AR035786A2 - Variantes de factores de coagulacion dependientes de vitamina k y composiciones que los contienen - Google Patents

Variantes de factores de coagulacion dependientes de vitamina k y composiciones que los contienen

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Publication number
AR035786A2
AR035786A2 ARP020101003A ARP020101003A AR035786A2 AR 035786 A2 AR035786 A2 AR 035786A2 AR P020101003 A ARP020101003 A AR P020101003A AR P020101003 A ARP020101003 A AR P020101003A AR 035786 A2 AR035786 A2 AR 035786A2
Authority
AR
Argentina
Prior art keywords
amino acid
vitamin
gla domain
protein
modified gla
Prior art date
Application number
ARP020101003A
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English (en)
Original Assignee
Univ Minnesota
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 Univ Minnesota filed Critical Univ Minnesota
Publication of AR035786A2 publication Critical patent/AR035786A2/es

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    • CCHEMISTRY; METALLURGY
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    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52Genes encoding for enzymes or proenzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6437Coagulation factor VIIa (3.4.21.21)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/644Coagulation factor IXa (3.4.21.22)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6464Protein C (3.4.21.69)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/647Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21021Coagulation factor VIIa (3.4.21.21)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21022Coagulation factor IXa (3.4.21.22)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21069Protein C activated (3.4.21.69)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Diabetes (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Se describen: polipéptidos dependientes de vitamina K que incluye un dominio GLA modificado que aumenta la afinidad de unión del polipéptido con las membranas con respecto al correspondiente polipéptido nativo dependiente de vitamina K. El dominio GLA modificado puede incluir por lo menos una sustitución de amino ácido. Por ejemplo, la sustitución de amino ácido puede ser en el amino ácido 11, 12, 29, 33 o 34. El dominio GLA modificado, puede incluir una secuencia de amino ácidos que, en el estado saturado de calcio, forma una estructura terciaria que tiene un núcleo catiónico con un halo de carga electro-negativa. El polipéptido dependiente de vitamina K, puede ser por ejemplo, proteína C, proteína C actividad, factor IX, factor IXa, factor VII, factor VIIa o factor VIIa de sitio activo modificado. El dominio GLA modificado de la proteína C o la proteína C activada puede incluir un residuo ácido glutámico en el amino ácido 33 y un residuo ácido aspártico en el amino ácido 34. El dominio GLA modificado de la proteína C o de la proteína C activada, puede también incluir un residuo glutamina o ácido glutámico en el amino ácido 11. Adicionalmente, un residuo glicina puede ser sustituido en el amino ácido 12 en el dominio GLA de la proteína C o de la proteína C activada. El dominio GLA modificado del factor VII, el factor VIIa y el factor VIIa de sitio activo modificado puede contener una sustitución en el amino ácido 11 y 33. Por ejemplo, un residuo glutamina en el amino ácido 11 y un residuo ácido glutámico en el amino ácido 33, pueden estar sustituidos. Un ácido nucleico aislado que codifica una polipéptido dependiente de vitamina K que contiene un dominio GLA modificado tal como se describe arriba. Además, la presente se refiere también a una célula hospedante de mamífero que incluye un vector ácido nucleico que codifica un polipéptido dependiente de vitamina K que contiene un dominio GLA modificado según se describe arriba. Una composición farmacéutica que incluye un vehículo farmacéuticamente aceptable y una cantidad de un polipéptido dependiente de vitamina K efectiva para inhibir o incrementar la formación de coágulos en un mamífero, donde el polipéptido dependiente de vitamina K incluye un dominio GLA modificado como se ha descripto anteriormente. Un polipéptido dependiente de la vitamina K para ser utilizado en el tratamiento de una trastorno relacionado con la coagulación o en la manufactura de un medicamento para el tratamiento de un trastorno de coagulación. Métodos para incrementar o disminuir la formación de coágulos en un mamífero.
ARP020101003A 1997-10-23 2002-03-20 Variantes de factores de coagulacion dependientes de vitamina k y composiciones que los contienen AR035786A2 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US08/955,636 US6017882A (en) 1997-10-23 1997-10-23 Modified vitamin K-dependent polypeptides

Publications (1)

Publication Number Publication Date
AR035786A2 true AR035786A2 (es) 2004-07-14

Family

ID=25497114

Family Applications (2)

Application Number Title Priority Date Filing Date
ARP980105278A AR020048A1 (es) 1997-10-23 1998-10-22 Un polipeptido dependiente de la vitamina k, una composicion farmaceutica que lo comprende, el uso del mismo para la manufactura de un medicamento, unacido nucleico aislado que codifica a dicho polipeptido y una celula hospedante de mamifero.
ARP020101003A AR035786A2 (es) 1997-10-23 2002-03-20 Variantes de factores de coagulacion dependientes de vitamina k y composiciones que los contienen

Family Applications Before (1)

Application Number Title Priority Date Filing Date
ARP980105278A AR020048A1 (es) 1997-10-23 1998-10-22 Un polipeptido dependiente de la vitamina k, una composicion farmaceutica que lo comprende, el uso del mismo para la manufactura de un medicamento, unacido nucleico aislado que codifica a dicho polipeptido y una celula hospedante de mamifero.

