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1. 发明申请

WO2006116886A1 METHOD AND DEVICE FOR CHROMATOGRAPHIC PURIFICATION 审中-公开
标题翻译：用于色谱纯化的方法和装置
公开(公告)号：WO2006116886A1
公开(公告)日：2006-11-09
申请号：PCT/CH2006/000232
申请日：2006-04-27
申请人： EIDGENÖSSISCHE TECHNISCHE HOCHSCHULE ZÜRICH , AUMANN, Lars , MORBIDELLI, Massimo
发明人： AUMANN, Lars , MORBIDELLI, Massimo
IPC分类号： B01D15/18 , G01N30/46
CPC分类号： G01N30/468 , B01D15/1828 , B01D15/1864
摘要： A process for continuous or quasi-continuous purification of a multi-component mixture (F) by means of individual chromatographic columns through which the mixture is fed by means of at least one solvent (s), is proposed. The multi-component mixture (F) at least comprises light impurities (A), an intermediate product (B) to be purified and heavy impurities (C), and the columns are grouped into at least four sections (α,β,γ,δ), in which the first section (α) is provided with at least one inlet of solvent (s) and at least one outlet for purified intermediate product (B), such that it washes the purified intermediate product (B) out of the system, but keeps the heavy impurities (C) inside the section (α), the second section (β) is provided with at least one inlet of solvent (s) and at least one outlet connected to an inlet of the fourth section (δ), such that it washes the intermediate product (B), which is contaminated with heavy impurities (C) into the fourth section (δ) through said outlet, but keeps the pure heavy impurities (C) inside the section (β), the third section (γ) is provided with at least one inlet of solvent (s) and an outlet for heavy impurities (C), such that it washes out the heavy impurities (C) through said outlet and cleans the chromatographic column(s), the fourth section (δ) is provided with at least one inlet to receive output of the outlet of the second section (β) as well as at least one inlet for feeding in the multi-component mixture (F) and at least one outlet for light impurities (A), such that it washes the light impurities (A) out of the system, but keeps the intermediate product (B) inside the section (δ), wherein after or within a switch time (t*) the last column from the first section (α) is moved to the first position of the second section (β), the last column of the second section (β) is moved to the first position of the third section (γ), the last column of the third section (γ) is moved to the first position of the fourth section (δ) and the last column of the fourth section (δ) is moved to become the first column of the first section (α).
摘要翻译：提出了通过单独的色谱柱连续或准连续纯化多组分混合物（F）的方法，混合物通过其通过至少一种溶剂进料。多组分混合物（F）至少包含轻质杂质（A），待纯化的中间产物（B）和重杂质（C），并且将列分成至少四个部分（a，β， d），其中第一部分（a）设置有至少一个溶剂入口和至少一个用于纯化的中间产物（B）的出口，使得其将纯化的中间产物（B）从系统，但是在部分（a）内保持重的杂质（C），第二部分（ß）设置有至少一个溶剂入口和连接到第四部分的入口的至少一个出口（d ），使得通过所述出口将被重杂质（C）污染的中间产物（B）洗涤到第四部分（d）中，但将部分（ß）内的纯重杂质（C）保持在第三部分（？）设置有至少一个溶剂入口和用于重质杂质（C）的出口，使得它将重的im 纯度（C）通过所述出口清洗色谱柱，第四部分（d）设置有至少一个入口以接收第二部分（ß）的出口的输出以及至少一个入口在多组分混合物（F）和至少一个轻杂质（A）的出口中进料，使得轻质杂质（A）从系统中洗出，但将中间产物（B）保持在部分（d ），其中在切换时间（t *）之后或之内，来自第一部分（a）的最后一列移动到第二部分（ß）的第一位置，第二部分（ß）的最后一列被移动到第三部分（？）的第一位置，第三部分（→）的最后一列被移动到第四部分（d）的第一位置，并且第四部分（d）的最后一列被移动成为第一部分（a）的第一列。

