KR100508289B1 - Cd19×cd3 특이 폴리펩티드 및 그의 용도 - Google Patents
Cd19×cd3 특이 폴리펩티드 및 그의 용도 Download PDFInfo
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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- A—HUMAN NECESSITIES
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- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C07K2319/00—Fusion polypeptide
Abstract
Description
Claims (32)
- (a) CD19 항원을 특이적으로 인식하는 면역글로불린 사슬 또는 항체의 결합 부위를 포함하는 제1 도메인(domain), 및(b) 인간 CD3 항원을 특이적으로 인식하는 면역글로불린 사슬 또는 항체의 결합 부위를 포함하는 제2 도메인을 포함하는 단쇄(單鎖) 다기능 폴리펩티드(single-chain multi-functional polypeptide)로서,상기 제1 도메인 및 상기 제2 도메인은 VLCD19-VHCD19-VHCD3-VLCD3의 순서로 배열되어 있는 것인 단쇄 다기능 폴리펩티드.
- 제 1 항에 있어서,상기 제1 도메인 및 상기 제2 도메인은 폴리펩티드 링커(polypeptide linker)에 의해 연결되어 있는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 삭제
- 제 1 항 또는 제 2 항에 있어서,상기 항체는 단일클론 항체, 합성 항체 또는 인간화(humanized) 항체인 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 1 항 또는 제 2 항에 있어서,상기 제1 도메인 또는 상기 제2 도메인은 항체의 가변 영역의 단쇄 단편인 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 삭제
- 제 2 항에 있어서,상기 폴리펩티드 링커는 글리신, 알라닌, 세린 및 이들의 조합으로 이루어진 군으로부터 선택되는 복수의 아미노산 잔기를 포함하는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 2 항에 있어서,상기 폴리펩티드 링커는 글리신, 알라닌, 세린 및 이들의 조합으로 이루어진 군으로부터 선택되는 복수의 아미노산 잔기를 포함하는 아미노산 서열의 복수의 연속 복제물을 포함하는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 2 항에 있어서,상기 폴리펩티드 링커는 1개 내지 5개의 아미노산 잔기를 포함하는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 2 항에 있어서,상기 폴리펩티드 링커는 아미노산 서열 Gly Gly Gly Gly Ser을 포함하는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 1 항 또는 제 2 항에 있어서,상기 제1 도메인은 도 8의 뉴클레오티드 82~414(VL) 및 뉴클레오티드 460~ 831(VH)로 표시되는 DNA 서열에 의해 코딩된 아미노산 서열을 포함하는 VH 및 VL 영역의 적어도 하나의 CDR을 포함하거나; 또는상기 제2 도메인은 도 8의 뉴클레오티드 847~1203(VH) 및 뉴클레오티드 1258~1575(VL)로 표시되는 DNA 서열에 의해 코딩된 아미노산 서열을 포함하는 VH 및 VL 영역의 적어도 하나의 CDR을 포함하는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 1 항 또는 제 2 항에 있어서,(a) 상기 제1 도메인의 결합 부위는 약 10-7M 이상의 친화도(affinity)를 가지거나; 또는(b) 상기 제2 도메인의 결합 부위는 약 10-7M 미만의 친화도를 가지는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 1 항 또는 제 2 항에 있어서,CD19 항원과 CD3 항원을 특이적으로 인식하는 단쇄 항체인 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 1 항 또는 제 2 항에 있어서,1개 이상의 추가의 도메인을 포함하는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 14 항에 있어서,상기 1개 이상의 추가의 도메인은 공유 결합 또는 비공유 결합에 의해 연결되는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 제 14 항에 있어서,상기 1개 이상의 추가의 도메인은 이온을 봉쇄(sequestering)할 수 있거나 고체 지지체 또는 예정된 결정기(determinant)에 선택적으로 결합될 수 있는, 생물학적 활성에 적당한 배좌(conformation)를 가지는 효과 인자(effector) 분자를 포함하는 것을 특징으로 하는 단쇄 다기능 폴리펩티드.
