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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20090053224
- Publication Date: February 26, 2009
- Appl. No: 12/185050
- Application Filed: August 01, 2008
- Assignees: ARRESTO BIOSCIENCES (Palo Alto, CA, US)
- Claim: 1. An isolated antibody or antigen binding fragment thereof, that specifically binds to an epitope having an amino acid sequence set forth as SEQ ID NO: 6.
- Claim: 2. The antibody or antigen binding fragment thereof, of claim 1, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 1 and a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 2.
- Claim: 3. An isolated antibody or antigen binding fragment thereof, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 1, and a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 2.
- Claim: 4. An antibody or antigen binding fragment thereof, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 1.
- Claim: 5. An isolated antibody or antigen binding fragment thereof, comprising a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 2.
- Claim: 6. An isolated antibody or antigen binding fragment thereof, that competes with, or specifically binds to, an antibody or antigen binding fragment thereof of any one of claims 1-5 for binding to LOXL2.
- Claim: 7. The antibody of any of the preceding claims that specifically binds to LOXL2 with a binding affinity of at least 2, 5, 10, 50, 100, 500 or 1000 times greater than to at least one of LOX, LOXL1, LOXL3 or LOXL4.
- Claim: 8. A humanized antibody or antigen binding fragment thereof, that specifically binds to an epitope having an amino acid sequence set forth as SEQ ID NO: 6.
- Claim: 9. The humanized antibody or antigen binding fragment thereof, of claim 8, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 25, 26, 27 or 28 and a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 30,31 or 32.
- Claim: 10. A humanized isolated antibody or antigen binding fragment thereof, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: SEQ ID NO: 25, 26, 27or 28, and a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 30, 31 or 32.
- Claim: 11. A humanized antibody or antigen binding fragment thereof, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 25, 26, 27 or 28.
- Claim: 12. A humanized antibody or antigen binding fragment thereof, comprising a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 30, 31 or 32.
- Claim: 13. A humanized antibody or antigen binding fragment thereof, that competes with, or specifically binds to, an antibody or antigen binding fragment thereof of any one of claims 8-12 for binding to LOXL2.
- Claim: 14. An isolated antibody or antigen binding fragment thereof, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 3 and a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 4 or 5.
- Claim: 15. An isolated antibody or antigen binding fragment thereof, comprising a variable heavy chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ED NO: 3.
- Claim: 16. An isolated antibody or antigen binding fragment thereof, comprising a variable light chain having at least 75% amino acid sequence identity to an amino acid sequence set forth as SEQ ID NO: 4 or 5.
- Claim: 17. An isolated antibody or antigen binding fragment thereof, that competes with, or specifically binds to, an antibody or antigen binding fragment thereof of any one of claims 14-16 for binding to LOX.
- Claim: 18. The antibody of any one of claims 14-17 that specifically binds to LOX with a binding affinity of at least 2, 5, 10, 50, 100, 500 or 1000 times greater than to at least one of LOXL1, LOXL2, LOXL3 or LOXL4.
- Claim: 19. An isolated antibody or antigen binding fragment thereof of any one of claims 1-18 that is labeled with a detectable label, a therapeutic label or both.
- Claim: 20. An antibody or antigen binding fragment thereof of any of the preceding claims that is a variable heavy chain, a variable light chain, a Fv, a scFv, a Fab, a F(ab′)2, a genetically engineered antibody, a monoclonal antibody, or a humanized antibody.
- Claim: 21. A kit for treating a condition associated with LOX or LOXL2 comprising a composition of an antibody or antigen binding fragment thereof of any one of the preceding claims and a pharmaceutically acceptable carrier or excipient.
- Claim: 22. The kit of claim 21, wherein said condition associated with LOX or LOXL2 is a tumor, a metastasis, angiogenesis, or fibrosis.
- Claim: 23. The kit of claim 21, further comprising a detectable label, a therapeutic label or both.
- Claim: 24. The kit of claim 23, further comprising written instructions describing how to conjugate the antibody or antigen binding fragment thereof with the detectable label, a therapeutic label or both.
- Claim: 25. The kit of claim 21, further comprising written instructions describing how to administer the antibody or antigen binding fragment thereof.
- Claim: 26. The kit of claim 21, wherein said composition is free of pyrogens.
- Claim: 27. The kit of claim 21, wherein said composition is lyophilized.
