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1. 发明申请

WO2008038000A8 DIAGNOSTIC METHOD FOR DETECTING OR MONITORING CANCER 审中-公开
标题翻译：用于检测或监测癌症的诊断方法
公开(公告)号：WO2008038000A8
公开(公告)日：2009-07-16
申请号：PCT/GB2007003674
申请日：2007-09-26
申请人： UNIV HONG KONG CHINESE , LO YUK MING DENNIS , CHAN KWAN CHEE ALLEN , DING CHUNMING
发明人： LO YUK MING DENNIS , CHAN KWAN CHEE ALLEN , DING CHUNMING
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/154
摘要： The present invention concerns a method for the detection or monitoring of cancer using a biological sample selected from blood, plasma, serum, saliva, urine from an individual, said method comprising: (a) obtaining DNA from the said biological sample; (b) digesting the DNA sample with one or more methylation-sensitive restriction enzymes; (c) quantifying or detecting a DNA sequence of interest after step (b), wherein the target sequence of interest contains at least two methylation-sensitive restriction enzyme recognition sites; and (d) comparing the level of the DNA sequence from the individual to a normal standard, to detect, prognosticate or monitor cancer.
摘要翻译：本发明涉及使用选自血液，血浆，血清，唾液，个体尿液的生物样品检测或监测癌症的方法，所述方法包括：（a）从所述生物样品中获得DNA; （b）用一种或多种甲基化敏感性限制酶消化DNA样品; （c）在步骤（b）之后量化或检测目标DNA序列，其中所述靶序列含有至少两个甲基化敏感性限制酶识别位点; 和（d）将来自个体的DNA序列的水平与正常标准进行比较，以检测，预测或监测癌症。

2. 发明申请

WO2007132167A3 NOVEL FETAL MARKERS FOR PRENATAL DIAGNOSIS AND MONITORING 审中-公开
标题翻译：用于临床诊断和监测的新型标记
公开(公告)号：WO2007132167A3
公开(公告)日：2008-05-22
申请号：PCT/GB2007001627
申请日：2007-05-03
申请人： UNIV HONG KONG CHINESE , LO YUK MING DENNIS , CHIU ROSSA WAI KWUN , CHIM STEPHEN SIU CHUNG , DING CHUNMING , JIN SHENGNAN , LEE TRACY YUEN HAN , LUN FIONA MIU FUN
发明人： LO YUK MING DENNIS , CHIU ROSSA WAI KWUN , CHIM STEPHEN SIU CHUNG , DING CHUNMING , JIN SHENGNAN , LEE TRACY YUEN HAN , LUN FIONA MIU FUN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/154 , C12Q2600/156 , C12Q2523/125
摘要： This application provides the use of novel fetal markers for prenatal diagnosis and monitoring of certain pregnancy-related conditions. More specifically, the invention resides in the discovery that certain CpG islands located on fetal chromosome 21 demonstrate a methylation profile that is distinct from that of the corresponding CpG islands located on maternal chromosome 21. This application also provides kits for diagnosing or monitoring of the relevant conditions.
摘要翻译：该应用提供了新颖的胎儿标记物用于产前诊断和监测某些妊娠相关病症的用途。更具体地，本发明在于发现位于胎儿染色体21上的某些CpG岛表现出与位于母体染色体21上的相应CpG岛不同的甲基化谱。该应用还提供用于诊断或监测相关条件。

3. 发明申请

WO2008038000A1 DIAGNOSTIC METHOD FOR DETECTING OR MONITORING CANCER 审中-公开
标题翻译：用于检测或监测癌症的诊断方法
公开(公告)号：WO2008038000A1
公开(公告)日：2008-04-03
申请号：PCT/GB2007/003674
申请日：2007-09-26
申请人： THE CHINESE UNIVERSITY OF HONG KONG , HO, Yuk, Ming, Dennis , CHAN, Kwan, Chee, Allen , DING, Chunming
发明人： HO, Yuk, Ming, Dennis , CHAN, Kwan, Chee, Allen , DING, Chunming
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/154
摘要： The present invention concerns a method for the detection or monitoring of cancer using a biological sample selected from blood, plasma, serum, saliva, urine from an individual, said method comprising: (a) obtaining DNA from the said biological sample; (b) digesting the DNA sample with one or more methylation-sensitive restriction enzymes; (c) quantifying or detecting a DNA sequence of interest after step (b), wherein the target sequence of interest contains at least two methylation-sensitive restriction enzyme recognition sites; and (d) comparing the level of the DNA sequence from the individual to a normal standard, to detect, prognosticate or monitor cancer.
摘要翻译：本发明涉及使用选自血液，血浆，血清，唾液，个体尿液的生物样品检测或监测癌症的方法，所述方法包括：（a）从所述生物样品中获得DNA; （b）用一种或多种甲基化敏感性限制酶消化DNA样品; （c）在步骤（b）之后量化或检测目标DNA序列，其中所述靶序列含有至少两个甲基化敏感性限制酶识别位点; 和（d）将来自个体的DNA序列的水平与正常标准进行比较，以检测，预测或监测癌症。

