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21. 发明申请

US20120003650A1 MARKER FOR PRENATAL DIAGNOSIS AND MONITORING 审中-公开
标题翻译：用于临床诊断和监测的标记
公开(公告)号：US20120003650A1
公开(公告)日：2012-01-05
申请号：US13215024
申请日：2011-08-22
申请人： Yuk Ming Dennis LO , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Yu-Kwan Tong , Chunming Ding
发明人： Yuk Ming Dennis LO , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Yu-Kwan Tong , Chunming Ding
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/154 , C12Q2600/156 , C12Q2521/331
摘要： The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.
摘要翻译：本发明涉及通过分析存在于母亲血液中的胎儿DNA来诊断妊娠相关疾病的新方法。更具体地说，本发明依赖于maspin基因在胎儿DNA和母体DNA中差异甲基化的发现，并提供了这些新的诊断方法，其将胎儿DNA与母体DNA区分开，并根据胎儿DNA水平和甲基化异常检测产前疾病状态。

22. 发明授权

US08026067B2 Marker for prenatal diagnosis and monitoring 有权
标题翻译：产前诊断和监测的标记
公开(公告)号：US08026067B2
公开(公告)日：2011-09-27
申请号：US12724335
申请日：2010-03-15
申请人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Yu-kwan Tong , Chunming Ding
发明人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Yu-kwan Tong , Chunming Ding
IPC分类号： C07H21/04 , C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/154 , C12Q2600/156 , C12Q2521/331
摘要： The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.
摘要翻译：本发明涉及通过分析存在于母亲血液中的胎儿DNA来诊断妊娠相关疾病的新方法。更具体地说，本发明依赖于maspin基因在胎儿DNA和母体DNA中差异甲基化的发现，并提供了这些新的诊断方法，其将胎儿DNA与母体DNA区分开，并根据胎儿DNA水平和甲基化异常检测产前疾病状态。

23. 发明授权

US07709262B2 Method for detecting and quantifying rare mutations/polymorphisms 有权
标题翻译：检测和定量稀有突变/多态性的方法
公开(公告)号：US07709262B2
公开(公告)日：2010-05-04
申请号：US10589709
申请日：2005-02-18
申请人： Charles R. Cantor , Chunming Ding
发明人： Charles R. Cantor , Chunming Ding
IPC分类号： C12Q1/68 , C12P19/34
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）。

24. 发明授权

US08501443B2 Haplotype analysis 有权
标题翻译：单倍型分析
公开(公告)号：US08501443B2
公开(公告)日：2013-08-06
申请号：US13565105
申请日：2012-08-02
申请人： Charles R Cantor , Chunming Ding
发明人： Charles R Cantor , Chunming Ding
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02
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。

25. 发明申请

US20110143342A1 NEW FETAL METHYLATION MARKERS 有权
标题翻译：新型甲基化标记
公开(公告)号：US20110143342A1
公开(公告)日：2011-06-16
申请号：US12791776
申请日：2010-06-01
申请人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Chunming Ding , Kwan Chee Chan , Hing Nam Ivy Wong , Ka Chun Ryan Yuen
发明人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Chunming Ding , Kwan Chee Chan , Hing Nam Ivy Wong , Ka Chun Ryan Yuen
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, DAB2IP, 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，DAB2IP，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。

26. 发明申请

US20110097712A1 METHOD FOR DETECTING AND QUANTIFYING RARE MUTATIONS/POLYMORPHISMS 有权
标题翻译：检测和量化稀有突变/多态性的方法
公开(公告)号：US20110097712A1
公开(公告)日：2011-04-28
申请号：US12496390
申请日：2009-07-01
申请人： Charles R. Cantor , Chunming Ding
发明人： Charles R. Cantor , Chunming Ding
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）。

27. 发明授权

US07901884B2 Markers for prenatal diagnosis and monitoring 有权
标题翻译：产前诊断和监测的标记
公开(公告)号：US07901884B2
公开(公告)日：2011-03-08
申请号：US11784499
申请日：2007-04-06
申请人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Chunming Ding , Shengnan Jin , Tracy Yuen Han Lee , Fiona Miu Fun Lun
发明人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Chunming Ding , Shengnan Jin , Tracy Yuen Han Lee , Fiona Miu Fun Lun
IPC分类号： C07H21/04 , 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。

28. 发明授权

US07754428B2 Fetal methylation markers 有权
标题翻译：胎儿甲基化标记
公开(公告)号：US07754428B2
公开(公告)日：2010-07-13
申请号：US11784501
申请日：2007-04-06
申请人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Chunming Ding , Kwan Chee Chan , Hing Nam Ivy Wong , Ka Chun Ryan Yuen
发明人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Chunming Ding , Kwan Chee Chan , Hing Nam Ivy Wong , Ka Chun Ryan Yuen
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
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, DAB2IP, 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，DAB2IP，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。

29. 发明授权

US07709194B2 Marker for prenatal diagnosis and monitoring 有权
标题翻译：产前诊断和监测的标记
公开(公告)号：US07709194B2
公开(公告)日：2010-05-04
申请号：US11144951
申请日：2005-06-03
申请人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Yu-kwan Tong , Chunming Ding
发明人： Yuk Ming Dennis Lo , Rossa Wai Kwun Chiu , Stephen Siu Chung Chim , Yu-kwan Tong , Chunming Ding
IPC分类号： C07H21/04 , C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/154 , C12Q2600/156 , C12Q2521/331
摘要： The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.
摘要翻译：本发明涉及通过分析存在于母亲血液中的胎儿DNA来诊断妊娠相关疾病的新方法。更具体地说，本发明依赖于maspin基因在胎儿DNA和母体DNA中差异甲基化的发现，并提供了这些新的诊断方法，其将胎儿DNA与母体DNA区分开，并根据胎儿DNA水平和甲基化异常检测产前疾病状态。

30. 发明授权

US07655399B2 Methods for prenatal diagnosis of chromosomal abnormalities 有权
标题翻译：产前诊断染色体异常的方法
公开(公告)号：US07655399B2
公开(公告)日：2010-02-02
申请号：US10575119
申请日：2004-10-08
申请人： Charles R Cantor , Chunming Ding
发明人： Charles R Cantor , Chunming Ding
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6806 , C12Q1/6827 , C12Q1/6876 , C12Q2600/154 , C12Q2600/156 , C12Q2600/166 , C12Q2521/331
摘要： Chromosomal abnormalities are responsible for a significant number of birth defects, including mental retardation. The present invention is related to methods for non-invasive and rapid, prenatal diagnosis of chromosomal abnormalities based on analysis of a maternal blood sample. The invention exploits the differences in DNA between the mother and fetus, for instance differences in their methylation states, as a means to enrich for fetal DNA in maternal plasma sample. The methods described herein can be used to detect chromosomal DNA deletions and duplications. In a preferred embodiment, the methods are used to diagnose chromosomal aneuploidy and related disorders, such as Down's and Turner's Syndrome.
摘要翻译：染色体异常负责大量的出生缺陷，包括精神发育迟滞。本发明涉及基于母体血液样品分析的非侵入性和快速，产前诊断染色体异常的方法。本发明利用母体和胎儿之间的DNA差异，例如甲基化状态的差异，作为富集母体血浆样品中胎儿DNA的手段。本文描述的方法可用于检测染色体DNA缺失和重复。在优选的实施方案中，所述方法用于诊断染色体非整倍体和相关疾病，例如唐氏和特纳综合征。

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