Abstract

The present disclosure relates to the field of gene therapies of thyroid-associated ophthalmopathy (TAO) and, in particular, to a use of an antisense oligonucleotide in preparation of a drug for treating a disease caused by an abnormal thyroid. Experimental results of the present application indicate that an antisense oligonucleotide S-ASODN-1 with a particular sequence targeting an insulin-like growth factor 1 receptor (IGF-1R) can effectively reduce concentrations of the IGF-1R and an anti-thyroid peroxidase antibody (TPO-Ab), thereby improving a level of thyroid-stimulating hormone (TSH) for treating thyroid-associated ophthalmopathy.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 5/08 - Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones

Abstract

The present disclosure provides a C6′-substituted locked nucleic acid-modified cap analog and a use thereof, wherein the cap analog improves the stability of mRNA and/or the translation efficiency of mRNA.

IPC Classes  ?

• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 9/1272 - Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers
• A61K 9/51 - Nanocapsules
• A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
• C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
• C12N 9/12 - Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
• C12N 9/14 - Hydrolases (3.)

Abstract

The invention relates to a siRNA for targeted regulation of PCSK9 gene expression and a use thereof. Experimental results show that some oligonucleotide sequences subject to alternate modification and specific template modification can significantly inhibit PCSK9 expression, and can be used for developing a drug for treating PCSK9-related diseases.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61P 3/06 - Antihyperlipidemics
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

A modification template for improving the inhibitory effect of a double-stranded oligonucleotide on a target gene, a combination thereof and the use thereof. The double-stranded oligonucleotide is an siRNA and contains a sense strand and an antisense strand, and each nucleotide of the sense strand and antisense strand is a modified nucleotide. The double-stranded oligonucleotide is modified with a special modification template, and has a significantly improved inhibition rate on a target gene compared with a basic sequence.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61K 38/46 - Hydrolases (3)
• A61P 9/12 - Antihypertensives
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

Provided in the present disclosure are a compound of formula (I), or an N-oxide, solvate, pharmaceutically acceptable salt or stereoisomer thereof. Further provided are a composition containing the aforementioned compound, and the use thereof in the delivery of a therapeutic agent or prophylactic agent. Provided in the present disclosure are a compound of formula (I), or an N-oxide, solvate, pharmaceutically acceptable salt or stereoisomer thereof. Further provided are a composition containing the aforementioned compound, and the use thereof in the delivery of a therapeutic agent or prophylactic agent.

IPC Classes  ?

• A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
• A61K 9/51 - Nanocapsules
• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids

Abstract

Provided in the present invention are a GalNAc compound comprising a ribose ring or a derivative structure thereof, and an oligonucleotide conjugate thereof. The oligonucleotide conjugate provided in the present invention enables efficient liver-targeted delivery, thereby improving the efficacy of a drug.

IPC Classes  ?

• C07H 15/18 - Acyclic radicals, substituted by carbocyclic rings
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61P 3/06 - Antihyperlipidemics
• A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

Provided in the present disclosure are a compound of formula (I), or an N-oxide, solvate, pharmaceutically acceptable salt or stereoisomer thereof. Further provided are a composition containing the aforementioned compound, and the use thereof in the delivery of a therapeutic agent or prophylactic agent.

IPC Classes  ?

• A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
• A61K 9/51 - Nanocapsules
• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids

Abstract

Provided in the present disclosure are a compound of formula (I), or an N-oxide, solvate, pharmaceutically acceptable salt or stereoisomer thereof. Further provided are a composition containing the aforementioned compound, and the use thereof in the delivery of a therapeutic agent or prophylactic agent.

IPC Classes  ?

• C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
• A61P 35/00 - Antineoplastic agents
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides