Isis Pharmaceuticals, Inc. Patent applications |
Patent application number | Title | Published |
20160138014 | ANTISENSE COMPOUNDS AND USES THEREOF - The present disclosure provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. | 05-19-2016 |
20160122761 | COMPOSITIONS AND METHODS FOR MODULATION OF TARGET NUCLEIC ACIDS - The present disclosure pertains generally to chemically-modified oligonucleotides for use in research, diagnostics, and/or therapeutics. In certain embodiments, the present disclosure describes compounds and methods for the modulation of a target nucleic acid. In certain embodiments, the present disclosure describes compounds and methods for the modulation of Apoliprotein C-III expression. | 05-05-2016 |
20160090596 | COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION - Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (a) [apo(a)]. In certain embodiments, the apo(a) targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo(a) for use in decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) and/or Lp(a). Certain diseases, disorders or conditions related to apo(a) and/or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof. | 03-31-2016 |
20160090595 | COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION - Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof. | 03-31-2016 |
20160076032 | COMPOSITIONS AND METHODS - Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine. | 03-17-2016 |
20160076031 | PHOSPHOROUS-LINKED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION - Oligonucleotide compositions comprising first and second oligonucleotides are provided wherein at least a portion of the first oligonucleotide is capable of hybridizing with at least a portion of the second oligonucleotide, at least a portion of the first oligonucleotide is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligonucleotides includes at least one nucleotide having a modified phosphorous-containing internucleoside linkage. Oligonucleotide/protein compositions are also provided comprising an oligonucleotide complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide of the oligonucleotide has a modified phosphorous-containing internucleoside linkage. | 03-17-2016 |
20160076030 | COMPOSITIONS AND METHODS FOR MODULATING HBV EXPRESSION - Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine. | 03-17-2016 |
20160076027 | COMPOSITIONS AND METHODS FOR MODULATION NUCLEIC ACIDS THROUGH NONSENSE MEDIATED DECAY - Disclosed herein are compounds, compositions and methods for modulating the amount or activity of a target nucleic acid. In certain embodiments, the amount or activity of a target nucleic acid is modulated through nonsense mediated decay. | 03-17-2016 |
20160068846 | MODULATION OF ANDROGEN RECEPTOR EXPRESSION - Certain embodiments are directed to compounds and compositions targeted to human androgen receptor (AR) for inhibiting androgen receptor levels in a cell, which can be useful for methods of treating cancer and inhibiting cancer cell growth or proliferation. | 03-10-2016 |
20160060626 | MODULATION OF ANGIOPOIETIN-LIKE 3 EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing plasma lipids, plasma glucose and atherosclerotic plaques in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disease, or a symptom thereof. | 03-03-2016 |
20160060625 | MODULATION OF APOLIPOPROTEIN CIII (APOCIII) EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disorder, or a symptom thereof. | 03-03-2016 |
20160053261 | COMPOSITIONS COMPRISING ALTERNATING 2'-MODIFIED NUCLEOSIDES FOR USE IN GENE MODULATION - The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression. | 02-25-2016 |
20160046945 | MODULATION OF HEPATITIS B VIRUS (HBV) EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing HBV mRNA, DNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate HBV-related diseases, disorders or conditions. | 02-18-2016 |
20160046939 | 5' MODIFIED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - The present invention provides 5′ modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5′-substituent and an optional 2′ substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 02-18-2016 |
20160032285 | COMPOSITIONS AND METHODS FOR MODULATING TAU EXPRESSION - Disclosed are methods for modulating splicing of Tau mRNA in an animal with Tau antisense compounds. Also disclosed herein are methods for reducing expression of Tau mRNA and protein in an animal with Tau antisense compounds. Such compounds and methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration Tau antisense oligonucleotides include Alzheimer's Disease, Fronto-temporal Dementia (FTD), FTDP-17, Progressive Supranuclear Palsy, Chronic Traumatic Encephalopathy, Epilepsy, and Dravet's Syndrome. | 02-04-2016 |
20160024496 | METHODS FOR MONITORING C9ORF72 EXPRESSION - Disclosed herein are methods for monitoring expression of C9ORF72 mRNA and protein in an animal with C9ORF72 specific inhibitors. Such C9ORF72 specific inhibitors include antisense compounds. | 01-28-2016 |
20160017328 | DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION - The present invention provides double stranded compositions wherein each strand is modified to have a motif defined by positioning of β-D-ribonucleosides and sugar modified nucleosides. More particularly, the present compositions comprise one strand having an alternating motif and another strand having a hemimer motif, a blockmer motif, a fully modified motif or a positionally modified motif. At least one of the strands has complementarity to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression. | 01-21-2016 |
20160017324 | CHIMERIC OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION - Oligomer compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes at least one nucleotide comprising a chimeric organic composition. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide comprising a chimeric organic composition. | 01-21-2016 |
20160017323 | CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE - Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine. | 01-21-2016 |
20160002627 | COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT - Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy. | 01-07-2016 |
20160002625 | CANCER TREATMENT - In certain embodiments, methods, compounds, and compositions for treating B-cell lymphoma or hepatocellular carcinoma by inhibiting expression of ST AT3 mRNA or protein in an animal are provided herein. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate B-cell lymphoma or hepatocellular carcinoma. The STAT (signal transducers and activators of transcription) family of proteins are DNA-binding proteins that play a dual role in signal transduction and activation of transcription. | 01-07-2016 |
20160002624 | ANTISENSE OLIGONUCLEOTIDE COMPOSITIONS - The present disclosure provides compositions comprising an antisense oligonucleotide and one or more excipients that modulates viscosity, turbidity or both viscosity and turbidity. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity are provided. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low turbidity are provided. In certain embodiments, pharmaceutical compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity and turbidity are provided. | 01-07-2016 |
20150376625 | SELECTIVE ANTISENSE COMPOUNDS AND USES THEREOF - The present disclosure provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, certain oligomeric compounds selectively reduce the expression of a target nucleic acid transcript relative to a non-target nucleic acid transcript. | 12-31-2015 |
20150376623 | ANTISENSE OLIGONUCLEOTIDES DIRECTED AGAINST CONNECTIVE TISSUE GROWTH FACTOR AND USES THEREOF - This invention provides compounds which comprise modified oligonucleotides capable of inhibitory expression of connective tissue factor and composition containing same as well as methods of treating hyperprolific disorders and fibrotic diseases, and of reducing scarring resulting from wound healing using such compounds. | 12-31-2015 |
20150376614 | MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS - Provided are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein for treating, preventing, delaying, or ameliorating Fredrickson Type I dyslipidemia/FCS/LPLD, in a patient. Such methods, compounds, and compositions increase HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in the patient, and are useful to treat, prevent, delay, or ameliorate any one or more of pancreatitis, cardiovascular disease, metabolic disorder, and associated symptoms. | 12-31-2015 |
