The present invention relates generally to novel depsipeptides, to methods for the preparation of these novel depsipeptides, to pharmaceutical compositions comprising the novel depsipeptides; and to methods of using the novel depsipeptides to treat or inhibit various disorders.

The present invention discloses methods and compositions for modulating the quality of an immune response to a target antigen in a mammal, which response results from the expression of a polynucleotide that encodes at least a portion of the target antigen, wherein the quality is modulated by replacing at least one codon of the polynucleotide with a synonymous codon that has a higher or lower preference of usage by the mammal to confer the immune response than the codon it replaces.

This invention relates to compounds useful for treating fungal infections, more specifically topical treatment of onychomycosis and/or cutaneous fungal infections. This invention is directed to compounds that are active against fungi and have properties that allow the compound, when placed in contact with a patient, to reach the particular part of the skin, nail, hair, claw or hoof infected by the fungus. In particular the present compounds have physiochemical properties that facilitate penetration of the nail plate.

A substituted alkenylbenzene compound of formula (4):

##STR00001##

wherein X.sup.1 is selected from the group consisting of halogen atom, SF.sub.5, C.sub.1-C.sub.6halo alkyl, hydroxy C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.8halocycloalkyl, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.3haloalkoxy C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl and C.sub.1-C.sub.6haloalkylsulfonyl; X.sup.3 is selected from the group consisting of a hydrogen atom, halogen atom, cyano, nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy and C.sub.1-C.sub.6 alkylthio; X.sup.4 is selected from the group consisting of a hydrogen atom, halogen atom, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.4haloalkoxy; R.sup.3 is C(R.sup.3a)(R.sup.3b)R.sup.3c, where R.sup.3a and R.sup.3b independently of each other are a halogen atom, or R.sup.3a and R.sup.3b together form 3- to 6-membered ring together with the carbon atom bonding them by forming a C.sub.2-C.sub.5haloalkylene chain, and R.sup.3c is selected from the group consisting of a hydrogen atom, halogen atom, C.sub.1-C.sub.5alkyl, C.sub.1-C.sub.5haloalkyl, C.sub.1-C.sub.4haloalkoxy and C.sub.1-C.sub.4haloalkylthio, with a proviso that in case where X.sup.1 is a fluorine atom, chlorine atom or trifluoromethyl, and both X.sup.2 and X.sup.3 are a hydrogen atom, in case where both X.sup.1 and X.sup.2 are fluorine atom and X.sup.3 is a hydrogen atom, and in case where both X.sup.1 and X.sup.2 are trifluoromethyl and X.sup.3 is a hydrogen atom, R.sup.3c is a hydrogen atom, chlorine atom, bromine atom, iodine atom, C.sub.1-C.sub.5alkyl, C.sub.1-C.sub.5haloalkyl, C.sub.1-C.sub.4haloalkoxy or C.sub.1-C.sub.4haloalkylthio.

The present invention relates to compounds which are active against parasitic infections, such as protozoan parasite infections (including flagellate parasite infections, ciliate parasite infections, amoeba parasite infections and apicomplexan parasite infections) and helminth infections. The present invention also relates to compositions comprising the compounds, and methods of treating or preventing parasitic infections, such as protozoan parasite infections (including flagellate parasite infections, ciliate parasite infections, amoeba parasite infections and apicomplexan parasite infections) and helminth infections, using the compounds.

The present invention relates to compounds which are active against parasitic infections, such as protozoan parasite infections (including flagellate parasite infections, ciliate parasite infections, amoeba parasite infections and apicomplexan parasite infections) and helminth infections. The present invention also relates to compositions comprising the compounds, and methods of treating or preventing parasitic infections, such as protozoan parasite infections (including flagellate parasite infections, ciliate parasite infections, amoeba parasite infections and apicomplexan parasite infections) and helminth infections, using the compounds.

The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.

The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.

The present invention relates to immunogenic compositions for modulating the immune system, comprising a therapeutically effective quantity of two or more immuno-active antigenic agents with pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs) and one or more physiologically acceptable carriers, excipients, diluents or solvents. The immunogenic compositions according to the present invention are used for producing medicaments for preventing and/or treating, and for preventing and/or treating infectious diseases, auto-immune diseases, allergic diseases, inflammation, arthritis, inflammatory diseases, transplant rejection, affections caused by vascular disorders, diseases caused by haemorrhagic or ischaemic cardiovascular accidents, ischaemia, heart attack and haemorrhagia leading to tissue destruction, heart, kidney, respiratory or liver insufficiency, cancer, malign and benign tumours and neoplasia. The present invention further relates to methods for inducing the regeneration of cells, tissues, organs and organic systems such as the circulatory, nervous and endocrine systems. Finally, the present invention relates to methods for restoring immune response in an animal, in particular a human being.

Provided are methods for reducing intraocular pressure in the eye of a subject by administering neutral active soluble active hyaluronidase glycoproteins (sHASEGPs) and modified forms thereof to the eye. The sHASEGPs are soluble forms of human PH20 hyaluronidase. Also provided are the sHASEGPs, methods of manufacture, and uses thereof. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described. The sHASEGPs include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain.