Immunoglobulin variable domains
VH domain, in which: (i) the amino acid residue at position 112 is one of K or Q; and/or (ii) the amino acid residue at position 89 is T; and/or (iii) the amino acid residue at position 89 is L and the amino acid residue at position 110 is one of K or Q; and (iv) in each of cases (i) to (iii), the amino acid at position 11 is preferably V; and in which said VH domain contains a C-terminal extension (X)n, in which n is 1 to 10, preferably 1 to 5, such as 1, 2, 3, 4 or 5 (and preferably 1 or 2, such as 1); and each X is an (preferably naturally occurring) amino acid residue that is independently chosen, and preferably independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
1. A heavy chain immunoglobulin single variable domain (ISVD) in which:
(i) the amino acid residue at Kabat position 110 is K or Q; and
(ii) the amino acid residue at Kabat position 11 is V, the amino acid residue at Kabat position 89 is L, or a combination thereof.
2. The heavy chain ISVD of claim 1 , wherein the amino acid residue at Kabat position 11 is V.
3. The heavy chain ISVD of claim 1 , wherein the amino acid residue at Kabat position 89 is L.
4. The heavy chain ISVD of claim 1 , wherein the amino acid residue at Kabat position 11 is V and the amino acid residue at Kabat position 89 is L.
5. The heavy chain ISVD of claim 1 , wherein the amino acid residue at Kabat position 14 is A or P.
6. The heavy chain ISVD of claim 1 , wherein the amino acid residue at Kabat position 41 is A or P.
7. The heavy chain ISVD of claim 1 , wherein the amino acid residue at Kabat position 108 is Q or L.
8. The heavy chain ISVD of claim 1 , further comprising a C-terminal extension (X) n , in which n is 1 to 10, wherein each X is an independently chosen amino acid.
9. The heavy chain ISVD of claim 8 , wherein each X is an amino acid independently chosen from the group consisting of A, G, V, L, and I.
10. The heavy chain ISVD of claim 1 , wherein the C-terminal end of the heavy-chain ISVD comprises an amino acid sequence selected from the group consisting of: VKVSS (SEQ ID NO: 95), VKVSS(X) n (SEQ ID NO:97), VQVSS (SEQ ID NO: 96), VQVSS(X) n (SEQ ID NO: 98), in which n is 1 to 10, wherein each X is an independently chosen amino acid.
11. The heavy chain ISVD of claim 10 , wherein each X is an amino acid independently chosen from the group consisting of A, G, V, L, and I.
12. The heavy chain ISVD of claim 1 , which is a VHH domain, a humanized VHH domain, or a camelized VH domain.
13. A fusion polypeptide comprising a heavy chain ISVD according to claim 1 fused to at least one other heavy chain ISVD.
14. The fusion polypeptide of claim 13 , wherein the heavy chain ISVDs are linked directly or via a suitable linker.
15. A composition comprising a heavy chain ISVD according to claim 1 or a polypeptide comprising said heavy chain ISVD and at least one pharmaceutically acceptable carrier, diluent or excipient.