The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents or siRNAs, able to inhibit Complement Component C3 (C3) gene expression. Also disclosed are pharmaceutical compositions that include C3 RNAi agents and methods of use thereof. The C3 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the delivery to hepatocyte cells. Delivery of the C3 RNAi agents in vivo provides for inhibition of C3 gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by C3 gene expression, including IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and/or other complement-mediated renal diseases.
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents or siRNAs, able to inhibit Complement Component C3 (C3) gene expression. Also disclosed are pharmaceutical compositions that include C3 RNAi agents and methods of use thereof. The C3 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosanine, to facilitate the delivery to hepatocyte cells. Delivery of the C3 RNAi agents in vivo provides for inhibition of C3 gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by C3 gene expression, including IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and/or other complement-mediated renal diseases.
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Myocilin (MYOC) gene. The MYOC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an MYOC gene. Pharmaceutical compositions that include one or more MYOC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MYOC RNAi agents to ocular tissue, in vivo, provides for inhibition of MYOC gene expression and a reduction in MYOC activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including glaucoma, e.g., primary open-angle glaucoma (POAG).
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
C07K 16/18 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains
36 - Services financiers, assurances et affaires immobilières
44 - Services médicaux, services vétérinaires, soins d'hygiène et de beauté; services d'agriculture, d'horticulture et de sylviculture.
Produits et services
Providing financial assistance to patients and healthcare providers for prescription drug costs in the field of cardiometabolic diseases and disorders; providing information about patient reimbursement and insurance coverage for pharmaceuticals Charitable services, namely, a patient assistance program to provide pharmaceuticals without prescription drug coverage; Providing medical and pharmaceutical information concerning pharmaceutical preparations
6.
RNAI AGENTS FOR INHIBITING EXPRESSION OF MICROTUBULE ASSOCIATED PROTEIN TAU (MAPT), COMPOSITIONS THEREOF, AND METHODS OF USE
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a microtubule associated protein tau (MAPT) gene. The MAPT RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a MAPT gene. The MAPT RNAi agents are conjugated to an antigen binding protein that may enable subcutaneous delivery of the RNAi agents by facilitating crossing of the blood brain barrier (BBB). Pharmaceutical compositions that include one or more MAPT RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MAPT RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of MAPT gene expression and a reduction in MAPT activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including Alzheimer's disease, Frontotemporal lobar degeneration dementia (FTLD), Progressive supranuclear palsy, and other tauopathies.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
7.
RNAi Agents for Inhibiting Expression of Microtubule Associated Protein Tau (MAPT), Compositions Thereof, and Methods of Use
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a microtubule associated protein tau (MAPT) gene. The MAPT RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a MAPT gene. The MAPT RNAi agents are conjugated to an antigen binding protein that may enable subcutaneous delivery of the RNAi agents by facilitating crossing of the blood brain barrier (BBB). Pharmaceutical compositions that include one or more MAPT RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MAPT RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of MAPT gene expression and a reduction in MAPT activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including Alzheimer's disease, Frontotemporal lobar degeneration dementia (FTLD), Progressive supranuclear palsy, and other tauopathies.
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
The present application provides synthetic processes for preparing N-acetyl-galactosamines (NAG) based compounds for targeted drug delivery. Also disclosed are Poly-NAG compounds, intermediates and targeting ligands, which are used and/or made by the methods described herein.
C07C 217/54 - Composés contenant des groupes amino et hydroxy éthérifiés liés au même squelette carboné ayant des groupes hydroxy éthérifiés liés à des atomes de carbone d'au moins un cycle aromatique à six chaînons et des groupes amino liés à des atomes de carbone acycliques ou à des atomes de carbone de cycles autres que des cycles aromatiques à six chaînons du même squelette carboné
C07H 1/00 - Procédés de préparation des dérivés du sucre
Described are methods of treatment of a non-alcoholic fatty liver disease via a reduction in HSD17B13 expression in a human subject in need of treatment.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
11.
RNAI AGENTS FOR DUAL INHIBITION OF EXPRESSION OF APOLIPOPROTEIN C-III (APOC3) AND PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 (PCSK9), COMPOSITIONS THEREOF, AND METHODS OF USE
Described are RNAi agents, compositions that include RNAi agents, and methods for dual inhibition of an Apolipoprotein C-III (APOC3) and Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene. The APOC3-PCSK9 RNAi agents disclosed herein inhibit the expression of an APOC3 and a PCSK9 gene. Pharmaceutical compositions that include one or more APOC3-PCSK9 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described TSLP RNAi agents to hepatic cells, in vivo, provides for inhibition of APOC3 and/or PCSK9 gene expression, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including hypertriglyceridemia and hypercholesterolemia.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/711 - Acides désoxyribonucléiques naturels, c.-à-d. contenant uniquement des 2'-désoxyriboses liés à l'adénine, la guanine, la cytosine ou la thymine et ayant des liaisons 3'-5' phosphodiester
A61K 31/7115 - Acides nucléiques ou oligonucléotides ayant des bases modifiées, c.-à-d. autres que l'adénine, la guanine, la cytosine, l'uracile ou la thymine
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
The present disclosure relates to RNAi agents useful in methods of treating Beta-Catenin-related diseases such as adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases, using a therapeutically effective amount of a RNAi agent to Beta-Catenin.
Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
C07H 15/04 - Radicaux acycliques non substitués par des structures cycliques liés à un atome d'oxygène d'un radical saccharide
14.
RNAI AGENTS FOR INHIBITING EXPRESSION OF ANDROGEN RECEPTOR (AR), COMPOSITIONS THEREOF, AND METHODS OF USE
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of an Androgen Receptor (AR) gene. The AR RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an AR gene. Pharmaceutical compositions that include one or more AR RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described AR RNAi agents to central nervous system (CNS) tissue and/or skeletal muscle tissue, in vivo, provides for inhibition of AR gene expression and a reduction in AR activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including spinal and bulbar muscular atrophy (SBMA).
The invention provides a transferrin receptor (TfR1) antibody for conjugation to therapeutic payloads. The TfR1 antibodies may be used for delivering the therapeutic payloads, for instance oligonucleotide-based agents, to CNS tissues, skeletal muscle tissues, or heart tissues in vivo.
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
16.
Improved Linkers and Methods for the Synthesis of Anti-Transferrin Receptor Antibody Conjugates
The present disclosure relates to improved linkers for conjugating oligonucleotidebased agents (e.g., RNAi agents) to an antibody or antibody fragment (e.g., anti-transferrin receptor (TfR1) antibodies or fragments).
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
The invention provides a transferrin receptor (TfR1) antibody for conjugation to therapeutic payloads. The TfR1 antibodies may be used for delivering the therapeutic payloads, for instance oligonucleotide-based agents, to CNS tissues, skeletal muscle tissues, or heart tissues in vivo.
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
19.
Methods For The Treatment Of ANGPTL3-Related Diseases And Disorders
Described are methods for treating diseases and disorders that can be mediated in part by a reduction in ANGPTL3 gene expression in a human subject in need of treatment, using pharmaceutical compositions that include ANGPTL3 RNAi agents. The disclosed pharmaceutical compositions that include ANGPTL3 RNAi agents, when administered to a human subject in need thereof according to the methods disclosed herein, treat diseases and disorders associated with elevated triglyceride (TG) levels and/or elevated low density lipoprotein cholesterol (LDL-C), for example, hypertriglyceridemia (including severe hypertriglyceridemia (SHTG)), homozygous familial hypercholesterolemia (HoFH), hypertriglyceridemia induced pancreatitis, metabolic syndrome, obesity, hyperlipidemia, mixed dyslipidemia, abnormal lipid and/or cholesterol metabolism, atherosclerosis, cardiovascular disease, type II diabetes mellitus, coronary artery disease, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, heterozygous familial hypercholesterolemia (HeFH), statin resistant hypercholesterolemia, other dyslipidemias, and other metabolic-related disorders and diseases.
Disclosed herein are compounds comprising lipid PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double-stranded RNAi agents, to certain cell types, such for example, CNS cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.
The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosanine, to facilitate the in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and/or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and/or other complement-mediated diseases.
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of an Activin Receptor-Like Kinase 7 (ALK7) gene. The ALK7 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an ALK7 gene. Pharmaceutical compositions that include one or more ALK7 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described ALK7 RNAi agents to adipose tissue, in vivo, provides for inhibition of ALK7 gene expression and a reduction in ALK7 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including obesity, diabetes, or insulin resistance.
in vivoin vivo, provides for inhibition of ALK7 gene expression and a reduction in ALK7 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including obesity, diabetes, or insulin resistance.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61P 3/00 - Médicaments pour le traitement des troubles du métabolisme
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
A61K 31/712 - Acides nucléiques ou oligonucléotides ayant des sucres modifiés, c.-à-d. autres que le ribose ou le 2'-désoxyribose
25.
COMPOSITIONS AND METHODS FOR INHIBITING GENE EXPRESSION OF ALPHA-1 ANTITRYPSIN
The invention relates to a RNA interference triggers for inhibiting the expression of an AAT gene through the mechanism of RNA interference. The invention also relates to a pharmaceutical composition comprising the AAT RNAi trigger together with an excipient capable of improving delivery of the RNAi trigger to a liver cell in vivo. Delivery of the AAT RNAi trigger to liver cells in vivo provides for inhibition of AAT gene expression and treatment of alpha 1-antitrypsin deficiency and associated diseases.
RNA interference (RNAi) agents and RNAi agent conjugates for inhibiting the expression of the LPA (apo(a)) gene are described. Pharmaceutical compositions comprising one or more LPA RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described LPA RNAi agents to liver cells in vivo provides for inhibition of LPA gene expression and treatment of cardiovascular and cardiovascular-related diseases.
Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.
C07F 9/06 - Composés du phosphore sans liaisons P—C
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
C07C 205/59 - Composés contenant des groupes nitro liés à un squelette carboné le squelette carboné étant substitué de plus par des groupes carboxyle ayant des groupes nitro et des groupes carboxyle liés à des atomes de carbone de cycles aromatiques à six chaînons du squelette carboné le squelette carboné étant substitué de plus par des atomes d'oxygène liés par des liaisons simples
C07C 235/34 - Amides d'acides carboxyliques, le squelette carboné de la partie acide étant substitué de plus par des atomes d'oxygène ayant des atomes de carbone de groupes carboxamide liés à des atomes de carbone acycliques et des atomes d'oxygène, liés par des liaisons simples, liés au même squelette carboné le squelette carboné contenant des cycles aromatiques à six chaînons ayant les atomes d'azote des groupes carboxamide liés à des atomes d'hydrogène ou à des atomes de carbone acycliques
C07D 403/14 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant au moins trois hétérocycles
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
28.
