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    • 8. 发明申请
    • METHOD FOR PREPARING ANTIBODIES SELECTIVE FOR ACTIVATING FC RECEPTORS
    • 制备选择性用于激活FC受体的抗体的方法
    • US20090029393A1
    • 2009-01-29
    • US12097022
    • 2006-12-15
    • Jean-Luc TeillaudSylvie JorieuxSophie SiberilRenee MenezEnrico SturaFrederic Ducancel
    • Jean-Luc TeillaudSylvie JorieuxSophie SiberilRenee MenezEnrico SturaFrederic Ducancel
    • G01N33/566C07K16/18
    • C07K16/00C07K16/34C07K2317/52C07K2317/71
    • The present invention relates to a method for preparing an antibody selective for activating antibody Fc region receptors (FcRs) comprising an ITAM motif or motifs (immunoreceptor tyrosine-based activation motif), comprising the steps of obtaining monoclonal antibodies from a hybridoma, from a heterohybridoma or from any animal, plant or human cell line, replacing each of the His 310 and His 435 residues (Cabat numbering) of the Fc region of said antibody with a residue chosen from lysine, alanine, glycine, valine, leucine, isoleucine, proline, methionine, tryptophan, phenylalanine, serine or threonine, and then selecting the antibodies for which the binding to inhibitory FcRs comprising ITIM motifs (immunoreceptor tyrosine-based inhibition motif) is decreased by at least 30%, preferably by at least 50%, 70%, 80% or else by at least 90% relative to the same antibody having a natural Fc region. The present invention also relates to the use of an antibody derived from the method of the invention in the production of a medicament for use in particular in the treatment of cancer and of infectious pathologies.
    • 本发明涉及一种制备用于激活包含ITAM基序或基序(基于免疫受体酪氨酸的激活基序)的抗体Fc区受体(FcR)的选择性抗体的方法,该方法包括以下步骤:从杂交瘤获得来自杂交瘤的单克隆抗体 或来自任何动物,植物或人类细胞系,用选自赖氨酸,丙氨酸,甘氨酸,缬氨酸,亮氨酸,异亮氨酸,脯氨酸的残基替代所述抗体的Fc区的每个His 310和His 435残基(Cabat编号) ,甲硫氨酸,色氨酸,苯丙氨酸,丝氨酸或苏氨酸,然后选择与包含ITIM基序(基于免疫受体酪氨酸的抑制基序)的抑制性FcR结合的抗体降低至少30%,优选至少50%,70 %,80%或者至少90%,相对于具有天然Fc区的相同抗体。 本发明还涉及衍生自本发明方法的抗体在制备特别用于治疗癌症和感染性病理学的药物中的用途。