Disclosed herein are lentiviral plasmid packaging compositions comprising unique mass ratios of four plasmids that are useful in producing lentiviral vectors. Also provided are methods of producing such lentiviral vectors by mixing a complexation solution comprising the lentiviral plasmid packaging composition with a transfection reagent and incubating the mixture for at least 10 minutes, transfecting a eukaryotic host cell with the lentiviral plasmid packaging composition, adding sodium butyrate to the transfected host cells about one day after transfection, and culturing the host cell. Exemplary embodiments of the method comprise a concentration of total plasmid in pg/mL of 0.25-3 and/or a mass ratio of total plasmid mass in pg to the mass of transfection reagent in pg extending from about 1:1 to about 1:3.
The disclosure relates to RNAi constructs, such as siRNA, for reducing expression of the GPAM gene. Methods of using such RNAi constructs to treat or prevent liver disease, such as nonalcoholic fatty liver disease (NAFLD), are also described.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/7115 - Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
Apparatuses, systems and methods are provided that characterize a rear sub-assembly for an autoinjector (Al). Apparatuses, systems and methods are also provided that generate injection time (IT) models for autoinjectors (Als). Autoinjectors (Als) (e.g., mechanical Als, spring-loaded Als, etc.), components for use within Als (e.g., prefilled syringes (PFS), rear sub-assemblies (RSAs), etc.), and related methods may utilize mathematical modeling along with design for six sigma (DFSS) and design for reliability and manufacturability (D RM) to establish upstream controls that ensure injection time (IT) robustness of mechanical autoinjectors (Als). For example, break-loose and extrusion (BLE) alert limit, rear sub-assembly (RSA) area under the curve (AUG), and RSA minimum force.
A61M 5/48 - 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 having means for varying, regulating, indicating or limiting injection pressure
A pore profile of a microfilter is determined by: (210) providing a saturated porous microfilter membrane comprising a first surface, a second surface, and a matrix disposed therebetween, wherein the matrix is saturated by a storage solution; (220) contacting the saturated porous microfilter membrane with an intermediate solvent, whereby the storage solution dissolves in the intermediate solvent, thereby de-saturating the membrane (230) applying a test fluid to the de-saturated membrane, thereby re-saturating the membrane; (240) applying a pressure to the first surface of the re-saturated membrane, wherein the pressure is applied by contacting the first surface with a gas or liquid; (250) detecting a flow of the gas, liquid, and/or test fluid from the second surface in response to said pressure; and (260) determining the pore size profile of the porous microfilter membrane based on a level of the pressure that results in the flow of the gas, liquid, and/or test fluid from the second surface. A filter to be used for filtering (281) a cell culture product may then be selected by choosing a filter having an appropriate pore size profile (171).
B01D 11/04 - Solvent extraction of solutions which are liquid
B01D 12/00 - Displacing liquid, e.g. from wet solids or from dispersions of liquids or from solids in liquids, by means of another liquid
B01D 35/00 - Filtering devices having features not specifically covered by groups , or for applications not specifically covered by groups ; Auxiliary devices for filtration; Filter housing constructions
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 to activatable anti-EGFR, anti-CD3, heteromultimeric bispecific polypeptide complexes (HBPCs) and methods of making and using the same.
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
7.
IMPACT ACTIVATED BRAKE FEATURE FOR DRUG DELIVERY DEVICE
A drug delivery device includes a housing having proximal and distal ends and a longitudinal axis extending therebetween, an injection assembly at least partially disposed within the housing at or near the proximal end, a shield slidably coupled with the housing, a drive assembly operably coupled with the injection assembly and the shield, and a cap. The injection assembly includes a needle or a cannula. The shield is positionable in an extended position in which at least a proximal end thereof extends a distance beyond the proximal end of the housing. The drive assembly is engageable to deliver a medicament via the injection assembly. The cap is removably coupled with at least one of the shield or the housing and is adapted to limit movement of the shield when coupled with the shield and/or the housing such that the drive assembly is restricted from delivering the medicament via the injection assembly.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
8.
IMPACT ACTIVATED RETENTION FEATURE FOR DRUG DELIVERY DEVICE
A drug delivery device includes a housing having proximal and distal ends and a longitudinal axis extending therebetween, an injection assembly at least partially disposed within the housing including a needle or a cannula, a drive assembly operably coupled with the injection assembly, a shield slidably coupled with the housing and operably coupled with the drive assembly, and a retention mechanism. The drive assembly is engageable to deliver a medicament via the injection assembly. The shield is positionable in an extended position in which at least a proximal end extends a distance beyond the proximal end of the housing and a retracted position where the proximal end of the housing protrudes a distance beyond the proximal end of the shield. Moving the shield to the retracted position engages the drive assembly to deliver the medicament via the injection assembly. The retention mechanism limits movement of the drive assembly to restrict engagement thereof such that the drive assembly is restricted from delivering the medicament via the injection assembly.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
A61M 5/24 - Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or cartridges, e.g. automatic
9.
COMPOSITIONS AND METHODS FOR ENHANCING GENE SILENCING ACTIVITY OF OLIGONUCLEOTIDE COMPOUNDS
The present invention relates to compositions and methods for enhancing the gene silencing activity of oligonucleotide compounds. In particular, the invention relates to inhibiting the expression or activity of suppressor proteins, such as RAB18, ZW10, STX18, SCFD2, NAPG, SAMD4B, or VPS37A, to increase the efficacy of ligand-conjugated oligonucleotide compounds in reducing the expression of target genes in a cell.
Provided herein are methods of determining product quality of an antibody composition, wherein the product quality is based on the Fc? receptor II (Fc?RII) binding level of the antibody composition. In exemplary embodiments, the method comprises (a) determining the afucosylated glycan content and/or ß-galactosylated glycan content of a sample of the antibody composition; (b) optionally, calculating a predicted Fc?RII binding level based on the afucosylated glycan content and/or ß-galactosylated glycan content as determined in (a); and (c) determining the product quality of the antibody composition as acceptable when (i) the afucosylated glycan content and/or ß-galactosylated glycan content is within a target range and/or (ii) the predicted Fc?RII binding level is within a target range. Related methods of monitoring product quality and methods of producing an antibody composition are further provided herein.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological 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
11.
