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
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
4.
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.
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
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
9.
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
10.
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.
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
14.
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:
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.
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.
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 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.
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
39.
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 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
43.
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
47.
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
49.
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
50.
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
52.
Predicting Shelf Life Stability of Lyophilized Drug Products
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]
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
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
62.
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.
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
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.
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 9/00 - Medicinal preparations characterised by special physical form
Drug delivery devices, sealing members for containers housed within such drug delivery devices, and related methods of assembly are disclosed. The drug delivery device may include a housing, a container disposed in the housing and having an interior volume, a drug disposed in the interior volume, and a septum. The container may have an opening formed in an end surface and which communicates with the interior volume. The septum may include a proximal end inserted through the opening into the interior volume of the container. Additionally, the septum may include a distal end having a flange disposed outwardly of the proximal end and contacting the end surface of the container. At least an end portion of the flange may be made of a material that is permeable to a gaseous sterilizing agent.
The invention relates to a polypeptide or polypeptide construct comprising a first target antigen binding domain, wherein said first target antigen binding domain comprises a VH and a VL variable region linked by a peptide linker, wherein the peptide linker comprises or consists of S(G4X)n or (G4X)n, wherein X is selected from the group consisting of Q, T, N, C, G, A, V, I, L, and M, and wherein n is an integer selected from integers 1 to 20. The invention also relates to a method for improving stability of a polypeptide or polypeptide construct. Moreover, the invention 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.
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 X1 is S or Q; and X2 is D, G, K, S, or E; and a CDR-H3 sequence of HX1NFGNSYX2SX3X4AY, where X1 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 X1 SSTGAVTX2X3X4YX5N, where X1 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 X1 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
68.
METHODS FOR ADMINISTERING THERAPEUTIC DOSES OF BISPECIFIC T-CELL ENGAGING MOLECULES FOR THE TREATMENT OF CANCER
The present invention relates to methods for administering therapeutic doses of bispecific T-cell engaging molecules for the treatment of cancer in a patient. The administration methods reduce the incidence and/or severity of adverse events, such as cytokine release syndrome, and entail administering to a patient a priming dose of the bispecific T-cell engaging molecule by continuous intravenous infusion over a period of days followed by administration of a therapeutic dose of the bispecific T-cell engaging molecule by a bolus intravenous infusion at dosing intervals of at least a week.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The disclosure provides methods, including automated methods, to detect levels of polyanions such as polyvinyl sulfonates in fluids such as buffers by complexometric or titration-based techniques. Such polyanionic compounds have been shown to inhibit enzymes involved in PCR that confounds efforts to monitor the purity of proteins obtained from cell culture, such as biologies and biosimilars.
G01N 31/16 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroups; Apparatus specially adapted for such methods using titration
A robotic inspection platform comprises a robotic arm, an imager, and a controller. The controller causes the robotic arm to retrieve, using its end effector, a container, and to manipulate the container such that the container is sequentially placed in a plurality of orientations while in view of the imager. The controller also causes the imager to capture images, with each of the images being captured while the container is in a respective one of the orientations. The controller also determines one or more attributes of the container, and/or a sample within the container, by analyzing the images using a pattern recognition model and, based on the attribute(s), determines whether the container and/or sample satisfies one or more criteria. If the container and/or sample fails to satisfy the criteria, the controller causes the robotic arm to place the container in an area (e.g., bin) reserved for rejected containers and/or samples.
Provided herein is a process comprising heating a composition comprising (P)-compound A or a salt thereof and a solvent to a temperature of 250° C. to 350° C. to form racemized compound A. Also provided is a process for isolating (P)-compound A from a composition comprising (P)-compound A and a tartrate, as described herein. Further provided herein, is a process for isolating a free acid of a tartrate or a hydrate thereof from a composition comprising a tartrate, (P)-compound A, and an organic solvent.
Provided herein is a process comprising heating a composition comprising (P)-compound A or a salt thereof and a solvent to a temperature of 250° C. to 350° C. to form racemized compound A. Also provided is a process for isolating (P)-compound A from a composition comprising (P)-compound A and a tartrate, as described herein. Further provided herein, is a process for isolating a free acid of a tartrate or a hydrate thereof from a composition comprising a tartrate, (P)-compound A, and an organic solvent.
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.
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
73.
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 5/42 - 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
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
Provided herein are IL-21 muteins and fusion proteins comprising the same for use in methods of treating a disease. Related conjugates, nucleic acids, vectors, host cells, pharmaceutical compositions and kits are also provided herein. Methods of making the IL-21 muteins and fusion proteins comprising the same, as well as methods of treating a subject in need thereof, are provided by the present disclosure. Further provided are PD-1 antigen-binding proteins.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
75.
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 5/32 - 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
76.
