公开(公告)号：US08496836B2

公开(公告)日：2013-07-30

申请号：US12916367

申请日：2010-10-29

申请人： Lars Aumann ,  Massimo Morbidelli

发明人： Lars Aumann ,  Massimo Morbidelli

IPC分类号： B01D15/08 ,  C02F1/28

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). 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). 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： 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（α，β，γ， 三角洲）。 在切换时间（t *）之后或之内，来自第一部分（α）的最后一列被移动到第二部分（β）的第一位置，第二部分（β）的最后一列被移动到第一部分 （γ）的第三部分（γ）的最后一列移动到第四部分（delta）的第一位置，并且第四部分（delta）的最后一列被移动成为第 第一部分（alpha）。

公开(公告)号：US07837881B2

公开(公告)日：2010-11-23

申请号：US11919540

申请日：2006-04-27

申请人： Lars Aumann ,  Massimo Morbidelli

发明人： Lars Aumann ,  Massimo Morbidelli

IPC分类号： B01D15/08 ,  C02F1/28

CPC分类号： G01N30/468 ,  B01D15/1828 ,  B01D15/1864

摘要： A process for continuous purification of a multi-component mixture by means of individual chromatographic columns though which the mixture is fed by means of at least one solvent. The multi-component mixture comprises at least light impurities, an intermediate product, and heavy impurities. The columns are grouped into at least four sections (α, β, γ, δ) and the fourth section contains three sub-sections (δr, δf, δg). The process operates, alternatingly, in a batch-mode position and in an interconnected-mode position. After or within a switch time, the columns are moved in their function in a counter direction to the general direction of flow of the solvent. The combination of batch chromatography with elements of simulated moving bed techniques, or rather, countercurrent-principles, allows for the separation of a true multi-component mixture, even if one of the products is only present in a small amount, comparatively.

摘要翻译： 通过单独的色谱柱连续纯化多组分混合物的方法，混合物通过至少一种溶剂进料。 多组分混合物至少包含轻质杂质，中间产物和重杂质。 列分成至少四个部分（α，＆bgr;γ，δ），第四部分包含三个子部分（δr，δf，δg）。 该过程以批处理模式位置和互连模式位置交替运行。 在开关时间之后或在开关时间之内，列以与溶剂的大致流动方向相反的方向在其功能中移动。 批量色谱与模拟移动床技术的元素的组合，或者逆流原理，允许分离真实的多组分混合物，即使其中一种产物仅存在于少量，相对而言。

公开(公告)号：US20090050567A1

公开(公告)日：2009-02-26

申请号：US11919540

申请日：2006-04-27

申请人： Lars Aumann ,  Massimo Morbidelli

发明人： Lars Aumann ,  Massimo Morbidelli

IPC分类号： B01D15/18

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 one inlet of solvent (β) 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).

公开(公告)号：US20140045725A1

公开(公告)日：2014-02-13

申请号：US14004021

申请日：2012-03-15

申请人： Thomas Muller-Spath ,  Lars Aumann ,  Guido Ströhlein ,  Michael Bavand

发明人： Thomas Muller-Spath ,  Lars Aumann ,  Guido Ströhlein ,  Michael Bavand

IPC分类号： C12N15/10

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 AB multicolumn 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： 该文献涉及纯化AA，AB，BB型二聚体抗体三元混合物的方法，其特征在于分离三种成分，特别是用于分离多特异性级分AB多列计数器 使用当前溶剂梯度纯化色谱法，每毫升固定相具有大于1mg抗体混合物的固定相负载。 它还涉及特别是鉴定特异性双特异性抗体系统的方法，其特别适用于这种纯化方法的应用。

公开(公告)号：US20110253631A1

公开(公告)日：2011-10-20

申请号：US13141937

申请日：2009-12-16

申请人： Thomas Muller-Spath ,  Lars Aumann

发明人： Thomas Muller-Spath ,  Lars Aumann

IPC分类号： B01D15/18

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 multicomponent 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 ((α1, . . . , αn-3, β1, . . . , βn-3, Y, δ), wherein each section ((α1, . . . , αn-3, βi, . . . , βn-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 (β1, . . . , βn-3), a strongly adsorbing component collection section (γ) and a feed section (δ) The functions of the sections ((α1, . . . , αn-3, βi, . . . , βn-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 ((α1, . . . , (an-3) are used to collect intermediate fractions (F2, . . . , Fn-3) as well as in at least continuous or quasi-continuous mode position, in which the outlets of at least two recycling section columns (β1, . . . , βn-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 ((α1, . . . , αn-3) is moved to the last position of the corresponding recycling section (β1, . . . , βn-3), the first column of the most upstream recycling section (β1) is moved to the first position of the strongly adsorbing component collection section (γ) and the first columns of the further recycling sections (β2, . . . , βn-3) are moved to the last position of the next upstream collection section ((α1, . . . , αn-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 ((αn-3).

公开(公告)号：US09018137B2

公开(公告)日：2015-04-28

申请号：US14004021

申请日：2012-03-15

申请人： Thomas Müller-Späth ,  Lars Aumann ,  Guido Ströhlein ,  Michael Bavand

发明人： Thomas Müller-Späth ,  Lars Aumann ,  Guido Ströhlein ,  Michael Bavand

IPC分类号： C40B30/10 ,  C12N15/10 ,  B01D15/16 ,  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, characterized in that for the separation of the three components and in particular for the isolation of the multi-specific fraction AB multicolumn counter current solvent gradient purification chromatography with a stationary phase load of more than 1 mg antibody mixture per milliliter 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： 该文献涉及纯化AA，AB，BB型二聚体抗体三元混合物的方法，其特征在于分离三种成分，特别是用于分离多特异性级分AB多列计数器 使用当前溶剂梯度纯化色谱法，每毫升固定相具有大于1mg抗体混合物的固定相负载。 它还涉及特别是鉴定特异性双特异性抗体系统的方法，其特别适用于这种纯化方法的应用。

公开(公告)号：US08440086B2

公开(公告)日：2013-05-14

申请号：US13141937

申请日：2009-12-16

申请人： Thomas Müller-Späth ,  Lars Aumann

发明人： Thomas Müller-Späth ,  Lars Aumann

IPC分类号： B01D15/08

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 by means of at least four individual chromatographic columns through which the mixture is fed by means of at least one solvent, is given, wherein the multi-component mixture is to be separated into an integer number n of fractions, wherein n is at least 5.

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的方法，混合物通过至少一种溶剂通过其进料，其中多组分混合物应为 分成n个分数的整数，其中n至少为5。