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    • 10. 发明申请
    • PRODUCTION OF HOMOTRIMERIC FUSION PROTEINS
    • 共培养融合蛋白的生产
    • US20090192291A1
    • 2009-07-30
    • US12353713
    • 2009-01-14
    • James W. WestCameron S. BrandtStephen R. Jaspers
    • James W. WestCameron S. BrandtStephen R. Jaspers
    • C07K14/00
    • C07K14/47C07K14/705C07K14/70575C07K14/70578C07K14/78C07K2319/00C07K2319/03C12N15/62
    • The present invention provides method for producing trimeric tumor necrosis factor receptors that are potent inhibitors of their cognate ligands. More particularly, the present invention provides polypeptides that comprise: (1) an extracellular domain of the transmembrane activator and CAML (calcium-signal modulating cyclophilin ligand) interactor (TACI), and (2) a trimerizing polypeptide. Suitable TACI extracellular domains include: (1) amino acid residues 30 to 110 of SEQ ID NO:4, (2) amino acid residues 1 to 110 of SEQ ID NO:4, (3) amino acid residues 30 to 154 of SEQ ID NO:4, and (4) amino acid residues 1 to 154 of SEQ ID NO:4. Illustrative trimerizing polypeptides include a trimerizing fragment of Heat Shock Binding Protein-1. The present invention further provides homotrimeric complexes of fusion proteins comprising a TACI extracellular domain and a trimerizing polypeptide.
    • 本发明提供了产生三聚体肿瘤坏死因子受体的方法,所述三聚体肿瘤坏死因子受体是其相关配体的有效抑制剂。 更具体地,本发明提供多肽,其包含:(1)跨膜激活剂的胞外结构域和CAML(钙信号调节亲环蛋白配体)相互作用体(TACI),和(2)三聚体多肽。 合适的TACI细胞外结构域包括:(1)SEQ ID NO:4的氨基酸残基30至110,(2)SEQ ID NO:4的氨基酸残基1至110,(3)SEQ ID NO:4的氨基酸残基30至154 NO.4和(4)SEQ ID NO:4的氨基酸残基1至154。 示例性的三聚化多肽包括热休克结合蛋白-1的三聚体片段。 本发明还提供了包含TACI胞外域和三聚多肽的融合蛋白的同源三聚体。