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1. 发明申请

US20100179252A1 POLYMER TWO PHASE SYSTEM AND USE THEREOF 有权
标题翻译：聚合物两相系统及其应用
公开(公告)号：US20100179252A1
公开(公告)日：2010-07-15
申请号：US12602840
申请日：2008-06-16
申请人： Hans O. Johansson , James Van Alstine , Rolf Hjorth , Karol Lacki , Emmanuel Macedo , Gunnar Malmquist , Jamil Shanagar
发明人： Hans O. Johansson , James Van Alstine , Rolf Hjorth , Karol Lacki , Emmanuel Macedo , Gunnar Malmquist , Jamil Shanagar
IPC分类号： C07H1/06 , C08K5/06 , C08L5/00
CPC分类号： C07K1/20 , C08G2650/58 , C08L33/02 , C08L33/08 , C08L33/10 , C08L71/02 , C08L2666/14 , C08L2666/04
摘要： The present invention relates to a liquid mixture comprising a first polymer, which is a poly(acid), a second polymer, which is a poly(ether), and at least one salt, wherein the molecular weight of the poly(acid) is in the range of 1000-100,000 Da. The second polymer is selected to be capable of forming immiscible aqueous phases in the presence of the poly(acid) and salt. The poly(acid) may be selected from the group consisting of poly(acrylic acid) and poly(methacrylic acid), and the second synthetic polymer may comprise ethylene oxide. The invention may be used for separation of biomolecules, cells or particles.
摘要翻译：本发明涉及一种液体混合物，其包含第一聚合物，其是聚（酸），第二聚合物，其是聚（醚）和至少一种盐，其中聚（酸）的分子量为在1000-100,000 Da的范围内。选择第二聚合物能够在聚（酸）和盐的存在下形成不混溶的水相。聚（酸）可以选自聚（丙烯酸）和聚（甲基丙烯酸），第二合成聚合物可以包含环氧乙烷。本发明可用于分离生物分子，细胞或颗粒。

2. 发明申请

US20100174052A1 SEPARATION METHOD USING POLYMER MULTI PHASE SYSTEMS 审中-公开
标题翻译：使用聚合物多相系统的分离方法
公开(公告)号：US20100174052A1
公开(公告)日：2010-07-08
申请号：US12663089
申请日：2008-06-16
申请人： Rolf Hjorth , Karol Lacki , Emmanuel Macedo , Gunnar Malmquist , Jamil Shanagar , James Van Alstine
发明人： Rolf Hjorth , Karol Lacki , Emmanuel Macedo , Gunnar Malmquist , Jamil Shanagar , James Van Alstine
IPC分类号： C07K1/36
CPC分类号： C07K1/145 , C07K1/20 , C07K1/22 , C08G2650/58 , C08L33/02 , C08L33/06 , C08L33/08 , C08L71/00 , C08L71/02 , C08L2666/14 , C08L2666/04
摘要： The present invention relates to a process of isolating one or more target compounds, wherein the clarification of feed is performed using partitioning in a multiphase system comprising a first polymer, which is a synthetic poly(acid), a second synthetic polymer, which is a poly(ether), and at least one salt, which clarification is followed by at least one step of affinity chromatography. The molecular weight of the poly(acid) may be in the range of 1000-100,000 Da. The target compound is preferably a biomolecule, such as a monoclonal antibody.
摘要翻译：本发明涉及一种分离一种或多种目标化合物的方法，其中使用多相体系中的分配进行进料澄清，所述多相体系包括第一聚合物，第一聚合物是合成聚（酸），第二合成聚合物，其为聚（醚）和至少一种盐，其中澄清之后是至少一个亲和层析步骤。聚（酸）的分子量可以在1000-100,000Da的范围内。目标化合物优选为生物分子，例如单克隆抗体。

