It is an object of the present invention to provide an antibody binding to CDH6 and having internalization activity, an antibody-drug conjugate of the antibody and a drug having antitumor activity, a pharmaceutical product comprising the antibody-drug conjugate and having therapeutic effects on a tumor, a method for treating a tumor using the antibody, the antibody-drug conjugate or the pharmaceutical product, and the like. The present invention provides an anti-CDH6 antibody having internalization activity, an antibody-drug conjugate of the antibody and a drug having antitumor activity, a pharmaceutical product comprising the antibody or the antibody-drug conjugate, and a method for treating a tumor.

Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

In some aspects, the disclosure relates to compositions and methods comprising ActRII polypeptides to treat, prevent, or reduce the progression rate and/or severity of pulmonary arterial hypertension, particularly treating, preventing or reducing the progression rate and/or severity of one or more pulmonary arterial hypertension associated complications.

Uncultured amniotic cell and protein fraction products derived from amniotic fluid and methods of preparing and using those compositions are provided. According to the methods of the present invention, uncultured amniotic cell and protein products may be derived from a large sample of amniotic fluid to provide a higher concentration of tissue regeneration components. Described are methods for separating uncultured amniotic cells or protein fractions from other components of amniotic fluid and the resulting uncultured amniotic cell and protein products. Furthermore, the present invention includes methods for delivering the uncultured amniotic cell and protein products to the skin and eye, including before, during, or after a treatment procedure.

A microneedle patch applicator housing, being formed from a single sheet or film having a top surface and an undersurface, the housing including a flat peripheral base part and a raised part surround by the peripheral base part and bulging vertically, with respect to the peripheral base part, from the undersurface toward the top surface, an undersurface portion of the raised part forming a surface supporting a microneedle patch, the raised part including a plurality of concavely bent parts, and the concavely bent parts each having a concave bottom toward a direction away from a center portion of the raised part.

The present invention provides a solution to increase the drug loading capacity and drug delivery precision of dissolving microneedles. These solutions include: (a) increasing the base of the microneedle cavities without substantially changing the microneedle's height and geometry, (b) use of drug suspension and sedimentation of drug by centrifugation, and (c) a specific centrifugation order for filling drug and matrix material. In the first preferred embodiment, a microneedle master mould comprising a plurality of pyramidal microneedles (5100), wherein each of the pyramidal microneedles further comprising a chamfered base (5200) which extends to and adjoins with its neighbouring chamfered bases is provided. In the second preferred embodiment, a method of making dissolving microneedles is provided, comprising (a) providing a microneedle template comprising a plurality of pyramidal microneedle cavities, wherein each of the pyramidal microneedle cavities further comprising a chamfered base which extends to and adjoins with its neighbouring chamfered bases; (b) loading a drug suspension in the substrate cavity on the microneedle template; (c) centrifuging the microneedle template which is loaded with a drug suspension, (d) loading a matrix material solution in the substrate cavity on the microneedle template; (d) centrifuging the microneedle template loaded with the drug suspension and the matrix material solution; and (e) drying the centrifuged microneedle template in a controlled environment.

A delivery device or patch is disclosed that includes a detachable hybrid microneedle depot (d-HMND) for cell delivery. The system includes, in one embodiment, an array of microneedles formed from an outer PLGA shell and an internal gelatin methacryloyl (GelMA)-mesenchymal stem cells (MSC) mixture (GMM). The array of microneedles project from a base substrate layer that may be flexible. The therapeutic device may be applied to a tissue site of interest and the base substrate layer is removed leaving the hybrid microneedles in the tissue at the site of application to deliver MSCs. Other stem/therapeutic cells may also be delivered with the hybrid microneedles.

The present invention provides a microneedle patch application system designed to facilitate the simple and expeditious deployment of a microneedle patch onto a tissue substrate such as the skin, for drug delivery or other applications, the system including a microneedle patch including arrays of opposing microneedles and an applicator operable to deploy the patch onto the tissue substrate by displacing the patch from an undeployed to a deployed state.

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface. In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent. In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent.

This disclosure relates to anti-coronavirus (e.g., SARS-CoV-2) antibodies or antigen-binding fragments and uses thereof.