Abstract: The present disclosure provides novel 15-hydroxy-prostaglandin dehydrogenase inhibitors, pharmaceutical compositions comprising such compounds, and methods of using such compounds and compositions in treating 15-hydroxy-prostaglandin dehydrogenase-mediated disease. Also provided are methods of making such compounds and intermediates thereof. The compounds have a structure of Formula (I). Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Abstract: Disclosed herein are compounds useful for the inhibition of IGF-1R. The compounds have a general Formula (I): or a pharmaceutically acceptable salt 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, an IGF-1R mediated disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

Abstract: The present disclosure provides combination therapy with GDF15 molecules. In some embodiments, the GDF15 molecule is a GDF15-Fc fusion, in which a GDF15 region is fused to an Fc region, optionally via a linker. In one embodiment, combination therapy comprises administration of a GDF15 molecule with a GLP-1R agonist. In another embodiment, combination therapy comprises administration of a GDF15 molecule with a GIPR antagonist.

Abstract: Automated systems and methods for low-pH viral inactivation include adding an elution pool to a first vessel with an acid. Once first vessel pH probes measure sufficiently low pH, the pool is transferred to a second vessel, where the pH is checked again, and the pool is held for a time sufficient to reduce virus concentration to a safe level, and neutralized, filtered, and transferred to a third vessel. Meanwhile, the first vessel is filled with a known-pH buffer, which is checked against readings from first vessel pH probes to determine whether recalibration is needed. After the pool is transferred to the third vessel, the second vessel is filled with a known-pH buffer, which is checked against readings from second vessel pH probes to determine whether recalibration is needed. The process repeats when the known-pH buffer is dumped and a new elution pool is added to the first vessel.

Abstract: The present invention relates to methods for purifying nucleic acids. In particular, the present invention relates to methods for purifying carbohydrate-conjugated oligonucleotides using a mixed-mode stationary phase and a mobile phase comprising a dual salt/organic solvent gradient. Methods for purifying carbohydrate-conjugated oligonucleotides using an anion exchange stationary phase and a mobile phase comprising a dual pH/salt gradient are also described.

Abstract: A drug delivery device is provided comprising a housing having a first opening, a drug storage device including a delivery member having an insertion end configured to extend at least partially through the first opening in the housing, a plunger, a drive mechanism activatable to drive the plunger in a distal direction to expel a drug from the drug storage container, and a needle guard moveably disposed adjacent to the first opening. The needle guard has an extended position where the needle guard extends at least partially through the first opening and a retracted position where the needle guard is positioned away from the extended position. The needle guard has a base surface configured to contact an injection site and having an inner diameter defining a second opening and an outer diameter. A ratio of the outer diameter to the inner diameter is between about 3:1 and about 2:1.

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

Abstract: Methods of determining relative unpaired glycan content of an IgG antibody composition are provided. In exemplary embodiments, the method comprises treating the IgG antibody composition with two enzymes to forma mixture of Fab fragments and Fc fragments, wherein one enzyme cleaves an antibody heavy chain at a site N-terminal to the hinge region disulfide linkages and the other enzyme cleaves the ?1,4 linkage between core GlcNAc residues to form Fc fragments each comprising a pair of core glycan structures, (b) separating the Fab fragments from the Fc fragments, and (c) quantifying the abundance of (i) paired afucosylated Fc fragments, (ii) unpaired afucosylated Fc fragments, (iii) paired high mannose Fc fragments, and/or (iv) unpaired high mannose Fc fragments, to determine the relative unpaired afucosylated (AF) glycan content and relative unpaired high mannose (HM) glycan content.

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: An example drug delivery device includes a syringe assembly including a needle. The drug delivery device includes a handle carrying the syringe assembly and including a first portion, a second portion, a tapered surface, and a window. The first portion being wider than the second portion. The tapered surface extending from the first portion to the second portion. The needle of the syringe assembly adapted to extend from adjacent the second portion during an injection procedure. The window positioned between the first portion and the second portion and adapted to allow contents of the drug delivery device to be viewed. The drug delivery device includes a base adapted to be positioned adjacent the second portion of the handle during at least the injection procedure. The base being wider than the second portion of the handle and adapted to increase stability of the drug delivery device during the injection procedure.