DRUG DELIVERY DEVICE WITH STERILE FLUID FLOWPATH AND RELATED METHOD OF ASSEMBLY
Drug delivery devices and related methods of assembly are disclosed. The drug delivery device may include a housing and a container disposed therein. The container may include a reservoir containing a drug and a movable stopper. A first seal member may be connected to the container at a distal end of the reservoir. A first removable membrane may cover an exterior surface of the first seal member to maintain sterility of that surface prior to operation of the device. A fluid pathway assembly may be configured to establish fluid communication with the reservoir during operation of the device. A second seal member may be connected to a first end of the fluid pathway assembly. A second removable membrane may cover an exterior surface of the second seal member to maintain sterility of that surface prior to operation of the device.
Provided herein is a synthesis for omecamtiv mecarbil dihydrochloride hydrate and various intermediates. (1)
Provided herein is a synthesis for omecamtiv mecarbil dihydrochloride hydrate and various intermediates. (1)
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 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
78.
RATIONAL SELECTION OF BUILDING BLOCKS FOR THE ASSEMBLY OF MULTISPECIFIC ANTIBODIES
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 antibody constructs, there are multiple modalities from which to choose and often multiple antigen binders as well. Described here is the discovery of new methods to optimally pair antigen binders with the proper format, including the selection of common light chains.
The present invention provides commercial processes for preparing 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid as well as intermediates thereof.
H04W 48/04 - Access restriction performed under specific conditions based on user or terminal location or mobility data, e.g. moving direction or speed
H04W 76/38 - Connection release triggered by timers
H04W 48/08 - Access restriction or access information delivery, e.g. discovery data delivery
80.
MACHINE LEARNING TECHNIQUES FOR PREDICTING THERMOSTABILITY
Techniques for computationally screening a set of single-chain variable fragments (scFvs). The techniques include determining, using a machine learning model, a thermostability indication for each scFv in a set of scFvs to obtain a plurality of thermostability indications, the set of scFvs comprising a first scFv having a first residue sequence, the determining comprising: obtaining, using information indicative of a 3D structure of the first scFv, interaction energy metrics for each of a plurality of pairs of residues in the first residue sequence; generating a first set of features using the interaction energy metrics; and providing the first set of features as input to the machine learning model to obtain a corresponding output indicative of a first thermostability for the first scFv; identifying a subset of the set of scFvs for subsequent production based on the plurality of thermostability indications; and producing at least one of the identified scFvs.
Disclosed herein are methods of processing a protein and detecting isoaspartic acid (isoAsp) in a protein. Also disclosed are mass spectrometry systems configured for of processing a protein and detecting isoAsp in a protein.
Provided herein are processes for synthesizing Mcl-1 inhibitors and intermediates such as compound Y that can be used to prepare them where the variable R1 is as defined herein. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof, compound A2, and salts and solvates thereof, and compound A3 and salts and solvates thereof.
Provided herein are processes for synthesizing Mcl-1 inhibitors and intermediates such as compound Y that can be used to prepare them where the variable R1 is as defined herein. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof, compound A2, and salts and solvates thereof, and compound A3 and salts and solvates thereof.
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 mcl-1 inhibitors and intermediates such as compound Z that can be used to prepare them. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof and compound A2, and salts and solvates thereof.
Provided herein are processes for synthesizing mcl-1 inhibitors and intermediates such as compound Z that can be used to prepare them. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof and compound A2, and salts and solvates thereof.
C07C 303/36 - Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
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
C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
C07D 301/24 - Synthesis of the oxirane ring by splitting-off Hal—Y from compounds containing the radical Hal—C—C—OY
C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
C07C 303/28 - Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
Methods and systems for determining a minimum number of cell line clones necessary to produce a product having a set of target product attributes are disclosed. An example method includes generating at least one cell line capable of expressing a polypeptide; measuring, using one or more analytical instruments, a plurality of measured product attribute values of a plurality of clones of a candidate cell line; receiving inputs, via a user interface, representing a set of target product attribute values for a product; projecting, by one or more processors based upon the plurality of measured values, a minimum number of subject clones of the product using the candidate cell line necessary to produce a subset of the subject clones having product attributes that satisfy one or more conditions associated with the set of target values; and generating the projected minimum number of subject clones of the product using the candidate cell line.
Provided herein are methods of treating a subject with heart failure, comprising administering to the subject an initial dose of a cardiac sarcomere activator (CSA) for an initial time period, and subsequently administering to the subject a dose of the CSA based on the subject's plasma concentration of the CSA at the end of the initial time period.
A drug delivery system is disclosed that includes a drug delivery device having a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end to be received within a patient. The drug delivery system may further include one or more sensors coupled to the drug delivery device, a wireless transmitter, and a controller coupled to the one or more sensors and the wireless transmitter. The controller may be configured to use the one or more sensors to determine a condition or an operational state of the drug delivery device, and control the wireless transmitter to wirelessly transmit one or more reports representative of the condition or the operational state of the drug delivery device. A method for use with a drug delivery device is also disclosed.
