Abstract: The present invention is directed to a combination therapy involving an anti-HER2 antibody-drug conjugate and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a HER2-expressing cancer.

Abstract: The present disclosure relates to a deep learning neural network that can identify corpora lutea in the ovaries and a rules-based technique that can count the corpora lutea identified in the ovaries and infer an ovarian toxicity of a compound based on the count of the corpora lutea (CL). Particularly, aspects of the present disclosure are directed to obtaining a set of images of tissue slices from ovaries treated with an amount of a compound; generating, using a neural network model, the set of images with a bounding box around objects that are identified as the CL within the set of images based on coordinates predicted for the bounding box; counting the bounding boxes within the set of images to obtain a CL count for the ovaries; and determining an ovarian toxicity of the compound at the amount based on the CL count.

Abstract: Heteroaryl pyridone and aza-pyridone compounds are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using heteroaryl pyridone and aza-pyridone compounds for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: Fixed dose HER2 antibody formulations for subcutaneous administration are provided along with their use in the treatment of cancer. The formulations include fixed dose subcutaneous formulations of pertuzumab and subcutaneous co-formulations of pertuzumab and trastuzumab, and their use in the treatment of cancer.

Abstract: Provided herein are combinations comprising: (i) one or more EGFR inhibitors; and (ii) one or more PERK activators, such as the specific EGFR inhibitors and PERK activators described herein. Also provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of such combinations.

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: 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: Provided are, inter alia, multispecific antigen binding proteins, or antigen-binding fragments thereof, comprising one or more mutations in the VH/VL domains and/or CH1/CL domains, pharmaceutical compositions comprising same, isolated nucleic acids, vectors, and host cells encoding/expressing same, method of making the multispecific antigen binding proteins, computer readable media for evaluating multispecific antigen binding proteins, and libraries.

Abstract: The present disclosure provides methods for treating lung cancer (such as non-small cell lung cancer, e.g., Stage IV non-squamous non-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), an antimetabolite (e.g., pemetrexed), and a platinum agent (e.g., cisplatin or carboplatin).

Abstract: Methods are provided for the adjuvant treatment of operable HER2-positive primary breast cancer in human patients by administration of pertuzumab in addition to chemotherapy and trastuzumab. The methods reduce the risk of recurrence of invasive breast cancer or death for a patient diagnosed with HER2-positive early breast cancer (eBC) compared to administration of trastuzumab and chemotherapy, without pertuzumab.

Abstract: The present disclosure relates to mammalian cells (e.g., Chinese Hamster Ovary (CHO) cells) that are modified to reduce or eliminate the expression of certain mammalian cell endogenous products (e.g., host cell proteins and virus-like particles), and methods of using such cells in the production of a recombinant product of interest, e.g., a recombinant protein, a recombinant viral particle, or a recombinant viral vector. These modifications were specifically chosen to generate engineered mammalian host cells with desired traits in several key areas, including improved cell culture performance (e.g., higher viability and product titers), improved product quality (e.g., more consistent and favorable glycosylation; more stable drug product), and decreased burden on purification for removing problematic or undesired endogenous host cell products (e.g., hydrolytic host cell proteins and virus-like particles) during biomanufacturing.

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: The invention relates to a new process for the purification of oligonucleotides which comprises the removal of the acid labile 5?hydroxy protecting group at the 5?-O-oligonucleotide terminus of the oligonucleotide by way of tangential flow filtration with an acidic buffer solution. The process requires less steps and allows a higher degree of automation.

Abstract: The invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein Z1, Z2, R3-R8, RA, ring A, and n have the meanings described herein, and compositions containing such compounds and methods for using such compounds and compositions for the treatment of pain.

Abstract: The presently disclosed subject matter relates to targeted integration (TI) host cells suitable for the expression of recombinant proteins where the TI host cells are also subjected to transposon-mediated genomic integration of one or more exogenous nucleic acids, as well as methods of producing and using said combined transposon-mediated genomic integration and TI host cells.

Abstract: The presently disclosed subject matter relates to combinatorial vector cloning and transfection strategies for the generation of targeted integration host cells suitable for the expression of recombinant proteins, as well as targeted integration host cells generated by said strategies and compositions comprising said targeted integration host cells.

Abstract: The invention provides anti-polyubiquitin antibodies and methods of using the same.

Abstract: The invention provides anti-kallikrein-related peptidase 5 (KLK5) antibodies and methods of using the same.

Abstract: The invention provides compounds of formulae I, II, IIa, and III: and pharmaceutically acceptable salts thereof, as well as compositions containing such compounds and methods for using such compounds and compositions.

Abstract: Provided herein are acyclic oxazepinyl compounds comprising a 6-aza moiety that are useful in the treatment of cancers.