Compositions and methods for the treatment of tumor of hematopoietic origin
The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.
1. A method of inhibiting the growth of a B-cell that expresses on its surface
(a) the polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) the polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide;
(c) the polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
said method comprising contacting said B-cell with an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 or chimeric or humanized forms thereof, or an antigen binding fragment thereof and which is conjugated to a cytotoxic agent, wherein the antibody to the extracellular domain of the polypeptide, thereby causing an inhibition of growth of said B-cell.
2. The method of claim 1 , wherein said B-cell is contacted with said antigen binding fragment.
3. The method of claim 1 , wherein said B-cell is contacted with said chimeric or humanized monoclonal antibody.
4. The method of claim 1 , wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.
5. The method of claim 4 , wherein the cytotoxic agent is a toxin.
6. The method of claim 5 , wherein the toxin is selected from the group consisting of maytansinoid, auristatin peptide and calicheamicin.
7. The method of claim 5 , wherein the toxin is a maytansinoid.
8. The method of claim 1 , wherein said humanized or chimeric monoclonal antibody or antigen binding fragment is produced in bacteria.
9. The method of claim 1 , wherein said humanized or chimeric monoclonal antibody or antigen binding fragment is produced in CHO cells.
10. The method of claim 5 , wherein the toxin is auristatin peptide.
11. The method of claim 1 wherein said B-cell is a cancer cell.
12. The method of claim 11 wherein said cancer cell is further exposed to radiation treatment or a chemotherapeutic agent.
13. The method of claim 12 , wherein said cancer cell is selected from the group consisting of a lymphoma cell, a myeloma cell and a leukemia cell.
14. The method of claim 1 which causes the death of said B-cell.
15. A method for treating a B-cell proliferative disorder associated with increased expression or activity of
(a) the polypeptide having the amino acid sequence shown as SEQ ID NO:19;
(b) the polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide;
(c) the polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
said method comprising administering to a subject in need of such treatment an effective amount of an isolated monoclonal antibody produced by a hybridoma 7D11.1 .1 designated ATCC Accession Number PTA-6340 and which is conjugated to a cytotoxic agent, wherein the antibody binds to the extracellular domain of the polypeptide, thereby effectively treating said B-cell proliferative disorder.
16. The method of claim 15 , wherein said B-cell proliferative disorder is cancer.
17. A method for inhibiting the growth of a B-cell, wherein the growth of said cell is at least in part dependent upon a growth potentiating effect of
(a) the polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) the polypeptide having the amino acid sequence shown as SEQ ID NO: 19, lacking its associated signal peptide;
(c) the polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO: 18,
said method comprising contacting said polypeptide with an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 or chimeric or humanized forms thereof, or an antigen binding fragment thereof and which is conjugated to a cytotoxic agent, wherein the antibody binds to the extracellular domain of said polypeptide thereby inhibiting the growth of said cell.
18. The method of claim 17 , wherein said B-cell is a cancer cell.
19. The method of claim 17 , wherein said polypeptide is expressed by said B-cell.
20. The method of claim 17 , wherein the binding of said antibody to said polypeptide includes the death of said cell.
21. The method of claim 17 , wherein said polypeptide is contacted with said antigen binding fragment.
22. The method of claim 1 , wherein said polypeptide is contacted with said chimeric or humanized monoclonal antibody.
23. The method of claim 17 , wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.
24. The method of claim 23 , wherein the cytotoxic agent is a toxin.
25. The method of claim 24 , wherein the toxin is selected from the group consisting of maytansinoid, auristatin peptide, and calicheamicin.
26. The method of claim 25 , wherein the toxin is a maytansinoid.
27. The method of claim 17 , wherein said humanized or chimeric monoclonal antibody or antigen binding fragment is produced in bacteria.
28. The method of claim 17 , wherein said humanized or chimeric monoclonal antibody or antigen binding fragment is produced in CHO cells.
29. The method of claim 25 , wherein the toxin is auristatin peptide.
30. The method of any one of claims 1 , 15 , and 17 , wherein the antibody is detectably labeled.
31. A method of inhibiting the growth of a B-cell that expresses on its surface:
(a) the polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) the polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide; or
(c) the polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
said method comprising contacting said cell with an isolated antibody that competes for binding with or binds to the same epitope as an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 which is and conjugated to a cytotoxic agent, wherein the antibody binds to the extracellular domain of the polypeptide, thereby causing an inhibition of growth of said B-cell.
32. A method for inhibiting the growth of a B-cell, wherein the growth of said cell is at least in part dependent upon a growth potentiating effect of:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19, lacking its associated signal peptide; or
(c) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO: 18,
said method comprising contacting said polypeptide with an isolated antibody that competes for binding with or binds to the same epitope as an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a cytotoxic agent, wherein the antibody binds to the extracellular domain of said polypeptide, thereby inhibiting the growth of said cell.
33. The method of claim 31 or 32 , wherein said antibody is an antigen binding fragment.
34. The method of claim 31 or 32 , wherein said antibody is a chimeric or a humanized antibody.
35. The method of claim 31 or 32 , wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.
36. The method of claim 35 , wherein the cytotoxic agent is a toxin.
37. The method of claim 36 , wherein the toxin is selected from the group consisting of maytansinoid, auristatin peptide and calicheamicin.
38. The method of claim 37 , wherein the toxin is a maytansinoid.
39. The method of claim 37 , wherein the toxin is auristatin peptide.
40. The method of claim 31 or 32 , wherein said antibody is produced in bacteria.
41. The method of claim 31 or 32 , wherein said antibody is produced in CHO cells.
42. The method of claim 31 or 32 , wherein said B-cell is a cancer cell.
43. The method of claim 42 wherein said cancer cell is further exposed to radiation treatment or a chemotherapeutic agent.
44. The method of claim 43 , wherein said cancer cell is selected from the group consisting of a lymphoma cell, a myeloma cell and a leukemia cell.
45. The method of claim 31 which causes the death of said B-cell.
46. The method of claim 32 , wherein said polypeptide is expressed by said B-cell.
47. The method of claim 32 , wherein the binding of said antibody to said polypeptide induces the death of said cell.
48. A method for treating a B-cell proliferative disorder associated with increased expression or activity of:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19, lacking its associated signal peptide; or
(c) s polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
said method comprising administering to a subject in need of such treatment an effective amount of an isolated antibody that competes for binding with or binds to the same epitope as an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a cytotoxic agent, wherein the antibody binds to the extracellular domain of the protein, thereby effectively treating said B-cell proliferative disorder.
49. The method of claim 48 , wherein said B-cell proliferative disorder is cancer.
50. A method of inhibiting the growth of a B-cell that expresses:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide; or
(c) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
said method comprising contacting said cell with an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a growth inhibitory agent, wherein the antibody binds to the extracellular domain of the polypeptide, thereby causing an inhibition of growth of said B-cell.
51. A method for treating a B-cell proliferative disorder associated with increased expression or activity of:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO:19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide;
(c) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
said method comprising administering to a subject in need of such treatment an effective amount of an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is and conjugated to a growth inhibitory agent, wherein the antibody binds to the extracellular domain of the protein, thereby effectively treating said B-cell proliferative disorder.
52. A method for inhibiting the growth of a B-cell, wherein the growth of said cell is at least in part dependent upon a growth potentiating effect of:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19, lacking its associated signal peptide; or
(d) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO: 18,
said method comprising contacting said polypeptide with an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a growth inhibitory agent, wherein the antibody binds to the extracellular domain of said polypeptide, thereby inhibiting the growth of said cell.
53. A method for treating a B-cell proliferative disorder associated with increased expression or activity of:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19, lacking its associated signal peptide; or
(c) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO: 18,
said method comprising administering to a subject in need of such treatment an effective amount of an isolated antibody that competes for binding with or binds to the same epitope as an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a growth inhibitory agent, wherein the antibody binds to the extracellular domain of the protein, thereby effectively treating said B-cell proliferative disorder.
54. The method of claim 48 , wherein said B-cell proliferative disorder is cancer.
55. A method of inhibiting the growth of a B-cell that expresses:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide; or
(c) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
wherein the polypeptide comprises an extracellular domain, said method comprising contacting said cell with an isolated antibody that competes for binding with or binds to the same epitope as an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a growth inhibitory agent, wherein the antibody binds to the extracellular domain of the polypeptide, thereby causing an inhibition of growth of said B-cell.
56. A method for treating a B-cell proliferative disorder associated with increased expression or activity of:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO:19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide; or
(c) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO:18,
said method comprising administering to a subject in need of such treatment an effective amount of an isolated antibody that competes for binding with or binds to the same epitope as an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a growth inhibitory agent, wherein the antibody binds to the extracellular domain of the protein, thereby effectively treating said B-cell proliferative disorder.
57. A method for inhibiting the growth of a B-cell, wherein the growth of said cell is at least in part dependent upon a growth potentiating effect of:
(a) a polypeptide having the amino acid sequence shown as SEQ ID NO: 19;
(b) a polypeptide having the amino acid sequence shown as SEQ ID NO:19, lacking its associated signal peptide;
(c) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown as SEQ ID NO: 18,
said method comprising contacting said polypeptide with an isolated antibody that competes for binding with or binds to the same epitope as an isolated monoclonal antibody produced by a hybridoma 7D11.1.1 designated ATCC Accession Number PTA-6340 and which is conjugated to a growth inhibitory agent, wherein the antibody binds to the extracellular domain of said polypeptide, thereby inhibiting the growth of said cell.
58. The method of any one of claims 1 , 15 , 17 , 31 - 32 , 48 , 50 - 51 , 52 , 53 , and 55 - 57 , wherein the extracellular domain of the polypeptide comprises an amino acid sequence shown as SEQ ID NO:6.