CLOSED SYSTEM TRANSFER DEVICE AND VIAL ASSEMBLY MACHINE
A closed system transfer device (CSTD) and vial assembly machine includes a linear travel assembly including a linear mount, and an actuator operably coupled to the linear mount. The linear mount is movable in an axial direction between a first position and a second position spaced from the first position. A CSTD fixture is configured to be removably coupleable to the linear mount. A vial mount is disposed adjacent to a portion of the linear travel assembly. A vial fixture is configured to be removably coupleable to the vial mount. The vial fixture is sized to hold a vial in axial alignment with a portion of the CSTD fixture when the vial fixture is coupled to the vial mount and the CSTD fixture is coupled to the linear mount. When the linear mount moves from the first position to the second position, the linear mount moves relative to the vial mount.
A61J 1/20 - Arrangements for transferring fluids, e.g. from vial to syringe
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
G16H 40/60 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
A61J 3/00 - Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
B65B 3/00 - Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans or jars
12.
APPARATUSES, SYSTEMS AND METHODS FOR PLUNGER-STOPPER DEPTH MEASUREMENT IN PRE-FILLED SYRINGES
Automatic prefilled syringe inspection systems, apparatus and methods are provided. The automatic syringe inspection systems, apparatus and methods may determine a plunger depth within a syringe that has been pre-filled with a medication. The plunger depth may be based on digital image data that is representative of a silhouette of at least a portion of a tubular vessel and at least a portion of a plunger within the tubular vessel.
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
G06V 10/25 - Determination of region of interest [ROI] or a volume of interest [VOI]
G06V 10/75 - Image or video pattern matching; Proximity measures in feature spaces using context analysis; Selection of dictionaries
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
G01B 11/22 - Measuring arrangements characterised by the use of optical techniques for measuring depth
G01F 11/02 - Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement
The present disclosure provides a method of treating cancer in a subject. The method including administering to the subject: a) a therapeutically effective amount of a compound of formula (I); and b) a therapeutically effective amount of sotorasib, wherein the compound of formula (I) is represented by (I), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, conformational isomer, tautomer, or a combination thereof. In particular, the present disclosure provides a method of treating a solid tumor (e.g., an advanced or metastatic non-small cell lung cancer) with a therapeutically effective amount of a compound of formula (10b) (i.e., 6- ((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(Ra)-(2,3- dichlorophenyl)-2,5-dimethylpyrimidin-4(3H)-one) in combination with sotorasib in a subject, wherein the subject has one or more mutations in KRAS, such as KRAS G12C.
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 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Provided herein are methods of separating molecular species of a guanine-rich oligonucleotide from a mixture of molecular species, wherein at least one molecular species of the mixture is a quadruplex formed from the guanine-rich oligonucleotide. In exemplary embodiments, the methods comprise (a) applying the mixture to a chromatographic matrix comprising a hydrophobic ligand, wherein said hydrophobic ligand comprises C4 to C8 alkyl chains, wherein molecular species bind to the hydrophobic ligand and (b) applying a mobile phase which comprises a gradient of acetate and a gradient of acetonitrile but no cationic ion pairing agent to the chromatographic matrix to elute molecular species of the guanine-rich oligonucleotide. In exemplary aspects, the guanine¬ rich oligonucleotide elutes in a first set of elution fractions and a quadruplex formed from the guanine-rich oligonucleotide elutes in a second set of elution fractions.
B01D 15/16 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction
C07K 1/20 - Partition-, reverse-phase or hydrophobic interaction chromatography
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
Provided herein are methods of treating cancer comprising a KRAS G12C mutation in a patient comprising administering to the patient sotorasib and an anti-epidermal growth factor receptor (EGFR) antibody in amounts effective to treat the cancer. Further provided herein are methods further comprising administering FOLFIRI (irinotecan, 5-FU and leucovorin) to the patient.
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 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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
Methods producing a recombinant protein of interest in a mammalian cell culture in media lacking IGF-1 are provided. Methods for producing mammalian cells capable of growing in media lacking IGF-1 are also provided.
C07D 265/30 - 1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
18.
APPARATUSES, SYSTEMS AND METHODS FOR VIAL SEAL INSPECTION
An apparatus, system, or method for vial seal inspection may be based on three-dimensional data that is representative of at least a portion of a vial seal. More particularly, apparatuses, systems, and methods for vial seal inspection may include at least one laser triangulation sensor.
G01B 11/25 - Measuring arrangements characterised by the use of optical techniques for measuring contours or curvatures by projecting a pattern, e.g. moiré fringes, on the object
Method for investigating subcutaneous administration of a therapeutic compound product comprising providing a live in vitro mammalian skin sample comprising a dermal layer and epidermal layer, administering a therapeutic compound product to the interface between the dermal layer and the epidermal layer and analysing the skin sample.
The present invention relates to stereoselective process for the preparation of a compound having formula (2) and (1) wherein X is defined in the specification.
The present invention relates to precious metal (Pd/Pt/Rh/Ru) free, preferably Pd free, processes for preparing a compound having formula (1) wherein: R1, R2, and X are as defined in the specification, or a salt thereof. Preferably, the compound is an iodo acrylate compound.
C07C 201/14 - Preparation of nitro compounds by formation of nitro groups together with reactions not involving the formation of nitro groups
C07C 205/58 - Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by halogen atoms
C07C 319/14 - Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
C07C 319/20 - Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
C07C 323/62 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
C07C 323/63 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
C12P 13/00 - Preparation of nitrogen-containing organic compounds
Provided herein are liquid compositions comprising a high concentration of a monoclonal antibody, e.g., greater than about 100 mg/mL, which demonstrate storage -stability and reduced viscosity. In exemplary embodiments, the liquid composition comprises about less than about 400 mM arginine glutamate, and, in alternative exemplary embodiments, the liquid composition comprises proline and a buffer.
