Modulation of antibody effector function by hinge domain engineering
    1.
    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

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

    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
    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

    IPC分类号: C07K16/00

    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。

    Periplasmic expression of antibodies using a single signal sequence
    3.
    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

    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
    5.
    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

    IPC分类号: C12P21/08 C07H21/04

    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。

    Humanization of antibodies
    8.
    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

    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。

    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

    IPC分类号: C07K16/18 C07H21/00

    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。

    Framework-Shuffling Of Antibodies
    10.
    发明申请
    Framework-Shuffling Of Antibodies 审中-公开
    框架洗牌抗体

    公开(公告)号:US20100216975A1

    公开(公告)日:2010-08-26

    申请号:US12697597

    申请日:2010-02-01

    IPC分类号: C07K16/00 C12P21/04

    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。