Patent ID: 8921524

Claim:
A method for the production of soluble, antigen-specific heavy chain only antibodies comprising: (a) immunising a transgenic mouse expressing a heterologous V H heavy chain locus with an antigen wherein: (i) the V H heavy chain locus comprises a variable region comprising at least one naturally occurring human V H gene segment, at least one D gene segment, at least one J gene segment and at least one heavy chain constant region; (ii) each constant region does not encode a functional C H 1 domain; (iii) the V H gene segment, D gene segment and J gene segment are capable of recombining to form a VDJ coding sequence; (iv) the recombined V H heavy chain locus, when expressed upon antigen challenge, is capable of forming a soluble, heavy chain-only antibody comprising a soluble, antigen-specific V H binding domain and a constant effector region devoid of a functional C H 1 domain with an antigen; (b) cloning a soluble heavy chain only antibody resulting from recombination between single V H , D and J gene segments and encoding a soluble, antigen-specific V H binding domain from an antibody-producing cell of said immunised transgenic mouse after affinity maturation via somatic mutation; and (c) producing said soluble, antigen specific heavy chain only antibody, or a soluble antigen-specific binding domain derived therefrom, from the clone of step (b).