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
The present disclosure provides compounds useful for the inhibition of KRAS G12D. The compounds have a general Formula (I) : wherein the variables of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, cancer.
The present disclosure provides compounds useful for the inhibition of KRAS G12D. The compounds have a general Formula I: wherein the variables of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, cancer.
A61K 31/519 - Pyrimidines; Hydrogenated 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
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
The present disclosure provides compounds useful for the inhibition of KRAS. The compounds have a general Formula I: wherein the variables of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, cancer.
Methods of isolating a therapeutic protein from a sample are described herein. Kits for isolating a therapeutic protein from a sample are described herein.
A elution product yield improvement system includes a processor, an estimation model and an elution controller application including instructions configured, when executed by the processors, to receive initialization data; instantiate a communication link to a remote process/automation system; determine collection criteria; initiate collection; read data values; computing an area ratio via the estimation model; and cease collection. A computer-implemented method for improving elution yield and purity includes receiving initialization data; instantiating a communication link to a remote process/automation system; determining collection criteria; initiating collection; reading data values; computing an area ratio; and ceasing collection. A non- transitory computer readable medium includes program instructions that when executed, cause a computer to receive initialization data; instantiate a communication link to a remote process/automation system; determine collection criteria; initiate collection; read data values; computing an area ratio via the estimation model; and cease collection.
B01D 15/24 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the treatment of the fractions to be distributed
Disclosed herein is a salt, a crystalline anhydrous form, a hydrate, a solvate, or a co-crystal of a free base compound 2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-[(2-hydroxyethanesulfonyl)amino]benzamide (Compound A); method of preparation, pharmaceutical compositions, and method of treating a disease mediated by a motor protein kinesin family member 18A (KIF18A) inhibition, wherein said disease is a neoplastic disease, including a cancer or a tumor.
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
Described herein is a method comprising (a) reconstituting a lyophilized formulation comprising a polypeptide, a saccharide, a surfactant, and a buffer, with a diluent comprising an aromatic alcohol, a phenolic compound, or an amino acid with aromatic side chain, and (b) administering the reconstituted formulation to a subject in need thereof within 12 hours of reconstitution, wherein the polypeptide is a bispecific antibody construct, such as a bispecific antibody construct that binds human DLL3 and human CD3 and optionally comprises the amino acid sequence of SEQ ID NO: 75 and SEQ ID NO: 9.
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 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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
30.
TREATMENT OF CARDIOVASCULAR DISEASE WITH TREM-1 ANTIGEN BINDING PROTEINS
The present disclosure relates, in general, to methods of treating cardiovascular disease, such as atherosclerosis or myocardial infarction, using antigen binding proteins that bind to TREM-1, and compositions 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
Syringes, assemblies for use in a filling process, and related methods of manufacture are disclosed. A syringe may include a reservoir filled or configured to be filled with a preselected volume of a drug, including, for example, a preselected volume of 3 mL or approximately 3 mL of the drug. The syringe may further include a wall comprising a cylindrical portion. The cylindrical portion of the wall may include: (a) an inner diameter equal to or approximately equal to a standard inner diameter of a 5 mL syringe or a standard outer diameter of any other syringe volume not equal to the preselected volume or 3 mL; and/or (b) an outer diameter equal to or approximately equal to a standard outer diameter of a 5 mL syringe or a standard outer diameter of any other syringe volume not equal to the preselected volume or 3 mL.
A drug delivery device is provided, including a housing, a drug storage container, a plunger, a plunger biasing member, a releaser, and a shock absorber. The housing defines a longitudinal axis and has an opening. The drug storage container includes a barrel, a stopper, and a delivery member, where the stopper is movably positioned within the barrel. The delivery member is positioned at a distal end of the barrel and has an insertion end configured to extend at least partially through the opening during a delivery state. The plunger is moveable toward the distal end of the drug storage container to engage the stopper and expel a drug from the drug storage container through the delivery member. The plunger biasing member is coupled with the plunger and configured to urge the plunger toward the distal end of the drug storage container. The releaser member has a first position wherein the releaser member prevents the plunger from moving into the delivery state and a second position wherein the releaser member does not prevent the plunger from moving into the delivery state. The shock absorber is configured to absorb an impact force and prevent unintended movement of the releaser member.
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
A61M 5/50 - 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 having means for preventing re-use, or for indicating if defective, used, tampered with or unsterile
33.
DRUG DELIVERY DEVICES, FINGER-GRIP ELEMENTS, AND RELATED METHODS
Drug delivery devices, finger-grip elements for use with syringes, and related methods are disclosed. A drug delivery device may include a syringe and a finger-grip element. The syringe may include a barrel, a barrel flange extending radially outwardly with respect to a longitudinal axis of the barrel, and a plunger moveably disposed within the barrel. The finger-grip element may be coupled with the barrel flange. The finger-grip element may have a first distally facing surface having a first contour configured to: inhibit or prevent at least a first finger of a user from moving in a radially outward direction with respect to the longitudinal axis during use of the syringe to deliver a drug, and/or exert a first reaction force on at least the first finger of the user in a direction parallel or substantially parallel to the longitudinal axis during use of the syringe to deliver the drug.
A61M 5/46 - 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 having means for controlling depth of insertion
34.
USING FUCOSIDASE TO CONTROL AFUCOSYLATION LEVEL OF GLYCOSYLATED PROTEINS
Provided herein are methods of obtaining a recombinant glycosylated protein having increased levels of afucosylated glycoforms. In exemplary embodiments, the methods comprise incubating purified recombinant glycosylated protein with a human broad specificity fucosidase and separating the recombinant glycosylated protein from the fucosidase.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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 9/44 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on alpha-1, 6-glucosidic bonds, e.g. isoamylase, pullulanase
A method of cell culture assessment (e.g., prior to a drug substance harvesting process) includes obtaining a plurality of parameters associated with a cell culture, and inferring or predicting a value or classification indicative of packed cell volume. Inferring or predicting the packed cell volume includes applying the plurality of parameters as inputs to a non-linear machine learning model. The method also includes generating an output indicative of the inferred or predicted value or classification.
