The present disclosure describes compounds of Formula (I) and pharmaceutically acceptable salts thereof:
The present disclosure describes compounds of Formula (I) and pharmaceutically acceptable salts thereof:
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 229/12 - 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 acyclic carbon skeletons
C07C 237/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 275/16 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by carboxyl groups
C07C 327/06 - Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of an acyclic saturated carbon skeleton
C07D 209/24 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
C07D 333/60 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07C 229/12 - 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 acyclic carbon skeletons
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
C07C 237/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 275/16 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by carboxyl groups
C07C 327/32 - Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07D 209/24 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
C07D 333/60 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
Provided herein are compositions that include mRNA molecules encoding transcription activator like effector nucleases (TALENs) for targeting hepatitis B virus (HBV) genes. Also provided herein are methods of HBV gene editing. Compositions and methods provided herein are useful for treating HBV infection and HBV-related diseases.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
Nucleic acid molecules encoding transcription activator like effector nucleases (TALENs) for targeting a hepatitis B virus (HBV) genome are described. Also described are compositions, host cells, lipids, and pharmaceutical compositions containing the TALENs. Methods for treating hepatitis infection, particularly in individuals having chronic HBV infection, using the pharmaceutical compositions of the invention are also described.
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
CONSORCIO CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED, M.P. (Spain)
INSTITUT D’INVESTIGACIÓ BIOMÉDICA DE GIRONA DR JOSEP TRUETA (Spain)
UNIVERSITAT DE BARCELONA (Spain)
Inventor
Trelles, Ramón Díaz
Tachikawa, Kiyoshi
Karmali, Priya Prakash
Mukthavaram, Rajesh
Chivukula, Padmanabh
Moreno-Navarrete, José María
Navarro, Aleix Gavaldá
Fernández-Real, José Manuel
Oms, Marta Giralt
Gombau, Francesc Villarroya
Abstract
Provided herein are compositions and methods for treating metabolic disorders, such as hepatic steatosis, adipose tissue dysfunction, and insulin resistance. Small interfering RNAs (siRNAs) targeting LPS-binding protein (LBP) that include unlocked nucleotides (UNA) and their therapeutic applications for the treatment of metabolic disorders are provided herein.
Provided herein are RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof, and lipids. RNA molecules and compositions including them are useful for inducing immune responses.
A method of producing lipid-encapsulated RNA nanoparticles includes flowing an aqueous solution comprising an RNA through a 1st tube having a first inner diameter (ID); the RNA comprises from about 6,000 to about 13,000 nucleotides; flowing an ethanol solution comprising lipids through a 2nd tube having a second inner diameter (ID), at a flow rate of about 0.2 to about 1 times relative to the aqueous solution through the 1st tube, the lipids comprise a cationic lipid; and mixing the ethanol solution with the aqueous solution; the first ID and second ID and flow rates through the 1st tube and 2nd tube are selected to produce a shear force sufficiently low to preserve the integrity of the RNA; the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about ethanol, the lipid-encapsulated RNA nanoparticles having a bilayer structure.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
8.
METHODS AND COMPOSITIONS FOR QUADRIVALENT INFLUENZA VACCINE
Provided herein are RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof, and lipids. RNA molecules and compositions including them are useful for inducing immune responses.
A61K 39/295 - Polyvalent viral antigens; Mixtures of viral and bacterial antigens
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
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 39/145 - Orthomyxoviridae, e.g. influenza virus
Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
C07K 14/18 - Togaviridae, e.g. flavivirus, pestivirus, yellow fever virus, hepatitis C virus, japanese encephalitis virus
C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
C07K 14/18 - Togaviridae, e.g. flavivirus, pestivirus, yellow fever virus, hepatitis C virus, japanese encephalitis virus
C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
The present disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5′ UTR derived from a gene expressed by Arabidopsis thaliana for use in treating OTC deficiency in a patient.
A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1st tube having an inner diameter (ID) of between about 0.1″ and 0.132″; b) flowing an ethanol solution comprising lipids through a 2nd tube having an ID of between about 0.005″ and 0.02″ at one third the flow rate of the aqueous solution through the 1st tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2nd tube perpendicularly joined to the 1st tube; wherein the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
15.
