KR20130108295A - 항원-제시 세포에 항체에 대한 보조제를 직접 표적화함을 기초로 하는 신규 백신 보조제 - Google Patents
항원-제시 세포에 항체에 대한 보조제를 직접 표적화함을 기초로 하는 신규 백신 보조제 Download PDFInfo
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Abstract
TLR 효능제의 적어도 일부에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편; 및 약제학적으로 허용되는 담체를 포함하는 보조제 조성물을 사용하여 면역 반응을 향상시키기 위한 조성물 및 방법이 본원에 기재되어 있다. 접합체 및 효능제는, 각각 다른 것과 함께 병용하여, 면역자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하기에 유효한 양으로 포함된다.
Description
본 발명은 수지상 세포(DC)-표적화 백신, 보다 구체적으로는 DC-표적화 백신에 직접적으로 보조제(예를 들면, TLR 리간드)를 직접 연결시킴으로써 백신 효능을 향상시키는 것에 관한 것이다.
본 발명의 범위를 제한하지 않고, 본 발명의 배경은 신규 보조제, 수지상 세포(DC) 백신, 및 DC 백신에 대한 면역 반응을 향상시키는 전략과 관련하여 기술되어 있다.
미국 특허출원 공보 제20090004194호(Kedl, 2007)는 항원 특이적인 세포 면역성을 촉진시키는 신규 단백질 및 DNA 접합체에 관한 것이다. 면역 보조제로서의 이들 폴리펩타이드 접합체 및 DNA 접합체의 용도는 암, 감염성 질환, 자가면역 질환, 알레르기 및 염증성 질환을 포함한 다양한 만성 질환을 치료하기 위한 것이다. Kedl 발명은 TLR/CD40/효능제 및 임의의 항원 병용물을 함유하는 융합 단백질 및 DNA 접합체를 기재하고 있다. 다양한 만성 질환의 치료를 위한 면역 보조제 및 백신으로서의 이들 단백질 및 DNA 접합체의 용도 또한 교시되어 있다.
미국 특허출원 공보 제20080220011호(Steven, 2008)는 플라겔린 보조제 및 종양 항원을 포함하는 융합 단백질을 제공한다. 또한, 플라겔린 보조제 및 종양 항원을 포함하는 조성물도 제공된다. 본 발명은 추가로 종양 항원에 대한 면역 반응을 유도하기 위한 약제학적 제형 및 방법, 및 대상체에서 종양을 치료하는 방법을 제공한다.
미국 특허출원 공보 제20080248068호(Ljunggren et al. 2008)는 플라겔린 및 백신접종용 보조제로서의 이의 용도에 관한 것이다. 본 발명은 동일한 국소 부위(localization)에 투여된 임의의 다른 항원에 대해서 면역성을 향상시키기 위한 백신 제형에 사용될 수 있다. 항원은 플라겔린과 동일한 작제물로 또는 동일한 국소 위치에 제공된 임의의 다른 제형으로서 투여될 수 있다. 대안으로서, 플라겔린은 특정 위치에서 발현된 항원에 대해 면역성을 자극하기 위해 사용될 수 있다. 또한, 플라겔린은 염증에 관련된 모델을 생성시킬 목적으로 국소 염증을 유도하는데 사용될 수 있다.
미국 특허 제7,404,963호[Sotomayor 및 Suarez(2008)에게 허여됨]는 면역 반응, 특히 종양 항원에 대한 면역 반응을 유발하는데 유용한 보조제, 백신, 및 관련 방법을 제공한다. Sotomayor 발명에 따르면, 플라겔린은 면역관용성 항원(tolerogenic antigen)과 함께 투여되는 경우 내성을 억제할 수 있다. 이러한 효과는 IL-10의 수준을 낮게 유지하면서 IL-12를 유도하는 플라겔린의 능력에 의해 매개되는 경향이 있다. 또한, 플라겔린은 플라겔린-발현 세포를 사용함으로써 연장된-방출 방식으로 제공될 수 있다. 바람직하게는, 플라겔린-발현 세포는 치사량 조사(lethal irradiation)와 같이, 더 이상 복제할 수 없으나, 플라겔린을 발현시키는 능력은 보유하도록 처리된다.
본 발명은 항원-제시 세포에 항체를 지닌 보조제를 직접 표적화함을 기초로 하는 신규 백신 보조제를 제조하기 위한 조성물 및 방법을 기술한다. 본 발명은 보조제(예를 들면, TLR 리간드)를 DC-표적화 백신에 직접 연결시킴으로써 백신 효능이 향상되는 것을 밝혀내었다. 본원에 나타낸 바와 같이, 본 발명의 조성물 및 방법은 모든 DC-표적화 백신에 광범위하게 적용가능하며 예상되지 않은 신규 특성들을 지닌 보조제의 제조로 확장시킬 수 있다.
하나의 실시형태에서, 본 발명은 TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 결합 단편; 및 적어도 하나의 항원을 포함하는 조성물로서, 상기 항원 및 상기 효능제는 면역자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 유효한, 조성물을 기재하고 있다.
상기에 기술된 DC-특이적 항체 또는 단편은 항-DCIR, MHC 부류 I, MHC 부류 II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, 만노스 수용체, 랑게린, DECTIN-1, B7-1, B7-2, IFN-γ 수용체 및 IL-2 수용체, ICAM-1, Fcγ 수용체, LOX-1, 또는 ASPGR로부터 선택된다. 하나의 양상에서, 상기에 기술된 조성물은 사람 면역결핍 바이러스(HIV) 항원 및 gag, pol 및 env 유전자로 이루어진 그룹으로부터 선택되는 유전자 생성물, Nef 단백질, 역전사효소, HIV 펩타이드의 스트링(string)(Hipo5), PSA (KLQCVDLHV)-4량체, HIVgag-유도된 p24-PLA HIV gag p24(gag) 및 다른 HIV 성분, 간염 바이러스 항원, 헤마글루티닌, 뉴라미니다제, H1N1 Flu 스트레인 유래의 인플루엔자 A 헤마글루티닌 HA-1, HLA-A201-FluMP (58-66) 펩타이드(GILGFVFTL) 4량체, 및 조류 Flu (HA5-1)로 이루어진 그룹으로부터 선택된 인플루엔자 바이러스 항원 및 펩타이드, 씨. 써모셀룸(C. thermocellum) 기원의 독커린 도메인(dockerin domain), 홍역 바이러스 항원, 풍진 바이러스 항원, 로타바이러스 항원, 사이토메갈로바이러스 항원, 호흡기 세포융합 바이러스 항원, 헤르페스 심플렉스 바이러스 항원, 바리셀라 조스터(varicella zoster) 바이러스 항원, 일본 뇌염 바이러스 항원, 광견병 바이러스 항원 또는 이들의 병용물 및 변형물로부터 선택된 항원성 펩타이드를 추가로 포함한다. 다른 양상에서, 당해 조성물은 하나 이상의 세균 항원으로부터 선택된 항원성 펩타이드를 포함하고, 여기서 세균 항원은 바실러스(Bacillus), 에스케리키아(Escherichia), 리스테리아(Listeria), 나이세리아(Neisseria), 노카르디아(Nocardia), 살모넬라(Salmonella), 스태필로코커스(Staphylococcus), 스트렙토코커스(Streptococcus), 또는 이들의 병용물 및 변형물로부터 유도된 항원을 포함한다.
또 다른 양상에서, 당해 조성물은 백혈병 및 림프종, 성상세포종 또는 교모세포종과 같은 신경계 종양, 흑색종, 유방암, 폐암, 두경부암, 위장 종양, 위암, 결장암, 간암, 췌장암, 자궁경부, 자궁, 난소암, 질암, 고환암, 전립선암 또는 음경암과 같은 비뇨생식기 종양, 골 종양, 혈관 종양, 또는 입술, 코인두, 인두 및 구강, 식도, 직장, 담낭, 담관가지, 후두, 폐 및 기관지, 방광, 신장, 뇌 및 신경계의 다른 부분, 갑상선의 암, 호지킨 질환(Hodgkin's disease), 비-호지킨 림프종(non-Hodgkin's lymphoma), 다발성 골수종 및 백혈병 유래의 항원을 포함하는 종양 관련 항원으로부터 선택된 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함한다. 구체적인 양상에서, 종양 관련 항원은 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC(뮤신)(예를 들면, MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 티로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA[엡스타인-바 바이러스(Epstein-Barr Virus) 핵 항원] 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된다.
본 발명의 조성물과 관련된 다른 양상에서, DC-특이적 항체는 사람화된다. 다른 양상에서, TLR 효능제는 살모넬라 엔테리카(Salmonella enterica) 유래의 플라겔린, 비브리오 콜레라에(Vibrio cholerae) 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 병용물 또는 변형물 중 적어도 하나를 포함한다. 또 다른 양상에서, 항원은 항체 및 TLR 효능제와 접합된다. 다른 양상에서, 항원 및 항체는 단일 융합 단백질이다. 다른 양상에서, 항체는 경쇄, 중쇄, 또는 중쇄 및 경쇄 중 적어도 하나를 포함한다.
다른 실시형태에서, 본 발명은 (i) 항원 및 (ii) 보조제(여기서 보조제는 면역 자극이 요구되는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 효과적인 양의 TLR 효능제의 적어도 일부에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함한다)를 포함하는 백신 조성물을 제공한다. 상기한 백신에 사용된 DC-특이적 항체 또는 단편은 항-DCIR, MHC 부류 I, MHC 부류 II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, 만노스 수용체, 랑게린, DECTIN-1, B7-1, B7-2, IFN-γ 수용체 및 IL-2 수용체, ICAM-1, Fcγ 수용체, LOX-1, 또는 ASPGR로부터 선택된다. 백신 조성물은 선택된 항원성 펩타이드를 추가로 포함한다. 본 발명의 백신 조성물에서 사용될 수 있는 항원성 펩타이드의 비-제한적 예는 이미 기술되어 있다. 백신 조성물은 하나 이상의 세균 항원으로부터 선택된 항원성 펩타이드를 추가로 포함한다. 비-제한적 세균 항원의 목록은 상기에 이미 기술되어 있다. 다른 양상에서, 백신은 앞서 기술된 항원을 포함하는 종양 관련 항원으로부터 선택된 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함한다.
또 다른 양상에서, 당해 조성물은 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC(뮤신)(예를 들면, MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 타이로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA[엡스타인-바 바이러스(Epstein-Barr Virus) 핵 항원] 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 종양 관련 항원으로부터 선택된 항원성 펩타이드를 추가로 포함한다. 하나의 양상에서, DC-특이적 항체는 사람화된다. 다른 양상에서, TLR 효능제는 살모넬라 엔테리카(Salmonella enterica) 유래의 플라겔린, 비브리오 콜레라에(Vibrio cholerae) 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 임의의 병용물 또는 변형물 중 적어도 하나를 포함한다. 또 다른 양상에서, 항원은 항체 및 TLR 효능제에 접합된다. 다른 양상에서, 항원 및 항체는 단일 융합 단백질이다. 또 다른 양상에서, 항체는 경쇄, 중쇄, 또는 중쇄 및 경쇄 중 적어도 하나를 포함한다.
또 다른 실시형태에서, 본 발명은 항원 제시 세포를, (i) 항원; 및 (ii) 보조제(여기서, 보조제는 TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 결합 단편을 포함하고, 여기서, 항원 및 보조제는 면역자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 유효한 양으로 제공된다)를 포함하는 조성물과 접촉시키는 단계를 포함하는 항원 제시 세포에 의한 항체 제시의 효능을 증가시키는 방법을 기재한다. 항원 제시 세포에 의한 항원 제시의 효능을 증가시키는 생체외(Ex vivo) 방법은 미국 특허출원 공보 제20100135994호(Banchereau et al. 2010) 및 미국 특허출원 일련 번호 제13/100,684 호(Banchereau et al. 2011)에 이미 기술되어 있으며, 이의 관련 부분은 본원에 참조로 인용된다.
하나의 양상에서, DC-특이적 항체 또는 단편은 항-DCIR, MHC 부류 I, MHC 부류 II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, 만노스 수용체, 랑게린, DECTIN-1, B7-1, B7-2, IFN-γ 수용체 및 IL-2 수용체, ICAM-1, Fcγ 수용체, LOX-1, 또는 ASPGR로부터 선택된다. 관련 양상에서, 항-DC-특이적 항체는 서열번호 7과 서열번호 9, 서열번호 11과 서열번호 13, 서열번호 15와 서열번호 17, 서열번호 19와 서열번호 21, 서열번호 23과 서열번호 25, 서열번호 27과 서열번호 29, 서열번호 31과 서열번호 33, 서열번호 35와 37, 서열번호 39와 서열번호 41, 서열번호 43과 서열번호 45, 서열번호 47과 서열번호 49, 서열번호 51과 서열번호 53, 서열번호 55와 서열번호 57, 서열번호 59와 서열번호 61, 서열번호 63과 서열번호 65, 서열번호 67과 서열번호 69, 서열번호 71과 서열번호 73, 서열번호 75와 서열번호 77, 서열번호 79와 서열번호 81, 서열번호 83과 서열번호 85, 서열번호 87과 서열번호 89, 서열번호 91과 서열번호 93, 서열번호 95와 서열번호 97, 서열번호 99와 서열번호 101, 서열번호 1 내지 서열번호 3과 서열번호 105, 서열번호 107과 서열번호 109, 서열번호 111과 서열번호 113, 서열번호 115와 서열번호 117, 서열번호 119와 서열번호 121, 서열번호 123과 서열번호 125, 서열번호 127과 서열번호 129, 서열번호 131과 서열번호 132, 서열번호 133과 서열번호 134의 쌍으로부터 선택된다.
하나의 양상에서, 당해 조성물은 항원성 펩타이드를 추가로 포함하고, 항원성 펩타이드의 비-제한적 예는 앞서 기술되어 있다. 다른 양상에서, 당해 조성물은 앞서 기술된 바와 같은 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함한다. 항원성 펩타이드는 종양 관련 항원으로부터 선택된다. 종양 관련 항원의 비-제한적 예는 본원의 상기에 기술되어 있다.
본 발명의 관련 양상에서, DC-특이적 항체는 사람화되고, 당해 조성물은 사람 또는 동물 대상체에게 경구 경로, 비강 경로, 국소 또는 주사(주사는 피내, 점막내, 피하, 정맥내, 복강내, 근육내 및 정맥내 주사로부터 선택된다)로 투여된다. 하나의 양상에서, TLR 효능제는 살모넬라 엔테리카(Salmonella enterica) 유래의 플라겔린, 비브리오 콜레라에(Vibrio cholerae) 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이의 임의의 병용물 또는 변형물 중 적어도 하나를 포함한다. 다른 양상에서, 항원은 항체 및 TLR 효능제에 접합된다. 또 다른 양상에서, 항원 및 항체는 단일 융합 단백질이다. 다른 양상에서, 항체는 경쇄, 중쇄, 또는 중쇄 및 경쇄 중 적어도 하나를 포함한다.
본 발명은 (i) 하나 이상의 암에 대한 치료, 예방 또는 이들의 조합을 필요로 하는 사람 대상체를 확인하는 단계, 및 (ii) a) 항원 및 b) 보조제(여기서, 보조제는 TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함한다); 및 약제학적으로 허용되는 담체를 포함하는 백신 조성물(여기서, 항원 및 보조제는 하나 이상의 암에 대해 치료, 예방 또는 이들의 조합을 위한 면역 반응을 생성하는데 유효한 양으로 제공된다)를 투여하는 단계를 포함하는, 사람 대상체에서 하나 이상의 암에 대한 치료, 예방 또는 이들의 조합을 위한 방법을 추가로 제공한다.
본 발명의 다른 실시형태는 (i) 하나 이상의 바이러스, 세균, 진균, 기생충, 원생생물, 및 기생충 질환, 및 알레르기 장애에 대한 치료, 예방 또는 이들의 조합을 위한 면역자극을 필요로 하는 사람 대상체를 확인하는 단계; (ii) 사람 대상체로부터 하나 이상의 DC를 분리하는 단계; (iii) 분리된 DC를, a) 항원 및 b) 보조제(여기서, 보조제는 TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함한다); 및 약제학적으로 허용되는 담체를 포함하는 활성화된 DC를 형성하는데 효과적인 양의 조성물을 면역자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 유효한 양으로 사용하여 활성화시키는 단계; 및 (iv) 활성화된 DC를 사람 대상체에게 재도입시키는 단계를 포함하는, 하나 이상의 바이러스, 세균, 진균, 기생충, 원생생물, 및 기생충 질환, 및 알레르기 장애에 대한 예방, 치료요법 또는 이들의 조합을 위해 사람 대상체에 대한 하나 이상의 수지상 세포(DC)를 활성화시켜 면역자극을 제공하는 방법에 관한 것이다.
또 다른 실시형태에서, 본 발명은 TLR 효능제의 적어도 일부에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함하는 보조제 조성물을 기재하며, 여기서, 항-DC-특이적 항체는 서열번호 7과 서열번호 9, 서열번호 11과 서열번호 13, 서열번호 15와 서열번호 17, 서열번호 19와 서열번호 21, 서열번호 23과 서열번호 25, 서열번호 27과 서열번호 29, 서열번호 31과 서열번호 33, 서열번호 35와 37, 서열번호 39와 서열번호 41, 서열번호 43과 서열번호 45, 서열번호 47과 서열번호 49, 서열번호 51과 서열번호 53, 서열번호 55와 서열번호 57, 서열번호 59와 서열번호 61, 서열번호 63과 서열번호 65, 서열번호 67과 서열번호 69, 서열번호 71과 서열번호 73, 서열번호 75와 서열번호 77, 서열번호 79와 서열번호 81, 서열번호 83과 서열번호 85, 서열번호 87과 서열번호 89, 서열번호 91과 서열번호 93, 서열번호 95와 서열번호 97, 서열번호 99와 서열번호 101, 서열번호 1 내지 서열번호 3과 서열번호 105, 서열번호 107과 서열번호 109, 서열번호 111과 서열번호 113, 서열번호 115와 서열번호 117, 서열번호 119와 서열번호 121, 서열번호 123과 서열번호 125, 서열번호 127과 서열번호 129, 서열번호 131과 서열번호 132, 서열번호 133과 서열번호 134의 쌍으로부터 선택된다.
상기한 보조제 조성물의 하나의 양상에서, 당해 조성물은 사람 면역결핍 바이러스(HIV) 항원 및 gag, pol 및 env 유전자로 이루어진 그룹 중에서 선택된 유전자 생성물, Nef 단백질, 역전사효소, HIV 펩타이드의 스트링(Hipo5), PSA (KLQCVDLHV)-4량체, HIVgag-유도된 p24-PLA HIV gag p24 (gag), 및 다른 HIV 성분, 간염 바이러스 항원, 헤마글루티닌, 뉴라미니다제, H1N1 Flu 스트레인 유래의 인플루엔자 A 헤마글루티닌 HA-1, HLA-A201-FluMP (58-66) 펩타이드(GILGFVFTL) 4량체, 및 조류 Flu (HA5-1)로 이루어진 그룹 중에서 선택된 인플루엔자 바이러스 항원 및 펩타이드, 씨. 써모셀룸 기원의 독커린 도메인, 홍역 바이러스 항원, 풍진 바이러스 항원, 로타바이러스 항원, 사이토메갈로바이러스 항원, 호흡기 세포융합 바이러스 항원, 헤르페스 심플렉스 바이러스 항원, 바리셀라 조스터 바이러스 항원, 일본 뇌염 바이러스 항원, 광견병 바이러스 항원 또는 이들의 병용물 및 변형물로부터 선택된 항원성 펩타이드를 추가로 포함한다.
다른 양상에서, 당해 조성물은 백혈병 및 림프종, 성상세포종 또는 교모세포종과 같은 신경계 종양, 흑색종, 유방암, 폐암, 두경부암, 위장 종양, 위암, 결장암, 간암, 췌장암, 자궁경부, 자궁, 난소암, 질암, 고환암, 전립선암 또는 음경암과 같은 비뇨생식기 종양, 골 종양, 혈관 종양, 또는 입술, 코인두, 인두 및 구강, 식도, 직장, 담낭, 담관가지, 후두, 폐 및 기관지, 방광, 신장, 뇌 및 신경계의 다른 부분, 갑상선의 암, 호지킨 질환, 비-호지킨 림프종, 다발성 골수색종 및 백혈병 유래의 항원을 포함하는 종양 관련 항원으로부터 선택된 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함한다. 또 다른 양상에서, 당해 조성물은 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC(뮤신)(예를 들면, MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 티로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA(엡스타인-바 바이러스 핵 항원) 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 항원성 펩타이드를 추가로 포함한다. DC-특이적 항체는 사람화된다. 다른 관련된 양상에서, TLR 효능제는 살모넬라 엔테리카 유래의 플라겔린, 비브리오 콜레라에 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 병용물 또는 변형물 중 적어도 하나를 포함하고, 항원 및 항체는 단일 융합 단백질이다. 다른 양상에서, 항체는 경쇄, 중쇄, 또는 중쇄 및 경쇄 중 적어도 하나를 포함한다.
본 발명의 특징 및 이점의 보다 완전한 이해를 위하여, 하기에 첨부된 도면과 함께 본 발명의 상세한 설명에 대해 참조하며, 여기서:
도 1a 내지 1d는 본 발명의 플라겔린 및 몇몇의 항체-플라겔린 작제물을 나타낸다: 도 1a는, 보존된 N-말단 및 C-말단 영역 유래의 잔기가 함께 TLR5를 활성화시키기에 충분하며 - 중심 잔기는 이의 기능에 대해 확장될 수 있음을 나타내고, 도 1b는, 특정 DC 수용체를 발현하여 플라겔린의 면역자극 특성과 항-DC 수용체 항체의 활성화 특성을 결합하는 세포에 대해 특이적으로 플라겔린 단편의 활성화 특성을 지시하는 DC-표적화 항체에 직접 융합된 플라겔린의 활성 입체구조의 예를 나타내며, 도 1c는 2개의 보존된 플라겔린 도메인의 단편이 링커 또는 항원 서열에 의해 분리된 1b의 변이체를 나타내고 - 도 3a에서 제공된 예에서, 특정 링커 서열을 갖는 당해 입체구조는 활성이 아니며, 도 1d는, 항원 또는 단백질-단백질 상호작용 도메인(이 경우 독커린)이 플라겔린과 항체 도메인 사이에 직접 연결된 도 1a의 변이체를 나타낸다. 도 3 및 도 4는 이러한 변이체에 의한 면역 자극의 예를 나타낸다.
도 2는 본 발명의 항체-플라겔린 작제물의 활성을 시험하는데 사용된 연구의 설계를 나타낸다;
도 3a 내지 도 3c는, 다양한 유형의 세포가 본 발명의 작제물을 이용하여 활성화된 경우 IL-6의 분비를 나타낸다;
도 4a 내지 도 4d는 IL-6 및 IL-1 베타의 분비에 의해 측정된 것으로서 다양한 작제물의 용량 적정을 나타낸다. 당해 데이터는, 플라겔린 단편에 의한 면역 자극이 작제물의 DC-표적화 항체 부분에 의해 매개된 DC 수용체 상호작용(이 경우 LOX-1)에 의존하게 되고 - 대조군 hIgG4-플라겔린 작제물이 훨씬 높은 농도에서만 활성임을 입증한다. 다른 대조군은, 이것이 향상된 면역자극 효능을 설명하는 DC-표적화 항체에 대한 플라겔린 단편의 직접적인 융합임을 나타낸다;
도 5는 연결된 플라겔린의 존재 또는 부재하에 항-LOX-1 항체를 사용하여 열거된 유전자에 대한 유전자 발현의 열 지도를 나타낸다. 상향-조절된 면역 자극 분자의 정확한 병용은, 표적 세포의 상이한 병용이 관여할 것이며 플라겔린 및 DC-표적화 항체를 통한 시그널링의 상이한 병용이 존재할 것이므로 플라겔린 단편에 연결된 상이한 항-DC 수용체 항체 작제물로 변할 것이다.
도 1a 내지 1d는 본 발명의 플라겔린 및 몇몇의 항체-플라겔린 작제물을 나타낸다: 도 1a는, 보존된 N-말단 및 C-말단 영역 유래의 잔기가 함께 TLR5를 활성화시키기에 충분하며 - 중심 잔기는 이의 기능에 대해 확장될 수 있음을 나타내고, 도 1b는, 특정 DC 수용체를 발현하여 플라겔린의 면역자극 특성과 항-DC 수용체 항체의 활성화 특성을 결합하는 세포에 대해 특이적으로 플라겔린 단편의 활성화 특성을 지시하는 DC-표적화 항체에 직접 융합된 플라겔린의 활성 입체구조의 예를 나타내며, 도 1c는 2개의 보존된 플라겔린 도메인의 단편이 링커 또는 항원 서열에 의해 분리된 1b의 변이체를 나타내고 - 도 3a에서 제공된 예에서, 특정 링커 서열을 갖는 당해 입체구조는 활성이 아니며, 도 1d는, 항원 또는 단백질-단백질 상호작용 도메인(이 경우 독커린)이 플라겔린과 항체 도메인 사이에 직접 연결된 도 1a의 변이체를 나타낸다. 도 3 및 도 4는 이러한 변이체에 의한 면역 자극의 예를 나타낸다.
도 2는 본 발명의 항체-플라겔린 작제물의 활성을 시험하는데 사용된 연구의 설계를 나타낸다;
도 3a 내지 도 3c는, 다양한 유형의 세포가 본 발명의 작제물을 이용하여 활성화된 경우 IL-6의 분비를 나타낸다;
도 4a 내지 도 4d는 IL-6 및 IL-1 베타의 분비에 의해 측정된 것으로서 다양한 작제물의 용량 적정을 나타낸다. 당해 데이터는, 플라겔린 단편에 의한 면역 자극이 작제물의 DC-표적화 항체 부분에 의해 매개된 DC 수용체 상호작용(이 경우 LOX-1)에 의존하게 되고 - 대조군 hIgG4-플라겔린 작제물이 훨씬 높은 농도에서만 활성임을 입증한다. 다른 대조군은, 이것이 향상된 면역자극 효능을 설명하는 DC-표적화 항체에 대한 플라겔린 단편의 직접적인 융합임을 나타낸다;
도 5는 연결된 플라겔린의 존재 또는 부재하에 항-LOX-1 항체를 사용하여 열거된 유전자에 대한 유전자 발현의 열 지도를 나타낸다. 상향-조절된 면역 자극 분자의 정확한 병용은, 표적 세포의 상이한 병용이 관여할 것이며 플라겔린 및 DC-표적화 항체를 통한 시그널링의 상이한 병용이 존재할 것이므로 플라겔린 단편에 연결된 상이한 항-DC 수용체 항체 작제물로 변할 것이다.
본 발명의 각종 실시형태의 제조 및 사용이 하기에 상세히 논의되어 있지만, 본 발명이 광범위한 구체적인 내용에서 구현될 수 있는 많은 적용가능한 본 발명의 개념을 제공한다는 것은 인식하여야 한다. 본원에 논의된 특정 실시형태는 본 발명을 제조하고 사용하기 위한 구체적인 방법의 단지 예이며 본 발명의 영역을 제한하지 않는다.
본 발명의 이해를 용이하게 하기 위해, 다수의 용어들이 하기 정의되어 있다. 본원에 정의된 용어는 본 발명과 관련된 분야에서 통상의 지식을 가진 자에 의해 일반적으로 이해되는 의미를 가진다. 하나("a", "an") 및 그("the")와 같은 용어들은 단수 실체만이 아니라, 이의 구체적인 예가 설명을 위해 사용될 수 있는 일반적인 부류를 포함한다. 본원의 전문용어는 본 발명의 구체적인 실시형태를 기술하는데 사용되지만, 이들의 사용이 특허청구범위에서 요약한 것을 제외하고는, 본 발명을 제한하지 않는다.
본원에 사용된 것으로서, 용어 "항원 제시 세포"(APC)는 T 세포를 활성화시킬 수 있는 세포이며, 특정의 대식세포, B 세포 및 수지상 세포를 포함하나, 이들에 한정되지 않는다. "수지상 세포"(DC)는 림프구 또는 비-림프구 조직에서 발견된 형태학적으로 유사한 세포 유형의 다양한 집단의 임의의 구성원을 말한다. 이들 세포는 이들의 명백한 형태, 고수준의 표면 MHC-부류 II 발현[참조: Steinman, et al., Ann. Rev. Immunol. 9:271 (1991); 이러한 세포의 이의 설명을 위해 참조로 본원에 인용됨]을 특징으로 한다. 이들 세포는 다수의 조직 공급원, 및 편리하게는 본원에 기술된 바와 같이, 말초 혈액으로부터 분리될 수 있다. 수지상 세포 결합 단백질은, 이에 대한 수용체가 수지상 세포 상에서 발현되는 임의의 단백질을 말한다. 예로는 GM-CSF, IL-1, TNF, IL-4, CD40L, CTLA4, CD28, 및 FLT-3 리간드가 포함된다.
본 발명의 목적을 위해서, 용어 "백신 조성물"은 면역계 반응을 유도하기 위해 사람에게 또는 동물에게 투여될 수 있는 조성물을 의미하도록 의도되며; 이러한 면역계 반응은 단순하게 특정 세포, 특히 항원-제시 세포, T 림프구 및 B 림프구의 활성화 또는 항체의 생산을 초래할 수 있다. 백신 조성물은 예방 목적을 위한 또는 치료 목적을 위한 또는 이들 둘 다를 위한 조성물일 수 있다. 본원에 사용된 것으로서, 용어 "항원"은, 백신이 전체 미생물 또는 이의 일부, 및 각종 유형: (예를 들면, 펩타이드, 단백질, 당단백질, 다당류, 당지질, 리포펩타이드 등)을 포함하는 것에 관계없이, 백신 중에 사용될 수 있는 임의의 항원을 말한다. 이들은 바이러스 항원, 세균 항원 등일 수 있으며; 용어 "항원"은 또한 폴리뉴클레오타이드를 포함하고, 이의 서열은 DNA 면역화로 언급되는 면역화 기술의 경우에, 폴리펩타이드가 투여된 개인에 의한 이의 발현이 바람직한 항원을 암호화하도록 선택된다. 이들은 또한 특히 수개의 질환에 대해 보호할 수 있는 항원을 포함하며, 이후에 일반적으로 백신 병용물로서 언급되는 다가 백신 조성물의 경우에, 또는 예를 들면, 백일해 또는 플루에 대한 특정 백신의 경우에서와 같이, 단일 질환에 대해 보호하기 위하여 수개의 상이한 항원을 포함하는 조성물의 경우에, 항원들의 세트일 수 있다. 용어 "항체"는 천연이거나 부분적으로 또는 전체적으로 인공 생산된, 예를 들면, 재조합체인 것에 관계없이 면역글로불린을 말한다. 항체는 모노클로날 또는 폴리클로날일 수 있다. 항체는, 일부 경우에, IgG, IgM, IgA, IgD, 및 IgE를 포함하는, 하나의 또는 병용 면역글로불린 부류의 구성원일 수 있다.
용어 "보조제" 또는 "면역보조제"는 상호교환적으로 사용될 수 있으며, 항원, 예를 들면, 백신의 일부인 항원에 대해 숙주의 면역 반응을 향상시키거나, 증강시키거나 효능화시키는 물질을 말한다. 일부 일반적으로 사용된 백신 보조제의 비-제한적인 예로는 불용성 알루미늄 화합물, 인산칼슘, 리포솜, VirosomesTM, ISCOMS®, 미세입자(예를 들면, PLG), 유액[예를 들면, MF59, 몬타나이드(Montanides)], 바이러스-유사 입자 및 바이러스 벡터가 포함된다. 플라겔린, 살모넬라 엔테리쿰 유래의 TLR5 효능제가 본 발명에서 보조제로 사용된다. 다른 세균 공급원(예를 들면, 비브리오 콜레라에) 유래의 플라겔린이 또한 사용될 수 있으며, 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 임의의 병용물 또는 변형물 또한 사용될 수 있음이 이해될 것이다.
본원에 사용된 것으로서 용어 "접합체"는 2개 부분을 함께 결합시켜 형성된 임의의 물질을 말한다. 본 발명에 따른 대표적인 접합체는 항원과 항체 및 TLR 효능제를 함께 결합시켜 형성된 것들을 포함한다. 용어 "접합체"는 접합체를 형성하는 공정을 말하며 일반적으로 물리적 커플링, 예를 들면, 공유결합, 동시-배위 공유결합, 또는 제2 결합력, 예를 들면, 반 데르 발스 결합력(Van der Waals bonding force)을 말한다. 항원을 항체 및 TLR 효능제에 연결시키는 공정은 또한 독커린-코헤신 연합(dockerin-cohesin association)과 같은 비-공유결합성 연합[(Banchereau) 등의 미국 특허 공보 제20100135994호, 본원에 참조로 인용된 부분과 관련됨]을 통해 또는 펩타이드 또는 화학적 결합을 형성함으로써 직접적인 화학적 연결에 의해 수행될 수 있다.
본원에 사용된 것으로서, 용어 "플라겔린"은 어떠한 세균 종을 포함하나, 이에 한정되지 않는 임의의 공급원으로부터의 플라겔린 단백질을 말한다. 플라겔린은 살모넬라의 종(본원에 예시된 바와 같은 살모넬라 엔테리카) 유래 또는 세균의 다른 종(예를 들면, 비브리오 콜레라에) 유래일 수 있다. 또한, 상기 플라겔린의 단편, 변이체, 유사체, 동족체, 또는 유도체, 및 이들의 병용물이 구체적으로 고려된다. 본원에 기술된 각종 단편, 변이체, 유사체, 동족체 또는 유도체는 특이적인 세균 종, 예를 들면, 살모넬라 유래의 야생형 플라겔린과 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 또는 99% 동일할 수 있다.
용어 "유전자"는 기능성 단백질, 폴리펩타이드 또는 펩타이드-암호화 단위를 나타내는 것으로 사용된다. 당해 분야의 숙련가에게 이해되는 바와 같이, 이러한 기능적 용어는 게놈 서열, cDNA 서열, 또는 이의 단편 또는 조합, 및 또한 사람의 손에 의해 변경될 수 있는 것을 포함하는 유전자 생성물을 포함한다. 정제된 유전자, 핵산, 단백질 등은, 이것이 일반적으로 관련된 적어도 하나의 오염 핵산 또는 단백질로부터 확인되고 분리되는 경우 이의 실체를 나타내기 위해 사용된다.
본원에 사용된 것으로서, 용어 "핵산" 또는 "핵산 분자"는 데옥시리보핵산(DNA) 또는 리보핵산(RNA)과 같은 폴리뉴클레오타이드, 올리고뉴클레오타이드, 폴리머라제 연쇄 반응(PCR)에 의해 생성된 단편, 및 라이게이션, 절제, 엔도뉴클레아제 작용, 및 엑소뉴클레아제 작용 중 어느 하나에 의해 생성된 단편을 말한다. 핵산 분자는 천연적으로 발생하는 뉴클레오타이드(예를 들면, DNA 및 RNA), 또는 천연적으로 발생하는 뉴클레오타이드의 유사체(예를 들면, 천연적으로 발생하는 뉴클레오타이드의 α-거울상이성체 형태)인 단량체, 또는 이들 둘 다의 병용물로 구성될 수 있다. 변형된 뉴클레오타이드는 당 모이어티 및/또는 피리미딘 또는 퓨린 염기 모이어티에서 변경을 가질 수 있다. 당 변형은 예를 들면, 하나 이상의 하이드록실 그룹을 할로겐, 알킬 그룹, 아민, 및 아지드 그룹으로 대체시킴을 포함하거나, 당은 에테르 또는 에스테르로 기능화될 수 있다. 또한, 전체 당 모이어티는 아자-당(aza-sugar) 및 카보사이클릭 당 유사체와 같은 입체적으로 및 전기적으로 유사한 구조로 대체될 수 있다. 염기 모이어티내에서 변형의 예는 알킬화된 퓨린 및 피리미딘, 아실화된 퓨린 또는 피리미딘, 또는 다른 널리-공지된 헤테로사이클릭 치환체를 포함한다. 핵산 단량체는 포스포디에스테르 결합 또는 이러한 결합의 유사체에 의해 연결될 수 있다. 포스포디에스테르 결합의 유사체는 포스포로티오에이트, 포스포로디티오에이트, 포스포로셀레노에이트, 포스포로디셀레노에이트, 포스포로아닐로티오에이트, 포스포르아닐리데이트, 포스포르아미데이트 등을 포함한다. 용어 "핵산 분자"는 또한 폴리아미드 골격에 부착된 천연적으로-발생하거나 변형된 핵산 염기를 포함하는 소위 "펩타이드 핵산"을 포함한다. 핵산은 단일 가닥 또는 이중 가닥일 수 있다.
본 출원에 사용된 것으로서, 용어 "아미노산"은, 이의 단백질이 포함된 천연적으로 발생하는 아미노 카복실산 중 하나를 의미한다. 본원에 기술된 것으로서 용어 "폴리펩타이드"는, 천연적으로 또는 합성적으로 생산되는 것에 관계없이, 펩타이드 결합에 의해 결합된 아미노산 잔기의 중합체를 말한다. 약 10개 미만의 아미노산 잔기의 폴리펩타이드는 일반적으로 "펩타이드"로서 언급된다. "단백질"은 하나 이상의 폴리펩타이드 쇄를 포함하는 거대분자이다. 단백질은 또한 탄수화물 그룹과 같은 비-펩타이드성 성분을 포함할 수 있다. 탄수화물 및 다른 비-펩타이드성 치환체는, 단백질이 생산되는 세포에 의해 단백질에 가해질 수 있으며, 세포의 유형에 따라 변할 것이다. 단백질은 이들의 아미노산 골격 구조의 측면에서 본원에 정의되며; 탄수화물 그룹과 같은 치환체들은 일반적으로 정의되지 않지만, 그럼에도 불구하고 존재할 수 있다.
본원에 사용된 것으로서, 용어 "생체내"는 체내에 존재함을 말한다. 본 출원에 사용된 것으로서 용어 "시험관내"는, 작업이 살아있지 않은 시스템에서 수행됨을 나타내는 것으로 이해되어야 한다.
본원에 사용된 것으로서, 용어 "치료" 또는 "치료하는"은 (1) 병리 또는 징후를 경험하거나 나타내는 이환 동물에서 질환을 억제하거나(즉, 병리 및/또는 징후의 추가의 발달을 정지시키거나), 또는 (2) 병리 또는 징후를 경험하거나 나타내는 동물에서 질환을 완화시키는(즉, 병리 및/또는 징후를 역전시키는) 것을 포함한다.
본 발명은 항원-제시 세포에 대해 항체를 지닌 보조제를 직접 표적화함을 기초로 하는 신규 백신 보조제를 기술한다. 본 발명은 DC-표적화 백신에 대해 보조제(예를 들면, TLR 리간드)를 직접 연결시킴으로써 백신 효능을 향상시킴을 발견하였다. 본원에 나타낸 바와 같이, 본 발명의 조성물 및 방법은 모든 DC-표적화 백신에 광범위하게 적용가능하며 예상치못한 신규 특성을 지닌 보조제를 제조하는 것으로 확장시킬 수 있다. 보조제(예를 들면, TLR)에 직접 연결된 항원, 예를 들면, CpG에 연결된 Hep B 백신(Dynavax) 또는 플라겔린에 연결된 Flu 항원(Vaxigen)의 개발이 당해 분야에 널리 공지되어 있지만, 본 발명은 DC-표적화 백신(예를 들면, 항원에 융합된 항-DC 수용체 항체)에 직접 연결된 보조제이다. 본 발명의 몇몇의 양상은 선행 기술에 비해, 용량-절약(항원을 실제로 수용하는 항원-제시 세포에 보조제를 직접 보냄으로써)을 포함하는 이점을 가지며, 예상치않게도, 이러한 발견은 표적화된 DC 수용체의 유형에 엄격하게 따라 보조제의 효능제 활성을 제조하는 방법을 제공한다.
본원에 기술된 조성물 및 방법은 하나 이상의 바이러스, 세균, 진균, 기생충, 원생생물, 및 기생충 질환, 알레르기 장애, 및 암에 대한 예방, 치료요법 또는 이들의 조합에 사용될 수 있다. 증상의 예방, 치료요법, 완화, 또는 이들의 조합이 본 발명의 조성물을 사용하여 달성될 수 있는 질환의 비-제한적 예는 HIV 감염, 간염, 인플루엔자, 조류 flu, 헤르페스, 비뇨생식기, 전립선, 및 신경학적 종양, 관절염, 천식, 습진, 탄저병, 담낭염, 균혈증, 담관염, 비뇨관 감염(UTI), 리스테리아증, 수막염균 감염, 살모넬라증, 괴사성 근막염 및 스트렙토코커스 독성 쇼크 증후군, 폐렴, 피부 감염 또는 이들의 임의의 조합 또는 변형으로부터 선택된 세균 감염을 포함한다.
살모넬라 엔테리카 유래의 플라겔린은 본 발명에서 예시되어 왔다. 그러나, 숙련가들은, 많은 세균 종(예를 들면, 비브리오 콜레라에) 유래의 플라겔린이 본원에 사용된 플라겔린대신 치환될 수 있음을 이해할 것이다. 플라겔린 이외에, 다른 TLR5 효능제도 또한 사용할 수 있다. 본 발명을 다른 TLR로 확장시키기 위하여, 다른 공지된 TLR 리간드 중 일부 또는 전부가 비-단백질이므로 화학 결합을 사용하는 것이 필수적일 수 있다. TLR7 및 TLR9와 같은 일부 효능제는 이들을 단백질에 연결시키는 잘 기술된 화학적 실체 및 방법이지만, 이들의 고유의 TLR 효능제 특성을 유지하는 것은 이미 기술되어 왔다. 일부 다른 효능제의 경우 활성 화합물이 공지되어 있지만, 이들의 단백질-연결 화학은 잘 기술되어 있지 않다.
상기에 기술된 조성물 및 방법은 항-수지상 세포(DC)-특이적 항체 또는 이의 결합 단편을 사용한다. 그러나, 숙련가는, 다른 비-TLR계 리간드, 효능제, 또는 다른 모이어티(예를 들면, 인팜마섬(infammasome)의 경우)가 항체에 접합되어 바람직한 생체내 또는 생체외 효과를 달성할 수 있음을 인식할 것이다.
숙련가들은, 항원-TLR 효능제-항체를 포함하는 조성물이 개별 종 또는 모이어티에 대해 상이한 가능한 배열을 가질 수 있음을 이해할 것이다. 예를 들면, TLR 효능제(또는 본원에 사용된 것으로서 플라겔린)는 항-수지상 세포(DC)-특이적 항체의 중쇄(항체 L쇄-항원 + H 쇄-TLR 효능제) 또는 경쇄(항체 H 쇄-항원 + L 쇄-TLR 효능제 또는 항체 H 쇄-항원-TLR 효능제 + L 쇄)에 연결될 수 있다. 접합체는 또한 TLR 효능제/플라겔린을 독커린-코헤신 부착을 통해 연결시켜 제조할 수 있다(예를 들면, 항체 H 쇄-항원-독커린:코헤신-FLGN). 본원에 사용된 플라겔린이 유사한 화학적 또는 물리적 방법에 의해 연결될 수 있는 임의의 TLR 효능제로 치환되거나 대체될 수 있음이 이해될 것이다. 본 발명은 또한, 항원 및 항체가 단일 융합 단백질인 병용물을 포함할 수 있다.
DC-표적화 연결된 보조제 부착 A(서열번호 1): 벡터 C959는 rAB-pIRES2[m항-DCIR_9E8_H-LV-hIgG4H-C-Flex-v1-Flgn-1-Flgn-2]를 암호화한다.
굵은 글씨체는 2-상 플라겔린[살모넬라 엔테리카] gb|AAL30512.1|AF425736_1 잔기 14-161의 N-말단 부분이다.
밑줄은 2-상 플라겔린[살모넬라 엔테리카] gb|AAL30512.1|AF425736_1 잔기 405-484의 C-말단 부분이다.
이탤릭체는 스캐폴딘(scaffoldin) B 전구체[박테로이데스 셀룰로솔벤스(Bacteroides cellulosolvens)]를 고정시키는(anchoring) gb|AAT79550.1| 셀룰로솜 유래의 가요성 링커 서열이다.
제1 AS 서열까지의 아미노 말단은 -hIgG4H 고정 영역에 융합된 마우스 항-DCIR_9E8 가변 영역의 중쇄이다. 굵은-이탤릭체의 AS 서열은 발현 벡터의 작제물 유래의 결합 서열이다.
적절한 L 쇄 발현 벡터를 사용하여 포유동물 세포(예를 들면, CHO-S 세포)내로 동시-형질감염시킨 경우, 당해 벡터는 플라겔린-계 보조제에 연결된 DC-표적화제의 대표적인 실시형태의 효율적인 분비를 지시한다.
C1099는 마우스 항-DCIR_9E8_H-LV-hIgG4H-C-독커린-v2-Flgn-1-Flgn-2](서열번호 2)를 암호화한다.
이탤릭체는 |YP_001036450.1| 알파-L-아라비노푸라노시다제 B [클로스트리디움 써모셀룸(Clostridium thermocellum) ATCC 27405| 잔기 166-274이며 - 이는 다른 도메인들 사이에 융합되는 경우 결합(예를 들면, 코헤신-항원 융합)에 완전히 기능하는 독커린 도메인이다.
굵은 활자체는 2-상 플라겔린[살모넬라 엔테리카] gb|AAL30512.1|AF425736_1 잔기 14-161의 N-말단 부분이다.
밑줄은 2-상 플라겔린[살모넬라 엔테리카] gb|AAL30512.1|AF425736_1 잔기 405-484의 C-말단 부분이다.
굵은-이탤릭체의 AS 서열은 발현 벡터의 작제물로부터의 결합 서열이다.
적절한 L 쇄 발현 벡터를 포유동물 세포(예를 들면, CHO-S 세포)내로 동시-형질감염시키는 경우, 당해 벡터는 플라겔린-계 보조제에 연결되고 독커린 도메인을 통해 코헤신-항원에 연결된 DC-표적화제의 대표적인 실시형태의 효율적인 분비를 지시한다. 관련 실시형태에서 - 임의의 바람직한 항원 또한 독커린 도메인 대신 직접 융합될 수 있다.
[코헤신-var1-FluM1-6xHis](서열번호 3)의 발현을 암호화하는 C566 이. 콜라이-pET28 벡터
굵은 글씨체는 독커린 결합을 유지하는 밑줄친 단일 C에서 A로의 변화 및 TLRL 부가물의 부위-특이적 말레이미드 결합을 허용하는 3C 잔기(굵은-밑줄 글씨체)를 나타내는 코헤신 도메인이다. 밑줄은 Flu M1 항원 서열이다. 굵은-이탤릭체의 AS 서열은 발현 벡터의 작제물로부터의 결합 서열이다.
관련된 형태에서, 유리 cys 잔기를 가진 임의의 코헤신-항원도 TLR7-L 화합물로 편리하게 장식되고 임의의 항-DC 수용체-독커린-항원 백신과도 연결될 수 있다.
C1450은 마우스 항-DCIR_9E8_H-LV-hIgG4H-C-Flex-v1-v1C2(서열번호 4)를 암호화한다:
굵은 글씨체는 TLRL 부가물의 부위-특이적 연결을 위한 2개의 C 잔기(밑줄)을 지닌 가요성 링커 서열이다. 적절한 L 쇄 발현 벡터를 사용하여 포유동물 세포(예를 들면, CHO-S 세포)내로 동시-형질감염시키는 경우, 당해 벡터는 화학물질-계 보조제에 연결된 DC-표적화제의 대표적인 실시형태의 효율적인 분비를 지시한다. 관련 실시형태에서 - 다른 벡터는 C-말단 코돈에 직접 융합된 임의의 바람직한 항원으로도 제조할 수 있다. 굵은-이탤릭체의 AS 서열은 발현 벡터의 작제물로부터의 결합 서열이다. 이탤릭체는 가요성 링커(상기 참조)이다.
C1180은 포유동물 세포 발현된 6xHis-코헤신-Flgn-1-Flgn-2 융합 단백질(서열번호 5)의 발현을 지시한다:
이탤릭체는 코헤신 도메인이다. 굵은 글씨체는 2-상 플라겔린[살모넬라 엔테리카] gb|AAL30512.1|AF425736_1 잔기 14-161의 N-말단 부분이다. 밑줄은 2-상 플라겔린[살모넬라 엔테리카] gb|AAL30512.1|AF425736_1 잔기 405-484의 C-말단 부분이다. 굵은-이탤릭체의 AS 서열은 발현 벡터의 작제물로부터의 결합 서열이다. 당해 형태는 임의의 항-DC 수용체-독커린-항원 백신에 대한 기능성 Flgn의 연결을 허용한다.
상이한 DC-특이적 항체 또는 단편을 지닌 작제물의 일부 다른 비-제한적인 예를 하기에 나타낸다:
항_CLEC_6_9B9.2G12_Hv-V-hIgG4H-C (서열번호 6):
항_CLEC_6_9B9.2G12_Hv-V-hIgG4H-C (서열번호 7):
항_CLEC_6_9B9.2G12_Kv-V-hIgGK-C (서열번호 8):
항_CLEC_6_9B9.2G12_Kv-V-hIgGK-C (서열번호 9):
항-ASGPR_49C11_7H-LV-hIgG4H-C (서열번호 10):
항-ASGPR_49C11_7H-LV-hIgG4H-C (서열번호 11):
항-ASGPR_49C11_7K-LV-hIgGK-C (서열번호 12):
항-ASGPR_49C11_7K-LV-hIgGK-C (서열번호 13):
항-ASGPR_4G2.2_Hv-V-hIgG4H-C (서열번호 14):
항-ASGPR_4G2.2_Hv-V-hIgG4H-C (서열번호 15):
항-ASGPR_4G2.2_Kv-V-hIgGK-C (서열번호 16):
항-ASGPR_4G2.2_Kv-V-hIgGK-C (서열번호 17):
항-ASGPR_5F10H-LV-hIgG4H-C (서열번호 18):
항-ASGPR_5F10H-LV-hIgG4H-C (서열번호 19):
항-ASGPR_5F10K-LV-hIgGK-C (서열번호 20):
항-ASGPR_5F10K-LV-hIgGK-C (서열번호 21):
항-ASGPR1H11_H-V-hIgG4H-C (서열번호 22):
항-ASGPR1H11_H-V-hIgG4H-C (서열번호 23):
항-ASGPR1H11K-LV-var2-hIgGK-C (서열번호 24):
항-ASGPR1H11K-LV-var2-hIgGK-C (서열번호 25):
항-CD1d_2B5.3G10_H-V-hIgG4H-C (서열번호 26):
항-CD1d_2B5.3G10_H-V-hIgG4H-C (서열번호 27):
항-CD1d_2B5.3G10_K-V-hIgGK-C (서열번호 28):
항-CD1d_2B5.3G10_K-V-hIgGK-C (서열번호 29):
항-CD1d_2H11.2G5_H-V-hIgG4H-C (서열번호 30):
항-CD1d_2H11.2G5_H-V-hIgG4H-C (서열번호 31):
항-CD1d_2H11.2G5_K-V-hIgGK-C (서열번호 32):
항-CD1d_2H11.2G5_K-V-hIgGK-C (서열번호 33):
항-CD40_11B6.1C3_H-LV-hIgG4H-C (서열번호 34):
항-CD40_11B6.1C3_H-LV-hIgG4H-C (서열번호 35):
항-CD40_11B6.1C3_K-LV-hIgGK-C (서열번호 36):
항-CD40_11B6.1C3_K-LV-hIgGK-C (서열번호 37):
항-CD40_12B4.2C10_H-LV-hIgG4H-C (서열번호 38):
항-CD40_12B4.2C10_H-LV-hIgG4H-C (서열번호 39):
항-CD40_12B4.2C10_K-LV-v2-hIgGK-C (서열번호 40):
항-CD40_12B4.2C10_K-LV-v2-hIgGK-C (서열번호 41):
항-CD40_12E12.3F3_H-V-hIgG4H-C (서열번호 42):
항-CD40_12E12.3F3_H-V-hIgG4H-C (서열번호 43):
항-CD40_12E12.3F3_K-LV-hIgGK-C (서열번호 44):
항-CD40_12E12.3F3_K-LV-hIgGK-C (서열번호 45):
항-DCIR_24A5.4A5_H-V-hIgG4H-C (서열번호 46):
항-DCIR_24A5.4A5_H-V-hIgG4H-C (서열번호 47):
항-DCIR_24A5.4A5_K-V-hIgGK-C (서열번호 48):
항-DCIR_24A5.4A5_K-V-hIgGK-C (서열번호 49):
항-DCIR_24E7.3H9_H-V-hIgG4H-C (서열번호 50):
항-DCIR_24E7.3H9_H-V-hIgG4H-C (서열번호 51):
항-DCIR_24E7.3H9_K-V-hIgGK-C (서열번호 52):
항-DCIR_24E7.3H9_K-V-hIgGK-C (서열번호 53):
항-DCIR_29E9.2E2_H-VhIgG4H-C (서열번호 54):
항-DCIR_29E9.2E2_H-VhIgG4H-C (서열번호 55):
항-DCIR_29E9.2E2_K-V-hIgGK-C (서열번호 56):
항-DCIR_29E9.2E2_K-V-hIgGK-C (서열번호 57):
항-DCIR_29G10.3D9_H-V-hIgG4H-C (서열번호 58):
항-DCIR_29G10.3D9_H-V-hIgG4H-C (서열번호 59):
항-DCIR_29G10.3D9_K-Var1-V-hIgGK-C (서열번호 60):
항-DCIR_29G10.3D9_K-Var1-V-hIgGK-C (서열번호 61):
항-DCIR_29G10.3D9_K-Var2-V-hIgGK-C (서열번호 62):
항-DCIR_29G10.3D9_K-Var2-V-hIgGK-C (서열번호 63):
항-DCIR_2C9K-V-hIgGK-C (서열번호 64):
항-DCIR_2C9K-V-hIgGK-C (서열번호 65):
항-DCIR_31A6.1F5_H-var2-V-hIgG4H-C (서열번호 66):
항-DCIR_31A6.1F5_H-var2-V-hIgG4H-C (서열번호 67):
항-DCIR_31A6.1F5_K-var2-V-hIgGK-C (서열번호 68):
항-DCIR_31A6.1F5_K-var2-V-hIgGK-C (서열번호 69):
항-DCIR_3C2.2D9_H-LV-hIgG4H-C (서열번호 70):
항-DCIR_3C2.2D9_H-LV-hIgG4H-C (서열번호 71):
항-DCIR_3C2.2D9_K-LV-hIgGK-C (서열번호 72):
항-DCIR_3C2.2D9_K-LV-hIgGK-C (서열번호 73):
항-DCIR_6C8.1G9_H-V-hIgG4H-C (서열번호 74):
항-DCIR_6C8.1G9_H-V-hIgG4H-C (서열번호 75):
항-DCIR_6C8.1G9_K-V-hIgGK-C (서열번호 76):
항-DCIR_6C8.1G9_K-V-hIgGK-C (서열번호 77):
항-DCIR_9E8.1E3_H-V-hIgG4H-C (서열번호 78):
항-DCIR_9E8.1E3_H-V-hIgG4H-C (서열번호 79):
항-DCIR_9E8.1E3_K-LV-hIgGK-C (서열번호 80):
항-DCIR_9E8.1E3_K-LV-hIgGK-C (서열번호 81):
항-DCIR2C9H-LV-hIgG4H-V-hIgG4H-C (서열번호 82):
항-DCIR2C9H-LV-hIgG4H-V-hIgG4H-C (서열번호 83):
항-DC-SIGNL16E3H (서열번호 84):
항-DC-SIGNL16E3H (서열번호 85):
항-DC-SIGNL16E3K (서열번호 86):
항-DC-SIGNL16E3K (서열번호 87):
항-DC-SIGNL16E7H-LV-hIgG4H-C (서열번호 88):
항-DC-SIGNL16E7H-LV-hIgG4H-C (서열번호 89):
항-DC-SIGNL16E7K-LV-hIgGK-C (서열번호 90):
항-DC-SIGNL16E7K-LV-hIgGK-C (서열번호 91):
항-덱틴(Dectin)_1_11B6.4_H-V-hIgG4H-C (서열번호 92):
항-덱틴_1_11B6.4_H-V-hIgG4H-C (서열번호 93):
항-덱틴_1_11B6.4_K-LV-hIgGK-C (서열번호 94):
항-덱틴_1_11B6.4_K-LV-hIgGK-C (서열번호 95):
항-덱틴_1_15E2.5_H-V-hIgG4H-C (서열번호 96):
항-덱틴_1_15E2.5_H-V-hIgG4H-C (서열번호 97):
항-덱틴_1_15E2.5_K-V-hIgGK-C (서열번호 98):
항-덱틴_1_15E2.5_K-V-hIgGK-C (서열번호 99):
항-덱틴_1_2D8.2D4H-V-hIgG4H-C (서열번호 100):
항-덱틴_1_2D8.2D4H-V-hIgG4H-C (서열번호 101):
항-덱틴_1_2D8.2D4K-V-hIgGK-C (서열번호 102):
항-덱틴_1_2D8.2D4K-V-hIgGK-C (서열번호 103):
항-랑게린 15B10H-LV-hIgG4H-C (서열번호 104):
항-랑게린 15B10H-LV-hIgG4H-C (서열번호 105):
항-랑게린15B10K-LV-hIgGK-C (서열번호 106):
항-랑게린15B10K-LV-hIgGK-C (서열번호 107):
항-랑게린2G3H-LV-hIgG4H-C (서열번호 108):
항-랑게린2G3H-LV-hIgG4H-C (서열번호 109):
항-랑게린2G3L-LV-hIgGK-C (서열번호 110):
항-랑게린2G3L-LV-hIgGK-C (서열번호 111):
항-Lox_1_10F9H-LV-hIgG4H-C (서열번호 112):
항-Lox_1_10F9H-LV-hIgG4H-C (서열번호 113):
항-Lox_1_10F9K-LV-hIgGK-C (서열번호 114):
항-Lox_1_10F9K-LV-hIgGK-C (서열번호 115):
항-LOX-111C8H-LV-hIgG4H-C (서열번호 116):
항-LOX-111C8H-LV-hIgG4H-C (서열번호 117):
항-LOX-111C8K-LV-hIgGK-C (서열번호 118):
항-LOX-111C8K-LV-hIgGK-C (서열번호 119):
항-LOX-115C4H-LV-hIgG4H-C (서열번호 120):
항-LOX-115C4H-LV-hIgG4H-C (서열번호 121):
항-LOX-115C4K-LV-hIgGK-C (서열번호 122):
항-LOX-115C4K-LV-hIgGK-C (서열번호 123):
항-마르코_10B7.3G4H-LV-hIgG4H-C (서열번호 124):
항-마르코(Marco)_10B7.3G4H-LV-hIgG4H-C (서열번호 125):
항-마르코_10B7.3G4K_H-V-hIgGK-C (서열번호 126):
항-마르코_10B7.3G4K_H-V-hIgGK-C (서열번호 127):
항-마르코_11A8.3C9_H-V-hIgG4H-C (서열번호 128):
항-마르코_11A8.3C9_H-V-hIgG4H-C (서열번호 129):
항-마르코_11A8.3C9_H-V-hIgGK-C (서열번호 130):
항-마르코_11A8.3C9_H-V-hIgGK-C (서열번호 131):
항-마르코_3H10.1F3_H-V-hIgG4H-C (서열번호 132):
항-마르코_3H10.1F3_H-V-hIgG4H-C (서열번호 133):
항-마르코_3H10.1F3_K-V-hIgGK-C (서열번호 134):
항-마르코_3H10.1F3_K-V-hIgGK-C (서열번호 135):
본 발명의 항원은 아데노바이러스, 레트로바이러스, 피코르나바이러스, 헤르페스바이러스, 로타바이러스, 한타바이러스, 코로나바이러스, 토가바이러스, 플라비바이러스, 라브도바이러스, 파라믹소바이러스, 오르토믹소바이러스, 분야바이러스, 아레나바이러스, 레오바이러스, 유두종 바이러스, 파르보바이러스, 폭스바이러스, 헤파드나바이러스, 또는 스폰지형 바이러스, HIV, CMV, A형 간염, B형 간염 및 C형 간염, 인플루엔자; 홍역, 소아마비, 천연두, 풍진; 호흡계 세포융합, 헤르페스 심플렉스, 바리셀라 조스터, 엡스타인-바, 일본 뇌염, 광견병, 플루 또는 감기 바이러스 유래의 하나 이상의 바이러스 항원 또는 펩타이드를 포함한다. 당해 항원은 Nef(66-97): 
(서열번호 136); Nef (116-145): 
(서열번호 137); Gag p17 (17-35): 
(서열번호 138); Gag p17-p24 (253-284): 
(서열번호 139); 및/또는 Pol 325-355 (RT 158-188): 
(서열번호 140)로부터 선택된다. 하나의 양상에서, 상기 항원은 19 내지 32개 잔기이고, MHC-부류 I 분자내에서 나타난 HIV-1 Nef, Gag 및 Env 단백질에서 확인된 세포독성 T 림프구(CTL) 에피토프로부터 선택된다. 다른 양상에서, Ag는 HIV gp120, gp41, Gag, p17, p24, p2, p7, p1, p6, Tat, Rev, PR, RT, IN, Vif, Vpr, Vpx, Vpu 및 Nef로부터 선택된다.
