KR20190041032A - 재조합 vwf의 투여에 의한 응고 질환의 치료 - Google Patents

재조합 vwf의 투여에 의한 응고 질환의 치료 Download PDF

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Publication number
KR20190041032A
KR20190041032A KR1020197010327A KR20197010327A KR20190041032A KR 20190041032 A KR20190041032 A KR 20190041032A KR 1020197010327 A KR1020197010327 A KR 1020197010327A KR 20197010327 A KR20197010327 A KR 20197010327A KR 20190041032 A KR20190041032 A KR 20190041032A
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South Korea
Prior art keywords
rvwf
composition
fviii
vwf
subject
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Ceased
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KR1020197010327A
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English (en)
Korean (ko)
Inventor
프리드리히 샤이플링거
페터 투레첵
브루스 에웬스타인
윙 옌 웡
토비아스 엠 주이터
Original Assignee
박스알타 인코퍼레이티드
박스앨타 게엠베하
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Priority to KR1020207020667A priority Critical patent/KR102319868B1/ko
Publication of KR20190041032A publication Critical patent/KR20190041032A/ko
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A61K38/37—Factors VIII
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
KR1020197010327A 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료 Ceased KR20190041032A (ko)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020207020667A KR102319868B1 (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201161495884P 2011-06-10 2011-06-10
US61/495,884 2011-06-10
US201161511901P 2011-07-26 2011-07-26
US61/511,901 2011-07-26
US201161523790P 2011-08-15 2011-08-15
US61/523,790 2011-08-15
PCT/US2012/041957 WO2012171031A1 (en) 2011-06-10 2012-06-11 Treatment of coagulation disease by administration of recombinant vwf

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
KR1020147000709A Division KR101969515B1 (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료

Related Child Applications (1)

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KR1020207020667A Division KR102319868B1 (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료

Publications (1)

Publication Number Publication Date
KR20190041032A true KR20190041032A (ko) 2019-04-19

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KR1020197010327A Ceased KR20190041032A (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료
KR1020147000709A Active KR101969515B1 (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료
KR1020207020667A Active KR102319868B1 (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료

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KR1020147000709A Active KR101969515B1 (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료
KR1020207020667A Active KR102319868B1 (ko) 2011-06-10 2012-06-11 재조합 vwf의 투여에 의한 응고 질환의 치료

Country Status (23)

Country Link
US (3) US9272021B2 (https=)
EP (3) EP3412305B1 (https=)
JP (3) JP6347468B2 (https=)
KR (3) KR20190041032A (https=)
CN (3) CN107412743B (https=)
AR (1) AR086904A1 (https=)
AU (5) AU2012267458A1 (https=)
CA (1) CA2838845C (https=)
DK (3) DK3858375T3 (https=)
ES (3) ES2682249T3 (https=)
FI (1) FI3858375T3 (https=)
HK (1) HK1257436A1 (https=)
HR (1) HRP20180962T1 (https=)
HU (1) HUE039317T2 (https=)
LT (1) LT2717905T (https=)
MX (2) MX350582B (https=)
PL (3) PL3858375T3 (https=)
PT (3) PT3412305T (https=)
RU (2) RU2680402C2 (https=)
SG (2) SG10201604684WA (https=)
SI (1) SI2717905T1 (https=)
TR (1) TR201808823T4 (https=)
WO (1) WO2012171031A1 (https=)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2682249T3 (es) * 2011-06-10 2018-09-19 Baxalta GmbH Tratamiento de una enfermedad de la coagulación mediante la administración de VWF recombinante
CN102776260B (zh) * 2012-07-26 2015-04-29 上海泰龙生物医药科技有限公司 一种高效表达重组人凝血八因子的方法
EP2796145B1 (en) * 2013-04-22 2017-11-01 CSL Ltd. A covalent complex of von willebrand factor and faktor viii linked by a disulphide bridge
NL2013007B1 (en) 2014-06-16 2016-07-05 Ablynx Nv Methods of treating TTP with immunoglobulin single variable domains and uses thereof.
FR3034669B1 (fr) * 2015-04-07 2020-02-14 Laboratoire Francais Du Fractionnement Et Des Biotechnologies Nouvelle utilisation du facteur von willebrand
KR102415992B1 (ko) 2016-04-15 2022-07-04 다케다 야쿠힌 고교 가부시키가이샤 약물동역학 약물 투약 요법을 제공하는 방법 및 장치
US10896749B2 (en) 2017-01-27 2021-01-19 Shire Human Genetic Therapies, Inc. Drug monitoring tool
CA3069295A1 (en) 2017-07-07 2019-01-10 Baxalta Incorporated Treatment of gastrointestinal bleeding in patients with severe von willebrand disease by administration of recombinant vwf
US20190091298A1 (en) * 2017-07-07 2019-03-28 Baxalta Incorporated Treatment of patients with severe von willebrand disease undergoing elective surgery by administration of recombinant vwf
WO2019154867A1 (en) 2018-02-06 2019-08-15 Ablynx Nv Methods of treating initial episode of ttp with immunoglobulin single variable domains
CA3094644A1 (en) * 2018-03-21 2019-09-26 Baxalta Incorporated Separation of vwf and vwf propeptide by chromatographic methods
US12128090B2 (en) 2019-02-01 2024-10-29 Takeda Pharmaceutical Company Limited Methods of prophylactic treatment using recombinant VWF (rVWF)
US20220401524A1 (en) 2019-09-11 2022-12-22 Takeda Pharmaceutical Company Limited Methods of treatment related to complexes of von willebrand factor and complement c1q
KR20220150303A (ko) 2020-02-04 2022-11-10 다케다 야쿠힌 고교 가부시키가이샤 재조합 vwf의 투여에 의한 중증 폰 빌레브란트병 환자의 월경과다 치료
US20240002861A1 (en) * 2020-11-24 2024-01-04 Band Therapeutics, Llc Compositions and methods for treatment of bleeding disorders
WO2024124136A1 (en) * 2022-12-09 2024-06-13 Vega Therapeutics, Inc. Von willebrand disease animal models

