KR920702425A - Cdr 이식된 항-cea 항체 및 그의 제조 - Google Patents

Cdr 이식된 항-cea 항체 및 그의 제조

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KR920702425A
KR920702425A KR1019920700490A KR920700490A KR920702425A KR 920702425 A KR920702425 A KR 920702425A KR 1019920700490 A KR1019920700490 A KR 1019920700490A KR 920700490 A KR920700490 A KR 920700490A KR 920702425 A KR920702425 A KR 920702425A
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ham
cdr
chain
derived
variable region
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존 로버트 어데어
마아크 윌리엄 보드머
앤드류 마우틴
레이몬드 존 오웬스
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원본미기재
셀텍크 리미티드
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3007—Carcino-embryonic Antigens
    • A—HUMAN NECESSITIES
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • A—HUMAN NECESSITIES
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    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
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    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/035—Fusion polypeptide containing a localisation/targetting motif containing a signal for targeting to the external surface of a cell, e.g. to the outer membrane of Gram negative bacteria, GPI- anchored eukaryote proteins

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Abstract

내용 없음

Description

CDR 이식된 항 -CEA 항체 및 그의 제조
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 예상되는 아미노산 서열과 함께 cDNA클론을 서열화하여 얻은 A5B7 MAb의 처리되지 않은 가변부위를 암호화하는 DNA서열이다. 제2도는 키메라화된 H사슬 유전자의 제한과 결찰에 의한 제조의 대략적 도표이다. 제3도는 키메라화된 L사슬 유전자의 부위-직접적 돌연변이 유발, 제한 및 결찰에 의한 제조의 대략적 도표이다.

Claims (17)

