PD-L1 binding fibronectin type III domains
FN3 domains that specifically bind to PD-L1, their conjugates, isolated nucleotides encoding the molecules, vectors, host cells, and methods of making and using them are useful in therapeutic and diagnostic applications.
1. A protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, and 124.
2. The protein of claim 1 , wherein the protein has at least one substitution at a residue selected from the group consisting of 11, 14, 17, 37, 46, 73, and 86 corresponding to SEQ ID NO: 4.
3. The protein of claim 1 , wherein the protein is conjugated to a heterologous molecule.
4. The protein of claim 3 , wherein the heterologous molecule is a detectable label or a cytotoxic agent, or both.
5. The protein of claim 4 , wherein the detectable label is a radioactive isotope, magnetic beads, metallic beads, colloidal particles, a fluorescent dye, an electron-dense reagent, an enzyme, biotin, digoxigenin, or hapten.
6. The protein of claim 4 , wherein the detectable label is auristatin, monomethyl auristatin phenylalanine, dolostatin, chemotherapeutic agent, a drug, a growth inhibitory agent, a toxin, or a radioactive isotope.
7. The protein of claim 1 , further comprising a methionine at the N-terminus of the protein.
8. The protein of claim 1 , wherein the protein is coupled to a half-life extending moiety.
9. The protein of claim 8 , wherein the half-life extending moiety is an albumin binding molecule, a polyethylene glygol (PEG), albumin, albumin variant, or at least a portion of an Fc region of an immunoglobulin.
10. A composition comprising the protein of claim 1 and a pharmaceutically acceptable carrier.
11. A kit comprising the protein of claim 1 .
12. The protein of claim 1 , wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, and 49.
13. The protein of claim 1 , wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, and 64.
14. The protein of claim 1 , wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, and 79.
15. The protein of claim 1 , wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, and 94.
16. The protein of claim 1 , wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, and 109.
17. The protein of claim 1 , wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, and 124.