Systems and methods for delayed delivery of a drug are disclosed. A drug delivery system may include a delivery member for insertion into a patient and a reservoir configured to receive a volume of a drug. An energy source may be activatable by the patient to actuate the reservoir to deliver the drug to the patient as a single bolus. A lockout system may be configured to have a locked state, wherein the lockout system prevents movement of the delivery member and/or activation of the energy source, and an unlocked state, wherein the lockout system permits movement of the delivery member and/or activation of the energy source. The lockout system may be configured to automatically change from the locked state to the unlocked state after a preselected time period has elapsed. An output element may generate a detectable output after the preselected time period has elapsed for notifying the patient.
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 5/50 - 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
09 - Scientific and electric apparatus and instruments
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Downloadable and recorded software to assist health care practitioners in assessment of patients at risk of osteoporosis-related disorders or conditions; Downloadable computer application software for mobile phones to assist health care practitioners in assessment of osteoporosis patients; downloadable and recorded computer application software for mobile phones, namely, software for integration in electronic medical systems to assist health care practitioners in assessment of osteoporosis patients Providing medical information in the field of osteoporosis-related disorders or conditions
A method of aligning images for 3D imaging of a sample includes, for each of multiple cameras located around a vessel, activating a respective light source that provides backlighting for the vessel, and capturing a respective 2D calibration image of the vessel. The method also includes, for each 2D calibration image, measuring a respective vertical position, horizontal position, and rotation of the image, in part by detecting edges of the vessel as depicted in the image. The method also includes generating calibration data based on the measured vertical positions, horizontal positions, and rotations for the respective 2D calibration images, capturing, by each camera, a respective set of 2D images of the sample in the vessel, and digitally resampling, using the calibration data, at least one of the respective sets of 2D images to correct for vertical offset, horizontal offset, and rotational offset of the set(s) of 2D images.
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
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:
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:
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 491/147 - 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
5.
HETEROCYCLIC COMPOUNDS AS TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2 AGONISTS AND METHODS OF USE
The present disclosure provides compounds of Formula I, useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 (“TREM2”).
The present disclosure provides compounds of Formula I, useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 (“TREM2”).
The present disclosure provides compounds of Formula I, useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 (“TREM2”).
This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula I.
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
A drug product reconstitution processing system includes a drug vial tray having a plurality of walls, a first robotic arm movable between a plurality of positions above the drug vial tray, and a second robotic arm movable between a plurality of positions above the drug vial tray. The first robotic arm includes a drug vial transfer system adapted to retrieve a drug vial disposed within one of the plurality of wells and a vial agitation system adapted to agitate the drug product contained within the drug vial. The second robotic arm includes a drug vial reconstitution system adapted to selectively add a fluid to the drug vial and/or remove a fluid from the drug vial.
Methods of treating cancer or enhancing an anti-cancer effect associated with administration of a T-cell redirecting therapy in a subject in need thereof, comprising administering to the subject an anti-IL-2Rβγ heavy chain-only antibody or antigen binding fragment thereof in combination with a T-cell redirecting therapy are disclosed, along with uses of anti-IL-2Rβγ heavy chain-only antibodies and antigen binding fragments thereof and/or T-cell redirecting therapies in the manufacture of a medicament adapted for use in a method described herein; pharmaceutical compositions comprising anti-IL-2Rβγ heavy chain-only antibodies and antigen binding fragments thereof and/or T-cell redirecting therapies for use in a method described herein; and combination products.
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 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 16/30 - 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
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
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
10.
THERAPEUTIC AGENTS FOR REDUCING PARATHYROID HORMONE LEVELS
Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1—X2—X3—X4—X5—X6—X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2—X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.
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
C07K 5/103 - Tetrapeptides the side chain of the first amino acid being acyclic, e.g. Gly, Ala
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
11.
TETHERED HETEROCYCLIC INHIBITORS OF KRAS G12C MUTANT PROTEINS AND USES THEREOF
KRASKRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic, and colorectal cancer. In particular, the disclosure provides compounds of Formula (II) and pharmaceutically acceptable salts thereof, wherein the substituents are as described.
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 405/00 - 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
C07D 413/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic, and colorectal cancer. In particular, the disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein the substituents are as described.
