe Gly Thr Gly Thr Lys Leu
115 120 125
Glu Leu Lys
130
<210> 155
<211> 135
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 155
Met Asp Ile Arg Leu Ser Leu Val Phe Leu Val Leu Phe Met Lys Gly
1 5 10 15
Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Arg Ser Leu Lys Leu Ser Cys Ala Ala Ser Arg Phe Thr Phe
35 40 45
Ser Asp Tyr Asn Met Ala Trp Val Arg Gln Ala Pro Lys Lys Gly Leu
50 55 60
Glu Trp Val Ala Thr Ile Tyr His Asp Asp Ser Gly Ser Tyr Tyr Arg
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asn Asn Ala Lys Ser
85 90 95
Thr Leu Tyr Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Met Ala Thr
100 105 110
Tyr Tyr Cys Ala Arg His Asn Asn Gly Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Val Met Val Thr Val Ala Ser
130 135
<210> 156
<211> 131
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 156
Met Lys Trp Pro Val Arg Leu Leu Val Leu Phe Phe Trp Ile Pro Ala
1 5 10 15
Ser Gly Gly Asp Val Val Met Thr Gln Thr Pro Val Ser Leu Pro Val
20 25 30
Arg Leu Gly Gly Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu
35 40 45
Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro
50 55 60
Gly Gln Ser Pro Gln Leu Leu Ile Asn Arg Val Ser Asn Arg Phe Ser
65 70 75 80
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Lys Ile Asn Arg Val Glu Pro Glu Asp Leu Gly Asp Tyr Tyr Cys
100 105 110
Leu Gln Ser Thr His Phe Pro Leu Thr Phe Gly Ser Gly Thr Lys Leu
115 120 125
Glu Thr Lys
130
<210> 157
<211> 136
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 157
Met Asp Ile Arg Leu Ser Leu Gly Phe Leu Val Leu Phe Ile Lys Gly
1 5 10 15
Asp Gln Cys Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Arg Ser Leu Lys Leu Ser Cys Ala Ala Ser Arg Ile Thr Phe
35 40 45
Thr Asp Tyr Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu
50 55 60
Glu Trp Val Ala Thr Ile Ser Ser Asp Gly Gly Asp Thr Phe Tyr Arg
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser
85 90 95
Thr Leu Tyr Leu Gln Met Val Ser Leu Arg Ser Glu Asp Thr Ala Thr
100 105 110
Tyr Tyr Cys Ser Thr Asp Arg Gly Ala Gln Phe Gly Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 158
<211> 126
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 158
Met Ala Pro Val Gln Leu Leu Gly Leu Leu Leu Ile Trp Leu Pro Ala
1 5 10 15
Met Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Phe Leu Ser Ala
20 25 30
Ser Val Gly Asp Arg Val Ser Ile Asn Cys Lys Ala Ser Gln Asn Val
35 40 45
His Glu Asn Leu Asn Trp Tyr Gln Gln Lys Leu Gly Glu Ala Pro Lys
50 55 60
Arg Leu Ile Tyr Asn Thr Asn Asn Leu Gln Thr Gly Ile Pro Ser Arg
65 70 75 80
Phe Ser Gly Ser Gly Ser Gly Ala Asp Tyr Thr Leu Thr Ile Ser Ser
85 90 95
Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Leu Gln His Asn Ala
100 105 110
Phe Pro Tyr Thr Phe Gly Pro Gly Thr Lys Leu Glu Leu Lys
115 120 125
<210> 159
<211> 455
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 159
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Phe Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys
20 25 30
Pro Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe
35 40 45
Asn Lys Asn Tyr Trp Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Gly Cys Ile Tyr Asn Gly Asp Gly Asn Thr Tyr Tyr
65 70 75 80
Ala Ser Trp Val Asn Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Val Ala Asp Thr Ala Ile
100 105 110
Tyr Phe Cys Ala Arg Leu Leu Asn Met Trp Gly Pro Gly Thr Leu Val
115 120 125
Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala
130 135 140
Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu
145 150 155 160
Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly
165 170 175
Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser
180 185 190
Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln
195 200 205
Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp
210 215 220
Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro
225 230 235 240
Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys
245 250 255
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn
275 280 285
Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe
290 295 300
Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp
305 310 315 320
Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu
325 330 335
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu
340 345 350
Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser
355 360 365
Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys
385 390 395 400
Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr
420 425 430
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 160
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 160
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Met Thr Gln Thr Pro Ala
20 25 30
Ser Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Glu Ser Ile Gly Asn Ala Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Thr Ala Ala Thr Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu
85 90 95
Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Ser Tyr Tyr Phe Thr Ser Val Ser Ser Tyr Gly Asn Ala Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 161
<211> 466
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 161
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Arg Val Ser Gly Phe Ser Phe Ser
35 40 45
Ser Ser Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala
65 70 75 80
Thr Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Ile Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Asp Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Arg Asp Ala Thr Gly Tyr Arg Ile Asn Thr Ile Gly Leu
115 120 125
Tyr Phe Asn Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly
130 135 140
Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp
145 150 155 160
Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu
165 170 175
Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly
180 185 190
Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn
210 215 220
Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro
225 230 235 240
Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly
245 250 255
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
260 265 270
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Asp
275 280 285
Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg
290 295 300
Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg
305 310 315 320
Val Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys
325 330 335
Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr
355 360 365
Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu
370 375 380
Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp
385 390 395 400
Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val
405 410 415
Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro
420 425 430
Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met His
435 440 445
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro
450 455 460
Gly Lys
465
<210> 162
<211> 237
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 162
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Phe Glu Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Pro Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Thr Ile Tyr Ser Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Glu Ala Ser Lys Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Ser
100 105 110
Tyr His Gly Thr Ala Ser Thr Glu Tyr Asn Thr Phe Gly Gly Gly Thr
115 120 125
Glu Val Val Val Arg Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe
130 135 140
Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys
145 150 155 160
Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp
165 170 175
Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn
180 185 190
Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser
195 200 205
Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly
210 215 220
Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 163
<211> 466
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 163
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Gln Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys
20 25 30
Pro Gly Ala Ala Leu Thr Phe Thr Cys Thr Ala Ser Gly Phe Ser Phe
35 40 45
Ser Gly Asn Tyr Trp Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Ile Gly Thr Ile Thr Ser Arg Thr Tyr Tyr
65 70 75 80
Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Gly Ala Val Val Ser Ser Gly Asn Ala Pro Tyr
115 120 125
Tyr Phe Thr Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly
130 135 140
Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp
145 150 155 160
Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu
165 170 175
Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly
180 185 190
Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn
210 215 220
Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro
225 230 235 240
Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly
245 250 255
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
260 265 270
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Asp
275 280 285
Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg
290 295 300
Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg
305 310 315 320
Val Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys
325 330 335
Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr
355 360 365
Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu
370 375 380
Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp
385 390 395 400
Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val
405 410 415
Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro
420 425 430
Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met His
435 440 445
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro
450 455 460
Gly Lys
465
<210> 164
<211> 236
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 164
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Phe Glu Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Ser Ser Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Glu Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Phe Cys Gln Ser
100 105 110
Tyr Tyr Gly Val Thr Phe Ser Gly Phe Ala Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro
130 135 140
Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val
145 150 155 160
Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly
165 170 175
Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser
180 185 190
Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr
195 200 205
Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr
210 215 220
Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 165
<211> 460
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 165
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Ile Asp Phe Asn
35 40 45
Asn Tyr Trp Ile Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Ala Cys Ile Tyr Val Gly Ile Thr Gly Arg Thr Trp Tyr Ala
65 70 75 80
Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Ala Ser Ser Thr Val
85 90 95
Asp Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe
100 105 110
Cys Ala Arg Asn Gly Asp Gly Gly Ile Tyr Ala Leu Asn Leu Trp Gly
115 120 125
Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val
145 150 155 160
Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val
165 170 175
Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser
180 185 190
Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val
195 200 205
Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr
210 215 220
Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro
225 230 235 240
Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe
245 250 255
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
260 265 270
Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe
275 280 285
Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu
290 295 300
Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro
305 310 315 320
Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val
325 330 335
His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
340 345 350
Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg
355 360 365
Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly
370 375 380
Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala
385 390 395 400
Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser
405 410 415
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg
420 425 430
Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His
435 440 445
Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 166
<211> 238
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 166
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Ala Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Ser Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Thr Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Gly Tyr Ser Gly Asn Ile Tyr Val Asn Asp Phe Gly Gly Gly
115 120 125
Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile
130 135 140
Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val
145 150 155 160
Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val
165 170 175
Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln
180 185 190
Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr
195 200 205
Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln
210 215 220
Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 167
<211> 459
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 167
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Glu Glu Ser Gly Gly Asp Leu Val Lys
20 25 30
Pro Gly Gly Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Phe Ser Phe
35 40 45
Ser Asn Thr Tyr Trp Ala Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Met Asn Pro Ala Ser Ser Gly Ser Ser Tyr
65 70 75 80
Tyr Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser
85 90 95
Thr Thr Val Thr Leu His Met Pro Ser Leu Thr Ala Ala Asp Thr Ala
100 105 110
Thr Tyr Phe Cys Ala Lys Trp Asp Thr Ala Phe Asp Val Trp Gly Pro
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr
145 150 155 160
Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr
165 170 175
Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val
180 185 190
Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr
195 200 205
Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn
210 215 220
Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met
225 230 235 240
Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro
245 250 255
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
260 265 270
Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr
275 280 285
Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg
290 295 300
Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile
305 310 315 320
Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His
325 330 335
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg
340 345 350
Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu
355 360 365
Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe
370 375 380
Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu
385 390 395 400
Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr
405 410 415
Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly
420 425 430
Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
435 440 445
Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 168
<211> 237
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 168
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Val Val Met Thr Gln Thr Pro Ser
20 25 30
Ser Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Gln Ser Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Glu Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Tyr Thr Leu
85 90 95
Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Asn Tyr Tyr Ala Ile Asp Thr Tyr Gly His Ala Phe Gly Gly Gly Thr
115 120 125
Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe
130 135 140
Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys
145 150 155 160
Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp
165 170 175
Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn
180 185 190
Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser
195 200 205
Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly
210 215 220
Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 169
<211> 455
