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1. 发明授权

US11130779B2 PPAR agonists and methods of use thereof 有权
公开(公告)号：US11130779B2
公开(公告)日：2021-09-28
申请号：US16717830
申请日：2019-12-17
申请人： The Salk Institute for Biological Studies
发明人： Ronald M. Evans , Michael Downes
IPC分类号： C07D405/12 , C07K5/062 , C07D309/04 , C07D407/12 , C07D271/12 , C07D295/13 , C07D213/40 , C07D213/64 , C07D307/68 , C07D309/06 , C07D231/12 , C07D333/24 , C07D401/04 , C07D401/12 , C07D405/04 , C07D405/10 , C07D409/12 , C07D413/04 , C07D413/12 , C07D417/04 , C07D417/10 , C07D417/12 , C07C233/87 , C07D205/04 , C07D209/34 , C07D295/155 , C07D213/56 , C07D305/06 , C07D307/54 , C07D307/81 , C07D307/83 , C07C255/57 , C07C259/06 , C07C233/73 , C07C235/42 , C07C235/48 , C07C235/84 , C07C237/32 , C07C317/44 , C07C233/75 , C07D333/38
摘要： Provided herein are deuterated compounds and compositions useful in increasing PPARδ activity. The compounds have a formula where L5 comprises at least one deuterium. Exemplary species include The compounds and compositions provided herein are useful for the treatment of PPARδ related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

2. 发明申请

US20170226154A1 PPAR AGONISTS AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：US20170226154A1
公开(公告)日：2017-08-10
申请号：US15482385
申请日：2017-04-07
申请人： The Salk Institute for Biological Studies
发明人： Ronald M. Evans , Michael Downes
IPC分类号： C07K5/062 , C07D213/56 , C07D231/12 , C07D307/54 , C07D409/12 , C07D295/13 , C07D213/40 , C07D401/12 , C07D405/12 , C07C233/75 , C07D333/38
CPC分类号： C07K5/06034 , C07C233/73 , C07C233/75 , C07C233/87 , C07C235/42 , C07C235/48 , C07C235/84 , C07C237/32 , C07C255/57 , C07C259/06 , C07C317/44 , C07C2601/02 , C07C2601/08 , C07D205/04 , C07D209/34 , C07D213/40 , C07D213/56 , C07D213/64 , C07D231/12 , C07D271/12 , C07D295/13 , C07D295/155 , C07D305/06 , C07D307/54 , C07D307/68 , C07D307/81 , C07D307/83 , C07D309/04 , C07D309/06 , C07D333/24 , C07D333/38 , C07D401/04 , C07D401/12 , C07D405/04 , C07D405/10 , C07D405/12 , C07D407/12 , C07D409/12 , C07D413/04 , C07D413/12 , C07D417/04 , C07D417/10 , C07D417/12 , C07K5/06026
摘要： Provided herein are deuterated compounds and compositions useful in increasing PPARδ activity. The compounds and compositions provided herein are useful for the treatment of PPARδ related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

3. 发明申请

US20150313498A1 CONFIGURATION AND SPATIAL PLACEMENT OF FRONTAL ELECTRODE SENSORS TO DETECT PHYSIOLOGICAL SIGNALS 审中-公开
标题翻译：正面电极传感器的配置和空间放置检测生理信号
公开(公告)号：US20150313498A1
公开(公告)日：2015-11-05
申请号：US14435398
申请日：2013-10-14
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , THE SALK INSTITUTE FOR BIOLOGICAL STUDIES
发明人： Todd Prentice Coleman , Rui Ma , Michael Bajema , Ricardo Gil Da Costa , Raynard Fung
IPC分类号： A61B5/0484 , A61B5/04 , A61B5/00 , A61B5/0478 , A61B5/0492
CPC分类号： A61B5/0478 , A61B5/04012 , A61B5/0482 , A61B5/0484 , A61B5/04842 , A61B5/04845 , A61B5/04847 , A61B5/0488 , A61B5/0492 , A61B5/165 , A61B5/167 , A61B5/168 , A61B5/6803 , A61B5/6814
摘要： Methods, systems, and devices are disclosed for acquiring and analyzing physiological signals. In one aspect, a physiological sensor device includes a substrate formed of an electrically insulative material and structured to allow physical contact of the device with the frontal region of the head of a user, a recording electrode configured at a first location on the substrate to acquire an electrophysiological signal of the user, a reference electrode configured at a second location on the substrate to acquire a reference signal to the electrophysiological signal, and a ground electrode configured at a third location at least partially between the first and the second locations on the substrate, in which the first location is posterior to the second and third locations, and in which the device is operable when electrically coupled to an electrical circuit to detect physiological signals of the user.
摘要翻译：公开了用于获取和分析生理信号的方法，系统和装置。一方面，一种生理传感器装置包括由电绝缘材料形成并被构造成允许该装置与使用者头部的前部区域的物理接触的记录电极，该记录电极配置在该基板上的第一位置以获得用户的电生理信号，在基板上的第二位置处配置以获取对电生理信号的参考信号的参考电极，以及配置在第三位置处的至少部分地在衬底上的第一和第二位置之间的接地电极，其中所述第一位置位于所述第二和第三位置之后，并且其中所述装置在电耦合到电路以操作以检测所述用户的生理信号时可操作。

