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1. 发明申请

WO2014043763A1 NON-INVASIVE DETERMINATION OF METHYLOME OF FETUS OR TUMOR FROM PLASMA 审中-公开
标题翻译：非侵入性确定来自等离子体的肿瘤或肿瘤的甲基化
公开(公告)号：WO2014043763A1
公开(公告)日：2014-03-27
申请号：PCT/AU2013/001088
申请日：2013-09-20
申请人： THE CHINESE UNIVERSITY OF HONG KONG , CHIU, Rossa, Wai, Kwun
发明人： CHIU, Rossa, Wai, Kwun , CHAN, Kwan, Chee , LO, Yuk-Ming, Dennis , LUN, Miu, Fan , JIANG, Peiyong , CHAN, Wai, Man
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C12Q1/6869 , C12Q1/6886 , C12Q2600/154 , C12Q2523/125
摘要： Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
摘要翻译：系统，方法和装置可以确定和使用各种组织和样品的甲基化谱。提供了实例。基于将血浆甲基化（或其他样品与无细胞DNA）与母亲/患者的甲基化谱进行比较，可推导出胎儿/肿瘤组织的甲基化谱。当样品具有DNA的混合物时，可以使用组织特异性等位基因确定胎儿/肿瘤组织的甲基化谱，以鉴定来自胎儿/肿瘤的DNA。甲基化谱可用于确定胎儿/肿瘤基因组中的拷贝数变异。已经通过各种技术鉴定了胎儿的甲基化标记。可以通过确定DNA片段的大小分布的大小参数来确定甲基化谱，其中可以使用尺寸参数的参考值来确定甲基化水平。另外，可以使用甲基化水平来确定癌症的水平。

2. 发明申请

WO2009019455A2 ANALYSIS OF NUCLEIC ACIDS BY DIGITAL PCR 审中-公开
标题翻译：通过数字PCR分析核酸
公开(公告)号：WO2009019455A2
公开(公告)日：2009-02-12
申请号：PCT/GB2008/002637
申请日：2008-08-01
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk, Ming, Dennis , CHIU, Rossa, Wai, Kwun
发明人： LO, Yuk, Ming, Dennis , CHIU, Rossa, Wai, Kwun
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6851 , C12Q2527/107 , C12Q2563/159 , C12Q2565/629
摘要： The present invention provides a method for analyzing nucleic acids for their lengths and relative abundance in a sample, based on digital amplification of individual template molecules. This invention has many applications, including those in noninvasive prenatal diagnosis, transplantation monitoring, and the detection and monitoring of cancers and virus-associated diseases.
摘要翻译：本发明提供了一种基于个体模板分子的数字扩增来分析样品中核酸长度和相对丰度的方法。本发明有许多应用，包括无创产前诊断，移植监测以及癌症和病毒相关疾病的检测和监测。

3. 发明申请

WO2005023091A3 METHOD FOR NON-INVASIVE PRENATAL DIAGNOSIS 审中-公开
标题翻译：无创性早期诊断方法
公开(公告)号：WO2005023091A3
公开(公告)日：2005-06-16
申请号：PCT/US2004028857
申请日：2004-09-07
申请人： UNIV BOSTON , UNIV HONG KONG CHINESE , 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： A61B20060101 , C07H21/04 , C12Q1/68
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的核酸的方法。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。该方法可以用于例如诊断，预后和治疗目的。该方法可以用于例如诊断，预后和治疗目的。该方法允许准确检测生物样品中存在的非常少量的核酸。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; 和移植受体中的供体特异性酸。在另一个实施方案中，可以检测生物样品中的病毒，细菌，真菌或其他外源核酸。

4. 发明申请

WO2009019455A3 ANALYSIS OF NUCLEIC ACIDS OF VARYING LENGTHS BY DIGITAL PCR 审中-公开
标题翻译：通过数字PCR分析变化长度的核酸
公开(公告)号：WO2009019455A3
公开(公告)日：2009-04-02
申请号：PCT/GB2008002637
申请日：2008-08-01
申请人： UNIV HONG KONG CHINESE , LO YUK MING DENNIS , CHIU ROSSA WAI KWUN
发明人： LO YUK MING DENNIS , CHIU ROSSA WAI KWUN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6851 , C12Q2527/107 , C12Q2563/159 , C12Q2565/629
摘要： The present invention provides a method for analyzing nucleic acids for their lengths and relative abundance in a sample, based on digital amplification of individual template molecules. This invention has many applications, including those in noninvasive prenatal diagnosis, transplantation monitoring, and the detection and monitoring of cancers and virus-associated diseases.
摘要翻译：本发明提供了一种基于个体模板分子的数字扩增来分析样品中核酸长度和相对丰度的方法。本发明有许多应用，包括无创产前诊断，移植监测以及癌症和病毒相关疾病的检测和监测。

