Antibodies that bind to lysyl oxidase-like 2 (LOXL2)

• US 8,680,246 B2
• Filed: 02/04/2011
• Issued: 03/25/2014
• Est. Priority Date: 02/04/2010
• Status: Active Grant

• Current Assignee: Gilead Biologics, Inc. (Gilead Sciences Inc.)
• Original Assignee: Gilead Biologics, Inc. (Gilead Sciences Inc.)
• Inventors: McCauley, Scott Alan, Rodriguez, Hector, Garcia, Carlos Aurelio, Smith, Victoria
• Primary Examiner(s): WEN, SHARON X
• Application Number:
  US13/021,555
• Publication Number:
  US 20110200606A1
• Time in Patent Office: 1,145 Days
• Field of Search: None
• US Class Current: 530/388.26
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2800/00 Detection or diagnosis of diseases
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

The present disclosure provides lysyl oxidase-like-2 (LOXL2) polypeptide binding agents, including, for example, antibodies that specifically bind a LOXL2 polypeptide; and further provides compositions comprising same. The binding agents can be used in various treatment and diagnostic methods, which are also provided.

Claims

1. An isolated monoclonal antibody to lysyl oxidase-like-2 (LOXL2) that specifically binds to an epitope within amino acids 325 through 434 of the sequence set forth in SEQ ID NO:

1, wherein the antibody does not compete for binding with antibody AB0023 or AB0024.

2. The antibody of claim 1, wherein the epitope comprises amino acids within the sequence TPAMGLQKK (SEQ ID NO:

2).

3. The isolated antibody of claim 1, wherein the antibody inhibits enzymatic activity of a LOXL2 polypeptide.

4. The isolated antibody of claim 1, wherein the antibody does not inhibit enzymatic activity of a LOXL2 polypeptide.

5. The isolated antibody of claim 1, wherein the antibody binds the epitope with an affinity of from about 10⁷ M⁻

1 to about 10¹² M<sup>−

1</sup>.

6. The isolated antibody of claim 1, wherein the antibody comprises a heavy chain, and wherein the heavy chain of the antibody is of the isotype IgG1, IgG2, IgG3, or IgG4.

7. The isolated antibody of claim 1, wherein the antibody is detectably labeled.

8. The isolated antibody of claim 1, wherein the antibody is a Fv, scFv, Fab, F(ab′

)2, or Fab′

.

9. The isolated antibody of claim 1, wherein the antibody is humanized.

10. The isolated antibody of claim 1, wherein the antibody is chimeric.

11. The isolated antibody of claim 1, wherein the antibody comprises a covalently linked moiety selected from the group consisting of a non-peptide synthetic polymer, a lipid, a fatty acid, a polysaccharide, a carbohydrate, or a contrast agent.

12. The isolated antibody of claim 11, wherein the synthetic polymer is poly(ethylene glycol) polymer.

13. The isolated antibody of claim 1, wherein the antibody is immobilized on a solid support.

14. The isolated antibody of claim 1, wherein the antibody comprises a cancer chemotherapeutic agent covalently or non-covalently linked to the antibody.

15. A kit for treating a condition associated with LOXL2 comprising a composition comprising an isolated antibody of claim 1 and a pharmaceutically acceptable carrier or excipient.

16. The kit of claim 15, wherein said condition associated with LOXL2 is a tumor, a metastasis, angiogenesis, or fibrosis.

17. The kit of claim 15, wherein the antibody comprises a detectable label, a therapeutic agent or both.

18. An isolated monoclonal antibody to lysyl oxidase-like-2 (LOXL2) that specifically binds to a peptide consisting of amino acids 325 through 434 of the sequence set forth in SEQ ID NO:

1, wherein the antibody does not compete for binding with antibody AB0023 or AB0024.

19. The antibody of claim 18, wherein the antibody specifically binds to an epitope comprising the sequence TPAMGLQKK (SEQ ID NO:

2).

20. The isolated antibody of claim 18, wherein the antibody inhibits enzymatic activity of a LOXL2 polypeptide.

21. The isolated antibody of claim 18, wherein the antibody does not inhibit enzymatic activity of a LOXL2 polypeptide.

22. The isolated antibody of claim 18, wherein the antibody binds the epitope with an affinity of from about 10⁷ M⁻

1 to about 10¹² M<sup>−

1</sup>.

23. The isolated antibody of claim 18, wherein the antibody comprises a heavy chain, and wherein the heavy chain of the antibody is of the isotype IgG1, IgG2, IgG3, or IgG4.

24. The isolated antibody of claim 18, wherein the antibody is detectably labeled.

25. The isolated antibody of claim 18, wherein the antibody is a Fv, scFv, Fab, F(ab′

)2, or Fab′

.

26. The isolated antibody of claim 18, wherein the antibody is humanized.

27. The isolated antibody of claim 18, wherein the antibody is chimeric.