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1. 发明授权

US5854067A Hexokinase inhibitors 失效
标题翻译：己糖激酶抑制剂
公开(公告)号：US5854067A
公开(公告)日：1998-12-29
申请号：US588983
申请日：1996-01-19
申请人： Christopher B. Newgard , He-Ping Han , Karl D. Normington
发明人： Christopher B. Newgard , He-Ping Han , Karl D. Normington
IPC分类号： C07K14/62 , C12N9/10 , C12N9/12 , C12N15/113 , C12N15/54 , C12N15/85 , C12N15/00 , C12N15/63 , C12Q1/68
CPC分类号： C12N15/1137 , C07K14/62 , C12N9/1051 , C12N9/1205 , C12Y207/01001 , C12N2310/121
摘要： Disclosed are compositions and methods for inhibiting hexokinase enzymes in mammalian cells. Specifically provided are proteins that stimulate the production of trehalose-6-phosphate and their respective genes; hexokinase-specific ribozymes and genes encoding such constructs; and agents that competitively reduce hexokinase activity, e.g., by displacing hexokinase from mitochondria, and their respective genes. The latter group of agents includes inactive hexokinases and fragments thereof that retain mitochondrial binding functions and hexokinase-glucokinase chimeras that further substitute glucokinase activity for hexokinase activity. Mammalian cells including such hexokinase inhibitors, methods of making such cells and various in vitro and in vivo methods of using cells with reduced hexokinase activity are also described herein.
摘要翻译：公开了用于在哺乳动物细胞中抑制己糖激酶的组合物和方法。具体提供的是刺激海藻糖-6-磷酸及其各自基因的产生的蛋白质; 己糖激酶特异性核酶和编码这种构建体的基因; 以及竞争性降低己糖激酶活性的试剂，例如通过从线粒体置换己糖激酶及其各自的基因。后一组试剂包括保留线粒体结合功能的失活的己糖激酶及其片段和进一步用葡萄糖激酶活性替代己糖激酶活性的己糖激酶 - 葡糖激酶嵌合体。本文还描述了包括这种己糖激酶抑制剂的哺乳动物细胞，制备这种细胞的方法以及使用具有降低的己糖激酶活性的细胞的各种体外和体内方法。

2. 发明授权

US6110707A Recombinant expression of proteins from secretory cell lines 失效
标题翻译：来自分泌细胞系的蛋白质的重组表达
公开(公告)号：US6110707A
公开(公告)日：2000-08-29
申请号：US784582
申请日：1997-01-17
申请人： Christopher B. Newgard , Philippe Halban , Karl D. Normington , Samuel A. Clark , Anice E. Thigpen , Christian Quaade , Fred Kruse , Dennis McGarry
发明人： Christopher B. Newgard , Philippe Halban , Karl D. Normington , Samuel A. Clark , Anice E. Thigpen , Christian Quaade , Fred Kruse , Dennis McGarry
IPC分类号： C07K14/575 , C12P21/00
CPC分类号： C07K14/575
摘要： The present invention a provides methods for production of heterologous polypeptides, for example amylin, using recombinantly engineered cell lines. Also described are methods engineering cells for high level expression, methods of large scale heterologous protein production, methods for treatment of disease in vivo using viral delivery systems and recombinant cell lines, and methods for isolating novel amylin receptors.
摘要翻译：本发明提供使用重组工程改造的细胞系生产异源多肽例如胰岛淀粉样多肽的方法。还描述了用于高水平表达的工程细胞方法，大规模异源蛋白质生产的方法，使用病毒递送系统和重组细胞系在体内治疗疾病的方法，以及分离新的胰岛淀粉样多肽受体的方法。

