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31.发明申请公开(公告)号：US20090124023A1
公开(公告)日：2009-05-14
申请号：US12227321
申请日：2007-05-11
申请人： Ailan Guo , Ting-Lei Gu , Jeffrey Mitchell , Peter Hornbeck
发明人： Ailan Guo , Ting-Lei Gu , Jeffrey Mitchell , Peter Hornbeck
IPC分类号： G01N33/566 , C07K16/18
CPC分类号： G01N33/68 , C07K16/18 , C07K16/44 , G01N33/6842
摘要： The invention discloses 432 novel acetylation sites identified in signal transduction proteins and pathways underlying human protein acetylation signaling pathways, and provides acetylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these acetylated sites/proteins, as well as methods of using the reagents for such purpose. Among the acetylation sites identified are sites occurring in the following protein types: Acetyltransferases, Adaptor/Scaffold proteins, Actin binding proteins, Adhesion proteins, Apoptosis proteins, Calcium-binding proteins, Cell Cycle Regulation proteins, Cell Surface proteins, DNA binding proteins, DNA replication proteins, Channel proteins, Chaperone proteins, Cellular Metabolism enzymes, Cytoskeletal proteins, DNA repair proteins, Endoplasmic reticulum proteins, Enzyme proteins, G protein and GTPase Activating proteins, Guanine Nucleotide Exchange Factors, Helicase proteins, Isomerase proteins, Extracelluar matrix proteins, Hydrolases, Ligase proteins, Lipid kinases, Inhibtor proteins, Lipid Binding proteins and Lyases.
摘要翻译： 本发明公开了在信号转导蛋白中鉴定的432个新的乙酰化位点和基于人蛋白质乙酰化信号通路的途径，并提供乙酰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乙酰化位点/蛋白质 ，以及使用试剂用于此目的的方法。 确定的乙酰化位点之间的位点是发生在以下蛋白质类型中的位点：乙酰转移酶，适配器/支架蛋白，肌动蛋白结合蛋白，粘附蛋白，细胞凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，细胞表面蛋白，DNA结合蛋白，DNA 复制蛋白，通道蛋白，伴侣蛋白，细胞代谢酶，细胞骨架蛋白，DNA修复蛋白，内质网蛋白，酶蛋白，G蛋白和GTP酶活化蛋白，鸟嘌呤核苷酸交换因子，Helicase蛋白，异构酶蛋白，Extracelluar基质蛋白，水解酶 ，连接酶蛋白，脂质激酶，抑制蛋白，脂质结合蛋白和裂解酶。
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公开(公告)号：US20110104820A1
公开(公告)日：2011-05-05
申请号：US12902261
申请日：2010-10-12
IPC分类号： G01N33/566 , C07K16/00
CPC分类号： C07K16/44 , C07K2317/34 , G01N33/574 , G01N33/6842
摘要： The invention discloses 94 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies that specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.
摘要翻译： 本发明公开了在癌和白血病中鉴定的94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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33.发明授权Reagents for the detection of protein phosphorylation in leukemia signaling pathways 有权用于检测白血病信号通路中蛋白质磷酸化的试剂公开(公告)号：US07888480B2
公开(公告)日：2011-02-15
申请号：US12074224
申请日：2008-02-29
IPC分类号： C07K16/00
CPC分类号： G01N33/6842 , C07K16/3061 , C07K16/44 , C07K2317/34 , G01N33/57426 , G01N2458/15
摘要： The invention discloses nearly 288 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, 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, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.
摘要翻译： 本发明公开了在信号转导蛋白中鉴定的近288个新的磷酸化位点和人类白血病潜在的途径，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。 所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。
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34.发明申请公开(公告)号：US20100093008A1
公开(公告)日：2010-04-15
申请号：US11681521
申请日：2007-03-02
申请人： Valerie GOSS , Roberto Polakiewicz , Kimberly Lee , Ting-Lei Gu , Albrecht Moritz , Jiong Wu
发明人： Valerie GOSS , Roberto Polakiewicz , Kimberly Lee , Ting-Lei Gu , Albrecht Moritz , Jiong Wu
CPC分类号： G01N33/573 , C07K16/2863 , C07K16/44 , C07K2317/34 , G01N33/57426 , G01N2333/9121 , G01N2800/52
摘要： The invention discloses a newly discovered Flt3 phosphorylation site, tyrosine 969 (Tyr969) in the intracellular domain, and provides reagents, including polyclonal and monoclonal antibodies, that selectively bind to Flt3 when phosphorylated at this site. Also provided are assays utilizing this reagent, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibody, that binds to Flt3 only when phosphorylated at Tyr969. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).
