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21.发明申请METHOD FOR HIGH-THROUGHPUT SCREENING OF COMPOUNDS AND COMBINATIONS OF COMPOUNDS FOR DISCOVERY AND QUANTIFICATION OF ACTIONS, PARTICULARLY UNANTICIPATED THERAPEUTIC OR TOXIC ACTIONS, IN BIOLOGICAL SYSTEMS 有权用于化合物的高通量筛选和化合物的组合的方法用于发现和定量的生物系统中的特别是非化学治疗或毒性作用的行为公开(公告)号：US20110195865A1
公开(公告)日：2011-08-11
申请号：US13031084
申请日：2011-02-18
申请人： Marc K. HELLERSTEIN
发明人： Marc K. HELLERSTEIN
IPC分类号： C40B30/06
CPC分类号： G01N33/5067 , A61K49/0008 , G01N33/5088 , G01N33/60 , G01N33/6848 , Y02A90/22
摘要： The invention enables high-throughput screening of compounds in living systems to detect unanticipated or unintended biological actions. The invention also allows for screening, detection, and confirmation of new indications for approved drugs. Screening and detection of toxic effects of compounds also can be achieved by using the methods of the invention. The methods comprise administering isotope-labeled substrates to a living system so that the label is incorporated into molecules in a manner that reveals flux rates through metabolic pathways thought to be involved in a disease. Comparisons between living systems exposed to compounds and living systems not so exposed reveals the effects of the compounds on the flux rates through the metabolic pathways. Combinations or mixtures of compounds can be systematically screened to detect unanticipated or unintended biological actions, including synergistic actions, in the same manner.
摘要翻译： 本发明使得生物系统中化合物的高通量筛选能够发现未预期的或非预期的生物作用。 本发明还允许筛选，检测和确认经批准的药物的新适应症。 化合物的毒性作用的筛选和检测也可以通过使用本发明的方法来实现。 所述方法包括向活体系统施用同位素标记的底物，使得将标记以通过被认为参与疾病的代谢途径揭示通量速率的方式并入分子中。 暴露于化合物的活体系与未暴露的生物体系之间的比较揭示了化合物对通过代谢途径的通量速率的影响。 可以以相同的方式系统地筛选化合物的组合或混合物以检测意外的或非预期的生物作用，包括协同作用。
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22.发明申请COMPOSITIONS AND METHODS OF TREATMENT USING MODULATORS OF MOTONEURON DISEASES 审中-公开使用MOTONEURON疾病调节剂的组合物和治疗方法公开(公告)号：US20110076236A1
公开(公告)日：2011-03-31
申请号：US12994098
申请日：2009-05-21
CPC分类号： G01N33/6896 , G01N33/5058 , G01N2500/10 , G01N2800/2835
摘要： The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); methods for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease; the discovery of drug agents that modulate neuronal microtubule dynamics in living subjects with motoneuron diseases; the discovery that administration of such agents, alone or in combinations, can improve MT-mediated transport of “synaptic vesicle cargo” molecules along and through axons; the discovery that such modulation of altered microtubule dynamics and improvement in MT-transport of molecules along axons can provide marked neuroprotective therapy for living subjects with motoneuron diseases, including delay in symptoms and prolongation of survival; and the discovery that monitoring of neuronal microtubule dynamics in response to therapeutic interventions in subjects with motoneuron diseases, allows diagnostic monitoring, to optimize therapeutic regimens and treatment strategies in individual subjects or in drug trials. The monitoring involves measuring isotope enrichment in secreted synaptic vesicle cargo molecules.
