KR910018406A - 폴리펩티드류 - Google Patents

폴리펩티드류 Download PDF

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KR910018406A
KR910018406A KR1019910006926A KR910006926A KR910018406A KR 910018406 A KR910018406 A KR 910018406A KR 1019910006926 A KR1019910006926 A KR 1019910006926A KR 910006926 A KR910006926 A KR 910006926A KR 910018406 A KR910018406 A KR 910018406A
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캠블 로저
칼 해더
팀스 데이비드
제임스 윌킨슨 안토니
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원본미기재
임페리얼 케미칼 인더스트리스 피엘씨
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Priority claimed from GB909009623A external-priority patent/GB9009623D0/en
Priority claimed from GB909013773A external-priority patent/GB9013773D0/en
Priority claimed from GB909016215A external-priority patent/GB9016215D0/en
Priority claimed from GB919102799A external-priority patent/GB9102799D0/en
Application filed by 원본미기재, 임페리얼 케미칼 인더스트리스 피엘씨 filed Critical 원본미기재
Publication of KR910018406A publication Critical patent/KR910018406A/ko

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70—Vectors or expression systems specially adapted for E. coli
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
    • C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/67—General methods for enhancing the expression
    • C12N15/68—Stabilisation of the vector
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S930/00—Peptide or protein sequence
    • Y10S930/01—Peptide or protein sequence
    • Y10S930/14—Lymphokine; related peptides
    • Y10S930/145—Colony stimulating factor

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  • Health & Medical Sciences (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract

내용 없음

Description

폴리펩티드류
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 실시예1에서 언급한 167bp 단편의 뉴클레오티드 서열을 나타낸 것이다.

Claims (15)

