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1. 发明授权

US09096855B2 Translocation and mutant ROS kinase in human non-small cell lung carcinoma 有权
标题翻译：人非小细胞肺癌易位和突变型ROS激酶
公开(公告)号：US09096855B2
公开(公告)日：2015-08-04
申请号：US12738210
申请日：2008-10-20
申请人： Ting-Lei Gu , Ailan Guo
发明人： Ting-Lei Gu , Ailan Guo
IPC分类号： C12Q1/68 , C12N15/11 , C12N15/12 , C12N15/113 , C07K14/74 , C07K14/82 , C07K16/40 , C12N9/99 , A61K39/00
CPC分类号： C12Q1/6886 , A61K2039/505 , C07K14/70539 , C07K14/82 , C07K16/40 , C07K2319/00 , C12N9/12 , C12N9/99 , C12N15/1137 , C12Q1/68 , C12Q1/6813 , C12Q1/6883 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001
摘要： In accordance with the invention, a novel gene translocation, (5q32, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of CD74 with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The CD74-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS 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.
摘要翻译：根据本发明，在人非小细胞肺癌（NSCLC）中的新基因易位（5q32,6q22），其导致将CD74的一部分与原癌基因酪氨酸蛋白激酶ROS前体（ROS）结合的融合蛋白，激酶现已被鉴定。预期CD74-ROS融合蛋白将驱动NSCLC肿瘤亚组的增殖和存活。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型ROS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融合和截短的多肽的试剂。所公开的新融合蛋白的鉴定使得能够确定生物样品中这些突变型ROS激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制以突变体多核苷酸为特征的癌症进展的方法或多肽，其也由本发明提供。

2. 发明申请

US20130209452A1 GENE DEFECTS AND MUTANT ALK KINASE IN HUMAN SOLID TUMORS 审中-公开
标题翻译：人类固体肿瘤中的基因缺陷和突变碱性激酶
公开(公告)号：US20130209452A1
公开(公告)日：2013-08-15
申请号：US13618400
申请日：2012-09-14
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： C12Q1/68 , A61K31/713 , G01N33/68
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have been identified herein in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK 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 enables 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.
摘要翻译：涉及染色体2的新型基因缺失和易位导致融合蛋白结合部分间变型淋巴瘤激酶（ALK）激酶与部分二级蛋白，已经在人体实体肿瘤中被鉴定，例如，非小细胞肺癌（NSCLC）。次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC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ALK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融合和截短的多肽的试剂。所公开的这种新的融合蛋白的鉴定使得能够筛选抑制蛋白质的化合物的方法，以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法。

3. 发明授权

US08466160B2 Identification of non-small cell lung carcinoma (NSCLC) tumors expressing PDGFR-alpha 有权
标题翻译：鉴定表达PDGFR-α的非小细胞肺癌（NSCLC）肿瘤
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。

4. 发明申请

US20130059304A1 TRANSLOCATION AND MUTANT ROS KINASE IN HUMAN NON-SMALL CELL LUNG CARCINOMA 审中-公开
公开(公告)号：US20130059304A1
公开(公告)日：2013-03-07
申请号：US13616097
申请日：2012-09-14
申请人： Ailan Guo , Anthony Possemato
发明人： Ailan Guo , Anthony Possemato
IPC分类号： G01N33/574 , G01N27/62 , G01N21/64 , C12Q1/68
CPC分类号： C12N15/1137 , C07K14/47 , C07K14/82 , C07K2319/00 , C12N9/1205 , C12N2310/14 , C12Q1/6841 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136 , C12Q2600/156 , G01N33/57423 , G01N33/57484
摘要： In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS 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.

5. 发明申请

US20110105732A1 Reagents for the Detection of Protein Phosphorylation in Carcinoma Signaling Pathways 审中-公开
标题翻译：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。

6. 发明申请

US20100120055A1 TYROSINE PHOSPHORYLATION SITES 审中-公开
标题翻译：酪氨酸磷酸化位点
公开(公告)号：US20100120055A1
公开(公告)日：2010-05-13
申请号：US12311464
申请日：2007-09-28
申请人： Peter Hornbeck , Ailan Guo , Klarisa Rikova , Albrecht Moritz , Erik Spek , Anthony Possemato , Charles Farnsworth , Francesco Boccalatte , Jian Yu , Jefrey Mitchell , John Rush , Valerie Goss , Ting-Lei Gu , Yu Li , Matthew Stokes
发明人： Peter Hornbeck , Ailan Guo , Klarisa Rikova , Albrecht Moritz , Erik Spek , Anthony Possemato , Charles Farnsworth , Francesco Boccalatte , Jian Yu , Jefrey Mitchell , John Rush , Valerie Goss , Ting-Lei Gu , Yu Li , Matthew Stokes
IPC分类号： G01N33/53 , C07K16/18
CPC分类号： C12Q1/485 , A61K38/00 , A61K39/0011 , C07K14/4748 , C07K16/30 , C07K16/3007 , C07K16/40 , C07K16/44 , C07K2317/34 , C12Q1/42 , G01N33/574 , G01N33/6812 , G01N33/6842
摘要： The invention discloses 318 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318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。

