DE411678T1 - Herstellungsverfahren fuer erythropoietin. - Google Patents
Herstellungsverfahren fuer erythropoietin.Info
- Publication number
- DE411678T1 DE411678T1 DE199090118215T DE90118215T DE411678T1 DE 411678 T1 DE411678 T1 DE 411678T1 DE 199090118215 T DE199090118215 T DE 199090118215T DE 90118215 T DE90118215 T DE 90118215T DE 411678 T1 DE411678 T1 DE 411678T1
- Authority
- DE
- Germany
- Prior art keywords
- cell
- dna
- epo
- human erythropoietin
- recombinant human
- 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.)
- Pending
Links
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 title claims 3
- 102000003951 Erythropoietin Human genes 0.000 title 1
- 108090000394 Erythropoietin Proteins 0.000 title 1
- 229940105423 erythropoietin Drugs 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 claims abstract 10
- 102000044890 human EPO Human genes 0.000 claims abstract 10
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 claims abstract 6
- 108020004414 DNA Proteins 0.000 claims abstract 4
- 239000002299 complementary DNA Substances 0.000 claims abstract 4
- 210000004962 mammalian cell Anatomy 0.000 claims abstract 4
- 239000013612 plasmid Substances 0.000 claims abstract 3
- 241000701822 Bovine papillomavirus Species 0.000 claims abstract 2
- 108020004511 Recombinant DNA Proteins 0.000 claims abstract 2
- 239000013600 plasmid vector Substances 0.000 claims abstract 2
- 239000013598 vector Substances 0.000 claims abstract 2
- 210000004027 cell Anatomy 0.000 claims 8
- 108010092408 Eosinophil Peroxidase Proteins 0.000 claims 2
- 102100031939 Erythropoietin Human genes 0.000 claims 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims 2
- 230000013595 glycosylation Effects 0.000 claims 2
- 238000006206 glycosylation reaction Methods 0.000 claims 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 claims 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 claims 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 claims 1
- 102000003792 Metallothionein Human genes 0.000 claims 1
- 108090000157 Metallothionein Proteins 0.000 claims 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims 1
- 230000004989 O-glycosylation Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 229930182830 galactose Natural products 0.000 claims 1
- 150000002402 hexoses Chemical class 0.000 claims 1
- 229950006780 n-acetylglucosamine Drugs 0.000 claims 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 claims 1
Classifications
-
- 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
- C12P21/00—Preparation of peptides or proteins
-
- 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
-
- 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
- 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
- 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
- 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
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
- C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
-
- 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
- C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
-
- 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
- C12N2830/60—Vector systems having a special element relevant for transcription from viruses
-
- 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
- C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
- C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian
-
- 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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/44—Vectors comprising a special translation-regulating system being a specific part of the splice mechanism, e.g. donor, acceptor
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (11)
1. Rekombinanter DNA Plasmidvektor, der für humanes EPO des Klons
Lambda HEPOFL13 (ATCC 40153) kodierende cDNA enthält.
2. Säugerzelle, die mit dem Transfervektor nach Anspruch 1
transformiert ist.
3. Zelle nach Anspruch 2, worin die Säugerzelle eine 3T3-, C127-
oder CHO-Zelle ist.
4. Säugerzelle, die ein Plasmid enthält, das die gesamte Rinder-Papillomavirus
DNA und die für humanes EPO kodierende cDNA-Sequenz gemäß Tabelle 3 enthält.
5. Zelle nach Anspruch 4, worin die Zelle eine C127- oder 3T3-Zelle
ist.
6. Zelle nach Anspruch 5, worin die EPO DNA unter transkriptionaler
Kontrolle eines Maus-Metallothioneinpromotors ist.
7. Zelle nach Anspruch 5, worin die Zelle ein Plasmid enthält, das
DNA aus pdBPV-MMTneo(342-12) (ATCC 37224) enthält.
