The present invention provides an anti-influenza virus agent that targets biomolecules of host cells including human cells and a method of screening a candidate molecule for the anti-influenza virus agent. That is, the present invention is an anti-influenza virus agent that has an effect of suppressing expression or a function of a gene that encodes a protein having an effect of suppressing incorporation of an influenza virus vRNA or an NP protein into influenza virus-like particles in host cells and the gene is at least one selected from the group including JAK1 gene and the like.

The present invention relates to modified forms of IL-12. These modified forms of IL-12 may be engineered to have a shortened in vivo half-life compared and/or enhanced localization of biological effects compared to that of corresponding non-modified form of IL-12. Short half-life and membrane bound forms of IL-12 may provide greater therapeutic control for in vivo therapeutic delivery, in particular when used in combination with ligand inducible delivery of IL-12. Modified forms of IL-12 engineered to have shortened in vivo half-life and/or enhanced localization of biological effects include heterodimeric p35/p40, single chain and membrane bound forms of IL-12 wherein a naturally occurring IL-12 amino acid sequence is genetically modified to enhance susceptibility of the IL-12 molecule to in vivo proteolytic degradation.

An antibody-drug conjugate having a cyclic benzylidene acetal linker represented by formula (1) or formula (2), wherein Y is an antibody; D is a drug; R.sup.1 and R.sup.6 are each independently a hydrogen atom or a hydrocarbon group; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; w is an integer of 1 to 20; and Z.sup.1 and Z.sup.2 are each independently a selected divalent spacer:

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Compounds, pharmaceutically acceptable salts, esters, prodrugs, and pharmaceutical compositions thereof are disclosed that are useful for inhibition of the biological activity of CCL5 on mammalian cells, as well as methods of treatment for diseases involving the increased biological activity of CCL5.

Compounds, pharmaceutically acceptable salts, esters, prodrugs, and pharmaceutical compositions thereof are disclosed that are useful for inhibition of the biological activity of CCL5 on mammalian cells, as well as methods of treatment for diseases involving the increased biological activity of CCL5.

The present invention concerns methods and compositions for differentiating cells, including human fibroblasts, into chondrocyte-like cells via in vivo mechanical strain. In particular aspects, fibroblasts are delivered to a joint, such as an intervertebral disc, following which the fibroblasts differentiate into chondrocyte-like cells to treat dysfunction of cartilage therein, including to repair degenerated discs, for example. The fibroblasts that do not differentiate to chondrocytic cells because of the location of the cells, as in the fissures of annulus, or other biomechanical and biochemical micro-environment factors, may produce fibrous matrix molecule(s) in aiding tissue repair and regeneration in both nucleus pulposus and annulus fibrosus. In certain aspects, the fibroblasts prior to delivery to the individual are managed in the absence of growth factors, in vitro mechanical strain, and/or matrix molecules, for example.

The present invention concerns methods and compositions for differentiating cells, including human fibroblasts, into chondrocyte-like cells via in vivo mechanical strain. In particular aspects, fibroblasts are delivered to a joint, such as an intervertebral disc, following which the fibroblasts differentiate into chondrocyte-like cells to treat dysfunction of cartilage therein, including to repair degenerated discs, for example. The fibroblasts that do not differentiate to chondrocytic cells because of the location of the cells, as in the fissures of annulus, or other biomechanical and biochemical micro-environment factors, may produce fibrous matrix molecule(s) in aiding tissue repair and regeneration in both nucleus pulposus and annulus fibrosus. In certain aspects, the fibroblasts prior to delivery to the individual are managed in the absence of growth factors, in vitro mechanical strain, and/or matrix molecules, for example.

A medicinal agent for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation is disclosed. A compound having antagonistic activity against the EP.sub.4 receptor is contained as an active ingredient in the medicinal agent. The compound represented by the following general formula (I) as defined in the specification, a salt, an N-oxide, or a solvate thereof, or a prodrug of these is useful as a medicinal component having antagonistic activity against the EP.sub.4 receptor for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation.

##STR00001##

A medicinal agent for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation is disclosed. A compound having antagonistic activity against the EP.sub.4 receptor is contained as an active ingredient in the medicinal agent. The compound represented by the following general formula (I) as defined in the specification, a salt, an N-oxide, or a solvate thereof, or a prodrug of these is useful as a medicinal component having antagonistic activity against the EP.sub.4 receptor for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation.

##STR00001##

The present disclosure relates to methods, uses, medicaments, pharmaceutical formulations, dosage forms, and kits for inhibiting the progression of structural damage in psoriatic arthritis (PsA) patients using IL-17 antagonists, e.g., IL-17 antibodies and antigen-binding fragments thereof, e.g., secukinumab.