Claims
- 1. An isolated molecule comprising an antibody variable region which specifically binds to an extracellular domain of TEM 3 protein as shown in SEQ ID NO: 200.
- 2. The isolated molecule of claim 1 which is an in tact antibody molecule.
- 3. The isolated molecule of claim 1 which is a single chain variable region (ScFv).
- 4. The isolated molecule of claim 1 which is a monoclonal antibody.
- 5. The isolated molecule of claim 1 which is a humanized antibody.
- 6. The isolated molecule of claim 1 which is a human antibody.
- 7. The isolated molecule of claim 1 which is bound to a cytotoxic moiety.
- 8. The isolated molecule of claim 1 which is bound to a therapeutic moiety.
- 9. The isolated molecule of claim 1 which is bound to a detectable moiety.
- 10. The isolated molecule of claim 1 which is bound to an anti-tumor agent.
- 11. A method of inhibiting neoangiogenesis, comprising:
administering to a subject in need thereof an effective amount of an isolated molecule comprising an antibody variable region which specifically binds to an extracellular domain of TEM 3 protein as shown in SEQ ID NO: 200, whereby neoangiogenesis is inhibited.
- 12. The method of claim 11 wherein the subject bears a vascularized tumor.
- 13. The method of claim 11 wherein the subject has polycystic kidney disease.
- 14. The method of claim 11 wherein the subject has diabetic retinopathy.
- 15. The method of claim 11 wherein the subject has rheumatoid arthritis.
- 16. The method of claim 11 wherein the subject has psoriasis.
- 17. A method of inhibiting tumor growth, comprising:
administering to a human subject bearing a tumor an effective amount of an isolated molecule comprising an antibody variable region which specifically binds to an extracellular domain of TEM 3 protein as shown in SEQ ID NO: 200, whereby growth of the tumor is inhibited.
- 18. An isolated molecule comprising an antibody variable region which specifically binds to TEM 3 protein as shown in SEQ ID NO: 200.
- 19. The isolated molecule of claim 18 which is a single chain variable region (ScFv).
- 20. The isolated molecule of claim 18 which is a monoclonal antibody.
- 21. The isolated molecule of claim 18 which is a humanized antibody.
- 22. The isolated molecule of claim 18 which is a human antibody.
- 23. The isolated molecule of claim 18 which is bound to a cytotoxic moiety.
- 24. The isolated molecule of claim 18 which is bound to a therapeutic moiety.
- 25. The isolated molecule of claim 18 which is bound to a detectable moiety.
- 26. The isolated molecule of claim 18 which is bound to an anti-tumor agent.
- 27. The isolated molecule of claim 18 which is an in tact antibody molecule.
- 28. An isolated and purified human transmembrane protein: TEM 3, as shown in SEQ ID NO: 200.
- 29. An isolated and purified nucleic acid molecule comprising a coding sequence for a transmembrane TEM 3 as shown in SEQ ID NO: 200.
- 30. The isolated and purified nucleic acid molecule of claim 29 which comprises a coding sequence selected from those shown in SEQ ID NO: 199 and 359.
- 31. A recombinant host cell which comprises a nucleic acid molecule comprising a coding sequence for a transmembrane TEM 3 as shown in SEQ ID NO: 200.
- 32. The recombinant host cell of claim 31 which comprises a coding sequence selected from those shown in SEQ ID NO: 199 and 359.
- 33. A method of inducing an immune response in a mammal, comprising:
administering to the mammal a nucleic acid molecule comprising a coding sequence for a human transmembrane protein TEM 3 as shown in SEQ ID NO: 200, whereby an immune response to the human transmembrane protein is induced in the mammal.
- 34. The method of claim 33 wherein the coding sequence is shown in SEQ ID NO: 199.
- 35. A method of inducing an immune response in a mammal, comprising:
administering to the mammal a purified human transmembrane protein TEM 3as shown in SEQ ID NO: 200, whereby an immune response to the human transmembrane protein is induced in the mammal.
