KR100911951B1 - 인터루킨 15 (il-15)에 대하여 특이적인 인간 항체 - Google Patents
인터루킨 15 (il-15)에 대하여 특이적인 인간 항체 Download PDFInfo
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- KR100911951B1 KR100911951B1 KR1020047002642A KR20047002642A KR100911951B1 KR 100911951 B1 KR100911951 B1 KR 100911951B1 KR 1020047002642 A KR1020047002642 A KR 1020047002642A KR 20047002642 A KR20047002642 A KR 20047002642A KR 100911951 B1 KR100911951 B1 KR 100911951B1
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Abstract
Description
마우스 | 혈청 IgM (마이크로그램/ml) | Ig H 쇄 유전자형 |
42 | < 0.002 | CMD/JHD |
43 | 196 | +/JHD |
44 | < 0.002 | CMD/JHD |
45 | 174 | +/JHD |
129 x BL6 F1 | 153 | +/+ |
JHD | < 0.002 | JHD/JHD |
Claims (70)
- CDR1, CDR2 및 CDR3 서열을 포함하는 중쇄 가변 영역 및 CDR1, CDR2 및 CDR3 서열을 포함하는 경쇄 가변 영역을 포함하며,(a) 중쇄 가변 영역 CDR3 서열은 서열 번호 2 (도 2)의 아미노산 잔기 100 내지 107 또는 그의 보존적 서열 변형을 포함하고,(b) 경쇄 가변 영역 CDR3 서열은 서열 번호 4 (도 3)의 아미노산 잔기 90 내지 97 또는 그의 보존적 서열 변형을 포함하는 것인,IL-15와 결합하는 단리된 모노클로날 항체.
- 제1항에 있어서, 중쇄 가변 영역 CDR2 서열이 서열 번호 2 (도 2)의 아미노산 잔기 50 내지 66 또는 그의 보존적 서열 변형을 포함하고, 경쇄 가변 영역 CDR2 서열이 서열 번호 4 (도 3)의 아미노산 잔기 51 내지 57 또는 그의 보존적 서열 변형을 포함하는 것인 항체.
- 제2항에 있어서, 중쇄 가변 영역 CDR1 서열이 서열 번호 2 (도 2)의 아미노산 잔기 31 내지 35 또는 그의 보존적 서열 변형을 포함하고, 경쇄 가변 영역 CDR1 서열이 서열 번호 4 (도 3)의 아미노산 잔기 24 내지 35 또는 그의 보존적 서열 변형을 포함하는 것인 항체.
- (a) 각각 서열 번호 5, 서열 번호 6 및 서열 번호 7에 나타낸 CDR1, CDR2 및 CDR3 서열 또는 그의 보존적 서열 변형을 포함하는 중쇄 가변 영역, 및(b) 각각 서열 번호 8, 서열 번호 9 및 서열 번호 10에 나타낸 CDR1, CDR2 및 CDR3 서열 또는 그의 보존적 서열 변형을 포함하는 경쇄 가변 영역을 포함하는, IL-15와 결합하는 단리된 모노클로날 항체.
- 각각 서열 번호 2 및 서열 번호 4에 기재된 아미노산 서열 또는 그의 보존적 서열 변형을 포함하는 중쇄 및 경쇄 가변 영역을 포함하는, IL-15와 결합하는 단리된 모노클로날 항체.
- 각각 서열 번호 1 및 서열 번호 3에 기재된 가변 영역 내의 뉴클레오티드 서열 또는 그의 보존적 서열 변형을 포함하는 핵산에 의해 코딩되는, IL-15와 결합하는 단리된 모노클로날 항체.
- 각각 서열 번호 2 및 서열 번호 4에 기재된 아미노산 서열을 포함하는 중쇄 및 경쇄 가변 영역을 포함하는 항체에 의해 인식되는 인간 IL-15 상의 에피토프에 결합하는 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, IL-15-유도된 전염증성 효과를 억제하는 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, IL-15-유도된 TNFα 생산 또는 T 세포 증식을 억제하는 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, 재조합 인간 IL-15를 분석물질로 사용하고 항체를 리간드로 사용하여 표면 플라스몬 공명 (SPR) 기법으로 측정시 10-7 M 미만의 해리 평형 상수 (KD)로 인간 IL-15에 결합하는 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, 인간 IL-15의 β-쇄 또는 γ-쇄 상호작용 도메인에 위치한 에피토프에 결합하는 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, 수용체에 결합된 인간 IL-15에 결합하는 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgAsec, IgD 및 IgE 항체로 구성된 군으로부터 선택되는 항체.
- 제13항에 있어서, IgG1 항체인 항체.
- 제14항에 있어서, IgG1 중쇄로부터의 가변 영역 및 카파 경쇄로부터의 가변 영역을 포함하는 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, Fab 단편 또는 단일 쇄 항체인 항체.
