Abstract: A drug delivery device includes a housing defining a shell having a proximal end and a distal end and a longitudinal axis extending between the proximal end and the distal end, a needle assembly at least partially disposed within the housing at the proximal end, a drive assembly at least partially disposed within the housing and operably coupled to the needle assembly, and an audible indicator operably coupled to the drive assembly. The needle assembly includes a syringe containing a medicament and a needle or a cannula. The drive assembly is movable between an initial position and a second position that results in the medicament being expelled from the syringe. Upon the drive assembly being positioned in the second position, the audible indicator engages the drive assembly to generate an audible sound indicating the medicament has been expelled from the syringe.

Abstract: The present disclosure provides compounds useful for the inhibition of KRAS G12D. The compounds have a general Formula (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: An insertion mechanism for a drug pump includes an insertion mechanism housing; a sleeve; a rotational biasing member initially held in an energized state; a retraction biasing member and a hub connected to a proximal end of a needle, wherein the retraction biasing member is held initially in an energized state between the hub and the sleeve. The needle is inserted into a target tissue by the rotational biasing member and interaction between the hub and housing. Retraction of the needle is caused by decompressing or de-energizing of the retraction biasing member. A drug delivery pump includes an activation mechanism, a drive mechanism, a sterile access connection, and the insertion mechanism. Assembly and operation methods are provided.

Abstract: A drug delivery device may include a housing having an opening and a drug storage container having a body portion with a proximal end and a distal end and a delivery member extending from the distal end of the body portion. The device may also include a plunger moveable toward the distal end of the drug storage container to expel a drug from the drug storage container through the delivery member and a plunger biasing member configured to urge the plunger toward the distal end of the drug storage container. The device may further include a container holder configured to support the drug storage container with respect to the housing such that a resultant force acting on the drug storage container from the plunger biasing member is at least substantially completely borne by the distal end of the body portion of the drug storage container.

Abstract: The present invention relates to a pharmaceutical adaptor system. The pharmaceutical adaptor system comprises a syringe assembly having an axial extension and comprising a first end part and a second end part, the first end part having a male tubular projection, the syringe assembly comprising a syringe and a connecting element having a first mechanical connection part, a unit such as a needle, a vial, a catheter or an IV line, and an adaptor providing fluid communication between the syringe and the unit and having a second mechanical connection part configured to engage with the first mechanical connection part in an engagement direction, thereby in fully engaged position preventing further relative axial movement between the adaptor and the male tubular projection, wherein the adaptor comprises a sealing element configured to receive the male tubular projection and provide sealing between the male tubular projection and the adaptor.

Abstract: A package for a pharmaceutical product and method of assembly is described that includes a subassembly with a body including a main panel and legs depending downwardly from opposite edges of the main panel, and a sheet of plastic having opposite ends fixed to the body with the sheet of plastic at least partially extending over the main panel. The sheet of plastic is configured to be tensioned over and deformed around one or more primary containers to hold the one or more primary containers in place relative to the main panel of the body.

Abstract: Modular fluid path assemblies are provided that include conduit, coupling, and needle portions of a fluid path fluidly coupled to an outlet of a container. The modular fluid path assemblies further include a needle shield having a tip of the needle embedded therein. So configured, in embodiments, the modular fluid path assemblies can be sterilized, a medicament can be filled in the container, and a stopper inserted in the container so that the pre-sterilized and pre-filled modular fluid path assemblies can have a closed container integrity (CCI) seal.

Abstract: A method of manufacturing a plunger of a drug delivery device includes forming a plunger body. The method includes loading the plunger body into a cavity of a first molding tool of a molding system. The cavity is at least partially defined by a first molding portion and a second molding portion. The method includes coupling a second molding tool to the first molding tool to form a plurality of channels defined by grooves in the first and second molding tools, and injecting molten plastic into the plurality of channels to form an overmolded plunger body. The overmolded plunger body includes a head coupled to the first end of the plunger body and a foot coupled to the second end of the plunger body. The foot is at least partially coupled to the inner wall and the head is coupled to the outer wall of the plunger body.

Abstract: Disclosed herein is a wearable drug delivery device including a container filled at least partially with a drug including at least one of a PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) specific antibody, a granulocyte colony-stimulating factor (G-CSF), a sclerostin antibody, or a calcitonin gene-related peptide (CGRP) antibody. The wearable drug delivery device may include a needle and an insertion mechanism configured to insert the needle into a patient. A fluid pathway connector may define a sterile fluid flowpath between the container and the insertion mechanism. Optionally, a cannula initially disposed about the needle may be included. The cannula may be retained in the patient at an injection site created by the needle after the needle is withdrawn from the patient. Methods of assembly and operation are also provided.