RNAi Agents for Inhibiting Expression of Inhibin Subunit Beta E (INHBE), Pharmaceutical Compositions Thereof, and Methods of Use
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents such as siRNAs, able to Inhibin Subunit Beta E (INHBE) gene expression. Also disclosed are pharmaceutical compositions that include INHBE RNAi agents and methods of use thereof. The INHBE RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the INHBE RNAi agents in vivo provides for inhibition of INHBE gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by INHBE gene expression, such as obesity, diabetes, liver inflammation, dyslipidemia, or metabolic disease.
e.g.in vivoin vivo provides for inhibition of INHBE gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by INHBE gene expression, such as obesity, diabetes, liver inflammation, dyslipidemia, or metabolic disease.
Disclosed herein are processes or methods for producing oligonucleotides, including in large single batch scales and with high purity and yields without a capping step.
C07H 1/00 - Procédés de préparation des dérivés du sucre
C07H 21/00 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
31.
RNAi Agents for Inhibiting Expression of PNPLA3, Pharmaceutical Compositions Thereof, and Methods of Use
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene expression. Also disclosed are pharmaceutical compositions that include PNPLA3 RNAi agents and methods of use thereof. The PNPLA3 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the PNPLA3 RNAi agents in vivo provides for inhibition of PNPLA3 gene expression. The RNAi agents can be used in methods of treatment of PNPLA3-related diseases and disorders, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic fibrosis, and alcoholic or non-alcoholic liver diseases, including cirrhosis.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
32.
Subcutaneous Delivery of RNAi Agents for Inhibiting Expression of Receptor for Advanced Glycation End-products
Described are methods for subcutaneously administering a therapeutic composition comprising a RNAi agent for inhibiting Receptor for Advanced Glycation End-products (AGER or RAGE). The RAGE RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an AGER gene when administered subcutaneously. Pharmaceutical compositions that include one or more RAGE RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described RAGE RNAi agents to pulmonary cells, in vivo, provides for inhibition of AGER gene expression and a reduction in membrane RAGE activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as severe asthma. Subcutaneous delivery of the RAGE RNAi agents described herein can provide certain advantages over inhaled delivery.
in vivoin vivo. The delivery platforms disclosed herein include metabolically stabilized N-Acetylgalactosamine (NAG or GalNAc) targeting ligands conjugated to two or more RNAi agents, to facilitate the delivery of the oligonucleotide-based payloads to cells, including to hepatocytes. Pharmaceutical compositions that include the metabolically stabilized multimeric RNAi agent conjugate delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a hepatocyte is desirable.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
34.
METABOLICALLY STABILIZED CARBOHYDRATE TARGETING LIGANDS FOR OLIGONUCLEOTIDE CONJUGATES
in vivoin vivo. The delivery platforms disclosed herein include metabolically stabilized N-Acetylgalactosamine (NAG or GalNAc) targeting ligands conjugated to one or more oligonucleotides through a metabolically stabilized linkage that is more stable than a phosphodiester linkage, to facilitate the delivery of the oligonucleotide-based payloads to cells, including to hepatocytes. Pharmaceutical compositions that include the metabolically stabilized RNAi agent conjugate delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a hepatocyte is desirable.
A61K 47/50 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
35.
RNAi Agents for Inhibiting Expression of Coronavirus (CoV) Viral Genomes, Compositions Thereof, and Methods of Use
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of coronavirus (CoV) viral genome. The CoV RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a SARS-CoV-2 viral genome, and the targeted portions of the genome are conserved across a variety of known coronaviruses. Pharmaceutical compositions that include one or more CoV RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described CoV RNAi agents to pulmonary cells, in vivo, provides for inhibition of CoV viral genome expression, including SARS-CoV-2, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including COVID-19.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61P 31/14 - Antiviraux pour le traitement des virus ARN
36.
RNAI AGENTS FOR INHIBITING EXPRESSION OF ATAXIN-2 (ATXN2), COMPOSITIONS THEREOF, AND METHODS OF USE
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Ataxin-2 (ATXN2) gene. The ATXN2 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an ATXN2 gene. Pharmaceutical compositions that include one or more ATXN2 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described ATXN2 RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of ATXN2 gene expression and a reduction in ATXN2 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including spinocerebellar ataxia type 2 (SCA2) or amyotrophic lateral sclerosis (ALS.)
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
37.
RNAI AGENTS FOR INHIBITING EXPRESSION OF COMPLEMENT FACTOR B (CFB), PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE
in vivo in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and/or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and/or other complement-mediated diseases.
e.g.in vivoin vivo provides for inhibition of MARC1 gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by MARC1 gene expression, including nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, autoimmune hepatitis, hepatic fibrosis, cirrhosis, elevated blood cholesterol levels, hypertriglyceridemia, liver disease, and/or other MARC1-related disease.
