KR870002264A - 폴리-크링글 플라스미노겐 활성화제의 제조방법 - Google Patents

폴리-크링글 플라스미노겐 활성화제의 제조방법 Download PDF

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KR870002264A
KR870002264A KR1019860006663A KR860006663A KR870002264A KR 870002264 A KR870002264 A KR 870002264A KR 1019860006663 A KR1019860006663 A KR 1019860006663A KR 860006663 A KR860006663 A KR 860006663A KR 870002264 A KR870002264 A KR 870002264A
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plasminogen activator
ser
hybrid plasminogen
expression vector
hybrid
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KR900007649B1 (ko
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포어웬 흥 폴
쿠마 카리얀 나렌더
린 리 쇼광
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조오지 데 모트
아메리칸 홈 프로덕츠 코포레이션
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52—Genes encoding for enzymes or proenzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6456—Plasminogen activators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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Abstract

내용 없음

Description

폴리-크링글 플라스미노겐 활성화제의 제조방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 본원에 개시된 방법에 의해 제조된 3개의 트리스-크링글 플라스미노겐 활성화제와 1개의 테트라-크링글 플라스미노겐 활성화제의 도식적 배열도[도시된 구조물 1(a-c)의 굵은 선 부분은 유로키나제크링글(ukk)을 함유하는 유로키나제 부분을 나타낸다(제 1도에서 a,b 및 c폴리펩타이드 코드화 DNA를 함유하는 이. 콜라이 MM 294 ATCC 33625가 1986년 8월 5일 ATCC에 기탁되어 기탁번호 각각 ATCC67175-P438, ATCC 67174-P504 및 ATCC 67176-P113을 부여받았음). 구조물 1(d)의 굵은선 부분은 프로트롬빈의 이중 크링글 영역(PTK1 및 PTK2)을 나타낸다. 약자 tPK 1 및 PTK2는 각기 조직 플라스미노겐 활성화제 크링글 1 및 2를 나타낸다]이다.
제2도는 조직 플라스미노겐 활성화제 재조합체 클론 pWP-42의 제한부위 지도를 나타낸다.
제3도는 pWP-42로부터 플라스미드 ptPBM-1을 제조하는 기술을 나타낸다. ptPBM-1은 완전 t-PA 분자를 제조하는데 필요한 유전 정보를 지니고 있다.
제4도는 플라스미드 pUK-53으로부터 플라스미드 pUKBM을 제조하는 기술을 나타낸다. pUKBM은 완전 유로키나제 단백질을 제조하는데 필요한 유전정보를 지닌다.
제5도는 제1(a)도에 도시된 트리스-크링글 생성물을 코드화하는 유전자를 제조하는 방법의 과정일람표를 나타낸다.
제6도는 유로키나제의 아미노산 51-131(u-PA 51-131)을 코드화하는 유전자를 제조하는 방법의 과정일람표를 나타낸다.

Claims (6)

  1. 하이브리드 플라스미노겐 활성화제를 코드화하는 DNA서열을 함유하는 복제가능한 발현 벡터를 제조합 DNA기술로 제조한 다음, 적절한 숙주세포를 상기 발현벡터내로 도입하여 형질전환시켜 형질전환된 숙주세포를 수득하고, 상기 형질전환제를 배양하여 하이브리드 플라스미노겐 활성화제를 발현시킨 다음, 상기 하이브리드 플라스미노겐 활성화제를 회수함을 특징으로 하여, 다수의 이중 폴리펩타이드 크링글(kringles)을 함유하는 하이브리드 플라스미노겐 활성화제를 제조하는 방법.
  2. 제1항에 있어서, 상기 복제가능한 발현 벡터가 하이브리드 플라스미노겐 활성화제를 코드화하는 DNA서열을 함유하고, 회수된 하이브리드 플라스미노겐 활성화제가 이종크링글 2내지 6개를 함유하는 방법.
  3. 제1항에 있어서, 상기 복제가능한 발현벡터가 하이브리드 플라스미노겐 활성화제를 코드화하는 DNA 서열을 함유하고, 회수된 하이브리드 플라스미노겐 활성화제가(유로키나제 아미노산 1-131-Ser-Glu-Gly-Asn-Ser-Asp) 1-91-조직플라스미노겐 활성화제인 방법.
  4. 제1항에 있어서, 상기 복제가능한 발현 벡터가 하이브리드 플라스미노겐 활성화제를 코드화하는 DNA 서열을 함유하고, 회수된 하이브리드 플라스미노겐 활성화제가 91-(유로키나제 아미노산 50-131-Ser-Glu-Gly-Asn-Ser-Asp) -92-조직플라스미노겐 활성화제인 방법.
  5. 제1항에 있어서, 상기 복제가능한 발현 벡터가 하이브리드 플라스미노겐 활성화제를 코드화하는 DNA 서열을 함유하고, 회수된 하이브리드 플라스미노겐 활성화제가 261-(Ser-Glu-Gly-Asn-Ser-Asp)-유로키나제 아미노산 50-131-조직 플라스미노겐 활성화제인 방법.
  6. 제1항에 있어서, 상기 복제가능한 발현 벡터가 하이브리드 플라스미노겐 활성화제를 코드화하는 DNA 서열을 함유하고, 회수된 하이브리드 플라스미노겐 활성화제가 91-(프로트롬빈 크링글 아미노산 65-248-Ser-Glu-Gly-Asn-Ser-Asp) -92-조직 플라스미노겐 활성화제인 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019860006663A 1985-08-14 1986-08-13 폴리-크링글 플라스미노겐 활성화제의 제조방법 KR900007649B1 (ko)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US76616385A 1985-08-14 1985-08-14
US766,163 1985-08-14
US06/884,835 US4916071A (en) 1985-08-14 1986-07-11 Poly-kringle plasminogen activator
US884,835 1986-07-11