4. 发明申请

US20040241754A1 Modulating neuronal plasticity 审中-公开
标题翻译：调节神经元的可塑性
公开(公告)号：US20040241754A1
公开(公告)日：2004-12-02
申请号：US10449715
申请日：2003-05-31
申请人： The Salk Institute for Biological Studies
发明人： Stephen F. Heinemann
IPC分类号： G01N033/53 , G01N033/567
CPC分类号： G01N33/6863 , A61K38/1787 , A61K38/1793 , G01N2500/02
摘要： Methods of identifying compounds that modulate neuronal plasticity including long-term potentiation are identified by their ability to modulate association between an Eph receptor and an ephrin ligand, or between an Eph receptor and a PDZ protein. In another embodiment the method for screening compounds involves applying the candidate compounds to a postsynaptic neuron and determining a biochemical affect on the presynaptic neuron, or by determining clustering of Eph receptors or ephrin ligands. Also provided are methods for using the invention compounds to modulate plasticity in an individual in need thereof or to improve cognition in an individual.
摘要翻译：识别调节神经元可塑性（包括长期增强）的化合物的方法通过调节Eph受体和ephrin配体之间或Eph受体和PDZ蛋白之间的缔合的能力来鉴定。在另一个实施方案中，用于筛选化合物的方法包括将候选化合物应用于突触后神经元并确定对突触前神经元的生化影响，或通过确定Eph受体或依夫芬配体的聚集。还提供了使用本发明化合物调节有需要的个体中的可塑性或改善个体认知的方法。

5. 发明申请

US20040171800A9 Gamma retinoic acid receptor 失效
标题翻译： γ视黄酸受体
公开(公告)号：US20040171800A9
公开(公告)日：2004-09-02
申请号：US09797727
申请日：2001-03-01
申请人： THE SALK INSTITUTE FOR BIOLOGICAL STUDIES , SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH
发明人： Fumimaro Takaku , Takashi Ishikawa , Michio Imawari , Ronald Mark Evans , Kazuhiko Umesono
IPC分类号： C12Q001/68 , C07H021/02 , C07H021/04 , C07K005/00 , C07K007/00 , C07K016/00 , C07K017/00 , A61K038/00 , C07K001/00 , C07K014/00
CPC分类号： C07K14/72 , A61K38/00 , C07K14/70567 , C07K14/721 , C07K2319/00 , C07K2319/715 , C07K2319/80 , Y10S530/826 , Y10S530/846
摘要： A novel gamma retinoic acid receptor is disclosed. The novel receptor is encoded for by cDNA carried on plasmid pGEM-hRARnull, which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera contain at least one functional domain from the new gamma retinoic acid receptor.
摘要翻译：公开了一种新型的视黄酸受体。新型受体由携带在质粒pGEM-hRARgamma上的cDNA编码，其已经保藏在美国典型培养物保藏中心用于专利。还公开了嵌合受体蛋白。嵌合体含有来自新的视黄酸受体的至少一个功能结构域。

