Disclosed herein are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein X1, Y1, X2, Y2, a, b, c, d, e and f are as defined herein. Also disclosed are lipid nanoparticles comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a plurality of lipid nanoparticles comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and a nucleic acid segment; as well as methods for delivering a nucleic acid segment comprising administering a plurality of lipid nanoparticles comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and a nucleic acid segment.
The disclosure provides chimeric antigen receptors and antibodies that comprise antigen-binding domains that specifically bind human STEAP2, nucleotides that encode the same, cells comprising the same, and methods of using the same in the treatment of cancer (e.g., prostate cancer).
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 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 37/00 - Drugs for immunological or allergic disorders
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
4.
CERTAIN 2,5-DIAZABICYCLO[4.2.0]OCTANES AS GLP-1 RECEPTOR MODULATORS
There are disclosed certain 2,5-diazabicyclo[4.2.0]octanes of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are GLP-1 receptor modulators and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disease and metabolic conditions, for example Type 2 diabetes.
A61P 9/00 - Drugs for disorders of the cardiovascular system
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
The specification relates to peptide dendrons comprising one or more residues derived from a modified lysine of formula (I), pharmaceutical delivery systems comprising these peptide dendrons, pharmaceutical compositions containing them, and to their use in therapy.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61P 31/16 - Antivirals for RNA viruses for influenza or rhinoviruses
The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.
The disclosure relates to methods, cells, and compositions for preparing cell populations and compositions for adoptive cell therapy. In particular, provided herein are methods for expansion and proliferation of primary immune cells including T cell populations.
The disclosure relates to methods and compositions for the treatment of systemic lupous erythematous (SLE). Specifically, the disclosure relates to methods comprising administering to a subject a type I IFN receptor inhibitor.
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 39/00 - Medicinal preparations containing antigens or antibodies
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
9.
DEVICES AND A SYSTEM FOR DETECTION AND ANALYSIS OF INHALER USE
Devices, methods and a system for detection and analysis of inhaler use, in particular breath detection modules and inhaler device counters. An electronic inhaler counter device (100) comprises a rocker arm (102) comprising a proximal end (110) providing a pivot (104) and a distal end (112) providing a head (114), a return spring (108) coupled to the rocker arm pivot, and a count switch (106), wherein, in response to a first selected degree of linear actuation motion, the rocker arm is arranged to perform a first rocker movement and engage the count switch with the rocker head; and in response to further linear actuation motion, the spring is engaged to enable the rocker arm to perform a second rocker movement, such to facilitate over travel. An inhaler breath detection module coupled to an airpath of the inhaler comprises a sensing means configured to provide signals indicative of a change in parameter in the inhaler airpath as a function of time caused by an inhalation breath, and a controller configured to determine the presence of breath, based on a change in parameter in the inhaler airpath as a function of time.
The specification generally relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, where R1, R2A, R2B, R2C, R2D, W, X, Y, and Z have the meanings defined herein. Such compounds are useful in inhibiting NLRP3 inflammasome activity and may be useful as therapeutic agents. The specification also relates to the use of such compounds to treat or prevent diseases and conditions in which the NLRP3 inflammasome is implicated. The specification further relates to compositions comprising such compounds.
Provided are methods of treating a liver disease in a subject, comprising administering to the subject: i) an inhibitor of patatin like phospholipase domain containing 3 (PNPLA3) expression; and ii) an agonist of glucagon receptor and/or glucagon-like peptide-1 (GLP-1) receptor. Also provided pharmaceutical and kits comprising i) an inhibitor of PNPLA3 expression; and ii) an agonist of glucagon receptor and/or GLP-1 receptor.
This disclosure relates to methods for the adjuvant treatment of a subject having germline mutated BRCA1 and/or BRCA2 breast cancer, wherein the subject has previously received local treatment for the breast cancer, and neoadjuvant or adjuvant chemotherapy.
Disclosed are methods for treating locally advanced (Stage III), unresectable non-small- cell lung cancer (NSCLC) with an antibody that inhibits PD-1/PD-L1 activity concurrently with chemoradiation therapy (cCRT).
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
14.
