公开(公告)号：US08466160B2

公开(公告)日：2013-06-18

申请号：US12982490

申请日：2010-12-30

申请人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Eleanor Crosby ,  Qingfu Zeng ,  Kimberly A Lee

发明人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Eleanor Crosby ,  Qingfu Zeng ,  Kimberly A Lee

IPC分类号： A01N43/54 ,  G01N33/574 ,  C12Q1/68

CPC分类号： A61K31/506 ,  G01N33/57423 ,  G01N33/6893 ,  G01N2333/71

摘要： The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFRα is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFRα-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFRα is expressed, and for determining whether a compound inhibits the progression of a PDGFRα-expressing mammalian NSCLC tumor.

摘要翻译： 本发明公开了一种以前未确定的哺乳动物非小细胞肺癌（NSCLC）的子集，其中血小板衍生生长因子受体α（PDGFRalpha）被表达并正在驱动该疾病，并且提供了鉴定属于哺乳动物的NSCLC肿瘤的方法 其中PDGFRα被表达的NSCLC肿瘤的子集，并用于鉴定可能对PDGFRα抑制性治疗反应的NSCLC肿瘤。 本发明还提供抑制其中表达PDGFRα的哺乳动物NSCLC肿瘤进展的方法，以及用于确定化合物是否抑制表达PDGFRα的哺乳动物NSCLC肿瘤的进展的方法。

公开(公告)号：US20070148711A1

公开(公告)日：2007-06-28

申请号：US11174051

申请日：2005-07-01

申请人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Crosby ,  Qingfu Zeng ,  Kimberly Lee

发明人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Crosby ,  Qingfu Zeng ,  Kimberly Lee

IPC分类号： G01N33/574 ,  A61K31/506

CPC分类号： A61K31/506 ,  G01N33/57423 ,  G01N33/6893 ,  G01N2333/71

摘要： The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFRα is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFRα-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFRα is expressed, and for determining whether a compound inhibits the progression of a PDGFRα-expressing mammalian NSCLC tumor.

摘要翻译： 本发明公开了一种以前未确定的哺乳动物非小细胞肺癌（NSCLC）的子集，其中血小板衍生生长因子受体α（PDGFRalpha）被表达并正在驱动该疾病，并且提供了鉴定属于哺乳动物的NSCLC肿瘤的方法 其中PDGFRα被表达的NSCLC肿瘤的子集，并用于鉴定可能对PDGFRα抑制性治疗反应的NSCLC肿瘤。 本发明还提供抑制其中表达PDGFRα的哺乳动物NSCLC肿瘤进展的方法，以及用于确定化合物是否抑制表达PDGFRα的哺乳动物NSCLC肿瘤的进展的方法。

公开(公告)号：US07932044B2

公开(公告)日：2011-04-26

申请号：US11174051

申请日：2005-07-01

申请人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Crosby ,  Qingfu Zeng ,  Kimberly Lee

发明人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Crosby ,  Qingfu Zeng ,  Kimberly Lee

IPC分类号： G01N33/53 ,  G01N33/574 ,  C12Q1/68

CPC分类号： A61K31/506 ,  G01N33/57423 ,  G01N33/6893 ,  G01N2333/71

摘要： The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFRα is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFRα-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFRα is expressed, and for determining whether a compound inhibits the progression of a PDGFRα-expressing mammalian NSCLC tumor.

