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Claims for Patent: 8,178,505

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Summary for Patent: 8,178,505
Title:Method of predicting and reducing risk of metastasis of breast cancer to lung
Abstract: A signature for breast cancer tissue derived from a patient is established that is indicative of the virulence and risk of lung metastasis by determining the expression levels to define a sample signature, and comparing this sample signature to a reference signature. The reference signature defines a standard expression level for each gene and a significant change direction, i.e., either overexpressed or underexpressed. A sample signature that differs from the reference signature in the significant change direction for a predetermined number of the genes tested is indicative of a significant risk of lung metastasis. This determination is used to define appropriate treatment and monitoring options for the patient. Risk of metastasis to the lung can be reduced by treatment with a therapeutic combination that either (1) contains a first agent effective to inhibit epiregulin activity and a second agent effective to inhibit activity of a protein selected from the group consisting of MMP1, MMP2 and PTGS2, or (2) contains a therapeutic agent or combination of agents effective to inhibit activity MMP1, MMP2 and PTGS2. Agents that inhibit the CXCL1 pathway also can be used individually or in combination with these combinations.
Inventor(s): Massague; Joan (New York, NY), Gupta; Gaorav P. (New York, NY), Minn; Andy (New York, NY)
Assignee: Sloan-Kettering Institute for Cancer Research (New York, NY)
Application Number:11/813,407
Patent Claims:1. A therapeutic combination comprising at least two agents, wherein the agents are inhibitors of a protein selected from the group consisting of MMP1, MMP2, CXCL1, PTSG2, and EREG.

2. The therapeutic combination of claim 1, wherein the combination comprises at least three agents, wherein the agents are inhibitors of a protein selected from the group consisting of MMP1, MMP2, CXCL1, PTSG2, and EREG.

3. The therapeutic combination of claim 1, comprising a first agent effective to inhibit epiregulin (EREG) activity and a second agent effective to inhibit activity of a protein selected from the group consisting of MMP1, MMP2 and PTGS2.

4. The therapeutic combination of claim 3, wherein the first agent is an oligonucleotide.

5. The therapeutic combination of claim 3, wherein the second agent is an oligonucleotide.

6. The therapeutic combination of claim 3, wherein the first agent is a small molecule inhibitor.

7. The therapeutic combination of claim 3, wherein the first agent is selected from the group consisting of Erbitux, Iressa and Tarceva.

8. The therapeutic combination of claim 3, wherein the first agent is targeted to HER2.

9. The therapeutic combination of claim 8, wherein the first agent is Herceptin.

10. The therapeutic combination of claim 3, wherein the second agent inhibits PTGS2.

11. The therapeutic combination of claim 10, wherein the second agent is selected from the group consisting of rofecoxib, celocoxib, valdecoxib, indocin, parecoxib.

12. The therapeutic combination of claim 3, wherein the second agent inhibits MMP1 and/or MMP2.

13. The therapeutic combination of claim 12, wherein the second agent is selected from the group consisting of Marimastat (BB-2516), Batimastat (BB-94), AG3340 (Agouron), 12-9566 (Bayer Corporation); D2163 (Chiroscience Group Plc); Metastat (Collagenex) and MMI270 (Novartis).

14. A therapeutic combination comprising a combination of agents effective to inhibit activity of MMP1, MMP2 and PTGS2.

15. The therapeutic combination of claim 14, wherein the combination comprises an agent effective to inhibit PTGS2 selected from the group consisting of rofecoxib, celocoxib, valdecoxib, indocin, parecoxib.

16. The therapeutic combination of claim 14, wherein the combination comprises an agent effective to inhibit MMP1 selected from the group consisting of Marimastat (BB-2516), Batimastat (BB-94), AG3340 (Agouron), 12-9566 (Bayer Corporation); D2163 (Chiroscience Group Plc); Metastat (Collagenex) and MMI270 (Novartis).

17. The therapeutic combination of claim 14, wherein the combination comprises an RNAi agent that targets a sequence selected from the group consisting of SEQ ID Nos. 7-11.

18. The therapeutic combination of claim 14, further comprising an agent effective to inhibit the CXCL1 pathway.

19. A method for reducing the risk of breast cancer metastasis to the lung in a patient previously diagnosed with breast cancer, comprising administering to the patient a therapeutic combination in accordance with claim 14.

