KR20190037261A - 항-스클레로스틴 항체를 사용한 결합 조직 부착 개선 방법 - Google Patents
항-스클레로스틴 항체를 사용한 결합 조직 부착 개선 방법 Download PDFInfo
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- KR20190037261A KR20190037261A KR1020197004537A KR20197004537A KR20190037261A KR 20190037261 A KR20190037261 A KR 20190037261A KR 1020197004537 A KR1020197004537 A KR 1020197004537A KR 20197004537 A KR20197004537 A KR 20197004537A KR 20190037261 A KR20190037261 A KR 20190037261A
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Abstract
본 출원은 대상체에서 결합 조직-골 치유 향상에 유효한 양의 항-스클레로스틴 항체를 대상체에 투여하는 단계를 포함하는, 필요로 하는 대상체에서 결합 조직-골 치유 향상 방법을 제공한다.
Description
정부 지원에 관한 설명
본 발명은 미국 국립 보건원 (NIH)이 지급하는 정부 보조급 지원 승인 번호 제 F31-AR066452호 및 제 R01-AR057836호에 의해 이루어졌다. 정보는 본 발명에 대해 일정한 권리를 가진다.
발명의 분야
본 발명은 결합 조직-골 치유를 향상시킬 수 있는 항-스클레로스틴 항체의 사용에 관한 것이다.
전자적으로 제출되는 자료의 참고자료 포함
다음과 같이 명명되어 본 출원과 함께 제출되는 컴퓨터-판독가능한 뉴클레오타이드/아미노산 서열은 모두 참고자료로 포함된다: 2017년 8월 7일 작성된 806,135 바이트의 파일명 "50928A_SeqListing.txt"의 ASCII (텍스트) 파일.
참고문헌으로 포함
다음의 출원들은 본 출원에 그 전문이 참고문헌으로 포함된다: 2011년 8월 4일 출원된 미국 가특허 출원 61/515,191호에 대한 우선권을 주장하는, 2012년 8월 2일 출원된 국제 특허 출원 제 PCT/US2012/049331호; 2006년 4월 17일 출원된 미국 가특허 출원 제 60/792,645호, 2006년 3월 13일 출원된 미국 가특허 출원 제 60/782,244호, 2006년 2월 24일 출원된 미국 가특허 출원 제 60/776,847호, 및 2005년 5월 3일 출원된 미국 가특허 출원 제 60/677,583호에 대한 우선권을 주장하는 2006년 4월 25일 출원된 미국 가특허출원 11/410,540호; 및 2006년 4월 17일 출원된 미국 가특허 출원 제 60/792,645호, 2006년 3월 13일 출원된 미국 가특허 출원 제 60/782,244호, 2006년 2월 24일 출원된 미국 가특허 출원 제 60/776,847호, 및 2005년 5월 3일 출원된 미국 가특허 출원 제 60/677,583호에 대한 우선권을 주장하는, 2006년 4월 25일 출원된 미국 특허 출원 제 11/411,003호 (미국 특허 7,592,429호로 등록됨). 다음 출원들 또한 본 출원에 참고문헌으로 포함된다: 2007년 9월 17일 출원된 미국 가특허 출원 제 60/973,024호에 대한 우선권을 주장하는 2008년 9월 17일 출원된, 미국 특허 출원 제 12/212,327호; 및 2008년 12월 15일 출원된 국제 특허 출원 제 PCT/US08/86864의, 35 U.S.C. § 371에 따른 미국 국내단계 출원으로, 2007년 12월 14일에 출원된 미국 가특허 출원 제 61/013,917호에 대한 우선권을 주장하는 2010년 6월 29일 출원된 미국 특허 출원 제 12/811,171호.
배경
회전근개 파열은 상지에 가장 흔한 부상 중 하나이며; 전층 파열은 60세 이상의 모집단에서 대략 25% 그리고 80세 이상의 모집단에서 50%로 발생한다 [1, 2]. 파열은 심신을 쇠약하게 하고 자발적으로 치유되지 않으며, 통상적으로 부상 후 수 년 내에 보다 커지게 된다 [3]. 이로 인해 미국에서 매년 250,000회 이상 회전근개 외과적 복원술이 시행된다. 유감스럽게도, 외과 복원술 이후 건-골 치유가 좋지 않음으로 인해 놀랄 정도로 높은 발생률의 재파열이 초래되는데, 그 범위는 작은 파열이 있는 젊은 건강한 환자들에서 20%에서부터 광범위 파열이 있는 나이든 환자들에서 94%까지에 이른다 [4, 5]. 좋지 못한 치유는 치유 경계면에서의 골 손실 그리고 건강한 부착에서 발견되는 기능적으로 등급화된 미네랄화 섬유연골의 재생 부족으로 특징된다 [6]. 따라서, 건-골 치유를 개선시킬 있는 치료제 및 치료요법에 대한 수요가 존재한다. 본 발명은 이러한 수요를 충족시키며 이와 관련된 이점들을 제공한다.
요약
한 양상에서, 본 출원은 대상체에서 결합 조직-골 치유 향상에 유효한 양의 항-스클레로스틴 항체를 대상체에 투여하는 단계를 포함하는, 필요로 하는 대상체에서 결합 조직-골 치유 향상 방법을 기재한다. 예시적인 결합 조직들에는, 제한없이, 인대, 건, 반달연골 또는 관절와순 (labrum)이 포함된다.
일부 또는 임의의 구체예들에서, 항-스클레로스틴 항체는 감소된 골 미네랄 밀도 또는 골절의 치료를 위한 제 2의 골-개선 치료제와 함께 투여된다. 이러한 유형의 많은 치료제들이 해당 분야에 공지되어 있다. 일부 구체예들에서, 골-개선 치료제는 항-흡수성 약물, 골 형성제, 에스트로겐 수용체 길항제 (랄록시펜, 바제독시펜 및 라소폭시펜을 포함하나 이에 제한되는 것은 아님) 및 파골세포에 대한 억제 효과를 가지는 약물로 구성된 그룹에서 선택된다. 일부 구체예들에서, 항-흡수성 약물에는, 부갑상선 호르몬, 비스포스포네이트 (알렌드로네이트, 리세드로네이트, 이반드로네이트 및 졸레드로네이트를 포함하나 이에 제한되는 것은 아님), 에스트로겐 또는 에스트로겐 유사체, 선택적 에스트로겐 수용체 조절제 (SERM) 및 칼슘 공급원, 티볼론, 칼시토닌, 칼시트리올 및 호르몬 대체 치료제가 포함되나 이에 제한되는 것은 아니다. 일부 구체예들에서, 골-개선제에는 부갑상선 호르몬 (PTH) 또는 이의 펩타이드 단편, PTH-관련 단백질 (PTHrp), 골형성 단백질, 오스테오제닌, NaF, PGE2 작용제, 스타틴, 항-DKK1 항체 또는 억제제, 항-RANK 리간드 (RANKL) 항체 또는 RANKL 억제제, 스트론튬 라넬레이트, 비타민 D, 또는 비타민 D 유도체 또는 이의 모방체가 포함되나 이에 제한되는 것은 아니다. 일부 구체예들에서, 골-개선제는 Forteo® (테리파라티드, 또는 재조합 인간 부갑상선 호르몬 1-34) 또는 Preotact® (부갑상선 호르몬)이다. 일부 또는 임의의 구체예들에서, 골-개선제는 Protelos®이다.
본 출원에 개시된 임의의 방법들에서 또는 본 출원에 개시된 임의의 방법들에 따라 투여하기 위한 약제들의 제조를 위한, 미국 공개특허 출원 제 20070110747호 (그 내용은 본 출원에 전문이 참고문헌으로 포함됨)에 개시된 항-스클레로스틴 항체의 사용이 특히 고려된다. 1회 이상의 항-스클레로스틴 항체 용량들은 대상체에서 결합 조직-골 치유를 개선하거나 결합 조직 재부착 과정의 결과를 개선시키기에 유효한 양 및 시간 동안 투여된다. 1회 이상의 항-스클레로스틴 항체 용량들은 약 70 mg 내지 약 300 mg 또는 약 90 mg 내지 약 270 mg를 포함할 수 있다. 예를 들어, 항-스클레로스틴 항체의 용량 범위는 최소한 약 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, 76 mg, 77 mg, 78 mg, 79 mg, 80 mg, 81 mg, 82 mg, 83 mg, 84 mg, 85 mg, 86 mg, 87 mg, 88 mg, 89 mg, 90 mg, 91 mg, 92 mg, 93 mg, 94 mg, 95 mg, 96 mg, 97 mg, 98 mg, 99 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg 또는 300 mg 일 수 있다. 이러한 결과 변수들에 관한 임의의 그리고 모든 범위들, 예컨대, 약 90 mg 내지 약 270 mg, 약 70 mg 내지 약 210 mg, 약 100 mg 내지 약 210 mg, 약 90 mg 내지 약 250 mg, 약 110 mg 내지 약 210 mg, 약 70 mg 내지 약 300 mg, 또는 약 175 내지 약 270 mg 범위 또한 고려된다.
또한 본 출원은 필요로 하는 포유동물 대상체에서 결합 조직 재부착 과정의 결과를 개선하기 위한 유효량의 항-스클레로스틴 항체의 사용을 기재한다. 예시적인 결합 조직 재부착 과정들에는, 회전근개 복원술, 아킬레스 건 복원술, 슬개건-슬개골 복원술, 내측 십자 인대 (MCL) 재건술, 전 십자 인대 (ACL) 재건술, 내측 측부 인대 (UCL), 반달연골 복원술 및 관절와순 복원술이 포함되나 이에 제한되는 것은 아니다.
일부 구체예들에서, 이러한 과정은 이식편 부착을 포함하고, 항-스클레로스틴 항체는 생체외에서 이식편에 적용된다.
본 출원에 기재된 임의의 방법들 또는 용도들에서, 일부 구체예들에서, 항-스클레로스틴 항체는 전신으로 투여된다 (예컨대, 피하 주사에 의해). 다른 구체예들에서, 항-스클레로스틴 항체는 겔, 스펀지, 또는 매트릭스에 혼입되어 국소적으로 이식된다.
일부 구체예들에서, 본 출원에 기재된 방법들에서 사용하기 위한 항-스클레로스틴 항체는 서열 번호: 1의 스클레로스틴에, 1 x 10 7 M 이하 (또는 1 x 10 8 M 이하, 또는 1 x 109 M 이하, 또는 1 x 1010 M 이하, 또는 1 x 1011 M 이하, 또는 1 x 1012 M 이하)의 친화도 (Kd)로 결합한다.
다양한 구체예들에서, 항-스클레로스틴 항체는 서열 번호: 1에 제시된 아미노산 서열을 포함하는 스클레로스틴 폴리펩타이드에 결합하며 서열 번호: 6의 서열의 서열에 결합한다 (CGPARLLPNAIGRGKWWRPSGPDFRC; 서열 번호: 1의 아미노산 86-111에 상응함). 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 서열 번호: 1에 제시된 아미노산 서열을 포함하는 스클레로스틴 폴리펩타이드에 결합하며 서열 번호: 1 내에서 서열 번호: 2 (DVSEYSCRELHFTR; 서열 번호: 1의 아미노산 51-64에 상응함), 서열 번호: 3 (SAKPVTELVCSGQCGPAR; 서열 번호: 1의 아미노산 73-90에 상응함), 서열 번호: 4 (WWRPSGPDFRCIPDRYR; 서열 번호: 1의 아미노산 101-117에 상응함), 서열 번호: 5 (LVASCKCKRLTR; 서열 번호: 1의 아미노산 138-149에 상응함), 서열 번호: 70 (SAKPVTELVCSGQC; 서열 번호: 1의 아미노산 73-86에 상응함), 서열 번호: 71 (LVASCKC; 서열 번호: 1의 아미노산 138-144에 상응함), 서열 번호: 72 (CRELHFTR; 서열 번호: 1의 아미노산 57-64에 상응함), 또는 서열 번호: 73 (CIPDRYR; 서열 번호: 1의 아미노산 111-117에 상응함) 중 최소한 하나의 서열에 결합한다. 예를 들어, 한 양상에서, 항-스클레로스틴 항체는 서열 번호: 2-5 (및/또는 서열 번호: 70-73)를 포함하는 서열 번호: 1의 스클레로스틴의 하위영역에, 선택적으로 그 고유의 3차원 구조로 결합한다. 선택적으로, 항-스클레로스틴 항체는 서열 번호: 2, 서열 번호: 3, 서열 번호: 4, 서열 번호: 5, 서열 번호: 6, 서열 번호: 70, 서열 번호: 71, 서열 번호: 72, 또는 서열 번호: 73 중 하나 이상으로 구성된 펩타이드 (예컨대, 서열 번호: 2, 서열 번호: 3, 서열 번호: 4, 및 서열 번호: 5로 구성된 펩타이드 또는 서열 번호: 70, 서열 번호: 71, 서열 번호: 72, 및 서열 번호: 73으로 구성된 펩타이드)에 결합한다.
다양한 양상들에서, 항-스클레로스틴 항체는 MC3T3 세포-기반 미네랄화 분석에서 웰 당 스클레로스틴의 몰수에 비해 웰 당 스클레로스틴 결합 부위들의 몰수가 6-배 과량 미만으로 존재할 때 인간 스클레로스틴을 중화시킬 수 있다.
항-스클레로스틴 항체는 선택적으로 세포-기반 분석법, 가령, 골 특이적 알칼리성 포스파타제 분석법에서 인간 스클레로스틴을 중화시키기 위하여 100 nM 또는 미만, 또는 75 nM 또는 미만, 또는 50 nM 또는 미만, 또는 25 nM 또는 미만의 IC50을 가진다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 HEK293 세포주들에서의 세포-기반 Wnt 신호전달 분석, 가령, STF 리포터 유전자의 Wnt1-매개 유도에 관여하는 Wnt 분석법에서 인간 스클레로스틴을 중화시키기 위해 100 nM 또는 미만 (예컨대, 75 nM 또는 미만, 또는 50 nM 또는 미만)의 IC50을 가진다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 MC3T3 세포들에서 BMP2-유도된 미네랄화 분석법에서 인간 스클레로스틴을 중화시키기 위해 500 nM 또는 미만 (예컨대, 250 nM 또는 미만, 150 nM 또는 미만, 100 nM 또는 미만, 또는 50 nM 또는 미만)의 IC50을 가진다.
한 구체예에서, 항-스클레로스틴 항체는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 중 최소한 하나의 스클레로스틴에 대한 결합을 교차-차단하며 및/또는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 중 최소한 하나에 의해 스클레로스틴에 대한 결합이 교차-차단된다.
일부 구체예들에서, 항-스클레로스틴 항체는 서열 번호:245의 CDR-H1, 서열 번호:246의 CDR-H2, 서열 번호:247의 CDR-H3, 서열 번호:78의 CDR-L1, 서열 번호:79의 CDR-L2 및 서열 번호:80의 CDR-L3를 포함한다.
한 구체예에서, 항-스클레로스틴 항체는 서열 번호: 378을 포함하는 중쇄 및 서열 번호: 376을 포함하는 경쇄를 포함한다. 또 다른 구체예에서, 항-스클레로스틴 항체는 서열 번호: 145 또는 서열 번호: 392의 중쇄 및 서열 번호: 141의 경쇄를 가진다.
또 다른 구체예에서, 항-스클레로스틴 항체는 국제 공개특허 출원 제 WO 2008/115732의 서열 번호: 20-25의 CDR (서열 번호: 416-421), 국제 공개특허 출원 제 WO 2008/115732의 서열 번호: 26-31의 CDR (서열 번호: 422-427), 국제 공개특허 출원 제 WO 2008/115732의 서열 번호: 32-37의 CDR (서열 번호: 428-433), 또는 국제 공개특허 출원 제 WO 2009/047356의 서열 번호: 4, 15, 26, 37, 48, 및 59의 CDR (각각 서열 번호: 443, 454, 465, 476, 487, 및 498)을 포함한다. 또한 또 다른 구체예에서, 항-스클레로스틴 항체는 서열 번호: 135-143, 153-161, 또는 171-179 of 국제 공개특허 출원 제 WO 2010/130830의 서열 번호: 135-143, 153-161, 또는 171-179 (각각 서열 번호: 745-753, 763-771, 781-789) 중 최소한 하나의 아미노산 서열을 포함한다.
일부 구체예들에서, 항-스클레로스틴 항체는 55 mM 아세테이트, 13 mm 칼슘, 6.0 % (w/v) 수크로스, 0.006% (w/v) 폴리소르베이트 20을 포함하는 pH 5.2의 제약학적 조성물로 제형화된다. 일부 구체예들에서, 제약학적 조성물은 90 mg/mL 항-스클레로스틴 항체를 포함한다.
본 출원에서 사용되는 구획 제목은 단지 구조화를 위한 것이며 기재된 주제를 제한하는 것으로 해석되어서는 안된다. 본 명세서의 내용에서 인용되는 모든 참고문헌들은 그 전문이 참고문헌으로 명확히 포함된다.
재조합 DNA, 올리고뉴클레오타이드 합성, 조직 배양 및 형질전환, 단백질 정제, 등을 위한 표준 기술들이 사용될 수 있다. 효소 반응 및 정제 기법들은 제조업체의 명세에 따라 또는 해당 분야에서 통상적으로 이루어지는 바에 따라 또는 본 출원에 기재된 바와 같이 실시될 수 있다. 하기 기술 및 절차들은 일반적으로 해당 분야에 널리 공지되어 있는 관례적인 방법에 따라 그리고 본 출원 전반에 걸쳐 인용되고 논의되는 다양한 일반적 그리고 보다 구체적인 참고문헌들에 따라 실시될 수 있다. 예컨대, Sambrook 외., 2001, Molecular Cloning: A Laboratory Manuel, 3rd ed., Cold Spring Harbor Laboratory Press, cold Spring Harbor, N.Y.를 참고하면 되며, 이는 본 출원에 임의의 목적으로 참고문헌으로 포함된다. 특정한 정의가 제공되지 않는 한, 본 출원에 기재된 내용과 관련하여 사용되는 명명법, 본 출원에 기재된 분석 화학, 유기 화학 및 약물 및 제약학적 화학의 실험 절차 및 기술들은 해당 기술 분야에서 널리 공지되어 있고 통상적으로 사용되는 것들이다. 화학적 합성, 화학적 분석, 제약학적 제제, 제형 및 환자들의 치료 및 전달에 대한 표준 기술들이 사용될 수 있다.
도면의 간단한 설명
도 1A-1D는 회전근개 동물 모델에서 Scl-Ab를 이용한 치료가 정상 (부상없음) 및 8주 치유 그룹들에서 건-골 치유 삽입 부위 주변의 영역에서 골 질량 지수 (도 1A) 총 부피 당 골 부피 (BV/TV), (도 1B) 골 미네랄 밀도 (BMD), (도 1C) 해면골소주의 수 (TbN), 및 (도 1D) 해면골소주의 두께 (TbTh)를 증가시켰음을 보여준다. Scl-Ab의 유의한 효과는 막대들 위에 선으로 나타낸다 (p<0.05; ANOVA 이후 그룹 내 CTL과 비교하여 Tukey의 사후 검정). 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정).
도 2A-2D는 회전근개 동물 모델에서 Scl-Ab를 이용한 치료가 8주 치유 후 부착 부위 (도 2A) 파열 하중, (도 2B) 강도, 및 (도 2C) 강성도를 증가시켰으며, 파열 하중 및 강성도는 대조에 비해 정상 (부상없음) 부착들과 유사하였던 수준으로 돌아갔음을 보여준다. 강성도 및 (도 2D) 모듈러스(Modulus)는 Scl-Ab 치료된 정상 (부상없음) 부착들에서 감소되었다. Scl-Ab의 유의한 효과는 막대들 위에 선으로 나타낸다 (p<0.05; ANOVA 이후 그룹 내 CTL과 비교하여 Tukey의 사후 검정). 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정).
도 3A-3D는 8주의 치유 후, Scl-Ab 치료가 CTL (도 3A 및 3C)에 비해 삽입 연속성, 통합성, 및 섬유 정렬 (도 3B 및 3D)을 개선시켰음을 보여준다. 인공물삽입 부위는 흰색 파선 상자로 그려져있으며, 도 3C 및 도 3D에 확대되어있다. 도 3A 및 3B에 대한 스케일 바 = 1 mm; 도 3C 및 3D에 대한 스케일 바 = 250 μm.
도 4A는 하우스키핑 유전자 RPL13a와 비교하여 건 인공물삽입부에 인접한 미네랄화 조직에서 스클레로스틴, Dkk1, Lrp5, OCN, Pth1r, RankL, OPG, DMP1, 오스테릭스, Runx2, Ctsk 및 Col2a1의 유전자 발현을 보여준다. 도 4B는 하우스키핑 유전자 RPL13a와 비교하여 건 인공물삽입부에 인접한 미네랄화 조직에서 Acan, TFGβ1, TGFβ3, MMP2, Sox9, Smo 및 Notch1의 유전자 발현을 보여준다. Scl-Ab의 유의한 효과는 막대들 위에 선으로 나타낸다 (p<0.05; ANOVA 이후 그룹 내 CTL과 비교하여 Tukey의 사후 검정). 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정). CTL 그룹에서 정상과 비교한 Scl-Ab의 유의한 효과는 막대 안에서 "b"로 나타낸다 (p<0,05, ANOVA 이후 Tukey의 사후 검정).
도 5A는 하우스키핑 유전자 RPL13a와 비교하여 건에서 스데락시스, 테노모둘린, Col1a1, 아그리칸, MMP2 및 Smp의 유전자 발현을 보여준다. 도 5B는 하우스키핑 유전자 RPL13a와 비교하여 건에서 Col1a2, Col2a1, Col3a1, Sox9, TGFβ1, TGFβ3 및 Notch1의 유전자 발현을 보여준다. 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정).
도 6은 본 출원에 기재된 다양한 항-스클레로스틴 항체의 차트 나열 아미노산 서열들 및 이러한 아미노산 서열들에 대한 서열 식별자들이다. 서열 식별자는 본 출원과 함께 제출되는 서열 목록에 제공되는 아미노산 서열들을 지칭한다. 아미노산 서열들은 또한 본 출원에 참고문헌으로 포함되는 미국 공개특허 출원 제 2007/0110747 또는 국제 공개특허 출원 제 WO 2008/115732, WO2009/047356, 또는 WO 2010/130830에 제시되어 있다.
도 1A-1D는 회전근개 동물 모델에서 Scl-Ab를 이용한 치료가 정상 (부상없음) 및 8주 치유 그룹들에서 건-골 치유 삽입 부위 주변의 영역에서 골 질량 지수 (도 1A) 총 부피 당 골 부피 (BV/TV), (도 1B) 골 미네랄 밀도 (BMD), (도 1C) 해면골소주의 수 (TbN), 및 (도 1D) 해면골소주의 두께 (TbTh)를 증가시켰음을 보여준다. Scl-Ab의 유의한 효과는 막대들 위에 선으로 나타낸다 (p<0.05; ANOVA 이후 그룹 내 CTL과 비교하여 Tukey의 사후 검정). 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정).
도 2A-2D는 회전근개 동물 모델에서 Scl-Ab를 이용한 치료가 8주 치유 후 부착 부위 (도 2A) 파열 하중, (도 2B) 강도, 및 (도 2C) 강성도를 증가시켰으며, 파열 하중 및 강성도는 대조에 비해 정상 (부상없음) 부착들과 유사하였던 수준으로 돌아갔음을 보여준다. 강성도 및 (도 2D) 모듈러스(Modulus)는 Scl-Ab 치료된 정상 (부상없음) 부착들에서 감소되었다. Scl-Ab의 유의한 효과는 막대들 위에 선으로 나타낸다 (p<0.05; ANOVA 이후 그룹 내 CTL과 비교하여 Tukey의 사후 검정). 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정).
도 3A-3D는 8주의 치유 후, Scl-Ab 치료가 CTL (도 3A 및 3C)에 비해 삽입 연속성, 통합성, 및 섬유 정렬 (도 3B 및 3D)을 개선시켰음을 보여준다. 인공물삽입 부위는 흰색 파선 상자로 그려져있으며, 도 3C 및 도 3D에 확대되어있다. 도 3A 및 3B에 대한 스케일 바 = 1 mm; 도 3C 및 3D에 대한 스케일 바 = 250 μm.
도 4A는 하우스키핑 유전자 RPL13a와 비교하여 건 인공물삽입부에 인접한 미네랄화 조직에서 스클레로스틴, Dkk1, Lrp5, OCN, Pth1r, RankL, OPG, DMP1, 오스테릭스, Runx2, Ctsk 및 Col2a1의 유전자 발현을 보여준다. 도 4B는 하우스키핑 유전자 RPL13a와 비교하여 건 인공물삽입부에 인접한 미네랄화 조직에서 Acan, TFGβ1, TGFβ3, MMP2, Sox9, Smo 및 Notch1의 유전자 발현을 보여준다. Scl-Ab의 유의한 효과는 막대들 위에 선으로 나타낸다 (p<0.05; ANOVA 이후 그룹 내 CTL과 비교하여 Tukey의 사후 검정). 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정). CTL 그룹에서 정상과 비교한 Scl-Ab의 유의한 효과는 막대 안에서 "b"로 나타낸다 (p<0,05, ANOVA 이후 Tukey의 사후 검정).
도 5A는 하우스키핑 유전자 RPL13a와 비교하여 건에서 스데락시스, 테노모둘린, Col1a1, 아그리칸, MMP2 및 Smp의 유전자 발현을 보여준다. 도 5B는 하우스키핑 유전자 RPL13a와 비교하여 건에서 Col1a2, Col2a1, Col3a1, Sox9, TGFβ1, TGFβ3 및 Notch1의 유전자 발현을 보여준다. 정상과 비교한 유의한 차이는 하나의 막대 안에서 "a"로 나타낸다 (p<0.05; 특정 치료 그룹 내에서 정상과 비교하여 ANOVA 후 Tukey의 사후 검정).
도 6은 본 출원에 기재된 다양한 항-스클레로스틴 항체의 차트 나열 아미노산 서열들 및 이러한 아미노산 서열들에 대한 서열 식별자들이다. 서열 식별자는 본 출원과 함께 제출되는 서열 목록에 제공되는 아미노산 서열들을 지칭한다. 아미노산 서열들은 또한 본 출원에 참고문헌으로 포함되는 미국 공개특허 출원 제 2007/0110747 또는 국제 공개특허 출원 제 WO 2008/115732, WO2009/047356, 또는 WO 2010/130830에 제시되어 있다.
상세한 설명
회전근개 파열은 흔하며 통증 및 장애를 초래한다. 외과적 복원술 이후 경계면에서 골의 유의한 손실을 비롯하여 치유 결과가 좋지 않으면 높은 재파열 발생률을 초래하게 된다. 실시예에 기재된 바와 같이, 항-스클레로스틴 항체를 이용한 치료는 동물 모델에서 골 손실을 방지하고 회전근개 치유를 향상시킨다. 본 출원에서 증명되는 바와 같이, 8주의 치유 후, 항-스클레로스틴 항체 (Scl-Ab) 치료를 받은 동물들은 매칭된 대조군에 비해 30% 더 큰 골 미네랄 밀도를 가졌다. 2주 및 4주의 치유 후 두 그룹들 모두에서 건강한 건-골 치유 부착에 비해 생역학적 성질의 감소가 관찰되었다. 8주 치유 후, Scl-Ab 치료된 동물들은 대조 동물들에 비해 강도 (38%) 및 강성도 (43%)를 개선시켰다. 조직학적 평가는 8주의 치유에 의해 Scl-Ab가 보다 우수한 건 및 골의 통합을 촉진하였음을 보여주었다. Scl-Ab는 또한 골에서 골모세포, 파골세포, 및 골전구세포 유전자 발현에 대하여, 향상된 골 형성을 포함한 유의한 효과를 가졌다. Scl-Ab 치료는 건에서 유전자들의 발현에 영향을 전혀 주지 않았다.
한 양상에서, 본 출원은 대상체에서 결합 조직-골 치유 향상에 유효한 양의 항-스클레로스틴 항체를 대상체에 투여하는 단계를 포함하는, 필요로 하는 대상체에서 결합 조직-골 치유 향상 방법을 기재한다. 일부 구체예들에서, 결합 조직은 인대, 건, 반달연골 또는 관절와순이다. 다른 구체예들에서, 결합 조직은 건이다. 또한 또 다른 구체예들에서, 결합 조직은 인대 및 건이다. 본 출원에서 사용되는 어구 "결합 조직-골 치유 향상"은 결합 조직과 골 사이의 보다 조기의, 보다 강한 부착을 지칭한다.
항체
용어 "항체"는 무손상 항체를 지칭한다. 항체는 완전 항체 (면역글로불린) 분자 (전장 중쇄 및/또는 경쇄를 가지는 다클론, 단클론, 키메라, 인간화, 및/또는 인간 형태를 포함)를 포함할 수 있다.
본 출원에서 사용된 용어 "항체 단편"은 항체의 항원-결합 부위를 지칭한다. 항체 단편들에는 F(ab')2, Fab, Fab', Fv, Fc, 및 Fd 단편들이 포함되며, 단일 도메인 항체 (예컨대, 나노바디), 단일-사슬 항체, 맥시바디, 미니바디, 인트라바디, 디아바디, 트리아바디, 테트라바디, v-NAR 및 비스-scFv에 통합될 수 있다 (예컨대, Hollinger and Hudson, Nature Biotechnology, 23(9):1126-1136 (2005) 참고). 피브로넥틴 폴리펩타이드 모노바디를 포함한 항체 폴리펩타이드들 또한 미국 특허 제 6,703,199에 개시되어 있다. 다른 항체 폴리펩타이드들은 미국 공개특허 출원 제 20050238646에 개시되어 있다. 본 출원에 기재된 방법들 및 항체 사슬들은 예를 들어, 미국 특허출원 공개공보 제 US 2014/154254에 기재된 바와 같이 이종이합체 항체를 생성함에 유용하며, 이 문헌에 개시된 내용은 그 전문이 본 출원에 참고문헌으로 포함된다. 본 출원에 기재된 항체의 특징들, 뿐만 아니라 투여 시간 및 경로에 관한 논의는 또한 항체 단편들에도 적용된다.
항체 단편은 합성 또는 유전자 조작된 단백질일 수 있다. 예를 들어, 항체 단편들은 경쇄 가변 영역으로 구성된 분리된 단편들, 중쇄 및 경쇄의 가변 영역들로 구성된 "Fv" 단편들, 및 경쇄 및 중쇄 가변 영역들이 펩타이드 링커에 의해 연결되어 있는 재조합 단일 사슬 폴리펩타이드 분자 (scFv 단백질)를 포함한다.
또 다른 항체 단편 형태는 항체의 하나 이상의 상보성 결정 영역 (CDR)을 포함하는 펩타이드이다. 본 출원에서 사용되는 용어 "CDR"은 항체 가변 서열들 내부에서의 상보성 결정 영역을 지칭한다. 중쇄 및 경쇄의 가변 영역들 각각에 3 개의 CDR이 존재하며, 가변 영역들 각각에 대해 CDR1, CDR2 및 CDR3로 명명된다. 본 출원에서 사용되는 용어 "CDR 세트"는 항원에 결합할 수 있는 하나의 단일 가변 영역에서 발견되는 3개 CDR들의 그룹을 지칭한다. 이러한 CDR들의 정확한 경계는 여러 시스템들에 따라 다르게 정의되어 왔다. Kabat (Kabat 외, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) 및 (1991))이 설명하는 시스템은 항체의 어떠한 가변 영역에도 적용가능한 명확한 잔기 넘버링 시스템을 제공할 뿐만 아니라, 3개의 CDR들을 정의하는 간결한 잔기 경계를 제공한다. 이러한 CDR들을 Kabat CDR로 지칭할 수 있다. Chothia 및 공동연구자들은 (Chothia & Lesk, J. Mol. Biol. 196:901-917 (1987) 및 Chothia 외, Nature 342:877-883 (1989)) Kabat CDR들 내 하위-부분들은 아미노산 서열의 수준에서 큰 다양성을 가짐에도 불구하고 거의 동일한 펩타이드 골격 입체형태를 채택함을 발견하였다. 이러한 하위 부분들은 L1, L2 및 L3 또는 H1, H2 및 H3로 표시되었으며 이 때 "L" 및 "H"는 경쇄 및 중쇄 영역들을 각각 표시한다. 이들 영역들은 Chothia CDRs로 지칭될 수 있으며, Kabat CDRs과 중첩되는 경계를 가진다 Kabat CDRs과 중첩되는 CDRs을 정의하는 다른 경계들은 Padlan (FASEB J. 9:133-139 (1995)) 및 MacCallum (J Mol Biol 262(5):73245 (1996))의 문헌에 기재된 바 있다. 특정 잔기들 또는 잔기들의 그룹들 또는 전체 CDRs 조차 항원 결합에 유의하게 영향을 주지 않는다는 예측 또는 실험적 발견에 비추어 볼 때 CDRs은 짧아지거나 길어질 수 있지만, 다른 CDR 경계 정의들은 여전히 상기 시스템들 중 하나를 엄격하게 따르지 않을 수 있으며, 그러나 그럼에도 불구하고 Kabat CDRs과 중첩될 것이다. 본 출원에서 사용된 방법들은 이러한 임의의 시스템들에 따라 정의된 CDR들을 이용할 수 있으나, 바람직한 구체예들은 Kabat 또는 Chothia 정의된 CDRs를 사용한다.
CDRs (또한 "최소 인식 단위" 또는 "초가변 영역"으로 명명됨)들은, 예컨대, 관심 CDR을 인코딩하는 폴리뉴클레오타이드를 작제함으로써 수득된다. 이러한 폴리뉴클레오타이드들은, 예를 들어, 중합효소 연쇄 반응을 사용하여, 항체-생성 세포들의 mRNA를 주형으로 사용하여 가변 영역을 합성하여 제조된다 (예를 들어, Larrick 외, Methods: A Companion to Methods in Enzymology, 2:106 (1991); Courtenay-Luck, "Genetic Manipulation of Monoclonal Antibodies," in Monoclonal Antibodies Production, Engineering and Clinical Application, Ritter 외 (eds.), 166 페이지, Cambridge University Press (1995); 및 Ward 외, "Genetic Manipulation and Expression of Antibodies," in Monoclonal Antibodies: Principles and Applications, Birch 외, (eds.), 137 페이지, Wiley-Liss, Inc. (1995)).
"항-스클레로스틴 항체"는 스클레로스틴 또는 이의 일부에 결합하여 하나 이상의 리간드들에 대한 인간 스클레로스틴의 결합을 차단 또는 방해한다. SOST 유전자의 생성물인 스클레로스틴은, 골 과성장 및 강한 밀도의 골로 특징되는 골격 질병인 경화협착증에는 없다 (Brunkow 외, Am. J. Hum. Genet., 68:577-589 (2001); Balemans 외, Hum. Mol. Genet., 10:537-543 (2001)). 인간 스클레로스틴의 아미노산 서열은 Brunkow 외의 문헌에 보고되며 서열 번호: 1로 미국 공개특허 출원 제 20070110747에 개시되어 있다 (이 특허 공개 문헌은 스클레로스틴 결합제에 관한 설명 및 서열 목록에 관하여 그 전문이 포함된다). 재조합 인간 스클레로스틴/SOST는 R&D Systems사 (Minneapolis, Minn., USA; 2006 카탈로그 #1406-ST-025)로부터 상업적으로 구입가능하다. 추가적으로, 재조합 생쥐 스클레로스틴/SOST는 R&D Systems사 (Minneapolis, Minn., USA; 2006 카탈로그 #1589-ST-025)로부터 상업적으로 구입가능하다. 연구 등급의 스클레로스틴-결합 단클론 항체는 R&D Systems사 (Minneapolis, Minn., USA; 생쥐 단클론: 2006 카탈로그 # MAB1406; 쥐 단클론: 2006 카탈로그 # MAB1589)로부터 상업적으로 구입가능하다. 미국 특허 제 6,395,511 및 6,803,453, 및 미국 공개 특허 출원 제 2004/0009535 및 2005/0106683은 항-스클레로스틴 항체를 일반적으로 설명한다. 본 발명의 내용에서 사용하기에 적합한 스클레로스틴 항체 또는 이의 단편들의 예들은 또한 미국 공개 특허 출원 제 2007/0110747 및 2007/0072797에 기재되어 있으며, 이는 본 출원에 참고문헌으로 포함된다. 스클레로스틴 결합제를 제조하기 위한 재료 및 방법들에 관한 추가 정보는 미국 공개특허 출원 제 20040158045에서 찾을 수 있다 (본 출원에 참고문헌으로 포함됨).
항-스클레로스틴 항체 또는 이의 단편들은 서열 번호: 1의 스클레로스틴, 또는 이의 자연 발생 변이체에, 1 x 10-7 M 이하, 1 x 10-8 M 이하, 1 x 10-9 M 이하, 1 x 10-10 M 이하, 1 x 10 -11 M 이하, 또는 1 x 10 -12 M 이하의 친화도 (Kd)로 결합할 수 있다. 예를 들어, 항-스클레로스틴 항체는 1 x 10-7 M 이하, 2 x 10-7 M 이하, 3 x 10-7 M 이하, 4 x 10-7 M 이하, 5 x 10-7 M 이하, 6 x 10-7 M 이하, 7 x 10-7 M 이하, 8 x 10-7 M 이하, 9 x 10-7 M 이하, 1 x 10-8 M 이하, 2 x 10-8 M 이하, 3 x 10-8 M 이하, 4 x 10-8 M 이하, 5 x 10-8 M 이하, 6 x 10-8 M 이하, 7 x 10-8 M 이하, 8 x 10-8 M 이하, 9 x 10-8 M 이하, 1 x 10-9 M 이하, 2 x 10-9 M 이하, 3 x 10-9 M 이하, 4 x 10-9 M 이하, 5 x 10-9 M 이하, 6 x 10-9 M 이하, 7 x 10-9 M 이하, 8 x 10-9 M 이하, 9 x 10-9 M 이하, 1 x 10-10 M 이하, 2 x 10-10 M 이하, 3 x 10-10 M 이하, 4 x 10-10 M 이하, 5 x 10-10 M 이하, 6 x 10-10 M 이하, 7 x 10-10 M 이하, 8 x 10-10 M 이하, 9 x 10-10 M 이하, 1 x 10-11 M 이하, 2 x 10-11 M 이하, 3 x 10-11 M 이하, 4 x 10-11 M 이하, 5 x 10-11 M 이하, 6 x 10-11 M 이하, 7 x 10-11 M 이하, 8 x 10-11 M 이하, 9 x 10-11 M 이하, 1 x 10-12 M 이하, 2 x 10-12 M 이하, 3 x 10-12 M 이하, 4 x 10-12 M 이하, 5 x 10-12 M 이하, 6 x 10-12 M 이하, 7 x 10-12 M 이하, 8 x 10-12 M 이하, 또는 9 x 10 -12 M 이하의 결합 친화도로 스클레로스틴에 결합한다. 본 출원에서 사용되는 "특이적으로 결합하다"는 항체 또는 이의 단편이 다른 단백질들 보다도 스클레로스틴에 결합함을 의미한다. 일부 구체예들에서 "특이적으로 결합하다"는 항체 또는 이의 단편이 다른 단백질들에 대하여 보다도 스클레로스틴에 더 높은 친화도를 가짐을 의미한다. 친화도는 다양한 기술들을 사용하여 결정되며, 이러한 기술의 한 예는 친화도 ELISA 분석이다. 다양한 구체예들에서, 친화도는 BIAcore 분석에 의해 결정된다. 다양한 구체예들에서, 친화도는 동적 방법 (kinetic method)에 의해 결정된다. 다양한 구체예들에서, 친화도는 평형/용액법에 의해 결정된다. 미국 공개특허 출원 제 2007/0110747은 스클레로스틴에 대한 항체의 친화도 (Kd)를 결정하기에 적합한 친화도 분석법에 관한 추가적인 기재를 포함한다. 예시적인 친화도 분석법들은 미국 공개특허 출원 제 2008/0110747의 실시예 10 및 11에 기재되어 있으며, 이 문헌은 본 출원에 그 전문이 참고문헌으로 포함된다.
일부 또는 임의의 구체예들에서, 항-스클레로스틴 항체 또는 항체 단편은 서열 번호: 1에 제시된 아미노산 서열을 포함하는 스클레로스틴 폴리펩타이드에 결합하고 서열 번호: 6의 서열 (CGPARLLPNAIGRGKWWRPSGPDFRC; 서열 번호: 1의 아미노산 86-111에 상응함)을 포함하는 스클레로스틴 영역에 결합한다. 이 영역은 또한 본 출원에서 스클레로스틴의 "루프 2" 영역으로도 지칭된다. 루프 2 영역 밖의 스클레로스틴 영역들은 본 출원에서 "비-루프 2 영역들"로 정의된다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 서열 번호: 1의 아미노산 57-146을 포함하는 스클레로스틴 폴리펩타이드에 결합한다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 서열 번호: 1의 아미노산 89-103 및/또는 서열 번호: 1의 아미노산 137-151을 포함하는 스클레로스틴 폴리펩타이드에 결합한다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 서열 번호: 1에 제시된 아미노산 서열을 포함하는 스클레로스틴 폴리펩타이드에 결합하며 서열 번호: 1 내에서 서열 번호: 2 (DVSEYSCRELHFTR; 서열 번호: 1의 아미노산 51-64에 상응함), 서열 번호: 3 (SAKPVTELVCSGQCGPAR; 서열 번호: 1의 아미노산 73-90에 상응함), 서열 번호: 4 (WWRPSGPDFRCIPDRYR; 서열 번호: 1의 아미노산 101-117에 상응함), 서열 번호: 5 (LVASCKCKRLTR; 서열 번호: 1의 아미노산 138-149에 상응함), 서열 번호: 70 (SAKPVTELVCSGQC; 서열 번호: 1의 아미노산 73-86에 상응함), 서열 번호: 71 (LVASCKC; 서열 번호: 1의 아미노산 138-144에 상응함), 서열 번호: 72 (C1RELHFTR; 서열 번호: 1의 아미노산 57-64에 상응함), 또는 서열 번호: 73 (CIPDRYR; 서열 번호: 1의 아미노산 111-117에 상응함) 중 최소한 하나의 서열에 결합한다. 예를 들어, 한 양상에서, 항-스클레로스틴 항체는 서열 번호: 2-5 (및/또는 서열 번호: 70-73)를 포함하는 서열 번호: 1의 스클레로스틴의 하위영역에, 선택적으로 그 고유의 3차원 구조로 결합한다. 선택적으로, 항-스클레로스틴 항체는 서열 번호: 2, 서열 번호: 3, 서열 번호: 4, 서열 번호: 5, 서열 번호: 6, 서열 번호: 70, 서열 번호: 71, 서열 번호: 72, 또는 서열 번호: 73 중 하나 이상으로 구성된 펩타이드 (예컨대, 서열 번호: 2, 서열 번호: 3, 서열 번호: 4, 및 서열 번호: 5로 구성된 펩타이드 또는 서열 번호: 70, 서열 번호: 71, 서열 번호: 72, 및 서열 번호: 73으로 구성된 펩타이드)에 결합한다.
일부 또는 임의의 구체예들에서, 항-스클레로스틴 항체는 서열 번호: 1의 아미노산 89-103 및 137-151을 포함하는 스클레로스틴 폴리펩타이드에 결합한다.
일부 또는 임의의 구체예들에서, 항-스클레로스틴 항체는 서열 번호:2, 서열 번호:3, 서열 번호:4 및 서열 번호:5의 아미노산 서열들을 가지는 스클레로스틴 폴리펩타이드에 결합하며, 이 때 서열 번호:2 및 4는 서열 번호:1에 관한 아미노산 위치 57 및 111에서 이황화 결합에 의해 결합되고, 그리고 서열 번호:3 및 5는 (a) 서열 번호:1에 관한 아미노산 위치 82 및 142에서 이황화 결합, 및 (b) 서열 번호:1에 관한 아미노산 위치 86 및 144에서 이황화 결합 중 최소한 하나에 의해 결합되고; 폴리펩타이드는 서열 번호:1의 인간 스클레로스틴의 상응하는 폴리펩타이드 영역의 3차 구조를 보유할 수 있다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 서열 번호: 70, 서열 번호: 71, 서열 번호: 72 및 서열 번호: 73의 아미노산 서열들을 가지는 폴리펩타이드에 결합하며, 이 때 서열 번호: 72 및 73은 서열 번호: 1에 관하여 아미노산 위치 57 및 111에서의 이황화 결합에 의해 결합되고, 서열 번호: 70 및 71은 (a) 서열 번호: 1에 관하여 아미노산 위치 82 및 142에서의 이황화 결합, 및 (b) 서열 번호: 1에 관하여 아미노산 위치 86 및 144에서의 이황화 결합 중 최소한 하나에 의해 결합된다.
선택적으로, 항-스클레로스틴 항체는 서열 번호: 2, 서열 번호: 3, 서열 번호: 4 및 서열 번호: 5의 아미노산 서열들로 본질적으로 구성된 펩타이드에 결합하고, 이 때 서열 번호: 2 및 4는 서열 번호: 1에 관하여 아미노산 위치 57 및 111에서 이황화 결합에 의해 결합되고, 서열 번호: 3 및 5는 (a) 서열 번호: 1에 관하여 아미노산 위치 82 및 142에서의 이황화 결합, 및 (b) 서열 번호: 1에 관하여 아미노산 위치 86 및 144에서의 이황화 결합 중 최소한 하나에 의해 결합된다.
선택적으로, 항-스클레로스틴 항체는 서열 번호: 1의 다수 절두된 인간 스클레로스틴 단백질로 본질적으로 구성된 폴리펩타이드에 결합하고, 이 때 (a) 서열 번호: 1의 아미노산 1-50, 65-72, 91-100, 118-137, 및 150-190은 상기 폴리펩타이드에 없으며 또는 (b) 서열 번호: 1의 아미노산 1-56, 65-72, 87-110, 118-137, 및 145-190은 상기 폴리펩타이드에 없다.
일부 또는 임의의 구체예들에서, 항-스클레로스틴 항체는 서열 번호: 70, 서열 번호: 71, 서열 번호: 72 및 서열 번호: 73의 아미노산 서열들을 가지는 폴리펩타이드에 결합하며, 이 때 서열 번호: 72 및 73은 서열 번호: 1에 관하여 아미노산 위치 57 및 111에서의 이황화 결합에 의해 결합되고, 서열 번호: 70 및 71은 (a) 서열 번호: 1에 관하여 아미노산 위치 82 및 142에서의 이황화 결합, 및 (b) 서열 번호: 1에 관하여 아미노산 위치 86 및 144에서의 이황화 결합 중 최소한 하나에 의해 결합된다.
일부 또는 임의의 구체예들에서, 스클레로스틴 폴리펩타이드는 서열 번호: 1의 인간 스클레로스틴의 상응하는 폴리펩타이드 영역의 3차 구조를 보유한다.
일부 또는 임의의 구체예들에서, 항-스클레로스틴 항체는 (i) 서열 번호: 1의 아미노산 51-64, 73-90, 101-117, 및 138-149를 포함하는 인간 스클레로스틴의 일부에 결합하며, 이 때 상기 일부는 다음 중 최소한 하나, 최소한 둘 또는 셋 모두를 가진다: (a) 아미노산 57과 111 사이의 이황화 결합; (b) 아미노산 82와 142 사이의 이황화 결합; 및 (c) 아미노산 86과 144 사이의 이황화 결합; 또는 (ii) 서열 번호: 1의 아미노산 57-64, 73-86, 111-117, 및 138-144를 포함하는 인간 스클레로스틴의 일부에 결합하며, 이 때 상기 일부는 다음 중 최소한 하나, 최소한 둘, 또는 셋 모두를 가진다: (a) 아미노산 57과 111 사이의 이황화 결합; (b) 아미노산 82와 142 사이의 이황화 결합; 및 (c) 아미노산 86과 144 사이의 이황화 결합.
일부 또는 임의의 구체예들에서, 항-스클레로스틴 항체는 또한 서열 번호: 6의 에피토프에 결합한다.
