Modified proteins and peptides

A single immunoglobulin variable domain (dAb) which is selected from the group consisting of:

• a human VH dAb, a human VL dAb (e.g. a V kappa) and a Camelid VHH and which monovalently binds to a target antigen, comprising:
• a. three complementarity determining (CDR) regions specific for said target antigen;
• such that said dAb binds said antigen with a KD in the range from 5 μM to 1 pM
• b. four framework (FW) regions;
• and
• c. a C-terminal sequence consisting of the sequence VTVS(S)nX or VEIKpRqX;
• and optionally
• d. one or more amino acid substitutions at positions 14, 41, 108, 110, or 112 compared to a human germline framework sequence
• wherein:
• n represents an integer independently selected from 0 or 1;
• p and q each represent 0 or 1 such that when p represents 1 q may be 0 or 1 and such that when p represents 0, q also represents 0;
• X may be present or absent, and if present represents an amino acid extension of 1 to 5 amino acids residues;
• with the further proviso that if X is absent;
• i. n is 0 and/or the dAb ending in VTVS(S)n comprises one or more of said amino acid substitutions;
• ii. p and/or q is 0, and/or the dAb ending in VEIKpRq comprises one or more of said amino acid substitutions.

A single immunoglobulin variable domain (dAb),) which is selected from the group consisting of:

• a human VH dAb, a human VL dAb (e.g. a V kappa) and a Camelid VHH and which comprises one or more modifications selected from:
• (a) a C-terminal extension which comprises an amino acid extension of from one amino acid to 5 amino acids;
• or
• (b) one or more amino acid framework substitutions wherein at least one substitution is a substitution selected from:
• a P14A substitution, a P41A substitution and a L108A substitution;
• (c) a C terminal deletion
• and which has reduced binding to pre-existing ADAs compared to the unmodified single immunoglobulin variable domain (dAb).