3. 发明授权

US6087129A Recombinant expression of proteins from secretory cell lines 失效
标题翻译：来自分泌细胞系的蛋白质的重组表达
公开(公告)号：US6087129A
公开(公告)日：2000-07-11
申请号：US589028
申请日：1996-01-19
申请人： Christopher B. Newgard , Karl D. Normington , Samuel A. Clark , Anice E. Thigpen , Christian Quaade , Fred Kruse
发明人： Christopher B. Newgard , Karl D. Normington , Samuel A. Clark , Anice E. Thigpen , Christian Quaade , Fred Kruse
IPC分类号： A61K38/00 , A61K48/00 , C07K14/47 , C07K14/575 , C07K14/605 , C07K14/61 , C07K14/62 , C07K14/705 , C07K14/72 , C12N9/12 , C12N15/12 , C12N15/16 , C12N15/85 , C12P21/00 , C12P21/06 , C12Q1/68
CPC分类号： C12N9/1205 , C07K14/4702 , C07K14/575 , C07K14/605 , C07K14/61 , C07K14/62 , C07K14/705 , C07K14/72 , C12N15/85 , A01K2217/075 , A61K38/00 , A61K48/00 , C12N2830/00 , C12N2830/85 , C12N2840/203
摘要： The present invention a provides methods for production of heterologous polypeptides using a variety recombinantly engineered secretory cell lines. The common feature of these cell lines is the absence of expression of at least one endogenous polypeptide. The host cell machinery normally used to produce the endogenous polypeptide is then usurped for the purpose of making the heterologous polypeptide. Also described are methods engineering cells for high level expression, methods of large scale protein production, and methods for treatment of disease in vivo using viral delivery systems and recombinant cell lines.
摘要翻译：本发明提供使用多种重组工程分泌细胞系生产异源多肽的方法。这些细胞系的共同特征是不存在至少一种内源多肽的表达。通常用于产生内源多肽的宿主细胞机制然后被篡改以产生异源多肽。还描述了用于高水平表达的工程细胞，大规模蛋白质生产的方法，以及使用病毒递送系统和重组细胞系在体内治疗疾病的方法。

4. 发明授权

US06194176B1 Recombinant expression of proteins from secretory cell lines 失效
标题翻译：来自分泌细胞系的蛋白质的重组表达
公开(公告)号：US06194176B1
公开(公告)日：2001-02-27
申请号：US08785271
申请日：1997-01-17
申请人： Christopher B. Newgard , Philippe Halban , Karl D. Normington , Samuel A. Clark , Anice E. Thigpen , Christian Quaade , Fred Kruse
发明人： Christopher B. Newgard , Philippe Halban , Karl D. Normington , Samuel A. Clark , Anice E. Thigpen , Christian Quaade , Fred Kruse
IPC分类号： C12P2106
CPC分类号： C12N9/1205 , A01K2217/075 , A61K38/00 , A61K48/00 , C07K14/4702 , C07K14/575 , C07K14/605 , C07K14/61 , C07K14/62 , C07K14/705 , C07K14/72 , C12N15/85 , C12N2830/00 , C12N2830/85 , C12N2840/203
摘要： The present invention a provides methods for production of heterologous polypeptides using a variety recombinantly engineered secretory cell lines. The common feature of these cell lines is the absence of expression of at least one endogenous polypeptide. The host cell machinery normally used to produce the endogenous polypeptide is then usurped for the purpose of making the heterologous polypeptide. Also described are methods engineering cells for high level expression, methods of large scale protein production, and methods for treatment of disease in vivo using viral delivery systems and recombinant cell lines.
摘要翻译：本发明提供使用多种重组工程分泌细胞系生产异源多肽的方法。这些细胞系的共同特征是不存在至少一种内源多肽的表达。通常用于产生内源多肽的宿主细胞机制然后被篡改以产生异源多肽。还描述了用于高水平表达的工程细胞，大规模蛋白质生产的方法，以及使用病毒递送系统和重组细胞系在体内治疗疾病的方法。

