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    Compositions for detecting mutant anaplastic lymphoma kinase in lung cancer
    2.
    发明授权
    Compositions for detecting mutant anaplastic lymphoma kinase in lung cancer 有权

    公开(公告)号：US11505833B2

    公开(公告)日：2022-11-22

    申请号：US17102639

    申请日：2020-11-24

    申请人： CELL SIGNALING TECHNOLOGY, INC.

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： C12N9/12 ,  C12Q1/6886 ,  C07K14/47 ,  G01N33/574 ,  A61K31/713 ,  G01N33/68 ,  A61K38/00

    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.

    COMPOSITIONS FOR DETECTING MUTANT ANAPLASTIC LYMPHOMA KINASE IN LUNG CANCER
    3.
    发明申请
    COMPOSITIONS FOR DETECTING MUTANT ANAPLASTIC LYMPHOMA KINASE IN LUNG CANCER 有权

    公开(公告)号：US20210371933A1

    公开(公告)日：2021-12-02

    申请号：US17102639

    申请日：2020-11-24

    申请人： CELL SIGNALING TECHNOLOGY, INC.

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： C12Q1/6886 ,  C07K14/47 ,  C12N9/12 ,  G01N33/574 ,  A61K31/713 ,  G01N33/68

    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.

    MASS SPECTROMETRY ANALYSIS OF MUTANT POLYPEPTIDES IN BIOLOGICAL SAMPLES
    4.
    发明申请
    MASS SPECTROMETRY ANALYSIS OF MUTANT POLYPEPTIDES IN BIOLOGICAL SAMPLES 有权

    公开(公告)号：US20210123924A1

    公开(公告)日：2021-04-29

    申请号：US16890379

    申请日：2020-06-02

    申请人： Cell Signaling Technology, Inc.

    发明人： Albrecht Moritz ,  John Edward Rush, II ,  Roberto Polakiewicz

    IPC分类号： G01N33/68 ,  B01D15/12 ,  B01D15/32 ,  B01D15/38 ,  B01D15/42 ,  G01N30/72

    摘要： The invention relates to a method for determining the presence of at least one distinct polypeptide in a biological sample comprising contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct polypeptide in a sequence-specific manner such that at least one distinct peptide having a predetermined peptide measured accurate mass would result if the at least one distinct polypeptide were present in the biological sample, to obtain a hydrolyzed sample; bringing the hydrolyzed sample in contact with a substrate comprising at least one immobilized binding partner, wherein the at least one immobilized binding partner is capable of specifically binding the distinct peptide; removing the hydrolyzed sample from the substrate in a manner such that the distinct peptide would remain bound to the immobilized binding partner; contacting the substrate with an elution solution, wherein the distinct peptide would dissociate from the immobilized binding partner into the elution solution; subjecting a portion of the elution solution to liquid chromatography to segregate a plurality of molecules in the portion of the elution solution to obtain sorted molecules; determining the measured accurate mass of at least one sorted molecule present in the elution solution; and determining the presence of the at least one distinct polypeptide in the biological sample when a measured accurate mass of at least one molecule is substantially equal to the predetermined peptide measured accurate mass.

    Multi Component Detection
    5.
    发明申请
    Multi Component Detection 有权

    公开(公告)号：US20210079445A1

    公开(公告)日：2021-03-18

    申请号：US16800394

    申请日：2020-02-25

    申请人： CELL SIGNALING TECHNOLOGY, INC.

    发明人： Khanh Duc HUYNH ,  Wan Cheung CHEUNG ,  Roberto POLAKIEWICZ

    IPC分类号： C12Q1/37 ,  C12N9/52 ,  G01N33/50 ,  G01N33/542 ,  G01N33/569 ,  G01N33/574 ,  C07K16/18 ,  G01N33/53

    摘要： The disclosure provides methods for detecting the concurrent presence of at least two targets within a biological sample. The method includes contacting said biological sample with a first binding agent, said first binding agent operably linked to a first sortase molecule, wherein said first binding agent specifically binds to a first target; contacting said biological simple with a second binding agent, said second binding agent operably linked to a first sortase recognition sequence peptide, wherein said second binding agent specifically binds to a second target; adding a sortase substrate under conditions where a first sortase-mediated ligation of the sortase substrate to the first sortase recognition sequence will produce a ligation product, and detecting the ligation product, wherein detection of said ligation product indicates the concurrent presence of the first target and the second target in the biological sample. Also disclosed are kits comprising reagents for performing the methods as claimed.

