The present invention relates to the field of pharmaceutical compositions. More particularly it is directed to pharmaceutical compositions comprising an antibody molecule, more particularly a Fab-PEG or a Fab′-PEG molecule, e.g., at high concentrations, and to methods of producing such formulations. Pharmaceutical compositions according to the invention can be lyophilised and are stable upon storage at a temperature from about 2 to 25° C. for an appropriate period of time.
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/60 - 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 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
A method for treatment of a human subject for Alzheimer's disease (AD) comprises sequentially administering two or more doses of a recombinant, fully human, anti-amyloid beta monoclonal antibody to the human subject. In preferred embodiments, the antibody is administered subcutaneously in tissue near or at an abdomen of a human subject in increasing amounts over a period of time.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
Provided are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables in Formula (I) are as defined herein; and methods for their use and production.
Provided are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables in Formula (I) are as defined herein; and methods for their use and production.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, which are useful for the inhibition of EBP and in the treatment of a variety of EBP mediated conditions or diseases, such as multiple sclerosis.
An implantable medical device for delivering therapeutic fluid to, and withdrawing cerebrospinal fluid (CSF) from, a CSF-containing space, includes a first inlet configured to be accessed by a needle of an aspiration device; a first outlet; a first fluid pathway extending from the first inlet to the first outlet; a second inlet; a second outlet; and a second fluid pathway extending from the second inlet to the second outlet. The first fluid pathway is free of a filter configured to prevent passage of a microbe.
A61M 27/00 - Drainage appliances for wounds, or the like
A61B 10/00 - Instruments for taking body samples for diagnostic purposesOther methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determinationThroat striking implements
A61M 5/14 - Infusion devices, e.g. infusing by gravityBlood infusionAccessories therefor
Provided are compounds of the Formula (I): or pharmaceutically acceptable salts thereof, which are useful for the inhibition of EBP and in the treatment of a variety of EBP mediated conditions or diseases, such as multiple sclerosis.
Disclosed is a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof. The variables in Formula (I) are defined herein. Compounds of Formula (I) are useful for regulating GPR17 activity and for treating disorders and diseases mediated by GPR17 in humans or non-humans.
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
An isolated protein comprising a mutant soluble activin II receptor (ActRIIA or ActRIIB) extracellular domain (Ac-tRIIA-ECD or ActRIIB-ECD), wherein said mutant soluble ActRIIA-ECD or ActRIIB-ECD comprises a mutation to remove the N-linked glycosylation site corresponding to position N18 of SEQ ID NO: 1.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/71 - ReceptorsCell surface antigensCell surface determinants for growth factorsReceptorsCell surface antigensCell surface determinants for growth regulators
The present disclosure pertains to methods for transducing host cells with nucleic acids using an in-line complexer and systems comprising an in-line complexer for transducing host cells. The disclosed methods and systems can be used to produce recombinant adeno-associated virus (rAAV) particles. Also disclosed herein are compositions comprising rAAV particles obtained from the disclosed methods and systems, and uses of the same.
Methods for evaluating subjects having conditions associated with loss of muscle function (e.g., a motor neuron disease, a neuromuscular disease, or a myopathy) by measuring muscle function (e.g., muscle strength) are disclosed.
Provided are compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables in Formula (I) are as defined herein; and methods for their use and production.
Provided are compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables in Formula (I) are as defined herein; and methods for their use and production.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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
12.
METHODS AND PRODUCTS FOR EVALUATING AN IMMUNE RESPONSE TO A THERAPEUTIC PROTEIN
The invention relates to methods and products for the identification of a clinically significant immune response in subjects treated with a therapeutic protein. Aspects of the invention relate to methods and compositions for identifying a clinically significant immune response in patients treated with therapeutic amounts of a VLA4 binding antibody (e.g., natalizumab).
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
13.
COMPOUNDS FOR TARGETING DEGRADATION OF IRAK4 PROTEINS
This disclosure relates to compounds of Formula (A): Formula (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; Formula (I) in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.
This disclosure relates to compounds of Formula (A): Formula (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; Formula (I) in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.
A61K 47/55 - 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 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
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
14.
HYDROPHOBIC INTERACTION CHROMATOGRAPHY FOR PURIFICATION OF OLIGONUCLEOTIDES
B01D 15/42 - Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
C07H 1/00 - Processes for the preparation of sugar derivatives
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
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
16.
METHOD FOR DETECTING A LIPIDATED PROTEIN VIA FLUORESCENCE RESONANCE ENERGY TRANSFER (FRET)
Aspects of the present invention relate to methods for detecting a lipidated protein in a sample from a subject using a protein binding agent and a lipid binding agent configured for detecting the lipidated protein via a fluorescence resonance energy transfer (FRET) assay. In some aspects, such methods are useful for diagnosing and treating a subject such as a subject having a neurological disorder.