20150368288 | METHOD OF PREPARING OLIGOMERIC COMPOUNDS USING MODIFIED COUPLING PROTOCOLS - Provided herein are methods for the synthesis of oligomeric compounds wherein the standard coupling protocols are modified when coupling bicyclic nucleosides of Formula I. More particularly, the modified coupling protocols provide for a decrease in the ratio of phosphoramidite solution to activator solution in the coupling reagent with an increased contact time. The modified coupling protocols provide for oligomeric compounds having comparable yields to similar oligomeric compounds having modified nucleosides other than bicyclic nucleosides of Formula I. | 12-24-2015 |
20150366894 | 2'-METHOXY SUBSTITUTED OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE MODULATIONS - Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2′-OCH | 12-24-2015 |
20150353929 | COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING - Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy. | 12-10-2015 |
20150344879 | COMPOUNDS AND METHODS FOR MODULATING GENE EXPRESSION - The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing. | 12-03-2015 |
20150337303 | METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) or Lp(a). Certain diseases, disorders or conditions related to apo(a) or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The antisense compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof. | 11-26-2015 |
20150329859 | SELECTIVE REDUCTION OF ALLELIC VARIANTS - Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative diseases, such as Huntington's Disease (HD). | 11-19-2015 |
20150322436 | OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR THE USE IN MODULATION OF MICRORNAS - Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activating in a cell. | 11-12-2015 |
20150322428 | COMPOUNDS AND METHODS FOR IMPROVED CELLULAR UPTAKE OF ANTISENSE COMPOUNDS - The present invention provides method of increasing the efficacy and potency of antisense compounds. In certain embodiments, the invention provides methods for improved cellular uptake. In certain embodiments, the resulting antisense activity is greater at a particular concentration of antisense compound than the antisense activity at the same concentration of the antisense compound in the absence of the ESCRT modulator. | 11-12-2015 |
20150315596 | ANTISENSE MODULATION OF PTP1B EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of PTP1B mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof. | 11-05-2015 |
20150315594 | COMPOSITIONS AND METHODS FOR MODULATING ANGIOPOIETIN-LIKE 3 EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof. | 11-05-2015 |
20150315580 | COMPOUNDS AND METHODS FOR IMPROVING CELLULAR UPTAKE OF OLIGOMERIC COMPOUNDS - The present invention provides method of optimizing the efficacy and potency of antisense drugs. In certain embodiments, the invention provides assays useful for determining favorable oligonucleotide characteristics and excipeints for improved cellular uptake. | 11-05-2015 |
20150315579 | DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION - The present invention provides double stranded compositions wherein the first strand is modified to have a particular motif and the second strand is modified a selected motif. The motifs are defined by positioning of differentially modified nucleosides wherein at least the sugar moieties are different. More particularly, the present compositions comprise an antisense strand that is modified to have a positional/full motif and the sense strand is modified to have an alternating motif, a hemimer motif, a blockmer motif, a gapped motif, a positional motif, a positional/full motif or a fully modified motif. Each strand further comprises one or more phosphorothioate internucleoside linkage. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression. | 11-05-2015 |
20150307877 | COMPOSITIONS AND THEIR USES DIRECTED TO HUNTINGTIN - Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's Disease (HD) progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntington's Disease (HD) in an individual susceptible to Huntington's Disease (HD). Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. | 10-29-2015 |
20150299789 | COMPETITIVE MODULATION OF MICRORNAS - The present invention provides compounds and methods for competitive modulation of microRNAs. Such compounds and methods have profound effects on cells. MicroRNAs (microRNAs), are small (approximately 18-24 nucleotides in length), non-coding RNA molecules encoded in the genomes of plants and animals. In certain instances, microRNAs regulate the expression of genes by binding to the 3′-untranslated regions (3′-UTR) of specific mRNAs. More than 1000 different microRNAs have been identified in plants and animals. | 10-22-2015 |
20150297629 | MODULATION OF RENIN-ANGIOTENSIN SYSTEM (RAS) RELATED DISEASES BY ANGIOTENSINOGEN - Disclosed herein are antisense compounds and methods for modulating AGT and modulating a RAS pathway related disease, disorder or condition in an individual in need thereof. RAS related diseases in an individual such as hypertension or organ damage can be treated, ameliorated or prevented with the administration of antisense compounds targeted to AGT. | 10-22-2015 |
20150292015 | SELECTIVE REDUCTION OF ALLELIC VARIANTS - Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD). | 10-15-2015 |
20150291960 | MODULATION OF CD40 EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing CD40. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to CD40 include hyperproliferative disorders, graft versus host disease (GVHD), graft rejection, asthma, airway hyperresponsiveness, chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and certain forms of arthritis. | 10-15-2015 |
20150291955 | ANTISENSE COMPOUNDS TARGETING GENES ASSOCIATED WITH FIBRONECTIN - Provided are compounds comprising oligonucleotides complementary to a fibronectin transcript. Certain such compounds are useful for hybridizing to a fibronectin transcript, including but not limited to a fibronectin transcript in a cell. Such hybridization results in modulation of splicing of the fibronectin transcript. Such compounds are used to treat one or more symptoms associated with fibrosis. Such compounds are used to treat one or more symptoms associated with renal fibrosis. | 10-15-2015 |
20150284725 | METHODS OF TREATING KENNEDY'S DISEASE - Certain embodiments are directed to methods of ameliorating, treating, or preventing Kennedy's Disease in a subject carrying a mutation in the Androgen Receptor (AR) gene, such as expansion of a CAG trinucleotide repeat, which is associated with Kennedy's Disease, by administering an antisense compound targeted to AR. Several embodiments provided herein relate to the discovery that antisense compounds targeting Androgen Receptor can ameliorate, treat, or prevent Kennedy's Disease in a subject carrying a mutation in the Androgen Receptor gene, such as expansion of a CAG trinucleotide repeat, which is associated with Kennedy's Disease. | 10-08-2015 |
20150275211 | ANTISENSE COMPOUNDS AND USES THEREOF - The present invention provides compounds comprising oligonucleotides complementary to a pyruvate kinase M transcript. Certain such compounds are useful for hybridizing to a pyruvate kinase M transcript, including but not limited to a pyruvate kinase M transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the pyruvate kinase M transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with cancer. | 10-01-2015 |
20150275208 | SELECTIVE ANTISENSE COMPOUNDS AND USES THEREOF - The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount, activity, or expression of the target nucleic acid in a cell. In certain embodiments, hybridization results in selective modulation of the amount, activity, or expression of a target Huntingtin gene or Huntingtin transcript in a cell. | 10-01-2015 |
20150267197 | METHODS FOR MODULATING C9ORF72 EXPRESSION - Disclosed herein are methods for reducing expression of C90RF72 mRNA and protein in an animal with C90RF72 specific inhibitors. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C90RF72 specific inhibitors include antisense compounds. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration C90RF72 specific inhibitors include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticalbasal degeneration syndrome (CBD), atypical Parkinsonian syndrome, and olivopontocerellar degeneration (OPCD). | 09-24-2015 |
20150267195 | OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC NUCLEOSIDES AND USES THEREOF - The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, the present invention provides compounds comprising oligonucleotides. In certain embodiments, such oligonucleotides comprise a region having a gapmer sugar motif. In certain embodiments, oligonucleotides comprise one or more type of modified sugar moieties and/or naturally occurring sugar moieties arranged along an oligonucleotide or region thereof in a defined pattern or sugar modification motif. | 09-24-2015 |
20150259681 | OLIGOMERIC COMPOUNDS COMPRISING TRICYCLIC NUCELOSIDES AND METHODS FOR THEIR USE - The present disclosure provides tricyclic nucleosides, oligomeric compounds comprising at least one of the tricyclic nucleosides and methods of using the oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 09-17-2015 |
20150252367 | MODULATION OF TRANSTHYRETIN EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof. | 09-10-2015 |
20150218205 | METHOD OF PREPARING OLIGOMERIC COMPOUNDS USING MODIFIED CAPPING PROTOCOLS - Provided herein are methods for the solid phase synthesis of oligomeric compounds wherein at least one of the capping steps has been modified. More particularly, methods are provided wherein one or more of the capping steps is omitted or performed using reduced equivalents of acetic anhydride. In certain embodiments, the methods provide an enhanced purity profile. In certain embodiments, the methods provide an increased yield. The methods provided herein also provide at least an economic advantage over currently used methods in that reduced amounts of the mixture of capping reagents are required. | 08-06-2015 |
20150191727 | BICYCLIC CYCLOHEXOSE NUCLEIC ACID ANALOGS - The present invention provides bicyclic cyclohexose nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance. | 07-09-2015 |
20150191723 | MODULATION OF UBE3A-ATS EXPRESSION - Certain embodiments are directed to methods and compounds for inhibiting UBE3A-ATS, the endogenous antisense transcript of ubiquitin protein ligase E3A (UBE3A). Such methods and compounds are useful for inducing expression of paternal UBE3A in cells and animals. | 07-09-2015 |
20150184164 | ANTISENSE MODULATION OF FIBROBLAST GROWTH FACTOR RECEPTOR 4 EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of fibroblast growth factor receptor 4 (FGFR4) mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a metabolic disease, or a symptom thereof. | 07-02-2015 |
20150184157 | MODULATION OF TRANSTHYRETIN EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of transthyretin. The compositions comprise oligonucleotides, targeted to nucleic acid encoding transthyretin. Methods of using these compounds for modulation of transthyretin expression and for diagnosis and treatment of diseases and conditions associated with expression of transthyretin are provided. | 07-02-2015 |
20150184156 | MODULATION OF APOLIPOPROTEIN (a) EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for diagnosis and treatment of disease associated with expression of apolipoprotein(a) are provided. | 07-02-2015 |
20150184153 | OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC NUCLEOTIDES AND USES THEREOF - The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. | 07-02-2015 |
20150176007 | COMPOSITIONS AND METHODS FOR MODULATING HBV EXPRESSION - Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine. | 06-25-2015 |
20150176005 | MODULATION OF ENHANCER RNA MEDIATED GENE EXPRESSION - Disclosed herein are methods and compounds for inhibiting gene expression by inhibiting enhancer RNAs (eRNAs). Such methods and compounds are useful for reducing expression of certain genes, many of which are associated with a variety of diseases and disorders. | 06-25-2015 |
20150159163 | MODIFIED NUCLEOSIDES, ANALOGS THEREOF AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 06-11-2015 |
20150159155 | MODULATION OF HUNTINGTIN EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of huntingtin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate Huntington's disease, or a symptom thereof. | 06-11-2015 |
20150152411 | METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing apo(a) to treat, prevent, ameliorate diseases, disorders or conditions related to apo(a) or Lp(a). Certain diseases, disorders or conditions related to apo(a) or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The antisense compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof. | 06-04-2015 |
20150141636 | OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC NUCLEOSIDES AND HAVING REDUCED TOXICITY - In certain embodiments, the present invention provides oligomeric compounds having favorable toxicity profiles and therapeutic indexes. Compounds of the present invention comprise bicyclic nucleosides. Certain such bicyclic nucleosides are pyrimidines that do not include a methyl group at the 5-carbon. Oligomeric compounds comprising such nucleosides are less toxic than compounds comprising bicyclic nucleosides that do include a methyl group at the 5-carbon. In certain embodiments, the present invention provides methods of preparing and using such compounds. | 05-21-2015 |
20150141493 | ANTISENSE MODULATION OF GCCR EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of GCCR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof. | 05-21-2015 |
20150126725 | 5' AND 2' BIS-SUBSTITUTED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - The present invention provides modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5′-substituent and a 2′-O-substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 05-07-2015 |
20150126720 | COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION - Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (a) [apo(a)]. In certain embodiments, the apo(a) targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo(a) for use in decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) and/or Lp(a). Certain diseases, disorders or conditions related to apo(a) and/or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof. | 05-07-2015 |
20150126719 | COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION - Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof. | 05-07-2015 |
20150126718 | CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE - Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine. | 05-07-2015 |
20150112055 | TRICYCLIC NUCLEIC ACID ANALOGS - The present disclosure provides tricyclic nucleosides and oligomeric compounds prepared therefrom. The tricyclic nucleosides each have a tricyclic ribosyl sugar moiety wherein a bridge between the 2′ and 4′ ribosyl ring carbon atoms further comprises a fused carbocyclic or heterocyclic ring. The tricyclic nucleosides are expected to be useful for enhancing properties of oligomeric compounds including for example binding affinity and nuclease resistance. | 04-23-2015 |
20150105444 | ANTISENSE COMPOUNDS TARGETING GENES ASSOCIATED WITH FIBRONECTIN - The present invention provides compounds comprising oligonucleotides complementary to a fibronectin transcript. Certain such compounds are useful for hybridizing to a fibronectin transcript, including but not limited to a fibronectin transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the fibronectin transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with fibrosis. In certain embodiments, such compounds are used to treat one or more symptoms associated with renal fibrosis. | 04-16-2015 |
20150099792 | ANTISENSE MODULATION OF GCGR EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of GCGR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof. | 04-09-2015 |
20150087691 | METHODS AND COMPOSITIONS FOR MODULATING ALPHA-1-ANTITRYPSIN EXPRESSION - Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, AIATD associated liver disease, and pulmonary disease, such as, AIATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting AIAT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, AIATD associated liver disease and pulmonary disease, such as, AIATD associated pulmonary disease. | 03-26-2015 |
20150057329 | COMPOUNDS AND METHODS FOR MODULATING EXPRESSION APOB - The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing. | 02-26-2015 |
20150051389 | SELECTIVE ANTISENSE COMPOUNDS AND USES THEREOF - Disclosed are oligomeric compounds which are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. The hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. | 02-19-2015 |
20150031747 | METHODS AND COMPOSITIONS FOR MODULATING FACTOR VII EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing Factor VII and treating, preventing, or slowing progression of thromboembolic complications, hyperproliferative disorders, or inflammatory conditions in an individual in need thereof. | 01-29-2015 |
20150025231 | COMPOSITIONS AND METHODS FOR MODULATION OF IKBKAP SPLICING - The present disclosure provides compounds comprising oligonucleotides complementary to a portion of the IKBKAP gene. Certain such compounds are useful for hybridizing to a portion of the IKBKAP gene, including but not limited to a portion of the IKBKAP gene in a cell. In certain embodiments, such hybridization results in modulation of splicing of the IKBKAP gene. In certain embodiments, the IKBKAP gene includes a mutation that results in defective splicing and a truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in a decrease in the amount of defective splicing and truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in an increase in the amount of normal splicing and functional, full-length IKAP protein. In certain embodiments, oligonucleotides are used to treat Familial Dysautonomia. | 01-22-2015 |