- 36. A method for identification of a ligand involved in endothelial cell regulation, comprising:
contacting a test compound with an isolated and purified human trasmembrane protein TEM 3 as shown in SEQ ID NO: 200; contacting the isolated and purified human trasmembrane protein with a molecule comprising an antibody variable region which specifically binds to an extracellular domain of a TEM protein 3, as shown in SEQ ID NO: 200; determining binding of the molecule comprising an antibody variable region to the human transmembrane protein, wherein a test compound which diminishes the binding of the molecule comprising an antibody variable region to the human transmembrane protein is identified as a ligand involved in endothelial cell regulation.
- 37. A method for identification of a ligand involved in endothelial cell regulation, comprising:
contacting a test compound with a cell comprising a human transmembrane protein 3 as shown in SEQ ID NO: 200; contacting the cell with a molecule comprising an antibody variable region which specifically binds to an extracellular domain of a TEM protein selected from the group consisting of: 3 as shown in SEQ ID NO:200; determining binding of the molecule comprising an antibody variable region to the cell, wherein a test compound which diminishes the binding of the molecule comprising an antibody variable region to the cell is identified as a ligand involved in endothelial cell regulation.
- 38. A soluble form of a human transmembrane protein TEM 3 as shown in SEQ ID NO: 200, respectively, wherein the soluble forms lack transmembrane domains.
- 39. The soluble form of claim 38 wherein the soluble form consists of an extracellular domain of the human transmembrane protein.
- 40. A method of inhibiting neoangiogenesis in a patient, comprising:
administering to the patient a soluble form of a human transmembrane protein according to claim 38, whereby neoangiogenesis in the patient is inhibited.
- 41. A method of inhibiting neoangiogenesis in a patient, comprising:
administering to the patient a soluble form of a human transmembrane protein according to claim 39, whereby neoangiogenesis in the patient is inhibited.
- 42. The method of claim 40 wherein the patient bears a vascularized tumor.
- 43. The method of claim 41 wherein the patient bears a vascularized tumor.
- 44. The method of claim 40 wherein the patient has polycystic kidney disease.
- 45. The method of claim 40 wherein the patient has diabetic retinopathy.
- 46. The method of claim 40 wherein the patient has rheumatoid arthritis.
- 47. The method of claim 40 wherein the patient has psoriasis.
- 48. The method of claim 41 wherein the patient has polycystic kidney disease.
- 49. The method of claim 41 wherein the patient has diabetic retinopathy.
- 50. The method of claim 41 wherein the patient has rheumatoid arthritis.
- 51. The method of claim 41 wherein the patient has psoriasis.
- 52. A method of identifying regions of neoangiogenesis in a patient, comprising:
administering to a patient a molecule comprising an antibody variable region which specifically binds to an extracellular domain of a TEM protein 3 as shown in SEQ ID NO: 200, wherein the molecule is bound to a detectable moiety; and
detecting the detectable moiety in the pateint, thereby identifying neoangiogenesis.
- 53. A method of screening for neoangiogenesis in a patient, comprising:
contacting a body fluid collected from the patient with a molecule comprising an antibody variable region which specifically binds to an extracellular domain of a TEM protein 3 as shown in SEQ ID NO: 200, wherein detection of cross-reactive material in the body fluid with the molecule indicates neoangiogenesis in the patient.
- 54. A method of inducing an immune response to tumor endothelial cells in a patient, comprising:
administering to a patient in need thereof a mouse TEM protein selected from the group consisting of: 1, 2, 3, 9, 13, 17, 19, 22, and 30 as shown in SEQ ID NO: 291, 293, 299, 295, 303, 297, 301, 305, and 307, whereby an immune response to a human TEM protein is induced.
- 55. A method to identify candidate drugs for treating tumors, comprising:
contacting cells which express TEM 3 gene as shown in SEQ ID NO: 199 with a test compound; determining expression of said one or more TEM genes by hybridization of mRNA of said cells to a nucleic acid probe which is complementary to said mRNA; and identifying a test compound as a candidate drug for treating tumors if it decreases expression of said one or more TEM genes.
