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1. 发明授权

US4656132A Method of improving the yield of heterologous protein produced by cultivating recombinant bacteria 失效
标题翻译：提高培养重组细菌产生的异源蛋白质产量的方法
公开(公告)号：US4656132A
公开(公告)日：1987-04-07
申请号：US594250
申请日：1984-03-28
申请人： Arie Ben-Bassat , Glenn Dorin , Keith Bauer , Leo Lin
发明人： Arie Ben-Bassat , Glenn Dorin , Keith Bauer , Leo Lin
IPC分类号： C12N15/09 , A61K38/00 , A61K38/21 , C07K14/52 , C12N1/38 , C12N15/00 , C12P21/00 , C12P21/02 , C12R1/19
CPC分类号： C12N1/38 , C07K14/52
摘要： A method for improving the yield of heterologous protein such as IFN-.alpha., IFN-.beta., and IL-2, produced by recombinant bacteria by supplementing the nutrient medium in which the bacteria are grown with a water soluble alcohol and/or amino acid mixture during the terminal phase of the cultivation.
摘要翻译：通过用水溶性醇和/或氨基酸混合物补充细菌生长的营养培养基来提高由重组细菌产生的异源蛋白如IFN-α，IFN-β和IL-2的产量的方法在栽培的最后阶段。

2. 发明授权

US4894334A Method of improving the yield of heterologous protein produced by cultivating recombinant bacteria 失效
标题翻译：提高培养重组细菌产生的异源蛋白质产量的方法
公开(公告)号：US4894334A
公开(公告)日：1990-01-16
申请号：US35069
申请日：1987-04-06
申请人： Arie Ben-Bassat , Glenn Dorin , Keith Bauer
发明人： Arie Ben-Bassat , Glenn Dorin , Keith Bauer
IPC分类号： C07K14/52 , C12N1/21 , C12N1/38
CPC分类号： C12N1/38 , C07K14/52
摘要： A method for improving the yield of heterologous protein such as ricin A toxin, produced by recombinant bacteria by supplementing the nutrient medium in which the bacteria are grown with an ethanol and/or amino acid mixture during the terminal phase of the cultivation. Also disclosed is a method for improving the yield of heterologous proteins under the control of the PL promoter.
摘要翻译：一种通过在培养的最后阶段补充细菌与乙醇和/或氨基酸混合物生长的营养培养基来提高重组细菌产生的异种蛋白质如蓖麻毒素A毒素的产量的方法。还公开了一种在PL启动子控制下提高异源蛋白质产量的方法。

3. 发明申请

US20060128947A1 Formulation, solubilization, purification, and refolding of tissue factor pathway inhibitor 失效
标题翻译：组织因子途径抑制剂的制剂，溶解，纯化和重折叠
公开(公告)号：US20060128947A1
公开(公告)日：2006-06-15
申请号：US11337518
申请日：2006-01-24
申请人： Glenn Dorin , Bo Arve , Gregory Pattison , Robert Halenbeck , Kirk Johnson , Bao-Lu Chen , Rajsharan Rana , Maninder Hora , Hassan Madani , Michael Tsang , Mark Gustafson , Gary Bild , Gary Johnson
发明人： Glenn Dorin , Bo Arve , Gregory Pattison , Robert Halenbeck , Kirk Johnson , Bao-Lu Chen , Rajsharan Rana , Maninder Hora , Hassan Madani , Michael Tsang , Mark Gustafson , Gary Bild , Gary Johnson
IPC分类号： A61K38/54 , C07K14/475
CPC分类号： C07K14/475 , A23L7/111 , A23L7/165 , A23L9/10 , A23L9/22 , A23L19/09 , A23L19/18 , A23L21/15 , A23L29/212 , A23L29/219 , A23P20/12 , A61K9/0019 , A61K9/08 , A61K38/57 , A61K47/02 , A61K47/12 , A61K47/183 , A61K47/36 , C07K1/1136 , C07K14/8114 , Y10S514/97 , Y10S514/973
摘要： Compositions are described that are suitable for formulating TFPI. Solubilizers and stabilizers facilitate the preparation of pharmaceutically acceptable compositions of TFPI at various concentrations.
摘要翻译：描述了适合配制TFPI的组合物。增溶剂和稳定剂有助于制备各种浓度的TFPI的药学上可接受的组合物。