The present invention relates to engineered neuregulin-1 variants that selectively activate ErbB4 receptors but do not activate ErbB3 receptors. The invention also provides methods for using such variants to treat heart failure.
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 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
Disclosed herein are accelerated methods of preparing lyophilized formulations comprising a protein, such as an antibody or a bispecific antigen-binding molecule that exhibit improved storage stability.
The present invention provides single chain T cell engager (TCE) molecules having an scFab that binds a target antigen and an scFv that binds CD3, and TCE molecules that bind CCR8 and CD3. Methods of treating cancer are also provided.
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 invention provides anti-CCR8 antibodies and antigen-binding fragments thereof, and methods of making and using said anti-CCR8 antibodies and antigen-binding fragments 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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Provided herein are oral dosage forms comprising a) a core tablet comprising (i) a drug layer comprising apremilast and hypromellose acetate succinate (HPMCAS) in an amorphous solid dispersion; and (ii) a swellable layer comprising one or more swellable polymers; and b) a coating layer disposed on the core tablet, wherein the oral dosage form surface comprises at least one drug release orifice. The disclosed oral dosage forms provide once-a-day dosing of apremilast and are suitable for treating diseases or disorders ameliorated by inhibiting phosphodiesterase subtype IV (PDE4).
Provided herein are methods of treating a cancer comprising a KRAS G12C mutation in a patient with active brain metastases, comprising administering sotorasib to the patient in amount effective to treat the cancer.
A method of filling a vial. The method includes providing a pump corresponding to a vial and setting a drip retraction parameter for the pump to any value equal to or less than 20 degrees. The method also includes setting a no adjustment limit for a fill weight of the vial to T1, with T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight T0, wherein a process performance index Cpk (Cpk) for the vial throughout a fill cycle exceeds a minimum value.
B65B 3/00 - Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans or jars
43.
DOSING REGIMEN FOR COMBINATION THERAPY TARGETING DLL3 AND PD-1
The present invention provides a method for the treatment of DLL3-positive cancer or SCLC, comprising administering to a subject in need thereof an anti-DLL3 agent and an anti-PD-1 antibody. Step dosing of the anti-DLL3 agent is also disclosed.
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 herein are pharmaceutical formulations comprising etelcalcetide or salt thereof and a surfactant in aqueous solution, wherein the formulation has a pH of 2.0 to 5Ø
Provided herein are processes for synthesizing apremilast comprising reacting 3-acetamidophthalic anhydride and (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethan-1 -amine or a salt thereof to form apremilast. Also provided are processes for isolating apremilast from the reaction mixture, as described herein.
The present disclosure provides compounds useful for the inhibition of KRAS G12D. The compounds have a general Formula I: (I) wherein the variables of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, cancer.
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
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/529 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim forming part of bridged ring systems
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
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
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 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
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
48.
MODULATING PRODUCT QUALITY OF ASYMMETRIC MULTISPECIFIC ANTIBODIES THROUGH THE USE OF TEMPERATURE
The present invention relates to the field of biopharmaceutical manufacturing. In particular, the invention relates to using temperature as a lever to modulate product quality during upstream operations.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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 provides compounds useful for the inhibition of KRAS G12D. The compounds have a general Formula I: (I) wherein the variables of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, cancer.
A system for out-patient treatment with immunotherapy that activates T cells of a patient to fight cancer is provided that may include an infusion pump; a patient wearable device configured to acquire sensor data related to detection of cytokines released by the patient in response to the patient receiving the immunotherapy that activates T cells; and remote wireless communication with a healthcare provider based on the acquired sensor data. A computer-readable medium having computer- readable instructions stored thereon that, when executed by a processor, cause the processor to monitor health of a patient may include a sensor data receiving module that, when executed by a processor, causes the processor to receive sensor data; and a warning data generation module that, when executed by a processor, causes the processor to generate at least one warning based on the sensor data, wherein a content of the sensor data is based on an out-patient treatment that includes an immunotherapy that activates T cells of the patient.
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
G16H 40/63 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
The present application relates, in general, to compositions or variants of anti-TSLP antibody tezepelumab having increased stability compared to tezepelumab when stored over long periods of time.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
52.
METHODS AND SYSTEMS FOR AUTOMATED SYRINGE QUALITY EVALUATION
Automatic syringe quality control systems, apparatus and methods are provided. The automatic syringe quality control systems, apparatus and methods may determine a plunger depth within a syringe that has been pre-filled with a medication. The plunger depth may be based on digital image data.
G01F 22/00 - Methods or apparatus for measuring volume of fluids or fluent solid material, not otherwise provided for
A61M 5/36 - 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 with means for eliminating or preventing injection or infusion of air into body
G01B 11/02 - Measuring arrangements characterised by the use of optical techniques for measuring length, width, or thickness
G01F 11/02 - Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement
A magnetic drive extension may be adapted to be positioned between a magnetic drive that generates a rotating magnetic field and a component, such as an agitator, driven by the magnetic drive, to increase the strength of the magnetic coupling between the drive and component. For example, a mechanical magnetic drive extension may house a rotating shaft around which a rotating magnet mount is configured to rotate, with two oppositely polarized magnets attached to opposite sides of the mount, such that the rotational force causes the rotating magnet mount to rotate, which in turn generates a second rotating magnetic field that causes a second rotational magnetic force to be applied to the component. As another example, a magnetically permeable magnetic drive extension may be comprised of an insulating material in which magnetic conductor components are embedded with even spacing around the interior perimeter of the magnetically permeable magnetic drive extension.
The clinical potential of multispecific antibodies like bispecific and trispecific antibodies shows great promise for targeting complex diseases. However, the generation of those molecules presents great challenges particularly in regard to achieving acceptable expression levels free from mis-paired polypeptides. The presently claimed invention is directed to multispecific antigen binding proteins which improve upon existing charge pair technologies by redistributing the engineered charges within the CH3 regions of a heteromultimer.
