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11. 发明授权

US06605424B1 Method of detecting inhibitors of agonist-specific desensitization 失效
标题翻译：检测激动剂特异性脱敏抑制剂的方法
公开(公告)号：US06605424B1
公开(公告)日：2003-08-12
申请号：US09568983
申请日：2000-05-11
申请人： Robert J. Lefkowitz , Martin J. Lohse , Jeffrey L. Benovic , Marc G. Caron
发明人： Robert J. Lefkowitz , Martin J. Lohse , Jeffrey L. Benovic , Marc G. Caron
IPC分类号： C12Q300
CPC分类号： A61K31/715 , A61K31/21 , A61K31/66 , A61K31/675 , A61K38/1787 , G01N33/566 , G01N33/573
摘要： The present invention relates to a method of inhibiting desensitization of a cell to the effects of a compound. The method comprises contacting the cell with an agent capable of inhibiting phosphorylation, by a protein kinase, of a receptor for the compound present on the surface of the cell. The present invention also relates to a method of screening a compound for its ability to inhibit desensitization. The method comprises: i) contacting a receptor specific kinase-containing sample with the compound under conditions such that interaction between receptor specific kinase present in the sample and the compound can occur, and ii) determining the ability of the receptor specific kinase to phosphorylate the receptor for which it is specific.
摘要翻译：本发明涉及抑制细胞对化合物作用的脱敏的方法。该方法包括使细胞与能够通过蛋白激酶抑制存在于细胞表面的化合物的受体的磷酸化的试剂接触。本发明还涉及一种筛选化合物抑制脱敏能力的方法。该方法包括：i）使受体特异性激酶样品与化合物在使得存在于样品中的受体特异性激酶与化合物之间发生相互作用的条件下接触，以及ii）确定受体特异性激酶使受体磷酸化的能力它是具体的。

12. 发明授权

US5739029A Vectors for expression of G protein coupled receptors in yeast 失效
标题翻译：用于在酵母中表达G蛋白偶联受体的载体
公开(公告)号：US5739029A
公开(公告)日：1998-04-14
申请号：US441291
申请日：1995-05-15
申请人： Klim King , Henrik G. Dohlman , Marc G. Caron , Robert J. Lefkowitz
发明人： Klim King , Henrik G. Dohlman , Marc G. Caron , Robert J. Lefkowitz
IPC分类号： C07K14/39 , C07K14/47 , C07K14/705 , C12N1/18 , C12N1/19 , C12N15/09 , C12N15/12 , C12N15/74 , C12N15/81 , C12P21/02 , C12Q1/00 , C12Q1/02 , C12Q1/68 , C12R1/865 , G01N33/566 , C12N15/62
CPC分类号： G01N33/566 , C07K14/39 , C07K14/4722 , C07K14/70571 , C12N15/81 , C12Q1/6897 , C07K2319/00 , C07K2319/02 , C07K2319/32 , C07K2319/61 , C07K2319/705 , G01N2333/726 , G01N2500/00
摘要： Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protein coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein .alpha. subunit (mammalian G.sub..alpha.). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein .alpha.-subunit (yeast G.sub..alpha.). The cells are useful for screening compounds which affect the rate of dissociation of G.sub..alpha. from G.sub..beta..tau. in a cell. Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein coupled receptor. A second segment is positioned downstream from the first segment (and in correct reading frame therewith), with the second segment comprising a DNA sequence encoding a heterologous G protein coupled receptor.
摘要翻译：公开了含有编码哺乳动物G蛋白偶联受体的第一异源DNA序列和编码哺乳动物G蛋白α亚基（哺乳动物Gα）的第二异源DNA序列的转化酵母细胞。第一和第二异源DNA序列能够在细胞中表达，但是细胞不能表达内源性G蛋白α亚基（酵母Gα）。细胞可用于筛选影响细胞中Gα从Gβtau解离速率的化合物。还公开了用于如上所述制备细胞的新型DNA表达载体。载体含有至少包含酵母G蛋白偶联受体的极端氨基末端编码序列的片段的第一片段。第二片段位于第一片段的下游（并且在其正确的阅读框架中），其中第二片段包含编码异源G蛋白偶联受体的DNA序列。

