Abstract: The present invention relates to a technology for easy chemical modification of only one heavy chain in the constituent unit of an antibody (immunoglobulin unit containing two heavy chains and optionally two light chains). More particularly, the present invention relates to a compound or a salt thereof, containing (A) an affinity substance containing first and second affinity moieties each having an affinity to the constant region in a heavy chain of an antibody; and (B) a reactive group for the antibody.

Abstract: The present invention is to provide a method for producing a peptide containing an N-alkylamino acid, which comprises the following Steps (1) to (3). Step (1): a step of mixing an N-terminal protected amino acid or an N-terminal protected peptide with a carboxylic acid halide or a halogenated alkyl formate; Step (2): a step of mixing an amino acid or a peptide in which the N-terminal and the C-terminal are not protected with a trialkylsilylating agent; and Step (3): a step of mixing the product obtained in Step (1) with the product obtained in Step (2).

Abstract: The disclosure provides uses of multispecific antigen-binding molecules that targets human DLL3 for the treatment of cancers.

Abstract: The present invention provides a technique enabling modification of a soluble protein and in particular regioselective modification of a soluble protein. More specifically, the present invention provides a compound having an affinity substance to a soluble protein, a cleavable portion, and a reactive group represented by the following Formula (I): A-L-B-R??(I) wherein A is an affinity substance to a soluble protein; L is a cleavable linker which is a divalent group comprising a cleavable portion; B is (a) a divalent group comprising a bioorthogonal functional group or (b) a divalent group comprising no bioorthogonal functional group; and R is a reactive group to the soluble protein; or a salt thereof.

Abstract: A conjugate of an antibody and a functional substance, comprising a structural unit represented by the following Formula (1): wherein Ig represents an immunoglobulin unit comprising two heavy chains and two light chains, and is bonded to LA adjacent to Ig via a thiol group in side chains of a plurality of cysteine residues in the two heavy chains and the two light chains, HG represents a hydrophilic group or a monovalent group comprising a hydrophilic group, CS represents a divalent group comprising a cleavable site, ring A represents a divalent aromatic ring group optionally having a substituent wherein the divalent aromatic ring group constitutes a ? electron conjugated system with the cleavable site, V represents an oxygen atom, a sulfur atom, or an amino group (NH), LA and LB each independently represent a divalent group, D represents a functional substance, and an average number n of the bonds per the immunoglobulin unit is 1.

Abstract: A regioselective conjugate of an antibody and a functional substance comprising a structural unit represented by the following Formula (I): wherein Ig represents an immunoglobulin unit comprising two heavy chains and two light chains, and is regioselectively bonded to L1 adjacent to Ig via an amino group in side chains of lysine residues in the two heavy chains, HG represents a hydrophilic group, RA represents a side chain of a valine residue, RB represents a side chain of a citrulline residue or the like, ring A represents a divalent aromatic ring group optionally having a substituent, R1 and R2 each independently represent a hydrogen atom or a monovalent group, L1 and L2 each independently represent a divalent D represents a functional substance, and r is 1.5 to 2.5, or a salt thereof, and substances related thereto, is excellent in desired properties while controlling a bonding ratio between the antibody and the functional substance within a specific range.

Abstract: A method for producing an intermediate antibody regioselectively modified, which comprises: (1) mixing a solution comprising an antibody material and a solution comprising a reagent for regioselectively modifying an antibody in a micromixer to form a mixture comprising the antibody material and the reagent, wherein the reagent comprises a compound comprising an affinity substance to an antibody and a reactive group to an antibody; and (2) passing the mixture through a reaction channel to allow the antibody material and the reagent to react in the reaction channel to form a solution comprising an intermediate antibody regioselectively modified, wherein the processes (1) and (2) are continuously performed in a flow microreactor, is capable of rapidly producing a desired antibody derivative regioselectively having a functional substance or functional substances.

Abstract: The present invention provides a technique enabling modification of a soluble protein and in particular regioselective modification of a soluble protein. More specifically, the present invention provides a compound having an affinity substance to a soluble protein, a cleavable portion, and a reactive group represented by the following Formula (I): A-L-B-R??(I) wherein A is an affinity substance to a soluble protein; L is a cleavable linker which is a divalent group comprising a cleavable portion; B is (a) a divalent group comprising a bioorthogonal functional group or (b) a divalent group comprising no bioorthogonal functional group; and R is a reactive group to the soluble protein; or a salt thereof.