다른 양상에서, 항원은 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC-관련된 단백질(뮤신)(MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 타이로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA[엡스타인-바 바이러스 핵 항원] 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 종양 관련 항원으로부터 선택된다. 다른 양상에서, Ag는 백혈병 및 림프종, 성상세포종 또는 교모세포종과 같은 신경계 종양, 흑색종, 유방암, 폐암, 두경부암, 위장 종양, 위암, 결장암, 간암, 췌장암, 자궁경부, 자궁, 난소암, 질암, 고환암, 전립선암 또는 음경암과 같은 비뇨생식기 종양, 골 종양, 혈관 종양, 또는 입술, 코인두, 인두 및 구강, 식도, 직장, 담낭, 담관가지, 후두, 폐 및 기관지, 방광, 신장, 뇌 및 신경계의 다른 부분, 갑상선의 암, 호지킨 질환, 비-호지킨 림프종, 다발성 골수종 및 백혈병 유래의 항원을 포함하는 종양 관련 항원으로부터 선택된다.
Ag는 다음 중 적어도 하나로부터 선택된다:
다른 양상에서, Ag는 다음 중 적어도 하나로부터 선택된다:
여전히 다른 양상에서, Ag는 다음 중 적어도 하나로부터 선택된다:
(서열번호 156); 및
다른 양상에서, Ag는 다음 중 적어도 하나로부터 선택된다:
다른 양상에서, Ag는, 길이 19 내지 32개의 아미노산이다. 다른 양상에서, Ag는 길이 17 내지 60개의 아미노산이고 PSA 또는 사이클린 1에서 확인된 세포독성 T 림프구(CTL) 에피토프로부터 선택된다.
다른 양상에서, 암 펩타이드는 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC-관련된 단백질(뮤신)(MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 티로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA(엡스타인-바 바이러스 핵 항원) 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 종양 관련 항원으로부터 선택된다.
세포의 제조: 사전 동의서가 수집된 후 건강한 개인에서 성분채집 과정(Apheresis procedure)을 수행하였다. 당해 프로토콜은 고찰되어 베일러 리서치 인스티튜트 인스티튜셔날 리뷰 보드(Baylor Research Institute Institutional Review Board)에 의해 승인되었다. PBMC를 성분채집 혈액 시료로부터 정제하고 동결보존 후 사용하였다. 단핵구-유도된 IFNa-DC를 GM-CSF(100ng/ml) 및 IFNα(500U/ml)(참조: Salluto et al, J. Exp. Med)와 함께 Cellgenix 중에서 3일 동안 배양한 동결된 사람 단핵구(정화 분획 5, 참조: Lemarie et al, J. Immunological Methods, 2007)로부터 제조하였다.
세포외 사이토킨 분비 검정. PBMC 또는 단핵구-유도된 IFNα-DC(2 x 106 세포/ml, 200μl/웰)을, 10% 사람 AB 혈청, 2mM L-글루타민, 50U 페니실린, 50㎍/ml의 스트렙토마이신, 1X의 필수 아미노산, 25mM의 헤페스(hepes), 55μM의 2-머캅토-에탄올을 함유하는 cRPMI에서, 목적하거나 24시간 동안 37℃에서 및 5% CO2에서 자극시키지 않은 상태로 둔(음성 대조군) DC-표적화 백신 및 TLR 리간드와 함께 배양하였다. 이어서, 배양 상청액을 수거한 후, 상기 배양 상청액 중에서 분비된 사이토킨을 BioPlex200 루미넥스(Luminex)(제조원: BioRad)를 사용하여 측정하였다.
도 1a 내지 도 1d는 플라겔린 및 본 발명의 수개의 항체-플라겔린 작제물을 나타낸다.
도 2는 본 발명의 항체-플라겔린 작제물의 활성을 시험하는데 사용된 연구의 설계를 나타낸다.
도 3a 내지 도 3c는, 각종 유형의 세포를 본 발명의 작제물로 활성화시킨 경우 IL-6의 분비를 나타낸다. 2개의 플라겔린 도메인(flgn1 및 flgn2) 사이에 가요성 링커(flex)를 첨가하여 활성을 제거한다. 각종 세포는 IFNα 활성화된 DC 및 말초 혈액 단핵 세포(PBMC)이었다.
도 4a 및 도 4b는 IL-6 및 IL-1 베타의 분비에 의해 측정된 각종 작제물의 용량 적정을 나타낸다. 플라겔린 활성은 표적화 항체에 의존적이며 최저 0.1 nM 투여량에서조차 효과적인 반면, 동형 대조군은 25nM 용량에서 단지 반응을 제공한다. 도 4c 및 도 4d는, IL-6 및 IL-1 베타의 분비에 의해 측정된 것으로서 각종 작제물의 용량 적정을 나타낸다. 플라겔린 활성은 표적화 항체에 의존적이며 최저 0.1nM 용량에서조차 효과적인 반면, 동형 대조군은 25nM 용량에서만 반응을 제공한다. 또한, 동형 대조군에 대한 유리 항체의 첨가는 플라겔린 활성을 회복하지 않는다.
도 5는 플라겔린의 존재 또는 부재하에 항-LOX-1 항체를 사용하여 열거된 유전자에 대한 유전자 발현의 열 지도를 나타낸다. α-LOX-1.flgn과 함께 배양된 IFNα-DC로부터 수득된 열 지도 중에서, 17개의 전사체가 αLOX-1.flgn 자극에 대한 반응시 과발현됨이 발견되었다.
본 명세서에서 논의된 어떠한 실시형태도 본 발명의 어떠한 방법, 키트(kit), 시약, 또는 조성물과 관련하여 및 이와 반대로도(vice versa) 구현될 수 있음이 고려된다. 또한, 본 발명의 조성물을 사용하여 본 발명의 방법을 달성할 수 있다.
본원에 기술된 특정 실시형태는 본 발명을 설명하기 위해 나타내며 제한하는 것이 아님이 이해될 수 있다. 본 발명의 기본적인 특징은 본 발명의 영역을 벗어남이 없이 각종 실시형태에서 사용될 수 있다. 당해 분야의 숙련가는 본원에 기술된 특정 과정에 대한 단지 통상의 실험, 다수의 등가물을 사용하여 인식하거나, 추정할 수 있을 것이다. 이러한 등가물은 본 발명의 영역내에 있는 것으로 고려되며 특허청구범위에 포함된다.
본 명세서에서 언급된 모든 공보 및 특허출원은 본 발명이 속한 당해 분야의 숙련가의 수준의 지표이다. 모든 공보 및 특허출원은, 각각의 개개의 공보 또는 특허출원이 구체적이고 개별적으로 참조로 인용되도록 나타낸 경우와 동일한 정도로 참조로 본원에 인용된다.
특허청구범위 및/또는 명세서에서 용어 "포함하는"과 함께 사용되는 경우 단어 하나("a" 또는 "an")의 사용은 "하나"를 의미할 수 있으나, 또한 "하나 이상", "적어도 하나" 및 "하나 또는 하나 이상"의 의미와 일치한다. 특허청구범위에서 용어 "또는"의 사용은, 비록 당해 기재내용이 대안들 및 "및/또는" 만을 언급하는 정의를 뒷받침한다고 해도, 당해 대안들 만이 언급되거나 대안들이 상호배타적임을 표현해서 나타내지 않는 경우 "및/또는"을 의미하기 위해 사용된다. 본 명세서 전체를 통해, 용어 "약"은, 하나의 값이 장치, 그 값을 측정하기 위해 사용된 방법, 또는 연구 대상체 중에 존재하는 변화에 대한 오차의 고유 변화를 포함함을 나타내기 위해 사용된다.
본 명세서 및 특허청구범위에서 사용된 것으로서, 단어 "포함하는"(및 "포함하다(comprise 및 comprises)"와 같은 '포함하는'의 어떠한 형태), "갖는"(및 "가지다(have 및 has)와 같은 '갖는'의 어떠한 형태), "포괄하는(including)"(및 "포괄하다(include 및 includes)"과 같은 '포괄하는'의 어떠한 형태) 또는 "함유하는"(및 "함유하다(contains 및 contain)"과 같은 '함유하는'의 어떠한 형태)는 포괄적이거나 개방형이며(open-ended) 추가의, 인용하지 않은 성분 또는 방법 단계를 제외하지 않는다.
본원에 사용된 것으로서 용어 "또는 이들의 병용물"은 당해 용어를 앞에 나열된 항목들의 조합 및 모든 순열을 말한다. 예를 들어, "A, B, C, 또는 이들의 조합"은 A, B, C, AB, AC, BC, 또는 ABC, 및 순서가 특정 내용에서 중요한 경우, 또한 BA, CA, CB, CBA, BCA, ACB, BAC, 또는 CAB 중 적어도 하나를 포함하는 것으로 의도된다. 이러한 실시예와 연속하여, BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, 등과 같은 하나 이상의 항목 또는 용어의 반복물을 함유하는 병용물이 표현적으로 포괄된다. 당해 분야의 숙련가는, 전형적으로 내용으로부터 달리 명백하지 않은 한, 어떠한 조합의 다수의 항목 또는 용어에 있어서 제한이 없음을 이해할 것이다.
본원에 기재되고 청구된 조성물 및/또는 방법 모두는 본 기재내용의 관점에서 과도한 실험없이 이루어지고 실행될 수 있다. 본 발명의 조성물 및 방법이 바람직한 실시형태의 측면에서 기술되어 있지만, 변화가 본 발명의 개념, 취지 및 영역에서 벗어남이 없이 본원에 기술된 조성물 및/또는 방법 및 방법의 단계 또는 단계의 순서에 적용될 수 있음이 당해 분야의 숙련가에게 명백할 수 있다. 당해 분야의 숙련가에게 명백한 모든 이러한 유사한 치환 및 변형은 첨부된 특허청구범위에 의해 정의된 것으로서 본 발명의 취지, 영역 및 개념내에 있는 것으로 고려된다.
참조문헌
미국 특허출원 공보 제20090004194호: TLR Agonist(Flagellin)/CD40 Agonist/Antigen Protein and DNA Conjugates and use Thereof for Inducing Synergistic Enhancement in Immunity.
미국 특허출원 공보 제20080220011호: Use of Flagellin in Tumor Immunotherapy.
미국 특허출원 공보 제20080248068호: Use of Flagellin as an Adjuvant for Vaccine.
미국 특허 제7,404,963호: Flagellin-Based Adjuvants and Vaccines.
SEQUENCE LISTING
<110> BAYLOR RESEARCH INSTITUTE
<120> NOVEL VACCINE ADJUVANTS BASED ON TARGETING ADJUVANTS TO
ANTIBODIES DIRECTLY TO ANTIGEN-PRESENTING CELLS
<130> BHCS:2468WO
<150> 61/373,763
<151> 2010-08-13
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<170> KopatentIn 1.71
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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 Leu Ser Trp Ile Arg Gln Pro Ser Gly Lys Gly Leu Glu
35 40 45
Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val
65 70 75 80
Phe Leu Lys Ile Thr Ile Val Asp Thr Ala Asp Ala Ala Thr Tyr Tyr
85 90 95
Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr Gly Gly Tyr Phe
100 105 110
Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys
195 200 205
Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
210 215 220
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Leu Gly Lys Ala Ser Gln Thr Pro Thr Asn Thr Ile Ser Val Thr
450 455 460
Pro Thr Asn Asn Ser Thr Pro Thr Asn Asn Ser Asn Pro Lys Pro Asn
465 470 475 480
Pro Ala Ser Ile Glu Arg Leu Ser Ser Gly Leu Arg Ile Asn Ser Ala
485 490 495
Lys Asp Asp Ala Ala Gly Gln Ala Ile Ala Asn Arg Phe Thr Ala Asn
500 505 510
Ile Lys Gly Leu Thr Gln Ala Ser Arg Asn Ala Asn Asp Gly Ile Ser
515 520 525
Ile Ala Gln Thr Thr Glu Gly Ala Leu Asn Glu Ile Asn Asn Asn Leu
530 535 540
Gln Arg Val Arg Glu Leu Ala Val Gln Ser Ala Asn Ser Thr Asn Ser
545 550 555 560
Gln Ser Asp Leu Asp Ser Ile Gln Ala Glu Ile Thr Gln Arg Leu Asn
565 570 575
Glu Ile Asp Arg Val Ser Gly Gln Thr Gln Phe Asn Gly Val Lys Val
580 585 590
Leu Ala Gln Asp Asn Thr Leu Thr Ile Gln Val Gly Ala Asn Asp Gly
595 600 605
Glu Thr Ile Asp Ile Asp Leu Lys Gln Ile Asn Ser Gln Thr Leu Gly
610 615 620
Leu Asp Ser Leu Asn Val Gln Ala Ser Gln Pro Glu Leu Ala Glu Ala
625 630 635 640
Ala Ala Lys Thr Thr Glu Asn Pro Leu Gln Lys Ile Asp Ala Ala Leu
645 650 655
Ala Gln Val Asp Ala Leu Arg Ser Asp Leu Gly Ala Val Gln Asn Arg
660 665 670
Phe Asn Ser Ala Ile Thr Asn Leu Gly Asn Thr Val Asn Asn Leu Ser
675 680 685
Glu Ala Arg Ser Arg Ile Glu Asp Ser Asp Tyr Ala Thr Glu Val Ser
690 695 700
Asn Met Ser Arg Ala Gln Ile Leu Gln Ala Ser
705 710 715
<210> 2
<211> 797
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 2
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 Leu Ser Trp Ile Arg Gln Pro Ser Gly Lys Gly Leu Glu
35 40 45
Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val
65 70 75 80
Phe Leu Lys Ile Thr Ile Val Asp Thr Ala Asp Ala Ala Thr Tyr Tyr
85 90 95
Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr Gly Gly Tyr Phe
100 105 110
Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys
195 200 205
Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
210 215 220
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Leu Gly Lys Ala Ser Ser Glu Asp Thr Gln Pro Pro Ala Pro Thr
450 455 460
Leu Ile Gly Asp Val Asn Ala Asp Gly Lys Ile Asp Ser Thr Asp Leu
465 470 475 480
Thr Leu Leu Lys Arg Tyr Leu Leu Arg Ser Ala Thr Leu Thr Glu Glu
485 490 495
Lys Ile Leu Asn Ala Asp Thr Asp Gly Asn Gly Thr Val Asn Ser Thr
500 505 510
Asp Leu Asn Tyr Leu Lys Lys Tyr Ile Leu Arg Val Ile Ser Val Phe
515 520 525
Pro Ala Glu Gly Asn Lys Pro Pro Thr Pro Thr Pro Thr Lys Thr Pro
530 535 540
Val Ala Thr Pro Ser Pro Thr Gln Pro Leu Phe Thr Pro Ser Phe Lys
545 550 555 560
Asp Val Thr Ala Ser Ile Glu Arg Leu Ser Ser Gly Leu Arg Ile Asn
565 570 575
Ser Ala Lys Asp Asp Ala Ala Gly Gln Ala Ile Ala Asn Arg Phe Thr
580 585 590
Ala Asn Ile Lys Gly Leu Thr Gln Ala Ser Arg Asn Ala Asn Asp Gly
595 600 605
Ile Ser Ile Ala Gln Thr Thr Glu Gly Ala Leu Asn Glu Ile Asn Asn
610 615 620
Asn Leu Gln Arg Val Arg Glu Leu Ala Val Gln Ser Ala Asn Ser Thr
625 630 635 640
Asn Ser Gln Ser Asp Leu Asp Ser Ile Gln Ala Glu Ile Thr Gln Arg
645 650 655
Leu Asn Glu Ile Asp Arg Val Ser Gly Gln Thr Gln Phe Asn Gly Val
660 665 670
Lys Val Leu Ala Gln Asp Asn Thr Leu Thr Ile Gln Val Gly Ala Asn
675 680 685
Asp Gly Glu Thr Ile Asp Ile Asp Leu Lys Gln Ile Asn Ser Gln Thr
690 695 700
Leu Gly Leu Asp Ser Leu Asn Val Gln Ala Ser Gln Pro Glu Leu Ala
705 710 715 720
Glu Ala Ala Ala Lys Thr Thr Glu Asn Pro Leu Gln Lys Ile Asp Ala
725 730 735
Ala Leu Ala Gln Val Asp Ala Leu Arg Ser Asp Leu Gly Ala Val Gln
740 745 750
Asn Arg Phe Asn Ser Ala Ile Thr Asn Leu Gly Asn Thr Val Asn Asn
755 760 765
Leu Ser Glu Ala Arg Ser Arg Ile Glu Asp Ser Asp Tyr Ala Thr Glu
770 775 780
Val Ser Asn Met Ser Arg Ala Gln Ile Leu Gln Ala Ser
785 790 795
<210> 3
<211> 430
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 3
Met Asp Leu Asp Ala Val Arg Ile Lys Val Asp Thr Val Asn Ala Lys
1 5 10 15
Pro Gly Asp Thr Val Asn Ile Pro Val Arg Phe Ser Gly Ile Pro Ser
20 25 30
Lys Gly Ile Ala Asn Ala Asp Phe Val Tyr Ser Tyr Asp Pro Asn Val
35 40 45
Leu Glu Ile Ile Glu Ile Lys Pro Gly Glu Leu Ile Val Asp Pro Asn
50 55 60
Pro Thr Lys Ser Phe Asp Thr Ala Val Tyr Pro Asp Arg Lys Met Ile
65 70 75 80
Val Phe Leu Phe Ala Glu Asp Ser Gly Thr Gly Ala Tyr Ala Ile Thr
85 90 95
Lys Asp Gly Val Phe Ala Thr Ile Val Ala Lys Val Lys Glu Gly Ala
100 105 110
Pro Asn Gly Leu Ser Val Ile Lys Phe Val Glu Val Gly Gly Phe Ala
115 120 125
Asn Asn Asp Leu Val Glu Gln Lys Thr Gln Phe Phe Asp Gly Gly Val
130 135 140
Asn Val Gly Asp Thr Thr Glu Pro Ala Thr Pro Thr Thr Pro Val Thr
145 150 155 160
Thr Pro Thr Thr Thr Asp Asp Leu Asp Ala Ala Ser Leu Leu Thr Glu
165 170 175
Val Glu Thr Tyr Val Leu Ser Ile Ile Pro Ser Gly Pro Leu Lys Ala
180 185 190
Glu Ile Ala Gln Arg Leu Glu Asp Val Phe Ala Gly Lys Asn Thr Asp
195 200 205
Leu Glu Val Leu Met Glu Trp Leu Lys Thr Arg Pro Ile Leu Ser Pro
210 215 220
Leu Thr Lys Gly Ile Leu Gly Phe Val Phe Thr Leu Thr Val Pro Ser
225 230 235 240
Glu Arg Gly Leu Gln Arg Arg Arg Phe Val Gln Asn Ala Leu Asn Gly
245 250 255
Asn Gly Asp Pro Asn Asn Met Asp Lys Ala Val Lys Leu Tyr Arg Lys
260 265 270
Leu Lys Arg Glu Ile Thr Phe His Gly Ala Lys Glu Ile Ala Leu Ser
275 280 285
Tyr Ser Ala Gly Ala Leu Ala Ser Cys Met Gly Leu Ile Tyr Asn Arg
290 295 300
Met Gly Ala Val Thr Thr Glu Val Ala Phe Gly Leu Val Cys Ala Thr
305 310 315 320
Cys Glu Gln Ile Ala Asp Ser Gln His Arg Ser His Arg Gln Met Val
325 330 335
Thr Thr Thr Asn Pro Leu Ile Arg His Glu Asn Arg Met Val Leu Ala
340 345 350
Ser Thr Thr Ala Lys Ala Met Glu Gln Met Ala Gly Ser Ser Glu Gln
355 360 365
Ala Ala Glu Ala Met Asp Ile Ala Ser Gln Ala Arg Gln Met Val Gln
370 375 380
Ala Met Arg Thr Ile Gly Thr His Pro Ser Ser Ser Ala Gly Leu Lys
385 390 395 400
Asp Asp Leu Leu Glu Asn Leu Gln Ala Tyr Gln Lys Arg Met Gly Val
405 410 415
Gln Met Gln Arg Phe Lys Leu Glu His His His His His His
420 425 430
<210> 4
<211> 513
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 4
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 Leu Ser Trp Ile Arg Gln Pro Ser Gly Lys Gly Leu Glu
35 40 45
Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val
65 70 75 80
Phe Leu Lys Ile Thr Ile Val Asp Thr Ala Asp Ala Ala Thr Tyr Tyr
85 90 95
Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr Gly Gly Tyr Phe
100 105 110
Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys
195 200 205
Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
210 215 220
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Leu Gly Lys Ala Ser Gln Thr Pro Thr Asn Thr Ile Ser Val Thr
450 455 460
Pro Thr Asn Asn Ser Thr Pro Thr Asn Asn Ser Asn Pro Lys Pro Asn
465 470 475 480
Pro Ala Ser Cys Gln Thr Pro Thr Asn Thr Ile Ser Val Thr Pro Thr
485 490 495
Asn Asn Ser Thr Pro Thr Asn Asn Ser Asn Pro Lys Pro Cys Pro Ala
500 505 510
Ser
<210> 5
<211> 415
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 5
Leu Asp Ile Thr Ser His His His His His His Asp Asp Leu Asp Ala
1 5 10 15
Val Arg Ile Lys Val Asp Thr Val Asn Ala Lys Pro Gly Asp Thr Val
20 25 30
Arg Ile Pro Val Arg Phe Ser Gly Ile Pro Ser Lys Gly Ile Ala Asn
35 40 45
Cys Asp Phe Val Tyr Ser Tyr Asp Pro Asn Val Leu Glu Ile Ile Glu
50 55 60
Ile Glu Pro Gly Asp Ile Ile Val Asp Pro Asn Pro Asp Lys Ser Phe
65 70 75 80
Asp Thr Ala Val Tyr Pro Asp Arg Lys Ile Ile Val Phe Leu Phe Ala
85 90 95
Glu Asp Ser Gly Thr Gly Ala Tyr Ala Ile Thr Lys Asp Gly Val Phe
100 105 110
Ala Thr Ile Val Ala Lys Val Lys Glu Gly Ala Pro Asn Gly Leu Ser
115 120 125
Val Ile Lys Phe Val Glu Val Gly Gly Phe Ala Asn Asn Asp Leu Val
130 135 140
Glu Gln Lys Thr Gln Phe Phe Asp Gly Gly Val Asn Val Gly Asp Thr
145 150 155 160
Thr Glu Pro Ala Thr Pro Thr Thr Pro Val Thr Thr Pro Thr Thr Thr
165 170 175
Asp Asp Leu Asp Ala Ala Ser Ile Glu Arg Leu Ser Ser Gly Leu Arg
180 185 190
Ile Asn Ser Ala Lys Asp Asp Ala Ala Gly Gln Ala Ile Ala Asn Arg
195 200 205
Phe Thr Ala Asn Ile Lys Gly Leu Thr Gln Ala Ser Arg Asn Ala Asn
210 215 220
Asp Gly Ile Ser Ile Ala Gln Thr Thr Glu Gly Ala Leu Asn Glu Ile
225 230 235 240
Asn Asn Asn Leu Gln Arg Val Arg Glu Leu Ala Val Gln Ser Ala Asn
245 250 255
Ser Thr Asn Ser Gln Ser Asp Leu Asp Ser Ile Gln Ala Glu Ile Thr
260 265 270
Gln Arg Leu Asn Glu Ile Asp Arg Val Ser Gly Gln Thr Gln Phe Asn
275 280 285
Gly Val Lys Val Leu Ala Gln Asp Asn Thr Leu Thr Ile Gln Val Gly
290 295 300
Ala Asn Asp Gly Glu Thr Ile Asp Ile Asp Leu Lys Gln Ile Asn Ser
305 310 315 320
Gln Thr Leu Gly Leu Asp Ser Leu Asn Val Gln Ala Ser Gln Pro Glu
325 330 335
Leu Ala Glu Ala Ala Ala Lys Thr Thr Glu Asn Pro Leu Gln Lys Ile
340 345 350
Asp Ala Ala Leu Ala Gln Val Asp Ala Leu Arg Ser Asp Leu Gly Ala
355 360 365
Val Gln Asn Arg Phe Asn Ser Ala Ile Thr Asn Leu Gly Asn Thr Val
370 375 380
Asn Asn Leu Ser Glu Ala Arg Ser Arg Ile Glu Asp Ser Asp Tyr Ala
385 390 395 400
Thr Glu Val Ser Asn Met Ser Arg Ala Gln Ile Leu Gln Ala Ser
405 410 415
<210> 6
<211> 1409
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 6
atgggcaggc ttacttcttc attcttgcta ctgattgtcc ctgcatatgt cctgtcccag 60
gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgacc 120
tgttctttct ctgggttttc actgagcact tctggtatga gtgtaggctg gattcgtcag 180
ccttcaggga agggtctgga gtggctggct cacatttggt ggaatgatga taagtactat 240
aatccagtcc tgaaaagccg gctcacaatc tccaaggaga cctccaacaa ccaggtattc 300
ctcaagatcg ccagtgtggt ctctgcagat actgccacat actactgtgc tcgattctat 360
ggtaactgtc ttgactactg gggccaaggc accactctca cagtctcctc ggccaaaaca 420
aagggcccat ccgtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc 480
gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 540
ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 600
tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 660
aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 720
cccccatgcc caccctgccc agcacctgag ttcgaagggg gaccatcagt cttcctgttc 780
cccccaaaac ccaaggacac tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg 840
gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag 900
gtgcataatg ccaagacaaa gccgcgggag gagcagttca acagcacgta ccgtgtggtc 960
agcgtcctca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc 1020
tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc 1080
cgagagccac aggtgtacac cctgccccca tcccaggagg agatgaccaa gaaccaggtc 1140
agcctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc 1200
aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1260
ttcttcctct acagcaggct aaccgtggac aagagcaggt ggcaggaggg gaatgtcttc 1320
tcatgctccg tgatgcatga ggctctgcac aaccactaca cacagaagag cctctccctg 1380
tctctgggta aagctagctg attaattaa 1409
<210> 7
<211> 466
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 7
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 Ser Val Gly Trp Ile Arg Gln Pro Ser Gly Lys
50 55 60
Gly Leu Glu Trp Leu Ala His Ile Trp Trp Asn Asp Asp Lys Tyr Tyr
65 70 75 80
Asn Pro Val Leu Lys Ser Arg Leu Thr Ile Ser Lys Glu Thr Ser Asn
85 90 95
Asn Gln Val Phe Leu Lys Ile Ala Ser Val Val Ser Ala Asp Thr Ala
100 105 110
Thr Tyr Tyr Cys Ala Arg Phe Tyr Gly Asn Cys Leu Asp Tyr Trp Gly
115 120 125
Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
145 150 155 160
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
165 170 175
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
180 185 190
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
195 200 205
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
210 215 220
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
225 230 235 240
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
260 265 270
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
275 280 285
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
450 455 460
Ala Ser
465
<210> 8
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 8
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactg ttaaactcct gatctactac acatcaatat tacaattagg agtcccatca 240
agattcagtg gcagtgggtc tgaaacagat tattctctca ccattagcaa cctggagcaa 300
gaagatattg ccacttactt ttgccaacag ggtgattcgc ttccattcac gttcggctcg 360
gggacaaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 9
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 9
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 Tyr Gln Gln Lys Pro Asp Gly Thr Val
50 55 60
Lys Leu Leu Ile Tyr Tyr Thr Ser Ile Leu Gln Leu Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Glu 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
Ser Leu Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 10
<211> 1403
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 10
atgagagcgc tgattctttt gtgcctgttc acagcctttc ctggtatcct gtctgatgtg 60
cagcttcagg agtcaggacc tgacctggtg aaaccttctc agtcactttc actcacctgc 120
actgtcactg gctactccat caccagtggt tatagctggc actggatccg gcagtttcca 180
ggaaacaaac tggaatggat gggctacata ctcttcagtg gtagcactaa ctacaaccca 240
tctctgaaaa gtcgaatctc tatcactcga gacacatcca agaaccagtt cttcctgcag 300
ttgaattctg tgactactga ggacacagcc acatatttct gtgcaagatc taactatggt 360
tcctttgctt cctggggcca agggactctg gtcactgtct ctgcagccaa aacaacgggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 540
ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgaccgtgcc ctccagcagc ttgggcacga agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 720
tgcccaccct gcccagcacc tgagttcgaa gggggaccat cagtcttcct gttcccccca 780
aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 900
aatgccaaga caaagccgcg ggaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc 960
ctcaccgtcc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag 1080
ccacaggtgt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1260
ctctacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacacaga agagcctctc cctgtctctg 1380
ggtaaagcta gctgattaat taa 1403
<210> 11
<211> 464
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 11
Met Arg Ala Leu Ile Leu Leu Cys Leu Phe Thr Ala Phe Pro Gly Ile
1 5 10 15
Leu Ser Asp Val Gln Leu Gln Glu Ser Gly Pro Asp Leu Val Lys Pro
20 25 30
Ser Gln Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr
35 40 45
Ser Gly Tyr Ser Trp His Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu
50 55 60
Glu Trp Met Gly Tyr Ile Leu Phe Ser Gly Ser Thr Asn Tyr Asn Pro
65 70 75 80
Ser Leu Lys Ser Arg Ile Ser Ile Thr Arg Asp Thr Ser Lys Asn Gln
85 90 95
Phe Phe Leu Gln Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Arg Ser Asn Tyr Gly Ser Phe Ala Ser Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
340 345 350
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Gln 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 Val Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Glu 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 Leu Gly Lys Ala Ser
450 455 460
<210> 12
<211> 708
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 12
atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt cataatatcc 60
agaggacaaa ttgttctcac ccagtctcca gcaatcatgt ctgcatctcc aggggagaag 120
gtcaccatga cctgcagtgc cagctcaagt gtaagtcaca tgcactggta ccagcagaag 180
tcaggcactt cccccaaaag atggatttat gacacatcca gactggcttc tggagtccct 240
gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagcatggag 300
gctgaagatg ctgccactta ttactgccag cagtggagta gtcacccatg gtcgttcggt 360
ggaggcacca aactcgagat caaacgaact 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 aaagtctatg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708
<210> 13
<211> 235
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 13
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Ile 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 Ser Ala Ser
35 40 45
Ser Ser Val Ser His Met His Trp Tyr Gln Gln Lys Ser Gly Thr Ser
50 55 60
Pro Lys Arg Trp Ile Tyr Asp Thr Ser Arg Leu Ala Ser Gly Val Pro
65 70 75 80
Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
85 90 95
Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser His Pro Trp Ser Phe Gly Gly Gly Thr Lys Leu 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> 14
<211> 1415
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 14
atggcttggg tgtggacctt gctattcctg atggcagctg cccaaagtgc ccaagcacag 60
atccagttgg tgcagtctgg acctgagctg aagaagcctg gagagacagt caagatctcc 120
tgcaaggctt ctgggtatac cttcacaaac tatggaatga actgggtgaa gcaggttcca 180
ggaaaaggtt taaggtggat gggctggatg gacaccttca ctggagagcc aacatatgct 240
gatgacttca agggacggtt tgccttctct ttggaaacct ctgccagcac tgcctatttg 300
cagatcaaca gcctcaaaaa tgaggacacg gctacttatt tctgtgcaag aggggggatt 360
ttacgactca actactttga ctactggggc caaggcacca ctctcacagt ctcctcagcc 420
aaaacgaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 600
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac gaagacctac 660
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa 720
tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc 780
ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 840
gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 900
gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt 960
gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 1020
aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1080
cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac 1140
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200
gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260
ggctccttct tcctctacag caggctaacc gtggacaaga gcaggtggca ggaggggaat 1320
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc 1380
tccctgtctc tgggtaaagc tagctgatta attaa 1415
<210> 15
<211> 468
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 15
Met Ala Trp Val Trp Thr Leu Leu Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Ala Gln Ala Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys
20 25 30
Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Val Pro Gly Lys Gly Leu
50 55 60
Arg Trp Met Gly Trp Met Asp Thr Phe Thr Gly Glu Pro Thr Tyr Ala
65 70 75 80
Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Leu Gln Ile Asn Ser Leu Lys Asn Glu Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Gly Gly Ile Leu Arg Leu Asn Tyr Phe Asp Tyr
115 120 125
Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val
210 215 220
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys
225 230 235 240
Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg
305 310 315 320
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
340 345 350
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
355 360 365
Thr Leu Pro Pro Ser Gln 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 Val
405 410 415
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp
420 425 430
Lys Ser Arg Trp Gln Glu 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 Leu
450 455 460
Gly Lys Ala Ser
465
<210> 16
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 16
atgaagtttc cttctcaact tctgctctta ctgctgtttg gaatcccagg catgatatgt 60
gacatccaga tgacacaatc ttcatcctcc ttttctgtat ctctaggaga cagagtcacc 120
attacttgca aggcaagtga ggacatatat aatcggttag gctggtatca gcagaaacca 180
ggaaatgctc ctaggctctt aatatctggt gcaaccagtt tggaaactgg ggttccttca 240
agattcagtg gcagtggatc tggaaaggat tacgctctca gcattaccag tcttcagact 300
gaagatcttg ctacttatta ctgtcaacag tgttggactt ctccgtacac gttcggaggg 360
gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 17
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 17
Met Lys Phe Pro Ser Gln Leu Leu Leu Leu Leu Leu Phe Gly Ile Pro
1 5 10 15
Gly Met Ile Cys Asp Ile Gln Met Thr Gln Ser Ser Ser Ser Phe Ser
20 25 30
Val Ser Leu Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asp
35 40 45
Ile Tyr Asn Arg Leu Gly Trp Tyr Gln Gln Lys Pro Gly Asn Ala Pro
50 55 60
Arg Leu Leu Ile Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Lys Asp Tyr Ala Leu Ser Ile Thr
85 90 95
Ser Leu Gln Thr Glu Asp Leu Ala Thr Tyr Tyr Cys Gln Gln Cys Trp
100 105 110
Thr Ser Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 18
<211> 1398
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 18
atgggatgga gctggatctt tctctttctc ttgtcaggaa ctggaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgagctg gtgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac cttcactgac tactacatga agtgggtgaa gcagagccat 180
ggaaagagcc ttgagtggat tggagatatt aatcctaact atggtgatac tttctacaac 240
cagaagttcg agggcaaggc cacattgact gtagacaaat cctccaggac agcctacatg 300
cagctcaaca gcctgacatc tgaggactct gcagtctatt attgtggaag aggggactat 360
ggatacttcg atgtctgggg cgcagggacc acggtcaccg tctcctcagc caaaacaaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc 720
ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780
ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 840
gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900
cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960
gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020
aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080
gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140
ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1200
gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260
ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320
tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380
ctgggtaaag ctagctga 1398
<210> 19
<211> 464
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 19
Met Gly Trp Ser Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Gly Gly
1 5 10 15
Val Leu 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 Lys Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Asn Tyr Gly Asp Thr Phe Tyr Asn
65 70 75 80
Gln Lys Phe Glu Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Arg
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 Gly Arg Gly Asp Tyr Gly Tyr Phe Asp Val Trp Gly Ala
115 120 125
Gly Thr Thr Val Thr Val Ser Ser Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
225 230 235 240
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val
245 250 255
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
260 265 270
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
275 280 285
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
290 295 300
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
305 310 315 320
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
325 330 335
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
340 345 350
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
355 360 365
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
370 375 380
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
385 390 395 400
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
405 410 415
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
420 425 430
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
435 440 445
His Asn His Tyr Thr Gln Lys Ser Leu Leu Ser Leu Gly Lys Ala Ser
450 455 460
<210> 20
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 20
atggagacac attctcaggt ctttgtatac atgttgctgt ggttgtctgg tgttgaagga 60
gacattgtga tgacccagtc tcacaaattc atgtccacat cagtaggaga cagggtcagc 120
atcacctgca aggccagtca ggatgtgggt actgctgtag cctggtatca acagaaacca 180
gggcaatctc ctaaactact gatttactgg gcatccaccc ggcacactgg agtccctgat 240
cgcttcacag gcagtggatc tgggacagat ttcactctca ccattaacaa tgtgcagtct 300
gaagacttgg cagattattt ctgtcagcaa tatagcagca atccgtacat gttcggaggg 360
gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 21
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 21
Met Glu Thr His Ser 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 Ser Ile Thr Cys Lys Ala Ser Gln Asp
35 40 45
Val Gly 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 Asn
85 90 95
Asn Val Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Ser
100 105 110
Ser Asn Pro Tyr Met Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 22
<211> 1413
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 22
atgggatgga gctggatctt tctctttctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgagttg gtgaagcctg gggcttcagt gaagatatcc 120
tgcaagactt ctggatacac attcactgaa tacaccatgc actgggtgag gcagagccat 180
