Patent EA-004634-B1 (EA)
Title: Treatment and diagnosis of cancer
Inventor: BANDER NEIL H
IPC: C07K16/30
Filed: 1997-07-17
Abstract: 1. An isolated monoclonal antibody or antigen-binding portion thereof which binds to an extracellular domain of prostate-specific membrane antigen (PSMA), wherein the antibody or antigen-binding portion binds live cells. 2. An isolated polyclonal antibody or antigen-binding portion thereof which binds to an extracellular domain of prostate-specific membrane antigen (PSMA), wherein the antibody or antigen-binding portion binds live cells. 3. An antibody or antigen-binding portion thereof according to claim 1 or 2 which are capable to use agents active in a cell. 4. An antibody or antigen-binding portion thereof according to claims 1-3, wherein the antibody or antigen-binding portion thereof is an IgG isotype antibody. 5. An antibody or antigen-binding portion thereof according to claims 1-4, wherein the antibody or antigen-binding portion are selected from a Fab fragment, F(ab`)2 fragment and Fv fragment. 6. An antibody or antigen-binding portion thereof according to claims 1-5, wherein the antibody or antigen-binding portion competes for binding PSMA to the antibody selected from the group consisting of monoclonal antibody E99, J533 and J591. 7. An antibody or antigen-binding portion thereof according to claim 6, wherein the antibody or antigen-binding portion competes for binding PSMA to the monoclonal antibody J591. 8. An antibody or antigen-binding portion thereof according to claims 1-5, which binds to an extracellular epitope PSMA which is also recognized by an antibody selected from the group consisting of monoclonal antibody E99, J533 and J591. 9. An antibody or antigen-binding portion thereof according to claim 8, which bind to an extracellular epitope PSMA which is also recognized by monoclonal antibody J591. 10. An antibody or antigen-binding portion thereof according to claims 1-5, wherein the antibody or antigen-binding portion competes for binding PSMA to the monoclonal antibody J415. 11. An antibody or antigen-binding portion thereof according to claim 10, which binds to an extracellular epitope PSMA which is also recognized by monoclonal antibody J415. 12. An antibody or antigen-binding portion thereof according to claims 1 or 3-5, wherein the antibody is selected from the group consisting of monoclonal antibody E99, J533, J415 and J591. 13. An isolated antibody or antigen-binding portion thereof according to claim 1 or 3-4, produced by a hybridoma having an ATCC Accession Number selected from the group consisting of HB-12101, HB-12109, HB-12127, and HB-12126. 14. Which comprises an antigen-binding portion of an amino acid sequence selected from the group consisting of SEQ ID NO:8 (variable heavy chain) and an amino acid sequence SEQ ID NO: 19 (variable light chain). 15. An antibody or antigen-binding portion thereof according to claim 14, which comprises an antigen-binding portion of an amino acid sequence of SEQ ID NO: 8 (variable heavy chain) and an amino acid sequence SEQ ID NO: 19 (variable light chain). 16. An antibody or antigen-binding portion thereof according to claims 1-5, which comprises an antigen-binding portion of an amino acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO:6 (variable heavy chain), and nucleic acid sequence SEQ ID NO: 17 (variable light chain). 17. An antibody or antigen-binding portion thereof according to claim 16, which comprises an antigen-binding portion of an amino acid sequence encoded by a nucleic acid sequence from SEQ ID NO:6 (variable heavy chain) and an antigen-binding portion of an amino acid sequence encoded by a nucleic acid sequence from SEQ ID NO: 17 (variable light chain). 18. An isolated antibody or antigen-binding portion thereof according to any one of claims 1 to 17, wherein the isolated antibody or antigen-binding portion thereof is bound with a cytotoxic drug. 19. An isolated antibody or antigen-binding portion thereof according to claim 18, wherein the cytotoxic drug is selected from the group consisting of a therapeutic drug, a compound emitting radiation, molecules of plant, fungal, or bacterial origin, biological proteins, and mixtures thereof. 20. An isolated antibody or antigen-binding portion thereof according to claim 19, wherein the cytotoxic drug is a compound emitting radiation. 21. An isolated antibody or antigen-binding portion thereof according to claim 20, wherein the compound emitting radiation is an alpha-emitter, beta emitter or gamma emitter. 22. An isolated antibody or antigen-binding portion thereof according to claim 21, wherein the compound is selected from the group consisting of <212>Bi, <213>Bi, <211>At, <186>Re, <90>Y and <131>L. 23. An isolated antibody or antigen-binding portion thereof according to claims 1-22, wherein isolated antibody or antigen-binding portion thereof is bound to a label. 