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1. 发明申请

US20090203011A1 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：US20090203011A1
公开(公告)日：2009-08-13
申请号：US12332703
申请日：2008-12-11
申请人： Volker Liebenberg , Juergen Distler , Joern Lewin , Fabian Model , Reimo Tetzner , Rene Cortese , Dimo Dietrich , Thomas Schlegel
发明人： Volker Liebenberg , Juergen Distler , Joern Lewin , Fabian Model , Reimo Tetzner , Rene Cortese , Dimo Dietrich , Thomas Schlegel
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q2600/154 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16
摘要： Particular aspects provide methods, nucleic acids and kits for detecting cell proliferative disorders. Preferred aspects provide genomic sequences, the methylation patterns of which have substantial utility for the improved detection of said disorders, providing for improved diagnosis and treatment of same in patients.
摘要翻译：具体方面提供用于检测细胞增殖性疾病的方法，核酸和试剂盒。优选的方面提供基因组序列，其甲基化模式具有用于改善所述疾病的检测的实质性用途，从而提供对患者的相似性的改善的诊断和治疗。

2. 发明申请

US20110003292A1 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：US20110003292A1
公开(公告)日：2011-01-06
申请号：US12747584
申请日：2008-12-11
申请人： Dimo Dietrich , Volker Liebenberg , Reimo Tetzner , Juergen Distler , Joern Lewin , Thomas Schlegel
发明人： Dimo Dietrich , Volker Liebenberg , Reimo Tetzner , Juergen Distler , Joern Lewin , Thomas Schlegel
IPC分类号： C12Q1/68 , G01N33/53 , C12M1/34
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 (FOXL2, ONECUT1, TFAP2E, EN2-2, EN2-3, SHOX2-2 and BARHL2) 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肺癌的方法，核酸和试剂盒。本发明公开了基因组（FOXL2，ONECUT1，TFAP2E，EN2-2，EN2-3，SHOX2-2和BARHL2）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。

3. 发明申请

US20110059432A1 METHOD FOR PROVIDING DNA FRAGMENTS DERIVED FROM A REMOTE SAMPLE 审中-公开
标题翻译：用于提供从远程样品衍生的DNA片段的方法
公开(公告)号：US20110059432A1
公开(公告)日：2011-03-10
申请号：US11910887
申请日：2006-04-17
申请人： Matthias Ballhause , Kurt Berlin , Theo De Vos , Dimo Dietrich , Volker Liebenberg , Catherine Lofton-Day , Joe Lograsso , Jennifer Maas , Fabian Model , Matthias Schuster , Andrew Z. Sledziewski , Reimo Tetzner
发明人： Matthias Ballhause , Kurt Berlin , Theo De Vos , Dimo Dietrich , Volker Liebenberg , Catherine Lofton-Day , Joe Lograsso , Jennifer Maas , Fabian Model , Matthias Schuster , Andrew Z. Sledziewski , Reimo Tetzner
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34 , G01N33/48
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。

4. 发明授权

US10731215B2 Method for determining the presence or absence of methylation in a sample 有权
公开(公告)号：US10731215B2
公开(公告)日：2020-08-04
申请号：US11910887
申请日：2006-04-17
申请人： Matthias Ballhause , Kurt Berlin , Theo De Vos , Dimo Dietrich , Volker Liebenberg , Catherine Lofton-Day , Joe Lograsso , Jennifer Maas , Fabian Model , Matthias Schuster , Andrew Z. Sledziewski , Reimo Tetzner
发明人： Matthias Ballhause , Kurt Berlin , Theo De Vos , Dimo Dietrich , Volker Liebenberg , Catherine Lofton-Day , Joe Lograsso , Jennifer Maas , Fabian Model , Matthias Schuster , Andrew Z. Sledziewski , Reimo Tetzner
IPC分类号： C12Q1/68 , C12Q1/6883 , C12N15/10 , C12Q1/6806 , C07H21/04
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. Other aspects provide methods for determining the presence or absence of methylation of at least one cytosine, or a series of cytosines in cis, in human DNA of a blood sample, a plasma sample, a serum sample or a urine sample from a human individual.

5. 发明申请

US20100143902A1 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：US20100143902A1
公开(公告)日：2010-06-10
申请号：US12374654
申请日：2007-07-23
申请人： Catherine E Lofton-Day , Andrew Z. Sledziewski , Fabian Model , Susan Cottrell , Juergen Distler , Reimo Tetzner , Dimo Dietrich
发明人： Catherine E Lofton-Day , Andrew Z. Sledziewski , Fabian Model , Susan Cottrell , Juergen Distler , Reimo Tetzner , Dimo Dietrich
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q2600/154
摘要： The invention provides methods, nucleic acids and kits for detecting colorectal cell proliferative disorders based on underexpression or methylation of a least one gene selected from RASSF2, TFAP2E, SND1, PCDHGC3, EDNRB, STOM, GLI3, RXFP3, LimK1, GPR73L1, PCDH1O, DOCKIO and MRPS21, and optionally Septin-9. 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基于选自RASSF2，TFAP2E，SND1，PCDHGC3，EDNRB，STOM，GLI3，RXFP3，LimK1，GPR73L1，PCDH1O，DOCKIO中的至少一种基因的低表达或甲基化的结肠直肠细胞增殖性疾病的方法，核酸和试剂盒和MRPS21，以及任选的Septin-9。本发明公开了基因组序列，其甲基化模式可用于改善所述疾病类别的检测，从而能够改善患者的诊断和治疗。

