HUMANIZED MONOCLONAL ADVANCED GLYCATION END-PRODUCT ANTIBODY

Abstract

A humanized monoclonal antibody that binds to an advanced glycation end-product-modified protein or peptide on a cell comprises a heavy chain and a light chain. The antibody binds a carboxymethyllysine-modified protein or peptide. A composition comprises a humanized monoclonal antibody that binds to an advanced glycation end-product-modified protein or peptide on a cell and a pharmaceutically acceptable carrier.

Description

Claims

1-17. (canceled)

18. A method of treating prostate cancer in a human subject, comprising: administering to the subject a composition comprising a humanized monoclonal advanced glycation end-product antibody, anda pharmaceutically acceptable carrier,wherein the antibody binds a carboxymethyllysine-modified protein or peptide.

19. The method of claim 18, further comprising: testing the subject for effectiveness of the administration at treating the prostate cancer,followed by repeating the administering of the antibody.

20. The method of claim 18, wherein the antibody is substantially non-immunogenic to humans.

21. The method of claim 18, wherein the antibody has a rate of dissociation (kd) of at most 6 × 10-3 (sec-1).

22. The method of claim 18, wherein the antibody is conjugated to an agent that causes the destruction of AGE-modified cells.

23. The method of claim 22, wherein the agent comprises at least one member selected from the group consisting of toxins, cytotoxic agents, magnetic nanoparticles and magnetic spin-vortex discs.

24. The method of claim 18, wherein the composition is in unit dosage form.

25. The method of claim 18, wherein the composition is in the form of a solution or suspension, for parenteral administration.

26. The method of claim 18, wherein the antibody comprises a heavy chain comprising an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, and a light chain comprising an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15.

27. The method of claim 18, wherein the antibody comprises, a heavy chain, having a heavy chain variable region, anda light chain, having a light chain variable region,wherein the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10, andthe light chain variable region comprises an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20.

28. The method of claim 18, wherein the humanized monoclonal advanced glycation end-product antibody, comprises a heavy chain, anda light chain,wherein the heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, andthe light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15.

29. The method of claim 18, wherein the antibody, comprises a heavy chain, having a heavy chain variable region, anda light chain, having a light chain variable region,wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10, andthe light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20.

30. The method of claim 18, wherein the composition is sterile.

31. A method of treating cancer in a human subject, comprising: administering to the subject a composition comprising a humanized monoclonal advanced glycation end-product antibody, anda pharmaceutically acceptable carrier,wherein the antibody binds a carboxymethyllysine-modified protein or peptide.

32. The method of claim 31, wherein the antibody comprises a heavy chain comprising an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, and a light chain comprising an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15.

33. The method of claim 31, wherein the antibody comprises, a heavy chain, having a heavy chain variable region, anda light chain, having a light chain variable region,wherein the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10, andthe light chain variable region comprises an amino acid sequence having at least 90% sequence identity with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20.

34. The method of claim 31, wherein the cancer is selected from the group consisting of breast cancer, triple negative breast cancer, lung cancer, melanoma, colon cancer, renal cell carcinoma, cancer of the cervix, bladder cancer, rectal cancer, esophageal cancer, liver cancer, mouth and throat cancer, multiple myeloma, ovarian cancer, stomach cancer and retinal blastoma cancers.

35. The method of claim 31, wherein the antibody is substantially non-immunogenic to humans.

36. The method of claim 31, wherein the antibody has a rate of dissociation (kd) of at most 6 × 10-3 (sec-1).

37. The method of claim 31, wherein the antibody, comprises a heavy chain, having a heavy chain variable region, anda light chain, having a light chain variable region,wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10, andthe light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20.