Nucleic acid encoding bispecific antibodies

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.

1 .- 16 . (canceled) 
     
     
         17 . Isolated nucleic acid encoding a bispecific antibody that specifically binds to blood coagulation factor IX and/or activated blood coagulation factor IX, and specifically binds to blood coagulation factor X, wherein the bispecific antibody comprises:
 a first antibody H chain comprising a variable region comprising complementarity determining regions (CDRs) 1, 2, and 3 that comprise SEQ ID NOs: 105-107, respectively;   a second antibody H chain comprising a variable region comprising CDRs 1, 2, and 3 that comprise SEQ ID NOs: 126-128, respectively; and   identical first and second antibody L chains, each L chain comprising a variable region comprising CDRs 1, 2, and 3 that comprise SEQ ID NOs: 156-158, respectively.   
     
     
         18 . Isolated nucleic acid encoding a bispecific antibody that specifically binds to blood coagulation factor IX and/or activated blood coagulation factor IX, and specifically binds to blood coagulation factor X, wherein the bispecific antibody comprises:
 a first antibody H chain comprising a variable region comprising SEQ ID NO: 45;   a second antibody H chain comprising a variable region comprising SEQ ID NO: 52; and   identical first and second L chains, each comprising a variable region comprising SEQ ID NO: 62.   
     
     
         19 . Isolated nucleic acid encoding a bispecific antibody that specifically binds to blood coagulation factor IX and/or activated blood coagulation factor IX, and specifically binds to blood coagulation factor X, wherein the bispecific antibody comprises:
 a first antibody H chain comprising SEQ ID NO: 20;   a second antibody H chain comprising SEQ ID NO: 25; and   identical first and second antibody L chains, each comprising SEQ ID NO: 32.   
     
     
         20 . A vector or vectors comprising the nucleic acid of  claim 17 . 
     
     
         21 . A vector or vectors comprising the nucleic acid of  claim 18 . 
     
     
         22 . A vector or vectors comprising the nucleic acid of  claim 19 . 
     
     
         23 . A cell or cells comprising the nucleic acid of  claim 17 . 
     
     
         24 . A cell or cells comprising the nucleic acid of  claim 18 . 
     
     
         25 . A cell or cells comprising the nucleic acid of  claim 19 . 
     
     
         26 . A method for producing a bispecific antibody comprising culturing the cell or cells of  claim 17  under conditions sufficient to produce the bispecific antibody. 
     
     
         27 . A method for producing a bispecific antibody comprising culturing the cell or cells of  claim 18  under conditions sufficient to produce the bispecific antibody. 
     
     
         28 . A method for producing a bispecific antibody comprising culturing the cell or cells of  claim 19  under conditions sufficient to produce the bispecific antibody. 
     
     
         29 . The method of  claim 26 , further comprising obtaining the bispecific antibody produced by the cultured cell or cells. 
     
     
         30 . The method of  claim 27 , further comprising obtaining the bispecific antibody produced by the cultured cell or cells. 
     
     
         31 . The method of  claim 28 , further comprising obtaining the bispecific antibody produced by the cultured cell or cells. 
     
     
         32 . The nucleic acid of  claim 17 , wherein the first antibody H chain variable region comprises SEQ ID NO: 45. 
     
     
         33 . The nucleic acid of  claim 17 , wherein the second antibody H chain variable region comprises SEQ ID NO: 52. 
     
     
         34 . The nucleic acid of  claim 17 , wherein the identical first and second antibody L chain variable regions each comprise SEQ ID NO: 62. 
     
     
         35 . The nucleic acid of  claim 17 , wherein the first antibody H chain comprises SEQ ID NO: 20. 
     
     
         36 . The nucleic acid of  claim 17 , wherein the second antibody H chain comprises SEQ ID NO: 25. 
     
     
         37 . The nucleic acid of  claim 17 , wherein the identical first and second antibody L chains each comprise SEQ ID NO: 32. 
     
     
         38 . The isolated nucleic acid of  claim 18 , wherein the variable region of the first antibody H chain consists of SEQ ID NO: 45, the variable region of the second antibody H chain consists of SEQ ID NO: 52, and the variable regions of the identical first and second antibody L chains each consist of SEQ ID NO: 62. 
     
     
         39 . The isolated nucleic acid of  claim 19 , wherein: the first antibody H chain consists of SEQ ID NO: 20, the second antibody H chain consists of SEQ ID NO: 25, and each of the identical first and second antibody L chains consists of SEQ ID NO: 32.