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1.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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2.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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3.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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4.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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5.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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6.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：US20090263832A1
公开(公告)日：2009-10-22
申请号：US12086609
申请日：2006-11-29
申请人： Roberto Polakiewicz , Ting-Lei Gu , Valerie Goss , Kimberly Lee
发明人： Roberto Polakiewicz , Ting-Lei Gu , Valerie Goss , Kimberly Lee
IPC分类号： G01N33/573 , C12Q1/48 , C07K16/18 , C12N5/16 , C12N5/18
CPC分类号： G01N33/57426
摘要： The invention discloses nearly 123 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: protein kinases, adaptor/scaffold proteins, phosphatase/phospholipases, G proteins/GTPase activating proteins/guanine nucleotide exchange factors, cellular metabolism enzymes, DNA binding proteins, cytoskeletal proteins, cell cycle regulation proteins, proteases, RNA binding proteins, transcription proteins, translation initiation complex proteins, transferases, ubiquitin conjugating system proteins, vesicle proteins, actin binding proteins, apoptosis proteins, chemokine proteins, enzyme proteins extra cellular matrix proteins, helicases, hydrolases, immunoglobin superfamily proteins, inhibitor proteins, isomerases, ligases, lipid binding proteins, methyltransferases, motor proteins, receptor proteins, and chaperone proteins.
摘要翻译： 本发明公开了在信号转导蛋白中识别的近123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，如 以及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：蛋白激酶，衔接子/支架蛋白，磷酸酶/磷脂酶，G蛋白/ GTPase激活蛋白/鸟嘌呤核苷酸交换因子，细胞代谢酶，DNA结合蛋白，细胞骨架蛋白，细胞 循环调节蛋白，蛋白酶，RNA结合蛋白，转录蛋白，翻译起始复合蛋白，转移酶，泛素缀合系统蛋白，囊泡蛋白，肌动蛋白结合蛋白，凋亡蛋白，趋化因子蛋白，酶蛋白超细胞基质蛋白，解旋酶，水解酶，免疫球蛋白 超家族蛋白，抑制蛋白，异构酶，连接酶，脂质结合蛋白，甲基转移酶，运动蛋白，受体蛋白和伴侣蛋白。
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公开(公告)号：US20090285796A1
公开(公告)日：2009-11-19
申请号：US12161512
申请日：2007-01-19
申请人： Valerie Goss , Ting-lei Gu , Roberto Polakiewicz , Brian Druker , Denise Walters
发明人： Valerie Goss , Ting-lei Gu , Roberto Polakiewicz , Brian Druker , Denise Walters
IPC分类号： A61K39/395 , C07H21/04 , C07K14/00 , C12N15/63 , C12N5/10 , C12N9/12 , C07K16/00 , C12Q1/68 , G01N33/53 , A61K31/7088 , A61P35/02
CPC分类号： C12N9/1205 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136
摘要： In accordance with the invention, a novel activating mutation (alanine 572 to valine) in JAK3 kinase has been discovered in human acute myelogenous leukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant protein and enables new methods for determining the presence of mutant JAK3 kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the mutant 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，已经在人类急性骨髓性白血病（AML）中发现JAK3激酶中的新的活化突变（丙氨酸572至缬氨酸）。 证实突变型JAK3激酶能够驱动急性巨核细胞白血病（AML-M7）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体JAK3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突变体多肽的试剂。 所公开的这种新的突变蛋白的鉴定并且使得能够确定生物样品中突变体JAK3激酶多肽的存在的新方法，用于筛选抑制突变蛋白质的化合物的方法，以及用于抑制突变体特征的癌症进展的方法 多核苷酸或多肽，其也由本发明提供。
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8.发明授权Reagents for the detection of protein phosphorylation in anaplastic large cell lymphoma signaling pathways 有权用于检测间变性大细胞淋巴瘤信号通路中蛋白质磷酸化的试剂公开(公告)号：US07973134B2
公开(公告)日：2011-07-05
申请号：US11503096
申请日：2006-08-11
申请人： Albrecht Moritz , Kimberly Lee , John Rush , Roberto Polakiewicz
发明人： Albrecht Moritz , Kimberly Lee , John Rush , Roberto Polakiewicz
CPC分类号： G01N33/6842 , C07K16/44
摘要： The invention discloses 211 novel phosphorylation sites identified in signal transduction proteins and pathways underlying Anaplastic Large Cell Lymphoma (ALCL) involving the ALK-NPM translocation/fusion, 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 (including Receptor Tyrosine Kinases), Adaptor/Scaffold Proteins, Cellular Metabolism or Miscellaneous Enzymes, Oxidoreductases, Transcription Factors, Cytoskeletal Proteins, Translation Initiation Complexes, RNA Binding Proteins, Proteases, Acetyltransferases, G protein regulators/GTPases, Helicases, Apoptosis/Cell Cycle Regulation proteins, and Hydrolases.
