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1. 发明申请

WO2011015348A2 RESPONSIVENESS TO ANGIOGENESIS INHIBITORS 审中-公开
标题翻译：对血管生成抑制剂的反应
公开(公告)号：WO2011015348A2
公开(公告)日：2011-02-10
申请号：PCT/EP2010/004761
申请日：2010-08-03
申请人： F. HOFFMANN-LA ROCHE AG , VIB VZW , LIFE SCIENCE RESEARCH PARTNERS VZW , FOERNZLER, Dorothee , DELMAR, Paul , SCHERER, Stefan , LAMBRECHTS, Diether , CARMELIET, Peter
发明人： FOERNZLER, Dorothee , DELMAR, Paul , SCHERER, Stefan , LAMBRECHTS, Diether , CARMELIET, Peter
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/156
摘要： The present invention relates to methods for improving the overall survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the vascular endothelial growth factor receptor 1 (VEGFR-1) gene. The present invention further provides methods for improving the progression-free survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the VEGFR-1 gene. The present invention also provides for methods for assessing the responsiveness of a patient to an angiogenesis inhibitor by determining the presence of one or more variant alleles of the VEGFR-1 gene.
摘要翻译：本发明涉及通过用血管生成抑制剂如贝伐单抗治疗，通过确定患者的存在来改善患有恶性疾病或涉及生理和病理血管生成的疾病的患者的总体存活的方法的血管内皮生长因子受体1（VEGFR-1）基因的一个或多个变异等位基因。本发明进一步提供了通过确定一种或多种变体等位基因的存在，通过用血管生成抑制剂如贝伐单抗治疗来改善患有恶性疾病或涉及生理和病理性血管生成的疾病的患者的无进展存活的方法的VEGFR-1基因。本发明还提供了通过确定VEGFR-1基因的一种或多种变体等位基因的存在来评估患者对血管生成抑制剂的反应性的方法。

2. 发明申请

WO2013076029A1 RESPONSIVENESS TO ANGIOGENESIS INHIBITORS 审中-公开
标题翻译：对血液生成抑制剂的反应
公开(公告)号：WO2013076029A1
公开(公告)日：2013-05-30
申请号：PCT/EP2012/072953
申请日：2012-11-19
申请人： F. HOFFMANN-LA ROCHE AG , VIB VZW , LIFE SCIENCES RESEARCH PARTNERS VZW , CARMELIET, Peter , DE HAAS, Sanne Lysbet , LAMBRECHTS, Diether , SCHERER, Stefan
发明人： CARMELIET, Peter , DE HAAS, Sanne Lysbet , LAMBRECHTS, Diether , SCHERER, Stefan
IPC分类号： C12Q1/68
CPC分类号： C07K16/22 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158
摘要： The invention is concerned with a method of determining whether a patient is more suitably treated by a therapy with an angiogenesis inhibitor, such as bevacizumab, by determing the genotype of VEGFR-1 gene. The invention further relates to a pharmaceutical composition comprising an angiogenesis inhibitor, such as bevacizumab, for the treatment of a patient suffering from cancer based on the genotype of VEGFR-1 gene. The invention further relates to a method for improving the treatment effect of chemotherapy of a patient suffering from cancer by adding an angiogenesis inhibitor, such as bevacizumab, based on the genotype of VEGFR-1 gene.
摘要翻译：本发明涉及通过确定VEGFR-1基因的基因型来确定患者是否通过用血管发生抑制剂如贝伐珠单抗的治疗更适当地治疗的方法。本发明还涉及包含血管生成抑制剂如贝伐珠单抗的基于VEGFR-1基因的基因型治疗患有癌症的患者的药物组合物。本发明还涉及基于VEGFR-1基因的基因型，通过添加血管发生抑制剂如贝伐珠单抗来改善患有癌症的患者的化疗的治疗效果的方法。

