Chugai Seiyaku Kabushiki Kaisha

Public University Corporation Nara Medical University

Sysmex Corporation

Tetsuhiro Soeda

Takehisa Kitazawa

Tomoyuki Igawa

Tetsuo Kojima

Midori Shima

Zenjiro Sampei

Atsushi Muto

Tsukasa Suzuki

Keiji Nogami

Hiroyuki Saito

Kazutaka Yoshihashi

Chifumi Imai

Yukiko Nishida

Kunihiro Hattori

Taro Miyazaki

Yuri Teranishi

Tomoko Matsumoto

Yuka Ikeda

Kazuki Kato

Hikaru Koga

Kazuki Yamaguchi

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.

Method for measuring reactivity of FVIII

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.

Method for evaluating blood coagulation reaction

Bispecific antibodies whose FIX activation-inhibiting activity is not elevated and whose FVIII cofactor function-substituting activity is elevated have been successfully discovered.

Multispecific antigen-binding molecules having blood coagulation factor VIII (FVIII) cofactor function-substituting activity and pharmaceutical formulations containing such a molecule as an active ingredient

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.

Methods of treatment that include the administration of bispecific antibodies

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.

Method for evaluating coagulation ability of blood specimen, and reagent, reagent kit and device to be used therein

Bispecific antibodies

The present inventors succeeded in constructing bispecific antibodies, which bind to both the blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X, and functionally substitute for blood coagulation factor VIII/activated blood coagulation factor VIII which enhances the enzymatic reaction.

Bispecific antibody substituting for functional proteins

Growing community of inventors

Shizuoka, Japan

Tetsuhiro Soeda