Abstract: The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the variables Y1-Y6, X, Z, Z1, Z2, R2-R3, and R6 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions. The compounds have sodium channel blocking activity that are useful for treating sodium channel-mediated diseases, in particular for treating pain.

Abstract: The present invention provides a method for preparing a composition comprising highly concentrated antibodies by ultrafiltration in batch concentration mode having a first constant feed rate step and a second controlled feed rate step.

Abstract: Described herein are methods for the efficient production of antibodies and other multimeric protein complexes (collectively referred to herein as heteromultimeric proteins) capable of specifically binding to more than one target. The targets may be, for example, different epitopes located on a single molecule or located on different molecules.

Abstract: A method includes, by a computing system, receiving a querying image depicting a sampling area, processing the querying image using a single cluster detection model to identify one or more regions of the querying image depicting a cluster in the sampling area, processing the one or more regions using a cluster verification deep-learning model to determine whether each depicted cluster is a cell cluster, and determining that exactly one of the identified one or more regions depicts a cluster that is a cell cluster. The method further includes processing the region depicting the cell cluster using a morphology deep-learning model to determine that there is only one cell in the cell cluster and to determine that die morphology of the cell is acceptable.

Abstract: The invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof wherein A, X, R1, R4 and n are as defined herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

Abstract: Methods are provided for the adjuvant treatment of operable HER2-positive primary breast cancer in human patients by administration of pertuzumab in addition to chemotherapy and trastuzumab. The methods reduce the risk of recurrence of invasive breast cancer or death for a patient diagnosed with HER2-positive early breast cancer (eBC) compared to administration of trastuzumab and chemotherapy, without pertuzumab.

Abstract: Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.

Abstract: Provided herein are antibodies such as human or humanized antibodies with a modified heavy chain variable (VH) domain such that the antibodies adopt a constrained conformation (e.g., an i-shaped format) upon engaging the antigen(s) the antibodies bind to, thereby confer agonistic activities. In some cases, the antibodies are full-length antibodies (e.g., IgG antibodies). In some cases, the antibodies are monovalent antibodies (e.g., Fabs). In some cases, the antibodies target receptors which require clustering for activation (e.g., TNFR superfamily receptors). In some cases, the antibodies target two antigens on a molecule that have two or more subunits (e.g., an IL-2 receptor). Also provided herein are methods of making and using such antibodies and libraries for discovering or screening such antibodies.

Abstract: The present disclosure provides methods and kits for treating or preventing an allergic reaction to a food allergen consumed by a human subject with one or more food allergies. In particular, the present disclosure provides prophylactic therapies comprising administration of an anti-IgE antibody at a specific dose to a human subject who is allergic to one or more food allergens.

Abstract: A compound, of formula (I): suitable for treating a cancer wherein the cancer is susceptible to inhibition of Cbl-B.

Abstract: Provided, inter alia, are macrocyclic compounds.

Abstract: The present disclosure relates generally to rapid-release pharmaceutical dosage unit tablets containing small molecule API medicines. In some instances the API is an inhibitor of Ras proteins, such as K-Ras, H-Ras, and N-Ras, that have a G12C mutation. Such tablets also contain a disintegrant and an excipient. More specifically, the present disclosure relates to pharmaceutical dosage unit tablets containing divarasib, or a pharmaceutically acceptable salt thereof, an extragranular disintegrant, and an extragranular excipient, and to processes for preparing the tablets from granules formed by dry granulation.

Abstract: The present disclosure relates to techniques for segmenting tumors with positron emission tomography (PET) using deep convolutional neural networks for image and lesion metabolism analysis.

Abstract: Described herein, in certain aspects, are nano-suspensions comprising a plurality of nanoparticles comprising a hydrophobic agent suspended in an aqueous carrier having a desired viscosity. In other aspects, the described herein are methods of use thereof, including methods of making a dosage form, components of the nano-suspensions, dispensing cartridges and composition therein, dosage forms, devices for dispensing a nano-suspension, and system and applications of the embodiments described herein.

Abstract: The invention provides interleukin-33 (IL-33) antibodies and methods of making and using the same, e.g., for detection of IL-33 in biological samples.

Abstract: The invention provides anti-KLK5 antibodies and methods of using the same.

Abstract: Provided herein are diagnostic and therapeutic methods for the treatment of cancer using polygenic risk scores (PRSs) for dermatological autoimmune diseases. In particular, the invention provides methods for patient selection and methods of treatment.

Abstract: The invention concerns methods and means for preventing the reduction of disulfide bonds during the recombinant production of disulfide-containing polypeptides. In particular, the invention concerns the prevention of disulfide bond reduction during harvesting of disulfide-containing polypeptides, including antibodies, from recombinant host cell cultures.

Abstract: The present application discloses high-concentration monoclonal antibody formulations suitable for subcutaneous administration, e.g. via a pre-filled syringe. In particular, it discloses a formulation comprising a spray dried monoclonal antibody at a concentration of about 200 mg/mL or more suspended in a non-aqueous suspension vehicle where the viscocity of the suspension vehicle is less than about 20 centipoise. Also disclosed are: a subcutaneous administration device with the formulation therein, a method of making the formulation, a method of making an article of manufacture comprising the suspension formulation, use of the formulation in the preparation of a medicament, and a method of treating a patient with the formulation.

Abstract: This application relates to random polymer libraries and specific polymers that can be used, for example, in stabilizing high concentration protein compositions, such as high concentration antibody compositions.