Anti-serum albumin binding variants
The invention relates to improved variants of the anti-serum albumin immunoglobulin single variable domain DOM7h-11, as well as ligands and drug conjugates comprising such variants, compositions, nucleic acids, vectors and hosts.
1. An anti-serum albumin (SA) immunoglobulin single variable domain variant of SEQ ID NO: 421, wherein the variant comprises a CDR1 amino acid sequence as shown in SEQ ID NO:344, a CDR2 amino acid sequence as shown in SEQ ID NO: 345, and a CDR3 amino acid sequence as shown in SEQ ID NO: 346.
2. An anti-serum albumin (SA) immunoglobulin single variable domain variant of SEQ ID NO: 421, wherein the variant comprises an amino acid sequence that is identical to the amino acid sequence of SEQ ID NO: 2.
3. The variant of claim 1 , wherein the variant comprises a binding site that specifically binds human SA with a dissociation constant (KD) of from about 0.1 to about 10000 nM, optionally from about 1 to about 6000 nM, as determined by surface plasmon resonance.
4. The variant of claim 1 , wherein the variant comprises a binding site that specifically binds human SA with an off-rate constant (K d ) of from about 1.5×10 −4 to about 0.1 sec −1 , optionally from about 3×10 −4 to about 0.1 sec −1 as determined by surface plasmon resonance.
5. The variant of claim 1 , wherein the variant comprises a binding site that specifically binds human SA with an on-rate constant (K a ) of from about 2×10 6 to about 1×10 4 M −1 sec −1 , optionally from about 1×10 6 to about 2×10 4 M −1 sec −1 as determined by surface plasmon resonance.
6. The variant of claim 1 , wherein the variant comprises a binding site that specifically binds Cynomolgus monkey SA with a dissociation constant (KD) of from about 0.1 to about 10000 nM, optionally from about 1 to about 6000 nM, as determined by surface plasmon resonance.
7. The variant of claim 1 , wherein the variant comprises a binding site that specifically binds Cynomolgus monkey SA with an off-rate constant (K d ) of from about 1.5×10 −4 to about 0.1 sec −1 , optionally from about 3×10 −4 to about 0.1 sec −1 as determined by surface plasmon resonance.
8. The variant of claim 1 , wherein the variant comprises a binding site that specifically binds Cynomolgus monkey SA with an on-rate constant (K a ) of from about 2×10 6 to about 1×10 4 M −1 sec −1 , optionally from about 1×10 6 to about 5×10 3 M −1 sec −1 as determined by surface plasmon resonance.
9. A multispecific ligand comprising an anti-SA variant of claim 1 and a binding moiety that specifically binds a target antigen other than SA.
10. The anti-serum albumin (SA) immunoglobulin single variable domain variant of claim 1 , wherein the variable domain is conjugated to an NCE drug.
11. A composition comprising a variant of claim 1 and a pharmaceutically acceptable diluent, carrier, excipient or vehicle.
12. A nucleic acid comprising a nucleotide sequence encoding a variant according to claim 1 .
13. A nucleic acid comprising the nucleotide sequence of SEQ ID NO: 7.
14. A vector comprising the nucleic acid of claim 12 .
15. An isolated host cell comprising the vector of claim 14 .
16. A nucleic acid comprising a nucleotide sequence encoding a variant according to claim 2 .