3. 发明授权

US08268915B2 Polymer two phase system and use thereof 有权
标题翻译：聚合物两相体系及其用途
公开(公告)号：US08268915B2
公开(公告)日：2012-09-18
申请号：US12602840
申请日：2008-06-16
申请人： Hans O. Johansson , James Van Alstine , Rolf Hjorth , Karol Lacki , Emmanuel Macedo , Gunnar Malmquist , Jamil Shanagar
发明人： Hans O. Johansson , James Van Alstine , Rolf Hjorth , Karol Lacki , Emmanuel Macedo , Gunnar Malmquist , Jamil Shanagar
IPC分类号： C08L89/00 , C08L31/00 , C08K5/06
CPC分类号： C07K1/20 , C08G2650/58 , C08L33/02 , C08L33/08 , C08L33/10 , C08L71/02 , C08L2666/14 , C08L2666/04
摘要： The present invention relates to a liquid mixture comprising a first polymer, which is a poly(acid), a second polymer, which is a poly(ether), and at least one salt, wherein the molecular weight of the poly(acid) is in the range of 1000-100,000 Da. The second polymer is selected to be capable of forming immiscible aqueous phases in the presence of the poly(acid) and salt. The poly(acid) may be selected from the group consisting of poly(acrylic acid) and poly(methacrylic acid), and the second synthetic polymer may comprise ethylene oxide. The invention may be used for separation of biomolecules, cells or particles.
摘要翻译：本发明涉及一种液体混合物，其包含第一聚合物，其为聚（酸），第二聚合物，其为聚（醚），和至少一种盐，其中聚（酸）的分子量为在1000-100,000 Da的范围内。选择第二聚合物能够在聚（酸）和盐的存在下形成不混溶的水相。聚（酸）可以选自聚（丙烯酸）和聚（甲基丙烯酸），第二合成聚合物可以包含环氧乙烷。本发明可用于分离生物分子，细胞或颗粒。

4. 发明申请

US20120022239A1 PRECIPITATION OF BIOMOLECULES WITH NEGATIVELY CHARGED POLYMERS 审中-公开
标题翻译：用负电荷聚合物降解生物分子
公开(公告)号：US20120022239A1
公开(公告)日：2012-01-26
申请号：US13144100
申请日：2010-01-11
申请人： James Van Alstine , Jamil Shanagar , Rolf Hjorth , Karol Lacki
发明人： James Van Alstine , Jamil Shanagar , Rolf Hjorth , Karol Lacki
IPC分类号： C07K1/32 , C07K16/00 , C07K14/575
CPC分类号： A61K39/39591 , B01D15/327 , B01D15/362 , B01D15/3809 , B01D15/3847 , C07K1/32 , C07K1/36
摘要： The present invention relates to methods of isolating biomolecules. More particularly, the invention relates to methods for isolating antibodies (mAbs) and related proteins including antibody fragments (Fabs) under conditions where they are positive and relatively hydrophobic and will react with negatively charged polymer to form polymer-protein complexes which precipitate. The isolation can be accomplished using inexpensive and biocompatible negatively charged polymers such as polyacrylic acid or carboxymethyldextran polymers of various molecular weights as precipitant. It occurs at relatively high concentrations of polymer (e.g. 10%) and high salt concentration (>50 mM) and conductivity (e.g. >10 mS/cm) over wide range of pH.
摘要翻译：本发明涉及分离生物分子的方法。更具体地说，本发明涉及在阳性和相对疏水的条件下分离抗体（mAb）和相关蛋白质（包括抗体片段（Fab））的方法，并且将与带负电荷的聚合物反应形成沉淀的聚合物 - 蛋白质复合物。可以使用廉价且生物相容性的带负电荷的聚合物如聚丙烯酸或各种分子量的羧甲基葡聚糖聚合物作为沉淀剂来实现分离。它在宽范围的pH下以相对高的聚合物浓度（例如10％）和高盐浓度（> 50mM）和电导率（例如> 10mS / cm）发生。

