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1. 发明申请

US20090298169A1 Pancreatic and Liver Endoderm Cells and Tissue by Differentiation of Definitive Endoderm Cells Obtained from Human Embryonic Stems 审中-公开
标题翻译：胰腺和肝脏内胚层细胞和通过分化人胚胎干细胞获得的确定性内胚层细胞的组织
公开(公告)号：US20090298169A1
公开(公告)日：2009-12-03
申请号：US12227913
申请日：2007-06-04
申请人： Stephen Dalton , David Reynolds , Michael Kulik
发明人： Stephen Dalton , David Reynolds , Michael Kulik
IPC分类号： C12N5/08
CPC分类号： C12N5/067 , C12N5/0676 , C12N2501/115 , C12N2501/119 , C12N2501/16 , C12N2501/385 , C12N2501/415 , C12N2501/70 , C12N2502/13 , C12N2506/02
摘要： The invention relates to methods that allow for the efficient differentiation to form pancreatic endoderm cells from pluripotent stem cells such as human embryonic stem cells and definitive endoderm cells. The invention is directly applicable to the ultimate generation of pancreatic beta cells that could be used as part of a therapy to treat or even cure diabetes. Additionally, the present invention may be used to generate liver endoderm cells from human embryonic stem cells and definite endoderm cells as well. This invention relates to a method for generating definitive endoderm and pancreatic endoderm cells from stem cells, preferably human embryonic stem cells using defined media in the absence of feeder cells. A simply two step procedure to provide pancreatic endoderm cells from embryonic stem cells represents further embodiments of the present invention.
摘要翻译：本发明涉及允许有效分化以从多能干细胞如人胚胎干细胞和确定性内胚层细胞形成胰腺内胚层细胞的方法。本发明可直接应用于可用作治疗或甚至治愈糖尿病的治疗的一部分的胰腺β细胞的最终产生。另外，本发明也可用于从人胚胎干细胞和确定的内胚层细胞产生肝内胚层细胞。本发明涉及一种用于在不存在饲养细胞的情况下使用限定的培养基从干细胞产生确定性内胚层和胰腺内胚层细胞的方法，优选人胚胎干细胞。从胚胎干细胞提供胰腺内胚层细胞的简单的两步法代表了本发明的另外的实施方案。

2. 发明申请

US20100166713A1 EARLY MESODERM CELLS, A STABLE POPULATION OF MESENDODERM CELLS THAT HAS UTILITY FOR GENERATION OF ENDODERM AND MESODERM LINEAGES AND MULTIPOTENT MIGRATORY CELLS (MMC) 有权
标题翻译：早期MESODERM细胞，具有用于产生内膜和MESODERM线粒体和多重迁移细胞的MESENDODERM细胞的稳定群体（MMC）
公开(公告)号：US20100166713A1
公开(公告)日：2010-07-01
申请号：US12449237
申请日：2008-01-30
申请人： Stephen Dalton , David Reynolds
发明人： Stephen Dalton , David Reynolds
IPC分类号： A61K35/12 , C12N5/07 , C12N5/071 , C12N5/02 , C12N5/00
CPC分类号： C12N5/0603 , C12N5/0606 , C12N2500/90 , C12N2500/99 , C12N2501/155 , C12N2501/16 , C12N2501/195 , C12N2501/415 , C12N2501/70 , C12N2506/02
摘要： The present invention relates to the production of multipotent migratory cell (MMCs) which can be differentiated into mesoderm or endoderm lineages. Multipotent Migratory Cells (MMC) are stable and robust and can be passaged at least 20 times (perhaps indefinitely), can be recovered after freezing, reamplified and differentiated into multiple lineages. They are therefore storage stable. The method of producing these cells points to a way to generate a multipotent cell type (mesendoderm) from blastocycts for the generation of therapeutically useful cell types without going through a classical hESC state. The production of multipotent migratory cells, mesendoderm cells and mesoderm cells (Isl1+) is also described.
摘要翻译：本发明涉及可以分化为中胚层或内胚层谱系的多能迁移细胞（MMC）的生产。多能迁移细胞（MMC）是稳定和健壮的，可以传代至少20次（可能无限期），可以在冷冻，再次扩增和分化成多个谱系后恢复。因此它们是稳定的。生产这些细胞的方法指向从胚胎产生多能细胞类型（中内胚层）以产生治疗有用的细胞类型而不经历经典的hESC状态的方法。还描述了多潜移植细胞，中胚层细胞和中胚层细胞（Isl1 +）的产生。