摘要翻译： 本发明公开了在信号转导蛋白中鉴定的211个新的磷酸化位点和涉及ALK-NPM易位/融合的间变性大细胞淋巴瘤（ALCL）的途径，并且为磷酸化位点特异性抗体和重同位素标记的肽（AQUA肽）提供了 这些磷酸化位点/蛋白质的选择性检测和定量，以及使用试剂用于此目的的方法。 鉴定的磷酸化位点是以下蛋白质类型发生的位点：蛋白激酶（包括受体酪氨酸激酶），适配器/支架蛋白，细胞代谢或其他酶，氧化还原酶，转录因子，细胞骨架蛋白，翻译起始复合物，RNA结合蛋白， 蛋白酶，乙酰转移酶，G蛋白调节剂/ GTP酶，Helicases，细胞凋亡/细胞周期调节蛋白和水解酶。
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9.发明申请Reagents for the detection of protein phosphorylation in carcinoma signaling pathways 审中-公开用于检测癌症信号通路中蛋白质磷酸化的试剂公开(公告)号：US20090099340A1
公开(公告)日：2009-04-16
申请号：US11974480
申请日：2007-10-12
申请人： Ailan Guo , Klarisa Rikova , Albrecht Moritz , Yu Li , Charles Farnsworth , Kimberly Lee , Roberto Polakiewicz
发明人： Ailan Guo , Klarisa Rikova , Albrecht Moritz , Yu Li , Charles Farnsworth , Kimberly Lee , Roberto Polakiewicz
IPC分类号： C07K16/18
CPC分类号： C07K16/32 , C07K16/30 , C07K16/44 , C07K2317/34 , G01N33/574 , G01N33/6842
摘要： The invention discloses 214 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human carcinoma, 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, Cytoskeleton proteins, GTP Signaling proteins, Kinases, Metabolism proteins, Phosphatases/Phospho-diesterases/Proteases, Receptor proteins, RNA Processing proteins, Transcription proteins, Translation proteins, Transporter proteins, and Ubitquitin proteins, as well as other protein types.
摘要翻译： 本发明公开了在信号转导蛋白中鉴定的214个新的磷酸化位点和人癌基因的途径，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：适配器/支架蛋白，细胞骨架蛋白，GTP信号蛋白，激酶，代谢蛋白，磷酸酶/磷酸二酯酶/蛋白酶，受体蛋白，RNA加工蛋白，转录蛋白，翻译 蛋白质，转运蛋白和Ubitquitin蛋白质，以及其他蛋白质类型。
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10.发明授权Reagents for the detection of protein phosphorylation in T-cell receptor signaling pathways 有权用于检测T细胞受体信号通路中蛋白质磷酸化的试剂公开(公告)号：US07935790B2
公开(公告)日：2011-05-03
申请号：US11503336
申请日：2006-08-11
CPC分类号： G01N33/6872 , C12Q1/25 , C12Q1/485 , G01N33/6842
摘要： The invention discloses 95 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of the T-cell receptor, 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: Actin Binding proteins, Adaptor/Scaffold proteins, Adhesion proteins, Calcium-binding proteins, Cell Cycle Regulation or Channel proteins, Chaperones, Cofactor proteins, Cytoskeletal proteins, DNA Binding proteins, G protein or GTPase Activating proteins, Ligases, Lipid Kinases and Binding proteins, Oxidoreductases, Protein Kinases, Protein Phosphatases, Receptor proteins, RNA Binding proteins, Transcription Factor/Initiation Complex proteins, Transcription Coactivator/Corepressor proteins, Translation Initiation Complex proteins, Ubitquitin Conjugating System proteins, and Vesicle proteins.
摘要翻译： 本发明公开了在T细胞受体下游的信号转导蛋白和途径中鉴定的95个新的磷酸化位点，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：肌动蛋白结合蛋白，衔接/支架蛋白，粘附蛋白，钙结合蛋白，细胞周期调节或通道蛋白，伴侣蛋白，辅因子蛋白，细胞骨架蛋白，DNA结合蛋白， G蛋白或GTPase激活蛋白，连接酶，脂质激酶和结合蛋白，氧化还原酶，蛋白激酶，蛋白磷酸酶，受体蛋白，RNA结合蛋白，转录因子/起始复合蛋白，转录共激活因子/ Corepressor蛋白，翻译起始复合蛋白，Ubitquitin缀合 系统蛋白和囊泡蛋白。
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