2. 发明申请

WO2013083482A1 CHROMATOGRAPHIC METHOD FOR THE SEPARATION OF FATTY ACID MIXTURES 审中-公开
标题翻译：用于分离脂肪酸混合物的色谱方法
公开(公告)号：WO2013083482A1
公开(公告)日：2013-06-13
申请号：PCT/EP2012/074047
申请日：2012-11-30
申请人： CHROMACON AG , MÜLLER-SPÄTH, Thomas , AUMANN, Lars , STRÖHLEIN, Guido , BAVAND, Michael
发明人： MÜLLER-SPÄTH, Thomas , AUMANN, Lars , STRÖHLEIN, Guido , BAVAND, Michael
IPC分类号： G01N30/42 , G01N30/44 , G01N30/46 , B01D15/18 , C11B7/00 , G01N30/80
CPC分类号： G01N30/42 , B01D15/166 , B01D15/1814 , B01D15/1864 , C11B7/00 , G01N30/44 , G01N30/468 , G01N30/80
摘要： The invention relates to a process for purification of a fatty acid containing, multi-component mixture (F) by means of at least two individual chromatographic columns through which the mixture (F) is fed by means of at least one solvent (s). According to the invention, the multi- component mixture (F) at least comprises weakly adsorbing impurities (W), a first target product (P1)to be purified, an intermediate impurity (S1), a second target product (P2) to be purified, and strongly adsorbing impurities (S2), the first target product (P1) is first fatty acid, e.g. eicosapentaenoic acid (EPA), or a derivative thereof, and the second target product (P2) is a second fatty acid different from the first target product (P1), or a derivative of said second fatty acid. For the purification a multicolumn countercurrent purification chromatography is used, and in this multicolumn countercurrent purification chromatography at least one outlet thereof is further separated by using outlet fractionation.
摘要翻译：本发明涉及通过至少两个单独的色谱柱纯化含有脂肪酸的多组分混合物（F）的方法，混合物（F）通过至少一种溶剂通过至少一种溶剂进料。根据本发明，多组分混合物（F）至少包含弱吸附杂质（W），待纯化的第一目标产物（P1），中间杂质（S1），第二目标产物（P2）纯化和强吸附杂质（S2），第一目标产物（P1）是第一种脂肪酸，例如，二十碳五烯酸（EPA）或其衍生物，第二目标产物（P2）是与第一目标产物（P1）不同的第二种脂肪酸或所述第二种脂肪酸的衍生物。对于纯化，使用多列逆流纯化色谱法，并且在该多列逆流纯化色谱中，通过使用出口分馏进一步分离其至少一个出口。

3. 发明申请

WO2012123520A1 METHOD FOR IDENTIFICATION AND PURIFICATION OF MULTI-SPECIFIC POLYPEPTIDES 审中-公开
标题翻译：多特异性多肽的鉴定和纯化方法
公开(公告)号：WO2012123520A1
公开(公告)日：2012-09-20
申请号：PCT/EP2012/054507
申请日：2012-03-15
申请人： CHROMACON AG , MÜLLER-SPÄTH, Thomas , AUMANN, Lars , STRÖHLEIN, Guido , BAVAND, Michael
发明人： MÜLLER-SPÄTH, Thomas , AUMANN, Lars , STRÖHLEIN, Guido , BAVAND, Michael
IPC分类号： B01D15/18 , G01N30/46
CPC分类号： C12N15/1082 , B01D15/166 , B01D15/1807 , B01D15/1864 , C07K1/18 , C07K1/22 , C07K1/36 , C07K2317/31 , G01N30/468
摘要： The document pertains to a method for the purification of a ternary mixture of dimeric antibodies of the type AA, AB, BB, characterised in that for the separation of the three components and in particular for the isolation of the multi-specific fraction ABmulticolumn counter current solvent gradient purification chromatography with a stationary phase load of more than 1 mg antibody mixture per millilitre stationary phase is used.It furthermore relates to a method for the identification of in particular bispecific antibody systems, which are particularly suitable for the application of such a purification method.
摘要翻译：该文献涉及一种用于纯化AA，AB，BB型二聚体抗体三元混合物的方法，其特征在于用于分离三种成分，特别是用于分离多特异性级分的多元柱反向电流使用具有大于1mg抗体混合物/毫升固定相的固定相负载的溶剂梯度纯化色谱法。此外，还涉及用于特异性鉴定特异性双特异性抗体系统的方法，其特别适用于施用这种纯化方法。