  1. 천연발생 G-CSF의 생물학적 특성중 적어도 하나의 특성을 갖고 있으며, 5㎎/㎖에서 최소한 35%의 용액 안정성(본 명세서에 정의됨)을 갖는 천연 발생 G-CSF의 유도체에 있어서, 이 유도체는 적어도 고유서열의 Cys17Ser17잔기로 치환되며, 고유서열의 Asp27이 Ser27잔기로 치환된 것을 특징으로하는 유도체.
  2. 제1항에 있어서, 하기 a)내지 r)로 구성된 것으로부터 선택된 적어도 하나의 추가 변형을 갖는 유도체: a) 고유 서열의 Leu15가 Glu15잔기로 치환됨; b)고유 서열의 Lys23이 Arg23잔기로 치환됨; c)고유 서열의Gly26이 Ala26잔기로 치환됨; d) 고유 서열의 Gly28이 Ala28잔기로 치환됨; e)고유 서열의 Ala30이 Lys30잔기 또는 Arg30자기로 치환됨; f)고유 서열의 Lys34가 Arg34잔기로 치환됨; g)고유 서열의 Lys40가 Arg40이 잔기로 치환됨; h)고유 서열의 Pro44가 Ala44잔기로 치환됨; i)고유 서열의 Leu49가 Lys49잔길 치환됨; j)고유 서열의 Gly51이 Ala51잔기로 치환됨; k)고유 서열의 Gly55가 Ala55잔기로 치환됨; l)고유 서열의 Trp58이 Lys58잔기로 치환됨; m)고유 서열의 Pro60이 Ser60잔기로 치환됨; n)고유 서열의 Pro65이 Ser65잔기로 치환됨; o)고유 서열의 Pro111이 Glu111잔기로 치환됨; p)고유 서열의 Thr115가 Ser115잔기로 치환됨; q)고유 서열의 Thr116이 Ser116잔기로 치환됨; 및 r)고유 서열의 Tyr165가 Arg165잔기로 치환됨.
  3. 제1항 또는 제2항에 있어서, 상기 추가변형은 하기(a) 내지 (i)중 적어도 하나를 포함하는 유도체.
    a)고유 서열의Gln11, Pro60'65가 Arg11, Ser60'65로 치환됨; b)고유서열의 Ala111, Thr115'116이 Glu111, Ser115'116으로 치환됨; c)고유서열이 Gln11, Trp58,Tyr165가 Arg11'165,Lys58으로 치환됨; d)고유서열의 Leu15,Gly26'28,Ala30이 Glu15, Ala26'28, Lys30으로 치환됨; e)고유서열의 Pro44,Leu49, Gly51'55, Trp58이 Lys49'58,Ala44'51'55로 치환됨; f)고유서열의 Leu15, Gly26'28,Ala30이 Glu15, Ala26'28, Arg30으로 치환됨; g)고유서열이 Pro55가 Ser65로 치환됨; h)고유서열의 Pro60'65가 Ser60'65로 치환됨; 또는 i)고유서열의 Glu11, Pro65가 Arg11, Ser65로 치환됨.
  4. 전술한 항들중 어느 한항에 있어서, 상기 유도체는 하기한 것들로부터 선택되며, 바람직하다면 전서열(presequence)메티오닌을 갖는 유도체.
    〔Arg11,Ser17'27'60'65〕hu G-CSF;〔Glu15,Ser17'27,Ala26'28,Lys30〕hu G-CSF;〔Arg11,Glu15,Ser17'27'60'65,Ala|26'28,Lys30〕hu G-CSF;〔Arg11'165,Glu15,Ser17'27'60'|65,Ala26'28,Lys30'58〕hu G-CSF;〔Arg11'23,Ser17'27'60'65〕hu G-CSF;〔Arg11'40,Ser17'27'60'65〕hu G-CSF;〔Glu15'111,Ser17'27'60'65'115'116,Ala26'28,Lys30〕hu G-CSF〔Ala1,Thr3,Tyr4,Arg5'11, Ser17'|27'60'65〕hu G-CSF;〔Glu15,Ser17'27,Ala|26'28,Arg30〕hu G-CSF;〔Arg11,Ser17'27'65〕huG-CSF〔Ser17'27'65〕hu G-CSF〔Ser17'27'60'65〕hu G-CSF.
  5. 전술한 항들중 어느 한항에서 청구된 유도체의 아미노산 서열의 일부 혹은 전부를 암호하는 DNA서열.
  6. 제5항에서 정의된 DNA 서열을 함유하는 재조합 벡터.
  7. 제5항에서, 정의된 DNA 서열을 벡테내로 삽입하는 것을 포함하는 제6항에서 정의된 재조합 벡터의 제조방법.
  8. 제6항에서 정의된 재조합 벡터에 의해 안정하게 형질전환 또는 형질감연된 원핵 또는 진핵의 숙주 세포.
  9. 제6항에서 정의된 재조합 벡터로 원핵 또는 진핵의 세포를 형질 전환 또는 형질감염 시킴으로써 안정하게 형질전환 또는 형질 감염된 원핵 또는 진핵숙주를 수득하는 단계를 포함하는 제8항에서 정의된 원핵 또는 진핵의 숙주 세포를 제조하는 방법.
  10. 제8항에서 정의된 원핵 또는 진핵의 숙주를 배향함으로써 제1항 내지 제4항중 어느 한항에서 정의된 천연발생 G-CSF의 유도체를 얻는것을 포함하는 상기 유도체의 제조방법.
  11. 제1항 내지 제4항중 어느 한항에서 청구된 천연 발생 G-CSF의 유도체중 최소한 하나를 활성성분으로 포함하며, 약학적 허용담체 또는 부형제를 함께 포함하는 약학적 조성물.
  12. 제1항 내지 4항중 어느 한항에서 청구된 유도체를 유효량으로 투여하는 것을 포함하는 포유류에 대한 조혈치료법을 제공하는 방법.
  13. 제1항 내지 4항중 어느 한항에서 정의된 유도체를 유효량 투여하는 것을 포함하는 백혈구 세포의 증식을 억제시키는 방법.
  14. 1) 제1항 내지 제4항중 어느 한항에서 청구된 유도체의 봉입체를 세척제내에 현탁시키는 단계, 2) 산화 단계. 3) 세척제를 제거하는 단계, 그리고 4) 세척제를 제거한뒤 얻어진 용액을 승온에서 유지시켜 오염된 박테리아 단백질, 울리고머 생성물 및/또는 분해 생성물을 침전시키고, 반면에 상기의 유도체는 용액중에 활성 형태로 유지시키는 단계를 포함하는 상기 유도체를 그것의 봉입체로 부터 추출하는 방법.
  15. 제14항에 있어서, 상기 유출된 유도체가 최소한 85%의 용액 안정성을 갖는 특징으로하는 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019910006926A 1990-04-30 1991-04-30 폴리펩티드류 KR910018406A (ko)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
GB909009623A GB9009623D0 (en) 1990-04-30 1990-04-30 Polypeptides
GB909013773A GB9013773D0 (en) 1990-06-20 1990-06-20 Polypeptides
GB909016215A GB9016215D0 (en) 1990-07-24 1990-07-24 Polypeptides
GB9013773.8 1991-02-11
GB9016215.7 1991-02-11
GB919102799A GB9102799D0 (en) 1991-02-11 1991-02-11 Polypeptides
GB9009623.1 1991-02-11
GB9102799.5 1991-02-11

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KR910018406A true KR910018406A (ko) 1991-11-30

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US (1) US5416195A (ko)
EP (1) EP0459630B1 (ko)
JP (1) JPH06100593A (ko)
KR (1) KR910018406A (ko)
AT (1) ATE169336T1 (ko)
AU (1) AU644647B2 (ko)
BG (1) BG94328A (ko)
CA (1) CA2041454A1 (ko)
CS (1) CS125091A3 (ko)
DE (1) DE69129927T2 (ko)
DK (1) DK0459630T3 (ko)
ES (1) ES2118737T3 (ko)
FI (1) FI912086A (ko)
GB (1) GB9107846D0 (ko)
GR (1) GR3027590T3 (ko)
HU (1) HUT60769A (ko)
IE (1) IE911440A1 (ko)
IL (1) IL97993A0 (ko)
NO (1) NO911696L (ko)
NZ (1) NZ237974A (ko)
PT (1) PT97529A (ko)
TW (1) TW226022B (ko)
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FI912086A0 (fi) 1991-04-30
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