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    Methods for the treatment of autoimmune disorders using monoclonal antibodies with reduced toxicity
    7.
    发明公开
    Methods for the treatment of autoimmune disorders using monoclonal antibodies with reduced toxicity 审中-公开
    根据具有减小了毒性单克隆抗体用于治疗自身免疫性疾病的方法

    公开(公告)号：EP2815764A1

    公开(公告)日：2014-12-24

    申请号：EP14166617.2

    申请日：2007-06-14

    申请人： MACROGENICS, INC.

    发明人： KOENIG, Scott ,  BONVINI, Ezio ,  JOHNSON, Leslie S. ,  WILDER, Ronald ,  PILLEMER, Stanley

    IPC分类号： A61K39/395 ,  A61K39/40 ,  A61K39/21 ,  A61P37/00 ,  C07K16/28

    CPC分类号： C07K16/2809 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/545 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/71

    摘要： The present disclosure provides methods of treating, preventing, slowing the progression of, or ameliorating the symptoms of T cell mediated immunological diseases, particularly autoimmune diseases (e.g., autoimmune diabetes ( i.e. type 1 diabetes or insulin-dependent diabetes mellitus (IDDM)) and multiple sclerosis) through the use of anti-human CD3 antibodies. The antibodies of the disclosure are preferably used in low dose dosing regimens, chronic dosing regimens or regimens that involve redosing after a certain period of time. The methods of the disclosure provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor/alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the methods of the disclosure provide for use of anti-human CD3 antibodies modified such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-human CD3 antibodies.

    摘要翻译： 本发明提供了治疗，预防，减缓进展，或改善T细胞的症状介导的免疫疾病，特别是自身免疫性疾病（例如，自身免疫性糖尿病（即1型糖尿病或胰岛素依赖型糖尿病（IDDM））和方法 多发性硬化）通过使用抗人CD3抗体。 本公开的抗体在低剂量给药方案优选使用的，慢性的给药方案或方案的一定时间之后也涉及再次给药。 本公开的方法提供了抗体的施用特异性结合所做的人CD3复合物内的ε亚基。 搜索抗体调节T细胞受体/同种异体抗原相互作用，并且因此调节与自身免疫性疾病相关联的T细胞介导的细胞毒性。 另外，本公开的方法提供了使用改性寻求thatthey表现出降低或消除效应子功能和T细胞活化相比于未修饰的抗人CD3抗体的抗人CD3抗体。