Provided are methods for treating Alzheimer's disease in a human subject in need thereof comprising administration of an anti-beta-amyloid antibody (e.g., aducanumab) to the subject.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
19.
GLYCOGEN SYNTHASE KINASE 3 INHIBITORS AND USES THEREOF
The present disclosure provides compounds of Formula I, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be glycogen synthase kinase 3 (GSK3) inhibitors. The present disclosure also provides pharmaceutical compositions, combination therapies, and kits comprising the compounds, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, or prodrugs thereof, and methods of treating or preventing diseases and disorders associated with GSK3.
A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
20.
DIROXIMEL FUMARATE PARTICLES HAVING IMPROVED FLOW PROPERTIES AND METHODS OF MAKING SAME
Many active pharmaceutical ingredients (API) are available in tablet form. Particles of the API should have a favorable compaction profile in order to be compressed into tablets, especially when the API is present in a large weight percentage in the tablet. Disclosed herein are particles of diroximel fumarate having improved characteristic for tablet formation, and methods of producing the same.
C07D 207/404 - 2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
A61K 31/4015 - 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 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
21.
METHODS OF TREATING INFLAMMATORY AND AUTOIMMUNE DISEASES
Natalizumab is a safe and efficacious treatment for inflammatory and autoimmune diseases, such as multiple sclerosis, Crohn's Disease, and rheumatoid arthritis. Rare occurrences of progressive multifocal leucoencephalopathy during treatment suggest the possibility that it may be related to natalizumab treatment. Monitoring for JCV and informing caregivers and patients about the manifestations of progressive multifocal leucoencephalopathy can improve the safety of natalizumab therapy.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 38/03 - Peptides having up to 20 amino acids in an undefined or only partially defined sequenceDerivatives thereof
The present disclosure provides methods of treating Multiple Sclerosis (MS) using Compound 1 as represented by the structure below: or a pharmaceutically acceptable salt thereof, in combination with diroximel fumarate (DRF).
A61K 31/215 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present disclosure provides methods of treating Multiple Sclerosis (MS) using Compound (1) as represented by the structure below or a pharmaceutically acceptable salt thereof.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
This disclosure relates to compounds of formula (I′), or pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the application. The compounds of the present disclosure are capable of inhibiting the activity of tyrosine kinase 2 (TYK2). The disclosure further provides methods of preparing the compounds of the disclosure, and methods for their therapeutic use.
This disclosure relates to compounds of formula (I′), or pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the application. The compounds of the present disclosure are capable of inhibiting the activity of tyrosine kinase 2 (TYK2). The disclosure further provides methods of preparing the compounds of the disclosure, and methods for their therapeutic use.
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 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
25.
COMPOUNDS FOR TARGETING DEGRADATION OF IRAK4 PROTEINS
This disclosure relates to compounds of Formula (A): IRAK-L-DSM (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.
This disclosure relates to compounds of Formula (A): IRAK-L-DSM (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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
Among other things, the present disclosure provides methods, e.g., methods of treating a subject, methods of immunosuppression, comprising administering a recombinant adeno-associated viral vector (rAAV) and an immunosuppressive regimen. In some embodiments, the present disclosure provides methods of reducing dorsal root ganglion (DRG) toxicity. In some embodiments, the present disclosure provides immunosuppressive regimens comprising, e.g., dexamethasone and one or more immunosuppressive agents, e.g., a calcineurin inhibitor.
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A61P 25/00 - Drugs for disorders of the nervous system
27.
1H-PYRROLO[2,3-B]PYRIDIN-4-YL]-2-OXOPYRROLIDINE-3-CARBONITRILE DERIVATIVES AS TYROSINE KINASE 2 (TYK2) INHIBITORS FOR THE TREATMENT OF INFLAMMATORY DISEASES
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contractionDrugs for heart failure
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 11/00 - Drugs for disorders of the respiratory system
A61P 15/02 - Drugs for genital or sexual disordersContraceptives for disorders of the vagina
A61P 17/14 - Drugs for dermatological disorders for baldness or alopecia
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 19/10 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
A61P 25/04 - Centrally acting analgesics, e.g. opioids
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Aspects of the present disclosure, at least in part, comprise methods and compositions for producing recombinant adeno-associated virus (rAAV) by (a) culturing host cells producing the rAAV in a condition suitable for rAAV production; (b) lysing the host cell under conditions sufficient to inactivate enveloped viruses by contacting the host cell with a lysis agent; (c) clarifying the cell lysate; and (d) purifying the rAAV.
Provided are compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R7, R8, R9, A1, A2, Q1, Q2, Q3, A, Z, m and n are as defined herein; pharmaceutical compositions comprising said compounds or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients; and methods of treating a disorder responsive to inhibition of Bruton's tyrosine kinase using said compounds, or pharmaceutically acceptable salts thereof, or said pharmaceutical compositions.
