Claims for Patent: 9,326,974

Summary for Patent: 9,326,974

Title:	Methods and related compositions for the treatment of cancer
Abstract:	A method of treatment and/or prevention of cancer comprises administering agents which cause increased intracellular granularity in cancer cells, at least in an amount sufficient to inhibit proliferation of such cells and preferably in an amount sufficient to lead to cancer cell death. The method is particularly directed to refractory cancer, particularly hormone refractory prostate cancer. The agents identified cause increased intracellular granularity in the cancer cells, and also convert adherent cancer cells to non-adherent cancer cells, leading to cancer cell death. Using the present invention, cancer cells undergo increased intracellular granularity at relatively low agent concentrations, while also inhibiting cell proliferation. Increased concentrations lead to conversion of adherent cancer cells to non-adherent cancer cells, then to cell death. While the exact mechanism of cancer cell degradation and death is not completely understood, the treated cancer cells, including refractory prostate cancer cells, give indications of cell death through an autophagic mechanism. Pharmaceutical compositions related to the presently disclosed methods are also disclosed.
Inventor(s):	Thompson; Todd A. (Albuquerque, NM), Mackenzie; Debra (Albuquerque, NM), Oprea; Tudor I. (Albuquerque, NM), Sklar; Larry A. (Albuquerque, NM), Edwards; Bruce S. (Albuquerque, NM), Haynes; Mark (Albuquerque, NM)
Assignee:	STC.UNM (Albuquerque, NM)
Application Number:	14/449,957
Patent Claims:	1. A method of treating cancer in a human patient with cancer in need comprising administering to said patient a composition comprising a therapeutically effective amount of securinine and/or pharmaceutically acceptable salt thereof and wherein said cancer is lung cancer, breast cancer,colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer. 2. The method according to claim 1 wherein said composition further comprises at least one secondary anticancer agent. 3. The method according to claim 1 wherein said composition is coadministered with an effective amount of at least one secondary anticancer agent. 4. The method according to claim 2 wherein said at least one secondary anticancer agent is selected from the group consisting of selected from the group consisting of antimetabolites, inhibitors of topoisomerase I and II, alkylating agents, microtubule inhibitors and mixtures thereof. 5. The method according to claim 2 wherein said at least one secondary anticancer agent is aldesleukin; alemtuzumab; alitretinoin; allopurinol; altretamine; amifostine; anastrozole; arsenic trioxide; asparaginase; BCG Live; bexarotene capsules; bexarotene gel; bleomycin; busulfan intravenous; busulfan oral; calusterone; capecitabine; carboplatin; carmustine; carmustine with Polifeprosan 20 Implant; celecoxib; chlorambucil; cisplatin; cladribine; cyclophosphamide; cytarabine; cytarabine liposomal; dacarbazine; dactinomycin; actinomycin D; Darbepoetin alfa; daunorubicin liposomal; daunorubicin, daunomycin; Denileukin diftitox, dexrazoxane; docetaxel; doxorubicin; doxorubicin liposomal; Dromostanolone propionate; Elliott's B Solution; epirubicin; Epoetin alfa estramustine; etoposide phosphate; etoposide (VP-16); exemestane; Filgrastim; floxuridine (intraarterial); fludarabine; fluorouracil (5-FU); fulvestrant; gemtuzumab ozogamicin; goserelin acetate; hydroxyurea; Ibritumomab Tiuxetan; idarubicin; ifosfamide; imatinib mesylate; Interferon alfa-2a ; Interferon alfa-2b; irinotecan; letrozole; leucovorin; levamisole; lomustine (CCNU); meclorethamine (nitrogen mustard); megestrol acetate; melphalan (L-PAM); mercaptopurine (6-MP); mesna; methotrexate; methoxsalen; mitomycin C; mitotane; mitoxantrone; nandrolone phenpropionate; Nofetumomab; LOddC; Oprelvekin; oxaliplatin; paclitaxel; pamidronate; pegademase; Pegaspargase; Pegfilgrastim; pentostatin; pipobroman; plicamycin; mithramycin; porfimer sodium; procarbazine; quinacrine; Rasburicase; Rituximab; Sargramostim; streptozocin; talbuvidine (LDT); talc; tamoxifen; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; or a mixture thereof. 6. The method according to claim 3 wherein said at least one secondary anticancer agent is selected from the group consisting of selected from the group consisting of antimetabolites, inhibitors of topoisomerase I and II, alkylating agents, microtubule inhibitors and mixtures thereof. 7. The method according to claim 3 whereien said at least one secondary anticancer agent is aldesleukin; alemtuzumab; alitretinoin; allopurinol; altretamine; amifostine; anastrozole; arsenic trioxide; asparaginase; BCG Live; bexarotene capsules; bexarotene gel; bleomycin; busulfan intravenous; busulfan oral; calusterone; capecitabine; carboplatin; carmustine; carmustine with Polifeprosan 20 Implant; celecoxib; chlorambucil; cisplatin; cladribine; cyclophosphamide; cytarabine; cytarabine liposomal; dacarbazine; dactinomycin; actinomycin D; Darbepoetin alfa; daunorubicin liposomal; daunorubicin, daunomycin; Denileukin diftitox, dexrazoxane; docetaxel; doxorubicin; doxorubicin liposomal; Dromostanolone propionate; Elliott's B Solution; epirubicin; Epoetin alfa estramustine; etoposide phosphate; etoposide (VP-16); exemestane; Filgrastim; floxuridine (intraarterial); fludarabine; fluorouracil (5-FU); fulvestrant; gemtuzumab ozogamicin; goserelin acetate; hydroxyurea; Ibritumomab Tiuxetan; idarubicin; ifosfamide; imatinib mesylate; Interferon alfa-2a; Interferon alfa-2b; irinotecan; letrozole; leucovorin; levamisole; lomustine (CCNU); meclorethamine (nitrogen mustard); megestrol acetate; melphalan (L-PAM); mercaptopurine (6-MP); mesna; methotrexate; methoxsalen; mitomycin C; mitotane; mitoxantrone; nandrolone phenpropionate; Nofetumomab; LOddC; Oprelvekin; oxaliplatin; paclitaxel; pamidronate; pegademase; Pegaspargase; Pegfilgrastim; pentostatin; pipobroman; plicamycin; mithramycin; porfimer sodium; procarbazine; quinacrine; Rasburicase; Rituximab; Sargramostim; streptozocin; talbuvidine (LDT); talc; tamoxifen; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; or a mixture thereof. 8. The method according to claim 1 which is used in combination with radiation therapy. 9. The method according to claim 2 which is used in combination with radiation therapy. 10. The method according to claim 3 which is used in combination with radiation therapy. 11. The method according to claim 4 which is used in combination with radiation therapy. 12. The method according to claim 5 which is used in combination with radiation therapy. 13. The method according to claim 6 which is used in combination with radiation therapy. 14. The method according to claim 7 which is used in combination with radiation therapy. 15. The method according to claim 1 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 16. The method according to claim 2 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 17. The method according to claim 3 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 18. The method according to claim 4 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 19. The method according to claim 5 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 20. The method according to claim 6 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 21. The method according to claim 7 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 22. The method according to claim 8 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 23. The method according to claim 9 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 24. The method according to claim 10 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer. 25. The method according to claim 1 wherein said composition is administered to said patient orally. 26. The method according to claim 1 wherein said composition is administered to said patient parenterally. 27. A method of treating cancer in a human patient with cancer in need comprising administering to said patient a therapeutically effective amount of a composition comprising securinine and/or a pharmaceutically acceptable salt thereof as the sole agent(s) causing increased intracellular granularity and/or converting adherent cancer cells to non-adherent cancer cells leading to cancer cell death in said patient, optionally in combination with at least one secondary anticancer agent and wherein said cancer is lung cancer, breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer. 28. The method according to claim 26 wherein said at least one secondary anticancer agent is aldesleukin; alemtuzumab; alitretinoin; allopurinol; altretamine; amifostine; anastrozole; arsenic trioxide; asparaginase; BCG Live; bexarotene capsules; bexarotene gel; bleomycin; busulfan intravenous; busulfan oral; calusterone; capecitabine; carboplatin; carmustine; carmustine with Polifeprosan 20 Implant; celecoxib; chlorambucil; cisplatin; cladribine; cyclophosphamide; cytarabine; cytarabine liposomal; dacarbazine; dactinomycin; actinomycin D; Darbepoetin alfa; daunorubicin liposomal; daunorubicin, daunomycin; Denileukin diftitox, dexrazoxane; docetaxel; doxorubicin; doxorubicin liposomal; Dromostanolone propionate; Elliott's B Solution; epirubicin; Epoetin alfa estramustine; etoposide phosphate; etoposide (VP-16); exemestane; Filgrastim; floxuridine (intraarterial); fludarabine; fluorouracil (5-FU); fulvestrant; gemtuzumab ozogamicin; goserelin acetate; hydroxyurea; Ibritumomab Tiuxetan; idarubicin; ifosfamide; imatinib mesylate; Interferon alfa-2a; Interferon alfa-2b; irinotecan; letrozole; leucovorin; levamisole; lomustine (CCNU); meclorethamine (nitrogen mustard); megestrol acetate; melphalan (L-PAM); mercaptopurine (6-MP); mesna; methotrexate; methoxsalen; mitomycin C; mitotane; mitoxantrone; nandrolone phenpropionate; Nofetumomab; LOddC; Oprelvekin; oxaliplatin; paclitaxel; pamidronate; pegademase; Pegaspargase; Pegfilgrastim; pentostatin; pipobroman; plicamycin; mithramycin; porfimer sodium; procarbazine; quinacrine; Rasburicase; Rituximab; Sargramostim; streptozocin; talbuvidine (LDT); talc; tamoxifen; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; or a mixture thereof. 29. The method according to claim 27 wherein said cancer is breast cancer, colon cancer, rectal cancer, brain/CNS cancer, liver cancer, ovarian cancer, pancreatic cancer and prostate cancer and wherein said lung cancer is small cell lung cancer.

Details for Patent 9,326,974

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2028-06-05
Merck Teknika Llc	TICE BCG	bcg live	For Injection	102821	06/21/1989		2028-06-05
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2028-06-05
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2028-06-05