Dual specificity antibody fusions
The present invention provides dual specificity antibody fusion proteins comprising an antibody Fab or Fab′ fragment with specificity for an antigen of interest, said fragment being fused to at least one single domain antibody which has specificity for a second antigen of interest.
1. A dual specificity antibody fusion protein comprising an antibody Fab fragment or an antibody Fab′ fragment with specificity for an antigen of interest, said fragment being fused to two single domain antibodies that have specificity for serum albumin, wherein one single domain antibody is fused to the C-terminus of the light chain of the Fab fragment or the Fab′ fragment and the other single domain antibody is fused to the C-terminus of the heavy chain of the Fab fragment or the Fab′ fragment, and wherein one single domain antibody is a VH domain comprising the sequence given in SEQ ID NO: 62 for CDR-H1, the sequence given in SEQ ID NO: 63 for CDR-H2 and the sequence given in SEQ ID NO: 64 for CDR-H3, and the other single domain antibody is a VL domain comprising the sequence given in SEQ ID NO: 65 for CDR-L1, the sequence given in SEQ ID NO: 66 for CDR-L2 and the sequence given in SEQ ID NO: 67 for CDR-L3, wherein the VH domain is fused to the C-terminus of the heavy chain of the Fab fragment or the Fab′ fragment and the VL domain is fused to the C-terminus of the light chain of the Fab fragment or the Fab′ fragment.
2. The fusion protein according to claim 1 wherein each single domain antibody is humanised.
3. The fusion protein according to claim 1 wherein the Fab or Fab′ is humanised.
4. The fusion protein according to claim 1 , wherein each single domain antibody fused to the antibody Fab or Fab′ fragment is fused via a linker of the amino acid sequence wherein the linker sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 45.
5. The fusion protein according to claim 1 , in which the VH domain is linked to the C-terminus of the heavy chain of the Fab or Fab′ fragment via a linker having the sequence given in SEQ ID NO: 2 or SEQ ID NO: 45 and the VL domain is linked to the C-terminus of the light chain of the Fab or Fab′ fragment via a linker having the sequence given in SEQ ID NO: 1 or SEQ ID NO: 45.
6. The fusion protein according to claim 1 , wherein the serum albumin is human serum albumin.
7. A pharmaceutical composition comprising a dual specificity antibody fusion protein of claim 1 .