Multivalent Antibodies

Abstract

The present invention provides a multivalent antibody or a heavy/light chain component thereof comprising: a heavy chain comprising a constant region fragment, said constant region fragment located between two variable domains which are not a cognate pair, the heavy chain further comprising an Fc region with at least one domain selected from CH2, CH3 and combinations thereof, with the proviso that the heavy chain contains no more than one CH1 domain and only contains two variable domains, and a light chain comprising a constant region fragment located between two variable domains which are not a cognate pair, wherein said heavy and light chains are aligned to provide a first binding site formed by a first cognate pair of variable domains and a second binding site formed by a second cognate pair of variable domains.

1 . A recombinant antibody or a heavy/light chain component thereof comprising:
 (a) a heavy chain comprising a constant region fragment, said constant region fragment located between two variable domains which are not a cognate pair, the heavy chain further comprising an Fc region with at least one domain selected from CH2, CH3 and combinations thereof, wherein the heavy chain contains no more than one CH1 domain and only contains two variable domains, and   (b) a light chain comprising a constant region fragment located between two variable domains which are not a cognate pair,   wherein said heavy and light chains are aligned to provide a first binding site formed by a first cognate pair of variable domains and a second binding site formed by a second cognate pair of variable domains.   
     
     
         2 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  wherein the constant region fragment of the heavy chain is either a CH1 domain or a CL domain,. with the proviso that where the constant region fragment in the heavy chain is a CH1 domain,. the constant region fragment in the light chain is a CL domain and the constant region fragment of the heavy chain is a CL domain, the constant region fragment of the light chain is a CH1 domain. 
     
     
         3 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  wherein the constant region fragment of the heavy chain is a CH1 domain and the constant region fragment of the light chain is a CL domain. 
     
     
         4 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  wherein each constant region fragment is fused to a variable domain. 
     
     
         5 . The recombinant antibody or a heavy/light chain component thereof according to  claim 4 , wherein each constant region fragment is also linked via a peptide to a further variable domain which is a non-cognate pair to the variable domain fused thereto. 
     
     
         6 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1 , wherein the variable domains of at least one cognate pair are linked by a disulfide bond. 
     
     
         7 . The recombinant antibody or a heavy/light chain component thereof according to  claim 6  in which the second cognate pair forming the second binding site are linked by a disulphide bond. 
     
     
         8 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1 , wherein the constant region fragment of the heavy chain is linked to the constant region fragment of the light chain by a disulfide bond. 
     
     
         9 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1 , wherein the constant region fragment of the heavy chain consists of CH1. 
     
     
         10 . The recombinant antibody or a heavy/light chain component thereof according  claim 1 , wherein the constant region fragment of the light chain consists of cKappa. 
     
     
         11 . The recombinant antibody or a heavy/light chain component thereof according to  claim 5 , wherein the peptide linker is an albumin binding peptide. 
     
     
         12 . The recombinant antibody or a heavy/light chain component thereof according to  claim 5 , wherein the peptide linker is the sequence given in SEQ ID NO: 72. 
     
     
         13 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  wherein the Fc region further comprises a hinge. 
     
     
         14 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  in which each variable domain in the heavy chain is a VH and each variable domain in the light chain is a VL. 
     
     
         15 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  in which the variable domains are humanized. 
     
     
         16 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  which is monospecific. 
     
     
         17 . The recombinant antibody or a heavy/light chain component thereof according to  claim 1  which is bispecific.