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    HINGE DOMAIN ENGINEERING
    2.
    发明申请
    HINGE DOMAIN ENGINEERING 审中-公开
    铰链工程

    公开(公告)号：US20110077383A1

    公开(公告)日：2011-03-31

    申请号：US12666331

    申请日：2008-07-02

    申请人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet ,  Raul Cachau

    发明人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet ,  Raul Cachau

    IPC分类号： C07K16/00

    CPC分类号： C07K16/00 ,  C07K16/2866 ,  C07K2317/21 ,  C07K2317/53 ,  C07K2317/56 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92

    摘要： The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which improves stability and/or alters the binding of Fc to one or more metal ion and/or one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that are less susceptible to metal ion-mediated cleavage and/or have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. Furthermore, the modified hinge of the Fc variants retains a similar flexibility to the wild type hinge. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.

    摘要翻译： 本发明涉及包含至少一个抗原结合区和Fc区的新分子（Fc变体），其还包含修饰的铰链，其改进稳定性和/或改变Fc与一个或多个金属离子和/或一个或多个金属离子的结合 更多的Fc配体（例如FcγR）和/或调节效应子功能。 更具体地，本发明提供对金属离子介导的切割较不敏感和/或具有对一个或多个FcγR和/或C1q的修饰的结合亲和力的Fc变体。 另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。 此外，Fc变体的修饰的铰链保持与野生型铰链相似的柔性。 本发明还提供了用于所述Fc变体的应用的方法和方案，特别是用于治疗目的。

    Modulation of antibody effector function by hinge domain engineering
    3.
    发明授权
    Modulation of antibody effector function by hinge domain engineering 有权
    通过铰链域工程调节抗体效应子功能

    公开(公告)号：US08697396B2

    公开(公告)日：2014-04-15

    申请号：US13190199

    申请日：2011-07-25

    申请人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet

    发明人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet

    IPC分类号： C12P21/04 ,  C12N15/00 ,  C07K16/00

    CPC分类号： C07K16/18 ,  C07K16/00 ,  C07K16/2866 ,  C07K2317/53 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/734

    摘要： The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.

    摘要翻译： 本发明涉及包含至少一个抗原结合区和Fc区的新分子（Fc变体），其还包含修饰的铰链，其改变Fc与一个或多个Fc配体（例如FcγR）的结合和/或调节效应子 功能。 更具体地，本发明提供了对一种或多种FcγR和/或C1q具有修饰的结合亲和力的Fc变体。 另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。 本发明还提供了用于所述Fc变体的应用的方法和方案，特别是用于治疗目的。

    Modulation Of Antibody Effector Function By Hinge Domain Engineering
    4.
    发明申请
    Modulation Of Antibody Effector Function By Hinge Domain Engineering 有权
    通过铰链域工程调制抗体效应器功能

    公开(公告)号：US20120046450A1

    公开(公告)日：2012-02-23

    申请号：US13190199

    申请日：2011-07-25

    申请人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet

    发明人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet

    IPC分类号： C07K16/18 ,  C07H21/00

    CPC分类号： C07K16/18 ,  C07K16/00 ,  C07K16/2866 ,  C07K2317/53 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/734

    摘要： The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.

    摘要翻译： 本发明涉及包含至少一个抗原结合区和Fc区的新分子（Fc变体），其还包含修饰的铰链，其改变Fc与一个或多个Fc配体（例如FcγR）的结合和/或调节效应子 功能。 更具体地，本发明提供了对一种或多种FcγR和/或C1q具有修饰的结合亲和力的Fc变体。 另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。 本发明还提供了用于所述Fc变体的应用的方法和方案，特别是用于治疗目的。

    Stabilized immunoglobulins
    5.
    发明授权
    Stabilized immunoglobulins 有权
    稳定的免疫球蛋白

    公开(公告)号：US07608260B2

    公开(公告)日：2009-10-27

    申请号：US10751744

    申请日：2004-01-05

    申请人： Mark A. Schenerman ,  Jose Casas-Finet ,  Jinhua Feng ,  Guillermo Tous

    发明人： Mark A. Schenerman ,  Jose Casas-Finet ,  Jinhua Feng ,  Guillermo Tous

    IPC分类号： A61K39/00 ,  A61K39/38 ,  A61K39/395

    CPC分类号： C07K16/2806 ,  C07K16/00 ,  C07K2317/53

    摘要： The present invention provides stabilized immunoglobulin molecules that have increased storage stability and/or in vivo half-lives due to the mutation of one or more amino acids that would otherwise render the immunoglobulin molecules susceptible to degradation. In a preferred embodiment, the stabilized immunoglobulins of the invention have mutations at the heavy chain constant domain hinge region. Such stabilized immunoglobulin molecules, i.e., immunoglobulin molecules with increased storage stability have one or more of the following advantages they are more readily transported and/storable for longer periods and/or less stringent conditions than non-stabilized counterparts; that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such stabilized molecules.

    摘要翻译： 本发明提供了稳定的免疫球蛋白分子，其由于一种或多种氨基酸的突变而具有增加的储存稳定性和/或体内半衰期，否则会导致免疫球蛋白分子易于降解。 在优选的实施方案中，本发明的稳定的免疫球蛋白在重链恒定域铰链区具有突变。 这种稳定的免疫球蛋白分子，即具有增加的储存稳定性的免疫球蛋白分子具有以下优点中的一个或多个，它们比非稳定的对应物更容易转运和/或更长时间地和/或较不严格的条件运输; 在治疗，预防或诊断使用这种稳定化分子时需要较小的量和或较少频率的给药。

    MODULATION OF ANTIBODY EFFECTOR FUNCTION BY HINGE DOMAIN ENGINEERING
    9.
    发明申请
    MODULATION OF ANTIBODY EFFECTOR FUNCTION BY HINGE DOMAIN ENGINEERING 有权
    通过兴奋剂工程调整抗体效应函数

    公开(公告)号：US20090221803A1

    公开(公告)日：2009-09-03

    申请号：US11912562

    申请日：2006-04-25

    申请人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet

    发明人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder ,  Jose Casas-Finet

    IPC分类号： C12P21/08 ,  C07H21/04

    CPC分类号： C07K16/18 ,  C07K16/00 ,  C07K16/2866 ,  C07K2317/53 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/734

    摘要： The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or CIq. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.

    摘要翻译： 本发明涉及包含至少一个抗原结合区和Fc区的新分子（Fc变体），其还包含修饰的铰链，其改变Fc与一个或多个Fc配体（例如，FcγRs）的结合和/或调节效应子 功能。 更具体地，本发明提供了对一种或多种FcγR和/或Clq具有修饰的结合亲和力的Fc变体。 另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。 本发明还提供了用于所述Fc变体的应用的方法和方案，特别是用于治疗目的。