Nucleic Acid Vaccine Composition Comprising a Lipid Formulation, and Method of Increasing the Potency of Nucleic Acid Vaccines
The Government of the United States, as Represented by the Secretary of the Army (USA)
Arcturus Therapeutics, Inc. (USA)
Inventor
Hooper, Jay W.
Mucker, Eric M.
Chivukula, Padmanabh
Abstract
A nucleic acid vaccine composition comprising one or more of a plasmid-based nucleic acid vaccine and immunotherapy, as well as a lipid formulation, is provided. In addition, the present invention provides a method of enhancing the potency of plasmid-based DNA vaccines and immunotherapies, by formulating a vaccine and/or immunotherapy in a lipid formulation, which is stable when refrigerated or stored frozen, is then delivered to a vaccinee by either needle/syringe, jet injection, or microneedles. The lipid formulation of the present invention comprises one or more lipid excipients selected from 1,2-Distearoyl-sn-glycero-3-phosphocholine, Cholest-5-en-3β-ol, 1,2-Dimyristoyl-rac-glycero-3-methylpolyoxyethlene, and or more symmetric ionizable cationic lipids. The present invention increases vaccine potency dramatically. It was unexpectedly discovered that the level of immunogen, or immune response molecules, produced in vivo is increased (versus administering merely the vaccine or immunotherapy) and, in the case of a vaccine immunogen, the immune response is enhanced.
An oligomer comprising a sense strand and an antisense strand that mediates RNA interference against a target RNA sequence having a trinucleotide repeat expansion is provided, wherein the antisense strand is complementary to the target RNA sequence and comprises a sequence having at least 80% identity to the sequence of Formula (I): rGrCrUrGrCrUrGrCX1X2rCrUrGrCrUrGrCrUrG (I), wherein X1 and X2 are each independently selected from the group consisting of rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X1 and X2 is a UNA monomer; the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomers are useful as therapeutics targeting polyglutamine diseases and other diseases stemming from a trinucleotide repeat expansion.
National University Corporation Tokai National Higher Education and Research System (Japan)
Inventor
Tachikawa, Kiyoshi
Leu, Angel I-Jou
Chivukula, Padmanabh
Karmali, Priya Prakash
Hirunagi, Tomoki
Sahashi, Kentaro
Katsuno, Masahisa
Abstract
A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX1X2rCrUrGrCrUrGrCrUrG (I), wherein X1 and X2 are each independently selected from rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X1 and X2 is a UNA monomer; b) the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.
Provided herein are RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof, and lipids. RNA molecules and compositions including them are useful for inducing immune responses.
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
C07K 14/18 - Togaviridae, e.g. flavivirus, pestivirus, yellow fever virus, hepatitis C virus, japanese encephalitis virus
C07K 14/165 - Coronaviridae, e.g. avian infectious bronchitis virus
C07K 14/11 - Orthomyxoviridae, e.g. influenza virus
The invention relates to a synthetic transfer RNA with an extended anticodon loop. The invention provides a synthetic suppressor transfer RNA useful for the treatment of a genetic disease like cystic fibrosis associated with a nonsense mutation. The synthetic transfer RNA contains an extended anticodon loop with two consecutive anticodon base triplets configured to base-pair to two consecutive codon base triplets on an mRNA. The first anticodon base triplet or the second anticodon base triplet is configured to base-pair to a stop codon base triplet on the mRNA.
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
20.
LIPID FORMULATIONS CONTAINING NUCLEIC ACIDS AND METHODS OF TREATMENT FOR CYSTIC FIBROSIS
Lipid formulations that encapsulate messenger RNA (mRNA) are provided herein. The mRNA can be used to express CFTR protein in vitro or in vivo. The lipid formulations can be administered via inhalation to treat cystic fibrosis.
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
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
C07C 327/34 - Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups with amino groups bound to the same hydrocarbon radicals
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
Nucleic acid immunization is achieved by delivering a nucleic acid (NA), e.g., a mRNA or a DNA, encapsulated within a lipid-NA nanoparticle. The NA encodes an immunogenic compound of interest. The lipid-NA nanoparticle is effective for in vivo delivery of NA to a vertebrate cell, including upon administration to a subject. The lipid-NA nanoparticle are incorporated in pharmaceutical compositions for immunizing subjects against various diseases.