5. 发明授权

US5891717A Methods and compositions for inhibiting hexokinase 失效
标题翻译：抑制己糖激酶的方法和组合物
公开(公告)号：US5891717A
公开(公告)日：1999-04-06
申请号：US588976
申请日：1996-01-19
申请人： Christopher B. Newgard , He-Ping Han , Thomas C. Becker , John E. Wilson
发明人： Christopher B. Newgard , He-Ping Han , Thomas C. Becker , John E. Wilson
IPC分类号： C07K14/62 , C12N9/12 , C12N5/10 , C12N15/56 , C12N15/62 , C12N15/85
CPC分类号： C12N9/1205 , C07K14/62
摘要： Disclosed are compositions and methods for inhibiting hexokinase enzymes in mammalian cells. Specifically provided are proteins that stimulate the production of trehalose-6-phosphate and their respective genes; hexokinase-specific ribozymes and genes encoding such constructs; and agents that competitively reduce hexokinase activity, e.g., by displacing hexokinase from mitochondria, and their respective genes. The latter group of agents includes inactive hexokinases and fragments thereof that retain mitochondrial binding functions and hexokinase-glucokinase chimeras that further substitute glucokinase activity for hexokinase activity. Mammalian cells including such hexokinase inhibitors, methods of making such cells and various in vitro and in vivo methods of using cells with reduced hexokinase activity are also described herein.
摘要翻译：公开了用于在哺乳动物细胞中抑制己糖激酶的组合物和方法。具体提供的是刺激海藻糖-6-磷酸及其各自基因的产生的蛋白质; 己糖激酶特异性核酶和编码这种构建体的基因; 以及竞争性降低己糖激酶活性的试剂，例如通过从线粒体置换己糖激酶及其各自的基因。后一组试剂包括保留线粒体结合功能的失活的己糖激酶及其片段和进一步用葡萄糖激酶活性替代己糖激酶活性的己糖激酶 - 葡糖激酶嵌合体。本文还描述了包括这种己糖激酶抑制剂的哺乳动物细胞，制备这种细胞的方法以及使用具有降低的己糖激酶活性的细胞的各种体外和体内方法。

6. 发明申请

US20100331247A1 PEPTIDE THERAPY FOR HYPERGLYCEMIA 有权
标题翻译：高血压药物治疗方法
公开(公告)号：US20100331247A1
公开(公告)日：2010-12-30
申请号：US12755907
申请日：2010-04-07
申请人： Christopher B. Newgard , Samuel B. Stephens , Jonathan C. Schisler
发明人： Christopher B. Newgard , Samuel B. Stephens , Jonathan C. Schisler
IPC分类号： A61K38/18 , A61K38/10 , A61K31/7088 , A61P3/10
CPC分类号： A61K31/7088 , A61K38/10
摘要： Methods of modulating blood glucose levels treating hyperglycemia and related complications and conditions by administration of a VGF biomolecule to a patient in need of such treatment are provided. Methods of enhancing insulin secretion from islet beta cells in a mammal exhibiting reduced insulin secretion by administration of a therapeutically effective amount of a VGF biomolecule are also provided.
摘要翻译：提供了通过向需要这种治疗的患者施用VGF生物分子来调节治疗高血糖症和相关并发症和病症的血糖水平的方法。还提供了通过施用治疗有效量的VGF生物分子来增强表现出胰岛素分泌降低的哺乳动物胰岛β细胞的胰岛素分泌的方法。

