公开(公告)号：US07601823B2

公开(公告)日：2009-10-13

申请号：US11256726

申请日：2005-10-24

申请人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

发明人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

IPC分类号： C07H21/02

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

摘要翻译： 本发明涉及结合并抑制离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）亚型的活化的新型核酸配体或适体。 还公开了技术的新型组合，即SELEX和激光脉冲光解用于选择和筛选抑制受体功能的适体，因此可用于治疗与离子型谷氨酸受体的过度活化相关的疾病。

公开(公告)号：US08076467B2

公开(公告)日：2011-12-13

申请号：US12578231

申请日：2009-10-13

申请人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

发明人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

IPC分类号： C07H21/02 ,  C07H21/04 ,  C40B40/06 ,  C40B40/00 ,  C40B50/00 ,  C40B30/00 ,  A61K48/00

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

摘要翻译： 本发明涉及结合并抑制离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）亚型的活化的新型核酸配体或适体。 还公开了技术的新型组合，即SELEX和激光脉冲光解用于选择和筛选抑制受体功能的适体，因此可用于治疗与离子型谷氨酸受体的过度活化相关的疾病。

公开(公告)号：US08450468B2

公开(公告)日：2013-05-28

申请号：US13323161

申请日：2011-12-12

申请人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

发明人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

IPC分类号： A61K48/00 ,  C07H19/00 ,  C07H21/00 ,  C07H21/02

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

公开(公告)号：US20060148746A1

公开(公告)日：2006-07-06

申请号：US11256726

申请日：2005-10-24

申请人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John Lis

发明人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John Lis

IPC分类号： A61K48/00 ,  C12Q1/68 ,  C07H21/04

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

公开(公告)号：US09200286B2

公开(公告)日：2015-12-01

申请号：US13810572

申请日：2011-07-15

申请人： Li Niu ,  Zhen Huang ,  Jae Seon Park

发明人： Li Niu ,  Zhen Huang ,  Jae Seon Park

IPC分类号： C07H21/04 ,  C12N15/115 ,  C12N15/11 ,  C12N15/113

CPC分类号： C12N15/115 ,  C12N15/111 ,  C12N15/1138 ,  C12N2310/16 ,  C12N2310/322 ,  C12N2310/3533 ,  C12N2320/13

摘要： Inhibitors of AMPA-type glutamate ion channels are useful as biochemical probes for structure-function studies and as drug candidates for a number of neurological disorders and diseases. Disclosed herein is the identification of an RNA inhibitor or aptamer by an in vitro evolution approach and characterization of its mechanism of inhibition on the sites of interaction by equilibrium binding and on the receptor channel-opening rate by a laser-pulse photolysis technique. The aptamer of the invention is a noncompetitive inhibitor of AMPA-type glutamate ion channels, one that selectively inhibits the GluA2Qflip AMPA receptor subunit without any effect on other AMPA receptor subunits or on kainate or NMDA receptors. Furthermore, the aptamer preferentially inhibits the closed-channel state of GluA2Qflip with a KI=1.5 μM or by ˜15-fold over the open-channel state. The potency and selectivity of this aptamer rival those of small molecule inhibitors. Together, these properties make the aptamers of the present invention promising water-soluble, highly potent, GluA2 subunit-selective drugs.

摘要翻译： AMPA型谷氨酸离子通道的抑制剂可用作结构功能研究的生物化学探针和许多神经障碍和疾病的候选药物。 本文公开了通过体外进化方法鉴定RNA抑制剂或适体，并通过激光脉冲光解技术通过平衡结合和受体通道开放速率表征其抑制作用位点的机制。 本发明的适体是AMPA型谷氨酸离子通道的非竞争性抑制剂，其选择性地抑制GluA2Qflip AMPA受体亚基而对其它AMPA受体亚基或红藻氨酸或NMDA受体没有任何作用。 此外，适体优先抑制GluA2Qflip的闭通道状态，KI =1.5μM或比开放通道状态约〜15倍。 该适配体的效力和选择性与小分子抑制剂的效力和选择性相当。 这些性质一起使得本发明的适体具有潜在的水溶性，高效的GluA2亚基选择性药物。

公开(公告)号：US20130289100A1

公开(公告)日：2013-10-31

申请号：US13810572

申请日：2011-07-15

申请人： Li Niu ,  Zhen Huang ,  Jae Seon Park

发明人： Li Niu ,  Zhen Huang ,  Jae Seon Park

IPC分类号： C12N15/115

CPC分类号： C12N15/115 ,  C12N15/111 ,  C12N15/1138 ,  C12N2310/16 ,  C12N2310/322 ,  C12N2310/3533 ,  C12N2320/13

摘要： Inhibitors of AMPA-type glutamate ion channels are useful as biochemical probes for structure-function studies and as drug candidates for a number of neurological disorders and diseases. Disclosed herein is the identification of an RNA inhibitor or aptamer by an in vitro evolution approach and characterization of its mechanism of inhibition on the sites of interaction by equilibrium binding and on the receptor channel-opening rate by a laser-pulse photolysis technique. The aptamer of the invention is a noncompetitive inhibitor of AMPA-type glutamate ion channels, one that selectively inhibits the GluA2Qflip AMPA receptor subunit without any effect on other AMPA receptor subunits or on kainate or NMDA receptors. Furthermore, the aptamer preferentially inhibits the closed-channel state of GluA2Qflip with a KI=1.5 μM or by ˜15-fold over the open-channel state. The potency and selectivity of this aptamer rival those of small molecule inhibitors. Together, these properties make the aptamers of the present invention promising water-soluble, highly potent, GluA2 subunit-selective drugs.