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 169
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Glu Glu Ser Gly Gly Asp Leu Val Lys
20 25 30
Pro Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe
35 40 45
Ser Ser Asn Tyr His Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Leu Ile Ala Cys Ile Tyr Val Gly Asp Gly Ser Thr Tyr Tyr
65 70 75 80
Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Ser Ser Ser Thr
85 90 95
Thr Val Ala Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Gly Arg Met Phe Asn Leu Trp Gly Pro Gly Thr Leu Val
115 120 125
Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala
130 135 140
Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu
145 150 155 160
Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly
165 170 175
Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser
180 185 190
Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln
195 200 205
Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp
210 215 220
Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro
225 230 235 240
Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys
245 250 255
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn
275 280 285
Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe
290 295 300
Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp
305 310 315 320
Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu
325 330 335
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu
340 345 350
Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser
355 360 365
Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys
385 390 395 400
Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr
420 425 430
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 170
<211> 235
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 170
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Ile Cys Asp Pro Val Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Val Thr Val Thr Ile Asn Cys Gln Ser Ser
35 40 45
Pro Ser Val Tyr Ser Asn Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Thr Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu
85 90 95
Thr Ile Ser Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Ala
100 105 110
Gly Thr Tyr Ser Gly Asn Ile Trp Ser Phe Gly Gly Gly Thr Glu Val
115 120 125
Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro Pro
130 135 140
Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val Ala
145 150 155 160
Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly Thr
165 170 175
Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser Ala
180 185 190
Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr Gln
195 200 205
Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr Thr
210 215 220
Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 171
<211> 460
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 171
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Gln Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys
20 25 30
Pro Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe
35 40 45
Ser Ser Gly Tyr His Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Phe Gly Val Tyr Thr Gly Thr Thr Thr Tyr
65 70 75 80
Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Val Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Ile Ser Ala Glu Asn Gly Gly Asp Leu Trp Gly
115 120 125
Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val
145 150 155 160
Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val
165 170 175
Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser
180 185 190
Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val
195 200 205
Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr
210 215 220
Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro
225 230 235 240
Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe
245 250 255
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
260 265 270
Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe
275 280 285
Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu
290 295 300
Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro
305 310 315 320
Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val
325 330 335
His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
340 345 350
Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg
355 360 365
Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly
370 375 380
Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala
385 390 395 400
Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser
405 410 415
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg
420 425 430
Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His
435 440 445
Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 172
<211> 236
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 172
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Ser Asn Tyr Phe Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ser Ala Thr Tyr Tyr Cys Gln Cys
100 105 110
Thr Tyr Gly Ser Ser Ser Thr Gly Phe Gly Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Pro Ile Phe Pro
130 135 140
Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val
145 150 155 160
Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly
165 170 175
Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser
180 185 190
Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr
195 200 205
Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr
210 215 220
Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 173
<211> 456
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 173
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Met Ala Ser Gly Ile Asp Phe Ser
35 40 45
Ser Gly Tyr Gly Met Trp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Tyr Ile Gly Tyr Ile Asp Thr Gly Asp Asp Asn Thr Tyr Tyr Ala
65 70 75 80
Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Val Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Lys Gly Gly Ala Ile Asp Leu Trp Gly Pro Gly Thr Leu
115 120 125
Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu
130 135 140
Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys
145 150 155 160
Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser
165 170 175
Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser
180 185 190
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser
195 200 205
Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val
210 215 220
Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro
225 230 235 240
Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
245 250 255
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
260 265 270
Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile
275 280 285
Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln
290 295 300
Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln
305 310 315 320
Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala
325 330 335
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro
340 345 350
Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser
355 360 365
Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser
370 375 380
Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr
385 390 395 400
Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr
405 410 415
Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe
420 425 430
Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
435 440 445
Ser Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 174
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 174
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Met Thr Gln Thr Pro Ala
20 25 30
Ser Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Gln Ser Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Arg Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Lys Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Tyr Thr Leu
85 90 95
Thr Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Ala Tyr Tyr Leu Ser Ser Ser Ile Ser Tyr Gly Asn Thr Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 175
<211> 456
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 175
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Ser Gly Tyr Gly Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Thr Asp Thr Ala Thr Gly Thr Ile His Tyr Ala
65 70 75 80
Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Lys Gly Gly Ala Met Asp Leu Trp Gly Pro Gly Thr Leu
115 120 125
Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu
130 135 140
Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys
145 150 155 160
Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser
165 170 175
Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser
180 185 190
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser
195 200 205
Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val
210 215 220
Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro
225 230 235 240
Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
245 250 255
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
260 265 270
Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile
275 280 285
Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln
290 295 300
Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln
305 310 315 320
Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala
325 330 335
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro
340 345 350
Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser
355 360 365
Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser
370 375 380
Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr
385 390 395 400
Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr
405 410 415
Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe
420 425 430
Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
435 440 445
Ser Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 176
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 176
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Met Thr Gln Thr Pro Ala
20 25 30
Ser Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Gln Ser Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Arg Thr Ser Thr Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Tyr Thr Leu
85 90 95
Thr Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Ser Tyr Ala Tyr Ser Ser Ser Ser Ser Tyr Gly Asn Ala Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 177
<211> 454
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 177
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Thr Gly Ser Gly Ile Asp Phe Ser
35 40 45
Ser Ser Tyr Trp Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Asp Gly Ser Asp Gly Asn Thr Tyr Tyr Ala
65 70 75 80
Ser Trp Ala Arg Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Ala Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Thr Arg Asp Leu Arg Leu Trp Gly Pro Gly Thr Leu Val Thr
115 120 125
Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala Pro
130 135 140
Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu Val
145 150 155 160
Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Thr
165 170 175
Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser Gly
180 185 190
Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln Pro
195 200 205
Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys
210 215 220
Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro Glu
225 230 235 240
Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn
275 280 285
Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn
290 295 300
Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp
305 310 315 320
Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro
325 330 335
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu
340 345 350
Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg
355 360 365
Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr
385 390 395 400
Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
405 410 415
Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile
435 440 445
Ser Arg Ser Pro Gly Lys
450
<210> 178
<211> 240
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 178
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Leu Thr Gln Thr Pro Ala
20 25 30
Ser Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala
35 40 45
Ser Gln Asn Val Tyr Ser Asn Asn Ala Leu Ala Trp His Gln Gln Lys
50 55 60
Pro Gly Gln Arg Pro Asn Leu Leu Ile Tyr Lys Ala Ser Thr Leu Ala
65 70 75 80
Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe
85 90 95
Thr Leu Thr Ile Ser Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr
100 105 110
Cys Leu Gly Glu Phe Ser Cys Ser Ser Gly Asp Cys Phe Val Phe Gly
115 120 125
Gly Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val
130 135 140
Leu Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr
145 150 155 160
Ile Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp
165 170 175
Glu Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr
180 185 190
Pro Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr
195 200 205
Leu Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val
210 215 220
Thr Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235 240
<210> 179
<211> 456
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 179
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Met Ala Ser Gly Ile Asp Phe Ser
35 40 45
Ser Gly Tyr Gly Met Trp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Tyr Ile Gly Tyr Ile Asp Thr Gly Asp Asp Asn Thr Tyr Tyr Ala
65 70 75 80
Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Val Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Lys Gly Gly Ala Ile Asp Leu Trp Gly Pro Gly Thr Leu
115 120 125
Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu
130 135 140
Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys
145 150 155 160
Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser
165 170 175
Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser
180 185 190
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser
195 200 205
Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val
210 215 220
Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro
225 230 235 240
Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
245 250 255
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
260 265 270
Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile
275 280 285
Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln
290 295 300
Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln
305 310 315 320
Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala
325 330 335
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro
340 345 350
Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser
355 360 365
Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser
370 375 380
Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr
385 390 395 400
Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr
405 410 415
Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe
420 425 430
Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
435 440 445
Ser Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 180
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 180
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Met Thr Gln Thr Pro Ala
20 25 30
Ser Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Gln Ser Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Arg Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Lys Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Tyr Thr Leu
85 90 95
Thr Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Ala Tyr Tyr Leu Ser Ser Ser Ile Ser Tyr Gly Asn Thr Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 181
<211> 471
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 181
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Gln Gln Leu Glu Glu Ser Gly Gly Gly Leu Val Lys
20 25 30
Pro Gly Gly Thr Leu Thr Leu Thr Cys Lys Ala Ser Gly Val Ala Leu
35 40 45
Asn Pro Tyr Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Val Asp Ala Asp Ser Ser Gly Ser Thr Tyr
65 70 75 80
Tyr Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser
85 90 95
Thr Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala
100 105 110
Thr Tyr Phe Cys Ala Arg Glu Ser Val Asp Tyr Ser Ser Val Gly Ile
115 120 125
Gly Tyr Val His Gly Thr Asp Gly Leu Trp Gly Pro Gly Thr Leu Val
130 135 140
Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala
145 150 155 160
Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu
165 170 175
Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly
180 185 190
Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser
195 200 205
Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln
210 215 220
Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp
225 230 235 240
Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro
245 250 255
Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys
260 265 270
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
275 280 285
Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn
290 295 300
Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe
305 310 315 320
Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp
325 330 335
Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu
340 345 350
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu
355 360 365
Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser
370 375 380
Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp
385 390 395 400
Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys
405 410 415
Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser
420 425 430
Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr
435 440 445
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
450 455 460
Ile Ser Arg Ser Pro Gly Lys
465 470
<210> 182
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 182
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Val Thr Gln Thr Pro Ser
20 25 30
Ser Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Gln Ser Ile Ser Asn Tyr Phe Ser Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu
85 90 95
Thr Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Cys Thr Tyr Gly Arg Ser Asn Ser Asn Phe Phe Tyr Gly Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 183
<211> 464
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 183
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Ser Ser Phe Ser
35 40 45
Ser Thr Tyr Trp Asn Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Asn Ala Gly Ser Gly Thr Thr Tyr Tyr Ala
65 70 75 80
Ser Trp Ala Lys Gly Arg Phe Thr Val Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Thr Arg Asp Ser Asp Gly Arg Phe Ser Ser Gly Tyr Tyr Phe
115 120 125
Asn Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro
130 135 140
Lys Ala Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro
145 150 155 160
Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu
165 170 175
Pro Val Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg
180 185 190
Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
195 200 205
Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala
210 215 220
His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr
225 230 235 240
Cys Ser Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
260 265 270
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro
275 280 285
Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala
290 295 300
Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val
305 310 315 320
Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe
325 330 335
Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met
355 360 365
Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys
370 375 380
Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys
385 390 395 400
Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp
405 410 415
Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser
420 425 430
Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 184
<211> 238
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 184
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Ala Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asp Asn Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Asp Asp Ala Ser Lys Leu Thr Ser
65 70 75 80
Gly Val Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Ala Tyr Tyr Ser Ser Gly Trp Tyr Trp Ala Phe Gly Gly Gly
115 120 125
Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile
130 135 140
Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val
145 150 155 160
Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val
165 170 175
Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln
180 185 190
Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr
195 200 205
Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln
210 215 220
Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 185
<211> 467
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 185
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Gln Gln Leu Glu Glu Ser Gly Gly Gly Leu Val Lys
20 25 30
Pro Gly Gly Thr Leu Thr Leu Thr Cys Lys Ala Ser Gly Ile Asp Phe
35 40 45
Ser Ser Tyr Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Leu Ile Val Cys Ile Tyr Thr Ser Ser Gly Gly Thr Trp Tyr
65 70 75 80
Ala Ser Trp Val Asn Gly Arg Leu Thr Ile Ser Arg Ser Thr Ser Leu
85 90 95
Asn Thr Val Asp Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala
100 105 110
Thr Tyr Phe Cys Ala Arg Gly Val Tyr Ser Gly Ser Ser Asp Tyr Pro
115 120 125
Thr Arg Leu Asp Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Leu
130 135 140
Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly
145 150 155 160
Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn
180 185 190
Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser
195 200 205
Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala
225 230 235 240
Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly
245 250 255
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val
290 295 300
Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile
305 310 315 320
Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly
325 330 335
Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val
355 360 365
Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser
370 375 380
Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu
385 390 395 400
Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr
405 410 415
Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
420 425 430
Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser
450 455 460
Pro Gly Lys
465
<210> 186
<211> 236
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 186
Met Asp Thr Ser Thr Ser Thr Ala Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Thr Gly Ala Arg Cys Ala Ile Glu Met Thr Gln Ser Pro Pro Ser
20 25 30
Leu Ser Ala Ser Val Gly Glu Thr Val Arg Ile Arg Cys Leu Ala Ser
35 40 45
Glu Asp Ile Tyr Ser Gly Ile Ser Trp Tyr Gln Gln Lys Pro Glu Lys
50 55 60
Pro Pro Thr Leu Leu Ile Ser Gly Ala Ser Asn Leu Glu Ser Gly Val
65 70 75 80
Pro Pro Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp Tyr Thr Leu Thr
85 90 95
Ile Gly Gly Val Gln Ala Glu Asp Val Ala Thr Tyr Tyr Cys Leu Gly
100 105 110
Gly Tyr Ser Phe Ser Ser Thr Gly Leu Thr Phe Gly Ala Gly Thr Lys
115 120 125
Val Glu Ile Lys Arg Asp Pro Val Ala Pro Ser Val Leu Leu Phe Pro
130 135 140
Pro Ser Lys Glu Glu Leu Thr Thr Gly Thr Ala Thr Ile Val Cys Val
145 150 155 160
Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly
165 170 175
Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser
180 185 190
Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr
195 200 205
Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr
210 215 220
Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 187
<211> 460
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 187
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Gln His Leu Val Glu Ser Gly Gly Gly Leu Val Lys
20 25 30
Pro Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe
35 40 45
Thr Thr Gly Tyr His Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Phe Gly Val Tyr Thr Ser Thr Thr Thr Tyr
65 70 75 80
Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Val Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Ile Ser Ala Glu Asp Gly Gly Asp Leu Trp Gly
115 120 125
Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val
145 150 155 160
Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val
165 170 175
Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser
180 185 190
Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val
195 200 205
Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr
210 215 220
Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro
225 230 235 240
Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe
245 250 255
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
260 265 270
Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe
275 280 285
Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu
290 295 300
Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro
305 310 315 320
Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val
325 330 335
His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
340 345 350
Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg
355 360 365
Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly
370 375 380
Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala
385 390 395 400
Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser
405 410 415
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg
420 425 430
Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His
435 440 445
Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 188
<211> 236
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 188
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Thr Cys Gln Ala Ser
35 40 45
Gln Ser Ile Ser Asn Tyr Phe Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ser Ala Thr Tyr Ala Cys Gln Cys
100 105 110
Thr Tyr Gly Ser Ser Ser Thr Gly Phe Gly Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro
130 135 140
Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val
145 150 155 160
Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly
165 170 175
Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser
180 185 190
Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr
195 200 205
Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr
210 215 220
Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 189
<211> 462
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 189
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Phe Ser Phe Ser
35 40 45
Ser Tyr Phe Trp Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ser Ala Cys Ile Tyr Gly Asp Ser Ser Gly Ser Ser Tyr Tyr
65 70 75 80
Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Ser Tyr Gly Ser Ser Ser Tyr Tyr Tyr Ser Asn Leu
115 120 125
Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala
130 135 140
Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser
145 150 155 160
Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val
165 170 175
Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe
180 185 190
Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
195 200 205
Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro
210 215 220
Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser
225 230 235 240
Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe
245 250 255
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
260 265 270
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val
275 280 285
Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro
290 295 300
Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr
305 310 315 320
Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys
325 330 335
Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro
355 360 365
Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile
370 375 380
Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly
385 390 395 400
Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp
405 410 415
Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp
420 425 430
Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 190
<211> 235
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 190
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Ile Cys Asp Pro Val Met Thr Gln Thr Pro Ser Ser
20 25 30
Thr Ser Ala Ala Val Gly Gly Thr Val Thr Ile Ser Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Arg Leu Ile Tyr Glu Ser Ser Lys Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Ala Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Leu Gly Ala Tyr Tyr Thr Thr Leu Asp Phe Gly Gly Gly Thr Glu Val
115 120 125
Val Val Arg Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro Pro
130 135 140
Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val Ala
145 150 155 160
Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly Thr
165 170 175
Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser Ala
180 185 190
Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr Gln
195 200 205
Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr Thr
210 215 220
Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 191
<211> 460
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 191
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Glu Gly Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Phe Asp Phe
35 40 45
Ser Ser Asn Ala Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Tyr Asn Gly Asp Gly Ser Thr Tyr Tyr Ala
65 70 75 80
Ser Trp Val Asn Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Arg Gly Leu Ser Asn Trp Asn Arg Asp Asn Leu Trp Gly
115 120 125
Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val
145 150 155 160
Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val
165 170 175
Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser
180 185 190
Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val
195 200 205
Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr
210 215 220
Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro
225 230 235 240
Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe
245 250 255
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
260 265 270
Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe
275 280 285
Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu
290 295 300
Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro
305 310 315 320
Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val
325 330 335
His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
340 345 350
Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg
355 360 365
Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly
370 375 380
Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala
385 390 395 400
Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser
405 410 415
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg
420 425 430
Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His
435 440 445
Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 192
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 192
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Ala Thr Ile Asn Cys Gln Ala Ser
35 40 45
Gln Ser Leu Tyr Ser Pro Lys Asn Leu Ala Trp Tyr Gln Gln Thr Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ser Ala Ser Lys Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Ile Tyr Tyr Cys
100 105 110
Gln Gly Glu Phe Ser Cys Thr Thr Ala Ala Cys Phe Ala Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 193
<211> 461
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 193
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Pro
20 25 30
Glu Gly Ser Leu Thr Leu Ala Cys Thr Ala Ser Gly Phe Ser Phe Ser
35 40 45
Ser Tyr Tyr Tyr Ile Cys Trp Val Arg Gln Ala Pro Gly Thr Gly Leu
50 55 60
Glu Trp Ile Gly Cys Ile Asn Thr Gly Ser Asp Asp Thr His Tyr Ala
65 70 75 80
Ser Trp Leu Lys Gly Arg Phe Thr Phe Ser Lys Ala Ser Ser Thr Thr
85 90 95
Leu Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Arg Ser Ser Gly Ser Ser Asp Asp Ala Tyr Asp Leu Trp
115 120 125
Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr
145 150 155 160
Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr
165 170 175
Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro
180 185 190
Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser
195 200 205
Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala
210 215 220
Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys
225 230 235 240
Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln
275 280 285
Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro
290 295 300
Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu
305 310 315 320
Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys
325 330 335
Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro
355 360 365
Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys
385 390 395 400
Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly
405 410 415
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln
420 425 430
Arg Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 194
<211> 235
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 194
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Ser Glu Pro Val Gly Gly Ala Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Gly Ser Asn Leu Ala Trp Tyr Gln His Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Phe Ala Ser Ser Leu Ala Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Gly Arg Ser Gly Thr Gln Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys His Cys
100 105 110
Thr Tyr Tyr Pro Leu Ser Tyr Val Thr Phe Gly Gly Gly Thr Glu Val
115 120 125
Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro Pro
130 135 140
Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val Ala
145 150 155 160
Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly Thr
165 170 175
Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser Ala
180 185 190
Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr Gln
195 200 205
Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr Thr
210 215 220
Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 195
<211> 464
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 195
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Thr Ser Leu Thr Leu Ser Cys Thr Ala Ser Gly Phe Ser Phe Gly
35 40 45
Ser Tyr Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Asp Val Gly Ser Ser Gly Asp Thr Tyr Tyr
65 70 75 80
Ala Ser Trp Val Asn Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Asp Asp Thr Ala Ala Gly Gly Phe Gly Asn Leu
115 120 125
Glu Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro
130 135 140
Lys Ala Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro
145 150 155 160
Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu
165 170 175
Pro Val Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg
180 185 190
Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
195 200 205
Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala
210 215 220
His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr
225 230 235 240
Cys Ser Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
260 265 270
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro
275 280 285
Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala
290 295 300
Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val
305 310 315 320
Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe
325 330 335
Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met
355 360 365
Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys
370 375 380
Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys
385 390 395 400
Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp
405 410 415
Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser
420 425 430
Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 196
<211> 238
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 196
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Phe Glu Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Glu Pro Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Tyr Ser Tyr Phe Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Arg Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Asn
100 105 110
Asn Tyr Gly Arg Gly Ser Gly Ser Tyr Phe Phe Gly Phe Gly Gly Gly
115 120 125
Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile
130 135 140
Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val
145 150 155 160
Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val
165 170 175
Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln
180 185 190
Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr
195 200 205
Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln
210 215 220
Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 197
<211> 456
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 197
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Ile Asp Phe Ser
35 40 45
Ser Gly Tyr Gly Met Trp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Tyr Ile Gly Tyr Ile Asp Thr Gly Ser Gly Ser Thr Tyr Tyr Ala
65 70 75 80
Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Met
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Val Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Lys Gly Gly Ala Ile Asp Leu Trp Gly Pro Gly Thr Leu
115 120 125
Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu
130 135 140
Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys
145 150 155 160
Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser
165 170 175
Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser
180 185 190
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser
195 200 205
Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val
210 215 220
Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro
225 230 235 240
Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
245 250 255
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
260 265 270
Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile
275 280 285
Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln
290 295 300
Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln
305 310 315 320
Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala
325 330 335
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro
340 345 350
Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser
355 360 365
Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser
370 375 380
Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr
385 390 395 400
Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr
405 410 415
Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe
420 425 430
Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
435 440 445
Ser Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 198
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 198
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Met Thr Gln Thr Pro Ala
20 25 30
Ser Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Gln Ser Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Arg Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu
85 90 95
Thr Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys His
100 105 110
Thr Tyr Tyr Leu Ser Ser Ser Ile Ser Tyr Gly Asn Thr Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 199
<211> 465
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 199
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Glu Glu Ser Gly Gly Asp Leu Val Lys
20 25 30
Pro Glu Gly Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Phe Ser Phe
35 40 45
Ser Ser Ile Tyr Trp Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Thr Thr Val Val Lys Ser Gly Arg Thr Tyr
65 70 75 80
Tyr Ala Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser
85 90 95
Thr Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala
100 105 110
Thr Tyr Phe Cys Ala Arg Glu Phe Val Asp Gly Gly Gly Ser Ser Gly
115 120 125
Arg Asp Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln
130 135 140
Pro Lys Ala Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr
145 150 155 160
Pro Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val
180 185 190
Arg Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser
195 200 205
Ser Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val
210 215 220
Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser
225 230 235 240
Thr Cys Ser Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro
245 250 255
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
260 265 270
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Asp Asp
275 280 285
Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr
290 295 300
Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val
305 310 315 320
Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu
325 330 335
Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr
355 360 365
Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr
370 375 380
Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu
385 390 395 400
Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu
405 410 415
Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr
420 425 430
Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met His Glu
435 440 445
Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly
450 455 460
Lys
465
<210> 200
<211> 236
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 200
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Ser Arg Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Arg Leu Ile Tyr Lys Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Ser Ser Ile Asp Val Asp Asn Asp Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro
130 135 140
Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val
145 150 155 160
Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly
165 170 175
Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser
180 185 190
Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr
195 200 205
Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr
210 215 220
Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 201
<211> 467
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 201
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Glu Glu Ser Gly Gly Gly Leu Val Lys
20 25 30
Pro Glu Gly Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Phe Asp Leu
35 40 45
Ser Ser Gly Tyr Asp Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Ile Tyr Ala Asp Tyr Ser Gly Ser Thr Tyr
65 70 75 80
Tyr Ala Ser Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Ser Thr Ser
85 90 95
Leu Asn Thr Val Asp Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr
100 105 110
Ala Thr Tyr Phe Cys Ala Arg Gly Ala Thr Gly Asn Gly Gly Tyr Gly
115 120 125
Tyr Tyr Phe Asn Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
130 135 140
Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly
145 150 155 160
Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn
180 185 190
Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser
195 200 205
Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala
225 230 235 240
Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly
245 250 255
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val
290 295 300
Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile
305 310 315 320
Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly
325 330 335
Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val
355 360 365
Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser
370 375 380
Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu
385 390 395 400
Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr
405 410 415
Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
420 425 430
Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser
450 455 460
Pro Gly Lys
465
<210> 202
<211> 238
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 202
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Asp Ile Val Met Thr Gln Thr Pro Ala
20 25 30
Ser Val Ser Glu Pro Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala
35 40 45
Ser Gln Asn Ile Asn Ser Gly Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Lys Ala Ser Thr Leu Ala Ser Gly
65 70 75 80
Val Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu
85 90 95
Thr Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Thr Tyr Tyr Tyr Ser Ser Ser Ser Ser Asp Asn Ala Phe Gly Gly Gly
115 120 125
Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile
130 135 140
Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val
145 150 155 160
Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val
165 170 175
Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln
180 185 190
Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr
195 200 205
Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln
210 215 220
Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 203
<211> 462
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 203
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe Ser
35 40 45
Ser Ser Tyr Trp Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Tyr Gly Gly Ser Ser Gly Asn Ile Ala Tyr
65 70 75 80
Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Asp Ile Pro Ser Asp Ala Phe Thr Leu Asp Leu
115 120 125
Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Lys Ala
130 135 140
Pro Ser Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser
145 150 155 160
Thr Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val
165 170 175
Thr Val Thr Trp Asn Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe
180 185 190
Pro Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
195 200 205
Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro
210 215 220
Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser
225 230 235 240
Lys Pro Met Cys Pro Pro Pro Glu Leu Pro Gly Gly Pro Ser Val Phe
245 250 255
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
260 265 270
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val
275 280 285
Gln Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro
290 295 300
Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr
305 310 315 320
Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys
325 330 335
Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Ala Arg Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro
355 360 365
Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile
370 375 380
Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly
385 390 395 400
Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Thr Val Leu Asp Ser Asp
405 410 415
Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp
420 425 430
Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys
450 455 460
<210> 204
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 204
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Ser Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Lys Asp Asn Asn Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Lys Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Glu Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Glu Phe Ser Cys Gly Ser Ala Asp Cys Ile Ala Phe Gly Gly
115 120 125
Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu
130 135 140
Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile
145 150 155 160
Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu
165 170 175
Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro
180 185 190
Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu
195 200 205
Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr
210 215 220
Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 205
<211> 456
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 205
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Lys Gly Ser Gly Ile Asp Phe Ser
35 40 45
Ser Gly Tyr Gly Met Trp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Tyr Ile Gly Tyr Ile Asp Thr Gly Tyr Gly Ser Thr Tyr Tyr Ala
65 70 75 80
Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Val Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Lys Gly Gly Ala Ile Asp Leu Trp Gly Pro Gly Thr Leu
115 120 125
Val Thr Val Ser Ser Gly Gln Pro Lys Ala Pro Ser Val Phe Pro Leu
130 135 140
Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys
145 150 155 160
Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser
165 170 175
Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser
180 185 190
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser
195 200 205
Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val
210 215 220
Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Met Cys Pro Pro
225 230 235 240
Pro Glu Leu Pro Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
245 250 255
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
260 265 270
Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile
275 280 285
Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln
290 295 300
Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln
305 310 315 320
Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala
325 330 335
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro
340 345 350
Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser
355 360 365
Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser
370 375 380
Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr
385 390 395 400
Lys Thr Thr Pro Thr Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr
405 410 415
Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe
420 425 430
Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
435 440 445
Ser Ile Ser Arg Ser Pro Gly Lys
450 455
<210> 206
<211> 238
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 206
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ala Ser
20 25 30
Thr Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Arg Ser Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Asp Val Phe Asn Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Ala Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Ser Tyr Tyr Ser Gly Asn Trp Tyr Ser Ala Phe Gly Gly Gly
115 120 125
Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile
130 135 140
Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val
145 150 155 160
Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val
165 170 175
Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln
180 185 190
Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr
195 200 205
Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln
210 215 220
Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg Gly Asp Cys
225 230 235
<210> 207
<211> 13
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 207
Ala Ala Trp Asp Asp Ser Leu Asn Gly Leu Asn Trp Val
1 5 10
<210> 208
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 208
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
20 25
<210> 209
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 209
Gly Phe Thr Phe Ser Asn Tyr Gly
1 5
<210> 210
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 210
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Tyr
<210> 211
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 211
Ile Ser Ser Ser Gly Ser Thr Val
1 5
<210> 212
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 212
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Asp Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Ser
35 40
<210> 213
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 213
Gly Gln Leu Asp Thr Ser Asp Ala Phe Asp Ile
1 5 10
<210> 214
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 214
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 215
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 215
Asp Ile Glu Met Thr Gln Ser Pro Ser Ser Pro Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
20 25
<210> 216
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 216
Gln Ser Ile Ser Ser Tyr
1 5
<210> 217
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 217
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 218
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 218
Ala Ala Ser
1
<210> 219
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 219
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 220
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 220
Gln Gln Ser Tyr Ser Thr Pro Leu Thr
1 5
<210> 221
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 221
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
1 5 10
<210> 222
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 222
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Val Val Gln Ser Gly Arg
1 5 10 15
Ser Leu Arg Val Ser Cys Ala Ala Ser
20 25
<210> 223
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 223
Gly Phe Ser Phe Ser Ser Tyr Gly
1 5
<210> 224
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 224
Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Tyr
<210> 225
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 225
Ile Ser Ser Ser Gly Ser Thr Ile
1 5
<210> 226
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 226
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ala Glu Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 227
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 227
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
20 25
<210> 228
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 228
Gln Gly Ile Ser Asn Tyr
1 5
<210> 229
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 229
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 230
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 230
Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 231
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 231
Phe Gly Gly Gly Thr Lys Val Glu Val Lys
1 5 10
<210> 232
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 232
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser
20 25
<210> 233
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 233
Ile Ser Ser Ser Ser Ser Thr Ile
1 5
<210> 234
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<220>
<221> MOD_RES
<222> (3)..(3)
<223> Any amino acid
<220>
<221> MOD_RES
<222> (5)..(5)
<223> Any amino acid
<400> 234
Gly Gln Xaa Asp Xaa Ser Asp Ala Phe Asp Ile
1 5 10
<210> 235
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<220>
<221> MOD_RES
<222> (3)..(3)
<223> Any amino acid
<220>
<221> MOD_RES
<222> (16)..(16)
<223> Any amino acid
<400> 235
Leu Asn Xaa Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Xaa
1 5 10 15
Tyr
<210> 236
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<220>
<221> MOD_RES
<222> (1)..(1)
<223> Any amino acid
<400> 236
Xaa Ala Ser
1
<210> 237
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<220>
<221> MOD_RES
<222> (31)..(31)
<223> Any amino acid
<400> 237
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Xaa Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 238
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<220>
<221> MOD_RES
<222> (5)..(5)
<223> Any amino acid
<220>
<221> MOD_RES
<222> (7)..(7)
<223> Any amino acid
<400> 238
Phe Gly Gly Gly Xaa Lys Xaa Glu Ile Lys
1 5 10
<210> 239
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 239
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Ala Ile Ser Arg Asp Asn
1 5 10 15
Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Leu Tyr Tyr Cys Ala Lys
35 40
<210> 240
<211> 19
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 240
Ala Thr Arg Tyr Asp Ile Leu Thr Gly Tyr Ser Asp Gly Val Asp Tyr
1 5 10 15
Phe Asp Tyr
<210> 241
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 241
His Gln Ser Tyr Ser Thr Pro Tyr Thr
1 5
<210> 242
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 242
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
1 5 10
<210> 243
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 243
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 Ala Ser
20 25
<210> 244
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 244
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
1 5 10 15
Asn
<210> 245
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 245
Ile Lys Gln Asp Gly Ser Glu Lys
1 5
<210> 246
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 246
Tyr Tyr Val Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 247
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 247
Val Thr Ser Pro His Ala Phe Asp Ile
1 5
<210> 248
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 248
Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 249
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 249
Asp Ile Gln Met Thr Gln Ser Pro Ser Ala Met Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
20 25
<210> 250
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 250
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu Ile
1 5 10 15
Tyr
<210> 251
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 251
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser
20 25
<210> 252
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 252
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Gly
<210> 253
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 253
Ile Asn Trp Asn Gly Gly Ser Thr
1 5
<210> 254
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 254
Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Gly Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Val Thr
35 40
<210> 255
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 255
Gln Gly Ser Ala Phe Asp Ile
1 5
<210> 256
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 256
Ser Tyr Glu Leu Thr Gln Pro Pro Ser Leu Ser Val Ser Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Ser Gly Asp
20 25
<210> 257
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 257
Ala Leu Ala Lys Gln Tyr
1 5
<210> 258
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 258
Ala Tyr Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Val Leu Val Ile
1 5 10 15
Tyr
<210> 259
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 259
Lys Asp Thr
1
<210> 260
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 260
Glu Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser Ser Ser Gly
1 5 10 15
Thr Thr Val Thr Leu Thr Ile Ser Gly Val Gln Ala Glu Asp Glu Val
20 25 30
Asp Tyr Tyr Cys
35
<210> 261
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 261
Gln Ser Thr Asp Ser Ser Gly Thr Tyr Gln Val
1 5 10
<210> 262
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 262
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
1 5 10
<210> 263
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 263
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
20 25
<210> 264
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 264
Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
1 5 10 15
Trp
<210> 265
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 265
Ile Ser Ala Tyr Asn Gly Asn Thr
1 5
<210> 266
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 266
Asn Tyr Ala Gln Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr
1 5 10 15
Ser Thr Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp
20 25 30
Thr Ala Ala Tyr Tyr Cys Ala Arg
35 40
<210> 267
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 267
Val Thr Gly Ile Thr Gly Thr Thr Ile Asp Pro
1 5 10
<210> 268
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 268
Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser
1 5 10
<210> 269
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 269
Asp Ala Ser
1
<210> 270
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 270
Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala
20 25 30
Val Tyr Tyr Cys
35
<210> 271
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 271
Gln Gln Tyr Asn Asn Trp Pro Gln Thr
1 5
<210> 272
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 272
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
1 5 10
<210> 273
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 273
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
20 25
<210> 274
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 274
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Ala
<210> 275
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 275
Ile Ser Gly Ser Gly Gly Ser Thr
1 5
<210> 276
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 276
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 277
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 277
Asp Tyr Gly Gly Tyr Asp Gly Val Tyr Phe Asp Tyr
1 5 10
<210> 278
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 278
Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp
20 25
<210> 279
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 279
Ser Leu Arg Ser Tyr Tyr
1 5
<210> 280
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 280
Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile
1 5 10 15
Tyr
<210> 281
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 281
Gly Lys Asn
1
<210> 282
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 282
Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly
1 5 10 15
Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 283
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 283
Asn Ser Arg Asp Ser Ser Gly Asn His Val Val
1 5 10
<210> 284
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 284
Phe Gly Gly Gly Thr Lys Val Thr Val Leu
1 5 10
<210> 285
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 285
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser
20 25
<210> 286
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 286
Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
1 5 10 15
Val
<210> 287
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 287
Ile Ser Tyr Asp Gly Ser Asn Lys
1 5
<210> 288
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 288
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Ala Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 289
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 289
Asp Arg Asp Val Gly Pro Thr Tyr Tyr Tyr Tyr Gly Met Asp Val
1 5 10 15
<210> 290
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 290
Ser Tyr Glu Leu Thr Gln Pro Pro Ser Leu Ser Val Ser Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Ser Gly His
20 25
<210> 291
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 291
Ala Leu Pro Lys Gln Tyr
1 5
<210> 292
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 292
Glu Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser Ser Ser Gly
1 5 10 15
Thr Thr Val Thr Leu Thr Ile Ser Gly Val Gln Ala Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 293
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 293
Gln Ser Ala Asp Ser Ser Gly Pro Tyr Gln Val
1 5 10
<210> 294
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 294
Phe Gly Gly Gly Thr Gln Leu Thr Val Leu
1 5 10
<210> 295
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 295
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Lys
35 40
<210> 296
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 296
Asp Arg Glu Tyr Ile Ala Val Ala Ala Asp Tyr
1 5 10
<210> 297
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 297
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 298
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 298
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Thr Ile Ser Ile Thr Cys Arg Ala Ser
20 25
<210> 299
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 299
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Arg
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 300
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 300
Gln Gln Ser Tyr Ser Thr Pro Phe Thr
1 5
<210> 301
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 301
Phe Gly Pro Gly Thr Lys Val Glu Ile Lys
1 5 10
<210> 302
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 302
Glu Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser
20 25
<210> 303
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 303
Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
1 5 10 15
Ile
<210> 304
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 304
Ile Asn Pro Ser Gly Gly Ser Thr
1 5
<210> 305
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 305
Ile Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr
1 5 10 15
Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 306
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 306
Ser Leu Arg Asp Gly Tyr Asn Tyr Ile Gly Ser Leu Gly Tyr
1 5 10
<210> 307
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 307
Gln Ser Glu Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Ser
20 25
<210> 308
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 308
Ser Ser Asn Ile Gly Ser Asn Tyr
1 5
<210> 309
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 309
Val Tyr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 310
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 310
Arg Asn Asn
1
<210> 311
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 311
Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly
1 5 10 15
Thr Ser Ala Ser Leu Ala Ile Arg Gly Leu Gln Ser Glu Asp Glu Ala
20 25 30
Gly Tyr Tyr Cys
35
<210> 312
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 312
Gly Phe Thr Phe Asp Asp Tyr Ala
1 5
<210> 313
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 313
Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Gly
<210> 314
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 314
Ile Ser Trp Asn Ser Gly Ser Thr
1 5
<210> 315
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 315
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Gly
35 40
<210> 316
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 316
Gly Ser Arg Arg Tyr Asp Ser Ser Gly Tyr Tyr Tyr Glu Ser Phe Asp
1 5 10 15
Tyr
<210> 317
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 317
Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 318
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 318
Gln Gln Ser Tyr His Thr Pro Tyr Thr
1 5
<210> 319
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 319
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser
20 25
<210> 320
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 320
Gly Gly Thr Phe Ser Ser Tyr Ala
1 5
<210> 321
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 321
Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
1 5 10 15
Arg
<210> 322
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 322
Ile Ile Pro Ile Leu Gly Ile Ala
1 5
<210> 323
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 323
Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys
1 5 10 15
Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 324
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 324
Asp Ile Asn Arg Tyr Asn Trp Asn Phe Arg Ala Phe Asp Ile
1 5 10
<210> 325
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 325
Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr
1 5 10
<210> 326
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 326
Leu Ala Trp Tyr Gln Gln Lys Pro Arg Gln Pro Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 327
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 327
Trp Ala Ser
1
<210> 328
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 328
Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Asn Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala
20 25 30
Ala Tyr Tyr Cys
35
<210> 329
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 329
Gln Gln His Tyr Ser Thr Pro Leu Thr
1 5
<210> 330
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 330
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser
20 25
<210> 331
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 331
Asn Tyr Ala Gln Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asn Thr
1 5 10 15
Ser Thr Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 332
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 332
Leu Asn Trp Tyr Arg Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 333
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 333
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Ala Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 334
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 334
Gln Gln Tyr Asp Ser Gln Ser Gly Thr
1 5
<210> 335
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 335
Glu 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
20 25
<210> 336
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 336
Ile Ser Tyr Asp Gly Val Lys Lys
1 5
<210> 337
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 337
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Ser Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Val Asp Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Lys
35 40
<210> 338
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 338
Asp Leu Gly Trp Gln Asn Asp Tyr
1 5
<210> 339
<211> 33
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 339
Gln Ser Val Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Asp Leu Gly Trp Gln Asn Asp
20 25 30
Tyr
<210> 340
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 340
Ser Ser Asp Val Gly Gly His Asn Tyr
1 5
<210> 341
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 341
Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile
1 5 10 15
Tyr
<210> 342
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 342
Asp Val Ser
1
<210> 343
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 343
Asn Arg Pro Ser Gly Val Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly
1 5 10 15
Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 344
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 344
Ser Ser Tyr Thr Ser Ser Ser Pro Trp Val
1 5 10
<210> 345
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 345
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
1 5 10
<210> 346
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 346
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
20 25
<210> 347
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 347
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Ala Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Arg Gly
35 40
<210> 348
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 348
Tyr Cys Ser Ser Thr Ser Cys Tyr Gly Arg Arg Gly Ala Phe Asp Ile
1 5 10 15
<210> 349
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 349
Ser Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 350
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 350
Gln Ala Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Arg
20 25
<210> 351
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 351
Asn Ser Asn Ile Gly Ser Asn Asn
1 5
<210> 352
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 352
Val Asn Trp Tyr Gln His Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 353
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 353
Ser Asn Asn
1
<210> 354
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 354
Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Ala Ser Lys Ser Gly
1 5 10 15
Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 355
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 355
Ala Ala Trp Asp Asp Arg Met Asn Gly Pro Val
1 5 10
<210> 356
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 356
Ile Gly Gly Gly Thr Lys Val Thr Val Leu Gly
1 5 10
<210> 357
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 357
Met His Trp Val Arg Gln Ala Pro Ala Lys Gly Leu Val Trp Val Ser
1 5 10 15
Arg
<210> 358
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 358
Ile Asn Ser Asp Gly Ser Ser Thr
1 5
<210> 359
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 359
Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 360
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 360
Asp Phe Trp Ser Gly Arg Pro Tyr Tyr Tyr Tyr Met Asp Val
1 5 10
<210> 361
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 361
Gln Asp Ile Gly Asp Asp
1 5
<210> 362
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 362
Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Ile
1 5 10 15
Tyr
<210> 363
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 363
Thr Leu Gln Gly Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 364
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 364
Gln Gln Ser Tyr Ser Thr Pro Arg Thr
1 5
<210> 365
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 365
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Arg Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 366
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 366
Trp Gly Ile Val Ala Ala Arg Pro Asn Tyr Tyr Tyr Gly Met Asp Val
1 5 10 15
<210> 367
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 367
Gln Ser Ala Leu Thr Gln Pro Arg Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ile Ser Cys Thr Gly Thr
20 25
<210> 368
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 368
Ser Ser Asp Val Gly Gly Tyr Asn Tyr
1 5
<210> 369
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 369
Ser Ser Tyr Ala Asn Asn Ser Pro Trp Val
1 5 10
<210> 370
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 370
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly
1 5 10
<210> 371
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 371
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser
20 25
<210> 372
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 372
Asn Tyr Ala Gln Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr
1 5 10 15
Ser Thr Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 373
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 373
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 Gln Ala Ser
20 25
<210> 374
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 374
Gln Asp Ile Ser Asn Tyr
1 5
<210> 375
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 375
Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 376
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 376
Gln Gln Tyr Ala Asn Leu Pro Leu Thr
1 5
<210> 377
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 377
Gly Phe Thr Val Ser Ser Asn Tyr
1 5
<210> 378
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 378
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Val
<210> 379
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 379
Ile Tyr Ser Gly Gly Ser Thr
1 5
<210> 380
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 380
Gly Gly Leu Thr Gly Asp Asp Ala Phe Asp Ile
1 5 10
<210> 381
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 381
Gln Ser Ile Ser Ser Phe
1 5
<210> 382
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 382
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Thr Ala Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 383
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 383
Thr Thr Ser
1
<210> 384
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 384
Gln Gln Gly Asn Ser Leu Pro Leu Thr
1 5
<210> 385
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 385
Asp Lys Glu Leu Ser Tyr
1 5
<210> 386
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 386
Gln Ser Gly Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr
20 25
<210> 387
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 387
Glu Val Ser
1
<210> 388
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 388
Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly
1 5 10 15
Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 389
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 389
Lys Thr Ser
1
<210> 390
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 390
Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
1 5 10 15
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala
20 25 30
Thr Tyr Tyr Cys
35
<210> 391
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 391
Met Ser Trp Val Arg Gln Ala Pro Ala Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Ala
<210> 392
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 392
Asp Arg Pro Tyr Ser Tyr Gly Lys Asn Asp Ala Phe Asp Ile
1 5 10
<210> 393
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 393
Gln Asp Val Ser Asn Tyr
1 5
<210> 394
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 394
Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
1 5 10
<210> 395
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 395
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser
20 25
<210> 396
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 396
Gly Tyr Thr Phe Thr Ser Tyr Tyr
1 5
<210> 397
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 397
Ser Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr
1 5 10 15
Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 398
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 398
Ala Gly Gly Tyr Tyr Tyr Tyr Tyr Met Asp Val
1 5 10
<210> 399
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 399
Gln Ser Gly Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Ser
20 25
<210> 400
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 400
Gly Pro Asn Ile Gly Asn Asn Tyr
1 5
<210> 401
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 401
Val Tyr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu Met
1 5 10 15
Tyr
<210> 402
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 402
Ser Pro Trp Leu Ile Thr Phe Gly Gly Val Ile Ala Met Gly Tyr
1 5 10 15
<210> 403
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 403
Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Ser
20 25
<210> 404
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 404
Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly
1 5 10 15
Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg Ser Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 405
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 405
Ala Ala Trp Asp Asp Ser Leu Ser Gly Val Val
1 5 10
<210> 406
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 406
Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly
1 5 10
<210> 407
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 407
Asp Ile Val 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
20 25
<210> 408
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 408
Gln Gln Phe Asn Asn Tyr Pro Leu Thr
1 5
<210> 409
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 409
Gln Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser
20 25
<210> 410
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 410
Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly
1 5 10 15
Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 411
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 411
Ala Ala Trp Asp Asp Ser Leu Asn Gly Tyr Val
1 5 10
<210> 412
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 412
Phe Gly Thr Gly Thr Lys Leu Thr Val Leu Gly
1 5 10
<210> 413
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 413
Gln Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ala Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Ile Ile Asn Thr Gln Thr Gly Lys Pro Lys Tyr Ser Pro Ser Phe
50 55 60
Gln Gly Gln Phe Ile Phe Ser Leu Asp Thr Ser Ile Asn Thr Thr Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Phe Cys
85 90 95
Thr Arg Leu Gly Thr Gly Asn Thr Lys Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 414
<211> 114
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 414
Asp Ile Gln Ile Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Lys Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Glu Asn Asn Gln Asp Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys
35 40 45
Ala Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Gln Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Arg Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Glu Gln
85 90 95
Thr Tyr Arg Tyr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile
100 105 110
Lys Arg
<210> 415
<211> 471
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 415
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Pro Asp Tyr Asn Met Asp Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
50 55 60
Glu Trp Met Gly Tyr Ile Asn Pro Asp Asn Gly Gly Thr Ile Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Val Thr Leu Thr Val Asp Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Asp Ser Ser Gly Tyr Gly Tyr Tyr Ala Met
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr
130 135 140
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
145 150 155 160
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
165 170 175
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
180 185 190
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
195 200 205
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
210 215 220
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
225 230 235 240
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
245 250 255
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
260 265 270
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
275 280 285
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
290 295 300
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
305 310 315 320
Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
325 330 335
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
340 345 350
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
355 360 365
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys
370 375 380
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
385 390 395 400
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
405 410 415
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
420 425 430
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
435 440 445