6. 发明申请

US20040162354A1 Treatment of disease states which result from neoplastic cell proliferation using PPAR-gamma activators and compositions useful therefor 审中-公开
标题翻译：使用PPAR-γ激活剂和对其有用的组合物治疗由肿瘤细胞增殖引起的疾病状态
公开(公告)号：US20040162354A1
公开(公告)日：2004-08-19
申请号：US10627160
申请日：2003-07-24
申请人： The Salk Institute for Biological Studies
发明人： Ronald M. Evans , Peter Tontonoz , Laszlo Nagy
IPC分类号： A61K031/557
CPC分类号： A61K31/44 , A61K31/12 , A61K31/19 , A61K31/192 , A61K31/205 , A61K31/445 , A61K31/557 , A61K31/5575 , A61K2300/00
摘要： In accordance with the present invention, it has been discovered that PPARnull is expressed consistently in tissues associated with each of a variety of disease states which result from neoplastic cell proliferation. It has further been discovered that maximal activation of PPARnull with exogenous ligand promotes terminal differentiation of primary cells which are otherwise subject to neoplastic cell proliferation. In accordance with another aspect of the invention, it has been discovered that RXR-specific ligands are also potent agents for induction of differentiation of cells expressing the PPARnull/RXRnull heterodimer, and that simultaneous treatment of cells subject to neoplastic cell proliferation with a PPARnull-selective ligand, in combination with an RXR-specific ligand, results in an additive stimulation of differentiation. Thus, the effect of neoplastic cell proliferation can be ameliorated by treatment of cells undergoing neoplastic cell proliferation with PPARnull agonists, optionally in the further presence of RXR agonists, thereby blocking further proliferation thereof. Accordingly, compounds and compositions which are useful for the treatment of a variety of disease states which result from neoplastic cell proliferation have been identified and are described herein.
摘要翻译：根据本发明，已经发现，PPARγ在与由肿瘤细胞增殖引起的各种疾病状态中的每一种相关的组织中一致地表达。进一步发现，具有外源性配体的PPARγ的最大活化促进了另外受到肿瘤细胞增殖的原代细胞的终末分化。根据本发明的另一方面，已经发现RXR特异性配体也是用于诱导表达PPARγ/RXRα异源二聚体的细胞分化的有效试剂，并且用PPARγ- 选择性配体与RXR特异性配体组合导致分化的加性刺激。因此，可以通过用PPARγ激动剂处理经历赘生性细胞增殖的细胞，任选地在RXR激动剂的进一步存在下，可以改善肿瘤细胞增殖的作用，从而阻断其进一步增殖。因此，已经鉴定并描述了可用于治疗由肿瘤细胞增殖引起的各种疾病状态的化合物和组合物。

7. 发明申请

US20040009892A1 Method for the identification and use of substances that modulate POD function and/or structure 审中-公开
标题翻译：用于鉴定和使用调节POD功能和/或结构的物质的方法
公开(公告)号：US20040009892A1
公开(公告)日：2004-01-15
申请号：US09990255
申请日：2001-11-20
申请人： The Salk Institute for Biological Studies
发明人： Vassilis Doucas , Ronald M. Evans , Didier Trono
IPC分类号： A61K038/16
CPC分类号： G01N33/5011 , C12Q1/6897 , G01N33/5008 , G01N33/6875
摘要： The invention disclosed herein comprises assay methods for identifying substances useful for treating pathogenic disorders. The assay methods disclosed herein are based on the discovery that POD function and structure are key elements in normal transcriptional processes. Disruption of POD function and/or structure contributes to the creation and/or maintenance of a variety of pathogenic disorders.
摘要翻译：本文公开的发明包括用于鉴定可用于治疗病原性疾病的物质的测定方法。本文公开的测定方法基于POD功能和结构是正常转录过程中的关键元素的发现。 POD功能和/或结构的破坏有助于产生和/或维持各种致病性疾病。