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents such as small interfering RNA (siRNA) molecules, able to inhibit proprotein convertase subtilisin kexin 9 (PCSK9) gene expression. Also disclosed are pharmaceutical compositions that include PCSK9 RNAi agents and methods of use thereof. The PCSK9 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetylgalactosamine, to facilitate the delivery to hepatocyte cells. Delivery of the PCSK9 RNAi agents in vivo provides for inhibition of PCSK9 gene expression and thereby reduction of PCSK9 protein. The RNAi agents can be used in methods of treatment of diseases or disorders mediated at least in part by PCSK9 gene expression, including among others hypercholesterolemia, familial hypercholesterolemia including heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), familial hypobetalipoproteinemia, hyperlipidemia, coronary artery disease, polygenic dyslipidemia, heart disease, cardiovascular disease (CVD) including clinical atherosclerotic cardiovascular disease (ASCVD).
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/712 - Acides nucléiques ou oligonucléotides ayant des sucres modifiés, c.-à-d. autres que le ribose ou le 2'-désoxyribose
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
in vivoin vivo, provides for inhibition of TSLP gene expression, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as asthma, including allergic asthma.
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
41.
BELT REACTOR MANUFACTURING PROCESS FOR OLIGOMER SYNTHESIS
A method and apparatus for synthesis of oligomers such as oligonucleotides and peptides are disclosed. The method employs a device including at least one deprotection station to carry out a step of deprotection, at least one coupling station to carry out a step of coupling, optionally, one or more oxidation and/or thiolation stations to carry out a step of oxidation or thiolation, optionally, one or more capping stations to carry out a step of capping, and, optionally, one or more washing stations to carry out a step of washing. A plurality of solid phase material for oligomer synthesis is moved to the stations via a conveyor device, wherein a fluid delivery device acts upon said solid phase material to produce an oligomer.
in vivoin vivo, provides for inhibition of CoV viral genome expression, including SARS-CoV-2, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including COVID-19.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61P 31/14 - Antiviraux pour le traitement des virus ARN
43.
RNAI AGENTS FOR INHIBITING INFLUENZA A VIRAL GENE EXPRESSION, COMPOSITIONS THEREOF, AND METHODS OF USE
in vivoin vivo, provides for inhibition of influenza A viral genome expression, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases, disorders, and/or symptoms caused by influenza A viral infection.
A61K 31/7115 - Acides nucléiques ou oligonucléotides ayant des bases modifiées, c.-à-d. autres que l'adénine, la guanine, la cytosine, l'uracile ou la thymine
A61K 31/712 - Acides nucléiques ou oligonucléotides ayant des sucres modifiés, c.-à-d. autres que le ribose ou le 2'-désoxyribose
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61P 31/16 - Antiviraux pour le traitement des virus ARN de la grippe ou des rhinovirus
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
44.
LIPID CONJUGATES FOR THE DELIVERY OF THERAPEUTIC AGENTS TO ADIPOSE TISSUE
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
The present disclosure relates to delivery platforms that specifically and efficiently direct payloads to skeletal muscle cells in a subject, in vivo. The delivery platforms disclosed herein include targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-6) and pharmacokinetic/pharmacodynamic (PK/PD) modulators, to facilitate the delivery of payloads to cells, including to skeletal muscle cells. Suitable payloads for use in the delivery platforms disclosed herein include RNAi agents, which can be linked or conjugated to the delivery platforms, and when delivered in vivo, provide for the inhibition of gene expression in skeletal muscle cells. Pharmaceutical compositions that include the skeletal muscle cell delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a skeletal muscle cell is desirable.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
RNAi agents for inhibiting the expression of the alpha-1 antitrypsin (AAT) gene, compositions including AAT RNAi agents, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the AAT RNAi agent(s) to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
49.
RNAI AGENTS FOR INHIBITING EXPRESSION OF COMPLEMENT COMPONENT C3 (C3), PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE
in vivoin vivo provides for inhibition of C3 gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by C3 gene expression, including IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and/or other complement-mediated renal diseases.
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
50.
RNAI AGENTS FOR INHIBITING EXPRESSION OF DM1 PROTEIN KINASE (DMPK) COMPOSITIONS THEREOF, AND METHODS OF USE
DMPKDMPKin vivoDMPKDMPK gene expression and a reduction in DMPK protein levels, and more specifically a reduction in mutant DMPK-CUG protein levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including myotonic dystrophy type 1.
A61K 31/712 - Acides nucléiques ou oligonucléotides ayant des sucres modifiés, c.-à-d. autres que le ribose ou le 2'-désoxyribose
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 47/58 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. poly[méth]acrylate, polyacrylamide, polystyrène, polyvinylpyrrolidone, alcool polyvinylique ou résine d’acide sulfonique de polystyrène
A61P 21/00 - Médicaments pour le traitement des troubles du système musculaire ou neuromusculaire
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
Synthetic αvβ6 integrin ligands of Formula I having serum stability and affinity for integrin αvβ6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin αvβ6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include αvβ6 integrin ligands and methods of use are also described.
Synthetic αvβ6 integrin ligands of Formula I having serum stability and affinity for integrin αvβ6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin αvβ6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include αvβ6 integrin ligands and methods of use are also described.
C07D 213/74 - Radicaux amino ou imino substitués par des radicaux hydrocarbonés ou par des radicaux hydrocarbonés substitués
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 47/56 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
C07D 409/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes de soufre comme uniques hétéro-atomes du cycle contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
C07D 413/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
52.
