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1. 发明授权

US09274120B2 Stratification of pancreatic and ovarian cancer patients for susceptibility to therapy with PTK2 inhibitors 有权
公开(公告)号：US09274120B2
公开(公告)日：2016-03-01
申请号：US14221370
申请日：2014-03-21
申请人： Guenther Adolf , Pilar Garin-Chesa , Ulrich Hirt
发明人： Guenther Adolf , Pilar Garin-Chesa , Ulrich Hirt
IPC分类号： G01N33/53 , C12Q1/00 , G01N33/574 , C12Q1/68
CPC分类号： G01N33/57492 , C12Q1/6886 , G01N33/57484 , G01N33/57496 , G01N2333/705 , G01N2333/91205 , G01N2800/52
摘要： The present invention relates to a method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. Said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is preferably conducted by way of an immunohistochemistry (IHC) method. Said IHC method preferably employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. The present invention also relates to a method of treating a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2, comprising administering to the patient a therapeutically effective amount of a PTK2 inhibitor. In a further aspect, the present invention relates to a PTK2 inhibitor for use in the treatment of a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2. The present invention also provides a method of screening for a therapeutically effective PTK2 inhibitor comprising the steps of (a) providing cancer cells or a cancer cell line which are characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being even more preferred); (b) contacting the cancer cell or the cancer cell line of (a) with a PTK2 inhibitor; and (c) evaluating whether the PTK2 inhibitor negatively affects the cancer cell/cancer cell lines. In a further aspect, the present invention relates to a method for stratifying cancer patients that are susceptible to treatment with a PTK2 inhibitor, comprising determining the E-cadherin IRS score in a cancer sample of said patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 (i.e. 2, 1, or 0) indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The present invention also relates to a pharmaceutical package comprising a PTK2 inhibitor, and (a) instructions and/or an imprint indicating that said PTK2 inhibitor is to be used for the treatment of patients which suffer from a cancer which is characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being more preferred); and/or (b) instructions and/or an imprint indicating that said patient is to be stratified by a method of the present invention; and/or (c) means to carry out a method as defined herein.

2. 发明授权

US08404674B2 Substituted 9H-purin-2-YL compounds, compositions thereof and uses thereof 有权
标题翻译：取代的9H-嘌呤-2-YL化合物，其组合物及其用途
公开(公告)号：US08404674B2
公开(公告)日：2013-03-26
申请号：US12595072
申请日：2008-03-04
申请人： Heinz Stadtmueller , Guido Boehmelt , Harald Engelhardt , Ulrich Hirt , Otmar Schaaf , Irene Waizenegger
发明人： Heinz Stadtmueller , Guido Boehmelt , Harald Engelhardt , Ulrich Hirt , Otmar Schaaf , Irene Waizenegger
IPC分类号： C07D519/00 , A61K31/52 , A61P35/00
CPC分类号： C07D519/00
摘要： The present invention encompasses compounds of general formula (1) wherein R1, R2 and R3 are defined as in claim 1, which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition having the above-mentioned properties.
摘要翻译：本发明包括通式（1）的化合物，其中R 1，R 2和R 3如权利要求1中所定义，其适用于治疗以细胞增殖过度或异常为特征的疾病，以及它们用于制备具有上述属性。