7. 发明授权

US5811266A Methods for producing human insulin 失效
标题翻译：生产人胰岛素的方法
公开(公告)号：US5811266A
公开(公告)日：1998-09-22
申请号：US312120
申请日：1994-09-26
申请人： Christopher B. Newgard
发明人： Christopher B. Newgard
IPC分类号： A61K35/39 , A61K48/00 , A61P3/10 , C07K14/62 , C12N9/12 , C12N15/113 , C12N15/12 , G01N33/50 , G01N33/564 , G01N33/566 , G01N33/567 , G01N33/569 , G01N33/66 , G01N33/74 , C12N15/17 , C12P21/02
CPC分类号： G01N33/564 , A61K35/39 , C07K14/62 , C12N15/1137 , C12N9/1205 , C12Y207/01001 , G01N33/50 , G01N33/566 , G01N33/567 , G01N33/56966 , G01N33/66 , G01N33/74 , A61K48/00 , C12N2310/111 , G01N2800/042
摘要： The present disclosure relates to the application of genetic engineering to provide artificial .beta. cells, i.e. cells which can secrete insulin in response to glucose. This is achieved preferably through the introduction of one or more genes selected from the insulin gene, glucokinase gene, and glucose transporter gene, so as to provide an engineered cell having all three of these genes in a biologically functional and responsive configuration. Assays for detecting the presence of diabetes-associated antibodies in biological samples using these and other engineered cells expressing diabetes-associated epitopes are described. Also disclosed are methods for the large-scale production of insulin by perfusing artificial .beta. cells, grown in liquid culture, with glucose-containing buffers.
摘要翻译：本公开涉及基因工程的应用以提供人造β细胞，即可响应葡萄糖分泌胰岛素的细胞。这优选通过引入选自胰岛素基因，葡糖激酶基因和葡萄糖转运蛋白基因的一种或多种基因来实现，从而提供具有生物学功能和反应性构型的这些基因全部三个的工程细胞。描述了使用这些和其它表达糖尿病相关表位的工程细胞来检测生物样品中糖尿病相关抗体的存在的测定。还公开了通过用含葡萄糖的缓冲液灌注在液体培养物中生长的人造β细胞大规模生产胰岛素的方法。

8. 发明申请

US20110318726A1 PREDICTING CORONARY ARTERY DISEASE AND RISK OF CARDIOVASCULAR EVENTS 审中-公开
标题翻译：预测冠状动脉疾病和心血管事件的风险
公开(公告)号：US20110318726A1
公开(公告)日：2011-12-29
申请号：US13255568
申请日：2010-03-10
申请人： Svati H. Shah , Christopher B. Newgard , William E. Kraus , Elizabeth R. Hauser , Geoffrey S. Ginsburg , L. Kristin Newby
发明人： Svati H. Shah , Christopher B. Newgard , William E. Kraus , Elizabeth R. Hauser , Geoffrey S. Ginsburg , L. Kristin Newby
IPC分类号： C12Q1/00 , H01J49/26 , G01N33/64 , G01N33/92 , G01N33/68 , G01N33/50
CPC分类号： G01N33/6887 , A61B5/00 , A61B5/14532 , A61B5/14546 , A61B5/4866 , A61B5/7275 , G01N21/78 , G01N2021/7786 , G01N2800/324 , G01N2800/50 , G16H50/30 , H01J49/0027 , Y10T436/174614 , Y10T436/200833 , Y10T436/201666
摘要： Methods of assessing the risk of cardiovascular disease in a subject by detecting the level of at least one metabolite in a sample from the subject are disclosed herein. The level of the metabolite is indicative of the risk of cardiovascular disease in the subject. The metabolites may be acylcarnitines, amino acids, ketones, free fatty acids or hydroxybutyrate. The cardiovascular disease may be risk of a cardiovascular event, presence of coronary artery disease or risk of development of coronary artery disease.
摘要翻译：本文公开了通过检测来自受试者的样品中至少一种代谢物的水平来评估受试者心血管疾病风险的方法。代谢物的水平表明受试者心血管疾病的风险。代谢物可以是酰基肉碱，氨基酸，酮类，游离脂肪酸或羟基丁酸酯。心血管疾病可能是心血管事件，冠状动脉疾病的存在或冠状动脉疾病发展的风险。