METHODS FOR THE TREATMENT OF ANGPTL3-RELATED DISEASES AND DISORDERS
Described are methods for treating diseases and disorders that can be mediated in part by a reduction in ANGPTL3 gene expression in a human subject in need of treatment, using pharmaceutical compositions that include ANGPTL3 RNAi agents. The disclosed pharmaceutical compositions that include ANGPTL3 RNAi agents, when administered to a human subject in need thereof according to the methods disclosed herein, treat diseases and disorders associated with elevated triglyceride (TG) levels and/or elevated low density lipoprotein cholesterol (LDL-C), for example, hypertriglyceridemia (including severe hypertriglyceridemia (SHTG)), homozygous familial hypercholesterolemia (HoFH), hypertriglyceridemia induced pancreatitis, metabolic syndrome, obesity, hyperlipidemia, mixed dyslipidemia, abnormal lipid and/or cholesterol metabolism, atherosclerosis, cardiovascular disease, type II diabetes mellitus, coronary artery disease, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, heterozygous familial hypercholesterolemia (HeFH), statin resistant hypercholesterolemia, other dyslipidemias, and other metabolicrelated disorders and diseases.
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
A61K 31/712 - Acides nucléiques ou oligonucléotides ayant des sucres modifiés, c.-à-d. autres que le ribose ou le 2'-désoxyribose
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
53.
RNAi agents for inhibiting expression of Superoxide Dismutase 1 (SOD1), compositions thereof, and methods of use
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Superoxide Dismutase 1 (SOD1) gene. The SOD1 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an SOD1 gene. Pharmaceutical compositions that include one or more SOD1 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described SOD1 RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of SOD1 gene expression and a reduction in SOD1 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including amyotrophic lateral sclerosis (ALS.).
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 (DUX4) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSID).
Synthetic αvβ6 integrin ligands of Formula I having serum stability and affinity for integrin αvβ6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin αvβ6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include αvβ6 integrin ligands and methods of use are also described.
Synthetic αvβ6 integrin ligands of Formula I having serum stability and affinity for integrin αvβ6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin αvβ6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include αvβ6 integrin ligands and methods of use are also described.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61P 21/00 - Médicaments pour le traitement des troubles du système musculaire ou neuromusculaire
C07H 19/00 - Composés contenant un hétérocycle partageant un hétéro-atome du cycle avec un radical saccharideNucléosidesMononucléotidesLeurs anhydro-dérivés
57.
RNAI AGENTS FOR INHIBITING EXPRESSION OF SUPEROXIDE DISMUTASE 1 (SOD1), COMPOSITIONS THEREOF, AND METHODS OF USE
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Superoxide Dismutase 1 (SOD1) gene. The SOD1 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an SOD1 gene. Pharmaceutical compositions that include one or more SOD1 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery' of the described SOD1 RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of SOD1 gene expression and a reduction in SOD1 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including amyotrophic lateral sclerosis (ALS.)
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
C12N 9/02 - Oxydoréductases (1.), p. ex. luciférase
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 31/712 - Acides nucléiques ou oligonucléotides ayant des sucres modifiés, c.-à-d. autres que le ribose ou le 2'-désoxyribose
A61K 31/7115 - Acides nucléiques ou oligonucléotides ayant des bases modifiées, c.-à-d. autres que l'adénine, la guanine, la cytosine, l'uracile ou la thymine
A61K 49/18 - Préparations de contraste pour la résonance magnétique nucléaire [RMN]Préparations de contraste pour l'imagerie par résonance magnétique [IRM] caractérisées par un aspect physique particulier, p. ex. émulsions, microcapsules, liposomes
58.
LIPID CONJUGATES FOR THE DELIVERY OF THERAPEUTIC AGENTS TO CNS TISSUE
in vivoin vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
A61K 31/70 - Hydrates de carboneSucresLeurs dérivés
Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hepatitis B virus gene are described. Pharmaceutical compositions comprising one or more HBV RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi triggers to infected liver in vivo provides for inhibition of HBV gene expression and treatment.
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 38/16 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 47/59 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes
Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61P 31/14 - Antiviraux pour le traitement des virus ARN
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/675 - Composés du phosphore ayant l'azote comme hétéro-atome d'un cycle, p. ex. phosphate de pyridoxal
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61P 31/20 - Antiviraux pour le traitement des virus ADN
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
Described are methods of reducing liver Z-AAT protein levels in a human subject with a PiZZ genotype of alpha-1 antitrypsin (AAT) by using pharmaceutical compositions that include AAT RNAi agents. The pharmaceutical compositions disclosed herein that include AAT RNAi agents, when administered to a human subject with a PiZZ mutation, lead to a reduction in liver Z-AAT protein levels, including both soluble and insoluble Z-AAT protein. Such reductions can lead to the treatment of liver diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, increased risk of hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, fulminant hepatic failure, and other liver-related diseases.
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
62.
RNAi agents and compositions for inhibiting expression of apolipoprotein C-III (APOC3)
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, capable of inhibiting Apolipoprotein C-III (also called APOC3, apoC-III, APOC-III, and APO C-III) gene expression, and compositions that include APOC3 RNAi agents. The APOC3 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that include N-acetyl-galactosamine, to facilitate the delivery to cells, including to hepatocytes. Pharmaceutical compositions that include one or more APOC3 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the APOC3 RNAi agents in vivo provides for inhibition of APOC3 gene expression, and can result in lower triglycerides and/or cholesterol levels in the subject. The APOC3 RNAi agents can be used in methods of treatment of APOC3-related diseases and disorders, including hypertriglyceridemia, cardiovascular disease, and other metabolic-related disorders and diseases.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61P 1/18 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles pancréatiques, p. ex. enzymes pancréatiques
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
Described are methods of treatment of a non-alcoholic fatty liver disease via a reduction in HSD17B13 expression in a human subject in need of treatment.
