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公开(公告)号：US6086871A
公开(公告)日：2000-07-11
申请号：US952967
申请日：1998-01-26
IPC分类号： C12N15/09 , A61K38/00 , A61K38/46 , A61K38/55 , A61P7/02 , C12N9/64 , C12N9/74 , C12N15/57 , C12P21/04 , C12Q1/56 , G01N33/53 , G01N33/86 , A61K38/48 , C12N1/20 , C12N15/00
CPC分类号： C12N9/6424 , C12N9/6429 , C12Y304/21005 , G01N33/86 , A61K38/00 , G01N2333/974
摘要： The invention relates to new prothrombin mutants or derivatives thereof which comprise one or more changes in their protein sequence as compared to natural protein, are either inactive or have an activity of approximately 10% at the most, preferably approximately 0.25% at the most, of the natural protein and which have a binding capacity relative to natural ligands (natural or synthetic anticoagulants) substantially corresponding to that of the natural protein. Furthermore, the use of mutated prothrombin mutants or derivatives, respectively, as pharmaceutical preparations is described.
摘要翻译： PCT No.PCT / AT96 / 00105 Sec。 371日期1998年1月26日 102（e）1998年1月26日PCT PCT 1996年6月12日PCT公布。 出版物WO96 / 41868 日期1996年12月27日本发明涉及与天然蛋白相比包含其蛋白质序列的一个或多个变化的新的凝血酶原突变体或其衍生物，其为无活性的或具有最多约10％的活性，优选约0.25％ 最多的天然蛋白质，并且相对于天然配体（天然或合成抗凝剂）具有与天然蛋白质天然配体相当的结合能力。 此外，描述了分别使用突变的凝血酶原突变体或衍生物作为药物制剂。
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公开(公告)号：US5854403A
公开(公告)日：1998-12-29
申请号：US653298
申请日：1996-05-24
申请人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
发明人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
IPC分类号： C12N15/09 , A61K35/14 , A61K38/00 , A61K38/43 , A61P7/04 , C07K1/18 , C07K1/22 , C07K14/47 , C07K14/755 , C12P21/00 , C07K1/14
CPC分类号： C07K14/755 , A61K38/00
摘要： The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt. The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant rvWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active. Further, the invention relates to a pharmaceutical preparation that contains rvWF, which comprises mulitimers with a high structural integrity.
摘要翻译： 本发明涉及一种用于分离高纯度血管性血友病因子的方法，其中重组血管性血友病因子（rvWF）通过阴离子交换色谱在季氨基型阴离子交换剂上在包含缓冲物质和任选盐的缓冲溶液中进行色谱纯化。 缓冲溶液优选不含稳定剂，氨基酸和其它添加剂。 根据该方法，可以获得高纯度的重组rvWF，其不含血浆蛋白质，特别是不含因子VIII，且具有生理活性。 此外，本发明涉及含有rvWF的药物制剂，其包含具有高结构完整性的多组分。
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公开(公告)号：US5880265A
公开(公告)日：1999-03-09
申请号：US898129
申请日：1997-07-22
申请人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
发明人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
IPC分类号： C12N15/09 , A61K35/14 , A61K38/00 , A61K38/43 , A61P7/04 , C07K1/18 , C07K1/22 , C07K14/47 , C07K14/755 , C12P21/00
CPC分类号： C07K14/755 , A61K38/00
摘要： The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt.The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant vWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active.Further, the invention relates to a pharmaceutical preparation that contains rvWF, which is comprised of multimers with a high structural integrity.