摘要翻译： 本文公开的发明描述了运动神经元疾病（神经元中微管的动力学改变）的新型治疗靶标; 用于测量具有确定的，初期的或潜在的运动神经元疾病的受试者中该治疗靶标的活性状态的方法; 发现在运动神经元疾病的活体中调节神经元微管动力学的药剂; 发现这种药物单独或组合地可以改善MT介导的“突触小泡载体”分子沿轴突和轴突的转运; 发现改变的微管动力学的这种调节和沿着轴突的分子的MT转运的改善可以为具有运动神经元疾病的活动受试者提供显着的神经保护疗法，包括延迟症状和延长生存期; 并且发现通过对具有运动神经元疾病的受试者的治疗干预来监测神经元微管动力学，允许诊断监测，优化个体受试者或药物试验中的治疗方案和治疗策略。 监测涉及测量分泌的突触囊泡货物分子中的同位素富集。
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23.发明申请公开(公告)号：US20100041082A1
公开(公告)日：2010-02-18
申请号：US12403331
申请日：2009-03-12
申请人： Marc K. HELLERSTEIN
发明人： Marc K. HELLERSTEIN
CPC分类号： G01N33/58 , A61K49/0004
摘要： Provided herein are methods for determining the metabolism of one or more sugars and/or fatty acids, and applications thereof. Such applications include determining the rate of glycogen synthesis and glycolysis, which are believed to be early markers for predicting elevated risk of diabetes and cardiovascular disease. Other applications include methods for screening drugs that effect sugar and/or fatty acid metabolism. The methods are useful for at least partially characterizing drugs for desirable or undesirable (toxic) characteristics. Drugs that are at least partially characterized using the methods of the invention can then be further developed in pre-clinical testing and clinical trials. Such drugs may be found to be useful in treating obesity, diabetes, cardiovascular disease, and other disorders of metabolism.
摘要翻译： 本文提供了确定一种或多种糖和/或脂肪酸的代谢的方法及其应用。 这些应用包括确定糖原合成和糖酵解的速率，这被认为是预测糖尿病和心血管疾病风险升高的早期标志物。 其他应用包括用于筛选影响糖和/或脂肪酸代谢的药物的方法。 所述方法可用于至少部分表征药物以获得期望的或不期望的（有毒的）特征。 可以在临床前临床试验和临床试验中进一步开发使用本发明方法至少部分表征的药物。 可以发现这些药物可用于治疗肥胖，糖尿病，心血管疾病和其他代谢紊乱。
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公开(公告)号：US6010846A
公开(公告)日：2000-01-04
申请号：US75309
申请日：1998-05-08
申请人： Marc K. Hellerstein
发明人： Marc K. Hellerstein
IPC分类号： G01N33/50 , A61K31/711 , A61K51/00 , C12Q1/02 , C12Q1/68 , C12Q1/70 , G01N33/15 , G01N33/60 , C12Q1/00
CPC分类号： A61K31/665 , C12Q1/48 , C12Q1/68 , C12Q1/6809 , C12Q1/70 , G01N33/5005 , G01N33/5088 , G01N33/60
摘要： The present invention relates to methods for measuring the proliferation and destruction rates of cells by measuring deoxyribonucleic acid (DNA) synthesis and/or destruction. In particular, the methods utilize non-radioactive stable isotope labels to endogenously label DNA synthesized through the de novo nucleotide synthesis pathway in a cell. The amount of label incorporated in the DNA is measured as an indication of cellular proliferation. The decay of labeled DNA over time is measured as an indication of cellular destruction. Such methods do not involve radioactivity or potentially toxic metabolites, and are suitable for use both in vitro and in vivo. Therefore, the invention is useful for measuring cellular proliferation or cellular destruction rates in humans for the diagnosis, prevention, or management of a variety of disease conditions in which cellular proliferation or cellular destruction is involved. The invention also provides methods for measuring proliferation or destruction of T cells in a subject infected with human immunodeficiency virus (HIV) and methods of screening an agent for a capacity to induce or inhibit cellular proliferation or destruction. In addition, the invention provides methods for measuring cellular proliferation in a proliferating population which utilize both radioactive isotope labels and stable isotopes to endogenously label DNA through the de novo nucleotide synthesis pathway.
