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    METHOD OF PRODUCING FACTOR VIII PROTEINS BY RECOMBINANT METHODS
    3.
    发明申请
    METHOD OF PRODUCING FACTOR VIII PROTEINS BY RECOMBINANT METHODS 审中-公开
    通过重组方法生产因子VIII蛋白的方法

    公开(公告)号：US20090203077A1

    公开(公告)日：2009-08-13

    申请号：US12252024

    申请日：2008-10-15

    申请人： Randal J. Kaufman ,  Steven W. Pipe ,  Michael Griffith

    发明人： Randal J. Kaufman ,  Steven W. Pipe ,  Michael Griffith

    IPC分类号： C12P21/02 ,  C12N15/12

    CPC分类号： C07K14/755

    摘要： Provided herein are methods and compositions for producing Factor VIII proteins. Such methods include introducing into a cell a nucleic acid molecule encoding a Factor VIII protein operably linked to a promoter, wherein the promoter is characterized by the ability to produce commercially viable Factor VIII protein; and incubating the cell under conditions for producing commercially viable Factor VIII protein. Also provided are nucleic acid molecules which encode a Factor VIII protein operably linked to a Chinese hamster elongation factor 1-α (CHEF1) promoter, which may be used in the methods provided herein.

    摘要翻译： 本文提供了用于产生因子VIII蛋白质的方法和组合物。 这样的方法包括向细胞中引入编码与启动子可操作连接的因子VIII蛋白的核酸分子，其中启动子的特征在于产生商业上可行的因子VIII蛋白的能力; 并在用于生产商业上可行的因子VIII蛋白的条件下孵育细胞。 还提供了编码与中国仓鼠延长因子1-α（CHEF1）启动子可操作地连接的因子VIII蛋白的核酸分子，其可用于本文提供的方法中。

    Inactivation resistant factor VIII
    4.
    发明授权
    Inactivation resistant factor VIII 失效
    灭活抗因子VIII

    公开(公告)号：US07459534B2

    公开(公告)日：2008-12-02

    申请号：US10974534

    申请日：2004-10-26

    申请人： Randal J. Kaufman ,  Steven W. Pipe ,  Kagehiro Amano

    发明人： Randal J. Kaufman ,  Steven W. Pipe ,  Kagehiro Amano

    IPC分类号： A61K38/00 ,  C07K14/00

    CPC分类号： C07K14/755 ,  A61K38/00

    摘要： The present invention provides novel purified and isolated nucleic acid sequences encoding procoagulant-active FVIII proteins. The nucleic acid sequences of the present invention encode amino acid sequences corresponding to known human FVIII sequences, wherein residue Phe309 is mutated. The nucleic acid sequences of the present invention also encode amino acid sequences corresponding to known human FVIII sequences, wherein the APC cleavage sites, Arg336 and Ile562, are mutated. The nucleic acid sequences of the present invention further encode amino acid sequences corresponding to known human FVIII sequences, wherein the B-domain is deleted, the von Willebrand factor binding site is deleted, a thrombin cleavage site is mutated and an amino acid sequence spacer is inserted between the A2- and A3-domains. Methods of producing the FVIII proteins of the invention, nucleotide sequences encoding such proteins, pharmaceutical compositions containing the nucleotide sequences or proteins, as well as methods of treating patients suffering from hemophilia, are also provided.

    摘要翻译： 本发明提供了编码促凝血活性FVIII蛋白的新型纯化和分离的核酸序列。 本发明的核酸序列编码对应于已知人FVIII序列的氨基酸序列，其中残基Phe309被突变。 本发明的核酸序列还编码对应于已知人FVIII序列的氨基酸序列，其中APC切割位点Arg336和Ile562突变。 本发明的核酸序列进一步编码对应于已知人FVIII序列的氨基酸序列，其中缺失B结构域，缺失血管性血友病因子结合位点，突变凝血酶切割位点，氨基酸序列间隔物为 插入在A2-和A3-域之间。 还提供了产生本发明的FVIII蛋白的方法，编码这种蛋白质的核苷酸序列，含有核苷酸序列或蛋白质的药物组合物，以及治疗患有血友病的患者的方法。

    DNA encoding the novel mammalian protein, Ire1p
    5.
    发明授权
    DNA encoding the novel mammalian protein, Ire1p 失效
    编码新型哺乳动物蛋白质的DNA，Ire1p

    公开(公告)号：US07439061B2

    公开(公告)日：2008-10-21

    申请号：US10891973

    申请日：2004-07-14

    申请人： Randal J. Kaufman ,  Witoon Tirasphon ,  Ajith A. Welihinda

    发明人： Randal J. Kaufman ,  Witoon Tirasphon ,  Ajith A. Welihinda

    IPC分类号： C12N15/85 ,  C12N15/79 ,  C12N15/63 ,  C12N15/52 ,  C12N1/21

    CPC分类号： C12N9/1205 ,  C07H21/04 ,  C12N9/22

    摘要： A novel polynucleotide encoding a mammalian bifunctional protein kinase\endoribonuclease referred to herein as hIre1p, is provided. hIre1p is expressed in the endoplasmic reticulum (ER) and upregulates the transcription of genes encoding ER protein chaperones, such as, but not limited to, glucose-related proteins (GRP's). Therapeutic, diagnostic and research methods employing the polynucleotide and protein are also provided.