4. 发明申请

WO2007132166A3 NEW FETAL METHYLATION MARKERS 审中-公开
标题翻译：新型甲基化标记
公开(公告)号：WO2007132166A3
公开(公告)日：2008-02-21
申请号：PCT/GB2007001625
申请日：2007-05-03
申请人： UNIV HONG KONG CHINESE , LO YUK MING DENNIS , CHIU ROSSA WAI KWUN , CHIM STEPHEN SIU CHUNG , DING CHUNMING , CHAN KWAN CHEE , WONG HING NAM IVY , YUEN KA CHUN RYAN
发明人： LO YUK MING DENNIS , CHIU ROSSA WAI KWUN , CHIM STEPHEN SIU CHUNG , DING CHUNMING , CHAN KWAN CHEE , WONG HING NAM IVY , YUEN KA CHUN RYAN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68 , C12Q1/6876 , C12Q1/6883 , C12Q2600/154 , C12Q2600/156
摘要： This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB21P, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.
摘要翻译：该应用描述了在孕妇中发现来自胎儿的某些基因（例如RASSF1A，APC，CASP8，RARB，SCGB3A1，DAB21P，PTPN6，THY1，TMEFF2和PYCARD）是高度甲基化的，而相同的基因产妇来源是未甲基化。该发现允许从孕妇的生物样品中容易地检测这些甲基化胎儿基因中的一种或多种，作为样品中胎儿DNA存在的通用指标。这些胎儿甲基化标记物作为非侵入性分析过程的阳性对照特别有用，在此过程中监测胎儿DNA的质量和数量。这些新确定的胎儿标记物也可以直接测量以诊断某些妊娠相关病症。

5. 发明申请

WO2007132166A2 NEW FETAL METHYLATION MARKERS 审中-公开
标题翻译：新型甲基化标记
公开(公告)号：WO2007132166A2
公开(公告)日：2007-11-22
申请号：PCT/GB2007/001625
申请日：2007-05-03
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk Ming, Dennis , CHIU, Rossa Wai Kwun , CHIM, Stephen Siu Chung , DING, Chunming , CHAN, Kwan Chee , WONG, Hing Nam Ivy , YUEN, Ka Chun Ryan
发明人： LO, Yuk Ming, Dennis , CHIU, Rossa Wai Kwun , CHIM, Stephen Siu Chung , DING, Chunming , CHAN, Kwan Chee , WONG, Hing Nam Ivy , YUEN, Ka Chun Ryan
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68 , C12Q1/6876 , C12Q1/6883 , C12Q2600/154 , C12Q2600/156
摘要： This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB21P , PTPN6, THY1, TMEFF2 , and PYCARD ) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.
摘要翻译：该应用描述了在孕妇中发现来自胎儿的某些基因（如RASSF1A，APC，CASP8，RARB，SCGB3A1，DAB21P，PTPN6，THY1，TMEFF2和PYCARD）高度甲基化，而相同的基因产妇来源是未甲基化。该发现允许从孕妇的生物样品中容易地检测这些甲基化胎儿基因中的一种或多种，作为样品中胎儿DNA存在的通用指标。这些胎儿甲基化标记物作为非侵入性分析过程的阳性对照特别有用，在此过程中监测胎儿DNA的质量和数量。这些新确定的胎儿标记物也可以直接测量以诊断某些妊娠相关病症。