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 47/61 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique le composé organique macromoléculaire étant un polysaccharide ou l’un de ses dérivés
64.
SUBCUTANEOUS DELIVERY OF RNAI AGENTS FOR INHIBITING EXPRESSION OF RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS (RAGE)
Described are methods for subcutaneously administering a therapeutic composition comprising a RNAi agent for inhibiting Receptor for Advanced Glycation End-products (AGER or RAGE),. The RAGE RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an AGER gene when administered subcutaneously. Pharmaceutical compositions that include one or more RAGE RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described RAGE RNAi agents to pulmonary cells, in vivo, provides for inhibition of AGER gene expression and a reduction in membrane RAGE activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as severe asthma. Subcutaneous delivery7 of the RAGE RNAi agents described herein can provide certain advantages over inhaled delivery.
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
The present disclosure relates to delivery vehicles that specifically and efficiently direct payloads to skeletal muscle cells in a subject, in vivo. The delivery vehicles disclosed herein include targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-6) and pharmacokinetic/pharmacodynamic (PK/PD) modulators, to facilitate the delivery of payloads to cells, including to skeletal muscle cells. Suitable payloads for use in the delivery vehicles disclosed herein include RNAi agents, which can be linked or conjugated to the delivery vehicles, and when delivered in vivo, provide for the inhibition of gene expression in skeletal muscle cells. Pharmaceutical compositions that include the skeletal muscle cell delivery vehicle are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a skeletal muscle cell is desirable.
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 (DUX4) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSHD).
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 47/64 - Conjugués médicament-peptide, médicament-protéine ou médicament-acide polyaminé, c.-à-d. l’agent de modification étant un peptide, une protéine ou un acide polyaminé lié par covalence ou complexé à un agent thérapeutiquement actif
A61P 21/00 - Médicaments pour le traitement des troubles du système musculaire ou neuromusculaire
67.
RNAi Agents for Inhibiting Expression of Matrix Metalloproteinase 7 (MMP7), Compositions Thereof, and Methods of Use
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a matrix metallopeptidase 7 (MMP7) gene. The MMP7 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an MMP7 gene. Pharmaceutical compositions that include one or more MMP7 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MMP7 RNAi agents to pulmonary cells, in vivo, provides for inhibition of MMP7 gene expression, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as idiopathic pulmonary fibrosis (IPF).
in vivo in vivo, provides for inhibition of CoV viral genome expression, including SARS-CoV-2, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including COVID-19.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 31/712 - Acides nucléiques ou oligonucléotides ayant des sucres modifiés, c.-à-d. autres que le ribose ou le 2'-désoxyribose
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
A61P 31/14 - Antiviraux pour le traitement des virus ARN
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
69.
LIPID CONJUGATES FOR THE DELIVERY OF THERAPEUTIC AGENTS
Disclosed herein are compounds according to Formula (I) comprising PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double stranded RNAi agents, to certain cell types, such for example skeletal muscle cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.
Disclosed herein are compounds according to Formula (I) comprising PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double stranded RNAi agents, to certain cell types, such for example skeletal muscle cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
70.
RNAi Agents for Inhibiting Expression of Xanthine Dehydrogenase (XDH), Pharmaceutical Compositions Thereof, and Methods of Use
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.
in vivoin vivo, provides for inhibition of MMP7 gene expression, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as idiopathic pulmonary fibrosis (IPF).
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a beta-ENaC (SCNN1B) gene. The beta-ENaC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a beta-ENaC gene. Pharmaceutical compositions that include one or more beta-ENaC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described beta-ENaC RNAi agents to epithelial cells, such as pulmonary epithelial cells, in vivo, provides for inhibition of beta-ENaC gene expression and a reduction in ENaC activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including chronic obstructive pulmonary disease (COPD).
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
74.
RNAi agents for inhibiting expression of xanthine dehydrogenase (XDH), pharmaceutical compositions thereof, and methods of use
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Mucin 5AC (MUC5AC) gene. The MUC5AC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an MUC5AC gene. Pharmaceutical compositions that include one or more MUC5AC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MUC5AC RNAi agents to pulmonary epithelial cells, in vivo, provides for inhibition of MUC5AC gene expression and a reduction in MUC5AC production, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including mucoobstructive lung disease such as severe asthma and various cancers.
The invention relates to a RNA interference triggers for inhibiting the expression of an AAT gene through the mechanism of RNA interference. The invention also relates to a pharmaceutical composition comprising the AAT RNAi trigger together with an excipient capable of improving delivery of the RNAi trigger to a liver cell in vivo. Delivery of the AAT RNAi trigger to liver cells in vivo provides for inhibition of AAT gene expression and treatment of alpha 1-antitrypsin deficiency and associated diseases.
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed arc pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytcs. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.
Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.
