Serum albumin binding molecules
The present invention relates to an antibody-like protein based on the tenth fibronectin type III domain ( 10 Fn3) that binds to serum albumin. The invention further relates to fusion molecules comprising a serum albumin-binding 10 Fn3 joined to a heterologous protein for use in diagnostic and therapeutic applications.
1. A nucleic acid encoding a polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain, wherein the 10 Fn3 domain binds to domain 1 or 2 of human serum albumin with a K D of 1 μM or less, and wherein the 10 Fn3 domain comprises a modified amino acid sequence in one or more of the BC, DE and FG loops relative to the wild-type human 10 Fn3 domain (SEQ ID NO: 1), and wherein the polypeptide comprises an amino acid sequence at least 75% identical to an amino acid sequence selected from SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.
2. A vector comprising a nucleic acid of claim 1 .
3. The vector of claim 2 , wherein the vector is an expression vector.
4. A host cell comprising the vector of claim 2 .
5. The host cell of claim 4 , wherein the cell is a bacterial cell.
6. The host cell of claim 4 , wherein the cell is a mammalian cell.
7. The nucleic acid of claim 1 , which encodes a polypeptide comprising an amino acid sequence at least 80% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.
8. The nucleic acid of claim 7 , which encodes a polypeptide comprising an amino acid sequence at least 85% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.
9. The nucleic acid of claim 8 , which encodes a polypeptide comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.
10. The nucleic acid of claim 9 , which encodes a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.
11. The nucleic acid of claim 1 , which encodes a polypeptide comprising an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO: 4.
12. The nucleic acid of claim 7 , which encodes a polypeptide comprising an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO: 4.
13. The nucleic acid of claim 8 , which encodes a polypeptide comprising an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 4.
14. The nucleic acid of claim 9 , which encodes a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 4.
15. The nucleic acid of claim 10 , which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 4.
16. A nucleic acid encoding a fusion polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain and a heterologous protein, wherein the 10 Fn3 domain binds to human serum albumin with a K D of 1 μM or less and comprises an amino acid sequence at least 75% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.
17. The nucleic acid of claim 16 , wherein the nucleic acid comprises a sequence selected from the group consisting of SEQ ID NOs: 176-214 and 401-405.
18. The nucleic acid of claim 16 , wherein the 10 Fn3 domain comprises an amino acid sequence at least 85% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.
19. The nucleic acid of claim 18 , wherein the 10 Fn3 domain comprises an amino acid sequence selected from SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.