Abstract: This disclosure relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

Abstract: Described herein are tetrahydro-pyrido[3,4-b]indol-1-yl compounds with estrogen receptor modulation activity or function having the Formula I structure: and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such estrogen receptor modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

Abstract: The invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein the variables Y1-Y6, X, Z, Z1, Z2, R2-R3, and R6 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

Abstract: The present disclosure relates to novel sulfonimidamide compounds and related compounds and their use in treating a disorder 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.

Abstract: A data set can be provided that includes an input data element and one or more label data portion definitions that each identify a feature of interest within the input data element. A machine-learning model can generate model-identified portions definitions that identify predicted feature of interests within the input data element. At least one false negative (where a feature of interest is identified without a corresponding predicted feature of interest) and at least one false positive (where a predicted feature of interest is identified without a corresponding feature of interest) can be a identified. A class-disparate loss function can be provided that is configured to penalize false negatives more than at least some false positives. A loss can be calculated using the class-disparate loss function. A set of parameter values of the machine-learning model can be determined based on the loss.

Abstract: The invention provides for methods of viral inactivation using high temperature short time (HTST) treatment and adjustment of various parameters such that generation of precipitate and depositions of precipitate are reduced and/or minimized.

Abstract: The invention provides a compound of formula (I): or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 have any of the values described in the specification, as well as compositions comprising a compound of formula (I) or a prodrug thereof, or a pharmaceutically acceptable salt thereof. The compounds are agonists of glycolytic enzyme phosphofructokinase-1 liver type and are useful for treating diseases associated with the activity of glycolytic enzyme phosphofructokinase-1 liver type, such as cancer, diabetes, sepsis, and septic shock.

Abstract: The invention relates generally crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the compound(S)-2-(3?-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino) -6-oxo-1,6-dihydro-[3,4?-bipyridin]-2?-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one that is an inhibitor of Bruton's tyrosine kinase. In some aspects, the crystalline salts are single polymorphs.

Abstract: The present disclosure relates to methods, cells, and compositions for producing a product of interest, e.g., a recombinant protein. In particular, the present disclosure provides improved mammalian cells expressing the product of interest, where the cells (e.g., Chinese Hamster Ovary (CHO) cells) have reduced or eliminated activity, e.g., expression, of certain host cell proteins, e.g., enzymes including, but not limited to, certain lipases, esterases, and/or hydrolases.

Abstract: The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. ?,?-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

Abstract: The invention disclosed concerns a fixed dose combination (FDC) of pertuzumab, trastuzumab, and, optionally, recombinant human hyaluronidase (rHuPH20), which is administered subcutaneously to patients. The final efficacy and safety data for the FeDeriCa clinical trial, United States Prescribing Information (USPI) (including home-use) methods, and primary analysis of the PHranceSCa clinical trial are disclosed and claimed.

Abstract: The present disclosure relates to compounds and salts thereof that are useful for inhibiting target polypeptides and proteins, in particular, bromodomain (e.g., BRD4) proteins. Also disclosed are pharmaceutical compositions comprising the compounds, or a salt (e.g., a pharmaceutically acceptable salt) thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated diseases or disorders.

Abstract: The present disclosure provides high viscosity ultrafiltration/diafiltration (UF/DF) and single-pass tangential flow filtration (SPTFF) processes used in the purification of polypeptides. A method for purifying a polypeptide from a polypeptide preparation may include the following steps in order: a) subjecting the polypeptide preparation to one or more purification processes and recovering a first resulting pool having a viscosity of about 5-40 cP; and b) subjecting the pool recovered from step a) to a SPTFF operation comprising use of membranes in either or both a serial membrane and/or a parallel membrane configuration and recovering a second resulting pool having an operating viscosity of about 41-400 cP, wherein, i) the operating temperature is about 15-55° C., and ii) the feed flux is about 5-50 L/m2/hr (LMH).

Abstract: The present application discloses variants of Pertuzumab. In particular, it discloses: an unpaired cysteine variant comprising Cys23/Cys88 unpaired cysteines in one or both variable light domains of Pertuzumab, an afucosylated variant of Pertuzumab, a low-molecular-weight-species (LMWS) of Pertuzumab, and a high-molecular-weight-species (HMWS) or Pertuzumab. The application further discloses the isolated variants, compositions, pharmaceutical compositions, and articles of manufacture comprising the variants, as well as methods of making and characterizing the variants and compositions thereof.

Abstract: Compounds of formula (I) wherein R1, R2, R3, R4, R5 and R6 are as defined herein, and salts thereof, that are useful as JAK kinase inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient.

Abstract: Provided herein are methods of synthesizing quinazoline compounds comprising at least one atropisomeric center.

Abstract: Provided herein are methods of treating B-cell proliferative disorders in particular Follicular Lymphoma and/or Diffuse Large B-Cell Lymphoma using immunoconjugates comprising anti-CD79b antibodies in combination with additional therapeutic agents.

Abstract: The subject matter described herein is directed to molecules referred to herein as chemical inducers of degradation (CIDEs) and antibody-conjugated CIDEs (Ab-CIDEs), wherein the Ab-CIDEs comprise an antibody covalently bound to the CIDE through a linker, wherein the CIDE can be further covalently bound to a phosphate moiety, and to the uses of the molecules in treating diseases and conditions where targeted protein degradation is beneficial.

Abstract: This disclosure relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

Abstract: An apparatus and method for direct drug infusion from a vial to a patient are provided. A movable hanger label is provided to adhere to and support the vial to facilitate direct infusion of a drug, such as one or more pharmaceuticals, biopharmaceuticals, and/or biologics, from the vial to the patient. Additionally, a process is provided in which the drug, contained in the vial with the movable hanger label, may be directly infused through a primed infusion line with a rapid infusion rate. A saline flush is incorporated at the end of the administration to flush the infusion line, resulting in a reduced amount of the drug remaining in the line.