Abstract: An objective of the present invention is to provide methods for promoting antigen uptake into cells by antigen-binding molecules, methods for increasing the number of times of antigen binding by one antigen-binding molecule, methods for promoting reduction of the antigen concentration in plasma by administering antigen-binding molecules, and methods for improving the plasma retention of an antigen-binding molecule, as well as antigen-binding molecules that allow enhanced antigen uptake into cells, antigen-binding molecules having an increased number of times of antigen binding, antigen-binding molecules that can promote reduction of the antigen concentration in plasma when administered, antigen-binding molecules with improved plasma retention, pharmaceutical compositions comprising the above antigen-binding molecules, and methods for producing them. The present inventors revealed that the above objective can be achieved by using antigen-binding molecules that show calcium-dependent antigen-antibody reaction.

Abstract: An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.

Abstract: The present inventors have successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against a molecule expressed on the surface of a T cell and a molecule expressed on the surface of any other immunocyte, but does not bind to these molecules at the same time. The present invention allows the preparation of an antigen-binding molecule capable of circumventing adverse reactions that may be caused by the cross-linking of T cells to other immunocytes, and provides an antigen-binding molecule suitable as a drug.

Abstract: In a non-limiting embodiment, there is provided a pharmaceutical composition for prevention and/or treatment of atopic dermatitis comprising an IL-31 antagonist as an active ingredient, wherein the IL-31 antagonist is repeatedly administered in equal amounts at the same dosing interval to a subject with or potentially with atopic dermatitis, at 0.1 to 1000 mg/body/1 day to 12 weeks, preferably at 0.1 to 1000 mg/body/2 weeks, 0.1 to 1000 mg/body/4 weeks, or 0.1 to 1000 mg/body/8 weeks.

Abstract: 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.

Abstract: The disclosure provides multispecific antigen-binding molecules that comprise a first antigen-binding moiety and a second antigen-binding moiety, each of which is capable of binding to CD3 and CD137, but does not bind to CD3 and CD137 at the same time; and a third antigen-binding moiety that is capable of binding to DLL3, preferably human DLL3, which induce T-cell dependent cytotoxity more efficiently whilst circumventing adverse toxicity concerns or side effects that other multispecific antigen-binding molecules may have. The present invention provides multispecific antigen-binding molecules and pharmaceutical compositions that can treat various cancers, especially those associated with DLL3, by comprising the antigen-binding molecule as an active ingredient.

Abstract: An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.

Abstract: It has become clear that the therapeutic effect of an IL-6 inhibitor for IL-6- and neutrophil-associated diseases can be predicted using the expression level of neutrophil-associated genes as an indicator. It has also become clear that an IL-6 inhibitor is effective for the treatment of IL-6- and neutrophil-associated diseases in patients with high expression levels of neutrophil-associated genes. The present invention provides a method for selecting cases of IL-6- and neutrophil-associated diseases in which treatment with an IL-6 inhibitor is effective, as well as a method for effectively treating patients with IL-6- and neutrophil-associated diseases and with high expression levels of neutrophil-associated genes.

Abstract: It was found that association between CH1 and CL can be suppressed by substituting amino acids that exist on the interface between CH1 and CL with electrically-charged amino acids, and that formation of heterogeneous molecules is enabled more efficiently than by introducing knobs into holes mutations into CH3 domain.

Abstract: A composition which comprises substance represented by Formula (I), [Meanings of the symbols that are included in the formula are given in the specification as definitions] a pharmaceutically acceptable carrier, and a dissolution aid. is useful for improving solubility, oral absorbability and/or absorbability in blood of a poorly water-soluble or water insoluble tetracyclic compounds having an ALK inhibitory activity that are useful as a prophylactic and/or therapeutic agent for cancer, depression, and cognitive function disorder.

Abstract: A syringe is provided with a barrel having a distal end part provided with an outlet opening; a filter disposed closer to a proximal side than the outlet opening inside the barrel; and a holding member. A proximal side part disposed closer to the proximal side than the filter of the holding member has a flow path, a proximal side space into which the medicine flows through the flow path is provided on the proximal side of the filter, a distal side space into which the medicine flows from the proximal side space via the filter is provided on the distal side of the filter, and an area of the outlet opening is smaller than an area of the proximal side space, smaller than an area of the distal side space, and smaller than an area of the flow path.

Abstract: Provided is a syringe cap including a projection extending in the circumferential direction of a cap body, wherein the projection includes an apex located radially outward of the cap body from the outer circumferential surface of the cap body, a first inclined surface having a starting end located at the apex and having a terminal end located at a position on the side closer to the proximal end of the cap body than the starting end is, and a second inclined surface having a starting end located at the apex and on the outer circumferential surface of the cap body having a terminal end located at a position on the side closer to the distal end of the cap body than the starting end is, on the outer circumferential surface of the cap body, and the shortest distance from the starting end to the terminal end of the first inclined surface is smaller than the shortest distance from the starting end to the terminal end of the second inclined surface.

Abstract: In a non-limiting embodiment, there is provided a pharmaceutical composition for prevention and/or treatment of uremic pruritus comprising an IL-31 antagonist as an active ingredient.

Abstract: The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.

Abstract: The present inventors newly discovered that even if an antigen-binding molecule inhibits in vitro some of the physiological activities of an antigen having two or more physiological activities without inhibiting the remaining physiological activities, the molecule can promote elimination of the antigen from blood (from serum or plasma) and as a result reduce the physiological activities in vivo, when the antigen-binding molecule is conferred with the properties: (i) of binding to human FcRn under an acidic pH range condition; (ii) of binding under a neutral pH range condition to human Fc receptor stronger than native human IgG, and (iii) that its antigen-binding activity alters according to the ion concentration.

Abstract: The present invention provides anti-MASP-1 (mannan-binding lectin (MBL)-associated serine protease 1) antibodies and methods of using the same. In some embodiments, an anti-MASP-1 antibody of the invention binds to MASP-1 but does not bind to MASP-3. The invention also provides nucleic acids comprising a nucleotide sequence encoding an anti-MASP-1 antibody of the present invention. The invention further provides pharmaceutical compositions comprising an anti-MASP-1 antibody of the present invention and a pharmaceutically acceptable carrier.

Abstract: The present inventors discovered that by forming a large immune complex comprising antigens containing two or more antigenic binding units (epitopes) and two or more antigen-binding molecules (for example, antibodies), elimination from the plasma of the antigens containing two or more antigenic binding units can be accelerated. Moreover, they found that by using this characteristic and by further using antigen-binding molecules having an ion-dependent antigen-binding activity, elimination of the antigens can further be accelerated and the above problem can be solved.