Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis

• US 8,679,485 B2
• Filed: 08/01/2008
• Issued: 03/25/2014
• Est. Priority Date: 08/02/2007
• Status: Active Grant

• Current Assignee: Gilead Biologics, Inc. (Gilead Sciences Inc.)
• Original Assignee: Gilead Biologics, Inc. (Gilead Sciences Inc.)
• Inventors: Smith, Victoria, Ogg, Scott, Van Vlasselaer, Peter, Barry, Vivian E., Marshall, Derek, Holzer, Alison Kay, Rodriguez, Hector, Oyasu, Miho, McCauley, Scott Alan, Garcia, Carlos Aurelio, Biermann, Donna Hiroko Tokuoka
• Primary Examiner(s): Sang, Hong
• Application Number:
  US12/185,054
• Publication Number:
  US 20090104201A1
• Time in Patent Office: 2,062 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• 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: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 16/40 : against enzymes
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/30 : characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C12Q 1/6886 : for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: G01N 2333/90633 : with oxygen as acceptor (1.4.3) in general
• CPC Class Codes: G01N 33/57423 : of lung
• CPC Class Codes: G01N 33/57438 : of liver, pancreas or kidney
• 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 methodology and compositions for preventing and treating various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, by using an inhibitor of processed forms of lysyl oxidase or lysyl oxidase-like proteins, an inhibitor of LOX or LOXL, or a synergistic combination thereof combined with other therapeutic agents. Methods and compositions for diagnosing or monitoring various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, are also provided. Also provided herein are methods and related compositions, medical devices, systems and kits for preventing or treating various diseases and conditions associated with fibrosis with compositions comprising inhibitors of LOX or LOXL.

Claims

1. A method of treating cancer, comprising:

administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to SEQ ID NO;

3, 7, 11, or 16.

2. The method of claim 1, wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.

3. The method of claim 1, wherein the antibody or fragment thereof is humanized or human.

4. The method of claim 1, further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.

5. The method of claim 1, wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.

6. The method of claim 1, wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.

7. The method of claim 1, wherein the cancer is a pancreatic cancer.

8. The method of claim 1, wherein the cancer is liver cancer.

9. The method of claim 1, wherein the cancer is lung cancer.

10. The method of claim 1, wherein the antibody or fragment thereof specifically binds to SEQ ID NO:

3.

11. The method of claim 1, wherein the antibody or fragment thereof specifically binds to SEQ ID NO:

7.

12. The method of claim 1, wherein the antibody or fragment thereof specifically binds to SEQ ID NO:

11.

13. The method of claim 1, wherein the antibody or fragment thereof specifically binds to SEQ ID NO:

16.

14. A method of treating cancer, comprising:

administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to a peptide consisting of SEQ ID NO;

3, SEQ ID NO;

7, SEQ ID NO;

11, or SEQ ID NO;

16.

15. The method of claim 14, wherein the peptide consists of SEQ ID NO:

3.

16. The method of claim 14, wherein the peptide consists of SEQ ID NO:

7.

17. The method of claim 14, wherein the peptide consists of SEQ ID NO:

11.

18. The method of claim 14, wherein the peptide consists of SEQ ID NO:

16.

19. The method of claim 14, wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.

20. The method of claim 14, wherein the antibody or fragment thereof is humanized or human.

21. The method of claim 14, further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.

22. The method of claim 14, wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.

23. The method of claim 14, wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.

24. The method of claim 14 wherein the cancer is a pancreatic cancer.

25. The method of claim 14, wherein the cancer is liver cancer.

26. The method of claim 14, wherein the cancer is lung cancer.

27. A method of treating cancer, comprising:

administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to SEQ ID NO;

5.

28. The method of claim 27, wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.

29. The method of claim 27, wherein the antibody or fragment thereof is humanized or human.

30. The method of claim 27, further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.

31. The method of claim 27, wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.

32. The method of claim 27, wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.

33. The method of claim 27, wherein the cancer is a pancreatic cancer.

34. The method of claim 27, wherein the cancer is liver cancer.

35. The method of claim 27, wherein the cancer is lung cancer.

36. A method of treating cancer, comprising:

administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to a peptide consisting of SEQ ID NO;

5.

37. The method of claim 36, wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.

38. The method of claim 36, wherein the antibody or fragment thereof is humanized or human.

39. The method of claim 36, further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.

40. The method of claim 36, wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.

41. The method of claim 36, wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.

42. The method of claim 36, wherein the cancer is a pancreatic cancer.

43. The method of claim 36, wherein the cancer is liver cancer.

44. The method of claim 36, wherein the cancer is lung cancer.