8. 发明申请

US20030096387A1 Peptidyl-prolyl cis-trans isomerase inhibitors and uses therefor 审中-公开
标题翻译：肽基脯氨酰顺式反式异构酶抑制剂及其用途
公开(公告)号：US20030096387A1
公开(公告)日：2003-05-22
申请号：US10282588
申请日：2002-10-28
申请人： The Salk institute for Biological Studies
发明人： Joseph P. Noel , Tony R. Hunter
IPC分类号： C12N009/00 , C12N009/99
CPC分类号： A61K38/05 , Y02A50/401 , Y02A50/406 , Y02A50/471 , Y02A50/473 , Y02A50/483 , Y02A90/26
摘要： The invention relates to inhibitors of PPIase activity and pharmaceutical compositions containing such inhibitors. Such compounds are useful for treatment of disorders characterized by inappropriate cell proliferation. In particular the compounds disclosed herein inhibit the activity of members of the Pin1/parvulin class of PPIases. These compounds have been designed based on the high resolution X-Ray derived crystal structure of the human enzyme Pin1.
摘要翻译：本发明涉及PPIase活性抑制剂和含有这些抑制剂的药物组合物。这些化合物可用于治疗以不适当的细胞增殖为特征的病症。特别地，本文公开的化合物抑制PP1 / parvulin类的PPI酶的成员的活性。这些化合物是基于人类酶Pin1的高分辨率X射线衍射的晶体结构而设计的。

9. 发明申请

US20020166138A1 FLP-mediated gene modification in mammalian cells, and compositions and cells useful therefor 失效
标题翻译：哺乳动物细胞中FLP介导的基因修饰，以及对其有用的组合物和细胞
公开(公告)号：US20020166138A1
公开(公告)日：2002-11-07
申请号：US10086542
申请日：2002-02-28
申请人： The Salk Institute for Biological Studies
发明人： Geoffrey M. Wahl , Stephen V. O'Gorman
IPC分类号： A01K067/027
CPC分类号： C12N15/90 , A61K38/00 , A61K48/00 , C12N9/00 , C12N15/52 , C12N15/85 , C12N15/907 , C12N2800/30
摘要： A gene activation/inactivation and site-specific integration system has been developed for mammalian cells. The invention system is based on the recombination of transfected sequences by FLP, a recombinase derived from Saccharomyces. In several cell lines, FLP has been shown to rapidly and precisely recombine copies of its specific target sequence. For example, a chromosomally integrated, silent null-galactosidase reporter gene was activated for expression by FLP-mediated removal of intervening sequences to generate clones of marked cells. Alternatively, the reverse reaction can be used to target transfected DNA to specific chromosomal sites. These results demonstrate that FLP can be used, for example, to mosaically activate or inactivate transgenes for a variety of therapeutic purposes, as well as for analysis of vertebrate development. The FLP recombination system of the present invention can be incorporated in transgenic, non-human mammals to achieve site-specific integration of transgenes, to construct functional genes or to disrupt existing genes.
摘要翻译：已经为哺乳动物细胞开发了基因激活/失活和位点特异性整合系统。本发明系统基于通过FLP转染的序列的重组，其是衍生自酵母属的重组酶。在几种细胞系中，已经显示FLP快速且精确地重组其特异性靶序列的拷贝。例如，染色体整合的沉默的β-半乳糖苷酶报道基因通过FLP介导的中间序列的去除被激活用于表达以产生标记细胞的克隆。或者，反向反应可用于将转染的DNA靶向特定的染色体位点。这些结果表明，FLP可以用于例如用于各种治疗目的的马赛克激活或灭活转基因，以及用于脊椎动物发育的分析。本发明的FLP重组系统可并入转基因非人哺乳动物中，以实现转基因的位点特异性整合，构建功能基因或破坏现有基因。

10. 发明申请

US20210321963A1 SYSTEMS AND METHODS FOR ENHANCED IMAGING AND ANALYSIS 有权
公开(公告)号：US20210321963A1
公开(公告)日：2021-10-21
申请号：US17269986
申请日：2019-08-21
申请人： THE SALK INSTITUTE FOR BIOLOGICAL STUDIES
发明人： Uri MANOR , Linjing FANG
IPC分类号： A61B6/00
摘要： A method to, is provided for collecting an image from a sample. The method includes selecting a radiation level for a first probe to meet a desired radiation dosage, and providing, with the first probe, a radiation at a selected point within a region of the sample. The method includes identifying a second selected point within the region of the sample based on a down sampling scheme, and providing a second radiation amount at the second selected point within the region of the sample. The method also includes interpolating a first datum and a second datum based on an up sampling scheme to obtain a plurality of data, and forming an image of the region of the sample with the plurality of data. A system to perform the above method and including the first probe is also provided.

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