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1. 发明申请

US20080026396A1 METHOD AND NUCLEIC ACIDS FOR THE ANALYSIS OF ASTROCYTOMAS 审中-公开
标题翻译：方法和核酸分析ASTROCYTOMAS
公开(公告)号：US20080026396A1
公开(公告)日：2008-01-31
申请号：US11835336
申请日：2007-08-07
申请人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
发明人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C07K14/82 , C07K14/4703 , C12Q1/6883 , C12Q1/6886 , C12Q2523/125 , C12Q2600/154 , C12Q2600/156
摘要： Chemically modified genomic sequences, oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genomic DNA. In addition, a method for ascertaining genetic and/or epigenetic parameters of genes for use in the characterization, classificaiton, differrentiation, grading, staging, treatment and/or diagnosis of astrocytomas, or the predisposition to astrocytomas.
摘要翻译：用于检测基因组DNA的胞嘧啶甲基化状态的化学修饰的基因组序列，寡核苷酸和/或PNA-低聚物。另外，确定用于星形细胞瘤的表征，分类，分化，分级，分期，治疗和/或诊断或对星形细胞瘤的易感性的基因的遗传和/或表观遗传参数的方法。

2. 发明申请

US20070026393A1 Detection of variations in the dna methylation profile 审中-公开
标题翻译：检测dna甲基化谱中的变异
公开(公告)号：US20070026393A1
公开(公告)日：2007-02-01
申请号：US10240970
申请日：2001-04-06
申请人： Kurt Berlin , Christian Piepenbrock , Alexander Olek
发明人： Kurt Berlin , Christian Piepenbrock , Alexander Olek
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C07K14/82 , C07K14/4703 , C12Q1/6883 , C12Q2600/154
摘要： The invention describes a set of oligonucleotides as probes for the detection of relevant variations of DNA methylation in a target group of genes, the use thereof for the detection of gene variants with respect to DNA methylation, a medical device which uses a set of oligonucleotides, a method for investigating the methylation state of an individual as well as a method for creating a model for evaluating the probability of occurrence of a health problem of an individual. Such disorders can be: undesired drug interactions cancer diseases CNS malfunctions, damage or disease symptoms of aggression or behavioral disturbances clinical, psychological and social consequences of brain lesions psychotic disturbances and personality disorders dementia and/or associated syndromes cardiovascular disorder, malfunction and damage malfunction, damage or disorder of the gastrointestinal tract malfunction, damage or disorder of the respiratory system lesion, inflammation, infection, immunity and/or convalescence malfunction, damage or disease of the body as an abnormality in the development process malfunction, damage or disorder of the skin, the muscles, the connective tissue or the bones endocrine and metabolic malfunction, damage or disorder headaches or sexual malfunction.
摘要翻译：本发明描述了一组寡核苷酸作为用于检测靶基因组中DNA甲基化的相关变异的探针，其用于检测关于DNA甲基化的基因变体的用途，使用一组寡核苷酸的医疗装置，用于研究个体的甲基化状态的方法以及用于创建用于评估个体的健康问题的发生概率的模型的方法。这种疾病可以是：不期望的药物相互作用癌症疾病中枢神经系统疾病，侵袭或行为障碍的损伤或疾病症状临床，脑损伤的心理和社会后果精神障碍和人格障碍痴呆和/或相关综合征心血管疾病，故障和损伤故障，胃肠道的损伤或紊乱，呼吸系统病变的损伤或紊乱，炎症，感染，免疫和/或康复失败，身体的损伤或疾病，作为发育过程失败的异常，皮肤的损伤或障碍，肌肉，结缔组织或骨骼内分泌和代谢功能障碍，损伤或障碍性头痛或性功能障碍。

