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1. 发明申请

WO1998010057A1 METHODS FOR TESTING COMPOUNDS FOR USE AS THERAPEUTIC ANTIOXIDANTS 审中-公开
标题翻译：测试化合物用作治疗抗氧化剂的方法
公开(公告)号：WO1998010057A1
公开(公告)日：1998-03-12
申请号：PCT/US1997015814
申请日：1997-09-05
申请人： EMORY UNIVERSITY , DUKE UNIVERSITY
发明人： EMORY UNIVERSITY , DUKE UNIVERSITY , WALLACE, Douglas, C. , MELOV, Simon, L. , CRAPO, James, D. , DAY, Brian, J.
IPC分类号： C12N05/00
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0393 , A61K49/0008 , C12N9/0089
摘要： The present application describes methods for the testing of compounds of potential usefulness as therapeutic antioxidants and/or as therapeutic free radical scavengers. The animal model for testing such compounds is the Sod2CJE homozygous Manganese Superoxide Dismutase-deficient mouse. When pups of these mice are treated with certain antioxidants, they survive past about 7 days of age, and later develop characteristic histological changes and characteristic neurobehavioral disorders. Those treated mice can be further treated with test compounds which may or may not cross the blood brain barrier, and the life span and physical and neurobehavioral characteristics of those mice provide information about the potential utility of the test compound as a therapeutic antioxidant. Phenotypes of the treated mice allow conclusions regarding targeted areas of the brain and thus, applications to particular disorders such as Parkinsonism.
摘要翻译：本申请描述了测试作为治疗性抗氧化剂和/或作为治疗性自由基清除剂的潜在有用性的化合物的方法。用于测试这些化合物的动物模型是Sod2CJE纯合的锰超氧化物歧化酶缺陷型小鼠。当这些小鼠的幼仔用某些抗氧化剂处理时，它们可以在约7天龄之后存活，并且随后发展特征性组织学变化和特征性神经行为障碍。那些治疗的小鼠可以进一步用可能或不可能穿过血脑屏障的测试化合物进行治疗，并且这些小鼠的寿命和物理和神经行为特征提供了关于测试化合物作为治疗性抗氧化剂的潜在效用的信息。经处理的小鼠的表型允许关于脑的目标区域的结论，因此可以应用于特定疾病如帕金森综合征。

2. 发明申请

WO2003018775A3 HUMAN MITOCHONDRIAL DNA POLYMORPHISMS, HAPLOGROUPS, ASSOCIATIONS WITH PHYSIOLOGICAL CONDITIONS, AND GENOTYPING ARRAYS 审中-公开
公开(公告)号：WO2003018775A3
公开(公告)日：2003-03-06
申请号：PCT/US2002/028471
申请日：2002-08-30
申请人： EMORY UNIVERSITY , WALLACE, Douglas, C. , HOSSEINI, Seyed , MISHMAR, Dan , RUIZ-PESINI, Eduardo , LOTT, Marie
发明人： WALLACE, Douglas, C. , HOSSEINI, Seyed , MISHMAR, Dan , RUIZ-PESINI, Eduardo , LOTT, Marie
IPC分类号： C12Q1/68
摘要： This inention provides human mtDNA polymorphisms that are diagnostic of all the major human haplogroups and methods of diagnosing those haplogroups and selected haplogroups.

3. 发明申请

WO2005058142A2 DIABETES DIAGNOSTIC 审中-公开
标题翻译：糖尿病诊断
公开(公告)号：WO2005058142A2
公开(公告)日：2005-06-30
申请号：PCT/US2004/042110
申请日：2004-12-16
申请人： EMORY UNIVERSITY , WALLACE, Douglas, C. , LEVY, Shawn , KERSTANN, Keith , PROCACCIO, Vincent
发明人： WALLACE, Douglas, C. , LEVY, Shawn , KERSTANN, Keith , PROCACCIO, Vincent
IPC分类号： A61B
CPC分类号： G01N33/6893 , C12Q1/6883 , C12Q2600/156 , C12Q2600/158 , G01N2800/042
摘要： A method for identifying a patient likely to have, or at risk of developing, Type II diabetes or insulin resistance is provided. The method is performed by identifying an expression profile typical of Type II diabetes in which selected genes are upregulated and/or selected genes are downregulated. This expression profile correlates with an A3243G mutation level of 10% to 55%.
摘要翻译：提供了用于鉴定可能具有或具有发展为II型糖尿病或胰岛素抵抗的风险的患者的方法。该方法通过鉴定典型的II型糖尿病的表达谱来进行，其中选择的基因被上调和/或选择的基因被下调。该表达谱与A3243G突变水平相关，为10％至55％。

