Abstract: A method of treating an autoimmune disease such as Sjögren's Syndrome is provided. The method comprises administration of an antibody or an antigen binding portion thereof that specifically binds an epitope of CD40 associated with antagonism. The antibody or the antigen binding portion thereof does not exhibit CD40 agonist activity in either in vitro or in vivo preclinical testing. The antibody inhibits CD40L-induced signaling on DCs, resulting at least in part to reduced production of pro-inflammatory cytokines, and reduction of cell surface activation markers, CD86 and CD54. The antibodies can comprise an Fc region containing a mutation that reduces or eliminates binding to Fc receptors, reducing or eliminating Fc gamma receptor (Fc?R)-mediated cross-linking or clustering.

Abstract: Provided herein are system, apparatus, device, method, and/or computer program product embodiments, and/or combinations and sub-combinations thereof, for classifying a document using image analysis. In an embodiment, a server may train and implement a deep learning model to classify documents using image representations of the documents.

Abstract: Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFN?, by acting on Tyk-2 to cause signal transduction inhibition.

Abstract: Provided herein are methods for treating a subject afflicted with a cancer, comprising administering to the subject a TIM3 agonist (e.g., an anti-TIM3 antibody), alone or in conjunction with another immune checkpoint inhibitor (e.g., a PD-1 antagonist), wherein the subject is identified as having a high frequency of TIM3 positive cells (e.g., on the tumor infiltrating inflammatory cells) or soluble TIM3 in peripheral blood. Also provided are methods for assessing the efficacy of a treatment comprising a TIM3 antagonist in a subject afflicted with a cancer, comprising measuring the frequency of TIM3 (and optionally PD-1) positive cells in certain populations of cells and/or the soluble TIM3 in peripheral blood of the subject, wherein a high frequency of TIM3 (and optionally PD-1) positive cells and/or the subject's peripheral blood titer of soluble TIM3 is indicative of the response to the treatment.

Abstract: The disclosure provides for antibodies that bind CD40, including a humanized antibody and a chimeric antibody with different Fc domains. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided.

Abstract: A method includes receiving an input histology image, processing, using a cell classification model, the input histology image to generate one or more lymphocyte density maps within the input histology image, and performing morphological image processing on the one or more lymphocyte density maps to identify one or more TLS regions within the input histology image. Each TLS region is represented by a respective cluster of lymphocyte cells. For each corresponding TLS region of the one or more TLS regions identified in the input histology image, the method also includes extracting, from the respective cluster of lymphocyte cells, a respective set of TLS features, and processing, using a TLS classification model, the respective set of TLS features to classify the corresponding TLS region as one of a first TLS maturation state, a second TLS maturation state, or a third TLS maturation state.

Abstract: This disclosure provides a novel method of controlling the glycosylation profile of a protein during production. The disclosure also provides a novel method of improving protein yield while controlling the glycosylation profile of a protein.

Abstract: This disclosure provides a novel method of controlling the glycosylation profile of a protein during production. The disclosure also provides a novel method of improving protein yield while controlling the glycosylation profile of a protein.

Abstract: The disclosure provides for antibodies that bind CD40, including a humanized antibody. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided.

Abstract: The present disclosure provides methods of identifying a subject suitable for an anti-PD-?PD-L1 antagonist therapy comprising measuring assay CD8 localization and PD-L1 expression in a tumor sample obtained from the subject. In some aspects, method further comprises administering (i) an anti-PD-?PD-L1 antagonist therapy or (ii) an anti-PD-?PD-L1 antagonist and anti-CT-LA-4 antagonist combination therapy to a subject identified as having a tumor exhibiting an excluded CD8 localization phenotype, wherein the tumor is PD-L1 negative.

Abstract: Described herein are methods and computer systems for classification of CD8 T-cell topology using artificial intelligence and machine learning. A plurality of histology images of tissue samples in a plurality of patients are received by a computer system. An image analysis of the plurality of histology images is performed to obtain a CD8+ T-cell abundance in the tumor parenchyma and stroma in each of the plurality of histology images. A machine learning algorithm is then trained using results of the image analysis and the CD8+ T-cell abundance in the tumor parenchyma and stroma. Based on the training, a machine learning feature space comprising a plurality of classifications is generated, and boundaries between the plurality of classifications in the machine learning feature space are identified.

Abstract: This disclosure provides a method for treating a subject afflicted with a tumor derived from a small cell lung cancer, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity or the combination of (a) an antibody or an antigen-binding portion thereof that specifically binds to a PD-1 receptor and inhibits PD-1 activity; and (b) an antibody or an antigen-binding portion thereof that specifically binds to a Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity.

Abstract: Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Abstract: Disclosed are antibodies that bind specifically to the receptor TNF superfamily member 15 (TNFSF15), also known as TL1A. Methods of making and using the anti-TL1A antibodies are also described.

Abstract: The disclosure provides a method for treating a subject afflicted with a tumor derived from a small cell lung cancer (SCLC) having a high tumor mutational burden (TMB) status comprising administering to the subject a monotherapy comprising an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody. The present disclosure also provides a method for identifying a subject suitable for treatment with an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody comprising measuring a TMB status of a biological sample of the subject. A high TMB status identifies the patient as suitable for treatment with an anti-PD-1 antibody or antigen-binding portion thereof. The TMB status can be determined by sequencing nucleic acids in the tumor and identifying a genomic alteration, e.g., a somatic nonsynonymous mutation, in the sequenced nucleic acids.

Abstract: The disclosure provides a method for treating a subject afflicted with a tumor, e.g., lung cancer, having a high tumor mutation burden (TMB) status comprising administering to the subject an immunotherapy, e.g., an anti-PD-1 antibody or antigen-binding portion thereof. The present disclosure also provides a method for identifying a subject suitable for an immunotherapy, e.g., a treatment with an anti-PD-1 antibody or antigen-binding portion thereof, comprising measuring a TMB status of a biological sample of the subject. A high TMB status identifies the patient as suitable for treatment with an anti-PD-1 antibody or antigen-binding portion thereof. The TMB status can be determined by sequencing nucleic acids in the tumor and identifying a genomic alteration, e.g., a somatic nonsynonymous mutation, in the sequenced nucleic acids.

Abstract: The present disclosure discloses methods for purifying antibodies providing an air overlay or headspace to single-use storage bags containing the antibody during purification. In specific embodiments, the application relates to purification of antibodies to human TIGIT (T cell immunoreceptor with Ig and ITIM domains), such as antibody 22G2, which decrease unwanted disulfide bond reduction. The application further provides depth filtration at lower throughput and/or flux, which also minimizes unwanted disulfide bond reduction.

Abstract: The present disclosure provides methods of using a calcium oscillation assay and/or a sequence score calculation to identify a molecule that is safe for administration. The disclosure also includes a method of selecting or identifying a molecule having tolerable in vivo neurotoxicity using a calcium oscillation assay, a sequence score method, an in vivo tolerability assay, or any combination thereof.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is: each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3a, R3b, L1, B, V, Y, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.