Antigen binding polypeptides
The invention relates to a platform technology for production of antigen binding polypeptides having specificity for a desired target antigen which is based on the conventional antibody repertoire of species in the family Camelidae, and to antigen binding polypeptides obtained using this technology platform. In particular, the invention provides an antigen binding polypeptide comprising a VH domain and a VL domain, wherein at least one hypervariable loop or complementarity determining region (CDR) in the VH domain or the VL domain is obtained from a VH or VL domain of a species in the family Camelidae.
1. A polynucleotide molecule encoding a VH domain and/or a VL domain of an antigen binding polypeptide, said VH domain comprising hypervariable loops H1, H2 and H3, and said VL domain comprising hypervariable loops L1, L2 and L3, wherein said VH domain and/or said VL domain are each fused to one or more IgG constant domains of a human antibody, wherein each of the hypervariable loops H1-H3 and L1-L3 are obtained from a conventional antibody of a Lama species by active immunization of the Lama species with the human target antigen, wherein said conventional antibody is a heterotetrameric IgG antibody composed of two identical light chains and two identical heavy chains, and 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 a human antibody.
2. An expression vector comprising the polynucleotide molecule of claim 1 operably linked to regulatory sequences which permit expression of the antigen binding polypeptide in a host cell or cell-free expression system.
3. A host cell or cell-free expression system containing the expression vector of claim 2 .
4. A method of producing a recombinant antigen binding polypeptide which comprises culturing the host cell or cell free expression system of claim 3 under conditions which permit expression of the antigen binding polypeptide and recovering the expressed antigen binding polypeptide.