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1. 发明公开

EP2748181A1 METHOD FOR PURIFICATION OF CLEAVED PRO-INSULIN 有权转让
标题翻译：程序用于清洗分流胰岛素原
公开(公告)号：EP2748181A1
公开(公告)日：2014-07-02
申请号：EP12837180.4
申请日：2012-09-28
申请人： GE Healthcare Bio-Sciences AB
发明人： BREKKAN, Eggert , ERIKSSON, Kjell , JOHANSSON, Bo-Lennart , SHANAGAR, Jamil
IPC分类号： C07K1/18 , A61K38/28 , B01D15/08 , B01D15/26 , B01D15/36 , B01J20/285 , B01J20/286 , B01J20/32 , C07K14/06 , C07K14/62
CPC分类号： C07K14/62 , B01D15/361 , B01D15/362 , B01J20/286 , B01J20/288 , B01J20/321 , B01J20/3212 , B01J20/3293 , B01J39/26
摘要： The present invention is within the field of biomolecule purification. More closely the invention relates to chromatographic purification of insulin using a specific kind of shell beads having an inner core and an outer functionalized layer. The method enables purification at high flow rates and high purity, over 90%.

2. 发明授权

EP1697416B1 PURIFICATION OF IMMUNOGLOBULINS 有权
标题翻译：免疫球蛋白纯化
公开(公告)号：EP1697416B1
公开(公告)日：2008-04-09
申请号：EP04809180.5
申请日：2004-12-21
申请人： GE Healthcare Bio-Sciences AB
发明人： GLAD, Gunnar , JOHANSSON, Bo-Lennart , MALOISEL, Jean-Luc , NORRMAN, Nils
IPC分类号： C07K16/06
CPC分类号： B01J20/262 , B01J20/267 , B01J20/28019 , B01J20/28023 , B01J20/28033 , B01J20/28042 , B01J20/286 , B01J20/289 , B01J20/3092 , B01J20/3208 , B01J20/3212 , B01J20/3219 , B01J20/3246 , B01J20/3248 , B01J20/3251 , B01J20/3255 , B01J20/3272 , B01J20/3285 , B01J2220/54 , B01J2220/58 , C07K16/065 , Y10T428/249963
摘要： The present invention relates to a separation matrix comprised of a porous support to which ligands have been immobilised, wherein said ligands comprise at least one aliphatic sulphonamide. The nitrogen of the sulphonamide may be a secondary or tertiary amine. The invention also relates to a chromatography column that contains the described separation matrix, as well as to a method of isolating immunoglobulin-like compounds by adsorption to a separation matrix that comprises aliphatic sulphonamide ligands.

3. 发明公开

EP1718386A1 A PROCESS FOR THE PURIFICATION OF ANTIBODIES 审中-公开
标题翻译：清理方法抗体的
公开(公告)号：EP1718386A1
公开(公告)日：2006-11-08
申请号：EP05722175.6
申请日：2005-02-25
申请人： GE Healthcare Bio-Sciences AB
发明人： GRÖNBERG, Anna , JOHANSSON, Bo-Lennart , JOHANSSON, Hans J. , MALOISEL, Jean-Luc , THEVENIN, Nicolas
IPC分类号： B01D15/08 , C07K16/00
CPC分类号： B01J20/3253 , B01D15/3847 , B01J20/3242 , B01J20/3246 , B01J20/3255 , B01J20/3285
摘要： The present invention relates to a process for the purification of antibodies from one or more impurities in a liquid, which process comprises contacting said liquid with a first chromatography resin comprised of a support to which multi-modal ligands have been immobilised to adsorb the antibodies to the resin, wherein each multi-modal ligand comprises at least one cation-exchanging group and at least one aromatic or heteroaromatic ring system; adding an eluent to release the antibodies from the resin; and contacting the eluate so obtained with a second chromatography resin. In one embodiment, the ring-forming atoms of the aromatic or heteroaromatic entity are selected from the group con-sisting of C, S and O, and the cation exchanging group is a weak cation exchanger.