  1. 암배항원에 대해 특이성이 있고 다양한 가변성 영역의 상보성 결정부위(CDR)의 적어도 한 부분은 마우스모노클로날 항체 A5B7(A5A7 MAb)에서 유도되고 HAM의 나머지 면역글로부린-유도부는 인간 면역글로부린에서 유도된 항원 결합부위를 가지는 인간형화 된 항체분자(HAM).
  2. 제1항에 있어서, 인간형화 된 키메라 항체분자임을 특징으로 하는 HAM.
  3. 제1항에 있어서, CDR-이식 인간형화된 항체임을 특징으로 하는 HAM.
  4. 제1-3항의 어느 한 항에 있어서, DNA재조합 기술에 의해 제조되는 경우 임을 특징으로 하는 HAM.
  5. 제1-4항의 어느 한 항에 있어서, 완전한 항체 분자나, 또는 Fab, Fab', (Fab')2나 Fv단편이나, 단일사슬 항체 단편을 포함함을 특징으로 하는 HMA.
  6. 제1-5항의 어느 한 항에 있어서, 효과기나 또는 보고기 분자가 거기에 부착되어 있음을 특징으로 하는 HMA.
  7. H사슬 및/또는 L사슬에 대한 LAY, POM, TUR, TEI, KOL, NEWM, REI 이나 EU가변부위 골격서열을 포함하는 제3-6항의 어느 한항에 따르는 CDR-이식 HMA.
  8. 제7항에 있어서, H사슬과 L사슬 모두에 대한 LAY가변부위 골격서열을 포함함을 특징으로 하는 CDR-이식 HAM.
  9. 제3-8항의 어느 한 항에 있어서, L사슬의 가변부위의 24-34위치(CDR1), 50-56위치(CDR2) 및 92-96위치나 또는 89-97위치(CDR3)에 A5B7 CDR을 가짐을 특징으로 하는 CDR-이식 HAM.
  10. 제3-9항의 어느 한항에 있어서, L사슬의 가변부위의 1,2 및/또는 3, 46, 47,49,60,70,84,85 및 87위치중의 하나나 그 이상의 위치, 바람직하게는 적어도 46과 47위치에 A5B7을 포함함을 특징으로 하는 CDR-이식 HAM.
  11. 제3-10항의 어느 한 항에 있어서, H사슬의 가변부위의 24-35위치나 또는 26-35위치(CDR1), 50-65위치(CDR2)및 95-100이나 94-100위치(CDR3)에 A5B7 CDR을 가짐을 특징으로 하는 CDR-이식 HAM.
  12. 제3-11항의 어느 한 항에 있어서, H사슬의 가변부위의 23 및/또는 24, 71 및/또는 48 및/또는 49,69,76 및/또는 78,80,88 및/또는 91과 6위치중의 하나나 그 이상의 위치에서 A5B7잔기를 가짐을 특징으로 하는 CDR-이식 HAM.
  13. 제8항에 있어서, L사슬의 1,2,3,4,46과 71위치와 특별히는 21,47과 73위치에서, H사슬의 1,24,48,49,72,73,76과 93과 특별히는 82b과 86위치에서 A5B7 잔기를 포함함을 특징으로 하는 CDR- 이식 HAM.
  14. 제13항에 있어서, L사슬의 24-34위치(CDR1), 50-56위치(CDR2)와, 89-97위치(CDR3)와, H사슬의 26-35위치(CDR1), 50-65위치(CDR2)와, 95-102위치(CDR3)에 A5B7을 포함함을 특징으로 하는 CDR-이식 HAM.
  15. 제약학적으로 허용가능한 부형제, 희석제나 담체와 결합되어 있는 전술한 항중의 어느 한항에 따르는 HAM을 포함하는 치료나 진단 조성물.
  16. 제15항에 따르는 치료나 진단조성물 사람에게 효과량으로 투여함을 포함하는 치료나 또는 진단 방법.
  17. 다음의 (a)∼(d)를 포함하는 제1-14항의 어느 한 항에 따르는 HAM의 제조방법. (a)가변성 영역의 CDR의 적어도 하나는 A5B7 MAb에서 유도되고 항체 사슬의 너머지 면역글로부린-유도부는 인간 면역글로부린에서 유도된 가변성 영역을 포함하는 항체의 H사슬이나 또는 L사슬을 암호화하는 DNA서열을 가지는 오페론을 발현 벡터내에서 제조; (b)가변성 영역의 CDR의 적어도 하나는 A5B7 MAb에서 유도되고 항체 사슬의 나머지 면역글로부린-유도부는 인간 면역글로부린에서 유도된 가변성 영역을 포함하는 상보성의 항체 H사슬이나 또는 L사슬을 암호화하는 DNA서열을 가지는 오페론을 발현 벡터내에서 제조; (c)숙주세포를 해당 벡터나 각각의 벡터로 형질감염시키고, (d) HAM을 제조하기 위해 형질감염된 세포주를 배양.
    ※ 참고사항 : 최초출원 내용에 의하여 공개되는 것임.
KR1019920700490A 1990-07-05 1991-07-05 Cdr 이식된 항-cea 항체 및 그의 제조 Withdrawn KR920702425A (ko)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB909014932A GB9014932D0 (en) 1990-07-05 1990-07-05 Recombinant dna product and method
GB90149329 1990-08-05
GBPCT/GB90/02017WO 1990-12-21
PCT/GB1990/002017 WO1991009967A1 (en) 1989-12-21 1990-12-21 Humanised antibodies
PCT/GB1991/001108 WO1992001059A1 (en) 1990-07-05 1991-07-05 Cdr grafted anti-cea antibodies and their production

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KR920702425A true KR920702425A (ko) 1992-09-04

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US (1) US5877293A (ko)
EP (1) EP0491031B1 (ko)
JP (1) JPH05502587A (ko)
KR (1) KR920702425A (ko)
AT (1) ATE137534T1 (ko)
AU (1) AU651984B2 (ko)
CA (1) CA2065325C (ko)
DE (1) DE69119211T2 (ko)
GB (2) GB9014932D0 (ko)
WO (1) WO1992001059A1 (ko)

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