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1. 发明申请

WO2016015788A1 MUTATIONS IN THE EXTRACELLULAR DOMAIN III OF EPIDERMAL GROWTH FACTOR RECEPTOR GENE 审中-公开
标题翻译：人类生长因子受体基因细胞外III区的突变
公开(公告)号：WO2016015788A1
公开(公告)日：2016-02-04
申请号：PCT/EP2014/079477
申请日：2014-12-30
申请人： FUNDACIÓ INSTITUT MAR D'INVESTIGACIONS MÈDIQUES (IMIM) , BARDELLI, Alberto , ARENA, Sabrina
发明人： BARDELLI, Alberto , ARENA, Sabrina , MONTAGUT VILADOT, Clara , ALBANELL MESTRES, Joan , ROVIRA GUERIN, Ana , BELLOSILLO PARICIO, Beatriz , DALMASES MASSEGÚ, Alba
IPC分类号： C07K14/71 , G01N33/574
CPC分类号： C07K14/71 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , G01N33/57419 , G01N33/74 , G01N2333/485 , G01N2333/71 , G01N2800/52
摘要： The invention relates to new identified mutations in the epidermal growth factor receptor gene, leading to amino acidic changes which highly correlate with the resistance to a therapy regimen comprising cetuximab. The invention includes peptide sequences and primers to detect the mutations, as well as kits for predicting the response of a subject to a therapy regime comprising cetuximab. In particular, the invention is useful in the therapy regimen applicable to metastasic colorectal cancer.
摘要翻译：本发明涉及表皮生长因子受体基因中新鉴定的突变，导致与包含西妥昔单抗的治疗方案的抗性高度相关的氨基酸变化。本发明包括用于检测突变的肽序列和引物，以及用于预测受试者对包含西妥昔单抗治疗方案的反应的试剂盒。特别地，本发明在适用于转移性结肠直肠癌的治疗方案中是有用的。

2. 发明申请

WO2010063300A1 ISOGENIC HUMAN CELL LINES COMPRISING MUTATED CANCER ALLELES AND PROCESS USING THE CELL LINES 审中-公开
标题翻译：含有突变型癌细胞的标准人体细胞系和使用细胞系的过程
公开(公告)号：WO2010063300A1
公开(公告)日：2010-06-10
申请号：PCT/EP2008/010218
申请日：2008-12-03
申请人： UNIVERSITÀ DEGLI STUDI DI TORINO , BARDELLI, Alberto , DI NICOLANTONIO, Federica , ARENA, Sabrina
发明人： BARDELLI, Alberto , DI NICOLANTONIO, Federica , ARENA, Sabrina
IPC分类号： C12N5/06 , C12N5/16 , C12N15/90
CPC分类号： C12N5/0693 , C12N2503/00 , C12N2799/025 , C12N2800/30 , G01N33/5011
摘要： Isogenic human cell lines comprising at least one mutated cancer allele under the control of the cell line endogenous promoter, which corresponds to the wild-type cancer allele promoter are disclosed, as well as an in vitro process for determining sensitivity/resistance of a patient suffering from a tumor to a pharmacological agent comprising the following steps: a) identifying at least one mutated cancer allele in a tissue affected by a tumor of said patient; b) providing an isogenic human cell line representative of the tissue, wherein the cell line comprises at least the identified mutated cancer allele, which is under the control of the cell line endogenous promoter corresponding to the wild-type cancer allele promoter; c) putting in contact said cell line with the pharmacological agent; d) determining a variation of proliferation, apoptosis or cytotoxicity of the cell line in presence of the pharmacological agent; wherein the variation of proliferation, apoptosis or cytotoxicity is indicative of the sensitivity/resistance of the patient tumor to the pharmacological agent.
摘要翻译：公开了包含对应于野生型癌症等位基因启动子的细胞系内源性启动子控制下的至少一个突变的癌症等位基因的同基因人细胞系，以及用于确定患者的敏感性/耐药性的体外方法从肿瘤到药理学试剂，包括以下步骤：a）鉴定受所述患者的肿瘤影响的组织中的至少一个突变的癌症等位基因; b）提供代表所述组织的同基因人细胞系，其中所述细胞系包含至少所识别的突变的癌症等位基因，其处于对应于野生型癌症等位基因启动子的细胞系内源性启动子的控制下; c）将药物接触所述细胞系; d）确定在药理学试剂存在下细胞系的增殖，凋亡或细胞毒性的变化; 其中增殖，凋亡或细胞毒性的变化指示患者肿瘤对药理学试剂的敏感性/抗性。