Provided are compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R7, R8, R9, A1, A2, Q1, Q2, Q3, A, Z, m and n are as defined herein; pharmaceutical compositions comprising said compounds or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients; and methods of treating a disorder responsive to inhibition of Bruton's tyrosine kinase using said compounds, or pharmaceutically acceptable salts thereof, or said pharmaceutical compositions.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Featured are methods for the treatment or prevention of spinal muscular atrophy. Effective dosage regimens are specified. Biomarkers and kits are also provided.
Disclosed is a method of preparing diroximel fumarate represented by the following structural formula (I) The method comprises reacting ethy lene carbonate with succinimide to form a hydroxyethyl succinimide intermediate; and reacting the intermediate with monomethyl fumarate to form the product compound.
Disclosed is a method of preparing diroximel fumarate represented by the following structural formula (I) The method comprises reacting ethy lene carbonate with succinimide to form a hydroxyethyl succinimide intermediate; and reacting the intermediate with monomethyl fumarate to form the product compound.
C07D 207/404 - 2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
32.
ENGINEERED CELLS AND CELL LINES FOR AAV PRODUCTION AND METHODS OF MAKING AND USING THE SAME
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives 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 diseasesGene therapy
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
Described herein are compounds represented by formulas (IA) or (IB)
Described herein are compounds represented by formulas (IA) or (IB)
Described herein are compounds represented by formulas (IA) or (IB)
or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same and methods of preparing and using the same. The variables R1, R3, R4, Y1, Y2, Ar, Z and n are as defined herein.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07D 417/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of Tau mRNA in a cell or animal, and in certain instances reducing the amount of Tau protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disease. Such symptoms include loss of memory, loss of motor function, and increase in the number and/or volume of neurofibrillary inclusions. Such neurodegenerative diseases include tauopathies, Alzheimer's Disease, Fronto-temporal Dementia (FTD), FTDP-17, Progressive Supranuclear Palsy (PSP), Chronic Traumatic Encephalopathy (CTE), Corticobasal Ganglionic Degeneration (CBD), Epilepsy, and Dravet's Syndrome.
A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
36.
ANTI-TRANSFERRIN RECEPTOR ANTIBODIES AND USES THEREOF
The present disclosure provides anti-transferrin receptor antibodies, compositions comprising the same and methods of use for delivery of cargo to brain tissue. This disclosure also provides polynucleotides and vectors encoding the anti-transferrin receptor antibodies and cells comprising the same, methods of making the antibodies, and molecules comprising the antibodies.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61P 25/00 - Drugs for disorders of the nervous system
37.
COMPOUNDS FOR TARGETING DEGRADATION OF BRUTON'S TYROSINE KINASE
This disclosure relates to compounds of Formula (A): BTK-L-DSM (A) or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches BTK to DSM, and BTK is a Btk binding moiety represented by Formula (I) or Formula (II) that is covalently attached to linker L: in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of Btk proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of Btk proteins. The present disclosure also provides methods of treating disorders responsive to modulation of Btk activity and/or degradation of Btk with at least one compound described herein.
This disclosure relates to compounds of Formula (A): BTK-L-DSM (A) or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches BTK to DSM, and BTK is a Btk binding moiety represented by Formula (I) or Formula (II) that is covalently attached to linker L: in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of Btk proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of Btk proteins. The present disclosure also provides methods of treating disorders responsive to modulation of Btk activity and/or degradation of Btk with at least one compound described herein.
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, which are activators of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and are useful to treat diseases caused by oxidative stress, such as neurodegenerative diseases or inflammation. Also provided are methods for their use and production.
The present disclosure pertains to muscle-targeting moieties comprising RGD- containing peptides which peptides can be inserted in the capsid of a recombinant adeno- associated virus (rAAV) vector. Also disclosed herein are compositions comprising muscle- targeting moieties disclosed herein and methods of making and using the same.
Provided are methods for treating Alzheimer's disease in a human subject in need thereof when the subject develops an Amyloid Related Imaging Abnormality (ARIA) or a hypersensitivity reaction during a treatment regimen comprising administration of multiple doses of an anti-beta-amyloid antibody to the subject.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The present disclosure provides combination therapies for treating an autoimmune disease in a subject in need thereof. The methods comprise administering to the subject an effective amount of a BTK inhibitor in combination with an effective amount of a fumaric acid ester (FAE). The autoimmune disease can be treated include, for example, multiple sclerosis (MS), lupus, rheumatoid arthritis (RA), Pemphigus Vugaris (PV), neuromyelitis optica (NMO), myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), anti-NMDA receptor encephalitis, or Sjogren's disease.
A61K 31/4015 - 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 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 37/00 - Drugs for immunological or allergic disorders
The present disclosure provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof and its use in, e.g., evaluating the biodistribution and/or concentration of a biomolecule in a subject.