- 발현시에 제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드를 코딩하는 폴리뉴클레오티드.
- 제 17 항의 폴리뉴클레오티드를 포함하는 벡터.
- 제 17 항의 폴리뉴클레오티드 또는 제 18 항의 벡터에 의해 형질전환된 세포.
- 제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드의 제조 방법으로서,제 19 항의 세포를 배양하는 단계 및 배양물로부터 단쇄 다기능 폴리펩티드를 단리(單離)하는 단계를 포함하는 것인 방법.
- 제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드, 제 17 항의 폴리뉴클레오티드 또는 제 18 항의 벡터를 포함하는 조성물.
- 제 21 항에 있어서,상기 조성물은 B-세포 악성 종양, B-세포 매개 자가면역 질환 또는 B-세포 결핍을 치료하거나 B-세포 장해에 의해 야기되는 병리학적 증상을 지연시키기 위한 약학 조성물로서, 약학적 허용 담체를 추가로 포함할 수 있는 약학 조성물인 것을 특징으로 하는 조성물.
- 제 21 항에 있어서,효소, 방사성 동위원소, 콜로이드 금속, 형광 화합물, 화학발광 화합물 및 생물발광 화합물을 포함하는 군으로부터 선택되는 검출 수단을 추가로 포함할 수 있는 진단용 조성물인 것을 특징으로 하는 조성물.
- B-세포 악성 종양, B-세포 매개 자가면역 질환 또는 B-세포 결핍을 치료하거나 B-세포 장해에 의해 야기되는 병리학적 증상을 지연시키기 위한 약학 조성물로서,제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드, 제 17 항의 폴리뉴클레오티드 또는 제 18 항의 벡터, 및 약학적 허용 담체 또는 부형제를 포함하는 것인 약학 조성물.
- 제 24 항에 있어서,상기 B-세포 악성 종양은 비(非)-호지킨 림프종인 것을 특징으로 하는 약학 조성물.
- 유전자 치료용 약학 조성물로서,제 17 항의 폴리뉴클레오티드 또는 제 18 항의 벡터, 및 약학적 허용 담체 또는 부형제를 포함하는 것인 약학 조성물.
- T-세포의 활성화 또는 자극의 활성화 인자(activator) 또는 억제 인자(inhibitor)를 동정(同定)하는 방법으로서,(a) 제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드의 존재하에서 또는 제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드와 T-세포 활성화에 대한 응답으로 검출가능한 신호를 제공할 수 있는 성분의 존재하에서, T-세포 활성화를 허용하는 조건하에 스크리닝 대상 화합물과 함께 T-세포, CD19 양성 세포 및 B-세포를 배양하는 단계; 및(b) 상기 화합물과 상기 세포들의 상호작용으로부터 발생된 신호의 존재 또는 부재를 검출하는 단계를 포함하는 것인 방법.
- 삭제
- 삭제
- 포유동물(인간을 제외함)의 B-세포 악성 종양, B-세포 매게 자가면역 질환 또는 B-세포 결핍을 치료하는 방법으로서,상기 B-세포 악성 종양, B-세포 매게 자가면역 질환 또는 B-세포 결핍이 있는 포유동물(인간을 제외함)의 체내에 제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드, 제 17 항의 폴리뉴클레오티드 또는 제 18 항의 벡터를 도입하는 단계를 포함하는 것인 방법.
- 포유동물(인간을 제외함)의 B-세포 장해에 의해 야기되는 병리학적 증상을 지연시키는 방법으로서,상기 B-세포 장해에 의해 야기되는 병리학적 증상이 있는 포유동물(인간을 제외함)의 체내에 제 1 항 또는 제 2 항의 단쇄 다기능 폴리펩티드, 제 17 항의 폴리뉴클레오티드 또는 제 18 항의 벡터를 도입하는 단계를 포함하는 것인 방법.
- 삭제
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