5. 发明申请

US20120010390A1 SEPARATION METHOD USING SINGLE POLYMER PHASE SYSTEMS 有权
标题翻译：使用单个聚合物相系统的分离方法
公开(公告)号：US20120010390A1
公开(公告)日：2012-01-12
申请号：US13143560
申请日：2010-01-07
申请人： James Van Alstine , Jamil Shanagar , Rolf Hjorth , Martin Hall , Camilla Estmer Nilsson
发明人： James Van Alstine , Jamil Shanagar , Rolf Hjorth , Martin Hall , Camilla Estmer Nilsson
IPC分类号： C07K16/00 , C07K1/36 , C07K14/00 , C07K1/14
CPC分类号： C07K16/00 , C07K1/14 , C07K1/36 , C07K16/04 , C07K16/065 , C07K2317/10
摘要： The present invention relates to a process of enriching one target compound from a liquid, which process comprises at least one step of isolation performed by differentially partitioning between two aqueous phases. In the present invention the phases are formed by adding a thermally responsive, self-associating (i.e. clouding) hydrophilic polymer, and if needed some additional salts, to an aqueous biotechnical solution (such as a fermentation sample or bioseparation process stream) under thermal and other conditions where the solution separates into a one polymer, two-phase system with one phase enriched in the polymer. The target compound is to be found in the phase not enriched in the polymer, while a significant though varying percentage of contaminants may differentially partition to the phase interface or the polymer enriched phase. With minor or no modification the target containing phase solution can be further processed via standard unit operations such as precipitation, chromatography, and filtration to further purify target and remove any residual polymer.
摘要翻译：本发明涉及从液体中富集一种目标化合物的方法，该方法包括通过在两个水相之间进行差异分配而进行的至少一个分离步骤。在本发明中，通过将热响应，自缔合（即，混浊）的亲水聚合物和如果需要的话添加一些额外的盐，在热和/或热处理下，向水生物技术溶液（例如发酵样品或生物分离工艺流）溶液分离成一种聚合物的其它条件，两相体系中一相富集聚合物。目标化合物可以在不富集聚合物的相中找到，而显着的不同百分比的污染物可以差异地分配到相界面或聚合物富集相。通过微量或不改变，可以通过标准单元操作（如沉淀，色谱和过滤）进一步处理包含相溶液的溶液，以进一步纯化目标物并除去任何残留的聚合物。

6. 发明授权

US09115181B2 Separation method using single polymer phase systems 有权
标题翻译：使用单聚合物相系统的分离方法
公开(公告)号：US09115181B2
公开(公告)日：2015-08-25
申请号：US13143560
申请日：2010-01-07
申请人： James Van Alstine , Jamil Shanagar , Rolf Hjorth , Martin Hall , Camilla Estmer Nilsson
发明人： James Van Alstine , Jamil Shanagar , Rolf Hjorth , Martin Hall , Camilla Estmer Nilsson
IPC分类号： A23J1/00 , C07K1/00 , C07K14/00 , C07K16/00 , C07K17/00 , C07K1/14 , C07K1/36 , C07K16/04 , C07K16/06
CPC分类号： C07K16/00 , C07K1/14 , C07K1/36 , C07K16/04 , C07K16/065 , C07K2317/10
摘要： The present invention relates to a process of enriching one target compound from a liquid, which process comprises at least one step of isolation performed by differentially partitioning between two aqueous phases. In the present invention the phases are formed by adding a thermally responsive, self-associating (i.e. clouding) hydrophilic polymer, and if needed some additional salts, to an aqueous biotechnical solution (such as a fermentation sample or bioseparation process stream) under thermal and other conditions where the solution separates into a one polymer, two-phase system with one phase enriched in the polymer. The target compound is to be found in the phase not enriched in the polymer, while a significant though varying percentage of contaminants may differentially partition to the phase interface or the polymer enriched phase. With minor or no modification the target containing phase solution can be further processed via standard unit operations such as precipitation, chromatography, and filtration to further purify target and remove any residual polymer.
摘要翻译：本发明涉及从液体中富集一种目标化合物的方法，该方法包括通过在两个水相之间进行差异分配而进行的至少一个分离步骤。在本发明中，通过将热响应，自缔合（即，混浊）的亲水聚合物和如果需要的话添加一些额外的盐，在热和/或热处理下，向水生物技术溶液（例如发酵样品或生物分离工艺流）溶液分离成一种聚合物的其它条件，两相体系中一相富集聚合物。目标化合物可以在不富集聚合物的相中找到，而显着的不同百分比的污染物可以差异地分配到相界面或聚合物富集相。通过微量或不改变，可以通过标准单元操作（如沉淀，色谱和过滤）进一步处理包含相溶液的溶液，以进一步纯化目标物并除去任何残留的聚合物。