항-스클레로스틴 항체는 바람직하게는 미국 공개특허 출원 제 2007/0110747에 기재된 세포-기반 분석에서 및/또는 미국 공개특허 출원 제 2007/0110747에 기재된 생체내 분석에서 스클레로스틴 기능을 조절하며 및/또는 미국 공개특허 출원 제 2007/0110747에 기재된 에피토프들 중 하나 이상에 결합하고 및/또는 미국 공개특허 출원 제 2007/0110747에 기재된 항체 중 하나의 결합을 교차-차단하며 및/또는 미국 공개특허 출원 제 2007/0110747에 기재된 항체 중 하나에 의한 스클레로스틴 결합으로부터 교차-차단된다 (항-스클레로스틴 항체를 특성화하기 위한 분석법들에 관한 설명에 관해 그리고 그 전문이 참고문헌으로 포함됨).
다양한 양상들에서, 항-스클레로스틴 항체는 또한 MC3T3 세포-기반 미네랄화 분석에서 웰 당 스클레로스틴의 몰수에 비해 웰 당 스클레로스틴 결합 부위들의 몰수가 6-배 과량 미만으로 존재할 때 인간 스클레로스틴을 중화시킬 수 있다. 일차 세포이든 세포주이든, 배양 중인 골모세포-계통 세포들에 의한 미네랄화는 골 형성의 시험관내 모델로서 사용된다. 예시적인 세포-기반 미네랄화 분석은 미국 공개특허 출원 제 20070110747에, 예컨대, 실시예 8에 기재되어 있다 (본 출원에 참고문헌으로 포함됨). MC3T3-E1 세포들 (Sudo 외, J. Cell Biol., 96:191-198 (1983)) 및 본래의 세포주의 서브클론들은 분화제의 존재에서 성장시 배양물에 미네랄을 형성할 수 있다. 이러한 서브클론들은 MC3T3-E1-BF를 포함한다 (Smith 외, J. Biol. Chem., 275:19992-20001 (2000)). MC3T3-E1-BF 서브클론 뿐만 아니라 본래 MC3T3-E1 세포들 모두에 있어서, 스클레로스틴은, 최대한 미네랄 침착을 초래하는 그리고 미네랄 침착을 포함한 사례들의 서열 중 하나 이상을 억제할 수 있다 (즉, 스클레로스틴은 미네랄화를 억제한다). 스클레로스틴의 억제 활성을 중화시킬 수 있는 항-스클레로스틴 항체는 스클레로스틴의 존재하에 배양물의 미네랄화를 가능하게 하므로, 예컨대, 칼슘 포스페이트의 침착 (칼슘으로 측정함)에 있어서 스클레로스틴-단독 (즉, 항체 없음) 치료 그룹에서 측정된 칼슘의 양과 비교시 통계적으로 유의한 증가가 존재한다.
특정한 항-스클레로스틴 항체 (또는 다른 스클레로스틴 억제제)가 스클레로스틴을 중화시킬 수 있는지 여부를 결정하기 위한 목적으로 분석법을 실시할 때, 이러한 분석에서 사용되는 스클레로스틴의 양은 바람직하게는, 스클레로스틴-단독 그룹에서 칼슘 포스페이트 침착(칼슘으로 측정함)에 있어서 스클레로스틴 없는 그룹에서 측정한 칼슘의 양과 비교하여 통계적으로 유의한 최소한 70% 감소를 유발하는 최소량의 스클레로스틴이다. 항-스클레로스틴 중화 항체는 칼슘 포스페이트의 침착 (칼슘으로 측정함)에 있어서 스클레로스틴-단독 (즉, 항체 없음) 치료 그룹에서 측정된 칼슘 양과 비교하여 통계적으로 유의한 증가를 유발하는 항체로 정의된다. 항-스클레로스틴 항체가 중화성인지 여부를 결정하기 위하여, 본 분석에서 사용된 항-스클레로스틴 항체의 양은 웰 당 스클레로스틴의 몰수와 비교하여 웰 당 스클레로스틴 결합 부위들의 과량의 몰수가 존재하도록 하는 양이다. 항체의 역가(potency)에 따라, 필요할 수 있는 과량의 배수는 24, 18, 12, 6, 3, 또는 1.5일 수 있으며, 숙련된 기술자는 하나 이상의 결합제 (항체) 농도를 테스트하는 관례적인 절차를 잘 알고 있을 것이다. 예를 들어, 매우 효능있는 항-스클레로스틴 중화 항체는 웰 당 스클레로스틴의 몰수와 비교하여 웰당 스클레로스틴 결합 부위들의 6-배 미만의 과량 몰수로 존재할 때 스클레로스틴을 중화할 것이다. 덜 효능있는 항-스클레로스틴 중화 항체는 12, 18 또는 24 배 과량에서만 스클레로스틴을 중화할 것이다.
항-스클레로스틴 항체는 선택적으로 세포-기반 분석, 가령, 골 특이적 알칼리성 포스파타제 분석, 예컨대, 국제 공개특허 출원 제 WO 2008/115732 및 미국 특허 제 7,744,874에 기재된 골 특이적 알칼리성 포스파타제 분석에서 인간 스클레로스틴을 중화하기 위한 100 nM 또는 미만, 또는 75 nM 또는 미만, 또는 50 nM 또는 미만, 또는 25 nM 또는 미만의 IC50을 가진다 (세포-기반 분석 및 항-스클레로스틴 항체에 관한 그 설명 부분에 관하여 그 전문이 본 출원에 참고문헌으로 포함됨). 골 특이적 알칼리성 포스파타제 분석으로 다능성 쥐과 세포주, C2C12에서 BMP-4 및 Wnt3a-자극된 알칼리성 포스파타제 수준을 감소시키는 스클레로스틴의 능력에 대해 예측한다. WO 2008/115732에 따르면, 중화성 항-스클레로스틴 항체는 이러한 분석에서 알칼리성 포스파타제 활성의 용량-의존성 증가를 매개한다.
대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 HEK293 세포주들에서의 세포-기반 Wnt 신호전달 분석, 가령, 예컨대, 국제 공개특허 출원 제 WO 2009/047356에 기재된 (항-스클레로스틴 항체 및 세포-기반 분석을 논의한 부분에 대해 참고문헌으로 포함됨) STF 리포터 유전자의 Wnt1-매개 유도에 관여하는 Wnt 분석법에서 인간 스클레로스틴을 중화시키기 위해 100 nM 또는 미만 (예컨대, 75 nM 또는 미만, 또는 50 nM 또는 미만)의 IC50을 가진다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 MC3T3 세포들에서 BMP2-유도된 미네랄화 분석법, 가령, 예컨대, 국제 공개특허 출원 제 WO 2009/047356에 기재된 미네랄화 분석법에서 인간 스클레로스틴을 중화시키기 위해 500 nM 또는 미만 (예컨대, 250 nM 또는 미만, 150 nM 또는 미만, 100 nM 또는 미만, 또는 50 nM 또는 미만)의 IC50을 가진다.
본 발명의 내용에서 사용하기에 적합한 항-스클레로스틴 항체의 예들은 미국 공개 특허 출원 제 2007/0110747 및 2007/0072797에 기재되어 있으며, 이는 본 출원에 참고문헌으로 포함된다. 일부 구체예들에서, 항-스클레로스틴 항체는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 (이들 모두는 미국 공개특허 출원 제 20070110747에 기재되어 있음) 중 최소한 하나의 스클레로스틴에 대한 결합을 교차-차단한다. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 (이들 모두는 미국 공개특허 출원 제 20070110747에 기재되어 있음) 중 최소한 하나에 의해 스클레로스틴에 대한 결합이 교차-차단된다. 용어 "교차-차단하다", "교차-차단된" 및 "교차-차단하는"은 본 출원에서 호환적으로 사용되며 스클레로스틴에 대한 다른 항체의 결합을 방해하는 항체의 능력을 의미한다. 하나의 항체가 스클레로스틴에 대한 또 다른 항체의 결합을 방해하는 정도, 그리고 그에 따라 그 항체가 교차-차단하는 것이라 말할 수 있는지 여부는 경쟁적 결합 분석을 사용하여 결정될 수 있다. 본 발명의 일부 양상들에서, 교차-차단 항체 또는 이의 단편은 기준 항체의 스클레로스틴 결합을 약 40% 내지 약 100%, 가령, 약 60% 내지 약 100%, 구체적으로, 70% 내지 100%, 그리고 더욱 구체적으로 80% 내지 100% 감소시킨다. 교차-차단을 탐지하기에 특히 적합한 정량적 분석법은 Biacore 기기를 사용하며, 이 기기는 표면 플라스몬 공명 기술을 사용하여 상호작용 정도를 측정한다. 또 다른 적합한 정량적 교차-차단 분석은 스클레로스틴에 대한 항체들의 결합에 관하여 항체들간의 경쟁을 측정하는 ELISA-기반 접근방법을 사용한다.
일부 구체예들에서, 항-스클레로스틴 항체는 서열 번호: 1의 스클레로스틴에 대한, 전장 중쇄 및 경쇄를 포함하는 면역글로불린의 결합을 교차-차단하거나 및/또는 전장 중쇄 및 경쇄를 포함하는 면역글로불린에 의해 서열 번호: 1의 스클레로스틴에 대한 결합이 교차-차단되며, 이 때 전장 중쇄 및 경쇄를 포함하는 면역글로불린은 본 출원에 개시된 CDR 서열들, 가령, 다음과 같은 3개 세트의 CDR 서열들 중 하나를 포함한다: a) 서열 번호: 284의 CDR-L1, 서열 번호: 285의 CDR-L2, 서열 번호: 286의 CDR-L3, 서열 번호: 296의 CDR-H1, 서열 번호: 297의 CDR-H2, 및 서열 번호: 298의 CDR-H3; b) 서열 번호: 48의 CDR-L1, 서열 번호: 49의 CDR-L2, 서열 번호: 50의 CDR-L3, 서열 번호: 45의 CDR-H1, 서열 번호: 46의 CDR-H2, 및 서열 번호: 47의 CDR-H3; 또는 c) 서열 번호: 42의 CDR-L1, 서열 번호: 43의 CDR-L2, 서열 번호: 44의 CDR-L3, 서열 번호: 39의 CDR-H1, 서열 번호: 40의 CDR-H2, 및 서열 번호: 41의 CDR-H3. 대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 서열 번호: 1의 스클레로스틴에 대한 전장 중쇄 및 경쇄를 포함하는 면역글로불린의 결합을 교차-차단하거나 및/또는 전장 중쇄 및 경쇄를 포함하는 면역글로불린에 의해 서열 번호: 1의 스클레로스틴에 대한 결합이 교차-차단되며, 이 때 전장 중쇄 및 경쇄를 포함하는 면역글로불린은 다음과 같은 CDR들을 포함한다: 서열 번호: 245의 CDR-H1, 서열 번호: 246의 CDR-H2, 서열 번호: 247의 CDR-H3, 서열 번호: 78의 CDR-L1, 서열 번호: 79의 CDR-L2 및 서열 번호: 80의 CDR-L3.
대안적으로 또는 추가적으로, 항-스클레로스틴 항체는 서열 번호: 1의 스클레로스틴에 대한 전장 중쇄 및 경쇄를 포함하는 면역글로불린의 결합을 교차-차단하거나 및/또는 전장 중쇄 및 경쇄를 포함하는 면역글로불린에 의해 서열 번호: 1의 스클레로스틴에 대한 결합이 교차-차단되며, 이 때 전장 중쇄 및 경쇄를 포함하는 면역글로불린은 다음과 같은 CDR들을 포함한다: 서열 번호: 269의 CDR-H1, 서열 번호: 270의 CDR-H2, 서열 번호: 271의 CDR-H3, 서열 번호: 239의 CDR-L1, 서열 번호: 240의 CDR-L2 및 서열 번호: 241의 CDR-L3.
적합한 항-스클레로스틴 항체 및 이의 단편들의 예들에는 구체적으로 본 출원에 개시된 그리고 미국 공개특허 출원 제 2007/0110747에 개시된 CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 및 CDR-L3 중 하나 이상을 가지는 항체 및 항체 단편들이 포함된다. CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, 및 CDR-L3의 영역들 중 최소한 하나는, 항체가 비-치환된 CDR의 결합 특이성을 보유하는 한, 최소한 하나의 아미노산 치환을 가질 수 있다. 항-스클레로스틴 항체의 예시에는, 미국 공개특허 출원 제 2007/0110747의 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24가 포함되나 이에 제한되는 것은 아니다. 다른 예시적인 항-스클레로스틴 항체에는, 27H6, 19D11 및 20C3이 포함되나 이에 제한되는 것은 아니다.
또한, 항-스클레로스틴 항체는 서열 번호: 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 78, 79, 80, 81, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 351, 352, 353, 358, 359, 및 360에서 선택된 CDR에 최소한 75% 동일성 (예컨대, 100% 동일성)을 가지는 최소한 하나의 CDR 서열을 포함할 수 있다. 또한, 항-스클레로스틴 항체는 서열 목록에 제공된 서열 번호: 417-422, 425-430 및 433-438에서 선택된 CDR에 최소한 75% 동일성 (예컨대, 100% 동일성)을 가지는 최소한 하나의 CDR 서열을 포함할 수 있다. 바람직하게는, 항-스클레로스틴 항체는 서열 번호: 245, 246, 247, 78, 79, 80, 269, 270, 271, 239, 240, 및 241에서 선택된 CDR에 최소한 75% 동일성을 가지는 최소한 하나의 CDR 서열을 포함한다. 항-스클레로스틴 항체는 다음을 포함할 수 있다: a) 서열 번호:54, 55, 및 56의 CDR 서열 및 서열 번호:51, 52, 및 53의 CDR 서열; b) 서열 번호:60, 61, 및 62의 CDR 서열 및 서열 번호:57, 58, 및 59의 CDR 서열; c) 서열 번호:48, 49, 및 50의 CDR 서열 및 서열 번호:45, 46, 및 47의 CDR 서열; d) 서열 번호:42, 43, 및 44의 CDR 서열 및 서열 번호:39, 40, 및 41의 CDR 서열; e) 서열 번호:275, 276, 및 277의 CDR 서열 및 서열 번호:287, 288, 및 289의 CDR 서열; f) 서열 번호:278, 279, 및 280의 CDR 서열 및 서열 번호:290, 291, 및 292의 CDR 서열; g) 서열 번호:78, 79, 및 80의 CDR 서열 및 서열 번호: 245, 246, 및 247의 CDR 서열; h) 서열 번호:81, 99, 및 100의 CDR 서열 및 서열 번호:248, 249, 및 250의 CDR 서열; i) 서열 번호:101, 102, 및 103의 CDR 서열 및 서열 번호:251, 252, 및 253의 CDR 서열; j) 서열 번호:104, 105, 및 106의 CDR 서열 및 서열 번호:254, 255, 및 256의 CDR 서열; k) 서열 번호:107, 108, 및 109의 CDR 서열 및 서열 번호:257, 258, 및 259의 CDR 서열; l) 서열 번호:110, 111, 및 112의 CDR 서열 및 서열 번호:260, 261, 및 262의 CDR 서열; m) 서열 번호:281, 282, 및 283의 CDR 서열 및 서열 번호:293, 294, 및 295의 CDR 서열; n) 서열 번호:113, 114, 및 115의 CDR 서열 및 서열 번호:263, 264, 및 265의 CDR 서열; o) 서열 번호:284, 285, 및 286의 CDR 서열 서열 번호:296, 297, 및 298의 CDR 서열; p) 서열 번호:116, 237, 및 238의 CDR 서열 및 서열 번호:266, 267, 및 268의 CDR 서열; q) 서열 번호:239, 240, 및 241의 CDR 서열 및 서열 번호:269, 270, 및 271의 CDR 서열; r) 서열 번호:242, 243, 및 244의 CDR 서열 및 서열 번호:272, 273, 및 274의 CDR 서열; 또는 s) 서열 번호:351, 352, 및 353의 CDR 서열 및 서열 번호:358, 359, 및 360의 CDR 서열.
항-스클레로스틴 항체는 CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, 및 CDR-L3에서 선택된 CDR에 최소한 75% 동일성을 가지는 (예컨대, 100% 동일한) 최소한 하나의 CDR 서열을 포함할 수 있으며 이 때 CDR-H1은 서열 번호: 245에 제공된 서열을 가지고, CDR-H2는 서열 번호: 246에 제공된 서열을 가지고, CDR-H3는 서열 번호: 247에 제공된 서열을 가지고, CDR-L1은 서열 번호: 78에 제공된 서열을 가지고, CDR-L2는 서열 번호: 79에 제공된 서열을 가지고 CDR-L3는 서열 번호: 80에 제공된 서열을 가진다. 항-스클레로스틴 항체는, 다양한 양상들에서, 2개의 CDRs 또는 6개의 CDRs을 포함한다. 선택적으로, 항-스클레로스틴 항체는 서열 번호: 378을 포함하는 중쇄의 모두 또는 일부 (예컨대, 2개의 중쇄들) 및 서열 번호 376을 포함하는 경쇄의 모두 또는 일부 (예컨대, 2개의 경쇄)를 포함한다.
항-스클레로스틴 항체는 CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, 및 CDR-L3에서 선택된 CDR에 최소한 75% 동일성을 가지는 (예컨대, 100% 동일한) 최소한 하나의 CDR 서열을 포함할 수 있으며 이 때 CDR-H1은 서열 번호: 269에 제공된 서열을 가지고, CDR-H2는 서열 번호: 270에 제공된 서열을 가지고, CDR-H3는 서열 번호: 271에 제공된 서열을 가지고, CDR-L1은 서열 번호: 239에 제공된 서열을 가지고, CDR-L2는 서열 번호: 240에 제공된 서열을 가지고 CDR-L3는 서열 번호: 241에 제공된 서열을 가진다. 항-스클레로스틴 항체는, 다양한 양상들에서, 최소한 2개의 CDRs 또는 6개의 CDRs을 포함한다. 선택적으로, 항-스클레로스틴 항체는 서열 번호: 366을 포함하는 중쇄의 모두 또는 일부 (예컨대, 2개의 중쇄들) 및 서열 번호 364를 포함하는 경쇄의 모두 또는 일부 (예컨대, 2개의 경쇄)를 포함한다.
대안적으로, 항-스클레로스틴 항체는 CDR의 H1, H2, 및 H3 를 포함하고 서열 번호: 137, 145, 또는 392에 제공된 서열을 가지는 폴리펩타이드 또는 이의 변이체를 포함하는 중쇄 (여기서 CDRs은 각각 서열 번호: 245, 246, 및 247에 최소한 75% 동일하고 (예컨대, 100% 동일)), 및 CDR의 L1, L2 및 L3을 포함하고 서열 번호: 133 또는 141에 제공된 서열을 가지는 폴리펩타이드 또는 이의 변이체를 포함하는 경쇄 (여기서 CDRs은 각각 서열 번호: 78, 79, 및 80에 최소한 75% 동일 (예컨대, 100% 동일))를 가질 수 있다.
항-스클레로스틴 항체는 CDR의 H1, H2, 및 H3를 포함하고 각각 서열 번호: 335, 331, 345, 또는 396에 제공된 서열을 가지는 폴리펩타이드 또는 전술한 임의의 변이체 (여기서 CDRs은 각각 서열 번호: 269, 270, 및 271에 최소한 75% 동일 (예컨대, 100% 동일)하고)를 포함하는 중쇄, 및 CDR의 L1, L2, 및 L3를 포함하고 서열 번호: 334 또는 341에 제공된 서열을 가지는 폴리펩타이드 또는 전술한 임의의 변이체 (여기서 CDR들은 각각 서열 번호: 239, 240, 및 241에 최소한 75% 동일 (예컨대, 100% 동일한)를 포함하는 경쇄를 가질 수 있다. 이러한 중쇄 및 경쇄 서열들의 모든 조합들이 고려된다 (예컨대, 서열 번호: 335을 포함하는 중쇄 및 서열 번호: 334를 포함하는 경쇄; 서열 번호: 331을 포함하는 중쇄 및 서열 번호: 334 또는 341을 포함하는 경쇄; 및 서열 번호: 345 또는 396을 포함하는 중쇄 및 서열 번호: 341을 포함하는 경쇄).
대안적으로, 항-스클레로스틴 항체는 서열 번호:137에 제공된 서열을 가지는 폴리펩타이드를 포함하는 중쇄, 및 서열 번호:133에 제공된 서열을 가지는 폴리펩타이드를 포함하는 경쇄; 서열 번호:145 또는 392에 제공된 서열을 가지는 폴리펩타이드를 포함하는 중쇄, 및 서열 번호: 141에 제공된 서열을 가지는 폴리펩타이드를 포함하는 경쇄; 서열 번호:335에 제공된 서열을 가지는 폴리펩타이드를 포함하는 중쇄, 및 서열 번호:334에 제공된 서열을 가지는 폴리펩타이드를 포함하는 경쇄; 서열 번호:331에 제공된 서열을 가지는 폴리펩타이드를 포함하는 중쇄, 및 서열 번호:341에 제공된 서열을 가지는 폴리펩타이드를 포함하는 경쇄; 또는 서열 번호:345 또는 396에 제공된 서열을 가지는 폴리펩타이드를 포함하는 중쇄, 및 서열 번호:341에 제공된 서열을 가지는 폴리펩타이드를 포함하는 경쇄를 가진다. 대안적으로, 항-스클레로스틴 항체는 스클레로스틴에 대한 전술한 임의의 항체를 교차-차단한다 (또는 이러한 항체에 의해 교차-차단된다).
일부 구체예들에서, 항-스클레로스틴 항체는 서열 번호: 1038, 서열 번호: 1046, 서열 번호: 1040 및 서열 번호: 1048로 구성된 그룹에서 선택된 아미노산 서열을 포함하는 중쇄를 포함하고; 선택적으로 서열 번호: 1039, 서열 번호: 1047, 서열 번호: 1041 및 서열 번호: 1049로 구성된 그룹에서 선택된 경쇄 아미노산 서열을 추가로 포함한다.
항-스클레로스틴 항체의 예들에는 또한 국제 공개특허 출원 제 WO 2008/092894, WO 2008/115732, WO 2009/056634, WO 2009/047356, WO 2010/100200, WO 2010/100179, WO 2010/115932, 및 WO 2010/130830에 개시된 항-스클레로스틴 항체 (이들 각각은 본 출원에 그 전문이 참고문헌으로 포함됨), 가령, 국제 공개특허 출원 제 WO 2008/115732의 서열 번호: 20-25 (본 출원의 서열 번호: 416-421)의 CDR들을 포함하는 항-스클레로스틴 항체, 국제 공개특허 출원 제 WO 2008/115732의 서열 번호: 26-31 (본 출원의 서열 번호: 422-427)의 CDR들을 포함하는 항-스클레로스틴 항체, 국제 공개특허 출원 제 WO 2008/115732의 서열 번호: 32-37 (본 출원의 서열 번호: 428-433)의 CDR들을 포함하는 항-스클레로스틴 항체, 국제 공개특허 출원 제 WO 2009/047356의 서열 번호: 4, 15, 26, 37, 48, 및 59 (본 출원에서 각각 서열 번호: 443, 454, 465, 476, 487 및 498)의 CDR들을 포함하는 항-스클레로스틴 항체, 또는 국제 공개특허 출원 제 WO 2010/130830의 서열 번호: 135-143, 153-161, 또는 171-179 (각각 본 출원에서 서열 번호: 745-753, 763-771, 781-789) 중 최소한 하나의 아미노산 서열을 포함하는 항-스클레로스틴 항체가 포함되나 이에 제한되는 것은 아니다.
투여 및 투약 시간
일부 구체예들에서, 본 출원에 기재된 항-스클레로스틴 항체의 한 번 이상의 투여는, 예를 들어, 약 1주 내지 약 18 개월 (예컨대, 약 1 개월 내지 약 12 개월, 약 1 개월 내지 약 9 개월 약 1 개월 내지 약 6 개월 또는 약 1 개월 내지 약 3 개월)의 치료 기간에 걸쳐 실시된다. 일부 구체예들에서, 대상체에게 본 출원에 기재된 항-스클레로스틴 항체가 1회 이상의 용량으로 일정한 치료 기간, 예를 들어, 약 1 개월 내지 약 12 개월 (52 주) (예컨대, 약 2 개월개월, 약 3 개월, 약 4 개월, 약 5 개월, 약 6 개월, 약 7 개월, 약 8 개월, 약 9 개월, 약 10 개월, 또는 약 11 개월)에 걸쳐 투여된다. 일부 구체예들에서, 골 미네랄 밀도를 유지하고 및/또는 결합 조직-골 부착을 개선하기 위하여 대상체에게 1회 이상의 용량의 항-스클레로스틴 항체가 투여된다 본 출원에서 사용되는 용어 "골 미네랄 밀도를 유지하다"는 초기 용량의 항-스클레로스틴 항체로부터 생성된 증가된 골 미네랄 밀도가 약 6 개월, 약 9 개월, 약 1년, 약 18 개월, 약 2년의 과정에 걸쳐 , 또는 환자의 삶의 과정에 걸쳐 약 1% 이상 내지 약 5%에 속하지 않음을 의미한다. 환자는 골 밀도를 증가시키고 골 밀도를 유지하기 위한 대안 치료기를 필요로 할 수 있음을 이해하여야 한다. 항-스클레로스틴 항체를 제공받은 대상체에서 개선된 결합 조직-골 부착은 다양한 방식들에서 평가될 수 있으며, 이러한 방식들에는, 인지되는 통증의 감소, 치유 과정에서 보다 초기에 영향받은 근육을 이용하는 대상체의 능력, 개선된 방사선사진 또는 MRI 파라미터, 및/또는 증가된 근육 강도가 포함되나 이에 제한되는 것은 아니다.
또한, 특정 대상체를 위해 선택된 치료적 투약법에 따라 복수회 용량의 항-스클레로스틴 항체를 투여하거나 용량들의 투여 간격을 두는 것이 유리할 수 있다. 일부 구체예들에서, 항-스클레로스틴 항체 또는 이의 단편은 1년 (12 개월, 52 주) 또는 미만 (예컨대, 9 개월 또는 미만, 6 개월 또는 미만, 또는 3 개월 또는 미만)의 시기에 걸쳐 주기적으로 투여된다. 이와 관련하여, 항-스클레로스틴 항체 또는 이의 단편은 인간에게 약 3일, 또는 약 7 일, 또는 2 주, 또는 3 주, 또는 4 주, 또는 5 주, 또는 6 주, 또는 7 주, 또는 8 주, 또는 9 주, 또는 10 주, 또는 11 주, 또는 12 주, 또는 13 주, 또는 14 주, 또는 15 주, 또는 16 주, 또는 17 주, 또는 18 주, 또는 19 주, 또는 20 주, 또는 21 주, 또는 22 주, 또는 23 주, 또는 6 개월, 또는 12 개월 마다 1회 투여된다.
일부 구체예들에서, 치료 기간은 골에 대한 결합 조직 부착에 있어서의 결함이 탐지된 직후 (또는 골에 대한 결합 조직의 외과수술 재부착 직후), 예컨대, 결함 30 분 이내, 1 시간 이내, 2 시간 이내, 6 시간 이내, 12 시간 이내 또는 24 시간 이내에 시작한다. 다른 구체예들에서, 억제제는 결함 1 일 이내, 결함 3 일 이내, 결함 5 일 이내, 결함 7 일 이내, 또는 결함 2주 이내에 투여되며, 여기서 항-스클레로스틴 항체 또는 이의 단편은 결함 후 최소한 4 주인 시기 동안 (예컨대, 4 주, 5 주, 6 주, 7 주, 8 주, 9 주, 10 주, 11 주, 12 주, 13 주, 14 주, 15 주, 16 주, 17 주, 18 주 19 주, 20 주, 21 주, 22 주, 23 주, 24 주, 25 주, 26 주, 27 주 28 주, 29 주, 30 주, 31 주 또는 그 이상 (예컨대, 8 개월, 9 개월, 10 개월, 11 개월, 1 년, 18 개월 또는 그 이상)) 투여된다. 다른 구체예들에서, 억제제는 외과수술 재부착 1일 이내, 외과수술 재부착 3일 이내, 외과수술 재부착 5일 이내, 외과수술 재부착 7일 이내, 또는 외과수술 재부착 2주 이내에 투여되며, 여기서 항-스클레로스틴 항체 또는 이의 단편은 외과수술 재부착 후 최소한 4 주인 기간 동안 (예컨대, 4 주, 5 주, 6 주, 7 주, 8 주, 9 주, 10 주, 11 주, 12 주, 13 주, 14 주, 15 주, 16 주, 17 주, 18 주 19 주, 20 주, 21 주, 22 주, 23 주, 24 주, 25 주, 26 주, 27 주 28 주, 29 주, 30 주, 31 주 또는 그 이상 (예컨대, 8 개월, 9 개월, 10 개월, 11 개월, 1 년, 18 개월 또는 그 이상)) 투여된다.
일부 구체예들에서, 항-스클레로스틴 항체 또는 이의 단편의 1회 이상의 용량들은 결합 조직-골 치유를 향상시키고 및/또는 결합 조직 재부착 과정의 결과를 개선시키기에 유효한 양으로 그리고 시간 동안 투여된다. 다양한 구체예들에서, 약 50 밀리그램 내지 약 1,000 밀리그램의 항-스클레로스틴 항체를 포함하는 1회 이상의 용량들이 대상체(예컨대, 인간 대상체)에게 매주 투여된다. 예를 들어, 항-스클레로스틴 항체의 용량은 최소한 약 5 mg, 15 mg, 25 mg, 50 mg, 약 60 mg, 약 70 mg, 약 80 mg, 약 90 mg, 약 100 mg, 약 120 mg, 약 150 mg, 약 200 mg, 약 240 mg, 약 250 mg, 약 280 mg, 약 300 mg, 약 350 mg, 약 400 mg, 약 420 mg, 약 450 mg, 약 500 mg, 약 550 mg, 약 600 mg, 약 650 mg, 약 700 mg, 약 750 mg, 약 800 mg, 약 850 mg, 약 900 mg, 약 950 mg 또는 최대 약 1,000 mg의 항-스클레로스틴 항체를 포함할 수 있다. 이러한 임의의 그리고 모든 결과 변수들 간의 범위들, 예컨대, 약 50 mg 내지 약 80 mg, 약 70 mg 내지 약 140 mg, 약 70 mg 내지 약 270 mg, 약 75 mg 내지 약 100 mg, 약 100 mg 내지 약 150 mg, 약 140 mg 내지 약 210 mg, 또는 약 150 mg 내지 약 200 mg, 또는 약 180 mg 내지 약 270 mg, 또는 약 280 내지 약 410 mg이 또한 고려된다. 상기 용량은 임의의 간격으로, 가령, 주 수 회 (예컨대, 매주 2회 또는 3회), 주 1회, 2주마다 1회, 3주마다 1회, 또는 4주마다 1회 투여된다. 일부 또는 임의의 구체예들에서, 약 120 mg 내지 약 210 mg 범위의 용량의 항-스클레로스틴 항체가 주 2회 투여된다. 일부 또는 임의의 구체예들에서, 약 140 mg 용량의 항-스클레로스틴 항체가 주 2회 투여된다.
일부 구체예들에서, 1회 이상의 항-스클레로스틴 항체 용량들은 체중 1 킬로그램 당 약 0.1 내지 약 50 밀리그램 (예컨대, 약 5 내지 약 50 밀리그램), 또는 약 1 내지 약 100 밀리그램의 항-스클레로스틴 항체 (mg/kg)를 포함할 수 있다. 예를 들어, 항-스클레로스틴 항체의 용량은 최소한 약 0.1 mg/kg, 0.5 mg/kg, 1 mg/kg, 약 2 mg/kg, 약 3 mg/kg, 약 4 mg/kg, 약 5 mg/kg, 약 6 mg/kg, 약 7 mg/kg, 약 8 mg/kg, 약 9 mg/kg, 약 10 mg/kg, 약 20 mg/kg, 약 25 mg/kg, 약 26 mg/kg, 약 27 mg/kg, 약 28 mg/kg, 약 29 mg/kg, 약 30 mg/kg, 약 31 mg/kg, 약 32 mg/kg, 약 33 mg/kg, 약 34 mg/kg, 약 35 mg/kg, 약 36 mg/kg, 약 37 mg/kg, 약 38 mg/kg, 약 39 mg/kg, 약 40 mg/kg, 약 41 mg/kg, 약 42 mg/kg, 약 43 mg/kg, 약 44 mg/kg, 약 45 mg/kg, 약 46 mg/kg, 약 47 mg/kg, 약 48 mg/kg, 또는 약 49 mg/kg, 또는 약 50 mg/kg, 약 55 mg/kg, 약 60 mg/kg, 약 65 mg/kg, 약 70 mg/kg, 약 75 mg/kg, 약 80 mg/kg, 약 85 mg/kg, 약 90 mg/kg, 약 95 mg/kg, 또는 최대 약 100 mg/kg을 포함할 수 있다. 이러한 임의의 그리고 모든 결과변수들 간의 범위들, 예컨대, 약 1 mg/kg 내지 약 3 mg/kg, 약 1 mg/kg 내지 약 5 mg/kg, 약 1 mg/kg 내지 약 8 mg/kb, 약 3 mg/kg 내지 약 8 mg.kg, 약 1 mg/kg 내지 약 10 mg/kg, 약 1 mg/kg 내지 약 20 mg/kg, 약 1 mg/kg 내지 약 40 mg/kg, 약 5 mg/kg 내지 약 30 mg/kg, 또는 약 5 mg/kg 내지 약 20 mg/kg 또한 고려된다.
병용 요법
동일한 병원체 또는 생화학적 경로 또는 생물학적 과정을 표적하는 둘 이상의 제제들을 병용함에 의한 병리학의 치료는 종종 각 제제 단독의 치료적 관련 용량을 사용하는 것에 비해 효능을 더 크게 하고 부작용을 감소시킨다. 일부 사례들에서, 약물 병용의 효능은 부가적 (병용 효능은 각 약물 단독의 효과의 합과 대략 동일하다)이지만, 다른 사례들에서 효과는 상승작용적 (병용 효능은 단독 제공되는 각 약물의 효과의 합보다 크다)이다. 본 출원에서 사용되는 용어 "병용 요법"은 둘 이상의 제제들이 일시 방식으로, 예컨대, 동시에 전달되거나, 또는 제제들 중 하나가 먼저 투여된 후, 두 번째 제제가, 예컨대, 순차적으로, 후속됨을 의미한다.
일부 구체예들에서, 항-스클레로스틴 항체는 골에 대한 결합 조직 부착의 결함 치료에 관한 표준 의료 치료와 함께 투여된다 (즉, 항-스클레로스틴 항체 및 표준 의료 치료는 동일한 치료 플랜의 일부이다). 본 출원에서 사용되는 용어 "표준 의료"는 일정한 유형의 질병을 진단받은 일정 유형의 환자에 대해 임상의가 일반적으로 허용하는 치료를 의미한다. 일부 구체예들에서, 항-스클레로스틴 항체는 감소된 골 미네랄 밀도 또는 골 결함의 치료에 유용한 제 2의 골-향상제와 함께 투여된다. 일부 구체예들에서, 골-개선제는 항-흡수성 제제, 골 형성제 (즉, 동화제), 에스트로겐 수용체 조절제 (랄록시펜, 바제독시펜 및 라소폭시펜을 포함하나 이에 제한되는 것은 아님) 및 파골세포에 대한 억제 효과를 가지는 약물로 구성된 그룹에서 선택된다. 일부 구체예들에서, 제 2의 골-향상제는 비스포스포네이트 (알렌드로네이트 소듐 (FOSAMAX®), 리세드로네이트, 이반드로네이트 소듐 (BONIVA®) 및 졸레드로닉 애시드 (RECLAST®)를 포함하나 이에 제한되는 것은 아님); 에스트로겐 또는 에스트로겐 유사체; 항-RANK 리간드 (RANKL) 억제제, 가령, 항-RANKL 항체 (예컨대, PROLIA®); 비타민 D, 또는 비타민 D 유도체 또는 이의 모방체; 칼슘 공급원, 카텝신-K (cat-K) 억제제 (예컨대 오다나카팁), 티볼론, 칼시토닌 또는 칼시트리올; 및 호르몬 대체 요법으로 구성된 그룹에서 선택된다. 일부 구체예들에서, 제 2의 골-향상제는, 부갑상선 호르몬 (PTH) 또는 이의 펩타이드 단편, PTH-관련 단백질 (PTHrp), 골형성 단백질, 오스테오제닌, NaF, PGE2 작용제, 스타틴, 스트론튬 라넬레이트, 스클레로스틴 억제제 (예컨대, 예를 들어, 미국 특허 제 7,592,429 또는 7,872,106에 기재된 항-스클레로스틴 항체), 및 항-DKK1 항체 또는 억제제를 포함하나 이에 제한되는 것은 아니다. 일부 구체예들에서, 제 2의 골-향상제는 Forteo® (테리파라티드), Preotact®, 또는 Protelos®이다. 일부 구체예들에서, 제 2의 골-향상제는 골형성 단백질 (예컨대, BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14 및/또는 BMP-15)를 포함한다.
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골 부상에 대한 결합 조직에 관한 표준 의료 치료 요법과 항-스클레로스틴 항체 치료를 병용하는 것 또한 고려된다. 골 부상에 대한 결합 조직에 관한 예시적인 표준 의료 치료제 또는 치료 요법은, 골수 흡인, 혈소판 풍부 혈장, 유전자 치료 (예컨대, bFGF, BMP 12-14, PDGF, IGF, TGF
, CTGF 및 VEGF), 성장 인자 치료 (예컨대, BMP2/Smad8, BMP12/TGF
1), 줄기 세포 치료 (예컨대, 골수 중간엽 간질 세포, 지방 중간엽 간질 세포, 배아 줄기 세포 유래 중간엽 간질 세포, 건-유래 세포) 및 자연 생체재료의 사용 (예컨대, 콜라겐-계 스캐폴드, 정렬된 콜라겐사, 탈세포화 건 이식편 및 진피 이식편)을 포함하나 이에 제한되는 것은 아니다.
일부 구체예들에서, 본 출원에 기재된 항-스클레로스틴 항체를 이용하는 병용 요법은 수 분 내지 수 주 내지 수 개월 범위의 간격으로 추가 치료제(들) (예컨대, 제 2의 골-향상제)의 투여를 선행하거나 수반할 수 있다. 예를 들어, 별도의 양상들이 서로 약 24 시간 이내에, 예컨대, 서로 약 6-12 시간 이내에, 또는 서로 약 1-2 시간 이내에, 또는 서로 약 10-30 분 이내에 투여된다. 일부 상황들에서, 치료 시기를 상당히 연장하는 것이 바람직할 수 있으며, 이 때 상이한 양상들의 각 투여들 사이에 수 일 (2, 3, 4, 5, 6 또는 7 일) 내지 수 주 (1, 2, 3, 4, 5, 6, 7 또는 8 주)가 경과한다. 병용 요법 중 하나 또는 두 제제들 모두를 이용한 반복 치료가 특히 고려된다.
유지 치료 요법
예컨대, 개선된 결합 조직-골 부착을 유지시키고 및/또는 비부하-유도된 골 손실을 방지하기 위한 유지 요법에서 본 출원에 기재된 제 2 골-향상제 및/또는 항-스클레로스틴 항체의 사용 또한 고려된다. 이와 관련하여, 본 출원에 기재된 방법 또는 용도는 선택적으로 항-스클레로스틴 항체를 이용한 치료 기간이 종료된 후 약 1 주 내지 약 5 년의 유지 기간 동안 유지시키기에 효과적인 제 2 골-향상제의 1회 이상의 양을 투여하는 것을 포함한다. 예를 들어, 일부 구체예들에서, 본 출원에 기재된 방법 또는 용도는 약 최소한 약 1 주, 2 주, 3 주, 4 주, 5 주, 6 주, 7 주, 8 주, 9 주, 10 주, 11 주, 12 주, 3 개월, 13 주, 14 주, 15 주, 16 주, 4 개월, 17 주, 18 주, 19 주, 20 주, 5 개월, 21 주, 22 주, 23 주, 24 주, 6 개월, 25 주, 26 주, 27 주 28 주, 7 개월, 29 주, 30 주, 31 주 또는 longer (예컨대, 8 개월, 9 개월, 10 개월, 11 개월, 1 년, 15 개월, 18 개월, 2 년, 3 년, 4 년, 5 년 또는 그 이상 (예컨대, 대상체의 생애에 걸쳐)의 유지 기간 동안 대상체에게 제 2 골-향상제의 투여를 포함한다. 일부 구체예들에서, 유지 기간은 약 6-12 주이다. 일부 구체예들에서, 유지 기간은 약 4-12 주, 또는 약 1-3 개월이다. 일부 구체예들에서, 유지 기간은 약 12-20 주, 또는 약 3-5 개월이다. 일부 구체예들에서, 유지 기간은 약 20-32 주, 또는 약 5-8 개월이다. 일부 구체예들에서, 유지 기간은 약 24-36 주, 또는 약 6-9 개월이다. 일부 구체예들에서, 유지 기간은 약 1 년, 약 2 년, 약 3 년, 약 4 년, 약 5 년 또는 그 이상이다. 개선된 결합 조직-골 부착을 "유지시키는 것"은 항-스클레로스틴 항체 치료를 받은 대상체에서 유사한 수준의 방사선사진 또는 MRI 파라미터 및/또는 근육 강도 측정을 경험하도록 유지하는 것을 포함한다.
유사하게, 본 출원에 기재된 방법 또는 용도는 선택적으로 치료 기간이 종료된 후 개선된 결합 조직-골 부착을 최소한 약 약 1 주, 2 주, 3 주, 4 주, 5 주, 6 주, 7 주, 8 주, 9 주, 10 주, 11 주, 12 주, 3 개월, 13 주, 14 주, 15 주, 16 주, 4 개월, 17 주, 18 주, 19 주, 20 주, 5 개월, 21 주, 22 주, 23 주, 24 주, 6 개월, 1 년, 2 년, 3 년, 4 년, 5 년 또는 그 이상 (예컨대, 대상체의 생애에 걸쳐)의 유지 기간 동안 유지시키는데 효과적인 항-스클레로스틴 항체의 1회 이상의 양을 후속하여 투여하는 것을 포함한다. 일부 구체예들에서, 유지 기간은 약 6-12 주이다. 일부 구체예들에서, 유지 기간은 약 4-12 주, 또는 약 1-3 개월이다. 일부 구체예들에서, 유지 기간은 약 12-20 주, 또는 약 3-5 개월이다. 일부 구체예들에서, 유지 기간은 약 20-32 주, 또는 약 5-8 개월이다. 일부 구체예들에서, 유지 기간은 약 24-36 주, 또는 약 6-9 개월이다. 일부 구체예들에서, 유지 기간은 약 1 년, 약 2 년, 약 3 년, 약 4 년, 약 5 년 또는 그 이상이다.
제약학적 조성물
일부 구체예들에서, 기재된 항-스클레로스틴은 제약학적으로 효과적인 희석제, 담체, 용해화제, 유화제, 보존제, 및/또는 보조제와 함께 제제화된다. 제약학적 조성물은, 액체, 동결된, 및 동결건조된 조성물을 포함하나 이에 제한되는 것은 아니다.
바람직하게는, 제제화 재료는 사용되는 용량 및 농도에서 수용자에게 비독성이다. 특정 구체예들에서, 치료적 유효량의 항-스클레로스틴 항체 또는 이의 단편을 포함하는 제약학적 조성물이 사용된다.
일부 구체예들에서, 제약학적 조성물은, 예를 들어, 조성물의 pH, 삼투압, 점도, 투명도, 색, 등장성, 향, 무균도, 안정성, 용해 또는 방출 속도, 흡착 또는 침투를 변형 유지 또는 보존하기 위한 제제화. 재료를 내포할 수 있다. 이러한 구체예들에서, 적합한 제제화 재료들에는, 아미노산 (가령, 글라이신, 글루타민, 아스파라긴, 아르기닌, 프롤린, 또는 라이신); 항균제; 항산화제 (가령, 아스코르브산, 소듐 설파이트 또는 소듐 하이드로겐-설파이트); 완충제 (가령, 보레이트, 바이카보네이트, 트리스-HCl, 시트레이트, 포스페이트 또는 다른 유기산); 벌크화제 (가령, 만니톨 또는 글라이신); 킬레이트제 (가령, 에틸렌다이아민 테트라아세트산 (EDTA)); 복합체화제 (가령, 카페인, 폴리비닐피롤리돈, 베타-시클로덱스트린 또는 하이드록시프로필-베타-시클로덱스트린); 충전제; 단당류; 이당류; 및 다른 탄수화물 (가령, 글루코스, 만노스 또는 덱스트린); 단백질 (가령, 혈청 알부민, 젤라틴 또는 면역글로불린); 착색, 착향, 및 희석제; 유화제; 친수성 폴리머 (가령, 폴리비닐피롤리돈); 저분자량 폴리펩타이드; 염-형성 반대이온 (가령, 소듐); 보존제 (가령, 벤잘코늄 클로라이드, 벤조산, 살리실산, 티메로살, 펜에틸 알콜, 메틸파라벤, 프로필파라벤, 클로르헥시딘, 소르브산 또는 과산화수소); 용매 (가령, 글리세린, 프로필렌 글리콜 또는 폴리에틸렌 글리콜); 당 알콜 (가령, 만니톨 또는 솔비톨); 현탁화제; 계면활성제 또는 습윤제 (가령, 플루로닉, PEG, 솔비탄 에스터, 폴리소르베이트, 가령, 폴리소르베이트 20, 폴리소르베이트, 트리톤, 트로메타민, 레시틴, 콜레스테롤, 틸록사팔); 안정성 향상제 (가령, 수크로스 또는 솔비톨); 등장성 향상제 (가령, 알칼리 금속 할로겐화물, 바람직하게는 소듐 또는 포타슘 클로라이드, 만니톨 솔비톨); 전달 비히클; 희석제; 부형제 및/또는 제약학적 보조제가 포함되나 이에 제한되는 것은 아니다. REMINGTON'S PHARMACEUTICAL SCIENCES, 18" Edition, (A. R. Genrmo, ed.), 1990, Mack Publishing Company를 참고하라.
일부 구체예들에서, 최적의 제약학적 조성물은 예를 들어, 의도한 투여 경로, 전달 형식 및 필요한 용량에 따라 해당 분야의 숙련된 기술자가 결정할 것이다. 예를 들어, 상기 REMINGTON'S PHARMACEUTICAL SCIENCES를 참고하라. 특정 구체예들에서, 이러한 조성물은 항-스클레로스틴 항체 또는 단편의 물리적 상태, 안정성, 생체내 방출 속도 및 생체내 제거 속도에 영향을 줄 수 있다. 특정 구체예들에서, 제약학적 조성물에서 일차 비히클 또는 담체는 성질상 수성 또는 비-수성일 수 있다. 예를 들어, 적합한 비히클 또는 담체는 가능하게는 비경구 투여를 위한 조성물에서 통상적인 다른 재료들로 보충된, 주사용수, 생리학적 식염수 또는 인공 뇌척수액일 수 있다. 중성의 완충 식염수 또는 혈청 알부민과 혼합된 식염수는 또 다른 예시적인 비히클이다. 특정 구체예들에서, 제약학적 조성물은 약 pH 7.0-8.5의 트리스 완충액, 또는 약 pH 4.0-5.5의 아세테이트 완충액을 포함하며 솔비톨 또는 적합한 이의 대체제를 추가로 포함할 수 있다. 본 발명의 특정 구체예들에서, 상기 조성물은 보관을 위해 원하는 정도의 순도를 가진 선택된 조성물을 선택적 제제화 제제들 (상기 REMINGTON'S PHARMACEUTICAL SCIENCES)과 혼합함으로써 동결건조된 케이크 또는 수용액 형태로 제조될 수 있다. 또한, 일부 구체예들에서, 항-스클레로스틴 항체 또는 단편은 적절한 부형제, 가령, 수크로스를 사용하여 동결건조물로서 제형화될 수 있다.
일부 구체예들에서, 제약학적 제제는 pH 5.2에서 55 mM 아세테이트, 13 mm 칼슘, 6.0 % (w/v) 수크로스, 0.006% (w/v) 폴리소르베이트 20을 포함한다. 일부 구체예들에서, 제약학적 조성물은 90 mg/mL 항-스클레로스틴 항체를 포함한다.