3. 发明授权

US09175260B2 Early mesoderm cells, a stable population of mesendoderm cells that has utility for generation of endoderm and mesoderm lineages and multipotent migratory cells (MMC) 有权
标题翻译：早期中胚层细胞，具有用于产生内胚层和中胚层谱系和多能迁移细胞（MMC）的稳定的中内胚层细胞群体，
公开(公告)号：US09175260B2
公开(公告)日：2015-11-03
申请号：US12449237
申请日：2008-01-30
申请人： Stephen Dalton , David Reynolds
发明人： Stephen Dalton , David Reynolds
IPC分类号： C12N5/02 , C12N5/00 , C12N5/071 , A61K35/12 , C12N5/07 , C12N5/073 , C12N5/0735
CPC分类号： C12N5/0603 , C12N5/0606 , C12N2500/90 , C12N2500/99 , C12N2501/155 , C12N2501/16 , C12N2501/195 , C12N2501/415 , C12N2501/70 , C12N2506/02
摘要： The present invention relates to the production of multipotent migratory cell (MMCs) which can be differentiated into mesoderm or endoderm lineages. Multipotent Migratory Cells (MMC) are stable and robust and can be passaged at least 20 times (perhaps indefinitely), can be recovered after freezing, reamplified and differentiated into multiple lineages. They are therefore storage stable. The method of producing these cells points to a way to generate a multipotent cell type (mesendoderm) from blastocycts for the generation of therapeutically useful cell types without going through a classical hESC state. The production of multipotent migratory cells, mesendoderm cells and mesoderm cells (Isl1+) is also described.
摘要翻译：本发明涉及可以分化为中胚层或内胚层谱系的多能迁移细胞（MMC）的生产。多能迁移细胞（MMC）是稳定和健壮的，可以传代至少20次（可能无限期），可以在冷冻，再次扩增和分化成多个谱系后恢复。因此它们是稳定的。生产这些细胞的方法指向从胚胎产生多能细胞类型（中内胚层）以产生治疗有用的细胞类型而不经历经典的hESC状态的方法。还描述了多潜移植细胞，中胚层细胞和中胚层细胞（Isl1 +）的产生。

4. 发明授权

US5637463A Method to detect protein-protein interactions 失效
标题翻译：检测蛋白质 - 蛋白质相互作用的方法
公开(公告)号：US5637463A
公开(公告)日：1997-06-10
申请号：US434730
申请日：1995-05-04
申请人： Stephen Dalton , Jarema P. Kochan , Mark A. Osborne
发明人： Stephen Dalton , Jarema P. Kochan , Mark A. Osborne
IPC分类号： C12Q1/02 , C12Q1/68 , C12Q1/08 , C07H21/04 , C07K1/00 , C12P21/00
CPC分类号： C12Q1/02 , C12Q1/6897
摘要： Methods are provided for studying protein-protein interactions which require posttranslational modification of one of the proteins. The interaction is detected by reconstituting the activity of a transcriptional activator. This activity is dependent on the interactions between three different proteins. These include two chimeric proteins, one of which must be posttranslationally modified by the activity of the third protein in order for the chimeric proteins to interact. One of the chimeric proteins contains a transcriptional activation domain fused to a test protein. The second chimeric protein contains a DNA-binding domain of a transcriptional activator fused to the other test protein.
摘要翻译：提供了研究需要蛋白质之一翻译后修饰的蛋白质 - 蛋白质相互作用的方法。通过重组转录激活物的活性来检测相互作用。该活性取决于三种不同蛋白质之间的相互作用。这些包括两个嵌合蛋白，其中之一必须通过第三蛋白的活性进行翻译后修饰，以使嵌合蛋白相互作用。嵌合蛋白之一含有与测试蛋白融合的转录激活结构域。第二嵌合蛋白含有与另一测试蛋白融合的转录激活物的DNA结合结构域。

5. 发明授权

US09329169B2 Vivo isotopic labeling method for quantitative glycomics 有权
标题翻译：用于定量糖基化的体内同位素标记方法
公开(公告)号：US09329169B2
公开(公告)日：2016-05-03
申请号：US12734102
申请日：2008-10-29
申请人： Robert Lance Wells , Ronald C. Orlando , Stephen Dalton , Kelley W. Moremen , James Michael Pierce , James A. Atwood, III , Michael Tiemeyer , William S. York
发明人： Robert Lance Wells , Ronald C. Orlando , Stephen Dalton , Kelley W. Moremen , James Michael Pierce , James A. Atwood, III , Michael Tiemeyer , William S. York
IPC分类号： C12Q1/02 , G01N33/50 , G01N33/68
CPC分类号： G01N33/502 , G01N33/6848 , G01N2400/00 , G01N2400/12 , G01N2400/38 , G01N2458/15
摘要： The present invention relates to a method of isotopically labeling glycans and in facilitating high throughput quantitative/comparative analysis of glycomic compositions of biological cells. The method is applicable inter alia for identifying differentiated cells and their glycomic characteristics, differentiation conditions, disease and/or therapeutic progression, diagnosing disease states, determining drug activity, establishing manufacturing efficiencies and for determining the half-life of glycans in cells.
摘要翻译：本发明涉及同位素标记聚糖并促进生物细胞的糖组成的高通量定量/比较分析方法。该方法特别适用于鉴定分化细胞及其糖基特征，分化条件，疾病和/或治疗进展，诊断疾病状态，确定药物活性，建立制造效率和确定细胞中聚糖的半衰期。