    摘要翻译： 提供了编码哺乳动物双功能蛋白激酶\内切核糖核酸酶的本文中称为hIre1p的新型多核苷酸。 hIre1p在内质网（ER）中表达，并且上调编码ER蛋白分子伴侣（例如但不限于葡萄糖相关蛋白（GRP's））的基因的转录。 还提供了使用多核苷酸和蛋白质的治疗，诊断和研究方法。

    Eucaryotic expression system
    6.
    发明授权
    Eucaryotic expression system 失效
    真核表达系统

    公开(公告)号：US4912040A

    公开(公告)日：1990-03-27

    申请号：US10351

    申请日：1987-02-03

    申请人： Randal J. Kaufman ,  Andrew Dorner

    发明人： Randal J. Kaufman ,  Andrew Dorner

    IPC分类号： C07K14/705 ,  C12N5/02 ,  C12N5/10 ,  C12N9/72 ,  C12N15/09 ,  C12N15/85 ,  C12P21/00 ,  C12R1/91

    CPC分类号： C12N15/85 ,  C07K14/705 ,  C12N9/6459 ,  C12Y304/21069

    摘要： This invention provides vectors, improved host cells and improved methods for producing a heterologous protein by culturing an improved eucaryotic host cell of this invention transformed or transfected with a vector capable of directing the expression of the heterologous protein. The preferred improved host cell of this invention is a mammalian host cell containing and capable of expressing an anti-sense GRP78 DNA sequence.

    摘要翻译： 本发明提供载体，改良的宿主细胞和通过培养用能够引导异源蛋白质的表达转化或转染的本发明的改良的真核宿主细胞产生异源蛋白质的改进方法。 本发明优选的改良宿主细胞是含有并能够表达反义GRP78 DNA序列的哺乳动物宿主细胞。

    Inactivation resistant factor VIII
    10.
    发明授权
    Inactivation resistant factor VIII 失效
    灭活抗因子VIII

    公开(公告)号：US06838437B2

    公开(公告)日：2005-01-04

    申请号：US09819098

    申请日：2001-04-11

    申请人： Randal J. Kaufman ,  Steven W. Pipe ,  Kagehiro Amano

    发明人： Randal J. Kaufman ,  Steven W. Pipe ,  Kagehiro Amano

    IPC分类号： C12N15/09 ,  A61K31/00 ,  A61K38/00 ,  A61K38/43 ,  A61K48/00 ,  A61P7/00 ,  A61P7/04 ,  C07K14/755 ,  C12N1/21 ,  C12P21/08

    CPC分类号： C07K14/755 ,  A61K38/00

    摘要： The present invention provides novel purified and isolated nucleic acid sequences encoding procoagulant-active FVIII proteins. The nucleic acid sequences of the present invention encode amino acid sequences corresponding to known human FVIII sequences, wherein residue Phe3O9 is mutated. The nucleic acid sequences of the present invention also encode amino acid sequences corresponding to known human FVIII sequences, wherein the APC cleavage sites, Arg336 and Ile562, are mutated. The nucleic acid sequences of the present invention further encode amino acid sequences corresponding to known human FVIII sequences, wherein the B-domain is deleted, the von Willebrand factor binding site is deleted, a thrombin cleavage site is mutated and an amino acid sequence spacer is inserted between the A2- and A3-domains. Methods of producing the FVIII proteins of the invention, nucleotide sequences encoding such proteins, pharmaceutical compositions containing the nucleotide sequences or proteins, as well as methods of treating patients suffering from hemophilia, are also provided.

    摘要翻译： 本发明提供了编码促凝血活性FVIII蛋白的新型纯化和分离的核酸序列。 本发明的核酸序列编码对应于已知人FVIII序列的氨基酸序列，其中残基Phe3O9被突变。 本发明的核酸序列还编码对应于已知人FVIII序列的氨基酸序列，其中APC切割位点Arg336和Ile562突变。 本发明的核酸序列进一步编码对应于已知人FVIII序列的氨基酸序列，其中缺失B结构域，缺失血管性血友病因子结合位点，突变凝血酶切割位点，氨基酸序列间隔物为 插入在A2-和A3-域之间。 还提供了产生本发明的FVIII蛋白的方法，编码这种蛋白质的核苷酸序列，含有核苷酸序列或蛋白质的药物组合物，以及治疗患有血友病的患者的方法。