The present application relates, in general, to compositions comprising anti-TSLP antibody tezepelumab and derivatives thereof having antibody quality attributes.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/06 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies from serum
56.
AUTOMATED OUTLIER REMOVAL FOR MULTIVARIATE MODELING
In a method for improving multivariate model performance, a first data set comprising values of a plurality of features and corresponding labels is obtained. A second data set is generated from the first data set. Generating the first data set includes generating an intermediate data set by removing a first set of outliers from the first data set using a univariate statistical technique, generating a first multivariate model using the intermediate data set, and removing a second set of outliers from the first data set using the first multivariate model and a multivariate statistical technique. A second multivariate model is generated using the second data set.
A real-time drug injection time duration measurement system includes a sound transducer, a waveform shaping circuit operably coupled therewith, a pulse clamping circuit operably coupled with the waveform shaping circuit, and a timer operably coupled with the pulse clamping circuit. The sound transducer detects a first sound associated with drug delivery initiation and a second sound associated with drug delivery completion and is further converts the detected first and second sounds into a first electronic waveform and a second electronic waveform, respectively. The waveform shaping circuit converts the first and second waveforms into a first pulse and a second pulse, respectively. The pulse clamping circuit triggers upon receiving the first pulse and generate a regenerated pulse. The timer initiates upon receiving the regenerated pulse and stop upon receiving a subsequent regenerated pulse via the pulse clamping circuit.
The present invention relates to binding constructs comprising a domain which binds to MAGEB2. Moreover, the invention provides polynucleotides encoding the binding constructs, a vector comprising said polynucleotides and a host cell transformed or transfected with said polynucleotides or vectors. Furthermore, the invention provides processes for producing the binding constructs, methods of treatment using the binding constructs, diagnostic uses of the binding constructs, and kits comprising the binding constructs.
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
A drug delivery device may include a housing defining a longitudinal axis and having an opening and a drug storage container including a barrel, a stopper and a delivery member, the stopper movably positioned within the barrel and the delivery member positioned at a distal end of the barrel and having an insertion end configured to extend at least partially through the opening during a delivery state. The device may also include plunger moveable toward the distal end of the drug storage container to engage the stopper and expel a drug from the drug storage container through the delivery member, the plunger including a body portion and a shock absorbing portion. The device may further include a plunger biasing member coupled with the plunger and configured to urge the plunger toward the distal end of the drug storage container.
Provided herein are methods of administering a 240 mg total daily dose of sotorasib to a patient suffering from a cancer having a KRAS G12C mutation. Also provided herein are methods of treating KRAS G12C mutated cancer in a patient comprising administering a total daily dose of 960 mg sotorasib to the patient, and reducing the total daily dose of sotorasib to 480 mg in a patient experiencing an adverse event to the 960 mg dose of sotorasib.
A method of reducing combination device variability includes identifying potential combinations of at least first and second components, where each combination can form one or more units of the combination device. The method also includes, for each potential combination, predicting a property or result of the units of the combination device when formed from at least the first and second components of the combination, at least by applying values of one or more characteristics of the first component of the combination, and values of one or more characteristics of the second component of the combination, as inputs to a predictive model. The method also includes selecting, based on the predicted properties or results for the potential combinations, a subset of combinations from among the potential combinations, and providing an indication of the selected subset of combinations.
G06Q 10/063 - Operations research, analysis or management
G06Q 10/04 - Forecasting or optimisation specially adapted for administrative or management purposes, e.g. linear programming or "cutting stock problem"
A drug delivery device including a housing, a drug storage container, and a removable cap is provided. The removable cap may be configured to be removably coupled with the housing such that the removable cap has a storage position where the removable cap is coupled with the housing and at least partially covering an opening in the housing and a removed position where the removable cap is not coupled with the housing. The removable cap may include an outer portion, an inner portion, and a gap separating at least a portion of the inner portion and at least a portion of the outer portion such that the at least a portion of the outer portion is allowed to bend with respect to the at least a portion of the inner portion if the at least a portion of the outer portion is subjected to an external force. Additionally or alternatively, the removable cap may be configured such that an external force applied to the removable cap induces at least one bending moment in a proximal end and/or a distal end of the removable cap.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
A method of manufacturing a plunger of a drug delivery device includes forming a plunger body. The method includes loading the plunger body into a cavity of a first molding tool of a molding system. The cavity is at least partially defined by a first molding portion and a second molding portion. The method includes coupling a second molding tool to the first molding tool to form a plurality of channels defined by grooves in the first and second molding tools, and injecting molten plastic into the plurality of channels to form an overmolded plunger body. The overmolded plunger body includes a head coupled to the first end of the plunger body and a foot coupled to the second end of the plunger body. The foot is at least partially coupled to the inner wall and the head is coupled to the outer wall of the plunger body.
Parallel chromatography systems and continuous manufacturing methods are described herein that utilize two or more chromatography column skids having columns operating in parallel with automation controls governing which column to load at a given time.
A drug delivery device including a housing, a drug storage container, and a removable cap is provided. The housing includes a housing camming feature and a longitudinal axis and includes an opening. The drug storage container includes a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state. The removable cap defines a cap camming feature and is configured to be removably coupled with the housing such that the removable cap has a storage position where the removable cap is coupled with the housing and at least partially covering the opening and a removed position where the removable cap is not coupled with the housing. The cap camming feature and the housing camming feature are configured to translate rotational motion into axial motion such that, upon rotational movement of the removable cap, the cap camming feature and/or the housing camming feature urge the removable cap along the longitudinal axis. The housing camming feature and the cap camming feature are each visible to a user of the drug delivery device to signal the camming function of the housing camming feature and the cap camming feature.
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
Parallel chromatography systems and continuous manufacturing methods are described herein that utilize two or more chromatography column skids having columns operating in parallel with automation controls governing which column to load at a given time.
