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1. 发明申请

WO2008061801A1 METHODS AND NUCLEIC ACIDS FOR THE ANALYSIS OF GENE EXPRESSION ASSOCIATED WITH THE DEVELOPMENT OF PROSTATE CELL PROLIFERATIVE DISORDERS 审中-公开
标题翻译：与前列腺细胞增殖性疾病相关的基因表达分析的方法和核酸
公开(公告)号：WO2008061801A1
公开(公告)日：2008-05-29
申请号：PCT/EP2007/010257
申请日：2007-11-26
申请人： EPIGENOMICS AG , SLEDZIEWSKI, Andrew , LOFTON-DAY, Catherine , TETZNER, Reimo , DISTLER, Jürgen , MODEL, Fabian , PAYNE, Shannon , DIETRICH, Dimo
发明人： SLEDZIEWSKI, Andrew , LOFTON-DAY, Catherine , TETZNER, Reimo , DISTLER, Jürgen , MODEL, Fabian , PAYNE, Shannon , DIETRICH, Dimo
IPC分类号： C12Q1/68
CPC分类号： C12Q1/686 , C12Q1/6886 , C12Q2523/125 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/156 , C12Q2600/158
摘要： The invention provides methods, nucleic acids and kits for detecting prostate cell proliferative disorders. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供用于检测前列腺细胞增殖性疾病的方法，核酸和试剂盒。本发明公开了基因组序列，其甲基化模式可用于改善所述病症的检测，从而能够改善患者的诊断和治疗。

2. 发明申请

WO2008011620A2 METHODS AND NUCLEIC ACIDS FOR ANALYSES OF CELLULAR PROLIFERATIVE DISORDERS 审中-公开
标题翻译：用于细胞增殖性疾病分析的方法和核酸
公开(公告)号：WO2008011620A2
公开(公告)日：2008-01-24
申请号：PCT/US2007/074106
申请日：2007-07-23
申请人： EPIGENOMICS AG , LOFTON-DAY, Catherine , SLEDZIEWSKI, Andrew , MODEL, Fabian , COTTRELL, Susan , DISTLER, Juergen , TETZNER, Reimo , DIETRICH, Dimo
发明人： LOFTON-DAY, Catherine , SLEDZIEWSKI, Andrew , MODEL, Fabian , COTTRELL, Susan , DISTLER, Juergen , TETZNER, Reimo , DIETRICH, Dimo
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/154
摘要： The invention provides methods, nucleic acids and kits for detecting colorectal cell proliferative disorders. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said class of disorders, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供用于检测结肠直肠细胞增殖性疾病的方法，核酸和试剂盒。本发明公开的基因组序列，其中的甲基化模式对所述类病症的改进的检测工具，从而使得患者的改进的诊断和治疗。

3. 发明申请

WO2008009479A1 METHODS AND NUCLEIC ACIDS FOR ANALYSES FOR CELLULAR PROLIFERATIVE DISORDERS 审中-公开
标题翻译：用于细胞增殖性疾病分析的方法和核酸
公开(公告)号：WO2008009479A1
公开(公告)日：2008-01-24
申请号：PCT/EP2007/006539
申请日：2007-07-23
申请人： EPIGENOMICS AG , DIETRICH, Dimo , LOFTON-DAY, Catherine , PAYNE, Shannon
发明人： DIETRICH, Dimo , LOFTON-DAY, Catherine , PAYNE, Shannon
IPC分类号： C12Q1/68
CPC分类号： G01N33/57434 , C12Q1/6844 , C12Q1/6886 , C12Q2600/112 , C12Q2600/154 , C12Q2600/158
摘要： The invention provides methods, nucleic acids and kits for detecting a cell proliferative disorder. The invention discloses genomic sequences of RASSF-2 the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供了用于检测细胞增殖性病症的方法，核酸和试剂盒。本发明公开了RASSF-2的基因组序列，其甲基化模式可用于改善所述病症的检测，从而能够改善患者的诊断和治疗。

