Abstract: The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3?, CD3?, and CD3? in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3?, CD3?, and CD3?. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.

Abstract: An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.

Abstract: The present invention relates to a pharmaceutical composition comprising an anti-PD-L1 antibody as an active ingredient, wherein the pharmaceutical composition is used in combination with camptothecin and/or a derivative thereof, or a pharmaceutically acceptable salt thereof.

Abstract: An object of the present invention is to establish a cell line that is useful as a host cell for use in recombinant protein production, highly expresses transgenes stably, and grows stably. The present invention provides a method for establishing a cell line for recombinant protein production capable of stably expressing two or more foreign genes, comprising transferring a gene of a non-coding RNA suppressing the expression of NfkBia to a cell.

Abstract: The present invention provides anti-sclerostin antibodies and methods of using the same. In some embodiments, an isolated anti-sclerostin antibody of the present invention is a multispecific antibody. The present invention also provides isolated nucleic acids encoding an anti-sclerostin antibody of the present invention. The present invention also provides host cells comprising a nucleic acid of the present invention. The present invention also provides a method of producing an antibody comprising culturing a host cell of the present invention so that the antibody is produced. The present invention also provides a pharmaceutical formulation comprising an anti-sclerostin antibody of the present invention and a pharmaceutically acceptable carrier.

Abstract: An objective of the invention is to provide anti-C5 antibodies and methods of using the same. The invention provides anti-C5 antibodies and methods of using the same. In some embodiments, an isolated anti-C5 antibody of the present invention binds to an epitope within the ? chain of C5 with a higher affinity at neutral pH than at acidic pH. The invention also provides isolated nucleic acids encoding an anti-C5 antibody of the present invention. The invention also provides host cells comprising a nucleic acid of the present invention. The invention also provides a method of producing an antibody comprising culturing a host cell of the present invention so that the antibody is produced. The invention further provides a method of producing an anti-C5 antibody comprising immunizing an animal against a polypeptide which comprises the MG1-MG2 domain of the ? chain of C5. Anti-C5 antibodies of the present invention may be for use as a medicament.

Abstract: The problem to be solved is to provide a humanized anti-IL-6 receptor antibody MRA-containing formulation which is suitable for subcutaneous administration, wherein dimerization or deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and histidine buffer. A method of inhibiting deamidation or dimerization of such an antibody in a concentrated liquid formulation includes histidine buffer in the liquid formulation.

Abstract: Provided is a novel anti-Plexin-A1 agonist antibody that promotes dendritic cell contraction. Also provided is a pharmaceutical composition comprising such an antibody and a pharmaceutically acceptable carrier.

Abstract: The present invention provides a hyaluronic acid derivative containing a disaccharide unit represented by formula (I) or formula (I) and (II), and a complex containing the hyaluronic acid derivative and a drug.

Abstract: By combining a compound having RET kinase inhibitory activity with a CDK4/6 inhibitor, the present inventors have found a drug, a combination, a pharmaceutical composition, and a preparation which are effective for treating or preventing cancer, a method for treating or preventing cancer, or a method for suppressing tumor growth.

Abstract: The present disclosure provides, for example, a compound represented by general formula (6) below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt: wherein X1, X2, X3 and X4 are each independently —CR2? or —N?, R2 is, for example, a halogen atom, R1 is, for example, —S(?O)2—NH—R8, R8 is, for example, a C1-6 alkyl group, R3 is, for example, a hydrogen atom, R5 is, for example, a halogen atom, R6 is, for example, a hydrogen atom, and R4 is, for example, a cyclopropyl group. The compounds, salts or solvates provided by the present disclosure exhibit high RAF/MEK complex-stabilizing activity and can be used for the treatment or prevention of cell proliferative disorders, particularly cancers.

Abstract: An object of the present invention is to provide an evaluation system capable of detecting an extracellular purinergic receptor ligand minimally invasively, chronologically and systemically, and the present invention provides a genetically modified non-human animal expressing a first fusion protein and a second fusion protein for detecting an extracellular purinergic receptor ligand, in which the first fusion protein comprises a membrane protein that binds to a purinergic receptor ligand, and a first reporter protein, and the second fusion protein comprises a protein that binds to the membrane protein bound to the ligand, and a second reporter protein; and a cell thereof.

Abstract: Methods of producing a peptide containing an N-substituted amino acid or N-substituted amino acid analog of the present invention include the steps of: preparing an Fmoc-protected amino acid, an Fmoc-protected amino acid analog, or an Fmoc-protected peptide; deprotecting a protecting group which have an Fmoc skeleton of the Fmoc-protected amino acid and such by using a base; and forming an amide bond by adding a new Fmoc-protected amino acid and such; and when the peptide is produced by a solid-phase method, the obtained peptide is cleaved off from the solid phase under conditions of weaker acidity than TFA. Furthermore, at least one side chain of the obtained peptide has a protecting group that is not deprotected under basic conditions and is deprotected under conditions of weaker acidity than TFA.

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: An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.

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 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: 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: Provided is a method for predicting sensitivity of a cancer cell to a helicase inhibitor, the method comprising the step of: predicting a cancer cell having at least one mutation detected selected from the first group consisting of TTK mutation and RAD 50 mutation, as having sensitivity to a helicase inhibitor, or predicting a cancer cell having at least one mutation detected selected from the second group consisting of RAD 50 mutation, MRE 11 mutation, NBN mutation, DNA 2 mutation and RBBP 8 mutation, as having sensitivity to a helicase inhibitor.