Abstract: The present invention relates to complement component 1s (C1S) inhibitors for use in treatment of neurological diseases. The invention in particular relates to the use of C1S inhibitors for down-regulation of C1S expression. The invention also relates to nucleic acid molecules, which are complementary to C1S and capable of reducing the level of an C1S mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of neurological diseases.

Abstract: The present disclosure relates to compounds comprising a VHL ligand moiety and to methods of using such compounds as ligands of VHL. The present disclosure further relates to the use of the compounds described herein, or pharmaceutical compositions thereof, to prevent and/or treat a range of diseases, disorders, and conditions.

Abstract: The invention provides novel compounds having the general formula I: wherein R1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Abstract: A method and system for normalizing a polymerase chain reaction (PCR) amplification process for a plurality of samples containing DNA. Cycle data for performing the PCR amplification process is identified for the plurality of samples. The cycle data includes a corresponding cycle count for each sample of the plurality of samples. The plurality of samples is sorted into a plurality of bins based on the cycle data such that cycle count variation between bins of the plurality of bins is reduced. A bin cycle count is assigned to each bin of the plurality of bins. The bin cycle count is unique to each bin of the plurality of bins. Identification information is generated for the bins. An output for performing a PCR amplification of the plurality of samples is generated using the bins and the bin cycle count for each bin of the plurality of bins.

Abstract: The present disclosure provides polysorbate 20 compositions with particular fatty acid ester concentrations. In some embodiments, they may be used in pharmaceutical formulations, for example, to improve stability.

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: Provided herein are combination therapies comprising GDC-9545 and ipatasertib for treating locally advanced breast cancer or metastatic breast cancer.

Abstract: Provided herein are combination therapies comprising GDC-9545 and abemaciclib or ribociclib for treating locally advanced breast cancer or metastatic breast cancer.

Abstract: Provided herein are combination therapies comprising GDC-9545 and GDC-0077 for treating locally advanced breast cancer or metastatic breast cancer.

Abstract: A method, system, and non-transitory computer readable medium for estimating mechanistic chromatography model uncertainty. A mechanistic model of chromatography that comprises a plurality of parameters is received. For each of the plurality of parameters, a corresponding region of values is identified based on a relationship between values for the plurality of parameters. Each parameter of the plurality of parameters is sampled within the corresponding region of values for each parameter to form a plurality of simulation sets. An uncertainty for the mechanistic model is quantified using the plurality of simulation sets.

Abstract: Presently provided are inhibitors of TD02 and IDO1 and pharmaceutical compositions thereof, useful for modulating an activity of tryptophan 2,3 dioxygenase and indoleamine 2,3-dioxygenase 1; treating immunosuppression; treating a medical conditions that benefit from the inhibition of tryptophan degradation; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; and treating tumor-specific immunosuppression associated with cancer.

Abstract: The present disclosure relates to modified mammalian cells having reduced or eliminated expression of certain cellular proteins, CRISPR/Cas9 multiplex knockout strategies for making such cells, and methods of using such cells, e.g., in the context of cell-based therapy or as host cells in the production of a product of interest.

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: 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 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: 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.