4. 发明授权

US5248769A Process for recovering refractile bodies containing heterologous proteins from microbial hosts 失效
$Process for recovering refractile bodies containing heterologous proteins from microbial hosts$
标题翻译：从微生物宿主回收含有异源蛋白质的折射体的方法
公开(公告)号：US5248769A
公开(公告)日：1993-09-28
申请号：US798837
申请日：1991-11-25
申请人： Glenn Dorin
发明人： Glenn Dorin
IPC分类号： C07K1/113 , C07K1/36 , C07K14/53 , C07K14/55 , C07K14/565 , C12N1/06
CPC分类号： C07K1/1133 , C07K1/113 , C07K1/36 , C07K14/53 , C07K14/55 , C07K14/565 , C12N1/06
摘要： A refractile material containing a heterologous protein is recovered from a host microorganism cell culture transformed to produce the protein. One recovery process involves first reducing the ionic strength of the culture medium prior to disruption to a level effective in preventing reaggregation of cellular debris with refractile material after disruption, disrupting the desalted culture, optionally adding material to the disruptate to create a density or viscosity gradient and separating the refractile material from the cellular debris by high-speed centrifugation. Preferably the salt removal step is carried out by diafiltration and the heterologous protein comprises recombinant M-CSF, IL-2 or IFN-.beta..
摘要翻译：从转化以产生蛋白质的宿主微生物细胞培养物中回收含有异源蛋白质的折射材料。一个回收过程包括首先将破坏前的培养基的离子强度降低到有效防止破碎后的折射材料的细胞碎片再聚集的水平，破坏脱盐培养物，任选地向破碎物中加入材料以产生密度或粘度梯度并通过高速离心从细胞碎片中分离折射材料。优选地，通过渗滤进行除盐步骤，异源蛋白质包含重组M-CSF，IL-2或IFN-β。

5. 发明授权

US07851433B2 Method of purifying TFPI and TFPI analogs 失效
标题翻译： TFPI和TFPI类似物的纯化方法
公开(公告)号：US07851433B2
公开(公告)日：2010-12-14
申请号：US10753078
申请日：2004-01-08
申请人： David H. Reifsnyder , Duane Inlow , Glenn Dorin , Patricio T. Riquelme , Cynthia A. Cowgill , Douglas G. Bolesch , Mark E. Gustafson
发明人： David H. Reifsnyder , Duane Inlow , Glenn Dorin , Patricio T. Riquelme , Cynthia A. Cowgill , Douglas G. Bolesch , Mark E. Gustafson
IPC分类号： C07K14/00
CPC分类号： C07K5/1008 , A61K38/00 , C07K5/1013 , C07K14/8114
摘要： Highly purified preparations of TFPI or TFPI analogs can be prepared using a method that generally involves the following steps: (1) expression of TFPI or TFPI analog in E. coli, (2) isolation of refractile bodies, (3) dissolution of the refractile bodies and refolding of the expressed TFPI or TFPI analog, (4) SP-Sepharose fast flow (FF) chromatography, (5) a first concentration and diafiltration step, (6) Q-Sepharose high (HP) performance chromatography, (7) butyl hydrophobic interaction chromatography (HIC), (8) SP-Sepharose HP chromatography, and (9) a second concentration/diafiltration step. Less than about 12% of the TFPI or TFPI analog molecules in such preparations are modified TFPI or TFPI analog species (i.e., oxidized, carbamylated, acetylated, deamidated, aggregated, or misfolded species).
摘要翻译： TFPI或TFPI类似物的高度纯化制剂可以使用通常包括以下步骤的方法制备：（1）在大肠杆菌中表达TFPI或TFPI类似物，（2）分离折射体，（3）折射体的溶解（4）SP-Sepharose快速流动（FF）色谱法，（5）第一次浓缩和渗滤步骤，（6）Q-Sepharose高（HP）性能色谱法，（7）表征TFPI或TFPI类似物的体内和重折叠，（4）丁基疏水相互作用层析（HIC），（8）SP-Sepharose HP层析，和（9）第二次浓缩/渗滤步骤。在这种制剂中，小于约12％的TFPI或TFPI类似物分子是修饰的TFPI或TFPI类似物（即氧化的，氨基甲酰化的，乙酰化的，脱酰胺的，聚集的或错误折叠的物种）。

