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1. 发明申请

US20100184100A1 Tyrosine Kinome 有权
标题翻译：酪氨酸激酶
公开(公告)号：US20100184100A1
公开(公告)日：2010-07-22
申请号：US12705760
申请日：2010-02-15
申请人： Alberto Bardelli , Will Parsons , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
发明人： Alberto Bardelli , Will Parsons , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： G01N33/574 , C07H21/00
CPC分类号： C12Q1/6886 , A61K31/506 , C12N9/1205 , C12Q1/025 , C12Q1/485 , C12Q1/6809 , C12Q1/6827 , C12Q2600/136 , C12Q2600/156 , G01N33/574
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.
摘要翻译：蛋白激酶是参与肿瘤发生的重要信号分子。人类酪氨酸激酶基因家族（98个基因）的突变分析鉴定了-20％的结肠直肠癌的体细胞变化，大部分突变发生在NTRK3，FES，GUCY2F和以前称为MCCK / MLK4的未表征的酪氨酸激酶基因。大多数改变是保守的残基影响激酶结构域的关键区域。这些数据代表了癌症中信号转导基因的无偏见分析的范例，并为治疗干预提供了有用的目标。

2. 发明授权

US08394598B2 Tyrosine kinome 有权
标题翻译：酪氨酸激酶
公开(公告)号：US08394598B2
公开(公告)日：2013-03-12
申请号：US12705760
申请日：2010-02-15
申请人： Alberto Bardelli , Will Parsons , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
发明人： Alberto Bardelli , Will Parsons , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： C12Q1/6886 , A61K31/506 , C12N9/1205 , C12Q1/025 , C12Q1/485 , C12Q1/6809 , C12Q1/6827 , C12Q2600/136 , C12Q2600/156 , G01N33/574
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.
摘要翻译：蛋白激酶是参与肿瘤发生的重要信号分子。人类酪氨酸激酶基因家族（98个基因）的突变分析鉴定了-20％的结肠直肠癌的体细胞变化，大部分突变发生在NTRK3，FES，GUCY2F和以前称为MCCK / MLK4的未表征的酪氨酸激酶基因。大多数改变是保守的残基影响激酶结构域的关键区域。这些数据代表了癌症中信号转导基因的无偏见分析的范例，并为治疗干预提供了有用的目标。

3. 发明授权

US09580750B2 P13K pathway mutations in cancer 有权
标题翻译：癌症中P13K通路突变
公开(公告)号：US09580750B2
公开(公告)日：2017-02-28
申请号：US11920860
申请日：2006-05-23
申请人： Donald William Parsons , Tian-li Wang , Yardena Samuels , Alberto Bardelli , Christopher Lengauer , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
发明人： Donald William Parsons , Tian-li Wang , Yardena Samuels , Alberto Bardelli , Christopher Lengauer , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12Q1/62 , G01N33/574 , C07K16/40 , C12Q1/68 , C12Q1/48 , G01N33/50
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。

4. 发明申请

US20110059434A1 P13k pathway mutations in cancer 有权
标题翻译：癌症中P13k通路突变
公开(公告)号：US20110059434A1
公开(公告)日：2011-03-10
申请号：US11920860
申请日：2006-05-23
申请人： Donald William Parsons , Tian-li Wang , Yardena Samuels , Alberto Bardelli , Christopher Lengauer , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
发明人： Donald William Parsons , Tian-li Wang , Yardena Samuels , Alberto Bardelli , Christopher Lengauer , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12Q1/68 , C12Q1/48 , C12N9/12 , G01N33/574
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。

5. 发明申请

US20070037150A1 Tyrosine kinome 审中-公开
标题翻译：酪氨酸激酶
公开(公告)号：US20070037150A1
公开(公告)日：2007-02-15
申请号：US10544536
申请日：2004-02-18
申请人： Alberto Bardelli , Will Parsons , Victor Velculescu , Kenneth Kinzler , Bert Vogelstein
发明人： Alberto Bardelli , Will Parsons , Victor Velculescu , Kenneth Kinzler , Bert Vogelstein
IPC分类号： C12Q1/68 , G06F19/00
CPC分类号： C12Q1/6886 , A61K31/506 , C12N9/1205 , C12Q1/025 , C12Q1/485 , C12Q1/6809 , C12Q1/6827 , C12Q2600/136 , C12Q2600/156 , G01N33/574
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.
摘要翻译：蛋白激酶是参与肿瘤发生的重要信号分子。人类酪氨酸激酶基因家族（98个基因）的突变分析鉴定了-20％的结肠直肠癌的体细胞变化，大部分突变发生在NTRK3，FES，GUCY2F和以前称为MCCK / MLK4的未表征的酪氨酸激酶基因。大多数改变是保守的残基影响激酶结构域的关键区域。这些数据代表了癌症中信号转导基因的无偏见分析的范例，并为治疗干预提供了有用的目标。