4. 发明授权

EP1345694B1 A METHOD FOR THE MANUFACTURE OF COMPOSITIONS CONTAINING LOW CONCENTRATIONS OF SALTS 有权
标题翻译：工艺生产具有低盐浓度组合物
公开(公告)号：EP1345694B1
公开(公告)日：2006-08-02
申请号：EP01985906.5
申请日：2001-12-19
申请人： GE Healthcare Bio-Sciences AB
发明人： BELEW, Makonnen , JOHANSSON, Bo-Lennart , MALOISEL, Jean-Luc
IPC分类号： B01J39/04 , B01J41/04 , B01J39/26 , B01J41/20
CPC分类号： B01J41/20 , B01J39/04 , B01J39/26 , B01J41/04
摘要： Method for desalting an aqueous liquid containing a charged substance comprising the steps of:(i) contacting liquid (I) with an ion-exchanger (1) under conditions permitting binding between ion-exchanger and substance, said ion-exchanger comprising a base matrix carrying an ion-exchange ligand (Ligand 1) with the opposite charge compared to the substance, (ii) desorbing said substance from said ion-exchanger by the use of a liquid (liquid (II)). Wherein: (A) ion-exchanger (1) is an ion-exchanger::(a) that can bind the substance in an aqueous reference liquid at an ionic strength corresponding to 0.1 M NaCl, preferably 0.25 M NaCl; and (b) permits a breakthrough capacity at the pH provided by liquid (I) which is more than 2 mg/ml of gel, at a breakthrough of 10% and linear flow velocity of 300 cm/h;and(B) in step (ii) the pH of liquid (II) is adjusted to a pH value where the charge difference between the substance, the ligand and/or the ion-exchanger is lowered.

5. 发明授权

EP1235749B1 A METHOD FOR ANION-EXCHANGE ADSORPTION 有权
标题翻译：阴离子交换吸附的方法
公开(公告)号：EP1235749B1
公开(公告)日：2011-01-19
申请号：EP00988740.7
申请日：2000-11-22
申请人： GE Healthcare Bio-Sciences AB
发明人： BELEW, Makonnen , JOHANSSON, Bo-Lennart , MALOISEL, Jean-Luc GE Healthcare
IPC分类号： C02F1/28 , B01J41/00
CPC分类号： B01J41/20 , B01D15/327 , B01J41/09 , C02F1/42
摘要： A method for the removal of a substance, which has a negative charge and which and which is present in an aqueous liquid (I). The method comprises the steps of: (i) contacting the liquid with an anion-exchanger (1) that comprises mixed mode anion-exchanging ligands in which there is a positively charged nitrogen allowing binding of the substance to the anion-exchanger; and (ii) desorbing said substance from said anion-exchanger. The characteristic feature is that (A) the mixed mode ligands have a thioether linkage within a distance of 1-7 atoms from their positively charged atom, and (B) the anion-exchanger (1) (i) is capable of binding the substance of interest in an aqueous reference liquid (II) at an ionic strength corresponding to 0.25 M NaCl, and (ii) permits in the pH interval 2-12 a maximal breakthrough capacity for the substance which is ≥200 % of the breakthrough capacity of the substance for Q-Sepharose Fast Flow (anion-exchanger 2).
摘要翻译：一种去除具有负电荷且存在于含水液体（I）中的物质的方法。该方法包括以下步骤：（i）使液体与阴离子交换剂（1）接触，阴离子交换剂（1）包含混合型阴离子交换配体，其中存在允许物质与阴离子交换剂结合的带正电的氮; 和（ii）从所述阴离子交换剂解吸所述物质。其特征是（A）混合模式的配体在距离其正电荷原子1-7个原子的距离内具有硫醚键，和（B）阴离子交换剂（1）（i）能够结合物质在对应于0.25M NaCl的离子强度下在水性参考液体（II）中感兴趣，和（ii）允许在pH 2-12的范围内物质的最大穿透能力≥该穿透能力的200％用于Q-Sepharose Fast Flow（阴离子交换剂2）的物质。