6. 发明授权

US08187878B2 Methods for increasing definitive endoderm differentiation of pluripotent human embryonic stem cells with PI-3 kinase inhibitors 有权
标题翻译：用PI-3激酶抑制剂增加多能人胚胎干细胞的确定性内胚层分化的方法
公开(公告)号：US08187878B2
公开(公告)日：2012-05-29
申请号：US11573662
申请日：2005-08-15
申请人： Stephen Dalton , Allan Sheppard , Karen Jones , E. Edward Baetge , Kevin A. D'Amour , Alan D. Agulnick
发明人： Stephen Dalton , Allan Sheppard , Karen Jones , E. Edward Baetge , Kevin A. D'Amour , Alan D. Agulnick
IPC分类号： C12N5/00 , C12N5/075
CPC分类号： C12N5/0606 , C12N2500/34 , C12N2501/16 , C12N2501/405
摘要： The present invention provides compositions and methods for the production of differentiated mammalian cells. More particularly, the present invention provides cellular differentiation methods employing culturing the cells on a feeder layer or under feeder-free conditions in cell culture and further contacting the cells with an inhibitor of the PI3-kinase pathway and a member of the TGFb family for the generation of differentiated mammalian cells from pluripotent mammalian stem cells. Preferably, the differentiated cell is selected from the group consisting of a mesendodermal cell, a mesodermal cell, and an endodermal cell.
摘要翻译：本发明提供用于产生分化的哺乳动物细胞的组合物和方法。更具体地，本发明提供细胞分化方法，其使用在饲养层上培养细胞或在无饲养条件下在细胞培养中培养细胞，并进一步使细胞与PI3-激酶途径的抑制剂和TGFb家族的成员接触，用于从多能哺乳动物干细胞中产生分化的哺乳动物细胞。优选地，分化细胞选自中胚层细胞，中胚层细胞和内胚层细胞。

7. 发明申请

US20100297609A1 VIVO ISOTOPIC LABELING METHOD FOR QUANTITATIVE GLYCOMICS 有权
标题翻译：用于定量糖蛋白的VIVO同位素标记方法
公开(公告)号：US20100297609A1
公开(公告)日：2010-11-25
申请号：US12734102
申请日：2008-10-29
申请人： Robert Lance Wells , Ronald C. Orlando , Stephen Dalton , Kelley W. Moreman , Michael J. Pierce , James A. Attwood, III , Michael Tiemeyer , William S. York
发明人： Robert Lance Wells , Ronald C. Orlando , Stephen Dalton , Kelley W. Moreman , Michael J. Pierce , James A. Attwood, III , Michael Tiemeyer , William S. York
IPC分类号： C12Q1/70 , C12Q1/02
CPC分类号： G01N33/502 , G01N33/6848 , G01N2400/00 , G01N2400/12 , G01N2400/38 , G01N2458/15
摘要： The present invention relates to a method of isotopically labeling glycans and in facilitating high throughput quantitative/comparative analysis of glycomic compositions of biological cells. The method is applicable inter alia for identifying differentiated cells and their glycomic characteristics, differentiation conditions, disease and/or therapeutic progression, diagnosing disease states, determining drug activity, establishing manufacturing efficiencies and for determining the half-life of glycans in cells.
摘要翻译：本发明涉及同位素标记聚糖并促进生物细胞的糖组合物的高通量定量/比较分析的方法。该方法特别适用于鉴定分化细胞及其糖基特征，分化条件，疾病和/或治疗进展，诊断疾病状态，确定药物活性，建立制造效率和确定细胞中聚糖的半衰期。

