Patents by Inventor Robert H. Silverman
Robert H. Silverman 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).
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Publication number: 20190002585Abstract: Provided herein are compositions, systems, kits, and methods for treating cancer by administering to a subject a first agent selected from: a PDE12 inhibiting agent, a AKAP7 inhibiting agent, an ADAR1 inhibiting agent, and/or a RNase L enhancer, and a second agent that comprises a DNA methylation inhibiting agent (e.g., a DNA methyltransferase demethylase inhibitor).Type: ApplicationFiled: June 7, 2018Publication date: January 3, 2019Inventors: Robert H. Silverman, Shuvojit Banerjee
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Publication number: 20130040369Abstract: The present invention provides for isolated nucleic acid sequences encoding viruses; isolated polypeptides comprising amino acid sequences of the virus; vectors comprising the viral nucleic acid sequences; cells comprising the vectors; antibodies and antigen binding fragments thereof which have binding specificity for the virus; methods of detecting or screening for the virus (e.g., in an individual); methods of identifying agents that inhibit the virus; methods of inducing an immune response to the virus; methods of treating disease associated with the presence of XMRV in an individual (e.g., cancer such as prostate cancer); methods of detecting asymptomatic cancer (e.g., prostate cancer); methods of identifying an individual at risk for developing cancer (e.g., prostate cancer); and kits for detecting the virus.Type: ApplicationFiled: July 17, 2012Publication date: February 14, 2013Applicants: The Regents of the University of California, The Cleveland Clinic FoundationInventors: Robert H. Silverman, Eric A. Klein, Graham Casey, Joseph DeRisi, Don Ganem
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Publication number: 20120251571Abstract: The invention is directed to one or more RNase L mediated cleavage products. In particular aspects, the RNase L mediated cleavage products are RNase L mediated cleavage products of a virus, referred to herein as a “suppressor of virus ribonucleic acid (RNA)” or “svRNA” and uses thereof.Type: ApplicationFiled: September 28, 2011Publication date: October 4, 2012Applicant: The Cleveland Clinic FoundationInventors: Robert H. Silverman, Malathi Krishnamurthy
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Patent number: 8263085Abstract: The present invention provides for isolated nucleic acid sequences encoding viruses; isolated polypeptides comprising amino acid sequences of the virus; vectors comprising the viral nucleic acid sequences; cells comprising the vectors; antibodies and antigen binding fragments thereof which have binding specificity for the virus; methods of detecting or screening for the virus (e.g., in an individual); methods of identifying agents that inhibit the virus; methods of inducing an immune response to the virus; methods of treating disease associated with the presence of XMRV in an individual (e.g., cancer such as prostate cancer); methods of detecting asymptomatic cancer (e.g., prostate cancer); methods of identifying an individual at risk for developing cancer (e.g., prostate cancer); and kits for detecting the virus.Type: GrantFiled: September 24, 2007Date of Patent: September 11, 2012Assignees: The Cleveland Clinic Foundation, The Regents of the University of CaliforniaInventors: Robert H. Silverman, Eric A. Klein, Graham Casey, Joseph DeRisi, Don Ganem
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Publication number: 20100184015Abstract: The present invention relates to the identification of Xenotropic murine leukemia virus (XMRV) nucleic acid by polymerase chain reaction (PCR) analysis (e.g., real time PCR (RT/PCR); nested RT/PCR using Tth DNA polymerase and Hot start polymerase) and the uses thereof. In particular, the invention provides methods for the detection, and in particular early detection, of XMRV in RNA isolated from samples (e.g., urine samples; expressed prostate secretion (EPS)) of prostate cancer patients and normal individuals.Type: ApplicationFiled: December 22, 2009Publication date: July 22, 2010Inventors: Robert H. Silverman, Eric A. Klein, Christopher J. Weight, Carvell T. Nguyen, Jaydip Das Gupta
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Publication number: 20100166797Abstract: The present invention provides for isolated nucleic acid sequences encoding viruses; isolated polypeptides comprising amino acid sequences of the virus; vectors comprising the viral nucleic acid sequences; cells comprising the vectors; antibodies and antigen binding fragments thereof which have binding specificity for the virus; methods of detecting or screening for the virus (e.g., in an individual); methods of identifying agents that inhibit the virus; methods of inducing an immune response to the virus; methods of treating disease associated with the presence of XMRV in an individual (e.g., cancer such as prostate cancer); methods of detecting asymptomatic cancer (e.g., prostate cancer); methods of identifying an individual at risk for developing cancer (e.g., prostate cancer); and kits for detecting the virus.Type: ApplicationFiled: September 24, 2007Publication date: July 1, 2010Inventors: Robert H. Silverman, Eric A. Klein, Graham Casey, Joseph DeRisi, Don Ganem
