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1. 发明授权

US11242564B2 Methods for predicting the survival time and treatment responsiveness of a patient suffering from a solid cancer with a signature of at least 7 genes 有权
公开(公告)号：US11242564B2
公开(公告)日：2022-02-08
申请号：US14413856
申请日：2013-07-12
申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) , UNIVERSITE PARIS DESCARTES , ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP)
发明人： Jerome Galon , Franck Pages , Bernard Mlecnik , Gabriela Bindea
IPC分类号： C12Q1/6886
摘要： The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.

2. 发明申请

US20150218650A1 METHODS AND KITS FOR SCREENING PATIENTS WITH A CANCER 审中-公开
标题翻译：用于筛选患有癌症的患者的方法和工具
公开(公告)号：US20150218650A1
公开(公告)日：2015-08-06
申请号：US14420053
申请日：2013-08-05
申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) , UNIVERSITE PARIS DESCARTES , ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
发明人： Jerome Galon , Franck Pages , Bernhard Mlecnik , Gabriela Bindea
IPC分类号： C12Q1/68
摘要： A method for screening patients with a cancer comprising i) determining in a tumor sample obtained from a patient an expression level ELA1-ELAn of one or several genes GA1-GAn representative of human adaptive immune response and an expression level ELI1-ELIn of one or several genes Gl1-GIn representative of human immunosuppressive response, ii) comparing the expression levels ELA1-ELAn and ELI1-ELIn determined at step i) with predetermined reference values ELRA1-ELRAn and ELRI1-ELRIn selected such as said predetermined reference values separate a panel of patients with a cancer into two groupings according to the expression level of said genes and to survival of patients according to Kaplan Meier curves analyses and associated logrank p values iii) concluding whether the patient has a good (level higher than the predetermined reference value) or a bad (level lower than the predetermined reference value) adaptive immune response and a good or a bad immunosuppressive response, optionally further comprising a step of concluding that a patient would or would not advantageously receive an antitumoral treatment, a kit comprising components for implementing step i) and a chemotherapeutic agent, an immunotherapeutic agent or a radiotherapeutic agent for use in the treatment of a cancer patient who is considered as responder to antitumoral treatment according to the method.
摘要翻译：一种用于筛选患有癌症的患者的方法，包括i）在从患者获得的肿瘤样品中确定代表人适应性免疫应答的一种或几种基因GA1-GAn的表达水平ELA1-ELAn和表达水平ELI1-ELIn 代表人免疫抑制反应的几个基因Gl1-GIn，ii）比较步骤i）确定的表达水平ELA1-ELAn和ELI1-ELIn与所选择的预定参考值ELRA1-ELRAn和ELRI1-ELRIn，例如所述预定参考值，将面板根据Kaplan Meier曲线分析和相关logrank p值，根据所述基因的表达水平和患者的存活率，将癌症患者分为两组; iii）推断患者是否具有良好的水平（高于预定参考值）或不良（低于预定参考值）适应性免疫应答和良好或不良免疫抑制反应进一步包括以下步骤：结论患者将或不会有利地接受抗肿瘤治疗，试剂盒包含用于实施步骤i）的组分和用于治疗癌症患者的化学治疗剂，免疫治疗剂或放射治疗剂根据该方法被认为是抗肿瘤治疗的反应者。

3. 发明申请

US20150153349A1 Method for Quantifying Immune Cells in Tumoral Tissues and its Applications 审中-公开
标题翻译：用于量化肿瘤组织中免疫细胞的方法及其应用
公开(公告)号：US20150153349A1
公开(公告)日：2015-06-04
申请号：US14407698
申请日：2013-06-14
申请人： INSERM (Institut National de la Sante et de la Recherche Medicale) , Universite Paris Descartes , Assistance Publique-Hopitaux de Paris
发明人： Jerome Galon , Franck Pages , Bernhard Mlecnik
IPC分类号： G01N33/574
CPC分类号： G01N33/57492 , G01N33/5047 , G01N33/574 , G01N2800/52
摘要： A method for assessment of a number or density of immune cells in tumoral tissues comprising the steps consisting in: a. providing one or more immunostained slices of tissue section obtained by an automated slide-staining system by using antibodies binding specifically to antigens (markers) expressed by immune cells. b. proceeding to digitalisation of the slides of step a. by high resolution scan capture, whereby a high definition (4.6 μm/pixel or better) digital picture of the slide to be analysed is obtained, c. detecting the slice of tissue section on the digital picture d. analyzing the slice of tissue section for defining (i) the tumour (CT) and (ii) the invasive margin of the tumour (IM), e. providing a size reference grid with uniformly distributed units having a same surface, said grid being adapted to the size of the tumour to be analyzed, e1. checking the quality of immunostaining, f. detecting and quantifying stained cells of each unit whereby the number or the density of immune cells stained of each unit is assessed.
摘要翻译：一种用于评估肿瘤组织中免疫细胞数量或密度的方法，包括以下步骤：a。通过使用由免疫细胞表达的抗原（标记）特异性结合的抗体，提供通过自动化载玻片染色系统获得的组织切片的一个或多个免疫染色切片。 b。进行步骤a的幻灯片的数字化。通过高分辨率扫描捕获，从而获得要分析的幻灯片的高清晰度（4.6μm/像素或更好）的数字图像，c。检测数字图像上的组织切片切片d。分析组织切片以确定（i）肿瘤（CT）和（ii）肿瘤（IM）的侵入性边缘，提供具有具有相同表面的均匀分布单元的尺寸参考网格，所述网格适于要分析的肿瘤的大小，e1。检查免疫染色的质量，f。检测和定量每个单位的染色细胞，从而评估每个单位染色的免疫细胞的数量或密度。