6. 发明申请

US20100203514A1 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：US20100203514A1
公开(公告)日：2010-08-12
申请号：US12515520
申请日：2007-11-26
申请人： Andrew Z. Sledziewski , Catherine E. Lofton-Day , Reimo Tetzner , Juergen Distler , Fabian Model , Shannon Payne , Dimo Dietrich
发明人： Andrew Z. Sledziewski , Catherine E. Lofton-Day , Reimo Tetzner , Juergen Distler , Fabian Model , Shannon Payne , Dimo Dietrich
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。

7. 发明授权

US07700282B2 Method for the carry-over protection in DNA amplification systems targeting methylation analysis achieved by a modified pre-treatment of nucleic acids 有权
标题翻译：用于DNA扩增系统中的遗传保护的方法，其靶向通过核酸的修饰预处理实现的甲基化分析
公开(公告)号：US07700282B2
公开(公告)日：2010-04-20
申请号：US11248721
申请日：2005-10-11
申请人： Reimo Tetzner , Dimo Dietrich
发明人： Reimo Tetzner , Dimo Dietrich
IPC分类号： C12Q1/70 , C12P19/34
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： Particular aspects provide methods for specific amplification of template DNA in the presence of potentially contaminating PCR products from previous amplification experiments. Particular embodiments comprise, in a first step, contacting DNA with a bisulfite solution, which sulfonates unmethylated (but not methylated) cytosines, resulting in cytosine deamination and generation of sulfonated uracil. Such sulfonation protects the template nucleic acid from being a target for the enzyme uracil-DNA-glycosylase (UNG), whereas any contaminating DNA, which contains unprotected unsulfonated or desulfonated uracils, is degraded enzymatically while the UNG is active. After UNG treatment and inactivation thereof, the sulfonated uracil bases are converted into uracil by desulfonation. Such aspects have substantial utility for decontamination of nucleic acid samples; e.g., for avoiding amplification of ‘carry over products’ in the context of DNA methylation analysis. In further aspects, the inventive methods can be generally used as simplified methods of bisulfite treatment.
摘要翻译：在以前的扩增实验中存在可能污染的PCR产物的情况下，特定方面提供用于特异性扩增模板DNA的方法。具体实施方案包括在第一步中使DNA与亚硫酸氢盐溶液接触，所述亚硫酸氢盐溶液磺化非甲基化（但不是甲基化的）胞嘧啶，导致胞嘧啶脱氨基并产生磺化的尿嘧啶。这种磺化保护模板核酸不是酶尿嘧啶-DNA-糖基化酶（UNG）的靶标，而任何含有未保护的未磺化或脱磺酸尿嘧啶的污染性DNA在UNG活性时被酶促降解。在UNG处理和灭活后，通过脱磺酸将磺化的尿嘧啶碱基转化成尿嘧啶。这些方面对于核酸样品的净化具有实质性的实用性; 例如，为了避免在DNA甲基化分析的上下文中“携带产物”的扩增。在另外的方面，本发明的方法通常可以用作亚硫酸氢盐处理的简化方法。

8. 发明申请

US20100092951A1 METHOD FOR METHYLATION ANALYSIS OF NUCLEIC ACID 有权
标题翻译：核酸甲基化分析方法
公开(公告)号：US20100092951A1
公开(公告)日：2010-04-15
申请号：US12310051
申请日：2007-08-01
申请人： Reimo Tetzner , Joern Lewin
发明人： Reimo Tetzner , Joern Lewin
IPC分类号： C12Q1/68 , G01N33/50
CPC分类号： C12Q1/6858 , C12Q2537/113 , C12Q2535/119 , C12Q2523/125
摘要： The present invention relates to a method for methylation analysis. It comprises the providing of a double stranded nucleic acid; its conversion, whereby unmethylated bases become distinguishable in their base-pairing behavior from methylated bases, and the analysis of both of the converted nucleic acid strands.
摘要翻译：本发明涉及甲基化分析方法。它包括提供双链核酸; 其转化，其中未甲基化的碱基在其碱基配对行为与甲基化碱基之间变得可区分，以及两个转化的核酸链的分析。

