Claims
- 1. A purified receptor protein having specific binding affinity for the Cys-Ser-Val-Thr-Cys-Gly (SEQ ID NO: 1)-specific region of thrombospondin (TSP-1).
- 2. The receptor of claim 1, comprising a sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 3, and fragments and mutations of SEQ ID NO. 2 and SEQ ID NO. 3.
- 3. The receptor of claim 2, wherein the fragment comprises SEQ ID NO. 24, and fragments and mutations of SEQ ID NO. 24.
- 4. A method of treating a patient with an antibody that inhibits thrombospondin activity comprising the steps of isolating the receptor of claim 1, generating antibodies to the receptor, and using the antibodies to treat the patient.
- 5. A method of treating a patient with an antibody that mimics thrombospondin activity comprising the steps of isolating the receptor of claim 1, generating antibodies to the receptor, and using the antibodies to treat the patient.
- 6. A method of treating a patient with a ligand that inhibits thrombospondin activity comprising the steps of isolating the receptor of claim 1, generating a ligand to the receptor, and using the ligand to treat the patient.
- 7. A method of detecting malignant cancer comprising the steps of measuring the presence of the receptor of claim 1, and determining whether malignant cancer is present.
- 8. A method of treating a patient with a ligand that mimics thrombospondin activity comprising isolating the receptor of claim 1, generating a ligand to the receptor, and using the ligand to treat the patient.
- 9. A method of treating a patient with the receptor of claim 1 comprising administering the receptor to the patient and allowing the receptor to competitively inhibit thrombospondin activity.
- 10. The method of claim 8, wherein the method of treatment inhibits or reverses angiogenesis.
- 11. The method of claim 8, wherein the method of treatment inhibits, prevents, or reverses tumor growth.
- 12. The method of claim 8, wherein the method extends the life of the patient.
- 13. A method of treating a patient with a fragment of the receptor of claim 1 comprising the steps of administering a fragment of the receptor is administered to the patient and allowing the fragment to competitively inhibit thrombospondin activity.
- 14. A method of diagnosing or determining the prognosis of a patient with cancer comprising the steps of determining the level of receptor of claim 1 and evaluating the level against known values for metastatic and nonmetastatic tumors.
- 15. A composition for treating cancer comprising a chemotherapy drug linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an antibody directed to the receptor of claim 1 or a ligand directed to the receptor of claim 1.
- 16. A composition for treating cancer comprising a radioactive moiety linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an antibody directed to the receptor of claim 1 or a ligand directed to the receptor of claim 1.
- 17. A method for treating cancer comprising administering a therapeutically effective amount of the composition of claim 16, optionally in a pharmaceutically acceptable carrier, allowing the targeting moiety to target the cancer, and allowing the radioactive moiety to treat the cancer.
- 18. A composition for radiological detection of cancer, diagnosis of cancer, and quantification of therapeutic response to treatment of cancer comprising a radioactive moiety linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an antibody directed to the receptor of claim 1 or a ligand directed to the receptor of claim 1.
- 19. A method for radiological detection of cancer, diagnosis of cancer, and quantification of therapeutic response to treatment of cancer comprising administering a effective amount of the composition of claim 18, optionally in a pharmaceutically acceptable carrier, allowing the targeting moiety to target the cancer, allowing the radioactive moiety to label the cancer, and detecting the cancer, diagnosing the cancer, or quantifying the therapeutic response to treatment of cancer.
- 20. A composition for MRI detection of cancer, diagnosis of cancer, and quantification of therapeutic response to treatment of cancer comprising an MRI enhancing agent linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an antibody directed to the receptor of claim 1 or a ligand directed to the receptor of claim 1.
- 21. The composition of claim 20, wherein the MRI enhancing agent is selected from the group consisting of gadolinium, manganese, and iron.
- 22. A method of MRI detection of cancer, diagnosis of cancer, and quantification of therapeutic response to treatment of cancer comprising administering an effective amount of the composition of claim 20, optionally in a pharmaceutically acceptable carrier, allowing the targeting moiety to target the cancer, using MRI to detect the cancer, diagnose the cancer, or quantify the therapeutic response of the cancer, and allowing the MRI enhancing agent to enhance the MRI.
- 23. A biomedical device comprising a means to remove cells, wherein the cell removing means is linked to a targeting moiety and the targeting moiety is selected from the group consisting of an antibody directed to the receptor of claim 1 or a ligand directed to the receptor of claim 1.
- 24. A method of designing a drug to mimic or inhibit thrombospondin activity comprising the steps of developing a candidate drug and evaluating its binding to the receptor of claim 1.
- 25. A method of decreasing endothelial cell viability comprising administering a pharmaceutically acceptable amount of the purified receptor protein of claim 1 and allowing it to interact with the endothelial cell to decrease endothelial cell viability.
- 26. A method of decreasing cell adhesion activity comprising administering a pharmaceutically acceptable amount of the purified receptor protein of claim 1 and allowing it to interact with the cell to decrease cell adhesion activity.
- 27. A method of treating a patient comprising administering to the patient a purified receptor protein having specific binding affinity for the Cys-Ser-Val-Thr-Cys-Gly (SEQ ID NO: 1)-specific region of thrombospondin (TSP-1), wherein the receptor protein is reactive with antibodies raised against SEQ ID NO:24, and allowing the receptor protein to competitively inhibit thrombospondin activity.
- 28. The method of claim 27, wherein the method of treatment inhibits or reverses angiogenesis.
- 29. The method of claim 27, wherein the method of treatment inhibits, prevents, or reverses tumor growth.
- 30. The method of claim 27, wherein the method extends the life of the patient.
- 31. The method of claim 27, wherein the method decreases endothelial cell viability.
- 32. The method of claim 27, wherein the method decreases cell adhesion activity.
- 33. The method of claim 27, wherein the receptor protein comprises a sequence chosen from SEQ ID NO: 2, SEQ ID NO: 3, fragments of SEQ ID NO:2 and SEQ ID NO:3, and mutations of SEQ ID NO:2 and SEQ ID NO:3.
- 34. The method of claim 27, wherein the receptor protein comprises a sequence chosen from SEQ ID NO: 24, fragments of SEQ ID NO:24, and mutations of SEQ ID NO:24.
PRIORITY INFORMATION
[0001] This application is a divisional of Ser. No. 09/597,845, filed Jun. 20, 2000, which is herein incorporated by reference, and claims the benefit of priority to two U.S. Provisional Application Serial No. 60/140,309, filed Jun. 21, 1999, and Serial No. 60/176,626, filed Jan. 19, 2000.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60140309 |
Jun 1999 |
US |
|
60176626 |
Jan 2000 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09597845 |
Jun 2000 |
US |
Child |
10122348 |
Apr 2002 |
US |