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1. 发明授权

US06884613B2 Selective precipitation of viruses 有权
标题翻译：选择性降解病毒
公开(公告)号：US06884613B2
公开(公告)日：2005-04-26
申请号：US09939065
申请日：2001-08-24
申请人： Joseph M. Le Doux , Martin L. Yarmush , Jeffrey R. Morgan
发明人： Joseph M. Le Doux , Martin L. Yarmush , Jeffrey R. Morgan
IPC分类号： A61K48/00 , C12N7/02 , C12N15/867
CPC分类号： C12N15/86 , A61K48/0091 , C12N7/00 , C12N2740/13043 , C12N2740/13051
摘要： The invention provides new methods for purifying and concentrating viruses. The inventors have discovered that high molecular weight proteoglycans present in retroviral stocks are co-concentrated with the retroviruses, and can inhibit retroviral transduction. The new purification and concentration methods feature treatment of virus stock with an anionic polyelectrolyte and a cationic polyelectrolyte, followed by centrifugation. The new methods minimize the amount of proteoglycan co-precipitated with the infectious virus.
摘要翻译：本发明提供了用于纯化和浓缩病毒的新方法。发明人已经发现存在于逆转录病毒原液中的高分子量蛋白聚糖与逆转录病毒共同浓缩，并且可以抑制逆转录病毒转导。新的纯化和浓缩方法特征是用阴离子聚电解质和阳离子聚电解质处理病毒原液，然后离心。新方法使与感染性病毒共沉淀的蛋白多糖的量最小化。

2. 发明授权

US07592170B2 Selective precipitation of viruses using polyectrolytes 有权
标题翻译：使用聚电解质选择性沉淀病毒
公开(公告)号：US07592170B2
公开(公告)日：2009-09-22
申请号：US11104161
申请日：2005-04-12
申请人： Joseph M. Le Doux , Martin L. Yarmush , Jeffrey R. Morgan
发明人： Joseph M. Le Doux , Martin L. Yarmush , Jeffrey R. Morgan
IPC分类号： C12N9/00
CPC分类号： C12N15/86 , A61K48/0091 , C12N7/00 , C12N2740/13043 , C12N2740/13051
摘要： The invention provides new methods for purifying and concentrating viruses. The inventors have discovered that high molecular weight proteoglycans present in retroviral stocks are co-concentrated with the retroviruses, and can inhibit retroviral transduction. The new purification and concentration methods feature treatment of virus stock with an anionic polyelectrolyte and a cationic polyelectrolyte, followed by centrifugation. The new methods minimize the amount of proteoglycan co-precipitated with the infectious virus.
摘要翻译：本发明提供了用于纯化和浓缩病毒的新方法。发明人已经发现存在于逆转录病毒原液中的高分子量蛋白聚糖与逆转录病毒共同浓缩，并且可以抑制逆转录病毒转导。新的纯化和浓缩方法特征是用阴离子聚电解质和阳离子聚电解质处理病毒原液，然后离心。新方法使与感染性病毒共沉淀的蛋白多糖的量最小化。