7. 发明申请

US20100093000A1 Tyrosine phosphorylation sites 审中-公开
标题翻译：酪氨酸磷酸化位点
公开(公告)号：US20100093000A1
公开(公告)日：2010-04-15
申请号：US12148550
申请日：2008-04-18
申请人： Jessica Cherry , Charles Farnsworth , Valerie L. Goss , Ting-Lei Gu , Ailan Guo , Peter Hornbeck , Yu Li , Albrecht Moritz , Anthony Possemato , Klarisa Rikova , Matthew Stokes , Jian Yu , Erik Spek , Corinne Michaud
发明人： Jessica Cherry , Charles Farnsworth , Valerie L. Goss , Ting-Lei Gu , Ailan Guo , Peter Hornbeck , Yu Li , Albrecht Moritz , Anthony Possemato , Klarisa Rikova , Matthew Stokes , Jian Yu , Erik Spek , Corinne Michaud
IPC分类号： G01N33/53 , C07K16/18
CPC分类号： C07K16/44 , G01N33/574 , G01N33/57426 , G01N2333/4725 , G01N2333/98
摘要： The invention discloses novel phosphorylation sites identified in carcinoma and/or 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/或白血病中鉴定的新的磷酸化位点，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。

8. 发明申请

US20100092992A1 LYSINE ACETYLATION SITES 审中-公开
标题翻译： LYSINE乙酰化网站
公开(公告)号：US20100092992A1
公开(公告)日：2010-04-15
申请号：US12310292
申请日：2007-08-17
申请人： Peter Hornbeck , Ting-Lei Gu , Ailan Guo , Charles Farnsworth , Yu Li , Jeffrey Mitchell
发明人： Peter Hornbeck , Ting-Lei Gu , Ailan Guo , Charles Farnsworth , Yu Li , Jeffrey Mitchell
IPC分类号： G01N33/53 , C07K16/00
CPC分类号： C07K16/44 , C07B59/008 , C07K14/47
摘要： The invention discloses 322 novel acetylation sites identified in various cancers, peptides (including AQUA peptides) comprising a acetylation site of the invention, antibodies specifically bind to a novel acetylation site of the invention, and diagnostic and therapeutic uses of the above.
摘要翻译：本发明公开了在各种癌症中鉴定的322个新的乙酰化位点，包含本发明的乙酰化位点的肽（包括AQUA肽），特异性结合本发明的新乙酰化位点的抗体，以及上述的诊断和治疗用途。

9. 发明申请

US20090124023A1 Reagens for the Detection of Protein Acetylation Signaling Pathways 审中-公开
标题翻译：用于检测蛋白质乙酰化信号通路的试剂
公开(公告)号：US20090124023A1
公开(公告)日：2009-05-14
申请号：US12227321
申请日：2007-05-11
申请人： Ailan Guo , Ting-Lei Gu , Jeffrey Mitchell , Peter Hornbeck
发明人： Ailan Guo , Ting-Lei Gu , Jeffrey Mitchell , Peter Hornbeck
IPC分类号： G01N33/566 , C07K16/18
CPC分类号： G01N33/68 , C07K16/18 , C07K16/44 , G01N33/6842
摘要： The invention discloses 432 novel acetylation sites identified in signal transduction proteins and pathways underlying human protein acetylation signaling pathways, and provides acetylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these acetylated sites/proteins, as well as methods of using the reagents for such purpose. Among the acetylation sites identified are sites occurring in the following protein types: Acetyltransferases, Adaptor/Scaffold proteins, Actin binding proteins, Adhesion proteins, Apoptosis proteins, Calcium-binding proteins, Cell Cycle Regulation proteins, Cell Surface proteins, DNA binding proteins, DNA replication proteins, Channel proteins, Chaperone proteins, Cellular Metabolism enzymes, Cytoskeletal proteins, DNA repair proteins, Endoplasmic reticulum proteins, Enzyme proteins, G protein and GTPase Activating proteins, Guanine Nucleotide Exchange Factors, Helicase proteins, Isomerase proteins, Extracelluar matrix proteins, Hydrolases, Ligase proteins, Lipid kinases, Inhibtor proteins, Lipid Binding proteins and Lyases.
摘要翻译：本发明公开了在信号转导蛋白中鉴定的432个新的乙酰化位点和基于人蛋白质乙酰化信号通路的途径，并提供乙酰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乙酰化位点/蛋白质，以及使用试剂用于此目的的方法。确定的乙酰化位点之间的位点是发生在以下蛋白质类型中的位点：乙酰转移酶，适配器/支架蛋白，肌动蛋白结合蛋白，粘附蛋白，细胞凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，细胞表面蛋白，DNA结合蛋白，DNA 复制蛋白，通道蛋白，伴侣蛋白，细胞代谢酶，细胞骨架蛋白，DNA修复蛋白，内质网蛋白，酶蛋白，G蛋白和GTP酶活化蛋白，鸟嘌呤核苷酸交换因子，Helicase蛋白，异构酶蛋白，Extracelluar基质蛋白，水解酶，连接酶蛋白，脂质激酶，抑制蛋白，脂质结合蛋白和裂解酶。

10. 发明申请

US20090053831A1 Tyrosine phosphorylation sites 审中-公开
标题翻译：酪氨酸磷酸化位点
公开(公告)号：US20090053831A1
公开(公告)日：2009-02-26
申请号：US12150903
申请日：2008-04-30
申请人： Peter Hornbeck , Ailan Guo , Ting-Lei Gu , Klarisa Rikova , Albrecht Moritz , Charles Farnsworth , Matthew Stokes , Jian Yu , Erik Spek , Yu Li , Valerie Goss , Francesco Boccalatte
发明人： Peter Hornbeck , Ailan Guo , Ting-Lei Gu , Klarisa Rikova , Albrecht Moritz , Charles Farnsworth , Matthew Stokes , Jian Yu , Erik Spek , Yu Li , Valerie Goss , Francesco Boccalatte
IPC分类号： G01N33/536 , C07K16/18
CPC分类号： C07K16/30 , C07K16/44 , G01N33/57426 , G01N33/57484 , G01N33/577
摘要： The invention discloses 405 novel phosphorylation sites identified in carcinoma and/or 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/或白血病中鉴定的405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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