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1. 发明申请

US20060029951A1 Polymorphism in tryptophan hydroxylase-2 controls brain serotonin synthesis 有权
公开(公告)号：US20060029951A1
公开(公告)日：2006-02-09
申请号：US11133949
申请日：2005-05-20
申请人： Marc Caron , Xiaodong Zhang , Martin Beaulieu , Raul Gainetdinov , Tatiana Sotnikova , Ranga Krishnan , David Schwartz , Lauranell Burch , Redford Williams
发明人： Marc Caron , Xiaodong Zhang , Martin Beaulieu , Raul Gainetdinov , Tatiana Sotnikova , Ranga Krishnan , David Schwartz , Lauranell Burch , Redford Williams
IPC分类号： C12Q1/68
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 screening a subject for a serotonergic neurotransmission dysregulation disorder comprises detecting the presence or absence of an Tph2 mutation in the subject; and then determining that the subject is at increased risk of a serotonergic neurotransmission dysregulation disorder due to the presence or absence of the Tph2 mutation.

2. 发明申请

US20060142375A1 Method for augmenting the effects of serotonin reuptake inhibitors 失效
公开(公告)号：US20060142375A1
公开(公告)日：2006-06-29
申请号：US11133867
申请日：2005-05-20
申请人： Ranga Krishnan , Marc Caron , Xiaodong Zhang , Martin Beaulieu , Raul Gainetdinova , Tatiana Sotnikova
发明人： Ranga Krishnan , Marc Caron , Xiaodong Zhang , Martin Beaulieu , Raul Gainetdinova , Tatiana Sotnikova
IPC分类号： A61K31/405 , A61K31/343 , A61K31/137
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 enahancer, (e.g., serotonin reuptake inhibitor). In preferred embodiments the disorder is depression, anxiety, or substance abuse.

3. 发明申请

US20080010692A1 Mammals carrying functional single nucleotide polymorphisms in brain-specific tryptophan hydroxylase 失效
标题翻译：在脑特异性色氨酸羟化酶中携带功能性单核苷酸多态性的哺乳动物
公开(公告)号：US20080010692A1
公开(公告)日：2008-01-10
申请号：US11825202
申请日：2007-07-05
申请人： Marc Caron , Xiaodong Zhang , Martin Beaulieu , Raul Gainetdinov , Tatyana Sotnikova
发明人： Marc Caron , Xiaodong Zhang , Martin Beaulieu , Raul Gainetdinov , Tatyana Sotnikova
IPC分类号： G01N33/00 , A01K67/00 , C12N5/00
CPC分类号： A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0356 , C12N9/0071 , C12N15/8509 , C12N2800/30
摘要： Recombinant or transgenic non-human mammals are described having a mutant tryptophan hydroxylase 2 (Tph2) gene resulting in altered synthesis of 5-hydroxytryptophan and serotonin in the brain. In some embodiments the mutant tryptophan hydroxylase 2 gene contains mouse R439H and/or P447R functional mutations, or their corresponding mutations in other species. Congenic non-human mammals having mutant tryptophan hydroxylase 2 genes are also provided. Methods of screening a compound for serotonergic activity or activity in treating a serotonergic neurotransmission dysregulation disorder are provided, which include administering a test compound to a recombinant non-human mammal and then detecting the presence or absence of serotonergic activity, or activity in treating a serotonergic neurotransmission dysregulation disorder, in the mammal. A cell such as a nerve cell (e.g., a central nervous system neuron) isolated from a transgenic or congenic mammal is also disclosed, along with cell cultures containing these cells. Such mammals and cells and cell cultures are useful in vitro for screening the activity of candidate compounds for their effect on serotonergic neurotransmission and for their activity in treating serotonergic neurotransmission dysregulation disorders.
摘要翻译：描述了具有突变色氨酸羟化酶2（Tph2）基因的重组或转基因非人哺乳动物，导致脑中5-羟色胺和5-羟色胺的合成改变。在一些实施方案中，突变色氨酸羟化酶2基因含有小鼠R439H和/或P447R功能性突变或其他物种中相应的突变。还提供了具有突变色氨酸羟化酶2基因的同种非人哺乳动物。提供了筛选化合物用于治疗血清素能神经递质调节障碍的5-羟色胺能活性或活性的方法，其包括向重组非人哺乳动物施用测试化合物，然后检测血清素能活性的存在或不存在或治疗血清素能的活性神经传递异常调节障碍。还公开了从转基因或同基因哺乳动物分离的细胞例如分离自转基因或同种哺乳动物的神经细胞（例如中枢神经系统神经元）以及含有这些细胞的细胞培养物。这样的哺乳动物和细胞和细胞培养物在体外可用于筛选候选化合物对5-羟色胺能神经传递的作用及其在治疗5-羟色胺能神经传递失调调节障碍中的活性。

