- NUCLEOSIDE DERIVATIVES AS INHIBITORS OF RNA-DEPENDENT RNA VIRAL POLYERMASE
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The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.
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Paragraph 0905; 0906
(2017/07/14)
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- METHODS FOR THE PREVENTION AND TREATMENT OF MAJOR ADVERSE CARDIOVASCULAR EVENTS USING COMPOUNDS THAT MODULATE APOLIPOPROTEIN B
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Provided herein, for example, are methods generally relating to preventing, treating and/or managing a major adverse cardiovascular event in a subject with a disease or condition at risk for a major adverse cardiovascular event, e.g., familial hypercholesterolemia. Also provided herein are methods relating to administering to the patient a therapeutically effective amount of an antisense oligonucleotide having a nucleobase SEQ ID NO: 247 (e.g., mipomersen).
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Paragraph 00649
(2016/03/22)
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- EFFECTS OF APOLIPOPROTEIN B INHIBITION ON GENE EXPRESSION PROFILES IN ANIMALS
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Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for treatment of diseases associated with expression of apolipoprotein B are provided. Methods are provided for modulating the expression of genes involved in lipid metabolism, useful in the treatment of conditions associated with cardiovascular risk. Antisense oligonucleotides targeted to apolipoprotein B reduce the level of apolipoprotein B mRNA, lower serum cholesterol and shift liver gene expression profiles from those of an obese animal towards those of a lean animal. Further provided are methods for improving the cardiovascular risk of a subject through antisense inhibition of apolipoprotein B. Also provided are methods for employing antisense oligonucleotides targeted to apolipoprotein B to modulate a cellular pathway or metabolic process.
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Paragraph 0252
(2015/11/17)
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- Antisense modulation of CD40 ligand expression
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Antisense compounds, compositions and methods are provided for modulating the expression of CD40 ligand. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD40 ligand. Methods of using these compounds for modulation of CD40 ligand expression and for treatment of diseases associated with expression of CD40 ligand are provided.
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Page/Page column 19
(2008/06/13)
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- ANTISENSE MODULATION OF STEAROYL-COA DESATURASE EXPRESSION
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Antisense compounds, compositions and methods are provided for modulating the expression of stearoyl-CoA desaturase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding stearoyl-CoA desaturase. Methods of using these compounds for modulation of stearoyl-CoA desaturase expression and for treatment of diseases associated with expression of stearoyl-CoA desaturase are provided.
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Page/Page column 96-97
(2010/02/10)
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- Antisense inhibition via RNAse H-independent reduction in mRNA
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The present invention provides compositions and methods for reducing levels of a preselected mRNA, using antisense compounds targeted to a splice site or a region up to 50 nucleobases upstream of an exon/intron junction on said mRNA. Preferably, said antisense compounds do not elicit RNAse H cleavage of the mRNA.
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Page/Page column 21
(2010/02/12)
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- Compositions and their uses directed to cell growth and maintenance proteins
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Antisense compounds, compositions and methods are provided for modulating the expression of G protein-coupled receptor kinase 6. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding G p
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- Antisense modulation of sterol regulatory element-binding protein-1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of sterol regulatory element-binding protein-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids enco
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- Modulation of DC-SIGN expression
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Compounds, compositions and methods are provided for modulating the expression of DC-SIGN. The compositions comprise oligonucleotides, targeted to nucleic acid encoding DC-SIGN. Methods of using these compounds for modulation of DC-SIGN expression and for diagnosis and treatment of diseases and conditions associated with expression of DC-SIGN are provided.
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Page/Page column 12
(2008/06/13)
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- Antisense modulation of superoxide dismutase 1, soluble expression
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Antisense compounds, compositions and methods are provided for modulating the expression of superoxide dismutase 1, soluble. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding superoxide dismutase 1, soluble. Methods of using these compounds for modulation of superoxide dismutase 1, soluble expression and for treatment of diseases associated with expression of superoxide dismutase 1, soluble are provided.
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- Antisense modulation of stearoyl-CoA desaturase expression
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Antisense compounds, compositions and methods are provided for modulating the expression of stearoyl-CoA desaturase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding stearoyl-CoA desaturase. Methods of using these compounds for modulation of stearoyl-CoA desaturase expression and for treatment of diseases associated with expression of stearoyl-CoA desaturase are provided.
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- Antisense modulation of interferon gamma receptor 2
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Antisense compounds, compositions and methods are provided for modulating the expression of Interferon gamma receptor 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interferon gamma receptor 2. Methods of using these compounds for modulation of Interferon gamma receptor 2 expression and for treatment of diseases associated with expression of Interferon gamma receptor 2 are provided.
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- Antisense modulation of EIF2C1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of EIF2C1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EIF2C1. Methods of using these compounds for modulation of EIF2C1 expression and for treatment of diseases associated with expression of EIF2C1 are provided.