Provided herein are methods for administering disease-modifying antibody therapies to asymptomatic and/or early-stage multiple sclerosis patients, including Radiologically Isolated Syndrome patients, based on the identification and/or co-localization of slowly expanding lesions and paramagnetic rim lesions in magnetic resonance images from said patients.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
The disclosure provides the use of neurofilament light chain levels for selecting a subject with a mutation in the superoxide dismutase 1 (SOD 1) gene for treatment with a SOD 1-targeting antisense oligonucleotide or salt thereof. The disclosed methods can be used in the treatment amyotrophic lateral sclerosis, including clinically presymptomatic amyotrophic lateral sclerosis.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
46.
NUCLEIC ACID DELIVERY TO THE CENTRAL NERVOUS SYSTEM
Featured are polymeric nanocarriers (e.g., PLGA nanoparticles) with encapsulated nucleic acid (e.g., an antisense oligonucleotide) for delivery (e.g., intrathecally) to the central nervous system. These polymeric nanocarriers are useful in the treatment of central nervous system disorders. They are capable of delivering their cargo (e.g., an antisense oligonucleotide) in higher amounts, for a longer period of time, and into deeper regions of the brain than a free or unformulated antisense oligonucleotide. The efficient delivery and distribution of antisense oligonucleotides results in reducing the number of administrations and patient compliance and improves patient experience.
A61K 47/59 - 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 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
47.
ANTI-TRANSFERRIN RECEPTOR ANTIBODIES AND USES THEREOF
The present disclosure provides anti-transferrin receptor antibodies, compositions comprising the same and methods of their use. This disclosure also provides polynucleotides and vectors encoding the anti-transferrin receptor antibodies and cells comprising the same, methods of making the antibodies, and molecules comprising the antibodies.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
48.
REDUCING HOST CELL IMPURITIES DURING RECOMBINANT PROTEIN PRODUCTION
In some instances, the application provides methods of culturing host cells comprising a gene encoding a recombinant N protein in a cell culture medium, wherein the cell culture medium comprises: (i) iron at a concentration of less than 1200 μM; and (ii) citrate at a concentration of less than 2400 μM. In some instances, the methods comprise culturing host cells expressing a recombinant protein in a cell culture medium at a first temperature; and decreasing the first temperature to a second temperature. In some instances, the methods comprise purifying the recombinant protein by a carbon depth filtration.
An implantable cranial medical device includes a housing configured to be positioned on a skull of a subject such that at least a portion of the housing covers a burr hole of the skull. The medical device also includes a brain catheter connector extending from the housing and configured to extend within the skull. The brain catheter connector includes a first connector and a second connector. The second connector extends farther away from the housing than the first connector. Additionally, the medical device includes a first fluid path extending through the housing and the first connector, and a second fluid path extending through the housing and the second connector. The first and second fluid paths are not in fluid communication with one another within the housing.
A61M 39/04 - Access sites having pierceable self-sealing members
A61M 1/00 - Suction or pumping devices for medical purposesDevices for carrying-off, for treatment of, or for carrying-over, body-liquidsDrainage systems
50.
COMPOSITIONS AND METHODS FOR TREATING RETINITIS PIGMENTOSA
Among other things, the present disclosure provides compositions, e.g., recombinant adeno- associated virus (rAAV) vectors, comprising, e.g., an inhibitory nucleic acid (e.g., a miRNA) and/or a therapeutic nucleic acid sequence encoding a therapeutic polypeptide. In some embodiments, the present disclosure provides methods of decreasing expression of a pathogenic polypeptide (e.g.. a mutant RHO polypeptide) and increasing expression of a therapeutic polypeptide (e.g., a wild-type RHO polypeptide), e.g., in a subject. In some embodiments, the present disclosure provides methods of treating retinal degeneration in a subject. In some embodiments, the present disclosure provides methods of treating retinitis pigmentosa (RP) in a subject.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Among other things, the present disclosure provides compositions, e.g., isolated nucleic acids, vectors, and recombinant adeno-associated viruses (rAAVs), comprising a nucleic acid sequence encoding a PRPF31 polypeptide. In some embodiments, the present disclosure provides methods of increasing expression of PRPF31, e.g., in a subject. In some embodiments, the present disclosure provides methods of treating retinal degeneration in a subject. In some embodiments, the present disclosure provides methods of treating retinitis pigmentosa (RP) in a subject.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
Disclosed are systems and methods for classifying brain lesions based on single point in time imaging, methods for training a machine learning model for classifying brain lesions, and a method of predicting formation of brain lesions based on single point in time imaging. A method of classifying brain lesions based on single point in time imaging can include; accessing patient image data from a single point in time; providing the patient image data as an input to a brain lesion classification model; generating a classification for each of one or more lesions identified in the patient image data; and providing the classification for each of the one or more lesions for display on one or more display devices; wherein the brain lesion classification model is trained using subject image data for a plurality of subjects, the subject image data being captured at two or more points in time.
