Patents Assigned to Cell Signaling Technology, Inc.
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Patent number: 10577640Abstract: 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 sample 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.Type: GrantFiled: January 31, 2017Date of Patent: March 3, 2020Assignee: CELL SIGNALING TECHNOLOGY, INC.Inventors: Khanh Duc Huynh, Wan Cheung Cheung, Roberto Polakiewicz
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Patent number: 10551383Abstract: The invention provides methods to identify, diagnose, and treat kidney cancer through the detection of expression and/or activity of anaplastic lymphoma kinase (ALK). The detection of the presence of a polypeptide with ALK kinase activity (e.g., by detecting expression and/or activity of the polypeptide), identify those kidney cancers that are likely to respond to an ALK-inhibiting therapeutic.Type: GrantFiled: September 3, 2015Date of Patent: February 4, 2020Assignee: CELL SIGNALING TECHNOLOGY, INC.Inventors: Herbert Haack, Katherine Eleanor Crosby, Victoria McGuinness Rimkunas, Matthew Ren Silver
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Patent number: 10526661Abstract: 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.Type: GrantFiled: April 12, 2016Date of Patent: January 7, 2020Assignee: CELL SIGNALING TECHNOLOGY, INC.Inventors: Ting-Lei Gu, Ailan Guo
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Publication number: 20190219581Abstract: This invention provides methods for determining or predicting response to HER2-directed therapy in an individual.Type: ApplicationFiled: January 18, 2019Publication date: July 18, 2019Applicants: Ventana Medical Systems, Inc., Cell Signaling Technology, Inc.Inventors: Sarah S. Bacus, Bradley L. Smith
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Publication number: 20190128889Abstract: The invention provides the identification of the presence of polypeptides with ROS kinase activity in mammalian lung cancer. In some embodiments, the polypeptide with ROS kinase activity is the result of a fusion between a ROS-encoding polynucleotide and a polynucleotide encoding a second (non-ROS) polypeptide. Three different fusion partners of ROS are described, namely proteins encoded by the FIG gene, the SLC34A2 gene, and the CD74 gene. The invention enables new methods for determining the presence of a polypeptide with ROS kinase activity in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer (e.g.Type: ApplicationFiled: May 31, 2018Publication date: May 2, 2019Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: Victoria McGuinness Rimkunas, Herbert Haack, Ting-Lei Gu, Ailan Guo, Anthony Paul Possemato, Katherine Eleanor Crosby, Meghan Ann Tucker, Cynthia Reeves
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Publication number: 20190127804Abstract: 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 (TFC). 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.Type: ApplicationFiled: May 8, 2018Publication date: May 2, 2019Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: Klarisa Rikova, Herbert Haack, Laura Sullivan, Ailan Guo, Anthony Possemato, Joan MacNeill, Ting-Lei Gu, Jian Yu
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Publication number: 20190049449Abstract: 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 now been identified 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 polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides.Type: ApplicationFiled: February 16, 2018Publication date: February 14, 2019Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: Klarisa Rikova, Herbert Haack, Laura Sullivan, Ailan Guo, Anthony Possemato, Joan MacNeill, Ting-Lei Gu, Jian Yu
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Publication number: 20190002532Abstract: In some embodiments, the invention relates to methods for creating a monoclonal antibody that specifically binds to antigen. The method may start from a polyclonal population of antibodies such as a non-specific polyclonal population or a polyclonal population of antibodies that specifically bind to the antigen. The method includes obtaining nucleic acid molecules encoding heavy and light immunoglobulin chains (or variable regions thereof) of multiple immunoglobulins from an animal; obtaining mass spectra information of peptide fragments of a population of polyclonal immunoglobulins that specifically bind to an antigen of choice; comparing and/or correlating the mass spectra information of the peptide fragments of the polyclonal immunoglobulins with predicted mass spectra information of predicted amino acid sequences encoded by the nucleic acid molecules, and then assembling the heavy and light chains to create an antibody (or variable region thereof) that specifically binds to the antigen.Type: ApplicationFiled: January 19, 2018Publication date: January 3, 2019Applicant: Cell Signaling Technology, Inc.Inventors: Roberto Polakiewicz, Wan Cheung Cheung, John Edward Rush, II, Sean Andre Beausoleil
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Patent number: 10036756Abstract: 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 partneType: GrantFiled: August 24, 2016Date of Patent: July 31, 2018Assignee: Cell Signaling Technology, Inc.Inventors: Albrecht Moritz, John Edward Rush, II, Roberto Polakiewicz
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Patent number: 10000568Abstract: The invention discloses binding agents to the E746-A750 deletion and the L858R point mutations in the epidermal growth factor receptor (EGFR) molecule, and methods for use thereof, including methods for the diagnosis and treatment of cancer.Type: GrantFiled: April 10, 2009Date of Patent: June 19, 2018Assignee: Cell Signaling Technology, Inc.Inventors: Ting-Lei Gu, Jiong Wu, Susan Kane, Jian Yu, Herbert Haack, James Wieler, Jun-Ming Cai, Victoria Rimkunas
