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1. 发明申请

WO2007015840A2 REAGENTS FOR THE DETECTION OF PHOSPHORYLATED ATR KINASE (SER 428/SER 2317) AND USES THEREOF 审中-公开
标题翻译：用于检测磷酸化ATR激酶（SER 428 / SER 2317）的试剂及其用途
公开(公告)号：WO2007015840A2
公开(公告)日：2007-02-08
申请号：PCT/US2006/027791
申请日：2006-07-18
申请人： CELL SIGNALING TECHNOLOGY, INC. , LIVINGSTONE, Mark , RUAN, Hong , POLAKIEWICZ, Roberto
发明人： LIVINGSTONE, Mark , RUAN, Hong , POLAKIEWICZ, Roberto
IPC分类号： G01N33/574
CPC分类号： G01N33/573 , C07K16/40 , C07K16/44 , C12N9/1205 , C12Q1/485 , G01N2500/00 , Y10S435/975
摘要： The invention discloses two novel phosphorylation sites in human ATR kinase, serine 428 (Ser428) and serine 2317 (Ser2317) respectively, and provides reagents, including antibodies and AQUA peptides, that selectively bind to and/or detect ATR only when phosphorylated at one or more of these respective sites, but do not bind to ATR when not phosphorylated at these respective sites. Also provided are methods for determining the phosphorylation of ATR kinase in a biological sample, by using a detectable reagent that binds to ATR only when phosphorylated at Ser428 and/or Ser2317. Kits comprising the ATR (Ser428, Ser2317)- specific reagents of the invention are also provided.
摘要翻译：本发明公开了分别在人ATR激酶，丝氨酸428（Ser428）和丝氨酸2317（Ser2317）中的两个新的磷酸化位点，并提供了选择性结合和/或检测ATR的试剂，包括抗体和AQUA肽，更多的这些各自的位点，但是当不在这些相应位点处未磷酸化时，不结合ATR。还提供了通过使用仅在Ser428和/或Ser2317磷酸化时仅结合ATR的可检测试剂来测定生物样品中ATR激酶的磷酸化的方法。还提供了包含本发明的ATR（Ser428，Ser2317）特异性试剂的试剂盒。

2. 发明申请

WO2008013954A2 TYROSINE PHOSPHORYLATION SITES 审中-公开
标题翻译：酪氨酸磷酸化位点
公开(公告)号：WO2008013954A2
公开(公告)日：2008-01-31
申请号：PCT/US2007/016937
申请日：2007-07-27
申请人： CELL SIGNALING TECHNOLOGY, INC. , RIKOVA, Klarisa , FARNSWORTH, Charles , MORITZ, Albrecht , LEE, Kimberly , POLAKIEWICZ, Roberto , GUO, Ailan , SPEK, Erik
发明人： RIKOVA, Klarisa , FARNSWORTH, Charles , MORITZ, Albrecht , LEE, Kimberly , POLAKIEWICZ, Roberto , GUO, Ailan , SPEK, Erik
IPC分类号： A61K39/395
CPC分类号： C07K16/44
摘要： The invention discloses 349 novel phosphorylation sites identified in carcinoma, 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：本发明公开了在癌中鉴定的349个新的磷酸化位点，包含本发明磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新型磷酸化位点的抗体，以及诊断和治疗用途以上。

3. 发明申请

WO2008013934A2 TYROSINE PHOSPHORYLATION SITES 审中-公开
标题翻译：酪氨酸磷酸化位点
公开(公告)号：WO2008013934A2
公开(公告)日：2008-01-31
申请号：PCT/US2007/016888
申请日：2007-07-27
申请人： CELL SIGNALING TECHNOLOGY, INC. , POLAKIEWICZ, Roberto , LEE, Kimberly , FARNSWORTH, Charles , GUO, Ailan , RIKOVA, Klarisa , MORITZ, Albrecht , SPEK, Erik
发明人： POLAKIEWICZ, Roberto , LEE, Kimberly , FARNSWORTH, Charles , GUO, Ailan , RIKOVA, Klarisa , MORITZ, Albrecht , SPEK, Erik
IPC分类号： C07K16/40
CPC分类号： C07K16/44 , C07K16/30 , C07K2317/34 , G01N33/573 , G01N33/574 , G01N33/6854
摘要： The invention discloses 347 novel phosphorylation sites identified in carcinoma, 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：本发明公开了在癌中鉴定的347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。