20150018540 | OLIGOMER-CONJUGATE COMPLEXES AND THEIR USE - Oligonucleotides, chemically-modified oligonucleotides, and oligonucleotide-conjugate compl in research, diagnostics, and/or therapeutics are described herein. | 01-15-2015 |
20150011001 | COMPOSITIONS AND METHODS FOR OPTIMIZING CLEAVAGE OF RNA BY RNASE H - The present invention provides compositions and methods for the optimization of cleavage of RNA species by RNase H. In some embodiments, the invention provides oligonucleotides that possess two or more regions of differing conformation, and at least one transitional nucleobase positioned between the regions that is capable of modulating transfer of the helical conformation characteristic of the region bound to the 3′ hydroxy thereof, to the region bound to the 5′ hydroxyl thereof. | 01-08-2015 |
20140378533 | MODULATION OF RNA BY REPEAT TARGETING - Disclosed herein are antisense compounds, compositions and methods for modulating an RNA target by targeting a repetitive sequence in the RNA target and modulating an associated disease, disorder and/or condition related to such RNA target. Also disclosed herein are methods of identifying such compounds and compositions. | 12-25-2014 |
20140371296 | METHODS FOR MODULATING METASTASIS-ASSOCIATED-IN-LUNG-ADENOCARCINOMA-TRANSCRIPT-1 (MALAT-1) EXPRESSION - The present embodiments provide compounds and methods for reducing expression of Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) RNA and/or protein in an animal. Such methods are useful for treating cancer, such as colon cancer, intestinal cancer, lung cancer (e.g. non-small cell lung cancer), liver cancer, and/or prostate cancer. In various aspects, the cancer is a primary cancer. | 12-18-2014 |
20140357856 | CHIMERIC OLIGOMERIC COMPOUNDS COMPRISING ALTERNATING REGIONS OF NORTHERN AND SOUTHERN CONFORMATIONAL GEOMETRY - The present invention relates to novel chimeric oligomeric compounds having a plurality of alternating regions having either RNA like having northern or 3′-endo conformational geometry (3′-endo regions) or DNA like having southern or C2′-endo/O4′-endo conformational geometry. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems and are useful, for example, for investigative and therapeutic purposes. | 12-04-2014 |
20140357701 | MODULATION OF HEPATITIS B VIRUS (HBV) EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing HBV mRNA, DNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate HBV-related diseases, disorders or conditions. | 12-04-2014 |
20140357558 | COMPOSITIONS AND METHODS FOR TREATMENT OF SPINAL MUSCULAR ATROPHY - Disclosed herein are compounds, compositions and methods for treatment of diseases and disorders, including spinal muscular atrophy. | 12-04-2014 |
20140343123 | CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE - Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine. | 11-20-2014 |
20140323707 | SELECTIVE ANTISENSE COMPOUNDS AND USES THEREOF - The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. | 10-30-2014 |
20140316121 | METHODS AND COMPOUNDS USEFUL IN CONDITIONS RELATED TO REPEAT EXPANSION - Described are compounds and methods useful for the treatment and investigation of diseases and disorders associated with expanded repeat-containing RNA molecules. | 10-23-2014 |
20140315979 | TETRAHYDROPYRAN NUCLEIC ACID ANALOGS - The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, tetrahydropyran nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including nuclease resistance and binding affinity. In some embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 10-23-2014 |
20140309286 | MODULATION OF TMPRSS6 EXPRESSION - Disclosed herein are antisense compounds and methods for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and/or condition in an individual in need thereof. Iron accumulation diseases in an individual such as hemochromatosis or β-thalassemia can be ameliorated or prevented with the administration of antisense compounds targeted to TM-PRSS6. | 10-16-2014 |
20140309282 | COMPOSITIONS AND METHODS FOR MODULATION OF LMNA EXPRESSION - Disclosed herein are compounds, compositions and methods for modulating the expression of LMNA in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Further provided are methods of identifying cis splicing regulatory elements of a selected mRNA using the disclosed compounds. | 10-16-2014 |
20140309279 | GAPPED OLIGOMERIC COMPOUNDS COMPRISING 5'-MODIFIED DEOXYRIBONUCLEOSIDES IN THE GAP AND USES THEREOF - The present invention provides gapped oligomeric compounds comprising at least one 5′-substituted P-D-2′-deoxyribonucleoside in the gap region. Certain such gapped oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited to, nucleic acids in a cell. The oligomeric compounds provided herein have improved properties such as selectivity, potency and improved proinflammatory profile. In certain embodiments, hybridization results in modulation of the amount of activity or expression of the target nucleic acid in a cell. | 10-16-2014 |
20140303235 | LINKAGE MODIFIED GAPPED OLIGOMERIC COMPOUNDS AND USES THEREOF - The present invention provides gapped oligomeric compounds. More particularly the gapped oligomeric compounds provided herein comprise at least one modified intemucleoside linkage in the gap region. Such gapped oligomeric compounds have one or more improved properties such as selectivity, potency, improved toxicity profile and or improved proinflammatory profile. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. | 10-09-2014 |
20140288291 | COMPOUNDS AND METHODS FOR MODULATING PROTEIN EXPRESSION - The present invention provides compounds and methods for modulating expression of a protein, including, but not limited to, modulating splicing of a pre-mRNA to modulate the amount of one or more variants of a protein. | 09-25-2014 |
20140275207 | ANTISENSE COMPOUNDS AND METHODS OF USE THEREOF - Disclosed herein are compounds, compositions and methods for modulating the expression of LMW-PTPase in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Also provided are methods for the prevention, amelioration and/or treatment of diabetes, insulin resistance, insulin deficiency, hypercholesterolemia, hyperglycemia, dyslipidemia, hyperlipidemia, hypertriglyceridemia, and hyperfattyacidemia. In some embodiments, the diabetes is type II diabetes by administration of antisense compounds targeted to LMW-PTPase. | 09-18-2014 |
20140256797 | MODULATION OF TRANSTHYRETIN EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof. | 09-11-2014 |
20140235694 | ANTISENSE MODULATION OF PTP1B EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of PTP1B mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof. | 08-21-2014 |
20140213631 | METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION - Disclosed herein are methods for decreasing kallikrein and treating or preventing inflammatory conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to kallikrein include hereditary angioedema (HAE). Methods for inhibiting kallikrein can also be used as a prophylactic treatment to prevent individuals at risk for developing an inflammatory condition, such as, hereditary angioedema. | 07-31-2014 |
20140206750 | MODULATION OF APOLIPOPROTEIN (a) EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for diagnosis and treatment of disease associated with expression of apolipoprotein(a) are provided. | 07-24-2014 |
20140206745 | METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION - Disclosed herein are methods for decreasing kallikrein and treating or preventing thromboembolic conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to kallikrein include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Methods for inhibiting kallikrein can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism. | 07-24-2014 |
20140194492 | METHODS FOR TREATING HYPERCHOLESTEROLEMIA - Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides. | 07-10-2014 |
20140193825 | MODULATION OF ANGIOPOIETIN-LIKE 3 EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing plasma lipids, plasma glucose and atherosclerotic plaques in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disease, or a symptom thereof. | 07-10-2014 |
20140128453 | MODULATION OF APOLIPOPROTEIN CIII (APOCIII) EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disorder, or a symptom thereof. | 05-08-2014 |
20140114057 | ANTISENSE COMPOUNDS TARGETING GENES ASSOCIATED WITH USHER SYNDROME - The present invention provides compounds comprising oligonucleotides complementary to an Usher transcript. Certain such compounds are useful for hybridizing to an Usher transcript, including but not limited, to an Usher transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the Usher transcript. In certain such embodiments, the Usher transcript includes a mutation that results in cryptic splicing and hybridization of the oligonucleotide results in a decrease in the amount of cryptic splicing. In certain embodiments, such compounds are used to treat Usher Syndrome. | 04-24-2014 |