3. 发明申请

WO2016172584A1 METHODS OF TREATING PATIENTS HAVING MUTATIONS IN THE EXTRACELLULAR DOMAIN OF EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) WITH A COMBINATION OF THREE FULLY HUMAN MONOCLONAL ANTI-EGFR ANTIBODIES 审中-公开
标题翻译：在具有三种完全人类单克隆抗EGFR抗体的组合的EPIDERMAL生长因子受体（EGFR）的细胞外区域中进行突变的患者的治疗方法
公开(公告)号：WO2016172584A1
公开(公告)日：2016-10-27
申请号：PCT/US2016/028987
申请日：2016-04-22
申请人： MERRIMACK PHARMACEUTICALS, INC. , ARENA, Sabrina
发明人： ARENA, Sabrina , BARDELLI, Alberto , KEARNS, Jeffrey, David , WOLF, Beni, B. , NERING, Rachel, C. , WANG, Hongfang
IPC分类号： C07K16/28 , C07K16/30 , A61K39/395 , A61P35/00 , G01N33/574
CPC分类号： C07K16/2863 , A61K2039/507 , A61K2039/55 , C07K16/30 , C07K16/3046 , C07K2317/21 , C07K2317/33 , C07K2317/51 , C07K2317/515 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156
摘要： Provided herein are methods of treating an epidermal growth factor receptor (EGFR) extracellular domain (ECD) mutant cancer in a human patient by administering to the patient an oligoclonal anti-epidermal growth factor receptor (anti-EGFR) antibody combination (e.g., MM-151, comprising a first monoclonal antibody (P1X), a second monoclonal antibody (P2X), and a third monoclonal antibody (P3X),wherein P1X, P2X and P3X are in a 2:2: 1 molar ratio). In one embodiment, the cancer comprises at least one mutation in the extracellular domain of EGFR selected from the group consisting of EGFR R451C, S464L, K467T, G465R, G465E, 1491M, and S492R.
摘要翻译：本文提供了通过向患者施用寡克隆抗表皮生长因子受体（抗EGFR）抗体组合（例如MM-1），治疗人类患者中表皮生长因子受体（EGFR）细胞外结构域（EGF）突变体癌症的方法， 151，包含第一单克隆抗体（P1X），第二单克隆抗体（P2X）和第三单克隆抗体（P3X），其中P1X，P2X和P3X的摩尔比为2:2:1）。在一个实施方案中，癌症包括选自EGFR R451C，S464L，K467T，G465R，G465E，1491M和S492R的EGFR细胞外结构域中的至少一个突变。

4. 发明申请

WO2004082458A3 TYROSINE KINOME 审中-公开
公开(公告)号：WO2004082458A3
公开(公告)日：2004-09-30
申请号：PCT/US2004/004452
申请日：2004-02-18
申请人： THE JOHNS HOPKINS UNIVERSITY , BARDELLI, Alberto , PARSONS, Will , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： BARDELLI, Alberto , PARSONS, Will , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
摘要： Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in -20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.

5. 发明申请

WO2017182783A2 INACTIVATION OF DNA REPAIR AS AN ANTICANCER THERAPY 审中-公开
标题翻译： DNA修复作为抗癌治疗的失活
公开(公告)号：WO2017182783A2
公开(公告)日：2017-10-26
申请号：PCT/GB2017/051062
申请日：2017-04-18
申请人： PHOREMOST LIMITED , BARDELLI, Alberto , GERMANO, Giovanni
发明人： BARDELLI, Alberto , GERMANO, Giovanni , TORRANCE, Chris
IPC分类号： A61K31/00 , C12N9/22 , C12Q1/00 , G01N33/68 , A61P35/00
摘要： This invention relates to the modulation of DNA repair and nucleic acid editing mechanisms for use in the treatment of cancer. This invention relates to the inactivation of DNA repair and mechanisms for use in the treatment of cancer. This invention also relates to screening for new anti-cancer agents.
摘要翻译：本发明涉及用于治疗癌症的DNA修复和核酸编辑机制的调节。本发明涉及DNA修复的失活和用于治疗癌症的机制。本发明还涉及筛选新的抗癌剂。