3. 发明授权

US06861001B2 Methods for removal, purification, and concentration of viruses, and methods of therapy based thereupon 失效
标题翻译：病毒的去除，纯化和浓缩方法及其治疗方法
公开(公告)号：US06861001B2
公开(公告)日：2005-03-01
申请号：US09728882
申请日：2000-12-01
申请人： William Lee , Jeffrey R. Morgan , Martin L. Yarmush
发明人： William Lee , Jeffrey R. Morgan , Martin L. Yarmush
IPC分类号： A61L2/00 , C12N7/02 , B01D61/00
CPC分类号： C12N7/00 , A61L2/0017 , A61L2/0082 , C12N2740/10051
摘要： The invention is based on the discovery that certain membranes, which include side chains or molecular “brushes” having, for example, tertiary amino functional groups, can be used as highly effective filters to capture viruses/virus particles from liquids without removal of proteins. New methods based on this discovery include removing viruses from liquids such as blood or plasma, removing viruses from pharmaceuticals, concentrating and/or purifying viruses, e.g., for use in gene therapy, and producing recombinant viruses in new bioreactors. The invention also includes new methods of therapy or adjunct therapy for viral infections, in which a patient's blood or plasma is filtered through the membranes to remove viruses to reduce the viral load. The invention also includes new bioreactors and viral filters containing the membranes.
摘要翻译：本发明基于以下发现：包括侧链的某些膜或具有例如叔氨基官能团的分子“刷”可用作高效过滤器，以从液体中捕获病毒/病毒颗粒而不除去蛋白质。基于该发现的新方法包括从诸如血液或血浆的液体中除去病毒，从药物中除去病毒，浓缩和/或纯化病毒，例如用于基因治疗，以及在新的生物反应器中产生重组病毒。本发明还包括用于病毒感染的新的治疗方法或辅助治疗方法，其中通过膜过滤患者的血液或血浆以除去病毒以减少病毒载量。本发明还包括含有膜的新的生物反应器和病毒过滤器。

4. 发明授权

US07160464B2 Methods for removal, purification, and concentration of viruses and methods of therapy based thereupon 有权
标题翻译：病毒的去除，纯化和浓缩方法及其治疗方法
公开(公告)号：US07160464B2
公开(公告)日：2007-01-09
申请号：US11018939
申请日：2004-12-21
申请人： William Lee , Jeffrey R. Morgan , Martin L. Yarmush
发明人： William Lee , Jeffrey R. Morgan , Martin L. Yarmush
IPC分类号： B01D61/00 , B01D63/00 , B01D15/04
CPC分类号： C12N7/00 , A61L2/0017 , A61L2/0082 , C12N2740/10051
摘要： The invention is based on the discovery that certain membranes, which include side chains or molecular “brushes” having, for example, tertiary amino functional groups, can be used as highly effective filters to capture viruses/virus particles from liquids without removal of proteins. New methods based on this discovery include removing viruses from liquids such as blood or plasma, removing viruses from pharmaceuticals, concentrating and/or purifying viruses, e.g., for use in gene therapy, and producing recombinant viruses in new bioreactors. The invention also includes new methods of therapy or adjunct therapy for viral infections, in which a patient's blood or plasma is filtered through the membranes to remove viruses to reduce the viral load. The invention also includes new bioreactors and viral filters containing the membranes.
摘要翻译：本发明基于以下发现：包括侧链的某些膜或具有例如叔氨基官能团的分子“刷”可用作高效过滤器，以从液体中捕获病毒/病毒颗粒而不除去蛋白质。基于该发现的新方法包括从诸如血液或血浆的液体中除去病毒，从药物中除去病毒，浓缩和/或纯化病毒，例如用于基因治疗，以及在新的生物反应器中产生重组病毒。本发明还包括用于病毒感染的新的治疗方法或辅助治疗方法，其中通过膜过滤患者的血液或血浆以除去病毒以减少病毒载量。本发明还包括含有膜的新的生物反应器和病毒过滤器。

5. 发明申请

US20130307170A1 BLOOD SUBSTITUTES AND USES THEREOF 有权
标题翻译：血液替代品及其用途
公开(公告)号：US20130307170A1
公开(公告)日：2013-11-21
申请号：US13805245
申请日：2011-06-28
申请人： Martin L. Yarmush , Eric Yang , Tali Konry , Erkin Seker , Dhruv Sarin , Prakash Rai
发明人： Martin L. Yarmush , Eric Yang , Tali Konry , Erkin Seker , Dhruv Sarin , Prakash Rai
IPC分类号： A61J3/07
CPC分类号： A61J3/07 , A61K9/0026 , A61K9/1271 , A61K38/42 , C12Y106/99 , C12Y111/01006 , C12Y115/01001 , A61K2300/00
摘要： The invention relates to blood substitute compositions, and methods of use thereof. Described herein are compositions in which hemoglobin is maintained substantially in the reduced form of hemoglobin as opposed to the oxidized methemoglobin form through inclusion of an oxido-reductase enzyme and reducing agent within a vesicle with the hemoglobin. The vesicles additionally can comprise a dismutase, a catalase, and an electron acceptor, each of which contribute to either the maintenance of hemoglobin in the active oxygen carrying state or provide a benefit not achieved with free hemoglobin.
摘要翻译：本发明涉及血液替代物组合物及其使用方法。本文描述的是通过在含有血红蛋白的囊泡内包含氧化还原酶和还原剂而将血红蛋白基本维持在血红蛋白的还原形式中而不是氧化的高铁血红蛋白形式的组合物。囊泡另外可以包含岐化酶，过氧化氢酶和电子受体，它们都有助于维持活性氧携带状态的血红蛋白，或提供用游离血红蛋白不能实现的益处。

6. 发明授权

US08435787B2 Alginate polyelectrolyte encapsulation of embryonic stem cells 有权
标题翻译：藻酸盐聚电解质包封胚胎干细胞
公开(公告)号：US08435787B2
公开(公告)日：2013-05-07
申请号：US11919407
申请日：2006-05-09
申请人： Tim Maguire , Rene S. Schloss , Martin L. Yarmush
发明人： Tim Maguire , Rene S. Schloss , Martin L. Yarmush
IPC分类号： C12N15/00
CPC分类号： C12N5/067 , A61K35/545 , C12N2506/02 , C12N2533/32 , C12N2533/74
摘要： Alginate polyelectrolyte encapsulation is used for the controlled differentiation of embryonic stem cells. An isolated cell population is provided. The cell population includes a single cell suspension of ES cells encapsulated within an alginate polyelectrolyte microenvironment. The encapsulated ES cells are capable of differentiating within said microenvironment into hepatocyte lineage cells in the absence of embryoid body intermediates or growth factor supplementation.
摘要翻译：藻酸盐聚电解质包封用于胚胎干细胞的受控分化。提供了一个孤立的细胞群。细胞群包括包封在藻酸盐聚电解质微环境中的ES细胞的单细胞悬浮液。在不存在胚状体中间体或生长因子补充的情况下，包封的ES细胞能够在所述微环境内分化为肝细胞谱系细胞。

7. 发明授权

US08172784B2 Compositions, methods, and devices for treating liver disease 有权
标题翻译：用于治疗肝脏疾病的组合物，方法和装置
公开(公告)号：US08172784B2
公开(公告)日：2012-05-08
申请号：US11871071
申请日：2007-10-11
申请人： Martin L. Yarmush , Biju Parekkadan
发明人： Martin L. Yarmush , Biju Parekkadan
IPC分类号： A61M37/00 , C02F1/44 , C12M3/06
CPC分类号： A61K35/28 , A61M1/3472 , A61M1/3489 , A61M1/3687 , A61M1/3689 , C12M29/16 , C12N5/0663 , C12N5/067 , C12N2502/1358 , G01N33/5067 , G01N33/5073 , G01N2500/00 , G01N2800/085
摘要： Described are compositions and methods for treating liver disease, e.g., acute liver disease, using bone marrow-derived stem cells and bone marrow-derived stem cell conditioned media.
摘要翻译：描述了使用骨髓来源的干细胞和来自骨髓的干细胞条件培养基治疗肝脏疾病，例如急性肝病的组合物和方法。