3. 发明申请

US20120244141A1 Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors 审中-公开
标题翻译：癌症患者对PTK2抑制剂治疗易感性的分层
公开(公告)号：US20120244141A1
公开(公告)日：2012-09-27
申请号：US13237833
申请日：2011-09-20
申请人： Guenther ADOLF , Pilar GARIN-CHESA , Ulrich HIRT
发明人： Guenther ADOLF , Pilar GARIN-CHESA , Ulrich HIRT
IPC分类号： A61K39/395 , A61P35/00 , A61K31/713 , A61K31/7105 , G01N21/76 , G01N33/574
CPC分类号： G01N33/57492 , C12Q1/6886 , G01N33/57484 , G01N33/57496 , G01N2333/705 , G01N2333/91205 , G01N2800/52
摘要： A method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The invention further encompasses treatment of a patient with a protein tyrosine kinase 2 (PTK2) inhibitor if it has been so determined that said patient is susceptible to such treatment.
摘要翻译：一种确定癌症患者是否易于用蛋白酪氨酸激酶2（PTK2）抑制剂治疗的方法，包括检测所述癌症患者的癌症样品中E-钙粘蛋白蛋白的表达，其中E-钙粘蛋白蛋白免疫反应性评分（IRS）为0-2表示癌症患者易于用PTK2抑制剂治疗。如果已经确定所述患者易于进行这种治疗，本发明还包括治疗患有蛋白酪氨酸激酶2（PTK2）抑制剂的患者。

4. 发明申请

US20100311721A1 COMPOUNDS 有权
标题翻译：化合物
公开(公告)号：US20100311721A1
公开(公告)日：2010-12-09
申请号：US12595072
申请日：2008-03-04
申请人： Heinz Stadtmueller , Guido Boehmelt , Harald Engelhardt , Ulrich Hirt , Otmar Schaaf , Irene Waizenegger
发明人： Heinz Stadtmueller , Guido Boehmelt , Harald Engelhardt , Ulrich Hirt , Otmar Schaaf , Irene Waizenegger
IPC分类号： A61K31/55 , C07D413/14 , A61K31/5377 , C07D473/16 , A61K31/52 , C07D519/00 , A61P35/00
CPC分类号： C07D519/00
摘要： The present invention encompasses compounds of general formula (1) wherein R1, R2 and R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition having the above-mentioned properties.
摘要翻译：本发明包括通式（1）的化合物，其中R 1，R 2和R 3如权利要求1中所定义，其适用于治疗以细胞增殖过度或异常为特征的疾病，以及它们用于制备具有上述属性。

5. 发明申请

US20140205592A1 Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors 审中-公开
公开(公告)号：US20140205592A1
公开(公告)日：2014-07-24
申请号：US14221370
申请日：2014-03-21
申请人： Guenther ADOLF , Pilar GARIN-CHESA , Ulrich HIRT
发明人： Guenther ADOLF , Pilar GARIN-CHESA , Ulrich HIRT
IPC分类号： G01N33/574 , C12Q1/68
CPC分类号： G01N33/57492 , C12Q1/6886 , G01N33/57484 , G01N33/57496 , G01N2333/705 , G01N2333/91205 , G01N2800/52
摘要： The present invention relates to a method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. Said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is preferably conducted by way of an immunohistochemistry (IHC) method. Said IHC method preferably employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. The present invention also relates to a method of treating a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2, comprising administering to the patient a therapeutically effective amount of a PTK2 inhibitor. In a further aspect, the present invention relates to a PTK2 inhibitor for use in the treatment of a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2. The present invention also provides a method of screening for a therapeutically effective PTK2 inhibitor comprising the steps of (a) providing cancer cells or a cancer cell line which are characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being even more preferred); (b) contacting the cancer cell or the cancer cell line of (a) with a PTK2 inhibitor; and (c) evaluating whether the PTK2 inhibitor negatively affects the cancer cell/cancer cell lines. In a further aspect, the present invention relates to a method for stratifying cancer patients that are susceptible to treatment with a PTK2 inhibitor, comprising determining the E-cadherin IRS score in a cancer sample of said patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 (i.e. 2, 1, or 0) indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The present invention also relates to a pharmaceutical package comprising a PTK2 inhibitor, and (a) instructions and/or an imprint indicating that said PTK2 inhibitor is to be used for the treatment of patients which suffer from a cancer which is characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being more preferred); and/or (b) instructions and/or an imprint indicating that said patient is to be stratified by a method of the present invention; and/or (c) means to carry out a method as defined herein.

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