Antibodies targeted against LOXL-2 for the treatment of collagen-associated pathologies

Patent metadata

Field	Value
Publication number	US-10040868-B2
Application number	US-201415328036-A
Country	US
Kind code	B2
Filing date	Jul 24, 2014
Priority date	Jul 24, 2014
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

An article of manufacture is disclosed which comprises at least two active agents, wherein a first of the two active agents comprises an anti-cancer agent or an antifibrotic agent and a second of the at least two active agents downregulates the activity and/or expression of lysyl-oxidase like protein-2 (LOXL-2) and which is capable of altering the structure of the extracellular matrix.

First claim

What is claimed is:

1. A method of treating a disease associated with aberrant collagen deposition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antibody which comprises an antigen recognition region which specifically binds to lysyl-oxidase like protein-2 (LOXL-2) and is capable of down-regulating crosslinking of type I collagen in vitro, and wherein said antigen recognition region of said antibody comprises CDR amino acid sequences as set forth in SEQ ID NOs: 3, 4, 5, 6, 7 and 8, thereby treating the disease.

2. The method of claim 1 , further comprising administering to the subject an agent selected from the group consisting of an anti-cancer agent and an antifibrotic agent, thereby treating the disease.

3. The method of claim 1 , wherein said disease is selected from the group consisting of cancer, pulmonary alveolar proteinosis (PAP) and a fibrotic disease.

4. The method of claim 3 , wherein said cancer is breast cancer or colon cancer.

5. The method of claim 4 , wherein said breast cancer is triple negative breast cancer.

6. The method of claim 1 , wherein said antibody specifically binds to the catalytic site of said LOXL-2.

7. The method of claim 1 , wherein said antibody does not bind to the fourth scavenger receptor-cysteine-rich (SRCR) domain of said LOXL-2.

8. The method of claim 1 , wherein the amino acid sequence of the V H of the antibody is as set forth in SEQ ID NO: 1.

9. The isolated antibody of claim 1 , wherein the amino acid sequence of the V L of the antibody is as set forth in SEQ ID NO: 2.

10. The method of claim 2 , wherein said anti-cancer agent is cisplatin or an antibody which binds specifically to Matrix metalloproteinase 9 (MMP-9).

11. A method of treating triple negative breast cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antibody which comprises an antigen recognition region which specifically binds to the catalytic site of lysyl-oxidase like protein-2 (LOXL-2), wherein said antigen recognition region of said antibody comprises CDR amino acid sequences as set forth in SEQ ID NOs: 3, 4, 5, 6, 7 and 8, thereby treating the triple negative breast cancer.

Assignees

• Yeda Res & Dev

Inventors

• Sagi Irit
• Grossman Moran
• Ben-Chetrit Nir

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title