Patent ID: 8921522

Claim:
A method for the production of a soluble, antigen-specific V H binding domain 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 I 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 I domain with an antigen; b. cloning a V H locus resulting from recombination between single V, D and J gene segments 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 V H binding domain from the clone of step b.