INHIBITOR OF TYPE 1 INTERFERON RECEPTOR STEROID SPARING IN SYSTEMIC LUPUS ERYTHEMATOSUS 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 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The disclosure relates to methods and compositions for the treatment of type I IFN mediated disease. Specifically, the disclosure relates to a subcutaneous dose of a type I IFN receptor inhibitor.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 33/00 - Medicinal preparations containing inorganic active ingredients
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
16.
TREATMENT OF LUPUS NEPHRITIS WITH ANTI-TYPE I INF RECEPTOR ANTIBODY ANIFROLUMAB
The disclosure relates to methods and compositions for the treatment of lupus nephritis (LN) with anti-type I IFN receptor inhibitor antibody Anifrolumab. Results of clinical trials with intravenous and subcutaneous administration of Anifrolumab. Identification of markers for LN and delivery devices and pre-filled syringe for administration of Anifrolumab.
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
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm rests
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
The disclosure relates to methods and compositions for the treatment of Cutaneous Lupus Erythematous (CLE). Specifically, the disclosure relates to methods comprising administering to a subject a type I IFN receptor inhibitor.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
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 39/00 - Medicinal preparations containing antigens or antibodies
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm rests
Combination Treatments for Melanoma This specification discloses the use of an ATR inhibitor in combination with an immune checkpoint inhibitor for the treatment of melanoma in a patient who has previously received immunotherapy.
A pharmaceutical formulation which comprises ceralasertib, dibasic calcium phosphate, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and magnesium stearate is described.
Provided herein are anti-IL5R antibody formulations containing an amount of surfactant below critical micelle concentration (CMC) of the surfactant and methods of using such formulations.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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 11/00 - Drugs for disorders of the respiratory system
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 39/00 - Medicinal preparations containing antigens or antibodies
21.
LIPOCALIN MUTEIN DRY POWDER FORMULATION FOR TREATMENT OF ASTHMA
The present invention relates to the treatment of asthma in a human subject by administering by oral inhalation a dry powder formulation comprising a therapeutically effective amount of an anti-IL-4 receptor alpha (IL-4R?) lipocalin mutein, or a variant or fragment thereof, to said subject. The invention also relates to the dry powder formulation comprising the anti-IL-4 receptor alpha (IL-4R?) lipocalin mutein, or a variant or fragment thereof.
Compounds having the structure of Formula (I): and pharmaceutically acceptable salts thereof, wherein X1, R1, R2, R3, R4, R5 and R6 are as defined in the specification; pharmaceutical compositions comprising such compounds and salts; use of such compounds and salts to treat or prevent Prolyl endopeptidase fibroblast activation protein (FAP)-mediated conditions; kits comprising such compounds and salts; and methods for manufacturing such compounds and salts.
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
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
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
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
N-(IMIDAZO[1,2-B]PYRIDAZIN-3-YL)-1-CYCLOHEXYL-2H-INDAZOLE-5-CARBOXAMIDE AND N-(PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-1-CYCLOHEXYL-2H-INDAZOLE-5-CARBOXAMIDE DERIVATIVES AS IRAK4 INHIBITORS FOR THE TREATMENT OF ASTHMA
The present application relates to a compound of Formula (A),wherein R1 is selected from Formula (II) and Formula (III) and R2 is selected from Formula (IV), Formula (V) and Formula (VI) as IRAK4 inhibitors for use in methods of treatment of e.g. asthma and chronic obstructive pulmonary disease (COPD), cancer, inflammatory diseases, and autoinflammatory/autoimmune diseases such as e.g. systemic lupus erythematosus, rheumatoid arthritis, myositis, Sjogren's syndrome, systemic sclerosis, gout, endometriosis, atopic dermatitis and psoriasis. Preferred compounds of the present invention are e.g.: N-(imidazo[1,2-b]pyridazin-3-yl)-1-cyclohexyl-2H-indazole-5- carboxamide, N-(pyrazolo[1,5-a]pyrimidin-3-yl)-1-cyclohexyl-2H-indazole-5- carboxamide, N-(imidazo[1,2-b]pyridazin-3-yl)-1-azaspiro[4.5]decan-8-yl-2H- indazole-5-carboxamide, and N-(pyrazolo[1,5-a]pyrimidin-3-yl)-1-azaspiro[4.5]decan-8-yl-2H- indazole-5-carboxamide derivatives. An exemplary compound of the present invention is e.g. N- (imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((5r,8r)-1-methyl-2-oxo-1- azaspiro[4.5]decan-8-yl)-2H-indazole-5-carboxamide (Example 1): Formula (VII).