4. 发明申请

US20060029983A1 Methods of screening compounds for GRK6 modulating activity 审中-公开
标题翻译：筛选化合物对GRK6调节活性的方法
公开(公告)号：US20060029983A1
公开(公告)日：2006-02-09
申请号：US11040218
申请日：2005-01-21
申请人： Robert Oakley , Christine Hudson , Marc Caron , Raul Gainetdinov , Robert Lefkowitz , Richard Premont
发明人： Robert Oakley , Christine Hudson , Marc Caron , Raul Gainetdinov , Robert Lefkowitz , Richard Premont
IPC分类号： G01N33/567 , G01N33/53
CPC分类号： C07K14/705 , C07K14/723 , C07K2319/033 , C12N9/1205 , G01N33/573 , G01N2333/726 , G01N2500/10
摘要： The present invention relates to methods of treating disease by altering G protein coupled receptor kinase (GRK) 6. This may be done by altering the expression or activity of the protein, for example. The present invention may be used for disease diagnosis, by detecting the expression or activity of GRK6. The present invention relates to a GRK6 deficient mouse, GRK6 splice variants, and methods of use. The present invention also relates to methods of identifying compounds that alter GRK6 activity. The present invention relates to disease treatment by altering GRK6 expression or activity.
摘要翻译：本发明涉及通过改变G蛋白偶联受体激酶（GRK）6来治疗疾病的方法。这可以通过例如改变蛋白质的表达或活性来进行。通过检测GRK6的表达或活性，可以将本发明用于疾病诊断。本发明涉及GRK6缺陷小鼠，GRK6剪接变体和使用方法。本发明还涉及鉴定改变GRK6活性的化合物的方法。本发明涉及通过改变GRK6表达或活性的疾病治疗。

5. 发明申请

US20080052785A1 ANIMAL MODEL OF CHOLINERGIC DYSFUNCTION TO EVALUATE COGNITIVE ENHANCERS AND DRUGS THAT IMPROVE MYASTHENIA 有权
标题翻译：用于评估增强认知增强剂和改善MYASTHENIA的药物的胆碱功能的动物模型
公开(公告)号：US20080052785A1
公开(公告)日：2008-02-28
申请号：US11842406
申请日：2007-08-21
申请人： Marc Caron , Vania Prado , Marco Prado , Raul Gainetdinov , Grace Pereira , Braulio Castro , Cristina Silva , Ivan Izquierdo
发明人： Marc Caron , Vania Prado , Marco Prado , Raul Gainetdinov , Grace Pereira , Braulio Castro , Cristina Silva , Ivan Izquierdo
IPC分类号： A01K67/027 , G01N33/00
CPC分类号： C07K14/70571 , A01K67/0276 , A01K2217/075 , A01K2217/20 , A01K2227/105 , A01K2267/0356 , C12N15/8509 , C12N2800/30
摘要： Recombinant non-human mammals having reduced or no expression of vesicular acetylcholine transporter protein (VAChT) as compared to the corresponding wild-type mammal are provided. The mammal may have, e.g., impaired performance in object and social recognition and/or impaired neuromuscular performance and/or alterations in autonomic nervous system function as compared to the corresponding wild-type mammal. Methods of screening a compound for cholinergic activity or activity in treating a cholinergic neurotransmission disorder are also provided. In addition, a cell such as a nerve cell isolated from a mammal as described herein is provided, along with cell cultures, which are useful in vitro for screening the activity of candidate compounds for their effect on cholinergic neurotransmission, and for their activity in treating cholinergic neurotransmission disorders.
摘要翻译：提供了与相应的野生型哺乳动物相比具有减少或不表达水泡乙酰胆碱转运蛋白（VAChT）的重组非人哺乳动物。与对应的野生型哺乳动物相比，哺乳动物可能具有例如对象和社会认知和/或受损的神经肌肉表现和/或自主神经系统功能的改变的性能受损。还提供了筛选化合物胆碱能活性或治疗胆碱能神经传递障碍的活性的方法。此外，提供了如本文所述的从哺乳动物分离的神经细胞的细胞以及细胞培养物，细胞培养物可用于体外筛选候选化合物对胆碱能神经传递的影响的活性，以及它们在治疗中的活性胆碱能神经传递障碍。