4. 发明申请

WO2007127335A2 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN ATM AND ATR KINASE SIGNALING PATHWAYS 审中-公开
标题翻译：用于检测ATM和ATR激酶信号途径中蛋白质磷酸化的试剂
公开(公告)号：WO2007127335A2
公开(公告)日：2007-11-08
申请号：PCT/US2007/010179
申请日：2007-04-27
申请人： CELL SIGNALING TECHNOLOGY, INC. , POLAKIEWICZ, Roberto , LEE, Kimberly , GUO, Ailan , STOKES, Matthew
发明人： POLAKIEWICZ, Roberto , LEE, Kimberly , GUO, Ailan , STOKES, Matthew
IPC分类号： C12Q1/68
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。

5. 发明申请

WO2007015886A2 PHOSPHORYLATED PROTEIN MARKERS OF GLEEVEC-RESISTANT CHRONIC MYELOGENOUS LEUKEMIA 审中-公开
标题翻译：耐药性慢性髓性白血病的磷酸化蛋白标记
公开(公告)号：WO2007015886A2
公开(公告)日：2007-02-08
申请号：PCT/US2006/027936
申请日：2006-07-19
申请人： CELL SIGNALING TECHNOLOGY, INC. , GOSS, Valerie , LEE, Kimberly , POLAKIEWICZ, Roberto , DRUKER, Brian , DENINGER, Michael , GRISWOLD, Ian
发明人： GOSS, Valerie , LEE, Kimberly , POLAKIEWICZ, Roberto , DRUKER, Brian , DENINGER, Michael , GRISWOLD, Ian
IPC分类号： G01N33/574
CPC分类号： G01N33/57426 , C12Q1/485 , G01N2500/04 , G01N2800/52
摘要： The invention discloses ten (10) phosphorylated protein markers that are only detected in Chronic Myelogenous Leukemia (CML) upon activation of Gleevec®-resistant BCR-ABL kinases, and provides reagents, including phosphorylation-site specific antibodies and AQUA peptides, for the selective detection and quantification of these marker phosphoproteins/sites. Also provided are methods for identifying a CML patient that has, or is likely to develop, resistance to Gleevec® (Imanitib mesylate, STI-571) by detecting and/or quantifying one or more of the disclosed phosphorylated sites/proteins in a biological sample from the patient. Methods for identifying a compound that inhibits a Gleevec®- resistant BCR-ABL mutant by determining the effect of the compound on one or more of the disclosed phosphorylated marker proteins are also provided.
摘要翻译：本发明公开了在激活Gleevec抗性BCR-ABL激酶时仅在慢性骨髓性白血病（CML）中检测到的十（10）种磷酸化蛋白质标记，并为选择性提供试剂，包括磷酸化位点特异性抗体和AQUA肽检测和定量这些标记磷酸蛋白/位点。还提供了通过检测和/或定量生物样品中一种或多种所公开的磷酸化位点/蛋白质来鉴定已经或可能发展为Gleevec（甲磺酸伊马尼替尼，STI-571）的CML患者的方法来自病人。还提供了通过确定化合物对一种或多种所公开的磷酸化标记蛋白的作用来鉴定抑制抗Gleevec抗性BCR-ABL突变体的化合物的方法。

6. 发明申请

WO2005083444A1 PROTEIN PHOSPHORYLATION IN T-CELL RECEPTOR SIGNALING PATHWAYS 审中-公开
标题翻译：蛋白质磷酸化在T细胞受体信号通路中的作用
公开(公告)号：WO2005083444A1
公开(公告)日：2005-09-09
申请号：PCT/US2004/032511
申请日：2004-10-04
申请人： CELL SIGNALING TECHNOLOGY, INC. , MORITZ, Albrecht , LEE, Kimberly , RUSH, John , POLAKIEWICZ, Roberto
发明人： MORITZ, Albrecht , LEE, Kimberly , RUSH, John , POLAKIEWICZ, Roberto
IPC分类号： G01N33/68
CPC分类号： G01N33/6872 , C07K14/47 , C07K16/44 , 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。