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 405/00 - 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
C07D 413/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
KRAS KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic, and colorectal cancer. In particular, the disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein the substituents are as described.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The present invention relates to a method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19xCD3 bispecific single chain antibody construct to an adult patient in the need 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
Provided here is a combination comprising (i) Compound A having the name of 1-((1S,1aS,6bS)-5-((7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yl)oxy)-1a,6b-dihydro-1H-cyclopropa[b]benzofuran-1-yl)-3- (2,4,5-trifluorophenyl) urea, or the structure of formula (I): or a pharmaceutically acceptable salt, tautomer, stereoisomer, enantiomer, isotopologue, solvate, or prodrug thereof; and an anti-EGFR antibody, e.g., panitumumab; compositions comprising the same; and methods of using such combinations and compositions in the treatment of cancer, e.g., colorectal cancer, pancreatic cancer, and non-small cell lung cancer.
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
C07D 307/81 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
The present disclosure provides method of administering sotorasib to a patient, e.g., a patient with a cancer comprising a KRAS G12C mutation, wherein the patient is further in need of treatment with a breast cancer resistance protein (BCRP) substrate, e.g., rosuvastatin.
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.
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
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
18.
TREM2 AGONIST BIOMARKERS AND METHODS OF USE THEREOF
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.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
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
19.
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.
A method for estimating tumor growth dynamics includes obtaining, by one or more processors, progression-free survival (PFS) data for a plurality of patients, the PFS data indicating (i) a plurality of observation times, and (ii) how many of the plurality of patients, at each of the plurality of observation times, had a PFS event within a most recent time window; determining, by the one or more processors and based on the PFS data, a population distribution for one or more patient-specific parameters; obtaining, by the one or more processors, measured tumor growth data for a particular patient subject to a drug treatment; estimating, by the one or more processors, tumor growth for the particular patient based on (i) the measured tumor growth data and (ii) the population distribution for the one or more patient-specific parameters; and causing, by the one or more processors, a display to present a visual indication of the estimated tumor growth for the particular patient.
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 Formula (I).
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 Formula (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 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 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
A drug processing system includes a workstation, at least one deck module movably positionable within the workstation, at least one filter plate operably coupled with the at least one deck module, an agitating member, and a liquid handler member. The at least one filter plate has a plurality of wells to receive a fluid therein. The agitating member is adapted to move the at least one filter plate according to an agitation system. The liquid handler member is adapted to selectively add a fluid to at least one of the plurality of wells and/or remove a fluid from the at least one of the plurality of wells according to a liquid handling system. The agitating member is adapted to move the at least one filter plate while the liquid handler member selectively adds and/or removes the fluid from the at least one of the plurality of wells.
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
G01N 35/04 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations - Details of the conveyor system
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
A method for estimating tumor growth dynamics includes obtaining, by one or more processors, progression-free survival (PFS) data for a plurality of patients, the PFS data indicating (i) a plurality of observation times, and (ii) how many of the plurality of patients, at each of the plurality of observation times, had a PFS event within a most recent time window; determining, by the one or more processors and based on the PFS data, a population distribution for one or more patient-specific parameters; obtaining, by the one or more processors, measured tumor growth data for a particular patient subject to a drug treatment; estimating, by the one or more processors, tumor growth for the particular patient based on (i) the measured tumor growth data and (ii) the population distribution for the one or more patient-specific parameters; and causing, by the one or more processors, a display to present a visual indication of the estimated tumor growth for the particular patient.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
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
24.
NEEDLE INSERTION MECHANISM FOR DRUG DELIVERY DEVICE
A drug delivery device includes a housing, a container disposed in the housing, an activation mechanism, a needle insertion mechanism, and a fluid flow path. The container has an inner volume to contain a medicament which is urged out of the container by the activation mechanism. The needle insertion mechanism includes an actuation assembly adapted to insert a needle and a cannula to deliver the medicament from the container and a valve assembly. The fluid flow connection is coupled with the container and the needle insertion mechanism and is adapted to allow the medicament to flow from the container to the needle insertion mechanism. The valve assembly is repeatedly movable between at least a valve open position and a valve closed position to selectively allow and restrict the medicament to flow through the needle and/or the cannula.
A drug delivery device may include a housing defining a longitudinal axis and having an opening and a drug storage container including a delivery member 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 expel a drug from the drug storage container through the delivery member, the plunger including a body portion having an inner wall defining an axial chamber and an outer wall cooperating with the inner wall to define a body thickness. The device may further include a plunger biasing member disposed at least partially within the axial chamber, the plunger biasing member configured to urge the plunger toward the distal end of the drug storage container.
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.