Disclosed is a method of classifying brain lesions (100) based on single point in time imaging by accessing patient image data from a single point in time (110); providing the patient image data as an input to a brain lesion classification model (120); generating a classification for each of one or more lesions identified in the patient image data (130); and providing the classification for each of the one or more lesions for display on one or more display devices (140); wherein the brain lesion classification model is trained using subject image data for a plurality of subjects, the subject image data being captured at two or more points in time.
The present disclosure provides compounds of Formulae T-A, I-B. II-A. II-B. lll-A, III-B, IV-A. IV-B, V-A, V-B, Vl-A, and VI-B. and compounds shown in Table 13, Table 13 A, and Table 14, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof, which are GSK3 inhibitors. The present disclosure also provides pharmaceutical compositions, combination therapies, and kits comprising the compounds, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crysials, tautomers, stereoisomers, isotopically labeled compounds, or prodrags thereof, and methods of treating or preventing diseases and disorders associated with GSK3.
This disclosure relates to imidazo[1,2-a]pyridinyl derivatives of formula (I), or pharmaceutically acceptable salts thereof, Formula (I) in which all of the variables are as defined in the specification, capable of modulating the activity of IRAK4. The disclosure further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including inflammatory disease, autoimmune disease, cancer, cardiovascular disease, a disease of the central nervous system, disease of the skin, an ophthalmic disease and condition, and a bone disease.
This disclosure relates to imidazo[1,2-a]pyridinyl derivatives of formula (I), or pharmaceutically acceptable salts thereof, Formula (I) in which all of the variables are as defined in the specification, capable of modulating the activity of IRAK4. The disclosure further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including inflammatory disease, autoimmune disease, cancer, cardiovascular disease, a disease of the central nervous system, disease of the skin, an ophthalmic disease and condition, and a bone disease.
Provided are compounds of Formula (I):
Provided are compounds of Formula (I):
Provided are compounds of Formula (I):
including compounds of Formulas (II), (III) and (IV), wherein X, R1, R2, R3 and n are as defined herein, and pharmaceutically acceptable salts thereof, and methods for their use and production. These compounds can be useful, e.g., in the treatment of disorders responsive to the inhibition of apoptosis signal-regulating kinase 1 (ASK1).
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
58.
MICROTUBULE DESTABILIZER ADDITIVES TO INCREASE RECOMBINANT VIRAL VECTOR TITERS
The present disclosure pertains to methods and compositions for the production of recombinant viral vectors, e.g., recombinant adeno-associated viruses (rAAVs), using at least one microtubule destabilizing agent described herein.
Provided are compounds of Formula (I′): or pharmaceutically acceptable salts thereof, wherein the variables in the formula are as defined herein; and methods for their use and production.
Provided are compounds of Formula (I′): or pharmaceutically acceptable salts thereof, wherein the variables in the formula are as defined herein; and methods for their use and production.
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
Pharmaceutical compositions containing anti-beta amyloid (Aβ) antibodies or Aβ-binding fragments thereof are provided. These pharmaceutical compositions find use in the treatment of abnormal accumulation or deposition of Aβ in the central nervous system, mild cognitive impairment, and Aβ-associated disorders such as Alzheimer's disease.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides 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
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Pharmaceutical preparations; pharmaceutical preparations for use in the treatment of psychiatric and neurodegenerative diseases and disorders; pharmaceutical preparations for the treatment of central nervous system diseases and disorders, depression, anxiety disorder, and bipolar depression.
The present disclosure provides a compound of Formula (I'), or a pharmaceutically acceptable salt thereof and its use in, e.g. treating a condition, disease, or disorder in which lowering mutant huntingtin protein ("mHTT") in a subject is of therapeutic benefit, specifically in treating Huntington disease ("HD"). This disclosure also features a composition containing the same as well as methods of using and making the same.
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
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
64.
METHODS FOR CLASSIFICATION OF LESIONS AND FOR PREDICTING LESION DEVELOPMENT
Disclosed are systems and methods for classifying brain lesions based on single point in time imaging, methods for training a machine learning model for classifying brain lesions, and a method of predicting formation of brain lesions based on single point in time imaging. A method of classifying brain lesions based on single point in time imaging can include; accessing patient image data from a single point in time; providing the patient image data as an input to a brain lesion classification model; generating a classification for each of one or more lesions identified in the patient image data; and providing the classification for each of the one or more lesions for display on one or more display devices; wherein the brain lesion classification model is trained using subject image data for a plurality of subjects, the subject image data being captured at two or more points in time.
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
65.
EMOPAMIL-BINDING PROTEIN INHIBITORS AND USES THEREOF
Provided are compounds of the Formula (I): or pharmaceutically acceptable salts thereof, which are useful for the inhibition of EBP and in the treatment of a variety of EBP mediated conditions or diseases, such as multiple sclerosis.