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- Antisense modulation of dual specific phosphatase 5 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of dual specific phosphatase 5. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding dual specific phosphatase 5. Methods of using these compounds for modulation of dual specific phosphatase 5 expression and for treatment of diseases associated with expression of dual specific phosphatase 5 are provided.
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- Antisense modulation of polo-like kinase expression
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Antisense compounds, compositions and methods are provided for modulating the expression of polo-like kinase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding polo-like kinase. Methods of using these compounds for modulation of polo-like kinase expression and for treatment of diseases associated with expression of polo-like kinase are provided.
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Page/Page column 21
(2008/06/13)
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- Antisense modulation of inducible nitric oxide synthase expression
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Antisense compounds, compositions and methods are provided for modulating the expression of inducible nitric oxide synthase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding inducible nitric oxide synthase. Methods of using these compounds for modulation of inducible nitric oxide synthase expression and for treatment of diseases associated with expression of inducible nitric oxide synthase are provided.
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- Antisense modulation of TFAP2C expression
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Antisense compounds, compositions and methods are provided for modulating the expression of TFAP2C. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding TFAP2C. Methods of using these compounds for modulation of TFAP2C expression and for treatment of diseases associated with expression of TFAP2C are provided.
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- Antisense modulation of PTPRM expression
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Antisense compounds, compositions and methods are provided for modulating the expression of PTPRM. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTPRM. Methods of using these compounds for modulation of PTPRM expression and for treatment of diseases associated with expression of PTPRM are provided.
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Page/Page column 21
(2008/06/13)
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- Antisense modulation of CD36 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of CD36. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD36. Methods of using these compounds for modulation of CD36 expression and for treatment of diseases associated with expression of CD36 are provided.
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Page/Page column 18
(2010/02/06)
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- Antisense modulation of NF-kappa-B p50 subunit expression
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Antisense compounds, compositions and methods are provided for modulating the expression of NF-kappa-B p50 subunit. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding NF-kappa-B p50 s
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- Antisense modulation of sap-1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of SAP-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding SAP-1. Methods of using these compounds for modulation of SAP-1 expression and for treatment of diseases associated with expression of SAP-1 are provided.
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- Antisense modulation of cyclin-dependent kinase 6 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of cyclin-dependent kinase 6. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding cyclin-dependent kinase 6. Methods of using these compounds for modulation of cyclin-dependent kinase 6 expression and for treatment of diseases associated with expression of cyclin-dependent kinase 6 are provided.
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Page/Page column 23
(2008/06/13)
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- Antisense modulation of hypothetical protein LOC51249 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of hypothetical protein LOC51249. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding hypothetical protein LOC51249. Methods of using these compounds for modulation of hypothetical protein LOC51249 expression and for treatment of diseases associated with expression of hypothetical protein LOC51249 are provided.
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Page/Page column 21
(2008/06/13)
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- Antisense modulation of selenophosphate synthetase 2 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of selenophosphate synthetase 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding selenophosphate synthetase 2. Methods of using these compounds for modulation of selenophosphate synthetase 2 expression and for treatment of diseases associated with expression of selenophosphate synthetase 2 are provided.
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Page/Page column 21
(2008/06/13)
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- Antisense modulation of ADAM12 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of ADAM12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding ADAM12. Methods of using these compounds for modulation of ADAM12 expression and for treatment of diseases associated with expression of ADAM12 are provided.
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Page/Page column 21-22
(2008/06/13)
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- Antisense modulation of SMRT expression
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Antisense compounds, compositions and methods are provided for modulating the expression of SMRT. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding SMRT. Methods of using these compounds for modulation of SMRT expression and for treatment of diseases associated with expression of SMRT are provided.
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Page/Page column 22
(2008/06/13)
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- Antisense modulation of cyclin-dependent kinase 4 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of cyclin-dependent kinase 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding cyclin-dependent kinase 4. Methods of using these compounds for modulation of cyclin-dependent kinase 4 expression and for treatment of diseases associated with expression of cyclin-dependent kinase 4 are provided.
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Page/Page column 24
(2008/06/13)
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- Antisense modulation of insulin-like growth factor 2 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of insulin-like growth factor 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding insulin-like growth factor 2. Methods of using these compounds for modulation of insulin-like growth factor 2 expression and for treatment of diseases associated with expression of insulin-like growth factor 2 are provided.
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Page/Page column 24
(2008/06/13)
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- Antisense modulation of HMG-CoA reductase expression
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Antisense compounds, compositions and methods are provided for modulating the expression of HMG-CoA reductase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding HMG-CoA reductase. Methods of using these compounds for modulation of HMG-CoA reductase expression and for treatment of diseases associated with expression of HMG-CoA reductase are provided.