8. Rekombinantes humanes Erythropoietin, gekennzeichnet durch das \
Vorhandensein von O-verknüpfter Glykosxlierung, erhältlich durch
die Schritte:
(a) Kultivieren von CHO-Zellen, die eine für humanes Erythropoietin
kodierende DNA-Sequenz enthalten, in einem geeigneten Medium, wobei die DNA-Sequenz operativ mit einer Expressions-
kontrollsequenz verknüpft ist, und
·*, (b) Gewinnen und Abtrennen des EPO von den Zellen und dem Medium.
·*, (b) Gewinnen und Abtrennen des EPO von den Zellen und dem Medium.
v
9. Rekombinantes humanes Erythropoietin nach Anspruch 8
gekennzeichnet durch ein Glykosilierungsmuster, das Fucose umfaßt.
10. Rekombinantes humanes Erythropoietin nach Anspruch 9 gekennzeichnet durch ein Glykosilierungsmuster, das relative
molare Mengen von Hexosen zu N-Acetylglucosamin (Nacglc) von
1,4 : 1, insbesondere Galactose : Nacglc =0,9 : 1 und Mannose : Nacglc =0,5 : 1 enthält.
11. Rekombinantes humanes Erythropoietin nach Anspruch 9 oder 10, gekennzeichnet durch das Vorhandensein von N-Acetylgalactosamin.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US67781384A | 1984-12-04 | 1984-12-04 | |
US68862285A | 1985-01-03 | 1985-01-03 | |
US69325885A | 1985-01-22 | 1985-01-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
DE411678T1 true DE411678T1 (de) | 1991-10-17 |
Family
ID=27418329
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE9090118215T Expired - Lifetime DE3585161D1 (de) | 1984-12-04 | 1985-12-03 | Herstellungsverfahren fuer erythropoietin. |
DE8686900439T Expired - Lifetime DE3582732D1 (de) | 1984-12-04 | 1985-12-03 | Herstellungsverfahren fuer erythropoietin. |
DE199090118215T Pending DE411678T1 (de) | 1984-12-04 | 1985-12-03 | Herstellungsverfahren fuer erythropoietin. |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE9090118215T Expired - Lifetime DE3585161D1 (de) | 1984-12-04 | 1985-12-03 | Herstellungsverfahren fuer erythropoietin. |
DE8686900439T Expired - Lifetime DE3582732D1 (de) | 1984-12-04 | 1985-12-03 | Herstellungsverfahren fuer erythropoietin. |
Country Status (24)
Country | Link |
---|---|
EP (2) | EP0411678B2 (de) |
JP (4) | JPH02104284A (de) |
KR (1) | KR890001011B1 (de) |
AT (2) | ATE71408T1 (de) |
AU (1) | AU621535B2 (de) |
CA (1) | CA1341502C (de) |
CZ (3) | CZ281756B6 (de) |
DE (3) | DE3585161D1 (de) |
DK (4) | DK172953B1 (de) |
ES (1) | ES8800049A1 (de) |
FI (2) | FI104261B1 (de) |
GE (1) | GEP19970775B (de) |
GR (1) | GR852890B (de) |
HK (2) | HK105693A (de) |
HU (1) | HU216079B (de) |
IL (1) | IL77081A (de) |
LV (2) | LV10505B (de) |
MD (1) | MD1639C2 (de) |
NO (1) | NO304469B1 (de) |
PL (2) | PL157926B1 (de) |
PT (1) | PT81590B (de) |
SK (2) | SK281799B6 (de) |
UA (1) | UA44882C2 (de) |
WO (1) | WO1986003520A1 (de) |
Families Citing this family (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR850004274A (ko) * | 1983-12-13 | 1985-07-11 | 원본미기재 | 에리트로포이에틴의 제조방법 |
NZ210501A (en) * | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
US4703008A (en) * | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
US4677195A (en) * | 1985-01-11 | 1987-06-30 | Genetics Institute, Inc. | Method for the purification of erythropoietin and erythropoietin compositions |