20140107330 | OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC NUCLEOTIDES AND USES THEREOF - The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. | 04-17-2014 |
20140107184 | MODULATION OF HEPATITIS B VIRUS (HBV) EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing HBV mRNA, DNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate HBV-related diseases, disorders or conditions. | 04-17-2014 |
20140107180 | MODULATION OF ANDROGEN RECEPTOR EXPRESSION - Certain embodiments are directed to compounds and compositions targeted to human androgen receptor (AR) for inhibiting androgen receptor levels in a cell, which can be useful for methods of treating cancer and inhibiting cancer cell growth or proliferation. | 04-17-2014 |
20140073786 | CYCLOHEXENYL NUCLEIC ACIDS ANALOGS - The present disclosure describes cyclohexenyl nucleic acid analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, cyclohexenyl nucleic acid analogs are provided, having one or more chiral substituents, that are expected to be useful for enhancing properties of oligomeric compounds including nuclease resistance and binding affinity. In some embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 03-13-2014 |
20140011860 | COMPOUNDS AND METHODS FOR MODULATING TARGET NUCLEAR AND SUB-NUCLEAR NUCLEIC ACID MOLECULES IN CELLS AND ANIMALS - Compounds and methods for modulating target nucleic acids found in organelles or sub-organelles of cells are provided. The compounds and methods modulate target nucleic acids in a sub-nuclear organelle include, but are not limited to, the nucleolus and/or a cajal body of animal cells. | 01-09-2014 |
20140005252 | MODULATION OF ALPHA SYNUCLEIN EXPRESSION | 01-02-2014 |
20130331435 | ANTISENSE MODULATION OF KINESIN-LIKE 1 EXPRESSION - Antisense compounds, compositions and methods are provided for modulating the expression of kinesin-like 1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding kinesin-like 1. Methods of using these compounds for modulation of kinesin-like 1 expression and for treatment of diseases associated with expression of kinesin-like 1 are provided. | 12-12-2013 |
20130331434 | METHODS FOR MODULATING FACTOR 12 EXPRESSION - Disclosed herein are methods for decreasing Factor 12 and treating or preventing thromboembolic conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 12 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and mesenteric thrombosis. Methods for inhibiting Factor 12 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism. | 12-12-2013 |
20130323836 | 5'-END DERIVATIVES - The present invention provides compounds of formula (1). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. | 12-05-2013 |
20130317085 | MODULATION OF APOLIPOPROTEIN C-III EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of apolipoprotein C-III. The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein C-III. Methods of using these compounds for modulation of apolipoprotein C-III expression and for diagnosis and treatment of disease associated with expression of apolipoprotein C-III are provided | 11-28-2013 |
20130296400 | ANTIDOTES TO ANTISENSE COMPOUNDS - The present invention relates to antisense antidote compounds and uses thereof. Such antidote compounds reduce the magnitude and/or duration of the antisense activity of an antisense compound. | 11-07-2013 |
20130289092 | COMPOUNDS AND METHODS FOR MODULATING INTERACTION BETWEEN PROTEINS AND TARGET NUCLEIC ACIDS - Provided herein are antisense compounds and methods for recruiting one or more non-cleaving protein to a target nucleic acid in a cell. In certain instances such recruitment of a non-cleaving protein alters the function or activity of the target nucleic acid. In certain such instances, the target nucleic acid a pre-mRNA and the recruitment of the non-cleaving protein results in a change in splicing of the pre-mRNA. | 10-31-2013 |
20130274309 | COMPOSITIONS AND METHODS FOR NON-PARENTERAL DELIVERY OF OLIGONUCLEOTIDES - The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes. The compositions and methods of the invention are utilized to effect the oral, buccal, rectal or vaginal administration of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic, palliative or prophylactic purposes | 10-17-2013 |
20130260460 | CONFORMATIONALLY RESTRICTED DINUCLEOTIDE MONOMERS AND OLIGONUCLEOTIDES - This invention relates to conformationally locked dinucleotide motifs for exo- and phosphate stabilization. For instance, oligonucleotides can be prepared having one or more of the following formulas (IV-IX). | 10-03-2013 |
20130252243 | METHODS OF DETERMINING POTENCY OF CHEMICALLY-SYNTHESIZED OLIGONUCLEOTIDES - Provided herein are methods for determining potency of RNAi agents. Such methods include, but are not limited to, cell-based and cell-free assays that measure binding of an RNAi agent with Ago2 or that measure Ago2 activity in the presence of such RNAi agents. Also provided are assays that determine potency of RNAi agents by assessing their ability to compete with other RNAi agents, including control RNAi agents, for binding and/or activation of Ago2. | 09-26-2013 |
20130237585 | MODULATION OF DYSTROPHIA MYOTONICA-PROTEIN KINASE (DMPK) EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of a DMPK mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate type 1 myotonic dystrophy, or a symptom thereof. | 09-12-2013 |
20130225659 | MODULATION OF NUCLEAR-RETAINED RNA - Provided herein are methods, compounds, and compositions for reducing expression of a nrRNA in an animal. Also provided herein are methods, compounds, and compositions for treating, ameliorating, delaying or reducing a symptom of a disease or disorder associated with a nuclear-retained RNA in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a disease or condition associated with a nuclear-retained RNA, or a symptom thereof. | 08-29-2013 |
20130217749 | MODULATION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE-MITCHONDRIAL (PEPCK-M) EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of phosphoenolpyruvate carboxykinase-mitochondrial (PEPCK-M) mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preventing or decreasing diabetes, obesity, metabolic syndrome, diabetic dyslipidemia, and/or hypertriglyceridemia in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of diabetes, obesity, metabolic syndrome, diabetic dyslipidemia, and/or hypertriglyceridemia, or a symptom thereof. | 08-22-2013 |
20130211064 | TETRAHYDROPYRAN NUCLEIC ACID ANALOGS - The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, tetrahydropyran nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including nuclease resistance and binding affinity. In some embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 08-15-2013 |
20130203836 | 2' AND 5' MODIFIED MONOMERS AND OLIGONUCLEOTIDES - The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least on nucleoside of formula (2):Formula (1) and Formula (2). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. | 08-08-2013 |
20130197062 | OLIGOMERIC COMPOUNDS COMPRISING TRICYCLIC NUCELOSIDES AND METHODS FOR THEIR USE - The present disclosure provides tricyclic nucleosides, oligomeric compounds comprising at least one of the tricyclic nucleosides and methods of using the oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 08-01-2013 |
20130190384 | MODULATION OF FACTOR 11 EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing Factor 11 and treating or preventing thromboembolic complications in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 11 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 11 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism. | 07-25-2013 |
20130190382 | METHODS FOR INHIBITING EXPRESSION OF CONNECTIVE TISSUE GROWTH FACTOR - This invention provides compounds which comprise modified oligonucleotides capable of inhibitory expression of connective tissue factor and composition containing same as well as methods of treating hyperprolific disorders and fibrotic diseases, and of reducing scarring resulting from wound healing using such compounds. | 07-25-2013 |
20130190380 | ANTISENSE OLIGONUCLEOTIDES DIRECTED AGAINST CONNECTIVE TISSUE GROWTH FACTOR AND USES THEREOF - This invention provides compounds which comprise modified oligonucleotides capable of inhibitory expression of connective tissue factor and composition containing same as well as methods of treating hyperprolific disorders and fibrotic diseases, and of reducing scarring resulting from wound healing using such compounds. | 07-25-2013 |
20130189782 | COMPOSITIONS AND THEIR USES DIRECTED TO HUNTINGTIN - Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's disease progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntingtin's disease in an individual susceptible to Huntingtin's Disease. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. | 07-25-2013 |