4-(2-FLUORO-4-METHOXY-5-3-(((1-METHYLCYCLOBUTYL)METHYL)CARBAMOYL)BICYCLO[2.2.1]HEPTAN-2-YL)CARBAMOYL)PHENOXY)-1-METHYLCYCLOHEXANE-1-CARBOXYLIC ACID DERIVATIVES AND SIMILAR COMPOUNDS AS RXFP1 MODULATORS FOR THE TREATMENT OF HEART FAILURE
The present invention relates to 4-(2-Fluoro-4-methoxy-5-3-(((l- methylcyclobutyl)methyl)carbamoyl)bicyclo[2.2.1]heptan-2-yl) carbamoyl)phenoxy)-l-methylcyclohexane-l-carboxylic acid derivatives and similar compounds of formula (I) as RXFP1 modulators for the treatment of heart failure, heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, heart failure with reduced ejection fraction, chronic kidney disease and acute kidney injury. The present invention also relates to crystalline forms of such compounds. An exemplary compound is e.g. (A).
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C07C 13/40 - Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with a bicyclo ring system containing seven carbon atoms with a bicycloheptane ring structure
C07C 235/62 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 231/14 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 241/12 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 263/40 - One oxygen atom attached in position 4
C07D 275/02 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
C07D 307/24 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
C07D 333/38 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
The present invention provides a pharmaceutical tablet formulation of tenapanor that is chemically stable and soluble comprising greater than about 6% w/w of amorphous tenapanor in its bis-HCl form, an acidifying agent, an antioxidant, a disintegrant, a lubricant, a glidant, a filler, and an immediate release coating, wherein the total chloride content of the active ingredient is greater than 5.82% and the particle diameter distribution D50 is from about from about 18µm to about 22µm.
The disclosure relates to methods and compositions for the treatment of Systemic Lupus Erythematosus (SLE). Specifically, the disclosure relates to methods comprising administering to a subject a type I IFN receptor inhibitor.
The disclosure generally relates to methods for treating cancer in a patient using durvalumab in combination with chemotherapy based on the patient's minimal residual status. Specifically, the disclosure relates to preventing or treating a recurrent tumor in a patient, wherein the patient is minimal residual disease-positive (MRD+), using durvalumab and chemotherapy.
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
The disclosure relates to methods and compositions for the treatment of Systemic Lupus Erythematosus (SLE). The disclosure particular relates to the treatment of flares in SLE across multiple organ domains.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
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
The present disclosure relates, in general, to therapeutic combinations, and to corresponding methods of treatment, pharmaceutical compositions, and kits.
The specification generally relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, where A, Z, Y, RA, Linker and v have any of the meanings defined herein. This specification also relates to the use of such compounds and pharmaceutically acceptable salts thereof in methods of treatment of the human or animal body, for example in the prevention or treatment of cancer. This specification also relates to processes and intermediate compounds involved in the preparation of such compounds and to pharmaceutical compositions containing them.
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
A61K 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
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 405/04 - 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 directly linked by a ring-member-to-ring- member bond
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 409/04 - 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 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 417/04 - 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 directly linked by a ring-member-to-ring- member bond
The present disclosure provides methods of treating or preventing fatty liver disease and/or lowering cholesterol and LDL cholesterol levels in a subject. The present disclosure further provides methods of lowering expression of Pleckstrin and Sec7 Domain Containing 3 (PSD3) in a subject.
A pharmaceutical composition comprising A) one or more ASO or a pharmaceutically acceptable salt thereof; B) one or more permeation enhancer; C) one or more optional pharmaceutically acceptable excipient; and D) one or more optional coating. Said composition for use in the treatment, prevention, or amelioration of a disease associated with PCSK9 or PNPLA3 in a subject.