EP0236059B1 (de) * | 1986-02-27 | 1994-04-27 | Snow Brand Milk Products Co. Ltd. | Herstellung von erythropoietinproduzierenden Zellen und Verfahren zur Herstellung von Erythropoietin mit Verwendung dieser Zellen |
DK173067B1 (da) * | 1986-06-27 | 1999-12-13 | Univ Washington | Humant erythropoietin-gen, fremgangsmåde til ekspression deraf i transficerede cellelinier, de transficerede cellelinier sa |
DE3730599A1 (de) * | 1986-09-12 | 1988-07-07 | Genentech Inc | Verfahren zur kontinuierlichen herstellung von heterologen proteinen in eukaryontischen wirtszellen |
US4954437A (en) * | 1986-09-15 | 1990-09-04 | Integrated Genetics, Inc. | Cell encoding recombinant human erythropoietin |
US4835260A (en) * | 1987-03-20 | 1989-05-30 | Genetics Institute, Inc. | Erythropoietin composition |
FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
US5888774A (en) * | 1994-12-19 | 1999-03-30 | Cangene Corporation | Recombinant DNA molecules and expression vectors for erythropoietin |
IL122614A0 (en) | 1995-06-15 | 1998-08-16 | Introgene Bv | Packaging systems for human recombinant adenovirus to be used in gene therapy |
EP0752474A1 (de) | 1995-07-07 | 1997-01-08 | Boehringer Mannheim Gmbh | Nukleinsäure, die eine CMP-N-Acetyl-Neuraminsäure kodiert und ihre Verwendung zur Herstellung von modifizierten Glykoproteine |
EP0837942A1 (de) * | 1995-07-07 | 1998-04-29 | Boehringer Mannheim Gmbh | Nukleinsäure, die für eine cmp-n-acetyl-neuraminsäure-hydroxylase kodiert und ihre verwendung zur herstellung von modifizierten glykoproteinen |
DE19535571A1 (de) | 1995-09-14 | 1997-03-20 | Boehringer Mannheim Gmbh | Pharmazeutische Kombinationspräparate und deren Verwendung zur Behandlung von Hämodialysepatienten |
US5952226A (en) * | 1996-11-05 | 1999-09-14 | Modex Therapeutiques | Hypoxia responsive EPO producing cells |
SI0977582T1 (en) | 1997-03-18 | 2002-12-31 | Roche Diagnostics Gmbh | Pharmaceutical combined preparations containing erythropoietin and iron preparations |
EP0885613A1 (de) | 1997-06-21 | 1998-12-23 | Roche Diagnostics GmbH | Verwendung von modifizierten Hämoglobinen zur Behandlung von Anämien und Kombinationspräparate umfassend Erythropoietin und modifiziertes Hämoglobin |
KR100641969B1 (ko) | 1997-07-23 | 2006-11-06 | 로셰 디아그노스틱스 게엠베하 | 내인성 유전자 활성화에 의한 에리트로포이에틴의제조방법 |
ATE341625T1 (de) * | 1997-07-23 | 2006-10-15 | Roche Diagnostics Gmbh | Herstellung von erythropoietin durch endogene genaktivierung mit viralen promotoren |
US6548296B1 (en) | 1997-07-23 | 2003-04-15 | Roche Diagnostics Gmbh | Methods for identifying human cell lines useful for endogenous gene activation, isolated human lines identified thereby, and uses thereof |
DK1000154T3 (da) | 1997-07-23 | 2007-06-18 | Roche Diagnostics Gmbh | Identificering af humane cellelinjer til produktion af humane proteiner ved endogen genaktivering |
KR100622203B1 (ko) | 1997-07-23 | 2006-09-07 | 로셰 디아그노스틱스 게엠베하 | 내인성 유전자 활성화에 의해 사람 단백질을 생성시키는 사람 세포주를 확인하는 방법 |
ATE255634T1 (de) * | 1997-09-01 | 2003-12-15 | Aventis Pharma Gmbh | Rekombinantes humanes erythropoietin mit vorteilhaftem glykosylierungsmuster |
