Treatment of cancer with a novel anti-IL13 monoclonal antibody
The present invention relates to the treatment of IL13 dependent neoplastic disorders comprising the administration of novel anti-IL13 antibodies, The invention also includes diagnosing such tumors or cancer using the antibodies of the present invention to detect overexpression of IL13 in the patient.
1. A method of treating cancer in a patient, comprising administering to a patient in need thereof an effective amount of an anti-IL-13 antibody or an antigen binding fragment thereof that binds specifically to human IL-13, wherein said antibody or antigen binding fragment thereof competes with an antibody produced by hybridoma 228B/C-1 having ATCC Accession No. PTA-5657.
2. The method of claim 1 , wherein the anti-IL-13 antibody or antigen-binding fragment binds an epitope having the amino acid sequence ESLINVSG (SEQ ID NO:18) or YCAALESIANVS (SEQ ID NO:19).
3. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising a CDRL1 having the amino acid sequence of SEQ ID NO: 99, a CDRL2 having the amino acid sequence of SEQ ID NO:104; and a CDRL3 having the amino acid sequence of SEQ ID NO: 115.
4. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a heavy chain comprising a CDRH1 having the amino acid sequence of SEQ ID NO: 117, a CDRH2 having the amino acid sequence of SEQ ID NO: 123; and a CDRH3 having the amino acid sequence of SEQ ID NO: 135.
5. The method of claim 4 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising a CDRL1 having the amino acid sequence of SEQ ID NO: 99, a CDRL2 having the amino acid sequence of SEQ ID NO:104; and a CDRL3 having the amino acid sequence of SEQ ID NO: 115.
6. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising the amino acid sequence of SEQ ID NO: 3, 142, 144 or 150; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 4, 143, 145, 146, 147, 148 or 149.
7. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises the amino acid sequence of SEQ ID NO: 142 or 143.
8. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising the amino acid sequence of SEQ ID NO: 142, and a heavy chain comprising the amino acid sequence of SEQ ID NO: 143.
9. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a heavy chain comprising:
(a) a CDRH1 having the amino acid sequence SEQ ID NO: 117, 118, 119, 120, 121 or 122;
(b) a CDRH2 having the amino acid sequence SEQ ID NO: 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133 or 134; and
(c) a CDRH3 having the amino acid sequence SEQ ID NO: 135, 136, 137, 138, 139, 140 or 141.
10. The method of claim 1 or 2 wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising:
(a) a CDRL1 having the amino acid sequence SEQ ID NO: 99, 100, 101, 102 or 103;
(b) a CDRL2 having the amino acid sequence SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, or 114; and
(c) a CDRL3 having the amino acid sequence of SEQ ID NO: 115 or 116.
11. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment is a monoclonal antibody.
12. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment is an IgG antibody or a fragment thereof.
13. The method of claim 12 , wherein the anti-IL-13 antibody or antigen-binding fragment is an IgG1, an IgG2, an IgG3 or an IgG4 antibody or a fragment thereof.
14. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment is a human antibody, a chimeric antibody or a humanized antibody or a fragment thereof.
15. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen-binding fragment is a single chain antibody.
16. The method of claim 1 or 2 , wherein the anti-IL-13 antibody mediates tumor cell killing by antibody dependent cell-mediated cytotoxicity and/or complement mediated cytotoxicity.
17. The method of claim 1 or 2 , wherein the anti-IL-13 antibody or antigen binding fragment is administered by inhalation, bolus injection, or infusion.
18. The method of claim 1 or 2 , wherein said cancer is Hodgkin's disease, skin cancer, stomach cancer, colon cancer, breast cancer, pancreatic cancer, liver cancer, prostate cancer, lung cancer, head-and-neck cancer, renal cell cancer, squamous cell carcinoma, AIDS-associated Kaposi's carcinoma or brain cancer.
19. The method of claim 1 or 2 , wherein the anti-IL-13 antibody is associated with a cytotoxic agent.
20. The method of claim 19 , wherein the cytotoxic agent is a radioisotope or a chemotherapeutic agent.
21. A method of diagnosing a cancer or tumor that overexpresses IL-13 in a biological sample, comprising detecting overexpression of IL-13 in the biological sample taken from a patient suspected of having said cancer or tumor by contacting the biological sample with an anti-IL-13 antibody or antigen-binding fragment thereof that binds specifically to human IL-13, wherein said antibody competes with an antibody produced by hybridoma 228B/C-1 having ATCC Accession No. PTA-5657 for binding to IL-13.
22. The method of claim 21 , wherein the anti-IL-13 antibody or antigen-binding fragment binds an epitope having the amino acid sequence ESLINVSG (SEQ ID NO:18) or YCAALESLINVS (SEQ ID NO:19).
23. The method of claim 21 or 22 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising a CDRL1 having the amino acid sequence of SEQ ID NO: 99, a CDRL2 having the amino acid sequence of SEQ ID NO: 104; and a CDRL3 having the amino acid sequence of SEQ ID NO: 115.
24. The method of claim 21 or 22 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a heavy chain comprising a CDRH1 having the amino acid sequence of SEQ ID NO: 117, a CDRH2 having the amino acid sequence of SEQ ID NO: 123, and a CDRH3 having the amino acid sequence of SEQ ID NO: 135.
25. The method of claim 24 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising a CDRL1 having the amino acid sequence of SEQ ID NO: 99, a CDRL2 having the amino acid sequence of SEQ ID NO: 104; and a CDRL3 having the amino acid sequence of SEQ ID NO: 115.
26. The method of claim 21 or 22 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising the amino acid sequence of SEQ ID NO: 3, 142, 144 or 150; and said antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 4, 143, 145, 146, 147, 148 or 149.
27. The method of claim 21 or 22 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises the amino acid sequence of SEQ ID NO: 142 or 143.
28. The method of claim 21 or 22 , wherein the anti-IL-13 antibody or antigen-binding fragment comprises a light chain comprising the amino acid sequence of SEQ ID NO: 142, and a heavy chain comprising the amino acid sequence of SEQ ID NO: 143.
29. The method of claim 21 or 22 , wherein the anti-IL-13 antibody or antigen-binding fragment is a human antibody, a chimeric antibody or a humanized antibody or a fragment thereof.
30. The method of claim 29 , wherein said cancer is Hodgkin's disease, skin cancer, stomach cancer, colon cancer, breast cancer, pancreatic cancer, liver cancer, prostate cancer, lung cancer, head-and-neck cancer, renal cell cancer, squamous cell carcinoma, AIDS-associated Kaposi's carcinoma or brain cancer.