公开(公告)号：US20100221737A1

公开(公告)日：2010-09-02

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 ,  C07H21/04 ,  C07K14/00 ,  C07K16/00 ,  G01N33/53

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，以及抑制以突变型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。

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。

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.

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。

公开(公告)号：US20120208985A1

公开(公告)日：2012-08-16

申请号：US13289651

申请日：2011-11-04

申请人： Michael Comb ,  Ailan Guo ,  John Edward Rush, II ,  Jun-Ming Cai ,  Jing Li ,  Jing Zhou

发明人： Michael Comb ,  Ailan Guo ,  John Edward Rush, II ,  Jun-Ming Cai ,  Jing Li ,  Jing Zhou

IPC分类号： C07K16/00

CPC分类号： C07K16/18 ,  C07K16/44 ,  C07K2317/14 ,  C07K2317/20 ,  C07K2317/33 ,  C07K2317/34

摘要： There is provided a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) at least one sumoylated lysine residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said sumoylated lysine residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs. Also provided is a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) a C-terminal aspartic acid residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said C-terminal aspartic acid residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs.

摘要翻译： 提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）至少一个sumoylated赖氨酸残基组成的复发性修饰基序，和（ii）通过肽键与所述sumoylated结合的一个或多个简并氨基酸 赖氨酸残基，所述抗体特异性结合所述基序在其再次发生的生物体内的多个非同源肽或蛋白质中。 还提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）C末端天冬氨酸残基组成的重复修饰基序，和（ii）一个或多个与肽键结合的简并氨基酸与所述 C末端天冬氨酸残基，所述抗体特异性结合所述基序在复制的生物体内的多个非同源肽或蛋白质。

公开(公告)号：US09249231B2

公开(公告)日：2016-02-02

申请号：US13289651

申请日：2011-11-04

申请人： Michael Comb ,  Ailan Guo ,  John Edward Rush, II ,  Jun-Ming Cai ,  Jing Li ,  Jing Zhou

发明人： Michael Comb ,  Ailan Guo ,  John Edward Rush, II ,  Jun-Ming Cai ,  Jing Li ,  Jing Zhou

IPC分类号： C07K16/44 ,  C07K16/00 ,  C12N5/07

CPC分类号： C07K16/18 ,  C07K16/44 ,  C07K2317/14 ,  C07K2317/20 ,  C07K2317/33 ,  C07K2317/34

摘要： There is provided a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) at least one sumoylated lysine residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said sumoylated lysine residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs. Also provided is a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) a C-terminal aspartic acid residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said C-terminal aspartic acid residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs.

摘要翻译： 提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）至少一个sumoylated赖氨酸残基组成的复发性修饰基序，和（ii）通过肽键与所述sumoylated结合的一个或多个简并氨基酸 赖氨酸残基，所述抗体特异性结合所述基序在其再次发生的生物体内的多个非同源肽或蛋白质中。 还提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）C末端天冬氨酸残基组成的重复修饰基序，和（ii）一个或多个与肽键结合的简并氨基酸与所述 C末端天冬氨酸残基，所述抗体特异性结合所述基序在其再次发生的生物体内的多个非同源肽或蛋白质中。

公开(公告)号：US20130059305A1

公开(公告)日：2013-03-07

申请号：US13616107

申请日：2012-09-14

申请人： Ailan Guo ,  Anthony Possemato

发明人： Ailan Guo ,  Anthony Possemato

IPC分类号： C12Q1/68 ,  G01N21/64

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.

公开(公告)号：US20110111424A1

公开(公告)日：2011-05-12

申请号：US12967284

申请日：2010-12-14

申请人： John Edward Rush, II ,  Jing Li ,  Ailan Guo

发明人： John Edward Rush, II ,  Jing Li ,  Ailan Guo

IPC分类号： G01N33/53 ,  C07K16/00

CPC分类号： C07K16/00 ,  G01N33/6842 ,  G01N2440/36

摘要： The invention relates to antibody reagents that specifically bind to peptides carrying a ubiquitin remnant from a digested or chemically treated biological sample. The reagents allow the technician to identify ubiquitinated polypeptides as well as the sites of ubiquitination on them. The reagents are preferably employed in proteomic analysis using mass spectrometry. The antibody reagents specifically bind to the remnant of ubiquitin (i.e., a diglycine modified epsilon amine of lysine) left on a peptide which as been generated by digesting or chemically treating ubiquitinated proteins. The inventive antibody reagents' affinity to the ubiquitin remnant does not depend on the remaining amino acid sequences flanking the modified (i.e., ubiquitinated) lysine, i.e., they are context independent.

摘要翻译： 本发明涉及与经消化或经化学处理的生物样品中携带泛素残基的肽特异性结合的抗体试剂。 试剂允许技术人员识别泛素化的多肽以及它们上泛素化的位点。 试剂优选用于使用质谱的蛋白质组学分析。 抗体试剂特异性结合残留在通过消化或化学处理泛素化蛋白质产生的肽上的泛素（即，赖氨酸的二甘氨酸修饰的ε胺）残基。 本发明的抗体试剂对泛素残留物的亲和力不依赖于修饰（即泛素化）赖氨酸侧翼的剩余氨基酸序列，即它们是上下文无关的。

公开(公告)号：US20090203043A1

公开(公告)日：2009-08-13

申请号：US12313571

申请日：2008-11-21

申请人： Peter Hornbeck ,  Ailan Guo

发明人： Peter Hornbeck ,  Ailan Guo

IPC分类号： G01N33/573 ,  C07K16/18 ,  G01N33/566

CPC分类号： G01N33/68 ,  G01N2333/4703 ,  G01N2333/91215

摘要： The invention discloses 142 novel phosphorylation sites identified in insulin 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： 本发明公开了在胰岛素信号通路中鉴定的142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。

公开(公告)号：US10889818B2

公开(公告)日：2021-01-12

申请号：US13616107

申请日：2012-09-14

申请人： Ailan Guo ,  Anthony Possemato

发明人： Ailan Guo ,  Anthony Possemato

IPC分类号： C12N15/113 ,  C12N9/12 ,  C12Q1/6886 ,  G01N33/574 ,  C07K14/82 ,  C07K14/47 ,  C12Q1/6841

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.