3. 发明申请

WO2013030167A1 RESPONSIVENESS TO ANGIOGENESIS INHIBITORS 审中-公开
标题翻译：对血液生成抑制剂的反应
公开(公告)号：WO2013030167A1
公开(公告)日：2013-03-07
申请号：PCT/EP2012/066630
申请日：2012-08-28
申请人： F. HOFFMANN-LA ROCHE AG , VIB vzw , Life Sciences Research Partners vzw , DE HAAS, Sanne Lysbet , DELMAR, Paul , LAMBRECHTS, Diether , SCHERER, Stefan
发明人： DE HAAS, Sanne Lysbet , DELMAR, Paul , LAMBRECHTS, Diether , SCHERER, Stefan
IPC分类号： C12Q1/68
CPC分类号： C07K16/22 , A61K39/3955 , A61K2039/505 , C12Q1/6827 , C12Q1/6883 , C12Q2600/106 , C12Q2600/156
摘要： The invention is concerned with a method of determining whether a patient is more suitably treated by a therapy with an angiogenesis inhibitor, such as bevacizumab, by determing the genotype of VEGF promoter gene and/or VEGFR2 gene. The invention further relates to a pharmaceutical composition comprising an angiogenesis inhibitor, such as bevacizumab, for the treatment of a patient suffering from cancer based on the genotype of VEGF promoter gene and/or VEGFR2 gene. The invention further relates to a method for improving the treatment effect of chemotherapy of a patient suffering from cancer by adding an angiogenesis inhibitor, such as bevacizumab, based on the genotype of VEGF promoter gene and/or VEGFR2 gene.
摘要翻译：本发明涉及通过确定VEGF启动子基因和/或VEGFR2基因的基因型来确定患者是否通过用血管发生抑制剂如贝伐珠单抗的治疗更适当地治疗的方法。本发明进一步涉及包含血管生成抑制剂如贝伐珠单抗的基于VEGF启动子基因和/或VEGFR2基因的基因型治疗患有癌症的患者的药物组合物。本发明还涉及基于VEGF启动子基因和/或VEGFR2基因的基因型，通过添加血管生成抑制剂（例如贝伐珠单抗）来改善患有癌症的患者的化疗的治疗效果的方法。

4. 发明申请

WO2013030168A1 METHOD FOR PREDICTING RISK OF HYPERTENSION ASSOCIATED WITH ANTI-ANGIOGENESIS THERAPY 审中-公开
标题翻译：预防与抗血栓形成治疗相关的高血压风险的方法
公开(公告)号：WO2013030168A1
公开(公告)日：2013-03-07
申请号：PCT/EP2012/066632
申请日：2012-08-28
申请人： F. HOFFMANN-LA ROCHE AG , VIB VZW , LIFE SCIENCES RESEARCH PARTNERS VZW , DE HAAS, Sanne, Lysbet , DELMAR, Paul , LAMBRECHTS, Diether , SCHERER, Stefan
发明人： DE HAAS, Sanne, Lysbet , DELMAR, Paul , LAMBRECHTS, Diether , SCHERER, Stefan
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , A61K39/3955 , A61K45/06 , C12Q2600/106 , C12Q2600/156
摘要： The invention is concerned with a method of predicting a patient's susceptibility to developing hypertension associated with an anti-angiogenesis treatment, such as bevacizumab, by determing the genotype of KDR gene and/or EGF gene. The invention further relates to a pharmaceutical composition comprising an angiogenesis inhibitor, such as bevacizumab, for the treatment of a patient suffering from cancer based on the genotype of KDR gene and/or EGF. The invention further relates to a method for reducing the risk of hypertension associated with an anti-angiogenesis therapy, such as bevacizumab, in a patient suffering from cancer by determining the genotype of KDR gene and/or EGF gene.
摘要翻译：本发明涉及通过确定KDR基因和/或EGF基因的基因型来预测患者与抗血管生成治疗相关的高血压易感性（例如贝伐珠单抗）的方法。本发明还涉及包含血管生成抑制剂如贝伐珠单抗的基于KDR基因和/或EGF的基因型治疗患有癌症的患者的药物组合物。本发明还涉及通过测定KDR基因和/或EGF基因的基因型，降低与患有癌症的患者中的抗血管生成治疗如贝伐珠单抗相关的高血压风险的方法。

