System for rapid continuous manufacturing of monoclonal antibodies

    公开(公告)号:US20170204446A1

    公开(公告)日:2017-07-20

    申请号:US14996226

    申请日:2016-01-15

    摘要: Described herein is a rapid continuous biomanufacturing platform process that combines a perfusion mammalian cell culture with a synchronized purification of the antibodies produced by the cell culture without the use of intermediate media holding tanks or other large retention devices. This method described herein includes continuous cell culture of mammalian cells expressing the biological of interest and comprising a cell retention device wherein the perfusion of fresh media into the reactor and hence the harvest rate of antibody containing spent media from the reactor has a rate of 1 vessel volume per day (vvd) or less obtained by glucose control with a cell density of between 40 million cell/ml and 60 million cell/nil. Immediate recovery and purification of the antibody is obtained by synchronizing the rate of perfusion with the antibody capture and elution step cycle in a column that contains affinity resin that is between 0.01 and 0.001 times the volume of the bioreactor. The perfusion rate and capture rate were perfectly synchronized by extensive method and media development resulting in equal rates and eliminating the need for holding tanks and cell bleeding. The result is an order of magnitude faster antibody production as compared to conventional fed-batch mode.

    Chromatography Membranes Stable Under Caustic Conditions
    2.
    发明申请
    Chromatography Membranes Stable Under Caustic Conditions 审中-公开
    色谱膜在苛性碱条件下稳定

    公开(公告)号:US20140273158A1

    公开(公告)日:2014-09-18

    申请号:US14200615

    申请日:2014-03-07

    发明人: Amro Ragheb

    IPC分类号: B01J20/291 B01D15/42

    摘要: Disclosed are composite materials and methods of using them for chromatography. The composite materials retain their performance characteristics, such as binding capacity, flux, or percent recovery, under caustic conditions (e.g., 1 M NaOH for 24 h). In certain embodiments, the composite materials or membranes comprise a support member, comprising a plurality of pores extending through the support member; and a cross-linked gel. Importantly, the cross-linker and the monomer do not contain backbone ester linkages. The composite materials may be used in the separation or purification of a biological molecule or biological ion.

    摘要翻译: 公开了将其用于色谱法的复合材料和方法。 在苛性碱条件下(例如1M NaOH 24小时),复合材料保持其性能特征,例如结合能力,通量或回收百分比。 在某些实施例中,复合材料或膜包括支撑构件,其包括延伸穿过支撑构件的多个孔; 和交联凝胶。 重要的是,交联剂和单体不含骨架酯键。 复合材料可用于分离或纯化生物分子或生物离子。

    PURIFICATION OF ORGANIC COMPOUNDS BY SURFACTANT MEDIATED PREPARATIVE HPLC
    4.
    发明申请
    PURIFICATION OF ORGANIC COMPOUNDS BY SURFACTANT MEDIATED PREPARATIVE HPLC 审中-公开
    通过表面活性剂介导的制备型HPLC纯化有机化合物

    公开(公告)号:US20160237112A1

    公开(公告)日:2016-08-18

    申请号:US15022983

    申请日:2014-09-18

    IPC分类号: C07K1/20 B01D15/32 C07K7/23

    摘要: A sample is provided that can be purified by preparative reversed phase high performance liquid chromatography (Prep-RP-HPLC) in a single run in spite of recent advances in the production of reversed phase derivatized silica stationary supports: (1) The traditional approach is to use a bigger column (greater amount of stationary phase); and (2) Use displacement chromatography which (while labor intensive to develop) uses the stationary phase more effectively. This disclosure describes a unique Prep-RP-HPLC technique that uses a C-18/C-8 derivatized silica coated with a surfactant such as Triton X-100 to result in 7 to 10 fold increase in sample loading (of the crude mixture of organic compounds including synthetic crude peptides) in contrast to the conventional Prep-RP-HPLC technique. This increase in sample loading capacity and output is due to the additional surrogate stationary phase characteristic of the C-18/C8 adsorbed (bound) surfactant.

    摘要翻译: 提供的样品可以通过制备型反相高效液相色谱(Prep-RP-HPLC)在单次运行中纯化,尽管反相衍生的二氧化硅固定支持物的生产最近有进展:(1)传统方法是 使用较大的柱(更大量的固定相); 和(2)使用置换色谱法(尽管劳动密集型开发)更有效地使用固定相。 本公开内容描述了独特的Prep-RP-HPLC技术,其使用涂覆有表面活性剂如Triton X-100的C-18 / C-8衍生化二氧化硅,导致样品负载量增加7至10倍 有机化合物,包括合成粗肽)与传统的Prep-RP-HPLC技术相反。 样品负载能力和产量的增加是由于C-18 / C8吸附(结合)表面活性剂的附加替代固定相特征。

    Purification Method of Azacyclohexapeptide or Its Salt
    7.
    发明申请
    Purification Method of Azacyclohexapeptide or Its Salt 有权
    氮杂六肽或其盐的纯化方法

    公开(公告)号:US20130030150A1

    公开(公告)日:2013-01-31

    申请号:US13640836

    申请日:2011-04-15

    IPC分类号: C07K1/14 C07K7/64

    摘要: A purification method of the compound represented by formula 1 is provided, which includes the following steps: (1) loading crude compound 1 on macroporous adsorbent resin, (2) washing the macroporous adsorbent resin with an aqueous solution, an organic solvent or a mixture solution of organic solvent and water, (3) eluting with an aqueous solution, an organic solvent or a mixture solution of organic solvent and water. The purified compound represented by formula 1 is obtained.

    摘要翻译: 提供由式1表示的化合物的纯化方法,其包括以下步骤:(1)在大孔吸附树脂上加载粗化合物1,(2)用水溶液,有机溶剂或混合物洗涤大孔吸附树脂 有机溶剂和水的溶液,(3)用水溶液,有机溶剂或有机溶剂和水的混合溶液洗脱。 得到由式1表示的纯化化合物。

    METHOD FOR SEPARATING PERFLUORO(POLY)ETHER-GROUP-CONTAINING ALCOHOL COMPOUNDS

    公开(公告)号:US20190185621A1

    公开(公告)日:2019-06-20

    申请号:US16327611

    申请日:2017-08-24

    摘要: A method for chromatographically separating a mixture containing a perfluoro(poly)ether group-containing monoalcohol compound represented by the following formula (2) and a perfluoro(poly)ether group-containing dialcohol compound represented by the following formula (3): A-Pf-Z   (2) Z-Pf-Z   (3) wherein Pf represents a divalent perfluoropolyether group and A and Z are as defined herein, the method including: adsorbing the mixture onto a stationary phase, and eluting the perfluoro(poly)ether group-containing monoalcohol compound represented by formula (2) by one mobile phase selected from hydrofluorocarbons, hydrochlorofluorocarbons, hydrofluoroethers, fluorine-containing ester solvents, and fluorine-containing aromatic solvents to separate the perfluoro(poly)ether group-containing monoalcohol compound represented by formula (2) from the perfluoro(poly)ether group-containing monoalcohol compound represented by formula (3).