C07D 205/12 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
66.
EMOPAMIL-BINDING PROTEIN INHIBITORS AND USES THEREOF
Provided are compounds of the Formula (I) or pharmaceutically acceptable salts thereof, which are useful for the inhibition of EBP and in the treatment of a variety of EBP mediated conditions or diseases, such as multiple sclerosis.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
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
A61P 25/00 - Drugs for disorders of the nervous system
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
67.
METHODS OF TREATING CUTANEOUS LUPUS ERYTHEMATOSUS AND SYSTEMIC LUPUS ERYTHEMATOSUS
Dosage regimens of anti-Blood Dendritic Cell Antigen 2 antibodies are provided for use in the treatment of cutaneous lupus erythematosus and systemic lupus erythematosus.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
A61K 9/00 - Medicinal preparations characterised by special physical form
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
This disclosure relates to compounds of Formula (I) or pharmaceutically acceptable salts thereof, in which all of the variables in Formula (I) are as defined in the application. The compounds of this disclosure are capable of inhibiting the activity of tyrosine kinase 2 (TYK2). The disclosure further provides methods of preparing the compounds of the disclosure, and methods for their therapeutic use.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
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
This disclosure relates to compounds of Formula (I), or pharmaceutically acceptable salt thereof: Formula (I) in which all of the variables are as defined in the application. The compounds of the present disclosure are capable of inhibiting the activity of tyrosine kinase 2 (TYK2). The disclosure further provides methods of preparing the compounds of the disclosure, and methods for their therapeutic use.
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
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Provided are compounds of the Formula (I): or pharmaceutically acceptable salts thereof, which are useful for the inhibition of TYK2 and in the treatment of a variety of TYK2 mediated conditions or diseases.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
71.
BIPHASIC SUBCUTANEOUS DOSING REGIMENS FOR ANTI-VLA-4 ANTIBODIES
Provided herein are biphasic dosing protocols for natalizumab therapy comprising both standard and extended interval dosing and subcutaneous administration.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61P 25/00 - Drugs for disorders of the nervous system
A61K 9/00 - Medicinal preparations characterised by special physical form
72.
OLIGONUCLEOTIDES, REAGENTS, AND PREPARATION THEREOF
The present disclosure describes novel reagents and processes for preparing oligonucleotides, which have two or more nucleotides. In one embodiment, the reagent is represented by Formula I′ or B.
The present disclosure describes novel reagents and processes for preparing oligonucleotides, which have two or more nucleotides. In one embodiment, the reagent is represented by Formula I′ or B.
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
C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
C07D 249/06 - 1,2,3-TriazolesHydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
C07H 23/00 - Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12
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
73.
HYDROPHOBIC INTERACTION PROTEIN CHROMATOGRAPHY UNDER NO-SALT CONDITIONS
Various aspects and embodiments of the present disclosure relate to the purification antibodies by hydrophobic interaction chromatography under no-salt conditions.
Disclosed is a method of treating a human subject with multiple sclerosis. The method comprises administering to the subject in the absence of a cholesterol lowering drug an effective amount of Compound 1: or a pharmaceutically acceptable salt thereof.
Disclosed is a method of treating a human subject with multiple sclerosis. The method comprises administering to the subject in the absence of a cholesterol lowering drug an effective amount of Compound 1: or a pharmaceutically acceptable salt thereof.
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
75.
HETEROCYCLIC COMPOUNDS FOR TREATING HUNTINGTON'S DISEASE
e.g. e.g. treating a condition, disease, or disorder in which lowering mutant huntingtin protein ("mHTT") in a subject is of therapeutic benefit, specifically in treating Huntington disease ("HD"). This disclosure also features a composition containing the same as well as methods of using and making the same.
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
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
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
An implantable device includes a housing having a bottom configured to face the skull and a top configured to face a scalp when implanted. The device includes a first catheter connector configured to couple to a first dual lumen catheter. The first connector extends from the housing. The device comprises a second catheter connector configured to couple to a single lumen catheter. The second catheter connector extends from the housing. The device includes an opening defined by the top of the housing. The opening is configured to be accessed by a needle percutaneously inserted through the scalp when the device is implanted. The device includes a first fluid pathway from the first catheter connector to the opening defined by the top of the housing, and the device includes a second fluid pathway from the first catheter connector to the second catheter connector.
Provided are crystalline forms of N-methyl-N-((ls,3s)-3-methyl-3-((6-(l-methyl-lH- pyrazol-4-yl)pyrazolo[l,5-a]pyrazin-4-yl)oxy)cyclobutyl)acrylamide, pharmaceutical compositions, methods of use and methods of making thereof.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
This disclosure relates to compounds of formula (I), or pharmaceutically acceptable salts thereof: in which all of the variables are as defined in the application. The compounds of the present disclosure are capable of inhibiting the activity of tyrosine kinase 2 (TYK2). The disclosure further provides methods of preparing the compounds of the disclosure, and methods for their therapeutic use.
