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 disclosure relates to techniques for service orchestration within a distributed pod based system. Particularly, aspects are directed to receiving, at a kernel residing on a distributed computing environment, a request to initiate deployment for a subservice or service on the distributed computing environment. The subservice or service has a type, and in order for the subservice or service to be deployed on the distributed computing environment, the type of the subservice or service has to be one that the distributed computing environment is configured to support. In response to receiving the request and the type of the subservice or service being one that the distributed computing environment is configured to support, specified resources are provisioned, and the subservice or service is deployed using a replica of a pod containing the provisioned specified resources and a modified image for the type of the subservice or service.

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 on a single molecule or located on different molecules. The methods combine efficient, high gene expression level, appropriate assembly, and ease of purification for the heteromultimeric proteins. The invention also provides methods of using these heteromultimeric proteins, and compositions, kits and articles of manufacture comprising these antibodies.

Abstract: The application disclosed concerns a method of treating pneumonia in a patient who is not mechanically ventilated comprising administering an IL-6 antagonist (e.g. tocilizumab) to the patient in an amount effective to prevent the patient from dying or receiving mechanical ventilation. The disclosure is based on the results of the EM PACTA clinical trial.

Abstract: In one embodiment, a method includes receiving one or more querying images associated with a container of a pharmaceutical product, each of the one or more querying images being based on a particular angle of the container of the pharmaceutical product, calculating one or more confidence scores associated with one or more defect indications, respectively for the container of the pharmaceutical product, by processing the one or more querying images using a target machine-learning model, and determining a defect indication for the container of the pharmaceutical product from the one or more defect indications based on a comparison between the one or more confidence scores and one or more predefined threshold scores, respectively.

Abstract: The present disclosure provides compositions, methods, and kits for detecting lipolytic activity. In some embodiments, the composition comprises an aqueous assay sample and an organic solvent, wherein the organic solvent comprises 4-methylumbellif-erryl caprylate (MU-C8). Also provided herein are methods for determining the stability of a protein preparation.

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

Abstract: The present application relates to methods of producing a protein in fucosylated and afucosylated forms at a predetermined ratio.

Abstract: The present disclosure provides methods and systems for high throughput assays for testing immune cell engager molecules and potential immune cell engager molecules. In some embodiments, multiple parameters, for example, in connection with engagement of tumor cells by immune cells such as T cells and in connection with tumor cell death, may be analyzed from the same samples in the assays, and, in some cases, may be analyzed simultaneously. In some embodiments, the methods and systems allow for determining the kinetics of various parameters.

Abstract: The invention relates generally crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the compound (S)-2-(3?-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro- [3,4?-bipyridin]-2?-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one that is an inhibitor of Bruton’s tyrosine kinase. In some aspects, the crystalline salts are single polymorphs.

Abstract: Compounds of Formula (I): salts thereof and methods of making and use as Janus kinase inhibitors are described herein.

Abstract: The subject matter described herein is directed to antibody-CIDE conjugates (Ab-CIDEs) that target BRM for degradation, to pharmaceutical compositions containing them, and to their use in treating diseases and conditions where BRM degradation is beneficial.

Abstract: Provided herein are high throughput methods for optimizing and manufacturing various lipid nanoparticle (LNP) compositions and uses thereof. For example, in some embodiments, the present disclosure provides a high-throughput screening method for manufacturing a LNP composition comprising, obtaining at least two intermixable solutions comprising a payload and a plurality of molecules capable of self-assembly and mixing said at least two solutions under a set of controlled conditions, by which injection sequence, speed, volume, phase ratio and mixing duration are varied. In various embodiments, the present disclosure enables optimal encapsulation efficiency, particle size distribution, purification and particle recovery rate, and formulation stability to be determined. The methods disclosed herein enable efficient optimization of manufacturing conditions for preparation of LNP-based therapeutics.

Abstract: The invention relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

Abstract: The present invention relates to complement C1r subcomponent (C1R) inhibitors for use in treatment of neurological diseases. The invention in particular relates to the use of C1R inhibitors for down-regulation of C1R expression. The invention also relates to nucleic acid molecules, which are complementary to C1R and capable of reducing the level of an C1R mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of neurological diseases.

Abstract: The invention provides anti-Notch2 antibodies and conjugates and methods of using the same.

Abstract: Provided herein are combination therapies comprising a KRasG12C inhibitor (e.g. GDC-6036) and an PI3K-inhibitor (e.g. inavolisib) and methods of using such combination therapies.

Abstract: The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention relates to therapies for the treatment of pathological conditions, such as cancer.

Abstract: Provided herein are solid forms, salts, and formulations of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol, processes and synthesis thereof, and methods of their use in the treatment of cancer.

Abstract: The present disclosure relates to methods and compositions for determining the relative distribution of glucuronidation, iduronidation, and/or galacturonidation of polypeptides, including stereoselective liquid chromatography-mass spectrometry (LC-MS) methods capable of achieving the simultaneous separation and relative quantitation of glucuronidation, iduronidation, and/or galacturonidation of polypeptides.