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 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
in vitroin vivoin vivo. The lipid formulations are typically lipid nanoparticles which comprise mixtures of cationic lipids such as DSPC and DOTAP, cholesterol and PEGylated lipids. Further the lipid formulations can be administered via inhalation to treat cystic fibrosis.
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
25.
LIPID FORMULATIONS CONTAINING NUCLEIC ACIDS AND METHODS OF TREATMENT FOR CYSTIC FIBROSIS
Lipid formulations that encapsulate messenger RNA (mRNA) are provided herein. The mRNA can be used to express CFTR protein in vitro or in vivo. The lipid formulations are typically lipid nanoparticles which comprise mixtures of cationic lipids such as DSPC and DOTAP, cholesterol and PEGylated lipids. Further the lipid formulations can be administered via inhalation to treat cystic fibrosis.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
26.
COMPOSITIONS AND METHODS FOR TREATING PHENYLKETONURIA
Phenylketonuria (PKU) is caused by a mutation in the phenylalanine hydroxylase (P AH) gene in the liver, Provided herein are compositions and methods for treating phenylketonuria (PKU) and related disorders. Polynucleotides for expressing bacterial and plant-derived phenylalanine ammonia lyase (PAL) are provided herein. Also provided herein are methods of treating PKU and related disorders that include administration of polynucleotides encoding PAL proteins.
A range of therapeutic mRNA molecules expressible to provide a target polypeptide or protein. The RNA molecules can contain one or more 5-methoxyuridines and 5-methylcytidines. Further provided are DNA templates, which can be transcribed to provide a target mRNA, and can have altered nucleotides, such as reduced deoxyadenosines. Also provided are processes for making the therapeutic mRNA molecules. The RNA molecules can be translated in vitro or in vivo to provide an active polypeptide or protein. The RNA molecules can be included in a composition used for preventing, treating, or ameliorating at least one symptom of a disease or condition in a subject in need thereof.
Provided herein are RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof, and lipids. RNA molecules and compositions including them are useful for inducing immune responses.
Provided herein are RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof, and lipids. RNA molecules and compositions including them are useful for inducing immune responses.
The present disclosure describes compounds of Formula (I) or a pharmaceutically acceptable salt thereof:
The present disclosure describes compounds of Formula (I) or a pharmaceutically acceptable salt thereof:
The present disclosure describes compounds of Formula (I) or a pharmaceutically acceptable salt thereof:
wherein: R1 and R2 are each independently (CH3(CH2)m)2CH—, (CH3(CH2)m)(CH3(CH2)m-1)CH, (CH3(CH2)m)(CH3(CH2)m-2)CH, (CH3(CH2)m)2CHCH2—, or (CH3(CH2)m)(CH3(CH2)m-1)CHCH2—, wherein m is 4-11; L1 and L2 are each independently absent, a linear C1-5 alkylene, or (CH2)p—O—(CH2)q, wherein p and q are each independently 1-3; R3 is a linear C2-5 alkylene optionally substituted with one or two methyl groups; R4 and R5 are each independently H or C1-6 alkyl; X is O or S; and n is 0-2.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C07C 327/34 - Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups with amino groups bound to the same hydrocarbon radicals
C07C 229/24 - 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 more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I)
Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I)
wherein,
A1 is selected from serine, threonine, O—C1-6 alkyl serine, and O—C1-6 alkyl threonine;
A2 is selected from serine, threonine, O—C1-6 alkyl serine, and O—C1-6 alkyl threonine;
A3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid;
A4 is proline;
each A5 is independently selected from a natural or modified amino acid;
The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
C07K 7/04 - Linear peptides containing only normal peptide links
C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
The present disclosure describes compounds of Formula (I) or a pharmaceutically acceptable salt thereof: wherein: R1 and R2 are each independently (CH3(CH2)m)2CH-, (CH3(CH2)m)(CH3(CH2)m- 1)CH, (CH3(CH2)m)(CH3(CH2)m-2)CH, (CH3(CH2)m)2CHCH2-, or (CH3(CH2)m)(CH3(CH2)m- 1)CHCH2-, wherein m is 4-11; L1 and L2 are each independently absent, a linear C1-5 alkylene, or (CH2)p-O-(CH2)q, wherein p and q are each independently 1-3; R3 is a linear C2-5 alkylene optionally substituted with one or two methyl groups; R4 and R5 are each independently H or C1-6 alkyl; X is O or S; and n is 0-2.