본 발명의 제약학적 조성물들은 비경구 전달을 위해 선택될 수 있다. 대안적으로, 조성물은 흡입을 위해 또는 소화관을 통한 전달을 위해, 가령, 경구 전달을 위해 선택될 수 있다. 이러한 제약학적으로 허용가능한 조성물의 제조는 해당 분야의 숙련된 기술자의 능력 범위에 속한다. 제제화 성분들은 바람직하게는 투여 부위에 허용가능한 농도로 존재한다. 특정 구체예들에서, 완충액은 전형적으로 약 5 내지 약 8의 pH 범위에 속하는 pH로 조성물을 유지시키기 위해 사용된다.
비경구 투여가 고려되는 경우, 본 발명에서 사용하기 위한 치료적 조성물은 제약학적으로 허용가능한 비히클에서 원하는 항-스클레로스틴 항체 또는 단편을 포함하는, 무-발열원의, 비경구적으로 허용가능한 수용액 형태로 제공될 수 있다. 비경구 주사에 특히 적합한 비히클은 무균 증류수이며, 이 때 항-스클레로스틴 항체 또는 단편은 무균의 등장성 용액으로 제형화되고, 바람직하게는 보존된다. 특정 구체예들에서, 제조는 데포 주사를 통해 전달될 수 있는 산물의 제어식 또는 지속형 방출을 제공할 수 있는 물질, 가령, 주사가능한 미세구, 생분해성 입자, 폴리머 화합물 (가령, 폴리락트산 또는 폴리글리콜산), 비드 또는 리포좀과 원하는 분자의 제제화를 포함한다. 특정 구체예들에서, 순환 내에서 지속되는 기간을 촉진시키는 효과를 가지는 히알루론산 또한 사용될 수 있다. 특정 구체예들에서, 원하는 항-스클레로스틴 항체 또는 이의 단편을 도입하기 위하여 이식가능한 약물 전달 장치가 사용될 수 있다.
항원 결합 단백질을 포함하는 지속형- 또는 제어형-전달 제형의 제제를 포함하는, 추가적인 제약학적 조성물은 해당 분야의 숙련된 기술자에게 자명할 것이다. 그 외 다른 다양한 지속형- 또는 제어형-전달 수단들, 가령, 리포좀 담체, 생분해성 미세입자 또는 다공성 비드 및 데포 주사를 제형화하는 기술들 또한 해당 분야의 숙련된 기술자들에게 공지되어 있다. 예를 들어, 참고문헌으로 포함되는 국제 특허 출원 제 PCT/US93/00829를 참고하면, 제약학적 조성물의 전달을 위한 다공성 폴리머 미세입자들의 제어형 방출을 기재한다. 지속형-방출 약제들은 성형된 제품 형태, 예컨대, 필름, 또는 미세캡슐에 반투과성 폴리머 매트릭스를 포함할 수 있다. 지속형 방출 매트릭스는 폴리에스터, 하이드로겔, 폴리락타이드 (미국 특허 제 3773919 및 유럽 공개 특허 출원 제 EP058481에 개시됨, 이들 각각은 참고문헌을 포함됨), L-글루탐산과 감마 에틸-L-글루타메이트의 코폴리머 (Sidman 외, 1983, Biopolymers 2:547-556), 폴리 (2-하이드록시에틸-메타크릴레이트) (Langer 외, 1981, J. Biomed. Mater. Res. 15:167-277 및 Langer, 1982, Chem. Tech. 12:98-105), 에틸렌 비닐 아세테이트 (Langer 외, 1981, supra) 또는 폴리-D(-)-3-하이드록시뷰티르산 (유럽 공개 특허 출원 제 EP133988)을 포함할 수 있다. 지속형 방출 조성물은 또한 해당 분야에 공지된 몇 가지 방법들 중 어느 하나에 의해 제조될 수 있는 리포좀들을 포함할 수 있다. 예컨대, 참고문헌으로 포함되는, Eppstein 외, 1985, Proc. Natl. Acad. Sci. U.S.A. 82:3688-3692; 유럽 공개 특허 출원 제 EP036676; EP088046 및 EP143949를 참고하라.
생체내 투여에 사용되는 제약학적 조성물은 전형적으로 무균 약제로 제공된다. 무균화는 무균 여과막을 통한 여과에 의해 구현될 수 있다. 조성물이 동결건조될 때, 이러한 방법을 사용한 무균화는 동결건조 및 재구성 이전 또는 이후에 실시될 수 있다. 비경구 투여를 위한 조성물은 동결건조 형태로 또는 용액으로 보관될 수 있다. 비경구 조성물은 일반적으로 무균 접근 포트를 가지는 용기, 예를 들어, 피하 주사 바늘에 의해 뚫릴수 있는 마개를 가진 바이얼 또는 정맥내 용액 백에 넣는다.
본 발명의 양상들은 자가-완충 항-스클레로스틴 항체 또는 단편 제제들을 포함하며, 이들은 국제 공개 특허 출원 WO 2006/138181A2 (PCT/US2006/022599)에 기재된 제약학적 조성물로서 사용될 수 있으며, 이 문헌은 본 출원에 그 전문이 참고문헌으로 포함된다.
상기 논의한 바와 같이, 특정 구체예들은, 항-스클레로스틴 항체 또는 단편 이외에도, 하나 이상의 부형제들, 가령, 본 섹션 및 본 출원의 다른 부분에 예시적으로 기재되어 있는 부형제들을 포함하는 ,항-스클레로스틴 항체 또는 단편 조성물, 특히 제약학적 항-스클레로스틴 항체 또는 단편 조성물을 제공한다. 부형제들은 이와 관련하여 널리 다양한 목적을 위해, 가령, 제제의 물리적, 화학적 또는 생물학적 성질들을 조절, 가령, 점도의 조절, 및 또는 효율성을 개선하기 위한 그리고 또는, 예를 들어, 제조, 선적, 저장, 사용전 준비, 투여 및 그 후 동안 발생하는 스트레스로 인한 분해 및 손상에 대해 이러한 제제들 및 과정들을 안정화하기 위한 본 발명의 과정들을 조절하기 위해 본 발명에서 사용될 수 있다.
키트
본 출원에 기재된 하나 이상의 항-스클레로스틴 항체를 포함하는 제약학적 조성물을 이러한 제약학적 조성물을 사용하는 것에 관한 지시사항을 제공하는 포장재와 함께 용기들 (예컨대, 바이얼 또는 주사기)에 넣을 수 있다. 일반적으로, 이러한 지시사항은 항-스클레로스틴 항체 농도, 뿐만 아니라, 특정 구체예들에서, 제약학적 조성물을 재구성하는데 필요할 수 있는 상대량의 부형제 성분들 또는 희석제 (예컨대, 물, 식염수 또는 PBS)를 설명하는 구체적인 표현을 포함할 것이다.
실시예
재료 및 방법
동물 및 수술: 성인 수컷 스프라그-돌리 쥐들이 본 연구에서 사용되었으며, 워싱턴 대학의 동물 연구 위원회에 의해 승인받았다. 수술시 쥐들은 대략 4개월령 이었으며 체중은 최소한 350g 였다. 극상 (SS) 건을 상완골두로부터 확실하게 들어올리고 양쪽 어?들 모두에서 전술한 바와 같이 복원하였다 [25]. 총 48마리 쥐들을 외과수술하였으며 34마리의 추가 쥐들을 건강한 정상 대조군 (N)으로 사용하였다. 동물들은 비치료 상태로 두거나 (CTL 그룹) 또는 서열 번호:245의 CDR-H1, 서열 번호:246의 CDR-H2, 서열 번호:247의 CDR-H3, 서열 번호:78의 CDR-L1 , 서열 번호:79의 CDR-L2, 및 서열 번호:80의 CDR-L3를 가지는 스클레로스틴 항체 (Scl-Ab VI, Amgen, Thousand Oaks, CA)를 부상-및-복원술 시에 그리고 희생시까지 2주마다 (Scl-Ab 그룹) 피하 주사 (25 mg/kg)를 통해 투여하였다 모든 동물들에게 자유로운 케이지 활동을 허락하였으며 2, 4, 또는 8 주의 치유 후 희생시켰다. 부상없는 동물들을 평균 5 개월령에 희생시켰으며이는 부상 후 대략 4주 치유에 해당한다.
골 형태계측: 희생 후, 극상 건 그리고 부착된 근육을 가지는 상완골을 한쪽 어깨로부터 주의하여 잘라내었다. 골 형태계측 (부상없음에 N=17, 2주 치유에 N=5, 4주 치유에 N=20, 및 8주 치유에 N=23)을 위해, 상완골두 및 건 인공물삽입부 영역 (~5mm)을 20 μm, 45kVp, 및 177 μA (μCT 40, Scanco Medical, Switzerland)의 해상도에서 전술한 바와 같이 마이크로 컴퓨터 단층촬영 (마이크로CT)을 사용하여 스캔하였다 [15, 26]. 관심 영역은 건 부착 근방의 상완골두 내부 그리고 성장판 근위에 해면골을 포함하였다. 관심 영역 내 골의 양을 계산하여 골 분율 부피 (BV/TV)를 결정하였다. 골 미네랄 밀도 (BMD), 해면골소주의 수 (Tb.N), 및 해면골소주의 두께 (Tb.Th) 를 또한 결정하였다.
생물역학: 희생, 절제, 및 마이크로CT 스캐닝 후, 테스트를 위한 준비로 전술한 바와 같이 극상 근육을 건으로부터 부드럽게 제거하였다 [15]. 복원-부위 봉합사를 빼내어 파열 하중 인장 테스트 동안 봉합사의 기계적 기여를 제거하였다. 상완골두 주변에 4/0 외과수술 강철 와이어를 감아 성장판을 보호하였다. 이후 상완골을 폴리-메틸-메타크릴레이트에 담았다. 표본들을 37 ℃의 0.9 % 식염수 조에서 테스트하였다. 단축 테스트 프레임 (Instron 5866, Instron Corporation, Norwood, MA) 및 얇은 필름의 건 그립 (Imada, Northbrook, IL)을 사용하여 생물역학 테스트를 실시할 것이다. 단축 파열 하중 인장 테스트는 0.2 %/s로 5 % 변형률까지 전처리하는 5회 주기, 후속하여 300s의 회복 기간, 그리고 0.2 %/s의 신전 파열로 구성된다. 각 건에 관한 초기 측정된 게이지 길이과 비교한 그립-대-그립 변위로 변형률을 측정하였다. 부착 부위 근방에서의 극상 건의 횡단면적 (CSA)을 상기 설명한 μCT 스캔으로부터 측정하였다. 측정된 힘을 CSA로 나누어 응력을 계산하였다. 하중-변형 곡선을 사용하여 최대 하중 및 강성도(곡선의 선형 부분의 기울기)를 결정하였다. 응력-변형 곡선을 사용하여 강도 (최대 응력), 모듈러스 (곡선의 선형 부분의 기울기) 및 복원력을 결정하였다. 파열의 기전은 테스트하는 동안 시각으로 결정하였으며 테스트 완료 후 육안 관찰을 통해 확인하였다.
조직학: 조직학을 위해, 절제한 상완골-극상 구조물들을 먼저 4% 파라포름알데히드에서 24 시간 동안 고정시켰다. 일부 시료들 (24개 중 18개)을 14% 에틸렌다이아민테트라아세트산에서 탈회시키고, 등급 에탄올에서 탈수시키고 파라핀에 함침시켰다. 5 μm 두께의 관상 절단면을 헤마톡실린 및 에오신, 톨루이딘 블루, 또는 골드너 삼색으로 염색하였다. 나머지 시료들 (24개 중 6개)을 24 시간 동안 4% 파라포름알데히드에서 고정시키고, 가소재에 함침시키고, 및 5 μm 두께의 관상 절단면들을 폰 코사로 염색하였다. 상기 절단면들을 한 명의 맹검 관찰자 (NH)가 Ide 외의 문헌에서 채택된 건-골 치유 성숙 점수를 사용하여 반-정량적으로 분석하였다 [26, 27]. 삽입 연속성, 골 흡수, 매트릭스 질, 세포 및 섬유 정렬, 및 세포충실성은 1-4의 스케일로 평가되는 9개 요인들의 일부였다 (표 1). 낮은 점수는 개선된 건-골 치유를 나타내고, 9의 점수는 건강한 부착에 해당한다 [26, 27].
표 1. 변형된 건-골 치유 성숙 점수는 9개 각각의 결과들에 관한 1-4 스케일의 평가를 포함하였다. A 건강한 (부상없는) 인공물삽입부는 종합 점수 9를 가진다. C - 연속성 R - 규칙성 F - 섬유연골.
유전자 발현: 유전자 발현 연구를 위해, 절제된 상완골-극상 시료들을 액체 질소에서 급속 동결시켰다. RNA를 건 부착 근방에 있는 성장판 근위에 있는 상완골두 부분 및 극상 건으로부터 별도로 분리하였다(RNAeasy Kit, Qiagen Valencia, CA). NanoDrop 2000 (Thermo Scientific, Waltham, MA)을 사용하여 RNA를 정량하였다. Biomark HD System (Fluidigm, San Francisco, CA)을 사용하여 골, 건, 및 섬유연골과 관련된 25개 유전자들의 패널에서 건과 골 RNA에 대해 정량적 실시간 PCR (qRT-PCR)을 실시하였다 (표 2). TaqMan 유전자 발현 분석법들 (Life Technologies, Carlsbad, CA)을 분석에 사용하였다. Rpl13a의 발현이 그룹들 간에 ± 0.5 CT 값 이상으로 변화하지 않았기 때문에 Rpl13a를 하우스키핑 유전자로 사용하였다. 결과들을 Rpl13a 발현과 비교한 상대 발현으로 제시한다 (2-△Ct).
표 2. 평가된 유전자명 및 관련 범주 및 TaqMan 분석 ID.
통계: 2인자 분산 분석 (ANOVA; 치료 및 치유 시간 인자) 후 Tukey의 사후 검정을 사용하여 치료 효과 및 치유 기간을 결정하였다. 부상없음 그룹과의 추가적인 통계적 비교를 양측 (2-tail) 스튜던트 t-검정으로 실시하였다. P < 0.05는 유의한 것으로 간주되었다.
결과
골 형태계측: 4 주 치유의 CTL 및 Scl-Ab 그룹에서 유의한 골 손실이, 8 주 치유 Scl-Ab 그룹에서 회복이 존재하였다 (도 1). 구체적으로, BV/TV, BMD, 및 TbN은 4 주시 부상없음 그룹과 비교하여 CTL 및 Scl-Ab 그룹들에서 유의하게 감소하였다. 그러나, 8 주의 치유 후, Scl-Ab 치료를 CTL과 비교시, BV/TV는 34% 만큼 증가하였으며, BMD는 30%만큼 증가하였고, TbN은 17%만큼 증가하였고, TbTh는 24% 만큼 증가하였고, 그리고 TbSp는 21% 만큼 감소하였고 (도 1A-1D), 이는 부상없는 대조 그룹에 필적가능한 수준에 도달한 것이었다. Scl-Ab를 이용한 치료는 또한 부상없는 그룹에서 BV/TV, BMD, 및 TbTh의 증가도 가져왔다. ANOVA를 사용하여 Scl-Ab 치료의 전체적인 효과를 평가할 때, Scl-Ab 치료된 동물들은 CTL 동물들과 비교하여 각각 19%, 18%, 및 20% 유의하게 더 높은 BV/TV, BMD, 및 TbTh를 가졌다.
생물역학:
부상은 CSA의 유의한 증가를 유발하였다 (15.9 ± 3.9 mm2 대. 6.6 ± 1.9 mm2; CSA 측정값들은 건 및 흉터를 비롯한, 인공물삽입부 근방의 모든 연조직을 포함하였음을 유의하라). 4 주 치유의 CTL 및 Scl-Ab 그룹들에서 기계적 특성들의 유의한 감소가, 8 주 치유의 Scl-Ab 그룹에서 회복이 존재하였다 (도 2). 구체적으로, 파열 하중, 강성도, 및 모듈러스는 4주시 부상없음 그룹에 비해 CTL 및 Scl-Ab 그룹들에서 유의하게 감소되었다. 그러나, 8 주의 치유 후, Scl-Ab 치료를 CTL과 비교시, 파열 하중은 48% 만큼 증가하였으며, 강도는 38% 만큼 증가하였고, 강성도는 43% 만큼 증가하였다. 놀랍게도, Scl-Ab를 이용한 치료는 또한 부상없는 그룹에서 강성도 및 모듈러스의 유의한 감소를 가져왔다.
조직학: 해부시 그리고 시료 준비 시 어떠한 복원 부위 파열 또는 갭들도 나타나지 않았다. 조직학적 절단면들은 섬유혈관 흉터를 통해 상완골두 골에 대한 극상 건 치유를 증명하였으며, 골 손실은 CTL 그룹의 상완골두에서 명확하였다 (도 3). CTL 및 Scl-Ab 치유 부착들은 2 및 4 주 치유시 유사해 보였다. 그러나, 8 주의 치유 후, Scl-Ab 치료는 CTL과 비교하여 개선된 삽입 연속성, 통합성, 및 섬유 정렬을 가져왔다. 반-정량적 맹검 분석은 이러한 관찰결과들을 뒷받침하였는데, 8 주시 CTL 그룹에 비해 Scl-Ab 그룹에서 보다 성숙한 건-골 치유 부착 및 새로운 골 형성을 보여주었다 (표 3).
표 3. 변형된 건-골 치유 성숙 점수는 Scl-Ab 치료받은 모든 그룹에서 시간이 지남에 따라 개선되었으며, 8 주 치유시 대조군 동물들과 비교하여 보다 성숙한 부착을 반영하는 보다 낮은 총 성숙도 점수가 생성되었다. 결과를 중앙값 (최소, 최대)으로 나타낸다.
미네랄화 조직 (골 및 섬유연골)에서 유전자 발현: Scl-Ab 치료는, 건 인공물삽입부 근방에 있는 미네랄화 조직에서 스클레로스틴, Dkk1, RankL, DMP1, 및 Runx2를 포함한 수많은 유전자들의 발현에 대해 유의한 효과를 가졌다 (도 4). 8 주의 치유 후, 스클레로스틴 및 Dkk1의 발현은 CTL과 비교하여 Scl-Ab에서 각각 3.3x 및 2.5x 더 컸다. Lrp5의 발현은 치료 또는 치유 시간에 영향을 받지 않았다. 골모세포 활성의 마커인 오스테오칼신 (OCN)은 부상 후 유의하게 증가되었던 반면, 파골세포 억제의 마커인 오스테오프로토게린 (OPG)은 모든 그룹에서 부상 후 유의하게 감소되었다. RankL 및 DMP1의 발현은 모두 Scl-Ab 치료로 증가되었다 (도 4). 섬유연골-관련 유전자들 TGFβ1, TGFβ3, MMP2, Col2a1, 및 Sox9에 대한 Scl-Ab 치료의 효과는 전혀 없었다 (도 4). 헤지호그 신호전달 경로의 구성원인 Smo 및 Notch1의 발현은 치료에 의해 영향을 받지 않았다.
건에서 유전자 발현 : Scl-Ab 치료는 건 유전자 발현에 대한 유의한 효과가 전혀 없었다 (도 5). 그러나 치유 시간은 모든 건-관련 유전자들: 스클레락시스, 테노모둘린, Col1a1, Col1a2, Col3a1에 유의하게 영향을 주었다. 변화는 2주 치유 시점에서 가장 자명하였으며 8주 치유 시점에서 정상에 가까운 성향을 나타내었다. 추가적으로, 아그리칸의 발현은 2 주 치유 후 CTL에서 20x 더 컸으며 Scl-Ab 치료에서 17x 더 컸다. 유사하게, Mmp2의 발현은 2 주 치유 후 CTL 및 Scl-Ab 치료 그룹 모두에서 4.1x 더 컸다.
[0001]
논의:
[0002]
회전근개 부상 및 복원술은 건-골 치유 경계면에서의 골 손실을 가져온다. 치유 경계면에서 골 양과 질의 감소는 외과적 복원술 후 높은 재-파열 비율의 원인이다 [5]. 본 출원에서 제공된 실시예는, 건 부착시 골 구조를 향상시키는 것이 회전근개 부상 및 복원술 후 개선된 치유를 초래하게 됨을 보여줌으로써, 스클레로스틴 항체 치료를 통한 건-골 치유 동안의 골 손실을 해결하였다. 스클레로스틴 항체 치료는 치유 건 부착에 가장 근방에 있는 상완골두에서 해면골 질량의 지수를 증가시켰다. 부상-관련 골 손실은 8 주 치유 후 대조 그룹에서 유지되었으나, 정상 골로의 신속한 회복은 치료된 동물들에서 8주 치유시 나타났다. 치유 경계면에서 골 형태의 개선은 개선된 부착 강도로 증명되는 바와 같이 기능적 결과를 가졌다. 중요한 것은, 조직학적 평가는, 8 주 치유 후 대조군에 비해 치료된 동물들에서 보다 성숙한 건-골 치유 경계면을 가지는 스클레로스틴 항체 치료의 이점을 추가로 확인시켜 주었다는 것이다.
[0003]
부상 후 골 미네랄 밀도 및 파열 하중을 개선시키기 위한, 골-형성 단백질 2 (BMP-2)와 유사한 골 동화 제제들의 부상 부위들로의 전달은 건-골 치유 복원술의 개 및 설치류 모델에서 효과적이지 않았다 [26, 28]. 그러나, 비스포스포네이트는 골 흡수를 감소시킴으로써 건-골 치유를 개선함에 있어 성공적인 것으로 기존에 나타났다 [18, 29]. 굽힘 건-골 치유의 개과 모델에서, 건 부상은 21 일 후 정상과 비교하여 건-골 치유 경계면 근방에서 골 미네랄 밀도의 29% 감소를 유발하였다 [18]. 알렌드로네이트의 경구 투약은 골 흡수 방지에 효과적이었으며, 정상과 비교하여 골 미네랄 밀도의 6% 감소만을 가져왔다. 골 손실의 방지는 21 일 치유 후 복원술의 파열 하중을 유의하게 개선시켰다. 별도의 연구에서, 난소절제된 쥐들에 대한 졸레드론산의 피하 주사는 대조군과 비교하여 극상 건 삽입 근방의 상완골두의 골 미네랄 밀도를 23% 증가시켰다 [29]. 증가된 골 미네랄 밀도는 치료 후 경계면에서의 24% 파열 하중 증가와 연관되어 있었으나, Scl-Ab와 달리 비스포스포네이트 투여시 건 조직학 점수에 있어서 어떠한 변화도 관찰되지 않았다. 본 연구에서, 8 주 치유 후, Scl-Ab 치료는 대조군과 비교하여 30%의 골 미네랄 밀도 증가 및 48%의 파열 하중 증가를 유발하였다.
[0004]
본 연구에서 사용된 스클레로스틴 항체는 Lrp5 수용체에 대한 스클레로스틴 결합을 방지함으로써 스클레로스틴을 중화시킨다 [30]. 건-골 치유 동안 골 형태의 개선이 이러한 기전을 통해 구현되었는지 여부를 결정하기 위하여, Wnt 신호전달-관련 유전자 발현을 측정하였다. Scl-Ab 치료로 인한 Lrp5의 발현에 있어서 통계적으로 유의한 변화는 존재하지 않았으나, 스클레로스틴 및 Dkk1의 발현은 건-골 치유 동안 치료된 골에서 증가되었다. 이는 건강한 골과 비교하여, 특히 그 이후의 시점들에서 대조군 골에서 이러한 2개 유전자들의 감소된 발현 수준들과 대조적이다. Scl-Ab 그룹에서 관찰된 변화는 중화된 스클레로스틴에 대한 보상적인 세포 반응을 나타내며 Wnt 신호전달을 개시하지 못했다.
[0005]
치유 부착시 미네랄화된 조직에서 유전자 발현의 추가 분석은 증가된 파골세포 억제 (증가된 OPG 발현으로 증명됨) 및 골모세포 활성의 증가 (증가된 오스테오칼신 발현으로 증명됨)를 제시하였으며, 이는 골 형태에 있어서 관찰된 개선과 일치하는 것이었다. 부상 및 복원술 이후, 골전구세포 마커 (오스테릭스 및 Runx2)의 유전자 발현은 또한 치료 및 대조 그룹들 모두에서 정상과 비교하여 유의하게 증가되었다. 더욱이, Scl-Ab 치료는 부상없는 정상 골에서 증가된 Runx2 유전자 발현을 가져왔다. 골모세포들로의 중간엽 세포들의 분화와 또한 연관되어 있는 [31, 32] 이러한 인자들의 증가된 발현은, 전구세포들 뿐만 아니라 Scl-Ab를 가진 성숙 골모세포들을 통한 전체적인 골 형성 유도를 나타낸다.
[0006]
건 부착의 강도는 경계면에서 미네랄화된 조직의 질에 의해 대부분 결정된다 [33, 34]. 건강한 건-골 치유 부착은 섬유연골 삽입부를 통과하여 해면골 내부로 미네랄 함량의 기울기를 가진다 [35]. Scl-Ab 치료로 인한 부착시 기계적 강도의 증가는 인접한 해면골에서 (마이크로CT로 측정됨) 뿐만 아니라 치유 경계면에서의 섬유연골에서의 개선된 미네랄화의 결과일 수 있다. 연골 및 섬유연골에서 세포외 매트릭스 마커인 아그리칸의 발현은, 8 주 치유 후 인공물삽입부에 인접한 미네랄화된 조직에서 Scl-Ab 치료시 유의하게 더 높았다 (도 6). 더욱이, 조직학적 절단면의 반-정량적 평가는 Scl-Ab 치료 4 및 8 주 치유 후 대조군과 비교하여 삽입 통합성을 포함한 건-골 치유 부착 성숙도에 있어서의 개선을 보여주었다.
[0007]
Scl-Ab 치료는 피하 주사를 통해 전신에 적용된다. 그러므로, 치유 경계면에 인접한 건 뿐만 아니라 다른 관절들에 있는 조직들을 포함한 모든 조직들 또한 Scl-Ab 치료를 받았다. 비-미네랄화된 조직들에 대한 Scl-Ab의 가능한 효과를 평가하기 위하여, 유전자 발현은 치유 경계면에 인접한 극상 건에서 조사되었다. Scl-Ab 치료는 건 조직에서 유전자들의 발현에 대한 유의한 효과를 보이지 않았으므로 (도 5), 가능한 오프-타겟 조직 치료 효과에 관한 문제를 경감시킨다. 그러나, Scl-Ab 치료는 건강한 건-골 치유 부착에서 모듈러스 및 강성도의 감소를 초래하였다 (도 2). 이러한 결과는 건-골 치유 동안 비스포스포네이트 치료가 강성도의 감소를 유발할 수 있다는 기존의 발견과 일치하는 것이다 [18]. 전형적인 생리학적 활성들에 관한 건 및 인대들의 고유한 기계적 안전성 요인으로 인해 [36], 강성도 및 모듈러스의 약간의 감소는 건강한 건이 부상을 쉽게 입도록 하지 않을 것이다.
[0008]
요약컨대, 본 출원에 제공된 데이터는 스클레로스틴 항체를 이용한 치료가 테스트한 동물 모델에서 대조군과 비교하여 개선된 건-골 치유 ㅂ착을 생성하였음을 입증한다. 예상한 대로, 스클레로스틴 항체는 인공물삽입부에 인접한 해면골 영역을 증가시켰다. 놀랍게도, 조직학적 평가 결과 스클레로스틴 항체 치료가 8 주 치유시 건과 골의 보다 우수한 통합을 촉진하였음을 보여주었다. 그러므로, 본 출원에 기재된 스클레로스틴 항체를 이용한 치료는 인접 삽입 부위에서 골 질량을 증가시킴으로써 뿐만 아니라, 부상입은 건의 조직학을 개선시킴으로써 건-골 치유 부착을 개선시킬 수 있다. 더욱이, 스클레로스틴 항체 치료는 파열된 건의 외과적 복원술에 앞서 일정 기간 동안 비하중-관련 골 손실을 방지하기 위하여 고려될 수 있다.
[0009]
참고문헌:
SEQUENCE LISTING
<110> AMGEN INC.
<120> METHOD OF IMPROVING CONNECTIVE TISSUE ATTACHMENT USING ANTI-SCLEROSTIN ANTIBODIES
<130> 31173/50928A
<150> 62/372,124
<151> 2016-08-08
<160> 809
<170> PatentIn version 3.5
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Gln Gly Trp Gln Ala Phe Lys Asn Asp Ala Thr Glu Ile Ile Pro Glu
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Leu Gly Glu Tyr Pro Glu Pro Pro Pro Glu Leu Glu Asn Asn Lys Thr
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Met Asn Arg Ala Glu Asn Gly Gly Arg Pro Pro His His Pro Phe Glu
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Thr Lys Asp Val Ser Glu Tyr Ser Cys Arg Glu Leu His Phe Thr Arg
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Tyr Val Thr Asp Gly Pro Cys Arg Ser Ala Lys Pro Val Thr Glu Leu
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Val Cys Ser Gly Gln Cys Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile
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Gly Arg Gly Lys Trp Trp Arg Pro Ser Gly Pro Asp Phe Arg Cys Ile
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Pro Asp Arg Tyr Arg Ala Gln Arg Val Gln Leu Leu Cys Pro Gly Gly
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Glu Ala Pro Arg Ala Arg Lys Val Arg Leu Val Ala Ser Cys Lys Cys
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Lys Arg Leu Thr Arg Phe His Asn Gln Ser Glu Leu Lys Asp Phe Gly
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Thr Glu Ala Ala Arg Pro Gln Lys Gly Arg Lys Pro Arg Pro Arg Ala
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Arg Ser Ala Lys Ala Asn Gln Ala Glu Leu Glu Asn Ala Tyr
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gatgtccaga tgattcagtc tccatcctcc ctgtctgcat ctttgggaga catagtcacc 60
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gggaaggctc ctaagctcct gatctatggt tcaagcaact tggaagatgg ggtcccatca 180
aggttcagtg gcagtagata tgggacagat ttcactctca ccatcagcag cctggaggat 240
gaagatctgg caacttattt ctgtctacaa catagttatc tcccgtacac gttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
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aaaccaggga aggctcctaa gctcctgatc tatggttcaa gcaacttgga agatggggtc 240
ccatcaaggt tcagtggcag tagatatggg acagatttca ctctcaccat cagcagcctg 300
gaggatgaag atctggcaac ttatttctgt ctacaacata gttatctccc gtacacgttc 360
ggagggggga ccaagctgga aataaaacgg gctgatgctg caccaactgt atccatcttc 420
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Met Glu Ile Arg Gly Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
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Ala Arg Asp Asp Tyr Asp Ala Ser Pro Phe Ala Tyr Trp Gly Gln Gly
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Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser Val Tyr
115 120 125
Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu
130 135 140
Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp
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Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser
180 185 190
Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser
195 200 205
Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys
210 215 220
Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
225 230 235 240
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
245 250 255
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
260 265 270
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
275 280 285
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
290 295 300
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
305 310 315 320
Ser Pro Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
325 330 335
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
340 345 350
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
355 360 365
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
370 375 380
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
385 390 395 400
Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
405 410 415
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
420 425 430
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 12
<211> 1332
<212> DNA
<213> Mus musculus
<400> 12
gaggtccagc tgcaacagtc tggacctgaa ctggtgacgc ctggggcttc agtgaagata 60
tcttgtaagg cttctggata cacattcact gaccactaca tgagctgggt gaagcagagt 120
catggaaaaa gccttgagtg gattggagat attaatccct attctggtga aactacctac 180
aaccagaagt tcaagggcac ggccacattg actgtagaca agtcttccag tatagcctac 240
atggagatcc gcggcctgac atctgaggac tctgcagtct attactgtgc aagagatgat 300
tacgacgcct ctccgtttgc ttactggggc caagggactc tggtcactgt ctctgcagcc 360
aaaacgacac ccccatctgt ctatccactg gcccctggat ctgctgccca aactaactcc 420
atggtgaccc tgggatgcct ggtcaagggc tatttccctg agccagtgac agtgacctgg 480
aactctggat ccctgtccag cggtgtgcac accttcccag ctgtcctgca gtctgacctc 540
tacactctga gcagctcagt gactgtcccc tccagcacct ggcccagcga gaccgtcacc 600
tgcaacgttg cccacccggc cagcagcacc aaggtggaca agaaaattgt gcccagggat 660
tgtggttgta agccttgcat atgtacagtc ccagaagtat catctgtctt catcttcccc 720
ccaaagccca aggatgtgct caccattact ctgactccta aggtcacgtg tgttgtggta 780
gacatcagca aggatgatcc cgaggtccag ttcagctggt ttgtagatga tgtggaggtg 840
cacacagctc agacgcaacc ccgggaggag cagttcaaca gcactttccg ctcagtcagt 900
gaacttccca tcatgcacca ggactggctc aatggcaagg agttcaaatg cagggtcaac 960
agtccagctt tccctgcccc catcgagaaa accatctcca aaaccaaagg cagaccgaag 1020
gctccacagg tgtacaccat tccacctccc aaggagcaga tggccaagga taaagtcagt 1080
ctgacctgca tgataacaga cttcttccct gaagacatta ctgtggagtg gcagtggaat 1140
gggcagccag cggagaacta caagaacact cagcccatca tggacacaga tggctcttac 1200
ttcatctaca gcaagctcaa tgtgcagaag agcaactggg aggcaggaaa tactttcacc 1260
tgctctgtgt tacatgaggg cctgcacaac caccatactg agaagagcct ctcccactct 1320
cctggtaaat ga 1332
<210> 13
<211> 462
<212> PRT
<213> Mus musculus
<400> 13
Met Arg Cys Arg Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Thr
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp His Tyr Met Ser Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Tyr Ser Gly Glu Thr Thr Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Thr Ala Thr Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Ile Ala Tyr Met Glu Ile Arg Gly Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Asp Tyr Asp Ala Ser Pro Phe Ala Tyr Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro
130 135 140
Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met
145 150 155 160
Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val
195 200 205
Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His
210 215 220
Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys
225 230 235 240
Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe
245 250 255
Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro
260 265 270
Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val
275 280 285
Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr
290 295 300
Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu
305 310 315 320
Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys
325 330 335
Arg Val Asn Ser Pro Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro
355 360 365
Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile
370 375 380
Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly
385 390 395 400
Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp
405 410 415
Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp
420 425 430
Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His
435 440 445
Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 14
<211> 1389
<212> DNA
<213> Mus musculus
<400> 14
atgagatgca ggtggatctt tctctttctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgaactg gtgacgcctg gggcttcagt gaagatatct 120
tgtaaggctt ctggatacac attcactgac cactacatga gctgggtgaa gcagagtcat 180
ggaaaaagcc ttgagtggat tggagatatt aatccctatt ctggtgaaac tacctacaac 240
cagaagttca agggcacggc cacattgact gtagacaagt cttccagtat agcctacatg 300
gagatccgcg gcctgacatc tgaggactct gcagtctatt actgtgcaag agatgattac 360
gacgcctctc cgtttgctta ctggggccaa gggactctgg tcactgtctc tgcagccaaa 420
acgacacccc catctgtcta tccactggcc cctggatctg ctgcccaaac taactccatg 480
gtgaccctgg gatgcctggt caagggctat ttccctgagc cagtgacagt gacctggaac 540
tctggatccc tgtccagcgg tgtgcacacc ttcccagctg tcctgcagtc tgacctctac 600
actctgagca gctcagtgac tgtcccctcc agcacctggc ccagcgagac cgtcacctgc 660
aacgttgccc acccggccag cagcaccaag gtggacaaga aaattgtgcc cagggattgt 720
ggttgtaagc cttgcatatg tacagtccca gaagtatcat ctgtcttcat cttcccccca 780
aagcccaagg atgtgctcac cattactctg actcctaagg tcacgtgtgt tgtggtagac 840
atcagcaagg atgatcccga ggtccagttc agctggtttg tagatgatgt ggaggtgcac 900
acagctcaga cgcaaccccg ggaggagcag ttcaacagca ctttccgctc agtcagtgaa 960
cttcccatca tgcaccagga ctggctcaat ggcaaggagt tcaaatgcag ggtcaacagt 1020
ccagctttcc ctgcccccat cgagaaaacc atctccaaaa ccaaaggcag accgaaggct 1080
ccacaggtgt acaccattcc acctcccaag gagcagatgg ccaaggataa agtcagtctg 1140
acctgcatga taacagactt cttccctgaa gacattactg tggagtggca gtggaatggg 1200
cagccagcgg agaactacaa gaacactcag cccatcatgg acacagatgg ctcttacttc 1260
atctacagca agctcaatgt gcagaagagc aactgggagg caggaaatac tttcacctgc 1320
tctgtgttac atgagggcct gcacaaccac catactgaga agagcctctc ccactctcct 1380
ggtaaatga 1389
<210> 15
<211> 218
<212> PRT
<213> Mus musculus
<400> 15
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Thr Val Ser Leu Gly
1 5 10 15
Leu Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp
20 25 30
Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala
50 55 60
Arg Phe Ser Gly Asn Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His
65 70 75 80
Pro Val Glu Glu Glu Asp Ala Val Thr Tyr Tyr Cys Gln Gln Ser Asn
85 90 95
Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105 110
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
115 120 125
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
130 135 140
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
145 150 155 160
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
165 170 175
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
180 185 190
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
195 200 205
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 16
<211> 657
<212> DNA
<213> Mus musculus
<400> 16
gacattgtgc tgacccaatc tccagcttct ttgactgtgt ctctaggcct gagggccacc 60
atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggtac 120
cagcagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 180
gggatcccag ccaggtttag tggcaatggg tctgggacag acttcaccct caacatccat 240
cctgtggagg aggaggatgc tgtaacctat tactgtcaac aaagtaatga ggatccgtgg 300
acgttcggtg gaggcaccaa gctggaaatc aaacgggctg atgctgcacc aactgtatcc 360
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 420
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 480
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 540
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 600
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 657
<210> 17
<211> 238
<212> PRT
<213> Mus musculus
<400> 17
Met Glu Thr Asp Thr Ile Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Thr
20 25 30
Val Ser Leu Gly Leu Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser
35 40 45
Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser
65 70 75 80
Gly Ile Pro Ala Arg Phe Ser Gly Asn Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Val Thr Tyr Tyr Cys
100 105 110
Gln Gln Ser Asn Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro
130 135 140
Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu
145 150 155 160
Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly
165 170 175
Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp
195 200 205
Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr
210 215 220
Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 18
<211> 717
<212> DNA
<213> Mus musculus
<400> 18
atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60
gacattgtgc tgacccaatc tccagcttct ttgactgtgt ctctaggcct gagggccacc 120
atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggtac 180
cagcagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 240
gggatcccag ccaggtttag tggcaatggg tctgggacag acttcaccct caacatccat 300
cctgtggagg aggaggatgc tgtaacctat tactgtcaac aaagtaatga ggatccgtgg 360
acgttcggtg gaggcaccaa gctggaaatc aaacgggctg atgctgcacc aactgtatcc 420
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 480
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 540
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 600
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 660
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 717
<210> 19
<211> 449
<212> PRT
<213> Mus musculus
<400> 19
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Cys
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 Phe Asn Gly Gly Thr Thr 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 Asp Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser His Tyr Tyr Phe Asp Gly Arg Val Pro Trp Asp Ala Met
100 105 110
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr
115 120 125
Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
130 135 140
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
180 185 190
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
195 200 205
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
210 215 220
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
245 250 255
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
260 265 270
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
290 295 300
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
340 345 350
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
355 360 365
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
370 375 380
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
385 390 395 400
Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys
405 410 415
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
420 425 430
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
435 440 445
Lys
<210> 20
<211> 1350
<212> DNA
<213> Mus musculus
<400> 20
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctgggacttc agtgaagatg 60
tcctgtaagg cttctggata cacattcact gactgctaca tgaactgggt gaagcagagc 120
catgggaaga gccttgaatg gattggagat attaatcctt tcaacggtgg tactacctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca aatcctccag cacagcctac 240
atgcagctca acagcctgac atctgacgac tctgcagtct attactgtgc aagatcccat 300
tattacttcg atggtagagt cccttgggat gctatggact actggggtca aggaacctca 360
gtcaccgtct cctcagccaa aacgacaccc ccatctgtct atccactggc ccctggatct 420
gctgcccaaa ctaactccat ggtgaccctg ggatgcctgg tcaagggcta tttccctgag 480
ccagtgacag tgacctggaa ctctggatcc ctgtccagcg gtgtgcacac cttcccagct 540
gtcctgcagt ctgacctcta cactctgagc agctcagtga ctgtcccctc cagcacctgg 600
cccagcgaga ccgtcacctg caacgttgcc cacccggcca gcagcaccaa ggtggacaag 660
aaaattgtgc ccagggattg tggttgtaag ccttgcatat gtacagtccc agaagtatca 720
tctgtcttca tcttcccccc aaagcccaag gatgtgctca ccattactct gactcctaag 780
gtcacgtgtg ttgtggtaga catcagcaag gatgatcccg aggtccagtt cagctggttt 840
gtagatgatg tggaggtgca cacagctcag acgcaacccc gggaggagca gttcaacagc 900
actttccgct cagtcagtga acttcccatc atgcaccagg actggctcaa tggcaaggag 960
ttcaaatgca gggtcaacag tgcagctttc cctgccccca tcgagaaaac catctccaaa 1020
accaaaggca gaccgaaggc tccacaggtg tacaccattc cacctcccaa ggagcagatg 1080
gccaaggata aagtcagtct gacctgcatg ataacagact tcttccctga agacattact 1140
gtggagtggc agtggaatgg gcagccagcg gagaactaca agaacactca gcccatcatg 1200
gacacagatg gctcttactt catctacagc aagctcaatg tgcagaagag caactgggag 1260
gcaggaaata ctttcacctg ctctgtgtta catgagggcc tgcacaacca ccatactgag 1320
aagagcctct cccactctcc tggtaaatga 1350
<210> 21
<211> 468
<212> PRT
<213> Mus musculus
<400> 21
Met Gly Trp Asn Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Tyr Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Thr Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Cys Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Phe Asn Gly Gly Thr Thr Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Asp Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser His Tyr Tyr Phe Asp Gly Arg Val Pro Trp
115 120 125
Asp Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
130 135 140
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
145 150 155 160
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
195 200 205
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
210 215 220
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
225 230 235 240
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
245 250 255
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
260 265 270
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
275 280 285
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
290 295 300
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
355 360 365
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
370 375 380
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
385 390 395 400
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
405 410 415
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn
420 425 430
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
435 440 445
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
450 455 460
Ser Pro Gly Lys
465
<210> 22
<211> 1407
<212> DNA
<213> Mus musculus
<400> 22
atgggatgga actggatctt tctcttcctc ttgtcaggaa ctgcaggtgt ctactctgag 60
gtccagctgc aacaatctgg acctgagctg gtgaagcctg ggacttcagt gaagatgtcc 120
tgtaaggctt ctggatacac attcactgac tgctacatga actgggtgaa gcagagccat 180
gggaagagcc ttgaatggat tggagatatt aatcctttca acggtggtac tacctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaaat cctccagcac agcctacatg 300
cagctcaaca gcctgacatc tgacgactct gcagtctatt actgtgcaag atcccattat 360
tacttcgatg gtagagtccc ttgggatgct atggactact ggggtcaagg aacctcagtc 420
accgtctcct cagccaaaac gacaccccca tctgtctatc cactggcccc tggatctgct 480
gcccaaacta actccatggt gaccctggga tgcctggtca agggctattt ccctgagcca 540
gtgacagtga cctggaactc tggatccctg tccagcggtg tgcacacctt cccagctgtc 600
ctgcagtctg acctctacac tctgagcagc tcagtgactg tcccctccag cacctggccc 660
agcgagaccg tcacctgcaa cgttgcccac ccggccagca gcaccaaggt ggacaagaaa 720
attgtgccca gggattgtgg ttgtaagcct tgcatatgta cagtcccaga agtatcatct 780
gtcttcatct tccccccaaa gcccaaggat gtgctcacca ttactctgac tcctaaggtc 840
acgtgtgttg tggtagacat cagcaaggat gatcccgagg tccagttcag ctggtttgta 900
gatgatgtgg aggtgcacac agctcagacg caaccccggg aggagcagtt caacagcact 960
ttccgctcag tcagtgaact tcccatcatg caccaggact ggctcaatgg caaggagttc 1020
aaatgcaggg tcaacagtgc agctttccct gcccccatcg agaaaaccat ctccaaaacc 1080
aaaggcagac cgaaggctcc acaggtgtac accattccac ctcccaagga gcagatggcc 1140
aaggataaag tcagtctgac ctgcatgata acagacttct tccctgaaga cattactgtg 1200
gagtggcagt ggaatgggca gccagcggag aactacaaga acactcagcc catcatggac 1260
acagatggct cttacttcat ctacagcaag ctcaatgtgc agaagagcaa ctgggaggca 1320
ggaaatactt tcacctgctc tgtgttacat gagggcctgc acaaccacca tactgagaag 1380
agcctctccc actctcctgg taaatga 1407
<210> 23
<211> 217
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 23
Ala Gln Val Leu Thr Gln Thr Pro Ala Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Asn Cys Gln Ser Ser Gln Ser Val Tyr Asp Asn
20 25 30
Asn Trp Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu
35 40 45
Leu Ile Tyr Asp Ala Ser Asp Leu Ala Ser Gly Val Pro Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Gly Val
65 70 75 80
Gln Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gly Ala Tyr Asn Asp
85 90 95
Val Ile Tyr Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys Arg Thr
100 105 110
Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu
115 120 125
Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro
130 135 140
Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn
145 150 155 160
Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr
165 170 175
Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His
180 185 190
Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile
195 200 205
Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 24
<211> 654
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Rabbit-mouse chimera
<400> 24
gcgcaagtgc tgacccagac tccagcctcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcaattgcc agtccagtca gagtgtttat gataacaact ggttagcctg gtttcagcag 120
aaaccagggc agcctcccaa gctcctgatt tatgatgcat ccgatctggc atctggggtc 180
ccatcgcggt tcagtggcag tggatctggg acacagttca ctctcaccat cagcggcgtg 240
cagtgtgccg atgctgccac ttactactgt caaggcgctt ataatgatgt tatttatgct 300
ttcggcggag ggaccgaggt ggtggtcaaa cgtacggatg ctgcaccaac tgtatccatc 360
ttcccaccat ccagtgagca gttaacatct ggaggtgcct cagtcgtgtg cttcttgaac 420
aacttctacc ccaaagacat caatgtcaag tggaagattg atggcagtga acgacaaaat 480
ggcgtcctga acagttggac tgatcaggac agcaaagaca gcacctacag catgagcagc 540
accctcacgt tgaccaagga cgagtatgaa cgacataaca gctatacctg tgaggccact 600
cacaagacat caacttcacc cattgtcaag agcttcaaca ggaatgagtg ttag 654
<210> 25
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 25
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 Ala Ser
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 Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asp Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Ser 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 Ala Tyr Asn Asp Val Ile Tyr Ala Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Arg Thr Asp Ala Ala Pro Thr Val Ser Ile Phe Pro
130 135 140
Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe
145 150 155 160
Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp
165 170 175
Gly Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp
180 185 190
Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys
195 200 205
Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys
210 215 220
Thr Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 26
<211> 720
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> misc_feature
<223> Rabbit-mouse chimera
<400> 26
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcgc aagtgctgac ccagactcca gcctccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgccagtc cagtcagagt gtttatgata acaactggtt agcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatttatg atgcatccga tctggcatct 240
ggggtcccat cgcggttcag tggcagtgga tctgggacac agttcactct caccatcagc 300
ggcgtgcagt gtgccgatgc tgccacttac tactgtcaag gcgcttataa tgatgttatt 360
tatgctttcg gcggagggac cgaggtggtg gtcaaacgta cggatgctgc accaactgta 420
tccatcttcc caccatccag tgagcagtta acatctggag gtgcctcagt cgtgtgcttc 480
ttgaacaact tctaccccaa agacatcaat gtcaagtgga agattgatgg cagtgaacga 540
caaaatggcg tcctgaacag ttggactgat caggacagca aagacagcac ctacagcatg 600
agcagcaccc tcacgttgac caaggacgag tatgaacgac ataacagcta tacctgtgag 660
gccactcaca agacatcaac ttcacccatt gtcaagagct tcaacaggaa tgagtgttag 720
<210> 27
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody
<400> 27
Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser Ser Tyr Trp
20 25 30
Met Asn Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Met Asp Leu Lys Met Thr
65 70 75 80
Ser Leu Thr Thr Gly Asp Thr Ala Arg Tyr Phe Cys Ala Arg Asn Trp
85 90 95
Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
100 105 110
Lys Gly Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
115 120 125
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
130 135 140
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
145 150 155 160
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
165 170 175
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
180 185 190
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
195 200 205
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
210 215 220
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
225 230 235 240
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
245 250 255
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
260 265 270
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
275 280 285
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
290 295 300
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
305 310 315 320
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
325 330 335
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
340 345 350
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
355 360 365
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
370 375 380
Asn Thr Asn Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys
385 390 395 400
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
405 410 415
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
420 425 430
Lys
<210> 28
<211> 1302
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody
<400> 28
cagtcgctgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagcct ctggattctc cctcagtagt tattggatga actgggtccg ccaggctcca 120
ggggaggggc tggaatggat cggaaccatt gattctggtg gtaggacgga ctacgcgagc 180
tgggcaaaag gccgattcac catctccaga acctcgacta cgatggatct gaaaatgacc 240
agtctgacga ccggggacac ggcccgttat ttctgtgcca gaaattggaa cttgtggggc 300
caaggcaccc tcgtcaccgt ctcgagcgct tctacaaagg gcccatctgt ctatccactg 360
gcccctggat ctgctgccca aactaactcc atggtgaccc tgggatgcct ggtcaagggc 420
tatttccctg agccagtgac agtgacctgg aactctggat ccctgtccag cggtgtgcac 480
accttcccag ctgtcctgca gtctgacctc tacactctga gcagctcagt gactgtcccc 540
tccagcacct ggcccagcga gaccgtcacc tgcaacgttg cccacccggc cagcagcacc 600
aaggtggaca agaaaattgt gcccagggat tgtggttgta agccttgcat atgtacagtc 660
ccagaagtat catctgtctt catcttcccc ccaaagccca aggatgtgct caccattact 720
ctgactccta aggtcacgtg tgttgtggta gacatcagca aggatgatcc cgaggtccag 780
ttcagctggt ttgtagatga tgtggaggtg cacacagctc agacgcaacc ccgggaggag 840
cagttcaaca gcactttccg ctcagtcagt gaacttccca tcatgcacca ggactggctc 900
aatggcaagg agttcaaatg cagggtcaac agtgcagctt tccctgcccc catcgagaaa 960
accatctcca aaaccaaagg cagaccgaag gctccacagg tgtacaccat tccacctccc 1020
aaggagcaga tggccaagga taaagtcagt ctgacctgca tgataacaga cttcttccct 1080
gaagacatta ctgtggagtg gcagtggaat gggcagccag cggagaacta caagaacact 1140
cagcccatca tggacacaga tggctcttac ttcgtctaca gcaagctcaa tgtgcagaag 1200
agcaactggg aggcaggaaa tactttcacc tgctctgtgt tacatgaggg cctgcacaac 1260
caccatactg agaagagcct ctcccactct cctggtaaat ga 1302
<210> 29
<211> 452
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody
<400> 29
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val His Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Trp Ile Gly Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Met Asp Leu
85 90 95
Lys Met Thr Ser Leu Thr Thr Gly Asp Thr Ala Arg Tyr Phe Cys Ala
100 105 110
Arg Asn Trp Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
Ala Ser Thr Lys Gly Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
130 135 140
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
145 150 155 160
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
165 170 175
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
180 185 190
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
195 200 205
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
210 215 220
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
225 230 235 240
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
245 250 255
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
260 265 270
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
275 280 285
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
290 295 300
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
340 345 350
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
355 360 365
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
370 375 380
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
385 390 395 400
Pro Ile Met Asn Thr Asn Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn
405 410 415
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
420 425 430
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 30
<211> 1359
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody
<400> 30
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccactgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtagttat tggatgaact gggtccgcca ggctccaggg 180
gaggggctgg aatggatcgg aaccattgat tctggtggta ggacggacta cgcgagctgg 240
gcaaaaggcc gattcaccat ctccagaacc tcgactacga tggatctgaa aatgaccagt 300
ctgacgaccg gggacacggc ccgttatttc tgtgccagaa attggaactt gtggggccaa 360
ggcaccctcg tcaccgtctc gagcgcttct acaaagggcc catctgtcta tccactggcc 420
cctggatctg ctgcccaaac taactccatg gtgaccctgg gatgcctggt caagggctat 480
ttccctgagc cagtgacagt gacctggaac tctggatccc tgtccagcgg tgtgcacacc 540
ttcccagctg tcctgcagtc tgacctctac actctgagca gctcagtgac tgtcccctcc 600
agcacctggc ccagcgagac cgtcacctgc aacgttgccc acccggccag cagcaccaag 660
gtggacaaga aaattgtgcc cagggattgt ggttgtaagc cttgcatatg tacagtccca 720
gaagtatcat ctgtcttcat cttcccccca aagcccaagg atgtgctcac cattactctg 780
actcctaagg tcacgtgtgt tgtggtagac atcagcaagg atgatcccga ggtccagttc 840
agctggtttg tagatgatgt ggaggtgcac acagctcaga cgcaaccccg ggaggagcag 900
ttcaacagca ctttccgctc agtcagtgaa cttcccatca tgcaccagga ctggctcaat 960
ggcaaggagt tcaaatgcag ggtcaacagt gcagctttcc ctgcccccat cgagaaaacc 1020
atctccaaaa ccaaaggcag accgaaggct ccacaggtgt acaccattcc acctcccaag 1080
gagcagatgg ccaaggataa agtcagtctg acctgcatga taacagactt cttccctgaa 1140
gacattactg tggagtggca gtggaatggg cagccagcgg agaactacaa gaacactcag 1200
cccatcatgg acacagatgg ctcttacttc gtctacagca agctcaatgt gcagaagagc 1260
aactgggagg caggaaatac tttcacctgc tctgtgttac atgagggcct gcacaaccac 1320
catactgaga agagcctctc ccactctcct ggtaaatga 1359
<210> 31
<211> 213
<212> PRT
<213> Mus musculus
<400> 31
Gln Ile Val Leu Thr Gln Ser Pro Thr Ile Val Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Leu Ile Cys Ser Ala Ser Ser Ser Val Ser Phe Val
20 25 30
Asp Trp Phe Gln Gln Lys Pro Gly Thr Ser Pro Lys Arg Trp Ile Tyr
35 40 45
Arg Thr Ser Asn Leu Gly Phe Gly Val Pro Ala Arg Phe Ser Gly Gly
50 55 60
Gly Ser Gly Thr Ser His Ser Leu Thr Ile Ser Arg Met Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Arg Ser Thr Tyr Pro Pro Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 32
<211> 642
<212> DNA
<213> Mus musculus
<400> 32
caaattgttc tcacccagtc tccaacaatc gtgtctgcat ctccagggga gaaggtcacc 60
ctaatctgca gtgccagttc aagtgtaagt ttcgtggact ggttccagca gaagccaggc 120
acttctccca aacgctggat ttacagaaca tccaacctgg gttttggagt ccctgctcgc 180
ttcagtggcg gtggatctgg gacctctcac tctctcacaa tcagccgaat ggaggctgaa 240
gatgctgcca cttattactg ccagcaaagg agtacttacc cacccacgtt cggtgctggg 300
accaagctgg aactgaaacg ggctgatgct gcaccaactg tatccatctt cccaccatcc 360
agtgagcagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420
aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480
agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540
accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600
acttcaccca ttgtcaagag cttcaacagg aatgagtgtt ag 642
<210> 33
<211> 235
<212> PRT
<213> Mus musculus
<400> 33
Met His Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Val Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Thr Ile
20 25 30
Val Ser Ala Ser Pro Gly Glu Lys Val Thr Leu Ile Cys Ser Ala Ser
35 40 45
Ser Ser Val Ser Phe Val Asp Trp Phe Gln Gln Lys Pro Gly Thr Ser
50 55 60
Pro Lys Arg Trp Ile Tyr Arg Thr Ser Asn Leu Gly Phe Gly Val Pro
65 70 75 80
Ala Arg Phe Ser Gly Gly Gly Ser Gly Thr Ser His Ser Leu Thr Ile
85 90 95
Ser Arg Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Arg
100 105 110
Ser Thr Tyr Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
115 120 125
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
130 135 140
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
145 150 155 160
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
165 170 175
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
195 200 205
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
210 215 220
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 34
<211> 708
<212> DNA
<213> Mus musculus
<400> 34
atgcattttc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt catagtgtcc 60
agagggcaaa ttgttctcac ccagtctcca acaatcgtgt ctgcatctcc aggggagaag 120
gtcaccctaa tctgcagtgc cagttcaagt gtaagtttcg tggactggtt ccagcagaag 180
ccaggcactt ctcccaaacg ctggatttac agaacatcca acctgggttt tggagtccct 240
gctcgcttca gtggcggtgg atctgggacc tctcactctc tcacaatcag ccgaatggag 300
gctgaagatg ctgccactta ttactgccag caaaggagta cttacccacc cacgttcggt 360
gctgggacca agctggaact gaaacgggct gatgctgcac caactgtatc catcttccca 420
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 480
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 540
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 600
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 660
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 708
<210> 35
<211> 449
<212> PRT
<213> Mus musculus
<400> 35
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 Ser
20 25 30
Gly Met Gly Val Gly Trp Ile Arg His Pro Ser Gly Lys Asn Leu Glu
35 40 45
Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Val
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Asn Ser 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 Ile Glu Asp Phe Asp Tyr Asp Glu Glu Tyr Tyr Ala Met
100 105 110
Asp Tyr Trp Gly Gln Gly Thr Ser Val Ile Val Ser Ser Ala Lys Thr
115 120 125
Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
130 135 140
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
180 185 190
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
195 200 205
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
210 215 220
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
245 250 255
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
260 265 270
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
290 295 300
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
340 345 350
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
355 360 365
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
370 375 380
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
385 390 395 400
Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys
405 410 415
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
420 425 430
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
435 440 445
Lys
<210> 36
<211> 1350
<212> DNA
<213> Mus musculus
<400> 36
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg 60
acttgttctt tctctgggtt ttcactgagc acttctggta tgggtgtagg ctggattcgt 120
cacccatcag ggaagaatct ggagtggctg gcacacattt ggtgggatga tgtcaagcgc 180
tataacccag tcctgaagag ccgactgact atctccaagg atacctccaa cagccaggta 240
ttcctcaaga tcgccaatgt ggacactgca gatactgcca catactactg tgctcgaata 300
gaggactttg attacgacga ggagtattat gctatggact actggggtca aggaacctca 360
gtcatcgtct cctcagccaa aacgacaccc ccatctgtct atccactggc ccctggatct 420
gctgcccaaa ctaactccat ggtgaccctg ggatgcctgg tcaagggcta tttccctgag 480
ccagtgacag tgacctggaa ctctggatcc ctgtccagcg gtgtgcacac cttcccagct 540
gtcctgcagt ctgacctcta cactctgagc agctcagtga ctgtcccctc cagcacctgg 600
cccagcgaga ccgtcacctg caacgttgcc cacccggcca gcagcaccaa ggtggacaag 660
aaaattgtgc ccagggattg tggttgtaag ccttgcatat gtacagtccc agaagtatca 720
tctgtcttca tcttcccccc aaagcccaag gatgtgctca ccattactct gactcctaag 780
gtcacgtgtg ttgtggtaga catcagcaag gatgatcccg aggtccagtt cagctggttt 840
gtagatgatg tggaggtgca cacagctcag acgcaacccc gggaggagca gttcaacagc 900
actttccgct cagtcagtga acttcccatc atgcaccagg actggctcaa tggcaaggag 960
ttcaaatgca gggtcaacag tgcagctttc cctgccccca tcgagaaaac catctccaaa 1020
accaaaggca gaccgaaggc tccacaggtg tacaccattc cacctcccaa ggagcagatg 1080
gccaaggata aagtcagtct gacctgcatg ataacagact tcttccctga agacattact 1140
gtggagtggc agtggaatgg gcagccagcg gagaactaca agaacactca gcccatcatg 1200
gacacagatg gctcttactt cgtctacagc aagctcaatg tgcagaagag caactgggag 1260
gcaggaaata ctttcacctg ctctgtgtta catgagggcc tgcacaacca ccatactgag 1320
aagagcctct cccactctcc tggtaaatga 1350
<210> 37
<211> 468
<212> PRT
<213> Mus musculus
<400> 37
Met Gly Arg Leu Thr Ser Ser Phe Leu Leu Leu Ile Val Pro Ala Tyr
1 5 10 15
Val Leu Ser Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln
20 25 30
Pro Ser Gln Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu
35 40 45
Ser Thr Ser Gly Met Gly Val Gly Trp Ile Arg His Pro Ser Gly Lys
50 55 60
Asn Leu Glu Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr
65 70 75 80
Asn Pro Val Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Asn
85 90 95
Ser Gln Val Phe Leu Lys Ile Ala Asn Val Asp Thr Ala Asp Thr Ala
100 105 110
Thr Tyr Tyr Cys Ala Arg Ile Glu Asp Phe Asp Tyr Asp Glu Glu Tyr
115 120 125
Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Ile Val Ser Ser
130 135 140
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
145 150 155 160
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
195 200 205
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
210 215 220
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
225 230 235 240
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
245 250 255
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
260 265 270
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
275 280 285
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
290 295 300
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
355 360 365
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
370 375 380
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
385 390 395 400
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
405 410 415
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn
420 425 430
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
435 440 445
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
450 455 460
Ser Pro Gly Lys
465
<210> 38
<211> 1407
<212> DNA
<213> Mus musculus
<400> 38
atgggcaggc ttacttcttc attcctgcta ctgattgtcc ctgcatatgt cctgtcccag 60
gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgact 120
tgttctttct ctgggttttc actgagcact tctggtatgg gtgtaggctg gattcgtcac 180
ccatcaggga agaatctgga gtggctggca cacatttggt gggatgatgt caagcgctat 240
aacccagtcc tgaagagccg actgactatc tccaaggata cctccaacag ccaggtattc 300
ctcaagatcg ccaatgtgga cactgcagat actgccacat actactgtgc tcgaatagag 360
gactttgatt acgacgagga gtattatgct atggactact ggggtcaagg aacctcagtc 420
atcgtctcct cagccaaaac gacaccccca tctgtctatc cactggcccc tggatctgct 480
gcccaaacta actccatggt gaccctggga tgcctggtca agggctattt ccctgagcca 540
gtgacagtga cctggaactc tggatccctg tccagcggtg tgcacacctt cccagctgtc 600
ctgcagtctg acctctacac tctgagcagc tcagtgactg tcccctccag cacctggccc 660
agcgagaccg tcacctgcaa cgttgcccac ccggccagca gcaccaaggt ggacaagaaa 720
attgtgccca gggattgtgg ttgtaagcct tgcatatgta cagtcccaga agtatcatct 780
gtcttcatct tccccccaaa gcccaaggat gtgctcacca ttactctgac tcctaaggtc 840
acgtgtgttg tggtagacat cagcaaggat gatcccgagg tccagttcag ctggtttgta 900
gatgatgtgg aggtgcacac agctcagacg caaccccggg aggagcagtt caacagcact 960
ttccgctcag tcagtgaact tcccatcatg caccaggact ggctcaatgg caaggagttc 1020
aaatgcaggg tcaacagtgc agctttccct gcccccatcg agaaaaccat ctccaaaacc 1080
aaaggcagac cgaaggctcc acaggtgtac accattccac ctcccaagga gcagatggcc 1140
aaggataaag tcagtctgac ctgcatgata acagacttct tccctgaaga cattactgtg 1200
gagtggcagt ggaatgggca gccagcggag aactacaaga acactcagcc catcatggac 1260
acagatggct cttacttcgt ctacagcaag ctcaatgtgc agaagagcaa ctgggaggca 1320
ggaaatactt tcacctgctc tgtgttacat gagggcctgc acaaccacca tactgagaag 1380
agcctctccc actctcctgg taaatga 1407
<210> 39
<211> 5
<212> PRT
<213> Mus musculus
<400> 39
Asp His Tyr Met Ser
1 5
<210> 40
<211> 17
<212> PRT
<213> Mus musculus
<400> 40
Asp Ile Asn Pro Tyr Ser Gly Glu Thr Thr Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 41
<211> 10
<212> PRT
<213> Mus musculus
<400> 41
Asp Asp Tyr Asp Ala Ser Pro Phe Ala Tyr
1 5 10
<210> 42
<211> 11
<212> PRT
<213> Mus musculus
<400> 42
Gln Ala Ser Gln Gly Thr Ser Ile Asn Leu Asn
1 5 10
<210> 43
<211> 7
<212> PRT
<213> Mus musculus
<400> 43
Gly Ser Ser Asn Leu Glu Asp
1 5
<210> 44
<211> 9
<212> PRT
<213> Mus musculus
<400> 44
Leu Gln His Ser Tyr Leu Pro Tyr Thr
1 5
<210> 45
<211> 5
<212> PRT
<213> Mus musculus
<400> 45
Asp Cys Tyr Met Asn
1 5
<210> 46
<211> 17
<212> PRT
<213> Mus musculus
<400> 46
Asp Ile Asn Pro Phe Asn Gly Gly Thr Thr Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 47
<211> 16
<212> PRT
<213> Mus musculus
<400> 47
Ser His Tyr Tyr Phe Asp Gly Arg Val Pro Trp Asp Ala Met Asp Tyr
1 5 10 15
<210> 48
<211> 15
<212> PRT
<213> Mus musculus
<400> 48
Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn
1 5 10 15
<210> 49
<211> 7
<212> PRT
<213> Mus musculus
<400> 49
Ala Ala Ser Asn Leu Glu Ser
1 5
<210> 50
<211> 9
<212> PRT
<213> Mus musculus
<400> 50
Gln Gln Ser Asn Glu Asp Pro Trp Thr
1 5
<210> 51
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 51
Ser Tyr Trp Met Asn
1 5
<210> 52
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 52
Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 53
<211> 4
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 53
Asn Trp Asn Leu
1
<210> 54
<211> 13
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 54
Gln Ser Ser Gln Ser Val Tyr Asp Asn Asn Trp Leu Ala
1 5 10
<210> 55
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 55
Asp Ala Ser Asp Leu Ala Ser
1 5
<210> 56
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Rabbit-mouse chimera
<400> 56
Gln Gly Ala Tyr Asn Asp Val Ile Tyr Ala
1 5 10
<210> 57
<211> 7
<212> PRT
<213> Mus musculus
<400> 57
Thr Ser Gly Met Gly Val Gly
1 5
<210> 58
<211> 16
<212> PRT
<213> Mus musculus
<400> 58
His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Val Leu Lys Ser
1 5 10 15
<210> 59
<211> 14
<212> PRT
<213> Mus musculus
<400> 59
Glu Asp Phe Asp Tyr Asp Glu Glu Tyr Tyr Ala Met Asp Tyr
1 5 10
<210> 60
<211> 10
<212> PRT
<213> Mus musculus
<400> 60
Ser Ala Ser Ser Ser Val Ser Phe Val Asp
1 5 10
<210> 61
<211> 7
<212> PRT
<213> Mus musculus
<400> 61
Arg Thr Ser Asn Leu Gly Phe
1 5
<210> 62
<211> 9
<212> PRT
<213> Mus musculus
<400> 62
Gln Gln Arg Ser Thr Tyr Pro Pro Thr
1 5
<210> 63
<211> 20
<212> PRT
<213> Homo sapiens
<400> 63
Cys Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp
1 5 10 15
Trp Arg Pro Ser
20
<210> 64
<211> 20
<212> PRT
<213> Homo sapiens
<400> 64
Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp
1 5 10 15
Arg Pro Ser Gly
20
<210> 65
<211> 20
<212> PRT
<213> Homo sapiens
<400> 65
Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg
1 5 10 15
Pro Ser Gly Pro
20
<210> 66
<211> 20
<212> PRT
<213> Homo sapiens
<400> 66
Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro
1 5 10 15
Ser Gly Pro Asp
20
<210> 67
<211> 20
<212> PRT
<213> Homo sapiens
<400> 67
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
1 5 10 15
Gly Pro Asp Phe
20
<210> 68
<211> 20
<212> PRT
<213> Homo sapiens
<400> 68
Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser Gly
1 5 10 15
Pro Asp Phe Arg
20
<210> 69
<211> 20
<212> PRT
<213> Homo sapiens
<400> 69
Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser Gly Pro
1 5 10 15
Asp Phe Arg Cys
20
<210> 70
<211> 14
<212> PRT
<213> Homo sapiens
<400> 70
Ser Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys
1 5 10
<210> 71
<211> 7
<212> PRT
<213> Homo sapiens
<400> 71
Leu Val Ala Ser Cys Lys Cys
1 5
<210> 72
<211> 8
<212> PRT
<213> Homo sapiens
<400> 72
Cys Arg Glu Leu His Phe Thr Arg
1 5
<210> 73
<211> 7
<212> PRT
<213> Homo sapiens
<400> 73
Cys Ile Pro Asp Arg Tyr Arg
1 5
<210> 74
<211> 399
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 74
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgctc aagttctgac ccagagtcca agcagtctct ccgccagcgt aggcgatcgt 120
gtgactatta cctgtcaatc tagtcagagc gtgtatgata acaattggct ggcgtggtac 180
cagcaaaaac cgggcaaagc cccgaagctg ctcatctatg acgcgtccga tctggctagc 240
ggtgtgccaa gccgtttcag tggcagtggc agcggtactg actttaccct cacaatttcg 300
tctctccagc cggaagattt cgccacttac tattgtcaag gtgcttacaa cgatgtgatt 360
tatgccttcg gtcagggcac taaagtagaa atcaaacgt 399
<210> 75
<211> 133
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 75
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 Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 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 Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asp Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Ala Tyr Asn Asp Val Ile Tyr Ala Phe Gly Gln Gly Thr Lys
115 120 125
Val Glu Ile Lys Arg
130
<210> 76
<211> 393
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 76
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccactgtgag 60
gtgcagctgt tggagtctgg aggcgggctt gtccagcctg gagggagcct gcgtctctct 120
tgtgcagcaa gcggcttcag cttatcctct tactggatga attgggtgcg gcaggcacct 180
gggaagggcc tggagtgggt gggcaccatt gattccggag gccgtacaga ctacgcgtct 240
tgggcaaagg gccgtttcac catttcccgc gacaactcca aaaataccat gtacctccag 300
atgaactctc tccgcgcaga ggacacagca cgttattact gtgcacgcaa ctggaatctg 360
tggggtcaag gtactcttgt aacagtctcg agc 393
<210> 77
<211> 131
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 77
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val His Cys Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu
35 40 45
Ser Ser Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Gly Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Met Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Arg Tyr
100 105 110
Tyr Cys Ala Arg Asn Trp Asn Leu Trp Gly Gln Gly Thr Leu Val Thr
115 120 125
Val Ser Ser
130
<210> 78
<211> 11
<212> PRT
<213> Mus musculus
<400> 78
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 79
<211> 7
<212> PRT
<213> Mus musculus
<400> 79
Tyr Thr Ser Arg Leu Leu Ser
1 5
<210> 80
<211> 9
<212> PRT
<213> Mus musculus
<400> 80
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 81
<211> 11
<212> PRT
<213> Mus musculus
<400> 81
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 82
<211> 24
<212> PRT
<213> Rattus norvegicus
<400> 82
Gln Gly Trp Gln Ala Phe Lys Asn Asp Ala Thr Glu Ile Ile Pro Gly
1 5 10 15
Leu Arg Glu Tyr Pro Glu Pro Pro
20
<210> 83
<211> 20
<212> PRT
<213> Rattus norvegicus
<400> 83
Thr Glu Ile Ile Pro Gly Leu Arg Glu Tyr Pro Glu Pro Pro Gln Glu
1 5 10 15
Leu Glu Asn Asn
20
<210> 84
<211> 20
<212> PRT
<213> Rattus norvegicus
<400> 84
Pro Glu Pro Pro Gln Glu Leu Glu Asn Asn Gln Thr Met Asn Arg Ala
1 5 10 15
Glu Asn Gly Gly
20
<210> 85
<211> 20
<212> PRT
<213> Rattus norvegicus
<400> 85
Glu Asn Gly Gly Arg Pro Pro His His Pro Tyr Asp Thr Lys Asp Val
1 5 10 15
Ser Glu Tyr Ser
20
<210> 86
<211> 14
<212> PRT
<213> Rattus norvegicus
<400> 86
Cys Arg Glu Leu His Tyr Thr Arg Phe Val Thr Asp Gly Pro
1 5 10
<210> 87
<211> 25
<212> PRT
<213> Rattus norvegicus
<400> 87
Cys Arg Glu Leu His Tyr Thr Arg Phe Val Thr Asp Gly Pro Ser Arg
1 5 10 15
Ser Ala Lys Pro Val Thr Glu Leu Val
20 25
<210> 88
<211> 23
<212> PRT
<213> Rattus norvegicus
<400> 88
Cys Arg Ser Ala Lys Pro Val Thr Glu Leu Val Ser Ser Gly Gln Ser
1 5 10 15
Gly Pro Arg Ala Arg Leu Leu
20
<210> 89
<211> 25
<212> PRT
<213> Rattus norvegicus
<400> 89
Cys Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Val Lys Trp
1 5 10 15
Trp Arg Pro Asn Gly Pro Asp Phe Arg
20 25
<210> 90
<211> 20
<212> PRT
<213> Rattus norvegicus
<400> 90
Arg Ala Gln Arg Val Gln Leu Leu Cys Pro Gly Gly Ala Ala Pro Arg
1 5 10 15
Ser Arg Lys Val
20
<210> 91
<211> 16
<212> PRT
<213> Rattus norvegicus
<400> 91
Pro Gly Gly Ala Ala Pro Arg Ser Arg Lys Val Arg Leu Val Ala Ser
1 5 10 15
<210> 92
<211> 23
<212> PRT
<213> Rattus norvegicus
<400> 92
Lys Arg Leu Thr Arg Phe His Asn Gln Ser Glu Leu Lys Asp Phe Gly
1 5 10 15
Pro Glu Thr Ala Arg Pro Gln
20
<210> 93
<211> 16
<212> PRT
<213> Rattus norvegicus
<400> 93
Ile Pro Asp Arg Tyr Ala Gln Arg Val Gln Leu Leu Ser Pro Gly Gly
1 5 10 15
<210> 94
<211> 24
<212> PRT
<213> Rattus norvegicus
<400> 94
Ser Glu Leu Lys Asp Phe Gly Pro Glu Thr Ala Arg Pro Gln Lys Gly
1 5 10 15
Arg Lys Pro Arg Pro Arg Ala Arg
20
<210> 95
<211> 23
<212> PRT
<213> Rattus norvegicus
<400> 95
Lys Gly Arg Lys Pro Arg Pro Arg Ala Arg Gly Ala Lys Ala Asn Gln
1 5 10 15
Ala Glu Leu Glu Asn Ala Tyr
20
<210> 96
<211> 18
<212> PRT
<213> Rattus norvegicus
<400> 96
Pro Asn Ala Ile Gly Arg Val Lys Trp Trp Arg Pro Asn Gly Pro Asp
1 5 10 15
Phe Arg
<210> 97
<211> 22
<212> PRT
<213> Rattus norvegicus
<400> 97
Lys Trp Trp Arg Pro Asn Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg
1 5 10 15
Tyr Arg Ala Gln Arg Val
20
<210> 98
<211> 213
<212> PRT
<213> Rattus norvegicus
<400> 98
Met Gln Leu Ser Leu Ala Pro Cys Leu Ala Cys Leu Leu Val His Ala
1 5 10 15
Ala Phe Val Ala Val Glu Ser Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Gly Leu Arg Glu Tyr Pro Glu Pro Pro Gln
35 40 45
Glu Leu Glu Asn Asn Gln Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Tyr Asp Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Tyr Thr Arg Phe Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Val Lys Trp Trp Arg Pro Asn
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Ala Ala Pro Arg Ser Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Pro Glu Thr Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Gly Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 99
<211> 7
<212> PRT
<213> Mus musculus
<400> 99
Tyr Thr Ser Arg Leu His Ser
1 5
<210> 100
<211> 9
<212> PRT
<213> Mus musculus
<400> 100
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 101
<211> 11
<212> PRT
<213> Mus musculus
<400> 101
Arg Ala Ser Gln Val Ile Thr Asn Tyr Leu Tyr
1 5 10
<210> 102
<211> 7
<212> PRT
<213> Mus musculus
<400> 102
Tyr Thr Ser Arg Leu His Ser
1 5
<210> 103
<211> 9
<212> PRT
<213> Mus musculus
<400> 103
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 104
<211> 11
<212> PRT
<213> Mus musculus
<400> 104
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 105
<211> 7
<212> PRT
<213> Mus musculus
<400> 105
Tyr Thr Ser Arg Leu Leu Ser
1 5
<210> 106
<211> 9
<212> PRT
<213> Mus musculus
<400> 106
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 107
<211> 11
<212> PRT
<213> Mus musculus
<400> 107
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 108
<211> 7
<212> PRT
<213> Mus musculus
<400> 108
Tyr Thr Ser Arg Leu Phe Ser
1 5
<210> 109
<211> 9
<212> PRT
<213> Mus musculus
<400> 109
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 110
<211> 11
<212> PRT
<213> Mus musculus
<400> 110
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 111
<211> 7
<212> PRT
<213> Mus musculus
<400> 111
Tyr Thr Ser Arg Leu Leu Ser
1 5
<210> 112
<211> 9
<212> PRT
<213> Mus musculus
<400> 112
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 113
<211> 11
<212> PRT
<213> Mus musculus
<400> 113
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 114
<211> 7
<212> PRT
<213> Mus musculus
<400> 114
Tyr Thr Ser Thr Leu Gln Ser
1 5
<210> 115
<211> 9
<212> PRT
<213> Mus musculus
<400> 115
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 116
<211> 12
<212> PRT
<213> Mus musculus
<400> 116
Ser Val Ser Ser Ser Ile Ser Ser Ser Asn Leu His
1 5 10
<210> 117
<211> 213
<212> PRT
<213> Mus musculus
<400> 117
Gln Ile Val Leu Ser Gln Ser Pro Ala Ile Leu Ser Thr Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Tyr Tyr Met
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Thr Arg Val Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 118
<211> 642
<212> DNA
<213> Mus musculus
<400> 118
caaattgttc tctcccagtc tccagcaatc ctgtctacat ctccagggga gaaggtcaca 60
atgacttgca gggccagctc aagtgtatat tacatgcact ggtaccagca gaagccagga 120
tcctccccca aaccctggat ttatgccaca tccaacctgg cttctggagt ccctgttcgc 180
ttcagtggca gtgggtctgg gacctcttac tctctcacaa tcaccagagt ggaggctgaa 240
gatgctgcca cttattactg ccagcagtgg agtagtgacc cactcacgtt cggtgctggg 300
accaagctgg agctgaaacg ggctgatgct gcaccaactg tatccatctt cccaccatcc 360
agtgagcagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420
aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480
agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540
accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600
acttcaccca ttgtcaagag cttcaacagg aatgagtgtt ag 642
<210> 119
<211> 235
<212> PRT
<213> Mus musculus
<400> 119
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Met Ser Arg Gly Gln Ile Val Leu Ser Gln Ser Pro Ala Ile
20 25 30
Leu Ser Thr Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser
35 40 45
Ser Ser Val Tyr Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Ser Ser
50 55 60
Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
85 90 95
Thr Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
115 120 125
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
130 135 140
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
145 150 155 160
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
165 170 175
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
195 200 205
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
210 215 220
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 120
<211> 708
<212> DNA
<213> Mus musculus
<400> 120
atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcttcagt cattatgtcc 60
aggggacaaa ttgttctctc ccagtctcca gcaatcctgt ctacatctcc aggggagaag 120
gtcacaatga cttgcagggc cagctcaagt gtatattaca tgcactggta ccagcagaag 180
ccaggatcct cccccaaacc ctggatttat gccacatcca acctggcttc tggagtccct 240
gttcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcac cagagtggag 300
gctgaagatg ctgccactta ttactgccag cagtggagta gtgacccact cacgttcggt 360
gctgggacca agctggagct gaaacgggct gatgctgcac caactgtatc catcttccca 420
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 480
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 540
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 600
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 660
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 708
<210> 121
<211> 445
<212> PRT
<213> Mus musculus
<400> 121
Glu Val Gln Val Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Phe Ile His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Leu Asp Pro Glu Asp Gly Glu Ser Asp Tyr Ala Pro Lys Phe
50 55 60
Gln Asp Lys Ala Ile Met Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Glu Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Phe Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser
115 120 125
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
130 135 140
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
180 185 190
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
210 215 220
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
245 250 255
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
260 265 270
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
290 295 300
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
305 310 315 320
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
340 345 350
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
355 360 365
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
370 375 380
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
385 390 395 400
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
405 410 415
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
420 425 430
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 122
<211> 1338
<212> DNA
<213> Mus musculus
<400> 122
gaggttcagg tgcagcagtc tgggccagaa cttgtgaagc caggggcctc agtcaagttg 60
tcctgcacag cttctggctt caacattaaa gactacttta tacactgggt gaagcagagg 120
cctgaacagg gcctggagtg gattggaagg cttgatcctg aggatggtga aagtgattat 180
gccccgaagt tccaggacaa ggccattatg acagcagaca catcatccaa cacagcctat 240
cttcagctca gaagcctgac atctgaggac actgccatct attattgtga gagagaggac 300
tacgatggta cctacacctt ttttccttac tggggccaag ggactctggt cactgtctct 360
gcagccaaaa cgacaccccc atctgtctat ccactggccc ctggatctgc tgcccaaact 420
aactccatgg tgaccctggg atgcctggtc aagggctatt tccctgagcc agtgacagtg 480
acctggaact ctggatccct gtccagcggt gtgcacacct tcccagctgt cctgcagtct 540
gacctctaca ctctgagcag ctcagtgact gtcccctcca gcacctggcc cagcgagacc 600
gtcacctgca acgttgccca cccggccagc agcaccaagg tggacaagaa aattgtgccc 660
agggattgtg gttgtaagcc ttgcatatgt acagtcccag aagtatcatc tgtcttcatc 720
ttccccccaa agcccaagga tgtgctcacc attactctga ctcctaaggt cacgtgtgtt 780
gtggtagaca tcagcaagga tgatcccgag gtccagttca gctggtttgt agatgatgtg 840
gaggtgcaca cagctcagac gcaaccccgg gaggagcagt tcaacagcac tttccgctca 900
gtcagtgaac ttcccatcat gcaccaggac tggctcaatg gcaaggagtt caaatgcagg 960
gtcaacagtg cagctttccc tgcccccatc gagaaaacca tctccaaaac caaaggcaga 1020
ccgaaggctc cacaggtgta caccattcca cctcccaagg agcagatggc caaggataaa 1080
gtcagtctga cctgcatgat aacagacttc ttccctgaag acattactgt ggagtggcag 1140
tggaatgggc agccagcgga gaactacaag aacactcagc ccatcatgga cacagatggc 1200
tcttacttca tctacagcaa gctcaatgtg cagaagagca actgggaggc aggaaatact 1260
ttcacctgct ctgtgttaca tgagggcctg cacaaccacc atactgagaa gagcctctcc 1320
cactctcctg gtaaatga 1338
<210> 123
<211> 464
<212> PRT
<213> Mus musculus
<400> 123
Met Lys Cys Ser Trp Val Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Val Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Phe Ile His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Leu Asp Pro Glu Asp Gly Glu Ser Asp Tyr Ala
65 70 75 80
Pro Lys Phe Gln Asp Lys Ala Ile Met Thr Ala Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Ile
100 105 110
Tyr Tyr Cys Glu Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Phe Phe Pro
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr
130 135 140
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn
145 150 155 160
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val
195 200 205
Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
225 230 235 240
Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
260 265 270
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
275 280 285
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
290 295 300
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
305 310 315 320
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
325 330 335
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
355 360 365
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
370 375 380
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
385 390 395 400
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
405 410 415
Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser
420 425 430
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
435 440 445
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 124
<211> 1395
<212> DNA
<213> Mus musculus
<400> 124
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gttcaggtgc agcagtctgg gccagaactt gtgaagccag gggcctcagt caagttgtcc 120
tgcacagctt ctggcttcaa cattaaagac tactttatac actgggtgaa gcagaggcct 180
gaacagggcc tggagtggat tggaaggctt gatcctgagg atggtgaaag tgattatgcc 240
ccgaagttcc aggacaaggc cattatgaca gcagacacat catccaacac agcctatctt 300
cagctcagaa gcctgacatc tgaggacact gccatctatt attgtgagag agaggactac 360
gatggtacct acaccttttt tccttactgg ggccaaggga ctctggtcac tgtctctgca 420
gccaaaacga cacccccatc tgtctatcca ctggcccctg gatctgctgc ccaaactaac 480
tccatggtga ccctgggatg cctggtcaag ggctatttcc ctgagccagt gacagtgacc 540
tggaactctg gatccctgtc cagcggtgtg cacaccttcc cagctgtcct gcagtctgac 600
ctctacactc tgagcagctc agtgactgtc ccctccagca cctggcccag cgagaccgtc 660
acctgcaacg ttgcccaccc ggccagcagc accaaggtgg acaagaaaat tgtgcccagg 720
gattgtggtt gtaagccttg catatgtaca gtcccagaag tatcatctgt cttcatcttc 780
cccccaaagc ccaaggatgt gctcaccatt actctgactc ctaaggtcac gtgtgttgtg 840
gtagacatca gcaaggatga tcccgaggtc cagttcagct ggtttgtaga tgatgtggag 900
gtgcacacag ctcagacgca accccgggag gagcagttca acagcacttt ccgctcagtc 960
agtgaacttc ccatcatgca ccaggactgg ctcaatggca aggagttcaa atgcagggtc 1020
aacagtgcag ctttccctgc ccccatcgag aaaaccatct ccaaaaccaa aggcagaccg 1080
aaggctccac aggtgtacac cattccacct cccaaggagc agatggccaa ggataaagtc 1140
agtctgacct gcatgataac agacttcttc cctgaagaca ttactgtgga gtggcagtgg 1200
aatgggcagc cagcggagaa ctacaagaac actcagccca tcatggacac agatggctct 1260
tacttcatct acagcaagct caatgtgcag aagagcaact gggaggcagg aaatactttc 1320
acctgctctg tgttacatga gggcctgcac aaccaccata ctgagaagag cctctcccac 1380
tctcctggta aatga 1395
<210> 125
<211> 215
<212> PRT
<213> Mus musculus
<400> 125
Glu Ile Val Leu Thr Gln Ser Pro Ala Leu Met Ala Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Ile Thr Cys Ser Val Ser Ser Thr Ile Ser Ser Asn
20 25 30
His Leu His Trp Phe Gln Gln Lys Ser Asp Thr Ser Pro Lys Pro Trp
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu
65 70 75 80
Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro
85 90 95
Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Arg Arg Ala Asp Ala
100 105 110
Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser
115 120 125
Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp
130 135 140
Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val
145 150 155 160
Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met
165 170 175
Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser
180 185 190
Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys
195 200 205
Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 126
<211> 648
<212> DNA
<213> Mus musculus
<400> 126
gaaattgtgc tcacccagtc tccagcactc atggctgcat ctccggggga gaaggtcacc 60
atcacctgca gtgtcagttc aactataagt tccaaccact tgcactggtt ccagcagaag 120
tcagacacct cccccaaacc ctggatttat ggcacatcca acctggcttc tggagtccct 180
gttcgcttca gtggcagtgg atctgggacc tcttattctc tcacaatcag cagcatggag 240
gctgaggatg ctgccactta ttactgtcaa cagtggagta gttacccact cacgttcggc 300
gctgggacca agctggagct gagacgggct gatgctgcac caactgtatc catcttccca 360
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 420
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 480
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 540
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 600
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 648
<210> 127
<211> 237
<212> PRT
<213> Mus musculus
<400> 127
Met Asp Phe His Val Gln Ile Phe Ser Phe Met Leu Ile Ser Val Thr
1 5 10 15
Val Ile Leu Ser Ser Gly Glu Ile Val Leu Thr Gln Ser Pro Ala Leu
20 25 30
Met Ala Ala Ser Pro Gly Glu Lys Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Thr Ile Ser Ser Asn His Leu His Trp Phe Gln Gln Lys Ser Asp
50 55 60
Thr Ser Pro Lys Pro Trp Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu
85 90 95
Thr Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Ser Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu
115 120 125
Leu Arg Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser
130 135 140
Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn
145 150 155 160
Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser
165 170 175
Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu
195 200 205
Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser
210 215 220
Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 128
<211> 714
<212> DNA
<213> Mus musculus
<400> 128
atggattttc atgtgcagat tttcagcttc atgctaatca gtgtcacagt cattttgtcc 60
agtggagaaa ttgtgctcac ccagtctcca gcactcatgg ctgcatctcc gggggagaag 120
gtcaccatca cctgcagtgt cagttcaact ataagttcca accacttgca ctggttccag 180
cagaagtcag acacctcccc caaaccctgg atttatggca catccaacct ggcttctgga 240
gtccctgttc gcttcagtgg cagtggatct gggacctctt attctctcac aatcagcagc 300
atggaggctg aggatgctgc cacttattac tgtcaacagt ggagtagtta cccactcacg 360
ttcggcgctg ggaccaagct ggagctgaga cgggctgatg ctgcaccaac tgtatccatc 420
ttcccaccat ccagtgagca gttaacatct ggaggtgcct cagtcgtgtg cttcttgaac 480
aacttctacc ccaaagacat caatgtcaag tggaagattg atggcagtga acgacaaaat 540
ggcgtcctga acagttggac tgatcaggac agcaaagaca gcacctacag catgagcagc 600
accctcacgt tgaccaagga cgagtatgaa cgacataaca gctatacctg tgaggccact 660
cacaagacat caacttcacc cattgtcaag agcttcaaca ggaatgagtg ttag 714
<210> 129
<211> 449
<212> PRT
<213> Mus musculus
<400> 129
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Leu Val Lys Leu Ser Cys Thr Ala Ser Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Met Arg Gln Arg Pro Glu Gln Gly Leu Asp Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Ala Thr Leu Thr Thr Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Gly Leu Thr Ser Glu Thr Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Ala Gly Thr Thr Ile Thr Val Ser Ser Ala Lys Thr
115 120 125
Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
130 135 140
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
180 185 190
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
195 200 205
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
210 215 220
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
245 250 255
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
260 265 270
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
290 295 300
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
340 345 350
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
355 360 365
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
370 375 380
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
385 390 395 400
Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys
405 410 415
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
420 425 430
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
435 440 445
Lys
<210> 130
<211> 1350
<212> DNA
<213> Mus musculus
<400> 130
gaggttcagc tgcagcagtc tggggctgaa cttgtgaggc caggggcctt agtcaagttg 60
tcctgcacag cttctgactt caacattaaa gacttctatc tacactggat gaggcagcgg 120
cctgaacagg gcctggactg gattggaagg attgatcctg agaatggtga tactttatat 180
gacccgaagt tccaggacaa ggccactctt acaacagaca catcctccaa cacagcctac 240
ctgcagctca gcggcctgac atctgagacc actgccgtct attactgttc tagagaggcg 300
gattatttcc acgatggtac ctcctactgg tacttcgatg tctggggcgc agggaccaca 360
atcaccgtct cctcagccaa aacgacaccc ccatctgtct atccactggc ccctggatct 420
gctgcccaaa ctaactccat ggtgaccctg ggatgcctgg tcaagggcta tttccctgag 480
ccagtgacag tgacctggaa ctctggatcc ctgtccagcg gtgtgcacac cttcccagct 540
gtcctgcagt ctgacctcta cactctgagc agctcagtga ctgtcccctc cagcacctgg 600
cccagcgaga ccgtcacctg caacgttgcc cacccggcca gcagcaccaa ggtggacaag 660
aaaattgtgc ccagggattg tggttgtaag ccttgcatat gtacagtccc agaagtatca 720
tctgtcttca tcttcccccc aaagcccaag gatgtgctca ccattactct gactcctaag 780
gtcacgtgtg ttgtggtaga catcagcaag gatgatcccg aggtccagtt cagctggttt 840
gtagatgatg tggaggtgca cacagctcag acgcaacccc gggaggagca gttcaacagc 900
actttccgct cagtcagtga acttcccatc atgcaccagg actggctcaa tggcaaggag 960
ttcaaatgca gggtcaacag tgcagctttc cctgccccca tcgagaaaac catctccaaa 1020
accaaaggca gaccgaaggc tccacaggtg tacaccattc cacctcccaa ggagcagatg 1080
gccaaggata aagtcagtct gacctgcatg ataacagact tcttccctga agacattact 1140
gtggagtggc agtggaatgg gcagccagcg gagaactaca agaacactca gcccatcatg 1200
gacacagatg gctcttactt catctacagc aagctcaatg tgcagaagag caactgggag 1260
gcaggaaata ctttcacctg ctctgtgtta catgagggcc tgcacaacca ccatactgag 1320
aagagcctct cccactctcc tggtaaatga 1350
<210> 131
<211> 468
<212> PRT
<213> Mus musculus
<400> 131
Met Lys Cys Ser Trp Val Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg
20 25 30
Pro Gly Ala Leu Val Lys Leu Ser Cys Thr Ala Ser Asp Phe Asn Ile
35 40 45
Lys Asp Phe Tyr Leu His Trp Met Arg Gln Arg Pro Glu Gln Gly Leu
50 55 60
Asp Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp
65 70 75 80
Pro Lys Phe Gln Asp Lys Ala Thr Leu Thr Thr Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Ser Gly Leu Thr Ser Glu Thr Thr Ala Val
100 105 110
Tyr Tyr Cys Ser Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr
115 120 125
Trp Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr Ile Thr Val Ser Ser
130 135 140
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
145 150 155 160
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
195 200 205
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
210 215 220
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
225 230 235 240
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
245 250 255
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
260 265 270
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
275 280 285
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
290 295 300
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
355 360 365
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
370 375 380
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
385 390 395 400
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
405 410 415
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn
420 425 430
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
435 440 445
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
450 455 460
Ser Pro Gly Lys
465
<210> 132
<211> 1407
<212> DNA
<213> Mus musculus
<400> 132
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gttcagctgc agcagtctgg ggctgaactt gtgaggccag gggccttagt caagttgtcc 120
tgcacagctt ctgacttcaa cattaaagac ttctatctac actggatgag gcagcggcct 180
gaacagggcc tggactggat tggaaggatt gatcctgaga atggtgatac tttatatgac 240
ccgaagttcc aggacaaggc cactcttaca acagacacat cctccaacac agcctacctg 300
cagctcagcg gcctgacatc tgagaccact gccgtctatt actgttctag agaggcggat 360
tatttccacg atggtacctc ctactggtac ttcgatgtct ggggcgcagg gaccacaatc 420
accgtctcct cagccaaaac gacaccccca tctgtctatc cactggcccc tggatctgct 480
gcccaaacta actccatggt gaccctggga tgcctggtca agggctattt ccctgagcca 540
gtgacagtga cctggaactc tggatccctg tccagcggtg tgcacacctt cccagctgtc 600
ctgcagtctg acctctacac tctgagcagc tcagtgactg tcccctccag cacctggccc 660
agcgagaccg tcacctgcaa cgttgcccac ccggccagca gcaccaaggt ggacaagaaa 720
attgtgccca gggattgtgg ttgtaagcct tgcatatgta cagtcccaga agtatcatct 780
gtcttcatct tccccccaaa gcccaaggat gtgctcacca ttactctgac tcctaaggtc 840
acgtgtgttg tggtagacat cagcaaggat gatcccgagg tccagttcag ctggtttgta 900
gatgatgtgg aggtgcacac agctcagacg caaccccggg aggagcagtt caacagcact 960
ttccgctcag tcagtgaact tcccatcatg caccaggact ggctcaatgg caaggagttc 1020
aaatgcaggg tcaacagtgc agctttccct gcccccatcg agaaaaccat ctccaaaacc 1080
aaaggcagac cgaaggctcc acaggtgtac accattccac ctcccaagga gcagatggcc 1140
aaggataaag tcagtctgac ctgcatgata acagacttct tccctgaaga cattactgtg 1200
gagtggcagt ggaatgggca gccagcggag aactacaaga acactcagcc catcatggac 1260
acagatggct cttacttcat ctacagcaag ctcaatgtgc agaagagcaa ctgggaggca 1320
ggaaatactt tcacctgctc tgtgttacat gagggcctgc acaaccacca tactgagaag 1380
agcctctccc actctcctgg taaatga 1407
<210> 133
<211> 214
<212> PRT
<213> Mus musculus
<400> 133
Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 134
<211> 645
<212> DNA
<213> Mus musculus
<400> 134
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 135
<211> 234
<212> PRT
<213> Mus musculus
<400> 135
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 136
<211> 705
<212> DNA
<213> Mus musculus
<400> 136
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 137
<211> 447
<212> PRT
<213> Mus musculus
<400> 137
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met 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
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr 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 Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 138
<211> 1344
<212> DNA
<213> Mus musculus
<400> 138
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagaac 120
caaggaaaga ccctagagtg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgatgata tctacgacga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 139
<211> 466
<212> PRT
<213> Mus musculus
<400> 139
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 140
<211> 1401
<212> DNA
<213> Mus musculus
<400> 140
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagaaccaa 180
ggaaagaccc tagagtggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gatgatatct acgacgactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 141
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 141
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 142
<211> 642
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 142
gacatccaga tgacccagtc tccatcctcc ctctccgcat ccgtaggcga ccgcgtaacc 60
ataacatgta gagcatctca agatatttcc aactatttga attggtacca acaaaaaccc 120
ggcaaagcac ctaaactcct catttactat acatcaagac tcctctccgg cgttccatca 180
cgattctcag gctccggctc cggcacagat ttcacactca ctatttcctc cctccaacca 240
gaagattttg caacctatta ctgtcaacaa ggcgatacac tcccatacac attcggcggc 300
ggcacaaaag ttgaaattaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642
<210> 143
<211> 236
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 143
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Gln Asp Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu Leu Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Asp Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
115 120 125
Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
130 135 140
Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn
145 150 155 160
Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu
165 170 175
Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp
180 185 190
Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr
195 200 205
Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser
210 215 220
Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 144
<211> 708
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 144
atggacatga gggtccccgc tcagctcctg gggctcctgc tactctggct ccgaggtgcc 60
agatgtgaca tccagatgac ccagtctcca tcctccctct ccgcatccgt aggcgaccgc 120
gtaaccataa catgtagagc atctcaagat atttccaact atttgaattg gtaccaacaa 180
aaacccggca aagcacctaa actcctcatt tactatacat caagactcct ctccggcgtt 240
ccatcacgat tctcaggctc cggctccggc acagatttca cactcactat ttcctccctc 300
caaccagaag attttgcaac ctattactgt caacaaggcg atacactccc atacacattc 360
ggcggcggca caaaagttga aattaaacgt acggtggctg caccatctgt cttcatcttc 420
ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 480
ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 540
tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcagcacc 600
ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct acgcctgcga agtcacccat 660
cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgt 708
<210> 145
<211> 449
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 145
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly
115 120 125
Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser
130 135 140
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
180 185 190
Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val
195 200 205
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys
210 215 220
Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val
290 295 300
Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<210> 146
<211> 1347
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 146
gaggtgcagc tggtgcagag cggcgccgag gtaaaaaaac caggagcaag cgttaaagtt 60
tcttgtaaag caagcggata tacatttaca gattacaaca tgcattgggt aagacaagcg 120
ccaggacaag gattggaatg gatgggcgaa attaacccta atagtggagg agcaggctac 180
aatcaaaaat tcaaagggag agttacaatg acaacagaca caagcacttc aacagcatat 240
atggaactgc gatcacttag aagcgacgat acagctgtat actattgcgc acgacttggg 300
tatgatgata tatatgatga ctggtatttc gatgtttggg gccagggaac aacagttacc 360
gtctctagtg cctccaccaa gggcccatcg gtcttccccc tggcgccctg ctccaggagc 420
acctccgaga gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 480
acggtgtcgt ggaactcagg cgctctgacc agcggcgtgc acaccttccc agctgtccta 540
cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag caacttcggc 600
acccagacct acacctgcaa cgtagatcac aagcccagca acaccaaggt ggacaagaca 660
gttgagcgca aatgttgtgt cgagtgccca ccgtgcccag caccacctgt ggcaggaccg 720
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780
gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtccagtt caactggtac 840
gtggacggcg tggaggtgca taatgccaag acaaagccac gggaggagca gttcaacagc 900
acgttccgtg tggtcagcgt cctcaccgtt gtgcaccagg actggctgaa cggcaaggag 960
tacaagtgca aggtctccaa caaaggcctc ccagccccca tcgagaaaac catctccaaa 1020
accaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1080
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1140
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacacc tcccatgctg 1200
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320
aagagcctct ccctgtctcc gggtaaa 1347
<210> 147
<211> 468
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 147
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu 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
Thr Asp Tyr Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser
130 135 140
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr
145 150 155 160
Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
195 200 205
Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr
210 215 220
Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val
225 230 235 240
Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val
245 250 255
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
260 265 270
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
275 280 285
His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
290 295 300
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln
355 360 365
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
370 375 380
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
385 390 395 400
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
405 410 415
Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
420 425 430
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
435 440 445
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
450 455 460
Ser Pro Gly Lys
465
<210> 148
<211> 1404
<212> DNA
<213> Mus musculus
<400> 148
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagagcgg cgccgaggta aaaaaaccag gagcaagcgt taaagtttct 120
tgtaaagcaa gcggatatac atttacagat tacaacatgc attgggtaag acaagcgcca 180
ggacaaggat tggaatggat gggcgaaatt aaccctaata gtggaggagc aggctacaat 240
caaaaattca aagggagagt tacaatgaca acagacacaa gcacttcaac agcatatatg 300
gaactgcgat cacttagaag cgacgataca gctgtatact attgcgcacg acttgggtat 360
gatgatatat atgatgactg gtatttcgat gtttggggcc agggaacaac agttaccgtc 420
tctagtgcct ccaccaaggg cccatcggtc ttccccctgg cgccctgctc caggagcacc 480
tccgagagca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 540
gtgtcgtgga actcaggcgc tctgaccagc ggcgtgcaca ccttcccagc tgtcctacag 600
tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcaa cttcggcacc 660
cagacctaca cctgcaacgt agatcacaag cccagcaaca ccaaggtgga caagacagtt 720
gagcgcaaat gttgtgtcga gtgcccaccg tgcccagcac cacctgtggc aggaccgtca 780
gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840
acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tccagttcaa ctggtacgtg 900
gacggcgtgg aggtgcataa tgccaagaca aagccacggg aggagcagtt caacagcacg 960
ttccgtgtgg tcagcgtcct caccgttgtg caccaggact ggctgaacgg caaggagtac 1020
aagtgcaagg tctccaacaa aggcctccca gcccccatcg agaaaaccat ctccaaaacc 1080
aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga ggagatgacc 1140
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catcgccgtg 1200
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacacctcc catgctggac 1260
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380
agcctctccc tgtctccggg taaa 1404
<210> 149
<211> 214
<212> PRT
<213> Mus musculus
<400> 149
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Phe Gln Gln Lys Pro Asp Gly Thr Leu Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Arg Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 150
<211> 645
<212> DNA
<213> Mus musculus
<400> 150
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 60
atcagttgca gggcaagtca ggacattagc aattatttaa actggtttca gcagaaacca 120
gatggaactc ttaaactcct gatcttctac acatcaagat tacactcagg agttccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa 240
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcgggggg 300
gggaccaagc tggaaataag acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 151
<211> 234
<212> PRT
<213> Mus musculus
<400> 151
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Phe Gln Gln Lys Pro Asp Gly Thr Leu
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser
85 90 95
Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Arg Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 152
<211> 705
<212> DNA
<213> Mus musculus
<400> 152
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atcagttgca gggcaagtca ggacattagc aattatttaa actggtttca gcagaaacca 180
gatggaactc ttaaactcct gatcttctac acatcaagat tacactcagg agttccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa 300
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcgggggg 360
gggaccaagc tggaaataag acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 153
<211> 447
<212> PRT
<213> Mus musculus
<400> 153
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met 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
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly 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 Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Val Tyr Asp Gly Ser Tyr Glu Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 154
<211> 1344
<212> DNA
<213> Mus musculus
<400> 154
gaggtccagc tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata cacattcact gactacaaca tgcactgggt gaaacagaac 120
caaggaaaga gcctagagtg gataggagaa attaatccta acagtggtgg tagtggctac 180
aaccaaaagt tcaaaggcaa ggccacattg actgtagaca agtcttccag cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattggtc 300
tacgatggca gctacgagga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 155
<211> 466
<212> PRT
<213> Mus musculus
<400> 155
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Val Tyr Asp Gly Ser Tyr Glu Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 156
<211> 1401
<212> DNA
<213> Mus musculus
<400> 156
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac attcactgac tacaacatgc actgggtgaa acagaaccaa 180
ggaaagagcc tagagtggat aggagaaatt aatcctaaca gtggtggtag tggctacaac 240
caaaagttca aaggcaaggc cacattgact gtagacaagt cttccagcac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attggtctac 360
gatggcagct acgaggactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 157
<211> 214
<212> PRT
<213> Mus musculus
<400> 157
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Cys Cys Arg Ala Ser Gln Val Ile Thr Asn Tyr
20 25 30
Leu Tyr Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 158
<211> 642
<212> DNA
<213> Mus musculus
<400> 158
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 60
atctgttgca gggcaagtca ggtcattacc aattatttat actggtatca gcagaaacca 120
gatggaactt ttaaactcct gatctactac acatcaagat tacactcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggaacag 240
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 642
<210> 159
<211> 234
<212> PRT
<213> Mus musculus
<400> 159
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Thr Ile Cys Cys Arg Ala Ser Gln Val
35 40 45
Ile Thr Asn Tyr Leu Tyr Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser
85 90 95
Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 160
<211> 702
<212> DNA
<213> Mus musculus
<400> 160
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atctgttgca gggcaagtca ggtcattacc aattatttat actggtatca gcagaaacca 180
gatggaactt ttaaactcct gatctactac acatcaagat tacactcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggaacag 300
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 360
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 702
<210> 161
<211> 447
<212> PRT
<213> Mus musculus
<400> 161
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met 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
Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Gln Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Arg 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 Arg Leu Gly Tyr Val Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 162
<211> 1341
<212> DNA
<213> Mus musculus
<400> 162
gaggtccagc tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata cacattcact gactacaaca tgcactggat gaagcagaac 120
caaggaaaga gcctagaatg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagcagt tcaaaggcaa ggccacattg actgtagaca agtcctccag gacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgttggta attacgagga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa a 1341
<210> 163
<211> 466
<212> PRT
<213> Mus musculus
<400> 163
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Gln Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Arg
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Val Gly Asn Tyr Glu Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 164
<211> 1398
<212> DNA
<213> Mus musculus
<400> 164
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac attcactgac tacaacatgc actggatgaa gcagaaccaa 180
ggaaagagcc tagaatggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagcagttca aaggcaaggc cacattgact gtagacaagt cctccaggac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gttggtaatt acgaggactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaa 1398
<210> 165
<211> 214
<212> PRT
<213> Mus musculus
<400> 165
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 166
<211> 645
<212> DNA
<213> Mus musculus
<400> 166
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 167
<211> 234
<212> PRT
<213> Mus musculus
<400> 167
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 168
<211> 705
<212> DNA
<213> Mus musculus
<400> 168
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 169
<211> 447
<212> PRT
<213> Mus musculus
<400> 169
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met 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
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu Asp Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr 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 Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 170
<211> 1344
<212> DNA
<213> Mus musculus
<400> 170
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagaac 120
caaggaaaga ccctagactg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgatgata tctacgacga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 171
<211> 466
<212> PRT
<213> Mus musculus
<400> 171
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu
50 55 60
Asp Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 172
<211> 1401
<212> DNA
<213> Mus musculus
<400> 172
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagaaccaa 180
ggaaagaccc tagactggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gatgatatct acgacgactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 173
<211> 214
<212> PRT
<213> Mus musculus
<400> 173
Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Phe Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 174
<211> 642
<212> DNA
<213> Mus musculus
<400> 174
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa attggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tattttcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaagg tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 642
<210> 175
<211> 234
<212> PRT
<213> Mus musculus
<400> 175
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Phe Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 176
<211> 702
<212> DNA
<213> Mus musculus
<400> 176
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa attggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tattttcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaagg tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 702
<210> 177
<211> 450
<212> PRT
<213> Mus musculus
<400> 177
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Gln Gly Lys Thr Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr 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 Lys Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Ala
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser
130 135 140
Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser Asp Val His Thr Phe
165 170 175
Pro Ala Leu Leu Gln Ser Gly Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Thr Thr Trp Pro Ser Gln Thr Ile Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Ser Pro
210 215 220
Thr His Lys Pro Cys Pro Pro Cys Pro Ala Pro Asn Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile
245 250 255
Ser Leu Ser Pro Met Val Thr Cys Val Val Val Asp Val Ser Glu Asp
260 265 270
Asp Pro Asp Val His Val Ser Trp Phe Val Asn Asn Val Glu Val His
275 280 285
Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile Arg
290 295 300
Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys
305 310 315 320
Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Pro Lys Gly Pro Val Arg Ala Pro Gln Val Tyr
340 345 350
Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu
355 360 365
Thr Cys Met Ile Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp
370 375 380
Thr Asn Asn Gly Gln Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu
405 410 415
Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His
420 425 430
Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro
435 440 445
Gly Lys
450
<210> 178
<211> 1350
<212> DNA
<213> Mus musculus
<400> 178
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctgggacttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagacc 120
caaggaaaga ccctagagtg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aaaattgggc 300
tacgatgata tctacgacga ctggtatttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacaac agccccatcg gtctatccac tggcccctgt gtgtggagat 420
acaactggct cctcggtgac tctaggatgc ctggtcaagg gttatttccc tgagccagtg 480
accttgacct ggaactctgg atccctgtcc agtgatgtgc acaccttccc agctctcctg 540
cagtctggcc tctacaccct cagcagctca gtgactgtaa ccacctggcc cagccagacc 600
atcacctgca atgtggccca cccggcaagc agcaccaaag tggacaagaa aattgagccc 660
agagggtccc caacacataa accctgtcct ccatgcccag ctcctaacct cttgggtgga 720
ccatccgtct tcatcttccc tccaaagatc aaggatgtac tcatgatctc cctgagcccc 780
atggtcacgt gtgtggtggt ggatgtgagc gaggatgacc cagatgtcca tgtcagctgg 840
ttcgtgaaca acgtggaagt acacacagct cagacacaaa cccatagaga ggattacaac 900
agtactatcc gggtggtcag tgccctcccc atccagcacc aggactggat gagtggcaag 960
gagttcaaat gcaaggtcaa caacaaagcc ctcccagcgc ccatcgagag aaccatctca 1020
aaacccaaag ggccagtaag agctccacag gtatatgtct tgcctccacc agaagaagag 1080
atgactaaga aacaggtcac tctgacctgc atgatcacag acttcatgcc tgaagacatt 1140
tacgtggagt ggaccaacaa cgggcaaaca gagctaaact acaagaacac tgaaccagtc 1200
ctggactctg atggttctta cttcatgtac agcaagctga gagtggaaaa gaagaactgg 1260
gtggaaagaa atagctactc ctgttcagtg gtccacgagg gtctgcacaa tcaccacacg 1320
actaagagct tctcccggac tccgggtaaa 1350
<210> 179
<211> 469
<212> PRT
<213> Mus musculus
<400> 179
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Thr Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Thr Gln Gly Lys Thr Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr
145 150 155 160
Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser Asp Val
180 185 190
His Thr Phe Pro Ala Leu Leu Gln Ser Gly Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Thr Thr Trp Pro Ser Gln Thr Ile Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg
225 230 235 240
Gly Ser Pro Thr His Lys Pro Cys Pro Pro Cys Pro Ala Pro Asn Leu
245 250 255
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val
260 265 270
Leu Met Ile Ser Leu Ser Pro Met Val Thr Cys Val Val Val Asp Val
275 280 285
Ser Glu Asp Asp Pro Asp Val His Val Ser Trp Phe Val Asn Asn Val
290 295 300
Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser
305 310 315 320
Thr Ile Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met
325 330 335
Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala
340 345 350
Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Pro Val Arg Ala Pro
355 360 365
Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln
370 375 380
Val Thr Leu Thr Cys Met Ile Thr Asp Phe Met Pro Glu Asp Ile Tyr
385 390 395 400
Val Glu Trp Thr Asn Asn Gly Gln Thr Glu Leu Asn Tyr Lys Asn Thr
405 410 415
Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu
420 425 430
Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser
435 440 445
Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser
450 455 460
Arg Thr Pro Gly Lys
465
<210> 180
<211> 1407
<212> DNA
<213> Mus musculus
<400> 180
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg ggacttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagacccaa 180
ggaaagaccc tagagtggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaaa attgggctac 360
gatgatatct acgacgactg gtatttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacaacagc cccatcggtc tatccactgg cccctgtgtg tggagataca 480
actggctcct cggtgactct aggatgcctg gtcaagggtt atttccctga gccagtgacc 540
ttgacctgga actctggatc cctgtccagt gatgtgcaca ccttcccagc tctcctgcag 600
tctggcctct acaccctcag cagctcagtg actgtaacca cctggcccag ccagaccatc 660
acctgcaatg tggcccaccc ggcaagcagc accaaagtgg acaagaaaat tgagcccaga 720
gggtccccaa cacataaacc ctgtcctcca tgcccagctc ctaacctctt gggtggacca 780
tccgtcttca tcttccctcc aaagatcaag gatgtactca tgatctccct gagccccatg 840
gtcacgtgtg tggtggtgga tgtgagcgag gatgacccag atgtccatgt cagctggttc 900
gtgaacaacg tggaagtaca cacagctcag acacaaaccc atagagagga ttacaacagt 960
actatccggg tggtcagtgc cctccccatc cagcaccagg actggatgag tggcaaggag 1020
ttcaaatgca aggtcaacaa caaagccctc ccagcgccca tcgagagaac catctcaaaa 1080
cccaaagggc cagtaagagc tccacaggta tatgtcttgc ctccaccaga agaagagatg 1140
actaagaaac aggtcactct gacctgcatg atcacagact tcatgcctga agacatttac 1200
gtggagtgga ccaacaacgg gcaaacagag ctaaactaca agaacactga accagtcctg 1260
gactctgatg gttcttactt catgtacagc aagctgagag tggaaaagaa gaactgggtg 1320
