Abstract: The invention provides a compound represented by structural formula (I): or a pharmaceutically acceptable salt, or a stereoisomer thereof useful for treating cancer.

Abstract: The current invention reports a method for purifying an antibody by reducing the content of a host cell protein. The method employs a wash step with a low conductivity aqueous solution in an affinity chromatography.

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 presently disclosed subject matter relates to “Randomized Configuration Targeted Integration” (also referred to herein as “Randomized Chain Targeted Integration”) (RCTI) strategies for the generation and identification of host cells capable of expressing recombinant proteins, e.g., monoclonal antibodies, as well as compositions derived from the same, e.g., bispecific antibodies, and other complex format proteins, e.g., membrane protein complexes and other difficult to express molecules.

Abstract: Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidases SpsB and/or LepB, an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Abstract: Embodiments disclosed herein generally relate to multi-arm machine learning models for lesion detection. Particularly, aspects of the present disclosure are directed to accessing a three-dimensional magnetic resonance imaging (MRI) images. Each of the three-dimensional MRI images depict a same volume of a brain of a subject. The volume of the brain includes at least part of one or more lesions. Each three-dimensional MRI image of the three-dimensional MRI images is processed using one or more corresponding encoder arms of a machine-learning model to generate an encoding of the three-dimensional MRI image. The encodings of the three-dimensional MRI images are concatenated to generate a concatenated representation. The concatenated representation is processed using a decoder arm of the machine-learning model to generate a prediction that identifies one or more portions of the volume of the brain predicted to depict at least part of a lesion.

Abstract: The present disclosure provides methods for treating lung cancer (such as small cell lung cancer, e.g., extensive stage small cell lung cancer) in an individual. The methods comprise administering to the individual a PD-1 axis binding antagonist (such as an anti-PD-L1 antibody, e.g., atezolizumab), a platinum agent (e.g., cisplatin or carboplatin), and a topoisomerase II inhibitor (e.g., etoposide).

Abstract: The present disclosure provides methods and kits for purifying an antigen binding protein comprising a VL domain using a Protein L chromatography material which includes kosmotrope salts in the buffer background.

Abstract: The present disclosure relates to techniques for privacy-preserving computing to protect a subject's privacy while using the subject's data for secondary purposes such as training and deploying artificial intelligence tools. Particularly, aspects are directed to receiving, at a local server, subject data regarding a first subject, performing, by the local server, a de-identifying operation, an anonymizing operation, or both on the subject data, sending the subject data to a remote server, receiving a production model from the remote server, the production model including parameters derived in part from the processed subject data, receiving, at the local server, subsequent data regarding a second subject, inputting, by the local server, the subsequent data into the production model to analyze the subsequent data and generate an inference or prediction from the analysis of the subsequent data; and sending, by the local server, the inference or the prediction to a computing device.

Abstract: Provided are CD8 binding agents comprising a VHH domain that specifically binds human CD8. Also provided are nucleic acids encoding such CD8 binding agents, vectors comprising such nucleic acids, host cells comprising same, and methods of making such CD8 binding agents. Also provided are CD8 binding agents having the VHH domain conjugated to a detectable label. Provided are methods of using such CD8 binding agents to detect CD8+ T cells, monitor disease progress, and monitor treatment progress in a subject having cancer, autoimmune disease or condition, transplant rejection or graft-versus-host disease.

Abstract: Provided herein are compounds and pharmaceutically acceptable salts thereof useful in the treatment of IRE1-related diseases and disorders described herein.

Abstract: The disclosure relates to multicyclic heteroatom-containing compounds which have CDK inhibitory activity, methods of making the same, and uses thereof. The compounds have the general structural formula (I): The compounds can be used for treating a type of cancer, for example by inhibiting a cyclin-dependent kinase (CDK), such as CDK2, CDK4, and/or CDK6. The disclosure further provides exemplary synthetic routes for such compounds.

Abstract: Combinations of the antibody-drug conjugate trastuzumab-MCC-DM1 and chemotherapeutic agents, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting tumor cell growth, and for treating disorders such as cancer mediated by HER2 and KDR (VEGFR receptor 1). Methods of using such combinations for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

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: Provided herein are methods of treating or preventing SARS-CoV-2 infection comprising modulating interactions between the SARS-CoV-2 spike protein and plasma membrane-expressed host cell proteins, as well as methods of identifying modulators of such interactions.

Abstract: In one embodiment, a method includes accessing a first scan image from a set of computed tomography (CT) scan images with each CT scan image being at a first resolution, generating a first downscaled image of the first scan image by resampling the first scan image to a second resolution that is lower than the first resolution, determining coarse segmentations corresponding to organs portrayed in the first scan image by first machine-learning models based on the first downscaled image, extracting segments of the first scan image based on the coarse segmentations with each extracted segment being at the first resolution, determining fine segmentations corresponding to the respective organs portrayed in the extracted segments by second machine-learning models based on the extracted segments, and generating a segmented image of the first scan image based on the fine segmentations, wherein the segmented image comprises confirmed segmentations corresponding to the organs.

Abstract: In one embodiment, a method includes, receiving a digital pathology image of a tissue sample and subdividing the digital pathology image into a plurality of patches. For each patch of the plurality of patches, the method includes identifying an image feature detected in the patch and generating one or more labels corresponding to the image feature identified in the patch using a machine-learning model. The method includes determining, based on the generated labels, a heterogeneity metric for the tissue sample. The method includes generating an assessment of the tissue sample based on the heterogeneity metric.

Abstract: The invention provides diagnostic methods for identifying individuals having a lung cancer (e.g., NSCLC) suitable for treatment a treatment regimen that includes a PD-1 axis binding antagonist (e.g., atezolizumab) after adjuvant therapy (e.g., after a platinum-based adjuvant therapy) and therapeutic methods for treating lung cancer (e.g., NSCLC) in an individual identified as one who may benefit from treatment with a treatment regimen that includes a PD-1 axis binding antagonist (e.g., atezolizumab) to the individual following an adjuvant therapy (e.g., after a platinum-based adjuvant therapy). Also provided are compositions (e.g., a PD-1 axis binding antagonist (e.g., atezolizumab), pharmaceutical compositions thereof, assays thereof, kits thereof, and articles of manufacture thereof) for use in identifying patients suitable for treatment and for treating lung cancer (e.g., NSCLC) in an identified individual.

Abstract: Methods of treating patients having HER2-positive cancer are provided. Certain methods involve treatment of HER2 positive breast cancer using a programmed cell death protein 1 (PD-1) binding antagonist or a programmed death ligand 1 (PD-L1) binding antagonist in combination with trastuzumab and pertuzumab or with trastuzumab emtansine. The treatment regimen may be used in various clinical settings, for example, for treatment in the neoadjuvant or metastatic setting.

Abstract: Provided herein are anti-KRas antibodies that bind to mutant KRas-GDP and alkylated mutant KRas-GDP and methods of using the same. Also provide herein are method of screening for KRas inhibitors and methods of measuring binding of KRas to the antibodies described herein.