ggaaagagcc ttgagtggat tggaggtatt aatcctatca atggtggtcc tacctacaac 240
cagaagttca agggcaaggc cacattgact gttgacaagt cctccagcac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag atgggactat 360
ggtagtcgag atgttatgga ctactggggt caaggaacct cagtcaccgt ctcctcagcc 420
aaaacgaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtacc ggtgacggtg 540
tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 600
tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcacgaag 660
acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gagagttgag 720
tccaaatatg gtcccccatg cccaccctgc ccagcacctg agttcgaagg gggaccatca 780
gtcttcctgt tccccccaaa acccaaggac actctcatga tctcccggac ccctgaggtc 840
acgtgcgtgg tggtggacgt gagccaggaa gaccccgagg tccagttcaa ctggtacgtg 900
gatggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagtt caacagcacg 960
taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaacgg caaggagtac 1020
aagtgcaagg tctccaacaa aggcctcccg tcctccatcg agaaaaccat ctccaaagcc 1080
aaagggcagc cccgagagcc acaggtgtac accctgcccc catcccagga ggagatgacc 1140
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catcgccgtg 1200
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260
tccgacggct ccttcttcct ctacagcagg ctaaccgtgg acaagagcag gtggcaggag 1320
gggaatgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacacagaag 1380
agcctctccc tgtctctggg taaagctagc tga 1413
<210> 23
<211> 469
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 23
Met Gly Trp Ser 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 Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe
35 40 45
Thr Glu Tyr Thr Met His Trp Val Arg Ser His Gly Lys Ser Leu Glu
50 55 60
Trp Ile Gly Gly Ile Asn Pro Ile Asn Gly Gly Pro Thr Tyr Asn Gln
65 70 75 80
Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr
85 90 95
Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Trp Asp Tyr Gly Ser Arg Asp Val Met Asp Tyr Trp
115 120 125
Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
225 230 235 240
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly
245 250 255
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
290 295 300
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
305 310 315 320
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
355 360 365
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
370 375 380
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
385 390 395 400
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
405 410 415
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
420 425 430
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
450 455 460
Leu Gly Lys Ala Ser
465
<210> 24
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 24
atggaatcac agactctggt cttcatatcc atactgctct ggttatatgg tgctgatggg 60
aacattgtaa tgactcaatc tcccaaatcc atgtccatgt cagtagggga gagggtcacc 120
ttgagctgca aggccagtga gaatgtggga acttatgtat cctggtatca acagagacca 180
gaacagtctc caaaactgct gatatacggg gcatccaacc ggtacactgg ggtccccgat 240
cgcttcacag gcagtggatc tgcaacagat ttcactctga ccatcagcag tgtgcaggct 300
gaggaccttg cagattatca ctgtggacag acttacagct atatattcac gttcggctcg 360
gggacaaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 25
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 25
Met Glu Thr His Ser Gln Val Phe Val Tyr Met Leu Leu Trp Leu Ser
1 5 10 15
Gly Val Glu Gly Asn Ile Val Met Thr Gln Ser Pro Lys Ser Met Ser
20 25 30
Met Ser Val Gly Glu Arg Val Thr Leu Ser Cys Lys Ala Ser Glu Asn
35 40 45
Val Gly Thr Tyr Val Ser Trp Tyr Gln Gln Arg Pro Glu Gln Ser Pro
50 55 60
Lys Leu Leu Ile Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp
65 70 75 80
Arg Phe Thr Gly Ser Gly Ser Ala Thr Asp Phe Thr Leu Thr Ile Ser
85 90 95
Ser Val Gln Ala Glu Asp Leu Ala Asp Tyr His Cys Gly Gln Thr Tyr
100 105 110
Ser Tyr Ile Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 26
<211> 1404
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 26
atgggatgga gccggatctt tctcttcctc ctgtcaataa ctgcaggtgt ccattgccag 60
gtccaggtgc agcagtcggg acctgagttg gtgaagcctg gggcctcagt gaagatttcc 120
tgcaaagcct ctggcgacgc attcagtagt tcttggatga actgggtgaa gcagaggcct 180
ggacagggtc ttgagtggat tggacggatt tatcttggag atggagatat taattacaat 240
gggaagttca agggcagggc cacactgact gcagacaaat cctccagcac agcctacatg 300
cagctcagca gcctgacctc tgtggactct gcggtctatt tctgcgcgag gcagctcggg 360
ctatggtatg ttatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa 420
acaaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720
ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg 780
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 960
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380
ctgtctctgg gtaaagctag ctga 1404
<210> 27
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 27
Met Gly Trp Ser Arg Ile Phe Leu Phe Leu Leu Ser Ile Thr Ala Gly
1 5 10 15
Val His Cys Gln Val Gln Val Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Asp Ala Phe
35 40 45
Ser Ser Ser Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Tyr Leu Gly Asp Gly Asp Ile Asn Tyr Asn
65 70 75 80
Gly Lys Phe Lys Gly Arg Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Val Asp Ser Ala Val
100 105 110
Tyr Phe Cys Ala Arg Gln Leu Gly Leu Trp Tyr Val Met Asp Tyr Trp
115 120 125
Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr
225 230 235 240
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Gln 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 Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Glu 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 Leu Gly
450 455 460
Lys Ala Ser
465
<210> 28
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 28
atgagtgtgc ccactcaggt cctggggttg ctgctgctgt ggcttacagg tgccagatgt 60
gacatccaga tggctcagtc tccagcctcc ctatctgcat ctgtgggaga aactgtcacc 120
atcacatgtc gagcaagtga gaatatttac agttatttag catggtatca gcagaaacag 180
ggaaaatctc ctcagctcct ggtctataat gcaaaaacct tagcagaagg tgtgccatca 240
aggttcagtg gcagtggatc aggcacacag ttttctctga agatcaacag cctgcagcct 300
gaagattttg ggagttatta ctgtcaacat cattatggtt ttccgtggac gttcggtgga 360
ggcaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 29
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 29
Met Ser Val Pro Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Ala Arg Cys Asp Ile Gln Met Ala Gln Ser Pro Ala Ser Leu Ser
20 25 30
Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn
35 40 45
Ile Tyr Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro
50 55 60
Gln Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Glu Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Ser Leu Lys Ile Asn
85 90 95
Ser Leu Gln Pro Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His His Tyr
100 105 110
Gly Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 30
<211> 1395
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 30
atgaacttcg ggctcagctt gattttcctt gtcctcattt taaaaggtgt ccagtgtgag 60
gtgcagctgg tggagtctgg gggagactta gtgaagcctg gagggtccct gaaactctcc 120
tgtgcagcct ctggattcac tttcagtagc tatggcatgt cttgggttcg ccagactcca 180
gacaagaggc tggagtgggt cgcagtcatt agtagtggtg gaagttccac cttctatcca 240
gacagtgtga aggggcgatt caccatctcc agagacaatg ccaagaacac cctgtacctg 300
caaatgagca gtctgaagtc tgaggacaca gccgtgtatt actgttcaag aggaggttac 360
tactttgact actggggcca aggcaccact ctcacagtct ccgcagccaa aacaaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 540
ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgaccgtgcc ctccagcagc ttgggcacga agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 720
tgcccaccct gcccagcacc tgagttcgaa gggggaccat cagtcttcct gttcccccca 780
aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 900
aatgccaaga caaagccgcg ggaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc 960
ctcaccgtcc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag 1080
ccacaggtgt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1260
ctctacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacacaga agagcctctc cctgtctctg 1380
ggtaaagcta gctga 1395
<210> 31
<211> 464
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 31
Met Asn Phe Gly Leu Ser Leu Ile Phe Leu Val Leu Ile Leu Lys Gly
1 5 10 15
Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys
20 25 30
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Ser Tyr Gly Met Ser Trp Val Arg Gln Thr Pro Asp Lys Arg Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Ser Gly Gly Ser Ser Thr Phe Tyr Pro
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Ser Ser Leu Lys Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ser Arg Gly Gly Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Thr Leu Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
340 345 350
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Gln 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 Val Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Glu 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 Leu Gly Lys Ala Ser
450 455 460
<210> 32
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 32
atgaggttcc aggttcaggt tctggggctc cttctgctct ggatatcagg tgcccagtgt 60
gatgtccaga taacccagtc tccatcttat cttgctgcat ctcctggaga aaccattact 120
attaattgca gggcaagcaa gaccattagc aaatatttag cctggtatca agagaaacct 180
gagaaaactg ataagcttct tatctactct ggatccactt tgcaatctgg aattccatca 240
aggttcagtg gcagtggatc tggtacagat ttcactctca ccatcagtgg cctggagcct 300
gaagattttg caatgtatta ctgtcaacag cataatgaat acccgtggac gttcggtgga 360
ggcaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 33
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 33
Met Arg Phe Gln Val Gln Val Leu Gly Leu Leu Leu Leu Trp Ile Ser
1 5 10 15
Gly Ala Gln Cys Asp Val Gln Ile Thr Gln Ser Pro Ser Tyr Leu Ala
20 25 30
Ala Ser Pro Gly Glu Thr Ile Thr Ile Asn Cys Arg Ala Ser Lys Thr
35 40 45
Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Glu Lys Pro Glu Lys Thr Asp
50 55 60
Lys Leu Leu Ile Tyr Ser Gly Ser Thr Leu Gln Ser Gly Ile 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
Gly Leu Glu Pro Glu Asp Phe Ala Met Tyr Tyr Cys Gln Gln His Asn
100 105 110
Glu Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 34
<211> 1389
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 34
atgggatgga gctggatctt tctctttctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgagctg gtgaagcctg gggcttcagt gaagatatcc 120
tgcaaggctt ctggttactc attcactggc tactacatgc actgggtgaa gcaaagccat 180
gtaaagagcc ttgagtggat tggacgtatt aatccttaca atggtgctac tagctacaac 240
cagaatttca aggacaaggc cagcttgact gtagataagt cctccagcac agcctacatg 300
gagctccaca gcctgacatc tgaggactct gcagtctatt actgtgcaag agaggactac 360
gtctactggg gccaaggcac cactctcaca gtctcctcag ccaaaacgaa gggcccatcc 420
gtcttccccc tggcgccctg ctccaggagc acctccgaga gcacagccgc cctgggctgc 480
ctggtcaagg actacttccc cgaaccggtg acggtgtcgt ggaactcagg cgccctgacc 540
agcggcgtgc acaccttccc ggctgtccta cagtcctcag gactctactc cctcagcagc 600
gtggtgaccg tgccctccag cagcttgggc acgaagacct acacctgcaa cgtagatcac 660
aagcccagca acaccaaggt ggacaagaga gttgagtcca aatatggtcc cccatgccca 720
ccctgcccag cacctgagtt cgaaggggga ccatcagtct tcctgttccc cccaaaaccc 780
aaggacactc tcatgatctc ccggacccct gaggtcacgt gcgtggtggt ggacgtgagc 840
caggaagacc ccgaggtcca gttcaactgg tacgtggatg gcgtggaggt gcataatgcc 900
aagacaaagc cgcgggagga gcagttcaac agcacgtacc gtgtggtcag cgtcctcacc 960
gtcctgcacc aggactggct gaacggcaag gagtacaagt gcaaggtctc caacaaaggc 1020
ctcccgtcct ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agagccacag 1080
gtgtacaccc tgcccccatc ccaggaggag atgaccaaga accaggtcag cctgacctgc 1140
ctggtcaaag gcttctaccc cagcgacatc gccgtggagt gggagagcaa tgggcagccg 1200
gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctac 1260
agcaggctaa ccgtggacaa gagcaggtgg caggagggga atgtcttctc atgctccgtg 1320
atgcatgagg ctctgcacaa ccactacaca cagaagagcc tctccctgtc tctgggtaaa 1380
gctagctga 1389
<210> 35
<211> 462
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 35
Met Gly Trp Ser 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 Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe
35 40 45
Thr Gly Tyr Tyr Met His Trp Val Lys Gln Ser His Val Lys Ser Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asn Pro Tyr Asn Gly Ala Thr Ser Tyr Asn
65 70 75 80
Gln Asn Phe Lys Asp Lys Ala Ser Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu His Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Asp Tyr Val Tyr Trp Gly Gln Gly Thr Thr
115 120 125
Leu Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser Val Phe Pro Leu
130 135 140
Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys
145 150 155 160
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
165 170 175
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser
180 185 190
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser
195 200 205
Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn
210 215 220
Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro
225 230 235 240
Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe
245 250 255
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
260 265 270
Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe
275 280 285
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
290 295 300
Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
305 310 315 320
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
325 330 335
Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala
340 345 350
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln
355 360 365
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
370 375 380
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
385 390 395 400
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
405 410 415
Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu
420 425 430
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
435 440 445
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala Ser
450 455 460
<210> 36
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 36
atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60
gttgtgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120
tcttgcagat ctagtcagag ccttgtacac agtaatggaa acacctattt acattggtac 180
ctgcagaagc caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240
ggggtcccag acaggttcag tggcagtgga tcagggacag atttcgcact caagatcagt 300
agagtggagg ctgaggatct gggagtttat ttctgctctc aaagtacaca tgttccgtgg 360
acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 37
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 37
Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala
1 5 10 15
Ser Ser Ser Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val
20 25 30
Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu
35 40 45
Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro
50 55 60
Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser
65 70 75 80
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ala
85 90 95
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys
100 105 110
Ser Gln Ser Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 38
<211> 1410
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 38
atggaatgga gttggatatt tctctttctt ctgtcaggaa ctgcaggtgt ccactctgag 60
gtccagctgc agcagtctgg acctgagctg gtaaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac attcactgac tatgttttgc actgggtgaa acagaagcct 180
gggcagggcc ttgagtggat tggatatatt aatccttaca atgatggtac taagtacaat 240
gagaagttca aaggcaaggc cacactgact tcagacaaat cctccagcac agcctacatg 300
gagctcagca gcctgacctc tgaggactct gcggtctatt actgtgcaag gggctatccg 360
gcctactctg ggtatgctat ggactactgg ggtcaaggaa cctcagtcac cgtctcctca 420
gccaaaacga agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720
aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780
ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840
tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900
ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 960
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020
tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080
gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1200
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260
gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320
aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380
ctctccctgt ctctgggtaa agctagctga 1410
<210> 39
<211> 469
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 39
Met Glu Trp Ser 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 Tyr Thr Phe
35 40 45
Thr Asp Tyr Val Leu 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 Gly Thr Lys 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 Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Gly Tyr Pro Ala Tyr Ser Gly Tyr Ala Met Asp
115 120 125
Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
225 230 235 240
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly
245 250 255
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
290 295 300
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
305 310 315 320
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
355 360 365
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
370 375 380
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
385 390 395 400
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
405 410 415
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
420 425 430
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
450 455 460
Leu Gly Lys Ala Ser
465
<210> 40
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 40
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactg ttaaactcct gatctactac acatcaagat tacactcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa 300
gaagatattg ccacttactt ttgccatcat ggtaatacgc ttccgtggac gttcggtgga 360
ggcaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 41
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 41
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 Tyr Gln Gln Lys Pro Asp Gly Thr Val
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 His His Gly Asn
100 105 110
Thr Leu Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 42
<211> 1404
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 42
atgaacttgg ggctcagctt gattttcctt gtccttgttt taaaaggtgt ccagtgtgaa 60
gtgaagctgg tggagtctgg gggaggctta gtgcagcctg gagggtccct gaaactctcc 120
tgtgcaacct ctggattcac tttcagtgac tattacatgt attgggttcg ccagactcca 180
gagaagaggc tggagtgggt cgcatacatt aattctggtg gtggtagcac ctattatcca 240
gacactgtaa agggccgatt caccatctcc agagacaatg ccaagaacac cctgtacctg 300
caaatgagcc ggctgaagtc tgaggacaca gccatgtatt actgtgcaag acgggggtta 360
ccgttccatg ctatggacta ttggggtcaa ggaacctcag tcaccgtctc ctcagccaaa 420
acgaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720
ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg 780
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 960
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380
ctgtctctgg gtaaagctag ctga 1404
<210> 43
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 43
Met Asn Leu Gly Leu Ser Leu Ile Phe Leu Val Leu Val Leu Lys Gly
1 5 10 15
Val Gln Cys Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe
35 40 45
Ser Asp Tyr Tyr Met Tyr Trp Val Arg Gln Thr Pro Glu Lys Arg Leu
50 55 60
Glu Trp Val Ala Tyr Ile Asn Ser Gly Gly Gly Ser Thr Tyr Tyr Pro
65 70 75 80
Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Ser Arg Leu Lys Ser Glu Asp Thr Ala Met
100 105 110
Tyr Tyr Cys Ala Arg Arg Gly Leu Pro Phe His Ala Met Asp Tyr Trp
115 120 125
Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr
225 230 235 240
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Gln 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 Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Glu 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 Leu Gly
450 455 460
Lys Ala Ser
465
<210> 44
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 44
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctaggaga cagagtcacc 120
atcagttgca gtgcaagtca gggcattagc aattatttaa actggtatca gcagaaacca 180
gatggaactg ttaaactcct gatctattac acatcaattt tacactcagg agtcccatca 240
aggttcagtg gcagtgggtc tgggacagat tattctctca ccatcggcaa cctggaacct 300
gaagatattg ccacttacta ttgtcagcag tttaataagc ttcctccgac gttcggtgga 360
ggcaccaaac tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 45
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 45
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 Ser Ala Ser Gln Gly
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 Tyr Tyr Thr Ser Ile 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 Gly
85 90 95
Asn Leu Glu Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Phe Asn
100 105 110
Lys Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 46
<211> 1405
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 46
atggattggc tgtggaactt gctattcctg atggcagctg cccaaagtgc ccaagcacag 60
atccagttgg tgcagtctgg acctgagctg aagaagcctg gagagacagt caagatctcc 120
tgcaaggctt ctgggtattc cttcacaaac tatggaatga actgggtgaa acaggctcca 180
ggaaagggtt taaagtggat gggctggata aacacctaca ctggagagtc aacatatgct 240
gatgacttca agggacggtt tgccttctct ttggaaacct ctgccagcac tgcctatttg 300
cagatcagta acctcaaaaa tgaggacatg gctacatatt tctgtgctag aggggacttt 360
aggtactact attttgacta ctggggccaa ggcaccactc tcacaggctc ctcagccaaa 420
acgaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720
ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg 780
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 960
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380
ctgtctctgg gtaaagctag ctgat 1405
<210> 47
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 47
Met Asp Trp Leu Trp Asn Leu Leu Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Ala Gln Ala Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys
20 25 30
Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe
35 40 45
Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu
50 55 60
Lys Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala
65 70 75 80
Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Leu Gln Ile Ser Asn Leu Lys Asn Glu Asp Met Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Gly Asp Phe Arg Tyr Tyr Tyr Phe Asp Tyr Trp
115 120 125
Gly Gln Gly Thr Thr Leu Thr Gly Ser Ser Ala Lys Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr
225 230 235 240
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Gln 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 Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Glu 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 Leu Gly
450 455 460
Lys Ala Ser
465
<210> 48
<211> 702
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 48
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tgccagatgt 60
gacatccaga tgactcagtc tccagcctcc ctatctgcat ctgtgggaga aactgtcacc 120
atcacgtgtc gagcaagtgg gaatattcac aattatttag catggtatca gcagaaacag 180
ggaaaatctc ctcagctcct ggtctataat gcaaaaacct tggcagatgg tgtgccatca 240
aggttcagtg gcagtggatc aggaacacaa tattctctca agatcaacac cctgcagcct 300
gaagattttg ggagttatta ctgtcaacat ttttgggatt cttggacgtt cggtggaggc 360
accaagctcg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct 420
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600
agcaaagcag actacgagaa acacaaagtc tatgcctgcg aagtcaccca tcagggcctg 660
agctcgcccg tcacaaagag cttcaacagg ggagagtgtt ag 702
<210> 49
<211> 233
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 49
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser
20 25 30
Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gly Asn
35 40 45
Ile His Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro
50 55 60
Gln Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Asp Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn
85 90 95
Thr Leu Gln Pro Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp
100 105 110
Asp Ser Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr
115 120 125
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
130 135 140
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
145 150 155 160
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
165 170 175
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
180 185 190
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
195 200 205
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
210 215 220
Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 50
<211> 1398
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 50
atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60
gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120
tgcaaggcta ctggctacac attcagtagc tactggatag agtgggtaaa gcagaggcct 180
ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtaggac taacgacaat 240
gagaagttca agggcaaggc cacattcact gcagatacat cctccaagaa agcctacatg 300
caactcagca gcctgacatc tgaggactct gccgtctatt attgtgcaag aaggggtggt 360
tactcctttg cttactgggg ccaagggact ctggtcactg tctctgcagc caaaacaaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc 720
ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780
ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 840
gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900
cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960
gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020
aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080
gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140
ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1200
gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260
ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320
tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380
ctgggtaaag ctagctga 1398
<210> 51
<211> 465
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 51
Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe
35 40 45
Ser Ser Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu
50 55 60
Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Arg Thr Asn Asp Asn
65 70 75 80
Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Lys
85 90 95
Lys Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Arg Gly Gly Tyr Ser Phe Ala Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
225 230 235 240
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val
245 250 255
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
260 265 270
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
275 280 285
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
290 295 300
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
305 310 315 320
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
325 330 335
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
340 345 350
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
355 360 365
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
370 375 380
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
385 390 395 400
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
405 410 415
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
420 425 430
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
435 440 445
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala
450 455 460
Ser
465
<210> 52
<211> 1422
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 52
atgaccatgt tctcactagc tcttctcctc agtcttcttc tcctctgtgt ctctgattct 60
agggcagaaa caactgtgac ccagtctatg accatgttct cactagctct tctcctcagt 120
cttcttctcc tctgtgtctc tgattctagg gcagaaacaa ctgtgaccca gtctccagca 180
tccctgtcca tggctatagg ggaaaaagtc accatcagat gcgtaaccag cactgatatt 240
gatgatgatg tgaactggta ccagcagaag ccaggggaac ctcctaaact ccttatttca 300
gaaggcaata ctcttcgtcc tggagtccca tcccgattct ccagcagtgg ctatggtaca 360
gattttgttt ttacaattga gaacatgctc tcagaagatg ttgcagatta ctactgtttg 420
caaagtggta acttgccgta cacgttcgga ggggggacca agctcgagat caaacgaact 480
gtggctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atctggaact 540
gcctctgttg tgtgcctgct gaataacttc tatcccagag aggccaaagt acagtggaag 600
gtggataacg ccctccaatc gggtaactcc caggagagtg tcacagagca ggacagcaag 660
gacagcacct acagcctcag cagcaccctg acgctgagca aagcagacta cgagaaacac 720
aaagtctatg cctgcgaagt cacccatcag ggcctgagct cgcccgtcac aaagagcttc 780
aacaggggag agtgttagcc agcatccctg tccatggcta taggggaaaa agtcaccatc 840
agatgcgtaa ccagcactga tattgatgat gatgtgaact ggtaccagca gaagccaggg 900
gaacctccta aactccttat ttcagaaggc aatactcttc gtcctggagt cccatcccga 960
ttctccagca gtggctatgg tacagatttt gtttttacaa ttgagaacat gctctcagaa 1020
gatgttgcag attactactg tttgcaaagt ggtaacttgc cgtacacgtt cggagggggg 1080
accaagctcg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct 1140
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 1200
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 1260
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 1320
agcaaagcag actacgagaa acacaaagtc tatgcctgcg aagtcaccca tcagggcctg 1380
agctcgcccg tcacaaagag cttcaacagg ggagagtgtt ag 1422
<210> 53
<211> 236
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 53
Met Thr Met Phe Ser Leu Ala Leu Leu Leu Ser Leu Leu Leu Leu Cys
1 5 10 15
Val Ser Asp Ser Arg Ala Glu Thr Thr Val Thr Gln Ser Pro Ala Ser
20 25 30
Leu Ser Met Ala Ile Gly Glu Lys Val Thr Ile Arg Cys Val Thr Ser
35 40 45
Thr Asp Ile Asp Asp Asp Val Asn Trp Tyr Gln Gln Lys Pro Gly Glu
50 55 60
Pro Pro Lys Leu Leu Ile Ser Glu Gly Asn Thr Leu Arg Pro Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Ser Ser Gly Tyr Gly Thr Asp Phe Val Phe Thr
85 90 95
Ile Glu Asn Met Leu Ser Glu Asp Val Ala Asp Tyr Tyr Cys Leu Gln
100 105 110
Ser Gly Asn Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu 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> 54
<211> 1404
