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    MOLECULES WITH REDUCED HALF-LIVES, COMPOSITIONS AND USES THEREOF
    15.
    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。

    INTEGRATED APPROACH FOR GENERATING MULTIDOMAIN PROTEIN THERAPEUTICS
    16.
    发明申请
    INTEGRATED APPROACH FOR GENERATING MULTIDOMAIN PROTEIN THERAPEUTICS 失效
    用于产生多种蛋白质治疗的综合方法

    公开(公告)号：US20100105873A1

    公开(公告)日：2010-04-29

    申请号：US11993680

    申请日：2006-06-30

    申请人： Christian Allan ,  Herren Wu ,  Jeffrey Swers ,  William Dall'Acqua

    发明人： Christian Allan ,  Herren Wu ,  Jeffrey Swers ,  William Dall'Acqua

    IPC分类号： C07K16/00 ,  C40B30/04

    CPC分类号： C07K16/00 ,  A61K39/39591 ,  C07K2317/52 ,  C07K2317/55

    摘要： The invention provides method for therapeutic protein drug development that incorporates therapeutic and/or formulation and/or manufacturing considerations in the early screening process. The approach involves screening a plurality of different variants of a domain that have been determined to have the desired therapeutic property to identify one or more variants that have desired therapeutic and/or formulation characteristics, and constructing the full multidomain proteins using the identified domain variants. The present invention also provides a method for determining the shelf life of multidomain proteins in formulations. The method comprises determining a thermal denaturation and/or renaturation curve of a domain of the protein whose unfolding leads to aggregation of the protein in a solution. The method evaluates the shelf life of the multidomain protein based on the denaturation/renaturation curve. The invention also provides methods for engineering multidomain proteins to improve their therapeutic and/or formulation characteristics.

    摘要翻译： 本发明提供了在早期筛选过程中结合治疗和/或制剂和/或制造考虑的治疗性蛋白质药物开发方法。 所述方法包括筛选已被确定具有所需治疗性质的结构域的多个不同变体以鉴定具有期望的治疗和/或制剂特征的一种或多种变体，以及使用鉴定的结构域变体构建完整的多结构域蛋白。 本发明还提供了一种确定制剂中多结构域蛋白质的保质期的方法。 该方法包括确定蛋白质的结构域的热变性和/或复性曲线，其解折叠导致蛋白质在溶液中聚集。 该方法基于变性/复性曲线评估多结构域蛋白质的保质期。 本发明还提供用于工程化多结构域蛋白质以改善其治疗和/或制剂特征的方法。

    MODULATION OF ANTIBODY EFFECTOR FUNCTION BY HINGE DOMAIN ENGINEERING
    17.
    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。

    Integrated approach for generating multidomain protein therapeutics
    18.
    发明授权
    Integrated approach for generating multidomain protein therapeutics 失效
    用于产生多结构域蛋白治疗剂的综合方法

    公开(公告)号：US08309690B2

    公开(公告)日：2012-11-13

    申请号：US11993680

    申请日：2006-06-30

    申请人： Christian Allan ,  Herren Wu ,  Jeffrey Swers ,  William Dall'Acqua

    发明人： Christian Allan ,  Herren Wu ,  Jeffrey Swers ,  William Dall'Acqua

    IPC分类号： C07K16/00

    CPC分类号： C07K16/00 ,  A61K39/39591 ,  C07K2317/52 ,  C07K2317/55

    摘要： The invention provides method for therapeutic protein drug development that incorporates therapeutic and/or formulation and/or manufacturing considerations in the early screening process. The approach involves screening a plurality of different variants of a domain that have been determined to have the desired therapeutic property to identify one or more variants that have desired therapeutic and/or formulation characteristics, and constructing the full multidomain proteins using the identified domain variants. The present invention also provides a method for determining the shelf life of multidomain proteins in formulations. The method comprises determining a thermal denaturation and/or renaturation curve of a domain of the protein whose unfolding leads to aggregation of the protein in a solution. The method evaluates the shelf life of the multidomain protein based on the denaturation/renaturation curve. The invention also provides methods for engineering multidomain proteins to improve their therapeutic and/or formulation characteristics.

    摘要翻译： 本发明提供了在早期筛选过程中结合治疗和/或制剂和/或制造考虑的治疗性蛋白质药物开发方法。 所述方法包括筛选已被确定具有所需治疗性质的结构域的多个不同变体以鉴定具有期望的治疗和/或制剂特征的一种或多种变体，以及使用鉴定的结构域变体构建完整的多结构域蛋白。 本发明还提供了一种确定制剂中多结构域蛋白质的保质期的方法。 该方法包括确定蛋白质的结构域的热变性和/或复性曲线，其解折叠导致蛋白质在溶液中聚集。 该方法基于变性/复性曲线评估多结构域蛋白质的保质期。 本发明还提供用于工程化多结构域蛋白质以改善其治疗和/或制剂特征的方法。

    Methods of Treating RSV Infections And Related Conditions
    19.
    发明申请
    Methods of Treating RSV Infections And Related Conditions 审中-公开
    治疗RSV感染和相关条件的方法

    公开(公告)号：US20110008329A1

    公开(公告)日：2011-01-13

    申请号：US12600292

    申请日：2008-06-25

    申请人： Subramaniam Krishnan ,  JoAnn Suzich ,  Peter Kiener ,  Genevieve Losonsky ,  Herren Wu ,  William Dall'Acqua ,  Bettina Richter

    发明人： Subramaniam Krishnan ,  JoAnn Suzich ,  Peter Kiener ,  Genevieve Losonsky ,  Herren Wu ,  William Dall'Acqua ,  Bettina Richter

    IPC分类号： A61K39/395 ,  C07K16/10 ,  A61P31/14 ,  A61P37/04

    CPC分类号： C07K16/1027 ,  A61K2039/505 ,  A61K2039/545 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/77

    摘要： The present invention provides methods for 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)), and/or a symptom or a long-term respiratory condition relating thereto (e.g., asthma, wheezing, reactive airway disease (RAD), or chronic obstructive pulmonary disease (COPD)) 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 and further comprise a modified IgG constant domain, or FcRn-binding fragment thereof, to not only decrease RSV infection, but also decrease the pro-inflammatory epithelial cell immune responses in order to mitigate the later development of asthma and/or wheezing and/or COPD in said patient.

    摘要翻译： 本发明提供了用于管理，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， 和/或与受试者相关的症状或长期呼吸道状况（例如，哮喘，喘鸣，反应性气道疾病（RAD）或慢性阻塞性肺疾病（COPD））），包括向所述人施用有效量的 一种或多种以高亲和性和/或高亲合力免疫特异性结合一种或多种RSV抗原的抗体，并且还包含经修饰的IgG恒定结构域或其FcRn结合片段，以不仅降低RSV感染，而且减少pro - 炎症性上皮细胞免疫应答，以减轻所述患者中哮喘和/或喘息和/或COPD的后期发展。

    METHODS OF PREVENTING AND TREATING RSV INFECTIONS AND RELATED CONDITIONS
    20.
    发明申请
    METHODS OF PREVENTING AND TREATING RSV INFECTIONS AND RELATED CONDITIONS 审中-公开
    预防和治疗RSV感染的方法及相关条件

    公开(公告)号：US20100098708A1

    公开(公告)日：2010-04-22

    申请号：US12559375

    申请日：2009-09-14

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

    发明人： Genevieve Losonsky ,  Edward M. Connor ,  James F. 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，喘息和/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一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 5 M-1s-1的缔合速率（kon）和 解离速率（koff）小于5×10-4 s-1。