公开(公告)号：EP3006462A1

公开(公告)日：2016-04-13

申请号：EP15193455.1

申请日：2003-12-19

申请人： CSL Behring LLC

发明人： Kee, Scott M. ,  Cook, Paul I. ,  Smith, James R. ,  Kling, Robert ,  Fowler, Scott A ,  Weber, David

IPC分类号： C07K14/81

CPC分类号： A61K38/57 ,  A61K9/19 ,  B01D15/327 ,  B01D15/363 ,  C07K14/8125 ,  G01N30/461

摘要： A streamlined method for purifying alpha-1-antitrypsin (AAT) from an AAT-containing protein mixture, such as a Cohn fraction IV precipitate, is provided. In the method of the invention, contaminating proteins are destabilized by cleavage of disulfide bonds with a reducing reagent, such as a dithiol, which does not affect AAT. The destabilized proteins are then preferentially adsorbed on a solid protein-adsorbing material, without the addition of a salt as a precipitant. Separation of the solid adsorbent from the solution leaves a purified AAT solution that is directly suitable for chromatographic purification, without the need for extensive desalting as in prior art processes. A process incorporating this method, which provides pharmaceutical grade AAT in high yield on a commercial scale, is also described.

摘要翻译： 提供了从含有AAT的蛋白质混合物如Cohn馏分IV沉淀物中纯化α-1-抗胰蛋白酶（AAT）的流线型方法。 在本发明的方法中，通过用不影响AAT的还原剂如二硫醇裂解二硫键，污染蛋白质不稳定。 然后将不稳定的蛋白质优先吸附在固体蛋白质吸附材料上，而不加入作为沉淀剂的盐。 固体吸附剂与溶液的分离留下直接适用于色谱纯化的纯化的AAT溶液，而不需像现有技术方法那样进行广泛的脱盐。 还描述了一种以商业规模提供高产量的药物级AAT的方法。

公开(公告)号：EP3006462B1

公开(公告)日：2019-04-10

申请号：EP15193455.1

申请日：2003-12-19

申请人： CSL Behring LLC

发明人： Kee, Scott M. ,  Cook, Paul I. ,  Smith, James R. ,  Kling, Robert ,  Fowler, Scott A ,  Weber, David

IPC分类号： C07K14/81

公开(公告)号：EP2295126B1

公开(公告)日：2015-12-16

申请号：EP10182334.2

申请日：2003-12-19

申请人： CSL Behring LLC

发明人： Cook, Paul I. ,  Fowler, Scott A ,  Kee, Scott M. ,  Smith, James R. ,  Weber, David ,  Kling, Robert

IPC分类号： C07K14/81

CPC分类号： A61K38/57 ,  A61K9/19 ,  B01D15/327 ,  B01D15/363 ,  C07K14/8125 ,  G01N30/461

摘要： A streamlined method for purifying alpha-1-antitrypsin (AAT) from an AAT-containing protein mixture, such as a Cohn fraction IV precipitate, is provided. In the method of the invention, contaminating proteins are destabilized by cleavage of disulfide bonds with a reducing reagent, such as a dithiol, which does not affect AAT. The destabilized proteins are then preferentially adsorbed on a solid protein-adsorbing material, without the addition of a salt as a precipitant. Separation of the solid adsorbent from the solution leaves a purified AAT solution that is directly suitable for chromatographic purification, without the need for extensive desalting as in prior art processes. A process incorporating this method, which provides pharmaceutical grade AAT in high yield on a commercial scale, is also described.

摘要翻译： 提供了从含有AAT的蛋白质混合物如Cohn馏分IV沉淀物中纯化α-1-抗胰蛋白酶（AAT）的流线型方法。 在本发明的方法中，通过用不影响AAT的还原剂如二硫醇裂解二硫键，污染蛋白质不稳定。 然后将不稳定的蛋白质优先吸附在固体蛋白质吸附材料上，而不加入作为沉淀剂的盐。 固体吸附剂与溶液的分离留下直接适用于色谱纯化的纯化的AAT溶液，而不需像现有技术方法那样进行广泛的脱盐。 还描述了一种以商业规模提供高产量的药物级AAT的方法。

公开(公告)号：EP2295126A1

公开(公告)日：2011-03-16

申请号：EP10182334.2

申请日：2003-12-19

申请人： CSL Behring LLC

发明人： Cook, Paul I. ,  Fowler, Scott A ,  Kee, Scott M. ,  Smith, James R. ,  Weber, David ,  Kling, Robert

IPC分类号： B01D15/08 ,  C07K14/81

CPC分类号： A61K38/57 ,  A61K9/19 ,  B01D15/327 ,  B01D15/363 ,  C07K14/8125 ,  G01N30/461

摘要： A streamlined method for purifying alpha-1-antitrypsin (AAT) from an AAT-containing protein mixture, such as a Cohn fraction IV precipitate, is provided. In the method of the invention, contaminating proteins are destabilized by cleavage of disulfide bonds with a reducing reagent, such as a dithiol, which does not affect AAT. The destabilized proteins are then preferentially adsorbed on a solid protein-adsorbing material, without the addition of a salt as a precipitant. Separation of the solid adsorbent from the solution leaves a purified AAT solution that is directly suitable for chromatographic purification, without the need for extensive desalting as in prior art processes. A process incorporating this method, which provides pharmaceutical grade AAT in high yield on a commercial scale, is also described.