Abstract: A conjugate of an antibody and a functional substance or a salt thereof, which comprises a structural unit represented by the following formula (I): wherein Ig represents an immunoglobulin unit comprising two heavy chains and two light chains, and regioselectively forms an amide bond with a carbonyl group adjacent to Ig via an amino group in side chains of lysine residues in the two heavy chains, L1 and L2 each represent a divalent group, R1 represents a monovalent group optionally comprising a hydrophilic group, X represents a predetermined divalent group, D represents a functional substance, RA represents a side chain of a valine residue, RB represents a side chain of a citrulline residue or an alanine residue, n is 0 or 1, and an average ratio r of the amide bonds per two heavy chains is 1.5 to 2.

Abstract: Compounds or salts thereof represented by formula (I): wherein X indicates a leaving group, Y indicates an affinity peptide having a binding region in a CH2 domain in an immunoglobulin unit comprising two heavy chains and two light chains, M indicates a trivalent group linking the carbon atom in C?O adjacent to M and the carbon atom in C?W via a main chain portion consisting of 3 to 5 carbon atoms, O indicates an oxygen atom, S indicates a sulfur atom, W indicates an oxygen atom or a sulfur atom, N3 indicates an azide group, La indicates a bond or a divalent group, and Lb indicates a bond or a divalent group; and antibodies or salts thereof which can be prepared using such a compound or salt thereof, are useful for controlling the bonding ratio of an antibody and a modifying group within a desired range.

Abstract: The present invention provides a highly controlled complex comprising an antibody and ferritin particles. More specifically, the present invention provides the inventions of a complex or salt thereof comprising (A) one IgG antibody and (B) two human ferritin particles comprising one or more human ferritin H chains linked thereto; and methods for producing the same.

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 desired antibody or antibody composition may be obtained by modifying a thiol group chemically introduced to an antibody to obtain an antibody composition comprising (A) an antibody intermediate or a salt thereof having a bioorthogonal functional group which may be protected, which is represented by the following formula (A): AbS-L-R]n??(A) wherein Ab is a certain antibody, S is a sulfur atom, L is a divalent group, R is a bioorthogonal functional group which may be protected, and n is an integer from 1 to 8, and (B) a thiol group-introduced antibody or a salt thereof, which is represented by the following formula (B): AbSH]n??(B) wherein Ab and n are the same as formulae (A), and SH is a thiol group; and the like.

Abstract: Compounds and salts thereof represented by the following formula (I): wherein X indicates a leaving group, Y indicates an affinity peptide having a binding region to a CH2 domain in an immunoglobulin unit containing two heavy chains and two light chains, O indicates an oxygen atom, S indicates a sulfur atom, W indicates an oxygen atom or a sulfur atom, La indicates a first linker, Lb indicates a second linker, and the total number of atoms constituting a main chain in the first linker and atoms constituting a main chain in the second linker are 5 to 7, facilitate regioselective modification of an antibody with a functional substance and control of the bonding ratio of the antibody to the functional substance within a desired range.

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: The present invention provides methods for treating or preventing cancer by administering an anticancer agent and an antigen-binding molecule 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 complex-binding domain. The present invention also provides pharmaceutical compositions for treating or preventing cancer, each comprising a combination of the anticancer agent and the antigen-binding molecule.

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: The invention aims to provide a method of screening for a therapeutic drug for cancer as a molecular-targeted drug targeting some protein from a number of candidate target proteins, without identifying the true target protein. In particular, the invention provides a method of screening for a therapeutic drug for cancer, including (i) a step of expressing an exogenous cell regulatory factor in a target cancer cell under contact or no contact with a test substance, (ii) a step of confirming change in the cancer cell, and (iii) a step of selecting the test substance as a therapeutic drug for cancer when the change of cancer cell increased under contact with the test substance as compared to no contact therewith.

Abstract: The present invention provides an exposure apparatus including a forming unit configured to form a mark on a resist film on a substrate, and a control unit configured to perform an exposure process to form a latent image by projecting a pattern onto a target position on the resist film on the substrate based on a measured position of the mark, wherein the control unit causes the forming unit to perform a formation process of forming, before the exposure process is performed on a reworked substrate on which a second resist film has been formed after removing a first resist film with a first mark, a second mark on the second resist film so the second mark will be positioned at a position shifted from a position of the first mark on the reworked substrate.

Abstract: Compounds having an affinity substance to an antibody and a bioorthogonal functional group, represented by the following Formula (I): A-L-E-B??(I) wherein A is an affinity substance to an antibody, L is a divalent group comprising a leaving group, E is a divalent group comprising an electrophilic group (i) coupled with the leaving group and (ii) having ability to react with a nucleophilic group in the antibody, B is a bioorthogonal functional group, and the leaving group has ability to be cleaved and eliminated from E by a reaction between the nucleophilic group and the electrophilic group, or a salt thereof, and the like are useful for labelling antibodies.