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    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。

    Methods of preventing and treating RSV infections and related conditions
    5.
    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
    6.
    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：US08008443B2

    公开(公告)日：2011-08-30

    申请号：US11912562

    申请日：2006-04-25

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

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

    IPC分类号： C07K16/00 ,  C12P21/08 ,  A61K38/00

    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 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。

    HINGE DOMAIN ENGINEERING
    7.
    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。

    Molecules with extended half-lives, compositions and uses thereof
    8.
    发明授权
    Molecules with extended half-lives, compositions and uses thereof 有权
    具有延长半衰期，组成和用途的分子

    公开(公告)号：US07658921B2

    公开(公告)日：2010-02-09

    申请号：US11762525

    申请日：2007-06-13

    申请人： William Dall'Acqua ,  Herren Wu ,  Peter Kiener

    发明人： William Dall'Acqua ,  Herren Wu ,  Peter Kiener

    IPC分类号： A61K39/40

    CPC分类号： C07K16/00 ,  A61K2039/505 ,  C07K16/1027 ,  C07K2317/52 ,  C07K2317/53 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00

    摘要： The present invention provides molecules, including IgGs, non-IgG immunoglobulin, proteins and non-protein agents, that have increased in vivo half-lives due to the presence of an IgG constant domain, or a portion thereof that binds the FcRn, having one or more amino acid modifications that increase the affinity of the constant domain or fragment for FcRn. Such proteins and molecules with increased half-lives have the advantage that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such molecules.

    摘要翻译： 本发明提供了由于存在IgG恒定结构域或其结合FcRn的部分而具有增加的体内半衰期的IgG，非IgG免疫球蛋白，蛋白质和非蛋白质试剂的分子，其具有一个 或更多的氨基酸修饰，其增加FcRn的恒定结构域或片段的亲和力。 具有增加的半衰期的这种蛋白质和分子具有在这种分子的治疗，预防或诊断使用中需要更少量和/或更低频率给药的优点。

    Periplasmic expression of antibodies using a single signal sequence
    9.
    发明申请
    Periplasmic expression of antibodies using a single signal sequence 审中-公开
    使用单个信号序列的抗体的周质表达

    公开(公告)号：US20050181479A1

    公开(公告)日：2005-08-18

    申请号：US11071304

    申请日：2005-03-04

    申请人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder

    发明人： William Dall'Acqua ,  Herren Wu ,  Melissa Damschroder

    IPC分类号： C07H21/04 ,  C07K16/00 ,  C07K16/18 ,  C07K16/40 ,  C12N5/06 ,  C12N15/09

    CPC分类号： C07K16/40 ,  C07H21/04 ,  C07K16/00 ,  C07K2317/55 ,  C07K2317/565

    摘要： The present invention relates to recombinant polynucleotides, expression vectors and methods for the production of multimeric proteins. The vectors and methods are useful for the production of multimeric protein and are unique in that they utilize a minimal number of signal sequences. More specifically, the present invention provides recombinant polynucleotide molecules and expression vectors comprising a promoter region operably linked to a transcription unit. The transcription unit is characterized by at least two DNA sequences encoding distinct polypeptides wherein at least one but not all DNA sequences further encodes a signal sequence operably linked to the DNA sequence encoding a polypeptide. The invention further provides methods of producing a multimeric protein using the expression vectors of the present invention.

    摘要翻译： 本发明涉及重组多核苷酸，表达载体和用于产生多聚体蛋白质的方法。 载体和方法可用于生产多聚体蛋白质，并且是唯一的，因为它们利用最少量的信号序列。 更具体地，本发明提供重组多核苷酸分子和包含可操作地连接到转录单位的启动子区的表达载体。 转录单元的特征在于编码不同多肽的至少两个DNA序列，其中至少一个但不是全部DNA序列进一步编码与编码多肽的DNA序列可操作地连接的信号序列。 本发明还提供使用本发明的表达载体产生多聚体蛋白质的方法。

    Modulation of antibody effector function by hinge domain engineering
    10.
    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。