Abstract: The invention provides a crystalline imidazo[4,5-b]pyridine compound, pharmaceutical compositions, methods of inhibiting tropomyosin-related kinase and/or c-FMS, and methods of treating medical diseases and conditions, such as pain.

Abstract: The present invention relates to a novel analytical method for detecting one or more analytes in a source sample by continuous flow 2D LC-MS/MS using a single LC system.

Abstract: The present disclosure is directed to adapters for mixing vials of drug products, and more specifically to multi-vial adapters for reconstituting lyophilized drug products and/or diluting concentrated drug products. It is an object to address one or more of drawbacks in connection with the drug preparation process, for example, by simplifying the procedure where multiple vials are required to be diluted or reconstituted in a serial manner. As such, the multi-vial adapters described herein simplify the complexity of preparing and handling multiple vials of drug product, which significantly reduces preparation time, addresses dosing-related challenges like weight-based preparation, reduces drug waste issues, and reduces risks associated sterility and contamination, among other benefits.

Abstract: A medicament delivery device includes a needle disposed at a distal end of the medicament delivery device. The medicament delivery device includes a body for a syringe and a needle cover axially movable relative to the body between an extended position in which the needle cover covers the needle and a retracted position in which the needle protrudes from the distal end of the needle cover. The medicament delivery device includes a plunger axially movable relative to the body to dispense medicament from the medicament delivery device. The medicament delivery device includes a needle cover biasing mechanism configured to bias the needle cover distally from the retracted position to the extended position. The medicament delivery device includes a locking mechanism configured to be moved by the plunger from an initial configuration to an engaged configuration to prevent a distal movement of the needle cover biasing mechanism.

Abstract: An injection device comprising: an injection device body; a plunger comprising one or more plunger recesses; biasing means for applying a biasing force to bias the plunger in a distal direction of the injection device; a casing at least partially enclosing the plunger, the casing comprising one or more toothed beams each comprising a tooth engageable with a corresponding plunger recess of the one or more plunger recesses; and a rotatable collar at least partially enclosing the casing and comprising one or more collar recesses on an inner surface of the rotatable collar.

Abstract: Some injection devices include an injection device body, a needle shroud retractable into the injection device body, a control spring coupled to the needle shroud and biased to cause the needle shroud to be at least partially extended from the injection device body in an initial position, and a hold detent mechanism coupled to at least the needle shroud. The hold detent mechanism is configured to (i) activate, when the needle shroud is retracted from the initial position into the injection device body to a hold position, to create a hold detent force, and (ii) deactivate, when the needle shroud is extracted from the hold position subsequent to the retraction, to release the hold detent force and enable the needle shroud to extend from the injection device body to substantially the initial position.

Abstract: A medicament delivery device for reducing a force required to activate the device includes a needle disposed at a distal end of the device, a needle cover, and a body. The needle cover is axially movable relative to the body between an initial position in which the needle cover covers the needle and an activated position for dispensing a medicament. The needle protrudes from a distal end of the needle cover when the needle cover is in the activated position. The medicament delivery device includes a carrier configured to support a syringe. The carrier is disposed within the needle cover and includes a deformable element configured to change from a first configuration in which the deformable element is engaged with the needle cover to a second configuration in which the deformable element is not engaged with the needle cover.

Abstract: An injection device includes a housing, a needle shroud movable within the housing between an extended position and a retracted position, and a needle shroud latch configured to hold the needle shroud in its retracted position. The needle shroud latch includes a button arranged at the housing such that a user can actuate the button by applying an actuation force to the button to hold the needle shroud in its retracted position.

Abstract: This application relates to an injector device for delivery of a medicament, particularly to an auto-injector device.

Abstract: A medicament delivery device reduces a force required for activation, and the medicament delivery device comprises: a needle at a distal end of the device; a needle cover and a body, wherein the needle cover is axially movable relative to the body between an initial position, in which the needle cover covers the needle, and an activated position for dispensing a medicament from the device; and a carrier configured to support a pre-filled syringe, wherein the carrier is disposed within the needle cover and comprises one or more resilient members, wherein the needle cover comprises one or more first slots and one or more second slots and the one or more resilient members are each configured to engage with a respective one of the one or more first slots when the needle cover is in the initial position, and to enter a respective one of the one or more second slots after a proximal movement of the needle cover from the initial position to an intermediate position.