A syringe holder for a drug delivery device is provided. The syringe holder may include a proximal end, a distal end, and a hollow interior configured to receive at least a portion of a syringe. The syringe holder may further include a side opening distal to the proximal end and an outwardly extending protrusion proximal to the side opening. During assembly of the syringe holder into a housing of the drug delivery device the outwardly extending protrusion may be configured to support the syringe holder at a first axial position or an intermediate position with respect to a longitudinal axis of the housing of the drug delivery device. Also provided is a drug delivery device incorporating a syringe holder and a subassembly for a drug delivery device incorporating a syringe holder. A method of assembling a syringe holder into a housing of a drug delivery device is also provided.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/24 - Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or cartridges, e.g. automatic
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
C07C 201/10 - Preparation of nitro compounds by substitution of functional groups by nitro groups
C07C 205/12 - Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings the six-membered aromatic ring or a condensed ring system containing that ring being substituted by halogen atoms
69.
NON-TERMINAL ANTIBODY DISCOVERY METHODS AND SINGLE CELL ASSAYS
Provided herein are methods of monitoring for the production of select antibodies in a non-human animal, comprising (a) immunizing a non-human animal with an immunogen; (b) obtaining a blood sample comprising antibody secreting cells (ASCs) from said non-human animal; and (c) individually assaying ASCs present in the blood sample, or a fraction thereof, for the production of select antibodies. Methods of guiding antibody production in a non-human animal for the production of select antibodies are also provided. In exemplary embodiments, the method comprises performing a cycle of (a) to (c), as above, and repeating the cycle when the percentage of ASCs producing select antibodies is below a threshold. In various aspects, the cycle is repeated until the percentage of ASCs producing select antibodies is at or above a threshold. Single cell assays are further provided herein.
Provided herein are methods of generating hybridomas and related methods of producing antigen-specific antibodies. In exemplary embodiments, the method comprises (a) preparing an enriched population of IgG-positive (IgG+) memory B cells from cells obtained from secondary lymphoid organs of one or more immunized non-human animals, wherein (i) less than or about 10% of the enriched population are IgM-positive (IgM+) B cells and/or (ii) the ratio of the IgG+ memory B cell count to IgM+ B cell count of the enriched population is greater than about 0.5, optionally, greater than about 1 or greater than about 2, (b) bulk-culturing the enriched population to obtain an expanded population; and (c) fusing cells of the expanded population with myeloma cells to obtain hybridomas. In exemplary aspects, the hybridomas obtained represent at least 10% or at least 15% of the IgG+ memory B cell repertoire produced by the immunized animals.
Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:
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
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 31/437 - 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 31/4375 - 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 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
C07D 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
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
72.
MATERIALS AND METHODS FOR MONITORING CANCER BY ADMINISTERING AN ANTI-MCL1 ANTIBODY
The disclosure provides anti-Mcl-1 antibodies of any form, and fragments thereof, that bind the antigen with unexpectedly high binding to Mcl-1, providing tools useful in methods of monitoring cancer cells expressing Mcl-1 and methods of treating cancers, particularly blood- borne cancers, comprising such cancer cells.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
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
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
The present disclosure provides uses for a KRASG12C inhibitor, such as the compound of Formula I (AMG 510, sotorasib) in treating cancers, such as non-small cell lung cancer, in subjects with certain characteristics.
A method of diagnosing or predicting performance of equipment includes determining values of one or more parameters associated with the equipment by monitoring the one or more parameters over a time period in which the equipment is in use. The method also includes determining, by processing the values of the one or more parameters using a classification model, a performance classification of the equipment, mapping the performance classification to a mitigating or preventative action, and generating an output indicative of the mitigating or preventative action.
The present disclosure provides materials and methods identifying, selecting, and characterizing cells that express and secrete non-Fc containing biomolecules.
Provided herein are T-cell receptors (TCRs) that when expressed recombinantly on the surface of a T cell are able to recognize the MAGE-B2-derived peptide GVYDGEEHSV (SEQ ID NO:1) when presented by HLA-A*02:01 sufficiently to activate the recombinant T cell. Certain TCRs provided herein also are able to recognize the MAGE-A4-derived peptide GVYDGREHTV (SEQ ID NO:2) sufficiently to activate the recombinant T cell. Importantly, exemplary TCRs provided herein were thoroughly screened for lack of cross-reactivity with similar peptides that may be presented by normal cells or tissue and for alloreactivity.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
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
BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (USA)
Inventor
Wu, Tian
Schneider, Michael
Khalaf, Ryan
Smyth, Hugh
Brunaugh, Ashlee
Ding, Li
Abstract
A forecasting modeling computing system includes a processors and a memory including a set of computer-executable instructions that, when executed by the processor, cause the forecasting modeling computing system to receive design parameters, determine a predicted median particle size, identify a predictive quadratic model, and display a response surface visualization. A computer-implemented method includes receiving design parameters, determining a predicted median particle size, identifying a predictive quadratic model; and display a response surface visualization.
G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:
A61K 31/4353 - 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 invention provides primer probe combinations for detecting DNA encoding Bovine parvovirus 3 (BPV-3) genomic DNA in the extracted DNA of a test sample. An internal positive control is also provided.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
Methods of manufacturing a biological therapy are described. The methods can comprise detecting a level of a molecular attribute of the biological therapy in a formulation, determining a rate of change of the molecular attribute under the storage conditions, and estimating a level of molecular attribute exposure received by the subjects at the time of said administration. Production lots of the biological therapy comprising the molecular attribute can be manufactured comprising the molecular attribute at or below a specified specification for permissible levels of the molecular attribute based on the estimated level of molecule attribute exposure. Methods of developing a manufacturing process for a biological therapy are described. Methods of assessing the clinical impact of a molecular attribute of a biological therapy are described.
New formats of multispecific molecules are described, as well as their methods of making. Additionally, uses in therapeutic indications are also described.
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 invention provides a method of treating a disease or conditions associated with a dysfunction of TREM2 in a human patient, such as Alzheimer's disease, comprising administering to the patient a TREM2 agonist. In another aspect, the invention provides a method of assaying a biological sample taken from a patient having Alzheimer's for biomarkers to determine potential benefit or if the disease has an increased probability of responding to treatment with a TREM2 agonist.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
83.