C07C 225/06 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and acyclic
The present disclosure describes compounds of Formula (I) or a pharmaceutically acceptable salt thereof: wherein: R1and R232m232m32m132m32m-232m2232m32m-122-, wherein m is 4-11; L1and L21-52p2qq, wherein p and q are each independently 1-3; R32-52-5 alkylene optionally substituted with one or two methyl groups; R4and R51-61-6 alkyl; X is O or S; and n is 0-2.
C07C 225/06 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and acyclic
A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.
A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.
Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I), wherein, A1 is selected from serine, threonine, O-C1-6 alkyl serine, and O-C1-6 alkyl threonine; A2 is selected from serine, threonine, O-C1-6 alkyl serine, and O-C1-6 alkyl threonine; A3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A4 is proline; each A5 is independently selected from a natural or modified amino acid; The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.
A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 a protein, peptide or polyamino acid
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I), wherein, A11-61-61-6 alkyl threonine; A21-61-61-6 alkyl threonine; A3is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A4is proline; each A5 is independently selected from a natural or modified amino acid; The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 a protein, peptide or polyamino acid
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
C07C 235/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07C 237/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
C07C 323/60 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
C11C 3/04 - Fats, oils or fatty acids obtained by chemical modification of fats, oils or fatty acids, e.g. by ozonolysis by esterification of fats or fatty oils
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
40.
IMPROVED IN VITRO TRANSCRIPTION PURIFICATION PLATFORM
Provided herein are methods for purification of RNA from a sample. The methods include obtaining a first sample including double stranded RNA in a loading buffer, loading the sample onto a ceramic hydroxyapatite column, washing the column with wash buffer, and eluting the column with an elution buffer to create an eluate.
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 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01D 15/42 - Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
Nucleic acid molecules encoding transcription activator like effector nucleases (TALENs) for targeting a hepatitis B virus (HBV) genome are described. Also described are compositions, host cells, lipids, and pharmaceutical compositions containing the TALENs. Methods for treating hepatitis infection, particularly in individuals having chronic HBV infection, using the pharmaceutical compositions of the invention are also described.
CONSORCIO CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED, M.P. (Spain)
INSTITUT D'INVESTIGACIÓ BIOMÈDICA DE GIRONA DR JOSEP TRUETA (Spain)
UNIVERSITAT DE BARCELONA (Spain)
Inventor
Trelles, Ramón Díaz
Tachikawa, Kiyoshi
Karmali, Priya Prakash
Mukthavaram, Rajesh
Chivukula, Padmanabh
Moreno-Navarrete, José María
Navarro, Aleix Gavaldà
Fernández-Real, José Manuel
Oms, Marta Giralt
Gombau, Francesc Villarroya
Abstract
Provided herein are compositions and methods for treating metabolic disorders, such as hepatic steatosis, adipose tissue dysfunction, and insulin resistance. Small interfering RNAs (siRNAs) targeting LPS -binding protein (LBP) that include unlocked nucleotides (UNA) and their therapeutic applications for the treatment of metabolic disorders are provided herein.
Nucleic acid molecules encoding transcription activator like effector nucleases (TALENs) for targeting a hepatitis B virus (HBV) genome are described. Also described are compositions, host cells, lipids, and pharmaceutical compositions containing the TALENs. Methods for treating hepatitis infection, particularly in individuals having chronic HBV infection, using the pharmaceutical compositions of the invention are also described.
st tube comprising a turbulent flow of the RNA and the lipids in between about ethanol, the lipid-encapsulated RNA nanoparticles having a bilayer structure.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
45.