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KR870002264A true KR870002264A (ko) 1987-03-30
KR900007649B1 KR900007649B1 (ko) 1990-10-17

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US (1) US4916071A (ko)
EP (1) EP0213794B1 (ko)
JP (2) JPH0829086B2 (ko)
KR (1) KR900007649B1 (ko)
AU (1) AU596369B2 (ko)
CA (1) CA1341449C (ko)
DE (1) DE3676760D1 (ko)
DK (1) DK175420B1 (ko)
GB (1) GB2179948B (ko)
GR (1) GR862076B (ko)
HU (1) HU200795B (ko)
IE (1) IE59380B1 (ko)
IL (1) IL79644A (ko)
PH (1) PH26199A (ko)
PT (1) PT83170B (ko)

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JP2581668B2 (ja) * 1985-11-27 1997-02-12 三井東圧化学株式会社 ヒト正常細胞由来のヒト組織プラスミノ−ゲン活性化因子をコ−ドする新しいｄｎａ配列とそれを含むベクタ−及び細胞
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US5204255A (en) * 1986-01-31 1993-04-20 Sagami Chemical Research Center Hybrid tissue plasminogen activator/urokinase polypeptides
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US5047241A (en) * 1986-07-11 1991-09-10 American Home Products Corporation Tris-Kringle plasminogen activator with novel K2 insert
US5242819A (en) * 1986-12-05 1993-09-07 Ciba-Geigy Corporation DNA molecules encoding hybrid proteins of tissue plasminogen activator and urokinase
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FI100106B (fi) * 1986-12-05 1997-09-30 Novartis Ag Menetelmä plasminogeenin yksisäikeisen yhdistelmäaktivaattorin valmist amiseksi
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GB8711957D0 (en) * 1987-05-20 1987-06-24 Beecham Group Plc Compounds
DK275788A (da) * 1987-05-22 1989-02-03 Zymogenetics Inc Fibrinolytiske proteiner
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IL86909A0 (en) * 1987-07-01 1988-11-30 Beecham Group Plc Hybrid plasminogen activator,dna coding therefor,derivatives of said plasminogen activator and pharmaceutical compositions containing said plasminogen activator or said derivatives
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JP2708749B2 (ja) * 1987-08-10 1998-02-04 エーザイ株式会社 修飾型ｔＰＡ含有注射用組成物
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US8333973B2 (en) * 2008-01-02 2012-12-18 The Trustees Of The University Of Pennsylvania Targeting recombinant therapeutics to circulating red blood cells
US11629198B2 (en) 2017-12-05 2023-04-18 The Trustees Of The University Of Pennsylvania Fusion proteins and antibodies targeting human red blood cell antigens

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FI88932C (fi) * 1982-04-15 1993-07-26 Genentech Inc Framstaellning av funktionellt maenskligt urokinasprotein
KR840004781A (ko) * 1982-05-05 1984-10-24 월터 에이치·드레거 인체의 조직 플라스미노겐 활성화제
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DK385686A (da) 1987-02-15
CA1341449C (en) 2003-12-09
JPH0829086B2 (ja) 1996-03-27
DK175420B1 (da) 2004-10-04
HUT41443A (en) 1987-04-28
AU596369B2 (en) 1990-05-03
GB2179948A (en) 1987-03-18
US4916071A (en) 1990-04-10
EP0213794A1 (en) 1987-03-11
PT83170B (pt) 1988-07-29
GB8619154D0 (en) 1986-09-17
JPS62104577A (ja) 1987-05-15
IE862178L (en) 1987-02-14
KR900007649B1 (ko) 1990-10-17
IE59380B1 (en) 1994-02-23
DE3676760D1 (de) 1991-02-14
IL79644A (en) 1991-06-10
JPH07147984A (ja) 1995-06-13
PT83170A (en) 1986-09-01
JP2610783B2 (ja) 1997-05-14
EP0213794B1 (en) 1991-01-09
AU6110286A (en) 1987-02-19
HU200795B (en) 1990-08-28
DK385686D0 (da) 1986-08-13
GB2179948B (en) 1989-08-16
GR862076B (en) 1986-12-24
PH26199A (en) 1992-03-18
IL79644A0 (en) 1986-11-30

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