公开(公告)号：US07807789B2

公开(公告)日：2010-10-05

申请号：US11821130

申请日：2007-06-21

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

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

IPC分类号： C12P21/08 ,  C07K16/28

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：US20100173322A1

公开(公告)日：2010-07-08

申请号：US12074876

申请日：2008-03-06

申请人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Kimberly Lee ,  Erik Spek ,  Charles Farnsworth ,  Francesco Boccalatte

发明人： Roberto Polakiewicz ,  Ailan Guo ,  Albrecht Moritz ,  Kimberly Lee ,  Erik Spek ,  Charles Farnsworth ,  Francesco Boccalatte

IPC分类号： G01N33/53 ,  C07K16/18 ,  G01N33/566

CPC分类号： C07K16/3061 ,  C07K2317/34 ,  G01N33/6842 ,  G01N33/6848

摘要： The invention discloses nearly 219 novel phosphorylation sites identified in signal transduction proteins and pathways underlying Anaplastic Large Cell Lymphoma (ALCL) involving the NPM-ALK 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.

摘要翻译： 本发明公开了在信号转导蛋白中鉴定的近219个新的磷酸化位点和涉及NPM-ALK易位/融合的间变性大细胞淋巴瘤（ALCL）的途径，并且提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于 这些磷酸化位点/蛋白质的选择性检测和定量，以及用于这些目的的试剂的方法。

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：US20090203034A1

公开(公告)日：2009-08-13

申请号：US12227318

申请日：2007-05-11

申请人： Ailan Guo ,  Roberto Polakiewicz ,  Kimberly Lee

发明人： Ailan Guo ,  Roberto Polakiewicz ,  Kimberly Lee

IPC分类号： G01N33/53 ,  C12Q1/48 ,  G01N33/536 ,  C07K16/18 ,  C07K14/47 ,  C07K7/06 ,  C07K7/08 ,  C12N5/16

CPC分类号： G01N33/6848 ,  C07K16/44 ,  G01N33/6842 ,  G01N33/6872 ,  G01N2800/2871

摘要： The invention discloses 99 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Brain Ischemia, 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, adhesion proteins, G proteins/GTPase/Guanine nucleotide exchange factors, Calcium binding proteins, cytoskeletal proteins, Channel proteins, Chaperone proteins, Helicases, Motor proteins, Translation proteins, RNA binding proteins, Ubiquitin conjugating system proteins, vesicle proteins and Receptor proteins.

摘要翻译： 本发明公开了在信号转导蛋白中识别的99个新的磷酸化位点和人类脑缺血的基因，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。 鉴定的磷酸化位点之间是以下蛋白质类型中发生的位点：蛋白激酶，衔接/支架蛋白，粘附蛋白，G蛋白/ GTP酶/鸟嘌呤核苷酸交换因子，钙结合蛋白，细胞骨架蛋白，通道蛋白，伴侣蛋白，Helicases， 运动蛋白，翻译蛋白，RNA结合蛋白，泛素缀合系统蛋白，囊泡蛋白和受体蛋白。

公开(公告)号：US20090298093A1

公开(公告)日：2009-12-03

申请号：US12226800

申请日：2007-04-27

申请人： Roberto Polakiewicz ,  Kimberly Lee ,  Ailan Guo ,  Matthew Stokes

发明人： Roberto Polakiewicz ,  Kimberly Lee ,  Ailan Guo ,  Matthew Stokes

IPC分类号： G01N33/573 ,  C12Q1/48 ,  C07K16/40

CPC分类号： C07K16/44 ,  C07B59/008

摘要： The invention discloses nearly 300 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human ATM/ATR kinase signaling pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection, profiling 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: DNA repair proteins, Adaptor/Scaffold proteins, Cell cycle regulation proteins, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, DNA binding proteins, DNA replication proteins, Kinases, Disease associated proteins proteins, Methyltransferase, Ubiquitin conjugating proteins, Proteases, Phosphatases, and Transcription proteins.

摘要翻译： 本发明公开了在信号转导蛋白中识别的近300个新的磷酸化位点和人类ATM / ATR激酶信号通路下的途径，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，分析和定量 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：DNA修复蛋白，适配器/支架蛋白，细胞周期调节蛋白，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，DNA结合蛋白，DNA复制蛋白，激酶， 疾病相关蛋白质蛋白，甲基转移酶，泛素缀合蛋白，蛋白酶，磷酸酶和转录蛋白。

公开(公告)号：US20100159477A1

公开(公告)日：2010-06-24

申请号：US12309311

申请日：2007-07-13

申请人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

发明人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

IPC分类号： G01N33/573 ,  G01N33/53 ,  C07K16/00 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00 ,  C12N5/071 ,  C12N5/16 ,  C12N5/18

CPC分类号： G01N33/68 ,  C12Q1/485 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/6848 ,  G01N33/6872

摘要： 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 suface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

摘要翻译： 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。

公开(公告)号：US20080248490A1

公开(公告)日：2008-10-09

申请号：US12074224

申请日：2008-02-29

申请人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

发明人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

IPC分类号： C07K16/18 ,  G01N33/53

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。

公开(公告)号：US07935790B2

公开(公告)日：2011-05-03

申请号：US11503336

申请日：2006-08-11

申请人： Albrecht Moritz ,  Roberto Polakiewicz ,  John Edward Rush ,  Kimberly Lee

发明人： Albrecht Moritz ,  Roberto Polakiewicz ,  John Edward Rush ,  Kimberly Lee

IPC分类号： C07K16/00 ,  C07K16/18

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。