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1. 发明申请

WO2010065863A2 ASSAYS FOR IDENTIFYING GENES ENCODING SALTY TASTE RECEPTORS AND MODULATORS 审中-公开
标题翻译：用于鉴定编码盐味受体和调节剂的基因的测定
公开(公告)号：WO2010065863A2
公开(公告)日：2010-06-10
申请号：PCT/US2009/066788
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： A01K67/00 , C12Q1/68 , C12Q1/02 , C12N5/10 , C12N1/00
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法的方法从下文公开的一组离体味觉特异性基因中选择咸味受体的基本原理以及功能其中这些咸味受体可以单独表达或与其他味道特异性多肽例如TRPML3，PKD2L1或GPR113结合表达。另外，本发明涉及鉴定的咸味受体在测定中的用途，优选高通量为了鉴定可能用作香料添加剂来调节咸味的调节剂。优选地，本发明提供了用于鉴定人TRPML3调节剂，优选TRPML3增强子的高通量哺乳动物和中等通量的基于卵母细胞的电生理学测定法。期望在测定中调节TRPML3功能的化合物影响人类的咸味。本发明的电生理学测定法，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用于检测促进（增强）或抑制TRPML3功能的化合物的有力筛选。因此增强或阻断TRPML3通道活性的化合物应调节咸味。此外，这些化合物可用于调节钠排泄，尿量和与钠水平有关的其他生物学功能。本发明涉及说明TRPML3参与包括人类和可能的其他哺乳动物（考虑到钠和其它离子对生理功能和条件的重要性，这种表型在不同动物中强烈保守）的灵长类中的咸味感知。 TRPML3基因还调节钠代谢，钠排泄，血压，体液潴留，心脏功能和泌尿功能如尿液产生和排泄中的一种或多种。

2. 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

3. 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。

4. 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。

5. 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。

6. 发明申请

WO2009008950A2 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 RELEASE 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：WO2009008950A2
公开(公告)日：2009-01-15
申请号：PCT/US2008/007101
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
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
IPC分类号： C40B30/04 , C12N5/10 , C12Q1/68
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： The present invention relates to 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 may be 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. The inventors have identified TRPML3 as encoding a salty taste receptor in primates and humans (and likely other mammals) based on gene expression assays which have determined that TRPML3 is expressed specifically in taste bud cells and not in lingual epithelial cells, similar assays that have determined that TRPML3 is specifically expressed or enriched in the top half of taste bud cells in a subset of taste cells which do not express TRPM5 or PKD2L1, prior reports that document the expression of TRPML3 in other sensory organs such as the ear (therefore further substantiating the role of TRPML3 as a "professional" sensory gene), the strong expression of TRPML3 in the adrenal glands which play a strong role in regulation of sodium metabolism (as they regulate aldosterone a key molecule in sodium metabolism), and related thereto the fact that an autoimmune disease that elicits strong salt cravings, Addison's disease, involves destruction of the adrenal glands, and functional (electrophysiological) studies which indicate that TRPML3 conducts sodium and exhibits biochemical characteristics consistent with a human salty taste receptor (passes K+, Li+, and is amiloride-insensitive.) This application also discloses novel rationales and methods for identifying primate taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, as well as genes involved in sweet, bitter, umami, and sour taste and other taste perceptions including fat taste, 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, can be used in assays for identifying taste modulators (enhancers or blockers) and potential t
摘要翻译：本发明涉及用于鉴定人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。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，这些化合物可用于调节与钠水平相关的钠排泄，泌尿生产和其他生物功能。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。发明人已经基于基因表达测定法将TrPML3鉴定为在灵长类动物和人类（以及可能的其他哺乳动物）中编码咸味受体，其已经确定TRPML3特异性地在味蕾细胞中表达，而不是在舌上皮细胞中表达， TRPML3在不表达TRPM5或PKD2L1的味觉细胞的子集中的特定表达或富集的上半部分的浓度中，先前报道了TRPML3在其他感觉器官如耳朵中的表达（因此进一步证实了 TRPML3作为“专业”感觉基因的作用），TRPML3在钠代谢调节中起重要作用的肾上腺中的强烈表达（因为它们调节醛固酮是钠代谢中的关键分子），与此相关的事实是引起强烈渴望的自身免疫性疾病艾迪生病涉及肾上腺的破坏和功能性（电极这些研究表明TRPML3可以进行钠化，并具有与人类咸味受体一致的生物化学特性（通过K +，Li +，而且是阿米洛利不敏感的）。本申请还公开了识别灵长类动物特异性基因的新理论和方法，包括涉及咸味感知的基因，特别是人类咸味感知，以及涉及甜味，苦味，鲜味和酸味以及其它味道感觉（包括脂肪味道）的基因，以及涉及其它味觉细胞或味觉受体相关活性的基因，例如消化功能和消化相关疾病，滋味细胞周转，口服和消化道的免疫调节，以及糖尿病和肥胖等代谢调节。使用这些方法鉴定的基因可用于鉴定味觉调节剂（增强子或阻断剂）和潜在t的测定

7. 发明申请

WO2008153924A3 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
公开(公告)号：WO2008153924A3
公开(公告)日：2008-12-18
申请号：PCT/US2008/007102
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： C12Q1/00 , C12N15/00
摘要： Methods for identifying human and primate taste-specific genes, including genes involved in salty, sweet, bitter, umami, and sour taste perception, especially human salty 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 are disclosed. The genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes are also disclosed.

8. 发明申请

WO2007146120A3 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
公开(公告)号：WO2007146120A3
公开(公告)日：2007-12-21
申请号：PCT/US2007/013502
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
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.

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