Abstract: The present invention provides an improved manufacturing method for the production of bispecific antibody products, which comprise at least two binding domains. The process comprises at least the method comprising a step of refolding the construct, wherein one or more of the domains comprise a disulfide bond, and wherein the construct is contacted with a refolding buffer to refold the construct to its native form, the buffer comprising (i) a redox and/or oxidizing agent having a concentration of at least 0.1 mM and (ii) a chaotropic agent having a concentration >1 M, and wherein the pH of the refolding buffer corresponds to +/?4.5 of the pI value of the first domain or +/?4.0 of the pI value of the entire construct.

Abstract: Detergents for use to inactivate enveloped viruses, including detergents that are considered eco-friendly that can be used in biomanufacturing operations.

Abstract: The present invention relates to antigen binding proteins, such as monoclonal antibodies, that specifically bind to and activate human triggering receptor expressed on myeloid cells-2 (TREM2) and pharmaceutical compositions comprising such antigen binding proteins. The agonist antigen binding proteins (e.g. antibodies) of the invention are capable of activating TREM2/DAP12 signaling in myeloid cells in the absence of Fc-mediated cross-linking of the antigen binding proteins. Methods of treating or preventing conditions associated with TREM2 loss of function, such as Alzheimer's disease and multiple sclerosis, using the antigen binding proteins are also described.

Abstract: Provided herein are solid dispersions comprising AMG 397, methods of preparing the solid dispersion, and pharmaceutical formulations comprising AMG 397.

Abstract: The present invention relates to variant Fc-containing molecules, such as antibodies and Fc-fusion molecules, having glycosylation characteristics favorable to large-scale production of therapeutic molecules containing such variant Fc.

Abstract: Drive assemblies for a drug delivery device and related methods are disclosed. A drive assembly comprises a casing having a proximal end, a distal end, and a longitudinal axis extending between the proximal end and the distal end, a plunger rod guide operably coupled to the casing, a spring at least partially disposed within the casing and wound around at least a portion of the plunger rod guide, and a lock component selectively coupled with the casing and configured to receive at least a portion of the plunger rod guide therein. The spring is configured to exert a force on the plunger rod guide that causes the plunger rod guide to rotate. The lock component is configured to prevent rotational movement of the plunger rod guide relative to the casing when the lock component is coupled with the casing.

Abstract: Provided herein are methods of treating, inhibiting, reducing, or ameliorating cardiovascular adverse events in a patient caused by administration of carfilzomib by administering to the patient at least one of a soluble guanylyl cyclase (sGC) activator, a PDE5 inhibitor, p38 inhibitor, and/or MAPKAPK-2 inhibitor.

Abstract: The present invention concerns a method for preparing antigen binding proteins specific for PCSK9 with reduced viscosity. The method proceeds by replacing residues in high viscosity variable domain subfamilies with residues in correlating low viscosity subfamilies. The method further comprises substituting residues in the Fc domain with residues associated with low viscosity and adding charged residues to the C-terminus of the Fc domain. The present invention further concerns antigen binding proteins produced by this method.

Abstract: Compounds of formula (I): (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

Abstract: The present disclosure relates, in general, to muteins of IL-10 that are stable as monomers, antigen binding proteins that bind to TREM-1, and antigen binding proteins comprising IL-10 muteins and antigen binding moieties, e.g., anti-TREM-1 antibodies, and compositions thereof. The disclosure also provides methods of treating inflammatory disease, such as inflammatory bowel disease or ulcerative colitis, using the compositions.

Abstract: The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic, and colorectal cancer. In particular, the disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein the substituents arm as described.

Abstract: Described herein are bispecific proteins specific for BAFF and B7RP1, nucleic acids encoding such proteins, methods of making such proteins, and uses for such proteins.

Abstract: Provided herein are processes for synthesizing intermediates useful in preparing Mcl-1 inhibitors. In particular, provided herein are processes for synthesizing compound F, or a salt thereof, wherein R1 and OPG2 are described herein. Compound F can be useful in synthesizing compound A1, or a salt of solvate thereof, and compound A2, or a salt of solvate thereof.

Abstract: This invention relates to combination therapies comprising a Programmed Death 1 receptor (PD-1) pathway inhibitor, and a Leukocyte Immunoglobulin Like Receptor B (LILRB) signaling inhibitor, and the use of the combination therapies for the treatment of cancer. The invention also relates to the treatment of cancer patients who are refractory to monotherapy with a PD-1 pathway inhibitor.

Abstract: The present disclosure is drawn to pharmaceutical formulations, aqueous solutions, and methods of treating cancer using the disclosed pharmaceutical formulations and aqueous solutions. The formulations and solutions comprise compounds of Formula I and may further comprise a cyclodextrin compound, such as hydroxypropyl-?-cyclodextrin and a buffer, such as glycine. The methods of treating cancer include the treatment of hematological malignances such as acute myelogenous leukemia, multiple myeloma, and non-Hodgkin's lymphoma.

Abstract: Disclosed herein are compounds useful for the inhibition of 15-PGDH. The compounds have a general Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a 15-PGDH-mediated disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Abstract: A drug delivery device and a method of using the drug delivery device may include a housing having an opening and a drug storage container including a delivery member. The drug storage container may be coupled with the housing such as to substantially prevent relative movement between the drug storage container and the housing. A guard may be positioned adjacent to the opening and operably coupled with a plunger biasing member such that a relative movement between the guard and the housing permits release of the plunger biasing member to urge a plunger in to expel a drug from the drug storage container. A lock component may be configured to resist the relative movement between the guard and the housing until the lock component is released by a user force, whereafter the user force drives the housing and the drug storage container toward an injection site.

Abstract: In a method for enhancing accuracy and efficiency in automated visual inspection of vessels, a vessel containing a sample is oriented such that a line scan camera has a profile view of an edge of a stopper of the vessel. A plurality of images of the edge of the stopper is captured by the first line scan camera while spinning the vessel, where each image of the plurality of images corresponds to a different rotational position of the vessel. A two-dimensional image of the edge of the stopper is generated based on at least the plurality of images, and pixels of the two-dimensional image are processed, by one or more processors executing an inference model that includes a trained neural network, to generate output data indicative of a likelihood that the sample is defective.

Abstract: Automatic syringe quality control systems, apparatus and methods are provided. The automatic syringe quality control systems, apparatus and methods may determine a plunger depth within a syringe that has been pre-filled with a medication. The plunger depth may be based on digital image data.