Diagnosis and therapy of cancer involving cancer stem cells

Patent metadata

Field	Value
Publication number	US-11795218-B2
Application number	US-202016795468-A
Country	US
Kind code	B2
Filing date	Feb 19, 2020
Priority date	Jul 31, 2013
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

The present invention provides methods for diagnosis or treatment of cancer diseases involving cancer stem cells comprising targeting CLDN6. In particular, the present invention provides a method of determining cancer stem cells comprising detecting cells expressing CLDN6. Furthermore, the present invention provides a method of treating or preventing cancer comprising inhibiting and/or eliminating cancer stem cells by administering an antibody having the ability of binding to CLDN6 to a cancer patient.

First claim

The invention claimed is:

1. A method for treating a cancer patient having a cancer characterized by cancer cells expressing CLDN6 on the cell surface, said method comprising:
administering to the patient (i) an anti-CLDN6 antibody and (ii) an agent of chemotherapy, wherein the antibody comprises (a) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 5 or a variant thereof wherein said variant comprises complementarity determining regions CDR1, CDR2, and CDR3 that are identical to complementarity determining regions of SEQ ID NO: 5 and said variant of SEQ ID NO: 5 has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 5 and (b) a light chain variable region (VL) comprising (b1) the amino acid sequence of SEQ ID NO: 4 or a variant thereof wherein said variant comprises complementarity determining regions CDR1, CDR2, and CDR3 that are identical to complementarity determining regions of SEQ ID NO: 4 and said variant of SEQ ID NO: 4 has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 4 or (b2) the amino acid sequence of SEQ ID NO: 12 or a variant thereof wherein said variant comprises complementarity determining regions CDR1, CDR2, and CDR3 that are identical to complementarity determining regions of SEQ ID NO: 12 and said variant of SEQ ID NO: 12 has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 12, and
wherein the agent of chemotherapy comprises a multi-chemotherapy comprising cisplatin, etoposide and bleomycin (PEB).

2. The method of claim 1 , wherein the cancer involves cancer stem cells expressing CLDN6.

3. The method of claim 1 , wherein administering the antibody results in inhibition or elimination of cancer stem cells expressing CLDN6.

4. The method of claim 1 , wherein administering the antibody having the ability of binding to CLDN6 enhances the anti-cancer effect of chemotherapy.

5. The method of claim 3 , wherein elimination of cancer stem cells results in curing of cancer.

6. The method of claim 2 , wherein the cancer stem cells are at a tumor site of the cancer patient.

7. The method of claim 1 , wherein the cancer is resistant to chemotherapy.

8. The method of claim 1 , wherein the antibody exerts its inhibitory and/or cytotoxic effect on the cancer cells by mediating one or more of complement dependent cytotoxicity (CDC) mediated lysis, antibody dependent cellular cytotoxicity (ADCC) mediated lysis, induction of apoptosis and inhibition of proliferation.

9. The method of claim 1 , wherein the antibody is coupled to a therapeutic moiety.

10. The method of claim 9 , wherein the therapeutic moiety is a cytotoxic agent, a chemotherapeutic agent or a radionuclide.

11. The method of claim 1 , wherein CLDN6 has the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

12. The method of claim 1 , wherein the cancer comprises primary cancer, advanced cancer, metastatic cancer, recurrent cancer or a combination thereof.

13. The method of claim 1 , wherein the antibody is an unconjugated antibody.

14. The method of claim 1 , wherein the cancer includes a germ cell tumor.

15. The method of claim 14 , wherein the germ cell tumor is a testicular germ cell tumor or metastatic form thereof.

16. The method of claim 1 , wherein the cancer is resistant to chemotherapy administered as monotherapy.

17. The method of claim 1 , wherein the cancer is testicular seminoma, testicular teratoma, or testicular embryonal carcinoma.

18. The method of claim 1 , wherein the heavy chain variable region (VH) comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 5 and the light chain variable region (VL) comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 12.

19. The method of claim 1 , wherein the antibody is a bispecific antibody.

20. The method of claim 1 , wherein the heavy chain variable region (VH) comprises said variant of SEQ ID NO: 5 and the light chain variable region (VL) comprises said variant of SEQ ID NO: 12.

21. The method of claim 20 , wherein the heavy chain variable region (VH) comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 5.

22. The method of claim 20 , wherein the light chain variable region (VL) comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 12.

Assignees

• Biontech Ag
• Ganymed Pharmaceuticals Gmbh
• Tron—Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ Mainz
• Astellas Pharma Inc
• Tron—Translationale Onkologie An Der Univ

Inventors

• Sahin Ugur
• Tureci Ozlem
• Walter Korden
• Wagner Meike
• Kreuzberg Maria
• Hacker Sabine
• Jacobs Stefan

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/5758 Primary

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/28 Primary

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

• A61K31/337 Primary

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