首页> 外国专利> POLYEPEPTIDES CONTAINING An Fc SITE WHICH DEMONSTRATE AN INCREASED EFFECTIVE FUNCTION THANKS TO CHANGES TO THE FOCOSILATION DEGREE, AND THE METHODS FOR THEIR APPLICATION

POLYEPEPTIDES CONTAINING An Fc SITE WHICH DEMONSTRATE AN INCREASED EFFECTIVE FUNCTION THANKS TO CHANGES TO THE FOCOSILATION DEGREE, AND THE METHODS FOR THEIR APPLICATION

机译:包含Fc站点的多肽,其证明其有效功能有所改变,从而改变了僵化度,及其应用方法

摘要

1. A method of attenuating post-translational fucosylation of a human IgG Fc region, which comprises modifying said Fc region to include amino acid substitution at position: L234, L235, F243, R292, Y300, V305 or P396, and expressing said Fc region in the host cell capable of mediating normal glycosylation. 2. The method of claim 1, wherein said Fc region comprises an amino acid substitution at position F243, R292, Y300, or P396.3. The method of claim 2, wherein: (a) said substitution at position F243 is F243C, F243L or F243R; (b) said substitution at position R292 is R292G, R292L, R292M, R292P, R292S or R292Y; (c) said substitution at position Y300 is Y300L; (d) said substitution at position P396 is P396L. 4. The method of claim 1, wherein said Fc region exhibits altered affinity for a CD16A receptor, a CD16B receptor, or a CD32A receptor. The method of claim 4, wherein said Fc region exhibits reduced affinity for the CD32B.6 receptor. The method of claim 4, wherein said Fc region exhibits increased affinity for the CD16A receptor. The method of claim 1, wherein said Fc region is an Fc region of a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, or a single chain antibody that contains said heavy and light chains. The method of claim 7, wherein said antibody specifically binds CD16A, CD32B, HER2 / neu, A33, CD5, CD11c, CD19, CD20, CD22, CD23, CD27, CD40, CD45, CD79a, CD79b, CD103, CTLA4, ErbB1, ErbB3 ErbB4, VEGF receptor, TNF-α receptor, TNF-ß receptor, or TNF-γ receptor CD16A. 9. The method of claim 7, wherein said antibody specifically binds a cancer antigen. The method according to claim 9, where the specified malignant tumor is a malignant tumor of the breast,
机译:1.一种减弱人IgG Fc区的翻译后岩藻糖基化的方法,其包括修饰所述Fc区以在以下位置包括氨基酸取代:L234,L235,F243,R292,Y300,V305或P396,并表达所述Fc区在能够介导正常糖基化的宿主细胞中。 2.权利要求1的方法,其中所述Fc区在位置F243,R292,Y300或P396.3处包含氨基酸取代。 3.根据权利要求2所述的方法,其中:(a)在位置F243处的所述取代是F243C,F243L或F243R; (b)在位置R292处的所述取代是R292G,R292L,R292M,R292P,R292S或R292Y; (c)在位置Y300处的所述取代为Y300L; (d)在位置P396处的所述取代是P396L。 4.权利要求1的方法,其中所述Fc区对CD16A受体,CD16B受体或CD32A受体表现出改变的亲和力。 5.根据权利要求4所述的方法,其中所述Fc区对CD32B.6受体表现出降低的亲和力。 5.权利要求4的方法,其中所述Fc区对CD16A受体表现出增加的亲和力。 2.权利要求1的方法,其中所述Fc区是包含所述重链和轻链的单克隆抗体,嵌合抗体,人源化抗体,人抗体或单链抗体的Fc区。 8.权利要求7的方法,其中所述抗体特异性结合CD16A,CD32B,HER2 / neu,A33,CD5,CD11c,CD19,CD20,CD22,CD23,CD27,CD40,CD45,CD79a,CD79b,CD103,CTLA4,ErbB1,ErbB3 ErbB4,VEGF受体,TNF-α受体,TNF-β受体或TNF-γ受体CD16A。 9.权利要求7的方法,其中所述抗体特异性结合癌症抗原。 10.根据权利要求9所述的方法,其中,所述特定的恶性肿瘤是乳房的恶性肿瘤,

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