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1. 发明专利

IL267300D0 Epigenetic markers and related methods and means for the detection and management of ovarian cancer 未知
公开(公告)号：IL267300D0
公开(公告)日：2019-08-29
申请号：IL26730019
申请日：2019-06-12
申请人： EUROFINS GENOMICS EUROPE SEQUENCING GMBH , GENEDATA AG , UCL BUSINESS PLC , MARTIN WIDSCHWENDTER , ALLISON JONES , IONA EVANS , HARRI LEMPPIAINEN , JOHANNES EICHNER , TAMAS RUJAN , TIMO WITTENBERGER , TOBIAS PAPROTKA , BENJAMIN WAHL
发明人： MARTIN WIDSCHWENDTER , ALLISON JONES , IONA EVANS , HARRI LEMPPIAINEN , JOHANNES EICHNER , TAMAS RUJAN , TIMO WITTENBERGER , TOBIAS PAPROTKA , BENJAMIN WAHL
IPC分类号： C12Q20060101
摘要： The present invention relates to methods of determining the presence or absence of an ovarian cancer in a woman, as well as to related methods to determine the response to therapy against ovarian cancer in a woman. Such methods are based on the detection - from cell-free DNA of said woman - of one or more methylated (or un-methylated) CpGs being associated with differentially methylated regions (DMRs) of the present invention; such as methylation (or un-methylation) at one or more or all of certain CpGs being associated with such DMRs. Accordingly, such methods have diagnostic, prognostic and/or predictive utility for detecting or managing ovarian cancer in women. The present invention further relates nucleic acids comprising certain sequences that may be detected during the method, or nucleic acids (such as probes and/or primers) that are useful to detect such sequences, as wells as compositions, kits, computer program products and other aspects that are useful for or related to the practice or application of such methods.

2. 发明专利

IL267302D0 Epigenetic markers and related methods and means for the detection and management of certain cancers 未知
公开(公告)号：IL267302D0
公开(公告)日：2019-08-29
申请号：IL26730219
申请日：2019-06-12
申请人： EUROFINS GENOMICS EUROPE SEQUENCING GMBH , GENEDATA AG , UCL BUSINESS PLC , MARTIN WIDSCHWENDTER , ALLISON JONES , IONA EVANS , HARRI LEMPPIAINEN , JOHANNES EICHNER , TAMAS RUJAN , TIMO WITTENBERGER , TOBIAS PAPROTKA , BENJAMIN WAHL
发明人： MARTIN WIDSCHWENDTER , ALLISON JONES , IONA EVANS , HARRI LEMPPIAINEN , JOHANNES EICHNER , TAMAS RUJAN , TIMO WITTENBERGER , TOBIAS PAPROTKA , BENJAMIN WAHL
IPC分类号： C12Q20060101
摘要： The present invention relates to methods of determining the presence or absence of an ovarian cancer in a woman, as well as to related methods to determine the response to therapy against ovarian cancer in a woman. Such methods are based on the detection - from cell-free DNA of said woman - of one or more methylated (or un-methylated) CpGs being associated with differentially methylated regions (DMRs) of the present invention; such as methylation (or un-methylation) at one or more or all of certain CpGs being associated with such DMRs. Accordingly, such methods have diagnostic, prognostic and/or predictive utility for detecting or managing ovarian cancer in women. The present invention further relates nucleic acids comprising certain sequences that may be detected during the method, or nucleic acids (such as probes and/or primers) that are useful to detect such sequences, as wells as compositions, kits, computer program products and other aspects that are useful for or related to the practice or application of such methods.