Country Status (30)

Country Link
US (1) US6017882A (es)
EP (2) EP1090128B1 (es)
JP (1) JP4276379B2 (es)
KR (1) KR20010031370A (es)
CN (1) CN1246462C (es)
AP (1) AP2000001811A0 (es)
AR (2) AR020048A1 (es)
AT (1) ATE390486T1 (es)
AU (1) AU749279C (es)
BR (1) BR9814611A (es)
CA (1) CA2307175C (es)
DE (1) DE69839313T2 (es)
DK (1) DK1090128T3 (es)
EA (1) EA200000449A1 (es)
ES (2) ES2303362T3 (es)
HR (1) HRP20000234A2 (es)
HU (1) HU225993B1 (es)
ID (1) ID26330A (es)
IL (1) IL135603A0 (es)
IS (1) IS5449A (es)
MY (1) MY136336A (es)
NO (1) NO20002025L (es)
NZ (1) NZ504114A (es)
PL (1) PL194194B1 (es)
PT (1) PT1090128E (es)
SG (1) SG105547A1 (es)
TR (1) TR200001105T2 (es)
TW (1) TW587081B (es)
WO (1) WO1999020767A1 (es)
ZA (1) ZA989597B (es)

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JP5335422B2 (ja) 2005-06-17 2013-11-06 ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト 少なくとも1つの非天然のシステインを含んでいる操作されたタンパク質の選択的な還元および誘導体化
JP5147692B2 (ja) 2005-07-13 2013-02-20 ノボ ノルディスク ヘルス ケア アーゲー 治療用タンパク質生成のための宿主細胞タンパク質ノックアウト細胞
EP1924689B1 (en) 2005-09-01 2014-08-13 Novo Nordisk Health Care AG Hydrophobic interaction chromatography purification of factor vii polypeptides
JP5690047B2 (ja) 2005-09-14 2015-03-25 ノボ ノルディスク ヘルス ケア アーゲー ヒト凝固第vii因子ポリペプチド
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Publication number Publication date
HUP0102257A2 (hu) 2001-09-28
JP4276379B2 (ja) 2009-06-10
JP2001520042A (ja) 2001-10-30
ZA989597B (en) 1999-04-23
TW587081B (en) 2004-05-11
AU2702499A (en) 1999-05-10
PL340284A1 (en) 2001-01-29
DE69839313D1 (de) 2008-05-08
EA200000449A1 (ru) 2000-12-25
NO20002025L (no) 2000-06-19
ATE390486T1 (de) 2008-04-15
AU749279B2 (en) 2002-06-20
PL194194B1 (pl) 2007-05-31
EP1676919A1 (en) 2006-07-05
CN1246462C (zh) 2006-03-22
PT1090128E (pt) 2008-04-17
AU749279C (en) 2004-09-16
IS5449A (is) 2000-04-14
CN1283231A (zh) 2001-02-07
CA2307175A1 (en) 1999-04-29
HUP0102257A3 (en) 2003-09-29
AR020048A1 (es) 2002-04-10
AP2000001811A0 (en) 2000-06-30
WO1999020767A1 (en) 1999-04-29
EP1676919B1 (en) 2014-07-23
ES2303362T3 (es) 2008-08-01
KR20010031370A (ko) 2001-04-16
DE69839313T2 (de) 2009-04-16
NO20002025D0 (no) 2000-04-18
EP1090128B1 (en) 2008-03-26
HRP20000234A2 (en) 2001-08-31
EP1090128A1 (en) 2001-04-11
HU225993B1 (en) 2008-02-28
US6017882A (en) 2000-01-25
IL135603A0 (en) 2001-05-20
MY136336A (en) 2008-09-30
ID26330A (id) 2000-12-14
NZ504114A (en) 2002-10-25
SG105547A1 (en) 2004-08-27
CA2307175C (en) 2009-04-14
DK1090128T3 (da) 2008-06-23
TR200001105T2 (tr) 2000-09-21
ES2496104T3 (es) 2014-09-18
BR9814611A (pt) 2000-10-03

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