Abstract: An autoinjector drug delivery device configured with a stall and endpoint detection algorithm is described that allows for variations in the fill of the drug, barrel, plunger, and other components. The stall or end point detection causes the autoinjector to stop an extrusion process.

Abstract: A drug delivery system is disclosed that includes a drug delivery device having a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end to be received within a patient, and one or more controllable elements. The drug delivery system may further include one or more sensors coupled to the drug delivery device, and a controller coupled to the one or more sensors and the one or more controllable elements. The controller may be configured to use the one or more sensors to determine a condition or an operational state of the drug delivery device. Furthermore, the controller may be configured to control the controllable element based on the condition or the operational state of the drug delivery device and/or identity information stored in a memory onboard the device. A method for use with a drug delivery device is also disclosed.

Abstract: Methods, devices, and components are provided to reduce tissue resistive pressure during a subcutaneous drug delivery operation by increasing the size of the injection cavity by partially retracting the drug delivery member after inserting the drug delivery member to a subcutaneous position. The drug delivery devices described herein include a magnetic actuator operably coupled to a primary container assembly including a drug delivery member. Power can be selectively provided to the magnetic actuator by a controller to retract the drug delivery member a predetermined distance to relieve pressure in an injection cavity in a patient. A force sensor can provide the controller with a drug delivery member insertion force. The controller can then estimate a tissue resistive pressure based on the drug delivery member insertion force and determine the predetermined distance for the drug delivery member retraction based on the tissue resistive pressure.

Abstract: A drug delivery system includes a storage container defining one or more storage compartments and having at least one container sensor coupled thereto, a container condition change mechanism coupled to the storage container for imparting a change on one or more conditions of the one or more storage compartments, at least one drug delivery device adapted to deliver a drug to a user and adapted to be at least partially disposed within one or more of the one or more storage compartments, at least one delivery device sensor, a delivery device condition change mechanism coupled to the drug delivery device, and a controller coupled to the storage container. The storage container may be adapted to hold a number of drug delivery devices within a number of sealable storage compartments. The container sensor is adapted to sense a condition of the storage container, and the delivery device sensor is adapted to sense a condition of the at least one drug delivery device.

Abstract: The present invention relates to methods for detecting and quantifying intact protein-polynucleotide conjugate molecules in various sample matrices. In particular, the methods utilize triplex forming oligonucleotides in combination with protein-specific binding partners to respectively detect the polynucleotide and protein components of the conjugate molecules.

Abstract: Methods of modulating the properties of a cell culture expressing a protein of interest are provided. In various embodiments the methods relate to the addition of cell-cycle inhibitors to growing cell cultures.

Abstract: The present invention provides a cyclobutyl dihydroquinoline sulfonamide compound of Formula (I), an enantiomer, diastereoisomer, atropisomer thereof, a mixture thereof, or a pharmaceutically acceptable salt thereof, that inhibits voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing the compounds of the present invention. Also further provided is an atropi-selective preparation of said compounds of Formula (I), and intermediate thereof.

Abstract: The present invention provides a compound of Formula (I): an enantiomer, diastereoisomer, atropisomer thereof, a mixture thereof, or a pharmaceutically acceptable salt thereof, that inhibits voltage-gated sodium channels, in particular NaV1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing the compounds of the present invention. Also further provided is an atropi-selective preparation of said compounds of Formula (I), and intermediate thereof.

Abstract: A method for determining predicted failure rates of drug injection devices includes receiving a set of parameters that specify physical properties of (i) a syringe, and (ii) a liquid drug, and (iii) a drug injection device configured to deliver the liquid drug to a patient via the syringe. The method further includes receiving failure rate data that specifies a measured rate of failure of the drug injection device in response to various peak pressures within the syringe, applying the received set of parameters to a kinematic model of the drug injection device to determine a predicted peak pressure within the syringe, including determining the predicted peak pressure as a function of impact velocity of the liquid drug, determining a probability of failure of the drug injection device using (i) the received failure rate data and (ii) the predicted peak pressure, and providing an indication of the determined probability of failure to an output device.

