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    • 9. 发明申请
    • ANTIBODIES DIRECTED AGAINST CD127
    • 针对CD127的抗体
    • WO2015189302A1
    • 2015-12-17
    • PCT/EP2015/062993
    • 2015-06-10
    • EFFIMUNE
    • POIRIER, NicolasMARY, CarolineVANHOVE, Bernard
    • C07K16/28A61K39/00
    • C07K16/2866A61K2039/505C07K2317/24C07K2317/34C07K2317/565C07K2317/732C07K2317/76C07K2317/77C07K2317/92C07K2317/94G01N33/5041G01N33/6854G01N2333/5418G01N2333/70546G01N2333/7155G01N2500/00
    • The invention relates to antibodies directed against CD127, the alpha chain of the interleukin 7 (IL-7) receptor IL-7R), and which have antagonist properties for IL-7-IL-7R interaction, may present cytotoxic activity against CD127 positive cells but do not increase the maturation of dendritic cells (DCs) induced by TSLP, a cytokine also using CD127 as part of its receptor. Alternatively, or in addition, these antibodies do not induce the internalization of CD127 and/or inhibit the IL7-induced internalization of CD127. According to another aspect of the invention antibodies are provided which recognize a human CD127 epitope comprising sequences from the 2b site of CD127, in particular the epitope comprising comprises the human CD127 sequences of domain D1 and of the 2b site of CD127, in particular the epitope comprises at least one sequence from D1 comprising SEQ ID No: 115 (in particular comprising SEQ ID No: 10) and/or SEQ ID No: 111 and / or a sequence from the 2b site comprising the sequence of SEQ ID No: 116 and optionally also comprises SEQ ID No: 117 (in particular comprises SEQ ID No: 111).The antibodies of the invention are suitable for use inorder to remedy to a condition diagnosed in a human patient which results from pathogenesis related to lymphopoiesis, when IL-7 signalling pathways provide contribution to said pathogenesis, especially when an increase in the maturation, more precisely the upregulation of costimulatory molecules, of dendritic cells is undesirable.
    • 本发明涉及针对CD127,白细胞介素7(IL-7)受体IL-7R的α链)并且具有IL-7-IL-7R相互作用的拮抗剂性质的抗体可能对CD127阳性细胞具有细胞毒活性 但不增加由TSLP诱导的树突细胞(DC)的成熟,细胞因子也使用CD127作为其受体的一部分。 或者或另外,这些抗体不诱导CD127的内化和/或抑制IL7诱导的CD127内化。 根据本发明的另一方面,提供了抗体,其识别包含来自CD127的2b位点的序列的人CD127表位,特别是包含结构域D1和CD127的2b位点的人CD127序列,特别是表位 包含至少一个包含SEQ ID No:115(特别是包含SEQ ID No:10)和/或SEQ ID No:111的D1的序列和/或来自包含SEQ ID No:116的序列的2b位点的序列和 任选地还包含SEQ ID No:117(特别是包含SEQ ID No:111)。本发明的抗体适合用于补救由淋巴细胞生成相关的发病机制导致的人类患者诊断的病症,当IL- 7信号途径对所述发病机制提供了贡献,特别是当树突状细胞的成熟增加,更确切地说共刺激分子的上调是不期望的。