- 56. The method of claim 55 wherein the cells are endothelial cells.
- 57. The method of claim 55 wherein the cells are recombinant host cells which are transfected with an expression construct which encodes said one or more TEMs.
- 58. A method to identify candidate drugs for treating tumors, comprising:
contacting cells which express TEM 3 protein as shown in SEQ ID NO: 200, with a test compound; determining amount of said one or more TEM proteins in said cells; and identifying a test compound as a candidate drug for treating tumors if it decreases the amount of one more TEM proteins in said cells.
- 59. The method of claim 58 wherein the cells are endothelial cells.
- 60. The method of claim 58 wherein the cells are recombinant host cells which are transfected with an expression construct which encodes said one or more TEMs.
- 61. A method to identify candidate drugs for treating tumors, comprising:
contacting cells which express TEM 3 protein as shown in SEQ ID NO: 200 with a test compound; determining activity of said one or more TEM proteins in said cells; and identifying a test compound as a candidate drug for treating tumors if it decreases the activity of of one more TEM proteins in said cells.
- 62. The method of claim 61 wherein the cells are endothelial cells.
- 63. The method of claim 61 wherein the cells are recombinant host cells which are transfected with an expression construct which encodes said one or more TEMs.
- 64. A method to identify candidate drugs for treating patients bearing tumors, comprising:
contacting a test compound with recombinant host cells which are transfected with an expession construct which encodes TEM 3 proteinas shown in SEQ ID NO: 200; determining proliferation of said cells; and identifying a test compound which inhibits proliferation of said cells as a candidate drug for treating patients bearing tumors.
- 65. A method for identification of a ligand involved in endothelial cell regulation, comprising:
contacting a test compound with a human transmembrane protein TEM 3 as shown in SEQ ID NO: 200; determining binding of a test compound to the human transmembrane protein, wherein a test compound which binds to the protein is identified as a ligand involved in endothelial cell regulation.
- 66. A method of inducing an immune response in a mammal, comprising:
administering to the mammal a cell which expresses a transmembrane protein TEM 3 as shown in SEQ ID NO: 200, wherein the cell is a recombinant cell which comprises a vector econding said transmembrane protein, or the cell is a fusion of a dendritic cell and a tumor endothelium cell, whereby an immune response to the human transmembrane protein is induced in the mammal.
- 67. A method of inhibiting neoangiogenesis, comprising:
administering to a subject in need thereof an effective amount of an isolated molecule comprising an antibody variable region which specifically binds to an extracellular domain of a mouse TEM protein selected from the group consisting of: 1, 2, 3, 9, 17, and 19, as shown in SEQ ID NO: 291, 293, 299, 295, 297, and 301, respectively, whereby neoangiogenesis is inhibited.
- 68. The method of claim 67 wherein the subject is a mouse.
- 69. The method of claim 67 wherein the subject bears a vascularized tumor.
- 70. The method of claim 67 wherein the subject has polycystic kidney disease.
- 71. The method of claim 67 wherein the subject has diabetic retinopathy.
- 72. The method of claim 67 wherein the subject has rheumatoid arthritis.
- 73. The method of claim 67 wherein the subject has psoriasis.
Parent Case Info
[0001] This application claims the benefit of provisional applications serial No. 60/282,850 filed Apr. 11, 2001, and 60,308,829 filed Aug. 1, 2001, the disclosures of which are expressly incorporated herein.
Government Interests
[0002] The U.S. government retains certain rights in the invention by virtue of the provisions of National Institutes of Heath grants CA57345 and CA43460, which supported this work.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US02/08253 |
4/10/2002 |
WO |
|
Provisional Applications (2)
|
Number |
Date |
Country |
|
60282850 |
Apr 2001 |
US |
|
60354262 |
Feb 2002 |
US |