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公开(公告)号：US5877152A
公开(公告)日：1999-03-02
申请号：US898131
申请日：1997-07-22
申请人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
发明人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
IPC分类号： C12N15/09 , A61K35/14 , A61K38/00 , A61K38/43 , A61P7/04 , C07K1/18 , C07K1/22 , C07K14/47 , C07K14/755 , C12P21/00 , A61K38/17
CPC分类号： C07K14/755 , A61K38/00
摘要： The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt.The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant vWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active.Further, the invention relates to a pharmaceutical preparation that contains rvWF, which is comprised of multimers with a high structural integrity
摘要翻译： 本发明涉及一种用于分离高纯度血管性血友病因子的方法，其中重组血管性血友病因子（rvWF）通过阴离子交换色谱在季氨基型阴离子交换剂上在包含缓冲物质和任选盐的缓冲溶液中进行色谱纯化。 缓冲溶液优选不含稳定剂，氨基酸和其它添加剂。 根据该方法，可以获得高纯度的重组vWF，其不含血浆蛋白质，特别是不含因子VIII，且具有生理活性。 此外，本发明涉及含有rvWF的药物制剂，其由具有高结构完整性的多聚体组成
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公开(公告)号：US6103693A
公开(公告)日：2000-08-15
申请号：US898130
申请日：1997-07-22
申请人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
发明人： Bernhard Fischer , Artur Mitterer , Friedrich Dorner , Hans-Peter Schwarz , Peter Turecek , Johann Eibl , Falko-Guenter Falkner , Uwe Schlokat , Wolfgang Mundt , Manfred Reiter , Renate Den-Bouwmeester
IPC分类号： C12N15/09 , A61K35/14 , A61K38/00 , A61K38/43 , A61P7/04 , C07K1/18 , C07K1/22 , C07K14/47 , C07K14/755 , C12P21/00 , A61K38/17 , C07K14/745
CPC分类号： C07K14/755 , A61K38/00
摘要： The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt.The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant vWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active.Further, the invention relates to a pharmaceutical preparation that contains rvWF, which is comprised of multimers with a high structural integrity.
摘要翻译： 本发明涉及一种用于分离高纯度血管性血友病因子的方法，其中重组血管性血友病因子（rvWF）通过阴离子交换色谱在季氨基型阴离子交换剂上在包含缓冲物质和任选盐的缓冲溶液中进行色谱纯化。 缓冲溶液优选不含稳定剂，氨基酸和其它添加剂。 根据该方法，可以获得高纯度的重组vWF，其不含血浆蛋白质，特别是不含因子VIII，且具有生理活性。 此外，本发明涉及含有rvWF的药物制剂，其由具有高结构完整性的多聚体组成。
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公开(公告)号：US06953837B2
公开(公告)日：2005-10-11
申请号：US10003621
申请日：2001-11-02
申请人： Artur Mitterer , Bernhard Fischer , Öyvind L. Schönberger , Kathrin Thomas-Urban , Friedrich Dorner , Johann Eibl
发明人： Artur Mitterer , Bernhard Fischer , Öyvind L. Schönberger , Kathrin Thomas-Urban , Friedrich Dorner , Johann Eibl
CPC分类号： A61K38/37 , C07K14/755
摘要： There is disclosed a method of recovering factor VIII/vWF-complex which is characterized in that factor VIII/vWF-complex from a protein solution is bound to a cation exchanger and is recovered by step-wise elution of factor VIII/vWF-complex, which particularly contains high-molecular vWF multimers, as well as a factor VIII/vWF-complex obtainable by means of cation exchange chromatography.
摘要翻译： 公开了一种回收因子VIII / vWF-复合物的方法，其特征在于将来自蛋白质溶液的因子VIII / vWF-复合物结合到阳离子交换剂并通过逐步洗脱因子VIII / vWF-复合物来回收， 其特别包含高分子vWF多聚体，以及通过阳离子交换层析可获得的因子VIII / vWF-络合物。
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公开(公告)号：US20050209154A1
公开(公告)日：2005-09-22
申请号：US11132326
申请日：2005-05-19
IPC分类号： A61K38/43 , A61K31/00 , A61K38/37 , A61P7/00 , A61P7/04 , C07K1/18 , C07K1/22 , C07K14/745 , C07K14/755
CPC分类号： C07K14/755 , Y10S514/834 , Y10T436/25375
摘要： There are disclosed a stable factor VIII/vWF-complex, particularly comprising high-molecular vWF multimers, being free from low-molecular vWF molecules and from proteolytic vWF degradation products, as well as a method of producing this complex.
