HK20093A - Production of erythropoietin - Google Patents

Production of erythropoietin Download PDF

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Publication number
HK20093A
HK20093A HK200/93A HK20093A HK20093A HK 20093 A HK20093 A HK 20093A HK 200/93 A HK200/93 A HK 200/93A HK 20093 A HK20093 A HK 20093A HK 20093 A HK20093 A HK 20093A
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HK
Hong Kong
Prior art keywords
dna
epo
polypeptide
erythropoietin
dna sequence
Prior art date
Application number
HK200/93A
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English (en)
French (fr)
Inventor
Fu-Kuen Lin
Original Assignee
Kirin-Amgen, Inc.
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Priority claimed from US06/675,298 external-priority patent/US4703008A/en
Application filed by Kirin-Amgen, Inc. filed Critical Kirin-Amgen, Inc.
Publication of HK20093A publication Critical patent/HK20093A/en

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • 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
    • A61P7/06—Antianaemics
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • 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
    • 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
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Saccharide Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (37)

1. DNA-Sequenz, die dafür verwendet wird, Expression in einer prokaryontischen oder eukaryontischen Wirtszelle eines Polypeptidprodukts zu erreichen, das zumindest teilweise die Primärstrukturkonformation von Erythropoietin aufweist, um den Besitz der biologischen Eigenschaft zu ermöglichen, Knochenmarkszellen zu veranlassen, die Produktion von Rektikulozyten und roten Blutkörperchen zu steigern und Hämoglobinsynthese oder Eisenaufnahme zu steigern, wobei besagte DNA-Sequenz aus der Gruppe ausgewählt ist, die aus:
(a) den in den Tabellen V und VI dargelegten DNA-Sequenzen oder deren Komplementärstränge;
(b) DNA-Sequenzen, die unter stringenten Bedingungen zu den proteincodierenden Bereichen der in (a) definierten DNA-Sequenzen oder Fragmenten derselben hybridisieren; und
(c) DNA-Sequenzen, die, ohne die Entartung des genetischen Codes, zu den in (a) und (b) definierten DNA-Sequenzen hybridisieren würden; besteht.
2. DNA-Sequenz nach Anspruch 1, die Human-Erythropoietin codiert.
3. cDNA-Sequenz nach Anspruch 1 oder 2.
4. DNA-Sequenz nach Anspruch 3, die ein Erythropoietin einer Affenart codiert.
5. DNA-Sequenz nach Anspruch 4, die den in Tabelle V dargestellten proteincodierenden Bereich einschließt.
6. Genomische DNA-Sequenz nach Anspruch 1 oder 2.
7. DNA-Sequenz nach Anspruch 6, die ein Erythropoietin einer menschlichen Spezies codiert.
8. DNA-Sequenz nach Anspruch 7, die den in Tabelle VI dargestellten proteincodierenden Bereich einschließt.
9. DNA-Sequenz nach Anspruch 1 oder 2, die kovalent mit einer nachweisbaren Markierungssubstanz verbunden ist.
10. DNA-Sequenz nach Anspruch 9, dadurch gekennzeichnet, daß die nachweisbare Markierung eine radioaktive Markierung ist.
11. Einzelsträngige DNA-Sequenz nach Anspruch 9 oder 10.
12. DNA-Sequenz nach Anspruch 1, die für [Phe15]hEPO, [Phe49]hEPO, [Phe145]hEPO, [His']hEPO, [Asnz des-Pro2 bis Ile6]hEPO, [des-Thr163 bis Arg166]hE0 oder [Δ27-55]hEPO codiert.
13. Prokaryontische oder eukaryontische Wirtszelle, transformiert oder transfiziert mit einer DNA-Sequenz nach einem der Ansprüche 1, 2, 3, 6, und 8, in einer Weise, die es der Wirtszelle erlaubt, besagtes Polypeptidprodukt zu exprimieren.
14. Transformierte oder transfizierte Wirtszelle nach Anspruch 13, dadurch gekennzeichnet, daß die Wirtszelle in der Lage ist, besagtes Polypeptid zu glykosylieren.
15. Transformierte oder transfizierte Säugetier-Wirtszelle nach Anspruch 14.
16. Transformierte oder transfizierte COS-Zelle nach Anspruch 14.
17. Transformierte oder transfizierte CHO-Zelle nach Anspruch 14.
18. Biologisch funktioneller Zirkular-Plasmid-oder Virus-DNA-Vektor, der eine DNA-Sequenz nach einem der Ansprüche 1, 2, 3, 6, 7, 8 oder 12 einschließt.
19. Prokaryontische oder eukaryontische Wirtszelle, die mit einem DNA-Vektor nach Anspruch 18 stabil transformiert oder transfiziert ist.
