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    Modified Antibody Constant Regions
    2.
    发明申请
    Modified Antibody Constant Regions 审中-公开
    改良抗体恒定区

    公开(公告)号：US20120238729A1

    公开(公告)日：2012-09-20

    申请号：US13497269

    申请日：2010-09-24

    申请人： Taichi Kuramochi ,  Shigero Tanba ,  Tomoyuki Igawa ,  Atsuhiko Maeda ,  Kiyoaki Sakata ,  Mika Endoh

    发明人： Taichi Kuramochi ,  Shigero Tanba ,  Tomoyuki Igawa ,  Atsuhiko Maeda ,  Kiyoaki Sakata ,  Mika Endoh

    IPC分类号： C07K16/00

    CPC分类号： C07K16/18 ,  C07K16/2833 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/73 ,  C07K2317/75

    摘要： The present inventors successfully provided constant regions capable of enhancing the agonist activity of antibodies through amino acid sequence alterations. Specifically, agonist activity was found to be enhanced in antibodies having a constant region in which amino acids of the antibody heavy chain constant region are substituted or deleted, or antibodies having a constant region in which the hinge region amino acids are substituted. Use of such antibodies as pharmaceutical formulations can provide pharmaceutical formulations with improved performance.

    摘要翻译： 本发明人成功地提供了能够通过氨基酸序列改变增强抗体激动剂活性的恒定区域。 具体地，发现在具有其抗体重链恒定区的氨基酸被取代或缺失的恒定区的抗体的抗体具有激动剂活性，或者具有铰链区氨基酸被取代的恒定区的抗体。 使用这样的抗体作为药物制剂可以提供具有改善的性能的药物制剂。

    METHOD FOR ALTERING PLASMA RETENTION AND IMMUNOGENICITY OF ANTIGEN-BINDING MOLECULE
    4.
    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。

    ANTIBODY CONSTANT REGION VARIANT
    5.
    发明申请
    ANTIBODY CONSTANT REGION VARIANT 审中-公开
    抗体恒定区变异

    公开(公告)号：US20130101581A1

    公开(公告)日：2013-04-25

    申请号：US13582073

    申请日：2011-03-04

    申请人： Taichi Kuramochi ,  Tomoyuki Igawa ,  Atsuhiko Maeda ,  Futa Mimoto

    发明人： Taichi Kuramochi ,  Tomoyuki Igawa ,  Atsuhiko Maeda ,  Futa Mimoto

    IPC分类号： C07K16/00

    CPC分类号： C07K16/00 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/71 ,  C07K2317/72

    摘要： The present inventors carried out dedicated research to generate antibody constant regions with reduced Fcγ receptor-binding activity by altering amino acid sequences in the antibody constant region. As a result, the present inventors successfully identified novel constant region sequences with reduced Fcγ receptor-binding activity compared to conventional antibody constant regions.

    摘要翻译： 本发明人进行了专门的研究，通过改变抗体恒定区中的氨基酸序列来产生具有降低的Fcγ受体结合活性的抗体恒定区。 结果，与常规抗体恒定区相比，本发明人成功地鉴定了具有降低的Fcγ受体结合活性的新型恒定区序列。

    Antibody Constant Region Variant
    7.
    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。