SYNTHETIC TRANSFER RNA WITH EXTENDED ANTICODON LOOP
The invention relates to a synthetic transfer RNA with an extended anticodon loop. The invention provides a synthetic suppressor transfer RNA useful for the treatment of a genetic disease like neurofibromatosis associated with a frameshift mutation. The synthetic transfer RNA comprises an extended anticodon loop having a four-nucleotide anticodon or a five-nucleotide anticodon.
The present disclosure provides a modified human protein having improved in vivo stability. The modified human protein has been altered from a wild-type human protein at either at least one ubiquitination site, at the signal peptide portion, or both. The protein of the disclosure can be produced from a codon optimized mRNA suitable for administration to a patient suffering from deficiency of the wild-type protein, wherein upon administration of the mRNA to the patient, the modified protein of the disclosure is expressed in the patient in therapeutically effective amounts.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
A method of producing lipid-encapsulated RNA nanoparticles includes flowing an aqueous solution comprising an RNA through a 1sttube having a first inner diameter (ID); the RNA comprises from about 6,000 to about 13,000 nucleotides; flowing an ethanol solution comprising lipids through a 2ndtube having a second inner diameter (ID), at a flow rate of about 0.2 to about 1 times relative to the aqueous solution through the 1sttube, the lipids comprise a cationic lipid; and mixing the ethanol solution with the aqueous solution; the first ID and second ID and flow rates through the 1sttube and 2ndtube are selected to produce a shear force sufficiently low to preserve the integrity of the RNA; the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about ethanol, the lipid-encapsulated RNA nanoparticles having a bilayer structure.
A method of producing lipid-encapsulated RNA nanoparticles includes flowing an aqueous solution comprising an RNA through a 1st tube having a first inner diameter (ID); the RNA comprises from about 6,000 to about 13,000 nucleotides; flowing an ethanol solution comprising lipids through a 2nd tube having a second inner diameter (ID), at a flow rate of about 0.2 to about 1 times relative to the aqueous solution through the 1st tube, the lipids comprise a cationic lipid; and mixing the ethanol solution with the aqueous solution; the first ID and second ID and flow rates through the 1st tube and 2nd tube are selected to produce a shear force sufficiently low to preserve the integrity of the RNA; the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about ethanol, the lipid-encapsulated RNA nanoparticles having a bilayer structure.
Methods of preparing lyophilized lipid nanoparticle-nucleic acid compositions are provided. The methods comprise preparing a suspension of lipid nanoparticles with a monosaccharide and one or more excipients selected from thiosulfate, potassium sorbate, sodium benzoate, and iodixanol. Lyophilized lipid nanoparticle-nucleic acid compositions and methods of reconstituting and administering the same are further provided.
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
Methods of preparing lyophilized lipid nanoparticle-nucleic acid compositions are provided. The methods comprise preparing a suspension of lipid nanoparticles with a monosaccharide and one or more excipients selected from thiosulfate, potassium sorbate, sodium benzoate, and iodixanol. Lyophilized lipid nanoparticle-nucleic acid compositions and methods of reconstituting and administering the same are further provided.
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Methods of preparing lyophilized lipid nanoparticle-nucleic acid compositions are provided. The methods comprise preparing a suspension of lipid nanoparticles with a monosaccharide and one or more excipients selected from thiosulfate, potassium sorbate, sodium benzoate, and iodixanol. Lyophilized lipid nanoparticle-nucleic acid compositions and methods of reconstituting and administering the same are further provided.
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
Nucleotides encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein are provided herein. Also describe are mRNA constructs that can be used to express CFTR protein in vitro or in vivo. The mRNA constructs can be formulated in a lipid formulation and administered via inhalation to treat cystic fibrosis.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 11/00 - Drugs for disorders of the respiratory system
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
53.
UNA OLIGOMERS FOR THE TREATMENT OF POLYGLUTAMINE DISEASES
An oligomer comprising a sense strand and an antisense strand that mediates RNA interference against a target RNA sequence having a trinucleotide repeat expansion is provided, wherein the antisense strand is complementary to the target RNA sequence and comprises a sequence having at least 80% identity to the sequence of Formula (I): rGrCrUrGrCrUrGrCX1X2rCrUrGrCrUrGrCrUrG (I), wherein X1and X2are each independently selected from the group consisting of rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X1and X2 is a UNA monomer; the oligomer comprises a UNA monomer at the first position at the 5'-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomers are useful as therapeutics targeting polyglutamine diseases and other diseases stemming from a trinucleotide repeat expansion.
