AU584628B2 - A genetic engineering process for the preparation of hirudins, and means for carrying out this process - Google Patents

A genetic engineering process for the preparation of hirudins, and means for carrying out this process

Info

Publication number
AU584628B2
AU584628B2 AU45977/85A AU4597785A AU584628B2 AU 584628 B2 AU584628 B2 AU 584628B2 AU 45977/85 A AU45977/85 A AU 45977/85A AU 4597785 A AU4597785 A AU 4597785A AU 584628 B2 AU584628 B2 AU 584628B2
Authority
AU
Australia
Prior art keywords
genetic engineering
hirudins
preparation
carrying
sequences
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
Application number
AU45977/85A
Other versions
AU4597785A (en
Inventor
Dieter Brauer
Joachim Engels
Paul Habermann
Eugen Uhlmann
Friedrich Wengenmayer
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.)
Bayer Pharma AG
Original Assignee
Hoechst AG
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
Application filed by Hoechst AG filed Critical Hoechst AG
Publication of AU4597785A publication Critical patent/AU4597785A/en
Application granted granted Critical
Publication of AU584628B2 publication Critical patent/AU584628B2/en
Assigned to AVENTIS PHARMA DEUTSCHLAND GMBH reassignment AVENTIS PHARMA DEUTSCHLAND GMBH Alteration of Name(s) in Register under S187 Assignors: HOECHST AKTIENGESELLSCHAFT
Assigned to SCHERING AKTIENGESELLSCHAFT reassignment SCHERING AKTIENGESELLSCHAFT Alteration of Name(s) in Register under S187 Assignors: AVENTIS PHARMA DEUTSCHLAND GMBH
Anticipated expiration legal-status Critical
Expired 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • 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
    • C07K14/815—Protease inhibitors from leeches, e.g. hirudin, eglin
    • 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
    • C12N15/72—Expression systems using regulatory sequences derived from the lac-operon
    • 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
    • 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
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/036—Fusion polypeptide containing a localisation/targetting motif targeting to the medium outside of the cell, e.g. type III secretion
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • Seal Device For Vehicle (AREA)
  • Extrusion Moulding Of Plastics Or The Like (AREA)
  • Luminescent Compositions (AREA)

Abstract

Hirudin can be obtained using a specific DNA sequence in a genetic engineering process. The gene is advantageously synthesised in the form of several fragments which are enzymatically ligated to give two larger part-sequences which are incorporated into hybrid plasmids and amplified in host organisms. The part-sequences are reisolated and then combined to form the complete gene which is incorporated into a hybrid plasmid and the latter is expressed in a host organism. <IMAGE>
AU45977/85A 1984-08-10 1985-08-09 A genetic engineering process for the preparation of hirudins, and means for carrying out this process Expired AU584628B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3429430 1984-08-10
DE19843429430 DE3429430A1 (en) 1984-08-10 1984-08-10 GENE TECHNOLOGICAL METHOD FOR PRODUCING HIRUDINE AND MEANS FOR IMPLEMENTING THIS METHOD

Publications (2)

Publication Number Publication Date
AU4597785A AU4597785A (en) 1986-02-13
AU584628B2 true AU584628B2 (en) 1989-06-01

Family

ID=6242746

Family Applications (1)

Application Number Title Priority Date Filing Date
AU45977/85A Expired AU584628B2 (en) 1984-08-10 1985-08-09 A genetic engineering process for the preparation of hirudins, and means for carrying out this process

Country Status (18)