7. 发明申请

US20140343253A1 PLASMA PROTEIN FRACTIONATION BY SEQUENTIAL POLYACID PRECIPITATION 有权
标题翻译：通过顺序聚酰亚胺降解的等离子体蛋白质分解
公开(公告)号：US20140343253A1
公开(公告)日：2014-11-20
申请号：US14345302
申请日：2012-09-14
申请人： James Van Alstine , Mikael Berg , Johanna Kjorning , JAMIL Shanagar
发明人： James Van Alstine , Mikael Berg , Johanna Kjorning , JAMIL Shanagar
IPC分类号： C07K1/30 , C07K16/18 , C07K14/76 , C07K14/75
CPC分类号： C07K1/30 , A61K35/16 , C07K1/303 , C07K14/75 , C07K14/76 , C07K16/18
摘要： There is a recognized need for novel, more simplified, approaches to isolation of plasma from whole blood, as well as a need to isolate cell-free plasma fractions containing different plasma proteins. Methods are divulged for use of aqueous phase systems, formed in blood or blood containing solutions via addition of a single polymer at relatively low concentration, to effect isolation (clarification) of plasma proteins from blood cells. Methods are also divulged to replace widely used Cohn-type plasma protein fractionation which is based on sequential addition of up to 40% (v/v) ethanol and other precipitants, with simple sequential addition of a polyacid. The latter results in isolation of plasma protein fractions (i.e. fibrinogen, immunoglobulin, albumin) in sequence similar to that obtained with Cohn Fractionation and therefore may be suitable for use to reduce solvent use and solvent-related process complications in existing plasma protein purification processes. It may also support use of polymeric film based containers in novel solvent free plasma fractionation processes. The methods disclosed may also be suitable for use in smaller scale plasma protein isolation, in research and diagnostic applications. The general methodologies are robust and can function over a broad range of process variables such as temperature and pH.
摘要翻译：公认需要新颖，更简化的方法来分离全血中的血浆，以及需要分离含有不同血浆蛋白的无细胞血浆级分。泄漏方法用于通过加入相对低浓度的单一聚合物在血液或含血液中形成的水相体系，以实现血细胞从血细胞中分离（澄清）血浆蛋白。也渗透方法代替广泛使用的Cohn型血浆蛋白分离，其基于连续添加高达40％（v / v）乙醇和其它沉淀剂，以简单的顺序加入多酸。后者导致血浆蛋白质部分（即纤维蛋白原，免疫球蛋白，白蛋白）的分离，其顺序类似于用Cohn分级法获得的，因此可能适合用于减少现有血浆蛋白纯化过程中的溶剂使用和溶剂相关的过程并发症。它还可以支持在无溶剂溶剂分级过程中使用基于聚合物膜的容器。所公开的方法也可适用于研究和诊断应用中较小规模的血浆蛋白分离。一般方法是稳健的，并且可以在宽范围的过程变量（例如温度和pH）上起作用。

8. 发明授权

US09624262B2 Plasma protein fractionation by sequential polyacid precipitation 有权
$Plasma protein fractionation by sequential polyacid precipitation$
公开(公告)号：US09624262B2
公开(公告)日：2017-04-18
申请号：US14345302
申请日：2012-09-14
申请人： James Van Alstine , Mikael Berg , Johanna Kjorning , Jamil Shanagar
发明人： James Van Alstine , Mikael Berg , Johanna Kjorning , Jamil Shanagar
IPC分类号： C07K1/30 , C07K14/75 , C07K14/76 , C07K14/765 , C07K16/06 , C07K16/18 , A61K35/16
CPC分类号： C07K1/30 , A61K35/16 , C07K1/303 , C07K14/75 , C07K14/76 , C07K16/18
摘要： There is a recognized need for novel, more simplified, approaches to isolation of plasma from whole blood, as well as a need to isolate cell-free plasma fractions containing different plasma proteins. Methods are divulged for use of aqueous phase systems, formed in blood or blood containing solutions via addition of a single polymer at relatively low concentration, to effect isolation (clarification) of plasma proteins from blood cells. Methods are also divulged to replace widely used Cohn-type plasma protein fractionation which is based on sequential addition of up to 40% (v/v) ethanol and other precipitants, with simple sequential addition of a polyacid. The latter results in isolation of plasma protein fractions (i.e. fibrinogen, immunoglobulin, albumin) in sequence similar to that obtained with Cohn Fractionation and therefore may be suitable for use to reduce solvent use and solvent-related process complications in existing plasma protein purification processes. It may also support use of polymeric film based containers in novel solvent free plasma fractionation processes. The methods disclosed may also be suitable for use in smaller scale plasma protein isolation, in research and diagnostic applications. The general methodologies are robust and can function over a broad range of process variables such as temperature and pH.