4. 发明申请

WO2003020220A2 MITOCHONDRIAL BIOLOGY EXPRESSION ARRAYS 审中-公开
标题翻译：微生物生物表达阵列
公开(公告)号：WO2003020220A2
公开(公告)日：2003-03-13
申请号：PCT/US2002/027886
申请日：2002-08-30
申请人： EMORY UNIVERSITY , WALLACE, Douglas, C. , LEVY, Shawn , KERSTANN, Keith , PROCACCIO, Vincent
发明人： WALLACE, Douglas, C. , LEVY, Shawn , KERSTANN, Keith , PROCACCIO, Vincent
IPC分类号： A61K
CPC分类号： C12Q1/6883 , C12Q1/6837 , C12Q2600/158
摘要： This invention provides a library of genes involved in mitochondrial biology, arrays containing probes for genes involved in mitochondrial biology, methods for making such arrays, and methods of using such arrays. Genes and probe sequences involved in mitochondrial biology in humans and mice are provided. The arrays of this invention are useful for determining mitochondrial biology gene expression profiles. Mitochondrial biology gene expression profiles are useful for determining expression profiles diagnostic of physiological conditions; diagnosing physiological conditions; identifying biochemical pathways, genes, and mutations involved in physiological conditions; identifying therapeutic agents useful for preventing and/or treating such physiological conditions; evaluating and/or monitoring the efficacy of such therapies, and creating and identifying animal models of human physiologic conditions. Arrays containing probes for all genes known to be involved in mitochondrial biology are provided, as well as arrays containing subsets of such probes.
摘要翻译：本发明提供了涉及线粒体生物学的基因文库，包含涉及线粒体生物学基因的探针的阵列，以及制备这种阵列的方法，以及使用这种阵列的方法。提供了涉及人和小鼠线粒体生物学的基因和探针序列。本发明的阵列可用于测定线粒体生物学基因表达谱。线粒体生物学基因表达谱可用于确定生理条件诊断的表达谱; 诊断生理条件; 识别涉及生理条件的生物化学途径，基因和突变; 鉴定可用于预防和/或治疗这种生理条件的治疗剂; 评估和/或监测这些疗法的功效，以及创建和鉴定人类生理状况的动物模型。提供了包含已知参与线粒体生物学的所有基因的探针的阵列，以及包含这种探针子集的阵列。

5. 发明申请

WO1994009162A1 DETECTION OF MITOCHONDRIAL DNA MUTATIONS ASSOCIATED WITH ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE 审中-公开
标题翻译：检测与阿尔茨海默病和帕金森病相关的麻醉DNA突变
公开(公告)号：WO1994009162A1
公开(公告)日：1994-04-28
申请号：PCT/US1993010072
申请日：1993-10-20
申请人： EMORY UNIVERSITY SCHOOL OF MEDICINE
发明人： EMORY UNIVERSITY SCHOOL OF MEDICINE , WALLACE, Douglas, C.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6883 , C12Q2600/156 , C12Q2600/172
摘要： This invention provides a method of diagnosing or predicting a predisposition to Alzeimer's disease and/or Parkinson's disease. The method comprises detecting in a sample from a subject the presence of a mutation, for example, in nucleotide position 4,336, 3,397, 3,196 or an insertion between positions 956 and 965, of mitochondrial DNA. The presence of the mutation indicates the presence of or a predisposition to Alzeimer's disease. Since each mutation increases the likelihood of developing or having Alzeimer's disease, the detection of more than one of the mutations in an individual can increase the probability of having or developing the disease. The invention also provides a method of determining mutations associated with the presence of or predisposition to Alzeimer's and/or Parkinson's disease. The method comprises: a) obtaining a mitochondrial DNA-containing sample from a subject with Alzeimer's disease; b) determining the presence of mutations in the mitochondrial DNA; c) comparing the mutations found in normal subject; and d) determining which mutations have a greater rate of occurence in the subject with Alzeimer's disease.
摘要翻译：本发明提供了诊断或预测阿尔茨海默病和/或帕金森病易感性的方法。该方法包括在受试者的样品中检测是否存在例如核苷酸位置4,336,3,397,3916或线粒体DNA的位置956和965之间的插入。突变的存在表明Alzeimer病的存在或倾向。由于每个突变增加了发生或具有阿尔茨海默病的可能性，所以检测个体中多于一个的突变可增加疾病发生或发展的可能性。本发明还提供了确定与Alzeimer's和/或帕金森氏病的存在或倾向相关的突变的方法。该方法包括：a）从患有Alzeimer病的受试者获得含有线粒体DNA的样品; b）确定线粒体DNA中突变的存在; c）比较正常受试者发现的突变; 和d）确定哪些突变在患有Alzeimer病的患者中具有更高的发生率。