6. 发明授权

US5814485A Production of interferon-.beta. (IFN-.beta.) in E. coli 失效
标题翻译：在大肠杆菌中产生干扰素-β（IFN-β）
公开(公告)号：US5814485A
公开(公告)日：1998-09-29
申请号：US477310
申请日：1995-06-06
申请人： Glenn Dorin , Patrick J. McAlary , Kathleen M. Wong
发明人： Glenn Dorin , Patrick J. McAlary , Kathleen M. Wong
IPC分类号： C12N15/09 , A61K38/21 , C07K14/565 , C12N1/21 , C12N15/22 , C12P21/02 , C12R1/19
CPC分类号： C12P21/02 , C07K14/565
摘要： Methods for the production of interferon-.beta. polypeptides by bacterial cells, by culturing cells capable of producing IFN-.beta. polypeptide under conditions that induce increased production of IFN-.beta. polypeptide. Such conditions include, for example, low potassium cation concentration and/or very low sodium cation concentration and/or specific pH ranges.
摘要翻译：通过在诱导IFN-β多肽的产生增加的条件下培养能够产生IFN-β多肽的细胞的细菌细胞产生干扰素-β多肽的方法。这些条件包括例如低钾阳离子浓度和/或非常低的钠离子浓度和/或特定的pH范围。

7. 发明申请

US20120040396A1 METHODS FOR PURIFYING BIO-ORGANIC COMPOUNDS 审中-公开
标题翻译：净化生物有机化合物的方法
公开(公告)号：US20120040396A1
公开(公告)日：2012-02-16
申请号：US13198711
申请日：2011-08-05
申请人： Pinar Tabur , Glenn Dorin
发明人： Pinar Tabur , Glenn Dorin
IPC分类号： C12P39/00 , C12P5/02 , C12N1/15 , C12N1/19 , C12N1/13 , C12P5/00 , C12N1/21
CPC分类号： C12P5/02 , C11B1/00 , C12P5/007 , Y02E50/343
摘要： Methods and systems for purifying bio-organic compounds are described. In certain embodiments, the methods comprise the steps of (a) providing a composition or an emulsion comprising a surfactant, host cells, an aqueous medium and a bio-organic compound produced by the host cells, wherein the solubility of the surfactant in the aqueous medium decreases with increasing temperature and wherein the temperature of the composition or emulsion is at least about 1° C. below a phase inversion temperature of the composition or emulsion; (b) raising the temperature of the composition or emulsion to at least about 1° C. above the phase inversion temperature; and (c) performing a liquid/liquid separation of the composition to provide a crude bio-organic composition or emulsion.
摘要翻译：描述了用于纯化生物有机化合物的方法和系统。在某些实施方案中，所述方法包括以下步骤：（a）提供包含表面活性剂，宿主细胞，水性介质和由宿主细胞产生的生物有机化合物的组合物或乳液，其中表面活性剂在水性介质随温度升高而降低，并且其中组合物或乳液的温度低于组合物或乳液的相转变温度至少约1℃; （b）将组合物或乳液的温度升高至相转变温度以上至少约1℃; 和（c）进行组合物的液/液分离以提供粗生物 - 有机组合物或乳液。