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25.发明授权Compositions and methods of treatment using modulators of motoneuron diseases 有权使用运动神经元疾病调节剂的组合物和治疗方法公开(公告)号：US08883847B2
公开(公告)日：2014-11-11
申请号：US11650020
申请日：2007-01-05
IPC分类号： A61K31/353 , A61K31/55 , A61P25/14 , A61P25/16 , G01N33/68 , A61K31/35 , A61K31/4748 , C07D407/04 , A61K31/4741 , A61K31/40 , A61K45/06
CPC分类号： G01N33/6896 , A61K31/35 , A61K31/40 , A61K31/4741 , A61K31/4748 , A61K45/06 , C07D407/04 , A61K2300/00
摘要： The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); a method for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease; the discovery of drug agents that modulate neuronal microtubule dynamics in living subjects with motoneuron diseases; the discovery that administration of such agents, alone or in combinations, can provide marked neuroprotective therapy for living subjects with motoneuron diseases including delay in symptoms and prolongation of survival; and the discovery that monitoring of neuronal microtubule dynamics in subjects with motoneuron diseases, in response to therapeutic interventions, allows diagnostic monitoring for optimization of therapeutic regimen and strategy for individual subjects or for drug trials.
摘要翻译： 本文公开的发明描述了运动神经元疾病（神经元中微管的动力学改变）的新型治疗靶标; 用于测量具有确定的，初期的或潜在的运动神经元疾病的受试者中该治疗靶标的活性状态的方法; 发现在运动神经元疾病的活体中调节神经元微管动力学的药剂; 发现这些药物单独或组合可以为运动神经元疾病（包括延迟症状和延长生存）的活体受体提供显着的神经保护疗法; 以及发现，运动神经元疾病受试者的神经元微管动力学监测作为对治疗干预的响应，允许诊断监测以优化个体受试者或药物试验的治疗方案和策略。
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公开(公告)号：US20140329274A1
公开(公告)日：2014-11-06
申请号：US14343334
申请日：2012-09-07
IPC分类号： G01N33/58
CPC分类号： G01N33/58 , G01N33/6848 , G01N2458/15 , G01N2570/00 , G01N2800/7028 , G16B20/00 , Y10T436/24
摘要： Provided herein are methods for measuring molecular flux rates of molecules of interest in a tissue sample in spatially-organized manner and generating output (e.g., an image, a heat map, a contour map, a table or a database) representing the molecular flux rates of each spatially-defined location of the sample. Provided herein are also the output, as well as systems and computer-readable medium with computer-executable instructions for determining molecular flux rates of molecules of interest in the sample.
摘要翻译： 本文提供了以空间有组织的方式测量组织样品中感兴趣的分子的分子通量速率并产生代表分子通量速率的输出（例如，图像，热图，轮廓图，表或数据库）的方法 的样品的每个空间定义的位置。 本文还提供了输出以及具有用于确定样品中感兴趣的分子的分子通量速率的计算机可执行指令的系统和计算机可读介质。
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公开(公告)号：US08481478B2
公开(公告)日：2013-07-09
申请号：US13410183
申请日：2012-03-01
申请人： Marc K. Hellerstein
发明人： Marc K. Hellerstein
IPC分类号： A61K38/00
CPC分类号： G01N33/6848 , A61K49/0002 , G01N33/6803 , G01N2458/15 , G01N2500/10 , G01N2570/00 , G01N2800/52 , G06Q50/22 , Y10T436/24
摘要： Disclosed here is a method for measuring the kinetics (i.e., the molecular flux rates—synthesis and breakdown or removal rates) of a plurality of proteins or organic metabolites in living systems. The methods may be accomplished in a high-throughput, large-scale automated manner, by using existing mass spectrometric profiling techniques and art well known in the fields of static proteomics and static organeomics, without the need for additional biochemical preparative steps or analytic/instrumental devices.
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28.发明申请METHOD FOR AUTOMATED, LARGE-SCALE MEASUREMENT OF THE MOLECULAR FLUX RATES OF THE PROTEOME OR THE ORGANEOME USING MASS SPECTROMETRY 有权自动化方法，大规模测量保护剂或使用大量光谱的有机物的分子量公开(公告)号：US20120190560A1
公开(公告)日：2012-07-26
申请号：US13410183
申请日：2012-03-01
申请人： Marc K. HELLERSTEIN
发明人： Marc K. HELLERSTEIN
CPC分类号： G01N33/6848 , A61K49/0002 , G01N33/6803 , G01N2458/15 , G01N2500/10 , G01N2570/00 , G01N2800/52 , G06Q50/22 , Y10T436/24
摘要： Disclosed here is a method for measuring the kinetics (i.e., the molecular flux rates—synthesis and breakdown or removal rates) of a plurality of proteins or organic metabolites inn living systems. The methods may be accomplished in a high-throughput, large-scale automated manner, by using existing mass spectrometric profiling techniques and art well known in the fields of static proteomics and static organeomics, without the need for additional biochemical preparative steps or analytic/instrumental devices.
