KR930002888B1 - 생물학적 활성 플라스미노겐 활성제의 제조방법 - Google Patents
생물학적 활성 플라스미노겐 활성제의 제조방법 Download PDFInfo
- Publication number
- KR930002888B1 KR930002888B1 KR1019870005638A KR870005638A KR930002888B1 KR 930002888 B1 KR930002888 B1 KR 930002888B1 KR 1019870005638 A KR1019870005638 A KR 1019870005638A KR 870005638 A KR870005638 A KR 870005638A KR 930002888 B1 KR930002888 B1 KR 930002888B1
- Authority
- KR
- South Korea
- Prior art keywords
- cell
- medium
- plasminogen activator
- human tissue
- tissue plasminogen
- 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
Links
- 238000004519 manufacturing process Methods 0.000 title description 15
- 239000002609 medium Substances 0.000 claims description 56
- 210000004027 cell Anatomy 0.000 claims description 49
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 41
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 41
- 229960000187 tissue plasminogen activator Drugs 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 27
- 238000004113 cell culture Methods 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 19
- 239000000725 suspension Substances 0.000 claims description 18
- 230000012010 growth Effects 0.000 claims description 16
- 239000006285 cell suspension Substances 0.000 claims description 13
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 13
- 239000012528 membrane Substances 0.000 claims description 11
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 claims description 7
- 238000009295 crossflow filtration Methods 0.000 claims description 7
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 229960000485 methotrexate Drugs 0.000 claims description 6
- 239000013604 expression vector Substances 0.000 claims description 5
- 239000012510 hollow fiber Substances 0.000 claims description 5
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 238000004114 suspension culture Methods 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 239000001963 growth medium Substances 0.000 claims description 3
- 238000011084 recovery Methods 0.000 claims description 3
- 108010022394 Threonine synthase Proteins 0.000 claims description 2
- 230000004071 biological effect Effects 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 claims description 2
- 239000012092 media component Substances 0.000 claims description 2
- 230000010076 replication Effects 0.000 claims description 2
- 230000003321 amplification Effects 0.000 claims 3
- 239000003550 marker Substances 0.000 claims 3
- 238000003199 nucleic acid amplification method Methods 0.000 claims 3
- 235000004237 Crocus Nutrition 0.000 claims 1
- 241000596148 Crocus Species 0.000 claims 1
- 210000000078 claw Anatomy 0.000 claims 1
- 238000007654 immersion Methods 0.000 claims 1
- 238000003259 recombinant expression Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 238000004804 winding Methods 0.000 claims 1
- 210000002966 serum Anatomy 0.000 description 29
- 239000000306 component Substances 0.000 description 27
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 21
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 19
- 102000001938 Plasminogen Activators Human genes 0.000 description 18
- 108010001014 Plasminogen Activators Proteins 0.000 description 18
- 229940127126 plasminogen activator Drugs 0.000 description 18
- 244000309466 calf Species 0.000 description 11
- 230000001605 fetal effect Effects 0.000 description 9
- 230000010261 cell growth Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 239000000835 fiber Substances 0.000 description 6
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 5
- 230000017854 proteolysis Effects 0.000 description 5
- 239000012679 serum free medium Substances 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 230000000254 damaging effect Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 229940012957 plasmin Drugs 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 229940044627 gamma-interferon Drugs 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- LVSPDZAGCBEQAV-UHFFFAOYSA-N 4-chloronaphthalen-1-ol Chemical compound C1=CC=C2C(O)=CC=C(Cl)C2=C1 LVSPDZAGCBEQAV-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000001279 glycosylating effect Effects 0.000 description 1