6. 发明申请

US20070027208A1 Antiparkinsonian Action of Phenylisopropylamines 有权
标题翻译：苯基异丙胺的抗帕金森病作用
公开(公告)号：US20070027208A1
公开(公告)日：2007-02-01
申请号：US11460046
申请日：2006-07-26
申请人： Marc Caron , Tatyana Sotnikova , Raul Gainetdinov
发明人： Marc Caron , Tatyana Sotnikova , Raul Gainetdinov
IPC分类号： A61K31/36 , A61K31/137
CPC分类号： A61K31/137 , A61K31/198 , A61K31/36 , A61K31/55 , A61K45/06
摘要： A method of treating a subject for Parkinson's disease comprises administering said subject a phenylisopropylamine in an amount effective to treat said Parkinson's disease. In some embodiments the method is used to treat at least a motor symptom of Parkinson's disease; in some embodiments the method is used to treat at least a non-motor symptom of Parkinson's disease.
摘要翻译：一种治疗受试者帕金森病的方法包括以有效治疗所述帕金森病的量给予所述受试者苯基异丙胺。在一些实施方案中，该方法用于治疗帕金森病的至少一种运动症状; 在一些实施方案中，该方法用于治疗帕金森病的至少一种非运动性症状。

7. 发明申请

US20060026702A1 Phosphoinositide 3-kinase mediated inhibition of GPCRs 审中-公开
公开(公告)号：US20060026702A1
公开(公告)日：2006-02-02
申请号：US10902137
申请日：2004-07-30
申请人： Howard Rockman , Sathyamangla Naga Prasad , Stephane Laporte , Larry Barak , Marc Caron
发明人： Howard Rockman , Sathyamangla Naga Prasad , Stephane Laporte , Larry Barak , Marc Caron
IPC分类号： G01N33/53 , G01N33/567 , A01K67/027
CPC分类号： A01K67/0275 , A01K2217/05 , G01N33/566 , G01N2333/726 , G01N2500/10
摘要： The present invention relates to compounds that alter GPCR internalization and new methods for their identification. Compounds of this invention include modified phosphoinositide 3-kinase (PI3K), modified HEAT domain, modified β-adrenergic receptor kinase 1 (βARK1), as well as other peptides or small molecules that alter GPCR internalization. The present invention also includes the use of such compounds to treat GPCR-related diseases, such as cardiovascular disease, heart failure, asthma, nephrogenic diabetes insipidus, or hypertension.

