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1. 发明申请

US20060149042A1 Process for concentration of macromolecules 有权
标题翻译：高分子浓缩方法
公开(公告)号：US20060149042A1
公开(公告)日：2006-07-06
申请号：US10532998
申请日：2003-11-01
申请人： Konstantin Konstantinov , Huong Nguyen , Jens Vogel
发明人： Konstantin Konstantinov , Huong Nguyen , Jens Vogel
IPC分类号： C07K1/14
CPC分类号： C07K14/55 , C07K1/34 , C07K1/36
摘要： The invention provides methods for concentrating a macromolecule from a solution comprising the macromolecule and an organic polymer by first subjecting the solution to ultrafiltration to produce a first retentate solution, then adjusting the conductivity of the first retentate solution such that any protein precipitation induced by the organic polymer is essentially prevented to produce a second retentate solution, and then subjecting the second retentate solution to ultrafiltration. In a preferred embodiment, the conductivity is adjusted by diafiltration against water, suitable diluent or buffer. Preferably, the invention pertains to the concentration of solutions of native or recombinant proteins. The invention further pertains preferably to methods for the concentration of cell culture supernatant comprising a product protein and organic polymers of the Pluronic family of block co-polymers, and more preferably comprising Pluronic F-68 block co-polymer.
摘要翻译：本发明提供了从包含大分子和有机聚合物的溶液中浓缩高分子的方法，首先使溶液经过超滤以产生第一滞留物溶液，然后调节第一渗余溶液的电导率，使得由有机物诱导的任何蛋白质沉淀基本上防止聚合物产生第二滞留物溶液，然后使第二滞留物溶液经过超滤。在优选的实施方案中，通过对水，合适的稀释剂或缓冲液进行渗滤来调节电导率。优选地，本发明涉及天然或重组蛋白质的溶液的浓度。本发明还优选地涉及浓缩包含产物蛋白质的细胞培养上清液和Pluronic族嵌段共聚物的有机聚合物，更优选包含Pluronic F-68嵌段共聚物的方法。

2. 发明授权

US07674885B2 Process for concentration of macromolecules 有权
标题翻译：高分子浓缩方法
公开(公告)号：US07674885B2
公开(公告)日：2010-03-09
申请号：US10532998
申请日：2003-11-01
申请人： Konstantin Konstantinov , Huong Nguyen , Jens H. Vogel
发明人： Konstantin Konstantinov , Huong Nguyen , Jens H. Vogel
IPC分类号： A23J1/00 , C07K1/00
CPC分类号： C07K14/55 , C07K1/34 , C07K1/36
摘要： The invention provides methods for concentrating a macromolecule from a solution comprising the macromolecule and an organic polymer by first subjecting the solution to ultrafiltration to produce a first retentate solution, then adjusting the conductivity of the first retentate solution such that any protein precipitation induced by the organic polymer is essentially prevented to produce a second retentate solution, and then subjecting the second retentate solution to ultrafiltration. In a preferred embodiment, the conductivity is adjusted by diafiltration against water, suitable diluent or buffer.Preferably, the invention pertains to the concentration of solutions of native or recombinant proteins. The invention further pertains preferably to methods for the concentration of cell culture supernatant comprising a product protein and organic polymers of the PLURONIC family of nonionic block co-polymers, and more preferably comprising PLURONIC F-68 nonionic block co-polymer.
摘要翻译：本发明提供了从包含大分子和有机聚合物的溶液中浓缩高分子的方法，首先使溶液经过超滤以产生第一滞留物溶液，然后调节第一渗余溶液的电导率，使得由有机物诱导的任何蛋白质沉淀基本上防止聚合物产生第二滞留物溶液，然后使第二滞留物溶液经过超滤。在优选的实施方案中，通过对水，合适的稀释剂或缓冲液进行渗滤来调节电导率。优选地，本发明涉及天然或重组蛋白质的溶液的浓度。本发明还优选地涉及浓缩包含产物蛋白质和PLURONIC系列非离子嵌段共聚物的有机聚合物的细胞培养上清液的方法，更优选包含PLURONIC F-68非离子嵌段共聚物。