6. 发明申请

WO2006127607A2 PI3K PATHWAY MUTATIONS IN CANCER 审中-公开
标题翻译：癌症中PI3K路径突变
公开(公告)号：WO2006127607A2
公开(公告)日：2006-11-30
申请号：PCT/US2006/019748
申请日：2006-05-23
申请人： THE JOHNS HOPKINS UNIVERSITY , PARSONS, Donald, William , WANG, Tian-li. Ph.D. , SAMUELS, Yardena , BARDELLI, Alberto , LENGAUER, Christopher , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： PARSONS, Donald, William , WANG, Tian-li. Ph.D. , SAMUELS, Yardena , BARDELLI, Alberto , LENGAUER, Christopher , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/485 , C12Q2600/136 , C12Q2600/156 , G01N33/5044 , G01N33/57419
摘要： Given the important role of protein kinases in pathways affecting cellular growth and invasion, we have analyzed 340 serine/threonine kinases for genetic mutations in colorectal cancers. Mutations in eight genes were identified, including three members of the phosphatidylinositol-3- kinase (PI3K) pathway; the alterations in the latter genes each occurred in different tumors and did not overlap with mutations in PIK3CA or other non-serine-threonine kinase (STK) members of the PI3K pathway, suggesting that mutations in any of these genes had equivalent tumorigenic effects. These data demonstrate that the PI3K pathway is a major target for mutational activation in colorectal cancers and provide new opportunities for therapeutic intervention.
摘要翻译：鉴于蛋白激酶在影响细胞生长和侵袭的途径中的重要作用，我们已经分析了340个丝氨酸/苏氨酸激酶在结肠直肠癌中的遗传突变。鉴定出8个基因的突变，包括磷脂酰肌醇-3-激酶（PI3K）通路的3个成员; 后一种基因的改变各自发生在不同的肿瘤中，并且不与PIK3CA或PI3K途径的其他非丝氨酸 - 苏氨酸激酶（STK）成员的突变重叠，这表明任何这些基因中的突变具有相等的致瘤作用。这些数据表明，PI3K途径是结肠直肠癌突变激活的主要靶标，为治疗干预提供新的机会。

7. 发明申请

WO2011158061A1 MLK4 GENE, A NEW DIAGNOSTIC AND PROGNOSTIC MARKER IN CANCERS 审中-公开
标题翻译： MLK4基因，癌症中的新诊断和预后标记
公开(公告)号：WO2011158061A1
公开(公告)日：2011-12-22
申请号：PCT/IB2010/052684
申请日：2010-06-15
申请人： BARDELLI, Alberto , MARTINI, Miriam
发明人： BARDELLI, Alberto , MARTINI, Miriam
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C07K16/40 , C12N15/1137 , C12N2310/14 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , C12Y207/11 , G01N33/57415 , G01N33/57419 , G01N33/57423 , G01N33/57446 , G01N33/6893 , C12N2310/531
摘要： An in vitro diagnostic method for determining invasive potential of cancer comprising measuring MLK4 gene expression in a cancer cell sample, wherein MLK4 gene overexpression is indicative of an invasive cancer, preferably a colorectal, bladder, breast, gastric, melanoma, lung, ovary or GMB cancer.
摘要翻译：一种用于确定癌症侵袭潜力的体外诊断方法，其包括测量癌细胞样品中的MLK4基因表达，其中MLK4基因过表达指示入侵性癌症，优选结肠直肠癌，膀胱癌，乳腺癌，胃癌，黑素瘤，肺癌，卵巢癌或GMB 癌症。

8. 发明申请

WO2006107854A3 EPIDERMAL GROWTH FACTOR RECEPTOR GENE COPY NUMBER 审中-公开
公开(公告)号：WO2006107854A3
公开(公告)日：2006-10-12
申请号：PCT/US2006/012267
申请日：2006-03-30
申请人： AMGEN INC. , SIENA, Salvatore , MORONI, Mauro , BARDELLI, Alberto
发明人： SIENA, Salvatore , MORONI, Mauro , BARDELLI, Alberto
IPC分类号： C12Q1/68
摘要： Methods of predicting whether an anti-epidermal growth factor receptor ("EGFr")-specific binding agent treatment will be efficacious in treating cancer, and methods of treating patients with anti-EGFr-specific binding agents, are provided, wherein the gene copy number of the EGFr gene is determined.

9. 发明申请

WO2003031930A3 A PHOSPHATASE ASSOCIATED WITH METASTASIS 审中-公开
公开(公告)号：WO2003031930A3
公开(公告)日：2003-04-17
申请号：PCT/US2002/031247
申请日：2002-10-02
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , SAHA, Saurabh , BARDELLI, Alberto
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , SAHA, Saurabh , BARDELLI, Alberto
IPC分类号： A61K49/18
摘要： Among the genes identified, in a comparison of the global gene expression profile of metastatic colorectal cancer to that of primary cancers, benign colorectal tumors, and normal colorectal epithelium, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. fu three of twelve metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions.

10. 发明申请

WO2017182783A3 INACTIVATION OF DNA REPAIR AS AN ANTICANCER THERAPY 审中-公开
公开(公告)号：WO2017182783A3
公开(公告)日：2017-10-26
申请号：PCT/GB2017/051062
申请日：2017-04-18
申请人： PHOREMOST LIMITED , BARDELLI, Alberto , GERMANO, Giovanni
发明人： BARDELLI, Alberto , GERMANO, Giovanni , TORRANCE, Chris
IPC分类号： A61K31/00 , C12N9/22 , C12Q1/00 , G01N33/68 , A61P35/00
摘要： This invention relates to the modulation of DNA repair and nucleic acid editing mechanisms for use in the treatment of cancer. This invention relates to the inactivation of DNA repair and mechanisms for use in the treatment of cancer. This invention also relates to screening for new anti-cancer agents.

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