Anti-TPBG antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10434184-B2
Application number	US-201815965517-A
Country	US
Kind code	B2
Filing date	Apr 27, 2018
Priority date	Oct 29, 2015
Publication date	Oct 8, 2019
Grant date	Oct 8, 2019

Abstract

The invention provides anti-TPBG antibodies and methods of using the same.

First claim

The invention claimed is:

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.

Assignees

• Hoffmann La Roche

Inventors

• Dengl Stefan
• Fenn Sebastian
• Fischer Jens
• Friess Thomas
• Imhof-Jung Sabine
• Krippendorff Ben-Fillippo
• Schantz Christian
• Schlothauer Tilman
• Sustmann Claudio
• Weiser Barbara
• Zwick Adrian

Classifications

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title

• A61K47/6829 Primary

  Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A · CPC title

• A61K47/68 Primary

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title