Abstract: The present invention provides methods for producing antibodies against peptides, proteins, or such to which immune tolerance is easily established, by using antigen-binding molecules comprising a domain that binds to a molecule expressed on the surface of a cell having an immune response-suppressing function and a T cell receptor (TCR) complex-binding domain. The present invention also provides pharmaceutical compositions for use in combination with therapeutic vaccines and agents for enhancing a humoral immune response, each comprising the antigen-binding molecules as active ingredients.

Abstract: The present invention provides antigen-binding molecules containing (i) an antigen-binding domain whose antigen-binding activity varies depending on ion concentration conditions, (ii) an Fc?R-binding domain having Fc? RIIb-selective binding activity, and (iii) an FcRn-binding domain having FcRn-binding activity under an acidic pH range condition, and methods of decreasing plasma antigen concentration as compared to before administering the molecule, which include the step of administering the molecule.

Abstract: An objective of the present invention is to provide stable antibody-containing formulations which are suitable for subcutaneous administration and in which aggregation formation is suppressed during long-term storage. The present inventors discovered that a significant stabilization effect was achieved by using an acidic amino acid, aspartic acid or glutamic acid as a counter ion species in histidine buffer or tris(hydroxymethyl)aminomethane, specifically by using histidine-aspartate buffer or histidine-glutamate buffer, or tris(hydroxymethyl)aminomethane-aspartate or tris(hydroxymethyl)aminomethane-glutamate as a buffer. The present inventors also discovered that a significant stabilization effect was achieved by using an acidic amino acid, aspartic acid or glutamic acid, as a counter ion species to a basic amino acid such as arginine, specifically by using arginine-aspartate or arginine-glutamate.

Abstract: An objective of the present invention is to provide a fusion protein that can activate its ligand moiety such as a cytokine or chemokine selectively in a target tissue. The present invention provides fusion proteins that include a ligand moiety such as a cytokine or chemokine connected via a peptide linker with a ligand-binding moiety that binds to the ligand moiety but is capable of releasing the ligand moiety in the presence of a protease. The present invention also provides their methods of production, their uses, and pharmaceutical compositions containing such a fusion protein. The present invention also relates to improved variants of such fusion proteins. Furthermore, for several cytokines, in vitro activities of the variants were evaluated.

Abstract: The present disclosure provides anti-CTLA-4 antibodies and methods of producing and using the antibodies. The present disclosure also provides nucleic acids encoding the anti-CTLA-4 antibodies and host cells containing the nucleic acids. Furthermore, the present disclosure provides polypeptides containing a variant Fc region and methods of producing and using the polypeptides.

Abstract: The present disclosure provides anti-CTLA-4 antibodies and methods of producing and using the antibodies. The present disclosure also provides nucleic acids encoding the anti-CTLA-4 antibodies and host cells containing the nucleic acids. Furthermore, the present disclosure provides polypeptides containing a variant Fc region containing amino acid alterations in a parent Fc region and methods of producing and using the polypeptides.

Abstract: A polypeptide containing an antibody Fc region variant which has an amino acid sequence in which an amino acid alteration at position 238 according to EU numbering is combined with other specific amino acid alteration(s), was found to have decreased binding activities to all activating Fc?Rs, in particular Fc?RIIa (R type), while maintaining its Fc?RIIb-binding activity, when compared to a polypeptide containing a native IgG Fc region.

Abstract: A multiple antigen-binding molecule fusion molecule containing a multiple antigen-binding molecule (?) having an immune cell antigen-binding region and a cancer antigen-binding region, a cancer tissue-specific protease-cleavable linker (?), and a masking molecule (?) containing a polypeptide having the amino acid sequence QDGNE, in which the multiple antigen-binding molecule (?) and the masking molecule (?) are linked via the cancer tissue-specific protease-cleavable linker (?).

