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1. 发明申请

WO2007047127A3 OPTIMIZED TRPM8 NUCLEIC ACID SEQUENCES AND THEIR USE IN CELL BASED ASSAYS AND TEST KITS TO IDENTIFY TRPM8 MODULATORS 审中-公开
标题翻译：优化的TRPM8核酸序列及其在基于细胞的测定和试剂盒中识别TRPM8调节子的应用
公开(公告)号：WO2007047127A3
公开(公告)日：2007-07-26
申请号：PCT/US2006038962
申请日：2006-10-04
申请人： SENOMYX INC , SERVANT GUY , BRUST PAUL , MOYER BRYAN , LU MIN , ECHEVERRI FERNANDO , DAHAN DAVID , ZOLLER MARK , WILLIAMS MARK , KIMMICH RACHEL , KAMDAR POONIT , DITSCHUN TANYA , PATRON ANDREW
发明人： SERVANT GUY , BRUST PAUL , MOYER BRYAN , LU MIN , ECHEVERRI FERNANDO , DAHAN DAVID , ZOLLER MARK , WILLIAMS MARK , KIMMICH RACHEL , KAMDAR POONIT , DITSCHUN TANYA , PATRON ANDREW
IPC分类号： G01N33/53 , C07H21/04 , C07K1/00
CPC分类号： C07K14/705
摘要： Modified human TRPM8 nucleic acid sequences which are efficiently expressed in human cells and cell-based assays and test kits containing same are provided. These assays identify TRPM8 modulators using cells that express a modified human TRPM8 nucleic acid sequence according to the invention, wherein said sequence has been modified relative to a wild-type human TRPM8 nucleic acid sequence in order to optimize ion channel expression in desired cells. Assays using these modified TRPM8 sequences have been shown to identify compounds that modulate the human TRPM8 ion channel better or comparably to known coolants such as menthol and icilin.
摘要翻译：提供了在人细胞中有效表达的修饰的人TRPM8核酸序列和基于细胞的测定法以及包含其的测试试剂盒。这些测定法使用表达根据本发明的修饰的人TRPM8核酸序列的细胞鉴定TRPM8调节剂，其中所述序列相对于野生型人TRPM8核酸序列进行了修饰以优化所需细胞中的离子通道表达。已显示使用这些修饰的TRPM8序列的测定鉴定了比已知的冷却剂如薄荷醇和icilin更好或更可比的调节人TRPM8离子通道的化合物。

2. 发明申请

WO2007047985A2 TRPM5 BASED ASSAYS AND THE USE THEREOF FOR THE IDENTIFICATION OF MODULATORS OF SWEET, BITTER OR UMAMI (SAVORY) TASTE 审中-公开
标题翻译：基于TRPM5的测定及其用于鉴定甜味剂，铋或麝香（调味品）调味剂的调味品的用途
公开(公告)号：WO2007047985A2
公开(公告)日：2007-04-26
申请号：PCT/US2006041152
申请日：2006-10-19
申请人： SENOMYX INC , SERVANT GUY , WILLIAMS MARK , PATRON ANDREW , KAMDAR POONIT , CHEN QING , MOYER BRYAN , DAHAN DAVID , DITSCHUN TANYA , RAY SUMITA , LIGANI AMY
发明人： SERVANT GUY , WILLIAMS MARK , PATRON ANDREW , KAMDAR POONIT , CHEN QING , MOYER BRYAN , DAHAN DAVID , DITSCHUN TANYA , RAY SUMITA , LIGANI AMY
IPC分类号： E01C3/06
CPC分类号： E01C3/06
摘要： Robust cell based assays are provided that use cells that express wild-type or modified TRPM5 nucleic acid sequences in order to identify putative taste modulators, preferably sweet, bitter and umami taste modulators. The preferred assays use HEK-293 cells that express TRPM5, optionally at least one GPCR, preferably a taste specific GPCR, and a G protein that couples therewith. These assays detect TRPM5 modulators by use of membrane potential dyes that emit fluorescence on changes in TRPM5 activity based on changes in membrane potential and these changes in fluorescence are detectable using Fluorimetric Imaging Plate Readers (FLIPR).
摘要翻译：提供了基于稳健细胞的测定法，其使用表达野生型或修饰型TRPM5核酸序列的细胞，以鉴定推定的味觉调节剂，优选甜味，苦味和鲜味调味剂。优选的测定法使用表达TRPM5，任选地至少一种GPCR，优选味道特异性GPCR的HEK-293细胞和与其偶联的G蛋白。这些测定法通过使用膜电位染料检测TRPM5调节剂，其基于膜电位的变化发射荧光的TRPM5活性的变化，并且使用荧光成像板读数器（FLIPR）检测这些荧光变化。