G06T 11/60 - Editing figures and text; Combining figures or text
G01N 21/90 - Investigating the presence of flaws, defects or contamination in a container or its contents
G06T 3/60 - Rotation of a whole image or part thereof
G06T 5/40 - Image enhancement or restoration by the use of histogram techniques
G06V 10/44 - Local feature extraction by analysis of parts of the pattern, e.g. by detecting edges, contours, loops, corners, strokes or intersections; Connectivity analysis, e.g. of connected components
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.
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.
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:
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:
The disclosure provides methods of purifying a target protein, e.g., an antibody, from a host cell such as a mammalian cell using purification protocols incorporating harvest recovery operations comprising a continuous solids discharge disc stack centrifugation step followed by flocculation and depth filtration steps. The protein harvest methods of the disclosure recover high yields of purified target protein from perfusion cultures having a packed cell volume of greater than or equal to 16%, using an unconventional yet effective process.
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.
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
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
A drug delivery device for delivering a medicament includes a housing, a pump, drive component, an inlet fluid path, an outlet fluid path, an inlet pressure sensor, an outlet pressure sensor, and a controller. The pump is coupled with the housing. The drive component is for driving the pump. The inlet fluid path is configured to deliver medicament to the pump. The outlet fluid path is configured to receive medicament from the pump. The inlet pressure sensor is positioned along the inlet fluid path and configured to measure inlet fluid pressure. The outlet pressure sensor is positioned along the outlet fluid path and configured to measure outlet fluid pressure. The controller is workingly coupled with the inlet pressure sensor, the outlet pressure sensor, and the drive component, wherein the controller is configured to adjust at least one parameter of the drive component based on input information received from the inlet pressure sensor and/or the outlet pressure sensor.
A method for monitoring and/or controlling a biopharmaceutical process includes querying, based on a first spectral scan vector of the biopharmaceutical process, an observation database comprising observation data sets associated with past scans. Each of the observation data sets includes spectral data and a corresponding actual analytical measurement. Querying the observation database includes determining first parameters defining a set of distributions for the first spectral scan vector, and selecting as training data, from among the observation data sets, particular observation data sets based on (i) the first parameters and (ii) other parameters defining respective sets of distributions for the observation data sets. The method also includes calibrating, using the selected training data, a local model specific to the biopharmaceutical process. The method also includes predicting an analytical measurement of the biopharmaceutical process, by using the local model to analyze spectral data generated when scanning the biopharmaceutical process.
The present invention provides provide a pharmaceutical composition comprising a bispecific antigen binding molecule at an increased concentration, wherein the composition comprises at least one buffer agent, at least one saccharide; and at least one stabilizing agent selected from Ethylenediaminetetraacetic acid (EDTA), Diethylenetriaminepentetic acid (DTP A), and citric acid in order to stabilize the bispecific antigen-binding agent even at higher concentration.
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
34.
LATTICE LEADING AWARENESS TO ACTION THROUGH IMPLEMENTATION OF CARDIOMETABOLIC EFFORTS
41 - Education, entertainment, sporting and cultural services
Goods & Services
Educational services, namely, providing online training, educational information, awareness, tools and resources in the fields of health, medicine, healthcare, diseases and treatments to improve the quality of cardiometabolic patient care
35.
RNAI CONSTRUCTS AND METHODS FOR INHIBITING FAM13A EXPRESSION
The present application relates to compositions and methods for modulating expression of Family with Sequence Similarity 13 Member A (FAM13A) protein. In particular, the present application relates to nucleic acid-based therapeutics for reducing FAM13A gene expression via RNA interference and methods of using such nucleic acid-based therapeutics to reduce abdominal adiposity, reduce body weight, reduce fat mass, improve metabolic parameters including insulin resistance and non-alcoholic steatohepatitis (NASH), and reduce risk of myocardial infarction.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A method for monitoring and/or controlling a biopharmaceutical process includes querying, based on a first spectral scan vector of the biopharmaceutical process, an observation database comprising observation data sets associated with past scans. Each of the observation data sets includes spectral data and a corresponding actual analytical measurement. Querying the observation database includes determining first parameters defining a set of distributions for the first spectral scan vector, and selecting as training data, from among the observation data sets, particular observation data sets based on (i) the first parameters and (ii) other parameters defining respective sets of distributions for the observation data sets. The method also includes calibrating, using the selected training data, a local model specific to the biopharmaceutical process. The method also includes predicting an analytical measurement of the biopharmaceutical process, by using the local model to analyze spectral data generated when scanning the biopharmaceutical process.
