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    Antibody constant region variant
    1.
    发明授权
    Antibody constant region variant 有权
    抗体恒定区变体

    公开(公告)号：US09228017B2

    公开(公告)日：2016-01-05

    申请号：US13257112

    申请日：2010-03-19

    申请人： Tomoyuki Igawa ,  Atsuhiko Maeda ,  Hirotake Shiraiwa

    发明人： Tomoyuki Igawa ,  Atsuhiko Maeda ,  Hirotake Shiraiwa

    IPC分类号： C07K16/28

    CPC分类号： C07K16/2866 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/90 ,  C07K2317/92 ,  C07K2317/94

    摘要： By altering amino acid sequence, the present inventors succeeded in providing constant regions that can confer antibodies with favorable properties, particularly as pharmaceuticals. The variants of the constant regions provided by the present invention will remarkably reduce heterogeneity when applied to antibody production. That is, homogeneity of antibodies can be maintained at a high level by introducing the alterations provided by the present invention into the antibody heavy chain constant regions. More specifically, decrease in homogeneity caused by —SS— bond linkage differences in the heavy chains of antibody molecules can be prevented. Furthermore, in a preferred embodiment of the present invention, pharmacokinetics of antibodies can be improved and decrease in homogeneity caused by deletion of the C terminus in the antibody constant region can be ameliorated.

    摘要翻译： 通过改变氨基酸序列，本发明人成功地提供了可赋予具有良好性质的抗体的恒定区域，特别是作为药物。 当应用于抗体生产时，由本发明提供的恒定区的变体将显着降低异质性。 也就是说，通过将本发明提供的改变引入抗体重链恒定区，可以将抗体的均一性保持在高水平。 更具体地，可以防止由抗体分子的重链中的-SS-键连接差引起的同质性的降低。 此外，在本发明的优选实施方案中，可以改善抗体的药代动力学，并且可以改善由抗体恒定区中的C末端缺失引起的同质性降低。

    Antibody Constant Region Variant
    5.
    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。

    Antibody Constant Region Variant
    6.
    发明申请
    Antibody Constant Region Variant 有权
    抗体恒定区变体

    公开(公告)号：US20120065379A1

    公开(公告)日：2012-03-15

    申请号：US13257112

    申请日：2010-03-19

    申请人： Tomoyuki Igawa ,  Atsuhiko Maeda ,  Hirotake Shiraiwa

    发明人： Tomoyuki Igawa ,  Atsuhiko Maeda ,  Hirotake Shiraiwa

    IPC分类号： C07K16/00

    CPC分类号： C07K16/2866 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/90 ,  C07K2317/92 ,  C07K2317/94

    摘要： By means of amino acid sequence alterations, the present inventors succeeded in providing constant regions that can confer antibodies with favorable properties, particularly as pharmaceuticals. The variants of the constant regions provided by the present invention will remarkably reduce heterogeneity when applied to antibody production. That is, homogeneity of antibodies can be maintained at a high level by introducing the alterations provided by the present invention into the antibody heavy chain constant regions. More specifically, decrease in homogeneity caused by —SS— bond linkage differences in the heavy chains of antibody molecules can be prevented. Furthermore, in a preferred embodiment of the present invention, pharmacokinetics of antibodies can be improved and decrease in homogeneity caused by deletion of the C terminus in the antibody constant region can be ameliorated.

    摘要翻译： 通过氨基酸序列改变，本发明人成功地提供了可赋予具有良好性质的抗体的恒定区域，特别是作为药物。 当应用于抗体生产时，由本发明提供的恒定区的变体将显着降低异质性。 也就是说，通过将本发明提供的改变引入抗体重链恒定区，可以将抗体的均一性保持在高水平。 更具体地，可以防止由抗体分子的重链中的-SS-键连接差引起的同质性的降低。 此外，在本发明的优选实施方案中，可以改善抗体的药代动力学，并且可以改善由抗体恒定区中的C末端缺失引起的同质性降低。

    Modified antibody constant region
    10.
    发明授权
    Modified antibody constant region 有权

    公开(公告)号：US09688762B2

    公开(公告)日：2017-06-27

    申请号：US12680082

    申请日：2008-09-26

    申请人： Tomoyuki Igawa ,  Hirotake Shiraiwa

    发明人： Tomoyuki Igawa ,  Hirotake Shiraiwa

    IPC分类号： C07K16/00 ,  C07K16/28

    CPC分类号： C07K16/2866 ,  C07K16/00 ,  C07K2317/52 ,  C07K2317/53 ,  C07K2317/71

    摘要： The present inventors succeeded in improving the antibody constant region to have increased stability under acid conditions, reduced heterogeneity originated from disulfide bonds in the hinge region, reduced heterogeneity originated from the H chain C terminus, and increased stability at high concentrations as well as in discovering novel constant region sequences having reduced Fcγ receptor-binding, while minimizing the generation of novel T-cell epitope peptides. As a result, the present inventors successfully discovered antibody constant regions with improved physicochemical properties (stability and homogeneity), immunogenicity, safety, and pharmacokinetics.