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
450 455 460
Leu Ser Leu Ser Pro Gly Lys
465 470
<210> 416
<211> 471
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 416
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Pro Asp Tyr Asn Met Asp Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Asp Asn Gly Gly Thr Ile Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Val Thr Leu Thr Val Asp Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Asp Ser Ser Gly Tyr Gly Tyr Tyr Ala Met
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr
130 135 140
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
145 150 155 160
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
165 170 175
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
180 185 190
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
195 200 205
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
210 215 220
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
225 230 235 240
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
245 250 255
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
260 265 270
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
275 280 285
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
290 295 300
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
305 310 315 320
Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
325 330 335
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
340 345 350
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
355 360 365
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys
370 375 380
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
385 390 395 400
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
405 410 415
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
420 425 430
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
435 440 445
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
450 455 460
Leu Ser Leu Ser Pro Gly Lys
465 470
<210> 417
<211> 471
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 417
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Pro Asp Tyr Asn Met Asp Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
50 55 60
Glu Trp Met Gly Tyr Ile Asn Pro Asp Asn Gly Gly Thr Ile Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Asp Ser Ser Gly Tyr Gly Tyr Tyr Ala Met
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr
130 135 140
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
145 150 155 160
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
165 170 175
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
180 185 190
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
195 200 205
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
210 215 220
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
225 230 235 240
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
245 250 255
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
260 265 270
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
275 280 285
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
290 295 300
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
305 310 315 320
Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
325 330 335
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
340 345 350
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
355 360 365
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys
370 375 380
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
385 390 395 400
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
405 410 415
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
420 425 430
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
435 440 445
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
450 455 460
Leu Ser Leu Ser Pro Gly Lys
465 470
<210> 418
<211> 471
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 418
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Pro Asp Tyr Asn Met Asp Trp Val Arg Gln Ala Pro Gly Gln Ser Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Asp Asn Gly Gly Thr Ile Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Asp Ser Ser Gly Tyr Gly Tyr Tyr Ala Met
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr
130 135 140
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
145 150 155 160
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
165 170 175
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
180 185 190
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
195 200 205
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
210 215 220
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
225 230 235 240
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
245 250 255
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
260 265 270
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
275 280 285
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
290 295 300
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
305 310 315 320
Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
325 330 335
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
340 345 350
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
355 360 365
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys
370 375 380
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
385 390 395 400
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
405 410 415
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
420 425 430
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
435 440 445
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
450 455 460
Leu Ser Leu Ser Pro Gly Lys
465 470
<210> 419
<211> 237
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 419
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val
20 25 30
Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Arg Ala Ser Glu Ser Val
35 40 45
Asp Asn Tyr Gly Ile Ser Phe Met His Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Asp Ser Gly
65 70 75 80
Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu
85 90 95
Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Ser Tyr Lys Asp Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu
115 120 125
Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser
130 135 140
Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn
145 150 155 160
Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala
165 170 175
Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp
195 200 205
Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu
210 215 220
Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 420
<211> 237
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 420
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val
20 25 30
Ser Pro Gly Gln Arg Ala Thr Ile Thr Cys Arg Ala Ser Glu Ser Val
35 40 45
Asp Asn Tyr Gly Ile Ser Phe Met His Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Asp Ser Glu
65 70 75 80
Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu
85 90 95
Thr Ile Asn Pro Val Glu Ala Asn Asp Thr Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Ser Tyr Lys Asp Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu
115 120 125
Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser
130 135 140
Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn
145 150 155 160
Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala
165 170 175
Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp
195 200 205
Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu
210 215 220
Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 421
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 421
Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Ala Ser
1 5 10 15
Leu Thr Leu Thr Cys Arg Val Ser Gly Phe Ser Phe Ser Ser Ser Tyr
20 25 30
Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Ala Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala Thr Trp Ala
50 55 60
Lys Gly Arg Phe Thr Ile Ser Lys Ile Ser Ser Thr Thr Val Thr Leu
65 70 75 80
Gln Met Thr Ser Leu Thr Asp Ala Asp Thr Ala Thr Tyr Phe Cys Ala
85 90 95
Arg Asp Ala Thr Gly Tyr Arg Ile Asn Thr Ile Gly Leu Tyr Phe Asn
100 105 110
Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 422
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 422
Gln Ser Leu Leu Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser
1 5 10 15
Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ser Phe Ser Ser Ser Tyr
20 25 30
Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala Asp Ser Ala
50 55 60
Lys Gly Arg Phe Thr Ile Ser Lys Ile Ser Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Thr Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala
85 90 95
Arg Asp Ala Thr Gly Tyr Arg Ile Asn Thr Ile Gly Leu Tyr Phe Asn
100 105 110
Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 423
<211> 126
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 423
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ser Phe Ser Ser Ser
20 25 30
Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
35 40 45
Val Ser Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala Asp Ser
50 55 60
Ala Lys Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Val
65 70 75 80
Tyr Leu Gln Met Thr Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe
85 90 95
Cys Ala Arg Asp Ala Thr Gly Tyr Arg Ile Asn Thr Ile Gly Leu Tyr
100 105 110
Phe Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 424
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 424
Gln Ser Leu Leu Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser
1 5 10 15
Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ser Phe Ser Ser Ser Tyr
20 25 30
Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala Asp Ser Ala
50 55 60
Lys Gly Arg Phe Thr Ile Ser Lys Glu Ser Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala
85 90 95
Arg Asp Ala Thr Gly Tyr Arg Ile Asn Thr Ile Gly Leu Tyr Phe Asn
100 105 110
Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 425
<211> 126
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 425
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ser Phe Ser Ser Ser
20 25 30
Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
35 40 45
Val Ser Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala Asp Ser
50 55 60
Ala Lys Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Val
65 70 75 80
Tyr Leu Gln Met Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe
85 90 95
Cys Ala Arg Asp Ala Thr Gly Tyr Arg Ile Asn Thr Ile Gly Leu Tyr
100 105 110
Phe Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 426
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 426
Gln Ser Leu Leu Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser
1 5 10 15
Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ser Phe Ser Ser Ser Tyr
20 25 30
Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala Asp Ser Ala
50 55 60
Lys Gly Arg Phe Thr Ile Ser Lys Glu Ser Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala
85 90 95
Arg Asp Ala Thr Gly Tyr Arg Ile Gln Thr Ile Gly Leu Tyr Phe Asn
100 105 110
Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 427
<211> 126
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 427
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ser Phe Ser Ser Ser
20 25 30
Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
35 40 45
Val Ser Cys Ile Gly Thr Thr Arg Gly Ser Thr Tyr Tyr Ala Asp Ser
50 55 60
Ala Lys Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Val
65 70 75 80
Tyr Leu Gln Met Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe
85 90 95
Cys Ala Arg Asp Ala Thr Gly Tyr Arg Ile Gln Thr Ile Gly Leu Tyr
100 105 110
Phe Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 428
<211> 109
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 428
Glu Leu Thr Gln Thr Pro Ser Ser Val Glu Ala Ala Val Gly Gly Thr
1 5 10 15
Pro Thr Ile Lys Cys Gln Ala Ser Gln Thr Ile Tyr Ser Tyr Leu Ser
20 25 30
Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Glu
35 40 45
Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly
50 55 60
Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Asp Leu Glu Cys Ala Asp
65 70 75 80
Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr His Gly Thr Ala Ser Thr Glu
85 90 95
Tyr Asn Thr Phe Gly Gly Gly Thr Glu Val Val Val Lys
100 105
<210> 429
<211> 109
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 429
Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg
1 5 10 15
Val Thr Ile Thr Cys Gln Ala Ser Gln Thr Ile Tyr Ser Tyr Leu Ser
20 25 30
Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile Tyr Glu
35 40 45
Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly
50 55 60
Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp
65 70 75 80
Phe Ala Thr Tyr Tyr Cys Gln Ser Tyr His Gly Thr Ala Ser Thr Glu
85 90 95
Tyr Asn Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 430
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 430
Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Thr Ile Tyr Ser Tyr
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Glu Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Tyr His Gly Thr Ala Ser
85 90 95
Thr Glu Tyr Asn Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 431
<211> 109
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 431
Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg
1 5 10 15
Val Thr Ile Thr Cys Gln Ala Ser Gln Thr Ile Tyr Ser Tyr Leu Ser
20 25 30
Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile Tyr Glu
35 40 45
Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly
50 55 60
Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp
65 70 75 80
Thr Ala Thr Tyr Tyr Cys Gln Ser Tyr His Gly Thr Ala Ser Thr Glu
85 90 95
Tyr Asn Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 432
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 432
Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Thr Ile Tyr Ser Tyr
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Glu Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Thr Ala Thr Tyr Tyr Cys Gln Ser Tyr His Gly Thr Ala Ser
85 90 95
Thr Glu Tyr Asn Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 433
<211> 109
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 433
Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg
1 5 10 15
Val Thr Ile Thr Cys Gln Ala Ser Gln Thr Ile Tyr Ser Tyr Leu Ser
20 25 30
Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile Tyr Glu
35 40 45
Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly
50 55 60
Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp
65 70 75 80
Thr Ala Thr Tyr Tyr Cys Gln Ser Tyr His Gly Thr Ala Ser Thr Glu
85 90 95
Tyr Gln Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 434
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 434
Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Thr Ile Tyr Ser Tyr
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Glu Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Thr Ala Thr Tyr Tyr Cys Gln Ser Tyr His Gly Thr Ala Ser
85 90 95
Thr Glu Tyr Gln Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 435
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 435
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser
20 25
<210> 436
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 436
Gly Phe Thr Phe Ser Thr Tyr Gly
1 5
<210> 437
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 437
Gly Phe Thr Phe Ser Ser Tyr Trp
1 5
<210> 438
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 438
Gly Phe Thr Phe Asp Asp Tyr Gly
1 5
<210> 439
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 439
Gly Tyr Thr Phe Thr Ser Tyr Gly
1 5
<210> 440
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 440
Gly Phe Thr Phe Ser Ser Tyr Ala
1 5
<210> 441
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 441
Gly Tyr Thr Phe Thr Arg Tyr Tyr
1 5
<210> 442
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 442
Asp Leu Gly His Phe Asp Ser Gly Ser Ser Tyr Phe Asp Tyr
1 5 10
<210> 443
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 443
Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly
1 5 10 15
Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala
20 25 30
Asp Tyr His Cys
35
Claims (23)
- SEQ ID NO: 103-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함하는, 항-인테그린 알파 11 베타 1(α11β1) 항체 또는 이의 항원 결합 단편.
- SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443 중 어느 하나에 포함된 CDR 서열을 포함하는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- SEQ ID NO: 103-206, 또는 413-435 중 어느 하나에 포함된 CDR1, CDR2 및 CDR3을 포함하는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제1항에 있어서, SEQ ID NO: 103-114, 207-311 및 312-443으로 이루어진 군으로부터 선택된 아미노산 서열을 포함하는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제2항에 있어서, SEQ ID NO: 103-114, 207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 또는 413-443 중 어느 하나에 포함된 CDR 서열을 포함하는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제2항에 있어서, SEQ ID NO: 103-114, 또는 413-434 중 어느 하나에 포함된 하나 이상의 CDR 서열을 포함하는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제3항에 있어서, SEQ ID NO: 103-114 또는 413-434 중 어느 하나에 포함된 CDR1, CDR2 및 CDR3을 포함하는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제1항 내지 제7항 중 어느 한 항에 있어서, 단일클론 항체 또는 이의 항원 결합 단편인, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제1항 내지 제8항 중 어느 한 항에 있어서, 인간화된 항체 또는 이의 항원 결합 단편인, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제1항 내지 제9항 중 어느 한 항에 있어서, 인간 α11β1 발현 세포에서 α11β1과 콜라겐의 상호작용을 감소시키는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제1항 내지 제10항 중 어느 한 항에 있어서, 상기 항체 또는 이의 항원 결합 단편과 경쟁하는, 항-α11β1 항체 또는 이의 항원 결합 단편.
- 제1항 내지 제11항 중 어느 한 항의 항체 또는 이의 항원 결합 단편을 코딩하는 핵산 서열을 포함하는 핵산.
- 제11항에 있어서, 상기 핵산 서열은 SEQ ID NO: 1-102로 이루어진 군으로부터 선택된 서열을 포함하는, 핵산.
- 제12항 또는 제13항의 핵산을 포함하는 벡터.
- 제12항 또는 제13항의 핵산 또는 제14항의 벡터를 포함하는 숙주 세포.
- 항체 또는 이의 항원 결합 단편을 생산하는 방법으로서, 상기 항체 또는 이의 항원 결합 단편의 발현에 적합한 조건 하에서 제14항의 숙주 세포를 배양하는 것을 포함하는, 방법.
- 만성 신장 질환을 갖거나 만성 신장 질환의 위험이 있는 대상체를 치료하는 방법으로서, 치료적 유효량의 제1항 내지 제11항 중 어느 한 항의 항체 또는 이의 항원 결합 단편을 상기 대상체에게 투여하는 것을 포함하는, 방법.
- 제17항에 있어서, 만성 신장 질환은 원발성 사구체 질환(IgA 신병증 및 국소 분절성 사구체 경화증을 포함하나 이에 제한되지 않음), 속발성 사구체 질환(루푸스 신염을 포함하나 이에 제한되지 않음), 혈전성 미세혈관병증, 세뇨관간질 질환(폐쇄성 요로병증을 포함하나 이에 제한되지 않음), 당뇨병성 신병증, 고혈압 신병증, 허혈성 신병증, CKD의 심신 증후군, 사구체의 유전성 장애(알포트 증후군을 포함하나 이에 제한되지 않음), 신장의 낭성 질환(다낭성 신장 질환을 포함하나 이에 제한되지 않음), 또는 세뇨관의 유전성 장애이거나 이를 포함하는, 방법.
- 제17항 또는 제18항에 있어서, 치료적 유효량의 항체 또는 이의 항원 결합 단편을 투여하는 것은 측정된 마커, 징후 및/또는 증상을 대조군에 비해 적어도 약 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% 또는 90% 감소시키는, 방법.
- 제19항에 있어서, 상기 대조군은 항체 투여 전에 대상체에서 측정된 마커, 징후 및/또는 증상의 수준을 포함하는, 방법.
- 제19항에 있어서, 상기 대조군은 신장 관련 장애를 앓고 있는 대상체에서 측정된 마커, 징후 및/또는 증상의 수준을 포함하는, 방법.
- 제19항에 있어서, 상기 대조군은 신장 관련 장애를 앓고 있는 대상체 집단에서 측정된 마커, 징후 및/또는 증상의 평균 수준을 포함하는, 방법.
- 제19항 내지 제22항 중 어느 한 항에 있어서, 상기 측정된 마커, 징후 및/또는 증상은 COL1A1, 피브로넥틴, PAI-1, IL-11, CXCL1, MCP-1, IL-6, TIMP-1, 히알루론산, TGFβ, CTGF, PDGF, MMP9, 또는 이들의 조합이거나 이를 포함하는, 방법.
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| US202063127849P | 2020-12-18 | 2020-12-18 | |
| US63/127,849 | 2020-12-18 | ||
| US202163213973P | 2021-06-23 | 2021-06-23 | |
| US63/213,973 | 2021-06-23 | ||
| PCT/IB2021/061926 WO2022130318A2 (en) | 2020-12-18 | 2021-12-17 | Antibodies against integrin alpha 11 beta 1 |
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| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| EP0228458B2 (en) | 1985-07-05 | 1997-10-22 | Whitehead Institute For Biomedical Research | Epithelial cells expressing foreign genetic material |
| DE3852823T2 (de) | 1987-09-11 | 1995-05-24 | Hughes Howard Med Inst | Transduktionsveränderte fibroblasten und ihre anwendung. |
| WO1989005345A1 (en) | 1987-12-11 | 1989-06-15 | Whitehead Institute For Biomedical Research | Genetic modification of endothelial cells |
| DE68927996T2 (de) | 1988-02-05 | 1997-12-04 | Hughes Howard Med Inst | Modifizierte hepatozyten und deren anwendung |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| DK0556345T3 (da) | 1990-10-31 | 1997-06-16 | Whitehead Biomedical Inst | Retrovirale vektorer,som er egnede til genterapi |
| SE9201984D0 (sv) | 1992-06-29 | 1992-06-29 | Pharmacia Biosensor Ab | Improvement in optical assays |
| US5308341A (en) | 1993-09-28 | 1994-05-03 | Becton, Dickinson And Company | Method of testing the dose accuracy of a medication delivery device |
| US6146361A (en) | 1996-09-26 | 2000-11-14 | Becton Dickinson And Company | Medication delivery pen having a 31 gauge needle |
| US6302855B1 (en) | 1998-05-20 | 2001-10-16 | Novo Nordisk A/S | Medical apparatus for use by a patient for medical self treatment of diabetes |
| US6192891B1 (en) | 1999-04-26 | 2001-02-27 | Becton Dickinson And Company | Integrated system including medication delivery pen, blood monitoring device, and lancer |
| US6277099B1 (en) | 1999-08-06 | 2001-08-21 | Becton, Dickinson And Company | Medication delivery pen |
| AU2002333554C1 (en) | 2001-09-12 | 2008-12-11 | Becton, Dickinson And Company | Microneedle-based pen device for drug delivery and method for using same |
| FR2849436B1 (fr) | 2002-12-27 | 2007-01-05 | Patrick Frayssinet | Particules et ceramiques de phosphates de calcium pour transfection in vivo et in vitro |
| EP3524625A1 (en) * | 2018-02-08 | 2019-08-14 | Bergen Teknologioverforing AS | Antibody against alpha-11 integrin and its use |
| CR20220288A (es) * | 2019-12-20 | 2022-10-07 | Momenta Pharmaceuticals Inc | Anticuerpos contra integrina alfa 11 beta 1 |
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- 2021-12-17 TW TW110147384A patent/TW202241946A/zh unknown
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| IL303741A (en) | 2023-08-01 |
| WO2022130318A3 (en) | 2022-08-04 |
| CL2023001757A1 (es) | 2024-01-05 |
| BR112023011777A2 (pt) | 2023-10-03 |
| JP2024505790A (ja) | 2024-02-08 |
| EP4263605A2 (en) | 2023-10-25 |
| MX2023007302A (es) | 2023-09-04 |
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