20. Polypeptid, das einen Teil oder die Gesamtheit der Primärstrukturonformation von Human- oder Affen-Erythropoietin, wie dargestellt in Tabelle VI oder Tabelle V, oder irgendeine allelische Variante oder ein Derivat desselben aufweist, das die biologische Eigenschaft besitzt, Knochenmarkszellen zu veranlassen, die Produktion von Rektikulozyten und roten Blutkörperchen zu steigern und Hämoglobinsynthese oder Eisenaufnahme zu steigern, dadurch gekennzeichnet, daß es das Produkt prokaryontischer oder eukaryontischer Expression einer exogenen DNA-Sequenz ist.
21. Polypeptid nach Anspruch 20, dadurch gekennzeichnet, daß es das Produkt eukaryontischer Expression einer exogenen DNA-Sequenz ist.
22. Glykoprotein-Polypeptid nach Anspruch 20, das eine mittlere Kohlehydratzusammensetzung aufweist, die sich von derjenigen von Human-Erythropoietin unterscheidet, das aus Harnquellen isoliert ist.
23. Polypeptid nach Anspruch 20, 21 oder 22, dadurch gekennzeichnet, daß die exogene DNA-Sequenz eine cDNA-Sequenz ist.
24. Polypeptid nach Anspruch 20, 21 oder 22, dadurch gekennzeichnet, daß die exogene DNA-Sequenz eine genomische DNA-Sequenz ist.
25. Polypeptid nach Anspruch 20, 21 oder 22, dadurch gekennzeichnet, daß die exogene DNA-Sequenz auf einem autonom replizierenden Zirkular-DNA-Plasmid- oder Virus-Vektor sitzt.
26. Popypeptid nach einem der Ansprüche 20 bis 25, weiter dadurch gekennzeichnet, daß es kovalent mit einer nachweisbaren Markierungssubstanz verbunden ist.
27. Polypeptid nach Anspruch 26, dadurch gekennzeichnet, daß besagte nachweisbarer Markierung ein radioaktive Markierung ist.
28. Polypeptidprodukt der Expression einer prokaryontischen oder eukaryontischen Wirtszelle einer DNA-Sequenz nach einem der Ansprüche 1, 2, 3, 6, 7 und 8.
29. Verfahren zur Herstellung eines Polypeptids, das zumindest teilweise die Primärstrukturonformation von Erythropoietin aufweist, um den Besitz der biologischen Eigenschaft zu ermöglichen, Knochenmarkszellen zu veranlassen, die Produktion von Rektikulozyten und roten Blutkörperchen zu steigern und Hämoglobinsynthese oder Eisenaufnahme zu steigern, dadurch gekennzeichnet, daß eine prokaryontische oder eukaryontische Wirtszelle, die mit einer DNA-Sequenz nach einem der Ansprüche 1, 2, 3, 6, 7 und 8 derart transformiert oder transfiziert worden ist, daß es der Wirtszelle emöglicht ist, besagtes Polypeptid zu exprimieren, unter geeigneten Nährbedingungen kultiviert wird; und daß fakultativ das gewünschte Polypeptidprodukt der Expression der DNA-Sequenz isoliert wird.
30. Verfahren nach Anspruch 29, dadurch gekennzeichnet, daß eine Wirtszelle nach einem der Ansprüche 13 bis 17 kultiviert wird.
31. Verfahren nach Anspruch 29 oder 30 zur Produktion eines Polypeptids nach einem der Ansprüche 20 bis 25 und 28.
32. Pharmazeutische Zusammensetzung, die ein Polypeptid, das gemäß dem Verfahren nach Anspruch 29, 30 oder 31 produziert ist, und ein pharmazeutisch annehmbares Verdünnungsmittel, Adjuvans oder Trägermittel umfaßt.
33. Pharmazeutische Zusammensetzung nach Anspruch 32, die ein Polypeptid nach einem der Ansprüche 20 bis 25 und 28 umfaßt.
34. Antikörpersubstanz, gekennzeichnet durch Immunoreaktivität mit Erythropoietin und mit einem synthetischen Polypeptid, das eine Primärstrukturkonformation aufweist, die im wesentlichen zu einer fortlaufenden Sequenz von Aminosäureresten duplikativ ist, die in Erythropoietin, das aus Harnquellen isoliert ist, vorhanden ist, mit Ausnahme von jedem Polypeptid, das eine Sequenz von Aminosäureresten umfaßt, die vollständig in folgender Sequenz enthalten ist
35. Antikörper nach Anspruch 34, dadurch gekennzeichnet, daß er ein monoklonaler Antikörper ist.
36. Antikörper nach Anspruch 34, dadurch gekennzeichnet, daß er ein polyklonaler antikörper ist.
37. Antikörper nach Anspruch 34, der mit Erythropoietin und einem synthetischen Polypeptid immunoreaktiv ist, das die Sequenz aufweist, die aus den folgenden Sequenzen ausgewählt ist:
HK200/93A 1983-12-13 1993-03-11 Production of erythropoietin HK20093A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US56102483A 1983-12-13 1983-12-13
US58218584A 1984-02-21 1984-02-21
US65584184A 1984-09-28 1984-09-28
US06/675,298 US4703008A (en) 1983-12-13 1984-11-30 DNA sequences encoding erythropoietin