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 54
atggcttggg tgtggacctt gctattcctg atggcagctg cccaaagtgc ccaagcacag 60
atccagttgg tgcagtctgg acctgagctg aagaagcctg gagagacagt caagatctcc 120
tgcaaggctt ctgggtatac cttcacaaac tatggaatga actgggtgaa gcaggctcca 180
ggaaagggtt taaagtgggt gggctggata aacaccttca ctggagagcc aacatatgtt 240
gatgacttca agggacggtt tgccttctct ttggaaacct ctgccagcac tgcctatttg 300
cagatcaaca acctcaaaaa tgaggacacg gctacatatt tctgtgcaag agggaatttt 360
aggtactact actttgacta ctggggccaa ggcaccactc tcacagtctc ctcagccaaa 420
acaaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720
ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg 780
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 960
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380
ctgtctctgg gtaaagctag ctga 1404
<210> 55
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 55
Met Ala Trp Val Trp Thr Leu Leu Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Ala Gln Ala Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys
20 25 30
Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu
50 55 60
Lys Trp Val Gly Trp Ile Asn Thr Phe Thr Gly Glu Pro Thr Tyr Val
65 70 75 80
Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Gly Asn Phe Arg Tyr Tyr Tyr Phe Asp Tyr Trp
115 120 125
Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Lys Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr
225 230 235 240
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Gln 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 Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Glu 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 Leu Gly
450 455 460
Lys Ala Ser
465
<210> 56
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 56
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tgccagatgt 60
gacatccaga tgactcagtc cccagcctcc ctatctgcat ctgtgggaga aactgtcacc 120
atcacatgtc gaacaagtgg gaatattcgc aattatttag catggtatca gcagaaacag 180
ggaaaatctc ctcaactcct ggtctataat gcaaaaacct tagcagatgg tgtgccatca 240
aggttcggtg gcagtggatc aggaacacaa tattctctca agatcaacag cctgcagcct 300
gaagattttg ggaattatta ctgtcaacat ttttggagta gtccgtacac gttcggaggg 360
gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 57
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 57
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser
20 25 30
Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Thr Ser Gly Asn
35 40 45
Ile Arg Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro
50 55 60
Gln Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Asp Gly Val Pro Ser
65 70 75 80
Arg Phe Gly Gly Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn
85 90 95
Ser Leu Gln Pro Glu Asp Phe Gly Asn Tyr Tyr Cys Gln His Phe Trp
100 105 110
Ser Ser Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 58
<211> 2811
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 58
atgatgggat ggagctatat catcctcttt ttggtagcaa cagctacaga tgtccactcc 60
caggtccaac tgcagcagcc tggggctgaa ctggtgaagc ctggggcttc agtgaagctg 120
tcctgcaagg cttctggcta caccttcacc agctactgga tgcactgggt gaagcagagg 180
cctggagaag gccttgagtg gattggagag attaatccta gctacggtcg tactgactac 240
aatgagaagt tcaagaacaa ggccacactg actgtagcca aatcctccag cacagcctac 300
atgcaactca gcagcctgac atctgaggac tctgcggtct attactgtgc aagaggagat 360
tactacggta gtagctcgtt tgcttactgg ggccaaggga ctctggtcac tgtctctgca 420
gccaaaacaa agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720
aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780
ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840
tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900
ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 960
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020
tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080
gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1200
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260
gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320
aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380
ctctccctgt ctctgggtaa agctagcgga tggagctata tcatcctctt tttggtagca 1440
acagctacag atgtccactc ccaggtccaa ctgcagcagc ctggggctga actggtgaag 1500
cctggggctt cagtgaagct gtcctgcaag gcttctggct acaccttcac cagctactgg 1560
atgcactggg tgaagcagag gcctggagaa ggccttgagt ggattggaga gattaatcct 1620
agctacggtc gtactgacta caatgggaag ttcaagaaca aggccacact gactgtagcc 1680
aaatcctcca gcacagccta catgcaactc agcagcctga catctgagga ctctgcggtc 1740
tattactgtg caagaggaga ttactacggt agtagctcgt ttgcttactg gggccaaggg 1800
actctggtca ctgtctctgc agccaaaaca aagggcccat ccgtcttccc cctggcgccc 1860
tgctccagga gcacctccga gagcacagcc gccctgggct gcctggtcaa ggactacttc 1920
cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc 1980
ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 2040
agcagcttgg gcacgaagac ctacacctgc aacgtagatc acaagcccag caacaccaag 2100
gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag 2160
ttcgaagggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgatc 2220
tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga ccccgaggtc 2280
cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa gccgcgggag 2340
gagcagttca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 2400
ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc ctccatcgag 2460
aaaaccatct ccaaagccaa agggcagccc cgagagccac aggtgtacac cctgccccca 2520
tcccaggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctac 2580
cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc 2640
acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaggct aaccgtggac 2700
aagagcaggt ggcaggaggg gaatgtcttc tcatgctccg tgatgcatga ggctctgcac 2760
aaccactaca cacagaagag cctctccctg tctctgggta aagctagctg a 2811
<210> 59
<211> 469
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 59
Met Met Gly Trp Ser Tyr Ile Ile Leu Phe Leu Val Ala Thr Ala Thr
1 5 10 15
Asp Val His Ser Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val
20 25 30
Lys Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr
35 40 45
Phe Thr Ser Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Glu Gly
50 55 60
Leu Glu Trp Ile Gly Glu Ile Asn Pro Ser Tyr Gly Arg Thr Asp Tyr
65 70 75 80
Asn Glu Lys Phe Lys Asn Lys Ala Thr Leu Thr Val Ala Lys Ser Ser
85 90 95
Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala
100 105 110
Val Tyr Tyr Cys Ala Arg Gly Asp Tyr Tyr Gly Ser Ser Ser Phe Ala
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
225 230 235 240
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly
245 250 255
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
290 295 300
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
305 310 315 320
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
355 360 365
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
370 375 380
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
385 390 395 400
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
405 410 415
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
420 425 430
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
450 455 460
Leu Gly Lys Ala Ser
465
<210> 60
<211> 708
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 60
atggattttc aagtgcagat tttcagcttc ctgctaatga gtgcctcagt cataatgtcc 60
aggggacaaa ttgttctcac ccagtctcca gcactcatgt ctgcatctcc aggggagaag 120
gtcaccatga cctgcagtgc cagctcaaat ataagttaca tgtactggta ccagcagaag 180
ccaagatcct cccccaaacc ctggatttat ctcacatcca acctggcttc tggagtccct 240
gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaaccag cagcatggag 300
gctgaagatg ctgccactta ttgctgccag cagtggagta gtaacccacc cacgttcggt 360
gctgggacca agctcgagat caaacgaact 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 aaagtctatg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708
<210> 61
<211> 235
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 61
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Met Ser Ala Ser
1 5 10 15
Val Ile Met Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Ala Leu
20 25 30
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser
35 40 45
Ser Asn Ile Ser Tyr Met Tyr Trp Tyr Gln Gln Lys Pro Arg Ser Ser
50 55 60
Pro Lys Pro Trp Ile Tyr Leu Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Thr
85 90 95
Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Cys Cys Gln Gln Trp
100 105 110
Ser Ser Asn Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu 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> 62
<211> 708
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 62
atggattttc gagtgcagat tttcagcttc ctgctaatga gtgcctcagt cataatgtcc 60
aggggacaaa ttgttctcac ccagtctcca gcactcatgt ctgcatctcc aggggagaag 120
gtcaccatga cctgcagtgc cagctcaaat ataagttaca tgtactggta ccagcagaag 180
ccaagatcct cccccaaacc ctggatttat ctcacatcca acctggcttc tggagtccct 240
gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagcatggag 300
gctgaagatg ctgccactta ttactgccag cagtggagta gtaacccacc cacgttcggt 360
gctgggacca agctcgagat caaacgaact 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 aaagtctatg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708
<210> 63
<211> 235
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 63
Met Asp Phe Arg Val Gln Ile Phe Ser Phe Leu Leu Met Ser Ala Ser
1 5 10 15
Val Ile Met Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Ala Leu
20 25 30
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser
35 40 45
Ser Asn Ile Ser Tyr Met Tyr Trp Tyr Gln Gln Lys Pro Arg Ser Ser
50 55 60
Pro Lys Pro Trp Ile Tyr Leu Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
85 90 95
Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asn Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu 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> 64
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 64
atggagacag acacactcct gctatgggtg ctgctgctct gggttccagg ttccacaggt 60
gacattgtgc tgatccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 120
atatcctgca gagccagtga aagtgttgat agttatgtca atagttttat gcactggtac 180
cagcagaaac caggacagcc acccaaactc ctcatctatc gtgtatccaa cctagaatct 240
gggatccctg ccaggttcag tggcagtggg tctaggacag acttcaccct caccattaat 300
cctgtggagg ctgatgatgt tgcaacctat tactgtcagc aaagtaatga ggatccattc 360
acgttcggct cggggacaaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 65
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 65
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Ile Gln Ser Pro Ala Ser Leu Ala
20 25 30
Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser
35 40 45
Val Asp Ser Tyr Val Asn Ser Phe Met His Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Arg Val Ser Asn Leu Glu Ser
65 70 75 80
Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr
85 90 95
Leu Thr Ile Asn Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys
100 105 110
Gln Gln Ser Asn Glu Asp Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 66
<211> 1398
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 66
atggaatgta actggatact tccttttatt ctgtcggtaa tttcaggggt ctactcagag 60
gttcagctcc agcagtctgg gactgtgctg gcaaggcctg gggcttccgt gaatatgtcc 120
tgtaaggctg ctggctacag ctttaccagt tactgggtgt actgggtcaa acagaggcct 180
ggacagggtc tggaatggat tggtgctatt taccctaaaa atagtagaac tagctacaac 240
cagaagttcc aggacaaggc cacactgact gcagtcacat ccgccagcac tgcctacatg 300
gagctcagca gcctgacaaa tgaggactct gcggtctatt actgtacaag acctcactat 360
gattcgtttg gttactgggg ccaagggact ctggtcactg tctctgcagc caaaacaaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc 720
ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780
ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 840
gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900
cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960
gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020
aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080
gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140
ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1200
gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260
ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320
tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380
ctgggtaaag ctagctga 1398
<210> 67
<211> 465
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 67
Met Glu Cys Asn Trp Ile Leu Pro Phe Ile Leu Ser Val Ile Ser Gly
1 5 10 15
Val Tyr Ser Glu Val Gln Leu Gln Gln Ser Gly Thr Val Leu Ala Arg
20 25 30
Pro Gly Ala Ser Val Asn Met Ser Cys Lys Ala Ala Gly Tyr Ser Phe
35 40 45
Thr Ser Tyr Trp Val Tyr Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Ala Ile Tyr Pro Lys Asn Ser Arg Thr Ser Tyr Asn
65 70 75 80
Gln Lys Phe Gln Asp Lys Ala Thr Leu Thr Ala Val Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Asn Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Thr Arg Pro His Tyr Asp Ser Phe Gly Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
225 230 235 240
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val
245 250 255
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
260 265 270
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
275 280 285
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
290 295 300
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
305 310 315 320
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
325 330 335
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
340 345 350
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
355 360 365
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
370 375 380
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
385 390 395 400
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
405 410 415
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
420 425 430
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
435 440 445
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala
450 455 460
Ser
465
<210> 68
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 68
atggagacag acacactcct gctatgggtg ctgctgctct gggttccagg ttccacaggt 60
gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 120
atatcctgca gagccagtga aagtgtagat agttatggca ttagttttat gcactggtac 180
cagcagaaac caggacagcc acccaaactc ctcatctatc gtgcatccaa ccaagaatct 240
gggatccctg ccaggttcag tggcagtggg tctaggacag acttcaccct caccattaat 300
cctgtggagg ctgatgatgt tgcaacctat tactgtcagc aaagtaatga ggatccgctc 360
acgttcggtg ctgggaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 69
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 69
Met Glu Thr Asp Thr Leu 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 Ser Cys Arg Ala Ser Glu Ser
35 40 45
Val Asp Ser Tyr Gly Ile Ser Phe Met His Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Gln Glu Ser
65 70 75 80
Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr
85 90 95
Leu Thr Ile Asn Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys
100 105 110
Gln Gln Ser Asn Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 70
<211> 1422
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 70
atgaacaggc ttacttcctc attgctgctg ctgattgtcc ctgcatatgt cctgtcccag 60
gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgact 120
tgttctttct ctgggttttc actgagcact tctggtatgg gtgtgagctg gattcgtcag 180
ccttcaggaa agggtctgga gtggctggca cacatttact gggatgatga caagcgctat 240
aatccatccc tgaagagccg gctcacaatc tttaaggatc cctccagcaa ccaggtattc 300
ctcaggatca ccagtgtgga cactgcagat actgccacat actactgtgc tcgaaactcc 360
cattactacg gtagtactta cgggggatac ttcgatgtct ggggcgcagg gaccacggtc 420
accgtctcct cagccaaaac aaagggccca tccgtcttcc ccctggcgcc ctgctccagg 480
agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccg 540
gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 600
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 660
ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 720
agagttgagt ccaaatatgg tcccccatgc ccaccctgcc cagcacctga gttcgaaggg 780
ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc 840
cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac 900
tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc 960
aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc 1020
aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc 1080
tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag 1140
gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1200
atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1260
gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg 1320
tggcaggagg ggaatgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1380
acacagaaga gcctctccct gtctctgggt aaagctagct ga 1422
<210> 71
<211> 473
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 71
Asn Arg Leu Thr Ser Ser Leu Leu Leu Leu Ile Val Pro Ala Tyr Val
1 5 10 15
Leu Ser Gln 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 Ser Trp Ile Arg Gln Pro Ser Gly Lys
50 55 60
Gly Leu Glu Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr
65 70 75 80
Asn Pro Ser Leu Lys Ser Arg Leu Thr Ile Phe Lys Asp Pro Ser Ser
85 90 95
Asn Gln Val Phe Leu Arg Ile Thr Ser Val Asp Thr Ala Asp Thr Ala
100 105 110
Thr Tyr Tyr Cys Ala Arg Asn Ser His Tyr Tyr Gly Ser Thr Tyr Gly
115 120 125
Gly Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser
130 135 140
Ala Lys 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 Ser Leu Gly Thr Lys Thr
210 215 220
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
225 230 235 240
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
245 250 255
Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
260 265 270
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
275 280 285
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
290 295 300
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
305 310 315 320
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
325 330 335
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
340 345 350
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
355 360 365
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
370 375 380
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
385 390 395 400
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
405 410 415
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
420 425 430
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
435 440 445
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
450 455 460
Leu Ser Leu Ser Leu Gly Lys Ala Ser
465 470
<210> 72
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 72
atggagacag acacactcct gctatgggtg ctgctgctcg gggttccagg ttccacaggt 60
aacattgtgc tgacccagtc tccaacttct ttcactgtgt ctcttgggca gagggccacc 120
atatcctgca gagccagtga aagtgttcat agttatggca atagttttat gcactggtac 180
cagcagaaac cagggcagcc acccaaactc ctcatctatc ttgcatccaa cgtagaatct 240
ggggtccctg ccaggttcag tggtagtggg tccaggacag acttcaccct caccattgat 300
cctgtggagg ctgatgatgc tgcaacctat tactgtcagc aaaatagtga ggatccgtgg 360
acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 73
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 73
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Gly Val Pro
1 5 10 15
Gly Ser Thr Gly Asn Ile Val Leu Thr Gln Ser Pro Thr Ser Phe Thr
20 25 30
Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser
35 40 45
Val His Ser Tyr Gly Asn Ser Phe Met His Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Val Glu Ser
65 70 75 80
Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr
85 90 95
Leu Thr Ile Asp Pro Val Glu Ala Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gln Asn Ser Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 74
<211> 1398
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 74
atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60
gttcagctgc agcagtctgg aactgagctg atgaagcctg gggcctcagt gaagatatcc 120
tgcaaggcta ctggctacac attcagtacc tactggatag agtgggtaaa gcagaggcct 180
ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtaggac taacgacaat 240
gagaagttca agggcaaggc cacaatcact gcagatacat cctccaagaa agcctacatg 300
caactcagca gcctgacatc tgaggactct gccgtctatt actgtgcaag aaggggtggt 360
tactcctttg ctttctgggg ccaagggact ctggtctctg tctctgcagc caaaacaaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc 720
ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780
ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 840
gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900
cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960
gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020
aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080
gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140
ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1200
gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260
ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320
tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380
ctgggtaaag ctagctga 1398
<210> 75
<211> 465
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 75
Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Thr Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe
35 40 45
Ser Thr Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu
50 55 60
Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Arg Thr Asn Asp Asn
65 70 75 80
Glu Lys Phe Lys Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Lys
85 90 95
Lys Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Arg Gly Gly Tyr Ser Phe Ala Phe Trp Gly Gln
115 120 125
Gly Thr Leu Val Ser Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
225 230 235 240
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val
245 250 255
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
260 265 270
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
275 280 285
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
290 295 300
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
305 310 315 320
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
325 330 335
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
340 345 350
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
355 360 365
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
370 375 380
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
385 390 395 400
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
405 410 415
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
420 425 430
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
435 440 445
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala
450 455 460
Ser
465
<210> 76
<211> 711
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 76
atgaccatgt tctcactagc tcttctcctc agtcttcttc tcctctgtgt ctctgattct 60
agggcagaaa caactgtgac ccagtctcca gcatccctgt ccatggctat aggagaaaaa 120
gtcaccatca gatgcgtaac cagcactgat attgatgatg atgtgaactg gtaccagcag 180
aagccagggg aacctcctaa gctccttatt tcagaaggca atactcttcg tgctggagtc 240
ccatcccgat tctccagcag tggctatggt acagattttg tttttacaat tgagaacatg 300
ctctcagaag atgttgcaga ttactactgt ttgcaaagtg gtaacttgcc gtacacgttc 360
ggagggggga ccaagctcga gatcaaacga actgtggctg 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 atgcctgcga agtcacccat 660
cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgtta g 711
<210> 77
<211> 236
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 77
Met Thr Met Phe Ser Leu Ala Leu Leu Leu Ser Leu Leu Leu Leu Cys
1 5 10 15
Val Ser Asp Ser Arg Ala Glu Thr Thr Val Thr Gln Ser Pro Ala Ser
20 25 30
Leu Ser Met Ala Ile Gly Glu Lys Val Thr Ile Arg Cys Val Thr Ser
35 40 45
Thr Asp Ile Asp Asp Asp Val Asn Trp Tyr Gln Gln Lys Pro Gly Glu
50 55 60
Pro Pro Lys Leu Leu Ile Ser Glu Gly Asn Thr Leu Arg Ala Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Ser Ser Gly Tyr Gly Thr Asp Phe Val Phe Thr
85 90 95
Ile Glu Asn Met Leu Ser Glu Asp Val Ala Asp Tyr Tyr Cys Leu Gln
100 105 110
Ser Gly Asn Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu 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> 78
<211> 1422
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 78
atgaacaggc ttacttcctc attgctgctg ctgattgtcc ctgcatatgt cctgtcccag 60
gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgact 120
tgttctttct ctgggttttc actgagcact tctggtatgg gtctgagctg gattcgtcag 180
ccttcaggaa agggtctgga gtggctggca cacatttact gggatgatga caagcgctat 240
aacccatccc tgaagagccg gctcacaatc tccaaggata cctccagcaa ccaggttttc 300
ctcaagatca ccattgtgga cactgcagat gctgccacat actactgtgc tcgaagctcc 360
cattactacg gttatggcta cgggggatac ttcgatgtct ggggcgcagg gaccacggtc 420
accgtctcct cagccaaaac gaagggccca tccgtcttcc ccctggcgcc ctgctccagg 480
agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccg 540
gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 600
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 660
ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 720
agagttgagt ccaaatatgg tcccccatgc ccaccctgcc cagcacctga gttcgaaggg 780
ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc 840
cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac 900
tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc 960
aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc 1020
aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc 1080
tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag 1140
gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1200
atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1260
gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg 1320
tggcaggagg ggaatgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1380
acacagaaga gcctctccct gtctctgggt aaagctagct ga 1422
<210> 79
<211> 473
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 79
Met Asn Arg Leu Thr Ser Ser Leu 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 Leu Ser Trp Ile Arg Gln Pro Ser Gly Lys
50 55 60
Gly Leu Glu Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr
65 70 75 80
Asn Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser
85 90 95
Asn Gln Val Phe Leu Lys Ile Thr Ile Val Asp Thr Ala Asp Ala Ala
100 105 110
Thr Tyr Tyr Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr Gly
115 120 125
Gly Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser
130 135 140
Ala Lys 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 Ser Leu Gly Thr Lys Thr
210 215 220
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
225 230 235 240
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
245 250 255
Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
260 265 270
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
275 280 285
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
290 295 300
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
305 310 315 320
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
325 330 335
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
340 345 350
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
355 360 365
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
370 375 380
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
385 390 395 400
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
405 410 415
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
420 425 430
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
435 440 445
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
450 455 460
Leu Ser Leu Ser Leu Gly Lys Ala Ser
465 470
<210> 80
<211> 823
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 80
atggagacag acacactcct gctatgggtg ctgctgctct gggttccagg ttccacaggt 60
aacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 120
atatcctgca gagccagtga aagtattcat agttatggca atagttttct gcactggtac 180
cagcagaaac caggacagcc acccaaactc ctcatctatc ttgcatccaa cctagaatct 240
ggggtccctg ccaggttcag cggcagtggg tctaggacag acttcaccct caccattgat 300
cctgtggagg ctgatgatgc tgcaacctat tactgtcagc aaaataatga ggatccgtgg 360
acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttaggcg 720
gccgcactag cgcgggccgc attcgaagag ctcggtaccc ggggatcctc tagagtcgac 780
ctgcaggcat gcaagctggc cgcgactcta gatcataatc agc 823
<210> 81
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 81
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asn Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala
20 25 30
Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser
35 40 45
Ile His Ser Tyr Gly Asn Ser Phe Leu His Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Ser
65 70 75 80
Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr
85 90 95
Leu Thr Ile Asp Pro Val Glu Ala Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gln Asn Asn Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 82
<211> 1404
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 82
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gttcagctgc agcagtctgg ggctgagctt gtgaggccag gggccttagt caagttgtcc 120
tgcaaagctt ctggcttcaa cattaatgac tactatatcc actgggtgaa gcagcggcct 180
gaacagggcc tggagcggat tggatggatt gatcctgaca atggtaatac tatatatgac 240
ccgaagttcc agggcaaggc cagtataaca gcagacacat cccccaacac agcctacctg 300
cagctcagca gcctgacatc tgaggacact gccgtctatt actgtgctag aacccgatct 360
cctatggtta cgacggggtt tgtttactgg ggccaaggga ctgtggtcac tgtctctgca 420
gccaaaacga agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720
aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780
ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840
tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900
ggcgtggagg tgcataatgc caagacraag ccgcgggagg agcagttcaa cagcacgtac 960
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020
tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080
gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1200
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260
gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320
aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380