Abstract: Disclosed are Fc-containing proteins comprising a binding region and a variant Fc region that can elicit one or more immune effector function and/or bind to an Fc receptor more effectively than a similar Fc-containing protein comprising a wild type Fc region. Also disclosed are nucleic acids encoding such Fc-containing proteins, methods for making such proteins, and methods of treatment utilizing such proteins.

Abstract: Disclosed herein are aqueous pharmaceutical formulations comprising denosumab or another human anti-RANKL monoclonal antibody or portion thereof, and characteristics of pH, buffer systems, and amino acid aggregation inhibitors. Also disclosed are presentation of the formulation for use, e.g. in a single-use vial, single-use syringe, or glass container, methods of using the formulations and articles for preventing or treating diseases, and related kits.

Abstract: A plunger configured as described herein provides geometry optimizations to minimize friction magnitude and variability during use by maintaining low deformation under large extrusion forces. More specifically, plunger embodiments described herein minimize a contact area between the plunger and a syringe or chamber, while also maintaining high contract pressures to maintain container closure integrity. Moreover, the plunger embodiments are configured to have minimal or no increase in the contact area under high loads associated with the delivery of viscous products.

Abstract: The invention provides for the removal of a large fraction of contaminants from protein preparations while maintaining a high level of recovery using tentacle anion exchange matrix chromatography medium. Using the methods of the invention, leached affinity chromatography contaminants can be removed from recombinant protein preparations.

Abstract: Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: (I), (II) where the definitions of the variables are provided herein.

Abstract: The present invention concerns a method for preparing antigen binding proteins specific for PCSK9 with reduced viscosity. The method proceeds by replacing residues in high viscosity variable domain subfamilies with residues in correlating low viscosity subfamilies. The method further comprises substituting residues in the Fc domain with residues associated with low viscosity and adding charged residues to the C-terminus of the Fc domain. The present invention further concerns antigen binding proteins produced by this method.

Abstract: This invention concerns a process for making a lyophilized pharmaceutical formulation of a therapeutic protein, which comprises (a) providing a formulation of a bulk amount of the therapeutic protein, (b) measuring the concentration of the therapeutic protein in said bulk formulation, (c) adjusting the fill weight of the protein in said bulk formulation to achieve a fixed dose of the protein, and (d) lyophilizing the protein fill weight-adjusted formulation to achieve a final formulation in a container, wherein the product concentration post reconstitution with a fixed volume is within a predetermined acceptance range. The process is particularly suitable for formulations with low protein concentrations (e.g., 0.05 mg/mL to 20 mg/mL).

Abstract: The present invention relates to antigen binding proteins, such as monoclonal antibodies, that specifically bind to and activate human triggering receptor expressed on myeloid cells-2 (TREM2) and pharmaceutical compositions comprising such antigen binding proteins. The agonist antigen binding proteins (e.g. antibodies) of the invention are capable of activating TREM2/DAP12 signaling in myeloid cells in the absence of Fc-mediated cross-linking of the antigen binding proteins. Methods of treating or preventing conditions associated with TREM2 loss of function, such as Alzheimer's disease and multiple sclerosis, using the antigen binding proteins are also described.

Abstract: The present invention relates to IL-17 Receptor A (IL-17RA or IL-17R) antigen binding proteins, such as antibodies, polynucleotide sequences encoding said antigen binding proteins, and compositions and methods for diagnosing and treating diseases mediated by IL-17 Receptor A activation by one or more IL-17 ligands. The present invention relates to the identification of neutralizing determinants on IL-17 Receptor A (IL-17RA or IL-17R) and antibodies that bind thereto. Aspects of the invention also include antibodies that compete for binding with the IL-17RA neutralizing antibodies described herein.

Abstract: Protein formulations and methods of making and using such formulations are provided herein. The formulation can be an ophthalmic formulation, such as for intravitreal administration. In some embodiments, the formulation comprises a VEGFR-Fc fusion protein, such as aflibercept. In some embodiments, the formulation comprises a Tris buffer.

Abstract: The present disclosure relates to a method of capping, reducing, and oxidizing cys-mAbs in order to provide homogenous material for subsequent conjugation reactions. The present method demonstrates robust ways to manufacture conjugates of cysteine-engineered antibodies that offer high yield and consistent product quality.