4. 发明申请

WO2010079060A1 MULTIFRACTION PURIFICATION PROCESSES AND DEVICES FOR SUCH PROCESSES 审中-公开
标题翻译：多处理纯化方法和这种方法的装置
公开(公告)号：WO2010079060A1
公开(公告)日：2010-07-15
申请号：PCT/EP2009/067277
申请日：2009-12-16
申请人： CHROMACON AG , MÜLLER-SPÄTH, Thomas , AUMANN, Lars
发明人： MÜLLER-SPÄTH, Thomas , AUMANN, Lars
IPC分类号： B01D15/18 , G01N30/46
CPC分类号： B01D15/1821 , B01D15/166 , B01D15/1864
摘要： A process for continuous or quasi-continuous purification of a multi-component mixture (Fd) by means of at least four individual chromatographic columns through which the mixture is fed by means of at least one solvent (s), is given, wherein the multi-component mixture (Fd) is to be separated into an integer number n of fractions (Fi), wherein n is at least 5. The columns are grouped into at least six sections ((α 1 ,..., α n-3 , β 1 ,..., β n-3 , Y, δ), wherein each section ((α 1 ,..., α n-3 , βi,...,β n-3 , γ, δ) comprises at least one column with the proviso that the function of sections can be fulfilled sequentially and can be realized by single columns. There are least two collection, at least two recycling sections (β 1 ,..., β n-3 ), a strongly adsorbing component collection section (γ) and a feed section (δ) The functions of the sections ((α 1 ,..., α n-3 , βi,...,β n-3 , γ, δ) are either fulfilled synchronously or sequentially, and columns are run in at least one batch mode position in which the outlets of one or at least two collection section columns ((α 1 ,..., (α n-3 ) are used to collect intermediate fractions (F 2 ,..., F n-3 ) as well as in at least continuous or quasi-continuous mode position, in which the outlets of at least two recycling section columns (β 1 ,...,β n-3 ) are fluidly connected with the corresponding inlets of subsequent downstream recycling sections or, in the absence of a subsequent downstream recycling section, into said feed section. In said batch mode and said continuous or quasi-continuous mode are either realized synchronously or sequentially, wherein after or within a switch time (t*) the columns are moved in their positions in a counter direction to the general direction of flow of the solvent, wherein after or within a switch time (t*) the first column from each collection section ((α 1 ,..., α n-3 ) is moved to the last position of the corresponding recycling section (β 1 ,...,β n-3 ), the first column of the most upstream recycling section (β 1 ) is moved to the first position of the strongly adsorbing component collection section (γ) and the first columns of the further recycling sections (β 2 ,...,β n-3 ) are moved to the last position of the next upstream collection section ((α 1 ,..., α n-4 ), the first column of the strongly adsorbing component collection section (γ) is moved to the last position of the feed section (δ) and the first column of the feed section (δ) is moved to become the last column of the most downstream collection section ((α n-3 ).
摘要翻译：给出了通过至少四个单独的色谱柱连续或准连续纯化多组分混合物（Fd）的方法，混合物通过至少一种溶剂通过至少一种溶剂进料，其中多 - 组分混合物（Fd）被分成整数n个级分（Fi），其中n至少为5.将列分成至少六个部分（（a1，...，an-3，ß1 ，...，ßn-3，Y，d），其中每个部分（（a1，...，an-3，ßi，...，ßn-3，ψ，d）包括至少一个列，条件是可以顺序完成部分的功能，并可以通过单柱实现，至少有两个集合，至少两个回收部分（ß1，...，ßn-3），强吸附组件收集部分（？）和馈送部分（d）部分（（a1，...，an-3，ßi，...，ßn-3，ψ，d）的功能可以同步或顺序完成，至少一个批模式位置使用一个或至少两个收集段列（（a1，...，（a-3））的出口来收集中间分数（F2，...，Fn-3）以及至少连续或准连续模式位置，其中至少两个回收段塔（ß1，...，ßn-3）的出口与随后的下游再循环部分的相应入口流体连接，或者在后续的下游回收段，进入所述进料部分。在所述分批模式中，所述连续模式或准连续模式可以同时或顺序实现，其中在开关时间（t *）之后或之内，所述塔在与溶剂的大致流动方向相反方向的位置上移动，其中在切换时间（t *）之后或之内，来自每个收集部分（（a1，...，an-3））的第一列被移动到相应的再循环部分（ß1，...，ßn）的最后位置 -3），最上游再循环部分（ß1）的第一列移动到强吸附部件收集部分（α）的第一位置，并且再循环部分（ß2，...，ßn- 3）移动到下一个上游收集部（（a1，...，an-4）的最后位置时，强吸附部收集部的第一列移动到供给部的最后位置（d）并且进给部分（d）的第一列被移动以成为最下面的最后一列流收集部分（（a-3））。

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