3. 发明申请

US20060136142A1 Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen based on the methylation status of the DNA 审中-公开
标题翻译：基于DNA的甲基化状态指导治疗方案选择的系统，方法和计算机程序产品
公开(公告)号：US20060136142A1
公开(公告)日：2006-06-22
申请号：US10774052
申请日：2004-02-06
申请人： Kurt Berlin , Alexander Olek , Christian Piepenbrock
发明人： Kurt Berlin , Alexander Olek , Christian Piepenbrock
IPC分类号： G06F19/00
CPC分类号： G06Q50/24 , G16B20/00 , Y02A90/22 , Y02A90/26
摘要： Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen or a preventive therapeutic treatment regimen are disclosed. The method comprises (A) providing to a computing device comprising a first knowledge base comprising information about a plurality of different methylation statuses at selected sites of the DNA in cells with a known disease or medical condition and/or healthy cells, a second knowledge base comprising a plurality of expert rules for evaluating and selecting a type of disease or medical condition based on the methylation status at selected sites of the DNA of a patient, (B) generating in said computing device a ranked listing of diseases or medical conditions based on the information about the methylation status at selected sites of the DNA of the patient, the first knowledge base and the second knowledge base.
摘要翻译：公开了用于指导选择治疗方案或预防性治疗方案的系统，方法和计算机程序产品。该方法包括（A）提供给包括第一知识库的计算设备，所述第一知识库包括关于具有已知疾病或医学状况和/或健康细胞的细胞中所述DNA的选定位点处的多个不同甲基化状态的信息，和第二知识库包括用于基于患者的DNA的选定位点处的甲基化状态来评估和选择疾病或医学状况的多种专家规则，（B）在所述计算设备中产生基于以下的疾病或医疗状况的排名列表：关于患者DNA选定位点甲基化状态的信息，第一知识库和第二知识库。

4. 发明授权

US09719131B2 Method for determining the degree of methylation of defined cytosines in genomic DNA in the sequence context of 5′-CpG-3′ 有权
公开(公告)号：US09719131B2
公开(公告)日：2017-08-01
申请号：US12847005
申请日：2010-07-30
申请人： Alexander Olek , Christian Piepenbrock , Kurt Berlin , David Guetig
发明人： Alexander Olek , Christian Piepenbrock , Kurt Berlin , David Guetig
IPC分类号： C07H21/02 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6883 , C12Q2600/154
摘要： A method is described for the detection of the degree of methylation of a specific cytosine in the sequence context 5′-CpG-3′ of a genomic DNA sample. In the first step, the genomic DNA is chemically treated in such a way that the cytosine bases are converted to uracil, but not the 5-methylcytosine bases. Then segments of the genomic DNA which contain the said specific cytosine are amplified, whereby the amplified products are given a detectable label and in the following steps the extent of hybridization of the amplified products on two classes of oligonucleotides is determined by detection of the label of the amplified products, and a conclusion is made on the extent of methylation of said specific cytosine in the genomic DNA sample from the ratio of the labels detected on the two classes of oligonucleotides as a consequence of the hybridization.

5. 发明申请

US20110136687A1 METHOD FOR DETERMINING THE DEGREE OF METHYLATION OF DEFINED CYTOSINES IN GENOMIC DNA IN THE SEQUENCE CONTEXT OF 5'-CpG-3' 有权
标题翻译：用于确定5'-CpG-3'序列序列中基因DNA中定义的细胞因子甲基化程度的方法
公开(公告)号：US20110136687A1
公开(公告)日：2011-06-09
申请号：US12847005
申请日：2010-07-30
申请人： Alexander Olek , Christian Piepenbrock , Kurt Berlin , David Guetig
发明人： Alexander Olek , Christian Piepenbrock , Kurt Berlin , David Guetig
IPC分类号： C40B30/04 , C12Q1/68 , C07H21/04 , C07H21/00 , C40B40/06 , C40B50/14
CPC分类号： C12Q1/6827 , C12Q1/6883 , C12Q2600/154
摘要： A method is described for the detection of the degree of methylation of a specific cytosine in the sequence context 5′-CpG-3′ of a genomic DNA sample. In the first step, the genomic DNA is chemically treated in such a way that the cytosine bases are converted to uracil, but not the 5-methylcytosine bases. Then segments of the genomic DNA which contain the said specific cytosine are amplified, whereby the amplified products are given a detectable label and in the following steps the extent of hybridization of the amplified products on two classes of oligonucleotides is determined by detection of the label of the amplified products, and a conclusion is made on the extent of methylation of said specific cytosine in the genomic DNA sample from the ratio of the labels detected on the two classes of oligonucleotides as a consequence of the hybridization.
摘要翻译：描述了用于检测基因组DNA样品的序列上下文5'-CpG-3'中特定胞嘧啶的甲基化程度的方法。在第一步中，以使胞嘧啶碱基转化成尿嘧啶而不是5-甲基胞嘧啶碱基的方式对基因组DNA进行化学处理。然后扩增含有所述特异性胞嘧啶的基因组DNA片段，由此扩增产物被给予可检测标记，并且在随后的步骤中，扩增产物在两类寡核苷酸上的杂交程度通过检测扩增产物，并且从基因组DNA样品中的两种类型的寡核苷酸上检测到的标记的比例作为杂交的结果，对所述特定胞嘧啶在基因组DNA样品中甲基化的程度进行了总结。