G05B 13/02 - Adaptive control systems, i.e. systems automatically adjusting themselves to have a performance which is optimum according to some preassigned criterion electric
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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 generally relates to electrophoretic mass spectrometry probes and systems and methods of uses thereof. In certain aspects, the invention provides a mass spectrometry probe having a hollow body with a distal tip, an electrically conductive hollow conduit, and an electrode. The electrically conductive hollow conduit may be operably coupled to a reservoir and a power source, and the electrically conductive hollow conduit may be configured to transport a liquid sample into the hollow body and polarize the liquid sample as it flows through the electrically conductive hollow conduit and into in the hollow body. The electrode and the electrically conductive hollow conduit are disposed within the hollow body (e.g., at different heights within the hollow body).
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
The present invention is directed to methods of identifying and treating a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and administering a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as high. The present invention is also directed to methods of identifying a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and withholding a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as low. The invention is also directed to methods of performing an ELISA, including sequential steps of contacting a solid surface with a plurality of solutions each comprising in turn a capture antibody, a blocking agent, a sample suspected of containing an analyte, a detection antibody and an enzyme conjugate, in which the solid surface is subjected to a wash process after each sequential step.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
G01N 33/569 - Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
The disclosure provides a method of producing etanercept from Chinese hamster ovary cells (CHO), the method comprising running an N-1 bioreactor system using a recirculating tangential flow filtration (RTF) or alternating tangential flow filtration (ATF) cell retention device under conditions that maintain a cell aggregate size of at least 20 μm, before running an N production bioreactor.
A drug reconstitution system includes a robotic arm movable between a plurality of positions, at least one bracket member operably coupled with the robotic arm, and at least one coaxial needle operably coupled with the robotic arm. The at least one bracket member includes a mounting region, a support surface, an upper surface, and a throughbore extending through the support surface and the upper surface. The at least one coaxial needle is movably disposed between the throughbore of the at least one bracket member. The at least one coaxial needle is adapted to pierce at least a portion of a vial and dispense a liquid into the vial during drug reconstitution.
A cassette for a drug delivery device is described that includes a sleeve, a syringe having a barrel disposed in the sleeve, and a plunger-stopper slidably disposed within the barrel. The cassette further includes a spacer that is configured to be coupled to the sleeve. The cassette can form a part of an apparatus for injection of a therapeutic product along with a drug delivery device.
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 drug delivery device may include a housing having an opening, a drug storage container, a plunger rod, and a drive mechanism. The drug storage container may have an inner surface at least partially defining a drug storage chamber and an outer surface defining an outer diameter. The drug storage container may further include a plunger stopper and a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state. The drive mechanism may be activatable to drive the plunger stopper in a distal direction to expel a drug from the drug storage container through the delivery member. The drive mechanism may have an inner surface with an inner diameter greater than the outer diameter of the outer surface of the drug storage container.
A large scale bioreactor system includes a stainless steel large scale bioreactor having at least one valve assembly, and an aseptic connector assembly coupled to the at least one valve assembly of the bioreactor. A perfusion device includes an Alternating Tangential Filtration assembly with an autoclaved valve assembly coupled to the aseptic connector assembly, and the aseptic connector assembly includes one of a triclamp aseptic connector or a hose assembly. Single use feed containers include an aseptic connector assembly.
A large scale bioreactor system includes a stainless steel large scale bioreactor having at least one valve assembly, and an aseptic connector assembly coupled to the at least one valve assembly of the bioreactor. A perfusion device includes an Alternating Tangential Filtration assembly with an autoclaved valve assembly coupled to the aseptic connector assembly, and the aseptic connector assembly includes one of a triclamp aseptic connector or a hose assembly. Single use feed containers include an aseptic connector assembly.
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 method of limiting subvisible particles in a syringe partially filled with a drug product. The method includes applying a quantity of silicon oil to a syringe barrel of a syringe, and the quantity of silicon oil is in a range of approximately 0.4 mg to approximately 0.6 mg. The syringe barrel includes a proximal end, a distal end, and a reservoir, and a drug product is disposed in a distal end of the reservoir at the distal end of the syringe barrel. The method also includes placing a plunger portion into the syringe barrel to a depth within the syringe barrel and creating an air gap between the plunger portion and the drug product. The plunger portion is spaced from the drug product, and the air gap includes an air gap length in a range of approximately 1.2 mm to approximately 3.5 mm.
