DE69033699T2 - Gegenüber eigenen inhibitoren resistente t-pa mutanten - Google Patents

Gegenüber eigenen inhibitoren resistente t-pa mutanten

Info

Publication number
DE69033699T2
DE69033699T2 DE69033699T DE69033699T DE69033699T2 DE 69033699 T2 DE69033699 T2 DE 69033699T2 DE 69033699 T DE69033699 T DE 69033699T DE 69033699 T DE69033699 T DE 69033699T DE 69033699 T2 DE69033699 T2 DE 69033699T2
Authority
DE
Germany
Prior art keywords
mutants
serine protease
inhibitors
mutants resistant
encode
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
DE69033699T
Other languages
English (en)
Other versions
DE69033699D1 (de
Inventor
F Sambrook
L Madison
J Goldsmith
H Gething
D Gerard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
Original Assignee
University of Texas System
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US07/434,748 external-priority patent/US5550042A/en
Application filed by University of Texas System filed Critical University of Texas System
Publication of DE69033699D1 publication Critical patent/DE69033699D1/de
Application granted granted Critical
Publication of DE69033699T2 publication Critical patent/DE69033699T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C07K14/8132—Plasminogen activator inhibitors
    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • 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
    • C12N15/70—Vectors or expression systems specially adapted for E. coli
    • C12N15/71—Expression systems using regulatory sequences derived from the trp-operon
    • 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
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • 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
    • 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)
    • 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
    • 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)
    • C12N9/6427—Chymotrypsins (3.4.21.1; 3.4.21.2); Trypsin (3.4.21.4)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21069—Protein C activated (3.4.21.69)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/10—Plasmid DNA
    • C12N2800/108—Plasmid DNA episomal vectors
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/55—Vector systems having a special element relevant for transcription from bacteria
    • 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
    • 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)
    • C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
DE69033699T 1989-03-06 1990-03-01 Gegenüber eigenen inhibitoren resistente t-pa mutanten Expired - Lifetime DE69033699T2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US31921289A 1989-03-06 1989-03-06
US07/434,748 US5550042A (en) 1989-03-06 1989-11-13 Serine protease mutants of the chymotrypsin superfamily resistant to inhibition by their cognate inhibitors and genes encoding the same and serine protease inhibitor mutants and genes encoding the same
PCT/US1990/000947 WO1990010649A1 (en) 1989-03-06 1990-03-01 Serpin resistant chymotrypsin superfamily proteases, particularly pai-1 resistant +-pa, complementary inhibitor mutants; compositions; genes; expression

Publications (2)

Publication Number Publication Date
DE69033699D1 DE69033699D1 (de) 2001-03-15
DE69033699T2 true DE69033699T2 (de) 2001-05-23

Family

ID=23241316

Family Applications (2)

Application Number Title Priority Date Filing Date
DE69033699T Expired - Lifetime DE69033699T2 (de) 1989-03-06 1990-03-01 Gegenüber eigenen inhibitoren resistente t-pa mutanten
DE69034013T Expired - Lifetime DE69034013T2 (de) 1989-03-06 1990-03-01 Serpin-resistenter T-PA; Mutanten; Gene

Family Applications After (1)

Application Number Title Priority Date Filing Date
DE69034013T Expired - Lifetime DE69034013T2 (de) 1989-03-06 1990-03-01 Serpin-resistenter T-PA; Mutanten; Gene

Country Status (10)

Country Link
US (1) US5728564A (de)
EP (2) EP1029921B1 (de)
JP (3) JP2991769B2 (de)
AT (2) ATE226636T1 (de)
AU (1) AU637791B2 (de)
CA (1) CA2047702C (de)
DE (2) DE69033699T2 (de)
DK (2) DK0462207T3 (de)
ES (2) ES2154629T3 (de)
WO (1) WO1990010649A1 (de)

Families Citing this family (31)

