Patents by Inventor Michael J. Comb
Michael J. Comb has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
-
Patent number: 11352418Abstract: The disclosure 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.Type: GrantFiled: July 11, 2019Date of Patent: June 7, 2022Assignee: CELL SIGNALING TECHNOLOGY, INC.Inventors: Michael J. Comb, John Edward Rush, II, Jing Li, Ailan Guo
-
Publication number: 20200131254Abstract: The disclosure 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.Type: ApplicationFiled: July 11, 2019Publication date: April 30, 2020Inventors: Michael J. Comb, John Edward Rush, II, Jing Li, Ailan Guo
-
Publication number: 20180009884Abstract: 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: ApplicationFiled: August 21, 2017Publication date: January 11, 2018Inventors: Michael J. Comb, Yi Tan, Peter Hornbeck
-
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
-
Patent number: 9587013Abstract: The invention provides methods for isolating a modified peptide from a complex mixture of peptides, the method comprising the steps of: (a) obtaining a proteinaceous preparation from an organism, wherein the preparation comprises modified peptides from two or more different proteins; (b) contacting the preparation with at least one immobilized modification-specific antibody; and (c) isolating at least one modified peptide specifically bound by the immobilized modification-specific antibody in step (b). The method may further comprise the step of (d) characterizing the modified peptide isolated in step (c) by mass spectrometry (MS), tandem mass spectrometry (MS-MS), and/or MS3 analysis, or the step of (e) utilizing a search program to substantially match the spectra obtained for the modified peptide during the characterization of step (d) with the spectra for a known peptide sequence, thereby identifying the parent protein(s) of the modified peptide.Type: GrantFiled: April 23, 2013Date of Patent: March 7, 2017Assignee: Cell Signaling Technology, Inc.Inventors: John Rush, Hui Zhang, Xiangming Zha, Michael J Comb, Yi Tan
-
Publication number: 20150259405Abstract: 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: ApplicationFiled: December 17, 2014Publication date: September 17, 2015Inventors: Michael J. Comb, Yi Tan, Peter Hornbeck
-
Patent number: 9085609Abstract: 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: July 11, 2006Date of Patent: July 21, 2015Assignee: Cell Signaling Technology, Inc.Inventors: Michael J. Comb, Peter Hornbeck, Patrick Li
-
Publication number: 20120244594Abstract: The invention provides methods for isolating a modified peptide from a complex mixture of peptides, the method comprising the steps of: (a) obtaining a proteinaceous preparation from an organism, wherein the preparation comprises modified peptides from two or more different proteins; (b) contacting the preparation with at least one immobilized modification-specific antibody; and (c) isolating at least one modified peptide specifically bound by the immobilized modification-specific antibody in step (b). The method may further comprise the step of (d) characterizing the modified peptide isolated in step (c) by mass spectrometry (MS), tandem mass spectrometry (MS-MS), and/or MS3 analysis, or the step of (e) utilizing a search program to substantially match the spectra obtained for the modified peptide during the characterization of step (d) with the spectra for a known peptide sequence, thereby identifying the parent protein(s) of the modified peptide.Type: ApplicationFiled: June 28, 2007Publication date: September 27, 2012Inventors: John Rush, Hui Zhang, Xiangming Zha, Michael J. Comb, Yi Tan
-
Publication number: 20110053242Abstract: The invention provides methods for isolating a modified peptide from a complex mixture of peptides, the method comprising the steps of: (a) obtaining a proteinaceous preparation from an organism, wherein the preparation comprises modified peptides from two or more different proteins; (b) contacting the preparation with at least one immobilized modification-specific antibody; and (c) isolating at least one modified peptide specifically bound by the immobilized modification-specific antibody in step (b). The method may further comprise the step of (d) characterizing the modified peptide isolated in step (c) by mass spectrometry (MS), tandem mass spectrometry (MS-MS), and/or MS3 analysis, or the step of (e) utilizing a search program to substantially match the spectra obtained for the modified peptide during the characterization of step (d) with the spectra for a known peptide sequence, thereby identifying the parent protein(s) of the modified peptide.Type: ApplicationFiled: June 28, 2007Publication date: March 3, 2011Inventors: John Rush, Hui Zhang, Xiangming Zha, Michael J. Comb, Yi Tan
-