摘要翻译： 公开了稳定的因子VIII / vWF-复合物，特别是包含不含低分子vWF分子和蛋白水解vWF降解产物的高分子vWF多聚体，以及生产该复合物的方法。
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8.发明授权Method of chromatographically purifying or fractionating, respectively, von Willebrand factor from a VWF-containing starting material 失效分别从含VWF的起始材料中色谱纯化或分馏von Willebrand因子的方法公开(公告)号：US06414125B1
公开(公告)日：2002-07-02
申请号：US09355865
申请日：1999-10-21
申请人： Juergen Siekmann , Peter Turecek , Hans-Peter Schwarz , Johann Eibl , Bernhard Fischer , Artur Mitterer , Friedrich Dorner
发明人： Juergen Siekmann , Peter Turecek , Hans-Peter Schwarz , Johann Eibl , Bernhard Fischer , Artur Mitterer , Friedrich Dorner
IPC分类号： A23J100
CPC分类号： C07K14/755
摘要： Disclosed is a method of chromatographically purifying or fractionating, respectively, von Willebrand factor (vWF) from a vWF-containing starting material, comprising the following steps: adsorbing the vWF from the starting material on avid collagen immobilized on a carrier, separating the non-adsorbed portion and, optionally, washing the carrier, eluting the vWF from immobilized collagen, and recovering the purified vWF, as well as a pharmaceutical preparation comprising biologically active vWF which is bound to collagen in a stable manner.
摘要翻译： 公开了一种从含有vWF的原料分别纯化或分馏von Willebrand因子（vWF）的方法，其包括以下步骤：将起始材料的vWF吸附在固定在载体上的avid胶原上， 吸附部分和任选地洗涤载体，从固定化胶原洗脱vWF，并回收纯化的vWF，以及包含以稳定方式与胶原结合的生物活性vWF的药物制剂。
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9.发明授权公开(公告)号：US06579723B1
公开(公告)日：2003-06-17
申请号：US09367362
申请日：1999-10-21
IPC分类号： G01N118
CPC分类号： C07K14/755 , A61K38/00 , Y10S436/824 , Y10T436/108331 , Y10T436/25 , Y10T436/25125 , Y10T436/2525 , Y10T436/25375 , Y10T436/255
摘要： A method for purifying factor VIII/vWF complex or free vWF by immunoaffinity chromatography in a form suitable for use as a medicament. Factor VIII/vWF complex or free vWF is recovered from an immunoaffinity adsorbent by using an eluting agent containing a zwitterionic species. The presence of the zwitterionic species allows for the use of mild conditions throughout the preparation, facilitating retention of molecular integrity, activity, and incorporation of the recovered proteins into pharmaceutical preparations without the need for additional stabilizers or preservatives.
摘要翻译： 通过免疫亲和层析以适合用作药物的形式来纯化因子VIII / vWF复合物或游离vWF的方法。 通过使用含有两性离子物质的洗脱剂，从免疫亲和吸附剂回收因子VIII / vWF复合物或游离vWF。 两性离子物质的存在允许在整个制备过程中使用温和的条件，有助于保留分子完整性，活性和将回收的蛋白质并入药物制剂中，而不需要额外的稳定剂或防腐剂。
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公开(公告)号：US06924151B2
公开(公告)日：2005-08-02
申请号：US09849484
申请日：2001-05-07
IPC分类号： A61K38/43 , A61K31/00 , A61K38/37 , A61P7/00 , A61P7/04 , C07K1/18 , C07K1/22 , C07K14/745 , C07K14/755 , G01N1/18
CPC分类号： C07K14/755 , Y10S514/834 , Y10T436/25375
摘要： There are disclosed a stable factor VIII/vWF-complex, particularly comprising high-molecular vWF multimers, being free from low-molecular vWF molecules and from proteolytic vWF degradation products, as well as a method of producing this complex.
摘要翻译： 公开了稳定的因子VIII / vWF-复合物，特别是包含不含低分子vWF分子和蛋白水解vWF降解产物的高分子vWF多聚体，以及生产该复合物的方法。
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