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公开(公告)号：US20090215998A1
公开(公告)日：2009-08-27
申请号：US12094398
申请日：2006-11-21
申请人： Jeffrey D. Antman , Ryan L. Crisman , Lyndal K. Hesterberg , Robert Nelson , Theodore W. Randolph , Matthew B. Seefeldt
发明人： Jeffrey D. Antman , Ryan L. Crisman , Lyndal K. Hesterberg , Robert Nelson , Theodore W. Randolph , Matthew B. Seefeldt
CPC分类号： B01L3/50825 , B01L3/50853 , B01L2200/0684 , B01L2300/042 , B01L2300/044 , B01L2300/045 , B01L2300/14 , B01L2400/0605
摘要： Disclosed are devices for holding samples, particularly liquid samples, during high-pressure treatment. The devices enable a variety of functions, such as high-throughput screening of samples in multi-compartment device embodiments, and adjustment of solution conditions during high-pressure treatment. The devices are designed to maintain integrity during the high-pressure conditions, and are optionally substantially impermeable to oxygen.
摘要翻译： 公开了用于在高压处理期间保持样品，特别是液体样品的装置。 这些装置能够实现多种功能，例如在多隔室装置实施例中的样品的高通量筛选，以及在高压处理期间调节溶液条件。 设备被设计成在高压条件下保持完整性，并且任选地基本上不透氧。
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2.发明申请公开(公告)号：US20080249286A1
公开(公告)日：2008-10-09
申请号：US12099009
申请日：2008-04-07
CPC分类号： C07K1/1136
摘要： Methods for producing biologically active protein from aggregated and/or denatured proteins which comprise subjecting the protein to high hydrostatic pressure in the presence of a ligand or specific binding agent are disclosed. The ligand can be a macromolecule, such as another protein, a nucleic acid, or other macromolecules, or the ligand can be a small organic molecule.
摘要翻译： 公开了从凝集和/或变性蛋白质生产生物活性蛋白质的方法，其包括在配体或特异性结合剂存在下使蛋白质达到高静水压力。 配体可以是大分子，例如另一种蛋白质，核酸或其他大分子，或者配体可以是小的有机分子。
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公开(公告)号：US20120245329A1
公开(公告)日：2012-09-27
申请号：US13405573
申请日：2012-02-27
CPC分类号： C07K16/2827 , C07K1/113 , C07K1/1136 , C07K14/70521 , C07K2319/30 , C07K2319/33
摘要： Methods for refolding antibodies, particularly monoclonal antibodies, from aggregated and/or denatured preparations by subjecting the antibody preparation to high hydrostatic pressure are provided. Refolded preparations of antibodies produced by the methods described herein are also provided.
摘要翻译： 提供了通过使抗体制剂进行高静水压力从聚合和/或变性制剂中重新折叠抗体，特别是单克隆抗体的方法。 还提供了通过本文所述方法产生的抗体的重折叠制剂。
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公开(公告)号：US20090076247A1
公开(公告)日：2009-03-19
申请号：US12208193
申请日：2008-09-10
CPC分类号： C07K16/2827 , C07K1/113 , C07K1/1136 , C07K14/70521 , C07K2319/30 , C07K2319/33
摘要： Methods for refolding antibodies, particularly monoclonal antibodies, from aggregated and/or denatured preparations by subjecting the antibody preparation to high hydrostatic pressure are provided. Refolded preparations of antibodies produced by the methods described herein are also provided.
摘要翻译： 提供了通过使抗体制剂进行高静水压力从聚合和/或变性制剂中重新折叠抗体，特别是单克隆抗体的方法。 还提供了通过本文所述方法产生的抗体的重折叠制剂。
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5.发明申请公开(公告)号：US20080248522A1
公开(公告)日：2008-10-09
申请号：US12098877
申请日：2008-04-07
摘要： Described herein are methods for the solubilization and proteolytic cleavage of fusion protein aggregates, including autocatalytic fusion proteins, at pressures greater than atmospheric pressure to yield soluble target polypeptides.
摘要翻译： 本文描述了在大于大气压的压力下溶解和蛋白水解切割融合蛋白聚集体（包括自催化融合蛋白）以产生可溶性靶多肽的方法。
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公开(公告)号：US20130058895A1
公开(公告)日：2013-03-07
申请号：US13560979
申请日：2012-07-27
IPC分类号： C07K14/555 , A61K38/21 , C07K14/57 , C07K14/56 , C07K14/565
CPC分类号： C07K14/555 , A61K38/212 , A61K38/215 , A61K38/217 , C07K14/565
摘要： Methods are provided using high pressure to treat aggregated interferons, to reduce the aggregate content of interferon material. In particular, recombinant human interferon-β may be so treated. Multiple strategies may be used in combination to make nonglycosylated IFN-β more amenable to high pressure treatment. When coupled with purification techniques, these strategies singly or in combination provide a low aggregate or substantially aggregate free, biologically active solution. In certain aspects, pharmaceutical compositions containing nonglycosylated interferon having less than about 5 weight percent of protein aggregation are provided.
