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1. 发明申请

US20050079584A1 Modified factor VIII 有权
标题翻译：修改因子VIII
公开(公告)号：US20050079584A1
公开(公告)日：2005-04-14
申请号：US10938414
申请日：2004-09-10
申请人： John Lollar
发明人： John Lollar
IPC分类号： C12N15/09 , A61K38/00 , A61K38/43 , A61P7/04 , C07K14/755 , C07K14/775 , C12N5/10 , C12P21/02 , C12P21/04 , C07H21/04
CPC分类号： C07K14/755 , A61K38/00 , C07K2319/00 , Y10S514/802 , Y10S514/834 , Y10S930/10
摘要： Specific amino acid loci of human factor VIII interact with inhibitory antibodies of hemophilia patients who have developed such antibodies after being treated with factor VIII. Modified factor VIII is disclosed in which the amino acid sequence is changed by a substitution at one or more of the specific loci. The modified factor VIII is not inhibited by inhibitory antibodies against the A2 or C2 domain epitopes. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory antibodies.
摘要翻译：人因子VIII的特异性氨基酸位点与用因子VIII处理后发展了这种抗体的血友病患者的抑制性抗体相互作用。公开了修饰因子VIII，其中通过在一个或多个特定基因座处的取代改变氨基酸序列。修饰因子VIII不受针对A2或C2结构域表位的抑制性抗体的抑制。修饰的因子VIII可用于血友病患者，以避免或预防抑制性抗体的作用。

2. 发明授权

US06458563B1 Modified factor VIII 有权
标题翻译：修改因子VIII
公开(公告)号：US06458563B1
公开(公告)日：2002-10-01
申请号：US09523656
申请日：2000-03-10
申请人： John S. Lollar
发明人： John S. Lollar
IPC分类号： C12P2100
CPC分类号： C07K14/755 , A61K38/00 , C07K2319/00 , Y10S514/802 , Y10S514/834 , Y10S930/10
摘要： The invention relates to a modified B-domainless form of porcine factor VIII, to a DNA encoding the same, and to the use thereof for treatment of hemophilia.
摘要翻译：本发明涉及修饰的B结构域的猪因子VIII形式，涉及编码它的DNA及其用于治疗血友病的用途。

3. 发明申请

US20010016340A1 Protein complexes having factor VIII:C activity and production thereof 审中-公开
标题翻译：具有因子VIII：C活性的蛋白质复合物及其生产
公开(公告)号：US20010016340A1
公开(公告)日：2001-08-23
申请号：US09748062
申请日：2000-12-22
申请人： Chiron Corporation and Novo Nordisk A/S
发明人： Barbara Chapman , Rae Lyn Burke , Mirella Ezban Rasmussen , Jan Moller Mikkelson
IPC分类号： C12P021/04 , C07H021/04
CPC分类号： C07K14/755 , A61K38/00 , C12N15/85 , C12N2800/108 , Y10S930/10
摘要： Recombinant protein complexes having human Factor VIII:C activity are expressed in a eukaryotic host cell by transforming the host cell with first and second expression cassettes encoding a first polypeptide substantially homologous to human Factor VIII:C A domain and a second polypeptide substantially homologous to human Factor VIII:C C domain, respectively. In the present invention, the first polypeptide may be extended having at its C-terminal a human Factor VIII:C B domain N-terminal peptide, a polypeptide spacer of 3-40 amino acids, and a human Factor VIII:C B domain C-terminal peptide. Expression of the second polypeptide is improved by employing an null1-antitrypsin signal sequence.
摘要翻译：通过用编码与人因子VIII：CA结构域基本上同源的第一多肽的第一和第二表达盒转化宿主细胞，在真核宿主细胞中表达具有人因子VIII：C活性的重组蛋白复合物，和与人因子基本上同源的第二多肽 VIII：CC域。在本发明中，第一多肽可以在其C末端延伸有人因子VIII：CB结构域N-末端肽，3-40个氨基酸的多肽间隔区和人因子VIII：CB结构域C末端肽。通过使用α1-抗胰蛋白酶信号序列来改善第二多肽的表达。

4. 发明授权

US6156888A Hybrid proteins with modified activity 失效
公开(公告)号：US6156888A
公开(公告)日：2000-12-05
申请号：US324934
申请日：1999-06-03
申请人： Johannes J. Voorberg
发明人： Johannes J. Voorberg
IPC分类号： G01N33/68 , A61K38/00 , A61K38/43 , A61K38/55 , C07K14/755 , C07K14/81 , C07K14/815 , C07K16/36 , C07K19/00 , C12N5/10 , C12N15/02 , C12N15/09 , C12P21/08 , G01N33/86 , C07H21/02 , A01N43/04 , C07H21/04
CPC分类号： C07K14/755 , C07K14/8121 , C07K14/815 , A61K38/00 , C07K2319/00 , Y10S514/834 , Y10S930/10
摘要： Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.

