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Last Updated: March 29, 2024

Claims for Patent: 7,517,962


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Summary for Patent: 7,517,962
Title:TWEAK receptor
Abstract: The present invention provides the TWEAK receptor and methods for identifying and using agonists and antagonists of the TWEAK receptor. In particular, the invention provides methods of screening for agonists and antagonists and for treating diseases or conditions mediated by angiogenesis, such as solid tumors and vascular deficiencies of cardiac or peripheral tissue.
Inventor(s): Wiley; Steven R. (Seattle, WA)
Assignee: Immunex Corporation (Thousand Oaks, CA)
Application Number:10/862,109
Patent Claims:1. An isolated monoclonal antibody, wherein said antibody binds to a polypeptide consisting of residues 28 to 68 of SEQ ID NO:4, binds to the extracellular domain of a human TWEAK receptor consisting of the amino acid sequence of SEQ ID NO:4, and inhibits binding of a TWEAK molecule to said TWEAK receptor.

2. The isolated monoclonal antibody of claim 1, wherein said antibody binds to the cysteine-rich repeat region of said TWEAK receptor.

3. The isolated monoclonal antibody of claim 1, wherein said antibody inhibits angiogenesis.

4. The isolated monoclonal antibody of claim 1, wherein said antibody promotes angiogenesis.

5. The isolated monoclonal antibody of claim 1, wherein said human TWEAK receptor is glycosylated.

6. The isolated monoclonal antibody of claim 1, wherein said antibody comprises a radioisotope, a plant-derived toxin, a fungus-derived toxin, a bacterial-derived toxin, ricin A, or diphtheria toxin.

7. The isolated antibody of claim 1, wherein said antibody comprises a detectable label.

8. The isolated antibody of claim 7, wherein said detectable label comprises a radioisotope, a chemiluminescent compound, a fluorescent compound, or an enzyme.

9. The isolated monoclonal antibody of claim 1, wherein said antibody is selected from the group consisting of: a) an intact human antibody; b) a human antibody fragment; c) an intact chimeric antibody; d) a chimeric antibody fragment; e) an intact humanized antibody; f) a humanized antibody fragment; g) a Fab fragment; h) an Fv fragment; i) an F(ab')2 fragment; and j) a single chain antibody.

10. An isolated polypeptide, wherein said polypeptide comprises the monoclonal antibody of claim 1 and inhibits binding of a TWEAK molecule to said TWEAK receptor.

11. An isolated cell, wherein said cell produces the monoclonal antibody of claim 1.

12. An isolated cell, wherein said cell produces the polypeptide of claim 10.

13. The isolated cell of claim 11, wherein said cell is a hybridoma.

14. The isolated cell of claim 11, wherein said cell is a recombinant cell.

15. The isolated cell of claim 12, wherein said cell is a recombinant cell.

16. A method of inhibiting binding of TWEAK to a TWEAK receptor in a subject in need of such treatment comprising administering to said subject an inhibition-effective amount of said antibody of claim 1.

17. The method of claim 16 wherein said subject is a human.

18. The method of claim 16 wherein the subject has a disease or condition mediated by angiogenesis.

19. The method of claim 18 wherein the disease or condition is characterized by ocular neovascularization.

20. The method of claim 18 wherein the disease or condition is a malignant or metastatic condition.

21. The method of claim 20 wherein the malignant or metastatic condition is a solid tumor.

22. The method of claim 20 wherein the method further comprises treating the subject with radiation.

23. The method of claim 20 wherein the method further comprises treating the subject with a second chemotherapeutic agent.

24. The method of claim 23 wherein the second chemotherapeutic agent is selected from the group consisting of alkylating agents, antimetabolites, vinca alkaloids and other plant-derived chemotherapeutics, nitrosoureas, antitumor antibiotics, antitumor enzymes, topoisomerase inhibitors, platinum analogs, adrenocortical suppressants, hormones, hormone agonists, hormone antagonists, antibodies, immunotherapeutics, blood cell factors, radiotherapeutics, and biological response modifiers.

25. The method of claim 23 wherein the second chemotherapeutic agent is selected from the group consisting of cisplatin, cyclophosphamide, mechloretamine, melphalan, bleomycin, carboplatin, fluorouracil, 5 -fluorodeoxyuridine, methotrexate, taxol, asparaginase, vincristine, and vinblastine, lymphokines, cytokines, interleukins, interferons, alpha interferon, beta interferon, delta interferon, TNF, chlorambucil, busulfan, carmustine, lomustine, semustine, streptozocin, dacarbazine, cytarabine, mercaptopurine, thioguanine, vindesine, etoposide, teniposide, dactinomycin, daunorubicin, doxorubicin, plicamycin, mitomycin, L-asparaginase, hydroxyurea, methylhydrazine, mitotane, tamoxifen, and fluoxymesterone.

26. The method of claim 23 wherein the second chemotherapeutic agent is selected from the group consisting of Flt3 ligand, CD40 ligand, interleukin-2, interleukin-12, 4-1BB ligand, anti-4-1BB antibodies, TNF antagonists and TNF receptor antagonists, TRAIL, CD148 agonists, VEGF antagonists, VEGF receptor antagonists, and Tek antagonists.

27. A method of inhibiting binding of TWEAK to a TWEAK receptor in a subject in need of such treatment comprising administering to said subject an inhibition-effective amount of said polypeptide of claim 10.

28. The method of claim 27 wherein said subject is a human.

29. The method of claim 27 wherein the subject has a disease or condition mediated by angiogenesis.

30. The method of claim 29 wherein the disease or condition is characterized by ocular neovascularization.

31. The method of claim 29 wherein the disease or condition is a malignant or metastatic condition.

32. The method of claim 31 wherein the malignant or metastatic condition is a solid tumor.

33. The method of claim 31 wherein the method further comprises treating the subject with radiation.

34. The method of claim 31 wherein the method further comprises treating the subject with a second chemotherapeutic agent.

35. The method of claim 34 wherein the second chemotherapeutic agent is selected from the group consisting of alkylating agents, antimetabolites, vinca alkaloids and other plant-derived chemotherapeutics, mitrosoureas, antitumor antibiotics, antitumor enzymes, topoisomerase inhibitors, platinum analogs, adrenocortical suppressants, hormones, hormone agonists, hormone antagonists, antibodies, immunotherapeutics, blood cell factors, radiotherapeutics, and biological response modifiers.

36. The method of claim 34 wherein the second chemotherapeutic agent is selected from the group consisting of cisplatin, cyclophosphamide, mechloretamine, melphalan, bleomycin, carboplatin, fluorouracil, 5-fluorodeoxyuridine, methotrexate, taxol, asparaginase, vincritine, and vinblastine, lymphokkines, cytokines, interleukins, interferons, alpha interferon, beta interferon, delta interferon, TNF, chlorambucil, busulfan, carmustine, lomustine, semustine, streptozocin, dacarbazine, cytarabine, mercaptopurine, thioguanine, vindesine, etoposide, teniposide, dactinomycin, daunorubicin, doxorubicin, plicamycin, mitomycin, L-asparaginase, hydroxyurea, methylhydrazine, mitotane, tamoxifen, and fluoxymesterone.

37. The method of claim 34 wherein the second chemotherapeutic agent is selected from the group consisting of Flt3 ligand, CD40 ligand, interleukin-2, interleukin-12, 4-1BB ligand, anti-4-BB antibodies, TNF antagonists and TNF receptor antagonists, TRAIL, CD148 agonists, VEGF antagonists, VEGF receptor antagonists, and Tek antagonists.

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