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1. 发明授权

US06495737B1 Methods and compositions for improving salicylic acid-independent systemic acquired disease resistance in plants 失效
标题翻译：用于改善植物中水杨酸独立系统获得性疾病抗性的方法和组合物
公开(公告)号：US06495737B1
公开(公告)日：2002-12-17
申请号：US08909125
申请日：1997-08-11
申请人： Daniel F. Klessig , Ailan Guo
发明人： Daniel F. Klessig , Ailan Guo
IPC分类号： C12N1582
CPC分类号： C12N15/8279 , C12N9/14
摘要： The present invention provides methods and materials that enhance a plant's resistance to certain pathogens. A novel pathway is described and has been designated with the acronym, SI-SAR pathway, for salicylic acid-independent systemic acquired resistance. DNA constructs and methodologies are provided that facilitate the identification of compounds that activate this pathway. Methods are provided to enable the identification of novel genes and signaling components that are expressed when the SI-SAR pathway is activated. Transgenic plants with altered expression of these novel genes or signaling components of the pathway are expected to have enhanced resistance to plant pathogens. Also provided is a novel, pathogen-induced epoxide hydrolase that is inducible in the absence of SA.
摘要翻译：本发明提供增强植物对某些病原体的抗性的方法和材料。描述了一条新途径，并且已经用缩写SI-SAR途径指定了水杨酸独立系统获得性抗性。提供DNA构建体和方法，其有助于鉴定激活该途径的化合物。提供了方法来确定当SI-SAR途径被激活时表达的新基因和信号传导成分。预期这些新基因或该途径的信号成分表达改变的转基因植物对植物病原体具有增强的抗性。还提供了一种新型的病原体诱导的环氧化物水解酶，其在不存在SA时可诱导。

2. 发明申请

US20120208824A1 ROS Kinase in Lung Cancer 审中-公开
标题翻译： ROS激酶在肺癌
公开(公告)号：US20120208824A1
公开(公告)日：2012-08-16
申请号：US13113676
申请日：2011-05-23
申请人： Victoria McGuinness Rimkunas , Herbert Haack , Ting-Lei Gu , Ailan Guo , Anthony Paul Possemato , Katherine Eleanor Crosby , Meghan Ann Tucker , Cynthia Reeves
发明人： Victoria McGuinness Rimkunas , Herbert Haack , Ting-Lei Gu , Ailan Guo , Anthony Paul Possemato , Katherine Eleanor Crosby , Meghan Ann Tucker , Cynthia Reeves
IPC分类号： A61K31/4545 , A61K31/506 , G01N33/574 , G01N33/53 , C12Q1/68 , A61P35/00 , G01N33/573
CPC分类号： G01N33/57423 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , G01N2333/912
摘要： The invention provides the identification of the presence of polypeptides with ROS kinase activity in mammalian lung cancer. In some embodiments, the polypeptide with ROS kinase activity is the result of a fusion between a ROS-encoding polynucleotide and a polynucleotide encoding a second (non-ROS) polypeptide. Three different fusion partners of ROS are described, namely proteins encoded by the FIG gene, the SLC34A2 gene, and the CD74 gene. The invention enables new methods for determining the presence of a polypeptide with ROS kinase activity in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer (e.g., an lung cancer).
摘要翻译：本发明提供了哺乳动物肺癌中存在具有ROS激酶活性的多肽的鉴定。在一些实施方案中，具有ROS激酶活性的多肽是编码ROS编码多核苷酸和编码第二（非ROS）多肽的多核苷酸之间融合的结果。描述了ROS的三种不同的融合配偶体，即由FIG基因编码的蛋白质，SLC34A2基因和CD74基因。本发明使得能够确定生物样品中具有ROS激酶活性的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，以及抑制癌症进展的方法（例如肺癌）。

3. 发明授权

US08168383B2 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：US08168383B2
公开(公告)日：2012-05-01
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 , C12Q1/48 , C07H21/00 , 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： 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 polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The invention also provides methods for determining the presence of these mutant 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.
摘要翻译：涉及染色体2的新型基因缺失和易位导致融合蛋白的结合，其部分的间变型淋巴瘤激酶（ALK）激酶与部分二级蛋白结合，已经在人类实体瘤中被鉴定。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多肽的载体，用于检测其的探针，分离的突变多肽和用于检测融合和截短的多肽的试剂。本发明还提供了用于确定生物样品中这些突变体多肽的存在的方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变多核苷酸或多肽特征的癌症进展抑制方法。

4. 发明申请

US20110223609A1 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：US20110223609A1
公开(公告)日：2011-09-15
申请号：US12584353
申请日：2009-09-03
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill
IPC分类号： C12Q1/68 , C12N9/96 , C12N5/10 , C12N1/00 , C12N15/63 , C07H21/04
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。

5. 发明申请

US20100304382A1 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：US20100304382A1
公开(公告)日：2010-12-02
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 , C12N15/12 , C12N15/85 , C12N5/10 , C12P21/02 , C12N9/96 , C12N5/00
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。