4. 发明授权

US10317408B2 Method for quantifying immune cells in tumoral tissues and its applications 有权
公开(公告)号：US10317408B2
公开(公告)日：2019-06-11
申请号：US14407698
申请日：2013-06-14
申请人： INSERM (Institut National de la Sante et de la Recherche Medicale) , Universite Paris Descartes , Assistance Publique-Hopitaux de Paris
发明人： Jerome Galon , Franck Pages , Bernhard Mlecnik
IPC分类号： G01N33/574 , G01N33/50
摘要： A method for assessment of a number or density of immune cells in tumoral tissues comprising the steps consisting in: a. providing one or more immunostained slices of tissue section obtained by an automated slide-staining system by using antibodies binding specifically to antigens (markers) expressed by immune cells. b. proceeding to digitalization of the slides of step a. by high resolution scan capture, whereby a high definition (4.6 μm/pixel or better) digital picture of the slide to be analyzed is obtained, c. detecting the slice of tissue section on the digital picture d. analyzing the slice of tissue section for defining (i) the tumor (CT) and (ii) the invasive margin of the tumor (IM), e. providing a size reference grid with uniformly distributed units having a same surface, said grid being adapted to the size of the tumor to be analyzed, e1. checking the quality of immunostaining, f. detecting and quantifying stained cells of each unit whereby the number or the density of immune cells stained of each unit is assessed.

5. 发明授权

US09945861B2 Methods for predicting the survival time of a patient suffering from a solid cancer based on density of B cells 有权
公开(公告)号：US09945861B2
公开(公告)日：2018-04-17
申请号：US14372757
申请日：2013-01-21
申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) , UNIVERSITE PARIS DESCARTES , ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP) , UNIVERSITE PIERRE ET MARIE CURIE—PARIS VI
发明人： Jerome Galon , Franck Pages , Bernhard Mlecnik , Gabriela Bindea , Herve Fridman
IPC分类号： G01N33/574 , C12Q1/6886
CPC分类号： G01N33/574 , G01N2333/7051 , G01N2333/70517 , G01N2333/70589 , G01N2333/70596 , G01N2800/52
摘要： The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising the steps consisting of i) determining the density of B cells at the invasive margin of the tumor (im) in a tumor tissue sample obtained from said patient, ii) comparing said density with a predetermined reference value and iii) providing a good prognosis when the density of B cells at the invasive margin of the tumor is higher than the predetermined reference value and a poor prognosis when the density of B cells at the invasive margin of the tumor is lower than the predetermined reference value.

6. 发明申请

US20200299784A1 METHODS AND KITS FOR SCREENING PATIENTS WITH CANCER 审中-公开
公开(公告)号：US20200299784A1
公开(公告)日：2020-09-24
申请号：US16896736
申请日：2020-06-09
申请人： INSERM (Institut National de la Sante et de la Recherche Medicale) , UNIVERSITE PARIS DESCARTES , ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
发明人： Jerome Galon , Franck Pages , Bernhard Milecnik , Gabriela Bindea
IPC分类号： C12Q1/6886
摘要： A method for screening patients with a cancer comprisingi) determining in a tumor sample obtained from a patient an expression level ELA1-ELAn of one or several genes GA1-GAn representative of human adaptive immune response and an expression level ELI1-ELIn of one or several genes GI1-GIn representative of human immunosuppressive response,ii) comparing the expression levels ELA1-ELAn and ELI1-ELIn determined at step i) with predetermined reference values ELRA1-ELRAn and ELRI1-ELRIn selected such as said predetermined reference values separate a panel of patients with a cancer into two groupings according to the expression level of said genes and to survival of patients according to Kaplan Meier curves analyses and associated logrank p valuesiii) concluding whether the patient has a good (level higher than the predetermined reference value) or a bad (level lower than the predetermined reference value) adaptive immune response and a good or a bad immunosuppressive response, optionally further comprising a step of concluding that a patient would or would not advantageously receive an antitumoral treatment, a kit comprising components for implementing step i) and a chemotherapeutic agent, an immunotherapeutic agent or a radiotherapeutic agent for use in the treatment of a cancer patient who is considered as responder to antitumoral treatment according to the method.

