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    Hybrid protein C
    41.
    发明授权
    Hybrid protein C 失效
    杂交蛋白C

    公开(公告)号：US5753224A

    公开(公告)日：1998-05-19

    申请号：US463585

    申请日：1995-06-05

    申请人： Donald C. Foster ,  Richard D. Holly

    发明人： Donald C. Foster ,  Richard D. Holly

    IPC分类号： C12N9/60 ,  C12N9/64 ,  A61K38/00 ,  A61K35/14 ,  A61K38/48 ,  G01N33/53

    CPC分类号： C12N9/6464 ,  C12N9/60 ,  C12Y304/21069 ,  C07K2319/00

    摘要： Human protein C molecules are modified to provide increased resistance to inactivation by human plasma factors while retaining substantially the biological activity of human protein C. The modifications are generally to the heavy chain of protein C, which chain may be substituted with a protein C heavy chain of non-human origin, such as bovine, yielding a chimeric protein C molecule. The human protein C heavy chain may also be modified to be human-like, in that at least one amino acid from a non-human sequence may be substituted for the corresponding residue(s) of the human sequence, thereby allowing the molecule to retain substantially human characteristics yet having increased resistance to inactivation. Also included are methods for producing the modified protein C molecules and pharmaceutical compositions thereof. The modified molecules, having an increased half-life in human plasma, are particularly useful for treating coagulation-related disorders, such as protein C deficiency or thrombosis, or for promoting fibrinolysis in a patient.

    摘要翻译： 人蛋白C分子被修饰以提供对人血浆因子的失活增强的抗性，同时保留人蛋白C的生物活性。修饰通常是蛋白C的重链，该链可被C蛋白重链取代 非人源的，如牛，产生嵌合蛋白C分子。 人蛋白C重链也可以被修饰为人样，因为来自非人序列的至少一个氨基酸可以被人序列的相应残基取代，从而允许分子保留 基本上人的特征，但具有增加的失活抗性。 还包括生产修饰的蛋白C分子的方法及其药物组合物。 在人血浆中具有增加的半衰期的改性分子对于治疗凝血相关疾病如蛋白C缺乏或血栓形成或促进患者的纤维蛋白溶解特别有用。

    Hybrid protein C
    44.
    发明授权
    Hybrid protein C 失效
    杂交蛋白C

    公开(公告)号：US5766921A

    公开(公告)日：1998-06-16

    申请号：US318579

    申请日：1994-10-05

    申请人： Donald C. Foster ,  Richard D. Holly

    发明人： Donald C. Foster ,  Richard D. Holly

    IPC分类号： A61K38/43 ,  A61P7/02 ,  C07K14/00 ,  C07K14/745 ,  C07K19/00 ,  C12N5/10 ,  C12N9/60 ,  C12N9/64 ,  C12N15/09 ,  C12N15/00 ,  C07H21/02 ,  C12N5/00 ,  C12P21/06

    CPC分类号： C12N9/6464 ,  C12N9/60 ,  C12Y304/21069 ,  C07K2319/00

    摘要： Human protein C molecules are modified to provide increased resistance to inactivation by human plasma factors while retaining substantially the biological activity of human protein C. The modifications are generally to the heavy chain of protein C, which chain may be substituted with a protein C heavy chain of non-human origin, such as bovine, yielding a chimeric protein C molecule. The human protein C heavy chain may also be modified to be human-like, in that at least one amino acid from a non-human sequence may be substituted for the corresponding residue(s) of the human sequence, thereby allowing the molecule to retain substantially human characteristics yet having increased resistance to inactivation. Also included are methods for producing the modified protein C molecules and pharmaceutical compositions thereof. The modified molecules, having an increased half-life in human plasma, are particularly useful for treating coagulation-related disorders, such as protein C deficiency or thrombosis, or for promoting fibrinolysis in a patient.

