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    Anti-glypican-3 antibody having improved kinetics in plasma
    5.
    发明授权
    Anti-glypican-3 antibody having improved kinetics in plasma 有权
    具有改善血浆动力学的抗磷脂酰肌醇蛋白聚糖-3抗体

    公开(公告)号：US08497355B2

    公开(公告)日：2013-07-30

    申请号：US12733933

    申请日：2008-09-26

    申请人： Tomoyuki Igawa ,  Taichi Kuramochi ,  Hirotake Shiraiwa ,  Hiroyuki Tsunoda ,  Tatsuhiko Tachibana ,  Takahiro Ishiguro

    发明人： Tomoyuki Igawa ,  Taichi Kuramochi ,  Hirotake Shiraiwa ,  Hiroyuki Tsunoda ,  Tatsuhiko Tachibana ,  Takahiro Ishiguro

    IPC分类号： C07K16/30 ,  A61K39/395 ,  C07H21/04 ,  C12P21/08 ,  C12N15/13

    CPC分类号： C07K16/2863 ,  A61K2039/505 ,  A61K2039/545 ,  C07K16/18 ,  C07K16/30 ,  C07K16/303 ,  C07K2317/14 ,  C07K2317/56 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/92 ,  C07K2317/94 ,  C12N15/8258

    摘要： A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.

    摘要翻译： 调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法，一种药物组合物，其包含具有调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分，制备抗磷脂酰肌醇蛋白聚糖的方法 提供了包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。 公开了通过改变暴露于抗磷脂酰肌醇蛋白聚糖3抗体表面的氨基酸残基来调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法; 和具有通过氨基酸残基修饰调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体，包含作为活性成分的磷脂酰肌醇蛋白聚糖3抗体的药物组合物，以及制备抗磷脂酰肌醇蛋白聚糖3抗体的方法和 制备包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。

    ANTI-GLYPICAN-3 ANTIBODY HAVING IMPROVED KINETICS IN PLASMA
    7.
    发明申请
    ANTI-GLYPICAN-3 ANTIBODY HAVING IMPROVED KINETICS IN PLASMA 有权
    具有等离子体改善动力学的抗GLYPICAN-3抗体

    公开(公告)号：US20100239577A1

    公开(公告)日：2010-09-23

    申请号：US12733933

    申请日：2008-09-26

    申请人： Tomoyuki Igawa ,  Taichi Kuramochi ,  Hirotake Shiraiwa ,  Hiroyuki Tsunoda ,  Tatsuhiko Tachibana ,  Takahiro Ishiguro

    发明人： Tomoyuki Igawa ,  Taichi Kuramochi ,  Hirotake Shiraiwa ,  Hiroyuki Tsunoda ,  Tatsuhiko Tachibana ,  Takahiro Ishiguro

    IPC分类号： A61K39/395 ,  C07K16/18 ,  C07H21/00 ,  C12N5/10 ,  C12P21/02 ,  A61P35/00

    CPC分类号： C07K16/2863 ,  A61K2039/505 ,  A61K2039/545 ,  C07K16/18 ,  C07K16/30 ,  C07K16/303 ,  C07K2317/14 ,  C07K2317/56 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/92 ,  C07K2317/94 ,  C12N15/8258

    摘要： A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.

    摘要翻译： 调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法，一种药物组合物，其包含具有调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分，制备抗磷脂酰肌醇蛋白聚糖的方法 提供了包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。 公开了通过改变暴露于抗磷脂酰肌醇蛋白聚糖3抗体表面的氨基酸残基来调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法; 和具有通过氨基酸残基修饰调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体，包含作为活性成分的磷脂酰肌醇蛋白聚糖3抗体的药物组合物，以及制备抗磷脂酰肌醇蛋白聚糖3抗体的方法和 制备包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。

    Antibody Constant Region Variant
    8.
    发明申请
    Antibody Constant Region Variant 审中-公开
    抗体恒定区变体

    公开(公告)号：US20120071634A1

    公开(公告)日：2012-03-22

    申请号：US13257145

    申请日：2010-03-19

    申请人： Tomoyuki Igawa ,  Taichi Kuramochi ,  Atsuhiko Maeda ,  Hirotake Shiraiwa

    发明人： Tomoyuki Igawa ,  Taichi Kuramochi ,  Atsuhiko Maeda ,  Hirotake Shiraiwa

    IPC分类号： C07K16/18

    CPC分类号： C07K16/00 ,  C07K16/2866 ,  C07K16/2875 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/528 ,  C07K2317/53 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2317/94

