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    • 7. 发明申请
    • PRODUCTION OF SECRETED THERAPEUTIC ANTIBODIES IN MICROALGAE
    • 微生物中分泌的治疗性抗体的生产
    • WO2013164095A1
    • 2013-11-07
    • PCT/EP2013/001302
    • 2013-05-02
    • ALGENICS
    • CARLIER, AudeMICHEL, RémyLEJEUNE, AlexandreCADORET, Jean-Paul
    • C12N15/82
    • C07K16/2887C07K16/2863C07K2317/13C07K2317/24C07K2317/732C07K2317/76C12N1/12C12N15/79C12N15/8258
    • The invention relates to a transformed microalga comprising a nucleic acid sequence operatively linked to a promoter, wherein said nucleic acid sequence encodes an amino acid sequence comprising (i) an heterologous signal peptide; and (ii) a therapeutic antibody, a functional fragment or a derivative thereof, said transformed microalga expressing the therapeutic antibody, functional fragment or derivative thereof secreted in the extracellular media and said microalga being selected among green algae except Volvocales, and among red algae, chromalveolates, and euglenids. Preferably, said therapeutic antibody, functional fragment or derivative thereof has an increased antibody-dependant cell-mediated cytotoxicity (ADCC) and a low fucose content. The present invention also relates to a method for producing said therapeutic antibody, a functional fragment or a derivative thereof, to the use of a transformed microalga according to the invention for the production and the secretion of a therapeutic antibody, a functional fragment or a derivative thereof in the extracellular medium, to a therapeutic antibody, a functional fragment or a derivative thereof produced and secreted in the extracellular medium of microalgae by a method according to the invention and to a pharmaceutical composition comprising said therapeutic antibody, functional fragment or derivative thereof.
    • 本发明涉及包含可操作地连接到启动子的核酸序列的转化微藻,其中所述核酸序列编码包含(i)异源信号肽的氨基酸序列; 和(ii)治疗性抗体,功能片段或其衍生物,所述转化微藻表达分泌在细胞外介质中的治疗性抗体,功能片段或衍生物,所述微藻选自除Volvocales之外的绿藻,以及红藻, 铬酸盐和黑醋酸盐。 优选地,所述治疗性抗体,其功能片段或衍生物具有增加的抗体依赖性细胞介导的细胞毒性(ADCC)和低岩藻糖含量。 本发明还涉及使用根据本发明的转化微藻用于产生和分泌治疗性抗体,功能片段或衍生物的所述治疗性抗体,功能片段或其衍生物的制备方法 通过本发明的方法产生和分泌在微藻细胞外培养基中的治疗性抗体,功能片段或衍生物,以及包含所述治疗性抗体,功能片段或衍生物的药物组合物。