13. 发明申请

US20090263317A1 METHOD OF SCREENING THE ACTIVITY OF THE SMOOTHENED RECEPTOR TO IDENTIFY THERAPUTIC MODULATION AGENTS OR DIAGNOSE DISEASE 审中-公开
标题翻译：筛选平滑肌受体活性鉴定治疗药物或诊断疾病的方法
公开(公告)号：US20090263317A1
公开(公告)日：2009-10-22
申请号：US12097697
申请日：2006-12-14
申请人： Wei Chen , Lawrence S. Barak , Marc G. Caron , Robert Lefkowitz
发明人： Wei Chen , Lawrence S. Barak , Marc G. Caron , Robert Lefkowitz
IPC分类号： A61K51/00 , C12Q1/48 , A61K49/00
CPC分类号： G01N33/5011 , G01N33/57492
摘要： The invention relates to a screening method for the Smoothened receptor for testing compositions as potential Smoothened receptor ligands, either agonist or antagonist activity, by use of an arrestin-reporter molecule conjugate. It also relates to testing cells and individuals by administering a smoothened receptor ligand-reporter molecule conjugate and observing locations where the ligand binds and then using an increased number of surface Smoothened receptors compared to a pre-established criteria as an indication of a cancerous growth or tumor.
摘要翻译：本发明涉及平滑化受体的筛选方法，通过使用抑制蛋白 - 报告分子缀合物将组合物测试为潜在的平滑受体配体，即激动剂或拮抗剂活性。它还涉及通过施用平滑化的受体配体 - 报告分子缀合物和观察配体结合的位置，然后使用增加数目的表面平滑受体来测试细胞和个体，与预先确定的标准相比，作为癌性生长的指示或瘤。

14. 发明申请

US20090226949A1 Single-cell biosensor for the measurement of GPCR ligands in a test sample 审中-公开
标题翻译：用于测试样品中GPCR配体的单细胞生物传感器
公开(公告)号：US20090226949A1
公开(公告)日：2009-09-10
申请号：US12398027
申请日：2009-03-04
申请人： Lawrence S. Barak , Michael A. Shetzline , Robert H. Oakley , Marc G. Caron
发明人： Lawrence S. Barak , Michael A. Shetzline , Robert H. Oakley , Marc G. Caron
IPC分类号： C12Q1/46
CPC分类号： G01N33/5035 , G01N33/5008 , G01N33/5014 , G01N33/5091 , G01N33/74 , G01N2333/5758 , G01N2333/70571 , G01N2333/726
摘要： The present invention is related to the detection of GPCR ligands in a test sample by using a single cell biosensor expressing a GPCR. Preferably, the test sample is derived from a biological or environmental sample. This invention may be used to detect the presence of a disease or to detect the presence of a harmful agent in the environment. Included in the present invention is an array of biosensors that detect ligands of various GPCRs.
摘要翻译：本发明涉及通过使用表达GPCR的单细胞生物传感器检测测试样品中的GPCR配体。优选地，测试样品来自生物或环境样品。本发明可用于检测疾病的存在或检测环境中有害物质的存在。本发明包括检测各种GPCR的配体的生物传感器阵列。

15. 发明申请

US20090192166A1 METHOD FOR AUGMENTING THE EFFECTS OF SEROTONIN REUPTAKE INHIBITORS 审中-公开
标题翻译：补充硒激酶抑制剂的作用方法
公开(公告)号：US20090192166A1
公开(公告)日：2009-07-30
申请号：US12397806
申请日：2009-03-04
申请人： Ranga R. Krishnan , Marc G. Caron , Xiaodong Zhang , Martin Beaulieu , Raul R. Gainetdinova , Tatiana D. Sotnikova
发明人： Ranga R. Krishnan , Marc G. Caron , Xiaodong Zhang , Martin Beaulieu , Raul R. Gainetdinova , Tatiana D. Sotnikova
IPC分类号： A61K31/405 , A61K31/519 , A61K31/4525 , A61K31/343 , A61K31/195 , A61K31/15 , A61K31/136 , A61K31/138
CPC分类号： A61K45/06 , A61K31/137 , A61K31/14 , A61K31/343 , A61K31/405 , C12Q1/6883 , C12Q2600/106 , C12Q2600/156
摘要： A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, comprises administering the subject a serotonin enhancer (e.g., a serotonin reuptake inhibitor) in an amount effective to treat the disorder; and concurrently administering the subject 5-hydroxytryptophan in an amount effective to enhance the activity of the serotonin enhancer, (e.g., serotonin reuptake inhibitor). In preferred embodiments the disorder is depression, anxiety, or substance abuse.
摘要翻译：用于治疗受试者血清素能神经递质调节障碍的方法包括以有效治疗该病症的量施用受试者血清素增强剂（例如5-羟色胺再摄取抑制剂）; 并且以有效增强5-羟色胺增强剂（例如5-羟色胺再摄取抑制剂）的活性的量同时施用受试者5-羟色氨酸。在优选的实施方案中，该疾病是抑郁，焦虑或药物滥用。