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Publication number Priority date Publication date Assignee Title
US5714145A (en) * 1988-09-02 1998-02-03 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties
US5262170A (en) * 1988-09-02 1993-11-16 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties and substituted at amino acid positions 296-299, DNA molecules encoding them, vectors, and host cells
US5866413A (en) * 1989-03-06 1999-02-02 Board Of Regents Of The University Of Texas System Pai-1 mutants
ATE163048T1 (de) * 1989-12-29 1998-02-15 Zymogenetics Inc Hybrides protein c
US5358932A (en) * 1989-12-29 1994-10-25 Zymogenetics, Inc. Hybrid protein C
GB9011861D0 (en) * 1990-05-26 1990-07-18 Beecham Group Plc Novel compounds
JP2532193B2 (ja) * 1990-12-18 1996-09-11 ジェネンテク，インコーポレイテッド 組織プラスミノ―ゲン活性化因子置換変異体
AU664469B2 (en) * 1992-06-03 1995-11-16 Genentech Inc. Tissue plasminogen activator glycosylation variants with improved therapeutic properties
GB9216558D0 (en) * 1992-08-04 1992-09-16 British Bio Technology Modified proteases
US5567602A (en) * 1992-08-12 1996-10-22 Arris Pharmaceutical Corporation Recombinant production of chymase
ES2080657B1 (es) * 1993-09-27 1996-11-01 Britisch Bio Technology Limite Proteasas modificadas.
EP0958833A1 (de) * 1998-05-20 1999-11-24 Erasmus Universiteit Rotterdam Verfahren und Mittel zur Vorbeugung oder Behandlung der Entzündung
AUPP508798A0 (en) 1998-08-05 1998-08-27 Biotech Australia Pty Limited Method of treating psoriasis
AU2001238721A1 (en) * 2000-03-03 2001-09-17 Zymogenetics Inc. Human serine protease
US6673623B1 (en) 2000-09-12 2004-01-06 Novocure, Inc. Methods and compositions that control lipid production
WO2002072786A2 (en) 2001-03-13 2002-09-19 Corvas International, Inc. Nucleic acid molecules encoding a transmembrane serine protease 7, the encoded polypeptides and methods based thereon
AU2002254357A1 (en) 2001-03-22 2002-10-08 Dendreon Corporation Nucleic acid molecules encoding serine protease cvsp14, the encoded polypeptides and methods based thereon
CA2442089A1 (en) 2001-03-27 2002-10-03 Dendreon San Diego Llc Nucleic acid molecules encoding a transmembran serine protease 9, the encoded polypeptides and methods based thereon
US7112430B2 (en) 2001-05-14 2006-09-26 Dendreon Corporation Nucleic acid molecules encoding a transmembrane serine protease 10, the encoded polypeptides and methods based thereon
US7001872B2 (en) * 2001-06-11 2006-02-21 Halliburton Energy Services, Inc. Subterranean formation treating fluid and methods of fracturing subterranean formations
US6488091B1 (en) * 2001-06-11 2002-12-03 Halliburton Energy Services, Inc. Subterranean formation treating fluid concentrates, treating fluids and methods
US20050137094A1 (en) * 2001-06-11 2005-06-23 Halliburton Energy Sevices, Inc. Subterranean formation treatment fluids and methods of using such fluids
WO2003004681A2 (en) * 2001-07-03 2003-01-16 Dendreon San Diego Llc Nucleic acid molecules encoding a transmembrane serine protease 20, the encoded polypeptides and methods based thereon
CA2453810A1 (en) * 2001-07-18 2003-07-03 American Red Cross Mutant proteinase inhibitors and uses thereof
AU2002357004A1 (en) * 2001-11-20 2003-06-10 Dendreon San Diego Llc Nucleic acid molecules encoding serine protease 17, the encoded polypeptides and methods based thereon
US20040001801A1 (en) * 2002-05-23 2004-01-01 Corvas International, Inc. Conjugates activated by cell surface proteases and therapeutic uses thereof
PT1616007E (pt) * 2003-04-04 2013-10-28 Univ Lausanne Proteínas inibidoras de uma protease e uso das mesmas
EP2046951B1 (de) 2006-07-05 2011-10-26 Catalyst Biosciences, Inc. Protease-screening-verfahren und dadurch identifizierte proteasen
WO2020140101A1 (en) * 2018-12-28 2020-07-02 Catalyst Biosciences, Inc. Modified urokinase-type plasminogen activator polypeptides and methods of use
US11613744B2 (en) 2018-12-28 2023-03-28 Vertex Pharmaceuticals Incorporated Modified urokinase-type plasminogen activator polypeptides and methods of use
CN112375131B (zh) * 2020-11-16 2021-10-01 西南大学 Seroin蛋白的截短体及其应用

