Modified protein or polypeptide

A modified immunoglobulin single variable domain, comprising a heavy chain framework sequence derived from a human germline, and having an amino acid modification of 112F or 112R at position 112 relative to the human germline heavy chain framework sequence;

• or,
• the immunoglobulin single variable domain has an amino acid modification of 112F or 112R at position 112 relative to the human germline heavy chain framework sequence, and an amino acid modification of 113P at position 113 relative to the human germline heavy chain framework sequence, or has an S at position 113;
• or,
• the immunoglobulin single variable domain has an amino acid residue combination of any one of the following (f)-(h) at position 112 and position 113 relative to the human germline framework sequence:
• (f) 112F and 113P;
• (g) 112R and 113S;
• and
• (h) 112F and 113S.

A method for reducing binding of an immunoglobulin single variable domain to pre-ADAs or ADAs, wherein the method comprises:

• allowing the C-terminus of the immunoglobulin single variable domain to comprise a C-terminus consisting of any one of the following (a)-(e):
• (a) SAA or VTVSAA;
• (b) FP or VTVFP;
• (c) FPA or VTVFPA;
• (d) RS or VTVRS;
• and
• (e) RSA or VTVRSA.