16. 发明授权

US07163800B2 Methods of screening compositions for G protein-coupled receptor desensitization inhibitory activity 有权
标题翻译：筛选G蛋白偶联受体脱敏抑制活性组合物的方法
公开(公告)号：US07163800B2
公开(公告)日：2007-01-16
申请号：US10633438
申请日：2003-08-01
申请人： Robert H. Oakley , Lawrence S. Barak , Stephane A. Laporte , Marc G. Caron
发明人： Robert H. Oakley , Lawrence S. Barak , Stephane A. Laporte , Marc G. Caron
IPC分类号： G01N33/566
CPC分类号： C07K14/705
摘要： The methods of the present invention allow the screening of a test composition for non-receptor-specific GPCR desensitization inhibitory activity. The methods involve screening a test composition for an indication of GPCR desensitization inhibitory activity against two or more GPCRs that are different from each other. When there is an indication that a particular test composition has GPCR desensitization inhibitory activity with respect to each of the two or more GPCRs that are different from one another, then, according to the present invention, there is an indication that the test composition has non-receptor-specific GPCR desensitization inhibitory activity.
摘要翻译：本发明的方法允许筛选非受体特异性GPCR脱敏抑制活性的测试组合物。所述方法包括筛选测试组合物以对于彼此不同的两个或多个GPCR的GPCR脱敏抑制活性的指示。当存在特定测试组合物相对于彼此不同的两个或更多个GPCR中的每一个具有GPCR脱敏抑制活性的指示时，根据本发明，存在测试组合物具有非 - - 受体特异性GPCR脱敏抑制活性。

17. 发明授权

US06855550B2 Expression of G protein coupled receptors in yeast 失效
标题翻译：酵母中G蛋白偶联受体的表达
公开(公告)号：US06855550B2
公开(公告)日：2005-02-15
申请号：US09752145
申请日：2000-12-29
申请人： Klim King , Henrik G. Dohlman , Marc G. Caron , Robert J. Lefkowitz
发明人： Klim King , Henrik G. Dohlman , Marc G. Caron , Robert J. Lefkowitz
IPC分类号： C07K14/39 , C07K14/47 , C07K14/705 , C12N1/18 , C12N1/19 , C12N15/09 , C12N15/12 , C12N15/74 , C12N15/81 , C12P21/02 , C12Q1/00 , C12Q1/02 , C12Q1/68 , C12R1/865 , G01N33/566 , C12P21/04 , G01N33/569
CPC分类号： G01N33/566 , C07K14/39 , C07K14/4722 , C07K14/70571 , C07K2319/00 , C07K2319/02 , C07K2319/32 , C07K2319/61 , C07K2319/705 , C12N15/81 , C12Q1/6897 , G01N2333/726 , G01N2500/00
摘要： Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protean coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein α subunit (mammalian Gα). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein α-subunit (yeast Gα). The cells are useful for screening compounds which affect the rate of dissociation of Gα from Gβτ in a cell.Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein coupled receptor. A second segment is positioned downstream from the first segment (and in correct reading frame therewith), with the second segment comprising a DNA sequence encoding a heterologous G protein coupled receptor.
摘要翻译：公开了含有编码哺乳动物G蛋白偶联受体的第一异源DNA序列和编码哺乳动物G蛋白α亚基（哺乳动物Galpha）的第二异源DNA序列的转化酵母细胞。第一和第二异源DNA序列能够在细胞中表达，但是细胞不能表达内源性G蛋白α亚基（酵母Galpha）。细胞可用于筛选影响细胞中Gbetatau中Galpha解离速率的化合物。还公开了一种用于如上所述制备细胞的新型DNA表达载体。载体含有至少包含酵母G蛋白偶联受体的极端氨基末端编码序列的片段的第一片段。第二片段位于第一片段的下游（并且在其正确的阅读框架中），其中第二片段包含编码异源G蛋白偶联受体的DNA序列。

