Abstract: A composition comprising a main species HER2 antibody that binds to domain II of HER2 and acidic variants thereof is described. Pharmaceutical formulations comprising the composition, and therapeutic uses for the composition are also disclosed.

Abstract: Methods of assessing or monitoring the effect, efficacy, responsiveness to treatment, and/or determining a dose or dosing regimen of therapeutic agents, such as integrin beta7 antagonists, for the treatment of gastrointestinal inflammatory disorders are provided. In certain aspects, methods of using integrin beta7 subunit-containing receptor occupancy by the integrin beta7 antagonist on colonic lymphocytes as an indicator (“biomarker”) of the effect, efficacy, or responsiveness to treatment, and/or as a means to determine dosing or dosing regimens of therapeutic agents such as beta7 integrin antagonists for the treatment of gastrointestinal inflammatory disorders are provided. In certain aspects, methods of assessing the effect, efficacy, or responsiveness to beta7 integrin antagonist treatment by measuring gene expression levels of one or more integrin receptor ligands, lymphocyte genes, cytokine genes, or the number of alphaE-positive cells in intestinal crypt epithelium are provided.

Abstract: Methods of treating patients having HER2-positive, locally advanced or previously untreated metastatic breast cancer having received prior treatment with a taxane using an anti-HER2-maytansinoid conjugate (for example trastuzumab emtansine) are provided.

Abstract: The invention provides novel compounds having the general formula I: wherein R1, X, Z1, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds.

Abstract: The present invention is directed to methods of using biomarkers to assess treatment of gastrointestinal inflammatory disorders with beta7 antagonists. More particularly, the present invention relates to methods of using the level of gut-homing lymphocytes in peripheral blood, the level of drug occupancy on gut-homing lymphocytes, and/or the level of beta7 integrin receptors on gut-homing lymphocytes as indicators (or biomarkers) of the effect, efficacy, safety, prognosis, and/or dosing of therapeutic agents, such as beta7 integrin antagonists, for the treatment of gastrointestinal inflammatory disorders.

Abstract: A Generative Adversarial Network (GAN) can be trained, where the GAN includes an anomaly-removing Generator network configured to modify a medical image to remove a depiction of a biological anomaly and one or more Discriminator networks (each configured to discriminate between real and fake images). The anomaly-removing Generator network can then receive a medical image that depicts a particular biological anomaly (or pre-processed version thereof) and generate a modified image predicted to lack any depiction of the particular biological anomaly. The size of the particular biological anomaly may be estimated based on the modified image and the received image (or pre-processed version thereof).

Abstract: The present invention relates to oligonucleotides that are complementary to and modulate the expression of TMEM106B. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of neurological disorders using the oligonucleotide.

Abstract: Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Abstract: The invention provides novel compounds having the general formula I: wherein R1, R2, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds.

Abstract: The present disclosure relates generally to rapid-release pharmaceutical dosage unit tablets containing a drug that is an inhibitor of the mitogen-activated protein kinase enzyme, a filler and a disintegrant, and to processes for forming the tablets. More specifically, the present disclosure relates to pharmaceutical dosage unit tablets containing cobimetinib, a least one filler, at least one lubricant and at least one disintegrant, and to methods for preparing the tablets from granules formed by dry granulation.

Abstract: The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.

Abstract: A method for treating an inflammatory or autoimmune disease with compounds of Formula 0, Formula I, and Formula II and methods of use as Interleukin-1 Receptor Associated Kinase (IRAK4) inhibitors are described herein.

Abstract: The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer (e.g., a bladder cancer (e.g., UC, e.g., mUC), a kidney cancer, a lung cancer, a liver cancer, an ovarian cancer, a pancreatic cancer, a colorectal cancer, or a breast cancer). The invention is based, at least in part, on the discovery that expression levels of one or more biomarkers described herein in a sample from an individual having cancer can be used in methods of identifying an individual having a cancer who may benefit with an anti-cancer therapy that includes an immunotherapy (e.g., a PD-L1 axis binding antagonist such as an anti-PD-L1 antibody (e.g., atezolizumab)) and a suppressive stromal antagonist (e.g.

Abstract: The present invention provides methods for purifying a polypeptide comprising a CH2/CH3 region, comprising binding the polypeptide to Protein A and eluting with a pH gradient starting at a low pH.

Abstract: The present invention relates to anti-CLL-1 antibodies including anti-CLL-1 antibodies comprising a CLL-1 binding domain and a CD3 binding domain (e.g., anti-CLL-1/CD3 T cell dependent bispecific (TDB) antibody) and methods of using the same.

Abstract: The invention provides methods of dosing for the treatment of cancers, such as B cell proliferative disorders, with anti-cluster of differentiation 20 (CD20)/anti-cluster of differentiation 3 (CD3) bispecific antibodies.

Abstract: Medical image(s) are input into a detection network to generate mask(s) identifying a set of regions within the medical image(s), where the detection network predicts that each region identified in the mask(s) includes a depiction of a tumor of one or more tumors within the subject. For each region, the region of the medical image(s) is processed using a tumor segmentation network to generate one or more tumor segmentation boundaries for the tumor present within the subject. For each tumor and by using a plurality of organ-specific segmentation networks, an organ is determined within which at least part of the tumor is located. An output is generated based on the one or more tumor segmentation boundaries and locations of the organs within which at least part of the one or more tumors are located.

Abstract: Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.

Abstract: Systems and methods relate to processing digital-pathology images. More specifically, aspects of the present disclosure are directed to accessing a whole-slide image depicting a slice of specimen, defining a set of tiles within at least part of the whole-slide image, generating one or more artifact prediction metrics by applying artifact detection to each tile of the set of tiles, wherein each of the one or more artifact prediction metrics corresponds to a predicted level of image quality of part or all of the whole-slide image, generating a quality heat map image corresponding to the whole-slide image, wherein the quality heat map image is based on the one or more artifact prediction metrics, and outputting the quality heat map image.

Abstract: The present disclosure relates to novel sulfonylurea and sulfonyl thiourea compounds and related compounds and their use in treating a disease or condition responsive to modulation of cytokines such as IL-1? and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.