Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/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: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/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: 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: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/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: 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: 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.

Abstract: The inventors produced substances that neutralize the activity of a bispecific antibody having an activity of functionally substituting for FVIII, and undertook the construction of methods for measuring the reactivity of FVIII that can ensure accuracy even in the presence of this bispecific antibody. As a result, the inventors discovered that in APTT-based one-stage clotting assay, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately, and also that in APTT-based Bethesda assay, FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately.

Abstract: Various methods for evaluating hemostatic effect and various blood coagulation initiation reagents were studied to construct a method for evaluating blood coagulation reaction mediated by a substance having an activity of substituting for coagulation factor VIII (FVIII). As a result, it was discovered that by using a coagulation initiation reagent containing activated coagulation factor XI (FXIa) and phospholipids, the effect of a substance having an activity of substituting for coagulation factor VIII (FVIII) on blood coagulation reaction can be evaluated using the amount of thrombin generated in the blood sample as an indicator.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/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: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/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: The present inventors have completed the present invention by finding that an excellent anticoagulation inhibitory effect is obtained by the administration of an agent inhibiting the activation of protein C.

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 wider 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 relates to a method for evaluating coagulability of a blood specimen obtained from a subject to whom a substance having a coagulation factor VIII-substituting activity is administered. The present invention also relates to a reagent for blood coagulation analysis, a reagent kit for blood coagulation analysis, and an apparatus for blood coagulation analysis. Furthermore, the present invention relates to an apparatus and computer program for evaluating coagulability of a blood specimen.

Abstract: The present invention relates to a method for evaluating coagulability of a blood specimen obtained from a subject to whom a substance having a coagulation factor VIII-substituting activity is administered. The present invention also relates to a reagent for blood coagulation analysis, a reagent kit for blood coagulation analysis, and an apparatus for blood coagulation analysis. Furthermore, the present invention relates to an apparatus and computer program for evaluating coagulability of a blood specimen.

Abstract: The inventors produced substances that neutralize the activity of a bispecific antibody having an activity of functionally substituting for FVIII, and undertook the construction of methods for measuring the reactivity of FVIII that can ensure accuracy even in the presence of this bispecific antibody. As a result, the inventors discovered that in APTT-based one-stage clotting assay, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately, and also that in APTT-based Bethesda assay, FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately.

Abstract: 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.

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: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/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: The present inventors have completed the present invention by finding that an excellent anticoagulation inhibitory effect is obtained by the administration of an agent inhibiting the activation of protein C.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/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.