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Publication number: 20180156802Abstract: 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 now been identified 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 polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides.Type: ApplicationFiled: July 5, 2017Publication date: June 7, 2018Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: Klarisa Rikova, Herbert Haack, Laura Sullivan, Ailan Guo, Anthony Possemato, Joan MacNeill, Ting-Lei Gu, Jian Yu
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Patent number: 9988688Abstract: 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.Type: GrantFiled: September 30, 2015Date of Patent: June 5, 2018Assignee: Cell Signaling Technology, Inc.Inventors: Klarisa Rikova, Herbert Haack, Laura Sullivan, Ailan Guo, Anthony Possemato, Joan MacNeill, Ting-Lei Gu, Jian Yu
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Patent number: 9920110Abstract: In some embodiments, the invention relates to methods for creating a monoclonal antibody that specifically binds to antigen. The method may start from a polyclonal population of antibodies such as a non-specific polyclonal population or a polyclonal population of antibodies that specifically bind to the antigen. The method includes obtaining nucleic acid molecules encoding heavy and light immunoglobulin chains (or variable regions thereof) of multiple immunoglobulins from an animal; obtaining mass spectra information of peptide fragments of a population of polyclonal immunoglobulins that specifically bind to an antigen of choice; comparing and/or correlating the mass spectra information of the peptide fragments of the polyclonal immunoglobulins with predicted mass spectra information of predicted amino acid sequences encoded by the nucleic acid molecules, and then assembling the heavy and light chains to create an antibody (or variable region thereof) that specifically binds to the antigen.Type: GrantFiled: March 9, 2012Date of Patent: March 20, 2018Assignee: Cell Signaling Technology, Inc.Inventors: Roberto Polakiewicz, Wan Cheung Cheung, John Edward Rush, II, Sean Andre Beausoleil
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Publication number: 20180031559Abstract: This invention provides methods for determining or predicting response to HER2-directed therapy in an individual.Type: ApplicationFiled: October 12, 2017Publication date: February 1, 2018Applicants: Ventana Medical Systems, Inc., Cell Signaling Technology, Inc.Inventors: Sarah S. Bacus, Bradley L. Smith
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Patent number: 9856315Abstract: The disclosure features over 5000 methylation and acetylation sites identified in human cell line, human serum and mouse tissues, peptides (including AQUA peptides) comprising a methylation or acetylation site of the disclosure, antibodies specifically bind to a methylation or acetylation site of the disclosure, and diagnostic and therapeutic uses of the above.Type: GrantFiled: October 15, 2015Date of Patent: January 2, 2018Assignee: Cell Signaling Technology, Inc.Inventors: Hongbo Gu, Ailan Guo, Daniel Mulhern, Jeffrey C. Silva, Jing Zhou
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Publication number: 20170275706Abstract: The invention provides a method for identifying a patient with cancer or suspected of having cancer as a patient likely to respond to an ALK- and/or ROS-inhibiting therapeutic, comprising: contacting a biological sample from a patient with a first reagent that specifically binds a polypeptide having ROS kinase activity and a second reagent that specifically binds to a polypeptide having ALK knase activity, and detecting whether the first reagent or the second reagent specifically binds to the biological sample, wherein detection of binding of either the first reagent or the second reagent to the biological sample identifies the patient as a patient likely to respond to an ALK-inhibiting and/or ROS-inhibiting therapeutic.Type: ApplicationFiled: June 7, 2017Publication date: September 28, 2017Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: Victoria McGuinness Rimkunas, Herbert Haack, Katherine Eleanor Crosby
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Patent number: 9738711Abstract: 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.Type: GrantFiled: December 17, 2014Date of Patent: August 22, 2017Assignee: Cell Signaling Technology, Inc.Inventors: Michael J. Comb, Yi Tan, Peter Hornbeck
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Publication number: 20170211124Abstract: 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 sample 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.Type: ApplicationFiled: January 31, 2017Publication date: July 27, 2017Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: Khanh Duc HUYNH, Wan Cheung CHEUNG, Roberto POLAKIEWICZ
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Publication number: 20170071941Abstract: 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.Type: ApplicationFiled: November 30, 2016Publication date: March 16, 2017Applicant: Cell Signaling Technology, Inc.Inventors: Ting-Lei Gu, Meghan Ann Tucker, Herbert Haack, Katherine Eleanor Crosby, Victoria McGuinness Rimkunas
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Patent number: 9588110Abstract: 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 sample 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.Type: GrantFiled: July 27, 2012Date of Patent: March 7, 2017Assignee: CELL SIGNALING TECHNOLOGY, INC.Inventors: Khanh Duc Huynh, Wan Cheung Cheung, Roberto Polakiewicz