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
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
33.
PCSK9 INHIBITORS AND METHODS OF TREATMENT USING SAME
The present disclosure provides dosages and methods for treating a disease associated with proprotein convertase subtilisin/kexin type 9 (PCSK9). The present disclosure also provides unit dosages, dosing regimens and methods for treating a disease associated with PCSK9.
A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/56 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
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
The present invention relates to methods for treating ischemic events in a patient, especially ST-segment elevation myocardial infarction and acute ischemic stroke, by administrating a recombinant apyrase protein in conjunction with a P2Y12 inhibitor.
A61K 31/4365 - 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 having sulfur as a ring hetero atom, e.g. ticlopidine
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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
35.
METHODS OF TREATING CHRONIC KIDNEY DISEASE WITH DAPAGLIFLOZIN
The present disclosure is directed to methods of treating patients with chronic kidney disease (CKD), with and without Type 2 diabetes, with an SGLT2 inhibitor, such as dapagliflozin.
A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin related diseases.
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
38.
METHODS FOR TREATING SEVERE ASTHMA IN PATIENTS WITH NASAL POLYPOSIS
Provided herein are methods of reducing exacerbations of asthma in an asthma patient with nasal polyposis, comprising administering to the patient an effective amount of the anti-interleukin-5 receptor (IL-5R) antibody benralizumab or an antigen-binding fragment thereof.
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
39.
EGFR TKIS FOR USE IN THE TREATMENT OF NON-SMALL CELL LUNG CANCER
The specification relates to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for use in the adjuvant treatment after tumour resection of patients with epidermal growth factor receptor- mutation-positive (EGFRm) non-small cell lung cancer (NSCLC).
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
The disclosure relates to methods for the treatment of, or for reducing the risk for development of, a cardiometabolic in a patient using an inhibitor of type I IFN signalling.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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 37/00 - Drugs for immunological or allergic disorders
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
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
This specification discloses the use of an ATR inhibitor, preferably in combination with a taxane, for the treatment of cancer in a particular subset of patients who have previously received immunotherapy.
The disclosure relates to methods, compositions, and combinations for the treatment of cancer. Specifically, the disclosure relates to methods comprising administering to a subject in need thereof at least one of an anti-CTLA-4 antibody or an antigen-binding fragment and an anti-PD- L1 antibody or an antigen-binding fragment thereof. The disclosure also relates to combinations comprising at least one of an anti-CTLA-4 antibody or an antigen-binding fragment and an anti- PD-L1 antibody or an antigen-binding fragment thereof.
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
The present specification relates to pharmaceutical formulations comprising N-(1-(3- fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine, microcrystalline cellulose (MCC) and dicalcium phosphate anhydrous (DCPA), for example tablets with immediate release properties.
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
44.
COMPOSITIONS AND METHODS OF TREATING CANCER WITH CHIMERIC ANTIGEN RECEPTORS
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
The present specification relates to AZD9833 for use in the treatment of cancer and methods of treatment of cancer involving administration of AZD9833 wherein, in each case, the AZD9833 is administered orally once daily at a dose between 25 mg and 450 mg. AZD9833 may be administered alone or its use may be in combination with an additional anti-cancer agent such as a CDK inhibitor, everolimus or an AKT inhibitor.
A61K 31/436 - 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 oxygen as a ring hetero atom, e.g. rapamycin
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The invention concerns compounds of Formula (I): (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R7 and ring A have any of the meanings hereinbefore defined in the description; process for their preparation; pharmaceutical compositions containing them and their use in treating KCC2 mediated diseases.
The specification relates to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for use in the treatment of cancer, wherein the EGFR TKI is administered in combination with a Smac mimetic.
The present disclosure relates, in general, to therapeutic combinations of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one and olaparib, and to corresponding methods of treatment, pharmaceutical compositions, and kits.
Solid pharmaceutical formulations including AZD4635 are described. The solid formulations can include a polymeric stabilizer (e.g., a polyvinylpyrollidone), an ionic surfactant (e.g., sodium docusate), and a non-ionic surfactant (e.g., a poloxamer).
