Abstract: Impact testing apparatuses are disclosed which simulate and measure various impact-related events associated with the operation of a drug delivery device. The impact testing apparatus may include an impactor configured to simulate a plunger rod of the drug delivery device, and a guide sleeve configured to receive a syringe corresponding to the drug delivery device. The syringe may have a proximal end, a distal end defining an outlet, and an interior chamber extending between the proximal and distal ends and carrying a plunger. Additionally, the impact testing apparatus may include an energy source configured to reduce a distance between the impactor and the plunger so that the impactor strikes the plunger. Various sensors may be included to measure characteristics of one or more impacts caused by the impactor. Methods of impact testing a syringe filled with a fluid and carrying a plunger are also disclosed.

Abstract: Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.

Abstract: Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders.

Abstract: Provided herein are methods of generating hybridomas and related methods of producing antigen-specific antibodies. In exemplary embodiments, the method comprises (a) preparing an enriched population of IgG-positive (IgG+) memory B cells from cells obtained from secondary lymphoid organs of one or more immunized non-human animals, wherein (i) less than or about 10% of the enriched population are IgM-positive (IgM+) B cells and/or (ii) the ratio of the IgG+ memory B cell count to IgM+ B cell count of the enriched population is greater than about 0.5, optionally, greater than about 1 or greater than about 2, (b) bulk-culturing the enriched population to obtain an expanded population; and (c) fusing cells of the expanded population with myeloma cells to obtain hybridomas. In exemplary aspects, the hybridomas obtained represent at least 10% or at least 15% of the IgG+ memory B cell repertoire produced by the immunized animals.

Abstract: A system and a method for filling an on-body injector includes a needle of the prefilled syringe being aligned with a fill port of the on-body injector. The needle may then be inserted into a guide of a needle cover attached to the on-body injector. An adapter attached to the syringe barrel may guide the needle into a center of the bore of the guide and into the fill port of the on-body injector. The needle may be inserted into the fill port and the adapter may be mechanically coupling to the guide. After the adapter is mechanically coupled to the guide, a volume of the drug of the prefilled syringe may be dispensed into a reservoir of the on-body injector. Once the reservoir is filled to a desired amount, the needle may be removed from the fill port by decoupling the adapter from the guide.

Abstract: Provided herein are methods of treating a subject with heart failure, comprising administering to the subject an initial dose of a cardiac sarcomere activator (CSA) for an initial time period, and subsequently administering to the subject a dose of the CSA based on the subject's plasma concentration of the CSA at the end of the initial time period.

Abstract: The present invention is directed to methods of identifying and treating a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and administering a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as high. The present invention is also directed to methods of identifying a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and withholding a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as low.

Abstract: The disclosure provides a method of producing etanercept from Chinese hamster ovary cells (CHO), the method comprising running an N-1 bioreactor system using a recirculating tangential flow filtration (RTF) or alternating tangential flow filtration (ATF) cell retention device under conditions that maintain a cell aggregate size of at least 20 ?m, before running an N production bioreactor.

Abstract: The present application relates to compositions and methods for modulating expression of Family with Sequence Similarity 13 Member A (FAM13A) protein. In particular, the present application relates to nucleic acid-based therapeutics for reducing FAM13A gene expression via RNA interference and methods of using such nucleic acid-based therapeutics to reduce abdominal adiposity, reduce body weight, reduce fat mass, improve metabolic parameters including insulin resistance and non-alcoholic steatohepatitis (NASH), and reduce risk of myocardial infarction.

Abstract: The present invention relates to a bispecific antibody construct comprising a first human binding domain which binds to human CDH3 on the surface of a target cell and a second binding domain which binds to human CDS on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Abstract: The present invention relates to uses of bispecific antibodies exhibiting cross-species specificity for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of the same in non-human species and humans. The present invention moreover relates to methods for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of said bispecific antibodies exhibiting cross-species specificity. The present invention also relates to methods of measuring the biological activity and/or efficacy of such bispecific antibodies exhibiting cross-species specificity. In addition, the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity and to methods for the preparation of pharmaceutical compositions comprising said bispecific single chain antibodies exhibiting cross-species specificity for the treatment of diseases.

Abstract: Provided herein are free base crystalline forms, crystalline salts, and an amorphous salts of omecamtiv mecarbil.

Abstract: The present invention relates to a human agonistic CD40 multispecific antibody construct for treatment of solid tumors by engineering a molecule that specifically targets the CD40 pathway on tumor-associated APCs, without systemic CD40 activation.

Abstract: The present invention relates to bispecific antigen binding proteins that are capable of binding to both the human CGRP receptor and the human PAC1 receptor. Pharmaceutical compositions comprising the bispecific antigen binding proteins as well as methods for producing them are also disclosed. Methods of using the bispecific antigen binding proteins to ameliorate or treat conditions associated with the two receptors, such as chronic pain, migraine, and cluster headache, are also described.

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 provides an improved pharmaceutical composition for storage and administration comprising (a) a bispecific antibody construct comprising a first domain binding to a target cell surface antigen and a second domain binding to a second antigen, wherein the bispecific antibody construct is present at a concentration in the range from about 0.5 ?g/ml to 20 mg/ml, (b) a preservative at a concentration effective to inhibit the growth of microbes, and (c) a diluent wherein bispecific antibody construct is stable and recoverable.

Abstract: Provided herein are TIGIT binding proteins, CD112R binding proteins, and combinations thereof. Also provided are compositions comprising TIGIT binding proteins and CD112R binding proteins, optionally further comprising PD-1 binding proteins. Related conjugates, fusion proteins, nucleic acids, vectors, host cells and kits are additionally provided. Further provided are pharmaceutical compositions comprising a TIGIT binding protein, CD112R binding protein, or a combination thereof, optionally, further comprising a PD-1 antigen binding protein, or a conjugate, fusion protein, nucleic acid, vector, or host cell, and a pharmaceutically acceptable carrier, diluent, or excipient, and methods of treating subjects in need thereof.

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: A method for reducing the viscosity of a pharmaceutical formulation is provided that utilizes a viscosity-reducing concentration of an excipient selected from the group consisting of the n-acetyl arginine, n-acetyl lysine, n-acetyl proline and mixtures thereof in combination with a therapeutiv protein. A stable pharmaceutical formulation is also provided.

Abstract: The present disclosure provides compounds of Formula I, useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 (“TREM2”). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula I.