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 9/00 - Drugs for disorders of the cardiovascular system
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
Disclosed is a one-pot process (without the isolation of three intermediates) of preparing diroximel fumarate represented by the following structural formula: The method comprises reacting ethylene carbonate with succinimide 5 to form 2-hydroxyethyl succinimide; reacting 2-hydroxyethyl succinimide with maleic anhydride to form a (Z)-4-(2- (2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate, isomerizing the (Z)-4- (2-(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate to an (E)-4-(2-(2,5- dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate, and reacting the (E)-4-(2- 10 (2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate with methanol to form the product compound.
C07D 207/404 - 2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
Disclosed is a one-pot process (without the isolation of three intermediates) of preparing diroximel fumarate represented by the following structural formula: The method comprises reacting ethylene carbonate with succinimide 5 to form 2-hydroxyethyl succinimide; reacting 2-hydroxyethyl succinimide with maleic anhydride to form a (Z)-4-(2- (2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate, isomerizing the (Z)-4- (2-(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate to an (E)-4-(2-(2,5- dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate, and reacting the (E)-4-(2- 10 (2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate with methanol to form the product compound.
C07D 207/404 - 2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
Methods for evaluating subjects having conditions associated with loss of muscle function (e.g., a motor neuron disease, a neuromuscular disease, or a myopathy) by measuring muscle function (e.g., muscle strength) are disclosed.
The present disclosure provides compositions and methods for treating amyotrophic lateral sclerosis (ALS). Among other things, the present disclosure provides inhibitory nucleic acids that inhibit the expression of genes that cause or are implicated in ALS pathogenesis. The present disclosure further provides recombinant adeno-associated virus (rAAV) vectors comprising inhibitory nucleic acids that inhibit the expression of genes that cause or are implicated in ALS pathogenesis.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
83.
METHODS OF DELIVERING NUCLEOTIDE SEQUENCES TO CELLS VIA SIMULTANEOUS TRANSDUCTION
[00128] Disclosed herein are methods of delivering exogenous genetic material into a population of cells, and methods of making a population of cells expressing an exogenous nucleic acid sequence. The methods may comprise simultaneously contacting a culture vessel with: (i) an aqueous viral vector composition comprising: a viral vector comprising exogenous genetic material, and an aqueous solution; and (ii) a population of cells; and incubating the culture vessel to deliver exogenous genetic material into the population of cells or a portion thereof.
Disclosed herein are antisense compounds and methods for decreasing Tau mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Tau-associated diseases, disorders, and conditions.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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
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
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
An implantable cranial medical device includes a first fluid flow path, a second fluid flow path, and upper flange portion, and a lower portion. The upper flange portion is configured to rest on a skull of a subject about a burr hole. The lower portion is configured to be placed within the burr hole. The first fluid flow path may extend from a first opening in the upper flange portion to a first opening in the lower portion. The second fluid flow path may extend from a second opening in the upper flange portion to a second opening in the lower portion.
Disclosed is a method of lowering elevated cholesterol plasma levels in a subject. Also disclosed is a method of treating hypercholesterolemia in a subject. The methods comprise administering to the subject in the absence of a cholesterol lowering drug an effective amount of Compound 1 or pharmaceutically acceptable salt thereof.
Disclosed is a method of lowering elevated cholesterol plasma levels in a subject. Also disclosed is a method of treating hypercholesterolemia in a subject. The methods comprise administering to the subject in the absence of a cholesterol lowering drug an effective amount of Compound 1 or pharmaceutically acceptable salt thereof.
Improved methods of separating particles in sample by field-flow fractionation. The methods comprise injecting the sample into a mobile phase that flows through a channel in a first direction that is parallel to the channel; and applying a force in the channel in a second direction that is transverse to the first direction (a "cross-force"), to separate the particles, active agent, and/or one or more impurities before they leave the channel. The application of the cross-force comprises at least three time periods: (i) a first time period, comprising applying the cross-force at a first magnitude; (ii) a second time period, comprising applying the cross-force at an increasing magnitude to a maximum magnitude that is greater than the first magnitude; and (iii) a third time period comprising applying the cross-force at a decreasing magnitude to a minimum magnitude that is less than the first magnitude.
Described herein are solid forms of N-(4-fluoro-5-(((2S,4R)-4-46-methoxypyrimidin-4-yl)oxy)-2-methylpyrrolidin-1-yl)methyl)thiazol-2-yl)acetamide, compound (I): (I) and the process of making said solid forms of compound (I). The present invention further relates to a pharmaceutical composition comprising crystalline Form A and Form B of compound (I), and methods of using said form and pharmaceutical composition in the treatment and prevention of Alzheimer's disease and related neurological disorders.