gaaagaaata gctactcctg ttcagtggtc cacgagggtc tgcacaatca ccacacgact 1380
aagagcttct cccggactcc gggtaaa 1407
<210> 181
<211> 214
<212> PRT
<213> Mus musculus
<400> 181
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Leu Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 182
<211> 645
<212> DNA
<213> Mus musculus
<400> 182
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacta 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 183
<211> 234
<212> PRT
<213> Mus musculus
<400> 183
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Leu Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 184
<211> 705
<212> DNA
<213> Mus musculus
<400> 184
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacta 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 185
<211> 447
<212> PRT
<213> Mus musculus
<400> 185
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met 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
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr 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 Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 186
<211> 1344
<212> DNA
<213> Mus musculus
<400> 186
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagaac 120
caaggaaaga ccctagaatg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgatgata tctacgacga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 187
<211> 466
<212> PRT
<213> Mus musculus
<400> 187
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 188
<211> 1401
<212> DNA
<213> Mus musculus
<400> 188
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagaaccaa 180
ggaaagaccc tagaatggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gatgatatct acgacgactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 189
<211> 213
<212> PRT
<213> Mus musculus
<400> 189
Gln Ile Val Leu Ser Gln Ser Pro Ala Phe Leu Ser Val Ser Pro Gly
1 5 10 15
Asp Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Ile Ser Tyr Ile
20 25 30
His Trp Phe Gln Gln Lys Pro Gly Ser Ser Pro Arg Ser Trp Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Gly Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 190
<211> 642
<212> DNA
<213> Mus musculus
<400> 190
caaattgttc tctcccagtc tccagcattc ctgtctgtat ctccagggga taaggtcaca 60
atgacttgca gggccagctc aagtataagt tacatacact ggtttcagca gaagccagga 120
tcctccccca gatcctggat ttatgccaca tccaacctgg cttctggagt ccctggtcgc 180
ttcagtggca gtgggtctgg gacctcttac tctctcacaa tcagcagagt ggaggctgag 240
gatgctgcca cttattactg ccagcagtgg agtagtgacc cactcacgtt cggtgctggg 300
accaagctgg agctgaaacg ggctgatgct gcaccaactg tatccatctt cccaccatcc 360
agtgagcagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420
aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480
agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540
accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600
acttcaccca ttgtcaagag cttcaacagg aatgagtgtt ag 642
<210> 191
<211> 235
<212> PRT
<213> Mus musculus
<400> 191
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Met Ser Arg Gly Gln Ile Val Leu Ser Gln Ser Pro Ala Phe
20 25 30
Leu Ser Val Ser Pro Gly Asp Lys Val Thr Met Thr Cys Arg Ala Ser
35 40 45
Ser Ser Ile Ser Tyr Ile His Trp Phe Gln Gln Lys Pro Gly Ser Ser
50 55 60
Pro Arg Ser Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Gly Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
85 90 95
Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
115 120 125
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
130 135 140
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
145 150 155 160
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
165 170 175
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
195 200 205
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
210 215 220
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 192
<211> 708
<212> DNA
<213> Mus musculus
<400> 192
atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcttcagt cataatgtcc 60
agaggacaaa ttgttctctc ccagtctcca gcattcctgt ctgtatctcc aggggataag 120
gtcacaatga cttgcagggc cagctcaagt ataagttaca tacactggtt tcagcagaag 180
ccaggatcct cccccagatc ctggatttat gccacatcca acctggcttc tggagtccct 240
ggtcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagagtggag 300
gctgaggatg ctgccactta ttactgccag cagtggagta gtgacccact cacgttcggt 360
gctgggacca agctggagct gaaacgggct gatgctgcac caactgtatc catcttccca 420
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 480
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 540
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 600
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 660
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 708
<210> 193
<211> 445
<212> PRT
<213> Mus musculus
<400> 193
Glu Val Gln Leu Gln Gln Ser Gly Ala Asp Leu Val Gln Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Thr Ala Ser Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Met Lys Gln Arg Pro Asp Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Ala Thr Phe Thr Thr Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Arg Gly Leu Thr Ser Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Gly Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser
115 120 125
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
130 135 140
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
180 185 190
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
210 215 220
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
245 250 255
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
260 265 270
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
290 295 300
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
305 310 315 320
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
340 345 350
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
355 360 365
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
370 375 380
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
385 390 395 400
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
405 410 415
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
420 425 430
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 194
<211> 1338
<212> DNA
<213> Mus musculus
<400> 194
gaagttcagc tgcaacagtc tggggcagac cttgtgcagc caggggcctc agtcaaggtg 60
tcctgcacag cttctggctt cgacattaag gactactata tacactggat gaaacagagg 120
cctgaccagg gcctggagtg gattggaagg gttgatcctg acaatggtga gactgaattt 180
gccccgaagt tcccgggcaa ggccactttt acaacagaca catcctccaa cacagcctac 240
ctacaactca gaggcctgac atctgaggac actgccatct attactgtgg gagagaagac 300
tacgatggta cctacacctg gtttccttat tggggccaag ggactctggt cactgtctct 360
gcagccaaaa cgacaccccc atctgtctat ccactggccc ctggatctgc tgcccaaact 420
aactccatgg tgaccctggg atgcctggtc aagggctatt tccctgagcc agtgacagtg 480
acctggaact ctggatccct gtccagcggt gtgcacacct tcccagctgt cctgcagtct 540
gacctctaca ctctgagcag ctcagtgact gtcccctcca gcacctggcc cagcgagacc 600
gtcacctgca acgttgccca cccggccagc agcaccaagg tggacaagaa aattgtgccc 660
agggattgtg gttgtaagcc ttgcatatgt acagtcccag aagtatcatc tgtcttcatc 720
ttccccccaa agcccaagga tgtgctcacc attactctga ctcctaaggt cacgtgtgtt 780
gtggtagaca tcagcaagga tgatcccgag gtccagttca gctggtttgt agatgatgtg 840
gaggtgcaca cagctcagac gcaaccccgg gaggagcagt tcaacagcac tttccgctca 900
gtcagtgaac ttcccatcat gcaccaggac tggctcaatg gcaaggagtt caaatgcagg 960
gtcaacagtg cagctttccc tgcccccatc gagaaaacca tctccaaaac caaaggcaga 1020
ccgaaggctc cacaggtgta caccattcca cctcccaagg agcagatggc caaggataaa 1080
gtcagtctga cctgcatgat aacagacttc ttccctgaag acattactgt ggagtggcag 1140
tggaatgggc agccagcgga gaactacaag aacactcagc ccatcatgga cacagatggc 1200
tcttacttca tctacagcaa gctcaatgtg cagaagagca actgggaggc aggaaatact 1260
ttcacctgct ctgtgttaca tgagggcctg cacaaccacc atactgagaa gagcctctcc 1320
cactctcctg gtaaatga 1338
<210> 195
<211> 464
<212> PRT
<213> Mus musculus
<400> 195
Met Lys Cys Ser Trp Val Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Asp Leu Val Gln
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Thr Ala Ser Gly Phe Asp Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Met Lys Gln Arg Pro Asp Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala
65 70 75 80
Pro Lys Phe Pro Gly Lys Ala Thr Phe Thr Thr Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Arg Gly Leu Thr Ser Glu Asp Thr Ala Ile
100 105 110
Tyr Tyr Cys Gly Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr
130 135 140
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn
145 150 155 160
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val
195 200 205
Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
225 230 235 240
Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
260 265 270
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
275 280 285
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
290 295 300
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
305 310 315 320
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
325 330 335
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
355 360 365
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
370 375 380
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
385 390 395 400
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
405 410 415
Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser
420 425 430
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
435 440 445
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 196
<211> 1395
<212> DNA
<213> Mus musculus
<400> 196
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcagaa 60
gttcagctgc aacagtctgg ggcagacctt gtgcagccag gggcctcagt caaggtgtcc 120
tgcacagctt ctggcttcga cattaaggac tactatatac actggatgaa acagaggcct 180
gaccagggcc tggagtggat tggaagggtt gatcctgaca atggtgagac tgaatttgcc 240
ccgaagttcc cgggcaaggc cacttttaca acagacacat cctccaacac agcctaccta 300
caactcagag gcctgacatc tgaggacact gccatctatt actgtgggag agaagactac 360
gatggtacct acacctggtt tccttattgg ggccaaggga ctctggtcac tgtctctgca 420
gccaaaacga cacccccatc tgtctatcca ctggcccctg gatctgctgc ccaaactaac 480
tccatggtga ccctgggatg cctggtcaag ggctatttcc ctgagccagt gacagtgacc 540
tggaactctg gatccctgtc cagcggtgtg cacaccttcc cagctgtcct gcagtctgac 600
ctctacactc tgagcagctc agtgactgtc ccctccagca cctggcccag cgagaccgtc 660
acctgcaacg ttgcccaccc ggccagcagc accaaggtgg acaagaaaat tgtgcccagg 720
gattgtggtt gtaagccttg catatgtaca gtcccagaag tatcatctgt cttcatcttc 780
cccccaaagc ccaaggatgt gctcaccatt actctgactc ctaaggtcac gtgtgttgtg 840
gtagacatca gcaaggatga tcccgaggtc cagttcagct ggtttgtaga tgatgtggag 900
gtgcacacag ctcagacgca accccgggag gagcagttca acagcacttt ccgctcagtc 960
agtgaacttc ccatcatgca ccaggactgg ctcaatggca aggagttcaa atgcagggtc 1020
aacagtgcag ctttccctgc ccccatcgag aaaaccatct ccaaaaccaa aggcagaccg 1080
aaggctccac aggtgtacac cattccacct cccaaggagc agatggccaa ggataaagtc 1140
agtctgacct gcatgataac agacttcttc cctgaagaca ttactgtgga gtggcagtgg 1200
aatgggcagc cagcggagaa ctacaagaac actcagccca tcatggacac agatggctct 1260
tacttcatct acagcaagct caatgtgcag aagagcaact gggaggcagg aaatactttc 1320
acctgctctg tgttacatga gggcctgcac aaccaccata ctgagaagag cctctcccac 1380
tctcctggta aatga 1395
<210> 197
<211> 214
<212> PRT
<213> Mus musculus
<400> 197
Asp Leu Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asn Tyr Ser Leu Thr Ile Thr Asn Leu Glu Gln
65 70 75 80
Asp Asp Ala Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 198
<211> 645
<212> DNA
<213> Mus musculus
<400> 198
gatctccaga tgacacagac tacttcctcc ctgtctgcct ctctgggaga cagagtcacc 60
atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactg ttaagctcct gatcttctac acatcaacat tacagtcagg agtcccatcg 180
aggttcagtg gcagtgggtc tggaacaaat tattctctca ccattaccaa cctggagcaa 240
gatgatgctg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 199
<211> 234
<212> PRT
<213> Mus musculus
<400> 199
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Ser Arg Cys Asp Leu Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Thr Leu Gln Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asn Tyr Ser Leu Thr Ile Thr
85 90 95
Asn Leu Glu Gln Asp Asp Ala Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 200
<211> 705
<212> DNA
<213> Mus musculus
<400> 200
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg ttccagatgt 60
gatctccaga tgacacagac tacttcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactg ttaagctcct gatcttctac acatcaacat tacagtcagg agtcccatcg 240
aggttcagtg gcagtgggtc tggaacaaat tattctctca ccattaccaa cctggagcaa 300
gatgatgctg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 360
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 201
<211> 447
<212> PRT
<213> Mus musculus
<400> 201
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met 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
Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly 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 Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Tyr Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 202
<211> 1344
<212> DNA
<213> Mus musculus
<400> 202
gaggtccagt tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata cacattcact gactacaaca tgcactggat gaagcagaac 120
caaggaaaga gcctagagtg gataggagag attaatccta acagtggtgg ttctggttac 180
aaccagaagt tcaaaggcaa ggccacattg actgtagaca agtcctccag cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tactatggta actacgagga ctggtatttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctctg ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 203
<211> 466
<212> PRT
<213> Mus musculus
<400> 203
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ser Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Tyr Gly Asn Tyr Glu Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 204
<211> 1401
<212> DNA
<213> Mus musculus
<400> 204
atgggatgga gctggacctt tctcttcctc ctgtcaggaa cttcgggtgt cctctctgag 60
gtccagttgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac attcactgac tacaacatgc actggatgaa gcagaaccaa 180
ggaaagagcc tagagtggat aggagagatt aatcctaaca gtggtggttc tggttacaac 240
cagaagttca aaggcaaggc cacattgact gtagacaagt cctccagcac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
tatggtaact acgaggactg gtatttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctctgcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 205
<211> 215
<212> PRT
<213> Mus musculus
<400> 205
Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Thr Ser Ser
20 25 30
Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Leu Trp
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Val Glu
65 70 75 80
Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Phe Phe Pro
85 90 95
Ser Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala
100 105 110
Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser
115 120 125
Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp
130 135 140
Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val
145 150 155 160
Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met
165 170 175
Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser
180 185 190
Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys
195 200 205
Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 206
<211> 645
<212> DNA
<213> Mus musculus
<400> 206
cagattgttc tcacccagtc tccagcaatc atgtctgcat ctccagggga gaaggtcacc 60
atgacctgca gggccagctc aagtgtaact tccagttact tgaactggta ccagcagaag 120
ccaggatctt cccccaaact ctggatttat agcacatcca acctggcttc aggagtccca 180
gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagtgtggag 240
gctgaggatg ctgccactta ttactgccag cagtatgatt ttttcccatc gacgttcggt 300
ggaggcacca agctggaaat caagcgggct gatgctgcac caactgtatc catcttccca 360
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 420
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 480
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 540
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 600
acatcaactt cacccatcgt caagagcttc aacaggaatg agtgt 645
<210> 207
<211> 237
<212> PRT
<213> Mus musculus
<400> 207
Met Asp Ser Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Leu
1 5 10 15
Val Lys Met Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Ala Ile
20 25 30
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser
35 40 45
Ser Ser Val Thr Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Ser Ser Pro Lys Leu Trp Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu
85 90 95
Thr Ile Ser Ser Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Tyr Asp Phe Phe Pro Ser Thr Phe Gly Gly Gly Thr Lys Leu Glu
115 120 125
Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser
130 135 140
Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn
145 150 155 160
Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser
165 170 175
Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu
195 200 205
Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser
210 215 220
Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 208
<211> 711
<212> DNA
<213> Mus musculus
<400> 208
atggattctc aagtgcagat tttcagcttc cttctaatca gtgccttagt caaaatgtcc 60
agaggacaga ttgttctcac ccagtctcca gcaatcatgt ctgcatctcc aggggagaag 120
gtcaccatga cctgcagggc cagctcaagt gtaacttcca gttacttgaa ctggtaccag 180
cagaagccag gatcttcccc caaactctgg atttatagca catccaacct ggcttcagga 240
gtcccagctc gcttcagtgg cagtgggtct gggacctctt actctctcac aatcagcagt 300
gtggaggctg aggatgctgc cacttattac tgccagcagt atgatttttt cccatcgacg 360
ttcggtggag gcaccaagct ggaaatcaag cgggctgatg ctgcaccaac tgtatccatc 420
ttcccaccat ccagtgagca gttaacatct ggaggtgcct cagtcgtgtg cttcttgaac 480
aacttctacc ccaaagacat caatgtcaag tggaagattg atggcagtga acgacaaaat 540
ggcgtcctga acagttggac tgatcaggac agcaaagaca gcacctacag catgagcagc 600
accctcacgt tgaccaagga cgagtatgaa cgacataaca gctatacctg tgaggccact 660
cacaagacat caacttcacc catcgtcaag agcttcaaca ggaatgagtg t 711
<210> 209
<211> 445
<212> PRT
<213> Mus musculus
<400> 209
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 Asn Trp Val Lys Gln Ser His Gly Glu Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn 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 Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser
115 120 125
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
130 135 140
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
180 185 190
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
210 215 220
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
245 250 255
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
260 265 270
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
290 295 300
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
305 310 315 320
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
340 345 350
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
355 360 365
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
370 375 380
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
385 390 395 400
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
405 410 415
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
420 425 430
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 210
<211> 1335
<212> DNA
<213> Mus musculus
<400> 210
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctggggcttc agtgaagatg 60
tcctgtaagg cttctggata cacattcact gactactaca tgaactgggt gaagcagagc 120
catggagaga gccttgagtg gattggagat attaatcctt acaacgatga tactacctac 180
aaccacaagt tcaagggcaa ggccacattg actgtagaca aatcctccaa cacagcctac 240
atgcagctca acagcctgac atctgaggac tctgcagtct attactgtgc aagagagacg 300
gccgttatta ctacgaatgc tatggactac tggggtcaag gaacctcagt caccgtctcc 360
tcagccaaaa cgacaccccc atctgtctat ccactggccc ctggatctgc tgcccaaact 420
aactccatgg tgaccctggg atgcctggtc aagggctatt tccctgagcc agtgacagtg 480
acctggaact ctggatccct gtccagcggt gtgcacacct tcccagctgt cctgcagtct 540
gacctctaca ctctgagcag ctcagtgact gtcccctcca gcacctggcc cagcgagacc 600
gtcacctgca acgttgccca cccggccagc agcaccaagg tggacaagaa aattgtgccc 660
agggattgtg gttgtaagcc ttgcatatgt acagtcccag aagtatcatc tgtcttcatc 720
ttccccccaa agcccaagga tgtgctcacc attactctga ctcctaaggt cacgtgtgtt 780
gtggtagaca tcagcaagga tgatcccgag gtccagttca gctggtttgt agatgatgtg 840
gaggtgcaca cagctcagac gcaaccccgg gaggagcagt tcaacagcac tttccgctca 900
gtcagtgaac ttcccatcat gcaccaggac tggctcaatg gcaaggagtt caaatgcagg 960
gtcaacagtg cagctttccc tgcccccatc gagaaaacca tctccaaaac caaaggcaga 1020
ccgaaggctc cacaggtgta caccattcca cctcccaagg agcagatggc caaggataaa 1080
gtcagtctga cctgcatgat aacagacttc ttccctgaag acattactgt ggagtggcag 1140
tggaatgggc agccagcgga gaactacaag aacactcagc ccatcatgga cacagatggc 1200
tcttacttca tctacagcaa gctcaatgtg cagaagagca actgggaggc aggaaatact 1260
ttcacctgct ctgtgttaca tgagggcctg cacaaccacc atactgagaa gagcctctcc 1320
cactctcctg gtaaa 1335
<210> 211
<211> 464
<212> PRT
<213> Mus musculus
<400> 211
Met Gly Trp Asn Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Tyr Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Tyr Met Asn Trp Val Lys Gln Ser His Gly Glu Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn
65 70 75 80
His Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn
85 90 95
Thr Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp
115 120 125
Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr
130 135 140
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn
145 150 155 160
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val
195 200 205
Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
225 230 235 240
Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
260 265 270
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
275 280 285
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
290 295 300
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
305 310 315 320
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
325 330 335
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
355 360 365
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
370 375 380
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
385 390 395 400
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
405 410 415
Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser
420 425 430
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
435 440 445
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 212
<211> 1392
<212> DNA
<213> Mus musculus
<400> 212
atgggatgga actggatctt tctcttcctc ttgtcaggaa ctgcaggtgt ctactctgag 60
gtccagctgc aacaatctgg acctgagctg gtgaagcctg gggcttcagt gaagatgtcc 120
tgtaaggctt ctggatacac attcactgac tactacatga actgggtgaa gcagagccat 180
ggagagagcc ttgagtggat tggagatatt aatccttaca acgatgatac tacctacaac 240
cacaagttca agggcaaggc cacattgact gtagacaaat cctccaacac agcctacatg 300
cagctcaaca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagacggcc 360
gttattacta cgaatgctat ggactactgg ggtcaaggaa cctcagtcac cgtctcctca 420
gccaaaacga cacccccatc tgtctatcca ctggcccctg gatctgctgc ccaaactaac 480
tccatggtga ccctgggatg cctggtcaag ggctatttcc ctgagccagt gacagtgacc 540
tggaactctg gatccctgtc cagcggtgtg cacaccttcc cagctgtcct gcagtctgac 600
ctctacactc tgagcagctc agtgactgtc ccctccagca cctggcccag cgagaccgtc 660
acctgcaacg ttgcccaccc ggccagcagc accaaggtgg acaagaaaat tgtgcccagg 720
gattgtggtt gtaagccttg catatgtaca gtcccagaag tatcatctgt cttcatcttc 780
cccccaaagc ccaaggatgt gctcaccatt actctgactc ctaaggtcac gtgtgttgtg 840
gtagacatca gcaaggatga tcccgaggtc cagttcagct ggtttgtaga tgatgtggag 900
gtgcacacag ctcagacgca accccgggag gagcagttca acagcacttt ccgctcagtc 960
agtgaacttc ccatcatgca ccaggactgg ctcaatggca aggagttcaa atgcagggtc 1020
aacagtgcag ctttccctgc ccccatcgag aaaaccatct ccaaaaccaa aggcagaccg 1080
aaggctccac aggtgtacac cattccacct cccaaggagc agatggccaa ggataaagtc 1140
agtctgacct gcatgataac agacttcttc cctgaagaca ttactgtgga gtggcagtgg 1200
aatgggcagc cagcggagaa ctacaagaac actcagccca tcatggacac agatggctct 1260
tacttcatct acagcaagct caatgtgcag aagagcaact gggaggcagg aaatactttc 1320
acctgctctg tgttacatga gggcctgcac aaccaccata ctgagaagag cctctcccac 1380
tctcctggta aa 1392
<210> 213
<211> 215
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 213
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Thr Ser Ser
20 25 30
Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Phe Phe Pro
85 90 95
Ser Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 214
<211> 645
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 214
gacatccagc tgacccagag ccccagcttc ctttccgcat ccgttggtga ccgagtaaca 60
atcacatgcc gcgcctcatc ttcagttaca tcttcttatc ttaattggta tcaacaaaaa 120
ccaggaaaag cacctaaact tcttatatac tctacatcta atctcgcatc aggagttccc 180
tctcgatttt caggatctgg atcaggcaca gaatttacac ttactatatc atcactccaa 240
ccagaagact tcgccactta ttactgccaa caatacgatt tttttccaag cacattcgga 300
ggaggtacaa aagtagaaat caagcgtacg gtggctgcac catctgtctt catcttcccg 360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 645
<210> 215
<211> 237
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 215
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Ser Ser Val Thr Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Lys Ala Pro Lys Leu Leu Ile Tyr Ser Thr Ser Asn 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 Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Tyr Asp Phe Phe Pro Ser Thr Phe Gly Gly Gly Thr Lys Val 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> 216
<211> 711
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 216
atggacatga gggtccccgc tcagctcctg gggctcctgc tactctggct cccaggtgcc 60
agatgtgaca tccagctgac ccagagcccc agcttccttt ccgcatccgt tggtgaccga 120
gtaacaatca catgccgcgc ctcatcttca gttacatctt cttatcttaa ttggtatcaa 180
caaaaaccag gaaaagcacc taaacttctt atatactcta catctaatct cgcatcagga 240
gttccctctc gattttcagg atctggatca ggcacagaat ttacacttac tatatcatca 300
ctccaaccag aagacttcgc cacttattac tgccaacaat acgatttttt tccaagcaca 360
ttcggaggag gtacaaaagt agaaatcaag cgtacggtgg ctgcaccatc tgtcttcatc 420
ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 480
aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 540
aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 600
accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 660
catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 711
<210> 217
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 217
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 218
<211> 1341
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 218
gaggtgcagc tggtgcagag cggcgccgag gtcaagaaac ctggagcaag cgtaaaggtt 60
agttgcaaag catctggata cacatttacc gactactaca tgaattgggt acgacaagcc 120
cctggacaaa gacttgaatg gatgggagac attaaccctt ataacgacga cactacatac 180
aatcataaat ttaaaggaag agttacaatt acaagagata catccgcatc aaccgcctat 240
atggaacttt cctcattgag atctgaagac actgctgttt attactgtgc aagagaaact 300
gccgttatta ctactaacgc tatggattac tggggtcaag gaaccactgt taccgtctct 360
agtgcctcca ccaagggccc atcggtcttc cccctggcgc cctgctccag gagcacctcc 420
gagagcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 480
tcgtggaact caggcgctct gaccagcggc gtgcacacct tcccagctgt cctacagtcc 540
tcaggactct actccctcag cagcgtggtg accgtgccct ccagcaactt cggcacccag 600
acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gacagttgag 660
cgcaaatgtt gtgtcgagtg cccaccgtgc ccagcaccac ctgtggcagg accgtcagtc 720
ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcacg 780
tgcgtggtgg tggacgtgag ccacgaagac cccgaggtcc agttcaactg gtacgtggac 840
ggcgtggagg tgcataatgc caagacaaag ccacgggagg agcagttcaa cagcacgttc 900
cgtgtggtca gcgtcctcac cgttgtgcac caggactggc tgaacggcaa ggagtacaag 960
tgcaaggtct ccaacaaagg cctcccagcc cccatcgaga aaaccatctc caaaaccaaa 1020
gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggagga gatgaccaag 1080
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1140
tgggagagca atgggcagcc ggagaacaac tacaagacca cacctcccat gctggactcc 1200
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 1260
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1320
ctctccctgt ctccgggtaa a 1341
<210> 219
<211> 466
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 219
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu 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
Thr Asp Tyr Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
50 55 60
Glu Trp Met Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn
65 70 75 80
His Lys Phe Lys Gly Arg Val Thr Ile Thr Arg 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 Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp
115 120 125
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
130 135 140
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
145 150 155 160
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
195 200 205
Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg
225 230 235 240
Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
245 250 255
Pro Ser Val Phe Leu 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 His Glu
275 280 285
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
290 295 300
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
355 360 365
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
370 375 380
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
385 390 395 400
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met
405 410 415
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
420 425 430
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
435 440 445
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
450 455 460
Gly Lys
465
<210> 220
<211> 1398
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 220
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagagcgg cgccgaggtc aagaaacctg gagcaagcgt aaaggttagt 120
tgcaaagcat ctggatacac atttaccgac tactacatga attgggtacg acaagcccct 180
ggacaaagac ttgaatggat gggagacatt aacccttata acgacgacac tacatacaat 240
cataaattta aaggaagagt tacaattaca agagatacat ccgcatcaac cgcctatatg 300
gaactttcct cattgagatc tgaagacact gctgtttatt actgtgcaag agaaactgcc 360
gttattacta ctaacgctat ggattactgg ggtcaaggaa ccactgttac cgtctctagt 420
gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgctctgac cagcggcgtg cacaccttcc cagctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcaacttcgg cacccagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagac agttgagcgc 720
aaatgttgtg tcgagtgccc accgtgccca gcaccacctg tggcaggacc gtcagtcttc 780
ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacgtgc 840
gtggtggtgg acgtgagcca cgaagacccc gaggtccagt tcaactggta cgtggacggc 900
gtggaggtgc ataatgccaa gacaaagcca cgggaggagc agttcaacag cacgttccgt 960
gtggtcagcg tcctcaccgt tgtgcaccag gactggctga acggcaagga gtacaagtgc 1020
aaggtctcca acaaaggcct cccagccccc atcgagaaaa ccatctccaa aaccaaaggg 1080
cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200
gagagcaatg ggcagccgga gaacaactac aagaccacac ctcccatgct ggactccgac 1260
ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380
tccctgtctc cgggtaaa 1398
<210> 221
<211> 215
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 221
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 Ser Val Ser Ser Thr Ile Ser Ser Asn
20 25 30
His Leu His Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 222
<211> 645
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 222
gacatccaga tgacccagtc tccatcctcc ctctcagcat ccgtaggcga tagagttaca 60
ataacatgca gcgtatcatc aactatatca tcaaatcatc ttcattggtt ccaacagaaa 120
cccggcaaag cacctaaatc acttatatac ggcacatcaa atctcgcatc aggcgttcct 180
tcaagatttt caggctctgg ctcaggcacc gactttactc ttacaatatc ctccctccaa 240
cccgaagact tcgcaaccta ttactgtcaa caatggtcct catatccact cacatttggc 300
ggcggcacaa aagtagaaat taaacgtacg gtggctgcac catctgtctt catcttcccg 360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 645
<210> 223
<211> 237
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 223
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Thr Ile Ser Ser Asn His Leu His Trp Phe Gln Gln Lys Pro Gly
50 55 60
Lys Ala Pro Lys Ser Leu Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu
85 90 95
Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Ser Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val 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> 224
<211> 711
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 224
atggacatga gggtccccgc tcagctcctg gggctcctgc tactctggct ccgaggtgcc 60
agatgtgaca tccagatgac ccagtctcca tcctccctct cagcatccgt aggcgataga 120
gttacaataa catgcagcgt atcatcaact atatcatcaa atcatcttca ttggttccaa 180
cagaaacccg gcaaagcacc taaatcactt atatacggca catcaaatct cgcatcaggc 240
gttccttcaa gattttcagg ctctggctca ggcaccgact ttactcttac aatatcctcc 300
ctccaacccg aagacttcgc aacctattac tgtcaacaat ggtcctcata tccactcaca 360
tttggcggcg gcacaaaagt agaaattaaa cgtacggtgg ctgcaccatc tgtcttcatc 420
ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 480
aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 540
aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 600
accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 660
catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 711
<210> 225
<211> 451
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 225
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 Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
115 120 125
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser
130 135 140
Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
180 185 190
Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys
195 200 205
Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu
210 215 220
Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
290 295 300
Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 226
<211> 1353
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<400> 226
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctgactt caacattaaa gacttctatc tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gattggaagg attgatcctg agaatggtga tactttatat 180
gacccgaagt tccaggacaa ggtcaccatg accacagaca cgtccaccag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagaggcg 300
gattatttcc acgatggtac ctcctactgg tacttcgatg tctggggccg tggcaccctg 360
gtcaccgtct ctagtgcctc caccaagggc ccatcggtct tccccctggc gccctgctcc 420
aggagcacct ccgagagcac agcggccctg ggctgcctgg tcaaggacta cttccccgaa 480
ccggtgacgg tgtcgtggaa ctcaggcgct ctgaccagcg gcgtgcacac cttcccagct 540
gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcaac 600
ttcggcaccc agacctacac ctgcaacgta gatcacaagc ccagcaacac caaggtggac 660
aagacagttg agcgcaaatg ttgtgtcgag tgcccaccgt gcccagcacc acctgtggca 720
ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc 780
cctgaggtca cgtgcgtggt ggtggacgtg agccacgaag accccgaggt ccagttcaac 840
tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccacggga ggagcagttc 900
aacagcacgt tccgtgtggt cagcgtcctc accgttgtgc accaggactg gctgaacggc 960
aaggagtaca agtgcaaggt ctccaacaaa ggcctcccag cccccatcga gaaaaccatc 1020
tccaaaacca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggag 1080
gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1140
atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacacctccc 1200
atgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg 1260
tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1320
acgcagaaga gcctctccct gtctccgggt aaa 1353
<210> 227
<211> 470
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 227
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu 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 Asp Phe Asn Ile
35 40 45
Lys Asp Phe Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp
65 70 75 80
Pro Lys Phe Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr
115 120 125
Trp Tyr Phe Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
130 135 140
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
145 150 155 160
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
195 200 205
Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr
210 215 220
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
225 230 235 240
Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro
245 250 255
Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
260 265 270
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
275 280 285
Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
290 295 300
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn
305 310 315 320
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp
325 330 335
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
340 345 350
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu
355 360 365
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
370 375 380
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
385 390 395 400
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
405 410 415
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
420 425 430
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
435 440 445
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
450 455 460
Ser Leu Ser Pro Gly Lys
465 470
<210> 228
<211> 1410
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 228
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120
tgcaaggctt ctgacttcaa cattaaagac ttctatctac actgggtgcg acaggcccct 180
ggacaagggc ttgagtggat tggaaggatt gatcctgaga atggtgatac tttatatgac 240
ccgaagttcc aggacaaggt caccatgacc acagacacgt ccaccagcac agcctacatg 300
gagctgagga gcctgagatc tgacgacacg gccgtgtatt actgtgcgag agaggcggat 360
tatttccacg atggtacctc ctactggtac ttcgatgtct ggggccgtgg caccctggtc 420
accgtctcta gtgcctccac caagggccca tcggtcttcc ccctggcgcc ctgctccagg 480
agcacctccg agagcacagc ggccctgggc tgcctggtca aggactactt ccccgaaccg 540
gtgacggtgt cgtggaactc aggcgctctg accagcggcg tgcacacctt cccagctgtc 600
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcaacttc 660
ggcacccaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 720
acagttgagc gcaaatgttg tgtcgagtgc ccaccgtgcc cagcaccacc tgtggcagga 780
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840
gaggtcacgt gcgtggtggt ggacgtgagc cacgaagacc ccgaggtcca gttcaactgg 900
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cacgggagga gcagttcaac 960
agcacgttcc gtgtggtcag cgtcctcacc gttgtgcacc aggactggct gaacggcaag 1020
gagtacaagt gcaaggtctc caacaaaggc ctcccagccc ccatcgagaa aaccatctcc 1080
aaaaccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140
atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctaccc cagcgacatc 1200
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac acctcccatg 1260
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1320
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380
cagaagagcc tctccctgtc tccgggtaaa 1410
<210> 229
<211> 213
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 229
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Ile Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu
65 70 75 80
Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 230
<211> 639
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 230
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca gggccagctc aagtataagt tacatacact ggtatcagca aaaaccaggg 120
aaagccccta agctcctgat ctatgccaca tccaacctgg cttctggggt cccatcaagg 180
ttcagcggca gtggatctgg gacagaattc actctcacaa tcagcagcct gcagcctgaa 240
gattttgcaa cttattactg tcagcagtgg agtagtgacc cactcacgtt cggcggaggg 300
accaaggtgg agatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 360
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540
agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600
agctcgcccg tcacaaagag cttcaacagg ggagagtgt 639
<210> 231
<211> 235
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 231
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Ser Ser Ile Ser Tyr Ile His Trp Tyr Gln Gln Lys Pro Gly Lys Ala
50 55 60
Pro Lys Leu Leu Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile
85 90 95
Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asp Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
115 120 125
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
130 135 140
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
145 150 155 160
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
165 170 175
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
195 200 205
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
210 215 220
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 232
<211> 705
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 232
atggacatga gggtccccgc tcagctcctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgaca tccagttgac ccagtctcca tccttcctgt ctgcatctgt aggagacaga 120
gtcaccatca cttgcagggc cagctcaagt ataagttaca tacactggta tcagcaaaaa 180
ccagggaaag cccctaagct cctgatctat gccacatcca acctggcttc tggggtccca 240
tcaaggttca gcggcagtgg atctgggaca gaattcactc tcacaatcag cagcctgcag 300
cctgaagatt ttgcaactta ttactgtcag cagtggagta gtgacccact cacgttcggc 360
ggagggacca aggtggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 420
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705
<210> 233
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 233
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 234
<211> 1341
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 234
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggatt cgacattaag gactactata tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatcggaagg gttgatcctg acaatggtga gactgaattt 180
gccccgaagt tcccgggcaa ggtcaccatg accacagaca cgtccatcag cacagcctac 240
atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagaagac 300
tacgatggta cctacacctg gtttccttat tggggccaag ggactctggt caccgtctct 360
agtgcctcca ccaagggccc atcggtcttc cccctggcgc cctgctccag gagcacctcc 420
gagagcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 480
tcgtggaact caggcgctct gaccagcggc gtgcacacct tcccagctgt cctacagtcc 540
tcaggactct actccctcag cagcgtggtg accgtgccct ccagcaactt cggcacccag 600
acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gacagttgag 660
cgcaaatgtt gtgtcgagtg cccaccgtgc ccagcaccac ctgtggcagg accgtcagtc 720
ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcacg 780
tgcgtggtgg tggacgtgag ccacgaagac cccgaggtcc agttcaactg gtacgtggac 840
ggcgtggagg tgcataatgc caagacaaag ccacgggagg agcagttcaa cagcacgttc 900
cgtgtggtca gcgtcctcac cgttgtgcac caggactggc tgaacggcaa ggagtacaag 960
tgcaaggtct ccaacaaagg cctcccagcc cccatcgaga aaaccatctc caaaaccaaa 1020
gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggagga gatgaccaag 1080
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1140
tgggagagca atgggcagcc ggagaacaac tacaagacca cacctcccat gctggactcc 1200
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 1260
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1320
ctctccctgt ctccgggtaa a 1341
<210> 235
<211> 466
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 235
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu 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 Phe Asp Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala
65 70 75 80
Pro Lys Phe Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
130 135 140
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
145 150 155 160
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
195 200 205
Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg
225 230 235 240
Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
245 250 255
Pro Ser Val Phe Leu 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 His Glu
275 280 285
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
290 295 300
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
355 360 365
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
370 375 380
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
385 390 395 400
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met
405 410 415
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
420 425 430
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
435 440 445
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
450 455 460
Gly Lys
465
<210> 236
<211> 1398
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 236
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120
tgcaaggctt ctggattcga cattaaggac tactatatac actgggtgcg acaggcccct 180
ggacaagggc ttgagtggat cggaagggtt gatcctgaca atggtgagac tgaatttgcc 240
ccgaagttcc cgggcaaggt caccatgacc acagacacgt ccatcagcac agcctacatg 300
gagctgagca ggctgagatc tgacgacacg gccgtgtatt actgtgcgag agaagactac 360
gatggtacct acacctggtt tccttattgg ggccaaggga ctctggtcac cgtctctagt 420
gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgctctgac cagcggcgtg cacaccttcc cagctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcaacttcgg cacccagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagac agttgagcgc 720
aaatgttgtg tcgagtgccc accgtgccca gcaccacctg tggcaggacc gtcagtcttc 780
ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacgtgc 840
gtggtggtgg acgtgagcca cgaagacccc gaggtccagt tcaactggta cgtggacggc 900
gtggaggtgc ataatgccaa gacaaagcca cgggaggagc agttcaacag cacgttccgt 960
gtggtcagcg tcctcaccgt tgtgcaccag gactggctga acggcaagga gtacaagtgc 1020
aaggtctcca acaaaggcct cccagccccc atcgagaaaa ccatctccaa aaccaaaggg 1080
cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200
gagagcaatg ggcagccgga gaacaactac aagaccacac ctcccatgct ggactccgac 1260
ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380
tccctgtctc cgggtaaa 1398
<210> 237
<211> 7
<212> PRT
<213> Mus musculus
<400> 237
Gly Thr Ser Asn Leu Ala Ser
1 5
<210> 238
<211> 8
<212> PRT
<213> Mus musculus
<400> 238
Gln Gln Trp Thr Thr Thr Tyr Thr
1 5
<210> 239
<211> 11
<212> PRT
<213> Mus musculus
<400> 239
Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn
1 5 10
<210> 240
<211> 7
<212> PRT
<213> Mus musculus
<400> 240
Ser Thr Ser Arg Leu Asn Ser
1 5
<210> 241
<211> 8
<212> PRT
<213> Mus musculus
<400> 241
Gln Gln Asp Ile Lys His Pro Thr
1 5
<210> 242
<211> 11
<212> PRT
<213> Mus musculus
<400> 242
Lys Ala Ser Gln Asp Val Phe Thr Ala Val Ala
1 5 10
<210> 243
<211> 7
<212> PRT
<213> Mus musculus
<400> 243
Trp Ala Ser Thr Arg His Thr
1 5
<210> 244
<211> 9
<212> PRT
<213> Mus musculus
<400> 244
Gln Gln Tyr Ser Ser Tyr Pro Leu Thr
1 5
<210> 245
<211> 5
<212> PRT
<213> Mus musculus
<400> 245
Asp Tyr Asn Met His
1 5
<210> 246
<211> 17
<212> PRT
<213> Mus musculus
<400> 246
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 247
<211> 14
<212> PRT
<213> Mus musculus
<400> 247
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 248
<211> 5
<212> PRT
<213> Mus musculus
<400> 248
Asp Tyr Asn Met His
1 5
<210> 249
<211> 17
<212> PRT
<213> Mus musculus
<400> 249
Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 250
<211> 14
<212> PRT
<213> Mus musculus
<400> 250
Leu Val Tyr Asp Gly Ser Tyr Glu Asp Trp Tyr Phe Asp Val
1 5 10
<210> 251
<211> 5
<212> PRT
<213> Mus musculus
<400> 251
Asp Tyr Asn Met His
1 5
<210> 252
<211> 17
<212> PRT
<213> Mus musculus
<400> 252
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Gln Phe Lys
1 5 10 15
Gly
<210> 253
<211> 14
<212> PRT
<213> Mus musculus
<400> 253
Leu Gly Tyr Val Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
1 5 10
<210> 254
<211> 5
<212> PRT
<213> Mus musculus
<400> 254
Asp Tyr Asn Met His
1 5
<210> 255
<211> 17
<212> PRT
<213> Mus musculus
<400> 255
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 256
<211> 14
<212> PRT
<213> Mus musculus
<400> 256
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 257
<211> 5
<212> PRT
<213> Mus musculus
<400> 257
Asp Tyr Asn Met His
1 5
<210> 258
<211> 17
<212> PRT
<213> Mus musculus
<400> 258
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 259
<211> 14
<212> PRT
<213> Mus musculus
<400> 259
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 260
<211> 5
<212> PRT
<213> Mus musculus
<400> 260
Asp Tyr Asn Met His
1 5
<210> 261
<211> 17
<212> PRT
<213> Mus musculus
<400> 261
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 262
<211> 14
<212> PRT
<213> Mus musculus
<400> 262
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 263
<211> 5
<212> PRT
<213> Mus musculus
<400> 263
Asp Tyr Asn Met His
1 5
<210> 264
<211> 17
<212> PRT
<213> Mus musculus
<400> 264
Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 265
<211> 14
<212> PRT
<213> Mus musculus
<400> 265
Leu Gly Tyr Tyr Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
1 5 10
<210> 266
<211> 5
<212> PRT
<213> Mus musculus
<400> 266
Asp Tyr Tyr Ile His
1 5
<210> 267
<211> 17
<212> PRT
<213> Mus musculus
<400> 267
Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val Pro Lys Phe Gln
1 5 10 15
Gly
<210> 268
<211> 13
<212> PRT
<213> Mus musculus
<400> 268
Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val Asp Tyr
1 5 10
<210> 269
<211> 5
<212> PRT
<213> Mus musculus
<400> 269
Asp Tyr Ile Met His
1 5
<210> 270
<211> 17
<212> PRT
<213> Mus musculus
<400> 270
Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe Lys
1 5 10 15
Gly
<210> 271
<211> 11
<212> PRT
<213> Mus musculus
<400> 271
Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
1 5 10
<210> 272
<211> 5
<212> PRT
<213> Mus musculus
<400> 272
Asp Tyr Tyr Met His
1 5
<210> 273
<211> 17
<212> PRT
<213> Mus musculus
<400> 273
Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp Pro Lys Phe Gln
1 5 10 15
Gly
<210> 274
<211> 10
<212> PRT
<213> Mus musculus
<400> 274
Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr
1 5 10
<210> 275
<211> 10
<212> PRT
<213> Mus musculus
<400> 275
Arg Ala Ser Ser Ser Val Tyr Tyr Met His
1 5 10
<210> 276
<211> 7
<212> PRT
<213> Mus musculus
<400> 276
Ala Thr Ser Asn Leu Ala Ser
1 5
<210> 277
<211> 9
<212> PRT
<213> Mus musculus
<400> 277
Gln Gln Trp Ser Ser Asp Pro Leu Thr
1 5
<210> 278
<211> 12
<212> PRT
<213> Mus musculus
<400> 278
Ser Val Ser Ser Thr Ile Ser Ser Asn His Leu His
1 5 10
<210> 279
<211> 7
<212> PRT
<213> Mus musculus
<400> 279
Gly Thr Ser Asn Leu Ala Ser
1 5
<210> 280
<211> 9
<212> PRT
<213> Mus musculus
<400> 280
Gln Gln Trp Ser Ser Tyr Pro Leu Thr
1 5
<210> 281
<211> 10
<212> PRT
<213> Mus musculus
<400> 281
Arg Ala Ser Ser Ser Ile Ser Tyr Ile His
1 5 10
<210> 282
<211> 7
<212> PRT
<213> Mus musculus
<400> 282
Ala Thr Ser Asn Leu Ala Ser
1 5
<210> 283
<211> 9
<212> PRT
<213> Mus musculus
<400> 283
Gln Gln Trp Ser Ser Asp Pro Leu Thr
1 5
<210> 284
<211> 12
<212> PRT
<213> Mus musculus
<400> 284
Arg Ala Ser Ser Ser Val Thr Ser Ser Tyr Leu Asn
1 5 10
<210> 285
<211> 7
<212> PRT
<213> Mus musculus
<400> 285
Ser Thr Ser Asn Leu Ala Ser
1 5
<210> 286
<211> 9
<212> PRT
<213> Mus musculus
<400> 286
Gln Gln Tyr Asp Phe Phe Pro Ser Thr
1 5
<210> 287
<211> 5
<212> PRT
<213> Mus musculus
<400> 287
Asp Tyr Phe Ile His
1 5
<210> 288
<211> 17
<212> PRT
<213> Mus musculus
<400> 288
Arg Leu Asp Pro Glu Asp Gly Glu Ser Asp Tyr Ala Pro Lys Phe Gln
1 5 10 15
Asp
<210> 289
<211> 12
<212> PRT
<213> Mus musculus
<400> 289
Glu Asp Tyr Asp Gly Thr Tyr Thr Phe Phe Pro Tyr
1 5 10
<210> 290
<211> 5
<212> PRT
<213> Mus musculus
<400> 290
Asp Phe Tyr Leu His
1 5
<210> 291
<211> 17
<212> PRT
<213> Mus musculus
<400> 291
Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe Gln
1 5 10 15
Asp
<210> 292
<211> 16
<212> PRT
<213> Mus musculus
<400> 292
Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe Asp Val
1 5 10 15
<210> 293
<211> 5
<212> PRT
<213> Mus musculus
<400> 293
Asp Tyr Tyr Ile His
1 5
<210> 294
<211> 17
<212> PRT
<213> Mus musculus
<400> 294
Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe Pro
1 5 10 15
Gly
<210> 295
<211> 12
<212> PRT
<213> Mus musculus
<400> 295
Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr
1 5 10
<210> 296
<211> 5
<212> PRT
<213> Mus musculus
<400> 296
Asp Tyr Tyr Met Asn
1 5
<210> 297
<211> 17
<212> PRT
<213> Mus musculus
<400> 297
Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe Lys
1 5 10 15
Gly
<210> 298
<211> 11
<212> PRT
<213> Mus musculus
<400> 298
Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp
1 5 10
<210> 299
<211> 130
<212> PRT
<213> Mus musculus
<400> 299
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Met Leu Ile Ser Val Thr
1 5 10 15
Val Ile Leu Ser Ser Gly Glu Ile Val Leu Thr Gln Ser Pro Ala Leu
20 25 30
Met Ala Ala Ser Pro Gly Glu Lys Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Ser Ile Ser Ser Ser Asn Leu His Trp Ser Gln Gln Lys Ser Gly
50 55 60
Thr Ser Pro Lys Leu Trp Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu
85 90 95
Thr Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Thr Thr Thr Tyr Thr Phe Gly Ser Gly Thr Lys Leu Glu Leu
115 120 125
Lys Arg
130
<210> 300
<211> 390
<212> DNA
<213> Mus musculus
<400> 300
atggattttc aggtgcagat tttcagcttc atgctaatca gtgtcacagt catattgtcc 60
agtggagaaa ttgtgctcac ccagtctcca gcactcatgg ctgcatctcc aggggagaag 120
gtcaccatca cctgcagtgt cagctcgagt ataagttcca gcaacttaca ctggtcccag 180