Patent number: 7344714Abstract: The present invention is related to a method for producing motif-specific, context-independent antibodies which are specific to at least one modified amino acid residue in the context of variable surrounding amino acid or peptide sequences. The method is particularly useful in producing antibodies which recognize phosphorylated serine, threonine, and tyrosine, or acetylated lysine, as well as other modified amino acids-containing motifs of one or more amino acids.Type: GrantFiled: May 7, 2002Date of Patent: March 18, 2008Assignee: Cell Signaling Technology, IncInventors: Michael J. Comb, Yi Tan
-
Patent number: 7300753Abstract: The invention provides methods for isolating a modified peptide from a complex mixture of peptides, the method comprising the steps of: (a) obtaining a proteinaceous preparation from an organism, wherein the preparation comprises modified peptides from two or more different proteins; (b) contacting the preparation with at least one immobilized modification-specific antibody; and (c) isolating at least one modified peptide specifically bound by the immobilized modification-specific antibody in step (b). The method may further comprise the step of (d) characterizing the modified peptide isolated in step (c) by mass spectrometry (MS), tandem mass spectrometry (MS—MS), and/or MS3 analysis, or the step of (e) utilizing a search program to substantially match the spectra obtained for the modified peptide during the characterization of step (d) with the spectra for a known peptide sequence, thereby identifying the parent protein(s) of the modified peptide.Type: GrantFiled: February 12, 2004Date of Patent: November 27, 2007Inventors: John Rush, Hui Zhang, Xiangming Zha, Michael J. Comb, Yi Tan
-
Patent number: 7259022Abstract: A method is provided for producing motif-specific, context-independent antibodies which recognize a plurality of peptides or proteins within a genome that contain the same 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 adds 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: November 13, 2001Date of Patent: August 21, 2007Assignee: Cell Signaling Technology, Inc.Inventors: Michael J. Comb, Yi Tan, Hui Zhang
-
Patent number: 7198896Abstract: The invention provides methods for isolating a modified peptide from a complex mixture of peptides, the method comprising the steps of: (a) obtaining a proteinaceous preparation from an organism, wherein the preparation comprises modified peptides from two or more different proteins; (b) contacting the preparation with at least one immobilized modification-specific antibody; and (c) isolating at least one modified peptide specifically bound by the immobilized modification-specific antibody in step (b). The method may further comprise the step of (d) characterizing the modified peptide isolated in step (c) by mass spectrometry (MS), tandem mass spectrometry (MS—MS), and/or MS3 analysis, or the step of (e) utilizing a search program to substantially match the spectra obtained for the modified peptide during the characterization of step (d) with the spectra for a known peptide sequence, thereby identifying the parent protein(s) of the modified peptide.Type: GrantFiled: June 19, 2002Date of Patent: April 3, 2007Assignee: Cell Signaling Technology, Inc.Inventors: John Rush, Hui Zhang, Xiangming Zha, Michael J. Comb, Yi Tan
-
Patent number: 7183385Abstract: The invention discloses two newly-discovered Flt3 phosphorylation sites, tyrosine 589 (Tyr589) and tyrosine 591 (Tyr591) in the intracellular domain, and provides antibodies, both polyclonal and monoclonal, that selectively bind to Flt3 when phosphorylated at these novel sites. Also provided are assays utilizing these reagents, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibodies, that binds to Flt3 when phosphorylated at Tyr589 or Tyr591. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).Type: GrantFiled: February 18, 2003Date of Patent: February 27, 2007Assignee: Cell Signaling Technology, Inc.Inventors: Michael J. Comb, Randall K. Wetzel, Jiong Wu, Katherine Crosby
-
Patent number: 6982318Abstract: A class of motif-specific, context-independent antibodies that bind conserved signal transduction motifs, such as kinase consensus substrate motifs and protein-protein binding motifs, containing one or more modified amino acids, such as a phosphorylated amino acid, is provided. The antibodies bind a plurality of peptides or proteins that contain the modified motif. Context-independent antibodies specific for single modified residues, such as phosphothreonine, are also provided. Methods for producing and using such antibodies are provided.Type: GrantFiled: March 24, 2000Date of Patent: January 3, 2006Assignee: Cell Signaling Technology, Inc.Inventors: Michael J. Comb, Yi Tan
-