24. An isolated antibody or antigen-binding portion thereof according to claim 23, wherein the label is selected from the group consisting of a fluorescent label, a biologically-active enzyme label, a radioactive label, a nuclear magnetic resonance active label, a luminescent label, and a chromophore label. 25. An isolated antibody or antigen-binding portion thereof according to claim 24, wherein the label is selected from the group consisting of <32>P, <125>I, <3>H, <14>C, <188>Rh, <131>I, <99>mTc and <111>In. 26. A composition comprising: an isolated antibody or antigen-binding portion thereof according to any one of claims 1-25 and a physiologically acceptable carrier, excipient, or stabilizer mixed with the isolated antibody or antigen-binding portion thereof. 27. A composition comprising: an isolated antibody or antigen-binding portion thereof according to any one of claims 1-25 and a pharmaceutically acceptable carrier, excipient, or stabilizer mixed with the isolated antibody or antigen-binding portion thereof. 28. A kit for detecting PSMA expressing cells comprising: an isolated antibody or antigen-binding portion thereof according to any one of claims 23-25 and means to detect the label. 29. A kit according to claim 28, wherein cells are cancerous cells. 30. A kit for detecting PSMA expressing cells comprising: an isolated antibody or antigen-binding portion thereof according to any one of claims 1-22, a label, means for binding the label to the isolated antibody or antigen-binding portion thereof and means to detect the label. 31. A kit according to claim 30, wherein cells are cancerous cells. 32. A kit according to claims 28-31, wherein further comprising a physiologically acceptable carrier, excipient, or stabilizer. 33. A kit according to claims 28-31, wherein further comprising a pharmaceutically acceptable carrier, excipient, or stabilizer. 34. A kit according to claims 28-31, wherein the label is selected from the group consisting of a fluorescent label, a biologically-active enzyme label, a radioactive label, a nuclear magnetic resonance active label, a luminescent label, and a chromophore label. 35. A kit according to claim 34, wherein the radioactive label is selected from the group consisting of <32>P, <125>I, <3>H, <14>C, <188>Rh, <131>I,99mTc and <111>In. 36. A kit according to claims 30-35, wherein cancer is prostate cancer. 37. A kit according to claims 30-35, wherein the cancer is selected from the group consisting of renal cancer, urothelial cancer, colon cancer, lung cancer, breast cancer, and metastatic adenocarcinoma to the liver. 38. A hybridoma cell line having an ATCC Accession Number HB-12101 that produces a monoclonal antibody E99. 39. A hybridoma cell line having an ATCC Accession Number HB-12109 that produces a monoclonal antibody J415. 40. A hybridoma cell line having an ATCC Accession Number HB-12127 that produces a monoclonal antibody J533. 41. A hybridoma cell line having an ATCC Accession Number HB-12126 that produces a monoclonal antibody J591. 42. A method for treating, preventing, or delaying development or progression in a subject comprising: providing an antibody or antigen-binding portion thereof according to claims 1-25; and administering the antibody or antigen-binding portion thereof to a subject in need of treatment under conditions effective to treat, prevent, or delay the development or progression of cancer. 43. A method according to claim 42, wherein cancer is prostate cancer. 44. A method according to claim 43, wherein the prostate cancer is metastatic. 45. A method according to claim 44, wherein the metastatic prostate cancer involves a bone marrow or a lymph node metastasis. 46. A method according to claims 43-45, wherein the administering is carried out after prostatectomy. 47. A method according to claim 42, wherein cancer is non prostate cancer. 48. A method according to claim 47, wherein the non-prostate cancer is selected from the group consisting of renal cancer, urothelial cancer, colon cancer, rectal cancer, lung cancer, breast cancer, and metastatic adenocarcinoma to the liver. 49. A method according to claim 47, wherein the antibody or antigen-binding portion thereof binds to vascular endothelial cells proximate to non-prostate cancerous cells or within the non-prostate cancerous tumor. 50. A method according to claims 42-49, wherein the administering is carried out by parenterally, intravenously, intracavitary, rectally or intramuscularly instillation. 51. A method according to claims 42-50, wherein the antibody or antibody-binding portion thereof is internalized with PSMA. 52. A method according to claims 42-51, wherein the antibody is administered in conjunction with a second therapeutic modality. 53. A method according to claim 52, wherein the second therapeutic modality is selected from the group consisting of surgery, radiation, chemotherapy, immunotherapy and hormone replacement therapy. 54. A method according to claim 52, wherein the hormone replacement therapy comprises treating by extrogen or an anti-androgen agent. 55. A method according to claim 54, wherein the anti-androgen agent is an agent for bl