5. 发明申请

WO2009013492A1 DETERMINING A NUCLEIC ACID SEQUENCE IMBALANCE 审中-公开
标题翻译：确定核酸序列不平衡
公开(公告)号：WO2009013492A1
公开(公告)日：2009-01-29
申请号：PCT/GB2008/002524
申请日：2008-07-23
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk-Ming Dennis , CHIU, Rossa Wai Kwun , CHAN, Kwan Chee , ZEE, Benny Chung Ying , CHONG, Ka Chun
发明人： LO, Yuk-Ming Dennis , CHIU, Rossa Wai Kwun , CHAN, Kwan Chee , ZEE, Benny Chung Ying , CHONG, Ka Chun
IPC分类号： G06F19/00 , C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q1/6888 , C12Q2600/112 , C12Q2600/154 , C12Q2600/156 , G01N2800/387 , G06F19/18 , G06F19/22 , C12Q2521/331 , C12Q2537/16
摘要： Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The cutoff value may also be determined based on an average concentration of a sequence per reaction. In one aspect, the cutoff value is determined from a proportion of informative wells that are estimated to contain a particular nucleic acid sequence, where the proportion is determined based on the above-mentioned percentage and/or average concentration. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).
摘要翻译：提供了用于确定生物样品中是否存在核酸序列不平衡的方法，系统和装置。选择用于确定例如两个序列（或序列集合）的比例的不平衡的一个或多个截断值。截止值可以至少部分地基于含有母体核酸序列背景的样品中的胎儿DNA（例如母体血浆）的百分比来确定。截止值也可以基于每个反应的序列的平均浓度来确定。在一个方面，截断值由估计含有特定核酸序列的信息井的比例确定，其中所述比例基于上述百分比和/或平均浓度来确定。截断值可以使用许多不同类型的方法来确定，例如顺序概率比测试（SPRT）。

6. 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。

7. 发明申请

WO2011029899A1 METHODS FOR ASSESSING LIVER PATHOLOGIES 审中-公开
标题翻译：评估肝病变的方法
公开(公告)号：WO2011029899A1
公开(公告)日：2011-03-17
申请号：PCT/EP2010/063300
申请日：2010-09-10
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk Ming Dennis , CHIU, Rossa Wai Kwun , CHIU, Rebecca Wing Kwun
发明人： LO, Yuk Ming Dennis , CHIU, Rossa Wai Kwun , CHIU, Rebecca Wing Kwun
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158 , Y10T436/143333
摘要： The present invention provides a new method for detecting or monitoring a liver disease in a subject that has no indication of any liver pathologies, by measuring the amount of concentration of albumin mRNA in an acellular blood sample from the subject, and then comparing the amount or concentration of albumin mRNA with a standard control.
摘要翻译：本发明提供了一种通过测量来自受试者的无细胞血液样品中的白蛋白mRNA浓度的量来检测或监测受试者中没有任何肝脏病征的肝脏疾病的新方法，然后比较用标准对照的白蛋白mRNA浓度。

8. 发明申请

WO2011018600A1 METHOD FOR DETECTING CHROMOSOMAL ANEUPLOIDY 审中-公开
标题翻译：检测染色体异常的方法
公开(公告)号：WO2011018600A1
公开(公告)日：2011-02-17
申请号：PCT/GB2010/001327
申请日：2010-07-12
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk Ming Dennis , CHIU, Rossa, Wai, Kwun , TONG, Yu Kwan , JIN, Shengnan , CHIM, Siu Chung Stephen , TSUI, Wai Yi
发明人： LO, Yuk Ming Dennis , CHIU, Rossa, Wai, Kwun , TONG, Yu Kwan , JIN, Shengnan , CHIM, Siu Chung Stephen , TSUI, Wai Yi
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q2523/125
摘要： The present invention relates to a new, non-invasive method for detecting chromosomal aneuploidy by analyzing a sample from a pregnant woman. The detection is based on the ratio between the amount of a fetal methylation marker located on a chromosome relevant to the aneuploidy and the amount of a fetal genetic marker located on a reference chromosome, offering improved accuracy.
摘要翻译：本发明涉及通过分析来自孕妇的样品来检测染色体非整倍体的新的非侵入性方法。检测是基于位于与非整倍性相关的染色体上的胎儿甲基化标记的量与位于参考染色体上的胎儿遗传标记的量之间的比例，提供更高的准确度。

9. 发明申请

WO2005118852A2 A 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：WO2005118852A2
公开(公告)日：2005-12-15
申请号：PCT/GB2005/002211
申请日：2005-06-06
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk Ming Dennis , CHIU, Rossa Wai Kwun , CHIM, Stephen Siu Chung , TONG, Yu-kwan , DING, Chunming
发明人： LO, Yuk Ming Dennis , CHIU, Rossa Wai Kwun , CHIM, Stephen Siu Chung , TONG, Yu-kwan , DING, Chunming
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，本发明依赖于发现maspin基因在胎儿DNA和母体DNA中差异甲基化，并提供了这些新的诊断方法，其将胎儿DNA与母体DNA区分开来，并根据胎儿DNA水平和甲基化异常检测产前疾病状态。

10. 发明申请

WO2009013496A1 DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING GENOMIC SEQUENCING 审中-公开
标题翻译：使用基因组序列诊断癌症染色体异常
公开(公告)号：WO2009013496A1
公开(公告)日：2009-01-29
申请号：PCT/GB2008/002530
申请日：2008-07-23
申请人： THE CHINESE UNIVERSITY OF HONG KONG , LO, Yuk-Ming Dennis , CHIU, Rossa Wai Kwun , CHAN, Kwan Chee
发明人： LO, Yuk-Ming Dennis , CHIU, Rossa Wai Kwun , CHAN, Kwan Chee
IPC分类号： G06F19/00 , C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q1/6888 , C12Q2600/112 , C12Q2600/154 , C12Q2600/156 , G01N2800/387 , G06F19/18 , G06F19/22 , C12Q2521/331 , C12Q2537/16
摘要： Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts ( e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.
摘要翻译：本发明的实施方案提供了用于确定从怀孕女性获得的生物样品中是否存在胎儿染色体非整倍性的方法，系统和装置。对生物样品的核酸分子进行测序，使得对基因组的一部分进行测序。根据测序结果确定相应量的临床相关染色体和背景染色体。将来自这些量（例如比例）的参数与一个或多个截断值进行比较，从而确定是否存在胎儿染色体非整倍性的分类。

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