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1. 发明申请

US20120184455A1 Method and Nucleic Acids for the Improved Treatment of Breast Cell Proliferative Disorders 审中-公开
标题翻译：改善乳腺增生性疾病治疗的方法和核酸
公开(公告)号：US20120184455A1
公开(公告)日：2012-07-19
申请号：US13352238
申请日：2012-01-17
申请人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Armin Schmitt , Manfred Schmitt , Maxime P. Look , Almuth Marx , Heinz Hoefler
发明人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Armin Schmitt , Manfred Schmitt , Maxime P. Look , Almuth Marx , Heinz Hoefler
IPC分类号： C40B30/00 , C40B40/06 , C40B30/04 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/154 , C12Q2600/158 , C12Q2600/16
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 response of a subject with a cell proliferative disorder of the breast tissues, to endocrine treatment.
摘要翻译：本发明涉及修饰和基因组序列，用于检测基因组DNA的胞嘧啶甲基化状态的寡核苷酸和/或PNA寡聚体，以及用于预测受试者与乳腺组织的细胞增殖性病症的反应的方法，进行内分泌治疗。

2. 发明授权

US08101359B2 Method for determining risk of relapse of breast cancer following tamoxifen adjuvant therapy 有权
标题翻译：替莫昔芬辅助治疗后确定乳腺癌复发风险的方法
公开(公告)号：US08101359B2
公开(公告)日：2012-01-24
申请号：US10517741
申请日：2003-10-01
申请人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John W. Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Armin Schmitt , Manfred Schmitt , Maxime P. Look , Almuth Marx , Heinz Hoefler
发明人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John W. Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Armin Schmitt , Manfred Schmitt , Maxime P. Look , Almuth Marx , Heinz Hoefler
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/154 , C12Q2600/158 , C12Q2600/16
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 response of a subject with a cell proliferative disorder of the breast tissues, to endocrine treatment.
摘要翻译：本发明涉及修饰和基因组序列，用于检测基因组DNA的胞嘧啶甲基化状态的寡核苷酸和/或PNA寡聚体，以及用于预测受试者与乳腺组织的细胞增殖性病症的反应的方法，进行内分泌治疗。

3. 发明申请

US20060121467A1 Method and nucleic acids for the improved treatment of breast cell proliferative disorders 有权
标题翻译：用于改善乳腺增生性疾病治疗的方法和核酸
公开(公告)号：US20060121467A1
公开(公告)日：2006-06-08
申请号：US10517741
申请日：2003-10-01
申请人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Armin Schmitt , Manfred Schmitt , Maxime Look , Almuth Marx , Heinz Hoefler
发明人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Armin Schmitt , Manfred Schmitt , Maxime Look , Almuth Marx , Heinz Hoefler
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/154 , C12Q2600/158 , C12Q2600/16
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 response of a subject with a cell proliferative disorder of the breast tissues, to endocrine treatment.
摘要翻译：本发明涉及修饰和基因组序列，用于检测基因组DNA的胞嘧啶甲基化状态的寡核苷酸和/或PNA寡聚体，以及用于预测受试者与乳腺组织的细胞增殖性病症的反应的方法，进行内分泌治疗。

4. 发明申请

US20080254447A1 Method and Nucleic Acids for the Improved Treatment of Breast Cell Proliferative Disorders 有权
标题翻译：改善乳腺增生性疾病治疗的方法和核酸
公开(公告)号：US20080254447A1
公开(公告)日：2008-10-16
申请号：US10582705
申请日：2004-12-13
申请人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Manfred Schmitt , Ralf Lesche , Dimo Dietrich , Volkmar Mueller , Antje Kluth , Ina Schwope , Oliver Hartmann , Peter Adorjan , Almuth Marx , Heinz Hoefler
发明人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Manfred Schmitt , Ralf Lesche , Dimo Dietrich , Volkmar Mueller , Antje Kluth , Ina Schwope , Oliver Hartmann , Peter Adorjan , Almuth Marx , Heinz Hoefler
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/158 , C12Q2600/16
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.
摘要翻译：本发明涉及修饰和基因组序列，用于检测基因组DNA的胞嘧啶甲基化状态的寡核苷酸和/或PNA寡聚体，以及用于预测受试者与细胞的无病存活和/或应答的方法乳腺组织增生性疾病，进行内分泌治疗。