- 102000047823 human PLAT Human genes 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000013408 indirect enzyme-linked immunoassay Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- 239000013028 medium composition Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- -1 neuramididases Substances 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000013587 production medium Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007560 sedimentation technique Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012090 serum-supplement Substances 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Images
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
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87164286A | 1986-06-06 | 1986-06-06 | |
| US871642 | 1986-06-06 | ||
| US06/871,642 | 1986-06-06 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR880000590A KR880000590A (ko) | 1988-03-28 |
| KR930002888B1 true KR930002888B1 (ko) | 1993-04-12 |
Family
ID=25357832
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019870005638A Expired - Lifetime KR930002888B1 (ko) | 1986-06-06 | 1987-06-04 | 생물학적 활성 플라스미노겐 활성제의 제조방법 |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US5053334A (https=) |
| EP (1) | EP0248675B1 (https=) |
| JP (1) | JPS6332484A (https=) |
| KR (1) | KR930002888B1 (https=) |
| AT (1) | ATE75775T1 (https=) |
| AU (1) | AU601984B2 (https=) |
| DD (1) | DD257087A5 (https=) |
| DE (2) | DE3778758D1 (https=) |
| DK (1) | DK175366B1 (https=) |
| ES (1) | ES2032444T3 (https=) |
| FI (1) | FI91886C (https=) |
| FR (1) | FR2599625B1 (https=) |
| GB (1) | GB2191493B (https=) |
| GR (1) | GR3005245T3 (https=) |
| HU (1) | HU205171B (https=) |
| IE (1) | IE60485B1 (https=) |
| IL (1) | IL82746A (https=) |
| NO (1) | NO170595C (https=) |
| NZ (1) | NZ220547A (https=) |
| PT (1) | PT84991B (https=) |
| ZA (1) | ZA874054B (https=) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT84991B (pt) * | 1986-06-06 | 1990-03-08 | Genentech Inc | Processo para a producao de actividador do plasminogenio biologicamente activo |
| JP2576200B2 (ja) * | 1988-03-09 | 1997-01-29 | 味の素株式会社 | 生理活性タンパク質の製造法 |
| EP0338716A3 (en) * | 1988-04-21 | 1990-04-11 | Berlex Laboratories, Inc. | Method and system for the production of non-degraded proteins from mammalian cells |
| DE3829244A1 (de) * | 1988-08-29 | 1990-03-01 | Boehringer Mannheim Gmbh | Verfahren zur herstellung von einkettigem t-pa |
| CA2011548A1 (en) * | 1989-03-07 | 1990-09-07 | Hubertus Stockinger | Process for the production of two-chain t-pa |
| GB2249099B (en) * | 1990-09-26 | 1995-05-03 | Squibb & Sons Inc | Squalene synthetase |
| US5677184A (en) * | 1994-04-19 | 1997-10-14 | Takeda Chemical Industries, Ltd. | CHO cells that express human LH-RH receptor |
| US6077940A (en) * | 1997-12-24 | 2000-06-20 | Genentech, Inc. | Free solution ligand interaction molecular separation method |
| WO2003087292A2 (en) | 2002-04-08 | 2003-10-23 | Millenium Biologix Inc. | Automated tissue engineering system |
| SI2041259T1 (sl) | 2006-07-14 | 2016-04-29 | Dpx Holdings B.V. | Izboljšan postopek kultiviranja celic |
| WO2009023562A2 (en) * | 2007-08-09 | 2009-02-19 | Wyeth | Use of perfusion to enhance production of fed-batch cell culture in bioreactors |
| JP2013517771A (ja) * | 2010-01-22 | 2013-05-20 | ロンザ ウォーカーズヴィル,インコーポレーテッド | タンジェンシャルフローフィルトレーションを用いた治療用細胞の容量減少および洗浄のための高収率法および装置 |
| US10934519B2 (en) | 2011-07-29 | 2021-03-02 | Global Life Sciences Solutions Usa Llc | Systems, methods and control laws for cell harvesting |
| CN104583386A (zh) * | 2012-08-20 | 2015-04-29 | 泰尔茂比司特公司 | 浓缩穿过细胞生长腔室循环的流体的组分 |
| CA3248436A1 (en) | 2017-09-01 | 2025-02-21 | Lonza Walkersville, Inc. | END-TO-END AUTOMATION OF CELL THERAPY |
| JP7396777B2 (ja) | 2018-09-28 | 2023-12-12 | オクタン バイオテック インコーポレーテッド | 磁気分離 |
| KR20210108406A (ko) | 2018-12-21 | 2021-09-02 | 론자 워커스빌 아이엔씨. | 바이러스 벡터의 자동화된 생산 |
| IL284214B2 (en) | 2018-12-21 | 2025-03-01 | Octane Biotech Inc | Carousel for modular biologic production units |
| SG11202106652WA (en) | 2018-12-28 | 2021-07-29 | Octane Biotech Inc | Cell culture and tissue engineering systems with controlled environmental zones |