Abstract: The present application provides methods of treating Pompe disease such as infantile-onset Pompe disease (IOPD) using a pharmaceutical composition comprising an oligosaccharide-acid ?-glucosidase (GAA) conjugate, such as avalglucosidase alfa. Also provided are formulations of the oligosaccharide-GAA conjugates.

Abstract: Provided herein are conjugates comprising a protein and an oligosaccharide of one of Formulae I-VI. Also provided herein are pharmaceutical compositions comprising such conjugates. Further provided herein are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-glycoprotein conjugate.

Abstract: Provided are recombinant and chemically-conjugated antibodies and fragments thereof modified with one or more poly-aspartate (poly-D) peptides (e.g., a D10 sequence) to improve localization of the antibodies or fragments to bone. Methods of making and using of these antibodies and fragments also are disclosed.

Abstract: Provided herein are improved rAAV (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of ocular disorders or CNS disorders wherein the rAAV comprise one or more substitutions of amino acids that interact with heparan sulfate proteoglycan. The invention provides methods for improved transduction of retinal cells and methods for treating ocular diseases with improved compositions of rAAV particles. Further provided herein are improved recombinant adeno-associated virus (rAAV) (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of disorders of the CNS. The invention provides methods for delivering the rAAV to the CNS, methods for treating disorders of the CNS with improved compositions of rAAV particles, and kits for delivering the rAAV to the CNS and/or treating a CNS disorder.

Abstract: The present disclosure provides using a double-stranded oligonucleotide compound as a novel therapy to improve the patient reported outcomes and quality of life of patients with hemophilia A or hemophilia B.

Abstract: A fluid transfer device for transferring a fluid between a diluent container and a medicament container includes a body, a first connecting portion to connect to the diluent container, and a second connecting portion to connect to the medicament container. The first connecting portion includes a first fluid channel to fluidically communicate with an interior of the diluent container, and the second connecting portion comprises a second fluid channel to fluidically communicate with an interior of the medicament container. A third fluid channel is configured to fluidically communicate with the interior of the medicament container and with a pump device. The first fluid channel merges into the second fluid channel to form a first flow path from the diluent container into the medicament container and to form a second flow path from the medicament container into the diluent container.

Abstract: A fluid transfer device includes a body, a first connecting portion comprising a first fluid channel to fluidically communicate with an interior of the diluent container, a second connecting portion comprising a second fluid channel to fluidically communicate with an interior of a medicament container, and a third fluid channel to fluidically communicate with a pump device. In a first configuration, the first fluid channel is fluidically coupled to the third fluid channel, and the third fluid channel is fluidically coupled to the second fluid channel to prevent a flow of fluid from the third fluid channel into the first fluid channel. In a second configuration, the second fluid channel is fluidically coupled to the third fluid channel, and the third fluid channel is fluidically coupled to the first fluid channel to prevent a flow of fluid from the third fluid channel into the second fluid channel.

Abstract: The present application provides methods of treating a disease, such as Pompe disease, in a subject, comprising detecting an erythropoiesis biomarker in a sample of the subject after administration of methotrexate and a therapeutic agent to the subject, and administering further treatment with or without concurrently administering additional immune tolerance induction or immunosuppression therapy based on the level of the erythropoiesis biomarker. Further provided by the present application are methods and kits for assessing the level of immune tolerance to a therapeutic agent in a subject based on detection of an erythropoiesis biomarker after administration of methotrexate and the therapeutic agent to the subject.

Abstract: This disclosure anti-human IgG antibodies and antigen-binding portions thereof derived from rabbits and methods of using these antibodies and portions.

Abstract: Provided herein are methods for preparing a SHP2 inhibitor and intermediates useful therein.