5. 发明授权

US5910481A Hybrid proteins with modified activity 失效
公开(公告)号：US5910481A
公开(公告)日：1999-06-08
申请号：US558107
申请日：1995-11-13
申请人： Johannes J. Voorberg
发明人： Johannes J. Voorberg
IPC分类号： G01N33/68 , A61K38/00 , A61K38/43 , A61K38/55 , C07K14/755 , C07K14/81 , C07K14/815 , C07K16/36 , C07K19/00 , C12N5/10 , C12N15/02 , C12N15/09 , C12P21/08 , G01N33/86 , A61K35/14 , C12P21/04 , C12P21/06
CPC分类号： C07K14/755 , C07K14/8121 , C07K14/815 , A61K38/00 , C07K2319/00 , Y10S514/834 , Y10S930/10
摘要： Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.

6. 发明授权

US5663060A Hybrid human/animal factor VIII 失效
标题翻译：混合人/动物因子VIII
公开(公告)号：US5663060A
公开(公告)日：1997-09-02
申请号：US212133
申请日：1994-03-11
申请人： John S. Lollar , Marschall S. Runge
发明人： John S. Lollar , Marschall S. Runge
IPC分类号： C12N15/09 , A61K38/00 , A61K38/43 , A61P7/04 , C07H21/04 , C07K14/745 , C07K14/755 , C07K19/00 , C12N5/10 , C12N15/12 , C12P21/02 , C12R1/91 , G01N33/53 , A61K38/37
CPC分类号： C07K14/755 , A61K38/00 , C07K2319/00 , Y10S930/10
摘要： A hybrid human/animal coagulation factor VIII is produced by isolation and recombination of human and other non-human mammalian factor VIII subunits or domains, or by genetic engineering of the human and animal factor VIII genes. Subunits or domains of factor VIII that have been purified from human or animal plasma are isolated, and hybrid human/animal factor VIII is produced by (1) mixing either animal heavy chain subunits with human light chain subunits or by mixing human heavy chain subunits with animal light chain subunits, thereby producing human light chain/animal heavy chain and human heavy chain/animal light chain hybrid molecules; or by (2) mixing one or more domains of one species with one or more domains of the other species. These hybrid molecules are isolated by ion exchange chromatography. Alternatively, recombinant DNA methods are used to change elements of animal factor VIII or human factor VIII to the corresponding elements of human factor VIII or animal factor VIII, respectively, to produce hybrid human/animal factor VIII.
摘要翻译：通过人和其他非人哺乳动物因子VIII亚基或结构域的分离和重组，或通过人和动物因子VIII基因的遗传工程产生杂交的人/动物凝血因子VIII。分离从人或动物血浆纯化的因子VIII的亚基或结构域，并且通过（1）将动物重链亚基与人轻链亚基混合或通过将人重链亚基与动物轻链亚基，从而产生人轻链/动物重链和人重链/动物轻链杂交分子; 或（2）将一种物质的一个或多个结构域与其它物种的一个或多个结构域混合。这些杂化分子通过离子交换色谱分离。或者，使用重组DNA方法将动物因子VIII或人因子VIII的元件分别改变成人因子VIII或动物因子VIII的相应元件，以产生杂交的人/动物因子VIII。

7. 发明授权

US5633150A Preparation of functional human factor VIII 失效
标题翻译：功能性人因子VIII的制备
公开(公告)号：US5633150A
公开(公告)日：1997-05-27
申请号：US595481
申请日：1990-10-09
申请人： William I. Wood , Daniel J. Capon , Richard M. Lawn , Gordon A. Vehar
发明人： William I. Wood , Daniel J. Capon , Richard M. Lawn , Gordon A. Vehar
IPC分类号： A61K38/00 , C07K14/755 , C12N15/10 , C12N15/12 , C12N15/62 , C12N15/85 , C12Q1/68 , C12N5/10 , A61K38/37
CPC分类号： C07K14/755 , C12N15/1034 , C12N15/62 , C12N15/85 , C12Q1/6832 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/80 , C12N2800/108 , C12N2830/00 , C12N2830/55 , C12N2840/105 , C12N2840/44 , Y10S435/948 , Y10S930/10
摘要： Functional human factor VIII produced recombinantly is used in the treatment of human beings diagnosed to be deficient in factor VIII coagulant activity. Also provided are DNA isolates and expression vehicles encoding functional human factor VIII, as well as transformed host cells and processes for producing human factor VIII by use of recombinant DNA technology.
摘要翻译：重组产生的功能性人因子VIII用于治疗被诊断为缺乏因子VIII凝血活性的人。还提供了编码功能性人因子VIII的DNA分离物和表达载体，以及通过使用重组DNA技术转化的宿主细胞和用于产生人因子VIII的方法。