6. 发明申请

WO2003020220A3 MITOCHONDRIAL BIOLOGY EXPRESSION ARRAYS 审中-公开
公开(公告)号：WO2003020220A3
公开(公告)日：2003-03-13
申请号：PCT/US2002/027886
申请日：2002-08-30
申请人： EMORY UNIVERSITY , WALLACE, Douglas, C. , LEVY, Shawn , KERSTANN, Keith , PROCACCIO, Vincent
发明人： WALLACE, Douglas, C. , LEVY, Shawn , KERSTANN, Keith , PROCACCIO, Vincent
IPC分类号： C12Q1/68
摘要： This invention provides a library of genes involved in mitochondrial biology, arrays containing probes for genes involved in mitochondrial biology, methods for making such arrays, and methods of using such arrays. Genes and probe sequences involved in mitochondrial biology in humans and mice are provided. The arrays of this invention are useful for determining mitochondrial biology gene expression profiles. Mitochondrial biology gene expression profiles are useful for determining expression profiles diagnostic of physiological conditions; diagnosing physiological conditions; identifying biochemical pathways, genes, and mutations involved in physiological conditions; identifying therapeutic agents useful for preventing and/or treating such physiological conditions; evaluating and/or monitoring the efficacy of such therapies, and creating and identifying animal models of human physiologic conditions. Arrays containing probes for all genes known to be involved in mitochondrial biology are provided, as well as arrays containing subsets of such probes.