4. 发明申请

WO2006113770A1 A METHOD FOR PROVIDING DNA FRAGMENTS DERIVED FROM A REMOTE SAMPLE 审中-公开
标题翻译：提供从远程样品衍生的DNA片段的方法
公开(公告)号：WO2006113770A1
公开(公告)日：2006-10-26
申请号：PCT/US2006/014667
申请日：2006-04-17
申请人： EPIGENOMICS, INC. , BALLHAUSE, Matthias , BERLIN, Kurt , DEVOS, Theo , DIETRICH, Dimo , LIEBENBERG, Volker , LOFTON-DAY, Cathy , LOGRASSO, Joe , MAAS, Jennifer , MODEL, Fabian , SCHUSTER, Matthias , SLEDZIEWSKI, Andrew , TETZNER, Reimo
发明人： BALLHAUSE, Matthias , BERLIN, Kurt , DEVOS, Theo , DIETRICH, Dimo , LIEBENBERG, Volker , LOFTON-DAY, Cathy , LOGRASSO, Joe , MAAS, Jennifer , MODEL, Fabian , SCHUSTER, Matthias , SLEDZIEWSKI, Andrew , TETZNER, Reimo
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12N15/1003 , C12Q1/6806 , C12Q2523/125 , C12Q2600/154 , Y10T436/143333 , C12Q2521/131 , C12Q2531/101
摘要： Aspects of the present invention relate to compositions and methods for providing DNA fragments from a remote sample. In particular aspects a remote sample comprising DNA is provided, DNA is isolated from the remote sample, and the isolated DNA is treated in a way which allows differentiation of methylated and unmethylated cytosine. Additional, particular embodiments provide compositions and methods for methylation analysis of DNA derived from a remote sample. Other aspects provide for compositions and methods of whole genome amplification of bisulfite treated DNA.
摘要翻译：本发明的方面涉及从远程样品提供DNA片段的组合物和方法。在特定方面，提供了包含DNA的远程样品，从远程样品中分离DNA，并以允许甲基化和非甲基化胞嘧啶分化的方式处理分离的DNA。另外，具体实施方案提供了用于从远程样品衍生的DNA的甲基化分析的组合物和方法。其他方面提供了亚硫酸氢盐处理的DNA的全基因组扩增的组合物和方法。

5. 发明申请

WO2009074328A2 METHODS AND NUCLEIC ACIDS FOR ANALYSES OF CELL PROLIFERATIVE DISORDERS 审中-公开
标题翻译：方法和细胞增殖性疾病分析的核酸
公开(公告)号：WO2009074328A2
公开(公告)日：2009-06-18
申请号：PCT/EP2008/010549
申请日：2008-12-11
申请人： EPIGENOMICS AG , DIETRICH, Dimo , LIEBENGERG, Volker , TETZNER, Reimo , DISTLER, Jürgen , LEWIN, Jörn , SCHLEGEL, Thomas
发明人： DIETRICH, Dimo , LIEBENGERG, Volker , TETZNER, Reimo , DISTLER, Jürgen , LEWIN, Jörn , SCHLEGEL, Thomas
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/154 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16
摘要： The invention provides methods, nucleic acids and kits for detecting lung carcinoma. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供了用于检测肺癌的方法，核酸和试剂盒。本发明公开了基因组序列，其甲基化模式可用于改善所述病症的检测，从而能够改善患者的诊断和治疗。

6. 发明申请

WO2007141034A1 CARRY-OVER PROTECTION IN ENZYME-BASED DNA AMPLIFICATION SYSTEMS TARGETING METHYLATION ANALYSIS 审中-公开
标题翻译：基于酶的DNA扩增系统的携带保护靶向甲基化分析
公开(公告)号：WO2007141034A1
公开(公告)日：2007-12-13
申请号：PCT/EP2007/005088
申请日：2007-06-08
申请人： EPIGENOMICS AG , TETZNER, Reimo , DIETRICH, Dimo
发明人： TETZNER, Reimo , DIETRICH, Dimo
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6848 , C12Q2525/131 , C12Q2523/125
摘要： The invention refers to a method for providing a decontaminated template nucleic acid for enzymatic amplification reactions suitable for DNA methylation analysis. This method is characterized by the following steps: a) incubating a nucleic acid with a chemical reagent or an enzyme-containing solution, whereby the unmethylated cytosine bases are converted into uracil bases, b) mixing the template nucleic acid from step a) with the components required for an enzyme-mediated amplification reaction, including at least two oligonucleotides, whereby at least one of said oligonucleotides comprises i) at least one sequence part that hybridizes with a sequence of the template nucleic acid to be amplified, andii) at least one sequence part that constitutes a recognition site for a DNA cleaving enzyme that cleaves DNA downstream of said recognition site and c) adding to this mixture a DNA cleaving enzyme, which specifically binds to the at least one sequence part that is a recognition site, and d) incubating the mixture, whereby nucleic acids containing said recognition site for a DNA cleaving enzyme are degraded.
摘要翻译：本发明涉及一种用于提供适用于DNA甲基化分析的酶扩增反应的去污染模板核酸的方法。该方法的特征在于以下步骤：a）将核酸与化学试剂或含酶溶液一起孵育，由此将未甲基化的胞嘧啶碱基转化成尿嘧啶碱基，b）将来自步骤a）的模板核酸与酶介导的扩增反应所需的组分，包括至少两个寡核苷酸，其中至少一个所述寡核苷酸包含i）至少一个与待扩增的模板核酸序列杂交的序列部分，和ii）至少一个构成用于切割所述识别位点下游的DNA的DNA切割酶的识别位点的序列部分，和c）向该混合物中加入特异性结合作为识别位点的至少一个序列部分的DNA切割酶，d ）孵育混合物，由此含有用于DNA切割酶的所述识别位点的核酸被降解。