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
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 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
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 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
Described herein are methods for identifying adenosine-driven cancers. The methods include determining a signature score of tumour adenosine signalling. The signature score reflects the expression levels of a signature group of genes whose pattern of expression levels is indicative of elevated adenosine signalling. Adenosine-driven cancers can be susceptible to treatment with an adenosine signalling inhibitor such as a CD39 inhibitor, a CD73 inhibitor, or an adenosine receptor antagonist. Methods of treating cancer are also described.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
54.
TYPE I INTERFERON INHIBITION IN SYSTEMIC LUPUS ERYTHEMATOSUS
The disclosure relates to methods and compositions for the treatment of Systemic Lupus Erythematosus (SLE). Specifically, the disclosure relates to methods comprising administering to a subject a type I IFN receptor inhibitor.
The present disclosure relates, in general, to therapeutic combinations of acalabrutinib and capivasertib, and to corresponding methods of treatment, pharmaceutical compositions, and kits.
Methods of treating cancer with a combination of a WEE1 inhibitor and a DNA-damaging agent in patients having SLFN11-deficient cancer cells are disclosed herein.
G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
Disclosed are methods of treating cancer comprising administering to a subject in need thereof an effective amount of (3R)?4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3?b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one or a pharmaceutically acceptable salt thereof and an effective amount of venetoclax or a pharmaceutically acceptable salt thereof.
A61K 31/5025 - Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 31/706 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
There is disclosed an inhaler (10) for delivery of a medicament by inhalation. The inhaler (10) comprises a drive mechanism comprising a canister drive (22) for receiving a canister (50) of medicament, a biasing means (20), and a trigger mechanism. The trigger mechanism comprises a latch (35). The latch (35) has a locked position in which it contacts the canister drive (22) to prevent linear movement of the canister drive (22) and holds the biasing means (20) in a loaded configuration; and an unlocked position in which the latch (35) is disengaged from the canister drive (22) and releases the biasing means (20) from the loaded configuration to drive the canister drive (22) from a rest position to an actuated position. The trigger mechanism comprises a blocker (32). The blocker (32) has a blocking position in which it contacts the latch (35) to block movement thereof from the locked position to the unlocked position; and a rotated position in which the blocker (32) is disengaged from the latch (35) and allows movement of the latch (35) from the locked position to the unlocked position. The blocker (32) is rotatable in response to a force applied to the blocker (32). A method of operation of an inhaler (10) is also disclosed.
Provided herein are methods of treating patients with late-onset asthma or asthma falling within Severe Asthma Research Program (SARP) clinical cluster 3 or 5 comprising administering to the patient a therapeutically effective amount of the anti-interleukin-5 receptor (IL-5R) antibody, benralizumab, or an antigen-binding fragment thereof. Also provided are methods of predicting an enhanced therapeutic response to benralizumab by determining the SARP clinical cluster of the patient's asthma prior to 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
60.
COMPOSITIONS AND METHODS FOR TREATING EXTENSIVE STAGE SMALL CELL LUNG CANCER (ES-SCLC)
Disclosed are methods for treating extensive-stage small-cell lung cancer (ES-SCLC) with an antibody that inhibits PD1/PD-L1 activity in combination with etoposide and a platinum- based therapeutic agent.
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
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
61.
METHODS OF TREATING HEART FAILURE WITH REDUCED EJECTION FRACTION WITH DAPAGLIFLOZIN
The present disclosure is directed to methods of treating patients with heart failure with reduced ejection fraction (HFrEF), with and without Type 2 diabetes, with an SGLT2 inhibitor, such as dapagliflozin. The methods disclosed herein can reduce the risk of a composite outcome of a first episode of worsening heart failure (hospitalization for heart failure or an urgent heart failure visit) or death from cardiovascular causes. Each of the three components of this composite outcome can also be reduced, as well as the total number of heart failure hospitalizations and deaths from cardiovascular causes. SGLT2 inhibitors, such as dapagliflozin, can also reduce a worsening of heart failure symptoms. The methods disclosed herein can also improve heart failure symptoms, health status, and quality of life.