ctctccctgt ctctgggtaa atga 1404
<210> 83
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<220>
<221> misc_feature
<222> (309)..(309)
<223> Xaa can be any naturally occurring amino acid
<400> 83
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 Lys Ala Ser Gly Phe Asn Ile
35 40 45
Asn Asp Tyr Tyr Ile His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu
50 55 60
Glu Arg Ile Gly Trp Ile Asp Pro Asp Asn Gly Asn Thr Ile Tyr Asp
65 70 75 80
Pro Lys Phe Gln Gly Lys Ala Ser Ile Thr Ala Asp Thr Ser Pro 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 Arg Thr Arg Ser Pro Met Val Thr Thr Gly Phe Val
115 120 125
Tyr Trp Gly Gln Gly Thr Val Val Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
225 230 235 240
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly
245 250 255
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
290 295 300
His Asn Ala Lys Xaa Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
305 310 315 320
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
355 360 365
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
370 375 380
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
385 390 395 400
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
405 410 415
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
420 425 430
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
450 455 460
Leu Gly Lys
465
<210> 84
<211> 1425
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 84
atggaaaggc actggatctt tctcttcctg ttttcagtaa ctgcaggtgt ccactcccag 60
gtccagcttc agcagtctgg ggctgagctg gcaaaacctg gggcctcagt gaagatgtcc 120
tgcaaggctt ctggctacac ctttactacc tactggatgc actgggtaaa acagaggcct 180
ggacagggtc tggaatggat tggatacatt aatcctatca ctggttatac tgagtacaat 240
cagaagttca aggacaaggc caccttgact gcagacaaat cctccagcac agcctacatg 300
caactgagca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagggttta 360
agtgctatgg actattgggg tcagggaacc tcagtcaccg tcacctcagc caaaacaaca 420
gccccatcgg tctatccact ggcccctgtg tgtggagata caactggctc ctcggtaact 480
ctaggatgcc tggtcaaggg ttatttccct gagccagtga ccttgacctg gaactctgga 540
tccctgtcca gtggtgtgca caccttccca gctgtcctgc agtctgacct ctacaccctc 600
agcagctcag tgactgtaac ctcgagcacc tggcccagcc agaccgtcac ctgcagcgtt 660
gctcacccag ccagcagcac cacggtggac aaaaaacttg agcccagcgg gcccatttca 720
acaatcaacc cctgtcctcc atgcaaggag tgtcacaaat gcccagctcc taacctcgag 780
ggtggaccat ccgtcttcat cttccctcca aatatcaagg atgtactcat gatctccctg 840
acacccaagg tcacgtgtgt ggtggtggat gtgagcgagg atgacccaga cgtccagatc 900
agctggtttg tgaacaacgt ggaagtacac acagctcaga cacaaaccca tagagaggat 960
tacaacagta ctatccgggt ggtcagcacc ctccccatcc agcaccagga ctggatgagt 1020
ggcaaggagt tcaaatgcaa ggtcaacaac aaagacctcc catcacccat cgagagaacc 1080
atctcaaaaa ttaaagggct agtcagagct ccacaagtat acatcttgcc gccaccagca 1140
gagcagttgt ccaggaaaga tgtcagtctc acttgcctgg tcgtgggctt caaccctgga 1200
gacatcagtg tggagtggac cagcaatggg catacagagg agaactacaa ggacaccgca 1260
ccagtcctgg actctgacgg ttcttacttc atatatagca agctcaatat gaaaacaagc 1320
aagtgggaga aaacagattc cttctcatgc aacgtgagac acgagggtct gaaaaattac 1380
tacctgaaga agaccatctc ccggtctccg ggtaaagcta gctga 1425
<210> 85
<211> 474
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 85
Met Glu Arg His Trp Ile Phe Leu Phe Leu Phe Ser Val Thr Ala Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Thr Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Ile Thr Gly Tyr Thr Glu Tyr Asn
65 70 75 80
Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Gly Leu Ser Ala Met Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Ser Val Thr Val Thr Ser Ala Lys Thr Thr Ala Pro Ser Val
130 135 140
Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr
145 150 155 160
Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr
165 170 175
Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val
180 185 190
Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser
195 200 205
Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Ser Val Ala His Pro Ala
210 215 220
Ser Ser Thr Thr Val Asp Lys Lys Leu Glu Pro Ser Gly Pro Ile Ser
225 230 235 240
Thr Ile Asn Pro Cys Pro Pro Cys Lys Glu Cys His Lys Cys Pro Ala
245 250 255
Pro Asn Leu Glu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Ile
260 265 270
Lys Asp Val Leu Met Ile Ser Leu Thr Pro Lys Val Thr Cys Val Val
275 280 285
Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val
290 295 300
Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp
305 310 315 320
Tyr Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Gln His Gln
325 330 335
Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp
340 345 350
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ile Lys Gly Leu Val
355 360 365
Arg Ala Pro Gln Val Tyr Ile Leu Pro Pro Pro Ala Glu Gln Leu Ser
370 375 380
Arg Lys Asp Val Ser Leu Thr Cys Leu Val Val Gly Phe Asn Pro Gly
385 390 395 400
Asp Ile Ser Val Glu Trp Thr Ser Asn Gly His Thr Glu Glu Asn Tyr
405 410 415
Lys Asp Thr Ala Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Ile Tyr
420 425 430
Ser Lys Leu Asn Met Lys Thr Ser Lys Trp Glu Lys Thr Asp Ser Phe
435 440 445
Ser Cys Asn Val Arg His Glu Gly Leu Lys Asn Tyr Tyr Leu Lys Lys
450 455 460
Thr Ile Ser Arg Ser Pro Gly Lys Ala Ser
465 470
<210> 86
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 86
atgggcatca agatggagtc acggattcag gcatttgtat tcgtgtttct ctggttgtct 60
ggtgttggcg gagacattgt gatgacccag tctcacaaat tcatgtccac atcagtagga 120
gacagggtca gcgtcacctg caaggccagt caggatgtga cttctgctgt agcctggtat 180
caacaaaaac cagggcaatc tcctaaacta ctgatttact gggcatccac ccggcacact 240
ggagtccctg atcgcttcac aggcagtgga tctgggacag attatactct caccatcagc 300
agtgggcagg ctgaagacct ggcactttat tactgtcacc aatattatag cgctcctcgg 360
acgttcggtg gaggcaccaa gctggaagtc 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 acccatcgtc aagagcttca ataggaatga gtgttag 717
<210> 87
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 87
Met Glu Ser Arg Ile Gln Ala Phe Val Phe Val Phe Leu Trp Leu Ser
1 5 10 15
Gly Val Gly Gly Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser
20 25 30
Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asp
35 40 45
Val Thr Ser 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 Tyr Thr Leu Thr Ile Ser
85 90 95
Ser Gly Gln Ala Glu Asp Leu Ala Leu Tyr Tyr Cys His Gln Tyr Tyr
100 105 110
Ser Ala Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Val 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> 88
<211> 1398
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 88
atggaaaggc actggatctt tctcttcctg ttttcagtaa ctgcaggtgt ccactcccag 60
gtccagcttc agcagtctgg ggctgagctg gcaaaacctg gggcctcagt gaagatgtcc 120
tgcaaggctt ctggctacac ctttactacc tactggatgc actgggtaaa acagaggcct 180
ggacagggtc tggaatggat tggatacatt aatcctatca ctggttatac tgagtacaat 240
cagaagttca aggacaaggc caccttgact gcagacaaat cctccagcac agcctacatg 300
caactgagca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagggttta 360
agtgctatgg actattgggg tcagggaacc tcagtcaccg tcacctcagc caaaacaacg 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc 720
ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780
ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 840
gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900
cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960
gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020
aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080
gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140
ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1200
gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260
ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320
tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380
ctgggtaaag ctagctga 1398
<210> 89
<211> 465
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 89
Met Glu Arg His Trp Ile Phe Leu Phe Leu Phe Ser Val Thr Ala Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Thr Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Ile Thr Gly Tyr Thr Glu Tyr Asn
65 70 75 80
Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Gly Leu Ser Ala Met Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Ser Val Thr Val Thr Ser Ala Lys Thr Thr 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
225 230 235 240
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val
245 250 255
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
260 265 270
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
275 280 285
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
290 295 300
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
305 310 315 320
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
325 330 335
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
340 345 350
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
355 360 365
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
370 375 380
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
385 390 395 400
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
405 410 415
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
420 425 430
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
435 440 445
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala
450 455 460
Ser
465
<210> 90
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 90
atgggcatca agatggagtc acagattcag gcatttgtat tcgtgtttct ctggttgtct 60
ggtgttggcg gagacattgt gatgacccag tctcacaaat tcatgtccac atcagtagga 120
gacagggtca gcgtcacctg caaggccagt caggatgtga cttctgctgt agcctggtat 180
caacaaaaac cagggcaatc tcctaaacta ctgatttact gggcatccac ccggcacact 240
ggagtccctg atcgcttcac aggcagtgga tctgggacag attatactct caccatcagc 300
agtgggcagg ctgaagacct ggcactttat tactgtcacc aatattatag cgctcctcgg 360
acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 91
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 91
Met Glu Ser Gln Ile Gln Ala Phe Val Phe Val Phe Leu Trp Leu Ser
1 5 10 15
Gly Val Gly Gly Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser
20 25 30
Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asp
35 40 45
Val Thr Ser 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 Tyr Thr Leu Thr Ile Ser
85 90 95
Ser Gly Gln Ala Glu Asp Leu Ala Leu Tyr Tyr Cys His Gln Tyr Tyr
100 105 110
Ser Ala Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 92
<211> 1401
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 92
atggctgtcc tggcactact cctctgcctg gtggctttcc caacttgtac cctgtcccag 60
gtgcaactga aggagtcagg acctggcctg gtggcgccct cacagagcct gtccattacc 120
tgctctgtct ctgggttctc attaagcaac tatgatataa gctggattcg ccagccacca 180
ggaaagggtc tggagtggct tggagtaatg tggactggtg gaggcgcaaa ttataattca 240
gctttcatgt ccagactgag catcaacaag gacaactcca agagccaagt ttttttaaaa 300
atgaacaatc tgcaaactga tgacacagcc atttattact gtgtcagaga tgcggtgagg 360
tactggaact tcgatgtctg gggcgcaggg accacggtca ccgtctcctc agccaaaacg 420
aagggcccat ccgtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc 480
gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 540
ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 600
tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 660
aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 720
cccccatgcc caccctgccc agcacctgag ttcgaagggg gaccatcagt cttcctgttc 780
cccccaaaac ccaaggacac tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg 840
gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag 900
gtgcataatg ccaagacaaa gccgcgggag gagcagttca acagcacgta ccgtgtggtc 960
agcgtcctca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc 1020
tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc 1080
cgagagccac aggtgtacac cctgccccca tcccaggagg agatgaccaa gaaccaggtc 1140
agcctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc 1200
aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1260
ttcttcctct acagcaggct aaccgtggac aagagcaggt ggcaggaggg gaatgtcttc 1320
tcatgctccg tgatgcatga ggctctgcac aaccactaca cacagaagag cctctccctg 1380
tctctgggta aagctagctg a 1401
<210> 93
<211> 466
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 93
Met Ala Val Leu Ala Leu Leu Leu Cys Leu Val Ala Phe Pro Thr Cys
1 5 10 15
Thr Leu Ser Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala
20 25 30
Pro Ser Gln Ser Leu Ser Ile Thr Cys Ser Val Ser Gly Phe Ser Leu
35 40 45
Ser Asn Tyr Asp Ile Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu
50 55 60
Glu Trp Leu Gly Val Met Trp Thr Gly Gly Gly Ala Asn Tyr Asn Ser
65 70 75 80
Ala Phe Met Ser Arg Leu Ser Ile Asn Lys Asp Asn Ser Lys Ser Gln
85 90 95
Val Phe Leu Lys Met Asn Asn Leu Gln Thr Asp Asp Thr Ala Ile Tyr
100 105 110
Tyr Cys Val Arg Asp Ala Val Arg Tyr Trp Asn Phe Asp Val Trp Gly
115 120 125
Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
145 150 155 160
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
165 170 175
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
180 185 190
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
195 200 205
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
210 215 220
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
225 230 235 240
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
260 265 270
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
275 280 285
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
450 455 460
Ala Ser
465
<210> 94
<211> 708
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 94
atggattttc aagcgcagat tttcagcttc ctgctaatca gtgcttcagt cataatgtcc 60
agaggacaaa ttgttctctc ccagtcacca gcaatcctgt ctgcatctcc aggggagaag 120
gtcacaatga cttgcagggc cagctcaagt gtaagttaca tacactggta ccagcagaag 180
ccaggatcct cccccaaacc ctggatttat gccacatccc acctggcttc tggagtccct 240
gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagagtggag 300
gctgaagata ctgccactta ttactgccag cagtggagta gtaacccatt cacgttcggc 360
tcggggacaa agctcgagat caaacgaact 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 aaagtctatg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708
<210> 95
<211> 235
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 95
Met Asp Phe Gln Ala 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 Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser
35 40 45
Ser Ser Val Ser Tyr Ile His Trp Tyr Gln Gln Lys Pro Gly Ser Ser
50 55 60
Pro Lys Pro Trp Ile Tyr Ala Thr Ser His Leu Ala Ser Gly Val Pro
65 70 75 80
Ala 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 Thr Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asn Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu 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> 96
<211> 1410
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 96
atggaaaggc actggatctt tctactcctg ttgtcagtaa ctgcaggtgt ccactcccag 60
gtccagctgc agcagtctgg ggctgaactg gcaagacctg gggcctcagt gaagatgtcc 120
tgcaaggctt ctggctacac ctttactacc tacactatgc actgggtaaa acagaggcct 180
ggacagggtc tggaatggat tggatacatt aatcctagca gtggttatac taattacaat 240
cagaagttca aggacaaggc cacattgact gcagacaaat cctccagcac agcctccatg 300
caactgagca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagagggcg 360
gtattagtcc cctatgctat ggactactgg ggtcaaggaa cctcagtcac cgtctcctca 420
gccaaaacaa agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720
aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780
ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840
tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900
ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 960
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020
tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080
gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1200
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260
gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320
aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380
ctctccctgt ctctgggtaa agctagctga 1410
<210> 97
<211> 469
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 97
Met Glu Arg His Trp Ile Phe Leu Leu Leu Leu Ser Val Thr Ala Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Thr Tyr Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Ser Ser Gly Tyr Thr Asn Tyr Asn
65 70 75 80
Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser
85 90 95
Thr Ala Ser Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Arg Ala Val Leu Val Pro Tyr Ala Met Asp
115 120 125
Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
225 230 235 240
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly
245 250 255
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
290 295 300
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
305 310 315 320
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
355 360 365
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
370 375 380
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
385 390 395 400
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
405 410 415
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
420 425 430
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
450 455 460
Leu Gly Lys Ala Ser
465
<210> 98
<211> 708
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 98
atgcattttc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt cataatgtcc 60
agaggacaaa ttgttctcac ccagtctcca gcagtcatgt ctgcatctcc aggggagaag 120
gtcaccataa cctgcactgc cagctcaagt ttaagttaca tgcactggtt ccagcagaag 180
ccaggcactt ctcccaaact ctggctttat agcacatcca tcctggcttc tggagtccct 240
actcgcttca gtggcagtgg atctgggacc tcttactctc tcacaatcag ccgaatggag 300
gctgaagatg ctgccactta ttactgccag caaaggagta gttccccatt cacgttcggc 360
tcggggacaa agctcgagat caaacgaact 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 aaagtctatg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708
<210> 99
<211> 235
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 99
Met His 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 Thr Gln Ser Pro Ala Val
20 25 30
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Ile Thr Cys Thr Ala Ser
35 40 45
Ser Ser Leu Ser Tyr Met His Trp Phe Gln Gln Lys Pro Gly Thr Ser
50 55 60
Pro Lys Leu Trp Leu Tyr Ser Thr Ser Ile Leu Ala Ser Gly Val Pro
65 70 75 80
Thr Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr 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 Ser Ser Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu 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> 100
<211> 1404
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 100
atgggatgga cctggatctt tattttaatc ctgtcagtta ctacaggtgt ccactctgag 60
gtccagctgc agcagtctgg acctgagctg gagaagcctg gcgcttcagt gaagatatcc 120
tgcaaggctt ctggttactc cttcactggc tacaacatga actgggtgaa acagagcaat 180
ggaaagagcc ttgagtggat tggaaatatt gatccttact atggtgatac taactacaac 240
cagaagttca agggcaaggc cacattgact gtagacaaat cctccagcac agcctacatg 300
cacctcaaga gcctgacatc tgaggactct gcagtctatt actgtgcaag accctacggt 360
agtgaggcct actttgctta ctggggccaa gggactctgg tcactgtctc tgcagccaaa 420
acgaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720
ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg 780
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 960
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380
ctgtctctgg gtaaagctag ctga 1404
<210> 101
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 101
Met Gly Trp Thr Trp Ile Phe Ile Leu Ile Leu Ser Val Thr Thr Gly
1 5 10 15
Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Glu Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe
35 40 45
Thr Gly Tyr Asn Met Asn Trp Val Lys Gln Ser Asn Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asn Ile Asp Pro Tyr Tyr Gly Asp Thr Asn 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 His Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Pro Tyr Gly Ser Glu Ala Tyr Phe Ala Tyr Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr
225 230 235 240
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Gln 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 Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Glu 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 Leu Gly
450 455 460
Lys Ala Ser
465
<210> 102
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 102
atggtgtcca cttctcagct ccttggactt ttgcttttct ggacttcagc ctccagatgt 60
gacattgtga tgactcagtc tccagccacc ctgtctgtga ctccaggaga tagagtctct 120
ctttcctgca gggccagcca gagtattagc gactacttac actggtatca acaaaaatca 180
catgagtctc caaggcttct catcaaatat gctgcccaat ccatctctgg gatcccctcc 240
aggttcagtg gcagtggatc agggtcagat ttcactctca gtatcaacgg tgtggaacct 300
gaagatgttg gagtgtatta ctgtcaaaat ggtcacagct ttccgtacac gttcggaggg 360
gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 103
<211> 214
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 103
Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Thr Pro Gly
1 5 10 15
Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Asp Tyr
20 25 30
Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu Leu Ile
35 40 45
Lys Tyr Ala Ala Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Ser Asp Phe Thr Leu Ser Ile Asn Gly Val Glu Pro
65 70 75 80
Glu Asp Val Gly Val Tyr Tyr Cys Gln Asn Gly His Ser Phe Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu 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> 104
<211> 1395
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 104
atggaatgga ggatctttct cttcatcctg tcaggaactg caggtgtcca ctcccaggtt 60
cagctgcggc agtctggacc tgagctggtg aagcctgggg cttcagtgaa gatgtcctgc 120
aaggcttctg gatacacatt tactgactat gttataagtt gggtgaagca gagaactgga 180
cagggccttg agtggattgg agatatttat cctggaagtg gttattcttt ctacaatgag 240
aacttcaagg gcaaggccac actgactgca gacaaatcct ccaccacagc ctacatgcag 300
ctcagcagcc tgacatctga ggactctgcg gtctatttct gtgcaaccta ctataactac 360
ccttttgctt actggggcca agggactctg gtcactgtct ctgcagccaa aacaacgggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 540
ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgaccgtgcc ctccagcagc ttgggcacga agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 720
tgcccaccct gcccagcacc tgagttcgaa gggggaccat cagtcttcct gttcccccca 780
aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 900
aatgccaaga caaagccgcg ggaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc 960
ctcaccgtcc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag 1080
ccacaggtgt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1260
ctctacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacacaga agagcctctc cctgtctctg 1380
ggtaaagcta gctga 1395
<210> 105
<211> 446
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 105
Gln Val Gln Leu Arg 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
Val Ile Ser Trp Val Lys Gln Arg Thr Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Tyr Pro Gly Ser Gly Tyr Ser Phe Tyr Asn Glu Asn Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Thr Tyr Tyr Asn Tyr Pro Phe Ala Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ala Ala Lys Thr Thr Gly Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys
130 135 140
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser
180 185 190
Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn
195 200 205
Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala Ser
435 440 445
<210> 106
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 106
atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60
gttgtgatga cccaaactcc actctccctg cctgtccgtc ttggagatca agcctccatc 120
tcttgcagat ctagtcagag ccttgtacac agtaatggaa acacctattt acattggtac 180
ctgcagaagc caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240
ggggtcccag acaggttcag tggcagtgga tcagggacaa atttcacact caagatcagc 300
agagtggagg ctgaggatct gggactttat ttctgctctc aaagtacaca tgttccgtac 360
acgttcggag gggggaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 107
<211> 219
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 107
Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Arg Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asn Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Leu Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 108
<211> 1410
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 108
atgacattga acatgctgtt ggggctgagg tgggttttct ttgttgtttt ttatcaaggt 60
gtgcattgtg aggtgcagct tgttgagtct ggtggaggat tggtgcagcc taaagggtca 120
ttgaaactct catgtgcagc ctctggatta accttcaata tctacgccat gaactgggtc 180
cgccaggctc caggaaaggg tttggaatgg gttgctcgca taagaaataa aagtaataat 240
tatgcaacat attatgccga ttcagtgaaa gacaggttca ccatctccag agatgattca 300
caaagcttgc tctatctgca aatgaacaac ttgaaaactg aggacacagc catgtattac 360
tgtgtgggac gggactggtt tgattactgg ggccaaggga ctctggtcac tgtctctgca 420
gccaaaacga agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720
aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780
ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840
tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900
ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 960
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020
tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080
gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1200
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260
gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320
aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380
ctctccctgt ctctgggtaa agctagctga 1410
<210> 109
<211> 469
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 109
Met Thr Leu Asn Met Leu Leu Gly Leu Arg Trp Val Phe Phe Val Val
1 5 10 15
Phe Tyr Gln Gly Val His Cys Glu Val Gln Leu Val Glu Ser Gly Gly
20 25 30
Gly Leu Val Gln Pro Lys Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
35 40 45
Gly Leu Thr Phe Asn Ile Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
50 55 60
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Asn Lys Ser Asn Asn
65 70 75 80
Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
85 90 95
Arg Asp Asp Ser Gln Ser Leu Leu Tyr Leu Gln Met Asn Asn Leu Lys
100 105 110
Thr Glu Asp Thr Ala Met Tyr Tyr Cys Val Gly Arg Asp Trp Phe Asp
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
225 230 235 240
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly
245 250 255
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
275 280 285
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
290 295 300
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
305 310 315 320
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
355 360 365
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
370 375 380
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
385 390 395 400
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
405 410 415
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
420 425 430
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
450 455 460
Leu Gly Lys Ala Ser
465
<210> 110
<211> 708
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 110
atggcctgga tttcacttat actctctctc ctggctctca gctcaggggc catttcccag 60
gctgttgtga ctcaggaatc tgcactcacc acatcacctg gtgaaacagt cacactcact 120
tgtcgctcaa gtactggggc tgttacaact agtaactatg ccaactgggt ccaagaaaaa 180
ccagatcatt tattcactgg tctaataggt ggtaccaaca accgagtttc aggtgttcct 240
gccagattct caggctccct gattggagac aaggctgccc tcaccatcac aggggcacag 300
actgaggatg aggcaatata tttctgtgct ctatggtaca gcaaccattg ggtgttcggt 360
ggaggaacca aactcgagat caaacgaact 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 aaagtctatg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708
<210> 111
<211> 235
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 111
Met Ala Trp Ile Ser Leu Ile Leu Ser Leu Leu Ala Leu Ser Ser Gly
1 5 10 15
Ala Ile Ser Gln Ala Val Val Thr Gln Glu Ser Ala Leu Thr Thr Ser
20 25 30
Pro Gly Glu Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val
35 40 45
Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Asp His Leu
50 55 60
Phe Thr Gly Leu Ile Gly Gly Thr Asn Asn Arg Val Ser Gly Val Pro
65 70 75 80
Ala Arg Phe Ser Gly Ser Leu Ile Gly Asp Lys Ala Ala Leu Thr Ile
85 90 95
Thr Gly Ala Gln Thr Glu Asp Glu Ala Ile Tyr Phe Cys Ala Leu Trp
100 105 110
Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu 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> 112
<211> 1386
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 112
atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60
gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120
tgcaaggcta ctggctacac attcggtagc tactggatag agtgggtaaa gcagaggcct 180
ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtaatac taactacaat 240
gagaacttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300
caactcacca gtctgacatc tgaggactct gccgtctatt actgtgctag ggcggggatt 360
tattggggcc aagggactct ggtcactgtc tctgcagcca aaacgaaggg cccatccgtc 420
ttccccctgg cgccctgctc caggagcacc tccgagagca cagccgccct gggctgcctg 480
gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc 540
ggcgtgcaca ccttcccggc tgtcctacag tcctcaggac tctactccct cagcagcgtg 600
gtgaccgtgc cctccagcag cttgggcacg aagacctaca cctgcaacgt agatcacaag 660
cccagcaaca ccaaggtgga caagagagtt gagtccaaat atggtccccc atgcccaccc 720
tgcccagcac ctgagttcga agggggacca tcagtcttcc tgttcccccc aaaacccaag 780
gacactctca tgatctcccg gacccctgag gtcacgtgcg tggtggtgga cgtgagccag 840
gaagaccccg aggtccagtt caactggtac gtggatggcg tggaggtgca taatgccaag 900
acaaagccgc gggaggagca gttcaacagc acgtaccgtg tggtcagcgt cctcaccgtc 960
ctgcaccagg actggctgaa cggcaaggag tacaagtgca aggtctccaa caaaggcctc 1020
ccgtcctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga gccacaggtg 1080
tacaccctgc ccccatccca ggaggagatg accaagaacc aggtcagcct gacctgcctg 1140
gtcaaaggct tctaccccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1200
aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc 1260
aggctaaccg tggacaagag caggtggcag gaggggaatg tcttctcatg ctccgtgatg 1320
catgaggctc tgcacaacca ctacacacag aagagcctct ccctgtctct gggtaaagct 1380
agctga 1386
<210> 113
<211> 461
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 113
Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe
35 40 45
Gly Ser Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu
50 55 60
Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Asn Thr Asn Tyr Asn
65 70 75 80
Glu Asn Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Met Gln Leu Thr Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ala Gly Ile Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Lys Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu
145 150 155 160
Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
165 170 175
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser
180 185 190
Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu
195 200 205
Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr
210 215 220
Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro
225 230 235 240
Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro
245 250 255
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
260 265 270
Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn
275 280 285
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
290 295 300
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
305 310 315 320
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
325 330 335
Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys
340 345 350
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu
355 360 365
Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
370 375 380
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
385 390 395 400
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
405 410 415
Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly
420 425 430
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
435 440 445
Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala Ser
450 455 460
<210> 114
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 114
atggagaaag acacactcct gctatgggtc ctgcttctct gggttccagg ttccacaggt 60
gacattgtgc tgacccaatc tccagctttt ttggctgtgt ctctagggca gagggccacc 120
atctcctgca gagccagcga aagtgttgat aattatggca ttagttttat gaactggttc 180
caacagaaac caggacagcc acccaaactc ctcatctatg ttgcatccaa gcaaggatcc 240
ggggtccctg ccaggtttag tggcagtggg tctgggacag acttcagcct caacatccat 300
cctatggagg aggatgatac tgcaatgtat ttctgtcagc aaagtaagga ggttcctcgg 360
acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 115
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 115
Met Glu Lys Asp Thr Leu 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 Phe Leu Ala
20 25 30
Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser
35 40 45
Val Asp Asn Tyr Gly Ile Ser Phe Met Asn Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Val Ala Ser Lys Gln Gly Ser
65 70 75 80
Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser
85 90 95
Leu Asn Ile His Pro Met Glu Glu Asp Asp Thr Ala Met Tyr Phe Cys
100 105 110
Gln Gln Ser Lys Glu Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 116
<211> 1392
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 116
atggaatgta actggatact tccttttatt ctgtcggtaa cttcaggggt ctactcagag 60
gttcagctcc agcagtctgg gactgtgctg gcaaggcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggctacac ctttaccagc tactggatgc actgggtaaa acagaggcct 180
ggacagggtc tggaatggat tggcgctatt tatcctggaa atagtgatac tacctacaac 240
cagaagttca agggcaaggc caaactgact gcagtcacat ccaccagcac tgcctacatg 300
gagctcagca gcctgacaaa tgaggactct gcggtctatt actgtacacc tacttactac 360
tttgactact ggggccaagg cacctctctc acagtctcct cagccaaaac gaagggccca 420
tccgtcttcc ccctggcgcc ctgctccagg agcacctccg agagcacagc cgccctgggc 480
tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg 540
accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 600
agcgtggtga ccgtgccctc cagcagcttg ggcacgaaga cctacacctg caacgtagat 660
cacaagccca gcaacaccaa ggtggacaag agagttgagt ccaaatatgg tcccccatgc 720
ccaccctgcc cagcacctga gttcgaaggg ggaccatcag tcttcctgtt ccccccaaaa 780
cccaaggaca ctctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccaggaag accccgaggt ccagttcaac tggtacgtgg atggcgtgga ggtgcataat 900
gccaagacaa agccgcggga ggagcagttc aacagcacgt accgtgtggt cagcgtcctc 960
accgtcctgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccgt cctccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagagcca 1080
caggtgtaca ccctgccccc atcccaggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc 1260
tacagcaggc taaccgtgga caagagcagg tggcaggagg ggaatgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acacagaaga gcctctccct gtctctgggt 1380
aaagctagct ga 1392
<210> 117
<211> 463
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 117
Met Glu Cys Asn Trp Ile Leu Pro Phe Ile Leu Ser Val Thr Ser Gly
1 5 10 15
Val Tyr Ser Glu Val Gln Leu Gln Gln Ser Gly Thr Val Leu Ala Arg
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Ala Ile Tyr Pro Gly Asn Ser Asp Thr Thr Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Lys Leu Thr Ala Val Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Asn Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Thr Pro Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Ser Leu Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
225 230 235 240
Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
340 345 350
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Gln 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 Val Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Glu 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 Leu Gly Lys Ala Ser
450 455 460
<210> 118
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 118
atgagtcctg cccaattcct gtttctgtta gtgctctgga ttcgggaaac caacggtgat 60
gttgtgatga cccagactcc actcactttg tcggttacca ttggacaacc agcctccatc 120
tcttgcaagt caagtcagag cctcttagat agtgatggaa agacatattt gaattggttc 180
ttacagaggc caggccagtc tccaaagcgc ctaatctatc tggtgtctaa actggactct 240
ggagtccctg acaggttcac tggcagtgga tcagggacag atttcacact gaaaatcagc 300
agagtggagg ctgaggattt gggagtttat tattgctggc aaggtacaca ttttccgtgg 360
acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 119
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 119
Met Ser Pro Ala Gln Phe Leu Phe Leu Leu Val Leu Trp Ile Arg Glu
1 5 10 15
Thr Asn Gly Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val
20 25 30
Thr Ile Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu
35 40 45
Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Phe Leu Gln Arg Pro
50 55 60
Gly Gln Ser Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser
65 70 75 80
Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys
100 105 110
Trp Gln Gly Thr His Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 120
<211> 1415
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 120
atgggaggga tctggatctt tctcttcctc ctgtcaggaa ctgcaggtgc ccactctgag 60
atccagctgc agcagactgg acctgagctg gtgaagcctg gggcttcagt gaagatatcc 120
tgcaaggctt ctggttatcc attcactgac tacatcatgg tctgggtgaa gcagagccat 180
ggaaagagcc ttgagtggat tggaaatatt agtccttact atggtactac taactacaat 240
ctgaagttca agggcaaggc cacattgact gtagacaaat cttccagcac agcctacatg 300
cagctcaaca gtctgacatc tgaggactct gcagtctatt actgtgcaag atcccctaac 360
tgggacgggg cctggtttgc tcactggggc caaggggctc tggtcactgt ctctgcagcc 420
aaaacaaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 600
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac gaagacctac 660
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa 720
tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc 780
ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 840
gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 900
gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt 960
gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 1020
aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1080
cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac 1140
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200
gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260
ggctccttct tcctctacag caggctaacc gtggacaaga gcaggtggca ggaggggaat 1320
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc 1380
tccctgtctc tgggtaaagc tagctgatta attaa 1415
<210> 121
<211> 468
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 121
Met Gly Gly Ile Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Ala His Ser Glu Ile Gln Leu Gln Gln Thr Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Pro Phe
35 40 45
Thr Asp Tyr Ile Met Val Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asn Ile Ser Pro Tyr Tyr Gly Thr Thr Asn Tyr Asn
65 70 75 80
Leu 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 Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Pro Asn Trp Asp Gly Ala Trp Phe Ala His
115 120 125
Trp Gly Gln Gly Ala Leu Val Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val
210 215 220
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys
225 230 235 240
Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg
305 310 315 320
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
340 345 350
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
355 360 365
Thr Leu Pro Pro Ser Gln 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 Val
405 410 415
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp
420 425 430
Lys Ser Arg Trp Gln Glu 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 Leu
450 455 460
Gly Lys Ala Ser
465
<210> 122
<211> 717
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 122
atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60
gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 120
atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggttc 180
caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 240
gggatcccag ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat 300
cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtaatga ggatccattc 360
acgttcggct cggggacaaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717
<210> 123
<211> 238
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 123
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 Ser Cys Lys Ala Ser Gln Ser
35 40 45
Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Phe 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 Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gln Ser Asn Glu Asp Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 124
<211> 1403
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 124
atggctgtcc tggggctgct tctctgcctg gtgacgttcc caagctgtgt cctgtcccag 60
gtgcagctga aggagtcagg acctggcctg gtggcaccct cacagagcct gtccatcaca 120
tgcactgtct ctgggttctc attatccaga tatagtgtat tttgggttcg ccagcctcca 180
ggaaagggtc tggagtggct gggattgata tggggtggtg gaagcacaga ctataattca 240
gctctcaaat ccagactgag catcagcaag gacaactcca agagccaagt tttcttaaaa 300
atgaacagtc tgcaaactga tgacacagcc atgtactact gtgccagaat ctactttgat 360
tacgacgggg ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa 420
acaacgggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720
ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg 780
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 960
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380
ctgtctctgg gtaaagctag ctg 1403
<210> 125
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 125
Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala
20 25 30
Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu
35 40 45
Ser Arg Tyr Ser Val Phe Trp Val Arg Gln Pro Pro Gly Lys Gly Leu
50 55 60
Glu Trp Leu Gly Leu Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser
65 70 75 80
Ala Leu Lys Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln
85 90 95
Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Met Tyr
100 105 110
Tyr Cys Ala Arg Ile Tyr Phe Asp Tyr Asp Gly Ala Met Asp Tyr Trp
115 120 125
Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr
225 230 235 240
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Gln 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 Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Glu 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 Leu Gly
450 455 460
Lys Ala Ser
465
<210> 126
<211> 732
<212> DNA
<213> Artificial sequence
<220>
<223> Syntehtic oligonucleotide.
<400> 126
atgcatcgca ccagcatggg catcaagatg gagtcacgga ttcaggcatt tgtattcgtg 60
tttctctggt tgtctggtgt tggcggagac attgtgatga cccagtctca caaattcatg 120
tccacatcag taggagacag ggtcagcgtc acctgcaagg ccagtcagga tgtgacttct 180
gctgtagcct ggtatcaaca aaaaccaggg caatctccta aactactgat ttactgggca 240
tccacccggc acactggagt ccctgatcgc ttcacaggca gtggatctgg gacagattat 300
actctcacca tcagcagtgg gcaggctgaa gacctggcac tttattactg tcaccaatat 360
tatagcgctc ctcggacgtt cggtggaggc accaagctcg agatcaaacg aactgtggct 420
gcaccatctg tcttcatctt cccgccatct gatgagcagt tgaaatctgg aactgcctct 480
gttgtgtgcc tgctgaataa cttctatccc agagaggcca aagtacagtg gaaggtggat 540
aacgccctcc aatcgggtaa ctcccaggag agtgtcacag agcaggacag caaggacagc 600
acctacagcc tcagcagcac cctgacgctg agcaaagcag actacgagaa acacaaagtc 660
tatgcctgcg aagtcaccca tcagggcctg agctcgcccg tcacaaagag cttcaacagg 720
ggagagtgtt ag 732
<210> 127
<211> 243
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 127
Met His Arg Thr Ser Met Gly Ile Lys Met Glu Ser Arg Ile Gln Ala
1 5 10 15
Phe Val Phe Val Phe Leu Trp Leu Ser Gly Val Gly Gly Asp Ile Val
20 25 30
Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly Asp Arg Val
35 40 45
Ser Val Thr Cys Lys Ala Ser Gln Asp Val Thr Ser Ala Val Ala Trp
50 55 60
Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Trp Ala
65 70 75 80
Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser
85 90 95
Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Gly Gln Ala Glu Asp Leu
100 105 110
Ala Leu Tyr Tyr Cys His Gln Tyr Tyr Ser Ala Pro Arg Thr Phe Gly
115 120 125
Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val
130 135 140
Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser
145 150 155 160
Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln
165 170 175
Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val
180 185 190
Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu
195 200 205
Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu
210 215 220
Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg
225 230 235 240
Gly Glu Cys
<210> 128
<211> 1404
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 128
atggaatgga actgggtcgt tctcttcctc ctgtcattaa ctgcaggtgt ctatgcccag 60
ggtcagatgc agcagtctgg agctgagctg gtgaagcctg gggcttcagt gaagctgtcc 120
tgcaagactt ctggcttcac cttcagcagt aactatataa gttggttgaa gcaaaagcct 180
ggacagagtc ttgagtggat tgcatggatt tatgctggaa ctggtggtat tacctataat 240
cagaagttca gaggcagggc ccaactgact gtagacacat cctccagcac agcctacatg 300
cagttcagca gcctgacaac tgatgactct gccatctatt actgtgcaag acacgtgagg 360
ggttaccatc ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa 420
acgaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720
ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg 780
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 960
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380
ctgtctctgg gtaaagctag ctga 1404
<210> 129
<211> 467
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 129
Met Glu Trp Asn Trp Val Val Leu Phe Leu Leu Ser Leu Thr Ala Gly
1 5 10 15
Val Tyr Ala Gln Gly Gln Met Gln Gln Ser Gly Ala Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Thr Ser Gly Phe Thr Phe
35 40 45
Ser Ser Asn Tyr Ile Ser Trp Leu Lys Gln Lys Pro Gly Gln Ser Leu
50 55 60
Glu Trp Ile Ala Trp Ile Tyr Ala Gly Thr Gly Gly Ile Thr Tyr Asn
65 70 75 80
Gln Lys Phe Arg Gly Arg Ala Gln Leu Thr Val Asp Thr Ser Ser Ser
85 90 95
Thr Ala Tyr Met Gln Phe Ser Ser Leu Thr Thr Asp Asp Ser Ala Ile
100 105 110
Tyr Tyr Cys Ala Arg His Val Arg Gly Tyr His Pro Met Asp Tyr Trp
115 120 125
Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr
225 230 235 240
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Gln 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 Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Glu 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 Leu Gly
450 455 460
Lys Ala Ser
465
<210> 130
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 130
atggagtcac agactcaggt ctttgtatac atgttgctgt ggttgtctgg tgttgatgga 60
gacattgtga tgacccagtc tcaaaaattc atgtccgcat cagtagggga cagggtcagc 120
gtcacctgca gggccagtca gaatgtggtt actaatgtag gctggtatca acagaaacca 180
gggcaatctc ctaaagtact gatttactcg gcatccttcc ggtacagtgg agtccctgat 240
cgcttcacag gcagtggatc tgggacagat ttcactctca ccatcaccaa tgtgcagtct 300
gaagacttgg cagagtattt ctgtcagcaa tataacaact atccgtacac gttcggaggg 360
gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 131
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 131
Met Glu Ser Gln Thr Gln Val Phe Val Tyr Met Leu Leu Trp Leu Ser
1 5 10 15
Gly Val Asp Gly Asp Ile Val Met Thr Gln Ser Gln Lys Phe Met Ser
20 25 30
Ala Ser Val Gly Asp Arg Val Ser Val Thr Cys Arg Ala Ser Gln Asn
35 40 45
Val Val Thr Asn Val Gly Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro
50 55 60
Lys Val Leu Ile Tyr Ser Ala Ser Phe Arg Tyr Ser Gly Val Pro Asp
65 70 75 80
Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Thr
85 90 95
Asn Val Gln Ser Glu Asp Leu Ala Glu Tyr Phe Cys Gln Gln Tyr Asn
100 105 110
Asn Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 132
<211> 1407
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 132
atgggatgga gctatatcat cctctttttg gtagcaacag ctacagatgt ccactcccag 60
gtccaactgc agcagcctgg ggctgaactg gtgaagcctg gggcttcagt gaagctgtcc 120
tgcaaggctt ctggctacac cttcaccagc tactggatgc actgggtgaa gcagaggcct 180
ggagaaggcc ttgagtggat tggagagatt aatcctagct acggtcgtac tgactacaat 240
gggaagttca agaacaaggc cacactgact gtagccaaat cctccagcac agcctacatg 300
caactcagca gcctgacatc tgaggactct gcggtctatt actgtgcaag aggagattac 360
tacggtagta gctcgtttgc ttactggggc caagggactc tggtcactgt ctctgcagcc 420
aaaacaaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 600
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac gaagacctac 660
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa 720
tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc 780
ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 840
gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 900
gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt 960
gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 1020
aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1080
cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac 1140
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200
gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260
ggctccttct tcctctacag caggctaacc gtggacaaga gcaggtggca ggaggggaat 1320
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc 1380
tccctgtctc tgggtaaagc tagctga 1407
<210> 133
<211> 468
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 133
Met Gly Trp Ser Tyr Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Asp
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Glu Gly Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Ser Tyr Gly Arg Thr Asp Tyr Asn
65 70 75 80
Gly Lys Phe Lys Asn Lys Ala Thr Leu Thr Val Ala Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Gly Asp Tyr Tyr Gly Ser Ser Ser Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys 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 Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val
210 215 220
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys
225 230 235 240
Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 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 Gln 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 Tyr Arg
305 310 315 320
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
340 345 350
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
355 360 365
Thr Leu Pro Pro Ser Gln 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 Val
405 410 415
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp
420 425 430
Lys Ser Arg Trp Gln Glu 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 Leu
450 455 460
Gly Lys Ala Ser
465
<210> 134
<211> 705
<212> DNA
<213> Artificial sequence
<220>
<223> Synthetic oligonucleotide.
<400> 134
atggagtcac agactcaggt ctttgtatac atgttgctgt ggttgtctgg tgttgatgga 60
gacattgtga tgacccagtc tcaaaaattc atgtccacat cattaggaga cagggtcagc 120
gtcacctgca aggccagtca gaatgtgggt actaatgtag cctggtatca acagaaacca 180
gggcactctc ctaaagcact gatttactcg gcatcctacc ggtacagtgg agtccctgat 240
cgcttcacag gcagtggatc tgggacagat ttcactctca ccatcagcaa tgtgcagtct 300
gaagacttgg cagagttttt ctgtcagcaa tataacaact atccgtacac gttcggaggg 360
gggaccacgc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705
<210> 135
<211> 234
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 135
Met Glu Ser Gln Thr Gln Val Phe Val Tyr Met Leu Leu Trp Leu Ser
1 5 10 15
Gly Val Asp Gly Asp Ile Val Met Thr Gln Ser Gln Lys Phe Met Ser
20 25 30
Thr Ser Leu Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asn
35 40 45
Val Gly Thr Asn Val Ala Trp Tyr Gln Gln Lys Pro Gly His Ser Pro
50 55 60
Lys Ala Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Ser 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 Glu Phe Phe Cys Gln Gln Tyr Asn
100 105 110
Asn Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Thr Leu Glu Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210> 136
<211> 32
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 136
Val Gly Phe Pro Val Thr Pro Gln Val Pro Leu Arg Pro Met Thr Tyr
1 5 10 15
Lys Ala Ala Val Asp Leu Ser His Phe Leu Lys Glu Lys Gly Gly Leu
20 25 30
<210> 137
<211> 30
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 137
His Thr Gln Gly Tyr Phe Pro Asp Trp Gln Asn Tyr Thr Pro Gly Pro
1 5 10 15
Gly Val Arg Tyr Pro Leu Thr Phe Gly Trp Leu Tyr Lys Leu
20 25 30
<210> 138
<211> 19
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 138
Glu Lys Ile Arg Leu Arg Pro Gly Gly Lys Lys Lys Tyr Lys Leu Lys
1 5 10 15
His Ile Val
<210> 139
<211> 32
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 139
Asn Pro Pro Ile Pro Val Gly Glu Ile Tyr Lys Arg Trp Ile Ile Leu
1 5 10 15
Gly Leu Asn Lys Ile Val Arg Met Tyr Ser Pro Thr Ser Ile Leu Asp
20 25 30
<210> 140
<211> 31
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 140
Ala Ile Phe Gln Ser Ser Met Thr Lys Ile Leu Glu Pro Phe Arg Lys
1 5 10 15
Gln Asn Pro Asp Ile Val Ile Tyr Gln Tyr Met Asp Asp Leu Tyr
20 25 30
<210> 141
<211> 60
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 141
Met Trp Val Pro Val Val Phe Leu Thr Leu Ser Val Thr Trp Ile Gly
1 5 10 15
Ala Ala Pro Leu Ile Leu Ser Arg Ile Val Gly Gly Trp Glu Cys Glu
20 25 30
Lys His Ser Gln Pro Trp Gln Val Leu Val Ala Ser Arg Gly Arg Ala
35 40 45
Val Cys Gly Gly Val Leu Val His Pro Gln Trp Val
50 55 60
<210> 142
<211> 60
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 142
Leu Thr Ala Ala His Cys Ile Arg Asn Lys Ser Val Ile Leu Leu Gly
1 5 10 15
Arg His Ser Leu Phe His Pro Glu Asp Thr Gly Gln Val Phe Gln Val
20 25 30
Ser His Ser Phe Pro His Pro Leu Tyr Asp Met Ser Leu Leu Lys Asn
35 40 45
Arg Phe Leu Arg Pro Gly Asp Asp Ser Ser His Asp
50 55 60
<210> 143
<211> 60
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 143
Leu Met Leu Leu Arg Leu Ser Glu Pro Ala Glu Leu Thr Asp Ala Val
1 5 10 15
Lys Val Met Asp Leu Pro Thr Gln Glu Pro Ala Leu Gly Thr Thr Cys
20 25 30
Tyr Ala Ser Gly Trp Gly Ser Ile Glu Pro Glu Glu Phe Leu Thr Pro
35 40 45
Lys Lys Leu Gln Cys Val Asp Leu His Val Ile Ser
50 55 60
<210> 144
<211> 60
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 144
Asn Asp Val Cys Ala Gln Val His Pro Gln Lys Val Thr Lys Phe Met
1 5 10 15
Leu Cys Ala Gly Arg Trp Thr Gly Gly Lys Ser Thr Cys Ser Gly Asp
20 25 30
Ser Gly Gly Pro Leu Val Cys Asn Gly Val Leu Gln Gly Ile Thr Ser
35 40 45
Trp Gly Ser Glu Pro Cys Ala Leu Pro Glu Arg Pro
50 55 60
<210> 145
<211> 21
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 145
Ser Leu Tyr Thr Lys Val Val His Tyr Arg Lys Trp Ile Lys Asp Thr
1 5 10 15
Ile Val Ala Asn Pro
20
<210> 146
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 146
Ile Met Asp Gln Val Pro Phe Ser Val
1 5
<210> 147
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 147
Ile Thr Asp Gln Val Pro Phe Ser Val
1 5
<210> 148
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 148
Tyr Leu Glu Pro Gly Pro Val Thr Val
1 5
<210> 149
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 149
Tyr Leu Glu Pro Gly Pro Val Thr Ala
1 5
<210> 150
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 150
Lys Thr Trp Gly Gln Tyr Trp Gln Val
1 5
<210> 151
<211> 230
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 151
Asp Thr Thr Glu Pro Ala Thr Pro Thr Thr Pro Val Thr Thr Pro Thr
1 5 10 15
Thr Thr Lys Val Pro Arg Asn Gln Asp Trp Leu Gly Val Ser Arg Gln
20 25 30
Leu Arg Thr Lys Ala Trp Asn Arg Gln Leu Tyr Pro Glu Trp Thr Glu
35 40 45
Ala Gln Arg Leu Asp Cys Trp Arg Gly Gly Gln Val Ser Leu Lys Val
50 55 60
Ser Asn Asp Gly Pro Thr Leu Ile Gly Ala Asn Ala Ser Phe Ser Ile
65 70 75 80
Ala Leu Asn Phe Pro Gly Ser Gln Lys Val Leu Pro Asp Gly Gln Val
85 90 95
Ile Trp Val Asn Asn Thr Ile Ile Asn Gly Ser Gln Val Trp Gly Gly
100 105 110
Gln Pro Val Tyr Pro Gln Glu Thr Asp Asp Ala Cys Ile Phe Pro Asp
115 120 125
Gly Gly Pro Cys Pro Ser Gly Ser Trp Ser Gln Lys Arg Ser Phe Val
130 135 140
Tyr Val Trp Lys Thr Trp Gly Gln Tyr Trp Gln Val Leu Gly Gly Pro
145 150 155 160
Val Ser Gly Leu Ser Ile Gly Thr Gly Arg Ala Met Leu Gly Thr His
165 170 175
Thr Met Glu Val Thr Val Tyr His Arg Arg Gly Ser Gln Ser Tyr Val
180 185 190
Pro Leu Ala His Ser Ser Ser Ala Phe Thr Ile Thr Asp Gln Val Pro
195 200 205
Phe Ser Val Ser Val Ser Gln Leu Arg Ala Leu Asp Gly Gly Asn Lys
210 215 220
His Phe Leu Arg Asn Gln
225 230
<210> 152
<211> 73
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<220>
<221> misc_feature
<222> (38)..(38)
<223> Xaa can be any naturally occurring amino acid
<400> 152
Pro Leu Thr Phe Ala Leu Gln Leu His Asp Pro Ser Gly Tyr Leu Ala
1 5 10 15
Glu Ala Asp Leu Ser Tyr Thr Trp Asp Phe Gly Asp Ser Ser Gly Thr
20 25 30
Leu Ile Ser Arg Ala Xaa Val Val Thr His Thr Tyr Leu Glu Pro Gly
35 40 45
Pro Val Thr Ala Gln Val Val Leu Gln Ala Ala Ile Pro Leu Thr Ser
50 55 60
Cys Gly Ser Ser Pro Val Pro Ala Ser
65 70
<210> 153
<211> 109
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 153
Gly Thr Thr Asp Gly His Arg Pro Thr Ala Glu Ala Pro Asn Thr Thr
1 5 10 15
Ala Gly Gln Val Pro Thr Thr Glu Val Val Gly Thr Thr Pro Gly Gln
20 25 30
Ala Pro Thr Ala Glu Pro Ser Gly Thr Thr Ser Val Gln Val Pro Thr
35 40 45
Thr Glu Val Ile Ser Thr Ala Pro Val Gln Met Pro Thr Ala Glu Ser
50 55 60
Thr Gly Met Thr Pro Glu Lys Val Pro Val Ser Glu Val Met Gly Thr
65 70 75 80
Thr Leu Ala Glu Met Ser Thr Pro Glu Ala Thr Gly Met Thr Pro Ala
85 90 95
Glu Val Ser Ile Val Val Leu Ser Gly Thr Thr Ala Ala
100 105
<210> 154
<211> 75
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 154
Gln Val Thr Thr Thr Glu Trp Val Glu Thr Thr Ala Arg Glu Leu Pro
1 5 10 15
Ile Pro Glu Pro Glu Gly Pro Asp Ala Ser Ser Ile Met Ser Thr Glu
20 25 30
Ser Ile Thr Gly Ser Leu Gly Pro Leu Leu Asp Gly Thr Ala Thr Leu
35 40 45
Arg Leu Val Lys Arg Gln Val Pro Leu Asp Cys Val Leu Tyr Arg Tyr
50 55 60
Gly Ser Phe Ser Val Thr Leu Asp Ile Val Gln
65 70 75
<210> 155
<211> 109
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 155
Gly Ile Glu Ser Ala Glu Ile Leu Gln Ala Val Pro Ser Gly Glu Gly
1 5 10 15
Asp Ala Phe Glu Leu Thr Val Ser Cys Gln Gly Gly Leu Pro Lys Glu
20 25 30
Ala Cys Met Glu Ile Ser Ser Pro Gly Cys Gln Pro Pro Ala Gln Arg
35 40 45
Leu Cys Gln Pro Val Leu Pro Ser Pro Ala Cys Gln Leu Val Leu His
50 55 60
Gln Ile Leu Lys Gly Gly Ser Gly Thr Tyr Cys Leu Asn Val Ser Leu
65 70 75 80
Ala Asp Thr Asn Ser Leu Ala Val Val Ser Thr Gln Leu Ile Val Pro
85 90 95
Gly Ile Leu Leu Thr Gly Gln Glu Ala Gly Leu Gly Gln
100 105
<210> 156
<211> 50
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 156
Met Glu Met Lys Ile Leu Arg Ala Leu Asn Phe Gly Leu Gly Arg Pro
1 5 10 15
Leu Pro Leu His Phe Leu Arg Arg Ala Ser Lys Ile Gly Glu Val Asp
20 25 30
Val Glu Gln His Thr Leu Ala Lys Tyr Leu Met Glu Leu Thr Met Leu
35 40 45
Asp Tyr
50
<210> 157
<211> 36
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 157
Asp Trp Leu Val Gln Val Gln Met Lys Phe Arg Leu Leu Gln Glu Thr
1 5 10 15
Met Tyr Met Thr Val Ser Ile Ile Asp Arg Phe Met Gln Asn Asn Cys
20 25 30
Val Pro Lys Lys
35
<210> 158
<211> 48
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 158
Met Glu His Gln Leu Leu Cys Cys Glu Val Glu Thr Ile Arg Arg Ala
1 5 10 15
Tyr Pro Asp Ala Asn Leu Leu Asn Asp Arg Val Leu Arg Ala Met Leu
20 25 30
Lys Ala Glu Glu Thr Cys Ala Pro Ser Val Ser Tyr Phe Lys Cys Val
35 40 45
<210> 159
<211> 95
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 159
Gln Lys Glu Val Leu Pro Ser Met Arg Lys Ile Val Ala Thr Trp Met
1 5 10 15
Leu Glu Val Cys Glu Glu Gln Lys Cys Glu Glu Glu Val Phe Pro Leu
20 25 30
Ala Met Asn Tyr Leu Asp Arg Phe Leu Ser Leu Glu Pro Val Lys Lys
35 40 45
Ser Arg Leu Gln Leu Leu Gly Ala Thr Cys Met Phe Val Ala Ser Lys
50 55 60
Met Lys Glu Thr Ile Pro Leu Thr Ala Glu Lys Leu Cys Ile Tyr Thr
65 70 75 80
Asp Asn Ser Ile Arg Pro Glu Glu Leu Leu Gln Met Glu Leu Leu
85 90 95
<210> 160
<211> 60
<212> PRT
<213> Artificial sequence
<220>
<223> Syntehtic peptide.