- Claim: 28. A method of diagnosing a condition associated with LOX or LOXL2 comprising assessing a level of LOX and/or LOXL2 in a sample of a subject by contacting said sample with an antibody or antigen binding fragment thereof of any of the preceding claims, wherein a change in level of LOX and/or LOXL2 in the sample in comparison with a reference sample indicates the presence or increase of a tumor or metastasis.
- Claim: 29. The method of claim 28, wherein said condition associated with LOX or LOXL2 is a tumor, a metastasis, angiogenesis, or fibrosis.
- Claim: 30. The method of claim 28 or 29, wherein an increase in LOX and/or LOXL2 levels in the sample in comparison with a reference sample indicates the presence of a tumor or metastasis or an or increase in tumor or metastatic growth.
- Claim: 31. The method of any one of claims 28-30, wherein the reference sample is a sample taken from the subject at an earlier time point or a sample from another individual.
- Claim: 32. The method of claim 28, wherein the level of LOX and/or LOXL2 levels in the sample are detected by contacting the sample with an antibody or antigen binding fragment thereof of any one of claims 1-14.
- Claim: 33. The method of claim 32 wherein said antibody or antigen binding fragment thereof is detectably labeled.
- Claim: 34. A method of inhibiting LOXL2 by contacting a sample or a cellular tissue with an antibody or antigen binding fragment thereof, of any one of claims 1-13.
- Claim: 35. The method of claim 34, wherein binding of said antibody or antigen binding fragment thereof to LOXL2 inhibits enzymatic activity of LOXL2.
- Claim: 36. A method of inhibiting LOX by contacting a sample or cellular tissue with an antibody or antigen binding fragment thereof, of any one of claims 14-20.
- Claim: 37. The method of claim 36, wherein binding of said antibody or antigen binding fragment thereof to LOX inhibits enzymatic activity of LOX.
- Claim: 38. The method of any one of claims 34-37, wherein contacting occurs in vitro, in vivo or ex vivo.
- Claim: 39. The method of any one of claims 34-37, wherein inhibiting LOX or LOXL2 reduces tumor growth in a subject.
- Claim: 40. The method of any one of claims 34-37, wherein inhibiting LOX or LOXL2 reduces angiogenesis in a subject.
- Claim: 41. The method of any one of claims 34-37, wherein inhibiting LOX or LOXL2 reduces fibrosis in a subject.
- Claim: 42. A method of reducing growth of a tumor in a subject, comprising administering an antibody or antigen binding fragment thereof, of any one of claims 1-20.
- Claim: 43. The method of claim 42, wherein said tumor is a primary tumor or a metastatic tumor.
- Claim: 44. The method of claim 42 or 43, wherein said tumor is selected from among lung cancer (including lung adenocarcinoma, squamous cell carcinoma, large cell carcinoma, bronchioloalveolar carcinoma, non-small-cell carcinoma, small cell carcinoma, mesothelioma); breast cancer (including ductal carcinoma, lobular carcinoma, inflammatory breast cancer, clear cell carcinoma, mucinous carcinoma,); colorectal cancer (colon cancer, rectal cancer); anal cancer; pancreatic cancer (including pancreatic adenocarcinoma, islet cell carcinoma, neuroendocrine tumors); prostate cancer; ovarian carcinoma (ovarian epithelial carcinoma or surface epithelial-stromal tumour including serous tumour, endometrioid tumor and mucinous cystadenocarcinoma, sex-cord-stromal tumor); liver and bile duct carcinoma (including hepatocelluar carcinoma, cholangiocarcinoma, hemangioma); esophageal carcinoma (including esophageal adenocarcinoma and squamous cell carcinoma); bladder carcinoma; carcinoma of the uterus (including endometrial adenocarcinoma, uterine papillary serous carcinoma, uterine clear-cell carcinoma, uterine sarcomas and leiomyosarcomas, mixed mullerian tumors), glioma, glioblastoma, medullablastoma, and other tumors of the brain; kidney cancers (including renal cell carcinoma, clear cell carcinoma, Wilm's tumor); cancer of the head and neck (including squamous cell carcinomas); cancer of the stomach (stomach adenocarcinoma, gastrointestinal stromal tumor); multiple myeloma; testicular cancer; germ cell tumor; neuroendocrine tumor; cervical cancer; carcinoids of the gastrointestinal tract, breast, and other organs; signet ring cell carcinoma; mesenchymal tumors including sarcomas, fibrosarcomas, haemangioma, angiomatosis, haemangiopericytoma, pseudoangiomatous stromal hyperplasia, myofibroblastoma, fibromatosis, inflammatory myofibroblastic tumour, lipoma, angioiipoma, granular cell tumour, neurofibroma, schwannoma, angiosarcoma, liposarcoma, rhabdomyosarcoma, osteosarcoma, leiomyoma, leiomysarcoma and non-Hodgkin's lymphoma.