NATIONAL UNIVERSITY CORPORATION TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM (Japan)
Inventor
Tachikawa, Kiyoshi
Leu, Angel I-Jou
Chivukula, Padmanabh
Karmali, Priya
Hirunagi, Tomoki
Sahashi, Kentaro
Katsuno, Masahisa
Abstract
A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX1X2rCrUrGrCrUrGrCrUrG (I), wherein X1and X2are each independently selected from rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X1and X2 is a UNA monomer; b) the oligomer comprises a UNA monomer at the first position at the 5'-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 11/00 - Drugs for disorders of the respiratory system
56.
NUCLEIC ACIDS AND METHODS OF TREATMENT FOR CYSTIC FIBROSIS
Nucleotides encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein are provided herein. Also describe are mRNA constructs that can be used to express CFTR protein in vitro or in vivo. The mRNA constructs can be formulated in a lipid formulation and administered via inhalation to treat cystic fibrosis.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Disclosed herein is a compound of Formula I, wherein R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt or solvate thereof.
Disclosed herein is a compound of Formula I, wherein R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt or solvate thereof.
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
58.
SYNTHESIS AND STRUCTURE OF HIGH POTENCY RNA THERAPEUTICS
This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5′ UTRs, where a 5′ UTR may be expressed by a gene of a plant. In some embodiments, a 5′ UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C07K 14/415 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
This disclosure encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting expression of PDGFRB in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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
Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.
Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.
The present disclosure provides a nucleic acid molecule comprising a first polynucleotide encoding one or more viral replication proteins, wherein the first polynucleotide is codon-optimized as compared to a wild-type polynucleotide encoding the one or more viral replication proteins; and a second polynucleotide comprising a first transgene encoding a first antigenic protein or a fragment thereof. In some embodiments, the one or more viral replication proteins may be alphavirus proteins or rubivirus proteins.
The present disclosure describes compositions and methods for treating ornithine transcarbamylase (OTC) deficiency. The compositions include a lipid formulation and messenger RNA (mRNA) encoding an OTC enzyme. The lipid formulations can comprise an ionizable cationic lipid in a lipid nanoparticle encapsulating the mRNA.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/221 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
66.
COMPOSITIONS AND METHODS FOR INDUCING IMMUNE RESPONSES
The present disclosure provides a nucleic acid molecule comprising a first polynucleotide encoding one or more viral replication proteins, wherein the first polynucleotide is codon-optimized as compared to a wild-type polynucleotide encoding the one or more viral replication proteins; and a second polynucleotide comprising a first transgene encoding a first antigenic protein or a fragment thereof. In some embodiments, the one or more viral replication proteins may be alphavirus proteins or rubivirus proteins.
The present disclosure describes compositions and methods for treating ornithine transcarbamylase (OTC) deficiency. The compositions include a lipid formulation and messenger RNA (mRNA) encoding an OTC enzyme. The lipid formulations can comprise an ionizable cationic lipid in a lipid nanoparticle encapsulating the mRNA.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 9/00 - Drugs for disorders of the cardiovascular system
The present disclosure describes compositions and methods for treating ornithine transcarbamylase (OTC) deficiency. The compositions include a lipid formulation and messenger RNA (mRNA) encoding an OTC enzyme. The lipid formulations can comprise an ionizable cationic lipid in a lipid nanoparticle encapsulating the mRNA.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 9/00 - Drugs for disorders of the cardiovascular system
What is described is a compound of formula I
What is described is a compound of formula I
What is described is a compound of formula I
consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a linear alkylene or alkenylene consisting of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
70.
ASIALOGLYCOPROTEIN RECEPTOR MEDIATED DELIVERY OF THERAPEUTICALLY ACTIVE CONJUGATES
ASGP-R binding molecular conjugates are provided. The conjugates are useful to deliver therapeutically effective amounts of biologically active molecules to target cells and tissues of a subject. Compositions are also provided comprising the molecular conjugates.