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
JPS6023084B2 (ja) 1979-07-11 1985-06-05 味の素株式会社 代用血液
US4640835A (en) 1981-10-30 1987-02-03 Nippon Chemiphar Company, Ltd. Plasminogen activator derivatives
US4496689A (en) 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
US4638028A (en) 1985-04-08 1987-01-20 Goodyear Tire & Rubber Company Rubber polymerases and methods for their production and use
JPS62502589A (ja) 1985-04-11 1987-10-08 ザ・チヤイルドレンズ・メデイカル・センタ−・コ−ポレ−シヨン フオン・ビルブラント因子
DE3675588D1 (de) 1985-06-19 1990-12-20 Ajinomoto Kk Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist.
US4791192A (en) 1986-06-26 1988-12-13 Takeda Chemical Industries, Ltd. Chemically modified protein with polyethyleneglycol
SE504074C2 (sv) * 1993-07-05 1996-11-04 Pharmacia Ab Proteinberedning för subkutan, intramuskulär eller intradermal administrering
DE4435485C1 (de) * 1994-10-04 1996-03-21 Immuno Ag Verfahren zur Gewinnung von hochreinem von Willebrand-Faktor
AT403764B (de) * 1996-03-15 1998-05-25 Immuno Ag Stabiler faktor viii/vwf-komplex
AT405403B (de) * 1997-02-27 1999-08-25 Immuno Ag Reinigung von von willebrand-faktor durch kationenaustauscherchromatographie
AT406373B (de) * 1997-02-27 2000-04-25 Immuno Ag Verfahren zur reinigung von faktor viii/vwf-komplex mittels kationenaustauscherchromatographie
US6531577B1 (en) 1997-12-15 2003-03-11 Hemasure Denmark A/S von Willebrand factor (vWF)-containing preparation, process for preparing vWF-containing preparations, and use of such preparations
US6864403B1 (en) 1998-10-15 2005-03-08 E. I. Du Pont De Nemours And Company Plant protein disulfide isomerases
US20040014657A1 (en) * 2001-11-05 2004-01-22 Jan Ohrstrom Use of blood coagulation factor XIII for treating haemophilia A
WO2005012354A1 (en) * 2003-07-31 2005-02-10 Zlb Behring Gmbh Method for extending the half-life of fviii
EP1593388A1 (en) * 2004-05-05 2005-11-09 ZLB Behring GmbH Therapeutic plasma protein-concentrates containing von willebrand factor as high molecular weight multimers
US20060094104A1 (en) 2004-10-29 2006-05-04 Leopold Grillberger Animal protein-free media for cultivation of cells
CA2591852A1 (en) * 2004-12-27 2006-07-06 Baxter International Inc. Polymer-von willebrand factor-conjugates
EP3653699A1 (en) 2006-01-04 2020-05-20 Baxalta Incorporated Oligopeptide-free cell culture media
ES2392569T3 (es) * 2007-06-13 2012-12-11 Csl Behring Gmbh Uso de preparaciones FVIII estabilizadas VWF para administración extravascular en la terapia y el tratamiento profiláctico de trastornos de hemorragias
CA2704234A1 (en) 2007-11-09 2009-05-14 Baxter International Inc. Modified recombinant factor viii and von willebrand factor and methods of use
JP2009127455A (ja) 2007-11-20 2009-06-11 Bando Kiko Co Ltd 往復動エンジン
CN105816858B (zh) * 2007-12-28 2024-10-18 武田药品工业株式会社 重组vwf配方
ES2298096B1 (es) * 2008-01-08 2009-01-01 Grifols, S.A. Procedimiento para la obtencion de un concentrado de factor von willebrand o del complejo de factor viii/factor von willebrand y utilizacionde los mismos.
KR101648734B1 (ko) * 2008-06-24 2016-08-18 체에스엘 베링 게엠베하 연장된 생체내 반감기를 갖는 인자 ｖｉｉｉ, 폰 빌레브란트 인자 또는 이들의 복합체
EP2349314B1 (en) * 2008-10-21 2013-02-27 Baxter International Inc. Lyophilized recombinant vwf formulations
AU2010279463A1 (en) * 2009-08-04 2012-03-01 Baxter Healthcare S.A. Transgenic mouse knockout for FVIII and VWF - model of hemophilia A
CA2805557A1 (en) 2010-07-08 2012-01-12 Baxter International Inc. Method of producing recombinant high molecular weight vwf in cell culture
US20120006800A1 (en) 2010-07-09 2012-01-12 Illinois Tool Works Inc. Weld bead feature communication systems and devices
ES2682249T3 (es) * 2011-06-10 2018-09-19 Baxalta GmbH Tratamiento de una enfermedad de la coagulación mediante la administración de VWF recombinante

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US20120316116A1 (en) 2012-12-13
US20250387455A1 (en) 2025-12-25
PT3858375T (pt) 2024-04-18
ES2682249T3 (es) 2018-09-19
US9272021B2 (en) 2016-03-01
CA2838845C (en) 2019-08-06
TR201808823T4 (tr) 2018-07-23
AU2022201518A1 (en) 2022-03-24
DK2717905T3 (en) 2018-07-02
JP6347468B2 (ja) 2018-06-27
JP2019048892A (ja) 2019-03-28
AU2012267458A1 (en) 2014-01-09
JP6527114B2 (ja) 2019-06-05
AU2020200026A1 (en) 2020-01-30
US20160184403A1 (en) 2016-06-30
PL3412305T3 (pl) 2021-05-31
LT2717905T (lt) 2018-10-10
KR20140039285A (ko) 2014-04-01
CN103732244A (zh) 2014-04-16
MX2013014543A (es) 2014-06-11
EP2717905B1 (en) 2018-05-23
RU2680402C2 (ru) 2019-02-21
EP3858375B1 (en) 2024-03-20
FI3858375T3 (fi) 2024-04-17
HK1257436A1 (zh) 2019-10-18
WO2012171031A1 (en) 2012-12-13
RU2014100107A (ru) 2015-07-20
RU2628537C2 (ru) 2017-08-18
EP3412305B1 (en) 2021-01-06
AU2016202299A1 (en) 2016-05-05
PT2717905T (pt) 2018-07-02
KR20200091476A (ko) 2020-07-30
JP2017019788A (ja) 2017-01-26
EP2717905A1 (en) 2014-04-16
KR102319868B1 (ko) 2021-11-01
SI2717905T1 (sl) 2018-09-28
AU2017206235A1 (en) 2017-08-03
AU2022201518B2 (en) 2025-07-03
BR112013031795A2 (pt) 2016-12-20
PT3412305T (pt) 2021-01-29
NZ618790A (en) 2015-07-31
PL2717905T3 (pl) 2018-10-31
MX2020000083A (es) 2020-08-06
CA2838845A1 (en) 2012-12-13
ES2976169T3 (es) 2024-07-24
EP3858375A1 (en) 2021-08-04
ES2860450T3 (es) 2021-10-05
AR086904A1 (es) 2014-01-29
HUE039317T2 (hu) 2018-12-28
CN107412743A (zh) 2017-12-01
RU2019103386A3 (https=) 2022-01-24
CN108210889A (zh) 2018-06-29
CN107412743B (zh) 2021-07-02
JP2014516088A (ja) 2014-07-07
AU2017206235B2 (en) 2019-10-17
RU2019103386A (ru) 2020-08-07
KR101969515B1 (ko) 2019-04-16
PL3858375T3 (pl) 2024-05-20
SG10202002591QA (en) 2020-05-28
EP3412305A1 (en) 2018-12-12
DK3858375T3 (da) 2024-04-15
RU2017102679A (ru) 2018-12-19
SG10201604684WA (en) 2016-07-28
HRP20180962T1 (hr) 2018-10-19
MX350582B (es) 2017-09-11
RU2017102679A3 (https=) 2018-12-19
AU2016202299B2 (en) 2017-07-20
DK3412305T3 (da) 2021-03-01

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