8. 发明授权

US4749780A Biologically active fragments of human antihemophilic factor and method for preparation thereof 失效
标题翻译：人类抗血友病因子的生物活性片段及其制备方法
公开(公告)号：US4749780A
公开(公告)日：1988-06-07
申请号：US835914
申请日：1986-03-04
申请人： Lars-Olof Andersson , Nanna Forsman , Kerstin E. I. Larsen , Annelie B. Lundin , Bohdan Pavlu , Inga H. Sandberg , Karin M. Sewerin
发明人： Lars-Olof Andersson , Nanna Forsman , Kerstin E. I. Larsen , Annelie B. Lundin , Bohdan Pavlu , Inga H. Sandberg , Karin M. Sewerin
IPC分类号： C07K14/745 , A61K38/00 , A61K38/16 , A61K38/43 , A61P7/04 , C07K1/22 , C07K14/00 , C07K14/755 , E02D31/00 , C07K15/12 , A61K37/02 , C07K3/18 , C07K3/22
CPC分类号： C07K14/755 , E02D31/00 , A61K38/00 , Y10S530/83 , Y10S930/10
摘要： Novel, biologically active fragments of human antihemophilic factor, processes for their preparation, pharmaceutical preparations containing them and the use of such fragments in the treatment of patients suffering from hemophilia.
摘要翻译：新颖的人类抗血友病因子的生物活性片段，其制备方法，含有它们的药物制剂以及这些片段在治疗患有血友病的患者中的用途。

9. 发明授权

US06770744B2 Modified factor VIII 失效
标题翻译：修改因子VIII
公开(公告)号：US06770744B2
公开(公告)日：2004-08-03
申请号：US09957641
申请日：2001-09-19
申请人： John S. Lollar
发明人： John S. Lollar
IPC分类号： A61K3514
CPC分类号： C07K14/755 , A61K38/37 , Y10S930/10
摘要： Specific amino acid loci of human factor VIII interact with inhibitory antibodies of hemophilia patients after being treated with factor VIII. Modified factor VIII is disclosed in which the amino acid sequence is changed by a substitution at one or more of the specific loci. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory antibodies.
摘要翻译：人因子VIII的特异性氨基酸位点与因子VIII治疗后血友病患者的抑制性抗体相互作用。公开了修饰因子VIII，其中通过在一个或多个特定基因座处的取代改变氨基酸序列。修饰的因子VIII可用于血友病患者，以避免或预防抑制性抗体的作用。

10. 发明申请

US20040137579A1 Protein complexes having factor VIII:C activity and production thereof 审中-公开
标题翻译：具有因子VIII：C活性的蛋白质复合物及其生产
公开(公告)号：US20040137579A1
公开(公告)日：2004-07-15
申请号：US10726199
申请日：2003-12-01
申请人： Chiron Corporation , Novo Nordisk A/S
发明人： Barbara Chapman , Rae Lyn Burke , Mirella Ezban Rasmussen , Jan Mollar Mikkelson
IPC分类号： C12P021/04 , C07K014/755
CPC分类号： C07K14/755 , A61K38/00 , C12N15/85 , C12N2800/108 , Y10S930/10
摘要： Recombinant protein complexes having human Factor VIII:C activity are expressed in a eukaryotic host cell by transforming the host cell with first and second expression cassettes encoding a first polypeptide substantially homologous to human Factor VIII:C A domain and a second polypeptide substantially homologous to human Factor VIII:C C domain, respectively. In the present invention, the first polypeptide may be extended having at its C-terminal a human Factor VIII:C B domain N-terminal peptide, a polypeptide spacer of 3-40 amino acids, and a human Factor VIII:C B domain C-terminal peptide. Expression of the second polypeptide is improved by employing an null1-antitrypsin signal sequence.
摘要翻译：通过用编码与人因子VIII：CA结构域基本上同源的第一多肽的第一和第二表达盒转化宿主细胞，在真核宿主细胞中表达具有人因子VIII：C活性的重组蛋白复合物，和与人因子基本上同源的第二多肽 VIII：CC域。在本发明中，第一多肽可以在其C末端延伸有人因子VIII：CB结构域N-末端肽，3-40个氨基酸的多肽间隔区和人因子VIII：CB结构域C末端肽。通过使用α1-抗胰蛋白酶信号序列来改善第二多肽的表达。

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