Anti-TPBG antibodies and methods of use
The invention provides anti-TPBG antibodies and methods of using the same.
1. An isolated antibody that binds to trophoblast glycoprotein (TPBG) comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 3, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8.
2. The antibody of claim 1 comprising a variable heavy chain domain (VH) having at least 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 9 and a variable light chain domain (VL) having at least 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 10.
3. The antibody of claim 1 comprising a variable heavy chain domain (VH) with the amino acid sequence of SEQ ID NO: 9 and a variable light chain domain (VL) with the amino acid sequence of SEQ ID NO: 10.
4. An isolated antibody that binds to trophoblast glycoprotein (TPBG) comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 12, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 14, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 16.
5. The antibody of claim 4 comprising a variable heavy chain domain (VH) having at least 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 17 and a variable light chain domain (VL) having at least 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 18.
6. The antibody of claim 4 comprising a variable heavy chain domain (VH) with the amino acid sequence of SEQ ID NO: 17 and a variable light chain domain (VL) with the amino acid sequence of SEQ ID NO: 18.
7. An isolated antibody that binds to trophoblast glycoprotein (TPBG) comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 19, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 20, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 21, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 22, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 24.
8. The antibody of claim 7 comprising a variable heavy chain domain (VH) having at least 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 25 and a variable light chain domain (VL) having at least 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 26.
9. The antibody of claim 7 comprising a variable heavy chain domain (VH) with the amino acid sequence of SEQ ID NO: 25 and a variable light chain domain (VL) with the amino acid sequence of SEQ ID NO: 26.
10. The antibody of any one of claim 1 , 4 or 7 , wherein the antibody is a Fab fragment that binds to TPBG.
11. An isolated nucleic acid encoding the antibody of any one of claim 1 , 4 or 7 .
12. A host cell comprising the nucleic acid of claim 11 .
13. A method of producing an antibody comprising culturing the host cell of claim 12 so that the antibody is produced.
14. An immunoconjugate comprising the antibody of any one of claim 1 , 4 or 7 , and a cytotoxic agent.
15. The immunoconjugate of claim 14 , wherein the cytotoxic agent is Pseudomonas exotoxin A or a variant thereof.
16. The immunoconjugate of claim 14 , wherein the antibody is a Fab fragment that binds to TPBG.
17. A pharmaceutical formulation comprising the antibody of any one of claim 1 , 4 or 7 , and a pharmaceutically acceptable carrier.
18. A pharmaceutical formulation comprising the immunoconjugate of claim 14 and a pharmaceutically acceptable carrier.
19. A method of treating cancer in a patient, comprising administering the antibody of any one of claim 1 , 4 or 7 to a patient in need thereof.
20. The method of claim 19 , wherein the cancer is non-small cell lung cancer.
21. A method of treating cancer in a patient, comprising administering the immunoconjugate of claim 14 to a patient in need thereof.
22. The method of claim 21 , wherein the cancer is non-small cell lung cancer.