Soluble heavy-chain only antibodies

摘要

The present invention provides a high affinity, antigen-specific, soluble heavy chain-only antibody which: lacks hallmark camelid-related amino acid substitutions and has FR2 substitutions which are not found in antibodies which comprise heavy and light chain; shows increased net hydrophobicity within CDRl and an increased number of charged amino acids present in CDR3; and comprises one or more amino acid substitutions within the frameworkβ-pleated sheet leading to increased net hydrophobicity within FRl and an increased number of charged amino acids present in FR3. Also provided are VH domains having the same properties, gene segments for their production, methods for their production, transgenic animals and uses of the antibody of the VH domains in therapy.