5. 发明授权

US09017944B2 Methods for the prognosis of breast cancer 有权
标题翻译：乳腺癌预后的方法
公开(公告)号：US09017944B2
公开(公告)日：2015-04-28
申请号：US10582705
申请日：2004-12-13
申请人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John W. Martens , Fabian Model , Inko Nimmrich , Manfred Schmitt , Ralf Lesche , Dimo Dietrich , Volkmar Mueller , Antje Kluth Lukas , Ina Schwope , Oliver Hartmann , Peter Adorjan , Almuth Marx , Heinz Hoefler
发明人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John W. Martens , Fabian Model , Inko Nimmrich , Manfred Schmitt , Ralf Lesche , Dimo Dietrich , Volkmar Mueller , Antje Kluth Lukas , Ina Schwope , Oliver Hartmann , Peter Adorjan , Almuth Marx , Heinz Hoefler
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/158 , C12Q2600/16
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.
摘要翻译：本发明涉及修饰和基因组序列，用于检测基因组DNA的胞嘧啶甲基化状态的寡核苷酸和/或PNA寡聚体，以及用于预测受试者与细胞的无病存活和/或应答的方法乳腺组织增生性疾病，进行内分泌治疗。

6. 发明申请

US20060024684A1 Prognostic markers for prediction of treatment response and/or survival of breast cell proliferative disorder patients 审中-公开
公开(公告)号：US20060024684A1
公开(公告)日：2006-02-02
申请号：US11011332
申请日：2004-12-13
申请人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Manfred Schmitt , Ralf Lesche , Dimo Dietrich , Volkmar Mueller , Antje Kluth , Ina Schwope , Oliver Hartmann , Peter Adorjan
发明人： John Foekens , Nadia Harbeck , Thomas Koenig , Sabine Maier , John Martens , Fabian Model , Inko Nimmrich , Tamas Rujan , Manfred Schmitt , Ralf Lesche , Dimo Dietrich , Volkmar Mueller , Antje Kluth , Ina Schwope , Oliver Hartmann , Peter Adorjan
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16
摘要： Aspects of the present invention provide compositions and methods for prognosis of, and/or predicting the estrogen treatment outcome of breast cell proliferative disorder patients, and in particular of patients with breast carcinoma. In preferred embodiments, this is achieved, at least in part, by determining the expression level of PITX2, and/or the genetic or the epigenetic modifications of the genomic DNA associated with the gene PITX2. Additional aspects of the invention provide novel sequences, oligomers (e.g., oligonucleotides or peptide nucleic acid (PNA)-oligomers), and antibodies, which have substantial utility in the described inventive methods and compositions.

7. 发明申请

US20090111707A1 MARKERS FOR THE PREDICTION OF OUTCOME OF ANTHRACYCLINE TREATMENT 有权
标题翻译：预防治疗精神分裂症患者的标志物
公开(公告)号：US20090111707A1
公开(公告)日：2009-04-30
申请号：US12067633
申请日：2006-09-21
申请人： John Foekens , John Martens , Serenella Eppenberger-Castori , Vincent Vuaroqueaux , Frederique Spyratos , Nadia Harbeck , Manfred Schmitt , Heinz Hoefler , Sabine Maier , Gunter Weiss , Ralf Lesche , Thomas Hildmann , Achim Plum
发明人： John Foekens , John Martens , Serenella Eppenberger-Castori , Vincent Vuaroqueaux , Frederique Spyratos , Nadia Harbeck , Manfred Schmitt , Heinz Hoefler , Sabine Maier , Gunter Weiss , Ralf Lesche , Thomas Hildmann , Achim Plum
IPC分类号： C40B30/04 , C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/156 , C12Q2600/16
摘要： The present invention relates to methods for predicting the outcome of anthracycline treatment of cell proliferative disorder patients. This is achieved by determining the expression level of at least one gene selected from the group consisting of PITX2; TFF1 and PLAU. The invention also relates to sequences, oligonucleotides and antibodies which can be used within the described methods.
摘要翻译：本发明涉及预测细胞增殖性疾病患者蒽环类治疗结果的方法。这通过确定选自PITX2的至少一种基因的表达水平来实现; TFF1和PLAU。本发明还涉及可以在所述方法中使用的序列，寡核苷酸和抗体。

8. 发明授权

US10053735B2 Markers for the prediction of outcome of anthracycline treatment 有权
公开(公告)号：US10053735B2
公开(公告)日：2018-08-21
申请号：US12067633
申请日：2006-09-21
申请人： John Foekens , John W. Martens , Serenella Eppenberger-Castori , Vincent Vuaroqueaux , Frederique Spyratos , Nadia Harbeck , Manfred Schmitt , Heinz Hoefler , Sabine Maier , Gunter Weiss , Ralf Lesche , Thomas Hildmann , Achim Plum
发明人： John Foekens , John W. Martens , Serenella Eppenberger-Castori , Vincent Vuaroqueaux , Frederique Spyratos , Nadia Harbeck , Manfred Schmitt , Heinz Hoefler , Sabine Maier , Gunter Weiss , Ralf Lesche , Thomas Hildmann , Achim Plum
IPC分类号： C07H21/04 , C12Q1/68 , C12Q1/6886
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/156 , C12Q2600/16
摘要： The present invention relates to methods for predicting the outcome of anthracycline treatment of cell proliferative disorder patients. This is achieved by determining the expression level of at least one gene selected from the group consisting of PITX2; TFF1 and PLAU. The invention also relates to sequences, oligonucleotides and antibodies which can be used within the described methods.

