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.

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.

The present inventors attempted to produce antibodies that neutralize the activity of a substance having an activity of functionally substituting for FVIII to be used for the method of measuring the reactivity of FVIII in the presence of a substance having an activity of functionally substituting for FVIII. As a result, the inventors discovered that by using the produced antibodies, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately by one-stage clotting assay based on APTT, and also that FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately by Bethesda assay based on APTT.

The present inventors attempted to produce antibodies that neutralize the activity of a substance having an activity of functionally substituting for FVIII to be used for the method of measuring the reactivity of FVIII in the presence of a substance having an activity of functionally substituting for FVIII. As a result, the inventors discovered that by using the produced antibodies, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately by one-stage clotting assay based on APTT, and also that FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately by Bethesda assay based on APTT.

The present invention discloses a polypeptide antigen sequence, its spatially sensitive position in von Willebrand factor (VWF), and use thereof in the production of preparations for the diagnosis and/or treatment of VWF-related blood diseases. The polypeptide antigen comprises the amino acid sequence as shown in SEQ ID NO: 1, or a biologically active fragment or a variant thereof. The spatial position of the polypeptide transits from non-solvent exposure to solvent exposure when VWF is in activation process upon exposing to blood shear stress, so as to be recognized by an antibody. The antibody that recognizes the active state of VWF prepared by using the polypeptide antigen is useful in diagnosing and treating a variety of VWF-related diseases.

The present invention discloses a polypeptide antigen sequence, its spatially sensitive position in von Willebrand factor (VWF), and use thereof in the production of preparations for the diagnosis and/or treatment of VWF-related blood diseases. The polypeptide antigen comprises the amino acid sequence as shown in SEQ ID NO: 1, or a biologically active fragment or a variant thereof. The spatial position of the polypeptide transits from non-solvent exposure to solvent exposure when VWF is in activation process upon exposing to blood shear stress, so as to be recognized by an antibody. The antibody that recognizes the active state of VWF prepared by using the polypeptide antigen is useful in diagnosing and treating a variety of VWF-related diseases.

The present inventors discovered that administration of a pharmaceutical composition comprising emicizumab according to a predetermined administration regimen has the potential to effectively prevent and/or treat acquired hemophilia A.

The present inventors discovered that administration of a pharmaceutical composition comprising emicizumab according to a predetermined administration regimen has the potential to effectively prevent and/or treat acquired hemophilia A.

Antibodies that bind the apple 2 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa are described.

Antibodies that bind the apple 2 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa are described.