Disclosed is a method of engineering an immunobinder, the immunobinder comprising a human VH1a family heavy chain variable region, or fragment thereof, the VH1a heavy chain variable region comprising VH framework residues, the method comprising: A) selecting one or more amino acid positions within the VH1a framework residues and B) mutating the one or more amino acid positions selected for mutation, wherein the mutating comprises one or more substitutions selected from the group consisting of: (i) glutamic acid (E) at amino acid position 1 using AHo or Kabat numbering system (ii) glutamic acid (E) at amino acid position 6 using AHo or Kabat numbering system (iii) methionine (M) at amino acid position 13 using AHo numbering system (amino acid position 12 using Kabat numbering system): (iv) glutamic acid (E) or glutamine (Q) at amino acid position 14 using AHo numbering system (amino acid position 13 using Kabat numbering system) (v) leucine (L) at amino acid position 19 using AHo numbering system (amino acid position 18 using Kabat numbering system) (vi) isoleucine (I) at amino acid position 21 using AHo numbering system (amino acid position 20 using Kabat numbering system) (vii) phenylalanine (F), serine (S), histidine (H) or aspartic acid (D) at amino acid position 90 using AHo numbering system (amino acid position 79 using Kabat numbering system) (viii) aspartic acid (D) or glutamine (Q) at amino acid position 92 using AHo numbering system (amino acid position 81 using Kabat numbering system) (ix) glycine (G), asparagine (N) or threonine (T) at amino acid position 95 using AHo numbering system (amino acid position 82b using Kabat numbering system) and (x) threonine (T), alanine (A), proline (P) or phenylalanine (F) at amino acid position 98 using AHo numbering (amino acid position 84 using Kabat numbering.