| IL285288B2 (en) | 2019-02-08 | 2026-04-01 | Lonza Walkersville Inc | Cell concentration methods and devices for use in automated bioreactors |
| CN114729292A (zh) | 2019-10-24 | 2022-07-08 | 奥克泰生物科技股份有限公司 | 具有经改进的细胞接触表面的细胞培养室 |
| EP4058563A4 (en) | 2019-11-11 | 2023-12-06 | Lonza Walkersville, Inc. | QUALITY CONTROL PROCEDURES FOR AUTOMATED CELL PROCESSING |
| US12187784B2 (en) | 2021-07-02 | 2025-01-07 | Combangio, Inc. | Processes for making a cellular fibronectin composition |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3904480A (en) * | 1972-10-24 | 1975-09-09 | Lilly Co Eli | Enhanced production of plasminogen activator |
| JPS5329985A (en) * | 1976-08-27 | 1978-03-20 | Kanegafuchi Chem Ind Co Ltd | High concentration culturing of yeast |
| JPS5571496A (en) * | 1978-11-24 | 1980-05-29 | Asahi Chem Ind Co Ltd | Preparation of living substance |
| US4409331A (en) * | 1979-03-28 | 1983-10-11 | Damon Corporation | Preparation of substances with encapsulated cells |
| US4232124A (en) * | 1979-04-23 | 1980-11-04 | Mann George F | Method of producing plasminogen activator |
| DE3015699C2 (de) * | 1979-04-26 | 1982-07-15 | Asahi Kasei Kogyo K.K., Osaka | Herstellung eines Plasminogen-Aktivators |
| JPS5642584A (en) * | 1979-09-18 | 1981-04-20 | Asahi Chem Ind Co Ltd | Cell cultivation method |
| US4420398A (en) * | 1981-08-13 | 1983-12-13 | American National Red Cross | Filteration method for cell produced antiviral substances |
| IL68561A (en) * | 1982-05-05 | 1991-01-31 | Genentech Inc | Preparation of polypeptide with human tissue plasminogen activator function,processes for making it,and dna and transformed cell intermediates thereof |
| JPS5951220A (ja) * | 1982-08-02 | 1984-03-24 | Asahi Chem Ind Co Ltd | 新規なプラスミノ−ゲン・アクチベ−タ−およびその製法ならびにこれを含有する薬剤 |
| US4537860A (en) * | 1982-12-08 | 1985-08-27 | Monsanto Company | Static cell culture maintenance system |
| NZ206699A (en) * | 1982-12-30 | 1989-08-29 | Bio Response Inc | Process for the production of serum independent cell lines |
| AU572108B2 (en) * | 1983-01-19 | 1988-05-05 | Genentech Inc. | Human tpa production using vectors coding for dhfr protein |
| JPS59121172U (ja) * | 1983-02-04 | 1984-08-15 | ミネソタ・マイニング・アンド・マニユフアクチユアリング・コンパニ− | ケーブル電線被覆の剥離部分のカバー装置 |
| US4546083A (en) * | 1983-04-22 | 1985-10-08 | Stolle Research & Development Corporation | Method and device for cell culture growth |
| PH22337A (en) * | 1983-11-21 | 1988-08-12 | Ciba Geigy Ag | Synthesis of fibrinolytic agents by yeast |
| US4740461A (en) * | 1983-12-27 | 1988-04-26 | Genetics Institute, Inc. | Vectors and methods for transformation of eucaryotic cells |
| US4888115A (en) * | 1983-12-29 | 1989-12-19 | Cuno, Incorporated | Cross-flow filtration |
| US4757005A (en) * | 1984-04-19 | 1988-07-12 | Miles Inc. | Method and cell line for obtaining plasminogen activators |
| DE3676604D1 (de) * | 1985-03-22 | 1991-02-07 | Chiron Corp | Expression von epa in saeugetierzellen. |
| AU593264B2 (en) * | 1985-07-10 | 1990-02-08 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Chromosomal DNA sequence, expression vector for human tissue plasminogen activating factor, cultured cells transfected with same and method of producing said activating factor |
| AU606582B2 (en) * | 1985-09-06 | 1991-02-14 | Codon | Methods for the recovery of tissue plasminogen activator |
| JPH07110232B2 (ja) * | 1985-10-14 | 1995-11-29 | 株式会社日立製作所 | 遺伝子組換え大腸菌の遺伝子生産物を採取する方法および装置 |
| PT84991B (pt) * | 1986-06-06 | 1990-03-08 | Genentech Inc | Processo para a producao de actividador do plasminogenio biologicamente activo |
-
1987
- 1987-06-02 PT PT84991A patent/PT84991B/pt unknown
- 1987-06-02 IL IL8274687A patent/IL82746A/en not_active IP Right Cessation
- 1987-06-03 HU HU872536A patent/HU205171B/hu unknown
- 1987-06-03 NZ NZ220547A patent/NZ220547A/en unknown
- 1987-06-04 KR KR1019870005638A patent/KR930002888B1/ko not_active Expired - Lifetime
- 1987-06-04 DK DK198702881A patent/DK175366B1/da not_active IP Right Cessation
- 1987-06-05 AU AU73872/87A patent/AU601984B2/en not_active Expired
- 1987-06-05 ES ES198787304995T patent/ES2032444T3/es not_active Expired - Lifetime
- 1987-06-05 FR FR878707905A patent/FR2599625B1/fr not_active Expired - Lifetime
- 1987-06-05 DE DE8787304995T patent/DE3778758D1/de not_active Expired - Lifetime