C07F 9/06 - Composés du phosphore sans liaisons P—C
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
C07C 205/59 - Composés contenant des groupes nitro liés à un squelette carboné le squelette carboné étant substitué de plus par des groupes carboxyle ayant des groupes nitro et des groupes carboxyle liés à des atomes de carbone de cycles aromatiques à six chaînons du squelette carboné le squelette carboné étant substitué de plus par des atomes d'oxygène liés par des liaisons simples
C07C 235/34 - Amides d'acides carboxyliques, le squelette carboné de la partie acide étant substitué de plus par des atomes d'oxygène ayant des atomes de carbone de groupes carboxamide liés à des atomes de carbone acycliques et des atomes d'oxygène, liés par des liaisons simples, liés au même squelette carboné le squelette carboné contenant des cycles aromatiques à six chaînons ayant les atomes d'azote des groupes carboxamide liés à des atomes d'hydrogène ou à des atomes de carbone acycliques
C07D 403/14 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant au moins trois hétérocycles
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
80.
RNAi Agents for Inhibiting Expression of Receptor for Advanced Glycation End-products, Compositions Thereof, and Methods of Use
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Receptor for Advanced Glycation End-products (AGER or RAGE) gene. The RAGE RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an AGER gene. Pharmaceutical compositions that include one or more RAGE RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described RAGE RNAi agents to pulmonary cells, in vivo, provides for inhibition of AGER gene expression and a reduction in membrane RAGE activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as severe asthma.
The present disclosure relates to methods of treating heat shock factor 1 (HSF1)-related diseases such as cancer and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 19/02 - Médicaments pour le traitement des troubles du squelette des troubles articulaires, p. ex. arthrites, arthroses
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
A61P 31/18 - Antiviraux pour le traitement des virus ARN du HIV
A61P 31/20 - Antiviraux pour le traitement des virus ADN
A61P 31/22 - Antiviraux pour le traitement des virus ADN des virus de l'herpès
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
82.
RNAI AGENTS FOR INHIBITING EXPRESSION OF MUCIN 5AC (MUC5AC), COMPOSITIONS THEREOF, AND METHODS OF USE
Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Mucin 5AC (MUC5AC) gene. The MUC5AC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an MUC5AC gene. Pharmaceutical compositions that include one or more MUC5AC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MUC5AC RNAi agents to pulmonary epithelial cells, in vivo, provides for inhibition of MUC5AC gene expression and a reduction in MUC5AC production, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including mucoobstructive lung disease such as severe asthma and various cancers.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
83.
RNAI AGENTS FOR INHIBITING EXPRESSION OF RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS, COMPOSITIONS THEREOF, AND METHODS OF USE
in vivoin vivo, provides for inhibition of AGER gene expression and a reduction in membrane RAGE activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as severe asthma.
Described are methods for treating alpha-1 antitrypsin deficiency (AATD) in a human patient in need of treatment, using pharmaceutical compositions that include AAT RNAi agents. The pharmaceutical compositions disclosed herein that include AAT RNAi agents, when administered to a human patient in need thereof, treat liver diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, increased risk of hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, fulminant hepatic failure, and other liver-related diseases.
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
The present disclosure relates to RNAi agents, for example, double stranded RNAi agents, able to inhibit HIF-2 alpha (EPAS1) gene expression. Also disclosed are pharmaceutical compositions that include HIF-2 alpha RNAi agents and methods of use thereof. The HIF-2 alpha RNAi agents disclosed herein may be linked or conjugated to targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-3 and alpha-v-beta-5 integrins) and pharmacokinetic (PK) enhancers, to facilitate the delivery to cells and tissues, including to clear cell renal cell carcinoma (ccRCC) cells and tumors. Delivery of compositions comprising the HIF-2 alpha RNAi agents in vivo provides for inhibition of HIF-2 alpha gene expression. The HIF-2 alpha RNAi agents can be used in methods of treatment of various diseases and disorders, including ccRCC.
RNAi agents for inhibiting the expression of the alpha-1 antitrypsin (AAT) gene, compositions including AAT RNAi agents, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the AAT RNAi agent(s) to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
87.
Methods For The Treatment Of APOC3-Related Diseases And Disorders
Described are methods for treating diseases and disorders that can be mediated in part by a reduction in APOC3 gene expression in a human subject in need of treatment, using pharmaceutical compositions that include APOC3 RNAi agents. The disclosed pharmaceutical compositions that include APOC3 RNAi agents, when administered to a human subject in need thereof according to the methods disclosed herein, treat diseases and disorders associated with elevated triglyceride (TG) levels, such as familial chylomicronemia syndrome (FCS), hypertriglyceridemia, obesity, dyslipidemia, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, hyperlipidemia, abnormal lipid and/or cholesterol metabolism, atherosclerosis, cardiovascular disease, coronary artery disease, hypertriglyceridemia induced pancreatitis, metabolic syndrome, type II diabetes mellitus, chylomicronemia, multifactorial chylomicronemia, or lipodystrophy syndromes including familial partial lipodystrophy.
Described are 5′-cyclo-phosphonate modified nucleotides, and oligonucleotides, such as interference (RNAi) agents, containing 5′-cyclo-phosphonate modified nucleotides. The RNAi agents having either double-stranded or single-stranded oligonucleotides described herein comprising 5′cyclo-phosphonate modified nucleotides are useful in modulating gene expression as well as therapeutic, diagnostic, target validation, and genomic discovery applications. The RNAi agents and single-stranded antisense oligonucleotides comprising 5′-cyclo-phosphonate modified nucleotides are useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.