Publications (1)

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HK20093A true HK20093A (en) 1993-03-19

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HK200/93A HK20093A (en) 1983-12-13 1993-03-11 Production of erythropoietin

Country Status (15)

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US (3) US5441868A (de)
EP (1) EP0148605B2 (de)
JP (9) JPH0655136B2 (de)
AU (5) AU5750490A (de)
CA (1) CA1339047C (de)
CY (1) CY1643A (de)
DE (1) DE3482828D1 (de)
ES (1) ES8802329A1 (de)
HK (1) HK20093A (de)
IL (1) IL73785A (de)
MX (1) MX9203598A (de)
NL (1) NL930128I1 (de)
NZ (1) NZ210501A (de)
SG (1) SG92891G (de)
WO (1) WO1985002610A1 (de)

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CY1643A (en) 1993-05-14
AU5272293A (en) 1994-03-24
AU3746785A (en) 1985-06-26
US5618698A (en) 1997-04-08
JPH1095799A (ja) 1998-04-14
EP0148605B2 (de) 1998-12-23
AU5750490A (en) 1990-10-04
JP2957974B2 (ja) 1999-10-06
NL930128I1 (nl) 1993-11-01
ES538519A0 (es) 1988-05-01
JP3375614B2 (ja) 2003-02-10
DE3482828D1 (de) 1990-08-30
AU2042192A (en) 1992-10-08
AU657555B2 (en) 1995-03-16
JPH0435159B2 (de) 1992-06-10
JPH03259098A (ja) 1991-11-19
JP2708099B2 (ja) 1998-02-04
CA1339047C (en) 1997-05-27
MX9203598A (es) 1992-09-01
EP0148605B1 (de) 1990-07-25
AU3612597A (en) 1997-12-18
JP2002045191A (ja) 2002-02-12
EP0148605A2 (de) 1985-07-17
IL73785A (en) 1992-11-15
JPH11253188A (ja) 1999-09-21
JPH03198792A (ja) 1991-08-29
JPS6455190A (en) 1989-03-02
JP3017962B2 (ja) 2000-03-13
EP0148605A3 (en) 1987-06-03
US5441868A (en) 1995-08-15
JP2655750B2 (ja) 1997-09-24
IL73785A0 (en) 1985-03-31
JPH0776239B2 (ja) 1995-08-16
JPH0693000A (ja) 1994-04-05
JP3276933B2 (ja) 2002-04-22
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US5756349A (en) 1998-05-26
JPH08269096A (ja) 1996-10-15
AU600650B2 (en) 1990-08-23
WO1985002610A1 (en) 1985-06-20
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AU1007495A (en) 1995-04-06
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ES8802329A1 (es) 1988-05-01

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