首页> 外国专利> FC REGION-CONTAINING POLYPEPTIDES THAT EXHIBIT IMPROVED EFFECTOR FUNCTION DUE TO ALTERATIONS OF THE EXTENT OF FUCOSYLATION, AND METHODS FOR THEIR USE

FC REGION-CONTAINING POLYPEPTIDES THAT EXHIBIT IMPROVED EFFECTOR FUNCTION DUE TO ALTERATIONS OF THE EXTENT OF FUCOSYLATION, AND METHODS FOR THEIR USE

机译:由于改变了岩藻糖基化程度而显示出改善的效应子功能的含有FC区域的多肽及其使用方法

摘要

The present invention relates to Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and to methods of using such polypeptides for treating or preventing cancer and other diseases. The Fc region-containing polypeptides of the present invention are preferably immunoglobulins (e.g., antibodies), in which the Fc region comprises at least one amino acid substitution relative to the corresponding amino acid sequence of a wild type Fc region, and which is sufficient to attenuate post-translational fucosylation and mediate improved binding to an activating Fc receptor and reduced binding to an inhibitory Fc receptor. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcR is desired (e.g., inflammation, autoimmune disease).
机译:本发明涉及由于岩藻糖基化程度的改变而表现出改善的效应子功能的含Fc区的多肽,并且涉及使用这种多肽治疗或预防癌症和其他疾病的方法。本发明的含有Fc区的多肽优选是免疫球蛋白(例如抗体),其中相对于野生型Fc区的相应氨基酸序列,Fc区包含至少一个氨基酸取代,并且足以减弱翻译后岩藻糖基化并介导与激活的Fc受体的结合增强,而与抑制性Fc受体的结合降低。本发明的方法在预防,治疗或改善与疾病,病症或感染有关的一种或多种症状方面特别有用,其中希望通过FcR介导的效应细胞功能的增强功效(例如,癌症,传染性疾病)或需要抑制由FcR介导的效应细胞反应(例如炎症,自身免疫性疾病)。

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