Described herein are solid forms of N-(4-fluoro-5-(((2S,4R)-4-46-methoxypyrimidin-4-yl)oxy)-2-methylpyrrolidin-1-yl)methyl)thiazol-2-yl)acetamide, compound (I): (I) and the process of making said solid forms of compound (I). The present invention further relates to a pharmaceutical composition comprising crystalline Form A and Form B of compound (I), and methods of using said form and pharmaceutical composition in the treatment and prevention of Alzheimer's disease and related neurological disorders.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
89.
IMPLANTABLE MEDICAL DEVICE FOR USE WITH OR HAVING RECORDING ELECTRODE
A burr hole device is configured to receive a catheter and a cable of a sheath. The sheath is configured to receive a portion of the catheter and has an electrode. When the catheter and sheath are implanted with the burr hole device, the catheter and electrode of the sheath are implanted in a brain. Systems and apparatuses may include the burr hole device and/or a cranial port device, the catheter, and the sheath.
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/537 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
Provided are compounds of the Formula (I): or pharmaceutically acceptable salts thereof, which are useful for the inhibition of EBP and in the treatment of a variety of EBP mediated conditions or diseases, such as multiple sclerosis.
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/537 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations; pharmaceutical preparations for
use in the treatment of psychiatric and neurodegenerative
diseases and disorders; pharmaceutical preparations for the
treatment of central nervous system diseases and disorders,
depression, anxiety disorder, and bipolar depression.
93.
EMOPAMIL-BINDING PROTEIN INHIBITORS AND USES THEREOF
Provided are compounds of the Formula (I) or pharmaceutically acceptable salts thereof, which are useful for the inhibition of EBP and in the treatment of a variety of EBP mediated conditions or diseases, such as multiple sclerosis.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/4355 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
A61P 9/00 - Drugs for disorders of the cardiovascular system
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations; pharmaceutical preparations for use in the treatment of psychiatric and neurodegenerative diseases and disorders; pharmaceutical preparations for the treatment of central nervous system diseases and disorders, depression, anxiety disorder, and bipolar depression.
95.
EMOPAMIL-BINDING PROTEIN INHIBITORS AND USES THEREOF
Provided are compounds of the Formula (I): (I), or pharmaceutically acceptable salts thereof, which are useful for the inhibition of EBP and in the treatment of a variety of EBP mediated conditions or diseases, such as multiple sclerosis.
A61P 25/00 - Drugs for disorders of the nervous system
C07D 451/04 - Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamineCyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropaneCyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring system
A61K 31/46 - 8-Azabicyclo [3.2.1] octaneDerivatives thereof, e.g. atropine, cocaine
96.
VENTRICULAR DRAIN OR SHUNT ASSSEMBLY WITH RECORDING ELECTRODE
A device is configured to receive a catheter. The catheter may be a catheter of a ventriculoperitoneal shunt or an external ventricular drain. The device includes (ii) an upper flange having an opening, and (ii) elongate body defining a lumen in communication with the opening. The catheter may be inserted through the opening and the lumen. The device includes an electrode disposed on the elongate body. When the device is implanted in a subject, the upper flange rests on a skull of the subject adjacent to a burr hole, the elongate body is inserted through the burr hole, and the electrode is positioned intracranially in the subject.
The present disclosure describes methods for quantifying %Empty capsids in a sample recombinant adeno-associated viruses (rAAV) preparation. In particular, methods described herein demonstrate that quantification of %Empty capsids can be achieved by: (i) measuring the capsid peak area of a sample rAAV preparation using a separation method as described herein to determine an A260/A280 ratio; and (ii) comparing the A260/A280 ratio of the sample rAAV preparation to a calibration curve generated using an orthogonal method as described herein. A separation method can comprise or be a chromatographic separation (e.g., an anion-exchange, cation exchange, hydrophobic interaction, or affinity chromatographic separation), asymmetrical flow field-flow fractionation, or electrophoresis. An orthogonal method can comprise or be electron microscopy (e.g., transmission electron microscopy or cryogenic electron microscopy) or analytical ultracentrifugation.
G01N 27/27 - Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
B01D 15/08 - Selective adsorption, e.g. chromatography
B01D 15/16 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
The present disclosure pertains to methods for transducing host cells with nucleic acids using an in-line complexer and systems comprising an in-line complexer for transducing host cells. The disclosed methods and systems can be used to produce recombinant adeno-associated virus (rAAV) particles. Also disclosed herein are compositions comprising rAAV particles obtained from the disclosed methods and systems, and uses of the same.
The present disclosure provides a method of detecting the presence or amount of a UBE3A protein in a sample, such as a human sample, using mass spectrometry based techniques. The methods described herein are useful for diagnosing Angelman syndrome, as well as monitoring disease progression and treatment effectiveness.
