Abstract: The present invention relates to methods of modulating the mannose content of recombinant proteins.

Abstract: Disclosed herein are compounds useful for the inhibition of insulin-like growth factor 1 receptor (IGF-1R). The compounds have a general Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, thyroid-associated ophthalmopathy, Graves' opthalmopathy or Graves' orbitopathy. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Abstract: The disclosure provides methods for treating small cell lung cancer (SCLC) in a subject expressing human delta-like ligand 3 (DLL3) protein. The methods comprise administering to the subject an antigen-binding molecule comprising at least a first binding domain that binds to human DLL3, wherein at least 25% of the SCLC cells express DLL3, or wherein at least 25% of the SCLC cells express DLL3 at an intensity equal to or greater than 2+ as determined by an IHC assay.

Abstract: Disclosed herein are pharmaceutical compositions (formulations) having reduced viscosity, using a low molecular weight polyvinylpyrrolidone (povidone) in the case of high therapeutic protein concentration (?70 mg/ml) formulations. The addition of arginine, such as arginine monohydrochloride or N-acetyl arginine, can further reduce viscosity. Appropriate therapeutic proteins include antibodies, such as monoclonal antibodies, and derivatives, fragments, and analogues thereof.

Abstract: Systems and methods for characterizing a recipe of a syringe filling system can include (a) receiving a value of a plunger depth for a syringe, (b) receiving values of product parameters, (c) determining, by applying the value of the plunger depth and the values of the product parameters as inputs to a model, values of vacuum parameters of the syringe filling system for use when filling the syringe with a product having the values of the product parameters, and (d) displaying or storing the values of the vacuum parameters. Further aspects include characterizing a recipe of the syringe filling system for use with a second value of the plunger depth for a second syringe. Still further aspects include causing one or more vacuum devices of the syringe filling system to operate at the values of the vacuum parameters.

Abstract: The invention relates to methods for preparing stable buffered and buffer-free protein compositions. The invention also relates to methods of purifying proteins from one or more impurities.

Abstract: The invention provides modified apelin polypeptides having increased stability, circulating half-life, and/or potency relative to the native apelin-13 polypeptide. Compositions comprising the modified apelin polypeptides and methods of using the polypeptides for treating cardiac disorders, such as heart failure, are also disclosed.

Abstract: The present invention provides combination therapy that includes an KRASG12C inhibitor, such as or a pharmaceutically acceptable salt thereof, and one or more additional pharmaceutically active agents, particularly for the treatment of cancers. The invention also relates to pharmaceutical compositions that contain an KRASG12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers.

Abstract: The present invention relates to RNAi constructs for reducing expression of the PNPLA3 gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

Abstract: Drug delivery devices and related methods of assembly are disclosed. The drug delivery device may include a container including a wall with an interior surface and a seal member with an end surface. The interior surface of the wall and the end surface of the seal member may define a reservoir filled with a drug. A fluid pathway assembly may be connected to the container and include an overmold member that covers a length of a container access needle and which defines an enclosed space with the seal member. The overmold member may be moveable relative to the seal member to carry the container access needle between a storage position, where a point of the container access needle is disposed exterior to the reservoir, and a delivery position, where the point extends through the end surface of the seal member into the reservoir.

Abstract: Antigen binding molecules, chimeric receptors, and engineered immune cells to STEAP1 are disclosed in accordance with the invention. The invention further relates to vectors, compositions, and methods of treatment and/or detection using the STEAP1 antigen binding molecules and engineered immune cells.

Abstract: The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic, and colorectal cancer. In particular, the disclosure provides compounds of Formula (II) and pharmaceutically acceptable salts thereof, wherein the substituents are as described.

Abstract: The disclosure provides solid forms of Compound A, as described herein. The disclosure also provides pharmaceutical compositions comprising the disclosed solid forms and methods of using the disclosed solid forms and pharmaceutical compositions (e.g., to treat cancer).

Abstract: The present disclosure provides techniques for accessing FADS1 activity in a patient. Also provided are techniques for determining the appropriateness of treatment of a patient with a FADS1 modulating (e.g., inhibiting) compound. This determination may be made by analyzing one or more biological indicators of FADS1-mediated disease or disorder in the subject. The one or more biological indicators may include one or more of a ratio of polyunsaturated fatty acids (“PUFAs”) in the subject, a relative abundance of one or more cell types, a relative abundance of one or more differentially expressed genes (“DEGs”) (or gene signatures, such as RNA, for such DEGs), and/or a relative abundance of one or more metabolites. Also disclosed are methods of using FADS1 inhibitors in methods of treating metabolic disorders and obesity.

Abstract: The present disclosure provides crystalline and amorphous forms of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, including several anhydrous, hydrate and solvate forms, and solid state forms thereof, pharmaceutical compositions, and methods of treating a disease mediated by KRAS G12C inhibition.

Abstract: The present invention relates to methods of upregulating the high mannose glycoform content of a recombinant protein during a mammalian cell culture by manipulating the mannose to total hexose ratio in the cell culture media formulation.

Abstract: The present disclosure provides compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G13D, Q61H, Q61L or G12C. The compounds have a general Formula I? (I?) wherein the variables of Formula I? are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, cancer.

Abstract: Pharmaceutical compositions comprising anti-interleukin 12 (IL-12) interleukin 23 (IL-23) antibodies are described. The pharmaceutical compositions may comprise molecular attributes, such as oxidation of light chain W32, isoaspartic acid at heavy chain position D55; high molecular weight species such as dimers and/or oligomers, high mannose, sialylation, or acidic peak species. Method comprising administering the pharmaceutical compositions are described. Methods of manufacturing the pharmaceutical compositions are described.

Abstract: Disclosed herein are compounds useful for the inhibition of STAT6. The compounds have a general Formula (I) or (II) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) and (II) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, diseases/disorders related to the activity of STAT6, such as an allergic disease or an inflammatory disease, including but not limited to atopic dermatitis or bronchial asthma. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I) and (II).

Abstract: The present invention relates to methods of treating obesity or type II diabetes using an antagonistic anti-GIPR antibody conjugated to a GLP-1R agonist. In particular, methods for treating obesity or type II diabetes in a patient in need thereof comprising administering to the patient an antagonistic anti-GIPR antibody conjugated to a GLP-1R agonist according to specific dosage regimens are disclosed. Pharmaceutical compositions and administration devices comprising an antagonistic anti-GIPR antibody conjugated to a GLP-1R agonist for use in the methods are also described.