3. 发明申请

WO2009008950A3 IDENTIFICATION OF TRPML3 (MCOLN3) AS A SALTY TASTE RECEPTOR AND USE IN ASSAYS FOR IDENTIFYING TASTE (SALTY) MODULATORS AND/OR THERAPEUTICS THAT MODULATE SODIUM TRANSPORT, ABSORPTION OR EXCRETION AND/OR ALDOSTERONE AND/OR VASOPRESSIN PRODUCTION OR REL 审中-公开
标题翻译：鉴定作为盐酸受体的TRPML3（MCOLN3）和用于鉴定调节运输，吸收或/或阿尔斯酮和/或维生素C生产或替代物的硫酸盐（SALTY）调节剂和/或治疗剂的测定中的用途
公开(公告)号：WO2009008950A3
公开(公告)日：2009-12-30
申请号：PCT/US2008007101
申请日：2008-06-06
申请人： SENOMYX INC , MOYER BRYAN , ZLOTNIK ALBERT , HEVEZI PETER , SOTO HORTENSIA , LU MIN , GAO NA , SERVANT GUY , BRUST PAUL , WILLIAMS MARK , KALABAT DALIA , WHITE EVAN CARL , SAGANICH MICHAEL , LAITA BIANCA , DAHAN DAVID
发明人： MOYER BRYAN , ZLOTNIK ALBERT , HEVEZI PETER , SOTO HORTENSIA , LU MIN , GAO NA , SERVANT GUY , BRUST PAUL , WILLIAMS MARK , KALABAT DALIA , WHITE EVAN CARL , SAGANICH MICHAEL , LAITA BIANCA , DAHAN DAVID
IPC分类号： C12N5/00
CPC分类号： C12Q1/6883 , C12Q2600/136 , C12Q2600/158 , C40B30/04 , C40B40/10 , G01N33/5044 , G01N33/566 , G01N33/6872 , G01N2333/726 , G01N2500/10
摘要： High-throughput mammalian and medium-throughput oocyte-based electrophysiological assays for identifying human TRPML3 modulators, preferably TRPML3 enhancers are disclosed Compounds that modulate TRPML3 function in the assay are expected to affect salty taste in humans The electrophysiological assays, such as the two-electrode voltage-clamp technique, facilitate the identification of compounds which specifically modulate human TRPML3 The assays provide a robust screen useful to detect compounds that facilitate (enhance) or inhibit TRPML3 function and thereby modulate salty taste In addition, these compounds may be used to regulate sodium excretion, urinary output and other biological functions relating to sodium levels
摘要翻译：公开了用于鉴定人TRPML3调节剂（优选TRPML3增强子）的高通量哺乳动物和中等吞吐量的基于卵母细胞的电生理测定法，优选调节TRPML3功能的化合物预期影响人体的咸味。电生理测定，例如两电极电压钳技术，有助于鉴定特异性调节人TRPML3的化合物。该测定提供了一个强大的屏幕，可用于检测促进（增强）或抑制TRPML3功能，从而调节咸味的化合物。此外，这些化合物可用于调节钠排泄，泌尿生产等与钠水平相关的生物功能

4. 发明申请

WO2010065863A3 ASSAYS FOR IDENTIFYING GENES ENCODING SALTY TASTE RECEPTORS AND MODULATORS 审中-公开
标题翻译：用于识别编码盐类受体和调节剂的基因的测定
公开(公告)号：WO2010065863A3
公开(公告)日：2010-10-14
申请号：PCT/US2009066788
申请日：2009-12-04
申请人： SENOMYX INC , MOYER BRYAN , ZLOTNIK ALBERT , HEVEZI PETER , SOTO HORTENSIA , LU MIN , GAO NA , SAGANICH MICHAEL , DAHAN MICHAEL , LAITA BIANCA , SERVANT GUY , BRUST PAUL , WILLIAMS MARK
发明人： MOYER BRYAN , ZLOTNIK ALBERT , HEVEZI PETER , SOTO HORTENSIA , LU MIN , GAO NA , SAGANICH MICHAEL , DAHAN MICHAEL , LAITA BIANCA , SERVANT GUY , BRUST PAUL , WILLIAMS MARK
IPC分类号： C07K14/705
CPC分类号： G01N33/5008 , A01K2267/03 , C07K14/705 , G01N2333/705
摘要： The present invention relates to rationales for selecting salty taste receptors from a discrete set of taste specific genes disclosed infra by use of methods including electrophysiology, bioiirformatics, and quantitative gene expression assays using transgenic animals as well as functional assays wherein these salty taste receptors may be expressed alone or in association with other taste specific polypeptides such as TRPML3, PKD2L1 or GPRl 13. In addition the invention relates to the use of the identified salty taste receptors in assays, preferably high- throughput, in order to identify modulators which maybe used as flavor additives to modulate salty taste. Preferably, the invention provides high- throughput mammalian and medium- throughput oocyte- based electrophysiological assays for identifying human TRPML3 modulators, preferably TRPML3 enhancers. Compounds that modulate TRPML3 function in the assay are expected to affect salty taste in humans. The inventive electrophysiological assays, such as the two-electrode voltage-clamp technique, facilitate the identification of compounds which specifically modulate human TRPML3. The assays of the invention provide a robust screen useful to detect compounds that facilitate (enhance) or inhibit TRPML3 function. Compounds that enhance or block TRPML3 channel activity should thereby modulate salty taste. In addition, these compounds maybe used to regulate sodium excretion, urinary output and other biological functions relating to sodium levels. This invention relates to the elucidation that TRPML3 is involved in salty taste perception in primates including humans and likely other mammals (given the significance of sodium and other ions to physiological functions and conditions this phenotype is likely strongly conserved in different animals). The TRPML3 gene also modulates one or more of sodium metabolism, sodium excretion, blood pressure, fluid retention, cardiac function and urinary functions such as urine production and excretion.
摘要翻译：本发明涉及通过使用包括电生理学，生物信息学和使用转基因动物的定量基因表达测定的方法以及其中这些咸味受体可能的功能测定法从下文所公开的离散的味道特异性基因组中选择咸味受体的理由单独表达或与其它味道特异性多肽如TRPML3，PKD2L1或GPR113共同表达。此外，本发明涉及鉴定的咸味受体在测定中的应用，优选高通量，以便鉴定可用作风味添加剂调味咸味。优选地，本发明提供用于鉴定人类TRPML3调节剂（优选TRPML3增强子）的高通量哺乳动物和中等通量的基于卵母细胞的电生理测定。在测定中调节TRPML3功能的化合物预期会影响人体的咸味。本发明的电生理测定，例如双电极电压钳技术，有助于鉴定特异性调节人TRPML3的化合物。本发明的测定法提供了一种可用于检测促进（增强）或抑制TRPML3功能的化合物的稳健筛选。增强或阻断TRPML3通道活性的化合物应该调节咸味。此外，这些化合物也可用于调节与钠水平相关的钠排泄，泌尿生产和其他生物学功能。本发明涉及TRPML3涉及包括人和可能的其他哺乳动物在内的灵长类动物的咸味感知（给出钠和其它离子对生理功能和条件的重要性，该表型可能在不同动物中强烈保守）。 TRPML3基因还调节钠代谢，钠排泄，血压，流体保留，心脏功能和尿液功能如尿液产生和排泄中的一种或多种。