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
Disclosed herein are optical systems and platforms for the simultaneous assessment of one or more properties of a sample, e.g., a biomolecule-containing pharmaceutical composition, including, e.g., aggregation, phase separation, and/or viscosity, as well as methods of using the same.
A method is provided, comprising: analyzing a first image, captured by a bright-field microscope, of cells distributed between pen regions, using an image segmentation technique to identify areas corresponding to cell locations in the first image; generating a first mask based on the identified areas corresponding to cell locations; generating a image mask, corresponding to locations without cells in the first image; applying the first mask and the second mask to a second image, captured by a fluorescence microscope, including the same cells distributed between the same pen regions; analyzing the second image to determine an indication of a first pixel intensity corresponding to the first mask for each pen region, and a second pixel intensity corresponding to the second mask for each pen region; and identifying indications of cell populations of each of the pen regions based on the first and second pixel intensities for each pen region.
Systems and methods for evaluating impacts of processing time of a process (such as a bioprocess) can include (a) obtaining a model trained using historical bioprocess data, (b) determining, by applying input to the model, predicted output that would result when operating the bioprocess in accordance with the input, wherein either: (i) the input includes a processing time and the predicted output includes a product quality, or (ii) the input includes a product quality parameter and the predicted output includes a processing time, and (c) displaying or storing the values of the predicted output. Further aspects include receiving the input as user input from a user. Still further aspects include presenting the predicted output to the user via a graphical user interface.
A drug delivery device for delivering a medicament includes a pump first housing, a pump second housing, an inlet fluid path, and an outlet fluid path. The pump first housing is at least partially supporting and/or surrounding a fluid displacement assembly. The pump second housing is at least partially supporting and/or surrounding a drive component for driving the fluid displacement assembly. The inlet fluid path is configured to deliver medicament to the fluid displacement assembly. The outlet fluid path is configured to receive medicament from the fluid displacement assembly. The pump first housing and the pump second housing are removably coupled with each other.
A drug delivery device includes a housing, a container disposed in the housing, an activation mechanism, a needle assembly, and a temperature indicator. The housing defines an inner volume and includes at least one opening. The container contains a medicament which is urged out of the container by the activation mechanism. The needle assembly has a needle and/or a cannula to deliver the medicament from the container. The temperature indicator is operably coupled with the outer surface of the container and is responsive to a change in temperature of the container.
A method for reducing the viscosity of a pharmaceutical formulation is provided that utilizes a viscosity-reducing concentration of an excipient selected from the group consisting of the n-acetyl arginine, n-acetyl lysine, n-acetyl proline and mixtures thereof in combination with a therapeutiv protein. A stable pharmaceutical formulation is also provided.
The present disclosure provides crystalline and amorphous forms of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, including several anhydrous, hydrate and solvate forms, and solid state forms thereof, pharmaceutical compositions, and methods of treating a disease mediated by KRAS G12C inhibition.
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 16/42 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against immunoglobulins (anti-idiotypic antibodies)
Provided are compounds of Formula (I) having activity as inhibitors of G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and uses and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic and colorectal cancers.
Provided are compounds of Formula (I) having activity as inhibitors of G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and uses and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic and colorectal cancers.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A syringe assembly includes a syringe having a barrel and a needle hub disposed at a distal end of the syringe and a needle shield including an inner surface and a cavity for receiving the needle hub. The inner surface of the needle shield engaging an outer surface of the needle hub to form a sealing interface therebetween and removably couple the needle hub and the needle shield when the needle shield is disposed on the syringe. In some examples, the sealing interface comprises at least one contoured feature configured to limit or reduce an amount of force required to remove the needle shield from the syringe.
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 needle shield assembly includes a first needle shield at least partially made of a first material and having a proximal end and a distal end, the proximal end of the first needle shield including a cavity; and a second needle shield at least partially made of a second material, the second needle shield mechanically coupled with at least the proximal end of the first needle shield. Additionally, the second material of the second needle shield is harder than the first material of the first needle shield.
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
62.
KRAS G12C INHIBITORS AND METHODS OF USING THE SAME
Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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
The present disclosure provides materials and methods identifying, selecting, and characterizing cells that express and secrete non-Fc containing biomolecules.
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.
Methods for mixing fluids including etanercept include providing a tank (100) having an impeller (118) with a 25.4 cm (10 inch) blade diameter disposed therein, filling a tank with a liquid composition comprising etanercept and one or more buffers to a level within the tank to cover the impeller, and operating the impeller to mix the liquid composition to a homogeneous state while maintaining a maximum shear stress imparted on the mixture of fluids at 125,000 s-1 or below.
