CN102971006A - 稳定的因子viii变体 - Google Patents

稳定的因子viii变体 Download PDF

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Publication number
CN102971006A
CN102971006A CN2011800348298A CN201180034829A CN102971006A CN 102971006 A CN102971006 A CN 102971006A CN 2011800348298 A CN2011800348298 A CN 2011800348298A CN 201180034829 A CN201180034829 A CN 201180034829A CN 102971006 A CN102971006 A CN 102971006A
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CN
China
Prior art keywords
fviii
variant
amino acid
fviii variant
domain
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.)
Withdrawn
Application number
CN2011800348298A
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English (en)
Chinese (zh)
Inventor
H.奥斯特加尔德
M.克贾尔克
O.H.奥尔森
L.蒂姆
H.R.施滕尼克
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Novo Nordisk AS
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Novo Nordisk AS
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Publication date
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Publication of CN102971006A publication Critical patent/CN102971006A/zh
Withdrawn legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745Blood coagulation or fibrinolysis factors
    • C07K14/755Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36Blood coagulation or fibrinolysis factors
    • A61K38/37Factors VIII
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • 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
    • C12N9/96Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
CN2011800348298A 2010-07-15 2011-07-06 稳定的因子viii变体 Withdrawn CN102971006A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP10169592.2 2010-07-15
EP10169592 2010-07-15
US36547810P 2010-07-19 2010-07-19
US61/365478 2010-07-19
PCT/EP2011/061349 WO2012007324A2 (en) 2010-07-15 2011-07-06 Stabilized factor viii variants

Publications (1)

Publication Number Publication Date
CN102971006A true CN102971006A (zh) 2013-03-13

Family

ID=42797590

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2011800348298A Withdrawn CN102971006A (zh) 2010-07-15 2011-07-06 稳定的因子viii变体

Country Status (5)

Country Link
US (2) US20130183280A1 (https=)
EP (1) EP2593130A2 (https=)
JP (1) JP2013532176A (https=)
CN (1) CN102971006A (https=)
WO (1) WO2012007324A2 (https=)

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US7855279B2 (en) 2005-09-27 2010-12-21 Amunix Operating, Inc. Unstructured recombinant polymers and uses thereof
ES2610356T3 (es) 2009-02-03 2017-04-27 Amunix Operating Inc. Polipéptidos recombinantes extendidos y composiciones que comprenden los mismos
CA2771999A1 (en) 2009-08-24 2011-03-10 Amunix Operating Inc. Coagulation factor vii compositions and methods of making and using same
US20130017997A1 (en) * 2010-08-19 2013-01-17 Amunix Operating Inc. Factor VIII Compositions and Methods of Making and Using Same
DK3424953T3 (en) * 2011-06-06 2020-11-02 Novo Nordisk As Terapeutiske antistoffer
JP6256882B2 (ja) * 2012-02-15 2018-01-10 アムニクス オペレーティング インコーポレイテッド 第viii因子組成物、ならびに組成物の作製方法および用途
EP2822577B1 (en) 2012-02-15 2019-02-06 Bioverativ Therapeutics Inc. Recombinant factor viii proteins
WO2013160005A1 (en) * 2012-04-24 2013-10-31 Novo Nordisk A/S Pharmaceutical composition suitable for treatment of haemophilia
CN104661685A (zh) 2012-10-15 2015-05-27 诺和诺德保健Ag(股份有限公司) 因子vii缀合物
UY35343A (es) * 2013-02-26 2014-09-30 Bayer Healthcare Llc Formulaciones y procedimientos para la producción de proteína recombinante aumentada
LT3013855T (lt) 2013-06-24 2021-01-25 Xiao, Weidong Mutavusio viii faktoriaus kompozicijos ir metodai
TW202003554A (zh) 2013-08-14 2020-01-16 美商百歐維拉提夫治療公司 因子viii-xten融合物及其用途
CA2927756A1 (en) 2013-10-15 2015-04-23 Novo Nordisk Health Care Ag Coagulation factor vii polypeptides
US20160252519A1 (en) * 2013-10-18 2016-09-01 Dr. Reddy's Laboratories Limited In-vitro method for determining fate of polypeptide variant
WO2015132724A1 (en) 2014-03-05 2015-09-11 Pfizer Inc. Improved muteins of clotting factor viii
CN106687126B (zh) 2014-08-04 2020-07-28 杰特有限公司 因子viii制剂
ES2772933T3 (es) 2015-03-06 2020-07-08 CSL Behring Lengnau AG Factor de von Willebrand modificado que tiene una semivida mejorada
EA201890423A1 (ru) 2015-08-03 2018-07-31 Биовератив Терапьютикс Инк. Слитые белки фактора ix, способы их получения и применения
MX2019006444A (es) 2016-12-02 2019-10-30 Bioverativ Therapeutics Inc Métodos de tratamiento de artropatía hemofílica utilizando factores de coagulación quiméricos.
PL3793588T3 (pl) 2018-05-18 2025-09-01 Bioverativ Therapeutics Inc. Sposoby leczenia hemofilii a
WO2021001522A1 (en) 2019-07-04 2021-01-07 CSL Behring Lengnau AG A truncated von willebrand factor (vwf) for increasing the in vitro stability of coagulation factor viii
CN114929735A (zh) * 2019-11-01 2022-08-19 自由行疗法有限公司 因子viii构建体
US20220348637A1 (en) 2019-11-11 2022-11-03 CSL Behring Lengnau AG Polypeptides for inducing tolerance to factor viii
CN116669755A (zh) * 2020-09-23 2023-08-29 艾柏力维亚生技有限公司 用于增加因子viii替代疗法的效力的化合物

Citations (3)

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US20030125232A1 (en) * 2001-06-14 2003-07-03 Griffin John H. Stabilized proteins with engineered disulfide bonds
US20080200651A1 (en) * 2005-06-17 2008-08-21 Novo Nordisk Healthcare A/G Selective Reduction and Derivatization of Engineered Proteins Comprising at Least One Non-Native Cysteine
WO2009108806A1 (en) * 2008-02-27 2009-09-03 Novo Nordisk A/S Conjugated factor viii molecules

Family Cites Families (11)

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AU2645588A (en) 1987-12-04 1989-06-15 Scripps Clinic And Research Foundation The von willebrand factor binding domain of factor viii
US5824784A (en) 1994-10-12 1998-10-20 Amgen Inc. N-terminally chemically modified protein compositions and methods
EE05214B1 (et) 1998-04-28 2009-10-15 Applied Research Systems ARS Holding N.V. Polool-IFN- β konjugaat, selle valmistamismeetod ja farmatseutiline kompositsioon
ES2411007T3 (es) 2001-10-10 2013-07-04 Novo Nordisk A/S Remodelación y glicoconjugación de péptidos
US20100143969A1 (en) 2005-03-24 2010-06-10 Neose Technologies, Inc. Expression of soluble, active eukaryotic glycosyltransferases in prokaryotic organisms
EP1871801A2 (en) * 2005-04-01 2008-01-02 Novo Nordisk Health Care AG Blood coagulation fviii analogues
US20090041744A1 (en) * 2005-06-17 2009-02-12 Novo Nordisk Healthcare A/G Dimeric and Multimeric FVIIa Compounds
WO2007056191A2 (en) 2005-11-03 2007-05-18 Neose Technologies, Inc. Nucleotide sugar purification using membranes
AU2007245190B2 (en) * 2006-03-31 2011-07-21 Takeda Pharmaceutical Company Limited Pegylated factor VIII
EP2049144B8 (en) * 2006-07-21 2015-02-18 ratiopharm GmbH Glycosylation of peptides via o-linked glycosylation sequences
US20100099616A1 (en) * 2008-10-17 2010-04-22 Baxter International Inc. Modified blood factors comprising a low degree of water soluble polymer

Patent Citations (3)

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US20030125232A1 (en) * 2001-06-14 2003-07-03 Griffin John H. Stabilized proteins with engineered disulfide bonds
US20080200651A1 (en) * 2005-06-17 2008-08-21 Novo Nordisk Healthcare A/G Selective Reduction and Derivatization of Engineered Proteins Comprising at Least One Non-Native Cysteine
WO2009108806A1 (en) * 2008-02-27 2009-09-03 Novo Nordisk A/S Conjugated factor viii molecules

Non-Patent Citations (1)

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Title
H. WAKABAYASHI,A. E. GRIFFITHS,P. J. FAY: "Combining mutations of charged residues at the A2 domain interface enhances factor VIII stability over single point mutations", 《JOURNAL OF THROMBOSIS AND HAEMOSTASIS》 *

Also Published As

Publication number Publication date
US20130183280A1 (en) 2013-07-18
JP2013532176A (ja) 2013-08-15
US20160264645A1 (en) 2016-09-15
WO2012007324A3 (en) 2012-03-08
WO2012007324A2 (en) 2012-01-19
EP2593130A2 (en) 2013-05-22

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Application publication date: 20130313