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    Modulation Of Antibody Effector Function By Hinge Domain Engineering
    1.
    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。

    Increasing The Production Of Recombinant Antibodies In Mammalian Cells By Site-Directed Mutagenesis
    3.
    发明申请
    Increasing The Production Of Recombinant Antibodies In Mammalian Cells By Site-Directed Mutagenesis 审中-公开
    通过定点突变增加哺乳动物细胞中重组抗体的产生

    公开(公告)号：US20100145028A1

    公开(公告)日：2010-06-10

    申请号：US12706264

    申请日：2010-02-16

    申请人： William DALL'ACQUA ,  Herren WU ,  Melissa DAMSCHRODER

    发明人： William DALL'ACQUA ,  Herren WU ,  Melissa DAMSCHRODER

    IPC分类号： C07K16/00 ,  C12P21/00

    CPC分类号： C07K16/2866 ,  C07K16/00 ,  C07K16/2848 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/92 ,  C12N2510/02

    摘要： The present invention relates to a reliable, reproducible method for improving the producibility of an antibody. More specifically, this invention provides a method for modifying the heavy chain of an antibody to improve its producibility in eukaryotic cells. Additionally, the method of the invention may improve both antibody producibility and one or more antigen binding characteristics. The invention further provides modified antibodies which are better produced and which have either no change in their antigen binding characteristics or exhibit improved antigen binding characteristics.

    摘要翻译： 本发明涉及提高抗体可生产性的可靠，可重现的方法。 更具体地，本发明提供了修饰抗体重链以改善其在真核细胞中的可生产性的方法。 此外，本发明的方法可以改善抗体可产生性和一种或多种抗原结合特征。 本发明还提供了更好地产生并且其抗原结合特征没有变化或表现出改善的抗原结合特征的修饰抗体。

    Methods of preventing and treating RSV infections and related conditions
    6.
    发明申请
    Methods of preventing and treating RSV infections and related conditions 审中-公开
    预防和治疗RSV感染和相关病症的方法

    公开(公告)号：US20060115485A1

    公开(公告)日：2006-06-01

    申请号：US11263230

    申请日：2005-10-31

    申请人： Genevieve Losonsky ,  Edward Connor ,  James Young ,  Herren Wu ,  William Dall'Acqua

    发明人： Genevieve Losonsky ,  Edward Connor ,  James Young ,  Herren Wu ,  William Dall'Acqua

    IPC分类号： A61K39/42

    CPC分类号： C07K16/1027 ,  A61K2039/505 ,  A61K2039/543 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/72 ,  C07K2317/92 ,  C07K2317/94

    摘要： The present invention provides methods for preventing, managing, treating and/or ameliorating a Respiratory Syncytial Virus (RSV) infection (e.g., acute RSV disease, or a RSV upper respiratory tract infection (URI) and/or lower respiratory tract infection (LRI)), otitis media (preferably, stemming from, caused by or associated with a RSV infection, such as a RSV URI and/or LRI), and/or a symptom or respiratory condition relating thereto (e.g., asthma, wheezing, and/or reactive airway disease (RAD)) in a subject, comprising administering to said human an effective amount of one or more antibodies that immunospecifically bind to one or more RSV antigens with a high affinity and/or high avidity. In some embodiments, one or more antibodies comprise a modified IgG constant domain, or FcRn-binding fragment thereof resulting in longer in vivo serum half-life. In particular embodiments the methods of the invention comprising administering to subject an effective amount of one or more modified antibodies that immunospecifically bind to one or more RSV antigens with an association rate (kon) of at least 2×105 M−1s−1 and a dissociation rate (koff) of less than 5×10−4 s−1.

    摘要翻译： 本发明提供了用于预防，治疗和/或改善呼吸道合胞病毒（RSV）感染（例如急性RSV疾病或RSV上呼吸道感染（URI））和/或下呼吸道感染（LRI）的方法， ），中耳炎（优选来源于，由RSV感染引起或与RSV感染相关联，例如RSV URI和/或LRI），和/或与其相关的症状或呼吸病症（例如，哮喘，喘鸣和/或 反应性气道疾病（RAD）），包括向所述人施用有效量的一种或多种以高亲和力和/或高亲合力免疫特异性结合一种或多种RSV抗原的抗体。 在一些实施方案中，一种或多种抗体包含修饰的IgG恒定结构域或其FcRn结合片段，导致更长的体内血清半衰期。 在具体实施方案中，本发明的方法包括施用有效量的一种或多种经免疫特异性结合一种或多种RSV抗原的修饰的抗体，其具有至少2×10 6的结合速率（kNI） 小于5×10-6的解离速率（k >） 4 -1 。

    Modulation of antibody effector function by hinge domain engineering
    7.
    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。