6. 发明申请

WO2005023091A2 METHOD FOR NON-INVASIVE PRENATAL DIAGNOSIS 审中-公开
标题翻译：非侵入性预后诊断方法
公开(公告)号：WO2005023091A2
公开(公告)日：2005-03-17
申请号：PCT/US2004/028857
申请日：2004-09-07
申请人： THE TRUSTEES OF BOSTON UNIVERSITY , THE CHINESE UNIVERSITY OF HONG KONG , CANTOR, Charles, R. , DING, Chunming , LO, Yuk, Ming, Dennis , CHIU, Rossa, Wai-Kwun
发明人： CANTOR, Charles, R. , DING, Chunming , LO, Yuk, Ming, Dennis , CHIU, Rossa, Wai-Kwun
IPC分类号： A61B
CPC分类号： C12Q1/6881 , C12Q1/6872 , C12Q2600/156 , C12Q2600/172 , C12Q2535/125
摘要： The present invention is directed to methods of detecting nucleic acids in a biological sample. The method is based on a novel combination of a base extension reaction, which provides excellent analytical specificity, and a mass spectrometric analysis, which provides excellent specificity. The method can be used, for example, for diagnostic, prognostic and treatment purposes. The method can be used, for example, for diagnostic, prognostic and treatment purposes. The method allows accurate detection of nucleic acids that are present in very small amounts in a biological sample. For example, the method of the present invention is preferably used to detect fetal nucleic acid in maternal blood sample; circulating tumor-specific nucleic acids in a blood, urine or stool sample; and donor-specific acids in transplant recipients. In another embodiment, one can detect viral, bacterial, fungal, or other foreign nucleic acids in biological sample.
摘要翻译：本发明涉及检测生物样品中核酸的方法。该方法基于提供优异分析特异性的碱基延伸反应和提供优异特异性的质谱分析的新型组合。该方法可用于例如诊断，预后和治疗目的。该方法可用于例如诊断，预后和治疗目的。该方法允许精确检测在生物样品中以非常少的量存在的核酸。例如，本发明的方法优选用于检测母体血液样品中的胎儿核酸; 在血液，尿液或粪便样品中循环肿瘤特异性核酸; 和供体特异性酸在移植受体。在另一个实施方案中，可以检测生物样品中的病毒，细菌，真菌或其它外来核酸。

7. 发明申请

WO2004022721A2 QUANTIFICATION OF GENE EXPRESSION 审中-公开
标题翻译：基因表达的定量
公开(公告)号：WO2004022721A2
公开(公告)日：2004-03-18
申请号：PCT/US2003/028081
申请日：2003-09-05
申请人： THE TRUSTEES OF BOSTON UNIVERSITY , CANTOR, Charles, R. , DING, Chunming
发明人： CANTOR, Charles, R. , DING, Chunming
IPC分类号： C12N
CPC分类号： C12Q1/6851 , C12Q2545/107 , C12Q2535/125 , C12Q2525/186
摘要： The present invention relates to a method for measuring the amount of a target nucleic acid in a sample using a standard which is designed to have one base difference compared with the gene of interest or a "target nucleic acid sequence." Use of such standard in combination with a method of "enhancing" the difference in the standard and the test nucleic acid sample using, for example, a base extension reaction carried right at the mutation site allowing amplification of the standard and target nucleic acids with the same efficiency and facilitating quantification of the target nucleic acid. Thereafter a means of quantifying the "enhanced" standard and target nucleic acid samples is used to determine the amount of the target nucleic acid. In the preferred embodiment, the quantification means is Mass Spectrometry.
摘要翻译：本发明涉及使用设计为与目的基因相比具有一个碱基差的标准或“靶核酸序列”来测量样品中靶核酸量的方法。使用这样的标准物与“增强”标准差异的方法和使用例如在突变位点上携带的碱基延伸反应的测试核酸样品的方法相结合，可以扩增标准品和靶核酸相同的效率和促进目标核酸的定量。此后，使用定量“增强”标准和靶核酸样品的手段来确定靶核酸的量。在优选实施方案中，定量方法是质谱法。