cagaagtcag gaacctcccc caaactctgg atttatggca catccaacct tgcttctgga 240
gtccctgttc gcttcagtgg cagtggatct gggacctctt attctctcac aatcagcagc 300
atggaggctg aagatgctgc cacttattac tgtcaacagt ggactactac gtatacgttc 360
ggatcgggga ccaagctgga gctgaaacgt 390
<210> 301
<211> 141
<212> PRT
<213> Mus musculus
<400> 301
Met Gly Trp Asn Trp Ile Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Arg Gln Ser Gly Ala Asp Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val
65 70 75 80
Pro Lys Phe Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Ile
100 105 110
Tyr Tyr Cys Gly Arg Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
130 135 140
<210> 302
<211> 423
<212> DNA
<213> Mus musculus
<400> 302
atgggatgga actggatcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gtgcagttgc ggcagtctgg ggcagacctt gtgaagccag gggcctcagt caagttgtcc 120
tgcacagctt ctggcttcaa cattaaagac tactatatac actgggtgaa gcagaggcct 180
gaacagggcc tggagtggat tggaaggatt gatcctgata atggtgaaag tacatatgtc 240
ccgaagttcc agggcaaggc cactataaca gcagacacat catccaacac agcctaccta 300
caactcagaa gcctgacatc tgaggacact gccatctatt attgtgggag agaggggctc 360
gactatggtg actactatgc tgtggactac tggggtcaag gaacctcggt cacagtctcg 420
agc 423
<210> 303
<211> 130
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 303
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Ser Ile Ser Ser Ser Asn Leu His Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Lys Ala Pro Lys Leu Leu Ile Tyr Gly Thr Ser Asn 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 Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Thr Thr Thr Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 304
<211> 390
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 304
atggatatgc gcgtgccggc gcagctgctg ggcctgctgc tgctgtggct gccgggcgcg 60
cgctgcgata ttcagctgac ccagagcccg agctttctga gcgcgagcgt gggcgatcgc 120
gtgaccatta cctgcagcgt gagcagcagc attagcagca gcaacctgca ttggtatcag 180
cagaaaccgg gcaaagcgcc gaaactgctg atttatggca ccagcaacct ggcgagcggc 240
gtgccgagcc gctttagcgg cagcggcagc ggcaccgaat ttaccctgac cattagcagc 300
ctgcagccgg aagattttgc gacctattat tgccagcagt ggaccaccac ctataccttt 360
ggccagggca ccaaactgga aattaaacgt 390
<210> 305
<211> 141
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 305
Met Asp Trp Thr Trp Ser Ile Leu Phe Leu Val Ala Ala Pro Thr Gly
1 5 10 15
Ala His Ser Glu 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 Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val
65 70 75 80
Pro Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135 140
<210> 306
<211> 423
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 306
atggattgga cctggagcat tctgtttctg gtggcggcgc cgaccggcgc gcatagcgaa 60
gtgcagctgg tgcagagcgg cgcggaagtg aaaaaaccgg gcgcgagcgt gaaagtgagc 120
tgcaaagcga gcggctttaa cattaaagat tattatattc attgggtgcg ccaggcgccg 180
ggccagggcc tggaatggat gggccgcatt gatccggata acggcgaaag cacctatgtg 240
ccgaaatttc agggccgcgt gaccatgacc accgatacca gcaccagcac cgcgtatatg 300
gaactgcgca gcctgcgcag cgatgatacc gcggtgtatt attgcgcgcg cgaaggcctg 360
gattatggcg attattatgc ggtggattat tggggccagg gcaccctggt gaccgtctcg 420
agc 423
<210> 307
<211> 127
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 307
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Asn Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val
50 55 60
Lys Leu Leu Ile Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser
85 90 95
Asn Leu Ala Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Asp Ile
100 105 110
Lys His Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg
115 120 125
<210> 308
<211> 381
<212> DNA
<213> Mus musculus
<400> 308
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcaac 120
atcagctgca gggcaagtca ggacattagc agttatttaa actggtatca gcagaaacca 180
gatggaactg ttaaactcct gatctactcc acatcaagat taaactcagg agtcccatca 240
aggttcagtg gcagtgggtc tgggacagat tattctctca ctattagcaa cctggcacaa 300
gaagatattg ccacttactt ttgccaacag gatattaagc atccgacgtt cggtggaggc 360
accaagttgg agctgaaacg t 381
<210> 309
<211> 139
<212> PRT
<213> Mus musculus
<400> 309
Met Glu Trp Ile Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Thr Phe
35 40 45
Thr Asp Tyr Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn
65 70 75 80
Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 310
<211> 417
<212> DNA
<213> Mus musculus
<400> 310
atggaatgga tctggatatt tctcttcctc ctgtcaggaa ctgcaggtgt ccactctgag 60
gtccagctgc agcagtctgg acctgagctg gtaaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctgggttcac attcactgac tacattatgc actgggtgaa gcagaagcct 180
gggcagggcc ttgagtggat tggatatatt aatccttaca atgatgatac tgaatacaat 240
gagaagttca aaggcaaggc cacactgact tcagacaaat cctccagcac agcctacatg 300
gatctcagca gtctgacctc tgagggctct gcggtctatt actgtgcaag atcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcacagt ctcgagc 417
<210> 311
<211> 127
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 311
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser
20 25 30
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro
50 55 60
Lys Leu Leu Ile Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
85 90 95
Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Ile
100 105 110
Lys His Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg
115 120 125
<210> 312
<211> 381
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 312
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggtga ccgtgtcacc 120
atcacttgcc gcgcaagtca ggatattagc agctatttaa attggtatca gcagaaacca 180
gggaaagccc ctaagctcct gatctattct acttcccgtt tgaatagtgg ggtcccatca 240
cgcttcagtg gcagtggctc tgggacagat ttcactctca ccatcagcag tctgcaacct 300
gaagattttg caacttacta ctgtcaacag gatattaaac accctacgtt cggtcaaggc 360
accaaggtgg agatcaaacg t 381
<210> 313
<211> 139
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 313
Met Glu Trp Ile Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe
35 40 45
Thr Asp Tyr Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn
65 70 75 80
Glu Lys Phe Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr 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 Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 314
<211> 107
<212> PRT
<213> Mus musculus
<400> 314
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Asn Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Ala Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg
100 105
<210> 315
<211> 128
<212> PRT
<213> Mus musculus
<400> 315
Met Lys Ser Gln Thr Gln Val Phe Val Tyr Met Leu Leu Trp Leu Ser
1 5 10 15
Gly Val Glu Gly Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser
20 25 30
Thr Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp
35 40 45
Val Phe Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro
50 55 60
Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp
65 70 75 80
Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
85 90 95
Asn Val Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Ser
100 105 110
Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg
115 120 125
<210> 316
<211> 381
<212> DNA
<213> Mus musculus
<400> 316
atgaagtcac agacccaggt ctttgtatac atgttgctgt ggttgtctgg tgttgaagga 60
gacattgtga tgacccagtc tcacaaattc atgtccacgt cagtaggaga cagggtcacc 120
atcacctgca aggccagtca ggatgtcttt actgctgtag cctggtatca acagaaacca 180
ggacaatctc ctaaactact gatttactgg gcatccaccc ggcacactgg agtccctgat 240
cgcttcacag gcagtggatc tgggacagat ttcactctca ccattagcaa tgtgcagtct 300
gaagacttgg cagattattt ctgtcaacaa tatagcagct atcctctcac gttcggtgct 360
gggaccaagt tggagctgaa a 381
<210> 317
<211> 138
<212> PRT
<213> Mus musculus
<400> 317
Met Gly Trp Asn Trp Ile Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg
20 25 30
Pro Gly Ala Leu Val Lys Leu Ser Cys Lys Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Met His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp
65 70 75 80
Pro Lys Phe Gln Gly Lys Ala Ser Ile Thr Thr Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 318
<211> 411
<212> DNA
<213> Mus musculus
<400> 318
atgggatgga actggatcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gttcagctgc agcagtctgg ggctgagctt gtgaggccag gggccttagt caagttgtcc 120
tgcaaagctt ctggcttcaa tattaaagac tactatatgc actgggtgaa gcagaggcct 180
gaacagggcc tggagtggat tggaaggatt gatcctgaga atggtgatat tatatatgac 240
ccgaagttcc agggcaaggc cagtataaca acagacacat cctccaacac agcctacctg 300
cagctcagca gcctgacgtc tgaggacact gccgtctatt actgtgctta cgatgctggt 360
gaccccgcct ggtttactta ctggggccaa gggactctgg tcaccgtctc g 411
<210> 319
<211> 130
<212> PRT
<213> Mus musculus
<400> 319
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser
35 40 45
Gln Asp Val Phe Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Tyr Ser Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
115 120 125
Lys Arg
130
<210> 320
<211> 390
<212> DNA
<213> Mus musculus
<400> 320
atggatatgc gcgtgccggc gcagctgctg ggcctgctgc tgctgtggct gcgcggcgcg 60
cgctgcgata tccagatgac ccagagcccg agcagcctga gcgcgagcgt gggcgatcgc 120
gtgaccatta cctgcaaagc gagccaggat gtgtttaccg cggtggcgtg gtatcagcag 180
aaaccgggca aagcgccgaa actgctgatt tattgggcga gcacccgcca taccggcgtg 240
ccgagtcgct ttagcggcag cggcagcggc accgatttta ccctgaccat tagcagcctg 300
cagccggaag attttgcgac ctattattgc cagcagtata gcagctatcc gctgaccttt 360
ggcggcggca ccaaagtgga aattaaacgt 390
<210> 321
<211> 138
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 321
Met Asp Trp Thr Trp Ser Ile Leu Phe Leu Val Ala Ala Pro Thr Gly
1 5 10 15
Ala His Ser Glu 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 Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp
65 70 75 80
Pro Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 322
<211> 414
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic Polynucleotide
<220>
<221> misc_feature
<223> Humanized Antibody Sequence
<400> 322
atggattgga cctggagcat tctgtttctg gtggcggcgc cgaccggcgc gcatagcgaa 60
gtgcagctgg tgcagagcgg cgcggaagtg aaaaaaccgg gcgcgagcgt gaaagtgagc 120
tgcaaagcga gcggctttaa cattaaagat tattatatgc attgggtgcg ccaggcgccg 180
ggccagggcc tggaatggat cggccgcatt gatccggaaa acggcgatat tatttatgat 240
ccgaaatttc agggccgcgt gaccatgacc accgatacca gcaccagcac cgcgtatatg 300
gaactgcgca gcctgcgcag cgatgatacc gcggtgtatt attgcgcgta tgatgcgggc 360
gatccggcgt ggtttaccta ttggggccag ggcaccctgg tgaccgtctc gagc 414
<210> 323
<211> 106
<212> PRT
<213> Mus musculus
<400> 323
Thr Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
1 5 10 15
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
20 25 30
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
35 40 45
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
50 55 60
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
65 70 75 80
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
85 90 95
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
100 105
<210> 324
<211> 320
<212> PRT
<213> Mus musculus
<400> 324
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
1 5 10 15
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
50 55 60
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
65 70 75 80
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
85 90 95
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
100 105 110
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
115 120 125
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
130 135 140
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
145 150 155 160
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
165 170 175
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
180 185 190
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
195 200 205
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
210 215 220
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
225 230 235 240
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
245 250 255
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
260 265 270
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn
275 280 285
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
290 295 300
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
305 310 315 320
<210> 325
<211> 106
<212> PRT
<213> Homo sapiens
<400> 325
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
1 5 10 15
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
20 25 30
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
35 40 45
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
50 55 60
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
65 70 75 80
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
85 90 95
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
100 105
<210> 326
<211> 327
<212> PRT
<213> Homo sapiens
<400> 326
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
<210> 327
<211> 120
<212> PRT
<213> Mus musculus
<400> 327
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 Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 328
<211> 120
<212> PRT
<213> Mus musculus
<400> 328
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 Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 329
<211> 120
<212> PRT
<213> Mus musculus
<400> 329
Glu 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 Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 330
<211> 226
<212> PRT
<213> Mus musculus
<400> 330
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 Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Thr Val Ala Ala Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val
130 135 140
Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp
145 150 155 160
Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr
165 170 175
Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr
180 185 190
Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val
195 200 205
Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly
210 215 220
Glu Cys
225
<210> 331
<211> 447
<212> PRT
<213> Mus musculus
<400> 331
Glu 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 Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
435 440 445
<210> 332
<211> 107
<212> PRT
<213> Mus musculus
<400> 332
Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 333
<211> 324
<212> PRT
<213> Mus musculus
<400> 333
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
1 5 10 15
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
50 55 60
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
65 70 75 80
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
85 90 95
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
100 105 110
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
115 120 125
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
130 135 140
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
145 150 155 160
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
165 170 175
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
180 185 190
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
195 200 205
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
210 215 220
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
225 230 235 240
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
245 250 255
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
260 265 270
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn
275 280 285
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
290 295 300
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
305 310 315 320
Ser Pro Gly Lys
<210> 334
<211> 213
<212> PRT
<213> Mus musculus
<400> 334
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Asn Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Ala Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg Thr Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 335
<211> 444
<212> PRT
<213> Mus musculus
<400> 335
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 Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val
115 120 125
Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr
130 135 140
Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr
145 150 155 160
Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser
180 185 190
Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala
195 200 205
Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys
210 215 220
Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val
245 250 255
Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe
260 265 270
Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro
275 280 285
Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro
290 295 300
Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val
305 310 315 320
Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr
325 330 335
Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys
340 345 350
Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp
355 360 365
Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro
370 375 380
Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser
385 390 395 400
Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala
405 410 415
Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His
420 425 430
His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 336
<211> 108
<212> PRT
<213> Mus musculus
<400> 336
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 Lys Ala Ser Gln Asp Val Phe Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 337
<211> 324
<212> DNA
<213> Mus musculus
<400> 337
gatatccaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60
attacctgca aagcgagcca ggatgtgttt accgcggtgg cgtggtatca gcagaaaccg 120
ggcaaagcgc cgaaactgct gatttattgg gcgagcaccc gccataccgg cgtgccgagt 180
cgctttagcg gcagcggcag cggcaccgat tttaccctga ccattagcag cctgcagccg 240
gaagattttg cgacctatta ttgccagcag tatagcagct atccgctgac ctttggcggc 300
ggcaccaaag tggaaattaa acgt 324
<210> 338
<211> 119
<212> PRT
<213> Mus musculus
<400> 338
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp Pro Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 339
<211> 357
<212> DNA
<213> Mus musculus
<400> 339
gaagtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60
agctgcaaag cgagcggctt taacattaaa gattattata tgcattgggt gcgccaggcg 120
ccgggccagg gcctggaatg gatcggccgc attgatccgg aaaacggcga tattatttat 180
gatccgaaat ttcagggccg cgtgaccatg accaccgata ccagcaccag caccgcgtat 240
atggaactgc gcagcctgcg cagcgatgat accgcggtgt attattgcgc gtatgatgcg 300
ggcgatccgg cgtggtttac ctattggggc cagggcaccc tggtgaccgt ctcgagc 357
<210> 340
<211> 1395
<212> DNA
<213> Mus musculus
<400> 340
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120
tgcaaggctt ctggttttac cttcaccgac tatattatgc actgggtgcg tcaggcccct 180
ggtcaagggc ttgagtggat gggctatatc aacccttata atgatgacac cgaatacaac 240
gagaagttca agggccgtgt cacgattacc gcggacaaat ccacgagcac agcctacatg 300
gagctgagca gcctgcgctc tgaggacacg gccgtgtatt actgtgcgcg ttcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcaccgt ctctagtgcc 420
tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540
aactcaggcg ctctgaccag cggcgtgcac accttcccag ctgtcctaca gtcctcagga 600
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac 660
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagacagt tgagcgcaaa 720
tgttgtgtcg agtgcccacc gtgcccagca ccacctgtgg caggaccgtc agtcttcctc 780
ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccacga agaccccgag gtccagttca actggtacgt ggacggcgtg 900
gaggtgcata atgccaagac aaagccacgg gaggagcagt tcaacagcac gttccgtgtg 960
gtcagcgtcc tcaccgttgt gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc agcccccatc gagaaaacca tctccaaaac caaagggcag 1080
ccccgagaac cacaggtgta caccctgccc ccatcccggg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacacctc ccatgctgga ctccgacggc 1260
tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1380
ctgtctccgg gtaaa 1395
<210> 341
<211> 213
<212> PRT
<213> Mus musculus
<400> 341
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 342
<211> 639
<212> DNA
<213> Mus musculus
<400> 342
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggtga ccgtgtcacc 60
atcacttgcc gcgcaagtca ggatattagc agctatttaa attggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattct acttcccgtt tgaatagtgg ggtcccatca 180
cgcttcagtg gcagtggctc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcaacag gatattaaac accctacgtt cggtcaaggc 300
accaaggtgg agatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 360
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540
agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600
agctcgcccg tcacaaagag cttcaacagg ggagagtgt 639
<210> 343
<211> 235
<212> PRT
<213> Mus musculus
<400> 343
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Asp Ile Lys His Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
115 120 125
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
130 135 140
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
145 150 155 160
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
165 170 175
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
195 200 205
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
210 215 220
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 344
<211> 705
<212> DNA
<213> Mus musculus
<400> 344
atggacatga gggtgcccgc tcagctcctg gggctcctgc tgctgtggct gagaggtgcc 60
agatgtgaca tccagatgac ccagtctcca tcctccctgt ctgcatctgt aggtgaccgt 120
gtcaccatca cttgccgcgc aagtcaggat attagcagct atttaaattg gtatcagcag 180
aaaccaggga aagcccctaa gctcctgatc tattctactt cccgtttgaa tagtggggtc 240
ccatcacgct tcagtggcag tggctctggg acagatttca ctctcaccat cagcagtctg 300
caacctgaag attttgcaac ttactactgt caacaggata ttaaacaccc tacgttcggt 360
caaggcacca aggtggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 420
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705
<210> 345
<211> 446
<212> PRT
<213> Mus musculus
<400> 345
Glu 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 Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
210 215 220
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
260 265 270
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
290 295 300
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
325 330 335
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 346
<211> 1338
<212> DNA
<213> Mus musculus
<400> 346
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60
tcctgcaagg cttctggttt taccttcacc gactatatta tgcactgggt gcgtcaggcc 120
cctggtcaag ggcttgagtg gatgggctat atcaaccctt ataatgatga caccgaatac 180
aacgagaagt tcaagggccg tgtcacgatt accgcggaca aatccacgag cacagcctac 240
atggagctga gcagcctgcg ctctgaggac acggccgtgt attactgtgc gcgttcgatt 300
tattactacg atgccccgtt tgcttactgg ggccaaggga ctctggtcac cgtctctagt 360
gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420
agcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgctctgac cagcggcgtg cacaccttcc cagctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcaacttcgg cacccagacc 600
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagac agttgagcgc 660
aaatgttgtg tcgagtgccc accgtgccca gcaccacctg tggcaggacc gtcagtcttc 720
ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacgtgc 780
gtggtggtgg acgtgagcca cgaagacccc gaggtccagt tcaactggta cgtggacggc 840
gtggaggtgc ataatgccaa gacaaagcca cgggaggagc agttcaacag cacgttccgt 900
gtggtcagcg tcctcaccgt tgtgcaccag gactggctga acggcaagga gtacaagtgc 960
aaggtctcca acaaaggcct cccagccccc atcgagaaaa ccatctccaa aaccaaaggg 1020
cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1080
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140
gagagcaatg ggcagccgga gaacaactac aagaccacac ctcccatgct ggactccgac 1200
ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1260
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1320
tccctgtctc cgggtaaa 1338
<210> 347
<211> 465
<212> PRT
<213> Mus musculus
<400> 347
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe
35 40 45
Thr Asp Tyr Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn
65 70 75 80
Glu Lys Phe Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr 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 Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
130 135 140
Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser
145 150 155 160
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
165 170 175
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
180 185 190
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
195 200 205
Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val
210 215 220
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys
225 230 235 240
Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
245 250 255
Ser Val Phe Leu 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 His Glu Asp
275 280 285
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
290 295 300
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys
340 345 350
Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
370 375 380
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
385 390 395 400
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
435 440 445
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
450 455 460
Lys
465
<210> 348
<211> 1395
<212> DNA
<213> Mus musculus
<400> 348
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120
tgcaaggctt ctggttttac cttcaccgac tatattatgc actgggtgcg tcaggcccct 180
ggtcaagggc ttgagtggat gggctatatc aacccttata atgatgacac cgaatacaac 240
gagaagttca agggccgtgt cacgattacc gcggacaaat ccacgagcac agcctacatg 300
gagctgagca gcctgcgctc tgaggacacg gccgtgtatt actgtgcgcg ttcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcaccgt ctctagtgcc 420
tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540
aactcaggcg ctctgaccag cggcgtgcac accttcccag ctgtcctaca gtcctcagga 600
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac 660
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagacagt tgagcgcaaa 720
tgttgtgtcg agtgcccacc gtgcccagca ccacctgtgg caggaccgtc agtcttcctc 780
ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccacga agaccccgag gtccagttca actggtacgt ggacggcgtg 900
gaggtgcata atgccaagac aaagccacgg gaggagcagt tcaacagcac gttccgtgtg 960
gtcagcgtcc tcaccgttgt gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc agcccccatc gagaaaacca tctccaaaac caaagggcag 1080
ccccgagaac cacaggtgta caccctgccc ccatcccggg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacacctc ccatgctgga ctccgacggc 1260
tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1380
ctgtctccgg gtaaa 1395
<210> 349
<211> 417
<212> DNA
<213> Mus musculus
<400> 349
atggaatgga tctggatatt tctcttcctc ctgtcaggaa ctgcaggtgt ccactctgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120
tgcaaggctt ctggttttac cttcaccgac tatattatgc actgggtgcg tcaggcccct 180
ggtcaagggc ttgagtggat gggctatatc aacccttata atgatgacac cgaatacaac 240
gagaagttca agggccgtgt cacgattacc gcggacaaat ccacgagcac agcctacatg 300
gagctgagca gcctgcgctc tgaggacacg gccgtgtatt actgtgcgcg ttcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcacagt ctcgagc 417
<210> 350
<211> 218
<212> PRT
<213> Mus musculus
<400> 350
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 Ala Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp
20 25 30
Gly Thr Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Glu Ile Pro Ala
50 55 60
Arg Phe Ser Gly Thr Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His
65 70 75 80
Pro Val Glu Glu Glu Asp Ile Thr Thr Tyr Tyr Cys Gln Gln Ser Asn
85 90 95
Glu Asp Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105 110
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
115 120 125
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
130 135 140
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
145 150 155 160
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
165 170 175
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
180 185 190
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
195 200 205
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 351
<211> 15
<212> PRT
<213> Mus musculus
<400> 351
Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Thr Ser Tyr Met Asn
1 5 10 15
<210> 352
<211> 7
<212> PRT
<213> Mus musculus
<400> 352
Ala Ala Ser Asn Leu Glu Ser
1 5
<210> 353
<211> 9
<212> PRT
<213> Mus musculus
<400> 353
Gln Gln Ser Asn Glu Asp Pro Phe Thr
1 5
<210> 354
<211> 657
<212> DNA
<213> Mus musculus
<400> 354
gacattgtgt tgacccagtc tccagcttct ttggctgtgt ctctagggca gagggccacc 60
atcgcctgca aggccagcca aagtgttgat tatgatggta ctagttatat gaattggtac 120
caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 180
gagatcccag ccaggtttag tggcactggg tctgggacag acttcaccct caacatccat 240
cctgtggagg aggaggatat cacaacctat tactgtcagc aaagtaatga ggatccgttc 300
acgttcggag gggggaccaa gttggaaata aaacgggctg atgctgcacc aactgtatcc 360
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 420
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 480
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 540
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 600
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 657
<210> 355
<211> 238
<212> PRT
<213> Mus musculus
<400> 355
Met Glu Thr Asp Thr Ile Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala
20 25 30
Val Ser Leu Gly Gln Arg Ala Thr Ile Ala Cys Lys Ala Ser Gln Ser
35 40 45
Val Asp Tyr Asp Gly Thr Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser
65 70 75 80
Glu Ile Pro Ala Arg Phe Ser Gly Thr Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Asn Ile His Pro Val Glu Glu Glu Asp Ile Thr Thr Tyr Tyr Cys
100 105 110
Gln Gln Ser Asn Glu Asp Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro
130 135 140
Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu
145 150 155 160
Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly
165 170 175
Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp
195 200 205
Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr
210 215 220
Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 356
<211> 717
<212> DNA
<213> Mus musculus
<400> 356
atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60
gacattgtgt tgacccagtc tccagcttct ttggctgtgt ctctagggca gagggccacc 120
atcgcctgca aggccagcca aagtgttgat tatgatggta ctagttatat gaattggtac 180
caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 240
gagatcccag ccaggtttag tggcactggg tctgggacag acttcaccct caacatccat 300
cctgtggagg aggaggatat cacaacctat tactgtcagc aaagtaatga ggatccgttc 360
acgttcggag gggggaccaa gttggaaata aaacgggctg atgctgcacc aactgtatcc 420
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 480
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 540
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 600
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 660
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 717
<210> 357
<211> 442
<212> PRT
<213> Mus musculus
<400> 357
Gln Val Gln Leu Gln Gln Pro Gly Thr Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Thr 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 His Pro Ser Ala Ser Glu Ile Arg Leu Asp Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Leu Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met His Leu Ser Gly Pro Thr Ser Val Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Glu Trp Gly Ser Met Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro
115 120 125
Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly
130 135 140
Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn
145 150 155 160
Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr
180 185 190
Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser
195 200 205
Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys Pro
210 215 220
Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
225 230 235 240
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
245 250 255
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
260 265 270
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
275 280 285
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
290 295 300
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
305 310 315 320
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
325 330 335
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
340 345 350
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
355 360 365
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
370 375 380
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
385 390 395 400
Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
405 410 415
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
420 425 430
Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 358
<211> 5
<212> PRT
<213> Mus musculus
<400> 358
Thr Tyr Trp Met Asn
1 5
<210> 359
<211> 17
<212> PRT
<213> Mus musculus
<400> 359
Met Ile His Pro Ser Ala Ser Glu Ile Arg Leu Asp Gln Lys Phe Lys
1 5 10 15
Asp
<210> 360
<211> 9
<212> PRT
<213> Mus musculus
<400> 360
Ser Gly Glu Trp Gly Ser Met Asp Tyr
1 5
<210> 361
<211> 1329
<212> DNA
<213> Mus musculus
<400> 361
caggtccaac tacagcagcc tgggactgag ctggtgaggc ctggaacttc agtgaagttg 60
tcctgtaagg cttctggcta catcttcacc acctactgga tgaactgggt gaaacagagg 120
cctggacaag gccttgagtg gattggcatg attcatcctt ccgcaagtga aattaggttg 180
gatcagaaat tcaaggacaa ggccacattg actcttgaca aatcctccag cacagcctat 240
atgcacctca gcggcccgac atctgtggat tctgcggtct attactgtgc aagatcaggg 300
gaatgggggt ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa 360
acgacacccc catctgtcta tccactggcc cctggatctg ctgcccaaac taactccatg 420
gtgaccctgg gatgcctggt caagggctat ttccctgagc cagtgacagt gacctggaac 480
tctggatccc tgtccagcgg tgtgcacacc ttcccagctg tcctgcagtc tgacctctac 540
actctgagca gctcagtgac tgtcccctcc agcacctggc ccagcgagac cgtcacctgc 600
aacgttgccc acccggccag cagcaccaag gtggacaaga aaattgtgcc cagggattgt 660
ggttgtaagc cttgcatatg tacagtccca gaagtatcat ctgtcttcat cttcccccca 720
aagcccaagg atgtgctcac cattactctg actcctaagg tcacgtgtgt tgtggtagac 780
atcagcaagg atgatcccga ggtccagttc agctggtttg tagatgatgt ggaggtgcac 840
acagctcaga cgcaaccccg ggaggagcag ttcaacagca ctttccgctc agtcagtgaa 900
cttcccatca tgcaccagga ctggctcaat ggcaaggagt tcaaatgcag ggtcaacagt 960
gcagctttcc ctgcccccat cgagaaaacc atctccaaaa ccaaaggcag accgaaggct 1020
ccacaggtgt acaccattcc acctcccaag gagcagatgg ccaaggataa agtcagtctg 1080
acctgcatga taacagactt cttccctgaa gacattactg tggagtggca gtggaatggg 1140
cagccagcgg agaactacaa gaacactcag cccatcatgg acacagatgg ctcttacttc 1200
atctacagca agctcaatgt gcagaagagc aactgggagg caggaaatac tttcacctgc 1260
tctgtgttac atgagggcct gcacaaccac catactgaga agagcctctc ccactctcct 1320
ggtaaatga 1329
<210> 362
<211> 461
<212> PRT
<213> Mus musculus
<400> 362
Met Gly Trp Ser Ser Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Pro Gly Thr Glu Leu Val Arg
20 25 30
Pro Gly Thr Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Ile Phe
35 40 45
Thr Thr Tyr Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Met Ile His Pro Ser Ala Ser Glu Ile Arg Leu Asp
65 70 75 80
Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Leu Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met His Leu Ser Gly Pro Thr Ser Val Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Gly Glu Trp Gly Ser Met Asp Tyr Trp Gly
115 120 125
Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser
130 135 140
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
145 150 155 160
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
165 170 175
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
180 185 190
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
195 200 205
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
210 215 220
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
225 230 235 240
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
245 250 255
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
260 265 270
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
275 280 285
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
305 310 315 320
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
325 330 335
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
355 360 365
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
370 375 380
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
385 390 395 400
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
405 410 415
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
420 425 430
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
435 440 445
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 363
<211> 1386
<212> DNA
<213> Mus musculus
<400> 363
atgggatgga gctctatcat cctcttcttg gtagcaacag ctacaggtgt ccactcccag 60
gtccaactac agcagcctgg gactgagctg gtgaggcctg gaacttcagt gaagttgtcc 120
tgtaaggctt ctggctacat cttcaccacc tactggatga actgggtgaa acagaggcct 180
ggacaaggcc ttgagtggat tggcatgatt catccttccg caagtgaaat taggttggat 240
cagaaattca aggacaaggc cacattgact cttgacaaat cctccagcac agcctatatg 300
cacctcagcg gcccgacatc tgtggattct gcggtctatt actgtgcaag atcaggggaa 360
tgggggtcta tggactactg gggtcaagga acctcagtca ccgtctcctc agccaaaacg 420
acacccccat ctgtctatcc actggcccct ggatctgctg cccaaactaa ctccatggtg 480
accctgggat gcctggtcaa gggctatttc cctgagccag tgacagtgac ctggaactct 540
ggatccctgt ccagcggtgt gcacaccttc ccagctgtcc tgcagtctga cctctacact 600
ctgagcagct cagtgactgt cccctccagc acctggccca gcgagaccgt cacctgcaac 660
gttgcccacc cggccagcag caccaaggtg gacaagaaaa ttgtgcccag ggattgtggt 720
tgtaagcctt gcatatgtac agtcccagaa gtatcatctg tcttcatctt ccccccaaag 780
cccaaggatg tgctcaccat tactctgact cctaaggtca cgtgtgttgt ggtagacatc 840
agcaaggatg atcccgaggt ccagttcagc tggtttgtag atgatgtgga ggtgcacaca 900
gctcagacgc aaccccggga ggagcagttc aacagcactt tccgctcagt cagtgaactt 960
cccatcatgc accaggactg gctcaatggc aaggagttca aatgcagggt caacagtgca 1020
gctttccctg cccccatcga gaaaaccatc tccaaaacca aaggcagacc gaaggctcca 1080
caggtgtaca ccattccacc tcccaaggag cagatggcca aggataaagt cagtctgacc 1140
tgcatgataa cagacttctt ccctgaagac attactgtgg agtggcagtg gaatgggcag 1200
ccagcggaga actacaagaa cactcagccc atcatggaca cagatggctc ttacttcatc 1260
tacagcaagc tcaatgtgca gaagagcaac tgggaggcag gaaatacttt cacctgctct 1320
gtgttacatg agggcctgca caaccaccat actgagaaga gcctctccca ctctcctggt 1380
aaatga 1386
<210> 364
<211> 106
<212> PRT
<213> Mus musculus
<400> 364
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 365
<211> 318
<212> DNA
<213> Mus musculus
<400> 365
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggtga ccgtgtcacc 60
atcacttgcc gcgcaagtca ggatattagc agctatttaa attggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattct acttcccgtt tgaatagtgg ggtcccatca 180
cgcttcagtg gcagtggctc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcaacag gatattaaac accctacgtt cggtcaaggc 300
accaaggtgg agatcaaa 318
<210> 366
<211> 120
<212> PRT
<213> Mus musculus
<400> 366
Glu 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 Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 367
<211> 360
<212> DNA
<213> Mus musculus
<400> 367
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60
tcctgcaagg cttctggttt taccttcacc gactatatta tgcactgggt gcgtcaggcc 120
cctggtcaag ggcttgagtg gatgggctat atcaaccctt ataatgatga caccgaatac 180
aacgagaagt tcaagggccg tgtcacgatt accgcggaca aatccacgag cacagcctac 240
atggagctga gcagcctgcg ctctgaggac acggccgtgt attactgtgc gcgttcgatt 300
tattactacg atgccccgtt tgcttactgg ggccaaggga ctctggtcac cgtctctagt 360
<210> 368
<211> 108
<212> PRT
<213> Mus musculus
<400> 368
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 Lys Ala Ser Gln Asp Val Phe Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 369
<211> 324
<212> DNA
<213> Mus musculus
<400> 369
gatatccaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60
attacctgca aagcgagcca ggatgtgttt accgcggtgg cgtggtatca gcagaaaccg 120
ggcaaagcgc cgaaactgct gatttattgg gcgagcaccc gccataccgg cgtgccgagt 180
cgctttagcg gcagcggcag cggcaccgat tttaccctga ccattagcag cctgcagccg 240
gaagattttg cgacctatta ttgccagcag tatagcagct atccgctgac ctttggcggc 300
ggcaccaaag tggaaattaa acgt 324
<210> 370
<211> 119
<212> PRT
<213> Mus musculus
<400> 370
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp Pro Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 371
<211> 357
<212> DNA
<213> Mus musculus
<400> 371
gaagtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60
agctgcaaag cgagcggctt taacattaaa gattattata tgcattgggt gcgccaggcg 120
ccgggccagg gcctggaatg gatcggccgc attgatccgg aaaacggcga tattatttat 180
gatccgaaat ttcagggccg cgtgaccatg accaccgata ccagcaccag caccgcgtat 240
atggaactgc gcagcctgcg cagcgatgat accgcggtgt attattgcgc gtatgatgcg 300
ggcgatccgg cgtggtttac ctattggggc cagggcaccc tggtgaccgt ctcgagc 357
<210> 372
<211> 108
<212> PRT
<213> Mus musculus
<400> 372
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Ser Val Ser Ser Ser Ile Ser Ser Ser
20 25 30
Asn Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Thr Thr Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 373
<211> 324
<212> DNA
<213> Mus musculus
<400> 373
gatattcagc tgacccagag cccgagcttt ctgagcgcga gcgtgggcga tcgcgtgacc 60
attacctgca gcgtgagcag cagcattagc agcagcaacc tgcattggta tcagcagaaa 120
ccgggcaaag cgccgaaact gctgatttat ggcaccagca acctggcgag cggcgtgccg 180
agccgcttta gcggcagcgg cagcggcacc gaatttaccc tgaccattag cagcctgcag 240
ccggaagatt ttgcgaccta ttattgccag cagtggacca ccacctatac ctttggccag 300
ggcaccaaac tggaaattaa acgt 324
<210> 374
<211> 122
<212> PRT
<213> Mus musculus
<400> 374
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val Pro Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 375
<211> 366
<212> DNA
<213> Mus musculus
<400> 375
gaagtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60
agctgcaaag cgagcggctt taacattaaa gattattata ttcattgggt gcgccaggcg 120
ccgggccagg gcctggaatg gatgggccgc attgatccgg ataacggcga aagcacctat 180
gtgccgaaat ttcagggccg cgtgaccatg accaccgata ccagcaccag caccgcgtat 240
atggaactgc gcagcctgcg cagcgatgat accgcggtgt attattgcgc gcgcgaaggc 300
ctggattatg gcgattatta tgcggtggat tattggggcc agggcaccct ggtgaccgtc 360
tcgagc 366
<210> 376
<211> 107
<212> PRT
<213> Mus musculus
<400> 376
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 377
<211> 321
<212> DNA
<213> Mus musculus
<400> 377
gacatccaga tgacccagtc tccatcctcc ctctccgcat ccgtaggcga ccgcgtaacc 60
ataacatgta gagcatctca agatatttcc aactatttga attggtacca acaaaaaccc 120
ggcaaagcac ctaaactcct catttactat acatcaagac tcctctccgg cgttccatca 180
cgattctcag gctccggctc cggcacagat ttcacactca ctatttcctc cctccaacca 240
gaagattttg caacctatta ctgtcaacaa ggcgatacac tcccatacac attcggcggc 300
ggcacaaaag ttgaaattaa a 321
<210> 378
<211> 123
<212> PRT
<213> Mus musculus
<400> 378
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 379
<211> 369
<212> DNA
<213> Mus musculus
<400> 379
gaggtgcagc tggtgcagag cggcgccgag gtaaaaaaac caggagcaag cgttaaagtt 60
tcttgtaaag caagcggata tacatttaca gattacaaca tgcattgggt aagacaagcg 120
ccaggacaag gattggaatg gatgggcgaa attaacccta atagtggagg agcaggctac 180
aatcaaaaat tcaaagggag agttacaatg acaacagaca caagcacttc aacagcatat 240
atggaactgc gatcacttag aagcgacgat acagctgtat actattgcgc acgacttggg 300
tatgatgata tatatgatga ctggtatttc gatgtttggg gccagggaac aacagttacc 360
gtctctagt 369
<210> 380
<211> 108
<212> PRT
<213> Mus musculus
<400> 380
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Thr Ser Ser
20 25 30
Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Phe Phe Pro
85 90 95
Ser Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 381
<211> 324
<212> DNA
<213> Mus musculus
<400> 381
gacatccagc tgacccagag ccccagcttc ctttccgcat ccgttggtga ccgagtaaca 60
atcacatgcc gcgcctcatc ttcagttaca tcttcttatc ttaattggta tcaacaaaaa 120
ccaggaaaag cacctaaact tcttatatac tctacatcta atctcgcatc aggagttccc 180
tctcgatttt caggatctgg atcaggcaca gaatttacac ttactatatc atcactccaa 240
ccagaagact tcgccactta ttactgccaa caatacgatt tttttccaag cacattcgga 300
ggaggtacaa aagtagaaat caag 324
<210> 382
<211> 121
<212> PRT
<213> Mus musculus
<400> 382
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 383
<211> 363
<212> DNA
<213> Mus musculus
<400> 383
gaggtgcagc tggtgcagag cggcgccgag gtcaagaaac ctggagcaag cgtaaaggtt 60
agttgcaaag catctggata cacatttacc gactactaca tgaattgggt acgacaagcc 120
cctggacaaa gacttgaatg gatgggagac attaaccctt ataacgacga cactacatac 180
aatcataaat ttaaaggaag agttacaatt acaagagata catccgcatc aaccgcctat 240
atggaacttt cctcattgag atctgaagac actgctgttt attactgtgc aagagaaact 300
gccgttatta ctactaacgc tatggattac tggggtcaag gaaccactgt taccgtctct 360
agt 363
<210> 384
<211> 108
<212> PRT
<213> Mus musculus
<400> 384
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 Ser Val Ser Ser Thr Ile Ser Ser Asn
20 25 30
His Leu His Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 385
<211> 324
<212> DNA
<213> Mus musculus
<400> 385
gacatccaga tgacccagtc tccatcctcc ctctcagcat ccgtaggcga tagagttaca 60
ataacatgca gcgtatcatc aactatatca tcaaatcatc ttcattggtt ccaacagaaa 120
cccggcaaag cacctaaatc acttatatac ggcacatcaa atctcgcatc aggcgttcct 180
tcaagatttt caggctctgg ctcaggcacc gactttactc ttacaatatc ctccctccaa 240
cccgaagact tcgcaaccta ttactgtcaa caatggtcct catatccact cacatttggc 300
ggcggcacaa aagtagaaat taaa 324
<210> 386
<211> 125
<212> PRT
<213> Mus musculus
<400> 386
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 Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 387
<211> 375
<212> DNA
<213> Mus musculus
<400> 387
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctgactt caacattaaa gacttctatc tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gattggaagg attgatcctg agaatggtga tactttatat 180
gacccgaagt tccaggacaa ggtcaccatg accacagaca cgtccaccag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagaggcg 300
gattatttcc acgatggtac ctcctactgg tacttcgatg tctggggccg tggcaccctg 360
gtcaccgtct ctagt 375
<210> 388
<211> 106
<212> PRT
<213> Mus musculus
<400> 388
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Ile Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu
65 70 75 80
Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 389
<211> 318
<212> DNA
<213> Mus musculus
<400> 389
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca gggccagctc aagtataagt tacatacact ggtatcagca aaaaccaggg 120
aaagccccta agctcctgat ctatgccaca tccaacctgg cttctggggt cccatcaagg 180
ttcagcggca gtggatctgg gacagaattc actctcacaa tcagcagcct gcagcctgaa 240
gattttgcaa cttattactg tcagcagtgg agtagtgacc cactcacgtt cggcggaggg 300
accaaggtgg agatcaaa 318
<210> 390
<211> 121
<212> PRT
<213> Mus musculus
<400> 390
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 391
<211> 363
<212> DNA
<213> Mus musculus
<400> 391
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggatt cgacattaag gactactata tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatcggaagg gttgatcctg acaatggtga gactgaattt 180
gccccgaagt tcccgggcaa ggtcaccatg accacagaca cgtccatcag cacagcctac 240
atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagaagac 300
tacgatggta cctacacctg gtttccttat tggggccaag ggactctggt caccgtctct 360
agt 363
<210> 392
<211> 448
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 392
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly
115 120 125
Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser
130 135 140
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
180 185 190
Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val
195 200 205
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys
210 215 220
Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val
290 295 300
Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 393
<211> 446
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 393
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 394
<211> 450
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 394
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 Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
115 120 125
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser
130 135 140
Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
180 185 190
Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys
195 200 205
Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu
210 215 220
Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
290 295 300
Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly
450
<210> 395
<211> 446
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<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 Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 396
<211> 445
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic Polypeptide
<220>
<221> MISC_FEATURE
<223> Humanized Antibody Sequence
<400> 396
Glu 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 Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
210 215 220
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
260 265 270
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
290 295 300
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
325 330 335
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 397
<211> 213
<212> PRT
<213> Homo sapiens
<400> 397
Met Gln Leu Pro Leu Ala Leu Cys Leu Val Cys Leu Leu Val His Thr
1 5 10 15
Ala Phe Arg Val Val Glu Gly Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 398
<211> 444
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 398
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 Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Phe Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Tyr His Asp Gly Thr Thr Tyr Ser Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Glu Asp Gly Gln Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
305 310 315 320
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440
<210> 399
<211> 444
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 399
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 Val Ser Gly Phe Pro Ile Lys Asp Thr
20 25 30
Phe Gln His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ser Asp Pro Glu Ile Gly Asp Thr Glu Tyr Ala Ser Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Gly Asp Thr Thr Tyr Lys Phe Asp Phe Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
305 310 315 320
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440
<210> 400
<211> 450
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 400
Glu Val 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 Gly Ser Asp Phe Glu Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Tyr Asp Gly Arg Asp Tyr Trp Tyr Phe Asp
100 105 110
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
130 135 140
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
195 200 205
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
210 215 220
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
260 265 270
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Leu Gly
450
<210> 401
<211> 214
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 401
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 Ser Ala Ser Gln Gly Ile Gln Trp Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Ser Lys Leu Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 402
<211> 214
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 402
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 Lys Ala Ser Gln Asp Val His Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg Trp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Asp Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 403
<211> 213
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 403
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Ser Ala Ser Ser Ser Val Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
35 40 45
Ser Thr Ser Glu Leu Ala Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu
65 70 75 80
Asp Phe Ala Val Tyr Tyr Cys Gln Gln Leu Ser His Leu Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 404
<211> 1332
<212> DNA
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 404
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc agtgaaggtt 60
tcctgcaagg catctggata cacattcact gactactttc tgaactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggaact atttatcctt accatgatgg tactacctac 180
tctcagaagt tcaagggcag agtcaccatt accgcggaca aatccacgag cacagcctac 240
atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagaggaa 300
gaggatggtc agttcgacta ctggggccaa ggaaccacgg tcaccgtctc ctcagcctcc 360
accaagggcc catcggtctt cccgctagcg ccctgctcca ggagcacctc cgagagcaca 420
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 600
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 660
ggtcccccat gcccaccctg cccagcacct gagttcctgg ggggaccatc agtcttcctg 720
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 900
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 960
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1080
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggaa 1140