5. 发明申请

WO2012020123A3 NEUROPILIN AS A BIOMARKER FOR BEVACIZUMAB COMBINATION THERAPIES 审中-公开
公开(公告)号：WO2012020123A3
公开(公告)日：2012-02-16
申请号：PCT/EP2011/063932
申请日：2011-08-12
申请人： F. HOFFMANN-LA ROCHE AG , DELMAR, Paul , FOERNZLER, Dorothee , SCHERER, Stefan
发明人： DELMAR, Paul , FOERNZLER, Dorothee , SCHERER, Stefan
IPC分类号： A61K45/06 , A61K39/395 , A61K31/505 , A61K31/7068 , A61K33/24 , G01N33/68 , A61P35/00
摘要： The present invention provides methods for improving treatment effect in a patient suffering from gastric cancer, in particular, adenocarcinoma of the stomach or gastro-esophageal junction ("GEJ"), by treatment with bevacizumab (Avastin®) in combination with a chemotherapy regimen by determining the expression level of neuropilin relative to a control level determined in patients suffering from gastric cancer, in particular, adenocarcinoma of the stomach or gastro-esophageal junction ("GEJ"). The improved treatment effect may be improved overall survival or improved progression free survival. The present invention further provides for methods for assessing the sensitivity or responsiveness of a patient to bevacizumab (Avastin®) in combination with a chemotherapy regimen, by determining the expression level of neuropilin relative to a control level determined in patients suffering from gastric cancer, in particular, adenocarcinoma of the stomach or gastro-esophageal junction ("GEJ").

6. 发明申请

WO2012010546A1 BLOOD PLASMA BIOMARKERS FOR BEVACIZUMAB COMBINATION THERAPIES FOR TREATMENT OF PANCREATIC CANCER 审中-公开
标题翻译：用于治疗胰腺癌的BEVACIZUMAB组合治疗的血浆等离子体生物标志物
公开(公告)号：WO2012010546A1
公开(公告)日：2012-01-26
申请号：PCT/EP2011/062226
申请日：2011-07-18
申请人： F. HOFFMANN-LA ROCHE AG , DELMAR, Paul , FOERNZLER, Dorothee , KRAUSE, Friedemann , SCHERER, Stefan
发明人： DELMAR, Paul , FOERNZLER, Dorothee , KRAUSE, Friedemann , SCHERER, Stefan
IPC分类号： G01N33/574
CPC分类号： G01N33/57438 , A61K31/517 , A61K31/7068 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61N5/10 , G01N33/57434 , G01N33/6893 , G01N2333/475 , G01N2800/52
摘要： The present invention provides methods for improving the treatment effect of a chemotherapy regimen of a patient suffering from pancreatic cancer, in particular metastatic pancreatic cancer by adding bevacizumab (Avastin®) to a chemotherapy regimen by determining the expression level, in particular the blood plasma expression level, of one or more of VEGFA, VEGFR2 and PLGF relative to control levels of patients diagnosed with pancreatic cancer, in particular metastatic pancreatic cancer. In particular, the present invention provides methods of improving the treatment effect, wherein the treatment effect is the overall survival and/or progression-free survival of the patient. The present invention further provides for methods for assessing the sensitivity or responsiveness of a patient to bevacizumab (Avastin®) in combination with a chemotherapy regimen, by determining the expression level, in particular the blood plasma expression level, of one or more of VEGFA, VEGFR2 and PLGF relative to control levels in patients diagnosed with pancreatic cancer, in particular metastatic pancreatic cancer.
摘要翻译：本发明提供了通过将化疗方案加入贝伐珠单抗（Avastin？）来改善患有胰腺癌，特别是转移性胰腺癌的患者化疗方案的治疗效果的方法，方法是通过确定表达水平，特别是血浆表达水平，相对于诊断为胰腺癌，特别是转移性胰腺癌的患者的对照水平，VEGFA，VEGFR2和PLGF中的一种或多种。特别地，本发明提供了改善治疗效果的方法，其中治疗效果是患者的总体存活和/或无进展生存期。本发明进一步提供了通过确定VEGFA的一种或多种的表达水平，特别是血浆表达水平来评估患者与贝伐珠单抗（Avastin？）联合化疗方案的敏感性或反应性的方法， VEGFR2和PLGF相对于诊断为胰腺癌，特别是转移性胰腺癌的患者的对照水平。