20130178513 | MODULATION OF EIF4E EXPRESSION - Oligomeric compounds, compositions and methods are provided for modulating the expression of eIF4E. The antisense compounds may be single- or double-stranded and are targeted to nucleic acid encoding eIF4E. Methods of using these compounds for modulation of eIF4E expression and for diagnosis and treatment of diseases and conditions associated with expression of eIF4E are provided. | 07-11-2013 |
20130165496 | COMPOUNDS AND METHODS FOR MODULATING EXPRESSION OF GCCR - The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing. | 06-27-2013 |
20130164844 | COMPOUNDS AND METHODS FOR IMPROVING CELLULAR UPTAKE OF OLIGOMERIC COMPOUNDS - The present invention provides method of optimizing the efficacy and potency of antisense drugs. In certain embodiments, the invention provides assays useful for determining favorable oligonucleotide characteristics and excipeints for improved cellular uptake. | 06-27-2013 |
20130156845 | LIPID FORMULATED SINGLE STRANDED RNA - The present invention provides compositions comprising a nucleic acid lipid particle and an oligomeric compound and uses thereof. In certain embodiments, such compositions are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds or as RNAi compounds. | 06-20-2013 |
20130150569 | BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - The present invention provides novel 3′,5′-linked bicyclic nucleosides and oligomeric compounds prepared therefrom. The bicyclic nucleosides provided herein are useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as nuclease resistance. | 06-13-2013 |
20130150425 | ANTISENSE MODULATION OF GCCR EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of GCCR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof. | 06-13-2013 |
20130144044 | ANTIBACTERIAL 4,6-SUBSTITUTED 6', 6'' AND 1 MODIFIED AMINOGLYCOSIDE ANALOGS - The present invention is directed to analogs of aminoglycoside compounds as well as their preparation and use as prophylactic or therapeutics against microbial infection. | 06-06-2013 |
20130143943 | MODULATION OF GLUCOCORTICOID RECEPTOR EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of glucocorticoid receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucocorticoid receptor. Methods of using these compounds for modulation of glucocorticoid receptor expression and for diagnosis and treatment of diseases and conditions associated with expression of glucocorticoid receptor are provided. | 06-06-2013 |
20130131147 | SUBSTITUTED 2'-AMINO AND 2'-THIO-BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - Provided herein are 2′-amino and 2′-thio bicyclic nucleosides and oligomenc compounds prepared therefrom. The novel bicyclic nucleosides provided herein are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as nuclease resistance. | 05-23-2013 |
20130123331 | MODULATION OF DIACYLGLYCEROL ACYLTRANSFERASE 2 EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 2. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 2. Methods of using these compounds for modulation of diacylglycerol acyltransferase 2 expression and for diagnosis and treatment of diseases and conditions associated with expression of diacylglycerol acyltransferase 2 are provided. | 05-16-2013 |
20130116420 | 5' MODIFIED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - The present invention provides 5′ modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5′-substituent and an optional 2′ substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 05-09-2013 |
20130116301 | ANTISENSE MODULATION OF GCGR EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of GCGR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof. | 05-09-2013 |
20130109850 | MODIFIED 5' DIPHOSPHATE NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM | 05-02-2013 |
20130109849 | COMPOSITIONS AND THEIR USES DIRECTED TO ACEYTL-COA CARBOXYLASES | 05-02-2013 |
20130084576 | MODIFIED NUCLEOSIDES, ANALOGS THEREOF AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 04-04-2013 |
20130079387 | ANTISENSE OLIGONUCLEOTIDE MODULATION OF RAF GENE EXPRESSION - Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating or preventing conditions, including hyperproliferative conditions, associated with raf expression. | 03-28-2013 |
20130059902 | METHODS AND COMPOSITIONS USEFUL IN TREATMENT OF DISEASES OR CONDITIONS RELATED TO REPEAT EXPANSION - The present invention is drawn to chemically-modified oligomers that are complementary to, and capable of hybridizing within the repeat region of CAG, CUG, or CCUG nucleotide repeat-containing RNAs (NRRs). | 03-07-2013 |
20130059777 | MODULATION OF GLUCOSE-6-PHOSPHATASE TRANSLOCASE EXPRESSION - Compositions and methods are provided for decreasing blood glucose levels in an animal, comprising administering to said animal an antisense inhibitor of glucose-6-phosphatase translocase expression alone or in combination with at least one glucose-lowering drug. Also provided are compositions and methods for treating diabetes and other metabolic disorders. | 03-07-2013 |
20130053431 | MODULATION OF GROWTH HORMONE RECEPTOR EXPRESSION AND INSULIN-LIKE GROWTH FACTOR EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of growth hormone receptor and/or insulin like growth factor-I (IGF-I). The compositions comprise oligonucleotides, targeted to nucleic acid encoding growth hormone receptor. Methods of using these compounds for modulation of growth hormone receptor expression and for diagnosis and treatment of disease associated with expression of growth hormone receptor and/or insulin-like growth factor-I are provided. Diagnostic methods and kits are also provided. | 02-28-2013 |
20130053430 | MODULATION OF CETP EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of a CETP mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL levels and/or HDL activity and reducing plasma lipids, plasma glucose and atherosclerotic plaques in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disease, or a symptom thereof. | 02-28-2013 |
20130046008 | SELECTIVE REDUCTION OF ALLELIC VARIANTS - Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD). | 02-21-2013 |
20130046007 | SELECTIVE REDUCTION OF ALLELIC VARIANTS - Disclosed herein are antisense compounds and methods for selectively of reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative, such as Huntington's Disease (HD). | 02-21-2013 |
20130041144 | 5'-SUBSTITUTED BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - Provided herein are novel 5′-(S)—CH | 02-14-2013 |
20130041011 | BASE MODIFIED BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - Provided herein are novel base modified bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, novel pyrimidine bicyclic nucleosides are provided wherein each pyrimidine base is substituted at the 5 position with an optionally substituted, aromatic or heteroaromatic ring system comprising from 5 to 7 ring atoms selected from C, N, O and S. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 02-14-2013 |
20130035370 | COMPOSITIONS AND METHODS FOR MODULATION OF LMNA EXPRESSION - Disclosed herein are compounds, compositions and methods for modulating the expression of LMNA in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Further provided are methods of identifying cis splicing regulatory elements of a selected mRNA using the disclosed compounds. | 02-07-2013 |
20130035369 | DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION - The present invention provides double stranded compositions wherein the first strand is modified to have a particular motif and the second strand is modified a selected motif. More particularly, the present compositions comprise an antisense strand that is modified to have a positional/full motif and the sense strand is modified to have an alternating motif, a hemimer motif, a blockmer motif, a gapped motif, a positional motif, a positional/full motif or a fully modified motif. Each strand further comprises one or more phosphorothioate internucleoside linkage. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. | 02-07-2013 |
20130023579 | MODULATION OF ANGIOPOIETIN-LIKE 3 EXPRESSION - Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing plasma lipids, plasma glucose and atherosclerotic plaques in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disease, or a symptom thereof. | 01-24-2013 |
20130005674 | ANTIBACTERIAL 4,5-SUBSTITUTED AMINOGLYCOSIDE ANALOGS HAVING MULTIPLE SUBSTITUENTS - The present invention is directed to analogs of aminoglycoside compounds as well as their preparation and use as prophylactic or therapeutics against microbial infection. | 01-03-2013 |
20120316221 | COMPOSITIONS AND THEIR USES DIRECTED TO IL-4R ALPHA - Disclosed herein are compounds, compositions and methods for modulating the expression of IL-4R alpha in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders related to expression of IL 4R-α, airway hyperresponsiveness, and/or pulmonary inflammation. | 12-13-2012 |