- Claim: 45. The method of any one of claims 42-44, wherein the tumor in the subject is reduced by at least 10%, 25%, 50%, 70%, 90%, 95%, or more as compared to the tumor in the subject prior to treatment.
- Claim: 46. The method of any one of claims 42-45, where in the survival of a subject with a tumor is increased by at least 10 days, 1 month, 3 months, 6 months, 1 year, 2 years, 5 years, 10 years, or more compared to a subject that is not administered the antibody or antigen binding fragment thereof.
- Claim: 47. The method of any one of claims 42-46, wherein metastatic tumor burden of a subject is stabilized.
- Claim: 48. The method of claim 47, wherein the metastatic tumor burden is stabilized for at least 10 days, 1 month, 3 months, 6 months, 1 year, 2 years, 5 years, 10 years or more.
- Claim: 49. The method of claim 42, wherein the antibody or antigen-binding fragment thereof specifically binds to a secreted or mature form of hLOX but not to a preproprotein of hLOX having an amino acid sequence of SEQ ID NO: 7.
- Claim: 50. The method of claim 49, wherein the secreted form of hLOX has an amino acid sequence of SEQ ID NO: 8, 62 or 63.
- Claim: 51. The method of claim 49, wherein the mature form of hLOX has an amino acid sequence of SEQ ID NO: 9.
- Claim: 52. A method of inhibiting angiogenesis in a subject by an antibody or antigen binding fragment thereof, of any one of claims 1-20.
- Claim: 53. A method of inhibiting a fibrotic disease in a subject by administering an antibody or antigen binding fragment thereof, of any one of claims 1-20.
- Claim: 54. The method of claim 48, wherein said fibrotic disease is a liver fibrosis, a lung fibrosis, a kidney fibrosis, a cardiac fibrosis or schleroderma.
- Claim: 55. The method of claim 54, wherein said kidney fibrosis is diabetic nephropathy, glomerulosclerosis, diabetic nephropathy, vesicoureteral reflux, tubulointerstitial renal fibrosis or glomerulonephritis.
- Claim: 56. A method of decreasing extracellular matrix formation by contacting a sample or cellular tissue with an antibody or antigen binding fragment thereof, of any one of claims 1-20.
- Claim: 57. The method of any one of claims 34-56 wherein administration or contacting is by parenteral administration.
- Claim: 58. A method of monitoring a subject's response to administration of an antibody or antigen binding fragment thereof, of any one of claims 42-56 by detecting by detecting LOX and/or LOXL levels and/or activity.
- Claim: 59. The method of any one of claims 42-57, wherein said antibody or antigen binding fragment thereof, is labeled with a therapeutic label.
- Claim: 60. The method of any one of claims 42-59, further comprising co-administering a second therapeutic agent.
- Claim: 61. The method of claim 60, wherein said second therapeutic agent is an antibody or a chemotherapeutic agent.
- Claim: 62. Use of an antibody or antigen binding fragment thereof, of any one of claims 1-20, in the preparation of a formulation for inhibiting LOXL2 or LOX, reducing tumor growth, inhibiting angiogenesis, inhibiting a fibrotic disease of decreasing extracellular matrix formation in a subject.
- Claim: 63. Use of claim 62, wherein said antibody or antigen binding fragment thereof is labeled with a therapeutic label and, optionally, a diagnostic label.
- Claim: 64. Use of an antibody or antigen binding fragment thereof, of any one of claims 1-20, in the preparation of a formulation for diagnosing a tumor or metastasis comprising assessing LOX and/or LOXL2 levels in a sample of a patient, wherein a change in LOX and/or LOXL2 levels in the sample in comparison with a reference sample indicates the presence of a rumor or metastasis or an increase in tumor or metastatic growth.
- Claim: 65. Use of claim 64, wherein said antibody or antigen binding fragment thereof is labeled with a diagnostic label.
- Current U.S. Class: 4241/351
- Current International Class: 61; 07; 01; 12; 12; 61; 61
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