6. 发明授权

US07745165B2 Phosphatase associated with metastasis 有权
标题翻译：与转移相关的磷酸酶
公开(公告)号：US07745165B2
公开(公告)日：2010-06-29
申请号：US10868658
申请日：2004-06-16
申请人： Bert Vogelstein , Kenneth W. Kinzler , Saurabh Saha , Alberto Bardelli
发明人： Bert Vogelstein , Kenneth W. Kinzler , Saurabh Saha , Alberto Bardelli
IPC分类号： C12Q1/48 , G01N33/567
CPC分类号： C12N9/16 , A61K39/00 , C12Q1/6886 , C12Q2600/112 , C12Q2600/136 , C12Q2600/158
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. In 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.
摘要翻译：在确定的基因中，在转移性结肠直肠癌与原发性癌症，良性结肠直肠肿瘤和正常结肠直肠上皮的全球基因表达谱比较中，PRL-3蛋白酪氨酸磷酸酶基因特别引人关注。在所研究的18个癌症转移中的每一个中表达高水平，但在非转移性肿瘤和正常结肠直肠上皮中的水平较低。在检查的十二个转移中的三个中，在位于染色体8q24.3的小扩增子中发现了PRL-3基因的多个拷贝。这些数据表明，PRL-3基因对结肠直肠癌转移很重要，为这些难治性病变提供了新的治疗靶点。

7. 发明申请

US20050047996A1 Phosphatase associated with metastasis 有权
标题翻译：与转移相关的磷酸酶
公开(公告)号：US20050047996A1
公开(公告)日：2005-03-03
申请号：US10868658
申请日：2004-06-16
申请人： Bert Vogelstein , Kenneth Kinzler , Saurabh Saha , Alberto Bardelli
发明人： Bert Vogelstein , Kenneth Kinzler , Saurabh Saha , Alberto Bardelli
IPC分类号： G01N33/50 , A61K39/00 , A61K39/395 , A61P35/00 , C12N9/16 , C12N15/09 , C12Q1/42 , C12Q1/68 , G01N33/15 , G01N33/543 , G01N33/573 , G01N33/574 , A61K51/00
CPC分类号： C12N9/16 , A61K39/00 , C12Q1/6886 , C12Q2600/112 , C12Q2600/136 , C12Q2600/158
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. In 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.
摘要翻译：在确定的基因中，在转移性结肠直肠癌与原发性癌症，良性结肠直肠肿瘤和正常结肠直肠上皮的全球基因表达谱比较中，PRL-3蛋白酪氨酸磷酸酶基因特别引人关注。在所研究的18个癌症转移中的每一个中表达高水平，但在非转移性肿瘤和正常结肠直肠上皮中的水平较低。在检查的十二个转移中的三个中，在位于染色体8q24.3的小扩增子中发现了PRL-3基因的多个拷贝。这些数据表明，PRL-3基因对结肠直肠癌转移很重要，为这些难治性病变提供了新的治疗靶点。

8. 发明申请

US20110212456A1 K-ras and B-raf mutations and anti-EGFr antibody therapy 审中-公开
标题翻译： K-ras和B-raf突变和抗EGFr抗体治疗
公开(公告)号：US20110212456A1
公开(公告)日：2011-09-01
申请号：US12976895
申请日：2010-12-22
申请人： Salvatore SIENA , Alberto Bardelli
发明人： Salvatore SIENA , Alberto Bardelli
IPC分类号： C12Q1/68 , G01N33/68
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/156
摘要： The present application relates to K-ras mutations, to polynucleotides encoding mutant K-ras polypeptides, and to methods of identifying K-ras mutations. The present application also relates to B-raf mutations, to polynucleotides encoding mutant B-raf polypeptides, to vectors containing those polynucleotides, and to methods of identifying B-raf mutations. The present application also relates to methods of diagnosing cancer; and methods and kits for predicting the usefulness of anti-EGFr specific binding agents in the treatment of tumors.
摘要翻译：本申请涉及K-ras突变，编码突变型K-ras多肽的多核苷酸以及鉴定K-ras突变的方法。本申请还涉及B-raf突变，编码突变体B-raf多肽的多核苷酸，含有这些多核苷酸的载体，以及鉴定B-raf突变的方法。本申请还涉及诊断癌症的方法; 以及用于预测抗EGFr特异性结合剂在治疗肿瘤中的有用性的方法和试剂盒。

9. 发明申请

US20130136755A1 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：US20130136755A1
公开(公告)日：2013-05-30
申请号：US13704784
申请日：2010-06-15
申请人： Alberto Bardelli , Miriam Martini
发明人： Alberto Bardelli , Miriam Martini
IPC分类号： C12Q1/68 , G01N33/68
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。

10. 发明申请

US20120115896A1 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：US20120115896A1
公开(公告)日：2012-05-10
申请号：US13132737
申请日：2008-12-03
申请人： Alberto Bardelli , Federica Di Nicolantonio , Sabrina Arena
发明人： Alberto Bardelli , Federica Di Nicolantonio , Sabrina Arena
IPC分类号： A61K31/4375 , A61P35/00 , C12Q1/04 , A61K31/405 , C12N5/10 , A01K67/027
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 car cytotoxicity 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，细胞凋亡小体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。

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