The H2L2 transgenic mice produce classical two heavy and two light immunoglobulin chain antibodies with fully human variable regions. The introduction of human heavy and light chain transgene loci into an engineered mouse background results in the production, in response to antigen challenge, of either a single class of conventional human antibodies carrying a specific set of effector function (eg IgG or IgA), or multiple classes of antibodies (eg.IgM and IgG), dependent on the design of the introduced heavy chain immunoglobulin loci. Antigen specific H2L2 monoclonal antibodies can be recovered using standard hybridoma technology. Harbour's H2L2 mice technology is covered by US and several international issued and pending patent rights.

Approaches of Human H2L2 in Transgenic Mice

  1. Endogenous murine antibody expression inactivated
  2. Transgenes introduced with human V regions and rodent constant regions (to improve efficiency of immune response relative to first gen TG mice)
  3. Recovery using standard hybridoma technology or any other methodology used for murine mAb isolation

Features of H2L2 mAb

  1. Transgenic animals have been challenged with more than dozens of different antigens, some of which had proved challenging in other platforms
  2. Immune response comparable to normal mice such as Balb/c
  3. mAbs have been successfully generated against all targets spanning multiple epitopes within the protein of interest
  4. H2L2 transgenic animals display normal antibody maturation in vivo

    ? Diverse V gene usage

    ? Antibody hypermutation

    ? Affinity maturation

    ? Class switching

    ? Affinities in the pM to nM range

    ? Stability, pharmacokinetics comparable to reference human H2L2 antibodies from other platforms

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