A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Disclosed are compounds of formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the same, and methods of treating cancer or a respiratory inflammatory disease using the same: (I) wherein R1 is selected from hydrogen, -CH3 and -(C=O)CH(R1a)NH2; R1a is C1-C4 alkyl; Y is -(CH2)n- or -(C=O)-; n is an integer selected from 1 and 2; R2 is selected from hydrogen, -CH3 and -(C=X)R4 and R3 is hydrogen or -CH3; or R2 and R3, together with the nitrogen to which they are attached, are linked to form a 6- membered heterocyclic ring; X is NH or O; R4 is -CH3 or -[CH(R4a)]mNH2; m is an integer selected from 0 or 1; and R4a is hydrogen or C1-C6 alkyl.
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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
Disclosed herein are pharmaceutical formulations comprising verinurad or a pharmaceutically acceptable salt thereof that are resistant to alcohol-induced dose dumping and may be used in therapeutic and/or prophylactic methods.
A61K 31/4418 - Non-condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
Provided herein is are methods of treating Chronic Obstructive Pulmonary Disease (COPD) in a patient, comprising administering to the patient an effective amount of benralizumab or an antigen-binding fragment thereof.
The specification relates to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for use in the treatment of EGFR TKI-naïve patients with locally-advanced or metastatic EGFR mutation-positive non-small cell lung cancer (NSCLC), wherein the EGFR TKI is administered in combination with pemetrexed and platinum chemotherapy.
The present invention relates to the treatment of asthma in a human subject by administering by inhalation a therapeutically effective amount of an anti-IL-4 receptor alpha (IL-4Ra) lipocalin mutein, or a variant or fragment thereof, to said subject, wherein the delivered dose of said lipocalin mutein, or variant or fragment thereof, is from about 0.1mg to about 160mg. The lipocalin mutein, or a variant or fragment thereof, may for example be administered at least once per day, once per day or twice per day.
The specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R1, R2, R3, R4, R6, R7, R8, Linker, A, G, D and E have any of the meanings defined herein. This specification also relates to the use of such compounds and pharmaceutically acceptable salts thereof in methods of treatment of the human or animal body, for example in prevention or treatment of cancer. This specification also relates to processes and intermediate compounds involved in the preparation of such compounds and to pharmaceutical compositions containing them.
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 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
The present application relates to affecting weight loss comprising administereing a therapeutically effective amount of (1r,1'R,4R)- 4-methoxy-5''-methyl-6'-[5-(prop-1-yn-1- yl)pyridin-3-yl]-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine, or a pharmaceutically acceptable salt thereof (e.g., the camsylate salt of (1r,1'R,4R)- 4-methoxy-5''-methyl-6'-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3'H-dispiro[cyclohexane-1,2'-indene-1',2''- imidazol]-4''-amine).
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present invention relates to the use of potassium-binding agents that are formulated to remove toxins, e.g., potassium ions, from the gastrointestinal tract at an elevated rate, without causing undesirable side effects, in hemodialysis patients. The compositions exhibit desired characteristics for the long term administration to treat or prevent the relapse or occurrence of certain conditions, for example hyperkalemia.
The specification relates to compounds of Formula (A) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.
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 498/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
The invention provides methods of identifying, diagnosing, treating, and monitoring or prognosing progression of type I IFN-mediated disease or disorder in subjects. The present invention further relates to methods of identifying candidate therapeutic agents for treating a type I interferon-mediated disease or disorder.
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
Disclosed are compounds of formula (Ib) or (Vc), or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ib) or (Vc) and methods of using the same for treating cancer, respiratory inflammatory disease, and inhibiting arginase; wherein R1 is -H or -C(O)CH(R1a)NHR1b; and R1a is selected from -H, -(C1-C4) alkyl and CH2OR1c; R1b is -H; or alternatively, R1a and R1b, together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R1c is H or -CH3.
The invention relates to novel heteroaryl compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cardiovascular diseases, and methods treating sepsis or septic shock, using the novel heterocyclic compounds disclosed herein.
