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: Novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies and have the general formula I: wherein R1, R2, R3, R4, R5 and R6 are as described herein.

Abstract: The present disclosure relates to techniques for segmenting objects within medical images using a deep learning network that is localized with object detection based on a derived contrast mechanism. Particularly, aspects are directed to localizing an object of interest within a first medical image having a first characteristic, projecting a bounding box or segmentation mask of the object of interest onto a second medical image having a second characteristic to define a portion of the second medical image, and inputting the portion of the second medical image into a deep learning model that is constructed as a detector using a weighted loss function capable of segmenting the portion of the second medical image and generating a segmentation boundary around the object of interest. The segmentation boundary may be used to calculate a volume of the object of interest for determining a diagnosis and/or a prognosis of a subject.

Abstract: The present disclosure relates to techniques for service to service communication and authentication via a network mesh. Particularly, aspects are directed to receiving, at a network mesh, a service request for a first service, and obtaining information associated with the first service. The information includes a location of a first pod encapsulating the first service. The network mesh using the location of the first pod, retrieves security rules specific for the first pod. The network mesh forwards the service request to the first service based on the security rules of the first pod and obtains results of the service request from the first service. The results include a sub result obtained from a second service in accordance with security rules for the first pod encapsulating the first service and security rules for a second pod encapsulating the second service.

Abstract: The present disclosure provides liquid formulations comprising polypeptides and surfactants. In particular, it discloses a liquid formulation comprising a polypeptide and a surfactant, wherein at least about 70% (wt %) of the surfactant are isosorbide polyoxyethylene (POE) fatty acid esters. The invention also provides methods for making such liquid formulations, articles of manufacture comprising such liquid formulations and methods of treating a patient with such liquid formulations.

Abstract: Techniques disclosed herein relate to inferring a type of multiple sclerosis and determining whether to output an alert based on codes detected within noisy assessment data corresponding to a subject. The noisy assessment data includes content originating from a care provider that identifies a characteristic of the subject or of a treatment for the subject, and the subject has been diagnosed with multiple sclerosis. A temporal dynamic or distribution is determined based on instances of the code detection, and a modulation is determined based on the temporal dynamic or the distribution. It is determined whether an alert criterion is satisfied based on whether the modulation is above a threshold so as to represent noise or a predicted transition across types of multiple sclerosis. The inferred type of multiple sclerosis is output. When the alert criterion is satisfied, an alert is output as well.

Abstract: The present invention concerns methods for treating progressive multiple sclerosis (MS) in a patient, and an article of manufacture with instructions for such use.

Abstract: The disclosure provides pharmaceutical compositions comprising mosunetuzumab and methods of using the same.

Abstract: The invention provides novel inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A, X, Y R1, R2, R3, R4, m and n are as described herein.

Abstract: Provided herein are therapies including dosage regimens for the treatment of cancer using B-RAF and an immune checkpoint inhibitor in combination with and/or without a MEK inhibitor.

Abstract: Provided herein are methods of treating B-cell proliferative disorders (such as diffuse large B-cell lymphoma “DLBCL”) using immunoconjugates comprising anti-CD79b antibodies in combination with an immunomodulatory agent (such as lenalidomide) and an anti-CD20 antibody (such as obinutuzumab or rituximab).

Abstract: The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a CD20-expressing cancer.

Abstract: Methods are provided to rapidly and accurately detect, characterize, measure, and quantify site-specific antibody drug conjugates, that may be present in pre-clinical animal biological samples, or human biological samples, including plasma/serum and tissue samples.

Abstract: Provided herein are antibodies that bind to a peptide of an N-terminally ubiquitinated polypeptide and methods of screening for such antibodies. Also provided herein are detection and enrichment methods using such antibodies for detecting or enriching a peptide of an N-terminally ubiquitinated polypeptide.

Abstract: Methods of enhancing efficiency of downstream chromatography steps for purification of proteins comprising: (a) passing a composition comprising a polypeptide of interest and various contaminants through an ion exchange membrane, wherein the polypeptide and the membrane have opposite charge, at operating conditions comprised of a buffer having a pH sufficiently distinct from the pi of the polypeptide to enhance the charge of the polypeptide and a low ionic strength effective to prevent the shielding of charges by buffer ions, which cause the membrane to bind the polypeptide and at least one contaminant, (b) overloading the ion exchange membrane such that at least one contaminant remains bound to the membrane while the polypeptide of interest is primarily in the effluent; (c) collecting the effluent from the ion exchange membrane comprising the polypeptide of interest; (d) subjecting the membrane effluent comprising the polypeptide of interest to a purification step of similar charge as the previous membrane,

Abstract: Azaindole compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the azaindole compounds.

Abstract: A machine-learning model (e.g., a clustering model) may be used to predict a phenotype of a tumor based on expression levels of a set of genes. The set of genes may have been identified using a same or different machine-learning model. The phenotype may include an immune-excluded, immune-desert or an inflamed/infiltrated phenotype. A treatment strategy and/or treatment recommendation may be identified based on the predicted phenotype.

Abstract: The present disclosure relates to a multispecific antibody platform for targeted degradation of cell surface proteins. The disclosure relates to multispecific (e.g., bispecific or trispecific) binding molecules such as multispecific antibodies that target at least one transmembrane E3 ubiquitin ligase protein and at least one cell surface protein, for example, a cell surface protein that is intended for degradation, and methods of using the same.

Abstract: The present invention relates to use of certain alkylglycoside compositions for the prevention of aggregation and oxidation of antibodies and other proteins in therapeutically useful formulations thereof.

Abstract: An apparatus and method to maintain pH within a range conducive for cell growth in a bicarbonate-containing cell culture system without the addition of base. The method relies on the gas transfer characteristics of the bioreactor system to modulate the CO2 transfer to and from the cell culture such that the pH of the cell culture can be maintained within a desired range.