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公开(公告)号：US09453845B2
公开(公告)日：2016-09-27
申请号：US12931445
申请日：2011-02-01
IPC分类号： C12Q1/70 , B01D59/44 , H01J49/00 , G01N15/06 , G01N33/00 , G01N33/48 , G01N33/53 , G01N33/68
CPC分类号： G01N33/6848 , B01D15/12 , B01D15/325 , B01D15/3809 , B01D15/3823 , B01D15/422 , G01N30/7233 , G01N2560/00 , G01N2570/00 , H01J49/00
摘要： The invention relates to a method for determining the presence of at least one distinct polypeptide in a biological sample comprising contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct polypeptide in a sequence-specific manner such that at least one distinct peptide having a predetermined peptide measured accurate mass would result if the at least one distinct polypeptide were present in the biological sample, to obtain a hydrolyzed sample; bringing the hydrolyzed sample in contact with a substrate comprising at least one immobilized binding partner, wherein the at least one immobilized binding partner is capable of specifically binding the distinct peptide; removing the hydrolyzed sample from the substrate in a manner such that the distinct peptide would remain bound to the immobilized binding partner; contacting the substrate with an elution solution, wherein the distinct peptide would dissociate from the immobilized binding partner into the elution solution; subjecting a portion of the elution solution to liquid chromatography to segregate a plurality of molecules in the portion of the elution solution to obtain sorted molecules; determining the measured accurate mass of at least one sorted molecule present in the elution solution; and determining the presence of the at least one distinct polypeptide in the biological sample when a measured accurate mass of at least one molecule is substantially equal to the predetermined peptide measured accurate mass.
摘要翻译： 本发明涉及一种用于确定生物样品中至少一种不同多肽的存在的方法，包括使生物样品与水解试剂接触，其中水解试剂能够以序列特异性方式水解不同的多肽， 如果至少一种不同的多肽存在于生物样品中，则得到具有测定精确质量的预定肽的至少一种不同的肽，以获得水解样品; 使水解的样品与包含至少一个固定的结合配偶体的底物接触，其中至少一个固定的结合配偶体能够特异性结合不同的肽; 以使得不同的肽保持与固定的结合配偶体结合的方式从底物中除去水解的样品; 使所述底物与洗脱溶液接触，其中所述不同的肽将从固定的结合配偶体解离成洗脱溶液; 使洗脱溶液的一部分进行液相色谱分离洗脱溶液部分中的多个分子，得到分选的分子; 确定洗脱溶液中存在的至少一种分选分子的测量精确质量; 以及当所测量的至少一个分子的精确质量基本上等于所测量的精确质量的预定肽时，确定生物样品中至少一种不同多肽的存在。
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公开(公告)号：US20110244445A1
公开(公告)日：2011-10-06
申请号：US12931445
申请日：2011-02-01
CPC分类号： G01N33/6848 , B01D15/12 , B01D15/325 , B01D15/3809 , B01D15/3823 , B01D15/422 , G01N30/7233 , G01N2560/00 , G01N2570/00 , H01J49/00
摘要： The invention relates to a method for determining the presence of at least one distinct polypeptide in a biological sample comprising contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct polypeptide in a sequence-specific manner such that at least one distinct peptide having a predetermined peptide measured accurate mass would result if the at least one distinct polypeptide were present in the biological sample, to obtain a hydrolyzed sample; bringing the hydrolyzed sample in contact with a substrate comprising at least one immobilized binding partner, wherein the at least one immobilized binding partner is capable of specifically binding the distinct peptide; removing the hydrolyzed sample from the substrate in a manner such that the distinct peptide would remain bound to the immobilized binding partner; contacting the substrate with an elution solution, wherein the distinct peptide would dissociate from the immobilized binding partner into the elution solution; subjecting a portion of the elution solution to liquid chromatography to segregate a plurality of molecules in the portion of the elution solution to obtain sorted molecules; determining the measured accurate mass of at least one sorted molecule present in the elution solution; and determining the presence of the at least one distinct polypeptide in the biological sample when a measured accurate mass of at least one molecule is substantially equal to the predetermined peptide measured accurate mass.
摘要翻译： 本发明涉及一种用于确定生物样品中至少一种不同多肽的存在的方法，包括使生物样品与水解试剂接触，其中水解试剂能够以序列特异性方式水解不同的多肽， 如果至少一种不同的多肽存在于生物样品中，则得到具有测定精确质量的预定肽的至少一种不同的肽，以获得水解样品; 使水解的样品与包含至少一个固定的结合配偶体的底物接触，其中至少一个固定的结合配偶体能够特异性结合不同的肽; 以使得不同的肽保持与固定的结合配偶体结合的方式从底物中除去水解的样品; 使所述底物与洗脱溶液接触，其中所述不同的肽将从固定的结合配偶体解离成洗脱溶液; 使洗脱溶液的一部分进行液相色谱分离洗脱溶液部分中的多个分子，得到分选的分子; 确定洗脱溶液中存在的至少一种分选分子的测量精确质量; 以及当所测量的至少一个分子的精确质量基本上等于所测量的精确质量的预定肽时，确定生物样品中至少一种不同多肽的存在。
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公开(公告)号：US20100173428A1
公开(公告)日：2010-07-08
申请号：US12683835
申请日：2010-01-07
申请人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Charles Farnsworth , Hong Ren , Klarisa Rikova , John Edward Rush, II , Matthew Stokes , Meghan Tucker , Yu Li
发明人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Charles Farnsworth , Hong Ren , Klarisa Rikova , John Edward Rush, II , Matthew Stokes , Meghan Tucker , Yu Li
CPC分类号： C07K16/18 , C07K16/40 , C12Q1/485 , G01N33/6872
摘要： The invention discloses 461 novel phosphorylation sites identified in basophilic Ser/Thr kinase signaling pathways, 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： 本发明公开了在嗜碱性Ser / Thr激酶信号通路中鉴定的461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 以上。
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公开(公告)号：US20110045603A1
公开(公告)日：2011-02-24
申请号：US12763886
申请日：2010-04-20
申请人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Ting-Lei Gu , Jian Yu , Charles Lawrence Farnsworth , Corinne Michaud , Hong Ren , Jessica Ann Cherry , Jing Zhou , Valerie Lee Goss , Erik Spek , Yu Li , Meghan Ann Tucker , John Edward Rush, II , Matthew Stokes , Klarisa Rikova
发明人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Ting-Lei Gu , Jian Yu , Charles Lawrence Farnsworth , Corinne Michaud , Hong Ren , Jessica Ann Cherry , Jing Zhou , Valerie Lee Goss , Erik Spek , Yu Li , Meghan Ann Tucker , John Edward Rush, II , Matthew Stokes , Klarisa Rikova
CPC分类号： C07K16/18 , C07K14/47 , C07K16/44 , G01N33/6842
摘要： The invention discloses 990 novel phosphorylation sites identified in carcinoma and leukemia, 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： 本发明公开了在癌和白血病中鉴定的990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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5.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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6.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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7.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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8.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：US20110105732A1
公开(公告)日：2011-05-05
申请号：US12985879
申请日：2011-01-06
申请人： Ailan Guo , Roberto Polakiewicz , Charles Farnsworth , Klarisa Rikova , Albrecht Moritz , Kimberly Lee , Yu Li
发明人： Ailan Guo , Roberto Polakiewicz , Charles Farnsworth , Klarisa Rikova , Albrecht Moritz , Kimberly Lee , Yu Li
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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9.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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10.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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