Serum albumin binding proteins
The present invention relates to amino acid sequences that are capable of binding to serum albumin, which sequences do not significantly reduce or inhibit the binding of serum albumin to FcRn or significantly reduce the half-life of serum albumin. It further relates to proteins and polypeptides comprising or essentially consisting of such amino acid sequences; to nucleic acids that encode such amino acid sequences, proteins or polypeptides; to compositions, and in particular pharmaceutical compositions, that comprise such amino acid sequences, proteins and polypeptides; and to uses of such amino acid sequences, proteins and polypeptides.
1. An isolated amino acid sequence that is an immunoglobulin sequence and that can bind to serum albumin, in which:
a) complementarity determining region 1 (CDR1) comprises or is SEQ ID NO:10; and in which:
b) complementarity determining region 2 (CDR2) comprises or is SEQ ID NO:24; and in which:
c) complementarity determining region 3 (CDR3) comprises or is SEQ ID NO:38.
2. The isolated amino acid sequence according to claim 1 , which is a single domain antibody or an immunoglobulin variable domain sequence.
3. The isolated amino acid sequence according to claim 2 , that is a V H -, V L - or V HH -sequence.
4. The isolated amino acid sequence according to claim 2 , which has at least 90% sequence identity with at least one of the amino acid sequences of SEQ ID NO's 50 to 64.
5. The isolated amino acid sequence according to claim 4 , which is chosen from the group consisting of PMP6A6 (ALB1; SEQ ID NO: 52) and humanized variants thereof.
6. The isolated amino acid sequence according to claim 5 , wherein the humanized variant of PMP6A6 (ALB1; SEQ ID NO: 52) is ALB 8 (SEQ ID NO: 62).
7. A fusion protein or construct, which comprises an amino acid sequence according to claim 1 and at least one therapeutic moiety.
8. The fusion protein or construct according to claim 7 , in which the amino acid sequence is either directly linked to the at least one therapeutic moiety or is linked to the at least one therapeutic moiety via a linker or spacer.
9. The fusion protein or construct according to claim 7 , in which the at least one therapeutic moiety comprises an immunoglobulin sequence or a fragment thereof.
10. The fusion protein or construct according to claim 9 , in which the at least one therapeutic moiety comprises a single domain antibody or an immunoglobulin variable domain sequence.
11. A multivalent and multispecific polypeptide construct, comprising at least one amino acid sequence according to claim 1 which is an immunoglobulin variable domain sequence and at least one further immunoglobulin variable domain sequence.
12. The multivalent and multispecific polypeptide construct according to claim 11 , in which the at least one amino acid sequence that is an immunoglobulin variable domain sequence is either directly linked to the at least one further immunoglobulin variable domain sequence or is linked to the at least one further immunoglobulin variable domain sequence via a linker or spacer.
13. The multivalent and multispecific polypeptide construct according to claim 11 , in which the at least one amino acid sequence that is an immunoglobulin variable domain sequence is linked to the at least one further immunoglobulin variable domain sequence via a linker or spacer, and in which the linker is an amino acid sequence.
14. A pharmaceutical composition that comprises at least one amino acid sequence of claim 1 , or a fusion protein or construct comprising the amino acid sequence of claim 1 , and optionally at least one pharmaceutically acceptable carrier, diluent or excipient.
15. The isolated amino acid sequence according to claim 1 , wherein the amino acid sequence binds to the same epitope on human serum albumin as PMP6A6 (ALB1; SEQ ID NO: 52).
16. The isolated amino acid sequence according to claim 1 , wherein the amino acid sequence competes for binding to human serum albumin with PMP6A6 (ALB 1; SEQ ID NO: 52).
17. The isolated amino acid sequence according to claim 1 , which has at least 90% sequence identity with at least one of the amino acid sequences of SEQ ID NOs: 52 or 57 to 64.
18. The isolated amino acid sequence according to claim 5 , which is chosen from the group consisting of ALB 3 (SEQ ID NO: 57); ALB 4 (SEQ ID NO: 58); ALB 5 (SEQ ID NO: 59); ALB 6 (SEQ ID NO: 60); ALB 7 (SEQ ID NO: 61); ALB 8 (SEQ ID NO: 62); ALB 9 (SEQ ID NO: 63); and ALB 10 (SEQ ID NO: 64).