9. 发明授权

US5744327A Methods for producing insulin in response to non-glucose secretagogues 失效
标题翻译：用于响应于非葡萄糖促分泌素而产生胰岛素的方法
公开(公告)号：US5744327A
公开(公告)日：1998-04-28
申请号：US162044
申请日：1994-06-23
申请人： Christopher B. Newgard
发明人： Christopher B. Newgard
IPC分类号： A61K35/39 , A61K48/00 , A61P3/10 , C07K14/62 , C12N9/12 , C12N15/113 , C12N15/12 , G01N33/50 , G01N33/564 , G01N33/566 , G01N33/567 , G01N33/569 , G01N33/66 , G01N33/74 , C12P21/02 , C12N15/00
CPC分类号： G01N33/564 , A61K35/39 , C07K14/62 , C12N15/1137 , C12N9/1205 , C12Y207/01001 , G01N33/50 , G01N33/566 , G01N33/567 , G01N33/56966 , G01N33/66 , G01N33/74 , A61K48/00 , C12N2310/111 , G01N2800/042
摘要： The present disclosure relates to the application of genetic engineering to provide artificial .beta. cells, i.e. cells which can secrete insulin in response to glucose. This is achieved preferably through the introduction of one or more genes selected from the insulin gene, glucokinase gene, and glucose transporter gene, so as to provide an engineered cell having all three of these genes in a biologically functional and responsive configuration. Assays for detecting the presence of diabetes-associated antibodies in biological samples using these and other engineered cells expressing diabetes-associated epitopes are described. Also disclosed are methods for the large-scale production of insulin by perfusing artificial .beta. cells, grown in liquid culture, with glucose-containing buffers.
摘要翻译： PCT No.PCT / US92 / 04737 Sec。 371日期1994年6月23日 102（e）日期1994年6月23日PCT提交1992年6月2日PCT公布。出版物WO92 / 21979 日期1992年12月10日本公开内容涉及基因工程的应用以提供人造β细胞，即可响应葡萄糖分泌胰岛素的细胞。这优选通过引入选自胰岛素基因，葡糖激酶基因和葡萄糖转运蛋白基因的一种或多种基因来实现，从而提供具有生物学功能和反应性构型的这些基因全部三个的工程细胞。描述了使用这些和其它表达糖尿病相关表位的工程细胞来检测生物样品中糖尿病相关抗体的存在的测定。还公开了通过用含葡萄糖的缓冲液灌注在液体培养物中生长的人造β细胞大规模生产胰岛素的方法。

10. 发明授权

US5427940A Engineered cells producing insulin in response to glucose 失效
标题翻译：反应葡萄糖产生胰岛素的工程细胞
公开(公告)号：US5427940A
公开(公告)日：1995-06-27
申请号：US819326
申请日：1992-01-13
申请人： Christopher B. Newgard
发明人： Christopher B. Newgard
IPC分类号： A61K35/12 , A61K35/39 , A61K48/00 , A61P3/08 , C07K14/575 , C07K14/62 , C12N5/10 , C12N15/09 , C12N15/113 , C12N15/12 , C12P21/02 , C12P21/08 , C12R1/91 , G01N33/50 , G01N33/53 , G01N33/564 , G01N33/567 , G01N33/569 , G01N33/74 , C12N5/00 , C12N15/00 , C12Q1/68 , C12P21/06
CPC分类号： C12N15/1137 , A61K35/39 , C07K14/62 , C12Y207/01001 , G01N33/50 , G01N33/564 , G01N33/567 , G01N33/56966 , G01N33/74 , A61K48/00 , C12N2310/111 , G01N2800/042
摘要： The present disclosure relates to the application of genetic engineering to provide artificial .beta. cells, i.e. cells which can secrete insulin in response to glucose. This is achieved preferably through the introduction of one or more genes selected from the insulin gene, glucokinase gene, and glucose transporter gene, so as to provide an engineered cell having all three of these genes in a biologically functional and responsive configuration. Assays for detecting the presence of diabetes-associated antibodies in biological samples using these and other engineered cells expressing diabetes-associated epitopes are described. Also disclosed are methods for the large-scale production of insulin by perfusing artificial .beta. cells, grown in liquid culture, with glucose-containing buffers.
摘要翻译：本公开涉及基因工程的应用以提供人造β细胞，即可响应葡萄糖分泌胰岛素的细胞。这优选通过引入选自胰岛素基因，葡糖激酶基因和葡萄糖转运蛋白基因的一种或多种基因来实现，从而提供具有生物学功能和反应性构型的这些基因全部三个的工程细胞。描述了使用这些和其它表达糖尿病相关表位的工程细胞来检测生物样品中糖尿病相关抗体的存在的测定。还公开了通过用含葡萄糖的缓冲液灌注在液体培养物中生长的人造β细胞大规模生产胰岛素的方法。

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