8. 发明申请

WO2007132167A2 NOVEL MARKERS FOR PRENATAL DIAGNOSIS AND MONITORING 审中-公开
标题翻译：用于临床诊断和监测的新标志
公开(公告)号：WO2007132167A2
公开(公告)日：2007-11-22
申请号：PCT/GB2007/001627
申请日：2007-05-03
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk Ming Dennis , CHIU, Rossa Wai Kwun , CHIM, Stephen Siu Chung , DING, Chunming , JIN, Shengnan , LEE, Tracy Yuen Han , LUN, Fiona Miu Fun
发明人： LO, Yuk Ming Dennis , CHIU, Rossa Wai Kwun , CHIM, Stephen Siu Chung , DING, Chunming , JIN, Shengnan , LEE, Tracy Yuen Han , LUN, Fiona Miu Fun
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/154 , C12Q2600/156 , C12Q2523/125
摘要： This application provides the use of novel fetal markers for prenatal diagnosis and monitoring of certain pregnancy-related conditions. More specifically, the invention resides in the discovery that certain CpG islands located on fetal chromosome 21 demonstrate a methylation profile that is distinct from that of the corresponding CpG islands located on maternal chromosome 21. This application also provides kits for diagnosing or monitoring of the relevant conditions.
摘要翻译：该应用提供了新颖的胎儿标记物用于产前诊断和监测某些妊娠相关病症的用途。更具体地，本发明在于发现位于胎儿染色体21上的某些CpG岛表现出与位于母体染色体21上的相应CpG岛不同的甲基化谱。该应用还提供用于诊断或监测相关条件。

9. 发明申请

WO2004065617A3 HAPLOTYPE ANALYSIS 审中-公开
标题翻译： HAPLOTYPE分析
公开(公告)号：WO2004065617A3
公开(公告)日：2006-06-15
申请号：PCT/US2004001329
申请日：2004-01-16
申请人： UNIV BOSTON , CANTOR CHARLES R , DING CHUNMING
发明人： CANTOR CHARLES R , DING CHUNMING
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q2600/156 , C12Q2527/137 , C12Q2537/143 , C12Q2565/627
摘要： The present invention provides an efficient way for high throughput haplotype analysis. Several polymorphic nucleic acid markers, such as SNPs, can be simultaneously and reliably determined through multiplex PCR of single nucleic acid molecules in several parallel single molecule dilutions and the consequent statistical analysis of the results from these parallel single molecule multiplex PCR reactions results in reliable determination of haplotypes present in the subject. The nucleic acid markers can be of any distance to each other on the chromosome. In addition, an approach wherein overlapping DNA markers are analyzed can be used to link smaller haplotypes into larger haplotypes. Consequently, the invention provides a powerful new tool for diagnostic haplotyping and identifying novel haplotypes.
摘要翻译：本发明提供了高通量单倍型分析的有效方法。可以通过多个平行的单分子稀释物中的单个核酸分子的多重PCR来同时并可靠地测定几种多态性核酸标记，例如SNP，并且随后对来自这些平行的单分子多重PCR反应的结果的统计分析导致可靠的测定的单倍体存在于受试者。核酸标记在染色体上可以彼此有任何距离。此外，分析重叠的DNA标记物的方法可用于将较小的单倍型连接到较大的单元型中。因此，本发明为诊断单倍型和鉴定新型单体型提供了强大的新工具。

10. 发明申请

WO2006019407A2 METHOD FOR DETECTING AND QUANTIFYING RARE MUTATIONS/POLYMORPHISMS 审中-公开
标题翻译：检测和量化稀有突变/多态性的方法
公开(公告)号：WO2006019407A2
公开(公告)日：2006-02-23
申请号：PCT/US2005/005255
申请日：2005-02-18
申请人： THE TRUSTEES OF BOSTON UNIVERSITY , CANTOR, Charles, R. , DING, Chunming
发明人： CANTOR, Charles, R. , DING, Chunming
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q2600/156 , C12Q2525/186 , C12Q2535/125 , C12Q2565/627 , C12Q2545/101
摘要： The present invention is directed to a method for detecting and quantifying rare mutations in a nucleic acid sample. The nucleic acid molecules under investigation can be either DNA or RNA. The rare mutation can be any type of functional or non-functional nucleic acid change or mutation, such as deletion, insertion, translocation, inversion, one or more base substitution or polymorphism. Therefore, the methods of the present invention are useful in detection of rare mutations in, for example, diagnostic, prognostic and follow-up applications, when the targets are rare known nucleic acid variants mixed in with the wildtype or the more common nucleic acid variant(s).
摘要翻译：本发明涉及一种用于检测和定量核酸样品中罕见突变的方法。正在研究的核酸分子可以是DNA或RNA。罕见突变可以是任何类型的功能或非功能性核酸变化或突变，例如缺失，插入，易位，反转，一个或多个碱基取代或多态性。因此，当目标是罕见的已知的与野生型或更常见的核酸变体混合的核酸变体时，本发明的方法可用于检测例如诊断，预后和随访应用中的罕见突变（S）。

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