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Publication number: 20090075830Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using a one or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U, or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2 wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3? untranslated region (UTR) that comprises one of the ARE search sequences.Type: ApplicationFiled: June 27, 2008Publication date: March 19, 2009Applicants: THE CLEVELAND CLINIC FOUNDATION, KING FAISAL SPECIALIST HOSPITAL AND RESEARCH CENTREInventors: Khalid S. Abu-Khabar, Bryan R.G. Williams, Mathias Frevel, Robert H. Silverman
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Publication number: 20090023592Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using aone or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U. or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2, wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3?untranslated region (UTR) that comprises one of the ARE search sequences.Type: ApplicationFiled: July 6, 2007Publication date: January 22, 2009Inventors: Khalid S. Abu-Khabar, Bryan R.G. Williams, Mathias Frevel, Robert H. Silverman
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Patent number: 6762038Abstract: Mammalian somatic cells having a homozygous disruption in the gene which encodes the endonbonuclease RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase PKR are provided. Methods for producing enhanced levels of recombinant proteins in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption in the PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein. In another aspect the methods employ mutant cells hating a homozygous disruption in the PKR gene, i.e. PKR null cells.Type: GrantFiled: September 9, 1999Date of Patent: July 13, 2004Assignee: The Cleveland Clinic FoundationInventors: Robert H. Silverman, Bryan R. G. Williams, Fulvia Terenzi, Aimin Zhou, Sandy Der
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Publication number: 20040023231Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using a one or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U. or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2, wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis.Type: ApplicationFiled: July 14, 2003Publication date: February 5, 2004Inventors: Khalid S. Abu-Khabar, Bryan R.G. Williams, Mathias Frevel, Robert H. Silverman
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Publication number: 20030104574Abstract: Mammalian somatic cells having a homozygous disruption in the gene which encodes the endoribonuclease known as RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase known as PKR. Methods for producing enhanced levels of recombinant proteins, or polypeptides, in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein, or polypeptide; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein.Type: ApplicationFiled: January 10, 2003Publication date: June 5, 2003Inventors: Robert H. Silverman, Bryan R.G. Williams, Fulvia Terenzi, Aimin Zhou, Sandy Der
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Patent number: 6468983Abstract: The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L (“activator-antisense complex”) which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.Type: GrantFiled: February 3, 1998Date of Patent: October 22, 2002Assignees: The Cleveland Clinic Foundation, The United States of America as represented by the Department of Health and Human ServicesInventors: Robert H. Silverman, Seiji Kondo, John K. Cowell, Guiying Li, Paul F. Torrence
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Publication number: 20020137905Abstract: The present invention is based on a family of membrane proteins, Phospholipid Scramblases (PLSCR), that mediate accelerated trans-bilayer movement of plasma membrane phospholipids in response to elevated cytoplasmic calcium. At least one Phospholipid Scramblase gene is highly inducible by interferon. Interferon-induced expression of Phospholipid Scramblase 1 (and/or related genes) alters the physical and functional properties of the cell surface so as to (1) inhibit tumor cell proliferation and survival; (2) inhibit maturation and release of membrane-enveloped viruses; and/or (3) promote clearance of virus-infected cells and cancer cells through the reticuloendothelial system. The present invention provides Phospholipid Scramblase polypeptides, polynucleotide sequences that encode Phospholipid Scramblase polypeptides, and antibodies that are immunoreactive with the polypeptides.Type: ApplicationFiled: March 30, 2001Publication date: September 26, 2002Inventors: Peter J. Sims, Therese Wiedmer, Robert H. Silverman
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Patent number: 6331396Abstract: Methods and model systems for identifying and characterizing new therapeutic agents, particularly proteins, which mimic or inhibit the activity of all interferons, Type I interferons, IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The method comprises administering an interferon selected from the group consisting of IFN-&agr;, IFN &bgr;, IFN-&tgr;, IFN-&ohgr;, IFN-&ggr;, and combinations thereof to cultured cells, administering the candidate agent to a duplicate culture of cells; and measuring the effect of the candidate agent and the interferon on the transcription or translation of one or, preferably, a plurality of the interferon stimulated genes or the interferon repressed genes (hereinafter referred to as “ISG's” and “IRGs”, respectively). The model system is an array with gene probes that hybridize with from about 100 to about 5000 ISG and IRG transcripts.Type: GrantFiled: September 23, 1999Date of Patent: December 18, 2001Assignee: The Cleveland Clinic FoundationInventors: Robert H. Silverman, Bryan R. G. Williams, Sandy Der