6. 发明公开

EP2167229A1 SEPARATION MATRIX 审中-实审转让
标题翻译：分离矩阵
公开(公告)号：EP2167229A1
公开(公告)日：2010-03-31
申请号：EP08794090.4
申请日：2008-07-22
申请人： GE Healthcare Bio-Sciences AB
发明人： AXÉN, Andreas , BERGSTRÖM, Jan , GLAD, Gunnar , JOHANSSON, Bo-Lennart , NORRMAN, Nils
IPC分类号： B01J20/289
CPC分类号： B01J20/289 , B01D15/362 , B01D15/363 , B01J20/3274 , B01J20/328
摘要： The present invention relates to a separation matrix, which comprises a support; extenders coupled to an outer part of said support; and ligands coupled to said extenders, wherein the part of the support to which the extenders are coupled constitutes less than 50% of the volume of the separation matrix. The invention also embraces a method of preparing such a separation matrix, as well as a process wherein the separation media is used.

7. 发明公开

EP2590736A1 CHROMATOGRAPHY METHOD AND MEDIA USED THEREFORE 审中-公开
标题翻译：色谱方法，以及其使用的媒体
公开(公告)号：EP2590736A1
公开(公告)日：2013-05-15
申请号：EP11803895.9
申请日：2011-06-28
申请人： GE Healthcare Bio-Sciences AB
发明人： BERGSTRÖM, Jan , JOHANSSON, Bo-Lennart
IPC分类号： B01J20/285 , B01D15/36 , B01J39/26 , B01J41/20 , C07K1/18
CPC分类号： B01D15/361 , C07K1/18
摘要： The present invention relates to a method for running ion exchange chromatography on a media comprising shell beads having an inner porous core and an outer shell, wherein the inner core is provided with ligands whose charge changes with pH and the shell is provided with charged ion exchange ligands, the method comprising the following steps: a) adsorbing sample molecules on the shell ligands at a first pH; b) causing a discharge of the inner core ligands at a second pH by addition of a buffer substance that is able to increase its charge having the same sign/type as that of the core ligands, which at the same time causes release of ions from the inner core ligands and thereby an increase in ionic strength that displaces the sample molecules from the shell ligands i.e. causes an elution.

8. 发明公开

EP2536499A1 METHOD FOR PRODUCTION OF CHROMATOGRAPHY MEDIA 审中-公开
标题翻译：用于生产色谱
公开(公告)号：EP2536499A1
公开(公告)日：2012-12-26
申请号：EP11744970.2
申请日：2011-02-16
申请人： GE Healthcare Bio-Sciences AB
发明人： BERGSTRÖM, Jan , JOHANSSON, Bo-Lennart
IPC分类号： B01J20/285 , B01D15/08 , B01J20/286
CPC分类号： B01J20/3293 , B01D15/361 , B01D15/3804 , B01J20/28004 , B01J20/286 , B01J20/3206 , B01J20/3248 , B01J20/3285 , B01J39/26 , B01J41/20 , C07K1/18
摘要： The present invention relates to a method of producing novel chromatography media and use thereof for purification of biomolecules, such as proteins. The chromatography media comprises shell beads having an inner porous core and an outer shell. The method comprises providing buffering ligands in the core of the beads, and providing binding ligands aimed for biomolecule binding in the outer shell of the beads. This method makes it possible to optimize binding properties and buffering properties independently of each other which is especially advantageous for production of chroma to focusing media.