8. 发明申请

US20110092422A1 ELASTIN BASED GROWTH FACTOR DELIVERY PLATFORM FOR WOUND HEALING AND REGENERATION 有权
标题翻译：基于ELASTIN的生长因子递送平台，用于伤口愈合和再生
公开(公告)号：US20110092422A1
公开(公告)日：2011-04-21
申请号：US12899141
申请日：2010-10-06
申请人： Piyush Koria , Martin L. Yarmush , Yaakov Nahmias
发明人： Piyush Koria , Martin L. Yarmush , Yaakov Nahmias
IPC分类号： A61K38/16 , C12N5/10 , C12N15/63 , C07K14/475 , C07H21/04 , A61P17/02
CPC分类号： C07K14/475 , A61K38/00 , C07K14/78 , C07K2319/70
摘要： The invention is based on the discovery of a potent growth factor delivery system by creating a fusion polypeptide that includes two portions: (i) keratinocyte growth factor protein, and (ii) an elastin-like peptide. This chimera can be administered directly to a wound site, accelerating recovery.
摘要翻译：本发明基于通过产生包含两部分的融合多肽来发现有效的生长因子递送系统：（i）角化细胞生长因子蛋白，和（ii）弹性蛋白样肽。该嵌合体可以直接施用于伤口部位，加速恢复。

9. 发明申请

US20100143313A1 HOMOGENEOUS DIFFERENTIATION OF HEPATOCYTE-LIKE CELLS FROM EMBRYONIC STEM CELLS 审中-公开
标题翻译：来自胚胎干细胞的肝细胞样细胞的均质分化
公开(公告)号：US20100143313A1
公开(公告)日：2010-06-10
申请号：US12634983
申请日：2009-12-10
申请人： Martin L. Yarmush , Cheul H. Cho , Arno W. Tilles
发明人： Martin L. Yarmush , Cheul H. Cho , Arno W. Tilles
IPC分类号： A61K35/407 , C12N5/074 , A61P1/16
CPC分类号： A61K35/407 , C12N5/067 , C12N2500/30 , C12N2500/62 , C12N2501/23 , C12N2501/385 , C12N2501/39 , C12N2502/14 , C12N2506/02
摘要： One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. Although embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. The present invention provides for a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. In one embodiment, mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiate and proliferate into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17 and AFP, and could further differentiate into hepatocyte-like cells that demonstrate hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.
摘要翻译：用于治疗肝衰竭的细胞疗法的主要障碍之一是功能性人肝细胞的可用性低。尽管胚胎干细胞（ES）细胞代表治疗的潜在细胞来源，但目前的分化方法导致混合细胞群体或感兴趣细胞的低产量。本发明提供快速，直接的分化方法，其产生具有95％纯度的内胚层样细胞的均匀群体。在一个实施方案中，在胶原夹心的肝细胞上培养的小鼠ES细胞分化并增殖成内胚层样细胞的均匀且均匀的细胞群。内皮样细胞群对Foxa2，Sox17和AFP呈阳性，可进一步分化为肝细胞样细胞，其表现出肝脏形态，功能，基因和蛋白质表达。将肝细胞样细胞结合到生物人工肝脏装置中以治疗暴发性肝衰竭改善了动物存活，从而强调了这些细胞的治疗潜力。

10. 发明授权

US5942436A Culturing liver cells 失效
标题翻译：培养肝细胞
公开(公告)号：US5942436A
公开(公告)日：1999-08-24
申请号：US797427
申请日：1997-02-10
申请人： James Dunn , Ronald G. Tompkins , Martin L. Yarmush
发明人： James Dunn , Ronald G. Tompkins , Martin L. Yarmush
IPC分类号： C12N5/00 , C12N5/02 , C12N5/071
CPC分类号： C12N5/067 , C12N5/0068 , C12N5/0671 , C12N2533/54
摘要： A method for maintaining hepatocytes in culture includes providing the hepatocytes with a support, the support including extracellular matrix, the support having a configuration that permits each of at least a portion of the hepatpocytes to form at least one apical surface and at least two discrete basal surfaces.
摘要翻译：用于在培养物中维持肝细胞的方法包括向肝细胞提供载体，所述载体包括细胞外基质，所述载体具有允许至少一部分肝细胞中的每一个形成至少一个顶端表面和至少两个离散基底表面。

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