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Last Updated: April 25, 2024

Claims for Patent: 10,188,728


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Summary for Patent: 10,188,728
Title:Compositions and methods for treatment of cancer
Abstract: Provided are compositions, methods and kits for treating cancer comprising targeted liposomes comprising a chemotherapy agent and a sensitizer for the chemotherapy agent, and non-targeted liposomes comprising an anti-angiogenic agent. In some embodiments, the targeted liposomes are immunoliposomes. In further embodiments, the immunoliposomes bind to Her-2/neu, and the composition is for treating breast cancer.
Inventor(s): Wang; Bin (Thornton, PA), Kiani; Mohammad F. (Wynnewood, PA), Tang; Yuan (Elkins Park, PA)
Assignee: Temple University--Of The Commonwealth System of Higher Education (Philadelphia, PA)
Application Number:14/650,355
Patent Claims:1. A composition for treating cancer comprising targeted liposomes comprising a chemotherapy agent and a sensitizer for the chemotherapy agent, and non-targeted liposomes comprising an anti-angiogenic agent, wherein: said targeted liposomes are immunoliposomes that bind to Her-2/neu; said chemotherapy agent is doxorubicin, carboplatin, cisplatin, cyclophosphamide, docetaxel, erlotinib, etoposide, fluorouracil, gemcitabine, imatinib mesylate, irinotecan, methotrexate, paclitaxel, sorafinib, sunitinib, topotecan, vincristine or vinblastine; said sensitizer is verapamil; and said anti-angiogenic agent is bevacizumab.

2. The composition of claim 1 wherein said targeted liposomes comprise hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and DSPE-PEG-maleimide.

3. The composition of claim 1 wherein said targeted liposomes comprise about 50 mole % hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), about 45 mole % cholesterol, about 3 mole % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and about 2 mole % DSPE-PEG-maleimide.

4. The composition of claim 1 wherein said non-targeted liposomes comprise hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and DSPE-PEG-maleimide.

5. The composition of claim 4 wherein said non-targeted liposomes comprise about 50 mole % hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), about 45 mole % cholesterol, about 3 mole % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and about 2 mole % DSPE-PEG-maleimide.

6. The composition of claim 1 wherein said non-targeted liposomes are conjugated to polyethylene glycol.

7. The composition of claim 1 wherein the chemotherapeutic agent is doxorubicin.

8. A method for treating cancer comprising administering to a subject in need of such treatment targeted liposomes comprising a chemotherapy agent and a sensitizer for the chemotherapy agent, and non-targeted liposomes comprising an anti-angiogenic agent wherein: said targeted liposomes are immunoliposomes that bind to Her-2/neu; said chemotherapy agent is doxorubicin, carboplatin, cisplatin, cyclophosphamide, docetaxel, erlotinib, etoposide, fluorouracil, gemcitabine, imatinib mesylate, irinotecan, methotrexate, paclitaxel, sorafinib, sunitinib, topotecan, vincristine or vinblastine; said sensitizer is verapamil; said anti-angiogenic agent is bevacizumab; and said cancer is breast cancer, cardiac cancer, lung cancer, gastrointestinal cancer, genitourinary tract cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, hematologic cancer, skin cancer or adrenal gland cancer.

9. The method of claim 8 wherein said targeted liposomes comprise hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and DSPE-PEG-maleimide.

10. The method of claim 8 wherein said targeted liposomes comprise about 50 mole % hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), about 45 mole % cholesterol, about 3 mole % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and about 2 mole % DSPE-PEG-maleimide.

11. The method of claim 8 wherein said non-targeted liposomes comprise hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and DSPE-PEG-maleimide.

12. The method of claim 8 wherein said non-targeted liposomes comprise about 50 mole % hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), about 45 mole % cholesterol, about 3 mole % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and about 2 mole % DSPE-PEG-maleimide.

13. The method of claim 8 wherein said non-targeted liposomes are conjugated to polyethylene glycol.

14. The method according to claim 8, wherein the chemotherapeutic agent is doxorubicin.

15. The method of claim 8 wherein said targeted liposomes are administered to said subject at the same time as said non-targeted liposomes.

16. The method of claim 8 wherein said targeted liposomes are administered to said subject prior to the administration of said non-targeted liposomes.

17. The method of claim 8 wherein said targeted liposomes are administered to said subject subsequent to the administration of said non-targeted liposomes.

18. The method of claim 8 wherein said cancer is breast cancer.

19. The method of claim 14, wherein said cancer is breast cancer.

20. A kit comprising, in a first compartment, a composition comprising targeted liposomes comprising a chemotherapy agent and a sensitizer for the chemotherapy agent, and, in a second compartment, a composition comprising non-targeted liposomes comprising an anti-angiogenic agent, wherein: said targeted liposomes are immunoliposomes that bind to Her-2/neu; said chemotherapy agent is doxorubicin, carboplatin, cisplatin, cyclophosphamide, docetaxel, erlotinib, etoposide, fluorouracil, gemcitabine, imatinib mesylate, irinotecan, methotrexate, paclitaxel, sorafinib, sunitinib, topotecan, vincristine or vinblastine; said sensitizer is verapamil; and said anti-angiogenic agent is bevacizumab.

21. The kit of claim 20 wherein said targeted liposomes comprise hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and DSPE-PEG-maleimide.

22. The kit of claim 20 wherein said targeted liposomes comprise about 50 mole % hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), about 45 mole % cholesterol, about 3 mole % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and about 2 mole % DSPE-PEG-maleimide.

23. The kit of claim 20 wherein said non-targeted liposomes comprise hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and DSPE-PEG-maleimide.

24. The kit of claim 23 wherein said non-targeted liposomes comprise about 50 mole % hydrogenated soy L-.alpha.-phosphatidylcholine (HSPC), about 45 mole % cholesterol, about 3 mole % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)2000] (DSPE-PEG2000) and about 2 mole % DSPE-PEG-maleimide.

25. The kit of claim 20 wherein said non-targeted liposomes are conjugated to polyethylene glycol.

26. The kit according to claim 20 wherein the chemotherapeutic agent is doxorubicin.

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