Monoclonal antibodies against claudin-18 for treatment of cancer

Patent metadata

Field	Value
Publication number	US-9751934-B2
Application number	US-201514661882-A
Country	US
Kind code	B2
Filing date	Mar 18, 2015
Priority date	Nov 24, 2005
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

Abstract

The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLD18, including tumor-related 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.

First claim

The invention claimed is:

1. An antibody that specifically binds CLD18A2, comprising:
a heavy chain variable region (V H ) having
a V H CDR1 of positions 45-52 of SEQ ID NO: 118,
a V H CDR2 of positions 70-77 of SEQ ID NO: 118, and
a V H CDR3 of positions 116-126 of SEQ ID NO: 118; and

a light chain variable region (V L ) having
a V L CDR1 of positions 47-58 of SEQ ID NO: 125,
a V L CDR2 of positions 76-78 of SEQ ID NO: 125, and
a V L CDR3 of positions 115-123 of SEQ ID NO: 125.

2. The antibody of claim 1 , wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, a secretory IgA, an IgD, and an IgE antibody.

3. The antibody of claim 1 , wherein the antibody is a chimeric antibody.

4. The antibody of claim 1 , wherein the antibody comprises a human IgG1 constant region.

5. The antibody of claim 1 , wherein the V H comprises an amino acid sequence represented by SEQ ID NO: 135.

6. The antibody of claim 1 , wherein the V L comprises an amino acid sequence represented by SEQ ID NO: 142.

7. The antibody of claim 1 , wherein the V H comprises an amino acid sequence represented by SEQ ID NO: 135 and the V L comprises an amino acid sequence represented by SEQ ID NO: 142.

8. The antibody of claim 7 , wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, a secretory IgA, an IgD, and an IgE antibody.

9. The antibody of claim 7 , wherein the antibody is a chimeric antibody.

10. The antibody of claim 7 , wherein the antibody comprises a human IgG1 constant region.

11. An antibody that specifically binds CLD18A2, comprising:
a heavy chain of SEQ ID NO: 118 and a light chain of SEQ ID NO: 125.

12. A method of treating a tumor-related disease selected from the group consisting of gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder, comprising:
administering to a subject the antibody of claim 1 .

13. The method of claim 12 , wherein the tumor-related disease is gastric cancer.

14. The method of claim 12 , wherein the tumor-related disease is pancreatic cancer.

15. The method of claim 12 , wherein the V H comprises an amino acid sequence represented by SEQ ID NO: 135 and the V L comprises an amino acid sequence represented by SEQ ID NO: 142.

16. The method of claim 12 , wherein the antibody comprises a heavy chain of SEQ ID NO: 118 and a light chain of SEQ ID NO: 125.

17. The method of claim 16 , further comprising administering to the subject a chemotherapeutic agent.

18. The method of claim 17 , wherein the chemotherapeutic agent is selected from the group consisting of doxorubicin, cisplatin, taxotere, 5-fluoruracil, methotrexate, gemcitabine and cyclophosphamide.

19. The method of claim 16 , wherein the tumor-related disease is gastric cancer.

20. The method of claim 16 , wherein the tumor-related disease is pancreatic cancer.

Assignees

• Ganymed Pharmaceuticals Ag
• Johannes Gutenberg-Universitat Mainz

Inventors

• Sahin Ugur
• Türeci Özlem
• Usener Dirk
• Fritz Stefan
• Uherek Christoph
• Brandenburg Gunda
• Geppert Harald-Gerhard
• Schröder Anja Kristina
• Thiel Phillippe

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07K16/3046

  Stomach, Intestines · CPC title

• A61K47/6807

  the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense · CPC title