3. 发明授权

US08586313B2 DNA methylation markers based on epigenetic stem cell signatures in cancer 有权
标题翻译：基于癌基因表型遗传干细胞特征的DNA甲基化标记
公开(公告)号：US08586313B2
公开(公告)日：2013-11-19
申请号：US12520841
申请日：2007-12-27
申请人： Peter W. Laird , Martin Widschwendter
发明人： Peter W. Laird , Martin Widschwendter
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/158
摘要： In particular aspects, stem-cell polycomb group (PcG) targets are more likely to have cancer-specific promoter DNA methylation than non-targets, indicating a stem-cell origin of cancer, where reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and predisposition to subsequent malignant transformation. Exemplary aspects provide methods for identifying preferred DNA methylation markers for a cellular proliferative disorder and/or cancer and markers for developmental lineages and/or stages, based on identifying PcG protein or PcG repressive complex genomic target loci within a precursor cell (e.g., stem or progenitor cell) population, and determining, in cells of the proliferative disorder and/or cancer or cell of the particular developmental lineages and/or stages, a characteristic methylation status of the PcG target loci. Additional aspects provide methods for validating and/or monitoring a precursor cell (e.g., stem cell) population. Diagnostic and prognostic methods for ovarian and breast cancer are provided.
摘要翻译：在特定方面，干细胞多梳组（PcG）靶标比非靶标更可能具有癌症特异性启动子DNA甲基化，表明癌症的干细胞来源，其中可逆基因抑制被永久性沉默替代，锁定细胞进入自我更新的永久状态，并且随之而来的恶性转化。基于识别前体细胞内的PcG蛋白或PcG抑制性复合基因组靶基因座（例如，茎或者其中），鉴定出用于细胞增殖性疾病和/或癌症的优选DNA甲基化标记物和用于发育谱系和/或阶段的标志物的方法，祖细胞）群体，并且在特定发育谱系和/或阶段的增殖性疾病和/或癌症或细胞的细胞中确定PcG靶基因座的特征性甲基化状态。另外的方面提供了验证和/或监测前体细胞（例如干细胞）群体的方法。提供卵巢癌和乳腺癌的诊断和预后方法。

4. 发明专利

IL288970D0 Methods of detecting and predicting breast cancer 未知
公开(公告)号：IL288970D0
公开(公告)日：2022-02-01
申请号：IL28897021
申请日：2021-12-13
申请人： UCL BUSINESS LTD , MARTIN WIDSCHWENDTER , JAMES BARRETT
发明人： MARTIN WIDSCHWENDTER , JAMES BARRETT
摘要： The present invention relates to assays for predicting the presence or development of breast cancer in an individual, by determining the methylation status of certain CpGs in DNA from the individual, deriving an index value based on the methylation status of the certain CpGs, and predicting the development of breast cancer in the individual based on the breast cancer index value.

5. 发明申请

US20090162836A1 Prognostic and Diagnostic Markers for Cell Proliferative Disorders of The Breast Tissues 审中-公开
标题翻译：乳腺组织细胞增殖性疾病的预后和诊断标记
公开(公告)号：US20090162836A1
公开(公告)日：2009-06-25
申请号：US10575753
申请日：2004-10-14
申请人： Martin Widschwendter
发明人： Martin Widschwendter
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q1/6827 , C12Q1/6837 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2531/113 , C12Q2525/107 , C12Q2523/125
摘要： The present invention relates to prognostic and diagnostic markers for cell proliferative disorders of the breast tissues. The present invention therefore provides methods and nucleic acids for the analysis of biological samples for features associated with the development of breast cell proliferative disorders. Furthermore, the invention provides for prognosis of treatment effects relating to drug therapy, in particular hormonal/antihormonal therapy, chemotherapy and/or adjuvant therapy.
摘要翻译：本发明涉及乳腺组织细胞增殖性疾病的预后和诊断标记。因此，本发明提供了用于分析与乳腺增生性疾病发展相关的特征的生物样品的方法和核酸。此外，本发明提供了关于药物治疗，特别是激素/抗激素治疗，化疗和/或辅助治疗的治疗效果的预后。