7. 发明申请

WO2012010552A1 BLOOD PLASMA BIOMARKERS FOR BEVACIZUMAB COMBINATION THERAPIES FOR TREATMENT OF BREAST CANCER 审中-公开
标题翻译：用于BEVACIZUMAB联合治疗乳腺癌的血浆等离子体生物标志物
公开(公告)号：WO2012010552A1
公开(公告)日：2012-01-26
申请号：PCT/EP2011/062232
申请日：2011-07-18
申请人： F. HOFFMANN-LA ROCHE AG , DE HAAS, Sanne Lysbet , DELMAR, Paul , FOERNZLER, Dorothee , KLAUSE, Ursula , SCHERER, Stefan
发明人： DE HAAS, Sanne Lysbet , DELMAR, Paul , FOERNZLER, Dorothee , KLAUSE, Ursula , SCHERER, Stefan
IPC分类号： G01N33/574
CPC分类号： G01N33/6893 , A61K31/337 , A61K39/3955 , G01N33/57415 , G01N2333/475 , G01N2800/52
摘要： The present invention provides methods for improving the treatment effect of a chemotherapy regimen of a patient suffering from breast cancer, in particular locally advanced, recurrent or metastatic HER-2 negative breast cancer, by adding bevacizumab (Avastin®) to a chemotherapy regimen by determining the expression level, in particular the blood plasma expression level, of one or more of VEGFA, VEGFR2 and PLGF relative to control levels of patients diagnosed with breast cancer, in particular locally advanced, recurrent or metastatic HER-2 negative breast cancer. In particular, the present invention provides methods of improving the treatment effect, wherein the treatment effect is the progression-free survival of the patient. The present invention further provides for methods for assessing the sensitivity or responsiveness of a patient to bevacizumab (Avastin®) in combination with a chemotherapy regimen, by determining the expression level, in particular the blood plasma expression level, of one or more of VEGFA, VEGFR2 and PLGF relative to control levels in patients diagnosed with breast cancer, in particular locally advanced, recurrent or metastatic HER-2 negative breast cancer.
摘要翻译：本发明提供了通过将化疗方案加入贝伐珠单抗（Avastin？）来改善患有乳腺癌，特别是局部晚期，复发或转移性HER-2阴性乳腺癌的患者化疗方案的治疗效果的方法，相对于诊断为乳腺癌，特别是局部晚期，复发或转移性HER-2阴性乳腺癌的患者的对照水平，VEGFA，VEGFR2和PLGF中的一种或多种的表达水平，特别是血浆表达水平。特别地，本发明提供了改善治疗效果的方法，其中治疗效果是患者的无进展生存期。本发明进一步提供了通过确定VEGFA的一种或多种的表达水平，特别是血浆表达水平来评估患者与贝伐珠单抗（Avastin？）联合化疗方案的敏感性或反应性的方法， VEGFR2和PLGF相对于诊断为乳腺癌，特别是局部晚期，复发或转移性HER-2阴性乳腺癌的患者的对照水平。

8. 发明申请

WO2011089101A1 TUMOR TISSUE BASED BIOMARKERS FOR BEVACIZUMAB COMBINATION THERAPIES 审中-公开
标题翻译：基于肿瘤组织的生物标记物用于组合联合治疗
公开(公告)号：WO2011089101A1
公开(公告)日：2011-07-28
申请号：PCT/EP2011/050564
申请日：2011-01-18
申请人： F. HOFFMANN-LA ROCHE AG , DELMAR, Paul , FOERNZLER, Dorothee , SCHERER, Stefan
发明人： DELMAR, Paul , FOERNZLER, Dorothee , SCHERER, Stefan
IPC分类号： A61K39/395 , G01N33/574
CPC分类号： G01N33/56966 , G01N33/57419 , G01N33/57446 , G01N2333/475 , G01N2333/71 , G01N2800/52
摘要： The present invention provides methods for improving the progression- free survival of a patient suffering from gastrointestinal cancer, in particular, metastatic colorectal cancer (mCRC), by treatment with bevacizumab (Avastin ® ) in combination with a chemotherapy regimen by determining the expression level of one or more of VEGFA, HER2 and neuropilin relative to control levels in patients diagnosed with gastrointestinal cancer, in particular, metastatic colorectal cancer (mCRC). The present invention further provides for methods for assessing the sensitivity or responsiveness of a patient to bevacizumab (Avastin ® ) in combination with a chemotherapy regimen, by determining the expression level of one or more of VEGFA, HER2 and neuropilin relative to control levels in patients diagnosed with gastrointestinal cancer, in particular, metastatic colorectal cancer (mCRC).
摘要翻译：本发明提供了通过用化疗方案与贝伐珠单抗联用来改善患有胃肠癌，特别是转移性结肠直肠癌（mCRC）的患者的无进展生存的方法，通过确定化疗方案的表达水平一个或多个VEGFA，HER2和神经纤维蛋白相对于诊断为胃肠癌的患者，特别是转移性结肠直肠癌（mCRC）中的对照水平。本发明进一步提供了通过相对于患者对照水平测定VEGFA，HER2和神经纤维中一种或多种的表达水平来评估患者与贝伐珠单抗联合化疗方案的敏感性或反应性的方法诊断为胃肠癌，特别是转移性结肠直肠癌（mCRC）。