9. 发明申请

US20100216152A1 Method for the Carry-Over Protection in DNA Amplification Systems Targeting Methylation Analysis Achieved by a Modified Pre-Treatment of Nucleic Acids 有权
标题翻译：靶向通过核酸修饰预处理实现的甲基化分析的DNA扩增系统中的转移保护方法
公开(公告)号：US20100216152A1
公开(公告)日：2010-08-26
申请号：US12709300
申请日：2010-02-19
申请人： Reimo Tetzner , Dimo Dietrich
发明人： Reimo Tetzner , Dimo Dietrich
IPC分类号： C12Q1/68 , C12P19/34 , C12N9/00
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： Particular aspects provide methods for specific amplification of template DNA in the presence of potentially contaminating PCR products from previous amplification experiments. Particular embodiments comprise, in a first step, contacting DNA with a bisulfite solution, which sulfonates unmethylated (but not methylated) cytosines, resulting in cytosine deamination and generation of sulfonated uracil. Such sulfonation protects the template nucleic acid from being a target for the enzyme uracil-DNA-glycosylase (UNG), whereas any contaminating DNA, which contains unprotected unsulfonated or desulfonated uracils, is degraded enzymatically while the UNG is active. After UNG treatment and inactivation thereof, the sulfonated uracil bases are converted into uracil by desulfonation. Such aspects have substantial utility for decontamination of nucleic acid samples; e.g., for avoiding amplification of ‘carry over products’ in the context of DNA methylation analysis. In further aspects, the inventive methods can be generally used as simplified methods of bisulfite treatment.
摘要翻译：在以前的扩增实验中存在可能污染的PCR产物的情况下，特定方面提供用于特异性扩增模板DNA的方法。具体实施方案包括在第一步中使DNA与亚硫酸氢盐溶液接触，所述亚硫酸氢盐溶液磺化非甲基化（但不是甲基化的）胞嘧啶，导致胞嘧啶脱氨基并产生磺化的尿嘧啶。这种磺化保护模板核酸不是酶尿嘧啶-DNA-糖基化酶（UNG）的靶标，而含有未保护的未磺化或脱磺酸尿嘧啶的任何污染性DNA在UNG活性时被酶促降解。在UNG处理和灭活后，通过脱磺酸将磺化的尿嘧啶碱基转化成尿嘧啶。这些方面对于核酸样品的净化具有实质性的实用性; 例如，为了避免在DNA甲基化分析的上下文中“携带产物”的扩增。在另外的方面，本发明的方法通常可以用作亚硫酸氢盐处理的简化方法。

10. 发明授权

US08753810B2 Method for the carry-over protection in DNA amplification systems targeting methylation analysis achieved by a modified pre-treatment of nucleic acids 有权
标题翻译：用于DNA扩增系统中的遗传保护的方法，其靶向通过核酸的修饰预处理实现的甲基化分析
公开(公告)号：US08753810B2
公开(公告)日：2014-06-17
申请号：US12709300
申请日：2010-02-19
申请人： Reimo Tetzner , Dimo Dietrich
发明人： Reimo Tetzner , Dimo Dietrich
IPC分类号： C12Q1/68 , C12P19/34
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： Particular aspects provide methods for specific amplification of template DNA in the presence of potentially contaminating PCR products from previous amplification experiments. Particular embodiments comprise, in a first step, contacting DNA with a bisulfite solution, which sulfonates unmethylated (but not methylated) cytosines, resulting in cytosine deamination and generation of sulfonated uracil. Such sulfonation protects the template nucleic acid from being a target for the enzyme uracil-DNA-glycosylase (UNG), whereas any contaminating DNA, which contains unprotected unsulfonated or desulfonated uracils, is degraded enzymatically while the UNG is active. After UNG treatment and inactivation thereof, the sulfonated uracil bases are converted into uracil by desulfonation. Such aspects have substantial utility for decontamination of nucleic acid samples; e.g., for avoiding amplification of ‘carry over products’ in the context of DNA methylation analysis. In further aspects, the inventive methods can be generally used as simplified methods of bisulfite treatment.
摘要翻译：在以前的扩增实验中存在可能污染的PCR产物的情况下，特定方面提供用于特异性扩增模板DNA的方法。具体实施方案包括在第一步中使DNA与亚硫酸氢盐溶液接触，所述亚硫酸氢盐溶液磺化非甲基化（但不是甲基化的）胞嘧啶，导致胞嘧啶脱氨基并产生磺化的尿嘧啶。这种磺化保护模板核酸不是酶尿嘧啶-DNA-糖基化酶（UNG）的靶标，而任何含有未保护的未磺化或脱磺酸尿嘧啶的污染性DNA在UNG活性时被酶促降解。在UNG处理和灭活后，通过脱磺酸将磺化的尿嘧啶碱基转化成尿嘧啶。这些方面对于核酸样品的净化具有实质性的实用性; 例如，为了避免在DNA甲基化分析的上下文中“携带产物”的扩增。在另外的方面，本发明的方法通常可以用作亚硫酸氢盐处理的简化方法。

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