Nucleic acid encoding 10FN3 polypeptide inhibitors of Type 2 vascular endothelial growth factor receptors
View Patent ↗The present disclosure relates to novel vascular endothelial growth factor receptor (VEGFR)-binding polypeptides and methods for using these polypeptides to inhibit biological activities mediated by vascular endothelial growth factors (VEGFs). The present disclosure also provides various improvements relating to single domain binding polypeptides.
1. An isolated nucleic acid comprising a sequence encoding a polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain having between about 80 and about 150 amino acids, wherein the 10 Fn3 domain binds to an extracellular domain of the human Kinase Insert Domain Receptor (KDR) protein with a dissociation constant (K D ) of less than 1×10 −6 M, and wherein the 10 Fn3 domain comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:192.
2. The nucleic acid of claim 1 , wherein the encoded polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:192.
3. The nucleic acid of claim 1 , wherein the encoded polypeptide comprises the amino acid sequence of SEQ ID NO:192.
4. The nucleic acid of claim 1 , wherein the encoded polypeptide comprises the amino acid sequence of SEQ ID NO:193.
5. The nucleic acid of claim 1 , wherein the encoded polypeptide comprises the amino acid sequence of SEQ ID NO:194.
6. An expression vector comprising the nucleic acid of claim 1 operably linked with a promoter.
7. A method of producing a polypeptide that binds KDR, comprising: expressing the nucleic acid of claim 1 .
8. An isolated host cell comprising a nucleic acid comprising a sequence encoding a polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain having between about 80 and about 150 amino acids, wherein the 10 Fn3 domain binds to an extracellular domain of the human Kinase Insert Domain Receptor (KDR) protein with a dissociation constant (K D ) of less than 1×10 −6 M, and wherein the 10 Fn3 domain comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:192.
9. The isolated host cell of claim 8 , wherein the nucleic acid comprises a sequence encoding a polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:192.
10. The isolated host cell of claim 8 , wherein the nucleic acid comprises a sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:192.