Methods of using an antibody to inhibit WNT-mediated signaling in cancer

Patent metadata

Field	Value
Publication number	US-9175090-B2
Application number	US-201414446073-A
Country	US
Kind code	B2
Filing date	Jul 29, 2014
Priority date	Apr 28, 2011
Publication date	Nov 3, 2015
Grant date	Nov 3, 2015

Abstract

The present invention is directed to monoclonal antibodies and fragments thereof directed to LRP5/6 that find use in the prevention and treatment of cardiac remodeling and cancer. Also disclosed are methods for using such monoclonal antibodies in the prevention and treatment of such diseases.

First claim

What is claimed is:

1. A method of inhibiting Wnt signaling in a cancer cell with a defect in Adenomatous polyposis coli tumor suppressor (APC) expression or activity comprising contacting said cancer cell with an antibody that binds to low density lipoprotein receptor-related protein 5 and/or 6 (LRP5/6) and has heavy chain complementarity determining regions from SEQ ID NO: 2 and light chain complementarity determining regions from SEQ ID NO: 4.

2. The method of claim 1 , wherein the antibody is a monoclonal antibody.

3. The method of claim 2 , wherein the monoclonal antibody is a humanized antibody.

4. The method of claim 1 , wherein the cancer cell is a multi-drug resistant cell.

5. The method of claim 1 , wherein the cancer cell has a mutation in APC.

6. The method of claim 5 , wherein the cancer cell is a lung cancer cell or a colorectal cancer cell.

7. The method of claim 1 , wherein the antibody has a heavy chain sequence of SEQ ID NO: 2 and a light chain sequence of SEQ ID NO:4.

8. The method of claim 1 , wherein said antibody is contacted more than once.

9. The method of claim 1 , wherein said cancer cell is located in an animal subject.

10. The method of claim 9 , wherein said antibody is administered to said subject by intravenous, intraarterial, or intratumoral administration.

11. The method of claim 9 , wherein the subject suffers from recurrent cancer.

12. The method of claim 9 , wherein the subject suffers from metastatic cancer.

13. The method of claim 9 , wherein the subject suffers from sarcoma, colorectal cancer, gastric cancer, breast cancer, liver cancer, lymphoma, cervical cancer, uterine cancer, prostate cancer, lung cancer or melanoma.

14. The method of claim 9 , further comprising administering to said subject a second anti-cancer therapy.

15. The method of claim 14 , wherein the second anti-cancer therapy is a chemotherapeutic, a radiotherapeutic, hormone therapy, toxin therapy, or immunotherapy.

16. The method of claim 14 , wherein the second anti-cancer therapy is administered at the same time as said antibody.

17. The method of claim 14 , wherein the second anti-cancer therapy is administered before and/or after the antibody.

18. The method of claim 9 , wherein said method achieves one or more therapeutic endpoints selected from the group consisting of increased life span, improved stamina, improved quality of life, reduced hospital stay duration and frequency.

Assignees

• Univ Vanderbilt

Inventors

• Lee Ethan
• Young Pampee P
• Eid Josiane
• Carnahan Robert
• Thorne Curtis
• Meyers Kelly

Classifications

• A61P9/06

  Antiarrhythmics · CPC title

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• C07K16/30 Primary

  from tumour cells · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title