7. 发明申请

WO2006040187A2 A METHOD FOR THE CARRY-OVER PROTECTION IN DNA AMPLIFICATION SYSTEMS TARGETING METHYLATION ANALYSIS ACHIEVED BY A MODIFIED PRE-TREATMENT OF NUCLEIC ACIDS 审中-公开
标题翻译：在DNA扩增系统中进行保护的方法通过改良的预处理核酸实现甲基化分析
公开(公告)号：WO2006040187A2
公开(公告)日：2006-04-20
申请号：PCT/EP2005/011133
申请日：2005-10-11
申请人： EPIGENOMICS AG , TETZNER, Reimo , DIETRICH, Dimo
发明人： TETZNER, Reimo , DIETRICH, Dimo
CPC分类号： C12Q1/6876 , C12P19/34 , C12Q1/6806 , C12Q1/6827 , C12Q1/6848 , C12Q1/6883 , C12Q1/6886 , C12Q2600/156 , C12Q2523/125 , C12Q2521/531 , C12Q2531/113
摘要： Disclosed is a method for the specific amplification of template DNA in the presence of potentially contaminating PCR products from previous amplification experiments. In the first step DNA is contacted with a bisulfite solution, which reacts with unmethylated cytosines but not with methylated cytosines, by sulfonating them. This results in deamination of the cytosine whereby sulfonated uracil is generated. Such sulfonation protects the template nucleic acid from being a target for the enzyme UNG. Any contaminating DNA, which contains unprotected unsulfonated or desulfonated uracils is degraded enzymatically while UNG is active. After UNG treatment and inactivation, the sulfonated uracil bases are converted into uracil by desulfonation. This method is useful for decontamination of nucleic acid samples, or rather for avoiding amplification of 'carry over products' in particular in the context of DNA methylation analysis. Furthermore it can be used as a simplified method of bisulfite treatment in gerneral.
摘要翻译：公开了在先前扩增实验中存在可能污染的PCR产物的情况下特异性扩增模板DNA的方法。在第一步中，DNA与亚硫酸氢盐溶液接触，其与未甲基化的胞嘧啶反应而不与甲基化的胞嘧啶反应，通过磺化它们。这导致胞嘧啶脱氨，从而产生磺化的尿嘧啶。这种磺化保护模板核酸不是酶UNG的靶标。含有未受保护的未磺化或脱磺酸尿嘧啶的任何污染性DNA在酶活性下降，而UNG活性。在UNG处理和灭活后，磺化的尿嘧啶碱基通过脱磺酸转化成尿嘧啶。该方法可用于核酸样品的去污，或者用于避免在DNA甲基化分析的背景下特别是“携带产物”的扩增。此外，它可以用作在gerneral中亚硫酸氢盐处理的简化方法。