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
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 40/00 - 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
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
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
G06Q 50/00 - Systems or methods specially adapted for specific business sectors, e.g. utilities or tourism
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 syringe is described with a plunger assembly that is adapted to have a dispensing stroke sized to dispense a fluid therapeutic product from the syringe without dispensing any air or headspace. The syringe includes a plunger rod having a stop feature that stops a dispensing stroke of the plunger rod at a distance corresponding to a level of air or headspace within the syringe avoiding additional air dispensing steps from a healthcare provider.
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
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
A method of selecting raw materials for use in a column chromatography purification process in which, for each of one or more candidate resins, a respective set of resin attribute values is received, including at least one analytical measurement of the candidate resin. The method also includes, for each candidate resin, predicting a respective value of a performance indicator for the column chromatography purification process by applying the respective set of resin attribute values, and possibly other parameter values (e.g., harvest filtrate and/or purification process parameters) as inputs to a multivariate statistical model. The method further includes selecting a resin of the one or more candidate resins based at least in part on the predicted respective value(s) of the performance indicator, and performing the column chromatography purification process using the selected resin as a stationary phase.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
A61K 9/19 - Particulate form, e.g. powders lyophilised
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
Provided herein are improved methods for measuring the concentration of carfilzomib in a sample. The method comprises the steps of diluting the sample with a diluent comprising water and less than 50% by volume acetonitrile to form an analytical sample; and subjecting the analytical sample to high performance liquid chromatography (HPLC) to determine the carfilzomib concentration in the sample.
Provided herein are methods of processing a polypeptide or protein for analysis, e.g., peptide mapping analysis by mass spectrometry. In exemplary embodiments, the method comprises incubating a digested sample at a mildly acidic pH and/or in the presence of a chaotrope, wherein the digested sample is produced by digesting a polypeptide with a protease to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with a protease which cleaves C-terminal to tryptophan to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with trypsin at an enzyme:substrate (E:S) weight ratio of about 1:1 to about 1:15 to produce a digested sample comprising at least two peptides. In exemplary aspects, the digested sample comprises at least one or two peptides each comprising a tyrosine at the C-terminus.
A drug delivery device includes a housing, a container disposed in the housing, a drive mechanism, a needle assembly, a fluid flow path, and a vortex flow adapter. The container contains a medicament which is urged out of the container by the drive mechanism. The needle assembly has a needle and/or a cannula to deliver the medicament from the container. The fluid flow path fluidically connects the container and the needle assembly. The vortex flow adapter is disposed within or defines at least a portion of the fluid flow path, and is adapted to urge the medicament to flow in a vortex pattern.
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
An apparatus for storing a medicament delivery device, the apparatus comprising: a container defining a storage cavity having an opening, the storage cavity configured to receive a syringe pre-filled with medicament; an absorbent disposed in the cavity, the absorbent at least partially hydrated with a liquid solution; and a seal member at least selectively connected with the cavity to form a seal that is at least substantially gas impermeable.
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
95.
MATERIALS AND METHODS TO REDUCE PROTEIN AGGREGATION
Provided herein are methods of treating a neoplastic disease in a subject. In exemplary embodiments, the method comprises administering to the subject an aqueous solution comprising an anti-EGFRvIII agent using an administration system, wherein one or more of the components of the administration system, or parts thereof, which contact the aqueous solution substantially lack a polyvinyl chloride (PVC) and/or air. In exemplary aspects, the administration system is an infusion system comprising an infusion line, wherein at least part of the infusion line substantially lacks PVC. In exemplary aspects, the administration system comprises a container for containing the aqueous solution wherein less than about 5% of the volume of the container is air, when the container comprises the aqueous solution. Related kits are further provided herein.
A61P 35/04 - Antineoplastic agents specific for metastasis
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
Antigen binding molecules, chimeric receptors, and engineered immune cells are disclosed in accordance with the invention. The invention further relates to vectors, compositions, and methods of treatment and/or detection using the antigen binding molecules and engineered immune cells.
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 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
The present invention relates to severe acute respiratory syndrome coronavirus 2 (“SARS-CoV2”) immunogens useful for the generation of therapeutic antibodies and vaccine development. Such therapeutic antibodies include human antibodies and antigen-binding portions thereof that specifically bind to human SARS-CoV2 S protein, and that function to neutralize SARS-CoV2. The present invention also relates to methods of generating antibodies and antigen-binding portions thereof that specifically bind to human SARS-CoV2 S protein.
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 placement for a non-canonical disulfide bond and as such the generation of an asymmetric cysteine interface between two Fabs present in the same molecule which will further enable the production of multispecifics.
Methods of mammalian cell culture for expressing a recombinant protein of interest are provided. In various embodiments the methods relate to the mammalian cells expressing an IGF1R mutant that is constitutively active.
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