Country Link
EP (1) EP0171024B1 (en)
JP (1) JPH0811073B2 (en)
KR (1) KR930009337B1 (en)
AT (1) ATE67245T1 (en)
AU (1) AU584628B2 (en)
CA (1) CA1341124C (en)
DE (2) DE3429430A1 (en)
DK (1) DK175337B1 (en)
ES (1) ES8605040A1 (en)
FI (1) FI91883C (en)
GR (1) GR851962B (en)
HU (1) HU206135B (en)
IE (1) IE58485B1 (en)
IL (1) IL76059A (en)
NO (1) NO177434C (en)
NZ (1) NZ213049A (en)
PT (1) PT80930B (en)
ZA (1) ZA856026B (en)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3438296A1 (en) * 1984-04-18 1985-11-07 Hoechst Ag, 6230 Frankfurt NEW POLYPEPTIDES WITH A BLOOD-CLOTHING EFFECT, METHOD FOR THE PRODUCTION OR THEIR RECOVERY, THEIR USE AND THE CONTAINERS THEREOF
DE3445517C2 (en) * 1984-12-13 1993-11-18 Ciba Geigy DNA sequence coding for a hirudin-like protein and method for producing a hirudin-like protein
DE3738541A1 (en) * 1987-11-13 1989-05-24 Hoechst Ag METHOD FOR INSULATING AND CLEANING HIRUDINE
FR2593518B1 (en) * 1985-05-02 1989-09-08 Transgene Sa VECTORS FOR THE EXPRESSION AND SECRETION OF HIRUDIN BY TRANSFORMED YEASTS
DE3689525D1 (en) * 1985-07-17 1994-02-24 Hoechst Ag New polypeptides with an anticoagulant effect, processes for their preparation or extraction, their use and agents containing them.
DE3541856A1 (en) * 1985-11-27 1987-06-04 Hoechst Ag EUKARYOTIC FUSION PROTEINS, THEIR PRODUCTION AND USE, AND MEANS FOR CARRYING OUT THE PROCESS
GB8530631D0 (en) 1985-12-12 1986-01-22 Ciba Geigy Ag Thrombin inhibitors
MY101203A (en) * 1985-12-12 1991-08-17 Ucp Gen Pharma Ag Production of thrombin iinhibitors.
GB2188322A (en) * 1986-03-26 1987-09-30 Bayer Ag Aprotinin and analogues thereof produced by a recombinant host
GB2188933A (en) * 1986-04-10 1987-10-14 Bayer Ag Expression vectors for production of polypeptides, method for enhanced expression of polypeptides, hosts containing the expression vectors, products manufactured thereby
MC1834A1 (en) * 1986-07-10 1988-06-03 Transgene Sa DNA FUNCTIONAL BLOCK AND PLASMID ENCODING HIRUDINE, TRANSFORMED YEAST, PROCESS FOR PREPARING HIRUDINE, HIRUDINE OBTAINED AND ITS USE
FR2607516B2 (en) * 1986-12-01 1989-12-22 Transgene Sa IMPROVED VECTORS FOR EXPRESSING A HIRUDIN VARIANT IN YEAST, PROCESS AND PRODUCT OBTAINED
FR2607517B2 (en) * 1986-12-01 1989-12-22 Transgene Sa VECTORS FOR EXPRESSING HIRUDIN VARIANTS IN YEAST, PROCESS AND PRODUCT OBTAINED
GB2199582A (en) * 1987-01-07 1988-07-13 Bayer Ag Analogues of pancreatic secretory trypsin inhibitor
US5032573A (en) * 1987-03-23 1991-07-16 Bayer Aktiengesellschaft Homologs of aprotinin produced from a recombinant host, process, expression vector and recombinant host therefor and pharmaceutical use thereof
US5192745A (en) * 1987-05-21 1993-03-09 Merrell Dow Pharmaceuticals Inc. Cyclic anticoagulant peptides
US5236898A (en) * 1987-05-21 1993-08-17 Merrell Dow Pharmaceuticals Inc. Cyclic anticoagulant peptides
GB8723661D0 (en) * 1987-10-08 1987-11-11 British Bio Technology Synthetic gene
GB8723662D0 (en) * 1987-10-08 1987-11-11 British Bio Technology Synthetic gene
US5256559A (en) * 1988-03-04 1993-10-26 Biogen, Inc. Methods and compositions for inhibiting platelet aggregation
FR2628429B1 (en) * 1988-03-08 1990-12-28 Transgene Sa HIRUDINE VARIANTS, USES THEREOF AND PROCESSES FOR OBTAINING THEM
DE3819079A1 (en) * 1988-06-04 1989-12-07 Hoechst Ag HIRUDINE DERIVATIVES WITH DELAYED EFFECT
US5112615A (en) * 1988-08-03 1992-05-12 New England Deaconess Hospital Corporation Soluble hirudin conjugates
US5167960A (en) * 1988-08-03 1992-12-01 New England Deaconess Hospital Corporation Hirudin-coated biocompatible substance
DE3835815A1 (en) * 1988-10-21 1990-04-26 Hoechst Ag NEW ISOHIRUDINE
US5192747A (en) * 1989-10-03 1993-03-09 Merrell Dow Pharmaceuticals Inc. Anticoagulant peptides
DE4009268A1 (en) * 1990-03-22 1991-09-26 Consortium Elektrochem Ind SECRETION OF HIRUDIN DERIVATIVES
GB9010552D0 (en) * 1990-05-10 1990-07-04 Erba Carlo Spa Method for the recombinant production of hirudins and novel hirudins
US6514730B1 (en) 1991-03-21 2003-02-04 Consortium für elektrochemische Industrie GmbH Secretion of hirudin derivatives
DE4140381A1 (en) * 1991-12-07 1993-06-09 Hoechst Ag, 6230 Frankfurt, De NEW SYNTHETIC ISOHIRUDINE WITH IMPROVED STABILITY
US5972648A (en) * 1993-09-28 1999-10-26 Japan Energy Corporation Hirudin analogs, methods of manufacture thereof and anticoagulant compositions having these as active ingredients
DE4404168A1 (en) * 1994-02-10 1995-08-17 Hoechst Ag Hirudin derivatives and process for their preparation
DE19529997C1 (en) 1995-08-16 1997-04-10 Hoechst Ag A method for inactivating carboxypeptidase Y in hirudin-containing culture broths
DE19543737A1 (en) 1995-11-24 1997-05-28 Hoechst Ag Process for the ultrafiltration of biological matrices containing peptides or proteins
DE19544233A1 (en) * 1995-11-28 1997-06-05 Hoechst Ag Process for using the yeast ADH II promoter system for the biotechnological production of heterologous proteins in high yields
DE19607239A1 (en) 1996-02-27 1997-08-28 Behringwerke Ag Pharmaceutical composition containing hirudin and process for its preparation
DE19944870A1 (en) * 1999-09-18 2001-03-29 Aventis Pharma Gmbh Signal sequences for the production of Leu-hirudin via secretion by E. coli in the culture medium
DE10149678A1 (en) 2001-10-09 2009-03-12 Novel Science International Gmbh New peptide compounds containing upto 6 aminoacid residues, are potent and specific thrombin inhibitors used for treating and diagnosing diseases associated with thrombin
DE10301255A1 (en) 2003-01-15 2004-07-29 Cpi Creative Pharma International Gmbh Organic compounds with biological action as thrombin inhibitors and their use