AR019025A1 (es) | 1998-04-09 | 2001-12-26 | Roche Diagnostics Gmbh | Uso de eritropoyetina en bajas dosis para producir un preparado farmaceutico para el tratamiento de hemocromatosis, preparado farmaceutico combinadoutilizado segun dicho uso y envase farmaceutico unitario que contiene al referido preparado farmaceutico combinado |
BR9905867A (pt) | 1998-11-06 | 2001-01-23 | Bio Sidus S A | Linhagem celular produtora de eritropoietina humana recombinante e a eritropoietina humana recombinante produzida por esta célula |
BR9917606A (pt) | 1998-11-06 | 2002-12-31 | Bio Sidus S A | Procedimento para a purificação de eritropoetina humana recombinante a partir de sobrenadantes de cultivo de células e eritropoetina humana recombinante obtida com tal procedimento |
BR9905868A (pt) | 1998-11-06 | 2001-01-23 | Bio Sidus S A | Procedimento de cultivo massivo de células de mamìfero para a obtenção de eritropoetina humana, recombinante e a eritropoetina humana recombinante obtida com tal procedimento |
US6777205B1 (en) | 1998-11-06 | 2004-08-17 | Sterrenbeld Biotechnologie North America, Inc. | Host cells expressing recombinant human erythropoietin |
DE19857609A1 (de) | 1998-12-14 | 2000-06-15 | Hannelore Ehrenreich | Verwendung von Erythropoietin zur Behandlung von cerebralen Ischämien des Menschen |
US7604960B2 (en) | 1999-04-15 | 2009-10-20 | Crucell Holland B.V. | Transient protein expression methods |
US7297680B2 (en) | 1999-04-15 | 2007-11-20 | Crucell Holland B.V. | Compositions of erythropoietin isoforms comprising Lewis-X structures and high sialic acid content |
US6855544B1 (en) | 1999-04-15 | 2005-02-15 | Crucell Holland B.V. | Recombinant protein production in a human cell |
US8236561B2 (en) | 1999-04-15 | 2012-08-07 | Crucell Holland B.V. | Efficient production of IgA in recombinant mammalian cells |
US7527961B2 (en) | 1999-11-26 | 2009-05-05 | Crucell Holland B.V. | Production of vaccines |
US7192759B1 (en) | 1999-11-26 | 2007-03-20 | Crucell Holland B.V. | Production of vaccines |
US7521220B2 (en) | 1999-11-26 | 2009-04-21 | Crucell Holland B.V. | Production of vaccines |
AU2002233230B2 (en) | 2000-12-20 | 2007-02-01 | F. Hoffmann-La Roche Ag | Erythropoietin conjugates |
DE10112825A1 (de) | 2001-03-16 | 2002-10-02 | Fresenius Kabi De Gmbh | HESylierung von Wirkstoffen in wässriger Lösung |
KR100505152B1 (ko) * | 2001-09-10 | 2005-08-03 | (주)가이아진 | 아스코르브산을 이용한 에리트로포이에틴의 생산방법 |
US6930086B2 (en) | 2001-09-25 | 2005-08-16 | Hoffmann-La Roche Inc. | Diglycosylated erythropoietin |
ATE384785T1 (de) | 2001-12-07 | 2008-02-15 | Crucell Holland Bv | Herstellung von viren, virusisolaten, und impfstoffen |
EP2277910A1 (de) | 2001-12-21 | 2011-01-26 | Human Genome Sciences, Inc. | Albumin Fusionsproteine |
DE10209821A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung von Proteinen an ein modifiziertes Polysaccharid |
DE10209822A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung niedermolekularer Substanzen an ein modifiziertes Polysaccharid |
DE10234192B4 (de) | 2002-07-26 | 2009-11-26 | Epoplus Gmbh Co.Kg | Verwendung von Erythropoetin |
