FIELD: biochemistry; biotechnology.
SUBSTANCE: invention relates to biochemistry and biotechnology. Described is a fragment of an antibody for use as a therapeutic agent, comprising one of the following solubility motifs in amino acid positions 12, 103 and 144 of the heavy chain (AIE numbering): Serine (S) at amino acid position 12 of the heavy chain; Serine (S) at amino acid position 103 of the heavy chain; and Threonine (T) at amino acid position 144 of the heavy chain; or Serine (S) at amino acid position 12 of the heavy chain; Threonine (T) at amino acid position 103 of the heavy chain; and Serine (S) at amino acid position 144 of the heavy chain; or Serine (S) at amino acid position 12 of the heavy chain; Threonine (T) at amino acid position 103 of the heavy chain; and Threonine (T) at amino acid position 144 of the heavy chain. Composition for therapy comprising a described fragment of the antibody is provided. Framework is also described. Method for increasing solubility of an antibody fragment in a native state comprising variable region (VH) of the heavy chain or a fragment thereof, comprising selecting for a mutation at least three amino acid positions within region VH, and carrying out a mutation in at least three amino acid positions, selected for mutation, wherein at least three amino acid positions are selected from the group of amino acid positions of the heavy chain, consisting of positions 12, 103 and 144 (in accordance with the AIE numbering rule), mutation involves replacing the amino acid at the selected amino acid position by a hydrophilic amino acid. Appropriate framework of the antibody heavy chain variable domain for use for preparing a therapeutic agent and a composition comprising such a framework are also provided.
EFFECT: invention provides improved solubility of immunosorbent agents, in particular single-chain antibodies (scFv).
17 cl, 6 dwg, 4 ex, 14 tbl
