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Binding molecules

  • US 8,921,524 B2
  • Filed: 12/23/2009
  • Issued: 12/30/2014
  • Est. Priority Date: 07/22/2004
  • Status: Active Grant
First Claim
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1. A method for the production of soluble, antigen-specific heavy chain only antibodies comprising:

  • (a) immunising a transgenic mouse expressing a heterologous VH heavy chain locus with an antigen wherein;

    (i) the VH heavy chain locus comprises a variable region comprising at least one naturally occurring human VH 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 CH1 domain;

    (iii) the VH gene segment, D gene segment and J gene segment are capable of recombining to form a VDJ coding sequence;

    (iv) the recombined VH heavy chain locus, when expressed upon antigen challenge, is capable of forming a soluble, heavy chain-only antibody comprising a soluble, antigen-specific VH binding domain and a constant effector region devoid of a functional CH1 domain with an antigen;

    (b) cloning a soluble heavy chain only antibody resulting from recombination between single VH, D and J gene segments and encoding a soluble, antigen-specific VH 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).

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