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1260
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1320
ctgtctctgg gt 1332
<210> 405
<211> 1332
<212> DNA
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 405
caggttcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg tttccggctt ccccattaag gacacctttc agcactgggt gcgacaggct 120
cctggaaaag ggcttgagtg gatgggatgg agcgatcctg agatcggtga tactgaatat 180
gcctcgaagt tccagggcag agtcaccatg accgaggaca catctacaga cacagcctac 240
atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc aacaggcgac 300
accacataca agtttgactt ctgggggcaa gggaccacgg tcaccgtctc ctcagcctcc 360
accaagggcc catcggtctt cccgctagcg ccctgctcca ggagcacctc cgagagcaca 420
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 600
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 660
ggtcccccat gcccaccctg cccagcacct gagttcctgg ggggaccatc agtcttcctg 720
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 900
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 960
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1080
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggaa 1140
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1260
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1320
ctgtctctgg gt 1332
<210> 406
<211> 1350
<212> DNA
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 406
gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaagatc 60
tcctgtaagg gttctgactt cgagattaaa gactactata tacattgggt gcgccagatg 120
cccgggaaag gcctggagtg gatggggcag attgatgctg aggatggtga aactgaatat 180
gccccgaggt tccagggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240
ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagagagggt 300
tattactacg atgggcgcga ctactggtac ttcgatgtct ggggccaagg gaccacggtc 360
accgtctcct cagcctccac caagggccca tcggtcttcc cgctagcgcc ctgctccagg 420
agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccg 480
gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 540
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 600
ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 660
agagttgagt ccaaatatgg tcccccatgc ccaccctgcc cagcacctga gttcctgggg 720
ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc 780
cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac 840
tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc 900
aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc 960
aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc 1020
tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag 1080
gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1140
atcgccgtgg agtgggaaag caatgggcag ccggagaaca actacaagac cacgcctccc 1200
gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg 1260
tggcaggagg ggaatgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1320
acacagaaga gcctctccct gtctctgggt 1350
<210> 407
<211> 642
<212> DNA
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 407
gacatccaga tgacccagtc tccatcctct ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca gtgcaagtca gggcattcag tggtatttaa actggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattac acatcaagtt tacactcagg ggtcccatca 180
aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcagcag catagtaaac ttcctcggac gttcggcgga 300
gggaccaagg tggagatcaa acggactgtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gc 642
<210> 408
<211> 642
<212> DNA
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 408
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca aggccagtca ggatgtgcac actgctgtag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattgg gcatccaccc ggtggactgg agtcccatca 180
aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcagcaa tatagcgatt atccgtggac gttcggcgga 300
gggaccaagg tggagatcaa acggactgtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gc 642
<210> 409
<211> 639
<212> DNA
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 409
gaaattgtgt tgacacagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gtgccagctc aagtgtaagt tacatccact ggtaccaaca gaaacctggc 120
caggctccca ggctcctcat ctatagcaca tccgagctgg cttctggcat cccagccagg 180
ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagcct agagcctgaa 240
gattttgcag tttattactg tcagcagctt agtcatctcc cgctcacgtt cggcggaggg 300
accaaggtgg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct 360
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540
agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600
agctcgcccg tcacaaagag cttcaacagg ggagagtgc 639
<210> 410
<211> 118
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 410
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 Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Phe Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Tyr His Asp Gly Thr Thr Tyr Ser Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Glu Asp Gly Gln Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 411
<211> 118
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 411
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 Val Ser Gly Phe Pro Ile Lys Asp Thr
20 25 30
Phe Gln His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ser Asp Pro Glu Ile Gly Asp Thr Glu Tyr Ala Ser Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Gly Asp Thr Thr Tyr Lys Phe Asp Phe Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 412
<211> 124
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 412
Glu Val 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 Gly Ser Asp Phe Glu Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Tyr Asp Gly Arg Asp Tyr Trp Tyr Phe Asp
100 105 110
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 413
<211> 107
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 413
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 Ser Ala Ser Gln Gly Ile Gln Trp Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Ser Lys Leu Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 414
<211> 107
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 414
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 Lys Ala Ser Gln Asp Val His Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg Trp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Asp Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 415
<211> 106
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 415
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Ser Ala Ser Ser Ser Val Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
35 40 45
Ser Thr Ser Glu Leu Ala Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu
65 70 75 80
Asp Phe Ala Val Tyr Tyr Cys Gln Gln Leu Ser His Leu Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 416
<211> 10
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 416
Gly Tyr Thr Phe Thr Asp Tyr Phe Leu Asn
1 5 10
<210> 417
<211> 17
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 417
Thr Ile Tyr Pro Tyr His Asp Gly Thr Thr Tyr Ser Gln Lys Phe Lys
1 5 10 15
Gly
<210> 418
<211> 9
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 418
Glu Glu Glu Asp Gly Gln Phe Asp Tyr
1 5
<210> 419
<211> 11
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 419
Ser Ala Ser Gln Gly Ile Gln Trp Tyr Leu Asn
1 5 10
<210> 420
<211> 7
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 420
Tyr Thr Ser Ser Leu His Ser
1 5
<210> 421
<211> 9
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 421
Gln Gln His Ser Lys Leu Pro Arg Thr
1 5
<210> 422
<211> 10
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 422
Gly Phe Pro Ile Lys Asp Thr Phe Gln His
1 5 10
<210> 423
<211> 17
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 423
Trp Ser Asp Pro Glu Ile Gly Asp Thr Glu Tyr Ala Ser Lys Phe Gln
1 5 10 15
Gly
<210> 424
<211> 9
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 424
Gly Asp Thr Thr Tyr Lys Phe Asp Phe
1 5
<210> 425
<211> 11
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 425
Lys Ala Ser Gln Asp Val His Thr Ala Val Ala
1 5 10
<210> 426
<211> 7
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 426
Trp Ala Ser Thr Arg Trp Thr
1 5
<210> 427
<211> 9
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 427
Gln Gln Tyr Ser Asp Tyr Pro Trp Thr
1 5
<210> 428
<211> 10
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 428
Asp Phe Glu Ile Lys Asp Tyr Tyr Ile His
1 5 10
<210> 429
<211> 17
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 429
Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe Gln
1 5 10 15
Gly
<210> 430
<211> 17
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 430
Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe Gln
1 5 10 15
Gly
<210> 431
<211> 17
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 431
Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe Gln
1 5 10 15
Gly
<210> 432
<211> 7
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 432
Ser Thr Ser Glu Leu Ala Ser
1 5
<210> 433
<211> 9
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 433
Gln Gln Leu Ser His Leu Pro Leu Thr
1 5
<210> 434
<211> 322
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 434
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
1 5 10 15
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
20 25 30
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
35 40 45
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
50 55 60
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
65 70 75 80
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
85 90 95
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly
100 105 110
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
115 120 125
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
130 135 140
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
145 150 155 160
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
165 170 175
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
180 185 190
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
195 200 205
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
210 215 220
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
225 230 235 240
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
245 250 255
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
260 265 270
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
275 280 285
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
290 295 300
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
305 310 315 320
Leu Gly
<210> 435
<211> 970
<212> DNA
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 435
ggcccatcgg tcttcccgct agcgccctgc tccaggagca cctccgagag cacagccgcc 60
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 120
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 180
gctcagcagc gtggtgaccg tgccctccag cagcttgggc acgaagacct acacctgcaa 240
cgtagatcac aagcccagca acaccaaggt ggacaagaga gttgagtcca aatatggtcc 300
cccatgccca ccctgcccag cacctgagtt cctgggggga ccatcagtct tcctgttccc 360
cccaaaaccc aaggacactc tcatgatctc ccggacccct gaggtcacgt gcgtggtggt 420
ggacgtgagc caggaagacc ccgaggtcca gttcaactgg tacgtggatg gcgtggaggt 480
gcataatgcc aagacaaagc cgcgggagga gcagttcaac agcacgtacc gtgtggtcag 540
cgtcctcacc gtcctgcacc aggactggct gaacggcaag gagtacaagt gcaaggtctc 600
caacaaaggc ctcccgtcct ccatcgagaa aaccatctcc aaagccaaag ggcagccccg 660
agagccacag gtgtacaccc tgcccccatc ccaggaggag atgaccaaga accaggtcag 720
cctgacctgc ctggtcaaag gcttctaccc cagcgacatc gccgtggagt gggaaagcaa 780
tgggcagccg gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt 840
cttcctctac agcaggctaa ccgtggacaa gagcaggtgg caggagggga atgtcttctc 900
atgctccgtg atgcatgagg ctctgcacaa ccactacaca cagaagagcc tctccctgtc 960
tctgggttga 970
<210> 436
<211> 444
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 436
Glu Val Gln Leu Gln Gln Ser Val Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Ser Thr
20 25 30
Phe Met His Trp Val Lys Gln Arg Pro Asp Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Asn Gly Asp Thr Glu Tyr Ala Ser Lys Phe
50 55 60
Gln Gly Lys Ala Thr Met Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Thr Gly Glu Ser Asn Tyr Asp Phe Asp Phe Trp Gly Leu Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro
115 120 125
Leu Ala Pro Gly Thr Ala Leu Lys Ser Asn Ser Met Val Thr Leu Gly
130 135 140
Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn
145 150 155 160
Ser Gly Ala Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Gly Leu Tyr Thr Leu Thr Ser Ser Val Thr Val Pro Ser Ser Thr
180 185 190
Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser
195 200 205
Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asn Cys Gly Gly Asp Cys
210 215 220
Lys Pro Cys Ile Cys Thr Gly Ser Glu Val Ser Ser Val Phe Ile Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val
245 250 255
Thr Cys Val Val Val Asp Ile Ser Gln Asp Asp Pro Glu Val His Phe
260 265 270
Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Arg Pro
275 280 285
Pro Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro
290 295 300
Ile Leu His Gln Asp Trp Leu Asn Gly Arg Thr Phe Arg Cys Lys Val
305 310 315 320
Thr Ser Ala Ala Phe Pro Ser Pro Ile Glu Lys Thr Ile Ser Lys Pro
325 330 335
Glu Gly Arg Thr Gln Val Pro His Val Tyr Thr Met Ser Pro Thr Lys
340 345 350
Glu Glu Met Thr Gln Asn Glu Val Ser Ile Thr Cys Met Val Lys Gly
355 360 365
Phe Tyr Pro Pro Asp Ile Tyr Val Glu Trp Gln Met Asn Gly Gln Pro
370 375 380
Gln Glu Asn Tyr Lys Asn Thr Pro Pro Thr Met Asp Thr Asp Gly Ser
385 390 395 400
Tyr Phe Leu Tyr Ser Lys Leu Asn Val Lys Lys Glu Lys Trp Gln Gln
405 410 415
Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His
420 425 430
His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 437
<211> 214
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 437
Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly
1 5 10 15
Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Asp Val Gln Ser
65 70 75 80
Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Ser Asn Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Thr Glu Gln Leu Ala Thr Gly
115 120 125
Gly Ala Ser Val Val Cys Leu Met Asn Asn Phe Tyr Pro Arg Asp Ile
130 135 140
Ser Val Lys Trp Lys Ile Asp Gly Thr Glu Arg Arg Asp Gly Val Leu
145 150 155 160
Asp Ser Val Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Ser Leu Ser Lys Ala Asp Tyr Glu Ser His Asn Leu Tyr
180 185 190
Thr Cys Glu Val Val His Lys Thr Ser Ser Ser Pro Val Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 438
<211> 450
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 438
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu His Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Asp Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Lys Gln Arg Thr Ala Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe
50 55 60
Gln Gly Lys Ala Thr Ile Ile Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Tyr Asp Ser Arg Asp Tyr Trp Tyr Phe Asp
100 105 110
Val Trp Gly Thr Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr
115 120 125
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Thr Ala Leu Lys Ser Asn
130 135 140
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Thr Trp Asn Ser Gly Ala Leu Ser Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Gly Leu Tyr Thr Leu Thr Ser Ser Val
180 185 190
Thr Val Pro Ser Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val
195 200 205
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
210 215 220
Asn Cys Gly Gly Asp Cys Lys Pro Cys Ile Cys Thr Gly Ser Glu Val
225 230 235 240
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
245 250 255
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Gln Asp
260 265 270
Asp Pro Glu Val His Phe Ser Trp Phe Val Asp Asp Val Glu Val His
275 280 285
Thr Ala Gln Thr Arg Pro Pro Glu Glu Gln Phe Asn Ser Thr Phe Arg
290 295 300
Ser Val Ser Glu Leu Pro Ile Leu His Gln Asp Trp Leu Asn Gly Arg
305 310 315 320
Thr Phe Arg Cys Lys Val Thr Ser Ala Ala Phe Pro Ser Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Pro Glu Gly Arg Thr Gln Val Pro His Val Tyr
340 345 350
Thr Met Ser Pro Thr Lys Glu Glu Met Thr Gln Asn Glu Val Ser Ile
355 360 365
Thr Cys Met Val Lys Gly Phe Tyr Pro Pro Asp Ile Tyr Val Glu Trp
370 375 380
Gln Met Asn Gly Gln Pro Gln Glu Asn Tyr Lys Asn Thr Pro Pro Thr
385 390 395 400
Met Asp Thr Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Asn Val Lys
405 410 415
Lys Glu Lys Trp Gln Gln Gly Asn Thr Phe Thr Cys Ser Val Leu His
420 425 430
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
435 440 445
Gly Lys
450
<210> 439
<211> 213
<212> PRT
<213> Artificial
<220>
<223> Miscellaneous construct
<400> 439
Glu Ile Val Leu Thr Gln Ser Pro Ala Leu Met Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met
20 25 30
His Trp Phe Gln Gln Lys Pro Gly Thr Ser Pro Lys Leu Trp Ile Tyr
35 40 45
Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Thr Glu Gln Leu Ala Thr Gly Gly
115 120 125
Ala Ser Val Val Cys Leu Met Asn Asn Phe Tyr Pro Arg Asp Ile Ser
130 135 140
Val Lys Trp Lys Ile Asp Gly Thr Glu Arg Arg Asp Gly Val Leu Asp
145 150 155 160
Ser Val Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Ser Leu Ser Lys Ala Asp Tyr Glu Ser His Asn Leu Tyr Thr
180 185 190
Cys Glu Val Val His Lys Thr Ser Ser Ser Pro Val Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 440
<211> 10
<212> PRT
<213> Homo sapiens
<400> 440
Gly Phe Thr Phe Ser Ser Tyr Val Met Asn
1 5 10
<210> 441
<211> 10
<212> PRT
<213> Homo sapiens
<400> 441
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 442
<211> 10
<212> PRT
<213> Homo sapiens
<400> 442
Gly Phe Thr Phe Ser Ser Tyr Val Met Asn
1 5 10
<210> 443
<211> 10
<212> PRT
<213> Homo sapiens
<400> 443
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 444
<211> 10
<212> PRT
<213> Homo sapiens
<400> 444
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 445
<211> 10
<212> PRT
<213> Homo sapiens
<400> 445
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 446
<211> 10
<212> PRT
<213> Homo sapiens
<400> 446
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 447
<211> 10
<212> PRT
<213> Homo sapiens
<400> 447
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 448
<211> 10
<212> PRT
<213> Homo sapiens
<400> 448
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 449
<211> 10
<212> PRT
<213> Homo sapiens
<400> 449
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 450
<211> 10
<212> PRT
<213> Homo sapiens
<400> 450
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 451
<211> 20
<212> PRT
<213> Homo sapiens
<400> 451
Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 452
<211> 20
<212> PRT
<213> Homo sapiens
<400> 452
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 453
<211> 20
<212> PRT
<213> Homo sapiens
<400> 453
Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 454
<211> 20
<212> PRT
<213> Homo sapiens
<400> 454
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 455
<211> 19
<212> PRT
<213> Homo sapiens
<400> 455
Trp Val Ser Val Thr Gly Val His Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 456
<211> 19
<212> PRT
<213> Homo sapiens
<400> 456
Trp Val Ser Val Ile Gly Asn Trp Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 457
<211> 19
<212> PRT
<213> Homo sapiens
<400> 457
Trp Val Ser Val Thr Thr His Gln Gly Tyr Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 458
<211> 19
<212> PRT
<213> Homo sapiens
<400> 458
Trp Val Ser Ala Thr Asn Arg Tyr Gly Tyr Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 459
<211> 20
<212> PRT
<213> Homo sapiens
<400> 459
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 460
<211> 19
<212> PRT
<213> Homo sapiens
<400> 460
Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 461
<211> 19
<212> PRT
<213> Homo sapiens
<400> 461
Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 462
<211> 15
<212> PRT
<213> Homo sapiens
<400> 462
Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp Phe
1 5 10 15
<210> 463
<211> 8
<212> PRT
<213> Homo sapiens
<400> 463
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 464
<211> 15
<212> PRT
<213> Homo sapiens
<400> 464
Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp Phe
1 5 10 15
<210> 465
<211> 8
<212> PRT
<213> Homo sapiens
<400> 465
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 466
<211> 8
<212> PRT
<213> Homo sapiens
<400> 466
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 467
<211> 8
<212> PRT
<213> Homo sapiens
<400> 467
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 468
<211> 8
<212> PRT
<213> Homo sapiens
<400> 468
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 469
<211> 8
<212> PRT
<213> Homo sapiens
<400> 469
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 470
<211> 8
<212> PRT
<213> Homo sapiens
<400> 470
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 471
<211> 8
<212> PRT
<213> Homo sapiens
<400> 471
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 472
<211> 8
<212> PRT
<213> Homo sapiens
<400> 472
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 473
<211> 11
<212> PRT
<213> Homo sapiens
<400> 473
Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val His
1 5 10
<210> 474
<211> 20
<212> PRT
<213> Homo sapiens
<400> 474
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 475
<211> 20
<212> PRT
<213> Homo sapiens
<400> 475
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 476
<211> 11
<212> PRT
<213> Homo sapiens
<400> 476
Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val His
1 5 10
<210> 477
<211> 14
<212> PRT
<213> Homo sapiens
<400> 477
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 478
<211> 14
<212> PRT
<213> Homo sapiens
<400> 478
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 479
<211> 14
<212> PRT
<213> Homo sapiens
<400> 479
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 480
<211> 14
<212> PRT
<213> Homo sapiens
<400> 480
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 481
<211> 14
<212> PRT
<213> Homo sapiens
<400> 481
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 482
<211> 14
<212> PRT
<213> Homo sapiens
<400> 482
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 483
<211> 14
<212> PRT
<213> Homo sapiens
<400> 483
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 484
<211> 11
<212> PRT
<213> Homo sapiens
<400> 484
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser
1 5 10
<210> 485
<211> 11
<212> PRT
<213> Homo sapiens
<400> 485
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 486
<211> 11
<212> PRT
<213> Homo sapiens
<400> 486
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser
1 5 10
<210> 487
<211> 11
<212> PRT
<213> Homo sapiens
<400> 487
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 488
<211> 11
<212> PRT
<213> Homo sapiens
<400> 488
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 489
<211> 11
<212> PRT
<213> Homo sapiens
<400> 489
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 490
<211> 11
<212> PRT
<213> Homo sapiens
<400> 490
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 491
<211> 11
<212> PRT
<213> Homo sapiens
<400> 491
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 492
<211> 11
<212> PRT
<213> Homo sapiens
<400> 492
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 493
<211> 11
<212> PRT
<213> Homo sapiens
<400> 493
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 494
<211> 11
<212> PRT
<213> Homo sapiens
<400> 494
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 495
<211> 10
<212> PRT
<213> Homo sapiens
<400> 495
Gly Ser Trp Ala Gly Ser Ser Gly Ser Tyr
1 5 10
<210> 496
<211> 10
<212> PRT
<213> Homo sapiens
<400> 496
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 497
<211> 10
<212> PRT
<213> Homo sapiens
<400> 497
Ala Ser Trp Thr Gly Val Glu Pro Asp Tyr
1 5 10
<210> 498
<211> 10
<212> PRT
<213> Homo sapiens
<400> 498
Gln Ser Tyr Ala Gly Ser Tyr Leu Ser Glu
1 5 10
<210> 499
<211> 10
<212> PRT
<213> Homo sapiens
<400> 499
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 500
<211> 10
<212> PRT
<213> Homo sapiens
<400> 500
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 501
<211> 10
<212> PRT
<213> Homo sapiens
<400> 501
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 502
<211> 10
<212> PRT
<213> Homo sapiens
<400> 502
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 503
<211> 10
<212> PRT
<213> Homo sapiens
<400> 503
Ser Thr Tyr Asp Gly Pro Gly Leu Ser Glu
1 5 10
<210> 504
<211> 10
<212> PRT
<213> Homo sapiens
<400> 504
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 505
<211> 10
<212> PRT
<213> Homo sapiens
<400> 505
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 506
<211> 124
<212> PRT
<213> Homo sapiens
<400> 506
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 Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp
100 105 110
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 507
<211> 117
<212> PRT
<213> Homo sapiens
<400> 507
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 508
<211> 124
<212> PRT
<213> Homo sapiens
<400> 508
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 Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp
100 105 110
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 509
<211> 117
<212> PRT
<213> Homo sapiens
<400> 509
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 510
<211> 116
<212> PRT
<213> Homo sapiens
<400> 510
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Thr Gly Val His Gly Asp Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 511
<211> 116
<212> PRT
<213> Homo sapiens
<400> 511
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Gly Asn Trp Gly Asp Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 512
<211> 116
<212> PRT
<213> Homo sapiens
<400> 512
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Thr Thr His Gln Gly Tyr Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 513
<211> 116
<212> PRT
<213> Homo sapiens
<400> 513
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Thr Asn Arg Tyr Gly Tyr Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 514
<211> 117
<212> PRT
<213> Homo sapiens
<400> 514
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 515
<211> 116
<212> PRT
<213> Homo sapiens
<400> 515
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 516
<211> 116
<212> PRT
<213> Homo sapiens
<400> 516
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 Gly Phe Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 517
<211> 110
<212> PRT
<213> Homo sapiens
<400> 517
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Ala Gly Ser Ser Gly Ser
85 90 95
Tyr Val Phe Gly Gly Arg Thr Lys Leu Thr Val Leu Gly Gln
100 105 110
<210> 518
<211> 113
<212> PRT
<213> Homo sapiens
<400> 518
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 519
<211> 110
<212> PRT
<213> Homo sapiens
<400> 519
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Ala Ser Trp Thr Gly Val Glu Pro Asp
85 90 95
Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln
100 105 110
<210> 520
<211> 113
<212> PRT
<213> Homo sapiens
<400> 520
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Ala Gly Ser
85 90 95
Tyr Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 521
<211> 113
<212> PRT
<213> Homo sapiens
<400> 521
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 522
<211> 113
<212> PRT
<213> Homo sapiens
<400> 522
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 523
<211> 113
<212> PRT
<213> Homo sapiens
<400> 523
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 524
<211> 113
<212> PRT
<213> Homo sapiens
<400> 524
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 525
<211> 113
<212> PRT
<213> Homo sapiens
<400> 525
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Tyr Asp Gly Pro
85 90 95
Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 526
<211> 113
<212> PRT
<213> Homo sapiens
<400> 526
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 527
<211> 113
<212> PRT
<213> Homo sapiens
<400> 527
Asp Ile Ala 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 Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Tyr Asp Gly Pro
85 90 95
Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 528
<211> 372
<212> DNA
<213> Homo sapiens
<400> 528
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt taccttttct tcttatgtta tgaattgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcttt atctctggtg attctagcaa tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtactttt 300
atgcatggtc atcttggtgg tggtctttct atggattttt ggggccaagg caccctggtg 360
acggttagct ca 372
<210> 529
<211> 350
<212> DNA
<213> Homo sapiens
<400> 529
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtcta 60
gctgcgcggc ctccggattt acctttcgtt ctcattggct ttcttgggtg cgccaagccc 120
ctgggaaggg tctcgagtgg gtgagcaata tcaattatga tggtagctct acctattatg 180
cggatagcgt gaaaggccgt tttaccattt cacgtgataa ttcgaaaaac accctgtatc 240
tgcaaatgaa cagcctgcgt gcggaagata cggccgtgta ttattgcgcg cgtgatactt 300
atcttcattt tgattattgg ggccaaggca ccctggtgac ggttagctca 350
<210> 530
<211> 372
<212> DNA
<213> Homo sapiens
<400> 530
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt taccttttct tcttatgtta tgaattgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcttt atctctggtg attctagcaa tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtactttt 300
atgcatggtc atcttggtgg tggtctttct atggattttt ggggccaagg caccctggtg 360
acggttagct ca 372
<210> 531
<211> 351
<212> DNA
<213> Homo sapiens
<400> 531
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcaat atcaattatg atggtagctc tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtgatact 300
tatcttcatt ttgattattg gggccaaggc accctggtga cggttagctc a 351
<210> 532
<211> 348
<212> DNA
<213> Homo sapiens
<400> 532
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt actggtgttc atggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 533
<211> 348
<212> DNA
<213> Homo sapiens
<400> 533
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt attggtaatt ggggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 534
<211> 348
<212> DNA
<213> Homo sapiens
<400> 534
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt actactcatc agggttatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 535
<211> 348
<212> DNA
<213> Homo sapiens
<400> 535
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgct actaatcgtt atggttatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 536
<211> 351
<212> DNA
<213> Homo sapiens
<400> 536
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcaat atcaattatg atggtagctc tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtgatact 300
tatcttcatt ttgattattg gggccaaggc accctggtga cggttagctc a 351
<210> 537
<211> 348
<212> DNA
<213> Homo sapiens
<400> 537
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt attactcctt atggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 538
<211> 348
<212> DNA
<213> Homo sapiens
<400> 538
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt attactcctt atggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 539
<211> 330
<212> DNA
<213> Homo sapiens
<400> 539
gatatcgaac tgacccagcc gccttcagtg agcgttgcac caggtcagac cgcgcgtatc 60
tcgtgtagcg gcgataatat tggttctttt tatgttcatt ggtaccagca gaaacccggg 120
caggcgccag ttcttgtgat ttatgatgat aataatcgtc cctcaggcat cccggaacgc 180
tttagcggat ccaacagcgg caacaccgcg accctgacca ttagcggcac tcaggcggaa 240
gacgaagcgg attattattg cggttcttgg gctggttctt ctggttctta tgtgtttggc 300
ggccgcacga agttaaccgt tcttggccag 330
<210> 540
<211> 339
<212> DNA
<213> Homo sapiens
<400> 540
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 541
<211> 330
<212> DNA
<213> Homo sapiens
<400> 541
gatatcgaac tgacccagcc gccttcagtg agcgttgcac caggtcagac cgcgcgtatc 60
tcgtgtagcg gcgataatat tggttctttt tatgttcatt ggtaccagca gaaacccggg 120
caggcgccag ttcttgtgat ttatgatgat aataatcgtc cctcaggcat cccggaacgc 180
tttagcggat ccaacagcgg caacaccgcg accctgacca ttagcggcac tcaggcggaa 240
gacgaagcgg attattattg cgcttcttgg actggtgttg agcctgatta tgtgtttggc 300
ggcggcacga agttaaccgt tcttggccag 330
<210> 542
<211> 339
<212> DNA
<213> Homo sapiens
<400> 542
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc cagtcttatg ctggttctta tctttctgag 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 543
<211> 339
<212> DNA
<213> Homo sapiens
<400> 543
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 544
<211> 339
<212> DNA
<213> Homo sapiens
<400> 544
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 545
<211> 339
<212> DNA
<213> Homo sapiens
<400> 545
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 546
<211> 339
<212> DNA
<213> Homo sapiens
<400> 546
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 547
<211> 339
<212> DNA
<213> Homo sapiens
<400> 547
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tctacttatg atggtcctgg tctttctgag 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 548
<211> 339
<212> DNA
<213> Homo sapiens
<400> 548
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 549
<211> 339
<212> DNA
<213> Homo sapiens
<400> 549
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tctacttatg atggtcctgg tctttctgag 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 550
<211> 469
<212> PRT
<213> Homo sapiens
<400> 550
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Ser Tyr Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu
115 120 125
Ser Met Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
130 135 140
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser
145 150 155 160
Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
165 170 175
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
180 185 190
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr
210 215 220
Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr
225 230 235 240
Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro
245 250 255
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
260 265 270
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
275 280 285
Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
290 295 300
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
305 310 315 320
Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu
325 330 335
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala
340 345 350
Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro
355 360 365
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
385 390 395 400
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
405 410 415
Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
420 425 430
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
435 440 445
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
450 455 460
Leu Ser Pro Gly Lys
465
<210> 551
<211> 462
<212> PRT
<213> Homo sapiens
<400> 551
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
165 170 175
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
180 185 190
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
195 200 205
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
225 230 235 240
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
245 250 255
Leu 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 His Glu Asp Pro Glu Val
275 280 285
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
290 295 300
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
370 375 380
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
385 390 395 400
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 552
<211> 469
<212> PRT
<213> Homo sapiens
<400> 552
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Ser Tyr Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu
115 120 125
Ser Met Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
130 135 140
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser
145 150 155 160
Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
165 170 175
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
180 185 190
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr
210 215 220
Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr
225 230 235 240
Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro
245 250 255
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
260 265 270
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
275 280 285
Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
290 295 300
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
305 310 315 320
Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu
325 330 335
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala
340 345 350
Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro
355 360 365
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
385 390 395 400
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
405 410 415
Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
420 425 430
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
435 440 445
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
450 455 460
Leu Ser Pro Gly Lys
465
<210> 553
<211> 462
<212> PRT
<213> Homo sapiens
<400> 553
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
165 170 175
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
180 185 190
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
195 200 205
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
225 230 235 240
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
245 250 255
Leu 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 His Glu Asp Pro Glu Val
275 280 285
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
290 295 300
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
370 375 380
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
385 390 395 400
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 554
<211> 461
<212> PRT
<213> Homo sapiens
<400> 554
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Thr Gly Val His Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
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 His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 555
<211> 461
<212> PRT
<213> Homo sapiens
<400> 555
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Ile Gly Asn Trp Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
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 His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 556
<211> 461
<212> PRT
<213> Homo sapiens
<400> 556
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Thr Thr His Gln Gly Tyr Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
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 His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 557
<211> 465
<212> PRT
<213> Homo sapiens
<400> 557
Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp
1 5 10 15
Val Leu Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Ala Thr Asn Arg Tyr Gly Tyr Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val Tyr
130 135 140
Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu
145 150 155 160
Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr Trp
165 170 175
Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser Ser
195 200 205
Thr Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala Ser
210 215 220
Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile Lys
225 230 235 240
Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro
245 250 255
Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser
260 265 270
Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp
275 280 285
Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr
290 295 300
Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val
305 310 315 320
Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu
325 330 335
Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg
340 345 350
Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val
355 360 365
Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr
370 375 380
Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr
385 390 395 400
Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu
405 410 415
Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys
420 425 430
Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu
435 440 445
Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly
450 455 460
Lys
465
<210> 558
<211> 462
<212> PRT
<213> Homo sapiens
<400> 558
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
165 170 175
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
180 185 190
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
195 200 205
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
225 230 235 240
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
245 250 255
Leu 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 His Glu Asp Pro Glu Val
275 280 285
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
290 295 300
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
370 375 380
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
385 390 395 400
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 559
<211> 461
<212> PRT
<213> Homo sapiens
<400> 559
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
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 His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 560
<211> 461
<212> PRT
<213> Homo sapiens
<400> 560
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
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 His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 561
<211> 130
<212> PRT
<213> Homo sapiens
<400> 561
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val
20 25 30
Ala Pro Gly Gln Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly
35 40 45
Ser Phe Tyr Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val
50 55 60
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg
65 70 75 80
Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly
85 90 95
Thr Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Ala Gly
100 105 110
Ser Ser Gly Ser Tyr Val Phe Gly Gly Arg Thr Lys Leu Thr Val Leu
115 120 125
Gly Gln
130
<210> 562
<211> 237
<212> PRT
<213> Homo sapiens
<400> 562
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 563
<211> 234
<212> PRT
<213> Homo sapiens
<400> 563
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val
20 25 30
Ala Pro Gly Gln Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly
35 40 45
Ser Phe Tyr Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val
50 55 60
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg
65 70 75 80
Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly
85 90 95
Thr Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ser Trp Thr Gly
100 105 110
Val Glu Pro Asp Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
115 120 125
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser
130 135 140
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
145 150 155 160
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro
165 170 175
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn
180 185 190
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
195 200 205
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
210 215 220
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230
<210> 564
<211> 237
<212> PRT
<213> Homo sapiens
<400> 564
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser
100 105 110
Tyr Ala Gly Ser Tyr Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 565
<211> 237
<212> PRT
<213> Homo sapiens
<400> 565
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 566
<211> 237
<212> PRT
<213> Homo sapiens
<400> 566
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 567
<211> 237
<212> PRT
<213> Homo sapiens
<400> 567
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 568
<211> 237
<212> PRT
<213> Homo sapiens
<400> 568
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 569
<211> 237
<212> PRT
<213> Homo sapiens
<400> 569
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr
100 105 110
Tyr Asp Gly Pro Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 570
<211> 237
<212> PRT
<213> Homo sapiens
<400> 570
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 571
<211> 237
<212> PRT
<213> Homo sapiens
<400> 571
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr
100 105 110
Tyr Asp Gly Pro Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 572
<211> 1410
<212> DNA
<213> Homo sapiens
<400> 572
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagcgt gcaggcccag 60
gtgcagctgg tcgagtctgg cggcggactg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagcagc tacgtgatga actgggtgcg gcaggcccct 180
ggcaagggcc tggagtgggt gtccttcatc agcggcgaca gcagcaacac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgcccg gaccttcatg 360
cacggccacc tgggcggagg actgagcatg gatttctggg gccagggcac cctggtcacc 420
gtctcctcag cttccaccaa gggcccatcc gtcttccccc tggcgccctg ctccaggagc 480
acctccgaga gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 540
acggtgtcgt ggaactcagg cgctctgacc agcggcgtgc acaccttccc agctgtccta 600
cagtcctcag gactctactc cctcagcagc gtggtgacag tgccctccag caacttcggc 660
acccagacct acacctgcaa cgtagatcac aagcccagca acaccaaggt ggacaagaca 720
gttgagcgca aatgttgtgt cgagtgccca ccgtgcccag caccacctgt ggcaggaccg 780
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 840
gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtccagtt caactggtac 900
gtggacggcg tggaggtgca taatgccaag acaaagccac gggaggagca gttcaacagc 960
acgttccgtg tggtcagcgt cctcaccgtt gtgcaccagg actggctgaa cggcaaggag 1020
tacaagtgca aggtctccaa caaaggcctc ccagccccca tcgagaaaac catctccaaa 1080
accaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1140
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1200
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacacc tcccatgctg 1260
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1320
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1380
aagagcctct ccctgtctcc gggtaaatga 1410
<210> 573
<211> 1389
<212> DNA
<213> Homo sapiens
<400> 573
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaggtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccaacatc aactacgacg gcagcagcac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgccag ggacacctac 360
ctgcacttcg actactgggg ccagggcacc ctggtcaccg tctcctcagc ttccaccaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagcggcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gctctgacca gcggcgtgca caccttccca gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgacagt gccctccagc aacttcggca cccagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagacag ttgagcgcaa atgttgtgtc 720
gagtgcccac cgtgcccagc accacctgtg gcaggaccgt cagtcttcct cttcccccca 780
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccacg aagaccccga ggtccagttc aactggtacg tggacggcgt ggaggtgcat 900
aatgccaaga caaagccacg ggaggagcag ttcaacagca cgttccgtgt ggtcagcgtc 960
ctcaccgttg tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cagcccccat cgagaaaacc atctccaaaa ccaaagggca gccccgagaa 1080
ccacaggtgt acaccctgcc cccatcccgg gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacacct cccatgctgg actccgacgg ctccttcttc 1260
ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380
ggtaaatga 1389
<210> 574
<211> 1410
<212> DNA
<213> Homo sapiens
<400> 574
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagcgt gcaggcccag 60
gtgcagctgg tcgagtctgg cggcggactg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagcagc tacgtgatga actgggtgcg gcaggcccct 180
ggcaagggcc tggagtgggt gtccttcatc agcggcgaca gcagcaacac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgcccg gaccttcatg 360
cacggccacc tgggcggagg actgagcatg gatttctggg gccagggcac cctggtcacc 420
gtctcctcag cttccaccaa gggcccatcc gtcttccccc tggcgccctg ctccaggagc 480
acctccgaga gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 540
acggtgtcgt ggaactcagg cgctctgacc agcggcgtgc acaccttccc agctgtccta 600
cagtcctcag gactctactc cctcagcagc gtggtgacag tgccctccag caacttcggc 660
acccagacct acacctgcaa cgtagatcac aagcccagca acaccaaggt ggacaagaca 720
gttgagcgca aatgttgtgt cgagtgccca ccgtgcccag caccacctgt ggcaggaccg 780
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 840
gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtccagtt caactggtac 900
gtggacggcg tggaggtgca taatgccaag acaaagccac gggaggagca gttcaacagc 960
acgttccgtg tggtcagcgt cctcaccgtt gtgcaccagg actggctgaa cggcaaggag 1020
tacaagtgca aggtctccaa caaaggcctc ccagccccca tcgagaaaac catctccaaa 1080
accaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1140
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1200
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacacc tcccatgctg 1260
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1320
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1380
aagagcctct ccctgtctcc gggtaaatga 1410
<210> 575
<211> 1389
<212> DNA
<213> Homo sapiens
<400> 575
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaggtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccaacatc aactacgacg gcagcagcac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgccag ggacacctac 360
ctgcacttcg actactgggg ccagggcacc ctggtcaccg tctcctcagc ttccaccaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagcggcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gctctgacca gcggcgtgca caccttccca gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgacagt gccctccagc aacttcggca cccagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagacag ttgagcgcaa atgttgtgtc 720
gagtgcccac cgtgcccagc accacctgtg gcaggaccgt cagtcttcct cttcccccca 780
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccacg aagaccccga ggtccagttc aactggtacg tggacggcgt ggaggtgcat 900
aatgccaaga caaagccacg ggaggagcag ttcaacagca cgttccgtgt ggtcagcgtc 960
ctcaccgttg tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cagcccccat cgagaaaacc atctccaaaa ccaaagggca gccccgagaa 1080
ccacaggtgt acaccctgcc cccatcccgg gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccaga gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacacct cccatgctgg actccgacgg ctccttcttc 1260
ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380
ggtaaatga 1389
<210> 576
<211> 1386
<212> DNA
<213> Homo sapiens
<400> 576
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgacc ggcgtgcacg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 577
<211> 1386
<212> DNA
<213> Homo sapiens
<400> 577
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgatc ggcaactggg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 578
<211> 1386
<212> DNA
<213> Homo sapiens
<400> 578
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgacc acccaccagg gctacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 579
<211> 1386
<212> DNA
<213> Homo sapiens
<400> 579
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgccacc aacagatacg gctacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 580
<211> 1389
<212> DNA
<213> Homo sapiens
<400> 580
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaggtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccaacatc aactacgacg gcagcagcac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgccag ggacacctac 360
ctgcacttcg actactgggg ccagggcacc ctggtcaccg tctcctcagc ttccaccaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagcggcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gctctgacca gcggcgtgca caccttccca gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgacagt gccctccagc aacttcggca cccagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagacag ttgagcgcaa atgttgtgtc 720
gagtgcccac cgtgcccagc accacctgtg gcaggaccgt cagtcttcct cttcccccca 780
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccacg aagaccccga ggtccagttc aactggtacg tggacggcgt ggaggtgcat 900
aatgccaaga caaagccacg ggaggagcag ttcaacagca cgttccgtgt ggtcagcgtc 960
ctcaccgttg tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cagcccccat cgagaaaacc atctccaaaa ccaaagggca gccccgagaa 1080
ccacaggtgt acaccctgcc cccatcccgg gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacacct cccatgctgg actccgacgg ctccttcttc 1260
ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380
ggtaaatga 1389
<210> 581
<211> 1386
<212> DNA
<213> Homo sapiens
<400> 581
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgatc accccctacg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 582
<211> 1386
<212> DNA
<213> Homo sapiens
<400> 582
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgatc accccctacg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 583
<211> 393
<212> DNA
<213> Homo sapiens
<400> 583
atgaaaaaga cagctatcgc gattgcagtg gcactggctg gtttcgctac cgtagcgcag 60
gccgatatcg aactgaccca gccgccttca gtgagcgttg caccaggtca gaccgcgcgt 120
atctcgtgta gcggcgataa tattggttct ttttatgttc attggtacca gcagaaaccc 180