18. 发明授权

US06528271B1 Inhibition of &bgr;arrestin mediated effects prolongs and potentiates opioid receptor-mediated analgesia 失效
标题翻译：抑制βarrestin介导的作用延长并增强阿片受体介导的镇痛作用
公开(公告)号：US06528271B1
公开(公告)日：2003-03-04
申请号：US09469554
申请日：1999-12-22
申请人： Laura M. Bohn , Fang-Tsyr Lin , Marc G. Caron , Robert J. Lefkowitz
发明人： Laura M. Bohn , Fang-Tsyr Lin , Marc G. Caron , Robert J. Lefkowitz
IPC分类号： C07K1400
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0356 , A01K2267/0393 , C07K14/47 , C07K14/4702 , C07K2319/00 , C07K2319/60 , C12N15/62
摘要： The present invention provides a &bgr;arrestin knockout mouse useful for screeening compounds for efficacy in controlling pain, methods of controlling pain in subjects by inhibiting binding of &bgr;arrestin to phosphorylated &mgr; opioid receptors, and methods of screening a compound for activity in potentiating &mgr; opioid receptor agonist activity (e.g., morphine activity) by determining whether or not said compound inhibits &bgr;arrestin binding to a phosphorylated &mgr; opioid receptor.
摘要翻译：本发明提供了一种可用于抑制化合物治疗疼痛疗效的贝伐星蛋白敲除小鼠，通过抑制βarrestin与磷酸化的阿片样物质受体的结合来控制受试者的疼痛的方法，以及筛选化合物以增强μ阿片受体激动剂活性的活性的方法（例如，吗啡活性），通过确定所述化合物是否抑制βarrestin与磷酸化的阿片样物质受体结合。

19. 发明授权

US06218595B1 Dopamine transporter knockout mice 有权
标题翻译：多巴胺转运蛋白敲除小鼠
公开(公告)号：US06218595B1
公开(公告)日：2001-04-17
申请号：US09134185
申请日：1998-08-14
申请人： Bruno Giros , Mohamed Jaber , Marc G. Caron
发明人： Bruno Giros , Mohamed Jaber , Marc G. Caron
IPC分类号： G01N3315
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0356 , A61K49/0008 , C07K14/47 , C07K14/4702
摘要： A recombinant rodent comprises cells containing a pair genomic dopamine transporter protein alleles, wherein at least one of said alleles is incapable of expressing endogenous dopamine transporter protein. The rodent may be a homozygote, where both of said alleles are incapable of expressing endogenous dopamine transporter protein, or the rodent may be a heterozygote, and one of said alleles expresses endogenous dopamine transporter protein. The rodent is preferably a mouse.
摘要翻译：重组啮齿动物包含含有一对基因组多巴胺转运蛋白等位基因的细胞，其中至少一个所述等位基因不能表达内源性多巴胺转运蛋白。啮齿动物可以是纯合子，其中两个所述等位基因都不能表达内源性多巴胺转运蛋白，或者啮齿动物可以是杂合子，并且所述等位基因之一表达内源性多巴胺转运蛋白。啮齿动物优选是小鼠。

20. 发明授权

US5215915A Cloned gene encoding rat D.sub.1B dopamine receptor 失效
标题翻译：克隆基因编码大鼠D1B多巴胺受体
公开(公告)号：US5215915A
公开(公告)日：1993-06-01
申请号：US686591
申请日：1991-04-16
申请人： Mario Tiberi , Keith R. Jarvie , Marc G. Caron
发明人： Mario Tiberi , Keith R. Jarvie , Marc G. Caron
IPC分类号： C07K14/705 , C12N15/12
CPC分类号： C07K14/70571
摘要： Disclosed is isolated DNA encoding a D.sub.1B -dopamine receptor selected from the group consisting of: (a) isolated DNA which encodes rat D.sub.1B -dopamine receptor; (b) isolated DNA which hybridizes to isolated DNA of (a) above and which encodes a D.sub.1B -dopamine receptor; and (c) isolated DNA differing from the isolated DNAs of (a) and (b) above in codon sequence due to the degeneracy of the genetic code, and which encodes a D.sub.1B dopamine receptor Vectors and host cells containing the same, assay procedures employing D.sub.1B -dopamine receptors, oligonucleotide probes for identifying D.sub.1B -dopamine receptors, and isolated and purified D.sub.1B -dopamine receptors are also disclosed.
摘要翻译：公开了编码D1B-多巴胺受体的分离的DNA，其选自：（a）编码大鼠D1B-多巴胺受体的分离的DNA; （b）分离的DNA，其与上述（a）的分离的DNA杂交并编码D1B-多巴胺受体; 和（c）由于遗传密码的简并性，编码D1B多巴胺受体载体和含有相同的宿主细胞的密码子序列中与上述（a）和（b）的分离的DNA不同的分离的DNA，采用还公开了D1B-多巴胺受体，用于鉴定D1B-多巴胺受体的寡核苷酸探针，以及分离和纯化的D1B-多巴胺受体。

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