6. 发明授权

US07195870B2 Diagnosis of diseases associated with gene regulation 失效
标题翻译：诊断与基因调控有关的疾病
公开(公告)号：US07195870B2
公开(公告)日：2007-03-27
申请号：US10239676
申请日：2001-04-06
申请人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
发明人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C07K14/4703 , C07K14/82 , C12Q1/6886 , C12Q2600/154 , C12Q2600/156
摘要： Chemically modified genomic sequences of genes associated with gene regulation, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genes associated with gene regulation which are directed against the sequence are disclosed. In addition, a method for ascertaining genetic and/or epigenetic parameters of genes associated with gene regulation is disclosed.
摘要翻译：公开了与基因调控相关的基因的化学修饰的基因组序列，用于检测针对该序列的与基因调控相关的基因的胞嘧啶甲基化状态的寡核苷酸和/或PNA-寡聚体。另外，公开了确定与基因调控相关基因的遗传和/或表观遗传学参数的方法。

7. 发明申请

US20080145839A1 Method and Nucleic Acids For the Differentiation of Astrocytoma, Oligoastrocytoma and Oligodenroglioma Tumor Cells 审中-公开
标题翻译：方法和核酸用于分化星形细胞瘤，低分化细胞瘤和少突胶质细胞瘤肿瘤细胞
公开(公告)号：US20080145839A1
公开(公告)日：2008-06-19
申请号：US10311506
申请日：2001-07-02
申请人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
发明人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
IPC分类号： C12Q1/68 , C07H21/04 , C40B40/06 , C40B50/14
CPC分类号： C07K14/82 , C07K14/4703 , C12Q1/6883 , C12Q1/6886 , C12Q2523/125 , C12Q2600/154 , C12Q2600/156
摘要： Chemically modified nucleic acid sequences of genomic DNA, oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genomic DNA. In addition, a method for ascertaining genetic and/or epigenetic parameters of genes for the characterization, classification, differentiation, grading, staging, treatment and diagnosis of oligodendrogliomas, astrocytomas and oligoastrocytomas.
摘要翻译：用于检测基因组DNA的胞嘧啶甲基化状态的基因组DNA，寡核苷酸和/或PNA-寡聚体的化学修饰的核酸序列。另外，确定少突神经胶质瘤，星形细胞瘤和寡视神经细胞瘤的表征，分类，分化，分级，分期，治疗和诊断的基因的遗传和/或表观遗传参数的方法。

8. 发明申请

US20050064401A1 Diagnosis of illnesses or predisposition to certain illnesses 审中-公开
标题翻译：诊断疾病或某些疾病的倾向
公开(公告)号：US20050064401A1
公开(公告)日：2005-03-24
申请号：US10363483
申请日：2001-09-01
申请人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
发明人： Alexander Olek , Christian Piepenbrock , Kurt Berlin
IPC分类号： G01N33/53 , C07K14/47 , C07K14/82 , C08H1/00 , C12M1/00 , C12N15/09 , C12Q1/68 , C12Q1/6883 , G01N33/58 , G01N37/00 , C07H21/04 , C07K16/00
CPC分类号： C12Q1/6883 , C07K14/4703 , C07K14/82 , C12Q2600/154
摘要： The present invention describes a set of oligomer probes (oligonucleotides and/or PNA oligomers), which serve for the detection of the cytosine methylation state in nucleic acids. These probes are particularly suitable for the diagnosis of existing diseases by analysis of a set of genetic and/or epigenetic parameters.
摘要翻译：本发明描述了一组低聚物探针（寡核苷酸和/或PNA寡聚体），其用于检测核酸中的胞嘧啶甲基化状态。这些探针特别适用于通过分析一组遗传和/或表观遗传参数来诊断现有疾病。