20120316219 | MODULATION OF APOLIPOPROTEIN(A) EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for diagnosis and treatment of disease associated with expression of apolipoprotein(a) are provided. | 12-13-2012 |
20120309815 | COMPOSITIONS AND METHODS FOR TOPICAL DELIVERY OF OLIGONUCLEOTIDES - The present invention relates to compositions and methods which enhance the delivery of nucleic acids and other nucleosidic moieties via topical routes of administration. The invention relates to the use of an aqueous solution to preferentially deliver nucleic acids preferentially to hair follicles. The invention relates to a method of inhibiting hair growth comprising administration of a nucleic acid preferentially to a hair follicle. | 12-06-2012 |
20120295958 | MODULATION OF GLUCAGON RECEPTOR EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of glucagon receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucagon receptor. Methods of using these compounds for modulation of glucagon receptor expression and for diagnosis and treatment of disease associated with expression of glucagon receptor are provided. | 11-22-2012 |
20120295272 | PROINFLAMMATORY NUCLEIC ACIDS - The present invention provides compositions and methods for identifying and utilizing proinflammatory nucleic acids. In particular, this invention relates to compounds, particularly oligonucleotides, which exert their effect through triggering receptors expressed by myeloid cells (TREMs), specifically TREM 2. | 11-22-2012 |
20120283312 | MODULATION OF EIF4E EXPRESSION - Oligomeric compounds, compositions and methods are provided for modulating the expression of eIF4E. The antisense compounds may be single- or double-stranded and are targeted to nucleic acid encoding eIF4E. Methods of using these compounds for modulation of eIF4E expression and for diagnosis and treatment of diseases and conditions associated with expression of eIF4E are provided. | 11-08-2012 |
20120270929 | MODULATION OF TTC39 EXPRESSION TO INCREASE HDL - Provided herein are methods, compounds, and compositions for reducing expression of a TTC39 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL and/or decreasing PCSK9 in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate cardiovascular disease, or a symptom thereof. | 10-25-2012 |
20120270920 | COMPOSITIONS AND METHODS FOR TREATMENT OF POUCHITIS - The present invention relates methods of treating pouchitis by administering a pharmaceutical formulation suitable for rectal use, such as an enema or suppository, comprising an antisense oligonucleotide targeted to ICAM-1 to an individual | 10-25-2012 |
20120232125 | MODULATION OF DIACYLGLYCEROL ACYLTRANSFERASE 1 EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 1. Methods of using these compounds for modulation of diacylglycerol acyltransferase 1 expression and for diagnosis and treatment of disease associated with expression of diacylglycerol acyltransferase 1, such as obesity and obesity-related conditions, are provided. | 09-13-2012 |
20120214865 | METHODS FOR SLOWING FAMILIAL ALS DISEASE PROGRESSION - Methods for slowing disease progression in an individual suffering from familial ALS are provided. Also provided are methods of increasing the survival time of an individual suffering from familial ALS. These methods employ antisense oligonucleotides targeted to SOD1, for use in inhibiting the expression of SOD1 in the central nervous system of an individual suffering from familial ALS. | 08-23-2012 |
20120214862 | MODULATION OF FACTOR 7 EXPRESSION - Disclosed herein are antisense compounds and methods for decreasing Factor 7 and treating or preventing thromboembolic complications in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 7 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 7 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism. | 08-23-2012 |
20120214736 | COMPOSITIONS AND METHODS FOR THE MODULATION OF JNK PROTEINS - The invention provides compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase 1 (JNK1 protein. | 08-23-2012 |
20120208864 | COMPOUNDS AND METHODS FOR MODULATING EXPRESSION OF GCGR - The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing. | 08-16-2012 |
20120202874 | ANTISENSE OLIGONUCLEOTIDE MODULATION OF STAT3 EXPRESSION - Compounds, compositions and methods are provided for inhibiting the expression of human STAT3. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding STAT3. Methods of using these oligonucleotides for inhibition of STAT3 expression and for promotion of apoptosis are provided. Methods for treatment of diseases, particularly inflammatory diseases and cancers, associated with overexpression or constitutive activation of STAT3 or insufficient apoptosis are also provided. | 08-09-2012 |
20120196921 | MODULATION OF SGLT-2 EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of SGLT2. The compositions comprise oligonucleotides, targeted to nucleic acid encoding SGLT2. Methods of using these compounds for modulation of SGLT2 expression and for diagnosis and treatment of diseases and conditions associated with expression of SGLT2 are provided. | 08-02-2012 |
20120184031 | ANTISENSE INHIBITION VIA RNASE H-INDEPENDENT REDUCTION IN MRNA - 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. | 07-19-2012 |
20120172414 | BICYCLIC CYCLOHEXOSE NUCLEIC ACID ANALOGS - The present invention provides bicyclic cyclohexose nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance. | 07-05-2012 |
20120165547 | SUPPORTS FOR OLIGOMER SYNTHESIS - Universal linkers, their facile processes of manufacture and methods of using the same are provided. | 06-28-2012 |
20120165396 | MODULATION OF EXPORTIN 5 EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of exportin 5. The compositions comprise oligonucleotides, targeted to nucleic acid encoding exportin 5. Methods of using these compounds for modulation of exportin 5 expression and for diagnosis and treatment of diseases and conditions associated with expression of exportin 5 are provided. | 06-28-2012 |
20120149893 | MODULATION OF EIF4E-BP2 - Compounds, compositions and methods are provided for modulating the expression of eIF4E-BP2. The compositions comprise oligonucleotides, targeted to nucleic acid encoding eIF4E-BP2. Methods of using these compounds for modulation of eIF4E-BP2 expression and for diagnosis and treatment of diseases and conditions associated with expression of eIF4E-BP2 are provided. | 06-14-2012 |
20120149755 | ANTISENSE OLIGONUCLEOTIDE MODULATION OF RAF GENE EXPRESSION - Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating or preventing conditions, including hyperproliferative conditions, associated with raf expression. | 06-14-2012 |
20120149109 | MODULATION OF TRANSTHYRETIN EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of transthyretin. The compositions comprise oligonucleotides, targeted to nucleic acid encoding transthyretin. Methods of using these compounds for modulation of transthyretin expression and for diagnosis and treatment of diseases and conditions associated with expression of transthyretin are provided. | 06-14-2012 |
20120123685 | SECONDARY STRUCTURE DEFINING DATABASE AND METHODS FOR DETERMINING IDENTITY AND GEOGRAPHIC ORIGIN OF AN UNKNOWN BIOAGENT THEREBY - The present invention relates generally to the field of investigational bioinformatics and more particularly to secondary structure defining databases. The present invention further relates to methods for interrogating a database as a source of molecular masses of known bioagents for comparing against the molecular mass of an unknown or selected bioagent to determine either the identity of the selected bioagent, and/or to determine the origin of the selected bioagent. The identification of the bioagent is important for determining a proper course of treatment and/or irradication of the bioagent in such cases as biological warfare. Furthermore, the determination of the geographic origin of a selected bioagent will facilitate the identification of potential criminal identity. | 05-17-2012 |
20120122086 | METHOD FOR RAPID DETECTION AND IDENTIFICATION OF BIOAGENTS IN EPIDEMIOLOGICAL AND FORENSIC INVESTIGATIONS - The present invention provides methods for rapid forensic investigations by identification of bioagents associated with biowarfare and acts of terrorism or crime. The methods are also useful for epidemiological investigations by genotyping of bioagents. | 05-17-2012 |
20120115932 | MODULATION OF STAT 6 EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of STAT 6. The compositions comprise oligonucleotides, targeted to nucleic acid encoding STAT 6. Methods of using these compounds for modulation of STAT 6 expression and for diagnosis and treatment of disease associated with expression of STAT 6 are provided. | 05-10-2012 |