B01F 23/40 - Mixing liquids with liquids; Emulsifying
B01F 23/43 - Mixing liquids with liquids; Emulsifying using driven stirrers
B01F 27/61 - Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a horizontal or inclined axis about an inclined axis
B01F 27/71 - Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a horizontal or inclined axis with propellers
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
B01F 33/453 - Magnetic mixers; Mixers with magnetically driven stirrers using supported or suspended stirring elements
B01F 35/53 - Mixing receptacles characterised by the configuration of the interior, e.g. baffles for facilitating the mixing of components
42 - Scientific, technological and industrial services, research and design
Goods & Services
Research and development of pharmaceutical preparations; research and development of pharmaceutical preparations in the field of metabolic diseases, namely weight management and diabetes; medical and scientific research information in clinical trials in the field of metabolic diseases, namely weight management and diabetes; providing websites featuring medical and scientific research information about the diagnostic, prophylactic and therapeutic properties of pharmaceuticals in the field of metabolic diseases, namely weight management and diabetes; providing websites featuring medical and scientific research information about pharmaceuticals preparations in the field of metabolic diseases, namely weight management and diabetes; providing websites that features non-downloadable computer software that enables users to access, manage, update and display electronic databases in the field of metabolic diseases, namely weight management and diabetes
67.
METHODS AND SYSTEMS OF DETERMINING A VISCOSITY OF LIQUID SAMPLES
Methods and systems for determining a viscosity of liquid samples are provided. The methods and systems utilize an acoustic liquid handler. The acoustic liquid handler has a first location adapted to receive a liquid sample. The acoustic liquid handler is configured to apply one or more acoustic signals to the liquid sample in the first location until a specified amount of the liquid sample has been transferred from the first location to a second location of the acoustic liquid handler. The acoustic liquid handler has a controller configured to determine the viscosity of the liquid sample based on a number of acoustic signals required to transfer the specified amount of the liquid sample from the first location to the second location.
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
68.
IMAGING-BASED SYSTEM FOR MONITORING QUALITY OF CELLS IN CULTURE
Described herein are techniques to regulate the treatment of a culture of cells having cells corresponding to different cell categories. Some techniques may be used together with a cell imaging and incubation system including an imaging sensor configured to obtain an image of the culture and an incubator configured to incubate the culture. Regulation of treatment of the culture may be based on the processing of an image of the culture obtained by the imaging sensor of the system. The processing may include segmenting the image of the culture into multiple image segments by assigning individual pixels of the image to corresponding cell categories. According to some embodiments, the techniques include determining, based on the image segments, an amount of the culture corresponding to a particular cell category. The amount of the culture corresponding to the particular cell category may inform regulation of the treatment of the culture.
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.
Provided herein are methods of producing an antibody composition comprising determining the relative unpaired afucosylated glycan content and/or the relative unpaired high mannose glycan content of a sample of the antibody composition and selecting the antibody composition for downstream processing based on the relative unpaired afucosylated glycan content and/or relative unpaired high mannose glycan content and/or the ADCC level of the antibody composition. Related methods of determining the relative unpaired glycan content of an antibody composition and methods of modifying the ADCC level of an antibody composition are provided herein.
The present invention is directed to methods of identifying and treating a human subject harboring a tumor or other disease comprising assessing HRG gene expression at an mRNA level in the human subject and administering a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at an mRNA level is assessed as high. The present invention is also directed to methods of identifying a human subject harboring a tumor or other disease comprising assessing HRG gene expression at an mRNA level in the human subject and withholding a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at an mRNA level is assessed as low.
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
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
72.
IMAGING-BASED SYSTEM FOR MONITORING QUALITY OF CELLS IN CULTURE
Described herein are techniques to regulate the treatment of a culture of cells having cells corresponding to different cell categories. Some techniques may be used together with a cell imaging and incubation system including an imaging sensor configured to obtain an image of the culture and an incubator configured to incubate the culture. Regulation of treatment of the culture may be based on the processing of an image of the culture obtained by the imaging sensor of the system. The processing may include segmenting the image of the culture into multiple image segments by assigning individual pixels of the image to corresponding cell categories. According to some embodiments, the techniques include determining, based on the image segments, an amount of the culture corresponding to a particular cell category. The amount of the culture corresponding to the particular cell category may inform regulation of the treatment of the culture.