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
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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 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 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 401/02 - 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
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/435 - 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
C07D 231/10 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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
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 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
The present disclosure concerns the large-scale manufacture of pharmaceutical compounds, and novel intermediates for use in the manufacture. International Patent Application WO2011154737 discloses morpholine pyrimidines useful for treating cancer, processes for their preparation and pharmaceutical compositions thereof. In particular, WO2011154737 discloses, as experimental Example 2.02 on page 60, the compound 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[l-((R)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-lH- pyrrolo[2,3 -b]pyridine (hereafter referred to as the compound of Formula (I)). The structure of the compound of Formula (I) is shown below. A synthetic route to the compound of Formula (I) is described at pages 51 to 57, 66 and 67 of WO2011154737, and is summarised below in Scheme 1.
C12P 17/16 - Preparation of heterocyclic carbon compounds with only O, N, S, Se, or Te as ring hetero atoms containing two or more hetero rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07C 255/58 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
C07D 209/88 - Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
C07D 239/24 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
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 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
The present disclosure provides compositions comprising verinurad, a xanthine oxidase inhibitor, and dapagliflozin useful in the reduction of serum uric acid levels, formulations containing them, and methods using them. In some embodiments, the methods and compositions described herein are used in the treatment or prevention of conditions associated with hyperuricemia, such as chronic kidney disease, heart failure, and gout.
A61K 31/4418 - Non-condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
78.
IMPROVED METHOD FOR THE MANUFACTURE OF 3-[(1S)-1-IMIDAZO[1,2-A]PYRIDIN-6-YLETHYL]-5-(1-METHYLPYRAZOL-4-YL)TRIAZOLO[4,5-B]PYRAZINE AND POLYMORPHIC FORMS THEREOF
This specification generally relates to an improved method for the manufacture of 3-[(lS)-l -imidazo[ 1,2-a]pyridin-6-ylethyl]-5-(l-methylpyrazol-4-yl)triazolo[4,5- bjpyrazine (I), or pharmaceutically acceptable salts thereof; polymorphic forms thereof; and intermediates useful in the manufacture of such compounds and salts thereof. Formula (I).
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
Disclosed include crystalline (S)-2-amino-N-((3R,5R)-8-hydroxy-6-oxo-7-oxa-1-aza-8- boraspiro[4.7]dodecan-3-yl)-3-methylbutanamide in Form D and in Form E: Formula (I); (3R,5R)-8-hydroxy-3-((S)-4-isopropyl-2,2-dimethyl-5-oxoimidazolidin-1-yl)-7-oxa-1-aza-8-boraspiro[4.7]dodecan-6-one or a pharmaceutically acceptable salt thereof or the crystalline Form 1 thereof: Formula (II); and pharmaceutical compositions and methods of using the same.
Disclosed are methods of treating cancer in a subject, comprising subcutaneously administering to the subject an effective amount of a dendrimer of formula (I): (I) and pharmaceutically acceptable salts thereof.
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
Disclosed are pharmaceutical compositions comprising a lyophilized compound of formula (I): (I) or a pharmaceutically acceptable salt thereof, and methods of using the same for treating cancer.
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 9/19 - Particulate form, e.g. powders lyophilised
Methods for treating and/or preventing HFpEF and/or at least one disease, disorder, and/or condition associated therewith in patients by the use of dapagliflozin and compositions comprising the same are disclosed.
The present disclosure relates to salts of compounds of Formula (I) prepared as a xinafoate (1-hydroxy-2-naphthoate) salt (Formula (Ia)), pharmaceutically acceptable compositions comprising same and methods of using 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
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
CANCER RESEARCH TECHNOLOGY LIMITED (United Kingdom)
Inventor
Finlay, Maurice Raymond Verschoyle
Goldberg, Frederick Woolf
Howard, Martin Richard
Ting, Attilla Kuan Tsuei
Abstract
The specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R1, A1, A2 and A3 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent DNA-PK mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating DNA-PK mediated disease, including cancer, using such compounds and salts.
A fumarate salt, in particular the hemi-fumarate salt, of 5-((5-methyl-2-((3,4,5-trimethylphenyl)amino)pyrimidin-4-yl)amino)-benzo[d]oxazol-2(3H)-one (Compound (I), compositions comprising such a salt, and processes for the manufacture of such a salt, in particular Compound (I) hemi-fumarate salt are described. The salt is useful for the treatment of conditions such as asthma and CORD, involving modulation of the JAK pathway or inhibition of JAK kinases particularly JAK1.