Abstract: The invention provides methods and materials for culturing mammalian cells and harvesting recombinant protein.

Abstract: Drug delivery devices and associated heating and/or cooling devices are disclosed. In an example, a drug delivery device includes a housing, a container, a therapy layer, and a first adhesive layer. The housing includes a top wall and a bottom wall. The container is at least partially disposed within the housing. The container has an inner volume to contain a drug. The therapy layer have a first side and a second side. The first side faces the bottom wall and the second side faces away from the bottom wall. The first adhesive layer couples the first side of the therapy layer and the bottom wall. The therapy layer is adapted to at least one of heat or cool an area adjacent an injection site.

Abstract: Provided herein are methods of treating heart failure in patients exhibiting one or more additional features, comprising administering to the patient a therapeutically effective amount of omecamtiv mecarbil, or a hydrate, salt, or salt of a hydrate thereof.

Abstract: Provided herein are T-cell receptors (TCRs) that when expressed recombinantly on the surface of a T cell are able to recognize the DCAF4L2-derived peptide ILQDGQFLV (SEQ ID NO:1) when presented by HLA-A*02:01 sufficiently to activate the recombinant T cell. Importantly, exemplary TCRs provided herein were thoroughly screened for lack of cross-reactivity with similar peptides that may be presented by normal cells or tissue and for alloreactivity.

Abstract: The present invention relates to compositions and methods for enhancing the gene silencing activity of oligonucleotide compounds. In particular, the invention relates to inhibiting the expression or activity of suppressor proteins, such as RAB18, ZW10, STX18, SCFD2, NAPG, SAMD4B, or VPS37A, to increase the efficacy of ligand-conjugated oligonucleotide compounds in reducing the expression of target genes in a cell.

Abstract: Provided herein are free base crystalline forms, crystalline salts, solvates, amorphous free base, and cocrystals of Compound A.

Abstract: A single-use auto-injector includes a housing and a dosing unit in at least part of the housing. The dosing unit includes a needle, a drug container with drug, a piston movable in the container, a first mechanical power supply for moving the piston to deliver the drug, an activation mechanism, and a mechanical escapement mechanism for controlling the movement of the piston. The auto-injector has a first state in which the needle is protected from needle damage or contamination, a second state in which the needle is ready to penetrate a human body, a third state in which the needle has penetrated the human body and is ready to dose, and a fourth state in which the needle is shielded to avoid unintended needle sticks. A second mechanical power supply is configured to shift state of the auto-injector from the third state to the fourth state.

Abstract: Systems and methods that facilitate the automatic (or substantially automatic) preparation of a sample of a product containing polypeptides for glycan analysis and automatic (or substantially automatic) performance of a glycan assay of that sample. Thus, the preparation and analysis can be performed substantially in-real time, or, in other words, much more quickly than presently allowed by conventional systems and methods.

Abstract: Configurable handheld biological analyzers and related biological analytics methods are described for identification of biological products based on Raman spectroscopy. A biological classification model configuration is loaded into a computer memory of a configurable handheld biological analyzer having a processor and a scanner. The biological classification model configuration includes a biological classification model configured to receive a Raman-based spectra dataset defining a biological product sample as scanned by the scanner. A spectral preprocessing algorithm is executed to reduce a spectral variance of the Raman-based spectra dataset. The biological classification model identifies a biological product type based on the Raman-based spectra dataset and further based on a classification component selected to reduce at least one of (1) a Q-residual error or (2) a summary-of-fit value of the biological classification model.

Abstract: An adhesive patch for a drug delivery device with a bacteria impermeable sterility margin surrounding an edge surface of the adhesive patch is disclosed, as well as a drug delivery device fixed to such an adhesive patch and a method of assembling a drug delivery device with such an adhesive patch. In some arrangements, the sterility margin is attached to or integral with a lower liner on a lower surface of the adhesive patch. In other arrangements, the sterility margin is attached to or integral with an upper liner on an upper surface of the adhesive patch.

Abstract: ultraviolet (UV) based imaging method for determining protein concentrations of unknown protein samples based on automated multi-wavelength calibration. In various embodiments, a processor receives each of a standard set of wavelength data and an unknown set of wavelength data as recorded by a detector. Each standard set of wavelength data and unknown set of wavelength data defines a series of absorbance-to-wavelength value pairs across a first range of wavelengths selected from a range of a single-wavelength light beams of a UV spectra. The processor generates a multi-wavelength calibration model based on each of a first series of first absorbance-to-wavelength value pairs of the standard set of wavelength data. The processor implements the multi-wavelength calibration model to determine, for each unknown protein sample of the given unknown protein samples, a plurality of protein concentration values.