7. 发明申请

WO2003018775A2 HUMAN MITOCHONDRIAL DNA POLYMORPHISMS, HAPLOGROUPS, ASSOCIATIONS WITH PHYSIOLOGICAL CONDITIONS, AND GENOTYPING ARRAYS 审中-公开
标题翻译：人类麻醉DNA多态性，HAPLOGROUPS，与生理条件的协会和基因组阵列
公开(公告)号：WO2003018775A2
公开(公告)日：2003-03-06
申请号：PCT/US2002/028471
申请日：2002-08-30
申请人： EMORY UNIVERSITY , WALLACE, Douglas, C. , HOSSEINI, Seyed , MISHMAR, Dan
发明人： WALLACE, Douglas, C. , HOSSEINI, Seyed , MISHMAR, Dan
IPC分类号： C12N
CPC分类号： C12Q1/6883 , C12Q2600/156
摘要： This inention provides human mtDNA polymorphisms that are diagnostic of all the major human haplogroups and methods of diagnosing those haplogroups and selected subhaplogroups. This invention also provides methods for identifying evolutionarily significant mitochondrial DNA genes, nucleotide alleles, and amino acid alleles. Evolutionarily significant genes and alleles are identified using one or two populations of a single species. The process of identifying evolutionarily significant nucleotide alleles involves identifying evolutionarily significant genes and then evolutionarily significant nucleotide alleles in those genes, and identifying evolutionarily significant amino acid alleles involves identifying amino acids encoded by all nonsynonymous alleles. Synonymous codings of the nucleotide alleles encoding evolutionarily significant amino acid alleles of this invention are equivalent to the evolutionarily significant amino acid alleles disclosed herein and are included within the scope of this invention. Synonymous codings include alleles at neighboring nucleotide loci that are within the same codon. This invention also provides methods for associating haplogroups and evolutionarily significant nucleotide and amino acid alleles with predispositions to physiological conditions. Methods for diagnosing predisposition to LHON, and methods for diagnosing increased likelihood of developing blindness, centenaria, and increased longevity that are not dependent on the geographical location of the individual being diagnosed are provided herein. Diagnosis of an individual with a predisposition to an energy metabolism-related physiological condition is dependent on the geographic region of the individual. Physiological conditions diagnosable by the methods of this invention include healthy conditions and pathological conditions. Physiological conditions that are associated with haplogroups and with alleles provided by this invention include energetic imbalance, metabolic disease, abnormal energy metabolism, abnormal temperature regulation, abnormal oxidative phosphorylation, abnormal electron transport, obesity, amount of body fat, diabetes, hypertension, and cardiovascular disease.
摘要翻译：这个意图提供了人类mtDNA多态性，其是所有主要人类单倍群的诊断和诊断这些单倍群和选择的亚群体的方法。本发明还提供了鉴定进化上重要的线粒体DNA基因，核苷酸等位基因和氨基酸等位基因的方法。使用单个物种的一个或两个群体来鉴定进化上重要的基因和等位基因。识别进化上重要的核苷酸等位基因的过程涉及鉴定进化上重要的基因，然后鉴定那些基因中的进化上重要的核苷酸等位基因，并且鉴定进化上重要的氨基酸等位基因涉及确定由所有非等位基因编码的氨基酸。编码本发明进化上重要氨基酸等位基因的核苷酸等位基因的同义编码等同于本文公开的进化上重要的氨基酸等位基因，并且包括在本发明的范围内。同义编码包括在相同密码子内的相邻核苷酸位点处的等位基因。本发明还提供了将单倍群和进化上重要的核苷酸和氨基酸等位基因与生理条件倾向相关联的方法。本文提供了用于诊断LHON倾向的方法，以及用于诊断不依赖于被诊断的个体的地理位置的发展失明，百日咳和增加的寿命的增加的可能性的方法。具有与能量代谢相关的生理状况倾向的个体的诊断取决于个体的地理区域。通过本发明的方法可诊断的生理条件包括健康状况和病理状况。与本发明提供的单体组和等位基因相关的生理条件包括能量不平衡，代谢疾病，异常能量代谢，异常温度调节，异常氧化磷酸化，异常电子转运，肥胖，体脂肪，糖尿病，高血压和心血管疾病。

8. 发明申请

WO1998019714A1 MOUSE LACKING HEART-MUSCLE ADENINE NUCLEOTIDE TRANSLOCATOR PROTEIN AND METHODS 审中-公开
标题翻译：小鼠USE ING LE LE LE INE INE S S S S S S S S S S S S
公开(公告)号：WO1998019714A1
公开(公告)日：1998-05-14
申请号：PCT/US1997019882
申请日：1997-10-31
申请人： EMORY UNIVERSITY
发明人： EMORY UNIVERSITY , WALLACE, Douglas, C. , GRAHAM, Brett, C. , MacGREGOR, Grant, R.
IPC分类号： A61K49/00
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A61K49/0008
摘要： Provided are transgenic mice genetically engineered for a deficiency of the heart-skeletal muscle isoform of the adenine nucleotide translocator protein (Ant1). These mice exhibit histological, biochemical, and physiological signs of deficiency in oxidative phosphorylation and energy generation, and these mice provide the first animal model for mitochondrial myopathy and hypertrophic cardiomyopathy. This animal model is used in methods for testing compounds for therapeutic value in treating failure to exchange ATP and ADP across the mitochondrial inner membrane, OXPHOS deficiency and in treating cardiac hypertrophy.
摘要翻译：提供基因工程用于腺嘌呤核苷酸转运蛋白（Ant1）的心脏 - 骨骼肌同种型缺陷的转基因小鼠。这些小鼠显示氧化磷酸化和能量产生缺乏的组织学，生物化学和生理学迹象，并且这些小鼠提供了线粒体肌病和肥大性心肌病的第一动物模型。该动物模型用于测试化合物治疗价值的方法，用于治疗在线粒体内膜，OXPHOS缺乏症和治疗心脏肥大中交换ATP和ADP的失败。

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