摘要翻译： 这里公开了一种用于测量生活系统中多种蛋白质或有机代谢物的动力学（即分子通量速率 - 合成和分解或除去速率）的方法。 这些方法可以通过使用现有的质谱分析技术和静态蛋白质组学和静态组织学领域众所周知的技术，以高通量，大规模的自动化方式完成，而不需要额外的生物化学制备步骤或分析/仪器 设备。
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29.发明申请MOLECULAR FLUX RATES THROUGH CRITICAL PATHWAYS MEASURED BY STABLE ISOTOPE LABELING IN VIVO, AS BIOMARKERS OF DRUG ACTION AND DISEASE ACTIVITY 有权通过作为药物作用和疾病活动的生物标记的生物体内稳定同位素标记测量的关键路径的分子量公开(公告)号：US20120115127A1
公开(公告)日：2012-05-10
申请号：US13215110
申请日：2011-08-22
申请人： Marc K. HELLERSTEIN
发明人： Marc K. HELLERSTEIN
CPC分类号： G01N33/6881 , G01N33/5008 , G01N33/5011 , G01N33/5014 , G01N33/5038 , G01N33/5088 , G01N33/58 , G01N33/60 , G01N33/6887 , G01N33/6893 , G01N33/92 , G01N2500/00 , G01N2800/042 , G01N2800/044 , G01N2800/323
摘要： The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through metabolic pathways of interest.
摘要翻译： 本文描述的方法能够评估受试者的化合物以评估其治疗功效或毒性作用。 分析的目标是被认为参与疾病发病机制的潜在的生化过程或过程（即代谢过程）。 一个或多个生物化学过程中的分子通量率用作生物标志物，并且与来自对照受试者（即未暴露于化合物的受试者）的分子通量速率（即，生物标志物）进行定量比较。 相对于对照受试者中的生物标志物，对象中生物标志物的任何变化提供了评估给药的药物或毒性作用的治疗功效的信息，并且如果需要，进一步开发化合物。 在本发明的一个方面，将稳定的同位素标记的底物分子施用于受试者，并且以通过感兴趣的代谢途径揭示分子通量速率的方式将标记并入靶向分子中。
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30.发明授权Method for automated, large-scale measurement of the molecular flux rates of the proteome or the organeome using mass spectrometry 有权使用质谱法自动，大规模测量蛋白质组或组织组分子通量速率的方法公开(公告)号：US08129335B2
公开(公告)日：2012-03-06
申请号：US12534807
申请日：2009-08-03
申请人： Marc K. Hellerstein
发明人： Marc K. Hellerstein
IPC分类号： A61K38/00
CPC分类号： G01N33/6848 , A61K49/0002 , G01N33/6803 , G01N2458/15 , G01N2500/10 , G01N2570/00 , G01N2800/52 , G06Q50/22 , Y10T436/24
摘要： Disclosed here is a method for measuring the kinetics (i.e., the molecular flux rates—synthesis and breakdown or removal rates) of a plurality of proteins or organic metabolites inn living systems. The methods may be accomplished in a high-throughput, large-scale automated manner, by using existing mass spectrometric profiling techniques and art well known in the fields of static proteomics and static organeomics, without the need for additional biochemical preparative steps or analytic/instrumental devices.
摘要翻译： 这里公开了一种用于测量生活系统中多种蛋白质或有机代谢物的动力学（即分子通量速率 - 合成和分解或除去速率）的方法。 这些方法可以通过使用现有的质谱分析技术和静态蛋白质组学和静态组织学领域众所周知的技术，以高通量，大规模的自动化方式完成，而不需要额外的生物化学制备步骤或分析/仪器 设备。
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