Combination therapy involving antibodies against Claudin 18.2 for treatment of cancer

Patent metadata

Field	Value
Publication number	US-10813996-B2
Application number	US-201815973116-A
Country	US
Kind code	B2
Filing date	May 7, 2018
Priority date	May 23, 2012
Publication date	Oct 27, 2020
Grant date	Oct 27, 2020

Abstract

The present invention provides a combination therapy for effectively treating and/or preventing diseases associated with cells expressing CLDN18.2, including cancer diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder and metastases thereof.

First claim

The invention claimed is:

1. A method of treating a cancer disease characterized by cells expressing claudin 18 splice variant 2, comprising administering to a patient an antibody having the ability of binding to claudin 18 splice variant 2 (CLDN18.2) in combination with an agent stabilizing or increasing expression of CLDN18.2, wherein the agent stabilizing or increasing expression of CLDN18.2 comprises (i) capecitabine and oxaliplatin; (ii) folinic acid, 5-fluorouracil or a prodrug thereof, and oxaliplatin; or (iii) epirubicin, oxaliplatin, and 5-fluorouracil or a prodrug thereof,
wherein the antibody comprises a heavy chain variable region (VH) having a CDR1 of positions 45-52 of SEQ ID NO: 17, a CDR2 of positions 70-77 of SEQ ID NO: 17, and a CDR3 of positions 116-126 of SEQ ID NO: 17, and a light chain variable region (VL) having a CDR1 of positions 47-58 of SEQ ID NO: 24, a CDR2 of positions 76-78 of SEQ ID NO: 24, and a CDR3 of positions 115-123 of SEQ ID NO: 24.

2. The method of claim 1 , wherein the antibody has a heavy chain variable region comprising an amino acid sequence represented by SEQ ID NO: 32.

3. The method of claim 1 , wherein the antibody has a light chain variable region comprising an amino acid sequence represented by SEQ ID NO: 39.

4. The method of claim 1 , wherein the antibody has a heavy chain variable region comprising an amino acid sequence represented by SEQ ID NO: 32 and a light chain variable region comprising an amino acid sequence represented by SEQ ID NO: 39.

5. The method of claim 4 , wherein the agent stabilizing or increasing expression of CLDN18.2 comprises capecitabine and oxaliplatin.

6. The method of claim 5 , wherein the antibody is a chimeric antibody comprising a human kappa light chain constant region and a human IgG1 heavy chain constant region.

7. The method of claim 6 , wherein the human kappa light chain constant region is allotype Km(3) and/or the human IgG1 heavy chain constant region is allotype G1m(3).

8. The method of claim 6 , wherein the human kappa light chain constant region comprises an amino acid sequence represented by SEQ ID NO: 12 and the human IgG1 heavy chain constant region comprises an amino acid sequence represented by SEQ ID NO: 13.

9. The method of claim 5 , wherein the cancer disease is selected from the group consisting of gastric cancer and cancer of the eso-gastric junction.

10. The method of claim 4 , wherein the cancer disease is selected from the group consisting of cancer of the esophagus, gastric cancer, cancer of the eso-gastric junction, and gastroesophageal cancer.

11. The method of claim 10 , wherein the agent stabilizing or increasing expression of CLDN18.2 comprises folinic acid, 5-fluorouracil, and oxaliplatin.

12. The method of claim 11 , wherein the antibody is a chimeric antibody comprising a human kappa light chain constant region and a human IgG1 heavy chain constant region.

13. The method of claim 12 , wherein the human kappa light chain constant region is allotype Km(3) and/or the human IgG1 heavy chain constant region is allotype G1m(3).

14. The method of claim 12 , wherein the human kappa light chain constant region comprises an amino acid sequence represented by SEQ ID NO: 12 and the human IgG1 heavy chain constant region comprises an amino acid sequence represented by SEQ ID NO: 13.

15. The method of claim 10 , wherein the agent stabilizing or increasing expression of CLDN18.2 comprises epirubicin, oxaliplatin and 5-fluorouracil.

16. The method of claim 15 , wherein the antibody is a chimeric antibody comprising a human kappa light chain constant region and a human IgG1 heavy chain constant region.

17. The method of claim 16 , wherein the human kappa light chain constant region is allotype Km(3) and/or the human IgG1 heavy chain constant region is allotype G1m(3).

18. The method of claim 16 , wherein the human kappa light chain constant region comprises an amino acid sequence represented by SEQ ID NO: 12 and the human IgG1 heavy chain constant region comprises an amino acid sequence represented by SEQ ID NO: 13.

Assignees

• Ganymed Pharmaceuticals Ag
• Tron—Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ Mainz Gemeinnutzige Gmb
• Astellas Pharma Inc
• Tron—Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ At Mainz Gemeinnutzige

Inventors

• Sahin Ugur
• Tureci Ozlem
• Mitnacht-Kraus Rita
• Jacobs Stefan Denis
• Utsch Magdalena Jadwiga
• Heinz Cornelia Adriana Maria
• Stadler Christiane Regina

Classifications

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title