6. 发明申请

US20090136921A1 Association of Breast Cancer DNA Methylation Profiles with Hormone Receptor Status and Response to Tamoxifen 有权
标题翻译：乳腺癌DNA甲基化配置文件与激素受体状态和他莫昔芬反应的关系
公开(公告)号：US20090136921A1
公开(公告)日：2009-05-28
申请号：US11628390
申请日：2005-06-01
申请人： Martin Widschwendter , Kimberly D. Siegmund , Peter A. Jones , Peter W. Laird
发明人： Martin Widschwendter , Kimberly D. Siegmund , Peter A. Jones , Peter W. Laird
IPC分类号： C12Q1/68 , C40B30/00
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154
摘要： Particular embodiments provide novel and clinically useful DNA methylation predictors of hormone receptor status, and predictors of response to endocrine (e.g., hormonal) and non-endocrine breast cancer therapy. The ESR1 gene, encoding the estrogen receptor (ER) alpha proved to be the preferred predictor of progesterone receptor (PR) status, while methylation of the PGR gene, encoding PR, was the preferred predictor of ER status. ESR1 methylation outperformed hormone receptor status as a predictor of clinical response in patients treated with antiestroges (e.g., tamoxifen), while promoter methylation of the CYP1B1 gene, encoding a tamoxifen and estradiol metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and non-treated patients. High levels of promoter methylation of the ARHI gene, encoding a RAS-related small G-protein, were shown to be preferred predictors of better survival in patients who had not received tamoxifen therapy.
摘要翻译：具体实施方案提供了激素受体状态的新型和临床有用的DNA甲基化预测因子，以及对内分泌（例如激素）和非内分泌乳腺癌治疗的预测因子。编码雌激素受体（ER）α的ESR1基因被证明是孕酮受体（PR）状态的优选预测因子，而编码PR的PGR基因的甲基化是ER状态的优选预测因子。 ESR1甲基化表现优于激素受体状态，作为用抗静脉药物治疗的患者（如他莫昔芬）的临床反应预测因子，而CYP1B1基因的启动子甲基化，编码他莫昔芬和雌二醇代谢细胞色素P450，预测了他莫昔芬治疗和非 - 治疗患者。编码RAS相关小G蛋白的ARHI基因的高水平启动子甲基化被证明是没有接受他莫昔芬治疗的患者更好的生存的优选预测因子。

7. 发明申请

US20130316374A1 BREAST CANCER DIAGNOSTICS 审中-公开
标题翻译：乳腺癌诊断
公开(公告)号：US20130316374A1
公开(公告)日：2013-11-28
申请号：US13825502
申请日：2011-09-22
申请人： Josef Penninger , Daniel Schramek , Georg Schett , Martin Widschwendter , Ian J. Jacobs , Usha Menon
发明人： Josef Penninger , Daniel Schramek , Georg Schett , Martin Widschwendter , Ian J. Jacobs , Usha Menon
IPC分类号： G01N33/68
CPC分类号： G01N33/57415 , G01N33/6893 , G01N2333/70575 , G01N2800/50 , G01N2800/56
摘要： The present invention relates to methods and means for detecting cancer or of predicting a patient developing cancer or of determining the rate of progression of cancer in a patient suffering from cancer, comprising determining RANKL activity and/or the amount of OPG in a sample of said patient.
摘要翻译：本发明涉及用于检测癌症或预测患有癌症的患者或确定患有癌症的患者的癌症进展速率的方法和手段，包括确定所述癌症的样品中的RANKL活性和/或OPG的量患者。

8. 发明申请

US20100172880A1 DNA METHYLATION MARKERS BASED ON EPIGENETIC STEM CELL SIGNATURES IN CANCER 有权
标题翻译：基于癌基因突变细胞标志物的DNA甲基化标记
公开(公告)号：US20100172880A1
公开(公告)日：2010-07-08
申请号：US12520841
申请日：2007-12-27
申请人： Peter W. Laird , Martin Widschwendter
发明人： Peter W. Laird , Martin Widschwendter
IPC分类号： A61K35/12 , C12Q1/68 , A61P35/04
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/158
摘要： In particular aspects, stem-cell polycomb group (PcG) targets are more likely to have cancer-specific promoter DNA methylation than non-targets, indicating a stem-cell origin of cancer, where reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and predisposition to subsequent malignant transformation. Exemplary aspects provide methods for identifying preferred DNA methylation markers for a cellular proliferative disorder and/or cancer and markers for developmental lineages and/or stages, based on identifying PcG protein or PcG repressive complex genomic target loci within a precursor cell (e.g., stem or progenitor cell) population, and determining, in cells of the proliferative disorder and/or cancer or cell of the particular developmental lineages and/or stages, a characteristic methylation status of the PcG target loci. Additional aspects provide methods for validating and/or monitoring a precursor cell (e.g., stem cell) population. Diagnostic and prognostic methods for ovarian and breast cancer are provided.
摘要翻译：在特定方面，干细胞多梳组（PcG）靶标比非靶标更可能具有癌症特异性启动子DNA甲基化，表明癌症的干细胞来源，其中可逆基因抑制被永久性沉默替代，锁定细胞进入自我更新的永久状态，并且随之而来的恶性转化。基于识别前体细胞内的PcG蛋白或PcG抑制性复合基因组靶基因座（例如，茎或者其中），鉴定出用于细胞增殖性病症和/或癌症的优选DNA甲基化标记物和用于发育谱系和/或阶段的标志物的方法，祖细胞）群体，并且在特定发育谱系和/或阶段的增殖性疾病和/或癌症或细胞的细胞中确定PcG靶基因座的特征性甲基化状态。另外的方面提供了验证和/或监测前体细胞（例如干细胞）群体的方法。提供卵巢癌和乳腺癌的诊断和预后方法。

