The present invention relates to methods and pharmaceutical composition for the treatment of T-helper type 2 (Th2)-mediated diseases. More particularly, the present invention relates to an inhibitor of the Suv39h1-HP1a silencing pathway for use in the treatment of a T-helper type 2 (Th2)-mediated disease, in particular allergic asthma.

The invention is in the field of antibodies useful in therapeutic and diagnostics applications targeting CD127, the alpha chain of the IL7 receptor, and provides in particular humanized monoclonal antibodies against CD127, particularly human CD127, therapeutic uses thereof, and diagnostics applications.

The present invention relates to improved Nanobodies™ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.

The present invention provides antibodies, or antigen-binding fragment thereof, which specifically bind to tumor necrosis factor (TNF)-like ligand 1A(TL1A) The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of TL1A mediated diseases, disorders or conditions.

A compound represented by general formula (I) wherein all the symbols are as defined in the specification has a selective S1P5 receptor agonist activity due to having a linker from a phenyl group to a cyclic substituent in a dihydronaphthalene skeleton; i.e., due to having a short linker of one atom or less as L in general formula (I), and can therefore serve as an agent for treating S1P5-mediated disease, e. g., neurodegenerative disease such as schizophrenia. ##STR00001##

The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

In one aspect, compounds of Formulae (I) and (II), or pharmaceutically acceptable salts thereof, are featured: Formulae (I) and (II), wherein the variables shown in Formulae (I) and (II) can be as defined anywhere herein. ##STR00001##

The present invention relates to a method for preparing coumarin compounds substituted by amidoalkyl at 3-position, and related intermediates thereof. The method includes: Step (A): reacting a compound of formula (VI) with a compound of formula (V) to give a compound of formula (VII)

##STR00001## wherein R.sub.1 and R.sub.2 are each independently selected from hydrogen, halogen, and —O(C.sub.1-8 alkyl), wherein the alkyl is optionally substituted with 1 or 2 groups selected from the group consisting of halogen, C.sub.1-8 alkyl substituted with 1-2 hydroxyl groups, —O(C.sub.1-8 alkyl); R.sub.3 is -L-C(O)NR.sub.5R.sub.6, L is C.sub.1-3 alkylene.

The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions.

The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.

The present invention provides for compounds of formula (I)

##STR00001## wherein A.sup.1, A.sup.2, A.sup.3, A.sup.4, X.sup.1, X.sup.2, Y.sup.1, L.sup.1, G.sup.1, R.sup.x, and R.sup.y have any of the values defined thereof in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).