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Patent number: 6271369Abstract: Chimeric molecules comprising a virus targeting antisense oligonucleotide moiety attached to an activator of 2-5A-dependent RNase.Type: GrantFiled: October 14, 1997Date of Patent: August 7, 2001Assignees: The United States of America as represented by the Department of Health and Human Services, The Cleveland Clinic FoundationInventors: Paul F. Torrence, Robert H. Silverman, Ratan K. Maitra, Krystyna Lesiak
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Publication number: 20010007902Abstract: The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L (“activator-antisense complex”) which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.Type: ApplicationFiled: February 3, 1998Publication date: July 12, 2001Inventors: ROBERT H. SILVERMAN, SEIJI KONDO, JOHN K. COWELL, GUIYING LI, PAUL F. TORRENCE
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Patent number: 6028243Abstract: The present invention provides a mutant, non-human mammal, particularly a mutant mouse, having a homozygous disruption in the RNase L gene thereof. Since the homozygous disruption in the RNase L gene leads to minimal if any production of RNase L in the mutant mammals, such mutant mammals are useful for assessing the effect of antiviral drugs on the induction, synthesis, or activation of RNase L. The present invention also relates to mutant, non-human, embryonic stem cell lines having a heterozygous disruption of the RNase L gene thereof, to isolated mammalian cells having a homozygous disruption in the RNase L gene thereof, and to a DNA construct comprising a DNA sequence of a disrupted coding exon of a RNase L gene.Type: GrantFiled: October 3, 1997Date of Patent: February 22, 2000Assignee: The Cleveland Clinic FoundationInventors: Robert H. Silverman, Aimin Zhou
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Patent number: 5972678Abstract: Isolated 2-5A-dependent RNases, an interferon-induced enzyme which is activated by 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) and implicated in both the molecular mechanisms of interferon action and in the fundamental control of RNA stability in mammalian cells, and encoding sequences therefor are disclosed. The expression cloning and analysis of murine and human 2-5A-dependent RNases is also disclosed. Recombinant human 2-5A-dependent RNase produced in vitro bound an activating affinity matrix, 2-5A-cellulose, resulting in ribonuclease activity. The 2-5A binding properties of the recombinant and naturally occurring forms of 2-5A-dependent RNase are basically identical. Interferon induction of 2-5A-dependent RNase expression is demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide.Type: GrantFiled: June 7, 1995Date of Patent: October 26, 1999Assignee: Cleveland Clinic FoundationInventors: Robert H. Silverman, Bret A. Hassel, Aimin Zhou
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Patent number: 5877019Abstract: 2-5A-dependent RNase, an endoribonuclease that requires 5'-phosphorylated 2',5'-linked oligoadenylates (2-5A), functions in the molecular mechanism of interferon action. Recombinant, 2-5A-dependent RNase was expressed to high levels (at least 10% of the soluble protein) in insect cells by infecting with baculovirus containing human cDNA to 2-5A-dependent RNase. In contrast, there was no 2-5A-dependent RNase present in control insect cells infected with nonrecombinant baculovirus. The purified, recombinant enzyme eluted from a gel-filtration column as a monomer that showed potent and highly specific, 2-5A-dependent RNase activity. Precise activitor requirements were determined using the purified enzyme of a variety of 2',5'-linked oligonucleotides. The activated enzyme was capable of cleaving both poly(rU) and, to a lesser extent, poly(rA) but not poly(rC), poly(rG), or poly(dT. Interestingly, poly(rU) was cleaved to a series of discrete products ranging between 5 and 22 nucleotides in length.Type: GrantFiled: August 21, 1996Date of Patent: March 2, 1999Assignee: Cleveland Clinic FoundationInventors: Robert H. Silverman, Bret A. Hassel, Aimin Zhou
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Patent number: 5866781Abstract: Isolated 2-5A-dependent RNases, an interferon-induced enzyme which is activated by 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) and implicated in both the molecular mechanisms of interferon action and in the fundamental control of RNA stability in mammalian cells, and encoding sequences therefor are disclosed. The expression cloning and analysis of murine and human 2-5A-dependent RNases is also disclosed. Recombinant human 2-5A-dependent RNase produced in vitro bound an activating affinity matrix, 2-5A-cellulose, resulting in ribonuclease activity. The 2-5A binding properties of the recombinant and naturally occurring forms of 2-5A-dependent RNase are basically identical. Interferon induction of 2-5A-dependent RNase expression is demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide.Type: GrantFiled: May 8, 1995Date of Patent: February 2, 1999Assignee: The Cleveland Clinic FoundationInventors: Robert H. Silverman, Dibyendu N. SenGupta