Abstract: A drug delivery device including a housing, a drug storage container, and a removable cap is provided. The removable cap may be configured to be removably coupled with the housing such that the removable cap has a storage position where the removable cap is coupled with the housing and at least partially covering an opening in the housing and a removed position where the removable cap is not coupled with the housing. The removable cap may include an outer portion, an inner portion, and a gap separating at least a portion of the inner portion and at least a portion of the outer portion such that the at least a portion of the outer portion is allowed to bend with respect to the at least a portion of the inner portion if the at least a portion of the outer portion is subjected to an external force.

Abstract: The present invention relates to the use of oncolytic viruses (e.g., modified HSV-1 viruses) for the treatment of various types of cancer. In addition, the present invention relates to compositions and kits relating to such uses of oncolytic viruses.

Abstract: Disclosed herein is an improved process for the synthesis of compound (A): (A), or a salt or solvate thereof via methylation of compound (B): (B), or a salt or solvate thereof, a crystalline hydrate of compound A, and pharmaceutical formulations comprising a crystalline hydrate of compound (A).

Abstract: The present invention relates to RNAi constructs for reducing expression of the LPA gene, which encodes apolipoprotein(a), a component of lipoprotein(a) (Lp(a)) particles. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease, peripheral artery disease, stroke, and myocardial infarction, and to reduce serum Lp(a) levels are also described.

Abstract: The present disclosure relates, in general, to muteins of IL-10 that are stable as monomers, antigen binding proteins that bind to TREM-1, and antigen binding proteins comprising IL-10 muteins and antigen binding moieties, e.g., anti-TREM-1 antibodies, and compositions thereof. The disclosure also provides methods of treating inflammatory disease, such as inflammatory bowel disease or ulcerative colitis, using the compositions.

Abstract: Systems for performing cellular analysis and related devices for conditioning environments adjacent chips in such systems. A device for conditioning an environment adjacent a chip in a system for performing cellular analysis, the device includes a cover for being disposed adjacent the chip and comprising a planar body having a top surface, a bottom surface, and an outer edge surface. The cover includes a central opening extending between the top surface and the bottom surface and bounded by an inner edge surface of the cover. The cover also includes a fluid inlet extending into the body from the outer edge surface between the top surface and the bottom surface the fluid inlet arranged to accept a gas to be delivered to the central opening. The cover also includes a plurality of fluid outlets defined in the inner edge surface and in fluid communication with the fluid inlet. The plurality of fluid outlets are arranged to receive the gas from the fluid inlet and exhaust the gas into the central opening.

Abstract: Provided herein is a process comprising heating a composition comprising (P)-compound A or a salt thereof and a solvent to a temperature of 250° C. to 350° C. to form racemized compound A. Also provided is a process for isolating (P)-compound A from a composition comprising (P)-compound A and a tartrate, as described herein. Further provided herein, is a process for isolating a free acid of a tartrate or a hydrate thereof from a composition comprising a tartrate, (P)-compound A, and an organic solvent.

Abstract: Described herein are techniques to regulate the treatment of a culture of cells having cells corresponding to different cell categories. Some techniques may be used together with a cell imaging and incubation system including an imaging sensor configured to obtain an image of the culture and an incubator configured to incubate the culture. Regulation of treatment of the culture may be based on the processing of an image of the culture obtained by the imaging sensor of the system. The processing may include segmenting the image of the culture into multiple image segments by assigning individual pixels of the image to corresponding cell categories. According to some embodiments, the techniques include determining, based on the image segments, an amount of the culture corresponding to a particular cell category. The amount of the culture corresponding to the particular cell category may inform regulation of the treatment of the culture.

Abstract: A drug delivery device assembly is provided, including an injector housing, a needle assembly, a drive assembly, and a reflective surface. The injector housing may include a body with a proximal end, a distal end, a longitudinal axis extending between the proximal end and the distal end, and at least one window. The needle assembly is at least partially disposed within the body and may include a syringe barrel containing a medicament and a needle or a cannula, wherein at least a portion of the syringe barrel positioned such as to be visible through the at least one window. The drive assembly is at least partially disposed within the body and operably coupled with the needle assembly to urge the medicament through the needle or cannula during an injection sequence. The reflective surface is positioned with respect to the window such as to increase visibility of the syringe barrel.