8. 发明授权

US06756484B1 IGF-I purification process 有权
标题翻译： IGF-I纯化方法
公开(公告)号：US06756484B1
公开(公告)日：2004-06-29
申请号：US09614947
申请日：2000-07-12
申请人： Russell A. Brierley , Joan N. Abrams , John M. Hanson , Francis C. Maslanka , Cynthia Cowgill , Luis G. Juarbe-Osorio , Patricio Riquelme , Glenn Dorin
发明人： Russell A. Brierley , Joan N. Abrams , John M. Hanson , Francis C. Maslanka , Cynthia Cowgill , Luis G. Juarbe-Osorio , Patricio Riquelme , Glenn Dorin
IPC分类号： C07K14475
CPC分类号： C07K14/65 , G01N30/02 , B01D15/422
摘要： Disclosed is an improved process for obtaining purified, monomeric, intact, correctly-folded insulin-like growth factor-I (also known as somatomedin-C). The improvements, consisting primarily of the addition of an IGF-I unfolding/refolding step and the substitution of a reverse phase chromatography step for a gel filtration chromatography step result in a three-fold increase in final yield. The process includes the following steps, in order: first cation exchange, unfolding/refolding, hydrophobic interaction chromatography, second cation exchange, and reverse phase chromatography.
摘要翻译：公开了用于获得纯化的，单体的，完整的，正确折叠的胰岛素样生长因子-I（也称为生长因子C）的改进方法。主要由IGF-I展开/重折叠步骤的添加和用于凝胶过滤层析步骤的反相色谱步骤的替代的改进导致最终产率增加三倍。该方法包括以下步骤：首先进行阳离子交换，展开/重折叠，疏水相互作用层析，第二次阳离子交换和反相色谱法。

9. 发明授权

US6117983A Methods for purifying authentic IGF from yeast hosts 失效
标题翻译：从酵母宿主纯化正确的IGF的方法
公开(公告)号：US6117983A
公开(公告)日：2000-09-12
申请号：US990490
申请日：1997-12-15
申请人： Cynthia Cowgill , Louis Juarbe , Patricio Riquelme , Glenn Dorin , Christopher M. Bussineau , Robert D. Kudrna , Ausman G. Otzurk
发明人： Cynthia Cowgill , Louis Juarbe , Patricio Riquelme , Glenn Dorin , Christopher M. Bussineau , Robert D. Kudrna , Ausman G. Otzurk
IPC分类号： C12N15/09 , C07K1/113 , C07K14/65 , C12P21/00 , C12P21/02 , C12R1/84 , C07K1/18 , C07K1/22 , C07K14/475
CPC分类号： C07K1/1133 , C07K14/65
摘要： Methods for purifying authentic, properly folded IGF polypeptides from yeast transformants are disclosed. The methods include a refolding step and provide for high yields of authentic IGF from a variety of yeast strains.
摘要翻译：公开了从酵母转化体纯化正确的，适当折叠的IGF多肽的方法。所述方法包括重折叠步骤，并提供来自各种酵母菌株的高产量的正确的IGF。

10. 发明授权

US07193042B1 Methods for purifying authentic IGF from yeast hosts 失效
标题翻译：从酵母宿主纯化正确的IGF的方法
公开(公告)号：US07193042B1
公开(公告)日：2007-03-20
申请号：US08477984
申请日：1995-06-07
申请人： Cynthia Cowgill , Luis Juarbe-Osorio , Patricio Riquelme , Glenn Dorin , Christopher M. Bussineau , Robert D. Kudrna , Carl Scandella , Russell A. Brierley , Joan N. Abrams , John M. Hanson , Francis C. Maslanka
发明人： Cynthia Cowgill , Luis Juarbe-Osorio , Patricio Riquelme , Glenn Dorin , Christopher M. Bussineau , Robert D. Kudrna , Carl Scandella , Russell A. Brierley , Joan N. Abrams , John M. Hanson , Francis C. Maslanka
IPC分类号： C07K1/18 , C07K1/20 , C07K1/22
CPC分类号： C07K14/65
摘要： Methods for purifying authentic, properly folded IGF polypeptides from yeast transformants are disclosed. The methods include a refolding step and provide for high yields of authentic IGF from a variety of yeast strains.
摘要翻译：公开了从酵母转化体纯化正确的，适当折叠的IGF多肽的方法。所述方法包括重折叠步骤，并提供来自各种酵母菌株的高产量的正确的IGF。

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