gggcaggcgc cagttcttgt gatttatgat gataataatc gtccctcagg catcccggaa 240
cgctttagcg gatccaacag cggcaacacc gcgaccctga ccattagcgg cactcaggcg 300
gaagacgaag cggattatta ttgcggttct tgggctggtt cttctggttc ttatgtgttt 360
ggcggccgca cgaagttaac cgttcttggc cag 393
<210> 584
<211> 714
<212> DNA
<213> Homo sapiens
<400> 584
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 585
<211> 705
<212> DNA
<213> Homo sapiens
<400> 585
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgagc tgacccagcc ccccagcgtg agcgtggccc ctggccagac cgcccggatc 120
agctgcagcg gcgacaacat cggcagcttc tacgtgcact ggtatcagca gaagcccggc 180
caggcccccg tgctggtgat ctacgacgac aacaaccggc ccagcggcat ccccgagcgg 240
ttcagcggca gcaacagcgg caacaccgcc accctgacca tcagcggcac ccaggccgag 300
gacgaggccg actactactg cgccagctgg accggcgtgg agcccgacta cgtgtttggc 360
ggcggaacaa agcttaccgt cctaggtcag cccaaggctg ccccctcggt cactctgttc 420
ccgccctcct ctgaggagct tcaagccaac aaggccacac tggtgtgtct cataagtgac 480
ttctacccgg gagccgtgac agtggcctgg aaggcagata gcagccccgt caaggcggga 540
gtggagacaa ccacaccctc caaacaaagc aacaacaagt acgcggccag cagctatctg 600
agcctgacgc ctgagcagtg gaagtcccac agaagctaca gctgccaggt cacgcatgaa 660
gggagcaccg tggaaaagac agtggcccct acagaatgtt catag 705
<210> 586
<211> 714
<212> DNA
<213> Homo sapiens
<400> 586
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc cagagctacg ccggcagcta cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 587
<211> 714
<212> DNA
<213> Homo sapiens
<400> 587
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 588
<211> 714
<212> DNA
<213> Homo sapiens
<400> 588
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 589
<211> 714
<212> DNA
<213> Homo sapiens
<400> 589
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 590
<211> 714
<212> DNA
<213> Homo sapiens
<400> 590
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 591
<211> 714
<212> DNA
<213> Homo sapiens
<400> 591
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcacctacg acggccctgg cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 592
<211> 714
<212> DNA
<213> Homo sapiens
<400> 592
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcacctacg acggccctgg cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 593
<211> 714
<212> DNA
<213> Homo sapiens
<400> 593
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcacctacg acggccctgg cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 594
<211> 213
<212> PRT
<213> Homo sapiens
<400> 594
Met Gln Leu Pro Leu Ala Leu Cys Leu Val Cys Leu Leu Val His Thr
1 5 10 15
Ala Phe Arg Val Val Glu Gly Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 595
<211> 14
<212> PRT
<213> Homo sapiens
<400> 595
Ala Arg Leu Leu Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg
1 5 10
<210> 596
<211> 15
<212> PRT
<213> Homo sapiens
<400> 596
Arg Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His
1 5 10 15
<210> 597
<211> 13
<212> PRT
<213> Homo sapiens
<400> 597
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
1 5 10
<210> 598
<211> 19
<212> PRT
<213> Homo sapiens
<400> 598
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly
<210> 599
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 599
taaattatca taaagtccta a 21
<210> 600
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 600
aggactttat gataatttat t 21
<210> 601
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 601
atagtggtta aataactcca g 21
<210> 602
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 602
ggagttattt aaccactatt t 21
<210> 603
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 603
taaattctcg tgatgtgcca t 21
<210> 604
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 604
ggcacatcac gagaatttat t 21
<210> 605
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 605
tttcttatag cacagctggt t 21
<210> 606
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 606
ccagctgtgc tataagaaat t 21
<210> 607
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 607
tagacctttc catccacgct g 21
<210> 608
<211> 21
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 608
gcgtggatgg aaaggtctat t 21
<210> 609
<211> 29
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 609
atgcagctcc cactggccct gtgtcttgt 29
<210> 610
<211> 30
<212> DNA
<213> Artificial
<220>
<223> siRNA
<400> 610
aatcaggccg agctggagaa cgcctactag 30
<210> 611
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 611
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile Pro Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Asp Ser Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Arg Cys Tyr Phe Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 612
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 612
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Gly Ser Gly Arg Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Leu Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Thr Ala Ser
50 55 60
Asn Arg Gly Tyr Leu His Met Asn Asn Leu Thr Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 613
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 613
Ala Val Gln Leu Val Asp Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Leu Thr Gly Gly Ala Phe Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Thr Pro Gly Arg Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Met Val Tyr Leu Arg Met Asn Ser Leu Ile Pro Glu Asp Ala Ala
65 70 75 80
Val Tyr Ser Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Leu Val Thr Val Ser Ser
100
<210> 614
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 614
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Glu Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Glu Ser Pro Phe Arg Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Thr Ser Gly Gln Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys
50 55 60
Asn Thr Val Trp Leu His Gly Ser Thr Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 615
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 615
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Gly Gly Gly
1 5 10 15
Ser Leu Arg Leu Ala Cys Ala Ala Ser Glu Arg Ile Phe Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Tyr Arg Gln Gly Pro Gly Asn Glu Arg Glu Leu Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Met Asp Tyr Thr Lys
50 55 60
Gln Thr Val Tyr Leu His Met Asn Ser Leu Arg Pro Glu Asp Thr Gly
65 70 75 80
Leu Tyr Tyr Cys Lys Ile Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 616
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 616
Asp Val Lys Phe Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Asn Phe Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Glu Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Ser Glu Lys Asp Lys
50 55 60
Asn Ser Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Leu Tyr Ile Cys Ala Gly Xaa Xaa Xaa Xaa Xaa Trp Gly Arg Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 617
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 617
Gln Val Arg Leu Ala Glu Ser Gly Gly Gly Leu Val Gln Ser Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Ser Thr Tyr Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Tyr Arg Gln Tyr Pro Gly Lys Gln Arg Ala Leu Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ala Arg Asp Ser Thr Lys
50 55 60
Asp Thr Phe Cys Leu Gln Met Asn Asn Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Tyr Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 618
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 618
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ser Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Pro Arg Glu Gly Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Thr Asp Asn Ala Lys
50 55 60
Asn Thr Val His Leu Leu Met Asn Arg Val Asn Ala Glu Asp Thr Ala
65 70 75 80
Leu Tyr Tyr Cys Ala Val Xaa Xaa Xaa Xaa Xaa Trp Gly Arg Gly Thr
85 90 95
Arg Val Thr Val Ser Ser
100
<210> 619
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 619
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 Gln Ala Ser Gly Asp Ile Ser Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Tyr Arg Gln Val Pro Gly Lys Leu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Gly Asp Asn Ala Lys
50 55 60
Arg Ala Ile Tyr Leu Gln Met Asn Asn Leu Lys Pro Asp Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Asn Arg Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Pro
100
<210> 620
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 620
Gln Val Pro Val Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Phe Cys Ala Val Pro Ser Phe Thr Ser Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asn Ala Thr Lys
50 55 60
Asn Thr Leu Thr Leu Arg Met Asp Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 621
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 621
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Phe Cys Thr Val Ser Gly Gly Thr Ala Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Glu Lys Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ala Arg Glu Asn Ala Gly
50 55 60
Asn Met Val Tyr Leu Gln Met Asn Asn Leu Lys Pro Asp Asp Thr Ala
65 70 75 80
Leu Tyr Thr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Arg Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 622
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 622
Ala Val Gln Leu Val Glu Ser Gly Gly Asp Ser Val Gln Pro Gly Asp
1 5 10 15
Ser Gln Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Asn Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Val Phe Leu
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Ser Ala Lys
50 55 60
Asn Met Met Tyr Leu Gln Met Asn Asn Leu Lys Pro Gln Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 623
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 623
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Val Ser Gly Leu Thr Ser Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Thr Pro Trp Gln Glu Arg Asp Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Tyr Lys
50 55 60
Asp Thr Val Leu Leu Glu Met Asn Phe Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Ile Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 624
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 624
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Ala
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Thr Ser Thr Arg Thr Leu Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Arg Asp Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Val Ser Arg Asp Ser Ala Glu
50 55 60
Asn Thr Val Ala Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Arg Val Thr Val Ser Ser
100
<210> 625
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 625
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 Thr Val Ser Arg Leu Thr Ala His Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Ala Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Tyr Ala Gly
50 55 60
Asn Thr Ala Phe Leu Gln Met Asp Ser Leu Lys Pro Glu Asp Thr Gly
65 70 75 80
Val Tyr Tyr Cys Ala Thr Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 626
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 626
Glu Val Gln Leu Val Glu Ser Gly Gly Glu Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Thr Ala Ser Gly Arg Asn Phe Val Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Arg Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Val Ser Arg Asp Asn Gly Lys
50 55 60
Asn Thr Ala Tyr Leu Arg Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Asp Tyr Tyr Cys Ala Val Xaa Xaa Xaa Xaa Xaa Leu Gly Ser Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 627
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 627
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg Gln Ala Pro Gly Lys Val Leu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Val Lys Xaa Xaa Xaa Xaa Xaa Gly Ser Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 628
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 628
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Cys Val Ser Ser Gly Cys Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Lys Ile Ser Arg Asp Asn Ala Lys
50 55 60
Lys Thr Leu Tyr Leu Gln Met Asn Ser Leu Gly Pro Glu Asp Thr Ala
65 70 75 80
Met Tyr Tyr Cys Gln Arg Xaa Xaa Xaa Xaa Xaa Arg Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 629
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 629
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Val Phe Ser Gly Ser Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg His Thr Pro Gly Lys Ala Glu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Leu Tyr Leu Glu Met Asn Ser Leu Ser Pro Glu Asp Thr Ala
65 70 75 80
Met Tyr Tyr Cys Gly Arg Xaa Xaa Xaa Xaa Xaa Arg Ser Lys Gly Ile
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 630
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 630
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Arg Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 631
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 631
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Leu Arg Gln Thr Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Met Leu Tyr Leu His Leu Asn Asn Leu Lys Ser Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Arg Arg Xaa Xaa Xaa Xaa Xaa Leu Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 632
<211> 102
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa is any amino acid
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa is any amino acid
<400> 632
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Cys Val Ser Ser Gly Cys Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Lys Ile Ser Arg Asp Asn Ala Lys
50 55 60
Lys Thr Leu Tyr Leu Gln Met Asn Ser Leu Gly Pro Glu Asp Thr Ala
65 70 75 80
Met Tyr Tyr Cys Gln Arg Xaa Xaa Xaa Xaa Xaa Arg Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 633
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 633
Gln Val Gln Arg Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Ser
20 25 30
<210> 634
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 634
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr Gly Asp
1 5 10 15
Ser Leu Ser Leu Ser Cys Ser Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 635
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 635
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Ala Phe Gly
20 25 30
<210> 636
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 636
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Glu
1 5 10 15
Ser Leu Gly Leu Ser Cys Val Ala Ser Gly Arg Asp Phe Val
20 25 30
<210> 637
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 637
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Val Leu Gly Arg Thr Ala Gly
20 25 30
<210> 638
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 638
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Trp Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Thr Ile Leu Ser
20 25 30
<210> 639
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 639
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Thr Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Asn Leu Ser Cys Val Ala Ser Gly Asn Thr Phe Asn
20 25 30
<210> 640
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly
1 5 10 15
Ser Leu Gln Leu Ser Cys Ser Ala Pro Gly Phe Thr Leu Asp
20 25 30
<210> 641
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 641
Ala Gln Glu Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn
20 25 30
<210> 642
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 642
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 643
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 643
Val Asp Ser Gly Gly Gly Leu Val Gln Ala Gly Asp Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Leu Thr Gly
20
<210> 644
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 644
Val Asp Ser Gly Gly Gly Leu Val Gln Ala Gly Asp Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 645
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 645
Val Asp Ser Gly Gly Gly Leu Val Glu Ala Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Gln Val Ser Glu
20
<210> 646
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 646
Gln Asp Ser Gly Gly Gly Ser Val Gln Ala Gly Gly Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 647
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 647
Val Gln Ser Gly Gly Arg Leu Val Gln Ala Gly Asp Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Glu
20
<210> 648
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 648
Val Glu Ser Gly Gly Thr Leu Val Gln Ser Gly Asp Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Ser Ser Thr
20
<210> 649
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 649
Met Glu Ser Gly Gly Asp Ser Val Gln Ser Gly Gly Ser Leu Thr Leu
1 5 10 15
Ser Cys Val Ala Ser Gly
20
<210> 650
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW1 sequence
<400> 650
Gln Ala Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ser Ala Ser Val
20
<210> 651
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 651
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala
1 5 10
<210> 652
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 652
Trp Phe Arg Gln Thr Pro Gly Arg Glu Arg Glu Phe Val Ala
1 5 10
<210> 653
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 653
Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Met Val Ala
1 5 10
<210> 654
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 654
Trp Tyr Arg Gln Gly Pro Gly Lys Gln Arg Glu Leu Val Ala
1 5 10
<210> 655
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 655
Trp Ile Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ser
1 5 10
<210> 656
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 656
Trp Phe Arg Glu Ala Pro Gly Lys Glu Arg Glu Gly Ile Ser
1 5 10
<210> 657
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 657
Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Asp Leu Val Ala
1 5 10
<210> 658
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 658
Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Glu Val Ser
1 5 10
<210> 659
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW2 sequence
<400> 659
Trp Phe Arg Gln Pro Pro Gly Lys Val Arg Glu Phe Val Gly
1 5 10
<210> 660
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 660
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Arg Cys Tyr Phe
20 25 30
<210> 661
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 661
Arg Phe Ala Ile Ser Arg Asp Asn Asn Lys Asn Thr Gly Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 662
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 662
Arg Phe Thr Val Ala Arg Asn Asn Ala Lys Asn Thr Val Asn Leu Glu
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 663
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 663
Arg Phe Thr Ile Ser Arg Asp Ile Ala Lys Asn Thr Val Asp Leu Leu
1 5 10 15
Met Asn Asn Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 664
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 664
Arg Leu Thr Ile Ser Arg Asp Asn Ala Val Asp Thr Met Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 665
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 665
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asp Asn Val Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
20 25 30
<210> 666
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 666
Arg Phe Thr Ile Ser Lys Asp Ser Gly Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Thr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 667
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 667
Arg Phe Thr Ile Ser Arg Asp Ser Ala Lys Asn Met Met Tyr Leu Gln
1 5 10 15
Met Asn Asn Leu Lys Pro Gln Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 668
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 668
Arg Phe Thr Ile Ser Arg Glu Asn Asp Lys Ser Thr Val Tyr Leu Gln
1 5 10 15
Leu Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 669
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW3 sequence
<400> 669
Arg Phe Thr Ile Ser Arg Asp Tyr Ala Gly Asn Thr Ala Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Gly Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 670
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW4 sequence
<400> 670
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 671
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW4 sequence
<400> 671
Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 672
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW4 sequence
<400> 672
Arg Gly Gln Gly Thr Arg Val Thr Val Ser Ser
1 5 10
<210> 673
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> KERE-class Nanobody FW4 sequence
<400> 673
Trp Gly Leu Gly Thr Gln Val Thr Ile Ser Ser
1 5 10
<210> 674
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 674
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 Gly Phe Thr Phe Ser
20 25 30
<210> 675
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 675
Glu Val His Leu Val Glu Ser Gly Gly Gly Leu Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Phe Gly Phe Ile Phe Lys
20 25 30
<210> 676
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 676
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser
20 25 30
<210> 677
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 677
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Cys Val Ser Ser Gly Cys Thr
20 25 30
<210> 678
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 678
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Val Phe Ser Gly Ser Thr Phe Ser
20 25 30
<210> 679
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 679
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 680
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 680
Glu Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Val Ala Ser Gly
20
<210> 681
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW1 sequence
<400> 681
Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly Ser Leu Thr Leu
1 5 10 15
Ser Cys Val Phe Ser Gly
20
<210> 682
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 682
Trp Val Arg Gln Ala Pro Gly Lys Val Leu Glu Trp Val Ser
1 5 10
<210> 683
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 683
Trp Val Arg Arg Pro Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10
<210> 684
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 684
Trp Val Arg Gln Ala Pro Gly Met Gly Leu Glu Trp Val Ser
1 5 10
<210> 685
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 685
Trp Val Arg Gln Ala Pro Gly Lys Glu Pro Glu Trp Val Ser
1 5 10
<210> 686
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 686
Trp Val Arg Gln Ala Pro Gly Lys Asp Gln Glu Trp Val Ser
1 5 10
<210> 687
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 687
Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Trp Val Ser
1 5 10
<210> 688
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 688
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
1 5 10
<210> 689
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW2 sequence
<400> 689
Trp Val Arg Gln Ala Pro Gly Arg Ala Thr Glu Trp Val Ser
1 5 10
<210> 690
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW3 sequence
<400> 690
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Val Lys
20 25 30
<210> 691
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW3 sequence
<400> 691
Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asp Ser Leu Ile Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Arg
20 25 30
<210> 692
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW3 sequence
<400> 692
Arg Phe Thr Ser Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Asp Leu Lys Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Arg
20 25 30
<210> 693
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW3 sequence
<400> 693
Arg Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Gly Pro Glu Asp Thr Ala Met Tyr Tyr Cys Gln Arg
20 25 30
<210> 694
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW3 sequence
<400> 694
Arg Phe Thr Ala Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Arg Tyr Tyr Cys Ala Arg
20 25 30
<210> 695
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW3 sequence
<400> 695
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asp Asp Leu Gln Ser Glu Asp Thr Ala Met Tyr Tyr Cys Gly Arg
20 25 30
<210> 696
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW4 sequence
<400> 696
Gly Ser Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 697
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW4 sequence
<400> 697
Leu Arg Gly Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 698
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW4 sequence
<400> 698
Arg Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 699
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW4 sequence
<400> 699
Arg Ser Arg Gly Ile Gln Val Thr Val Ser Ser
1 5 10
<210> 700
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW4 sequence
<400> 700
Trp Gly Lys Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 701
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> GLEW-class Nanobody FW4 sequence
<400> 701
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 702
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 702
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 703
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 703
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Met Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Gly
20 25 30
<210> 704
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 704
Glu Val His Leu Val Glu Ser Gly Gly Gly Leu Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Phe Gly Phe Ile Phe Lys
20 25 30
<210> 705
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 705
Gln Val Gln Leu Ala Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Arg Thr Ile Val Ser
20 25 30
<210> 706
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 706
Gln Glu His Leu Val Glu Ser Gly Gly Gly Leu Val Asp Ile Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Arg Ile Phe Ser
20 25 30
<210> 707
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 707
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser
20 25 30
<210> 708
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 708
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Cys Val Ser Ser Gly Cys Thr
20 25 30
<210> 709
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 709
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Val Phe Ser Gly Ser Thr Phe Ser
20 25 30
<210> 710
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 710
Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 711
<211> 22
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW1 sequence
<400> 711
Ala Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Ala Ser Arg
20
<210> 712
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 712
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala
1 5 10
<210> 713
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 713
Trp Val Arg Gln Ala Pro Gly Lys Val Leu Glu Trp Val Ser
1 5 10
<210> 714
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 714
Trp Val Arg Arg Pro Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10
<210> 715
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 715
Trp Ile Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ser
1 5 10
<210> 716
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 716
Trp Val Arg Gln Tyr Pro Gly Lys Glu Pro Glu Trp Val Ser
1 5 10
<210> 717
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 717
Trp Phe Arg Gln Pro Pro Gly Lys Glu His Glu Phe Val Ala
1 5 10
<210> 718
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 718
Trp Tyr Arg Gln Ala Pro Gly Lys Arg Thr Glu Leu Val Ala
1 5 10
<210> 719
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 719
Trp Leu Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val Ser
1 5 10
<210> 720
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 720
Trp Leu Arg Gln Thr Pro Gly Lys Gly Leu Glu Trp Val Gly
1 5 10
<210> 721
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW2 sequence
<400> 721
Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Phe Val Ser
1 5 10
<210> 722
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 722
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 723
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 723
Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asp Ser Leu Ile Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Arg
20 25 30
<210> 724
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 724
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Glu Met Tyr Leu Gln
1 5 10 15
Met Asn Asn Leu Lys Thr Glu Asp Thr Gly Val Tyr Trp Cys Gly Ala
20 25 30
<210> 725
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 725
Arg Phe Thr Ile Ser Ser Asp Ser Asn Arg Asn Met Ile Tyr Leu Gln
1 5 10 15
Met Asn Asn Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 726
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 726
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Met Leu Tyr Leu His
1 5 10 15
Leu Asn Asn Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys Arg Arg
20 25 30
<210> 727
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 727
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Thr Val Tyr Leu Arg
1 5 10 15
Leu Asn Ser Leu Asn Pro Glu Asp Thr Ala Val Tyr Ser Cys Asn Leu
20 25 30
<210> 728
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 728
Arg Phe Lys Ile Ser Arg Asp Asn Ala Lys Lys Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Gly Pro Glu Asp Thr Ala Met Tyr Tyr Cys Gln Arg
20 25 30
<210> 729
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW3 sequence
<400> 729
Arg Phe Thr Val Ser Arg Asp Asn Gly Lys Asn Thr Ala Tyr Leu Arg
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Asp Tyr Tyr Cys Ala Val
20 25 30
<210> 730
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW4 sequence
<400> 730
Arg Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 731
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW4 sequence
<400> 731
Leu Arg Gly Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 732
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW4 sequence
<400> 732
Gly Asn Lys Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 733
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW4 sequence
<400> 733
Ser Ser Pro Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 734
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW4 sequence
<400> 734
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 735
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> P,R,S 103-class Nanobody FW4 sequence
<400> 735
Arg Ser Arg Gly Ile Gln Val Thr Val Ser Ser
1 5 10
<210> 736
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 736
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Ile Phe Ser
20 25 30
<210> 737
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 737
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Thr Gly Arg Thr Ser Ser
20 25 30
<210> 738
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 738
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser
20 25 30
<210> 739
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 739
Lys Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 740
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 740
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser
20 25 30
<210> 741
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 741
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Arg Thr Leu Arg
20 25 30
<210> 742
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 742
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 743
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 743
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Phe Asn
20 25 30
<210> 744
<211> 30
<212> PRT
<213> Artificial Sequence
<220>
<223> FR1 sequence
<400> 744
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser
20 25 30
<210> 745
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 745
Asp Asn Val Met Gly
1 5
<210> 746
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 746
Ile Tyr Asn Met Asp
1 5
<210> 747
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 747
Arg Phe Asp Met Ser
1 5
<210> 748
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 748
Ser Tyr Phe Met Gly
1 5
<210> 749
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 749
Ile Tyr Asn Met Asp
1 5
<210> 750
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 750
Arg Tyr Val Thr Gly
1 5
<210> 751
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 751
Ser Phe Val Ile Gly
1 5
<210> 752
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 752
Gln Tyr Thr Ile Thr
1 5
<210> 753
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 753
Ile Tyr Asn Met Asp
1 5
<210> 754
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 754
Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val Ala
1 5 10
<210> 755
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 755
Trp Phe Arg Gln Thr Pro Gly Lys Glu Arg Glu Leu Ile Ala
1 5 10
<210> 756
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 756
Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Phe Ile Ala
1 5 10
<210> 757
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 757
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val Ala
1 5 10
<210> 758
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 758
Trp Phe Leu Gln Ala Pro Gly Lys Glu Arg Glu Leu Ile Ala
1 5 10
<210> 759
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 759
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val Ala
1 5 10
<210> 760
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 760
Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Val Val Ala
1 5 10
<210> 761
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 761
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala
1 5 10
<210> 762
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> FR2 sequence
<400> 762
Trp Phe Arg Gln Gly Ser Gly Lys Gly Arg Glu Leu Ile Ala
1 5 10
<210> 763
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 763
Thr Ile Trp Ser Ser Gly His Thr Asn Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 764
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 764
Arg Leu Trp Trp Arg Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 765
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 765
Thr Ile Phe Ser Gly Gly Asp Thr Asp Tyr Ile Asp Ser Val Lys Gly
1 5 10 15
<210> 766
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 766
Thr Ile Arg Trp Ser Asp Gly Ser Thr Tyr Tyr Glu Asp Ser Val Lys
1 5 10 15
Gly
<210> 767
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 767
Arg Ile Trp Trp Arg Ser Gly Ala Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 768
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 768
Ser Ile Ser Trp Ser Gly Glu Ser Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 769
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 769
Ser Ile Thr Ser Gly Gly Ser Thr Tyr Tyr Glu Asp Ser Gly Lys Gly
1 5 10 15
<210> 770
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 770
Ala Val Ser Trp Ser Gly Ser Ser Glu Ser Val Ser Asn Ser Val Lys
1 5 10 15
Gly
<210> 771
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 771
Arg Ile Trp Trp Arg Ser Gly Glu Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 772
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 772
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn Leu
20 25 30
<210> 773
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 773
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ser Val Tyr Ile Cys Thr Ala
20 25 30
<210> 774
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 774
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Cys Pro
20 25 30
<210> 775
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 775
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 776
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 776
Arg Phe Thr Ile Ser Arg Gly Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Gly Val Tyr His Cys Thr Ala
20 25 30
<210> 777
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 777
Arg Phe Ala Ile Ser Arg Asp Asn Ala Lys Asn Ala Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Asn Leu Glu Asp Thr Gly Val Tyr Tyr Cys Ala Glu
20 25 30
<210> 778
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 778
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Arg Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 779
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 779
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Ala Tyr Leu Ala
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 780
<211> 32
<212> PRT
<213> Artificial Sequence
<220>
<223> FR3 sequence
<400> 780
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Asn Val Tyr His Cys Ala Ala
20 25 30
<210> 781
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 781
Gly Thr Ile Val Thr Gly Thr Trp Arg Ser Asp Tyr
1 5 10
<210> 782
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 782
Gly Asp Thr Gly Gly Ala Ala Tyr Gly Tyr
1 5 10
<210> 783
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 783
Leu Gly Ile Glu Tyr Ala
1 5
<210> 784
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 784
Ala Lys Gly Ile Gly Val Tyr Gly Tyr
1 5
<210> 785
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 785
Gly Val Thr Gly Gly Ala Ala Tyr Gly Tyr
1 5 10
<210> 786
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 786
Ala Glu Leu Pro Gly Thr Tyr Asp Tyr
1 5
<210> 787
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 787
Ala Glu Pro Ala Gly Val Tyr Asp Val
1 5
<210> 788
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 788
Asp Arg Arg Gly Leu Ala Ser Thr Arg Ala Ala Asp Tyr Asp Tyr
1 5 10 15
<210> 789
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> CDR sequence
<400> 789
Gly Asp Thr Gly Gly Ala Ser Tyr Gly Tyr
1 5 10
<210> 790
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 790
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 791
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 791
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 792
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 792
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 793
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 793
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 794
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 794
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 795
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 795
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 796
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 796
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 797
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 797
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 798
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> FR4 sequence
<400> 798
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 799
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 799
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Ile Phe Ser Asp Asn
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Thr Ile Trp Ser Ser Gly His Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Leu Gly Thr Ile Val Thr Gly Thr Trp Arg Ser Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 800
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 800
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Thr Gly Arg Thr Ser Ser Ile Tyr
20 25 30
Asn Met Asp Trp Phe Arg Gln Thr Pro Gly Lys Glu Arg Glu Leu Ile
35 40 45
Ala Arg Leu Trp Trp Arg Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ser Val Tyr Ile Cys
85 90 95
Thr Ala Gly Asp Thr Gly Gly Ala Ala Tyr Gly Tyr Trp Gly Gln Gly
100 105 110
Thr Gln Val Thr Val Ser Ser
115
<210> 801
<211> 114
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 801
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser Arg Phe
20 25 30
Asp Met Ser Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Phe Ile
35 40 45
Ala Thr Ile Phe Ser Gly Gly Asp Thr Asp Tyr Ile Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Cys
85 90 95
Pro Leu Gly Ile Glu Tyr Ala Trp Gly Gln Gly Thr Gln Val Thr Val
100 105 110
Ser Ser
<210> 802
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 802
Lys Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr
20 25 30
Phe Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val
35 40 45
Ala Thr Ile Arg Trp Ser Asp Gly Ser Thr Tyr Tyr Glu Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Ala Lys Gly Ile Gly Val Tyr Gly Tyr Trp Gly Gln Gly Thr
100 105 110
Gln Val Thr Val Ser Ser
115
<210> 803
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 803
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser Ile Tyr
20 25 30
Asn Met Asp Trp Phe Leu Gln Ala Pro Gly Lys Glu Arg Glu Leu Ile
35 40 45
Ala Arg Ile Trp Trp Arg Ser Gly Ala Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Gly Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Gly Val Tyr His Cys
85 90 95
Thr Ala Gly Val Thr Gly Gly Ala Ala Tyr Gly Tyr Trp Gly Gln Gly
100 105 110
Thr Gln Val Thr Val Ser Ser
115
<210> 804
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 804
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Arg Thr Leu Arg Arg Tyr
20 25 30
Val Thr Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val
35 40 45
Ala Ser Ile Ser Trp Ser Gly Glu Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Ala Ile Ser Arg Asp Asn Ala Lys Asn Ala Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Asn Leu Glu Asp Thr Gly Val Tyr Tyr Cys
85 90 95
Ala Glu Ala Glu Leu Pro Gly Thr Tyr Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Gln Val Thr Val Ser Ser
115
<210> 805
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 805
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Phe
20 25 30
Val Ile Gly Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Val Val
35 40 45
Ala Ser Ile Thr Ser Gly Gly Ser Thr Tyr Tyr Glu Asp Ser Gly Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Arg Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Ala Ala Glu Pro Ala Gly Val Tyr Asp Val Trp Gly Gln Gly Thr Gln
100 105 110
Val Thr Val Ser Ser
115
<210> 806
<211> 124
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 806
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Phe Asn Gln Tyr
20 25 30
Thr Ile Thr Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Ala Val Ser Trp Ser Gly Ser Ser Glu Ser Val Ser Asn Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Ala Tyr
65 70 75 80
Leu Ala Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Asp Arg Arg Gly Leu Ala Ser Thr Arg Ala Ala Asp Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 807
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Nanobody
<400> 807
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser Ile Tyr
20 25 30
Asn Met Asp Trp Phe Arg Gln Gly Ser Gly Lys Gly Arg Glu Leu Ile
35 40 45
Ala Arg Ile Trp Trp Arg Ser Gly Glu Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Asn Val Tyr His Cys
85 90 95
Ala Ala Gly Asp Thr Gly Gly Ala Ser Tyr Gly Tyr Trp Gly Gln Gly
100 105 110
Thr Gln Val Thr Val Ser Ser
115
<210> 808
<211> 213
<212> PRT
<213> Homo sapiens
<400> 808
Met Gln Leu Pro Leu Ala Leu Cys Leu Val Cys Leu Leu Val His Thr
1 5 10 15
Ala Phe Arg Val Val Glu Gly Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Thr Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 809
<211> 213
<212> PRT
<213> Artificial Sequence
<220>
<223> Recombinant sclerostin
<400> 809
Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala
1 5 10 15
His His His His His His His Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
Claims (27)
- 대상체에서 결합 조직-골 치유 향상에 유효한 양의 항-스클레로스틴 항체를 대상체에 투여하는 단계를 포함하는, 필요로 하는 대상체에서 결합 조직-골 치유 향상 방법.
- 청구항 1에 있어서, 결합 조직은 인대, 건, 반달연골 또는 관절와순임을 특징으로 하는 방법.
- 청구항 1에 있어서, 결합 조직은 건임을 특징으로 하는 방법.
- 청구항 1-3 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 약 90-270 mg의 양으로 투여됨을 특징으로 하는 방법.
- 청구항 1-4 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 전신에 투여됨을 특징으로 하는 방법.
- 청구항 1-4 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 겔, 스펀지, 또는 매트릭스에 혼입되어 국소적으로 이식됨을 특징으로 하는 방법.
- 청구항 1-3 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 중쇄 및 경쇄를 포함하는 면역글로불린임을 특징으로 하는 방법.
- 청구항 1-7 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 서열 번호: 1의 스클레로스틴에 대하여 1 x 10-9 M의 결합 친화도를 나타내는 항체 또는 이의 단편임을 특징으로 하는 방법.
- 청구항 1-8 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 중 최소한 하나의 스클레로스틴에 대한 결합을 교차-차단하며 및/또는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 중 최소한 하나에 의해 스클레로스틴에 대한 결합이 교차-차단됨을 특징으로 하는 방법.
- 청구항 1-8 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 서열 번호:245의 CDR-H1, 서열 번호:246의 CDR-H2, 서열 번호:247의 CDR-H3, 서열 번호:78의 CDR-L1, 서열 번호:79의 CDR-L2 및 서열 번호:80의 CDR-L3를 포함함을 특징으로 하는 방법.
- 청구항 10에 있어서, 항-스클레로스틴 항체는 서열 번호: 378을 포함하는 중쇄 및 서열 번호: 376을 포함하는 경쇄를 포함함을 특징으로 하는 방법.
- 청구항 1-10 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 55 mM 아세테이트, 13 mm 칼슘, 6.0 % (w/v) 수크로스, 0.006% (w/v) 폴리소르베이트 20을 포함하는 pH 5.2의 제약학적 조성물로 제형화됨을 특징으로 하는 방법.
- 청구항 12에 있어서, 제약학적 조성물은 90 mg/mL의 항-스클레로스틴 항체를 포함함을 특징으로 하는 방법.
- 필요로 하는 대상체에서 결합 조직 재부착 과정의 결과를 개선시키는 방법으로서, 상기 과정의 결과를 개선시킴에 유효한 양의 항-스클레로스틴 항체를 상기 대상체에 투여하는 것을 포함하는 방법.
- 청구항 4에 있어서, 상기 과정은 회전근개 복원술, 아킬레스 건 복원술, 슬개건-슬개골 건 복원술, 내측 십자 인대 (MCL) 재건술, 전 십자 인대 (ACL) 재건술, 내측 측부 인대 (UCL), 반달연골 복원술, 또는 관절와순 복원술임을 특징으로 하는 방법.
- 청구항 14에 있어서, 상기 과정은 이식편 부착을 포함하고, 항-스클레로스틴 항체는 생체외에서 이식편에 적용됨을 특징으로 하는 방법.
- 청구항 14-16 중 어느 한 항에 있어서, 결합 조직은 인대, 건, 반달연골 또는 관절와순임을 특징으로 하는 방법.
- 청구항 14-16 중 어느 한 항에 있어서, 결합 조직은 건임을 특징으로 하는 방법.
- 청구항 14-18 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 약 90 mg-270 mg의 양으로 투여됨을 특징으로 하는 방법.
- 청구항 14-19 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 전신에 투여됨을 특징으로 하는 방법.
- 청구항 14-19 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 겔, 스펀지, 또는 매트릭스에 혼입되어 국소적으로 이식됨을 특징으로 하는 방법.
- 청구항 14-21 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 중쇄 및 경쇄를 포함하는 면역글로불린임을 특징으로 하는 방법.
- 청구항 14-22 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 서열 번호: 1의 스클레로스틴에 대하여 1 x 10-9 M의 결합 친화도를 나타내는 항체 또는 이의 단편임을 특징으로 하는 방법.
- 청구항 14-23 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 중 최소한 하나의 스클레로스틴에 대한 결합을 교차-차단하며 및/또는 항체 Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, 및 Ab-24 중 최소한 하나에 의해 스클레로스틴에 대한 결합이 교차-차단됨을 특징으로 하는 방법.
24. 청구항 14-23 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 서열 번호:245의 CDR-H1, 서열 번호:246의 CDR-H2, 서열 번호:247의 CDR-H3, 서열 번호:78의 CDR-L1, 서열 번호:79의 CDR-L2 및 서열 번호:80의 CDR-L3를 포함함을 특징으로 하는 방법. - 청구항 24에 있어서, 항-스클레로스틴 항체는 서열 번호: 378을 포함하는 중쇄 및 서열 번호: 376을 포함하는 경쇄를 포함함을 특징으로 하는 방법.
- 청구항 14-25 중 어느 한 항에 있어서, 항-스클레로스틴 항체는 55 mM 아세테이트, 13 mm 칼슘, 6.0 % (w/v) 수크로스, 0.006% (w/v) 폴리소르베이트 20을 포함하는 pH 5.2의 제약학적 조성물로 제형화됨을 특징으로 하는 방법.
- 청구항 26에 있어서, 제약학적 조성물은 90 mg/mL의 항-스클레로스틴 항체를 포함함을 특징으로 하는 방법.
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| US201662372124P | 2016-08-08 | 2016-08-08 | |
| US62/372,124 | 2016-08-08 | ||
| PCT/US2017/045705 WO2018031454A1 (en) | 2016-08-08 | 2017-08-07 | Method of improving connective tissue attachment using anti-sclerostin antibodies |
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| KR20190037261A true KR20190037261A (ko) | 2019-04-05 |
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| KR1020197004537A KR20190037261A (ko) | 2016-08-08 | 2017-08-07 | 항-스클레로스틴 항체를 사용한 결합 조직 부착 개선 방법 |
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| US (1) | US20190185556A1 (ko) |
| EP (1) | EP3496744A1 (ko) |
| JP (1) | JP2019527710A (ko) |
| KR (1) | KR20190037261A (ko) |
| CN (1) | CN110214021A (ko) |
| AU (1) | AU2017310412A1 (ko) |
| CA (1) | CA3032348A1 (ko) |
| MA (1) | MA45921A (ko) |
| WO (1) | WO2018031454A1 (ko) |
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| US10961305B2 (en) | 2016-12-21 | 2021-03-30 | Mereo Biopharma 3 Limited | Use of anti-sclerostin antibodies in the treatment of osteogenesis imperfecta |
| UA127219C2 (uk) * | 2017-07-27 | 2023-06-14 | Джянгсу Хенгруй Медісін Ко., Лтд. | Фармацевтична композиція, що містить анти-sost антитіло, та її застосування |
| EP3787645A4 (en) * | 2018-05-02 | 2022-06-01 | Ortheus, Inc. | SYSTEMS AND METHODS FOR LOCAL MODULATION OF THE WNT SIGNALING PATHWAY |
| GB201810746D0 (en) * | 2018-06-29 | 2018-08-15 | Mereo Biopharma 3 Ltd | Use of sclerostin antagonist |
| US20220275073A1 (en) * | 2019-08-12 | 2022-09-01 | Amgen Inc. | Anti-Sclerostin Antibody Formulations |
| US20220151950A1 (en) * | 2020-11-16 | 2022-05-19 | University Of Utah Research Foundation | Enthesis healing |
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| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4263428A (en) | 1978-03-24 | 1981-04-21 | The Regents Of The University Of California | Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| DE3374837D1 (en) | 1982-02-17 | 1988-01-21 | Ciba Geigy Ag | Lipids in the aqueous phase |
| HUT35524A (en) | 1983-08-02 | 1985-07-29 | Hoechst Ag | Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance |
| EP0143949B1 (en) | 1983-11-01 | 1988-10-12 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Pharmaceutical composition containing urokinase |
| DK0985039T3 (da) | 1997-06-12 | 2008-06-09 | Novartis Int Pharm Ltd | Kunstige antistof-polypeptider |
| PT2261335T (pt) | 1998-11-27 | 2017-09-08 | Ucb Pharma Sa | Composições e métodos para aumentar a mineralização óssea |
| US20040009535A1 (en) | 1998-11-27 | 2004-01-15 | Celltech R&D, Inc. | Compositions and methods for increasing bone mineralization |
| US8696875B2 (en) | 1999-10-08 | 2014-04-15 | Applied Materials, Inc. | Self-ionized and inductively-coupled plasma for sputtering and resputtering |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| MEP2808A (xx) | 2003-06-16 | 2010-02-10 | Celltech R & D Inc | Antitijela specifična za sklerositin i metode za povećanje mineralizacije kostiju |
| US7592429B2 (en) | 2005-05-03 | 2009-09-22 | Ucb Sa | Sclerostin-binding antibody |
| US8003108B2 (en) | 2005-05-03 | 2011-08-23 | Amgen Inc. | Sclerostin epitopes |
| AU2006259664A1 (en) | 2005-06-14 | 2006-12-28 | Amgen Inc. | Self-buffering protein formulations |
| US20100028335A1 (en) | 2007-02-02 | 2010-02-04 | Novartis Ag | Compositions and Methods to Treat Bone Related Disorders |
| US7744874B2 (en) | 2007-03-20 | 2010-06-29 | Eli Lilly And Company | Anti-sclerostin antibodies |
| TWI489993B (zh) | 2007-10-12 | 2015-07-01 | Novartis Ag | 骨硬化素（ｓｃｌｅｒｏｓｔｉｎ）抗體組合物及使用方法 |
| EA201000718A1 (ru) | 2007-11-02 | 2011-06-30 | Новартис Аг | Молекулы и способы, предназначенные для модуляции родственного рецептору липопротеидов низкой плотности белка 6 (lrp6) |
| WO2010100200A2 (en) | 2009-03-05 | 2010-09-10 | Novartis Ag | Lyophilised antibody formulation |
| WO2010100179A2 (en) | 2009-03-05 | 2010-09-10 | Novartis Ag | Self-forming gel system for sustained drug delivery |
| WO2010115932A1 (en) | 2009-04-08 | 2010-10-14 | Novartis Ag | Combination for the treatment of bone loss |
| WO2010130830A2 (en) | 2009-05-15 | 2010-11-18 | Ablynx N.V. | Amino acid sequences directed against sclerostin and polypeptides comprising the same for the treatment of bone diseases and disorders |
| CN104619342A (zh) * | 2012-07-05 | 2015-05-13 | Ucb医药有限公司 | 骨疾病的治疗 |
| UY35148A (es) | 2012-11-21 | 2014-05-30 | Amgen Inc | Immunoglobulinas heterodiméricas |
| US9300829B2 (en) | 2014-04-04 | 2016-03-29 | Canon Kabushiki Kaisha | Image reading apparatus and correction method thereof |
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2017
- 2017-08-07 JP JP2019506683A patent/JP2019527710A/ja active Pending
- 2017-08-07 US US16/323,470 patent/US20190185556A1/en not_active Abandoned
- 2017-08-07 CN CN201780048630.8A patent/CN110214021A/zh active Pending
- 2017-08-07 WO PCT/US2017/045705 patent/WO2018031454A1/en unknown
- 2017-08-07 KR KR1020197004537A patent/KR20190037261A/ko unknown
- 2017-08-07 AU AU2017310412A patent/AU2017310412A1/en not_active Abandoned
- 2017-08-07 MA MA045921A patent/MA45921A/fr unknown
- 2017-08-07 EP EP17754559.7A patent/EP3496744A1/en not_active Withdrawn
- 2017-08-07 CA CA3032348A patent/CA3032348A1/en not_active Abandoned
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| AU2017310412A8 (en) | 2019-03-07 |
| US20190185556A1 (en) | 2019-06-20 |
| CN110214021A (zh) | 2019-09-06 |
| EP3496744A1 (en) | 2019-06-19 |
| JP2019527710A (ja) | 2019-10-03 |
| AU2017310412A1 (en) | 2019-02-21 |
| WO2018031454A1 (en) | 2018-02-15 |
| MA45921A (fr) | 2019-06-19 |
| CA3032348A1 (en) | 2018-02-15 |
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