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CN101511390A 制备胰岛素样生长因子-1与聚(乙二醇)的偶联物的方法 失效 - 权利终止

制备胰岛素样生长因子-1与聚(乙二醇)的偶联物的方法
摘要：
制备赖氨酸聚(乙二醇)化IGF－I或IGF－I变体的方法，所述变体包含的选自第27位、第65位和/或第68位赖氨酸的一个或两个氨基酸独立地被另一个极性氨基酸取代，其特征在于培养包含表达载体的原核宿主细胞，所述表达载体含有编码融合蛋白的核酸，所述融合蛋白包含的所述IGF－I或IGF－I变体的N末端与前肽的C末端连接，所述前肽C末端以氨基酸－Y－Pro终止，其中Y选自Pro、Pro－Ala、Pro－Gly、Pro－Thr、Ala－Pro、Gly－Pro、Thr－Pro、Arg－Pro或Pro－Arg－Pro；回收并聚(乙二醇)化所述融合蛋白；用IgA蛋白酶切割所述聚(乙二醇)化的融合蛋白；并回收所述聚(乙二醇)化的IGF－I或IGF－I变体。所述IGF－I或IGF－I变体用于治疗神经变性疾病，如阿尔茨默氏病。
摘要（英）：

Method for the production of a lysine-PEGylated IGF-I or IGF-I variant, said variant comprising one or two amino acid(s) selected from the group consisting of lysine 27, 65 and/or 68 substituted independently by another polar amino acid, characterized in cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding a fusion protein comprising said IGF-I orIGF-I variant N-terminally linked to the C-terminus of a propeptide, that said propeptide ends C-terminally with amino acids -Y-Pro, wherein Y is selected from the group consisting of Pro, Pro-Ala, Pro-Gly, Pro-Thr, Ala-Pro, Gly-Pro, Thr-Pro, Arg-Pro, or Pro-Arg-Pro, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering said PEGylated IGF-I or IGF-I variant. The PEGylated IGF-I or IGF-I variant is useful for the treatment of neurodegenerative disorders like Alzheimer's Disease.

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