    摘要： By altering amino acid sequences, the present inventors successfully produced constant regions that can confer antibodies with particularly favorable properties for pharmaceutical agents. When used to produce antibodies, the altered constant regions produced according to the present invention significantly reduce heterogeneity. Specifically, the antibody homogeneity can be achieved by using antibody heavy chain and light chain constant regions introduced with alterations provided by the present invention. More specifically, the alterations can prevent the loss of homogeneity of antibody molecules due to disulfide bond differences in the heavy chain. Furthermore, in a preferred embodiment, the present invention can improve antibody pharmacokinetics as well as prevent the loss of homogeneity due to C-terminal deletion in antibody constant region.

    摘要翻译： 通过改变氨基酸序列，本发明人成功地制备了可赋予具有特别有利于药剂特性的抗体的恒定区域。 当用于产生抗体时，根据本发明产生的改变的恒定区域显着降低异质性。 具体而言，抗体均一性可以通过使用由本发明提供的改变引入的抗体重链和轻链恒定区来实现。 更具体地，改变可以防止由于重链中的二硫键差异导致的抗体分子的均匀性的丧失。 此外，在优选的实施方案中，本发明可以改善抗体药代动力学，并且可以防止由于抗体恒定区域中的C-末端缺失导致的均一性丧失。

    METHOD FOR ALTERING PLASMA RETENTION AND IMMUNOGENICITY OF ANTIGEN-BINDING MOLECULE
    9.
    发明申请
    METHOD FOR ALTERING PLASMA RETENTION AND IMMUNOGENICITY OF ANTIGEN-BINDING MOLECULE 审中-公开
    改变抗原结合分子的等离子体保持和免疫原性的方法

    公开(公告)号：US20140105889A1

    公开(公告)日：2014-04-17

    申请号：US14007947

    申请日：2012-03-30

    申请人： Tomoyuki Igawa ,  Atsuhiko Maeda ,  Kenta Haraya ,  Yuki Iwayanagi ,  Tatsuhiko Tachibana ,  Futa Mimoto ,  Taichi Kuramochi ,  Hitoshi Katada ,  Shojiro Kadono

    发明人： Tomoyuki Igawa ,  Atsuhiko Maeda ,  Kenta Haraya ,  Yuki Iwayanagi ,  Tatsuhiko Tachibana ,  Futa Mimoto ,  Taichi Kuramochi ,  Hitoshi Katada ,  Shojiro Kadono

    IPC分类号： C07K16/28

    CPC分类号： C07K16/2866 ,  C07K16/08 ,  C07K16/18 ,  C07K16/303 ,  C07K2317/524 ,  C07K2317/72

    摘要： The present invention demonstrated that the modification of the Fc region of an antigen-binding molecule into an Fc region that does not form in a neutral pH range a heterotetramer complex containing two molecules of FcRn and an active Fcγ receptor improved the pharmacokinetics of the antigen-binding molecule and reduced the immune response to the antigen-binding molecule. The present invention also revealed methods for producing antigen-binding molecules having the properties described above, and successfully demonstrated that pharmaceutical compositions containing as an active ingredient such an antigen-binding molecule or an antigen-binding molecule produced by a production method of the present invention have excellent features over conventional antigen-binding molecules in that when administered, they exhibit improved pharmacokinetics and reduced in vivo immune response.

    摘要翻译： 本发明证明，将抗原结合分子的Fc区修饰成在中性pH范围内不形成的Fc区，含有两分子FcRn和活性Fcγ受体的异四聚体复合物改善了抗原结合分子的药代动力学， 并降低对抗原结合分子的免疫应答。 本发明还公开了具有上述性质的抗原结合分子的制造方法，成功地证明了通过本发明的制造方法制造的含有作为活性成分的抗原结合分子或抗原结合分子的药物组合物 与常规抗原结合分子相比，具有优异的特征，因为当其施用时，它们表现出改善的药代动力学和体内免疫应答降低。