C07H 19/207 - Radicaux purine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques les acides phosphoriques ou polyphosphoriques étant estérifiés par un autre composé hydroxylique, p. ex. les dinucléotides de la flavine-adénine ou de la nicotinamide-adénine
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
Described are methods of reducing liver Z-AAT protein levels in a human subject with a PiZZ genotype of alpha-1 antitrypsin (AAT) by using pharmaceutical compositions that include AAT RNAi agents. The pharmaceutical compositions disclosed herein that include AAT RNAi agents, when administered to a human subject with a PiZZ mutation, lead to a reduction in liver Z-AAT protein levels, including both soluble and insoluble Z-AAT protein. Such reductions can lead to the treatment of liver diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, increased risk of hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, fulminant hepatic failure, and other liver-related diseases.
Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61P 31/14 - Antiviraux pour le traitement des virus ARN
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/675 - Composés du phosphore ayant l'azote comme hétéro-atome d'un cycle, p. ex. phosphate de pyridoxal
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61P 31/20 - Antiviraux pour le traitement des virus ADN
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
91.
RNAI AGENTS FOR INHIBITING EXPRESSION OF DUX4, COMPOSITIONS THEREOF, AND METHODS OF USE
DUX4DUX4invivoDUX4DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSHD).
in vivo.in vivoin vivo, provide for the inhibition of gene expression in skeletal muscle cells. Pharmaceutical compositions that include the skeletal muscle cell delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a skeletal muscle cell is desirable.
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
93.
SKELETAL MUSCLE DELIVERY PLATFORMS AND METHODS OF USE
in vivoin vivoin vivo, provide for the inhibition of gene expression in skeletal muscle cells. Pharmaceutical compositions that include the skeletal muscle cell delivery vehicle are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a skeletal muscle cell is desirable.
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
Synthetic ανβ6 integrin ligands of Formula (I) having serum stability and affinity for integrin ανβ6, which is a receptor expressed in a variety of cell types, are described. The described ligands are usful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin ανβ6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include ανβ6 integrin ligands and methods of use are also described Formula (I).
C07C 13/47 - Hydrocarbures polycycliques ou leurs dérivés hydrocarbonés acycliques à cycles condensés à système bicyclique contenant dix atomes de carbone
Disclosed herein are compounds according to Formula (I) comprising PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double stranded RNAi agents, to certain cell types, such for example skeletal muscle cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
96.
RNAi Agents for Inhibiting Expression of 17beta-HSD Type 13 (HSD17B13), Compositions Thereof, and Methods of Use
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit 17P-hydroxy steroid dehydrogenase type 13 (HSD17B13 or 17β-H8013) gene expression. Also disclosed are pharmaceutical compositions that include HSD17B13 RNAi agents and methods of use thereof. The HSD17B13 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery′ to cells, including to hepatocytes. Delivery 7 of the HSD17B13 RNAi agents in vivo provides for inhibition of HSD17B13 gene expression. The RNAi agents can be used in methods of treatment of HSD17B13-related diseases and disorders, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic fibrosis, and alcoholic or non-alcoholic liver diseases, including cirrhosis.
Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds that are useful in directing the compounds to the in vivo target. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to a therapeutic compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/711 - Acides désoxyribonucléiques naturels, c.-à-d. contenant uniquement des 2'-désoxyriboses liés à l'adénine, la guanine, la cytosine ou la thymine et ayant des liaisons 3'-5' phosphodiester
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
A61K 31/7008 - Composés ayant un groupe amino lié directement à un atome de carbone du radical saccharide, p. ex. D-galactosamine, ranimustine
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
98.
RNAi agents for inhibiting expression of PNPLA3, pharmaceutical compositions thereof, and methods of use
Described are RNAi agents, e.g., double stranded RNAi agents, for inhibiting patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene expression. Also disclosed are pharmaceutical compositions that include PNPLA3 RNAi agents and methods of use thereof. The PNPLA3 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the PNPLA3 RNAi agents in vivo provides for inhibition of PNPLA3 gene expression. The RNAi agents can be used in methods of treatment of PNPLA3-related diseases and disorders, including non-alcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), hepatic fibrosis, and alcoholic or non-alcoholic liver diseases, including cirrhosis.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques
99.
RNAi AGENTS FOR INHIBITING EXPRESSION OF PNPLA3, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE
e.gin vivoin vivo provides for inhibition of PNPLA3 gene expression. The RNAi agents can be used in methods of treatment of PNPLA3 -related diseases and disorders, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic fibrosis, and alcoholic or non-alcoholic liver diseases, including cirrhosis.
The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit Angiopoietin-like 3 (also called ANGPTL3, ANGPL3, angiopoietin-like protein 3) gene expression, and compositions that include ANGPTL3 RNAi agents. Also disclosed are methods of use of ANGPTL3 RNAi agents and compositions. The ANGPTL3 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Pharmaceutical compositions that include one or more ANGPTL3 RNAi agents, optionally with one or more additional therapeutics, are described. Delivery of the ANGPTL3 RNAi agents in vivo provides for inhibition of ANGPTL3 gene expression, and can result in lower triglycerides and/or cholesterol levels in the subject. The RNAi agents can be used in methods of treatment of ANGPTL3-related diseases and disorders, including cardiometabolic diseases such as hypertriglyceridemia and hyperlipidemia.