IMAGE AUGMENTATION TECHNIQUES FOR AUTOMATED VISUAL INSPECTION
Various techniques facilitate the development of an image library that can be used to train and/or validate an automated visual inspection (AVI) model, such an AVI neural network for image classification. In one aspect, an arithmetic transposition algorithm is used to generate synthetic images from original images by transposing features (e.g., defects) onto the original images, with pixel-level realism. In other aspects, digital inpainting techniques are used to generate realistic synthetic images from original images. Deep learning-based inpainting techniques may be used to add, remove, and/or modify defects or other depicted features. In still other aspects, quality control techniques are used to assess the suitability of image libraries for training and/or validation of AVI models, and/or to assess whether individual images are suitable for inclusion in such libraries.
Systems and methods of using a surrogate machine learning model, based on a CFD model, to predict the mixing quality in steady state mixing tanks are provided. An exemplary method includes generating a plurality of training CFD models for a plurality of training steady state mixing configurations based on a plurality of steady state mixing factors associated with each training steady state mixing configuration; calculating a mixing quality for each training steady state mixing configuration using each respective training CFD model; generating a training dataset that includes the steady state mixing factors associated with each training steady state mixing configuration, and the calculated mixing quality for each training steady state mixing configuration; and training a machine learning model, using the training dataset, to predict mixing qualities for steady state mixing configurations based on based on steady state mixing factors associated with the steady state mixing configurations.
B01F 27/808 - Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with stirrers driven from the bottom of the receptacle
G06F 30/28 - Design optimisation, verification or simulation using fluid dynamics, e.g. using Navier-Stokes equations or computational fluid dynamics [CFD]
Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formule (I).
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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 31/444 - 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 31/473 - Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
A61K 31/4741 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
A61K 31/4743 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having sulfur as a ring hetero atom
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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - Pyrimidines; Hydrogenated 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
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 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
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
Provided herein are processes for synthesizing intermediates useful in preparing Mcl-1 inhibitors. In particular, provided herein are processes for synthesizing compound IA, wherein R1 is described herein. Compound IA can be useful in synthesizing compound A1, or a salt or solvate thereof, and compound A2, or a salt of solvate thereof.
B01J 31/28 - Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups of the platinum group metals, iron group metals or copper
C07C 67/14 - Preparation of carboxylic acid esters from carboxylic acid halides
C07C 67/293 - Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton
C07C 69/16 - Acetic acid esters of dihydroxylic compounds
Provided herein is a process for preparing compound A comprising (a) admixing 2-isopropyl-4-methylpyridin-3-amine (Compound B), or a salt thereof, a first base, and a reactive compound comprising phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanato-2-isopropyl-4-methylpyridine (Compound C); (b) admixing Compound C and 2,6-dichloro-5-fluoronicotinamide (Compound D) to form 2,6-dichloro-5-fluoro-N-((2-isopropy1-4-methylpyridin-3-yl)carbamoyl)nicotinamide (Compound E); and (c) admixing Compound E and a second base to form a product mixture comprising Compound A and the second base. Also provided herein is a process for synthesizing AMG 510 comprising using Compound A prepared according to the disclosed processes [Insert Structure] (Compound A).
Methods and systems for determining a viscosity of liquid samples are provided. The methods and systems utilize an acoustic liquid handler (101). The acoustic liquid handler (101) has a first location (105) adapted to receive a liquid sample. The acoustic liquid handler (101) is configured to apply one or more acoustic signals (217) to the liquid sample in the first location (105) until a specified amount of the liquid sample has been transferred from the first location to a second location (109) of the acoustic liquid handler (101). The acoustic liquid handler (101) has a controller (202) configured to determine the viscosity of the liquid sample based on a number of acoustic signals (217) required to transfer the specified amount of the liquid sample from the first location (105) to the second location (109).
G01N 11/02 - Investigating flow properties of materials, e.g. viscosity or plasticity; Analysing materials by determining flow properties by measuring flow of the material
The ability to generate a single antibody-based construct that can recognize multiple targets simultaneously, is paramount to advance many therapeutics candidates to clinic. Often, this implies extensive protein design with vary degrees of success. In the case of multispecific antibodies, the driving of the HC/LC pairing in the Fab region represents one of the most difficult challenges yet in the field of multispecific engineering. Described here is the discovery of a new single chain Fab module that utilizes a novel linker between VL-CL and VH-CH1 domains which will further enable the production of multispecifics.
Provided herein are methods of treating heart failure in patients exhibiting one or more additional features, comprising administering to the patient a therapeutically effective amount of omecamtiv mecarbil, or a hydrate, salt, or salt of a hydrate thereof.
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs 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
91.
IN-PROCESS VERIFICATION OF CALIBRATION STATUS OF PH PROBES
Automated systems and methods for low-pH viral inactivation include adding an elution pool to a first vessel with an acid. Once first vessel pH probes measure sufficiently low pH, the pool is transferred to a second vessel, where the pH is checked again, and the pool is held for a time sufficient to reduce virus concentration to a safe level, and neutralized, filtered, and transferred to a third vessel. Meanwhile, the first vessel is filled with a known-pH buffer, which is checked against readings from first vessel pH probes to determine whether recalibration is needed. After the pool is transferred to the third vessel, the second vessel is filled with a known-pH buffer, which is checked against readings from second vessel pH probes to determine whether recalibration is needed. The process repeats when the known-pH buffer is dumped and a new elution pool is added to the first vessel.
A drug delivery device assembly is provided, including an injector housing, a needle assembly, a drive assembly, and a reflective surface. The injector housing may include a body with a proximal end, a distal end, a longitudinal axis extending between the proximal end and the distal end, and at least one window. The needle assembly is at least partially disposed within the body and may include a syringe barrel containing a medicament and a needle or a cannula, wherein at least a portion of the syringe barrel positioned such as to be visible through the at least one window. The drive assembly is at least partially disposed within the body and operably coupled with the needle assembly to urge the medicament through the needle or cannula during an injection sequence. The reflective surface is positioned with respect to the window such as to increase visibility of the syringe barrel.
