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    Humanization of antibodies
    11.
    发明申请
    Humanization of antibodies 审中-公开
    抗体的人源化

    公开(公告)号：US20050048617A1

    公开(公告)日：2005-03-03

    申请号：US10920899

    申请日：2004-08-18

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

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

    IPC分类号： C07H21/04 ,  C07K16/00 ,  C07K16/40 ,  C12N15/13 ,  A61K39/395 ,  C07K16/18

    CPC分类号： C07K16/005 ,  C07H21/04 ,  C07K16/40 ,  C12N15/1037 ,  C12Q2563/131

    摘要： The present invention relates to methods of reengineering or reshaping antibodies to reduce the immunogenicity of the antibodies, while maintaining the immunospecificity of the antibodies for an antigen. In particular, the present invention provides methods of producing antibodies immunospecific for an antigen by synthesizing a combinatorial library comprising complementarity determining regions (CDRs) from a donor antibody fused in frame to framework regions from a sub-bank of framework regions. The present invention also provides antibodies produced by the methods of the invention.

    摘要翻译： 本发明涉及重新设计或重塑抗体以降低抗体免疫原性的方法，同时保持针对抗原的抗体的免疫特异性。 特别地，本发明提供了通过合成包含来自框架区域的子库的框架区域融合的供体抗体的互补决定区（CDR）的组合文库的组合文库来产生针对抗原免疫特异性的抗体的方法。 本发明还提供通过本发明的方法制备的抗体。

    Humanization of antibodies
    12.
    发明申请
    Humanization of antibodies 审中-公开
    抗体的人源化

    公开(公告)号：US20050042664A1

    公开(公告)日：2005-02-24

    申请号：US10923068

    申请日：2004-08-20

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

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

    IPC分类号： C07K16/46 ,  C12Q1/68

    CPC分类号： C07K16/465

    摘要： The present invention provides methods of re-engineering or re-shaping an antibody from a first species, wherein the re-engineered or re-shaped antibody does not elicit undesired immune response in a second species, and the re-engineered or re-shaped antibody retains substantially the same antigen binding-ability of the antibody from the first species. In accordance with the present invention, a combinatorial library comprising the CDRs of the antibody from the first species fused in frame with framework regions derived from a second species can be constructed and screened for the desired modified antibody. In particular, the present invention provides methods utilizing low homology acceptor antibody frameworks for efficiently humanizing an antibody or a fragment thereof. The present invention also provides antibodies produced by the methods of the invention.

    摘要翻译： 本发明提供了重新设计或重新形成来自第一种类的抗体的方法，其中重新设计或重新形成的抗体在第二种物种中不引发不期望的免疫应答，并且重新设计或重新形成 抗体保留了来自第一物种的抗体基本相同的抗原结合能力。 根据本发明，可以构建包含来自与来自第二种类的框架区域框架融合的第一物种的抗体的CDR的组合文库，并筛选所需的修饰抗体。 特别地，本发明提供利用低同源受体抗体框架有效地使抗体或其片段人源化的方法。 本发明还提供通过本发明的方法制备的抗体。

    Framework-shuffling of antibodies
    13.
    发明申请
    Framework-shuffling of antibodies 审中-公开
    框架改组抗体

    公开(公告)号：US20060228350A1

    公开(公告)日：2006-10-12

    申请号：US11377148

    申请日：2006-03-17

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

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

    IPC分类号： A61K39/395 ,  C07H21/04 ,  C12P21/06 ,  C07K16/44 ,  C12N5/06

    CPC分类号： C07K16/005 ,  C07H21/04 ,  C07K16/2863 ,  C07K16/40 ,  C07K16/464 ,  C07K2317/55 ,  C07K2317/92 ,  C12N15/1027

    摘要： The present invention relates to methods of reengineering or reshaping antibodies to reduce the immunogenicity of the antibodies, while maintaining the immunospecificity of the antibodies for an antigen. In particular, the present invention provides methods of producing antibodies immunospecific for an antigen by synthesizing a combinatorial library comprising complementarity determining regions (CDRs) from a donor antibody fused in frame to framework regions from a sub-bank of framework regions. The invention also provides method of producing improved humanized antibodies. The present invention also provides antibodies produced by the methods of the invention.

    摘要翻译： 本发明涉及重新设计或重塑抗体以降低抗体免疫原性的方法，同时保持针对抗原的抗体的免疫特异性。 特别地，本发明提供了通过合成包含来自框架区域的子库的框架区域融合的供体抗体的互补决定区（CDR）的组合文库的组合文库来产生针对抗原免疫特异性的抗体的方法。 本发明还提供了生产改良的人源化抗体的方法。 本发明还提供通过本发明的方法制备的抗体。

    Methods of preventing and treating RSV infections and related conditions
    14.
    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 。

    Molecules with extended half-lives, compositions and uses thereof
    15.
    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。

    MOLECULES WITH REDUCED HALF-LIVES, COMPOSITIONS AND USES THEREOF
    20.
    发明申请
    MOLECULES WITH REDUCED HALF-LIVES, COMPOSITIONS AND USES THEREOF 审中-公开
    具有减少半衰期的组合物，组合物及其用途

    公开(公告)号：US20100143254A1

    公开(公告)日：2010-06-10

    申请号：US12443257

    申请日：2007-10-16

    申请人： William Dall'Acqua ,  Herren Wu

    发明人： William Dall'Acqua ,  Herren Wu

    IPC分类号： A61K49/00 ,  C07K16/00

    CPC分类号： C07K16/1027 ,  C07K2317/52

    摘要： The present invention provides polypeptides containing at least the FcRn binding portion of an Fc region of an immunoglobulin molecule and that have altered amino acid sequences relative to wild type immunoglobulin molecules. The polypeptides have decreased in vivo serum half-lives and can be employed in various methods.

    摘要翻译： 本发明提供了至少含有免疫球蛋白分子的Fc区的FcRn结合部分并且相对于野生型免疫球蛋白分子具有改变的氨基酸序列的多肽。 多肽具有降低的体内血清半衰期并且可以以各种方法使用。