Publication number: 20030219827Abstract: The invention discloses two newly-discovered Flt3 phosphorylation sites, tyrosine 589 (Tyr589) and tyrosine 591 (Tyr591) in the intracellular domain, and provides antibodies, both polyclonal and monoclonal, that selectively bind to Flt3 when phosphorylated at these novel sites. Also provided are assays utilizing these reagents, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibodies, that binds to Flt3 when phosphorylated at Tyr589 or Tyr591. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).Type: ApplicationFiled: February 18, 2003Publication date: November 27, 2003Inventors: Michael J. Comb, Randall K. Wetzel, Jiong Wu, Katherine Crosby
-
Publication number: 20030186254Abstract: The present invention discloses complexes of cellular signaling proteins that interact in vivo with the HIV-encoded auxiliary proteins Nef and Tat to modulate their activity. This complex includes the novel serine/threonine kinase PAK4 and the novel guanine nucleotide exchange factor Cdc42-GEF, which synergize to stimulate Tat transcriptional activity, and the acetyl-transferase Tip60 which modifies Nef. These cellular partners of the HIV auxiliary proteins represent novel targets for HIV therapeutics. The invention provides isolated DNA and vectors encoding PAK4 and Cdc42-GEF, and methods of producing recombinant forms of these proteins. The invention also provides methods for identifying compounds that modulate the activity of HIV-Tat, HIV-Nef or Tip60, and methods for modulating the activity of these enzymes.Type: ApplicationFiled: April 29, 2002Publication date: October 2, 2003Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: Michael B. Melnick, Albrecht Moritz, Michael J. Comb
-
Publication number: 20030068652Abstract: The invention provides a method for producing antibodies that selectively recognize short, modified amino acid motifs substantially independent of the surrounding amino acid context in which the motif occurs. A novel class of motif-specific, context-independent antibodies is also provided. The invention encompasses modified motifs consisting of single modified amino acids, for example phosphotyrosine or acetylated lysine, as well other modified motifs of multiple amino acids, such as kinase consensus substrate motifs and protein-protein binding motifs relevant to cell signal transduction. Also provided are methods of profiling large and diverse protein populations on a genome-wide basis by utilizing the antibodies of the invention, and methods for the positive identification of cellular phosphoproteins using one or more motif-specific, context-independent antibodies of the invention coupled with protein database searching.Type: ApplicationFiled: June 18, 2002Publication date: April 10, 2003Applicant: Cell Signaling Technology, Inc.Inventors: Michael J. Comb, Yi Tan, Hui Zhang
-
Publication number: 20030044848Abstract: The invention provides methods for isolating a modified peptide from a complex mixture of peptides, the method comprising the steps of: (a) obtaining a proteinaceous preparation from an organism, wherein the preparation comprises modified peptides from two or more different proteins; (b) contacting the preparation with at least one immobilized modification-specific antibody; and (c) isolating at least one modified peptide specifically bound by the immobilized modification-specific antibody in step (b). The method may further comprise the step of (d) characterizing the modified peptide isolated in step (c) by mass spectrometry (MS), tandem mass spectrometry (MS-MS), and/or MS3 analysis, or the step of (e) utilizing a search program to substantially match the spectra obtained for the modified peptide during the characterization of step (d) with the spectra for a known peptide sequence, thereby identifying the parent protein(s) of the modified peptide.Type: ApplicationFiled: June 19, 2002Publication date: March 6, 2003Applicant: CELL SIGNALING TECHNOLOGY, INC.Inventors: John Rush, Hui Zhang, Xiangming Zha, Michael J. Comb, Yi Tan
-
Publication number: 20020169668Abstract: According to an embodiment of the present invention, a method, article of manufacture including a computer readable medium, and a system including a processing device provides promotions over the Internet. In an embodiment of the present invention, a first entity (which in one example is an offline brand) distributes a product with an alphanumeric sequence. In an embodiment of the present invention, the alphanumeric sequence is hidden from view until the product is purchased. For example, the alphanumeric sequence is positioned on the inside of packaging. When a user purchases the product, the user can view the alphanumeric sequence. Printed with the alphanumeric sequence is an address on the Internet in an embodiment of the present invention. The user can enter the address into a browser and access the addressed page, which in one embodiment is part of the first entity's web page. The user selects a link indicating a desire to redeem a prize using the alphanumeric sequence.Type: ApplicationFiled: February 8, 2002Publication date: November 14, 2002Inventors: Edward L. Bank, Michael J. Comb, Juan Carlos Velten Funcia