9. 发明申请

US20220205049A1 METHODS OF DETECTING AND PREDICTING BREAST CANCER 有权
公开(公告)号：US20220205049A1
公开(公告)日：2022-06-30
申请号：US17596594
申请日：2020-06-12
申请人： Martin Widschwendter
发明人： Martin Widschwendter
IPC分类号： C12Q1/6886 , C12Q1/6827 , C12Q1/6837 , G01N33/50 , A61K31/567 , C07K16/28 , A61P35/00
摘要： The present invention relates to assays for predicting the presence or development of breast cancer in an individual, by determining the methylation status of certain CpGs in DNA from the individual, deriving an index value based on the methylation status of the certain CpGs, and predicting the development of breast cancer in the individual based on the breast cancer index value.

10. 发明授权

US08367336B2 Association of the DNA methylation profile of the CYP1B1 gene with response to adjuvant therapy in breast cancer 有权
标题翻译： CYP1B1基因DNA甲基化谱与乳腺癌辅助治疗反应的关系
公开(公告)号：US08367336B2
公开(公告)日：2013-02-05
申请号：US11628390
申请日：2005-06-01
申请人： Martin Widschwendter , Kimberly D. Siegmund , Peter A. Jones , Peter W. Laird
发明人： Martin Widschwendter , Kimberly D. Siegmund , Peter A. Jones , Peter W. Laird
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154
摘要： Particular embodiments provide novel and clinically useful DNA methylation predictors of hormone receptor status, and predictors of response to endocrine (e.g., hormonal) and non-endocrine breast cancer therapy. The ESR1 gene, encoding the estrogen receptor (ER) alpha proved to be the preferred predictor of progesterone receptor (PR) status, while methylation of the PGR gene, encoding PR, was the preferred predictor of ER status. ESR1 methylation outperformed hormone receptor status as a predictor of clinical response in patients treated with antiestroges (e.g., tamoxifen), while promoter methylation of the CYP1B1 gene, encoding a tamoxifen and estradiol metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and non-treated patients. High levels of promoter methylation of the ARH1 gene, encoding a RAS-related small G-protein, were shown to be preferred predictors of better survival in patients who had not received tamoxifen therapy.
摘要翻译：具体实施方案提供了激素受体状态的新型和临床有用的DNA甲基化预测因子，以及对内分泌（例如激素）和非内分泌乳腺癌治疗的预测因子。编码雌激素受体（ER）α的ESR1基因被证明是孕酮受体（PR）状态的优选预测因子，而编码PR的PGR基因的甲基化是ER状态的优选预测因子。 ESR1甲基化优于激素受体状态，作为抗前列腺治疗患者临床反应的预测因子（如他莫昔芬），而CYP1B1基因的启动子甲基化，编码他莫昔芬和雌二醇代谢细胞色素P450，预测了他莫昔芬治疗和非 - 治疗患者。编码RAS相关小G蛋白的ARH1基因的高水平启动子甲基化被证明是没有接受他莫昔芬治疗的患者更好的生存的优选预测因子。

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