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1. 发明申请

WO2011120984A1 METHOD FOR BREAST CANCER RECURRENCE PREDICTION UNDER ENDOCRINE TREATMENT 审中-公开
标题翻译：乳腺癌复发预后的内镜治疗方法
公开(公告)号：WO2011120984A1
公开(公告)日：2011-10-06
申请号：PCT/EP2011/054855
申请日：2011-03-29
申请人： SIVIDON DIAGNOSTICS GMBH , DARTMANN, Mareike , FEDER, Inke Sabine , GEHRMANN, Mathias , HENNING, Guido , WEBER, Karsten , VON TÖRNE, Christian , KRONENWETT, Ralf , PETRY, Christoph
发明人： DARTMANN, Mareike , FEDER, Inke Sabine , GEHRMANN, Mathias , HENNING, Guido , WEBER, Karsten , VON TÖRNE, Christian , KRONENWETT, Ralf , PETRY, Christoph
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/158
摘要： The present invention relates to methods, kits and systems for the prognosis of the disease outcome of breast cancer, said method comprising : (a) determining in a tumor sample from said patient the RNA expression levels of at least 2 of the following 9 genes: UBE2C, BIRC5, RACGAP1, DHCR7, STC2, AZGP1, RBBP8, IL6ST, and MGP (b) mathematically combining expression level values for the genes of the said set which values were determined in the tumor sample to yield a combined score, wherein said combined score is indicative of a prognosis of said patient; and kits and systems for performing said method.
摘要翻译：本发明涉及用于乳腺癌疾病预后的方法，试剂盒和系统，所述方法包括：（a）在来自所述患者的肿瘤样品中测定以下9个基因中的至少2个的RNA表达水平： UBE2C，BIRC5，RACGAP1，DHCR7，STC2，AZGP1，RBBP8，IL6ST和MGP（b）在数学上组合所述组的基因的表达水平值，其在肿瘤样品中测定得到组合得分，其中所述组合评分表示所述患者的预后; 以及用于执行所述方法的套件和系统。

2. 发明申请

WO2013014296A1 METHOD FOR PREDICTING THE RESPONSE TO CHEMOTHERAPY IN A PATIENT SUFFERING FROM OR AT RISK OF DEVELOPING RECURRENT BREAST CANCER 审中-公开
标题翻译：预防患者发生反应性乳腺癌风险的患者反应的方法
公开(公告)号：WO2013014296A1
公开(公告)日：2013-01-31
申请号：PCT/EP2012/064865
申请日：2012-07-30
申请人： SIVIDON DIAGNOSTICS GMBH , GEHRMANN, Mathias , WEBER, Karsten , KRONENWETT, Ralf , PETRY, Christoph , BRASE, Jan
发明人： GEHRMANN, Mathias , WEBER, Karsten , KRONENWETT, Ralf , PETRY, Christoph , BRASE, Jan
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6809 , C12Q2600/106 , C12Q2600/118 , C12Q2600/158 , C12Q2600/178
摘要： A method for predicting a response to and/or benefit of chemotherapy, including neoadjuvant chemotherapy, in a patient suffering from or at risk of developing recurrent neoplastic disease, in particular breast cancer, said method comprising the steps of: (a) determining in a tumor sample from said patient the RNA expression levels of the following 8 genes: UBE2C, RACGAP1, DHCR7, STC2, AZGP1, RBBP8, IL6ST, and MGP, indicative of a response to chemotherapy for a tumor, or (b) determining in a tumor sample from said patient the RNA expression levels of the following 8 genes: UBE2C, BIRC5, DHCR7, STC2, AZGP1, RBBP8, IL6ST, and MGP; indicative of a response to chemotherapy for a tumor (c) mathematically combining expression level values for the genes of the said set which values were determined in the tumor sample to yield a combined score, wherein said combined score is predicting said response and/or benefit of chemotherapy.
摘要翻译：一种在患有或有发生复发性肿瘤疾病，特别是乳腺癌风险的患者中预测化疗（包括新辅助化疗）的反应和/或益处的方法，所述方法包括以下步骤：（a）在来自所述患者的肿瘤样品包括以下8个基因的RNA表达水平：UBE2C，RACGAP1，DHCR7，STC2，AZGP1，RBBP8，IL6ST和MGP，指示对肿瘤的化学疗法的反应，或（b）在肿瘤中测定来自所述患者的样品来自以下8个基因的RNA表达水平：UBE2C，BIRC5，DHCR7，STC2，AZGP1，RBBP8，IL6ST和MGP; 指示对肿瘤的化学疗法的反应（c）在数学上组合所述组的基因的表达水平值，所述基因在肿瘤样品中测定以产生组合评分，其中所述组合评分预测所述应答和/或益处的化疗。

3. 发明申请

WO2010003773A1 ALGORITHMS FOR OUTCOME PREDICTION IN PATIENTS WITH NODE-POSITIVE CHEMOTHERAPY-TREATED BREAST CANCER 审中-公开
标题翻译：患有结直肠癌治疗乳腺癌的患者的预后预测方法
公开(公告)号：WO2010003773A1
公开(公告)日：2010-01-14
申请号：PCT/EP2009/057426
申请日：2009-06-16
申请人： SIEMENS MEDICAL SOLUTIONS DIAGNOSTICS GMBH , GEHRMANN, Mathias , KRONENWETT, Ralf , STROPP, Udo , WEBER, Karsten , VON TÖRNE, Christian
发明人： GEHRMANN, Mathias , KRONENWETT, Ralf , STROPP, Udo , WEBER, Karsten , VON TÖRNE, Christian
IPC分类号： G06F19/00 , C12Q1/68
CPC分类号： G06F19/24 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/158 , G06F19/18 , G06F19/20
摘要： The invention relates to methods for predicting an outcome of cancer in a patient suffering from cancer, said patient having been previously diagnosed as node positive and treated with cytotoxic chemotherapy, said method comprising determining in a biological sample from said patient an expression level of a plurality of genes selected from the group consisting of ACTG1, CA12, CALM2, CCND1, CHPT1, CLEC2B, CTSB, CXCL13, DCN, DHRS2, EIF4B, ERBB2, ESR1, FBXO28, GABRP, GAPDH, H2AFZ, IGFBP3, IGHG1, IGKC, KCTD3, KIAA0101, KRT17, MLPH, MMP1, NAT1, NEK2, NR2F2, OAZ1, PCNA, PDLIM5, PGR, PPIA, PRC1, RACGAP1, RPL37A, SOX4, TOP2A, UBE2C and VEGF; ABCB1, ABCG2, ADAM15, AKR1C1, AKR1C3, AKT1, BANF1, BCL2, BIRC5, BRMS1, CASP10, CCNE2, CENPJ, CHPT1, EGFR, CTTN, ERBB3, ERBB4, FBLN1, FIP1L1, FLT1, FLT4, FNTA, GATA3, GSTP1, Herstatin, IGF1R, IGHM, KDR, KIT, CKRT5, SLC39A6, MAPK3, MAPT, MKI67, MMP7, MTA1, FRAP1, MUC1, MYC, NCOA3, NFIB, OLFM1, TP53, PCNA, PI3K, PPERLD1, RAB31, RAD54B, RAF1, SCUBE2, STAU, TINF2, TMSL8, VGLL1, TRA@, TUBA1, TUBB, TUBB2A.
摘要翻译：本发明涉及用于预测患有癌症的患者的癌症结果的方法，所述患者先前被诊断为淋巴结阳性并用细胞毒性化疗治疗，所述方法包括在来自所述患者的生物样品中确定多个的表达水平选自ACTG1，CA12，CALM2，CCND1，CHPT1，CLEC2B，CTSB，CXCL13，DCN，DHRS2，EIF4B，ERBB2，ESR1，FBXO28，GABRP，GAPDH，H2AFZ，IGFBP3，IGHG1，IGKC，KCTD3， KIAA0101，KRT17，MLPH，MMP1，NAT1，NEK2，NR2F2，OAZ1，PCNA，PDLIM5，PGR，PPIA，PRC1，RACGAP1，RPL37A，SOX4，TOP2A，UBE2C及VEGF; ABCB1，ABCG2，ADAM15，AKR1C1，AKR1C3，AKT1，BANF1，BCL2，BIRC5，BRMS1，CASP10，CCNE2，CENPJ，CHPT1，EGFR，CTTN，ERBB3，ERBB4，FBLN1，FIP1L1，FLT1，FLT4，FNTA，GATA3，GSTP1， Herbatin，IGF1R，IGHM，KDR，KIT，CKRT5，SLC39A6，MAPK3，MAPT，MKI67，MMP7，MTA1，FRAP1，MUC1，MYC，NCOA3，NFIB，OLFM1，TP53，PCNA，PI3K，PPERLD1，RAB31，RAD54B，RAF1， SCUBE2，STAU，TINF2，TMSL8，VGLL1，TRA @，TUBA1，TUBB，TUBB2A。