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU3575984A (en) * 1983-11-22 1985-05-30 Ucp Gen-Pharma Ag Desulfatohirudins, the preparation thereof and pharmaceutical compositions containing them
WO1985004418A1 (en) * 1984-03-27 1985-10-10 Transgene S.A. Vectors for the expression of hirudine, transformed cells and process for the preparation of hirudine
EP0168342B1 (en) * 1984-06-14 1991-07-03 Ciba-Geigy Ag Process for the preparation of thrombin inhibitors

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IE53166B1 (en) * 1980-08-05 1988-08-03 Searle & Co Synthetic urogastrone gene,corresponding plasmid recombinants,transformed cells,production thereof and urogastrone expression

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU3575984A (en) * 1983-11-22 1985-05-30 Ucp Gen-Pharma Ag Desulfatohirudins, the preparation thereof and pharmaceutical compositions containing them
WO1985004418A1 (en) * 1984-03-27 1985-10-10 Transgene S.A. Vectors for the expression of hirudine, transformed cells and process for the preparation of hirudine
EP0168342B1 (en) * 1984-06-14 1991-07-03 Ciba-Geigy Ag Process for the preparation of thrombin inhibitors

Also Published As

Publication number Publication date
FI853056L (en) 1986-02-11
EP0171024B1 (en) 1991-09-11
HU206135B (en) 1992-08-28
DE3429430A1 (en) 1986-02-20
JPH0811073B2 (en) 1996-02-07
KR930009337B1 (en) 1993-09-27
CA1341124C (en) 2000-10-24
ES545994A0 (en) 1986-02-16
FI91883B (en) 1994-05-13
ATE67245T1 (en) 1991-09-15
DK175337B1 (en) 2004-08-30
JPS6147198A (en) 1986-03-07
ES8605040A1 (en) 1986-02-16
KR870002257A (en) 1987-03-30
NO177434B (en) 1995-06-06
IE851973L (en) 1986-02-10
IL76059A (en) 1993-08-18
NO177434C (en) 1995-09-13
PT80930A (en) 1985-09-01
IL76059A0 (en) 1985-12-31
EP0171024A1 (en) 1986-02-12
HUT38968A (en) 1986-07-28
DE3584053D1 (en) 1991-10-17
AU4597785A (en) 1986-02-13
DK364585D0 (en) 1985-08-09
FI853056A0 (en) 1985-08-08
ZA856026B (en) 1986-03-26
IE58485B1 (en) 1993-09-22
GR851962B (en) 1985-12-03
NO853155L (en) 1986-02-11
DK364585A (en) 1986-02-11
PT80930B (en) 1987-11-11
NZ213049A (en) 1988-05-30
FI91883C (en) 1994-08-25

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Legal Events

Date Code Title Description
PC Assignment registered

Owner name: AVENTIS PHARMA DEUTSCHLAND GMBH

Free format text: FORMER OWNER WAS: HOECHST AKTIENGESELLSCHAFT

PC Assignment registered

Owner name: SCHERING AKTIENGESELLSCHAFT

Free format text: FORMER OWNER WAS: AVENTIS PHARMA DEUTSCHLAND GMBH