    Mutant ROS expression in human cancer
    8.
    发明授权
    Mutant ROS expression in human cancer 有权
    突变型ROS在人类癌症中的表达

    公开(公告)号：US09364477B2

    公开(公告)日：2016-06-14

    申请号：US13146705

    申请日：2010-02-12

    申请人： Ting-Lei Gu ,  Meghan Ann Tucker ,  Herbert Haack ,  Katherine Eleanor Crosby ,  Victoria McGuinness Rimkunas

    发明人： Ting-Lei Gu ,  Meghan Ann Tucker ,  Herbert Haack ,  Katherine Eleanor Crosby ,  Victoria McGuinness Rimkunas

    IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07H21/04 ,  A61K31/506 ,  G01N33/574 ,  G01N33/547

    CPC分类号： A61K31/506 ,  A61K31/4545 ,  C12Q1/6827 ,  C12Q1/6858 ,  C12Q1/6869 ,  C12Q1/6886 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57438 ,  G01N33/57484 ,  G01N2333/9121 ,  G01N2800/52

    摘要： The invention provides the identification of the presence of mutant ROS protein in human cancer. In some embodiments, the mutant ROS are FIG-ROS fusion proteins comprising part of the FIG protein fused to the kinase domain of the ROS kinase. In some embodiments, the mutant ROS is the overexpression of wild-type ROS in cancerous tissues (or tissues suspected of being cancerous) where, in normal tissue of that same tissue type, ROS is not expressed or is expressed at lower levels. The mutant ROS proteins of the invention are anticipated to drive the proliferation and survival of a subgroup of human cancers, particularly in cancers of the liver (including bile duct), pancreas, kidney, and testes. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS polypeptides (e.g., a FIG-ROS(S) fusion polypeptide), probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The identification of the mutant ROS polypeptides enables new methods for determining the presence of these mutant ROS 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： 本发明提供了人类癌症中突变型ROS蛋白的存在的鉴定。 在一些实施方案中，突变体ROS是包含与ROS激酶的激酶结构域融合的FIG蛋白的部分的FIG-ROS融合蛋白。 在一些实施方案中，突变体ROS是野生型ROS在癌组织（或怀疑是癌性的组织）中的过表达，其中在相同组织类型的正常组织中ROS不被表达或以较低水平表达。 预期本发明的突变体ROS蛋白质可以驱动人类癌症亚群的增殖和存活，特别是在肝脏（包括胆管），胰腺，肾脏和睾丸癌。 因此，本发明部分地提供了分离的多核苷酸和编码所公开的突变型ROS多肽的载体（例如，FIG-ROS（S）融合多肽），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的试剂 和截短的多肽。 鉴定突变体ROS多肽使得能够确定生物样品中这些突变型ROS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，以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法 ，其也由本发明提供。

    Production of motif-specific and context-independent antibodies using peptide libraries as antigens
    10.
    发明授权
    Production of motif-specific and context-independent antibodies using peptide libraries as antigens 有权
    使用肽文库作为抗原产生基序特异性和上下文相关抗体

    公开(公告)号：US09085609B2

    公开(公告)日：2015-07-21

    申请号：US11484485

    申请日：2006-07-11

    申请人： Michael J. Comb ,  Peter Hornbeck ,  Patrick Li

    发明人： Michael J. Comb ,  Yi Tan ,  Peter Hornbeck

    IPC分类号： C07K16/00 ,  C07K16/18

    CPC分类号： C07K16/18 ,  C07K16/00 ,  C07K16/44 ,  C07K2317/20

    摘要： A method is provided for producing motif-specific, context-independent antibodies that recognize a plurality of peptides or proteins within a genome that contain the same post-translationally modified motif. The method includes the step of immunizing a host with a degenerate peptide library antigen featuring (i) a fixed target motif containing one or more invariant amino acids including at least one modified amino acid, and (ii) a plurality of degenerate amino acids flanking the motif. Motif-specific, context-independent antibodies produced by the disclosed method are also provided. The method encompasses motifs consisting of a single modified amino acid, as well as short motifs comprising multiple invariant amino acids including one or more modified amino acids, such as all or part of kinase consensus substrate motifs, protein-protein binding motifs, or other cell signaling motifs. Methods of using the antibodies, e.g. for genome-wide profiling, are also provided.

    摘要翻译： 提供了一种用于产生基序特异性，背景无关抗体的方法，其识别基因组内含有相同翻译后修饰基序的多个肽或蛋白质。 该方法包括用简并肽文库抗原免疫宿主的步骤，其特征在于（i）含有一个或多个包含至少一个修饰的氨基酸的不变氨基酸的固定靶基序，和（ii）多个位于 主题。 还提供了通过公开的方法产生的基于特异性的，与环境无关的抗体。 该方法包括由单个修饰的氨基酸组成的基序，以及包含多个不变氨基酸的短基序，包括一个或多个修饰的氨基酸，例如全部或部分激酶共有底物基序，蛋白质 - 蛋白质结合基序或其他细胞 信号图案。 使用抗体的方法，例如 也提供了全基因组图谱。