Abstract: The present invention provides efficient methods based on alteration of the protein A-binding ability, for producing or purifying multispecific antibodies having the activity of binding to two or more types of antigens to high purity through a protein A-based purification step alone. The methods of the present invention for producing or purifying multispecific antibodies which feature altering amino acid residues of antibody heavy chain constant region and/or variable region. Multispecific antibodies with an altered protein A-binding ability, which exhibit plasma retention comparable or longer than that of human IgG1, can be efficiently prepared in high purity by introducing amino acid alterations of the present invention into antibodies.

Abstract: The present inventors created antigen-binding molecules containing an antigen-binding domain and an Fc?-receptor-binding domain, wherein the molecules have human-FcRn-binding activity in an acidic pH range condition, the antigen-binding domain changes the antigen-binding activity of the antigen-binding molecules depending on the ion-concentration condition, and the Fc? receptor-binding domain has higher binding activity to the Fc? receptor in a neutral pH range condition than an Fc region of a native human IgG in which the sugar chain bound at position 297 (EU numbering) is a fucose-containing sugar chain.

Abstract: The present inventors provide methods for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The present invention also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies, comprising modifying isoelectric point. The present invention further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.

Abstract: It was discovered that antigen-binding molecules comprising (i) a domain that binds to a molecule expressed on the surface of cells having immune response-suppressing functions, and (ii) a T cell receptor complex-binding domain exhibit more superior antitumor effects than conventional antigen-binding molecules by crosslinking T cells with cells having immune response-suppressing functions, and damaging the cells having immune response-suppressing functions.

Abstract: It was discovered that the use of an antigen-binding molecule having a cancer-specific antigen-binding domain, and a TNF superfamily-binding domain or a TNF receptor superfamily-binding domain enables agonist activity against a factor belonging to the TNF superfamily or the TNF receptor superfamily to be exhibited only in the presence of cancer-specific antigen-expressing cells, thus leading to activation of immune cells and thereby maintain anti-tumor activity while avoiding side effects such as hepatotoxicity. It was also discovered that concomitant use of the antigen-binding molecule with an antigen-binding molecule having a cancer-specific antigen-binding domain and a T cell receptor complex-binding domain can avoid side effects while increasing the anti-tumor activity.

Abstract: The present disclosure provides a pharmaceutical composition comprising an antibody having ADCC activity, a T cell-redirecting antibody, or a cell expressing a chimeric receptor, for use in combination with the administration of an antigen binding molecule capable of binding to a target antigen, wherein the primary molecule comprises a linker that is cleaved by protease, the antigen binding molecule obtained through the cleavage of the linker has the ability to bind to the target antigen, variable regions of the antibody having ADCC activity or the T cell-redirecting antibody, and an extracellular binding domain of the chimeric receptor bind to a cell expressing the target antigen via binding to the antigen binding molecule resulting from the cleavage of the cleavable linker.

Abstract: Disclosed are an antigen-binding molecule containing a sugar chain receptor-binding domain and having a weak antigen-binding activity in the pH of early-stage endosome compared to the antigen-binding activity in the pH of plasma; a pharmaceutical composition containing the antigen-binding molecule; and a method for producing these. Use of the antigen-binding molecule of the invention enables to promote uptake of an antigen into a cell and increase the number of antigens that a single antibody molecule can bind. Administration of the antibody enables to reduce the number of antigens in plasma more and more and improve pharmacokinetics of the antibody.

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 anti-myostatin antibodies and methods of making and using the same. Nucleic acids encoding the anti-myostatin antibodies and host cells comprising the nucleic acids are also provided. The anti-myostatin antibodies have uses that include treating a muscle wasting disease, reducing body fat accumulation, and increasing mass and strength of muscle tissue. The disclosure also provides polypeptides containing a variant Fc region and methods of making and using the same. Nucleic acids encoding the polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include suppressing the activation of immune cells; treating an immunological inflammatory disease, autoimmune disease, or viral infection; and increasing muscle mass and strength or reducing body fat accumulation.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor DC/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

Abstract: In the course of the present invention, it was discovered that one could regulate association between polypeptides by modifying amino acid residues that form the interface during the association to amino acids carrying the same type of charge. In this context, the present invention enables efficient formation of heterologous molecules. For example, the present invention can be suitably applied to the preparation of bispecific antibodies.

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.