7. 发明申请

WO2005083113A1 PROTEIN PHOSPHORYLATION IN C-SRC SIGNALING PATHWAYS 审中-公开
标题翻译： C-SRC信号通路中的蛋白质磷酸化
公开(公告)号：WO2005083113A1
公开(公告)日：2005-09-09
申请号：PCT/US2004/026199
申请日：2004-08-12
申请人： CELL SIGNALING TECHNOLOGY, INC. , MORITZ, Albrecht , LEE, Kimberly , RUSH, John , POLAKIEWICZ, Roberto
发明人： MORITZ, Albrecht , LEE, Kimberly , RUSH, John , POLAKIEWICZ, Roberto
IPC分类号： C12Q1/48
CPC分类号： G01N33/6872 , C07K14/47 , C07K16/44 , C12Q1/25 , C12Q1/485 , G01N33/6842
摘要： The invention discloses 102 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of c-Src 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: Adaptor/ Scaffold proteins, Actin Binding proteins, Cytoskeletal proteins, G protein/ GTPase Activating protein/Guanine Nucleotide Exchange Factor proteins, Helicases, RNA Binding proteins, Transcription/Translation Factor or Initiation Complex proteins, Cellular Metabolism Enzymes, and Vesicle proteins.
摘要翻译：本发明公开了在c-Src激酶下游的信号转导蛋白和途径中鉴定的102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以下蛋白质类型的位点：适配器/支架蛋白，肌动蛋白结合蛋白，细胞骨架蛋白，G蛋白/ GTPase激活蛋白/鸟嘌呤核苷酸交换因子蛋白，Helicases，RNA结合蛋白，转录因子/翻译因子或起始复合蛋白，细胞代谢酶和囊泡蛋白。

8. 发明申请

WO2008013948A3 TYROSINE PHOSPHORYLATION SITES 审中-公开
公开(公告)号：WO2008013948A3
公开(公告)日：2008-01-31
申请号：PCT/US2007/016927
申请日：2007-07-27
申请人： CELL SIGNALING TECHNOLOGY, INC. , POLAKIEWICZ, Roberto , LEE, Kimberly , FARNSWORTH, Charles , GUO, Ailan , RIKOVA, Klarisa , MORITZ, Albrecht , SPEK, Erik
发明人： POLAKIEWICZ, Roberto , LEE, Kimberly , FARNSWORTH, Charles , GUO, Ailan , RIKOVA, Klarisa , MORITZ, Albrecht , SPEK, Erik
IPC分类号： A61K39/395
摘要： The invention discloses 349 novel phosphorylation sites identified in carcinoma, 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.

9. 发明申请

WO2007133688A2 REAGENTS FOR THE DETECTION OF TYROSINE PHOSPHORYLATION IN BRAIN ISCHEMIA SIGNALING PATHWAYS 审中-公开
标题翻译：用于检测脑缺血信号通路中酪氨酸磷酸化的试剂
公开(公告)号：WO2007133688A2
公开(公告)日：2007-11-22
申请号：PCT/US2007/011418
申请日：2007-05-11
申请人： CELL SIGNALING TECHNOLOGY, INC. , GUO, Ailan , POLAKIEWICZ, Roberto , LEE, Kimberly
发明人： GUO, Ailan , POLAKIEWICZ, Roberto , LEE, Kimberly
IPC分类号： B22D11/00 , B22D11/126
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，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。

10. 发明申请

WO2007075933A3 TRANSLOCATION AND MUTANT CSF1R KINASE IN HUMAN LEUKEMIA 审中-公开
公开(公告)号：WO2007075933A3
公开(公告)日：2007-07-05
申请号：PCT/US2006/048867
申请日：2006-12-21
申请人： CELL SIGNALING TECHNOLOGY, INC. , GU, Ting-lei , GOSS, Valerie , POLAKIEWICZ, Roberto , DRUKER, Brian , WALTERS, Denise
发明人： GU, Ting-lei , GOSS, Valerie , POLAKIEWICZ, Roberto , DRUKER, Brian , WALTERS, Denise
IPC分类号： C07K14/00 , C07K19/00 , C07H21/04 , C12N5/00 , C12N15/00
摘要： In accordance with the invention, a novel gene translocation, (3p21 , 5q33), in human myelogenous leukemia (AML) that results in a fusion protein combining part of RNA Binding Protein-6 (RBM6) with Macrophage Colony Stimulating Factor-1 Receptor (CSF1 R) kinase has now been identified. The RBM6-CSF1 R fusion protein and truncated CSF1R kinase itself, which both retain CSF1 R tyrosine kinase activity, were 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 CSF1R kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein and truncated kinase enables new methods for determining the presence of these mutant CSF 1 R 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.

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