PDL1-binding proteins
This invention relates generally to molecules that specifically engage 41BB, a member of the TNF receptor superfamily (TNFRSF). More specifically, this invention relates to multivalent and multispecific molecules that bind at least 41BB.
1. An isolated polypeptide comprising at least one VHH domain that binds PDL1, wherein at least one VHH domain that binds PDL1 comprises a CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 101, 105, and 109; a CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 102, 106, 110, and 117; and a CDR3 comprising an amino acid sequence selected from SEQ ID NO: 103, 107, 111, 113, 115, and 118.
2. The isolated polypeptide of claim 1 , wherein at least one VHH domain that binds PDL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 107.
3. The isolated polypeptide of claim 1 , wherein at least one VHH domain that binds PDL1 is humanized.
4. The isolated polypeptide of claim 1 , wherein each VHH domain that binds PDL1 is humanized.
5. The isolated polypeptide of claim 1 , wherein the polypeptide is monospecific.
6. The isolated polypeptide of claim 1 , wherein at least one VHH domain that binds PDL1 comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NOs: 100, 104, 108, 112, 114, 116, and 119-124.
7. The isolated polypeptide of claim 1 , wherein at least one VHH domain that binds PDL1 comprises an amino acid sequence selected from SEQ ID NOs: 100, 104, 108, 112, 114, 116, and 119-124.
8. The isolated polypeptide of claim 1 , wherein at least one VHH domain that binds PDL1 comprises the amino acid sequence of SEQ ID NO: 124.
9. The isolated polypeptide of claim 1 , wherein the polypeptide comprises one VHH domain that binds PDL1.
10. The isolated polypeptide of claim 9 , wherein the VHH domain that binds PDL1 is humanized.
11. The isolated polypeptide of claim 9 , wherein the VHH domain that binds PDL1 comprises the amino acid sequence of SEQ ID NO: 124.
12. The isolated polypeptide of claim 1 , wherein the polypeptide comprises two VHH domains that bind PDL1.
13. The isolated polypeptide of claim 12 , wherein the VHH domains that bind PDL1 are humanized.
14. The isolated polypeptide of claim 12 , wherein each VHH domain that binds PDL1 comprises the amino acid sequence of SEQ ID NO: 124.
15. The isolated polypeptide of claim 1 , wherein the isolated polypeptide comprises an Fc region.
16. The isolated polypeptide of claim 15 , wherein the Fc region comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from SEQ ID NOs: 1-6.
17. The isolated polypeptide of claim 15 , wherein the Fc region comprises an amino acid sequence selected from SEQ ID NOs: 1-6.
18. The isolated polypeptide of claim 15 , which forms a homodimer under physiological conditions.
19. The isolated polypeptide of claim 15 , wherein the polypeptide has the structure VHH-Linker-VHH-Linker-Hinge-Fc.
20. The isolated polypeptide of claim 19 , wherein each linker is, independently, 5-20 amino acids in length.
21. The isolated polypeptide of claim 19 , wherein the hinge comprises a sequence selected from SEQ ID NOs: 7-9.
22. The isolated polypeptide of claim 1 , wherein the PDL1 is human PDL 1.