9. 发明申请

US20050021240A1 Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen based on the methylation status of the DNA 审中-公开
标题翻译：基于DNA的甲基化状态指导治疗方案选择的系统，方法和计算机程序产品
公开(公告)号：US20050021240A1
公开(公告)日：2005-01-27
申请号：US10857105
申请日：2004-05-28
申请人： Kurt Berlin , Alexander Olek , Christian Piepenbrock
发明人： Kurt Berlin , Alexander Olek , Christian Piepenbrock
IPC分类号： C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/00 , G06F17/60
CPC分类号： G06Q50/24 , G16B20/00 , G16B40/00 , Y02A90/22 , Y02A90/26
摘要： Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen or a preventive therapeutic treatment regimen are disclosed. The method comprises (A) providing to a computing device comprising a first knowledge base comprising information about a plurality of different methylation statuses at selected sites of the DNA in cells with a known disease or medical condition and/or healthy cells, a second knowledge base comprising a plurality of expert rules for evaluating and selecting a type of disease or medical condition based on the methylation status at selected sites of the DNA of a patient, (B) generating in said computing device a ranked listing of diseases or medical conditions based on the information about the methylation status at selected sites of the DNA of the patient, the first knowledge base and the second knowledge base.
摘要翻译：公开了用于指导选择治疗方案或预防性治疗方案的系统，方法和计算机程序产品。该方法包括（A）提供给包括第一知识库的计算设备，所述第一知识库包括关于具有已知疾病或医学状况和/或健康细胞的细胞中所述DNA的选定位点处的多个不同甲基化状态的信息，和第二知识库包括用于基于患者的DNA的选定位点处的甲基化状态来评估和选择疾病或医学状况的多种专家规则，（B）在所述计算设备中产生基于以下的疾病或医疗状况的排名列表：关于患者DNA选定位点甲基化状态的信息，第一知识库和第二知识库。

10. 发明申请

US20130190205A1 METHOD FOR DETECTING CYTOSINE METHYLATION IN DNA SAMPLES 审中-公开
标题翻译：检测DNA样品中胞嘧啶甲基化的方法
公开(公告)号：US20130190205A1
公开(公告)日：2013-07-25
申请号：US13773480
申请日：2013-02-21
申请人： Alexander Olek , Kurt Berlin
发明人： Alexander Olek , Kurt Berlin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/686 , C12Q1/6816 , C12Q1/6827 , C12Q1/6837 , C12Q1/6872 , C12Q2523/125 , C12Q2565/519 , C12Q2565/627
摘要： Described is a method for detecting 5-methylcytosine in genomic DNA samples. First, a genomic DNA from a DNA sample is chemically converted with a reagent, 5-methylcytosine and cytosine reacting differently, and the pretreated DNA is subsequently amplified using a polymerase and at least one primer. In the next step, the amplified genomic DNA is hybridized to at least one oligonucleotide, forming a duplex, and said oligonucleotide is elongated by at least one nucleotide, the nucleotide carrying a detectable label, and the elongation depending on the methylation status of the specific cytosine in the genomic DNA sample. In the next step, the elongated oligonucleotides are analyzed for the presence of the label.
摘要翻译：描述了在基因组DNA样品中检测5-甲基胞嘧啶的方法。首先，DNA样品的基因组DNA用试剂化学转化，5-甲基胞嘧啶和胞嘧啶的反应不同，然后使用聚合酶和至少一种引物扩增预处理的DNA。在下一步骤中，将扩增的基因组DNA与至少一种形成双链体的寡核苷酸杂交，并且所述寡核苷酸由至少一个核苷酸延伸，所述核苷酸携带可检测标记，延伸取决于具体的甲基化状态基因组DNA样品中的胞嘧啶。在下一步骤中，分析细长寡核苷酸的标记物的存在。

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