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: Drug delivery devices and related methods of assembly are disclosed. The drug delivery device may include a housing, a container, a trigger member, and an interlock assembly. The trigger member may be selectively moveable relative to the housing to activate operation of at least one activatable element of the drug delivery device. The interlock assembly may include a lever mounted rotatably relative to the housing, a proximity sensor moveable between a first position extending beyond an exterior surface of the housing and a second position retracted toward the housing, and a rotational biasing member operably connected to the proximity sensor via the lever. When the proximity sensor is in the first position, the interlock assembly may limit movement of the trigger member relative to the housing. The rotational biasing member may be configured to exert a torque biasing the proximity sensor toward the first sensor position.

Abstract: Provided herein are processes for synthesizing mcl-1 inhibitors and intermediates such as compound Z that can be used to prepare them. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof and compound A2, and salts and solvates thereof.

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: Compounds of Formula I and Formula II, pharmaceutically acceptable salts 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: Figure I and Figure II where the definitions of the variables are provided herein.

Abstract: A drug delivery device includes a casing and a storage container with a dose delivery member, at least a portion of which extends through an opening in the casing. A guard is movable relative to the casing between extended and retracted positions. The guard surrounds the extended portion of the dose delivery member in the extended position, and exposes the extended portion in the retracted position. An interference arrangement is included for providing selected threshold of resistance to movement of the guard from the extended position to the retracted position during insertion of the dose delivery member into body tissue. The arrangement has first and second members engaging one another to retain the guard in the extended position. The first or second member can move if the selected threshold of resistance is exceeded to allow the members to slide and allow the guard to move into the retracted position.

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: Provided herein are methods of processing a polypeptide or protein for analysis, e.g., peptide mapping analysis by mass spectrometry. In exemplary embodiments, the method comprises incubating a digested sample at a mildly acidic pH and/or in the presence of a chaotrope, wherein the digested sample is produced by digesting a polypeptide with a protease to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with a protease which cleaves C-terminal to tryptophan to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with trypsin at an enzyme:substrate (E:S) weight ratio of about 1:1 to about 1:15 to produce a digested sample comprising at least two peptides. In exemplary aspects, the digested sample comprises at least one or two peptides each comprising a tyrosine at the C-terminus.

Abstract: An apparatus for nondestructive detection of transparent or reflective objects in a vessel includes an imager configured to acquire data that represent light reflected from spatial locations in the vessel as a function of time, a memory operably coupled to the imager and configured to store the data, and a processor operably coupled to the memory and configured to detect the objects based on the data by (i) identifying a respective maximum amount of reflected light, over time, for each location in the spatial locations based on the data representing light reflected from the spatial locations as a function of time, and (ii) determining a presence or absence of the objects in the vessel based on the number of spatial locations whose respective maximum amount of reflected light, over time, exceeds a predetermined value.

Abstract: Systems and methods used to control tangential flow filtration are provided, including control systems and methods for use with connected systems with upstream processing units, such as chromatography processing units, in fluid communication with a tangential flow filtration processing unit. Also included are control systems and methods for performing continuous concentration using single-pass tangential flow filtration with permeate flow control.

Abstract: The present invention relates to severe acute respiratory syndrome coronavirus 2 (“SARS-CoV2”) immunogens useful for the generation of therapeutic antibodies and vaccine development. Such therapeutic antibodies include human antibodies and antigen-binding portions thereof that specifically bind to human SARS-CoV2 S protein, and that function to neutralize SARS-CoV2. The present invention also relates to methods of generating antibodies and antigen-binding portions thereof that specifically bind to human SARS-CoV2 S protein.

Abstract: The ability to generate a single antibody-based construct that can recognize multiple targets simultaneously, is paramount to advance many therapeutics candidates to clinic. Often, this implies extensive protein design with vary degrees of success. In the case of multispecific antibodies, the driving of the HC/LC pairing in the Fab region represents one of the most difficult challenges yet in the field of multispecific engineering. Described here is the discovery of a new placement for a non-canonical disulfide bond and as such the generation of an asymmetric cysteine interface between two Fabs present in the same molecule which will further enable the production of multispecifics.

Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.

Abstract: The present invention relates to monoclonal antibodies that specifically bind to chemically-modified nucleic acid molecules, including pan-specific antibodies that bind to chemically-modified nucleic acid molecules independent of nucleotide sequence. The invention also relates to methods of generating monoclonal antibodies to chemically-modified nucleic acid molecules as well as methods of using such antibodies to detect nucleic acid molecules in biological samples. Various immunoassays incorporating the monoclonal antibodies of the invention are also disclosed.

Abstract: Provided herein are solid dispersions comprising AMG 397, methods of preparing the solid dispersion, and pharmaceutical formulations comprising AMG 397.

Abstract: A syringe de-capper including a base having a lower surface and an upper surface opposite the lower surface. The syringe de-capper also includes a de-capping member extending from the upper surface of the base, the de-capping feature including a proximal end adjacent to the base, a distal end spaced away from the base. The de-capping feature includes opposing first and second lateral surfaces defining a proximal thickness at the proximal end and a distal thickness at the distal end, the distal thickness is smaller than the proximal thickness. Also, the syringe de-capper includes a slot disposed in the de-capping member, the slot extending from the distal end of the de-capping member toward the proximal end of the de-capping member and configured to slidably receive a distal end of a syringe for removing a cap therefrom.

Abstract: The present invention provides processes for making 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid as well as intermediates and processes for making the intermediates. Also provided are crystalline forms of the compound and the intermediates.

Abstract: A robotic inspection platform comprises a robotic arm, an imager, and a controller. The controller causes the robotic arm to retrieve, using its end effector, a container, and to manipulate the container such that the container is sequentially placed in a plurality of orientations while in view of the imager. The controller also causes the imager to capture images, with each of the images being captured while the container is in a respective one of the orientations. The controller also determines one or more attributes of the container, and/or a sample within the container, by analyzing the images using a pattern recognition model and, based on the attribute(s), determines whether the container and/or sample satisfies one or more criteria. If the container and/or sample fails to satisfy the criteria, the controller causes the robotic arm to place the container in an area (e.g., bin) reserved for rejected containers and/or samples.