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
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 11/00 - Drugs for disorders of the respiratory system
The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.
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
Disclosed are methods of treating cancer comprising administering 17-chloro- 5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6, 12,13,22- pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta- 1 (37), 4(38), 6, 11, 14, 16, 18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, a pharmaceutically acceptable salt thereof; and acalabrutinib, or a pharmaceutically acceptable salt thereof.
Described herein are measures of the relative expression levels, within a given sample from a subject, of an ACPP transmembrane splice variant to the expression level of one or more ACPP non-transmembrane splice variant(s). The measures, designated ?, show correlation with clinical outcome for the subject. In some cases, values of ? exceeding a predetermined cutoff can be associated with poorer outcomes. Methods of determining ? and assigning the predetermined cutoff value are described. Methods of treating cancer are also described.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
An inhaler for delivery of a medicament by inhalation is disclosed. The inhaler comprises the following components. An inhaler body for receiving a canister having a dispensing valve. A drive mechanism comprising a biasing means such as a spring and a moving component such as a yoke, the drive mechanism for driving the canister, when received in the inhaler body, from a rest position in which the valve is closed to at least an actuating position in which the valve is open. The drive mechanism drives the canister when the biasing means is released from a loaded configuration to move the moving component from a first position to a second position. A resetting mechanism, for example a mouthpiece cap arrangement for pushing upwardly on the yoke, for resetting the drive mechanism by moving the moving component from the second position to the first position and reloading the biasing means to the loaded configuration. A return mechanism for returning the canister from the actuating position to the rest position, wherein the return mechanism comprises a damping system, the damping system configured to enable the canister to automatically return from the actuating position to the rest position within a predetermined time period measured from the release of the biasing means from the loaded configuration. A method of operation of an inhaler is also disclosed.
Disclosed are methods for treating late stage (e.g., clinical stage III or IV), unresectable non-small-cell lung cancer (NSCLC) with an antibody that inhibits PD1/PD-L1 activity in a patient identified as having not progressed following definitive chemoradiation therapy.
A61K 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
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
The present disclosure relates to pharmaceutical compositions suitable for oral administration, and more particularly to pharmaceutical compositions, including pharmaceutical tablet compositions, containing (2S)-N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo- 2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide (Compound A) or a pharmaceutically acceptable salt thereof.
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
Disclosed are compounds of formula (Ia) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ia) and methods of using the same for treating cancer or a respiratory inflammatory disease and inhibiting arginase, wherein R1 is -NHR1a; R1a is -H or -C(O)CH(R1b)NHR1c; and R1b is selected from -H, -(C1-C4 ) alkyl and CH2OR1d and R1cis -H; or R1b and R1c, together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R1d is H or -CH3.
The specification relates to osimertinib or a pharmaceutically acceptable salt thereof for use in the treatment of patients with locally advanced unresectable epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (Stage III)), and in particular to the treatment of patients whose disease has not progressed following definitive platinum-based chemoradiation therapy.
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/475 - Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/66 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
The present invention relates to combination of a BTK inhibitor and an inhibitor of CDK9 for use in the treatment of cancer in a subject. The BTK inhibitor can be acalabrutinib, ibrutinib, or ONO/GS-4059; and the inhibitor of CDK9 can be AZD4573, BAY-1251152, BAY- 1143572, CYC065, alvocidib, AT7519, voruciclib, roniciclib, or dinaciclib.
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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
The invention concerns compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and R4 have any of the meanings hereinbefore defined in the description; process for their preparation; pharmaceutical compositions containing them and their use in treating KIT mediated diseases.
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
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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
98.
PHENOXYQUINAZOLINE COMPOUNDS AND THEIR USE IN TREATING CANCER
The invention concerns compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and R4 have any of the meanings hereinbefore defined in the description; process for their preparation, pharmaceutical compositions containing them and their use in treating KIT mediated diseases.
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
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07C 245/06 - Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic 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
Disclosed are dendrimers of formula (I): and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising the dendrimer of formula (I) and methods of using the same for treating cancer.
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
patents