9. 发明授权

EP1235748B1 A METHOD FOR ANION-EXCHANGE ADSORPTION AND ANION-EXCHANGERS 有权
标题翻译：阴离子交换吸附和阴离子交换剂的方法
公开(公告)号：EP1235748B1
公开(公告)日：2011-07-20
申请号：EP00979615.2
申请日：2000-11-22
申请人： GE Healthcare Bio-Sciences AB
发明人： JOHANSSON, Bo-Lennart , ANDERSSON, Mikael , GUSTAVSSON, Jan , BELEW, Makonnen , MALOISEL, Jean-Luc
IPC分类号： C02F1/28 , B01J41/00
CPC分类号： B01J41/20 , B01D15/327 , B01J41/09 , C02F1/42
摘要： A method for the removal of a substance carrying a negative charge and being present in an aqueous liquid (I). The method comprises the steps of: (i) contacting the liquid with a matrix carrying a plurality of ligands comprising a positively charged structure and a hydrophobic structure, and (ii) desorbing the substance. The characterizing feature is that (I) each of said ligands together with a spacer has the formula: -- SP---[Ar-R1-N+(R2R3R4)] where (A) [Ar-R1-N+(R2R3R4)] represents a ligand a) Ar is an aromatic ring, b) R1 is [(L)nR'1]m where n and m are integers selected amongst zero or 1; L is amino nitrogen, ether oxygen or thioether sulphur; R'1 is a linker selected among 1) hydrocarbon groups; 2) -C(=NH)-; c) R2-4 are selected among hydrogen and alkyls; (B) SP is a spacer providing a carbon or a heteroatom directly attached to Ar-R1-N+(R2R3R4); (C) --- represents that SP replaces a hydrogen in (Ar-R1-N+(R2R3R4); (D) -- represents binding to the matrix; and (II) desorption. There is also described (a) anion-exchangers having high breakthrough capacities, (b) a screening method and (c) a desalting protocol.
摘要翻译：一种去除携带负电荷并存在于含水液体（I）中的物质的方法。该方法包括以下步骤：（i）使液体与携带多个包含带正电荷结构和疏水结构的配体的基质接触，和（ii）解吸物质。其特征在于：（I）每个所述配体与间隔基一起具有下式：其中（A）[Ar-R1-N +（R2R3R4）] 表示配体a）Ar为芳环，b）R1为[（L）nR'1] m，其中n和m为选自0或1之间的整数; L是氨基氮，醚氧或硫醚硫; R'1是选自1）个烃基的连接基团; 2）-C（= NH） - ; c）R2-4选自氢和烷基; （B）SP是提供直接连接于Ar-R1-N +（R2R3R4）的碳或杂原子的间隔基; （C）---代表SP代替（Ar-R1-N +（R2R3R4）中的氢;（D） - 代表与基质的结合;和（II）解吸。（b）筛选方法和（c）脱盐方案。

10. 发明授权

EP1718668B1 ANTIBODY PURIFICATION 有权转让
标题翻译：纯化抗体的
公开(公告)号：EP1718668B1
公开(公告)日：2009-08-26
申请号：EP05722174.9
申请日：2005-02-24
申请人： GE Healthcare Bio-Sciences AB
发明人： JOHANSSON, Bo-Lennart , JOHANSSON, Hans, J. , LUNGLÖF, Anders , MALOISEL, Jean-Luc , THEVENIN, Nicolas
IPC分类号： C07K1/16 , C07K1/36
CPC分类号： C07K1/18 , B01D15/362 , B01D15/3809 , B01D15/3847 , B01J39/07 , B01J39/26 , B01J47/014 , C07K1/165 , B01D15/327
摘要： The present invention relates to a method of separating antibodies from contaminants in a solution, which method comprises contacting the solution with a chromatography resin comprised of a support to which multi-modal ligands have been immobilised, wherein a multi-modal ligand comprises at least one cation-exchanging group and at least one aromatic or heteroaromatic ring system. In one embodiment, the ring-forming atoms of the aromatic or hereoaromatic entity are selected among C, S or O, and the cation exchanging group is a weak cation exchanger. The present method may be used as a single step procedure or as a polishing step following a capture on a Protein A column.

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