8. 发明申请

US20050106623A1 Modified G-protein coupled receptors 有权
标题翻译：修饰的G蛋白偶联受体
公开(公告)号：US20050106623A1
公开(公告)日：2005-05-19
申请号：US11026435
申请日：2004-12-30
申请人： Robert Oakley , Lawrence Barak , Stephane Laporte , Marc Caron
发明人： Robert Oakley , Lawrence Barak , Stephane Laporte , Marc Caron
IPC分类号： C07K14/705 , C12Q1/68 , C07H21/04
CPC分类号： C07K14/705
摘要： The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have carboxyl terminal tails comprising one or more sites of phosphorylation, preferably one or more clusters of phosphorylation sites. The modified GPCRs of the present invention may comprise a retained portion of a carboxyl-terminus region from a first GPCR fused to a polypeptide, wherein the polypeptide comprises the one or more clusters of phosphorylation. The present invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRS.
摘要翻译：本发明涉及修饰的G蛋白偶联受体（GPCR）。本发明的修饰的GPCR包括已被修饰为具有包含一个或多个磷酸化位点的羧基末端尾，优选一个或多个磷酸化位点簇的GPCR。本发明的修饰的GPCR可以包含与多肽融合的第一GPCR的羧基末端区域的保留部分，其中多肽包含一个或多个磷酸化簇。本发明还涉及使用修饰的GPCRS筛选化合物和GPCR活性的样品溶液的方法。

9. 发明申请

US20060188944A1 METHODS OF ASSAYING RECEPTOR ACTIVITY 有权
标题翻译：测定受体活性的方法
公开(公告)号：US20060188944A1
公开(公告)日：2006-08-24
申请号：US10141725
申请日：2002-05-09
申请人： Lawrence Barak , Marc Caron , Stephen Ferguson , Jie Zhang
发明人： Lawrence Barak , Marc Caron , Stephen Ferguson , Jie Zhang
IPC分类号： G01N33/53 , G01N33/567
CPC分类号： G01N33/5008 , C07K14/47 , C07K2319/00 , C07K2319/60 , C12N15/62 , G01N2333/726 , G01N2333/91
摘要： Described are methods of detecting G-protein coupled receptor (GPCR) activity in vivo and in vitro; methods of assaying GPCR activity; and methods of screening for GPCR ligands, G Protein-coupled receptor kinase (GRK) activity, and compounds that interact with components of the GPCR regulatory process.
摘要翻译：描述了体内和体外检测G蛋白偶联受体（GPCR）活性的方法; 测定GPCR活性的方法; 和筛选GPCR配体，G蛋白偶联受体激酶（GRK）活性和与GPCR调节过程的组分相互作用的化合物的方法。

10. 发明申请

US20060031369A1 Method, system, and edge multimedia messaging service (MMS) relay/server for multi-staged MMS 审中-公开
标题翻译：用于多级彩信的方法，系统和边缘多媒体消息业务（MMS）中继/服务器
公开(公告)号：US20060031369A1
公开(公告)日：2006-02-09
申请号：US10880473
申请日：2004-07-01
申请人： Marc Caron , Per Andersson , Andre Beliveau , Peter Helfer , Bernhard Meier
发明人： Marc Caron , Per Andersson , Andre Beliveau , Peter Helfer , Bernhard Meier
IPC分类号： G06F15/16
CPC分类号： H04M3/42382 , H04L51/14 , H04L51/38 , H04M3/537
摘要： A method, system and Edge Multimedia Messaging Service (MMS) Relay/Server for handling MMS messages in an MMS system, wherein incoming MMS messages are received at the Edge MMS Relay/Server from User Agents (UAs). The former determines criteria associated with the MMS messages and based on the criteria, selectively forwards the MMS messages to the proper MMS Relay/Server of a second stage of the MMS system, where the MMS messages are handled based on their type, and further delivered to the MMS recipients. Such criteria may include the retrieval time of the messages, the type of subscription of the user (prepaid vs postpaid), the need for transcoding the MMS message, and immediate vs future delivery time.
摘要翻译：用于在MMS系统中处理MMS消息的方法，系统和边缘多媒体消息服务（MMS）中继/服务器，其中在来自用户代理（UA）的边缘MMS中继/服务器处接收传入MMS消息。前者确定与MMS消息相关的标准并且基于标准，选择性地将MMS消息转发到MMS系统的第二阶段的适当的MMS中继/服务器，其中基于MMS类型的MMS消息被处理，并进一步传送给MMS收件人。这样的标准可以包括消息的检索时间，用户的订阅类型（预付费vs后付费），对MMS消息进行转码的需要，以及即时与未来的传送时间。

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