Serum albumin binding immunoglobulin single variable domains
The present invention relates to amino acid sequences that can bind to serum albumin. In particular, the present invention relates to immunoglobulin single variable domains, and in particular heavy-chain immunoglobulin single variable domains, that can bind to serum albumin. The invention also relates to proteins, polypeptides and other constructs, compounds, molecules or chemical entities that comprise at least one of the immunoglobulin single variable domains binding to serum albumin that are described herein.
1 . An immunoglobulin single variable domain (ISVD) capable of binding to human serum albumin that comprises three complementarity determining regions (CDR1 to CDR3, respectively), wherein the CDR1 to CDR3 of the ISVD correspond to the CDRs of SEQ ID NO: 15.
2 . The ISVD according to claim 1 , that is a heavy-chain immunoglobulin single variable domain.
3 . The ISVD according to claim 1 , that is a VHH, a humanized VHH or a camelized VH.
4 . The ISVD according to claim 1 , that has:
a degree of sequence identity with the sequence of SEQ ID NO: 15 of at least 95%;
or that has:
no more than 3, no more than 2, or no more than 1 amino acid differences with the sequence of SEQ ID NO: 15;
wherein the CDRs are not taken into account for determining the degree of sequence identity or the amino acid differences.
5 . The ISVD according to claim 1 , that is a VHH and that contains, compared to the sequence of SEQ ID NO:15, one or more humanizing substitutions.
6 . A polypeptide that comprises at least one ISVD according to claim 1 .
7 . The polypeptide according to claim 6 , that is a fusion protein.
8 . The polypeptide according to claim 6 , wherein the polypeptide further comprises a N-terminal ISVD, wherein the N-terminal ISVD-comprises a D at position 1.
9 . The polypeptide according to claim 6 , that comprises at least one therapeutic moiety or entity.
10 . A pharmaceutical composition comprising a polypeptide according to claim 6 .
11 . A nucleic acid that encodes an ISVD according to claim 1 .
12 . An expression vector that comprises the nucleic acid of claim 11 .
13 . A host cell that comprises an expression vector according to claim 12 .
14 . A method for preparing a polypeptide comprising cultivating or maintaining a host cell according to claim 13 under conditions such that said host cell produces or expresses the polypeptide.
15 . An immunoglobulin single variable domain (ISVD) capable of binding to human serum albumin, wherein the ISVD comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 15, wherein the amino acid sequence comprises relative to SEQ ID NO: 15, an R at position 47, an S at position 52, an R at position 53, a G at position 56, a Y at position 57, a Y at position 59, a K at position 65, a Y at position 101, a W at position 102, an A at position 103, a T at position 104, an S at position 106, an E at position 107, and a Y at position 108, wherein positions are determined sequentially according to the amino acid sequence of SEQ ID NO: 15.
16 . A polypeptide that comprises at least one ISVD according to claim 15 .
17 . The ISVD according to claim 1 , wherein the CDR1 to CDR3 are determined according to Kabat numbering.
18 . The ISVD according to claim 3 , wherein the camelized VH is a camelized human VH.
19 . The method according to claim 14 , further comprising isolating the polypeptide.