5. 发明申请

WO2007092185A3 ASSAYS AND ENHANCERS OF THE HUMAN DELTA ENAC SODIUM CHANNEL 审中-公开
标题翻译：人类DELTA ENAC SODIUM CHANNEL的测定和增强
公开(公告)号：WO2007092185A3
公开(公告)日：2008-02-28
申请号：PCT/US2007002293
申请日：2007-01-26
申请人： SENOMYX INC , MOYER BRYAN , LU MIN , ECHEVERRI FERNANDO
发明人： MOYER BRYAN , LU MIN , ECHEVERRI FERNANDO
IPC分类号： G01N33/53
CPC分类号： G01N33/6872 , G01N33/02 , G01N33/14
摘要： This invention relates to electrophysiological assays that measure sodium conductance activity of a delta human epithelial sodium channel (ENaC) in the presence and absence of delta hENaC enhancers. Also, the invention generally relates to assays for identifying compounds that enhance the activity of delta hENaC, especially in an oocyte expression system. These compounds have potential application in modulating (enhancing) salty taste perception.
摘要翻译：本发明涉及在存在和不存在δHENaC增强子的情况下测量δ人上皮钠通道（ENaC）的钠电导活性的电生理测定。此外，本发明一般涉及用于鉴定增强δHENaC活性的化合物的测定法，特别是在卵母细胞表达系统中。这些化合物在调节（增强）咸味感觉方面具有潜在的应用。

6. 发明申请

WO2007146120A2 RATIONALE, METHODS, AND ASSAYS FOR IDENTIFYING NOVEL TASTE CELL GENES AND SALTY TASTE RECEPTOR TARGETS AND ASSAYS USING THESE IDENTIFIED GENES OR GENE PRODUCTS 审中-公开
标题翻译：用于鉴定新型重组细胞基因和盐酸受体靶标的方法和方法以及使用这些鉴定基因或基因产物的测定
公开(公告)号：WO2007146120A2
公开(公告)日：2007-12-21
申请号：PCT/US2007013502
申请日：2007-06-08
申请人： SENOMYX INC , MOYER BRYAN , LU MIN , ECHEVERRI FERNANDO , KALABAT DALIA , GAO NA , HEVEZI PETER
发明人： MOYER BRYAN , LU MIN , ECHEVERRI FERNANDO , KALABAT DALIA , GAO NA , HEVEZI PETER
IPC分类号： C12Q1/68
CPC分类号： C12N15/1072 , C12N15/1086 , C12Q1/6809 , C12Q1/6883 , C12Q2600/158
摘要： This invention relates to novel rationale and methods for identifying taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, but also genes involved in sweet, bitter, umami, and sour taste perception, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity, the genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes. These compounds have potential application in modulating (enhancing or blocking) taste perception, especially salty taste perception and as potential therapeutics. In addition, this invention relates to novel methods for identifying taste- specific genes that can be used as markers for different taste cell types, including sweet, bitter, umami, sour, salt, and other taste cells in mammals as well as assays that measure the activity of the sweet, bitter, umami, or sour receptor in the presence of these genes to identify modulators of sweet, bitter, umami, and sour taste and to identify therapeutics especially for treating digestive or metabolic disorders, taste loss, and oral infections. Further, the invention provides specific methods of purifying, enriching, isolating or marking desired taste cell subtypes or lineages such as sweet, umami, bitter, salty, sour, fat or stem cells et al. e.g., by use of FACS, magnetic beads or other selection methods that purify, enrich, mark, or eliminate such as by use of labeled cytotoxins, cells that express or do not express one or more taste specific genes.
摘要翻译：本发明涉及用于鉴定味道特异性基因的新的理论和方法，包括涉及咸味感知的基因，特别是人类咸味感知，以及参与甜味，苦味，鲜味和酸味感知的基因以及参与其他基因的基因味觉细胞或味觉受体相关活性如消化功能和消化相关疾病，味觉细胞周转，口腔和消化道的免疫调节，以及代谢调节如糖尿病和肥胖症，使用这些方法鉴定的基因，以及用于鉴定味道的测定调节剂（增强子或阻断剂）和使用这些基因的潜在治疗剂。这些化合物具有潜在的应用于调节（增强或阻断）味觉，特别是咸味感和作为潜在的疗法。此外，本发明涉及用于鉴定可用作不同味道细胞类型（包括哺乳动物中的甜味，苦味，鲜味，酸味，盐类和其他味觉细胞）的标记物的味道特异性基因的新方法，以及测量在这些基因存在下甜味，苦味，鲜味或酸性受体的活性，以鉴定甜味，苦味，鲜味和酸味的调节剂，并鉴定治疗剂，特别是用于治疗消化或代谢紊乱，口味丧失和口腔感染。此外，本发明提供了纯化，富集，分离或标记所需味道细胞亚型或谱系如甜味，鲜味，苦味，咸味，酸性，脂肪或干细胞等的具体方法。例如通过使用FACS，磁珠或其它选择方法来纯化，富集，标记或消除，例如通过使用标记的细胞毒素，表达或不表达一种或多种味道特异性基因的细胞。