9. 发明授权

US08137559B2 Liquid clarification 失效
标题翻译：液体澄清
公开(公告)号：US08137559B2
公开(公告)日：2012-03-20
申请号：US12523322
申请日：2008-01-28
申请人： Michael Katzke , Ola Lind , Tobias Soderman , James Van Alstine
发明人： Michael Katzke , Ola Lind , Tobias Soderman , James Van Alstine
IPC分类号： B01D15/08
CPC分类号： A23L2/80 , A23L2/02 , B01D15/00 , B01J20/26 , B01J20/264 , B01J20/265 , C12H1/0424
摘要： The present invention relates to liquid clarification. More closely, the invention relates to beverage clarification, such as reduction of colloidal (not microbial) haze-causing substances in beer or related beverages such as wine, juices, flavorings etc. The method of the invention uses a hydrophilic surface for adsorption of haze-forming substances by hydrogen bonding interaction properties between the surface and the haze-forming substances.
摘要翻译：本发明涉及液体澄清。更具体地，本发明涉及饮料澄清，例如在啤酒或相关饮料如葡萄酒，果汁，调味料等中减少胶体（非微生物）雾状物质。本发明的方法使用亲水表面吸附雾度通过表面和雾状物质之间的氢键相互作用特性形成物质。

10. 发明申请

US20110053225A1 MULTIFUNCTIONAL TAGS 审中-公开
标题翻译：多功能标签
公开(公告)号：US20110053225A1
公开(公告)日：2011-03-03
申请号：US12863284
申请日：2009-01-23
申请人： Kristian Becker , Leif Bulow , Ake Danielsson , Peter Lindahl , James Van Alstine
发明人： Kristian Becker , Leif Bulow , Ake Danielsson , Peter Lindahl , James Van Alstine
IPC分类号： C12P21/00 , C07K7/06 , C12N15/63
CPC分类号： B01D15/361 , B01D15/327 , B01D15/3804 , B01D15/3828 , B01D15/3847 , C07K1/13 , C07K1/14 , C07K1/18 , C07K1/20 , C07K1/22 , C07K1/36 , C07K2319/20
摘要： The present invention relates to multifunctional protein production tags comprising at least 4, preferably 4-8 amino acids, for optimising expression of proteins and purification thereof by various multi-step processes including chromatographic or filtration, as well as batch unit operations. The tags include sequences of multiple defined purposes which are not generated in defined linear sequence regions related to one purpose but as integrated sequences often overlapping each other, i.e. the defined purposes are not discrete separate units on the tag but rather heterogeneously distributed in the tag. The invention also relates to an expression vector encoding the multipurpose tag and a method for protein purification, comprising expressing a protein in the expression vector and purifying the protein in several steps using functionalities of the multipurpose tag.
摘要翻译：本发明涉及包含至少4个，优选4-8个氨基酸的多功能蛋白质生产标签，用于优化蛋白质的表达并通过包括色谱或过滤的各种多步骤过程以及批次单元操作来纯化蛋白质。标签包括多个定义的目的的序列，其不是在与一个目的相关的定义的线性序列区域中生成的，而是通常彼此重叠的集成序列，即，所定义的目的不是标签上的离散分离单元，而是非均匀地分布在标签中。本发明还涉及编码多用途标签的表达载体和蛋白质纯化方法，其包括在表达载体中表达蛋白质并使用多用途标签的功能在几个步骤中纯化蛋白质。

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