9. 发明申请

WO2011033006A1 METHODS AND COMPOSITIONS FOR DIAGNOSTICS USE IN CANCER PATIENTS 审中-公开
标题翻译：用于诊断癌症患者的方法和组合物
公开(公告)号：WO2011033006A1
公开(公告)日：2011-03-24
申请号：PCT/EP2010/063584
申请日：2010-09-16
申请人： F. HOFFMANN-LA ROCHE AG , DE HAAS, Sanne Lysbet , DELMAR, Paul , SCHERER, Stefan
发明人： DE HAAS, Sanne Lysbet , DELMAR, Paul , SCHERER, Stefan
IPC分类号： C12Q1/68
CPC分类号： G01N33/6893 , A61K31/7068 , A61K33/24 , A61K39/39558 , A61K2039/505 , A61K2039/545 , C07K16/22 , C07K2317/24 , C07K2317/76
摘要： Disclosed herein are methods and compositions useful for identifying therapies likely to confer optimal clinical benefit for patients with cancer.
摘要翻译：本文公开了可用于鉴定可能为癌症患者赋予最佳临床益处的疗法的方法和组合物。

10. 发明申请

WO2013083499A1 BLOOD PLASMA BIOMARKERS FOR BEVACIZUMAB COMBINATION THERAPIES FOR TREATMENT OF BREAST CANCER 审中-公开
标题翻译：用于BEVACIZUMAB联合治疗乳腺癌的血浆等离子体生物标志物
公开(公告)号：WO2013083499A1
公开(公告)日：2013-06-13
申请号：PCT/EP2012/074184
申请日：2012-12-03
申请人： F. HOFFMANN-LA ROCHE AG , GENENTECH, INC. , ANDRES, Herbert , DE HAAS, Sanne Lysbet , ELLIOTT, Rebecca , KARL, Johann , MENG, Yu-Ju Gloria , PLOWMAN, Gregory D. , SCHERER, Stefan , WILD, Norbert
发明人： ANDRES, Herbert , DE HAAS, Sanne Lysbet , ELLIOTT, Rebecca , KARL, Johann , MENG, Yu-Ju Gloria , PLOWMAN, Gregory D. , SCHERER, Stefan , WILD, Norbert
IPC分类号： G01N33/574
CPC分类号： A61K39/39558 , A61K31/337 , C07K16/22 , G01N33/57415 , G01N2333/475
摘要： The present invention provides methods for improving the treatment effect of a chemotherapy regimen of a patient suffering from HER2 positive breast cancer, in particular locally recurrent or metastatic HER2 positive breast cancer, by adding bevacizumab (Avastin®) to a chemotherapy regimen by determining the expression level, in particular the blood plasma expression level, of VEGFA and/or VEGFR2 relative to control levels of patients diagnosed with HER2 positive breast cancer, in particular locally recurrent or metastatic HER2 positive breast cancer. The present invention also provides for methods for assessing the sensitivity or responsiveness of a patient to bevacizumab (Avastin®) in combination with a chemotherapy regimen, by determining the expression level, in particular the blood plasma expression level, of VEGFA and/or VEGFR2 relative to control levels in patients diagnosed with HER2 positive breast cancer, in particular locally recurrent or metastatic HER2 positive breast cancer.
摘要翻译：本发明提供了通过将化疗方案添加到化疗方案中来改善患有HER2阳性乳腺癌，特别是局部复发或转移性HER2阳性乳腺癌的患者的化疗方案的治疗效果的方法，相对于诊断为HER2阳性乳腺癌，特别是局部复发或转移性HER2阳性乳腺癌的患者的对照水平，VEGFA和/或VEGFR2的水平，特别是血浆表达水平。本发明还提供了通过确定VEGFA和/或VEGFR2相对的表达水平，特别是血浆表达水平来评估患者与贝伐珠单抗（Avastin？）联合化疗方案的敏感性或反应性的方法以控制诊断为HER2阳性乳腺癌，特别是局部复发或转移性HER2阳性乳腺癌患者的水平。

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