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    • 21. 发明申请
    • Gene defects and mutant ALK kinase in human solid tumors
    • 人类实体瘤中的基因缺陷和突变ALK激酶
    • US20100240034A1
    • 2010-09-23
    • US12589176
    • 2009-10-19
    • Klarisa RikovaHerbert HaackLaura SullivanAilan GuoAnthony PossematoJoan MacNeillTing-Lei GuJian Yu
    • Klarisa RikovaHerbert HaackLaura SullivanAilan GuoAnthony PossematoJoan MacNeillTing-Lei GuJian Yu
    • C12Q1/68C07H21/04C12N5/02
    • G01N33/574A61K38/00C07K2319/00C12N9/1205C12Q1/6886C12Q2600/136C12Q2600/156G01N33/57484G01N2333/9121Y10T436/117497
    • 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.
    • 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。
    • 28. 发明申请
    • TRANSLOCATION AND MUTANT ROS KINASE IN HUMAN NON-SMALL CELL LUNG CARCINOMA
    • 人类非小细胞肺癌转移和突变ROS激酶
    • US20100143918A1
    • 2010-06-10
    • US12581126
    • 2009-10-17
    • Ailan GuoTing-Lei GuAnthony Possemato
    • Ailan GuoTing-Lei GuAnthony Possemato
    • C12Q1/68C07H21/00C12N15/74C12N5/07C07K14/00C07K16/00G01N33/53G01N33/574
    • C07K14/82C07K14/47C07K2319/00C12N9/1205C12Q1/6841C12Q1/6886C12Q2600/106C12Q2600/136C12Q2600/156G01N33/57423
    • In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion proteins are anticipated to drive the proliferation and survival of cancer cells, and particularly drive the proliferation and survival of a subgroup of NSCLC tumor cells. 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.
    • 根据本发明,在人非小细胞肺癌(NSCLC)中的新型基因易位(4p15,6q22),其导致将部分钠依赖性磷酸转运蛋白同种型NaPi-3b蛋白(SLC34A2)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融合蛋白将驱动癌细胞的增殖和存活,特别是促进NSCLC肿瘤细胞亚群的增殖和存活。 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。
    • 29. 发明授权
    • Reagents for the detection of protein phosphorylation in signaling pathways
    • 用于检测信号通路中蛋白质磷酸化的试剂
    • US07999080B2
    • 2011-08-16
    • US12309310
    • 2007-07-13
    • Peter HornbeckValerie GossKimberly LeeTing-Lei GuAlbrecht Moritz
    • Peter HornbeckValerie GossKimberly LeeTing-Lei GuAlbrecht Moritz
    • C07K16/18
    • C12Q1/485C07K16/18C07K16/40C07K16/44G01N33/68G01N33/6842G01N33/6845G01N33/6848G01N33/6872
    • The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, 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: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, Protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.
    • 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点,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,以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点:衔接子/支架蛋白,粘附/细胞外基质蛋白,凋亡蛋白,钙结合蛋白,细胞周期调节蛋白,伴侣蛋白,染色质,DNA结合/修复/复制蛋白, 细胞骨架蛋白,内质网或高尔基体蛋白,酶蛋白,G /调节蛋白,抑制蛋白,运动/收缩蛋白,磷酸酶,蛋白酶,Ser / Thr蛋白激酶,蛋白激酶(Tyr),受体/通道/细胞表面蛋白, RNA结合蛋白,转录调节物,肿瘤抑制蛋白,泛素偶联系统蛋白和功能未知的蛋白。
    • 30. 发明申请
    • Reagents for the detection of protein phosphorylation in signaling pathways
    • 用于检测信号通路中蛋白质磷酸化的试剂
    • US20100009463A1
    • 2010-01-14
    • US12309313
    • 2007-07-13
    • Peter HornbeckValerie GossKimberly LeeTing-Lei GuAlbrecht Moritz
    • Peter HornbeckValerie GossKimberly LeeTing-Lei GuAlbrecht Moritz
    • G01N33/566C07K16/18C07K14/47C12N5/16C12N5/18
    • G01N33/57426C07B59/008C07K14/47C07K16/44G01N33/6842G01N2458/15
    • The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, 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: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.
    • 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点,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,以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点:衔接子/支架蛋白,粘附/细胞外基质蛋白,凋亡蛋白,钙结合蛋白,细胞周期调节蛋白,伴侣蛋白,染色质,DNA结合/修复/复制蛋白, 细胞骨架蛋白,内质网或高尔基体蛋白,酶蛋白,G /调节蛋白,抑制蛋白,运动/收缩蛋白,磷酸酶,蛋白酶,Ser / Thr蛋白激酶,蛋白激酶(Tyr),受体/通道/细胞表面蛋白, RNA结合蛋白,转录调节物,肿瘤抑制蛋白,泛素偶联系统蛋白和功能未知的蛋白。