    摘要翻译： 人蛋白C分子被修饰以提供对人血浆因子的失活增强的抗性，同时保留人蛋白C的生物活性。修饰通常是蛋白C的重链，该链可被C蛋白重链取代 非人源的，如牛，产生嵌合蛋白C分子。 人蛋白C重链也可以被修饰为人样，因为来自非人序列的至少一个氨基酸可以被人序列的相应残基取代，从而允许分子保留 基本上人的特征，但具有增加的失活抗性。 还包括生产修饰的蛋白C分子的方法及其药物组合物。 在人血浆中具有增加的半衰期的改性分子对于治疗凝血相关疾病如蛋白C缺乏或血栓形成或促进患者的纤维蛋白溶解特别有用。

    Methods for preparing polynucleotides encoding orphan receptor ligands
    48.
    发明授权
    Methods for preparing polynucleotides encoding orphan receptor ligands 失效
    编制孤儿受体配体的多核苷酸的方法

    公开(公告)号：US5705349A

    公开(公告)日：1998-01-06

    申请号：US490803

    申请日：1995-06-15

    申请人： Richard D. Holly ,  Steven K. Burkhead

    发明人： Richard D. Holly ,  Steven K. Burkhead

    IPC分类号： A61K35/12 ,  C07K14/47 ,  C07K14/705 ,  C07K14/715 ,  C12N5/0787 ,  G01N33/50 ,  C12N15/12 ,  C12N15/19

    CPC分类号： G01N33/502 ,  C07K14/47 ,  C07K14/705 ,  C07K14/715 ,  C12N5/0642 ,  G01N33/5005 ,  G01N33/5008 ,  A61K2035/124 ,  C12N2501/145 ,  C12N2501/22

    摘要： Methods for obtaining cells that produce a ligand for an orphan receptor and methods for preparing polynucleotide molecules that encode ligands for orphan receptors are disclosed. The methods utilize growth factor-dependent parent cells that are transfected with a DNA construct encoding an orphan receptor. The transfected cells are exposed to mutagenizing conditions, and the mutagenized cells are cultured under conditions in which cell survival is dependent upon autocrine growth factor production. Progeny cells are recovered and screened to identify those that produce a ligand for the orphan receptor. Polynucleotide molecules encoding the ligand can be prepared from the identified cells.

    摘要翻译： 公开了获得产生孤儿受体配体的细胞的方法和制备编码孤儿受体配体的多核苷酸分子的方法。 该方法利用用编码孤儿受体的DNA构建体转染的生长因子依赖性亲本细胞。 将转染的细胞暴露于诱变条件下，并且在细胞存活取决于自分泌生长因子产生的条件下培养诱变的细胞。 回收和筛选后代细胞以鉴定产生孤儿受体配体的那些。 可以从鉴定的细胞制备编码配体的多核苷酸分子。

    Method for preparing orphan receptor ligands
    50.
    发明授权
    Method for preparing orphan receptor ligands 失效
    制备孤儿受体配体的方法

    公开(公告)号：US5541085A

    公开(公告)日：1996-07-30

    申请号：US250859

    申请日：1994-05-27

    申请人： Richard D. Holly ,  Steven K. Burkhead

    发明人： Richard D. Holly ,  Steven K. Burkhead

    IPC分类号： C12N15/19 ,  A61K35/12 ,  A61K38/19 ,  C07K14/47 ,  C07K14/705 ,  C07K14/715 ,  C12N1/19 ,  C12N5/0787 ,  C12N5/10 ,  C12N15/81 ,  C12N15/85 ,  C12P21/02 ,  G01N33/50 ,  C12N15/12

    CPC分类号： G01N33/5008 ,  C07K14/47 ,  C07K14/705 ,  C07K14/715 ,  C12N5/0642 ,  A61K2035/124 ,  C12N2501/145 ,  C12N2501/22

    摘要： Methods for obtaining cells that produce a ligand for an orphan receptor and methods for preparing polynucleotide molecules that encode ligands for orphan receptors are disclosed. The methods utilize growth factor-dependent parent cells that are transfected with a DNA construct encoding an orphan receptor. The transfected cells are exposed to mutagenizing conditions, and the mutagenized cells are cultured under conditions in which cell survival is dependent upon autocrine growth factor production. Progeny cells are recovered and screened to identify those that produce a ligand for the orphan receptor. Polynucleotide molecules encoding the ligand can be prepared from the identified cells.

    摘要翻译： 公开了获得产生孤儿受体配体的细胞的方法和制备编码孤儿受体配体的多核苷酸分子的方法。 该方法利用用编码孤儿受体的DNA构建体转染的生长因子依赖性亲本细胞。 将转染的细胞暴露于诱变条件下，并且在细胞存活取决于自分泌生长因子产生的条件下培养诱变的细胞。 回收和筛选后代细胞以鉴定产生孤儿受体配体的那些。 可以从鉴定的细胞制备编码配体的多核苷酸分子。