KR100516133B1 - 항-인간항원 수용체의 신규한 제조방법 및 용도 - Google Patents
항-인간항원 수용체의 신규한 제조방법 및 용도 Download PDFInfo
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- KR100516133B1 KR100516133B1 KR10-1999-7009425A KR19997009425A KR100516133B1 KR 100516133 B1 KR100516133 B1 KR 100516133B1 KR 19997009425 A KR19997009425 A KR 19997009425A KR 100516133 B1 KR100516133 B1 KR 100516133B1
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Landscapes
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Abstract
Description
Claims (33)
- 항-인간 항원 수용체의 제조방법으로서,기능적으로 재배열된 VH 및 VL면역글로블린 사슬의 조합을 선택하며, 이에 있어서 적어도 상기 VH사슬은 초회항원 자극되지 않은 성숙한 인간 B-림프구로부터 얻어지고 상기 VL사슬은 자연적으로 발생하는 인간 B세포 레퍼토리로부터 얻어지며, 상기 사슬들은 재조합 벡터로부터 발현되는 단계와,인간항원에 결합하기 위해 인 비트로 디스플레이 시스템을 이용하는 단계로 구성되며,상기 선택단계 이전에 다른 종으로부터의 목표항원 특이항체(target antigen-specific antibody from a different species)의 V사슬과 함께 상기 항원에 결합하기 위해 상기 VH사슬이나 상기 VL사슬을 선택하는 단계가 실행되는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항에 있어서,상기 수용체는 면역글로블린 또는 Fv-단편과 같은 면역글로블린 단편인 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 삭제
- 제 1항 또는 제 2항에 있어서,적어도 상기 VH와 선택적으로 상기 VL면역글로블린 사슬은 인간 IgD레퍼토리에서 얻어지는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,상기 인 비트로 디스플레이 시스템은 파지 디스플레이 시스템인 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,상기 재배열된 사슬의 조합은 하나 이상의 다른 라이브러리로부터 발현되는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,상기 인간 항원은 인간 17-1A항원과 같은 종양 항원인 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 삭제
- 제 7항에 있어서,상기 VH사슬은 도 7(뉴클레오티드 1 내지 381)과 도 8(뉴클레오티드 1 내지 339)에 나타낸 두 개의 서열 중 하나로 구성되고 상기 VL사슬은 도 6(뉴클레오티드 1 내지 321)과 도 9(뉴클레오티드 1 내지 321)에 나타낸 두 개의 서열 중 하나로 구성되는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,상기 선택단계는,(ⅰ)항원수용체를 발현하는 표시비히클(display vehicle)을,(a)고정된 목표 항원 또는 그 단편;(b)목표 항원 또는 그 단편을 발현하는 선택적으로 표지된 세포;(c)가용성의, 바람직하게는 표지된 목표 항원 또는 그 단편과 결합시키고,(ⅱ)비특이적으로 결합한 표시비히클(a와 b)을 세척한 후, 특이적으로 결합한 표시비히클을 추출하거나,(ⅲ)목표 항원 용액 또는 목표항원을 발현하는 세포의 현탁액에서 목표항원과 결합한 표시비히클(b와 c)의 포지티브를 증가시켜서;항원 수용체를 포함하는 표시비히클을 분리하여 선택적으로 복제에 의해 배가시키고, 상기 (ⅰ) 내지 (ⅲ)의 인 비트로 선택을 수 차례 더 행하도록 하는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 삭제
- 제 1항 또는 제 2항에 있어서,상기 다른 종으로부터의 목표항원 특이항체의 사슬은 쥐의 VH사슬 또는 VL사슬인 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,상기 적절한 조합의 선택은,(a)상기 인간 항원에 결합하기 위해 서로 다른 다양한 VL사슬을 조합하여 동일한 VH사슬을 테스트하거나,(b)상기 인간 항원에 결합하기 위해 서로 다른 다양한 VH사슬을 조합하여 동일한 VL사슬을 테스트하는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,선택단계 후, 인간 VH사슬과 인간 VL사슬 또는 그에 해당하는 핵산을 얻는 단계와,상기 사슬을 동일하거나 또는 다른 VH사슬 또는 VL사슬과 융합하여, 무거운 사슬(CH) 또는 가벼운 사슬(CL)의 면역글로블린 불변영역 또는 그 일부나 혹은 비면역글로블린 사슬과 그에 해당하는 핵산으로 만드는 단계를 더 포함하여 구성되는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 14항에 있어서,상기 불변영역의 사슬은 인간 IgG1 또는 IgG3로부터 얻어지는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,선택단계 후에, 인간 VH사슬과 VL사슬을 얻는 단계와,상기 사슬을 방사성 동위원소 또는 화학치료에 사용되는 물질과 같은 낮은 분자량의 비단백질 약물과 물리적으로 결합시키는 단계를 더 포함하여 구성되는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
- 제 1항 또는 제 2항에 있어서,상기 VH사슬 또는 VL사슬은 초회항원 자극되지 않은 성숙한 인간 B-림프구로부터 얻어지는 mRNA의 RT-PCR 증폭의 결과인 핵산서열로부터 발현되는 것을 특징으로 하는 항-인간 항원 수용체의 제조방법.
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PCT/EP1998/002180 WO1998046645A2 (en) | 1997-04-14 | 1998-04-14 | Method for the production of antihuman antigen receptors and uses thereof |
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KR10-1999-7009425A KR100516133B1 (ko) | 1997-04-14 | 1998-04-14 | 항-인간항원 수용체의 신규한 제조방법 및 용도 |
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