摘要翻译： 本发明公开了新发现的Flt3磷酸化位点，细胞内结构域中的酪氨酸969（Tyr969），并提供了在该位点磷酸化时选择性结合Flt3的试剂，包括多克隆和单克隆抗体。 还提供了使用该试剂的测定法，包括用于测定生物样品中Flt3的磷酸化的方法，选择适合Flt3抑制剂治疗的患者，在测试组织中分析Flt3活化，以及鉴定在测试中调节Flt3的磷酸化的化合物 通过使用仅在Tyr969磷酸化时与Flt3结合的可检测试剂，例如所公开的抗体。 样品或测试组织可以从疑似患有癌症的受试者中获取，例如急性骨髓性白血病（AML）。
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35.发明申请Reagents for the detection of protein phosphorylation in leukemia signaling pathways 审中-公开用于检测白血病信号通路中蛋白质磷酸化的试剂公开(公告)号：US20090220991A1
公开(公告)日：2009-09-03
申请号：US12074214
申请日：2008-02-29
IPC分类号： G01N33/53 , G01N33/536 , C07K16/18 , C12N5/18
CPC分类号： C07K16/40 , C07K16/18 , C07K16/2803 , C07K16/2896 , C07K16/3061 , C07K2317/34 , G01N33/57426 , G01N33/6854
摘要： The invention discloses nearly 480 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, 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, acetyltransferases, actin binding proteins, adhesion proteins, apoptosis proteins, calcium-binding proteins, cell cycle regulation proteins, cell surface proteins, channel proteins, chaperone proteins, contractile proteins, cytokine proteins, cytoskeletal proteins, G protein regulators and GTPase activating proteins, guanine nucleotide exchange factors, helicase proteins, immunoglobulin superfamily proteins, inhibitor proteins, protein kinases, lipid kinases, ligases, lipid binding proteins, methytransferases, motor proteins, oxidoreductases, phosphotases, phosphodiesterases, phospholipases, proteases, receptor proteins, trascription factors, transferases, translation/transporter proteins, and ubiquitin conjugating system proteins.
摘要翻译： 本发明公开了在信号转导蛋白中识别的近480个新的磷酸化位点和人类白血病下游的途径，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 作为使用试剂用于此目的的方法。 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，乙酰转移酶，肌动蛋白结合蛋白，粘附蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，细胞表面蛋白，通道蛋白，伴侣蛋白 鸟嘌呤核苷酸交换因子，解旋酶蛋白，免疫球蛋白超家族蛋白，抑制蛋白，蛋白激酶，脂质激酶，连接酶，脂质结合蛋白，甲基转移酶，运动蛋白，肌动蛋白， 氧化还原酶，磷酸二酯酶，磷脂酶，蛋白酶，受体蛋白，trascription因子，转移酶，翻译/转运蛋白和泛素缀合系统蛋白。
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36.发明申请Reagents for the detection of protein phosphorylation in leukemia signaling pathways 审中-公开用于检测白血病信号通路中蛋白质磷酸化的试剂公开(公告)号：US20090142777A1
公开(公告)日：2009-06-04
申请号：US11973019
申请日：2007-10-05
IPC分类号： G01N33/573 , G01N33/566 , C07K16/18 , C07K14/00 , C12N5/06
CPC分类号： C07K16/3061 , C07K16/40
摘要： The invention discloses 424 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, 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, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.
摘要翻译： 本发明公开了在信号转导蛋白中鉴定的424个新的磷酸化位点和人类白血病的途径，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 作为使用试剂用于此目的的方法。 所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。
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37.发明申请Reagents for the detection of protein phosphorylation in Leukemia signaling pathways 有权用于检测白血病信号通路中蛋白质磷酸化的试剂公开(公告)号：US20080248490A1
公开(公告)日：2008-10-09
申请号：US12074224
申请日：2008-02-29
CPC分类号： G01N33/6842 , C07K16/3061 , C07K16/44 , C07K2317/34 , G01N33/57426 , G01N2458/15
摘要： The invention discloses nearly 288 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, 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, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.
摘要翻译： 本发明公开了在信号转导蛋白中鉴定的近288个新的磷酸化位点和人类白血病潜在的途径，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，如 以及使用试剂用于此目的的方法。 所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。
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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）。
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39.发明申请公开(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
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。
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40.发明授权公开(公告)号：US09096855B2
公开(公告)日：2015-08-04
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 , C12N15/11 , C12N15/12 , C12N15/113 , C07K14/74 , C07K14/82 , C07K16/40 , C12N9/99 , A61K39/00
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。
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