- 제1항 내지 제7항 중 어느 한 항에 있어서, 인간 중쇄 트랜스유전자 및 인간 경쇄 트랜스유전자를 포함하는 게놈을 가지는 트랜스제닉 비인간 동물로부터 얻어지며 불멸화 세포에 융합된 B 세포를 포함하는 하이브리도마에 의해 생성되는 항체.
- 인간 중쇄 트랜스유전자 및 인간 경쇄 트랜스유전자를 포함하는 게놈을 가지는 트랜스제닉 비인간 동물로부터 얻어지며 불멸화 세포에 융합된 B 세포를 포함하는, 제1항 내지 제7항 중 어느 한 항의 항체를 생성하는 하이브리도마.
- 제1항 내지 제7항 중 어느 한 항에 있어서, 인간 중쇄 및 인간 경쇄를 코딩하는 핵산을 포함하는 트랜스펙토마에 의해 생성되는 항체.
- 제1항 내지 제7항 중 어느 한 항의 항체 및 치료제를 포함하는 면역접합체.
- 제20항에 있어서, 치료제가 면역억제제인 면역접합체.
- 제20항에 있어서, 치료제가 스테로이드성 항염증제, 비스테로이드성 항염증제 및 질환 조절 항류마티스성 약물 (disease-modifying anti-rheumatic drug; DMARD)로 구성된 군으로부터 선택된 항염증제인 면역접합체.
- 제20항에 있어서, 치료제가 세포독성제인 면역접합체.
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- 제1항 내지 제7항 중 어느 한 항의 항체를 포함하는, 건선, 관절염, 염증성 장 질환, 암, 이식 거부반응 및 HIV 감염으로 구성된 군으로부터 선택되는 장애의 치료 또는 예방용 제약 조성물.
- 제27항에 있어서, 관절염이 류마티스성 관절염인 제약 조성물.
- 제27항에 있어서, 치료제를 추가로 포함하는 제약 조성물.
- 제29항에 있어서, 치료제가 면역억제제인 제약 조성물.
- 제30항에 있어서, 면역억제제가 시클로스포린인 제약 조성물.
- 제29항에 있어서, 치료제가 스테로이드성 항염증제 및 비스테로이드성 항염증제로 구성된 군으로부터 선택되는 항염증제인 제약 조성물.
- 제32항에 있어서, 치료제가 메토트렉세이트, 에타네르셉트 및 인플릭시마브로 구성된 군으로부터 선택되는 질환 조절 항류마티스성 약물(DMARD)인 제약 조성물.
- 제29항에 있어서, 치료제가 독소루비신, 시스플라틴, 블레오마이신, 카르무스틴, 시클로포스파미드 및 클로람부실로 구성된 군으로부터 선택되는 화학치료제인 제약 조성물.
- 제29항에 있어서, 치료제가 건선 치료제인 제약 조성물.
- 제29항에 있어서, 치료제가 항체인 제약 조성물.
- 제36항에 있어서, 항체가 CD4 특이적 항체 및 IL-2 특이적 항체로 구성된 군으로부터 선택되는 것인 제약 조성물.
- 제1항 내지 제7항 중 어느 한 항의 항체를 포함하는, 건선 치료 또는 예방용 제약 조성물.
- 제38항에 있어서, 항체가 IL-15의 부전각화증 유도능을 억제하는 것인 제약 조성물.
- 제38항에 있어서, 항체가 IL-15의 표피 비후 유도능을 억제하는 것인 제약 조성물.
- 제38항에 있어서, 항체가 IL-15의 케라틴생성세포 증식 유도능을 억제하는 것인 제약 조성물.
- IL-15가 그의 수용체와 결합하여 전염증성 효과를 유도하는 능력을 억제하는 제1항 내지 제7항 중 어느 한 항의 항체를 포함하는, 류마티스성 관절염 치료 또는 예방용 제약 조성물.
- 제42항에 있어서, 항체가 활성화된 백혈구의 화학주성을 유도하는 IL-15의 능력을 억제하는 것인 제약 조성물.
- 제1항 내지 제7항 중 어느 한 항의 항체를 포함하는, 샘플에서 IL-15 항원 또는 IL-15 발현 세포의 존재를 검출함으로써 건선, 관절염, 염증성 장 질환, 암, 이식 거부반응 및 HIV 감염으로 구성된 군으로부터 선택되는 장애를 진단하기 위한 제약 조성물.
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Applications Claiming Priority (3)
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US31473101P | 2001-08-23 | 2001-08-23 | |
US60/314,731 | 2001-08-23 | ||
PCT/US2002/026769 WO2003017935A2 (en) | 2001-08-23 | 2002-08-23 | Human antibodies specific for interleukin 15 (il-15) |
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KR100911951B1 true KR100911951B1 (ko) | 2009-08-13 |
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