3. 发明授权

US06953692B2 Device and method for seed-train expansion of mammalian cells 有权
标题翻译：哺乳动物细胞种子培养扩增的装置和方法
公开(公告)号：US06953692B2
公开(公告)日：2005-10-11
申请号：US10029779
申请日：2001-12-18
申请人： Rudiger Heidemann , Mokhtar Mered , James D. Michaels , Konstantin Konstantinov
发明人： Rudiger Heidemann , Mokhtar Mered , James D. Michaels , Konstantin Konstantinov
IPC分类号： C12M1/36 , C12M3/00 , C12N5/00 , C12N5/02
CPC分类号： C12M41/26 , C12M33/00 , C12M41/12 , C12M41/34 , C12M41/46
摘要： A device and method for seed-train expansion of a source of mammalian cells and their use in production of proteins expressed by the cells comprising the use of a dedicated inoculation bioreactor for expanding the cells prior to the transfer to a production bioreactor is disclosed.The novel inoculation bioreactor is designed to facilitate an improved method of mammalian cell seed-train expansion, and is distinguished by the presence of an “inoculation well” which communicates with the interior of the bioreactor and which facilitates the growth of mammalian cells for commercial seed-train expansion.The method comprises adding the cryopreserved cells to media within the inoculation well of the inoculation bioreactor, enabling the cells to grow to a predetermined concentration within the inoculation well by monitoring and adjusting the condition of the media and environment, and thereafter incrementally increasing the volume of the media within the reactor so that optimal cell growth is maintained.
摘要翻译：公开了用于种子培养哺乳动物细胞源的装置和方法及其在生产由细胞表达的蛋白质中的用途，所述细胞包括在转移至生产生物反应器之前使用专用接种生物反应器来扩增细胞。新颖的接种生物反应器设计用于促进哺乳动物细胞种子培养扩展的改进方法，并且通过存在与生物反应器内部连通的“接种孔”的区别，并且促进用于商业种子的哺乳动物细胞的生长火车扩张。该方法包括将冷冻保存的细胞加入到接种生物反应器的接种孔内的培养基中，使细胞通过监测和调节培养基和环境的状况使细胞在接种孔内生长至预定浓度，然后逐渐增加反应器内的培养基，使得保持最佳的细胞生长。

4. 发明申请

US20090288960A1 Rapid Detection of Anti-Chromatin Autoantibodies in Human Serum using a Portable Electrochemical Biosensor 审中-公开
标题翻译：使用便携式电化学生物传感器快速检测人血清中的抗染色质自身抗体
公开(公告)号：US20090288960A1
公开(公告)日：2009-11-26
申请号：US12370403
申请日：2009-02-12
申请人： Robert Rubin , Ravil Sitdikov , Plamen Atanassov , Gabriel Lopez , Konstantin Konstantinov
发明人： Robert Rubin , Ravil Sitdikov , Plamen Atanassov , Gabriel Lopez , Konstantin Konstantinov
IPC分类号： G01N27/416 , G01N27/26
CPC分类号： G01N33/564 , G01N33/5438 , G01N2800/104
摘要： A rapid electrochemical flow-through sensor and method for detecting the presence of autoantibodies in a fluid sample such as blood is shown and described. The sensor may take either a single- or multi-plexed form. The sensor comprises a fluid inlet, a reaction region comprising immobilized autoantigens and an electrode assembly, and a fluid outlet.
摘要翻译：显示和描述了用于检测流体样品如血液中自身抗体的存在的快速电化学流通传感器和方法。传感器可以采用单层或多层复合形式。传感器包括流体入口，包含固定的自身抗原的反应区域和电极组件以及流体出口。

5. 发明授权

US06338964B1 Process and medium for mammalian cell culture under low dissolved carbon dioxide concentration 有权
标题翻译：在低溶解二氧化碳浓度下哺乳动物细胞培养的方法和培养基
公开(公告)号：US06338964B1
公开(公告)日：2002-01-15
申请号：US09307175
申请日：1999-05-07
申请人： Ricaredo Matanguihan , Eva Sajan , Konstantin Konstantinov , Michael Zachariou , Charles Olson
发明人： Ricaredo Matanguihan , Eva Sajan , Konstantin Konstantinov , Michael Zachariou , Charles Olson
IPC分类号： C12N500
CPC分类号： C12N5/0018 , C12N2500/10 , C12N2500/32 , C12N2500/60
摘要： A cell culture medium which is low in dissolved carbon dioxide is disclosed. The medium contains less than about 1 g/L added sodium bicarbonate and includes an organic buffer and a metal complexing agent. The medium is preferably essentially free of added sodium bicarbonate. Methods of use of the medium in culturing mammalian cells, particularly cells engineered to produce recombinant factor VIII, are also disclosed.
摘要翻译：公开了一种低溶解二氧化碳的细胞培养基。所述培养基含有少于约1g / L的碳酸氢钠，并且包括有机缓冲剂和金属络合剂。该介质优选基本上不含加入的碳酸氢钠。还公开了培养哺乳动物细胞，特别是工程改造以产生重组因子VIII的细胞的培养基的使用方法。

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