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
71.
ASIALOGLYCOPROTEIN RECEPTOR MEDIATED DELIVERY OF THERAPEUTICALLY ACTIVE CONJUGATES
ASGP-R binding molecular conjugates are provided. The conjugates are useful to deliver therapeutically effective amounts of biologically active molecules to target cells and tissues of a subject. Compositions are also provided comprising the molecular conjugates.
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
72.
ASIALOGLYCOPROTEIN RECEPTOR MEDIATED DELIVERY OF THERAPEUTICALLY ACTIVE CONJUGATES
ASGP-R binding molecular conjugates are provided. The conjugates are useful to deliver therapeutically effective amounts of biologically active molecules to target cells and tissues of a subject. Compositions are also provided comprising the molecular conjugates.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
C07H 15/04 - Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of a saccharide radical
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
73.
METHOD OF SYNTHESIS OF AN IONIZABLE CATIONIC LIPID
What is described is a method of synthesis of the compound of formula 1A,
What is described is a method of synthesis of the compound of formula 1A,
or a salt thereof, wherein
R3 is a linear or branched alkene of 1, 2, 3, 4, 5 or 6 carbons;
R4 and R5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons; and
L3 is a bond or an alkane of 1, 2, 3, 4, 5 or 6 carbons.
C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 235/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07C 237/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C07C 323/60 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
C11C 3/04 - Fats, oils or fatty acids obtained by chemical modification of fats, oils or fatty acids, e.g. by ozonolysis by esterification of fats or fatty oils
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
74.
Synthetic transfer RNA with extended anticodon loop
A synthetic transfer RNA with an extended anticodon loop. A synthetic suppressor transfer RNA useful for the treatment of a genetic disease like cystic fibrosis associated with a nonsense mutation. The synthetic transfer RNA contains an extended anticodon loop with two consecutive anticodon base triplets configured to base-pair to two consecutive codon base triplets on an mRNA. The first anticodon base triplet or the second anticodon base triplet is configured to base-pair to a stop codon base triplet on the mRNA.
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
75.
IMPROVED IN VITRO TRANSCRIPTION PURIFICATION PLATFORM
Provided herein are methods for purification of RNA from a sample. The methods include obtaining a first sample including double stranded RNA in a loading buffer, loading the sample onto a ceramic hydroxyapatite column, washing the column with wash buffer, and eluting the column with an elution buffer to create an eluate.
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Biological compounds for medical use in the nature of
enhanced ribonucleic acid delivered into patient cells;
biological compounds being a component in vaccines;
therapeutic agents for generating protective immune
response; biological therapeutic agents, namely molecularly
engineered RNA for increasing expression and extending
duration of expression of therapeutic proteins upon delivery
into patient cells.
78.
SYNTHETIC TRANSFER RNA WITH EXTENDED ANTICODON LOOP
The invention relates to a synthetic transfer RNA with an extended anticodon loop. The invention provides a synthetic suppressor transfer RNA useful for the treatment of a genetic disease like neurofibromatosis associated with a frameshift mutation. The synthetic transfer RNA comprises an extended anticodon loop having a four-nucleotide anticodon or a five- nucleotide anticodon.
A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1sttube having an inner diameter (ID) of between about 0.1" and 0.132"; b) flowing an ethanol solution comprising lipids through a 2ndtube having an ID of between about 0.005" and 0.02" at one third the flow rate of the aqueous solution through the 1st tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2ndtube perpendicularly joined to the 1sttube; wherein the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.
A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1st tube having an inner diameter (ID) of between about 0.1" and 0.132"; b) flowing an ethanol solution comprising lipids through a 2nd tube having an ID of between about 0.005" and 0.02" at one third the flow rate of the aqueous solution through the 1st tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2nd tube perpendicularly joined to the 1st tube; wherein the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.
st tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
82.
Compositions and methods for treating ornithine transcarbamylase deficiency
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
C07H 21/04 - 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 deoxyribosyl as saccharide radical
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
83.
COMPOSITIONS AND METHODS FOR TREATING ORNITHINE TRANSCARBAMYLASE DEFICIENCY
The present disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5' UTR derived from a gene expressed by Arabidopsis thaliana for use in treating OTC deficiency in a patient.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
in vivo stabilityin vivo stability. The modified human protein has been altered from a wild-type human protein at either at least one ubitquitination site, at the signal peptide portion, or both. The protein of the disclosure can be produced from a codon optimized mRNA suitable for administration to a patient suffering from deficiency of the wild-type protein, wherein upon administration of the mRNA to the patient, the modified protein of the disclosure is expressed in the patient in therapeutically effective amounts.
Disclosed herein is a lipid composition comprising a compound having the formula IA, or a pharmaceutically acceptable salt thereof,
3 is a bond or an alkane of 1-6 carbons.
C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
C07C 323/60 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 235/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07C 237/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
C11C 3/04 - Fats, oils or fatty acids obtained by chemical modification of fats, oils or fatty acids, e.g. by ozonolysis by esterification of fats or fatty oils
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
87.
Molecules and agents for treating hepatitis B virus
This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting Hepatitis B virus in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of an HBV genome.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
This invention provides a range of translatable polynucleotide and oligomer molecules for expressing a human phenylalanine hydroxylase (PAH), or a fragment thereof having PAH activity. The polynucleotide and oligomer molecules are expressible to provide the human PAH or a fragment thereof having PAH activity. The molecules can be used as active agents to express an active polypeptide or protein in cells or subjects. The agents can be used in methods for ameliorating, preventing, delaying onset, or treating a disease or condition associated with phenylketonuria, decreased metabolism of phenylalanine, or increased levels of phenylalanine in a subject.
A61K 31/7115 - Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt or solvate thereof.
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
91.
COMPOSITIONS AND AGENTS AGAINST NONALCOHOLIC STEATOHEPATITIS
This disclosure encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting expression of PDGFRB in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Biological compound for medical use, namely, enhanced ribonucleic acid delivered into patient cells; Biological compounds being a component in vaccines; Therapeutic agents for generating protective immune response; Molecularly engineered RNA for increasing expression, and extending duration of expression, of therapeutic proteins upon delivery into patient cells
What is described is a compound of formula I
5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
C07C 333/04 - Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
Nucleic acid immunization is achieved by delivering a nucleic acid (NA), e.g., a mRNA or a DNA, encapsulated within a lipid-NA nanoparticle. The NA encodes an immunogenic compound of interest. The lipid-NA nanoparticle is effective for in vivo delivery of NA to a vertebrate cell, including upon administration to a subject. The lipid-NA nanoparticle are incorporated in pharmaceutical compositions for immunizing subjects against various diseases.
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
The invention relates to a synthetic transfer RNA with an extended anticodon loop. The invention provides a synthetic suppressor transfer RNA useful for the treatment of a genetic disease like cystic fibrosis associated with a nonsense mutation.The synthetic transfer RNA contains an extended anticodon loop with two consecutive anticodon base triplets configured to base-pair to two consecutive codon base triplets on an mRNA. The first anticodon base triplet or the second anticodon base triplet is configured to base-pair to a stop codon base triplet on the mRNA.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C07K 14/415 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting Hepatitis B virus in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of an HBV genome.
This invention provides UNA oligomers for gene silencing with reduced off-target effects. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and various nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis with reduced off-target effects by administering a UNA oligomer to a subject.
This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5' UTRs, where a 5' UTR may be expressed by a gene of a plant. In some embodiments, a 5 UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.
A range of therapeutic mRNA molecules expressible to provide a target polypeptide or protein. The RNA molecules can contain one or more 5-methoxyuridines and 5-methylcytidines. Further provided are DNA templates, which can be transcribed to provide a target mRNA, and can have altered nucleotides, such as reduced deoxyadenosines. Also provided are processes for making the therapeutic mRNA molecules. The RNA molecules can be translated in vitro or in vivo to provide an active polypeptide or protein. The RNA molecules can be included in a composition used for preventing, treating, or ameliorating at least one symptom of a disease or condition in a subject in need thereof.