7. 发明申请

US20150203919A1 METHODS FOR PREDICTING THE SURVIVAL TIME AND TREATMENT RESPONSIVENESS OF A PATIENT SUFFERING FROM A SOLID CANCER WITH A SIGNATURE OF AT LEAST 7 GENES 审中-公开
标题翻译：用于预测具有至少7个基因的签名的实体癌症患者的存活时间和治疗反应的方法
公开(公告)号：US20150203919A1
公开(公告)日：2015-07-23
申请号：US14413856
申请日：2013-07-12
申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) , UNIVERSITE PARIS DESCARTES , ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP)
发明人： Jerome Galon , Franck Pages , Bernard Mlecnik , Gabriela Bindea
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2537/143 , C12Q2600/112 , C12Q2600/118 , C12Q2600/158 , C12Q2600/16
摘要： The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.
摘要翻译：本发明涉及一种用于预测患有固体癌症的患者的存活时间的方法，包括：i）在从患者获得的肿瘤样品中确定选自CCR2，CD3D中的至少7种基因的基因表达水平，CD3E，CD3G，CD8A，CXCL10，CXCL11，GZMA，GZMB，GZMK，GZMM，IL15，IRF1，PRF1，STAT1，CD69，ICOS，CXCR3，STAT4，CCL2和TBX21，ii）比较在步骤i确定的每个表达水平）和iii）当在步骤i）确定的所有表达水平高于其预定参考值时提供良好预后，或当在步骤i）确定的所有表达水平低于其预定参考值时提供不良预后值或当至少一个表达水平确定值高于其预定值时提供中间预后。该方法还特别适用于预测患者对治疗的反应性。

8. 发明申请

US20140363472A1 METHODS FOR PREDICTING THE SURVIVAL TIME OF A PATIENT SUFFERING FROM A SOLID CANCER BASED ON DENSITY OF B CELLS 有权
标题翻译：用于预测基于B细胞密度的实体癌患者生存时间的方法
公开(公告)号：US20140363472A1
公开(公告)日：2014-12-11
申请号：US14372757
申请日：2013-01-21
申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) , UNIVERSITE PARIS DESCARTES , ASSISTANCE PUBLIQUE-HOPITAUX PARIS (APHP)
发明人： Jerome Galon , Franck Pages , Bernhard Mlecnik , Gabriela Bindea , Herve Fridman
IPC分类号： G01N33/574
CPC分类号： G01N33/574 , G01N2333/7051 , G01N2333/70517 , G01N2333/70589 , G01N2333/70596 , G01N2800/52
摘要： The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising the steps consisting of i) determining the density of B cells at the invasive margin of the tumor (im) in a tumor tissue sample obtained from said patient, ii) comparing said density with a predetermined reference value and iii) providing a good prognosis when the density of B cells at the invasive margin of the tumor is higher than the predetermined reference value and a poor prognosis when the density of B cells at the invasive margin of the tumor is lower than the predetermined reference value.
摘要翻译：本发明涉及一种用于预测患有实体癌症的患者的存活时间的方法，包括以下步骤：i）确定肿瘤组织样品中侵袭性边缘的肿瘤组织样本中的B细胞的密度（im）所述患者，ii）将所述密度与预定参考值进行比较，以及iii）当肿瘤侵袭性边缘处的B细胞的密度高于预定参考值时，提供良好的预后，并且当B细胞的密度在肿瘤的侵入性边缘低于预定的参考值。

9. 发明授权

US11300569B2 In vitro method for the prognosis of progression of a cancer and of the outcome in a patient and means for performing said method 有权
公开(公告)号：US11300569B2
公开(公告)日：2022-04-12
申请号：US16220014
申请日：2018-12-14
申请人： Institut National de la Sante et de la Recherche Medicale (INSERM) , Universite Paris Descartes
发明人： Jerome Galon , Franck Pages , Wolf-Herman Fridman
IPC分类号： G01N33/574 , C12Q1/6886
摘要： The present invention relates to the prognosis of the outcome of a cancer in a patient, which prognosis is based on the quantification of one or several biological markers that are indicative of the presence of, or alternatively the level of, the adaptive immune response of said patient against said cancer.

10. 发明申请

US20190178892A1 IN VITRO METHOD FOR THE PROGNOSIS OF PROGRESSION OF A CANCER AND OF THE OUTCOME IN A PATIENT AND MEANS FOR PERFORMING SAID METHOD 审中-公开
公开(公告)号：US20190178892A1
公开(公告)日：2019-06-13
申请号：US16220014
申请日：2018-12-14
申请人： Institut National de la Sante et de la Recherche Medicale (INSERM) , Universite Paris Descartes
发明人： Jerome Galon , Franck Pages , Wolf-Herman Fridman
IPC分类号： G01N33/574 , C12Q1/6886
摘要： The present invention relates to the prognosis of the outcome of a cancer in a patient, which prognosis is based on the quantification of one or several biological markers that are indicative of the presence of, or alternatively the level of, the adaptive immune response of said patient against said cancer.

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