4. 发明申请

WO2011131490A3 CURVE PROCESSOR ALGORITHM FOR THE QUALITY CONTROL OF (RT-)qPCR CURVES 审中-公开
公开(公告)号：WO2011131490A3
公开(公告)日：2011-10-27
申请号：PCT/EP2011/055406
申请日：2011-04-07
申请人： SIEMENS HEALTHCARE DIAGNOSTICS INC. , DARTMANN, Mareike , WEBER, Karsten , ALTMANN, Gabriela , FEDER, Inke Sabine , ROPERS, Tanja , ROTH, Claudia
发明人： DARTMANN, Mareike , WEBER, Karsten , ALTMANN, Gabriela , FEDER, Inke Sabine , ROPERS, Tanja , ROTH, Claudia
IPC分类号： G06F19/24 , C12Q1/68
摘要： The invention is in the field of analytical technology and relates to an improved procedure for determining the concentration or activity of an analyte in a sample. Specifically the invention provides an automated algorithm for the quality control of (RT-)qPCR reactions. Plotting the fluorescence intensity of a reporter dye divided by the fluorescence intensity of a passive reference dye against the cycle number leads to a so-called sigmoid function which is characterized by a background phase, an exponential growth phase and a plateau phase. Since the fluorescence intensity as a function of cycles relates to the initial number of template molecules in the sample, qPCR curves can be used to quantify the amount of RNA or DNA fragments in the sample by determination of a so-called Cq value.

5. 发明申请

WO2010003771A1 MOLECULAR MARKERS FOR CANCER PROGNOSIS 审中-公开
标题翻译：癌症预防分子标记
公开(公告)号：WO2010003771A1
公开(公告)日：2010-01-14
申请号：PCT/EP2009/057418
申请日：2009-06-16
申请人： SIEMENS HEALTHCARE DIAGNOSTICS GMBH , GEHRMANN, Mathias , STROPP, Udo , WEBER, Karsten , VON TÖRNE, Christian , SCHMIDT, Marcus
发明人： GEHRMANN, Mathias , STROPP, Udo , WEBER, Karsten , VON TÖRNE, Christian , SCHMIDT, Marcus
IPC分类号： G06F19/00 , C12Q1/68
CPC分类号： G06F19/24 , C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , G06F19/18 , G06F19/20
摘要： The present invention relates to methods for prediction of an outcome of neoplastic disease or cancer. More specifically, the present invention relates to a method for the prediction of breast cancer by determining in a biological sample from said patient an expression level of a plurality of genes selected from the group consisting of ACTG1, CA12, CALM2, CCND1, CHPT1, CLEC2B, CTSB, CXCL13, DCN, DHRS2, EIF4B, ERBB2, ESR1, FBXO28, GABRP, GAPDH, H2AFZ, IGFBP3, IGHG1, IGKC, KCTD3, KIAA0101, KRT17, MLPH, MMP1, NAT1, NEK2, NR2F2, OAZ1, PCNA, PDLIM5, PGR, PPIA, PRC1, RACGAP1, RPL37A, SOX4, TOP2A, UBE2C and VEGF.
摘要翻译：本发明涉及用于预测肿瘤性疾病或癌症的结果的方法。更具体地，本发明涉及通过在来自所述患者的生物样品中测定多种选自ACTG1，CA12，CALM2，CCND1，CHPT1，CLEC2B的多种基因的表达水平来预测乳腺癌的方法，CTSB，CXCL13，DCN，DHRS2，EIF4B，ERBB2，ESR1，FBXO28，GABRP，GAPDH，H2AFZ，IGFBP3，IGHG1，IGKC，KCTD3，KIAA0101，KRT17，MLPH，MMP1，NAT1，NEK2，NR2F2，OAZ1，PCNA，PDLIM5 ，PGR，PPIA，PRC1，RACGAP1，RPL37A，SOX4，TOP2A，UBE2C和VEGF。