8. 发明申请

WO2005059172A3 METHOD AND NUCLEIC ACIDS FOR THE IMPROVED TREATMENT OF BREAST CELL PROLIFERATIVE DISORDERS 审中-公开
公开(公告)号：WO2005059172A3
公开(公告)日：2005-06-30
申请号：PCT/EP2004/014170
申请日：2004-12-13
申请人： EPIGENOMICS AG , FOEKENS, John , HARBECK, Nadia , KÖNIG, Thomas , MAIER, Sabine , MARTENS, John , MODEL, Fabian , NIMMRICH, Inko , RUJAN, Tamas , SCHMITT, Manfred , LESCHE, Ralf , DIETRICH, Dimo , MÜLLER, Volkmar , KLUTH, Antje , SCHWOPE, Ina , HARTMANN, Oliver , ADORJAN, Peter , MARX, Almuth
发明人： FOEKENS, John , HARBECK, Nadia , KÖNIG, Thomas , MAIER, Sabine , MARTENS, John , MODEL, Fabian , NIMMRICH, Inko , RUJAN, Tamas , SCHMITT, Manfred , LESCHE, Ralf , DIETRICH, Dimo , MÜLLER, Volkmar , KLUTH, Antje , SCHWOPE, Ina , HARTMANN, Oliver , ADORJAN, Peter , MARX, Almuth
IPC分类号： C12Q1/68
摘要： The present invention relates to modified and genomic sequences, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genomic DNA, as well as to a method for predicting the disease free survival and/or response of a subject with a cell proliferative disorder of the breast tissues, to endocrine treatment.

9. 发明申请

WO2011009073A1 A METHOD FOR AMPLIFICATION OF NUCLEIC ACIDS 审中-公开
标题翻译：一种放大核酸的方法
公开(公告)号：WO2011009073A1
公开(公告)日：2011-01-20
申请号：PCT/US2010/042323
申请日：2010-07-16
申请人： ABBOTT LABORATORIES , GRACE, John, P. , DIETRICH, Dimo , FASSBENDER, Anne , SCHATZ, Philipp , SOLOMON, Natalie , TETZNER, Reimo
发明人： GRACE, John, P. , DIETRICH, Dimo , FASSBENDER, Anne , SCHATZ, Philipp , SOLOMON, Natalie , TETZNER, Reimo
IPC分类号： C12Q1/68
CPC分类号： C12Q1/686 , C12Q2527/107 , C12Q2527/101
摘要： The invention here concerns a method for increasing the uniformity of nucleic acid amplification. A method is described to add stopping periods during the ramp step(s), which minimizes the effect of temperature overshoot or undershoot. Many cyclers' algorithms cause the target temperature to be passed during ramp and then returned to within a short period of time. This overshoot or undershoot can cause non-uniformity between reactions in a micro¬ liter plate. The addition of stopping periods reduces the effects of overshoot or undershoot and increases uniformity between different reactions wells on a plate.
摘要翻译：本发明涉及增加核酸扩增的均匀性的方法。描述了在斜坡步骤期间增加停止时间的方法，其使温度过冲或下冲的影响最小化。许多循环仪的算法使得目标温度在斜坡期间通过，然后在短时间内返回。这种过冲或下冲可能导致微升板之间的反应之间的不均匀。加入停止时间可减少过冲或下冲的影响，并增加板上不同反应孔之间的均匀性。

10. 发明申请

WO2008009365A3 A METHOD FOR DETERMINING THE METHYLATION RATE OF A NUCLEIC ACID 审中-公开
公开(公告)号：WO2008009365A3
公开(公告)日：2008-01-24
申请号：PCT/EP2007/006064
申请日：2007-07-09
申请人： EPIGENOMICS AG , LEWIN, Jörn , LESCHE, Ralf , SCHUSTER, Matthias , DIETRICH, Dimo
发明人： LEWIN, Jörn , LESCHE, Ralf , SCHUSTER, Matthias , DIETRICH, Dimo
IPC分类号： C12Q1/68
摘要： The invention relates to a method for quantitatively determining the methylation rate of a nucleic acid through sequencing. According to the invention, the method comprises at least the following steps: a) treating the nucleic acid with a chemical reagent or an enzyme containing solution, whereby the base pairing behavior of methylated cytosine bases and/or unmethylated cytosine bases of the nucleic acid are altered such that methylated cytosine bases become distinguishable from unmethylated cytosine bases, and b) introducing into the nucleic acid at least one base for generating a sequencing signal to be used as a reference signal for normalization, and c) sequencing the nucleic acid, whereby a signal from each cytosine base of the nucleic acid, or a signal from each guanine base of the nucleic acid and a reference signal from the at least on introduced base is obtained, and d) normalizing the signal obtained from each cytosine base of the nucleic acid, or the signal obtained from each guanine base of the nucleic acid to the reference signal from the at least one introduced base.

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