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5112755A (en) * 1982-04-15 1992-05-12 Genentech, Inc. Preparation of functional human urokinase proteins
GR79202B (de) * 1982-05-05 1984-10-22 Genentech Inc
AU560584B2 (en) * 1983-07-28 1987-04-09 Bayer Aktiengesellschaft Homologues of aprotinin
US5073494A (en) * 1985-04-22 1991-12-17 Genentech, Inc. Human tissue plasminogen activator substituted at position 275 or at positions 275 and 277
JPH084501B2 (ja) * 1987-03-20 1996-01-24 エーザイ株式会社 糖鎖に関する変異ｔＰＡ
MY103358A (en) * 1987-04-15 1993-06-30 Novartis Ag Process for the production of protiens.
FI882407A (fi) * 1987-05-22 1988-11-23 Zymogenetics Inc Fibrinolytiska proteiner.
US5200340A (en) * 1987-05-22 1993-04-06 Zymogenetics, Inc. Thrombin-activated tissue plasminogen activators
GB2208511A (en) * 1987-08-07 1989-04-05 Bayer Ag Variants of bovine pancreatic trypsin inhibitor produced by recombinant dna technology
US5188829A (en) * 1987-08-19 1993-02-23 Sagami Chemical Research Center Rapidly acting prourokinase
EP0398962A1 (de) * 1988-02-05 1990-11-28 Genzyme Corporation Geänderte gewebsplasminogenaktivatoren und verfahren zu ihrer herstellung
EP0400054A1 (de) * 1988-02-05 1990-12-05 Genzyme Corporation Für modifizierte tpa-moleküle kodierende gensequenzen und deren produkte
US5108901A (en) * 1988-09-02 1992-04-28 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties
US5262170A (en) * 1988-09-02 1993-11-16 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties and substituted at amino acid positions 296-299, DNA molecules encoding them, vectors, and host cells

Also Published As

Publication number Publication date
EP0462207A1 (de) 1991-12-27
DK0462207T3 (da) 2001-06-18
EP1029921B1 (de) 2002-10-23
JP2000078990A (ja) 2000-03-21
JP3076034B2 (ja) 2000-08-14
JP2991769B2 (ja) 1999-12-20
ATE226636T1 (de) 2002-11-15
JP2000037195A (ja) 2000-02-08
DE69033699D1 (de) 2001-03-15
CA2047702A1 (en) 1990-09-07
DE69034013T2 (de) 2003-07-31
AU637791B2 (en) 1993-06-10
ES2185529T3 (es) 2003-05-01
ATE199090T1 (de) 2001-02-15
DK1029921T3 (da) 2003-02-24
WO1990010649A1 (en) 1990-09-20
AU5278090A (en) 1990-10-09
ES2154629T3 (es) 2001-04-16
US5728564A (en) 1998-03-17
EP0462207A4 (en) 1992-06-24
DE69034013D1 (de) 2002-11-28
CA2047702C (en) 2000-10-24
EP1029921A1 (de) 2000-08-23
EP0462207B1 (de) 2001-02-07
JPH04504952A (ja) 1992-09-03
JP3076035B2 (ja) 2000-08-14

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