6. 发明申请

WO2011121028A1 ALGORITHM FOR PREDICTION OF BENEFIT FROM ADDITION OF TAXANE TO STANDARD CHEMOTHERAPY IN PATIENTS WITH BREAST CANCER 审中-公开
标题翻译：将TAXANE增加益处的优点与乳腺癌患者标准化疗相关的算法
公开(公告)号：WO2011121028A1
公开(公告)日：2011-10-06
申请号：PCT/EP2011/054915
申请日：2011-03-30
申请人： SIEMENS HEALTHCARE DIAGNOSTICS INC. , FOUNTZILAS, George , GEHRMANN, Mathias , KRONENWETT, Ralf , STROPP, Udo , WEBER, Karsten , WIRTZ, Ralph
发明人： FOUNTZILAS, George , GEHRMANN, Mathias , KRONENWETT, Ralf , STROPP, Udo , WEBER, Karsten , WIRTZ, Ralph
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , G06F19/20 , G06F19/24
摘要： The invention relates to a method or predicting an outcome of cancer in a patient suffering from cancer, said method comprising : (a) determining in a biological sample from said patient the expression level of at least one marker gene selected from AKR1C3, MAP4, SPP1, CXCL9, PTGER3, and VEGFC; (b) comparing said expression level to a reference pattern of expression, wherein an increased expression of said at least one marker gene is indicative of said patient having a benefit from microtubule stabilizing agent-based cytotoxic chemotherapy.
摘要翻译：本发明涉及一种方法或预测患有癌症的患者的癌症结果，所述方法包括：（a）在来自所述患者的生物样品中测定至少一种选自AKR1C3，MAP4，SPP1的标志物基因的表达水平，CXCL9，PTGER3和VEGFC; （b）将所述表达水平与表达的参考模式进行比较，其中所述至少一种标记基因的增加的表达指示所述患者具有基于微管稳定剂的细胞毒性化学疗法的益处。