摘要翻译： 本发明公开了一种以前未确认的哺乳动物非小细胞肺癌（NSCLC）的亚群，其中血小板衍生生长因子受体α（PDGFRα）被表达并正在驱动该疾病，并且提供了鉴定哺乳动物NSCLC肿瘤属于 其中表达PDGFRα的NSCLC肿瘤的子集，以及用于鉴定可能对PDGFRα抑制性治疗反应的NSCLC肿瘤。 本发明还提供抑制其中表达PDGFRα的哺乳动物NSCLC肿瘤进展的方法，以及用于确定化合物是否抑制表达PDGFRα的哺乳动物NSCLC肿瘤进展的方法。

公开(公告)号：US20110195447A1

公开(公告)日：2011-08-11

申请号：US12982490

申请日：2010-12-30

申请人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Crosby ,  Qingfu Zeng ,  Kimberly Lee

发明人： Klarisa Rikova ,  Roberto Polakiewicz ,  Ailan Guo ,  Katherine Crosby ,  Qingfu Zeng ,  Kimberly Lee

IPC分类号： C12Q1/18

CPC分类号： A61K31/506 ,  G01N33/57423 ,  G01N33/6893 ,  G01N2333/71

摘要： The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFRα is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFRα-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFRα is expressed, and for determining whether a compound inhibits the progression of a PDGFRα-expressing mammalian NSCLC tumor.

摘要翻译： 本发明公开了一种以前未确认的哺乳动物非小细胞肺癌（NSCLC）的亚群，其中血小板衍生生长因子受体α（PDGFRα）被表达并正在驱动该疾病，并且提供了鉴定哺乳动物NSCLC肿瘤属于 其中表达PDGFRα的NSCLC肿瘤的子集，以及用于鉴定可能对PDGFRα抑制性治疗反应的NSCLC肿瘤。 本发明还提供抑制其中表达PDGFRα的哺乳动物NSCLC肿瘤进展的方法，以及用于确定化合物是否抑制表达PDGFRα的哺乳动物NSCLC肿瘤进展的方法。

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。

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。

公开(公告)号：US20100151495A9

公开(公告)日：2010-06-17

申请号：US12074228

申请日：2008-02-29

申请人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Klarisa Rikova ,  Kimberly Lee ,  Erik Spek ,  Yu Li ,  Charles Farnsworth

发明人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Klarisa Rikova ,  Kimberly Lee ,  Erik Spek ,  Yu Li ,  Charles Farnsworth

IPC分类号： G01N33/53 ,  C07K16/18 ,  C07K14/00 ,  C12N5/18

CPC分类号： C07K16/44 ,  G01N33/57426

摘要： The invention discloses nearly 443 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: Protein kinases (including Serine/Threonine dual specificity, and Tyrosine kinases), Adaptor/Scaffold proteins, Transcription factors, Phospoatases, Tumor supressors, Ubiquitin conjugating system proteins, Translation initiation complex proteins, RNA binding proteins, Apoptosis proteins, Adhesion proteins, G protein regulators/GTPase activating protein/Guanine nucleotide exchange factor proteins, and DNA binding/replication/repair 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近443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，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（包括丝氨酸/苏氨酸双特异性和酪氨酸激酶），适配器/支架蛋白，转录因子，磷酸酶，肿瘤抑制因子，泛素缀合系统蛋白，翻译起始复合体 蛋白质，RNA结合蛋白，细胞凋亡蛋白，粘附蛋白，G蛋白调节剂/ GTPase激活蛋白/鸟嘌呤核苷酸交换因子蛋白，以及DNA结合/复制/修复蛋白，以及其他蛋白质类型。

公开(公告)号：US20090258442A1

公开(公告)日：2009-10-15

申请号：US12074199

申请日：2008-02-29

申请人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Klarisa Rikova ,  Kimberly Lee ,  Erik Spek ,  Yu Li ,  Charles Farnsworth

发明人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Klarisa Rikova ,  Kimberly Lee ,  Erik Spek ,  Yu Li ,  Charles Farnsworth

IPC分类号： G01N33/536 ,  C07K16/18

CPC分类号： C07K16/30 ,  C07K16/44 ,  G01N33/57426 ,  G01N33/57496

摘要： The invention discloses nearly 474 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: Kinase, Adaptor/Scaffold proteins, Phosphatase, G protein Regulator/Guanine Nucleotide Exchange Factors/GTPase Activating Proteins, Cytoskeleton Proteins, DNA Binding Proteins, Phospholipase, Receptor Proteins, Enzymes, DNA Repair/Replication Proteins, Adhesion Proteins, and Proteases, 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近474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，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：激酶，适配器/支架蛋白，磷酸酶，G蛋白调节剂/鸟嘌呤核苷酸交换因子/ GTP酶活化蛋白，细胞骨架蛋白，DNA结合蛋白，磷脂酶，受体蛋白，酶， DNA修复/复制蛋白，粘附蛋白和蛋白酶，以及其他蛋白质类型。

公开(公告)号：US20110130547A1

公开(公告)日：2011-06-02

申请号：US12897363

申请日：2010-10-04

申请人： Ailan Guo ,  Kimberly Lee ,  Klarisa Rikova ,  Charles Farnsworth ,  Albrecht Moritz ,  Yu Li ,  Roberto Polakiewicz

发明人： Ailan Guo ,  Kimberly Lee ,  Klarisa Rikova ,  Charles Farnsworth ,  Albrecht Moritz ,  Yu Li ,  Roberto Polakiewicz

IPC分类号： C07K16/18

CPC分类号： C07K16/2863 ,  C07B59/008 ,  C07K2317/34

摘要： The invention discloses 168 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of, and including, EGFR kinase, 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, Calcium-Binding Proteins, Cell Cycle Regulation proteins, Cytoskeletal proteins, DNA Binding and Replication Proteins, GTPase Activating proteins, Guanine Nucleotide Exchange Factor proteins, Lipid Kinases, Receptor Tyrosine Kinases, Receptor Tyrosine Kinase ligands, Protein Kinases, Receptor and Protein Phosphatases, Transcription Factor proteins, Tumor Suppressor proteins, and Vesicle proteins.

摘要翻译： 本发明公开了在信号转导蛋白中识别的168个新的磷酸化位点和EGFR激酶下游和包括EGFR激酶的途径，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，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：肌动蛋白结合蛋白，衔接/支架蛋白，钙结合蛋白，细胞周期调节蛋白，细胞骨架蛋白，DNA结合和复制蛋白，GTP酶激活蛋白，鸟嘌呤核苷酸交换因子 蛋白质，脂质激酶，受体酪氨酸激酶，受体酪氨酸激酶配体，蛋白激酶，受体和蛋白磷酸酶，转录因子蛋白，肿瘤抑制蛋白和囊泡蛋白。

公开(公告)号：US20090061459A1

公开(公告)日：2009-03-05

申请号：US12074228

申请日：2008-02-29

申请人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Klarisa Rikova ,  Kimberly Lee ,  Erik Spek ,  Yu Li ,  Charles Farnsworth

发明人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Klarisa Rikova ,  Kimberly Lee ,  Erik Spek ,  Yu Li ,  Charles Farnsworth

IPC分类号： G01N33/53 ,  C07K16/18 ,  C07K14/00 ,  C12N5/18

CPC分类号： C07K16/44 ,  G01N33/57426

摘要： The invention discloses nearly 443 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: Protein kinases (including Serine/Threonine dual specificity, and Tyrosine kinases), Adaptor/Scaffold proteins, Transcription factors, Phospoatases, Tumor supressors, Ubiquitin conjugating system proteins, Translation initiation complex proteins, RNA binding proteins, Apoptosis proteins, Adhesion proteins, G protein regulators/GTPase activating protein/Guanine nucleotide exchange factor proteins, and DNA binding/replication/repair 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近443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，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（包括丝氨酸/苏氨酸双特异性和酪氨酸激酶），适配器/支架蛋白，转录因子，磷酸酶，肿瘤抑制因子，泛素缀合系统蛋白，翻译起始复合体 蛋白质，RNA结合蛋白，细胞凋亡蛋白，粘附蛋白，G蛋白调节剂/ GTPase激活蛋白/鸟嘌呤核苷酸交换因子蛋白，以及DNA结合/复制/修复蛋白，以及其他蛋白质类型。