Pharmacokinetic modulation and compositions for modified FN3 polypeptides
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. A polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain of 80 to 150 amino acids, wherein the 10 Fn3 domain binds to a target molecule with a K D of less than 100 nM and comprises an amino acid sequence at least 60% identical to SEQ ID NO:5; wherein the 10 Fn3 domain further comprises a C-terminal tail having the sequence of EIDKPCQ (residues 97-103 of SEQ ID NO: 199), and wherein the cysteine residue of the C-terminal tail is conjugated to a moiety selected from the group consisting of: a polyoxyalkylene moiety, a radioactive moiety, a chemotherapeutic agent, and a label.
2. The polypeptide of claim 1 , wherein the polypeptide binds to the target molecule with a K D of less than 10 nM.
3. The polypeptide of claim 1 , wherein the moiety is a polyoxyalkylene moiety.
4. The polypeptide of claim 3 , wherein the polyoxyalkylene moiety is a polyethylene glycol (PEG) moiety.
5. The polypeptide of claim 4 , wherein the PEG moiety has a mass of 40 kDa.
6. The polypeptide of claim 1 , wherein the moiety is a radioactive moiety.
7. The polypeptide of claim 1 , wherein the moiety is a chemotherapeutic agent.
8. The polypeptide of claim 1 , wherein the moiety is a label.
9. A pharmaceutical preparation comprising a polypeptide of claim 1 and a pharmaceutically acceptable carrier.
10. The pharmaceutical preparation of claim 9 , wherein the moiety is a polyoxyalkylene moiety.
11. The pharmaceutical preparation of claim 10 , wherein the polyoxyalkylene moiety is a polyethylene glycol (PEG) moiety.
12. The pharmaceutical preparation of claim 11 , wherein the PEG moiety has a mass of 40 kDa.
13. The pharmaceutical preparation of claim 9 , wherein the moiety is a radioactive moiety.
14. The pharmaceutical preparation of claim 9 , wherein the moiety is a chemotherapeutic agent.
15. The pharmaceutical preparation of claim 9 , wherein the moiety is a label.