摘要翻译： AMPA型谷氨酸离子通道的抑制剂可用作结构功能研究的生物化学探针和许多神经障碍和疾病的候选药物。 本文公开了通过体外进化方法鉴定RNA抑制剂或适体，并通过激光脉冲光解技术通过平衡结合和受体通道开放速率表征其抑制作用位点的机制。 本发明的适体是AMPA型谷氨酸离子通道的非竞争性抑制剂，其选择性地抑制GluA2Qflip AMPA受体亚基而对其它AMPA受体亚基或红藻氨酸或NMDA受体没有任何作用。 此外，适体优先抑制GluA2Qflip的闭通道状态，KI =1.5μM或比开放通道状态约15倍。 该适配体的效力和选择性与小分子抑制剂的效力和选择性相当。 这些性质一起使得本发明的适体具有潜在的水溶性，高效的GluA2亚基选择性药物。

公开(公告)号：US08383794B2

公开(公告)日：2013-02-26

申请号：US12900636

申请日：2010-10-08

申请人： Li Niu ,  Zhen Huang

发明人： Li Niu ,  Zhen Huang

IPC分类号： A61K48/00 ,  C07H21/02

CPC分类号： C07H21/02 ,  C07H21/00 ,  C07H21/04 ,  G01N2333/70571

摘要： The present invention relates to novel nucleic acid ligands or aptamers that demonstrate potent and selective inhibition of the open-channel conformation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors.

摘要翻译： 本发明涉及新的核酸配体或适体，其表现出对离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）亚型的开放通道构象的有效和选择性抑制。

公开(公告)号：US10851003B2

公开(公告)日：2020-12-01

申请号：US13811149

申请日：2011-07-21

申请人： Matthew Silver ,  Justin Buck ,  Patrick Kiely ,  Juan J. Guzman ,  Zhen Huang

发明人： Matthew Silver ,  Justin Buck ,  Patrick Kiely ,  Juan J. Guzman ,  Zhen Huang

IPC分类号： C02F3/02 ,  A01K63/04 ,  C02F3/00 ,  C02F3/30

摘要： In one aspect, the present invention provides reactor designs, component designs, and operating schemes for removing nitrates and chemical oxygen demand from any suitable wastewater stream. In another aspect, the invention also provides reactor designs, component designs, and operating schemes designed to modify and improve pH and water quality in wastewater streams.

公开(公告)号：US20130183765A1

公开(公告)日：2013-07-18

申请号：US13823028

申请日：2011-09-13

申请人： Zhen Huang

发明人： Zhen Huang

IPC分类号： G01N21/63

CPC分类号： G01N21/631 ,  C12Q1/6883 ,  C12Q2523/313 ,  C12Q2525/313 ,  G01N21/33 ,  G01N30/06 ,  G01N2030/8827 ,  Y10T436/143333

摘要： Disclosed are compositions which can mimic DNA and/or RNA in cells of a subject and methods of using them as a substrate in testing efficacy of one or more compositions in reducing and/or preventing radiation, such as ultraviolet (UV) radiation-caused DNA and/or RNA damage of said subject. Also disclosed are systems related to the disclosed methods.

摘要翻译： 公开了可以模拟受试者细胞中的DNA和/或RNA的组合物以及在测试一种或多种组合物在减少和/或预防辐射中的功效（例如紫外线（UV）辐射引起的DNA）中使用它们作为底物的方法 和/或所述受试者的RNA损伤。 还公开了与所公开的方法相关的系统。

公开(公告)号：US08427274B2

公开(公告)日：2013-04-23

申请号：US12344054

申请日：2008-12-24

申请人： Scott A. Jones ,  Zhen Huang ,  Paul W. Bonham ,  Chuan Li ,  Cameron D. Jiles

发明人： Scott A. Jones ,  Zhen Huang ,  Paul W. Bonham ,  Chuan Li ,  Cameron D. Jiles

IPC分类号： G05B23/02 ,  G09G5/00 ,  G03B15/02 ,  F21V7/04

CPC分类号： H05B37/029

摘要： The present invention is related to a method, system and apparatus, in particular, a lighting system and method of controlling the lighting system, comprising a computer readable medium and a programmable device capable of controlling and manipulating individually addressable lights to realize a visual display at a pixel level.

摘要翻译： 本发明涉及一种方法，系统和装置，特别是控制照明系统的照明系统和方法，包括计算机可读介质和可编程设备，其能够控制和操纵单独寻址的光以实现视觉显示 像素级别。