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21. 发明授权

US07700339B2 Gene defects and mutant ALK kinase in human solid tumors 有权
公开(公告)号：US07700339B2
公开(公告)日：2010-04-20
申请号：US11787132
申请日：2007-04-13
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： C12N15/63 , C12N15/00 , C12N1/21 , C12N5/10 , C12P21/00 , C12Q1/68 , C07H21/00 , C12N9/12 , C12Q1/48 , C07K14/00
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

22. 发明申请

US20090156475A1 Gene defects and mutant ALK kinase in human solid tumors 有权
标题翻译：人类实体瘤中的基因缺陷和突变ALK激酶
公开(公告)号：US20090156475A1
公开(公告)日：2009-06-18
申请号：US11787132
申请日：2007-04-13
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： A61K38/16 , C07H21/04 , C12N15/74 , C07K14/00 , C07K16/00 , G01N33/53 , C12Q1/68 , A61P35/00
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译：根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。非小细胞肺癌（NSCLC）。次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变突变型多核苷酸特征的癌症进展抑制方法或多肽，其也由本发明提供。

23. 发明申请

US20110021546A1 Gene Defects And Mutant ALK Kinase In Human Solid Tumors 有权
标题翻译：人类实体肿瘤中的基因缺陷和突变ALK激酶
公开(公告)号：US20110021546A1
公开(公告)日：2011-01-27
申请号：US12891987
申请日：2010-09-28
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： A61K31/517 , C12N9/12 , C07K16/40 , C07K2/00 , C07H21/00 , G01N33/573 , C12Q1/68 , G01N33/566 , A61P35/00
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译：根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。非小细胞肺癌（NSCLC）。次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变突变型多核苷酸特征的癌症进展抑制方法或多肽，其也由本发明提供。

24. 发明申请

US20100240034A1 Gene defects and mutant ALK kinase in human solid tumors 有权
标题翻译：人类实体瘤中的基因缺陷和突变ALK激酶
公开(公告)号：US20100240034A1
公开(公告)日：2010-09-23
申请号：US12589176
申请日：2009-10-19
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： C12Q1/68 , C07H21/04 , C12N5/02
CPC分类号： G01N33/574 , A61K38/00 , C07K2319/00 , C12N9/1205 , C12Q1/6886 , C12Q2600/136 , C12Q2600/156 , G01N33/57484 , G01N2333/9121 , Y10T436/117497
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译：根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。非小细胞肺癌（NSCLC）。次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变突变型多核苷酸特征的癌症进展抑制方法或多肽，其也由本发明提供。

25. 发明授权

US08481279B2 Methods of treating lung cancer using inhibitors anaplastic lymphoma kinase 有权
标题翻译：使用抑制剂间变性淋巴瘤激酶治疗肺癌的方法
公开(公告)号：US08481279B2
公开(公告)日：2013-07-09
申请号：US13366679
申请日：2012-02-06
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： C12Q1/48 , A61K31/00 , C12N9/12
CPC分类号： G01N33/574 , A61K38/00 , C07K2319/00 , C12N9/1205 , C12Q1/6886 , C12Q2600/136 , C12Q2600/156 , G01N33/57484 , G01N2333/9121 , Y10T436/117497
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides.
摘要翻译：根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。非小细胞肺癌（NSCLC）。次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。所公开的这种新的融合蛋白的鉴定使得能够筛选抑制蛋白质的化合物的方法，以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法。

26. 发明授权

US08377642B2 Gene defects and mutant ALK kinase in human solid tumors 有权
公开(公告)号：US08377642B2
公开(公告)日：2013-02-19
申请号：US12891987
申请日：2010-09-28
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： C12Q1/68 , C07H21/00 , C12N9/12
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

27. 发明授权

US08288102B2 Gene defects and mutant ALK kinase in human solid tumors 有权
公开(公告)号：US08288102B2
公开(公告)日：2012-10-16
申请号：US12714457
申请日：2010-02-27
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： C12Q1/68 , C12N9/12 , C07H21/00
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

28. 发明申请

US20120171696A1 Gene Defects And Mutant ALK Kinase In Human Solid Tumors 有权
标题翻译：人类实体肿瘤中的基因缺陷和突变ALK激酶
公开(公告)号：US20120171696A1
公开(公告)日：2012-07-05
申请号：US13366679
申请日：2012-02-06
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： G01N33/573 , C12Q1/48
CPC分类号： G01N33/574 , A61K38/00 , C07K2319/00 , C12N9/1205 , C12Q1/6886 , C12Q2600/136 , C12Q2600/156 , G01N33/57484 , G01N2333/9121 , Y10T436/117497
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides.
摘要翻译：根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。非小细胞肺癌（NSCLC）。次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。所公开的这种新的融合蛋白的鉴定使得能够筛选抑制蛋白质的化合物的方法，以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法。

29. 发明申请

US20100129928A1 Tyrosine Phosphorylation Sites 审中-公开
标题翻译：酪氨酸磷酸化位点
公开(公告)号：US20100129928A1
公开(公告)日：2010-05-27
申请号：US12309726
申请日：2007-07-27
申请人： Roberto Polakewicz , Charles Farnsworth , Ailan Guo , Klarisa Rikova , Albrecht Moritz , Kimberly Lee , Erik Spek
发明人： Roberto Polakewicz , Charles Farnsworth , Ailan Guo , Klarisa Rikova , Albrecht Moritz , Kimberly Lee , Erik Spek
IPC分类号： G01N33/53 , C07K16/18
CPC分类号： C07K16/44 , C07K16/30 , C07K2317/34 , G01N33/573 , G01N33/574 , G01N33/6854
摘要： The invention discloses 347 novel phosphorylation sites identified in carcinoma, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.
摘要翻译：本发明公开了在癌中鉴定的347个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体，以及上述的诊断和治疗用途。

30. 发明申请

US20100129930A1 Tyrosine Phosphorylation Sites 审中-公开
标题翻译：酪氨酸磷酸化位点
公开(公告)号：US20100129930A1
公开(公告)日：2010-05-27
申请号：US12309728
申请日：2007-07-27
申请人： Roberto Polakewicz , Charles Farnsworth , Ailan Guo , Klarisa Rikova , Albrecht Moritz , Kimberly Lee , Erik Spek
发明人： Roberto Polakewicz , Charles Farnsworth , Ailan Guo , Klarisa Rikova , Albrecht Moritz , Kimberly Lee , Erik Spek
IPC分类号： G01N33/53 , C07K16/18
CPC分类号： C07K16/44 , C07K16/30 , G01N33/573 , G01N33/574 , G01N33/6842
摘要： The invention discloses 351 novel phosphorylation sites identified in carcinoma, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.
摘要翻译：本发明公开了在癌中鉴定的351个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体，以及上述的诊断和治疗用途。

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