- 1987-06-05 FI FI872526A patent/FI91886C/fi not_active IP Right Cessation
- 1987-06-05 NO NO872395A patent/NO170595C/no unknown
- 1987-06-05 DE DE3718939A patent/DE3718939C2/de not_active Expired - Lifetime
- 1987-06-05 EP EP87304995A patent/EP0248675B1/en not_active Expired - Lifetime
- 1987-06-05 JP JP62142121A patent/JPS6332484A/ja active Granted
- 1987-06-05 GB GB8713267A patent/GB2191493B/en not_active Expired - Lifetime
- 1987-06-05 AT AT87304995T patent/ATE75775T1/de not_active IP Right Cessation
- 1987-06-05 IE IE150487A patent/IE60485B1/en not_active IP Right Cessation
- 1987-06-05 DD DD30357587A patent/DD257087A5/de unknown
- 1987-06-05 ZA ZA874054A patent/ZA874054B/xx unknown
-
1990
- 1990-05-09 US US07/522,073 patent/US5053334A/en not_active Expired - Lifetime
-
1992
- 1992-07-21 GR GR920401579T patent/GR3005245T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR930002888B1 (ko) | 생물학적 활성 플라스미노겐 활성제의 제조방법 | |
| Lillie et al. | Fine structure of subcultivated stratified squamous epithelium grown on collagen rafts | |
| US20050019914A1 (en) | Perfusion process for producing erythropoietin | |
| JPS59139324A (ja) | 血清非依存性セルラインの確立方法 | |
| JP6282467B2 (ja) | タンパク質を生産するための方法 | |
| EP0317874B1 (en) | Continuous cell dispersion, cultivation and substance recovery system | |
| US5576194A (en) | Recombinant protein production | |
| AU772144B2 (en) | A method for the production of pharmaceutically active recombinant proteins | |
| Hauser et al. | The isolation and cultivation of rabbit bone marrow mononuclear phagocytes | |
| JP2879906B2 (ja) | プロコラゲナーゼの製造方法 | |
| CN115838686A (zh) | 一种规模化纯化人间充质干细胞来源的小细胞外囊泡的方法 | |
| Bentley et al. | Characterization of Marrow‐Derived Adherent Cells: Evidence Against an Endothelial Subpopulation | |
| EP0640125A1 (en) | Improved recombinant protein production | |
| EP1078041B1 (en) | Process for continuous purification and concentration of leukocytes from blood | |
| JPS61126031A (ja) | コロニ−形成刺激因子の製造法 | |
| JP2837549B2 (ja) | プロコラゲナーゼの製造方法 | |
| JPH05252951A (ja) | プロコラゲナーゼの製造方法 | |
| JPH0532025B2 (https=) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 19870604 |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 19900629 Comment text: Request for Examination of Application Patent event code: PA02011R01I Patent event date: 19870604 Comment text: Patent Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 19920922 Patent event code: PE09021S01D |
|
| G160 | Decision to publish patent application | ||
| PG1605 | Publication of application before grant of patent |
Comment text: Decision on Publication of Application Patent event code: PG16051S01I Patent event date: 19930317 |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 19930628 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 19930714 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 19930714 End annual number: 3 Start annual number: 1 |
|
| PR1001 | Payment of annual fee |
Payment date: 19960403 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 19970408 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 19980410 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 19990402 Start annual number: 7 End annual number: 7 |
|
| PR1001 | Payment of annual fee |
Payment date: 20000408 Start annual number: 8 End annual number: 8 |
|
| PR1001 | Payment of annual fee |
Payment date: 20010404 Start annual number: 9 End annual number: 9 |
|
| PR1001 | Payment of annual fee |
Payment date: 20020403 Start annual number: 10 End annual number: 10 |
|
| PR1001 | Payment of annual fee |
Payment date: 20030410 Start annual number: 11 End annual number: 11 |
|
| PR1001 | Payment of annual fee |
Payment date: 20040323 Start annual number: 12 End annual number: 12 |
|
| PR1001 | Payment of annual fee |
Payment date: 20050408 Start annual number: 13 End annual number: 13 |
|
| PR1001 | Payment of annual fee |
Payment date: 20060410 Start annual number: 14 End annual number: 14 |
|
| FPAY | Annual fee payment |
Payment date: 20070411 Year of fee payment: 15 |
|
| PR1001 | Payment of annual fee |
Payment date: 20070411 Start annual number: 15 End annual number: 15 |
|
| EXPY | Expiration of term | ||
| PC1801 | Expiration of term |