6. 发明申请

US20100298404A1 Translocation and mutant ROS kinase in human non-small cell lung carcinoma 有权
标题翻译：人非小细胞肺癌易位和突变型ROS激酶
公开(公告)号：US20100298404A1
公开(公告)日：2010-11-25
申请号：US12218834
申请日：2008-07-18
申请人： Ailan Guo , Anthony Possemato
发明人： Ailan Guo , Anthony Possemato
IPC分类号： A61K31/713 , C12Q1/68 , G01N33/53 , C12P21/02 , C12N15/09 , C12N5/10 , C12N1/21 , A61P35/00 , C12N1/15 , C12N1/19 , C12N15/63 , C07K14/47 , C07K16/18 , C07H21/04
CPC分类号： C12N15/1137 , C07K14/47 , C07K14/82 , C07K2319/00 , C12N9/1205 , C12N2310/14 , C12Q1/6841 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136 , C12Q2600/156 , G01N33/57423 , G01N33/57484
摘要： In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3h protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS 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，在人非小细胞肺癌（NSCLC）中的新型基因易位（4p15,6q22），其导致结合部分钠依赖性磷酸转运蛋白同种型NaPi-3h蛋白（SLC34A2）的融合蛋白，与原癌基因酪氨酸蛋白激酶ROS前体（ROS）激酶现已被鉴定。预期SLC34A2-ROS融合蛋白将驱动NSCLC肿瘤亚组的增殖和存活。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型ROS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。所公开的新融合蛋白的鉴定使得能够确定生物样品中这些突变型ROS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，以及抑制以突变体多核苷酸为特征的癌症进展的方法或多肽，其也由本发明提供。

7. 发明申请

US20100221737A1 Translocation and Mutant ROS Kinase in Human Non-Small Cell Lung Carcinoma 有权
标题翻译：人非小细胞肺癌易位和突变型ROS激酶
公开(公告)号：US20100221737A1
公开(公告)日：2010-09-02
申请号：US12738210
申请日：2008-10-20
申请人： Ting-Lei Gu , Ailan Guo
发明人： Ting-Lei Gu , Ailan Guo
IPC分类号： C12Q1/68 , C07H21/04 , C07K14/00 , C07K16/00 , G01N33/53
CPC分类号： C12Q1/6886 , A61K2039/505 , C07K14/70539 , C07K14/82 , C07K16/40 , C07K2319/00 , C12N9/12 , C12N9/99 , C12N15/1137 , C12Q1/68 , C12Q1/6813 , C12Q1/6883 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001
摘要： In accordance with the invention, a novel gene translocation, (5q32, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of CD74 with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The CD74-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS 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，在人非小细胞肺癌（NSCLC）中的新基因易位（5q32,6q22），其导致将CD74的一部分与原癌基因酪氨酸蛋白激酶ROS前体（ROS）结合的融合蛋白，激酶现已被鉴定。预期CD74-ROS融合蛋白将驱动NSCLC肿瘤亚组的增殖和存活。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型ROS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。所公开的新融合蛋白的鉴定使得能够确定生物样品中这些突变型ROS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，以及抑制以突变型多核苷酸为特征的癌症进展的方法或多肽，其也由本发明提供。

8. 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.

9. 发明申请

US20090203034A1 Reagents for the detection of tyrosine phosphorylation in brain ischemia signaling pathways 审中-公开
标题翻译：用于检测脑缺血信号通路中酪氨酸磷酸化的试剂
公开(公告)号：US20090203034A1
公开(公告)日：2009-08-13
申请号：US12227318
申请日：2007-05-11
申请人： Ailan Guo , Roberto Polakiewicz , Kimberly Lee
发明人： Ailan Guo , Roberto Polakiewicz , Kimberly Lee
IPC分类号： G01N33/53 , C12Q1/48 , G01N33/536 , C07K16/18 , C07K14/47 , C07K7/06 , C07K7/08 , C12N5/16
CPC分类号： G01N33/6848 , C07K16/44 , G01N33/6842 , G01N33/6872 , G01N2800/2871
摘要： The invention discloses 99 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Brain Ischemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: protein kinases, adaptor/scaffold proteins, adhesion proteins, G proteins/GTPase/Guanine nucleotide exchange factors, Calcium binding proteins, cytoskeletal proteins, Channel proteins, Chaperone proteins, Helicases, Motor proteins, Translation proteins, RNA binding proteins, Ubiquitin conjugating system proteins, vesicle proteins and Receptor proteins.
摘要翻译：本发明公开了在信号转导蛋白中识别的99个新的磷酸化位点和人类脑缺血的基因，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，如以及使用试剂用于此目的的方法。鉴定的磷酸化位点之间是以下蛋白质类型中发生的位点：蛋白激酶，衔接/支架蛋白，粘附蛋白，G蛋白/ GTP酶/鸟嘌呤核苷酸交换因子，钙结合蛋白，细胞骨架蛋白，通道蛋白，伴侣蛋白，Helicases，运动蛋白，翻译蛋白，RNA结合蛋白，泛素缀合系统蛋白，囊泡蛋白和受体蛋白。

10. 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。

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