<400> 160
Leu Val Asn Lys Leu Lys Trp Asn Leu Ala Ala Met Thr Pro His Asp
1 5 10 15
Phe Ile Glu His Phe Leu Ser Lys Met Pro Glu Ala Glu Glu Asn Lys
20 25 30
Gln Ile Ile Arg Lys His Ala Gln Thr Phe Val Ala Leu Cys Ala Thr
35 40 45
Asp Val Lys Phe Ile Ser Asn Pro Pro Ser Met Val
50 55 60
<210> 161
<211> 91
<212> PRT
<213> Artificial sequence
<220>
<223> Synthetic peptide.
<400> 161
Ala Gly Ser Val Val Ala Ala Val Gln Gly Leu Asn Leu Arg Ser Pro
1 5 10 15
Asn Asn Phe Leu Ser Tyr Tyr Arg Leu Thr Arg Phe Leu Ser Arg Val
20 25 30
Ile Lys Cys Asp Pro Asp Cys Leu Arg Ala Cys Gln Glu Gln Ile Glu
35 40 45
Ala Leu Leu Glu Ser Ser Leu Arg Gln Ala Gln Gln Asn Met Asp Pro
50 55 60
Lys Ala Ala Glu Glu Glu Glu Glu Glu Glu Glu Glu Val Asp Leu Ala
65 70 75 80
Cys Thr Pro Thr Asp Val Arg Asp Val Asp Ile
85 90
Claims (47)
- TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 결합 단편; 및 적어도 하나의 항원을 포함하는 조성물로서,
상기 항원 및 상기 효능제는 면역자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 유효한, 조성물. - 제1항에 있어서, 상기 DC-특이적 항체 또는 단편이 항-DCIR, MHC 부류 I, MHC 부류 II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, 만노스 수용체, 랑게린, DECTIN-1, B7-1, B7-2, IFN-γ 수용체 및 IL-2 수용체, ICAM-1, Fcγ 수용체, LOX-1, 또는 ASPGR로부터 선택되는, 조성물.
- 제1항에 있어서, 상기 조성물이 사람 면역결핍 바이러스(HIV) 항원, 및 gag, pol 및 env 유전자로 이루어진 그룹으로부터 선택되는 유전자 생성물, Nef 단백질, 역전사효소, HIV 펩타이드의 스트링(string)(Hipo5), PSA (KLQCVDLHV)-4량체, HIVgag-유도된 p24-PLA HIV gag p24(gag) 및 다른 HIV 성분, 간염 바이러스 항원, 헤마글루티닌, 뉴라미니다제, H1N1 Flu 스트레인 유래의 인플루엔자 A 헤마글루티닌 HA-1, HLA-A201-FluMP (58-66) 펩타이드(GILGFVFTL) 4량체, 및 조류 Flu (HA5-1)로 이루어진 그룹으로부터 선택된 인플루엔자 바이러스 항원 및 펩타이드, 씨. 써모셀룸(C. thermocellum) 기원의 독커린 도메인(dockerin domain), 홍역 바이러스 항원, 풍진 바이러스 항원, 로타바이러스 항원, 사이토메갈로바이러스 항원, 호흡기 세포융합 바이러스 항원, 헤르페스 심플렉스 바이러스 항원, 바리셀라 조스터(varicella zoster) 바이러스 항원, 일본 뇌염 바이러스 항원, 광견병 바이러스 항원 또는 이들의 병용물 및 변형물로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제1항에 있어서, 상기 조성물이 하나 이상의 세균 항원으로부터 선택된 항원성 펩타이드를 추가로 포함하고, 여기서, 상기 세균 항원은 바실러스(Bacillus), 에스케리키아(Escherichia), 리스테리아(Listeria), 나이세리아(Neisseria), 노카르디아(Nocardia), 살모넬라(Salmonella), 스태필로코커스(Staphylococcus), 스트렙토코커스(Streptococcus)로부터 유도된 항원, 또는 이들의 병용물 및 변형물을 포함하는, 조성물.
- 제1항에 있어서, 상기 조성물이 백혈병 및 림프종, 성상세포종 또는 교모세포종과 같은 신경계 종양, 흑색종, 유방암, 폐암, 두경부암, 위장 종양, 위암, 결장암, 간암, 췌장암, 자궁경부, 자궁, 난소암, 질암, 고환암, 전립선암 또는 음경암과 같은 비뇨생식기 종양, 골 종양, 혈관 종양, 또는 입술, 코인두, 인두 및 구강, 식도, 직장, 담낭, 담관가지, 후두, 폐 및 기관지, 방광, 신장, 뇌 및 신경계의 다른 부분, 갑상선의 암, 호지킨 질환(Hodgkin's disease), 비-호지킨 림프종(non-Hodgkin's lymphoma), 다발성 골수종 및 백혈병 유래의 항원을 포함하는 종양 관련 항원으로부터 선택된 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제1항에 있어서, 상기 조성물이 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC(뮤신)(예를 들면, MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 티로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA[엡스타인-바 바이러스(Epstein-Barr Virus) 핵 항원] 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 종양 관련 항원으로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제1항에 있어서, 상기 DC-특이적 항체가 사람화된, 조성물.
- 제1항에 있어서, 상기 TLR 효능제가 살모넬라 엔테리카(Salmonella enterica) 유래의 플라겔린, 비브리오 콜레라에(Vibrio cholerae) 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 임의의 병용물 또는 변형물 중 적어도 하나를 포함하는, 조성물.
- 제1항에 있어서, 상기 항원이 상기 항체 및 TLR 효능제와 접합된, 조성물.
- 제1항에 있어서, 상기 항원 및 상기 항체가 단일 융합 단백질인, 조성물.
- 제1항에 있어서, 상기 항체가 경쇄, 중쇄, 또는 중쇄 및 경쇄 중 적어도 하나를 포함하는, 조성물.
- 항원; 및
보조제(여기서, 상기 보조제는 면역 자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 유효한 양으로 TLR 효능제의 적어도 일부에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함한다)를 포함하는, 백신 조성물. - 제12항에 있어서, 상기 DC-특이적 항체 또는 단편이 항-DCIR, MHC 부류 I, MHC 부류 II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, 만노스 수용체, 랑게린, DECTIN-1, B7-1, B7-2, IFN-γ 수용체 및 IL-2 수용체, ICAM-1, Fcγ 수용체, LOX-1, 또는 ASPGR로부터 선택되는, 조성물.
- 제12항에 있어서, 상기 조성물이 사람 면역결핍 바이러스(HIV) 항원, 및 gag, pol 및 env 유전자로 이루어진 그룹으로부터 선택되는 유전자 생성물, Nef 단백질, 역전사효소, HIV 펩타이드의 스트링(Hipo5), PSA (KLQCVDLHV)-4량체, HIVgag-유도된 p24-PLA HIV gag p24(gag) 및 다른 HIV 성분, 간염 바이러스 항원, 헤마글루티닌, 뉴라미니다제, H1N1 Flu 스트레인 유래의 인플루엔자 A 헤마글루티닌 HA-1, HLA-A201-FluMP (58-66) 펩타이드(GILGFVFTL) 4량체, 및 조류 Flu (HA5-1)로 이루어진 그룹으로부터 선택된 인플루엔자 바이러스 항원 및 펩타이드, 씨. 써모셀룸 기원의 독커린 도메인, 홍역 바이러스 항원, 풍진 바이러스 항원, 로타바이러스 항원, 사이토메갈로바이러스 항원, 호흡기 세포융합 바이러스 항원, 헤르페스 심플렉스 바이러스 항원, 바리셀라 조스터 바이러스 항원, 일본 뇌염 바이러스 항원, 광견병 바이러스 항원 또는 이들의 병용물 및 변형물로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제12항에 있어서, 상기 조성물이 하나 이상의 세균 항원으로부터 선택된 항원성 펩타이드를 추가로 포함하고, 여기서, 상기 세균 항원은 바실러스, 에스케리키아, 리스테리아, 나이세리아, 노카르디아, 살모넬라, 스태필로코커스, 스트렙토코커스, 또는 이들의 병용물 및 변형물로부터 유도된 항원을 포함하는, 조성물.
- 제12항에 있어서, 상기 조성물이 백혈병 및 림프종, 성상세포종 또는 교모세포종과 같은 신경계 종양, 흑색종, 유방암, 폐암, 두경부암, 위장 종양, 위암, 결장암, 간암, 췌장암, 자궁경부, 자궁, 난소암, 질암, 고환암, 전립선암 또는 음경암과 같은 비뇨생식기 종양, 골 종양, 혈관 종양, 또는 입술, 코인두, 인두 및 구강, 식도, 직장, 담낭, 담관가지, 후두, 폐 및 기관지, 방광, 신장, 뇌 및 신경계의 다른 부분, 갑상선의 암, 호지킨 질환, 비-호지킨 림프종, 다발성 골수종 및 백혈병 유래의 항원을 포함하는 종양 관련 항원으로부터 선택된 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제12항에 있어서, 상기 조성물이 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC(뮤신)(예를 들면, MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 티로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA(엡스타인-바 바이러스 핵 항원) 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 종양 관련 항원으로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제12항에 있어서, 상기 DC-특이적 항체가 사람화된, 조성물.
- 제12항에 있어서, 상기 TLR 효능제가 살모넬라 엔테리카 유래의 플라겔린, 비브리오 콜레라에 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 임의의 병용물 또는 변형물 중 적어도 하나를 포함하는, 조성물.
- 제12항에 있어서, 상기 항원이 항체 및 TLR 효능제와 접합된, 조성물.
- 제12항에 있어서, 상기 항원 및 상기 항체가 단일 융합 단백질인, 조성물.
- 제12항에 있어서, 상기 항체가 경쇄, 중쇄, 또는 중쇄 및 경쇄 중 적어도 하나를 포함하는, 조성물.
- 항원 제시 세포에 의한 항원 제시의 효능을 증가시키는 방법으로서,
상기 항원 제시 세포를
항원; 및
보조제(여기서, 상기 보조제는 TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 결합 단편을 포함한다)를 포함하는 조성물(여기서, 상기 항원 및 상기 보조제는 면역 자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 유효한 양으로 제공된다)과 접촉시키는 단계를 포함하는, 항원 제시 세포에 의한 항원 제시의 효능을 증가시키는 방법. - 제23항에 있어서, 상기 DC-특이적 항체 또는 단편이 항-DCIR, MHC 부류 I, MHC 부류 II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, 만노스 수용체, 랑게린, DECTIN-1, B7-1, B7-2, IFN-γ 수용체 및 IL-2 수용체, ICAM-1, Fcγ 수용체, LOX-1, 또는 ASPGR로부터 선택되는 방법.
- 제23항에 있어서, 상기 항-DC-특이적 항체가 서열번호 7과 서열번호 9, 서열번호 11과 서열번호 13, 서열번호 15와 서열번호 17, 서열번호 19와 서열번호 21, 서열번호 23과 서열번호 25, 서열번호 27과 서열번호 29, 서열번호 31과 서열번호 33, 서열번호 35와 37, 서열번호 39와 서열번호 41, 서열번호 43과 서열번호 45, 서열번호 47과 서열번호 49, 서열번호 51과 서열번호 53, 서열번호 55와 서열번호 57, 서열번호 59와 서열번호 61, 서열번호 63과 서열번호 65, 서열번호 67과 서열번호 69, 서열번호 71과 서열번호 73, 서열번호 75와 서열번호 77, 서열번호 79와 서열번호 81, 서열번호 83과 서열번호 85, 서열번호 87과 서열번호 89, 서열번호 91과 서열번호 93, 서열번호 95와 서열번호 97, 서열번호 99와 서열번호 101, 서열번호 1 내지 서열번호 3과 서열번호 105, 서열번호 107과 서열번호 109, 서열번호 111과 서열번호 113, 서열번호 115와 서열번호 117, 서열번호 119와 서열번호 121, 서열번호 123과 서열번호 125, 서열번호 127과 서열번호 129, 서열번호 131과 서열번호 132, 서열번호 133과 서열번호 134의 쌍으로부터 선택되는, 방법.
- 제23항에 있어서, 상기 조성물이 사람 면역결핍 바이러스(HIV) 항원, 및 gag, pol 및 env 유전자로 이루어진 그룹으로부터 선택되는 유전자 생성물, Nef 단백질, 역전사효소, HIV 펩타이드의 스트링(Hipo5), PSA (KLQCVDLHV)-4량체, HIVgag-유도된 p24-PLA HIV gag p24(gag) 및 다른 HIV 성분, 간염 바이러스 항원, 헤마글루티닌, 뉴라미니다제, H1N1 Flu 스트레인 유래의 인플루엔자 A 헤마글루티닌 HA-1, HLA-A201-FluMP (58-66) 펩타이드(GILGFVFTL) 4량체, 및 조류 Flu (HA5-1)로 이루어진 그룹으로부터 선택된 인플루엔자 바이러스 항원 및 펩타이드, 씨. 써모셀룸 기원의 독커린 도메인, 홍역 바이러스 항원, 풍진 바이러스 항원, 로타바이러스 항원, 사이토메갈로바이러스 항원, 호흡기 세포융합 바이러스 항원, 헤르페스 심플렉스 바이러스 항원, 바리셀라 조스터 바이러스 항원, 일본 뇌염 바이러스 항원, 광견병 바이러스 항원 또는 이들의 병용물 및 변형물로부터 선택된 항원성 펩타이드를 추가로 포함하는 방법.
- 제23항에 있어서, 상기 조성물이 백혈병 및 림프종, 성상세포종 또는 교모세포종과 같은 신경계 종양, 흑색종, 유방암, 폐암, 두경부암, 위장 종양, 위암, 결장암, 간암, 췌장암, 자궁경부, 자궁, 난소암, 질암, 고환암, 전립선암 또는 음경암과 같은 비뇨생식기 종양, 골 종양, 혈관 종양, 또는 입술, 코인두, 인두 및 구강, 식도, 직장, 담낭, 담관가지, 후두, 폐 및 기관지, 방광, 신장, 뇌 및 신경계의 다른 부분, 갑상선의 암, 호지킨 질환, 비-호지킨 림프종, 다발성 골수종 및 백혈병 유래의 항원을 포함하는 종양 관련 항원으로부터 선택된 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함하는, 방법.
- 제23항에 있어서, 상기 조성물이 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC(뮤신)(예를 들면, MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 티로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA(엡스타인-바 바이러스 핵 항원) 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 종양 관련 항원으로부터 선택된 항원성 펩타이드를 추가로 포함하는, 방법.
- 제23항에 있어서, 상기 DC-특이적 항체가 사람화된, 방법.
- 제23항에 있어서, 상기 조성물이 사람 또는 동물 대상체에게 경구 경로, 비강 경로, 국소적으로 또는 주사로서 투여되는, 방법.
- 제23항에 있어서, 상기 주사가 피내, 점막내, 피하, 정맥내, 복강내, 근육내 및 정맥내 주사로 이루어진 그룹으로부터 선택되는, 방법.
- 제23항에 있어서, 상기 TLR 효능제가 살모넬라 엔테리카 유래의 플라겔린, 비브리오 콜레라에 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 임의의 병용물 또는 변형물 중 적어도 하나를 포함하는, 방법.
- 제23항에 있어서, 상기 항원이 항체 및 TLR 효능제와 접합된, 방법.
- 제23항에 있어서, 상기 항원 및 상기 항체가 단일 융합 단백질인, 방법.
- 제23항에 있어서, 상기 항체가 경쇄, 중쇄, 또는 중쇄와 경쇄 중 적어도 하나를 포함하는, 방법.
- 사람 대상체에서 하나 이상의 암에 대한 치료, 예방 또는 이들의 조합을 위한 방법으로서,
하나 이상의 암에 대한 치료, 예방 또는 이들의 조합을 필요로 하는 사람 대상체를 확인하는 단계; 및
항원; 및
보조제(여기서, 상기 보조제는 TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함한다); 및 약제학적으로 허용되는 담체를 포함하는 백신 조성물(여기서, 상기 항원 및 상기 보조제는 하나 이상의 암에 대한 치료, 예방 또는 이들의 조합을 위한 면역 반응을 생성하는데 유효한 양으로 제공된다)을 투여하는 단계를 포함하는, 사람 대상체에서 하나 이상의 암에 대한 치료, 예방 또는 이들의 조합을 위한 방법. - 제36항에 있어서, 상기 조성물이 사람 또는 동물 대상체에게 경구 경로, 비강 경로, 국소적으로 또는 주사로서 투여되는, 방법.
- 제37항에 있어서, 상기 주사가 피내, 점막내, 피하, 정맥내, 복강내, 근육내 및 정맥내 주사로 이루어진 그룹으로부터 선택되는, 방법.
- 하나 이상의 바이러스, 세균, 진균, 기생충, 원생생물, 및 기생충 질환, 및 알레르기 장애에 대한 예방, 치료 또는 이들의 조합을 위해 사람 대상체에 대한 하나 이상의 수지상 세포(DC)를 활성화시켜 면역자극을 제공하는 방법으로서,
하나 이상의 바이러스, 세균, 진균, 기생충, 원생생물, 및 기생충 질환, 및 알레르기 장애에 대한 예방, 치료, 또는 이들의 조합을 위한 면역자극을 필요로 하는 사람 대상체를 확인하는 단계;
상기 사람 대상체로부터 하나 이상의 DC를 분리하는 단계;
상기 분리된 DC를
항원; 및
보조제(여기서, 보조제는 TLR 효능제에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함한다); 및 약제학적으로 허용되는 담체를 포함하는 활성화된 DC를 형성하는데 유효한 양의 조성물을 면역자극을 필요로 하는 사람 또는 동물 대상체에서 면역 반응을 생성하는데 유효한 양으로 사용하여 활성화시키는 단계; 및
상기 활성화된 DC를 사람 대상체에게 재도입시키는 단계를 포함하는, 하나 이상의 바이러스, 세균, 진균, 기생충, 원생생물, 및 기생충 질환, 및 알레르기 장애에 대한 예방, 치료 또는 이들의 조합을 위해 사람 대상체에 대한 하나 이상의 수지상 세포(DC)를 활성화시켜 면역자극을 제공하는 방법. - TLR 효능제의 적어도 일부에 접합된 항-수지상 세포(DC)-특이적 항체 또는 이의 단편을 포함하는 보조제 조성물로서,
상기 항-수지상 세포(DC)-특이적 항체가, 서열번호 7과 서열번호 9, 서열번호 11과 서열번호 13, 서열번호 15와 서열번호 17, 서열번호 19와 서열번호 21, 서열번호 23과 서열번호 25, 서열번호 27과 서열번호 29, 서열번호 31과 서열번호 33, 서열번호 35와 37, 서열번호 39와 서열번호 41, 서열번호 43과 서열번호 45, 서열번호 47과 서열번호 49, 서열번호 51과 서열번호 53, 서열번호 55와 서열번호 57, 서열번호 59와 서열번호 61, 서열번호 63과 서열번호 65, 서열번호 67과 서열번호 69, 서열번호 71과 서열번호 73, 서열번호 75와 서열번호 77, 서열번호 79와 서열번호 81, 서열번호 83과 서열번호 85, 서열번호 87과 서열번호 89, 서열번호 91과 서열번호 93, 서열번호 95와 서열번호 97, 서열번호 99와 서열번호 101, 서열번호 1 내지 서열번호 3과 서열번호 105, 서열번호 107과 서열번호 109, 서열번호 111과 서열번호 113, 서열번호 115와 서열번호 117, 서열번호 119와 서열번호 121, 서열번호 123과 서열번호 125, 서열번호 127과 서열번호 129, 서열번호 131과 서열번호 132, 서열번호 133과 서열번호 134의 쌍으로부터 선택되는, 보조제 조성물. - 제40항에 있어서, 상기 조성물이 사람 면역결핍 바이러스(HIV) 항원, 및 gag, pol 및 env 유전자로 이루어진 그룹으로부터 선택되는 유전자 생성물, Nef 단백질, 역전사효소, HIV 펩타이드의 스트링(Hipo5), PSA (KLQCVDLHV)-4량체, HIVgag-유도된 p24-PLA HIV gag p24(gag) 및 다른 HIV 성분, 간염 바이러스 항원, 헤마글루티닌, 뉴라미니다제, H1N1 Flu 스트레인 유래의 인플루엔자 A 헤마글루티닌 HA-1, HLA-A201-FluMP (58-66) 펩타이드(GILGFVFTL) 4량체, 및 조류 Flu (HA5-1)로 이루어진 그룹으로부터 선택된 인플루엔자 바이러스 항원 및 펩타이드, 씨. 써모셀룸 기원의 독커린 도메인, 홍역 바이러스 항원, 풍진 바이러스 항원, 로타바이러스 항원, 사이토메갈로바이러스 항원, 호흡기 세포융합 바이러스 항원, 헤르페스 심플렉스 바이러스 항원, 바리셀라 조스터 바이러스 항원, 일본 뇌염 바이러스 항원, 광견병 바이러스 항원 또는 이들의 병용물 및 변형물로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제40항에 있어서, 상기 조성물이 백혈병 및 림프종, 성상세포종 또는 교모세포종과 같은 신경계 종양, 흑색종, 유방암, 폐암, 두경부암, 위장 종양, 위암, 결장암, 간암, 췌장암, 자궁경부, 자궁, 난소암, 질암, 고환암, 전립선암 또는 음경암과 같은 비뇨생식기 종양, 골 종양, 혈관 종양, 또는 입술, 코인두, 인두 및 구강, 식도, 직장, 담낭, 담관가지, 후두, 폐 및 기관지, 방광, 신장, 뇌 및 신경계의 다른 부분, 갑상선의 암, 호지킨 질환, 비-호지킨 림프종, 다발성 골수종 및 백혈병 유래의 항원을 포함하는 종양 관련 항원으로부터 선택된 암 펩타이드로부터 선택된 항원성 펩타이드를 추가로 포함하는, 조성물.
- 제40항에 있어서, 상기 조성물이 CEA, 전립선 특이적 항원(PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 및 12, MUC(뮤신)(예를 들면, MUC-1, MUC-2 등), GM2 및 GD2 강글리오사이드, ras, myc, 타이로시나제, MART(흑색종 항원), MARCO-MART, 사이클린 B1, 사이클린 D, Pmel 17(gp100), GnT-V 인트론 V 서열(N-아세틸글루코아미닐트랜스퍼라제 V 인트론 V 서열), 전립선 Ca psm, 전립선 혈청 항원(PSA), PRAME(흑색종 항원), β-카테닌, MUM-1-B(흑색종 편재 돌연변이 유전자 생성물), GAGE(흑색종 항원) 1, BAGE(흑색종 항원) 2-10, c-ERB2 (Her2/neu), EBNA(엡스타인-바 바이러스 핵 항원) 1-6, gp75, 사람 유두종 바이러스(HPV) E6 및 E7, p53, 폐 내성 단백질(LRP), Bcl-2, 및 Ki-67로부터 선택된 종양 관련 항원으로부터 선택된 항원성 펩타이드를 포함하는, 조성물.
- 제40항에 있어서, 상기 DC-특이적 항체가 사람화된, 조성물.
- 제40항에 있어서, 상기 TLR 효능제가 살모넬라 엔테리카 유래의 플라겔린, 비브리오 콜레라에 유래의 플라겔린, 임의의 다른 TLR5 효능제, TLR7 효능제, TLR9 효능제, 또는 이들의 임의의 병용물 또는 변형물 중 적어도 하나를 포함하는, 조성물.
- 제40항에 있어서, 상기 항원 및 상기 항체가 단일 융합 단백질인, 조성물.
- 제40항에 있어서, 상기 항체가 경쇄, 중쇄, 또는 중쇄 및 경쇄 중 적어도 하나를 포함하는, 조성물.
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2011
- 2011-08-12 AR ARP110102955A patent/AR082686A1/es not_active Application Discontinuation
- 2011-08-12 TW TW100128970A patent/TWI506035B/zh not_active IP Right Cessation
- 2011-08-12 CA CA2807585A patent/CA2807585A1/en not_active Abandoned
- 2011-08-12 EP EP11817128.9A patent/EP2603235A4/en not_active Withdrawn
- 2011-08-12 US US13/208,993 patent/US20120039916A1/en not_active Abandoned
- 2011-08-12 RU RU2013110889/10A patent/RU2013110889A/ru unknown
- 2011-08-12 JP JP2013524253A patent/JP2013535508A/ja active Pending
- 2011-08-12 AU AU2011289234A patent/AU2011289234B2/en not_active Ceased
- 2011-08-12 BR BR112013002940A patent/BR112013002940A2/pt not_active IP Right Cessation
- 2011-08-12 WO PCT/US2011/047633 patent/WO2012021834A1/en active Application Filing
- 2011-08-12 KR KR1020137006354A patent/KR20130108295A/ko not_active Application Discontinuation
- 2011-08-12 MX MX2013001527A patent/MX2013001527A/es not_active Application Discontinuation
- 2011-08-12 CN CN2011800489046A patent/CN103328005A/zh active Pending
-
2013
- 2013-02-06 ZA ZA2013/01013A patent/ZA201301013B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR082686A1 (es) | 2012-12-26 |
| AU2011289234B2 (en) | 2014-09-11 |
| ZA201301013B (en) | 2015-10-28 |
| RU2013110889A (ru) | 2014-09-20 |
| MX2013001527A (es) | 2013-04-24 |
| EP2603235A4 (en) | 2014-04-09 |
| TWI506035B (zh) | 2015-11-01 |
| CN103328005A (zh) | 2013-09-25 |
| WO2012021834A1 (en) | 2012-02-16 |
| CA2807585A1 (en) | 2012-02-16 |
| TW201208696A (en) | 2012-03-01 |
| EP2603235A1 (en) | 2013-06-19 |
| US20120039916A1 (en) | 2012-02-16 |
| BR112013002940A2 (pt) | 2019-09-24 |
| JP2013535508A (ja) | 2013-09-12 |
| AU2011289234A1 (en) | 2013-02-21 |
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