8. 发明申请

US20080268533A1 Methods and Compositions Utilizing Myc and Gsk3Beta to Manipulate the Pluripotency of Embryonic Stem Cells 审中-公开
标题翻译：使用Myc和Gsk3Beta操纵胚胎干细胞多能性的方法和组合
公开(公告)号：US20080268533A1
公开(公告)日：2008-10-30
申请号：US11574280
申请日：2005-08-25
申请人： Stephen Dalton , Allan Sheppard , Cameron McLean
发明人： Stephen Dalton , Allan Sheppard , Cameron McLean
IPC分类号： C12N5/06
CPC分类号： C12N5/0606 , C12N2501/40 , C12N2501/70
摘要： The present invention provides methods for stabilizing pluripotent cells through the transcriptional activation of c-myc. Alternatively, the cells are stabilized through the transcriptional activation of c-myc, and the stabilization of c-myc protein levels. c-myc protein can be stabilized through the inhibition of GSK3β or through other components of the cellular machinery that impact on c-myc stability. The invention contemplates the stabilized pluripotent cells produced using the methods described herein. Methods for the identification of compounds that modulate the stabilization of pluripotent cells through modulating transcriptional activation of c-myc, stabilization of c-myc protein levels, and/or inhibition of GSK3β activity are also contemplated.
摘要翻译：本发明提供了通过c-myc的转录激活来稳定多能细胞的方法。或者，通过c-myc的转录激活和c-myc蛋白水平的稳定来稳定细胞。 c-myc蛋白可以通过抑制GSK3β或通过影响c-myc稳定性的细胞机器的其他成分来稳定。本发明考虑使用本文所述的方法产生的稳定的多能细胞。还考虑了通过调节c-myc的转录激活，c-myc蛋白水平的稳定和/或GSK3β活性的抑制来鉴定调节多能细胞稳定化合物的方法。

9. 发明申请

US20050017511A1 Gravity air motion concept 审中-公开
标题翻译：重力空气运动概念
公开(公告)号：US20050017511A1
公开(公告)日：2005-01-27
申请号：US10637114
申请日：2003-08-11
申请人： Stephen Dalton
发明人： Stephen Dalton
IPC分类号： F03G3/02 , F03G7/08 , F03G7/10 , H02P9/04
CPC分类号： F03G7/08 , F03G3/00
摘要： The G.A.M. machine or design can be adapted to any size of power source. The engineering calculus has been instructed at today's date which will result in an exact science of the use of weight, gravity and measurements of distance involved to create the torque or resistance. The machine requires no fossil fuels nor does it omit any poisonous gases or effluent. The workings housed within the arms air compressor, piston, piston shaft and weight will be combined in a unique system to ultimately result in the rotation of the arms (windmill style) which will turn a drive shaft to generate power for any purpose.
摘要翻译： G.A.M. 机器或设计可以适应任何尺寸的电源。工程演算在今天已经被指示，这将导致使用重量，重力和测量距离的精确科学来产生扭矩或阻力。该机器不需要化石燃料，也不排除任何有毒气体或废水。臂内空气压缩机，活塞，活塞轴和重量中的工作将结合在一个独特的系统中，最终导致臂（风车式）的旋转，这将转动驱动轴以产生任何用途的动力。

10. 发明申请

US20130280804A1 DIFFERENTIATION OF HUMAN PLURIPOTENT STEM CELLS TO MULTIPOTENT NEURAL CREST CELLS 审中-公开
标题翻译：人多能干细胞分化为多发性神经细胞
公开(公告)号：US20130280804A1
公开(公告)日：2013-10-24
申请号：US13977387
申请日：2011-12-19
申请人： Stephen Dalton , Laura M. Menendez
发明人： Stephen Dalton , Laura M. Menendez
IPC分类号： C12N5/0797
CPC分类号： C12N5/0623 , C12N2501/155 , C12N2501/16 , C12N2501/415 , C12N2501/998 , C12N2506/02 , C12N2506/45
摘要： The present invention relates to the differentiation of human pluripotent cells, including human pluripotent stems cells to produce a self-renewing multipotent neural crest cell population in a single step method without the requirement of isolation of intermediate cells and without appreciable contamination (in certain preferred instances, virtually none) with Pax6+ neural progenitor cells in the population of p75+ Hnk1+ Ap2+ multipotent neural crest-like cells. The multipotent neural crest cell population obtained can be clonally amplified and maintained for >25 passages (>100 days) while retaining the capacity to differentiate into peripheral neurons, smooth muscle cells and mesenchymal precursor cells.
摘要翻译：本发明涉及人多能细胞的分化，包括人多能干细胞，以在单步法中产生自我更新的多能神经嵴细胞群体，而不需要分离中间细胞并且没有明显的污染（在某些优选实例中，几乎没有）与P75 + Hnk1 + Ap2 +多能神经嵴样细胞群体中的Pax6 +神经祖细胞。获得的多能神经嵴细胞群可以被克隆扩增并维持> 25代（> 100天），同时保留分化为周围神经元，平滑肌细胞和间充质前体细胞的能力。

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