7. 发明申请

WO2011157501A1 ESTIMATION OF DELTA-CQ VALUES WITH CONFIDENCE FROM QPCR DATA 审中-公开
标题翻译：从QPCR数据的信心估计DELTA-CQ值
公开(公告)号：WO2011157501A1
公开(公告)日：2011-12-22
申请号：PCT/EP2011/057863
申请日：2011-05-16
申请人： SIEMENS HEALTHCARE DIAGNOSTICS INC. , WEBER, Karsten , FEDER, Inke Sabine
发明人： WEBER, Karsten , FEDER, Inke Sabine
IPC分类号： G06F19/20
CPC分类号： G06F19/24 , C12Q1/6851 , G06F19/20 , C12Q2537/165
摘要： The invention describes how to estimate delta-Cq values from measured (raw-) Cq values gained from PCR measurements and how to calculate confidence intervals for them. This is realized by the following processing steps: A noise model, which might be constructed on some training PCR data, calculates the distribution of the true target material concentration of a single well for an observed measurement results. Said distribution is calculated for all types of measurement results including "Numeric" raw-Cq values as well as Cq being "Undetected", which denotes that no fluorescence signal was detected during all cycles and thus corresponds to no or very few target molecules. Based on this distribution information from several replicate wells of a gene of interest and several replicate wells of one or more reference genes the distribution of the true delta-Cq value is calculated. In order to come out with a finite variance of the delta-Cq value (which so far would not be the case if all replicates are "Undetected") a lower bound is defined on the delta-Cq value. This lower bound is chosen so small that no useful information about the clinical implications is lost but so large that even for samples with low total material yield a reliable estimation of the delta-Cq value is possible.
摘要翻译：本发明描述了如何从从PCR测量获得的测量（原始）Cq值估计Δ-Cq值，以及如何计算它们的置信区间。这通过以下处理步骤来实现：可以在一些训练PCR数据上构建的噪声模型计算观察测量结果的单井真实目标物质浓度的分布。对于包括“数字”原始Cq值以及Cq为“未检测到”的所有类型的测量结果计算所述分布，其表示在所有循环期间没有检测到荧光信号，因此对应于没有或非常少的目标分子。基于来自目的基因的几个重复孔的分布信息和一个或多个参考基因的几个重复孔，计算真实Δ-Cq值的分布。为了出现delta-Cq值的有限方差（到目前为止，如果所有重复都是“未检测到”），则下限是在delta-Cq值上定义的。这个下限被选择得如此之小，以致没有关于临床意义的有用信息丢失但是如此之大，即使对于具有低总材料产量的样品也可能对delta-Cq值的可靠估计是可能的。

8. 发明申请

WO2015121300A1 METHOD FOR PREDICTING THE RESPONSE AND SURVIVAL FROM CHEMOTHERAPY IN PATIENTS WITH BREAST CANCER 审中-公开
标题翻译：在乳腺癌患者中预防化疗反应和存活的方法
公开(公告)号：WO2015121300A1
公开(公告)日：2015-08-20
申请号：PCT/EP2015/052869
申请日：2015-02-11
申请人： SIVIDON DIAGNOSTICS GMBH
发明人： BRASE, Jan Christoph , SCHMIDT, Marcus , KRONENWETT, Ralf , FISCH, Karin , WEBER, Karsten
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/158
摘要： A method for predicting the residual risk of recurrence after standard chemotherapy treatment, in particular a taxane-free chemotherapy, and the benefit from inclusion of taxane in a chemotherapy regimen in a patient suffering from or at risk of developing recurrent neoplastic disease, in particular breast cancer. Said method comprises the steps of: (a) determining in a tumor sample from said patient the expression levels of the following 6 genes: UBE2C, KIF20A, PTGER3, OSBPL1A, CYP27A1, IGKC, and (b) mathematically combining said expression level values for the genes of the said set which values were determined in the tumor sample to yield a prognostic combined score and (c) comparing said prognostic combined score to one or more thresholds and classifying said patient in a good, intermediate or poor outcome group and (d) determining in said tumor sample from said patient the expression levels of three genes: STC1, PCSK6, S100P, and (e) mathematically combining said expression level values for STC1, PCSK6 and S100P to yield a predictive combined score, whereas a high predictive combined score generally indicates an increased likelihood of benefit from inclusion of taxane in a chemotherapy regimen in a patient classified to said poor and/or intermediate outcome group.
摘要翻译：一种用于预测标准化学治疗后特别是无紫杉烷化疗的复发的残留风险的方法，以及在发生复发性肿瘤性疾病，特别是乳腺癌的患者的化疗方案中纳入紫杉烷的益处癌症。所述方法包括以下步骤：（a）在来自所述患者的肿瘤样品中确定以下6个基因的表达水平：UBE2C，KIF20A，PTGER3，OSBPL1A，CYP27A1，IGKC，和（b）将所述表达水平值所述组的基因在肿瘤样品中测定值以产生预后组合评分，和（c）将所述预后组合评分与一个或多个阈值进行比较，并将所述患者在良好，中间或不良结果组中进行分类，和（d ）在所述患者的所述肿瘤样品中确定三种基因的表达水平：STC1，PCSK6，S100P和（e）在数学上组合STC1，PCSK6和S100P的所述表达水平值以产生预测性组合评分，而高预测性组合评分通常表明在分类为所述贫困和/或中间结果组的患者中，在化疗方案中纳入紫杉烷的益处的可能性增加。