9. 发明申请

US20060084056A1 Methods for selecting treatment regimens and predicting outcomes in cancer patients 审中-公开
标题翻译：选择治疗方案和预测癌症患者结局的方法
公开(公告)号：US20060084056A1
公开(公告)日：2006-04-20
申请号：US10504287
申请日：2003-02-13
申请人： Nadia Harbeck , Manfred Schmitt , John Foekens , Ronald Kates
发明人： Nadia Harbeck , Manfred Schmitt , John Foekens , Ronald Kates
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , G01N33/57415 , G01N2800/52 , Y02A90/26
摘要： The present invention relates to methods for determining a treatment regimen beyond surgical removal of tumor tissue for node negative or node positive breast cancer patient. The method comprises measuring the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in a subject, preferably a tumor; and, based upon the values, predicting the expected benefit including disease-free survival and/or overall survival for the patient without treatment (beyond the surgical removal of tumor tissue) or with a particular treatment and using that information to select a treatment regimen for the subject. High risk subject is identified by high levels of both uPA and PAI-1, high level of uPA and low level of PAI-1 or, low level of uPA and high level of PAI-1. Treatment options for high risk subjects include, but are not limited to, adjuvant CMF chemotherapy, adjuvant non-CMF chemotherapy, adjuvant endocrine therapy, adjuvant anthracyclin-containing chemotherapy, radiation therapy, and gene therapy. Treatment options for low risk subjects include, but are not limited to, no treatment, radiation, and adjuvant endocrine therapy.
摘要翻译：本发明涉及用于确定除了手术切除淋巴结阴性或淋巴结阳性乳腺癌患者的肿瘤组织之外的治疗方案的方法。该方法包括测量受试者，优选肿瘤中尿激酶型纤溶酶原激活物（uPA）和纤溶酶原激活物抑制剂-1（PAI-1）的水平; 并且基于这些值，预测未经治疗的患者（超过手术切除肿瘤组织）或特定治疗的患者的无病生存期和/或总生存期的预期益处，并且使用该信息来选择治疗方案主题。 uPA和PAI-1水平高，uPA水平高，PAI-1水平低，uPA水平低，PAI-1水平高。高风险患者的治疗方案包括但不限于辅助性CMF化疗，辅助性非CMF化疗，辅助内分泌治疗，含蒽环类化疗，放射治疗和基因治疗。低风险患者的治疗方案包括但不限于治疗，放射和辅助内分泌治疗。

10. 发明授权

US06968327B1 Method for training a neural network 有权
标题翻译：训练神经网络的方法
公开(公告)号：US06968327B1
公开(公告)日：2005-11-22
申请号：US10049650
申请日：2000-08-24
申请人： Ronald Kates , Nadia Harbeck , Manfred Schmitt
发明人： Ronald Kates , Nadia Harbeck , Manfred Schmitt
IPC分类号： A61B5/00 , G06F19/00 , G06N3/08 , G06E1/00 , G06E3/00 , G06F15/18 , G06G7/00
CPC分类号： G06N3/08 , A61B5/00 , A61B5/415 , A61B5/418 , A61B5/7267 , G06F19/00
摘要： A method for training a neural network in order to optimize the structure of the neural network includes identifying and eliminating synapses that have no significant influence on the curve of the risk function. First and second sending neurons are selected that are connected to the same receiving neuron by respective first and second synapses. It is assumed that there is a correlation of response signals from the first and second sending neurons to the same receiving neuron. The first synapse is interrupted and a weight of the second synapse is adapted in its place. The output signals of the changed neural network are compared with the output signals of the unchanged neural network. If the comparison result does not exceed a predetermined level, the first synapse is eliminated, thereby simplifying the structure of the neural network.
摘要翻译：用于训练神经网络以优化神经网络的结构的方法包括识别和消除对风险函数的曲线没有显着影响的突触。选择通过相应的第一和第二突触连接到相同接收神经元的第一和第二发送神经元。假设存在来自第一和第二发送神经元到相同接收神经元的响应信号的相关性。第一突触中断，第二突触的重量适应其位置。将改变的神经网络的输出信号与不变神经网络的输出信号进行比较。如果比较结果不超过预定水平，则消除第一突触，从而简化了神经网络的结构。

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