US7459435B2 (en) | 2002-08-29 | 2008-12-02 | Hoffmann-La Roche Inc. | Treatment of disturbances of iron distribution |
RU2329274C2 (ru) | 2002-09-11 | 2008-07-20 | Фрезениус Каби Дойчланд Гмбх | Способ получения производных гидроксиалкилкрахмала |
EP1681303B1 (de) | 2002-09-11 | 2013-09-04 | Fresenius Kabi Deutschland GmbH | HASylierte Polypeptide, besonders HASyliertes Erythropoietin |
ES2314238T3 (es) | 2002-10-08 | 2009-03-16 | Fresenius Kabi Deutschland Gmbh | Conjugados de oligosacaridos farmaceuticamente activos. |
US7459436B2 (en) | 2002-11-22 | 2008-12-02 | Hoffmann-La Roche Inc. | Treatment of disturbances of iron distribution |
DK1623023T3 (da) | 2003-05-09 | 2009-03-02 | Crucell Holland Bv | Kulturer af E1-immortaliserede celler og fremgangsmåder til dyrkning deraf til forögelse af produktudbytter derfra |
WO2005014655A2 (en) | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
CA2539440A1 (en) | 2003-09-29 | 2005-04-14 | Warren Pharmaceuticals, Inc. | Tissue protective cytokines for the treatment and prevention of sepsis and the formation of adhesions |
DK1699915T3 (da) | 2003-12-30 | 2010-09-13 | Augustinus Bader | Anvendelse af erythropoietin til levervævsregenerering |
DE102004063927A1 (de) | 2004-01-23 | 2005-12-15 | Epoplus Gmbh Co.Kg | Einsatz von niedrig dosiertem Erythropoietin zur Stimulation endothelialer Vorläuferzellen sowie zur Organregeneration und Progressionsverlangsamung von Endorganschäden |
EP1732609B1 (de) | 2004-03-11 | 2012-07-11 | Fresenius Kabi Deutschland GmbH | Konjugate von hydroxyalkyl-stärke und einem protein |
TWI417303B (zh) | 2004-03-11 | 2013-12-01 | Fresenius Kabi De Gmbh | 經由還原胺化作用製得之羥烷基澱粉及蛋白質的接合物 |
GB0507123D0 (en) * | 2005-04-08 | 2005-05-11 | Isis Innovation | Method |
EP1762250A1 (de) | 2005-09-12 | 2007-03-14 | Fresenius Kabi Deutschland GmbH | Konjugate welche durch chemische Ligation zwischen Hydroxyalkylstärken und aktiven Substanzen mit Bildung eines Thiazolidin-Ringes entstehen |
AR053416A1 (es) * | 2005-11-10 | 2007-05-09 | Protech Pharma S A | Combinacion de glicoisoformas para el tratamiento o prevencion de la septicemia, linea celular transgenica productora de glicoformas de eritropoyetina, composicion farmaceutica que comprende a dicha combinacion, procedimientos para obtener la linea celular, procedimiento para producir dicha combinac |
TW200804415A (en) | 2006-01-18 | 2008-01-16 | Chugai Pharmaceutical Co Ltd | Method of removing sialic acid and process for producing asialoerythropoietin |
DE102006004008A1 (de) | 2006-01-27 | 2007-08-02 | Hannelore Prof. Dr. Dr. Ehrenreich | Verfahren zur Behandlung und/oder Prophylaxe von Multipler Sklerose, sowie Verwendung von Erythropoietin zur Herstellung eines Arzneimittels zur intermittierenden Behandlung und/oder intermittierenden Prophylaxe von Multipler Sklerose |
EP1991569A4 (de) * | 2006-03-07 | 2009-12-23 | Regenetech Inc | Durch elektromagnetisch stimulierte, lebende säugetierzellen produzierte native glykosylierte biologische säugetiermoleküle |
JP5553506B2 (ja) | 2006-03-22 | 2014-07-16 | 中外製薬株式会社 | エリスロポエチン溶液製剤 |
CA2659990C (en) | 2006-08-04 | 2016-03-22 | Prolong Pharmaceuticals, Inc. | Polyethylene glycol erythropoietin conjugates |