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Page/Page column 22
(2010/02/05)
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- Antisense modulation of resistin expression
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Antisense compounds, compositions and methods are provided for modulating the expression of resistin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding resistin. Methods of using these compounds for modulation of resistin expression and for treatment of diseases associated with expression of resistin are provided.
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Page/Page column 21
(2010/02/05)
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- Antisense modulation of fatty acid synthase expression
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Antisense compounds, compositions and methods are provided for modulating the expression of fatty acid synthase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding fatty acid synthase. Methods of using these compounds for modulation of fatty acid synthase expression and for treatment of diseases associated with expression of fatty acid synthase are provided.
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Page/Page column 21
(2010/02/06)
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- Modulation of forkhead box O1A expression
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Antisense compounds, compositions and methods are provided for modulating the expression of forkhead box O1A. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding forkhead box O1A. Methods of using these compounds for modulation of forkhead box O1A expression and for treatment of diseases associated with expression of forkhead box O1A are provided, in particular, for methods of treating diabetes.
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Page/Page column 24
(2010/02/06)
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- Antisense modulation of G protein-coupled receptor 12 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of G protein-coupled receptor 12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding G protein-coupled receptor 12. Methods of using these compounds for modulation of G protein-coupled receptor 12 expression and for treatment of diseases associated with expression of G protein-coupled receptor 12 are provided.
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Page/Page column 22
(2010/11/30)
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- Antisense modulation of P2X4 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of P2X4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding P2X4. Methods of using these compounds for modulation of P2X4 expression and for treatment of diseases associated with expression of P2X4 are provided.
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Page/Page column 21
(2008/06/13)
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- Antisense modulation of histone deacetylase 4 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Histone deacetylase 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Histone deacetylase 4. Methods of using these compounds for modulation of Histone deacetylase 4 expression and for treatment of diseases associated with expression of Histone deacetylase 4 are provided.
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- Antisense modulation of Notch (Drosophila) homolog 4 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Notch (Drosophila) homolog 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Notch (Drosophila) homolog 4. Methods of using these compounds for modulation of Notch (Drosophila) homolog 4 expression and for treatment of diseases associated with expression of Notch (Drosophila) homolog 4 are provided.
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Page/Page column 17-18
(2010/02/06)
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- Antisense modulation of CDC14A expression
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Antisense compounds, compositions and methods are provided for modulating the expression of CDC14A. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CDC14A. Methods of using these compounds for modulation of CDC14A expression and for treatment of diseases associated with expression of CDC14A are provided.
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Page/Page column 17
(2010/02/06)
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- Antisense modulation of CD36 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of CD36. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD36. Methods of using these compounds for modulation of CD36 expression and for treatment of diseases associated with expression of CD36 are provided.
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Page/Page column 18
(2010/02/06)
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- Antisense modulation of histone deacetylase I expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Histone deacetylase 1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Histone deacetylase 1. Methods of using these compounds for modulation of Histone deacetylase 1 expression and for treatment of diseases associated with expression of Histone deacetylase 1 are provided.
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Page/Page column 18
(2010/02/08)
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- Antisense modulation of GFAT expression
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Antisense compounds, compositions, and methods are provided for modulating the expression of Glutamine-fructose-6-phosphate amidotransferase (GFAT). The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding GFAT. Methods of using these compounds for modulation of GFAT expression and for treatment of diseases associated with expression of GFAT are provided.
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Page/Page column 17
(2010/11/30)
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- Antisense modulation of integrin beta 5 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of integrin beta 5. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding integrin beta 5. Method
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- Antisense modulation of livin expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Livin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Livin. Methods of using these com
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- Antisense modulation of dual specific phosphatase 6 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of dual specific phosphatase 6. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding dual specific phosphatase 6. Methods of using these compounds for modulation of dual specific phosphatase 6 expression and for treatment of diseases associated with expression of dual specific phosphatase 6 are provided.
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- Antisense modulation of cell division cycle 2 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of cell division cycle 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding cell division cyc
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- Antisense modulation of breast cancer-1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of breast cancer-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding breast cancer-1. Method
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- Oligonucleotides having modified nucleoside units
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Disclosed are oligonucleotides and oligonucleosides that include one or more modified nucleoside units. The oligonucleotides and oligonucleosides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.
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- Oligonucleotides having modified nucleoside units
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Disclosed are oligonucleotide that include one or more modified nucleoside units. The oligonucleotides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.
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- Antisense modulation of geranylgeranyl diphosphate synthase 1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of geranylgeranyl diphosphate synthase 1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding g
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- Antisense modulation of p21-activated kinase 2 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of p21-activated kinase 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding p21-activated ki
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- Antisense modulation of LIM domain kinase 1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of LIM domain kinase 1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding LIM domain kinase 1
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