20. A method for reducing the risk of breast cancer metastasis to the lung in a patient previously diagnosed with breast cancer, comprising administering to the patient a therapeutic agent effective to inhibit the CXCL1 pathway.

21. The therapeutic combination of claim 3, further comprising an agent effective to inhibit the CXCL1 pathway.

22. A method for reducing the risk of breast cancer metastasis to the lung in a patient previously diagnosed with breast cancer, comprising administering to the patient a therapeutic combination in accordance with claim 3.

23. The therapeutic combination of claim 7, wherein the second agent inhibits PTGS2.

24. The therapeutic combination of claim 23, further comprising an agent effective to inhibit the CXCL1 pathway.

25. The therapeutic combination of claim 7, wherein the second agent is selected from the group consisting of rofecoxib, celocoxib, valdecoxib, indocin, parecoxib.

26. The therapeutic combination of claim 25, further comprising an agent effective to inhibit the CXCL1 pathway.

27. The therapeutic combination of claim 5, wherein the second agent inhibits PTGS2.

28. The therapeutic combination of claim 27, further comprising an agent effective to inhibit the CXCL1 pathway.

29. The therapeutic combination of claim 27, wherein the second agent is selected from the group consisting of rofecoxib, celocoxib, valdecoxib, indocin, parecoxib.

30. The therapeutic combination of claim 29, further comprising an agent effective to inhibit the CXCL1 pathway.

31. The therapeutic combination of claim 4, wherein the second agent inhibits PTGS2.

32. The therapeutic combination of claim 31, further comprising an agent effective to inhibit the CXCL1 pathway.

33. The therapeutic combination of claim 31, wherein the second agent is selected from the group consisting of rofecoxib, celocoxib, valdecoxib, indocin, parecoxib.

34. The therapeutic combination of claim 33, further comprising an agent effective to inhibit the CXCL1 pathway.

35. The therapeutic combination of claim 8, wherein the second agent inhibits PTGS2.

36. The therapeutic combination of claim 35, further comprising an agent effective to inhibit the CXCL1 pathway.

37. The therapeutic combination of claim 35, wherein the second agent is selected from the group consisting of rofecoxib, celocoxib, valdecoxib, indocin, parecoxib.

38. The therapeutic combination of claim 37, further comprising an agent effective to inhibit the CXCL1 pathway.

39. The therapeutic combination of claim 10, the second agent further comprises inhibitors of MMP1 and/or MMP2.

40. A therapeutic combination comprising at least two agents, wherein the first agent is a means for inhibiting a first protein selected from the group consisting of MMP1, MMP2, CXCL1, PTSG2, and EREG, and the second agent is a means for inhibiting a second protein, different from the first protein, and selected from the group consisting of MMP1, MMP2, CXCL1, PTSG2, and EREG.

41. The therapeutic combination of claim 40, further comprising a third agent, wherein the third agent is a means for inhibiting a third protein, different from the first and second proteins, and selected from the group consisting of MMP1, MMP2, CXCL1, PTSG2, and EREG.

42. The therapeutic combination of claim 40, wherein the first agent is a means for inhibiting epiregulin (EREG) activity and the second agent is a means for inhibiting a protein selected from the group consisting of MMP1, MMP2 and PTGS2.

43. The therapeutic combination of claim 42, wherein the second agent is a means for inhibiting PTGS2.

Summary for Patent: ➤ Sign Up

PCT Information
PCT FiledJanuary 05, 2006PCT Application Number:PCT/US2006/000461
PCT Publication Date:July 13, 2006PCT Publication Number:WO2006/074367

Details for Patent 8,178,505

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Genentech HERCEPTIN trastuzumab VIAL; INTRAVENOUS 103792 001 1998-09-25 ➤ Sign Up Sloan-Kettering Institute for Cancer Research (New York, NY) 2025-01-05 RX Orphan search
Imclone ERBITUX cetuximab VIAL; INTRAVENOUS 125084 001 2004-06-18 ➤ Sign Up Sloan-Kettering Institute for Cancer Research (New York, NY) 2025-01-05 RX Orphan search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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