A61M 5/42 - 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 having means for desensitising skin, for protruding skin to facilitate piercing, or for locating point where body is to be pierced
93.
DRUG DELIVERY DEVICE ASSEMBLY AND ACCESSORY FOR DRUG DELIVERY DEVICE
A drug delivery device assembly is provided, including an injector housing, a needle assembly, a drive assembly, and a dose feedback accessory. The injector housing may include a body with a proximal end, a distal end, a longitudinal axis extending between the proximal end and the distal end, and at least one window. The needle assembly is at least partially disposed within the body and may include a syringe barrel containing a medicament, a plunger stopper disposed in the syringe barrel, and a needle or a cannula. The drive assembly is at least partially disposed within the body and operably coupled with the needle assembly to urge the medicament through the needle or cannula during an injection sequence. The dose feedback accessory includes an accessory body configured to be selectively coupled with the injector housing and a feedback indicator configured to convey to a user information relating to an injection status event.
The present invention relates to methods for treating or preventing atherosclerotic cardiovascular disease and other conditions associated with elevated levels of lipoprotein (a) (Lp(a)) using RNAi constructs targeting the LPA gene, which encodes apolipoprotein(a), a component of Lp(a) particles. In particular, the present invention relates to methods for reducing serum Lp(a) levels and reducing the risk of cardiovascular events in patients with elevated levels of Lp(a) comprising administering an LPA-targeted RNAi construct according to specific dosage regimens. Pharmaceutical compositions comprising the LPA-targeted RNAi constructs for use in the methods are also disclosed.
The invention relates to a polypeptide or polypeptide construct comprising: a binding domain binding to an extracellular epitope of the human CD3s chain comprising or consisting of a VH region and a VL region, wherein i) the VH region comprises: a CDR- H1 sequence of X1YAX2N, where X1 is K, V, S, G, R, T, or I; and X2 is M or I; a CDR-H2 sequence of RIRSKYNNYATYYADX1VKX2, where ?1 is S or Q; and X2 is D, G, K, S, or E; and a CDR-H3 sequence of HX1NFGNSYX2SX3X4AY, where ?? is G, R, or A; X2 is I, L, V, or T; X3 is Y, W or F; and X4 is W, F or Y; and ii) wherein the VL region comprises: a CDR-L1 sequence of ?? SSTGAVTX2X3X4YX5N, where ?? is G, R, or A; X2 is S or T; X3 is G or S; X4 is N or Y; and X5 is P or A; a CDR-L2 sequence of X1TX2X3X4X5X6; where ?1 is G or A; X2 is K, D, or N; X3 is F, M or K; X4 is L or R; X5 is A, P, or V; and X6 is P or S; and a CDR-L3 sequence of X1LWYSNX2VW, where X1 is V, A, or T; and X2 is R or L; and iii) wherein one or more of CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one amino acid substitution or a combination thereof selected from X24V and X24F in CDR-H1; D15, and X116A in CDR-H2; H1, X12E, F4, and N6 in CDR-H3; and X11L and W3 in CDR-L3. The invention also relates to a polynucleotide encoding the polypeptide or polypeptide construct of the invention, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or with said vector. Moreover, the invention also provides for a process for the production of said polypeptide or polypeptide construct and a pharmaceutical composition comprising said polypeptide or polypeptide construct of the invention. Furthermore, the invention relates to medical uses of said polypeptide or polypeptide construct and kits comprising said polypeptide or polypeptide construct.
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 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
The present invention relates to a polypeptide or a polypeptide construct comprising a domain which binds to Claudin 6 (CLDN6) and another domain which binds to CD3. Moreover, the invention provides a polynucleotide encoding the construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for producing the construct of the invention, a medical use of said construct and a kit comprising said construct.
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 invention provides multitargeting bispecific antigen-binding molecules characterized by comprising a first and a second bispecific entity each comprising a domain binding to target, a second domain binding to an extracellular epitope of the human and the Macaca CD3e chain, wherein both bispecific entities are linked to each other by a spacer which spaces apart the first and the second bispecific entity. Moreover, the invention provides a polynucleotide, encoding the multitargeting bispecific antigen-binding molecule, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.
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 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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
99.
DRUG DELIVERY DEVICE ASSEMBLY AND ACCESSORY FOR DRUG DELIVERY DEVICE
A drug delivery device assembly is provided, including an injector housing, a needle assembly, a drive assembly, and an alignment accessory. The injector housing may include a body with a proximal end, a distal end, and a longitudinal axis extending between the proximal end and the distal end. The needle assembly is at least partially disposed within the body and may include a syringe barrel containing a medicament and a needle or a cannula. The drive assembly is at least partially disposed within the body and operably coupled with the needle assembly to urge the medicament through the needle or cannula during an injection sequence. The needle or cannula is configured to pierce a patient's skin at an injection site. The alignment accessory includes an accessory body configured to be selectively coupled with the injector housing and an alignment aid configured to aid alignment of the accessory body with respect to the patient's skin at the injection site.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
A61M 5/42 - 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 having means for desensitising skin, for protruding skin to facilitate piercing, or for locating point where body is to be pierced
100.
DRUG DELIVERY DEVICE ASSEMBLY AND ACCESSORY FOR DRUG DELIVERY DEVICE
A drug delivery device assembly is provided, including an injector housing, a needle assembly, a drive assembly, and a needle shield indicator accessory. The injector housing may include a body with a proximal end, a distal end, and a longitudinal axis extending between the proximal end and the distal end, and a needle shield positioned adjacent to the distal end and movable between an extended position and a retracted position. The needle assembly is at least partially disposed within the body and may include a syringe barrel containing a medicament and a needle or a cannula. The drive assembly is at least partially disposed within the body and operably coupled with the needle assembly to urge the medicament through the needle or cannula during an injection sequence. The needle shield indicator accessory includes an accessory body configured to be selectively coupled with the injector housing and a needle shield indicator configured to indicate to a user whether the needle shield is in the retracted position.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
patents