FAM13AFAM13A gene expression via RNA interference and methods of using such nucleic acid-based therapeutics to reduce abdominal adiposity, reduce body weight, reduce fat mass, improve metabolic parameters including insulin resistance and non-alcoholic steatohepatitis (NASH), and reduce risk of myocardial infarction.
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
75.
PROCESS FOR PREPARING 7-CHLORO-6-FLUORO-1-(2-ISOPROPYL-4-METHYLPYRIDIN-3-YL)PYRIDO[2,3-D]PYRIMIDINE-2,4(1H,3H)-DIONE
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-isopropyl-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).
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-isopropyl-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).
The disclosure provides materials and methods for assessing the presence and level of polyanionic compounds in a sample that inhibit PCR reactions, including assays for the presence, and optionally the amount, of polyvinyl sulfonate, as well as materials and methods for the reduction or removal of such compounds from buffer solutions and from protein solutions using a variety of approaches, including titration-based techniques.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
77.
REAL TIME PCR METHOD TO DETECT BOVINE PARVOVIRUS 3
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
78.
METHODS AND SYSTEMS FOR SELECTING CONDITIONS FOR MAKING INHALATION FORMULATIONS
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.
A device, method, and system for drug delivery includes a casing for housing a drug storage container, the drug storage container including a dose delivery member, at least a portion of the dose delivery member extending through an opening in the casing; a guard movable relative to the casing between extended and retracted positions, the portion of the dose delivery member being surrounded by the guard in the extended position and the portion of the dose delivery member being at least partially exposed when the guard is in the retracted position; an interference arrangement for providing selected threshold of resistance to movement of the guard from the extended position to the retracted position during insertion of the dose delivery member into body tissue at an injection site, the detent arrangement having a first member associated with a surface within the casing, and a second member extending from the guard, the first and second members engaging one another to retain the guard in the extended position, one of the first and second members moving if the selected threshold of resistance is exceeded to allow the members to slide past one another to allow the guard to move into the retracted position when the device is pressed toward the injection site during insertion of the dose delivery member.
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
Provided herein are methods of treating erosive hand osteoarthritis (OA) in a subject in need thereof, methods of reducing radiographic erosive progression, joint space narrowing, cartilage degradation, and/or bone formation in a subject in need thereof (e.g., a subject suffering from erosive hand OA), methods of inhibiting the development of new erosive joints in a subject in need thereof (e.g., a subject suffering from erosive hand OA), and methods of reducing pain in a subject with erosive hand OA. Also provided herein are uses of denosumab in the manufacture of a medicament adapted for use in a method described herein, as well as pharmaceutical compositions comprising denosumab for use in a method described herein.
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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
Provided herein are methods of treating a cancer in a patient wherein the patient has a KRAS G12C mutation, comprising administering to the patient a therapeutically effective combination of sotorasib and RMC- 4630.
A method of computational modeling to predict stability of a lyophilized drug product includes receiving model parameters describing a virtual cake, a virtual vial, a virtual stopper, and a virtual ambient environment. The method also includes computing, by implementing a computational model and at each of a plurality of virtual time steps, a change in water amount or concentration in the virtual cake, virtual air within the virtual vial, and the virtual stopper, in part by applying the model parameters to the computational model. The method also includes generating information for display to a user via a user interface.
G16C 60/00 - Computational materials science, i.e. ICT specially adapted for investigating the physical or chemical properties of materials or phenomena associated with their design, synthesis, processing, characterisation or utilisation
G16C 20/70 - Machine learning, data mining or chemometrics
The present invention provides to a antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody 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
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
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
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.
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
B01F 35/00 - Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
G06F 30/28 - Design optimisation, verification or simulation using fluid dynamics, e.g. using Navier-Stokes equations or computational fluid dynamics [CFD]
89.
FLEXIBLE FACILITY CONFIGURATIONS FOR THERAPEUTIC PRODUCT MANUFACTURING
Disclosed herein are flexible facilities for manufacturing at least one therapeutic product, where the flexible facilities include a reconfigurable, single-use area and a stainless steel area that may be optionally segregated by a partition.
In a method for scaling data across different processes, first time-series data indicative of one or more input, state, and/or output parameters of a first process over time, and second time-series data indicative of one or more input, state, and/or output parameters of a second process over time, are obtained. The method also includes generating a scaling model specifying time-varying relationships between the input, state, and/or output parameters of the first and second processes, and transferring, using the scaling model, source time-series data associated with a source process to target time-series data associated with a target process. The source time-series data is indicative of one or more input, state, and/or output parameters of the source process over time, and the target time-series data is indicative of input, state, and/or output parameters of the target process over time. The method further includes storing the target time-series data in memory.
G05B 13/04 - Adaptive control systems, i.e. systems automatically adjusting themselves to have a performance which is optimum according to some preassigned criterion electric involving the use of models or simulators
G05B 17/02 - Systems involving the use of models or simulators of said systems electric
G05B 19/418 - Total factory control, i.e. centrally controlling a plurality of machines, e.g. direct or distributed numerical control (DNC), flexible manufacturing systems (FMS), integrated manufacturing systems (IMS), computer integrated manufacturing (CIM)
C12M 1/36 - Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
In some aspects, the present disclosure describes stable formulations comprising pembrolizumab, methods of making stable pharmaceutical formulations thereof, and methods of using stable pharmaceutical formulations 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
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.
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.
C07D 513/00 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups , or
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
93.
COMBINATION TREATMENT FOR TREATING CANCER CARRYING KRAS G12C MUTATIONS
KRAS G12CKRAS G12C mutation in a patient comprising (a) administering to the patient a therapeutically effective amount of sotorasib for 14 to 48 days ("an induction period''), and (b) administering to the patient a therapeutically effective amount of sotorasib and a therapeutically effective amount of an anti-PD 1 antibody or an anti-PD-L1 antibody after the induction period for the duration of a combination period.
The disclosure provides methods for decreasing mortality risk and/or improving health in a subject. In some aspects, the disclosure provides methods of using one or more biomarkers to determine the risk of mortality, detect an increase or decrease over time in the risk of mortality, or detect an improvement or decline in health of a subject that occurs, for example, over time, in response to therapeutic intervention, or as a result of changes in diet, fitness, or other lifestyle changes. In some other aspects, the disclosure provides methods for treating a subject to reduce the mortality risk of the subject. Additionally, the disclosure provides methods for using changes in the risk of mortality of a subject to monitor the effectiveness of a therapeutic treatment, dietary restrictions, fitness regimen, or other intervention in a subject, and for continuing, discontinuing, or altering the treatment, restrictions, regimen, or intervention accordingly. Further, the disclosure provides methods for predicting effectiveness of a therapeutic treatment in a subject determined to be at an increased risk of mortality and subsequently treating the subject with the therapeutic treatment if the biomarker level is indicative of effectiveness of the treatment of the subject.
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
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
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
96.
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 method for improving the harvest or purification of a target protein such as a biologic or biosimilar is provided. The method improves conventional harvest/purification methodologies by adding a chromatography step, such as a mixed-mode or ion exchange chromatography step, towards the end of the polishing phase of harvest/purification, after conventional chromatographic polishing steps such as protein A or ion exchange chromatography steps have been completed and the resultant eluate subjected to filtration, such as ultrafiltration/diafiltration. The surprising result of returning to chromatographic polishing after filtration is that all forms of high molecular weight products are reduced, facilitating the purification of target protein sufficient to meet government regulations, such as Quality Target Protein Profiles.
Systems and methods for characterizing a recipe of a syringe filling system can include (a) receiving a value of a plunger depth for a syringe, (b) receiving values of product parameters, (c) determining, by applying the value of the plunger depth and the values of the product parameters as inputs to a model, values of vacuum parameters of the syringe filling system for use when filling the syringe with a product having the values of the product parameters, and (d) displaying or storing the values of the vacuum parameters. Further aspects include characterizing a recipe of the syringe filling system for use with a second value of the plunger depth for a second syringe. Still further aspects include causing one or more vacuum devices of the syringe filling system to operate at the values of the vacuum parameters.
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
B65B 31/02 - Filling, closing, or filling and closing, containers in chambers maintained under vacuum or superatmospheric pressure or containing a special atmosphere, e.g. of inert gas
G16H 40/20 - 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 management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms
Provided herein are recombinant T-cell receptors (TCRs) that can selectively recognize the MAGE-A4-derived peptide GVYDGEEHSV or KVEEHVVRV when presented by HLA-A*0201 sufficiently to activate the recombinant T cell. 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 alloreactivitv.
The present disclosure provides compounds of Formula (I) having activity as inhibitors of G12C mutant KRAS protein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic and colorectal cancers.
The present disclosure provides compounds of Formula (I) having activity as inhibitors of G12C mutant KRAS protein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic and colorectal cancers.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
