Antigen binding polypeptides

1. A chimeric antigen binding polypeptide that specifically binds to a target antigen, the polypeptide comprising a VH domain and a VL domain, said VH domain comprising hypervariable loops H1, H2 and H3, wherein said VH domain polypeptide is paired with a VL domain comprising hypervariable loops L1, L2 and L3, wherein said VH domain and said VL domain are each fused to one or more IgG constant domains of a human antibody, wherein at least the H3 hypervariable loop is obtained from a conventional antibody of a species in the family Camelidae, and wherein said conventional antibody is a heterotetrameric IgG antibody composed of two identical light chains and two identical heavy chains, wherein at least one of the hypervariable loops H1, H2, L1, L2 and L3 exhibits a predicted or actual canonical fold structure which is identical or substantially identical to a canonical fold structure of a corresponding H1, H2, L1, L2 or L3 hypervariable loop which occurs in human antibodies.

2. The chimeric antigen binding polypeptide of claim 1 wherein either hypervariable loop H1 or hypervariable loop H2, or both hypervariable loop H1 and hypervariable loop H2 are obtained from the conventional antibody of a species in the family Camelidae.

3. The chimeric antigen binding polypeptide of claim 1 wherein either hypervariable loop L1 or hypervariable loop L2 or both hypervariable loop L1 and hypervariable loop L2 are obtained from the conventional antibody of a species in the family Camelidae.

4. The chimeric antigen binding polypeptide of claim 1 wherein hypervariable loop L3 is obtained from the conventional antibody of a species in the family Camelidae.

5. The chimeric antigen binding polypeptide of claim 1 wherein each of the hypervariable loops H1-H3 and L1-L3 are obtained from the conventional antibody of a species in the family Camelidae.

6. The chimeric antigen binding polypeptide of claim 1 wherein the conventional antibody is obtained by active immunisation of the species in the family Camelidae with the target antigen, or with a polynucleotide encoding said target antigen.

7. The chimeric antigen binding polypeptide of claim 6 which contains at least one amino acid substitution in at least one hypervariable loop in comparison to a corresponding hypervariable loop in the conventional antibody.

8. The chimeric antigen binding polypeptide of claim 6 which contains at least one amino acid substitution in at least one framework region of either the VH domain or the VL domain, in comparison to a corresponding framework region in the conventional antibody.

9. The chimeric antigen binding polypeptide of claim 1 wherein the VH domain of the polypeptide exhibits a sequence identity of 90% or greater with one or more human VH domains across the framework regions FR1, FR2, FR3 and FR4.

10. The chimeric antigen binding polypeptide of claim 9 wherein the VH domain of the polypeptide exhibits a sequence identity of 95% or greater with one or more human VH domains across the framework regions FR1, FR2, FR3 and FR4.

11. The chimeric antigen binding polypeptide of claim 10 wherein the VH domain of the polypeptide exhibits a sequence identity of 97% or greater with one or more human VH domains across the framework regions FR1, FR2, FR3 and FR4.

12. The chimeric antigen binding polypeptide of claim 1 wherein the VL domain of the polypeptide exhibits a sequence identity of 90% or greater with one or more human VL domains across the framework regions FR1, FR2, FR3 and FR4.

13. The chimeric antigen binding polypeptide of claim 12 wherein the VL domain of the polypeptide exhibits a sequence identity of 95% or greater with one or more human VL domains across the framework regions FR1, FR2, FR3 and FR4.

14. The chimeric antigen binding polypeptide of claim 13 wherein the VL domain of the polypeptide exhibits a sequence identity of 97% or greater with one or more human VL domains across the framework regions FR1, FR2, FR3 and FR4.

15. The chimeric antigen binding polypeptide of claim 1 wherein hypervariable loop H1 and hypervariable loop H2 each exhibit a predicted or actual canonical fold structure which is identical or substantially identical to a canonical fold structure of a corresponding H1 or H2 hypervariable loop which occurs in human antibodies.

16. The chimeric antigen binding polypeptide of claim 15 wherein hypervariable loop L1 and hypervariable loop L2 each exhibit a predicted or actual canonical fold structure which is substantially identical or substantially identical to a canonical fold structure of a corresponding L1 or L2 hypervariable loop which occurs in human antibodies.

17. The chimeric antigen binding polypeptide of claim 16 wherein hypervariable loop L1 and hypervariable loop L2 in the VL domain form a combination of predicted or actual canonical fold structures which is identical or substantially identical to a combination of canonical fold structures known to occur in corresponding hypervariable loops in a human germline VL domain.

18. The chimeric antigen binding polypeptide of claim 17 wherein the combination of canonical fold structures occurring in the human VL domain is selected from the group consisting of: 11-7, 13-7(A,B,C), 14-7(A,B), 12-11, 14-11, 12-12, 2-1, 3-1, 4-1 and 6-1.

19. The chimeric antigen binding polypeptide of claim 1 wherein hypervariable loop H1 and hypervariable loop H2 form a combination of predicted or actual canonical fold structures which is identical or substantially identical to a combination of canonical fold structures known to occur in corresponding hypervariable loops in a human germline VH domain.

20. The chimeric antigen binding polypeptide of claim 19 wherein the combination of canonical fold structures occurring in the human VH domain is selected from the group consisting of: 1-1, 1-2, 1-3, 1-4, 1-6, 2-1, 3-1 and 3-5.

21. The chimeric antigen binding polypeptide of claim 1 wherein the target antigen is a non-camelid antigen.

22. The chimeric antigen binding polypeptide of claim 21 wherein the target antigen is a human antigen.

23. The chimeric antigen binding polypeptide of claim 21 wherein the target antigen is a viral antigen or a bacterial antigen.

24. The chimeric antigen binding polypeptide of claim 1 wherein the target antigen is a target of therapeutic importance.

25. The chimeric antigen binding polypeptide of claim 1 which is an Fab, Fab', F(ab′)2, bi-specific Fab′, Fv fragments, diabody, linear antibody, a single chain variable fragment (scFv), antibody or multispecific antibody formed from antibody fragments.

26. The chimeric antigen binding polypeptide of claim 1 , wherein the species in the family Camelidae is camel, llama, dromedary, vicunia, guanaco or alpaca.

27. The chimeric antigen binding polypeptide of claim 1 , which is an antibody.

28. The chimeric antigen binding polypeptide of claim 1 , wherein said IgG constant domains comprise at least one of a CH1 domain, hinge region, CH2 domain, and CH3 domain of the human antibody.

29. The chimeric antigen binding polypeptide of claim 28 , wherein the IgG constant domains further comprise a human CL domain.

30. A pharmaceutical formulation comprising the chimeric antigen binding polypeptide of claim 1 and at least one pharmaceutically acceptable diluent, excipient or carrier.

31. A test kit comprising the chimeric antigen binding polypeptide of claim 1 .

32. The test kit of claim 31 which additionally comprises at least one additional reagent required to perform an immunoassay using said chimeric antigen binding polypeptide.