20120115930 | COMPOSITIONS AND THEIR USES DIRECTED TO HEPCIDIN - Disclosed herein are compounds, compositions and methods for modulating the expression of hepcidin in a cell, tissue or animal or preventing, ameliorating or treating anemia. Also provided are methods for prevention, amelioration or treatment of anemia, and for increasing red blood cell count in an animal. Also provided are methods for the prevention, amelioration and/or treatment of low serum iron levels, low red blood cell count and other clinical endpoints of anemia in an animal. These methods may be achieved by administration of compounds or compositions including antisense compounds targeted to a nucleic acid that expresses hepcidin polypeptide combined with an erythropoiesis stimulating agent. | 05-10-2012 |
20120115228 | OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR THE USE IN MODULATION OF MICRORNAS - Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activing in a cell. | 05-10-2012 |
20120088814 | METHODS OF MODULATING AN IMMUNE RESPONSE TO A VIRAL INFECTION - Disclosed herein are methods for treating respiratory disorders via administration of antisense compounds targeting IL-4Rα. Provided herein, for example, are compositions and methods of modulating immune responses to a viral infection in a subject. Also provided, for example, are compositions and methods for managing, treating, ameliorating, preventing and/or delaying the onset of pulmonary inflammation, airway hyperreactivity and/or loss of lung function, or a symptom thereof in a subject during the course of or resulting from a viral infection. Further provided, for example, are compositions and methods of inducing or augmenting hypo-responsiveness, non-responsiveness or tolerance to a virus in a subject. Also provided, for example, are compositions and methods of enhancing the efficacy of a viral vaccine in a subject. In certain embodiments, the compositions and methods provided herein utilize an antisense compound 12 to 35 nucleobases in length targeted to a nucleic acid molecule encoding human IL-4 receptor alpha IL-4Rα, wherein said antisense compound inhibits expression of human IL-4Rα protein and/or expression of functional IL-4 and IL-13 receptors. | 04-12-2012 |
20120077866 | ANTISENSE MODULATION OF C-REACTIVE PROTEIN EXPRESSION - Antisense compounds, compositions and methods are provided for modulating the expression of C-reactive protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding C-reactive protein. Methods of using these compounds for modulation of C-reactive protein expression and for treatment of diseases associated with expression of C-reactive protein are provided. | 03-29-2012 |
20120077865 | METHODS FOR TREATING HYPERCHOLESTEROLEMIA - Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides. | 03-29-2012 |
20120077862 | ANTISENSE MODULATION OF PTP1B EXPRESSION - Compounds, compositions and methods are provided for modulating the expression of PTP1B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTP1B. Methods of using these compounds for modulation of PTP1B expression and for treatment of diseases associated with expression of PTP1B are provided. | 03-29-2012 |
20120077276 | METHODS OF DETERMINING POTENCY OF CHEMICALLY-SYNTHESIZED OLIGONUCLEOTIDES - Provided herein are methods for determining potency of RNAi agents. Such methods include, but are not limited to, cell-based and cell-free assays that measure binding of an RNAi agent with Ago2 or that measure Ago2 activity in the presence of such RNAi agents. Also provided are assays that determine potency of RNAi agents by assessing their ability to compete with other RNAi agents, including control RNAi agents, for binding and/or activation of Ago2. | 03-29-2012 |
20120071645 | TETRAHYDROPYRAN NUCLEIC ACID ANALOGS - The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, tetrahydropyran nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including nuclease resistance and binding affinity. In some embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 03-22-2012 |
20120059045 | METHODS OF USING OLIGOMERIC COMPOUNDS COMPRISING 2'-SUBSTITUTED NUCLEOSIDES - The present disclosure provides oligomeric compounds comprising at least one 2′-fluoroethoxy modified nucleoside of formula I and methods of using these oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 03-08-2012 |
20120029050 | COMPOSITIONS AND THEIR USES DIRECTED TO DIACYLGLYCEROL ACYLTRANSFERASE 1 - Disclosed herein are compounds, compositions and methods for modulating DGAT-1 activity. Preferably, the expression of DGAT-1 from a nucleic acid is inhibited. Methods are provided for treating, ameliorating or treating liver fibrosis, either directly or by treating an underlying etiological factor. Preferably, the treatment, amelioration or prevention comprises administering a DGAT-1 activity modulator. | 02-02-2012 |
20120022133 | ANTISENSE MODULATION OF CHOLESTERYL ESTER TRANSFER PROTEIN EXPRESSION - Antisense compounds, compositions and methods are provided for modulating the expression of cholesteryl ester transfer protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding cholesteryl ester transfer protein. Methods of using these compounds for modulation of cholesteryl ester transfer protein expression and for treatment of diseases associated with expression of cholesteryl ester transfer protein are provided. | 01-26-2012 |
20120010393 | 5'-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS - The present invention provides 5′-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5′-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance. | 01-12-2012 |
20110313019 | OLIGOMERIC COMPOUNDS AND METHODS - The present invention provides oligomeric compounds and uses thereof. In certain embodiments, such oligomeric compounds are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds or as RNAi compounds. | 12-22-2011 |
20110306652 | COMPOSITIONS AND THEIR USES DIRECTED TO HUNTINGTIN - Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's Disease (HD) progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntington's Disease (HD) in an individual susceptible to Huntington's Disease (HD). Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. | 12-15-2011 |
20110301222 | COMBINATION THERAPY FOR THE TREATMENT OF CANCER - The present invention provides methods of sensitizing cancer cells to docetaxel and inhibiting the growth of various tumors by employing a modified eIF-4E antisense oligonucleotide and docetaxel in combination. | 12-08-2011 |
20110280963 | COMBINATION THERAPY FOR THE TREATMENT OF CANCER - The present invention provides methods of sensitizing lung cancer cells to cisplatin and inhibiting the growth of lung cancer tumors by employing a modified eIF-4E antisense oligonucleotide and cisplatin in combination. | 11-17-2011 |
20110269821 | 5' AND 2' BIS-SUBSTITUTED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM - The present invention provides modified nucleosides and oligomeric compounds prepared therefrom. More particularyl, the present invention provides modified nucleosides having at least one 5′-substituent and a 2′-O-substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. | 11-03-2011 |
20110269818 | MODULATION OF PRION EXPRESSION - Disclosed herein are compounds and methods for decreasing PrP and preventing, ameliorating, or treating a prion disease or conformational neurodegenerative disorder, in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to PrP include Creutzfeldt-Jakob disease (CJD); variant Creutzfeldt-Jakob Disease (vCJD); Gerstmann-Straussler-Scheinker syndrome; fatal familial insomnia; kuru; Bovine Spongiform Encephalopathy (BSE), e.g. “mad cow disease”; Chronic Wasting Disease (CWD); scrapie; transmissible mink encephalopathy; feline spongiform encephalopathy; ungulate spongiform encephalopathy; Alzheimer's disease; Parkinson's disease; Huntington's disease; and Amyotrophic Lateral Sclerosis (ALS). | 11-03-2011 |
20110256217 | PULSATILE RELEASE COMPOSITIONS AND METHODS FOR ENHANCED INTESTINAL DRUG ABSORPTION - Delayed release oral pharmaceutical formulations and methods for enhanced intestinal drug absorption. The formulation comprises a first population of carrier particles comprising a drug and a penetration enhancer which are released at a first location in the intestine, and a second population of carrier particles comprising a penetration enhancer and a delayed release coating or matrix. This penetration enhancer is released at a second location in the intestine downstream from the first location and enhances absorption of the drug when it reaches the second location. | 10-20-2011 |
20110245476 | ANTIBACTERIAL 4,6-SUBSTITUTED 6', 6" AND 1 MODIFIED AMINOGLYCOSIDE ANALOGS - The present invention is directed to analogs of aminoglycoside compounds as well as their preparation and use as prophylactic or therapeutics against microbial infection. | 10-06-2011 |