7. 发明申请

WO2008153924A2 RATIONALE, METHODS, AND ASSAYS FOR IDENTIFYING HUMAN AND NON-HUMAN PRIMATE TASTE SPECIFIC GENES AND USE THEREOF IN TASTE MODULATOR AND THERAPEUTIC SCREENING ASSAYS 审中-公开
标题翻译：识别人类和非人类初乳特定基因的原理，方法和测定及其在制剂调制剂和治疗筛选试验中的应用
公开(公告)号：WO2008153924A2
公开(公告)日：2008-12-18
申请号：PCT/US2008007102
申请日：2008-06-06
申请人： SENOMYX INC , MOYER BRYAN , ZLOTNIK ALBERT , HEVEZI PETER , SOTO HORTENSIA , KALABAT DALIA , LU MIN , GAO NA , WHITE EVAN
发明人： MOYER BRYAN , ZLOTNIK ALBERT , HEVEZI PETER , SOTO HORTENSIA , KALABAT DALIA , LU MIN , GAO NA , WHITE EVAN
IPC分类号： C40B30/04 , C12N5/10 , C12Q1/68
CPC分类号： G01N33/566 , C12Q1/6806 , C12Q1/6876 , C12Q1/6883 , C12Q2600/136 , C12Q2600/158 , C40B30/04 , C40B40/10 , G01N33/5005 , G01N33/5044 , G01N33/6872 , G01N2333/726 , G01N2500/10
摘要： This invention relates to novel rationale and methods for identifying human and primate taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, but also genes involved in sweet, bitter, umami, and sour taste perception, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity, the genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes. These compounds have potential application in modulating (enhancing or blocking) taste perception, especially salty taste perception and as potential therapeutics. In addition, this invention relates to novel methods for identifying taste-specific genes that can be used as markers for different taste cell types, including sweet, bitter, umami, sour, salty, and other taste cells in mammals as well as assays that measure the activity of the sweet, bitter, umami, or sour receptor in the presence of these genes to identify modulators of sweet, bitter, umami, and sour taste and to identify therapeutics especially for treating digestive or metabolic disorders, taste loss, and oral infections. Particularly, the genes identified herein and antibodies or oligos thereto can be used as markers to identify and/or purify specific taste cells e.g., from taste cell suspensions by use of FACS or magnetic bead cell selection or other known cell purification and isolation procedures.
摘要翻译：本发明涉及用于鉴定人类和灵长类动物特异性基因的新的理论和方法，包括涉及咸味感知的基因，特别是人类咸味感知，以及参与甜味，苦味，鲜味和酸味感觉的基因以及基因参与其他味觉细胞或味觉受体相关活性，如消化功能和消化相关疾病，味觉细胞周转，口服和消化道的免疫调节，以及代谢调节，如糖尿病和肥胖症，使用这些方法鉴定的基因和测定用于鉴定使用这些基因的味觉调节剂（增强子或阻断剂）和潜在的治疗剂。这些化合物具有潜在的应用于调节（增强或阻断）味觉，特别是咸味感和作为潜在的疗法。此外，本发明涉及用于鉴定可用作哺乳动物中不同味道细胞类型（包括甜味，苦味，鲜味，酸味，咸味和其他味觉细胞）的标记的味道特异性基因的新方法，以及测量在这些基因存在下甜味，苦味，鲜味或酸性受体的活性，以鉴定甜味，苦味，鲜味和酸味的调节剂，并鉴定治疗剂，特别是用于治疗消化或代谢紊乱，口味丧失和口腔感染。特别地，本文鉴定的基因和其抗体或寡核苷酸可以用作标识物，以通过使用FACS或磁珠细胞选择或其他已知的细胞纯化和分离程序来鉴定和/或纯化特定的味细胞，例如来自味细胞悬浮液。

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