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    Production of TNFR-Ig in a large-scale production cell culture
    4.
    发明授权
    Production of TNFR-Ig in a large-scale production cell culture 有权
    在大规模生产细胞培养物中产生TNFR-Ig

    公开(公告)号：EP1789571B1

    公开(公告)日：2017-04-26

    申请号：EP05792494.6

    申请日：2005-08-26

    申请人： Pfizer Ireland Pharmaceuticals

    发明人： DRAPEAU, Denis ,  LUAN, Yen-Tung ,  MERCER, James, R. ,  WANG, Wenge ,  LASKO, Daniel R.

    IPC分类号： C12P21/02 ,  C07K16/00 ,  C12N5/00 ,  C07K16/22 ,  C07K16/30

    CPC分类号： C12P21/02 ,  C07K16/18 ,  C07K16/22 ,  C07K16/2896 ,  C07K2317/24 ,  C12N5/0037 ,  C12N2500/22 ,  C12N2500/32 ,  C12N2500/38 ,  C12N2500/60 ,  C12N2510/02

    摘要： An improved system for large scale production of proteins and/or polypeptides in cell culture, particularly in media characterized by one or more of: i) a cumulative amino acid concentration greater than about 70 mM; ii) a molar cumulative glutamine to cumulative asparagine ratio of less than about 2; iii) a molar cumulative glutamine to cumulative total amino acid ratio of less than about 0.2; iv) a molar cumulative inorganic ion to cumulative total amino acid ratio between about 0.4 to 1; or v) a combined cumulative glutamine and cumulative asparagine concentration between about 16 and 36 mM, is provided. The use of such a system allows high levels of protein production and lessens accumulation of certain undesirable factors such as ammonium and/or lactate. Additionally, culture methods including a temperature shift, typically including a decrease in temperature when the culture has reached about 20-80% of it maximal cell density, are provided. Alternatively or additionally, the present invention provides methods such that, after reaching a peak, lactate and/or ammonium levels in the culture decrease.

    摘要翻译： 一种用于在细胞培养物中大规模生产蛋白质和/或多肽的改良系统，特别是在具有以下一种或多种特征的培养基中：i）累积氨基酸浓度大于约70mM; ii）小于约2的摩尔累积的谷氨酰胺与累积的天冬酰胺的比例; iii）小于约0.2的摩尔累积的谷氨酰胺与累积的总氨基酸比例; iv）摩尔累积无机离子与累积总氨基酸比率在约0.4至1之间; 或v）提供约16至36mM的组合累积谷氨酰胺和累积天冬酰胺浓度。 使用这样的系统允许高水平的蛋白质生产并减少某些不需要的因素如铵和/或乳酸盐的积累。 另外，提供了包括温度变化的培养方法，通常包括当培养物达到其最大细胞密度的约20-80％时的温度降低。 备选地或另外地，本发明提供了在达到峰值之后，培养物中的乳酸盐和/或铵水平降低的方法。

    Production of polypeptides
    7.
    发明公开
    Production of polypeptides 审中-公开
    多肽的生产

    公开(公告)号：EP2357250A3

    公开(公告)日：2014-07-02

    申请号：EP11156236.9

    申请日：2005-08-26

    申请人： Pfizer Ireland Pharmaceuticals

    发明人： Drapeau, Denis ,  Luan, Yen-Tung ,  Mercer, James, R. ,  Wang, Wenge ,  Lasko, Daniel, R.

    IPC分类号： C12P21/02 ,  C07K16/18 ,  C12N5/00 ,  C07K16/22 ,  C07K16/28

    CPC分类号： C12P21/02 ,  C07K16/18 ,  C07K16/22 ,  C07K16/2896 ,  C07K2317/24 ,  C12N5/0037 ,  C12N2500/22 ,  C12N2500/32 ,  C12N2500/38 ,  C12N2500/60 ,  C12N2510/02

    摘要： An improved system for large scale production of proteins and/or polypeptides in cell culture, particularly in media characterized by one or more of: i) a cumulative amino acid concentration greater than about 70 mM; ii) a molar cumulative glutamine to cumulative asparagine ratio of less than about 2; iii) a molar cumulative glutamine to cumulative total amino acid ratio of less than about 0.2; iv) a molar cumulative inorganic ion to cumulative total amino acid ratio between about 0.4 to 1; or v) a combined cumulative glutamine and cumulative asparagine concentration between about 16 and 36 mM, is provided. The use of such a system allows high levels of protein production and lessens accumulation of certain undesirable factors such as ammonium and/or lactate. Additionally, culture methods including a temperature shift, typically including a decrease in temperature when the culture has reached about 20-80% of it maximal cell density, are provided. Alternatively or additionally, the present invention provides methods such that, after reaching a peak, lactate and/or ammonium levels in the culture decrease.