WO2009010107A1 (en) | 2007-07-19 | 2009-01-22 | Hannelore Ehrenreich | Use of epo receptor activation or stimulation for the improvement of the edss score in patients with multiple sclerosis |
EP2070950A1 (de) | 2007-12-14 | 2009-06-17 | Fresenius Kabi Deutschland GmbH | Hydroxyalkylstärkederivate und deren Herstellungsverfahren |
EP2095829A1 (de) | 2008-02-27 | 2009-09-02 | LEK Pharmaceuticals D.D. | Selenhaltige Modifizierungsmittel und Konjugate |
DE102008002209A1 (de) | 2008-06-04 | 2009-12-10 | Evonik Degussa Gmbh | Verfahren zur Aufreinigung von Erythropoietin |
DE102008002210A1 (de) | 2008-06-04 | 2009-12-10 | Evonik Degussa Gmbh | Verfahren zur fermentativen Herstellung von Erythropoietin |
ES2435272T3 (es) | 2008-09-23 | 2013-12-17 | F. Hoffmann-La Roche Ag | Purificación de la eritropoyetina |
DE102008054716A1 (de) | 2008-12-16 | 2010-06-17 | Evonik Degussa Gmbh | Inprozesskontrolle in einem Verfahren zur Herstellung von EPO |
US20100272816A1 (en) | 2009-04-27 | 2010-10-28 | Wolfgang Rudinger | Microcapsules comprising liver cells and erythropoietin, methods for preparing said microcapsules and methods for treating a patient comprising applying said microcapsules to the patient |
CN102712688B (zh) | 2009-09-23 | 2015-06-24 | 通益制药有限公司 | 重组人红细胞生成素(epo)的纯化方法、由此纯化的epo以及包含纯化的epo的药物组合物 |
WO2017068051A1 (en) | 2015-10-21 | 2017-04-27 | Lek Pharmaceuticals D.D. | Peg-based dendron and process for producing the same |
CN106906359B (zh) | 2015-12-22 | 2018-12-11 | 理查德.亨威克 | 从硅酸盐矿物收取锂 |
JP2020511499A (ja) | 2017-03-20 | 2020-04-16 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 赤血球生成刺激タンパク質のインビトロでの糖鎖改変のための方法 |
WO2022159414A1 (en) | 2021-01-22 | 2022-07-28 | University Of Rochester | Erythropoietin for gastroinfestinal dysfunction |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US439780A (en) * | 1890-11-04 | Method of and apparatus for casting ingots | ||
US3865801A (en) * | 1973-06-15 | 1975-02-11 | Atomic Energy Commission | Stabilization of urinary erythropoietin using sodium p-aminosalicylate and extracting into phenol |
JPS5455790A (en) * | 1977-10-05 | 1979-05-04 | Tomoyuki Tajima | Production of erythropoetin |
JPS5653696A (en) * | 1979-10-09 | 1981-05-13 | Ajinomoto Co Inc | Isolation of erythropoietin by adsorption |
JPS6045849B2 (ja) * | 1980-08-25 | 1985-10-12 | 林原 健 | ヒトエリトロポエチンの製造方法 |
US4419446A (en) * | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
JPS6043395A (ja) * | 1983-08-19 | 1985-03-07 | Sumitomo Chem Co Ltd | エリスロポエチンの製造法 |
NZ210501A (en) * | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
IT1185503B (it) * | 1984-01-11 | 1987-11-12 | Univ New York | Cloni di odna di eritropietina umana |
JPS60215632A (ja) * | 1984-04-12 | 1985-10-29 | Japan Found Cancer | エリスロポエチンの製造法 |
US4732889A (en) * | 1985-02-06 | 1988-03-22 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical composition for the treatment of the anemia of rheumatoid arthritis |
JPH062070B2 (ja) * | 1988-07-06 | 1994-01-12 | 農林水産省食品総合研究所長 | ▲o下−▼アシルアミノ酸の製造方法 |
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