9. 发明授权

EP2737081B1 METHOD FOR PREDICTING THE RESPONSE TO CHEMOTHERAPY IN A PATIENT SUFFERING FROM OR AT RISK OF DEVELOPING RECURRENT BREAST CANCER 有权转让
标题翻译：一种用于预测对化疗的反应患者的乳房或类似的复发风险
公开(公告)号：EP2737081B1
公开(公告)日：2016-09-28
申请号：EP12740974.6
申请日：2012-07-30
申请人： Sividon Diagnostics GmbH
发明人： GEHRMANN, Mathias , WEBER, Karsten , KRONENWETT, Ralf , PETRY, Christoph , BRASE, Jan
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6809 , C12Q2600/106 , C12Q2600/118 , C12Q2600/158 , C12Q2600/178

10. 发明公开

EP2737081A1 METHOD FOR PREDICTING THE RESPONSE TO CHEMOTHERAPY IN A PATIENT SUFFERING FROM OR AT RISK OF DEVELOPING RECURRENT BREAST CANCER 有权转让
标题翻译：一种用于预测对化疗的反应患者的乳房或类似的复发风险
公开(公告)号：EP2737081A1
公开(公告)日：2014-06-04
申请号：EP12740974.6
申请日：2012-07-30
申请人： Sividon Diagnostics GmbH
发明人： GEHRMANN, Mathias , WEBER, Karsten , KRONENWETT, Ralf , PETRY, Christoph , BRASE, Jan
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6809 , C12Q2600/106 , C12Q2600/118 , C12Q2600/158 , C12Q2600/178
摘要： A method for predicting a response to and/or benefit of chemotherapy, including neoadjuvant chemotherapy, in a patient suffering from or at risk of developing recurrent neoplastic disease, in particular breast cancer, said method comprising the steps of: (a) determining in a tumor sample from said patient the RNA expression levels of the following 8 genes: UBE2C, RACGAP1, DHCR7, STC2, AZGP1, RBBP8, IL6ST, and MGP, indicative of a response to chemotherapy for a tumor, or (b) determining in a tumor sample from said patient the RNA expression levels of the following 8 genes: UBE2C, BIRC5, DHCR7, STC2, AZGP1, RBBP8, IL6ST, and MGP; indicative of a response to chemotherapy for a tumor (c) mathematically combining expression level values for the genes of the said set which values were determined in the tumor sample to yield a combined score, wherein said combined score is predicting said response and/or benefit of chemotherapy.
摘要翻译：一种用于预测到的响应和/或化疗的益处，包括在从或有发展复发性肿瘤疾病的风险的患者新辅助化疗，特别是乳腺癌的方法，所述方法包括的步骤：（a）确定的开采于来自所述患者的肿瘤样品下列8个基因的RNA表达水平：UBE2C，RACGAP1，DHCR7，STC 2，AZGP1，RBBP8，IL6ST，和MGP，指示在肿瘤对化疗的响应针对肿瘤，或（b）确定的挖掘所述样品从病人下列8个基因的RNA表达水平：UBE2C，BIRC5，DHCR7，STC 2，AZGP1，RBBP8，IL6ST，和MGP; 指示对化疗的响应针对肿瘤（C）在数学上用于所述组的基因，其值确定肿瘤样品中开采，以产生组合分值组合的表达水平的值，worin所述组合分值被预测所述响应和/或有益的化疗。

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