Abstract: 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.

Abstract: An injector includes a housing having a syringe assembly and an actuating mechanism at least partially disposed within the housing. The syringe assembly includes a syringe barrel that stores a medicament to be injected into a user, a needle assembly, and a filter member disposed adjacent to the needle assembly. The actuating mechanism is operatively coupled to the syringe assembly and includes a torque spring that exerts a torque to urge the medicament through the filter member to be injected into the user. The actuating mechanism further includes a damper mechanism that exerts an opposing force to dampen the motion exerted by the torque spring.

Abstract: 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.

Abstract: Methods of treating conditions related to lung disease using an antigen binding protein specific for the Jagged1 polypeptide are provided.

Abstract: A method for 3D imaging of a sample, in a vessel having a longitudinal axis orthogonal to a horizontal plane, includes capturing, by at least three cameras located at different positions around the vessel, respective 2D images of the sample. Each image comprises pixels having associated pixel values. The optical axis of a first camera is inclined or declined at a first angle relative to the horizontal plane, with the first angle being greater than or equal to zero degrees. The optical axis of a second camera is inclined or declined at a second, larger angle relative to the horizontal plane. The method also includes generating a 3D image of the sample based on the pixel values associated with the 2D image pixels, and one or more look-up tables that collectively indicate, for pixels in each image, expected paths for light traversing the vessel and the sample.

Abstract: Methods of treating conditions related to lung disease using an antigen binding protein specific for the Jagged1 polypeptide are provided.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A drug delivery device includes a housing defining a shell and an inner volume, a container, a drive mechanism, a needle assembly, a fluid flow connection, and a backflow prevention mechanism. The container has an inner volume to contain a medicament to be administered to a user. The drive mechanism is at least partially disposed within the housing and exerts a force to urge the medicament out the container. The fluid flow connection is coupled to the container and the needle assembly and allows the medicament to flow from the container to the needle assembly to be administered. The backflow prevention mechanism is associated with at least one of the container, the fluid flow connection, or the needle assembly and includes at least one flow restrictor to restrict a fluid from flowing from the needle assembly to the container.

Abstract: The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

Abstract: A method for detecting cytopathic effect (CPE) in a well sample includes generating a well image depicting a well containing cells and a medium (and possibly viruses), and pre-processing the well image at least by partitioning the well image into sub-images each corresponding to a different portion of the well. The method also includes, for each of some or all of the sub-images, determining, by analyzing the sub-image using a convolutional neural network, a respective score indicative of a likelihood that any cells in the portion of the well corresponding to the sub-image exhibit CPE. The method further includes determining a CPE status of the cells contained in the well based on the respective scores for the sub-images, and generating output data indicating the CPE status.

Abstract: The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human MSLN on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Abstract: 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.

Abstract: 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.

Abstract: 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).

Abstract: 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.

Abstract: In a method for imaging a container holding a sample, the container is illuminated with a laser sheet of a first color, and one or more images of the container are capturing by a first imager configured to filter out colors other than the first color. Simultaneously with illuminating the container with the laser sheet of the first color, the container is illuminated with light of a second color different than the first color, wherein the light of the second color illuminates at least a majority of an entire volume of the container. One or more additional imagers of the container are captured by a second imager configured to filter out colors other than the second color. The one or more images and the one or more additional images are analyzed to detect particles within, and/or on an exterior surface of, the container.

Abstract: A device and method for drug delivery includes a casing for housing a drug storage container, the 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; 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 arrangement having a first member and a second member, 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.

Abstract: Disclosed herein are aqueous pharmaceutical formulations comprising denosumab or another human anti-RANKL monoclonal antibody or portion thereof, and characteristics of pH, buffer systems, and amino acid aggregation inhibitors. Also disclosed are presentation of the formulation for use, e.g. in a single-use vial, single-use syringe, or glass container, methods of using the formulations and articles for preventing or treating diseases, and related kits.