摘要翻译： 提供使用高压处理聚集的干扰素的方法，以减少干扰素材料的总含量。 特别是重组人干扰素 可能会如此对待 可以组合使用多种策略以制备非糖基化IFN-和bgr; 更适合高压处理。 当与纯化技术结合时，这些策略单独或组合提供了低聚集体或基本上聚集的游离的生物活性溶液。 在某些方面，提供了含有小于约5重量％蛋白质聚集的非糖基化干扰素的药物组合物。
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公开(公告)号：US08273561B2
公开(公告)日：2012-09-25
申请号：US12287262
申请日：2008-10-06
CPC分类号： C07K14/555 , A61K38/212 , A61K38/215 , A61K38/217 , C07K14/565
摘要： High pressure to treat aggregated interferons, particularly recombinant human interferon-β, to reduce the aggregate content of interferon material. Highly pure, soluble monomeric recombinant interferon-β is prepared in representative embodiments. Multiple strategies may be used in combination that make nonglycosylated IFN-β more amenable to high pressure treatment. It has been found that refolding yields of high pressure treatment can be significantly improved by use of a combination of strategies, including, or example a pre-treatment of the IFN-β that involves solubilizing and then precipitating the protein. This pre-treatment is particularly effective with respect to recombinant IFN-β inclusion bodies recovered from host cells such as E. coli cells. According to another strategy, refolding under high pressure is much more effective when the refolding reagent incorporating the IFN-β incorporates a zwitterionic surfactant and/or a cholate salt. When a solubilization and precipitation pre-treatment is used, the effectiveness of the high pressure treatment is further enhanced when the refolding reagent incorporating the protein incorporates a disulfide shuffling chemistry such as cysteine/cystine. According to still yet another strategy, high pressure treatment is more effective when using atypically high treatment pressures. When coupled with purification techniques, these strategies singly or in combination provide a low aggregate or substantially aggregate free, biologically active solution. Biologically active solutions comprising nonglycosylated interferon, said interferon comprising less than about 5 weight percent of protein aggregation has been found to exhibit improved PK/PD characteristics.
摘要翻译： 高压处理聚集的干扰素，特别是重组人类干扰素，以减少干扰素材料的总含量。 高纯度，可溶性单体重组干扰素 在代表性的实施方案中制备。 可以组合使用多种策略，使得非糖基化IFN-和bgr 更适合高压处理。 已经发现，通过使用策略的组合（包括或例如IFN-α的预处理）可以显着改善高压治疗的重折叠产率。 这涉及使蛋白质溶解并沉淀。 该预处理对于重组IFN-和bgr是特别有效的; 从宿主细胞如大肠杆菌细胞中回收的包涵体。 根据另一种策略，当加入IFN-和bgr的重折叠试剂时，在高压下重折叠更有效。 加入两性离子表面活性剂和/或胆酸盐。 当使用溶解和沉淀预处理时，当掺入蛋白质的重折叠剂包含二硫化物改组化学物质如半胱氨酸/胱氨酸时，高压处理的有效性进一步增强。 根据还有另一个策略，当使用非常高的处理压力时，高压处理更有效。 当与纯化技术结合时，这些策略单独或组合提供了低聚集体或基本上聚集的游离的生物活性溶液。 已经发现包含非糖基化干扰素的生物活性溶液，所述干扰素包含小于约5重量％的蛋白质聚集体已经表现出改善的PK / PD特征。
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8.发明授权High-pressure inclusion body solubilization and protease clipping of recombinant fusion proteins 有权重组融合蛋白的高压包涵体溶解和蛋白酶剪切公开(公告)号：US07829681B2
公开(公告)日：2010-11-09
申请号：US12098877
申请日：2008-04-07
摘要： Described herein are methods for the solubilization and proteolytic cleavage of fusion protein aggregates, including autocatalytic fusion proteins, at pressures greater than atmospheric pressure to yield soluble target polypeptides.
摘要翻译： 本文描述了在大于大气压的压力下溶解和蛋白水解切割融合蛋白聚集体（包括自催化融合蛋白）以产生可溶性靶多肽的方法。
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公开(公告)号：US08802828B2
公开(公告)日：2014-08-12
申请号：US13405573
申请日：2012-02-27
IPC分类号： C07K17/00
CPC分类号： C07K16/2827 , C07K1/113 , C07K1/1136 , C07K14/70521 , C07K2319/30 , C07K2319/33
摘要： Methods for refolding antibodies, particularly monoclonal antibodies, from aggregated and/or denatured preparations by subjecting the antibody preparation to high hydrostatic pressure are provided. Refolded preparations of antibodies produced by the methods described herein are also provided.
摘要翻译： 提供了通过使抗体制剂进行高静水压力从聚合和/或变性制剂中重新折叠抗体，特别是单克隆抗体的方法。 还提供了通过本文所述方法产生的抗体的重折叠制剂。
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公开(公告)号：US20110070219A1
公开(公告)日：2011-03-24
申请号：US12768333
申请日：2010-04-27
CPC分类号： C07K14/61 , C07K2299/00 , C12N9/248 , C12N9/2482 , C12Y302/01008 , C30B7/00 , C30B29/58
摘要： The present disclosure provides an effective method for the crystallization of proteins at high pressure. A preferential excluding agent, and optionally other reagents may be incorporated into the method. The method is applicable to substantially all proteins.
摘要翻译： 本公开提供了在高压下结晶蛋白质的有效方法。 优选排除剂和任选的其它试剂可以并入该方法中。 该方法适用于基本上所有的蛋白质。
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