Claims for Patent: 7,951,788

Summary for Patent: 7,951,788

Title:	Method of treating cancer and other conditions or disease states using L-cytosine nucleoside analogs
Abstract:	The present invention relates to the use of the compound according to formula (I) Where S is (A) or (B); X is H or F; R.sup.1 is H, an acyl group, a C.sub.1-C.sub.20 alkyl or ether group, a phosphate, diphosphate, triphosphate or a phosphodiester group, a (C) or (D) group; Where Nu is a radical of a biologically active compound such as an anticancer, antihyperproliferative or antiviral compound such that an amino group or hydroxyl group from said biologically active agent forms a phosphate, phosphoramidate, carbonate or urethane group with the adjacent moiety; Each R.sup.8 is independently H, or a C.sub.1-C.sub.20 alkyl or ether group, preferably H or a C.sub.1-C.sub.2 alkyl group; k is 0-12, preferably, 0-2; R.sup.2 is H, an acyl group or a C.sub.1-C.sub.20 alkyl or ether group; and pharmaceutically acceptable salts, solvates or polymorphs thereof for the treatment of tumors, cancer and hyperproliferative diseases, among other conditions or disease states. ##STR00001##
Inventor(s):	Cheng; Yung-chi (Woodbridge, CT)
Assignee:	Yale University (New Haven, CT)
Application Number:	11/992,044
Patent Claims:	1. A method of treating cancer in a patient or subject in need thereof comprising administering to said patient an effective amount of at least one compound according to the structure: ##STR00011## Where S is ##STR00012## X is F; R.sup.1 and R.sup.2 are independently H, an acyl group, a C.sub.1-C.sub.20 alkyl or ether group, a phosphate, diphosphate, triphosphate or a phosphodiester group, or a pharmaceutically acceptable salt thereof, wherein said cancer is stomach, colon, rectal, pancreatic, lung, breast, cervix uteri, corpus uteri, ovary, prostate, testis, bladder, renal, brain/CNS, head and neck, throat, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, leukemia, melanoma, Ewing's sarcoma, small cell lung cancer, choriocarcinoma, rhabdomyosarcoma, Wilms' tumor, neuroblastoma, hairy cell leukemia, mouth/pharynx, oesophagus, larynx, kidney cancer or lymphoma cancer. 2. The method according to claim 1 wherein said patient or subject is human and R.sup.1 and R.sup.2 are each independently H, a C.sub.2-C.sub.18 acyl group or a phosphate group. 3. The method according to claim 2 wherein R.sup.1 and R.sup.2 are each independently H or a C.sub.2-C.sub.18 acyl group. 4. The method according to claim 2 wherein R.sup.1 and R.sup.2 are each H. 5. The method according to claim 1 wherein said cancer is a canderous tumor. 6. The method according to claim 5 wherein said cancer is selected from the group consisting of colon, rectal, pancreatic and melanoma. 7. The method according to claim 1 wherein said cancer is pancreatic cancer or leukemia. 8. The method according to claim 5 wherein said cancer is pancreatic or colon. 9. The method according to claim 5 wherein said cancer is bladder. 10. The method according to claim 5 wherein said cancer is prostate. 11. The method according to claim 5 wherein said cancer is breast. 12. The method according to claim 5 wherein said cancer is lung. 13. The method according to claim 5 wherein said cancer is nasopharyngeal. 14. The method according to claim 5 wherein said cancer is ovarian. 15. The method according to claim 5 wherein said cancer is lymphoma. 16. The method according to claim 5 wherein said cancer is melanoma. 17. The method according to claim 5 wherein said cancer is pancreatic. 18. A method of treating cancer in a patient or subject in need thereof comprising administering to said patient an effective amount of at least one compound according to the structure: ##STR00013## Where S is ##STR00014## X is F; R.sup.1 and R.sup.2 are independently H, an acyl group, a C.sub.1-C.sub.20 alkyl or ether group, a phosphate, diphosphate, triphosphate or a phosphodiester group, and pharmaceutically acceptable salts thereof in combination with at least one additional anticancer agent, wherein said cancer is stomach, colon, rectal, pancreatic, lung, breast, cervix uteri, corpus uteri, ovary, prostate, testis, bladder, renal, brain/CNS, head and neck, throat, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, leukemia, melanoma, Ewing's sarcoma, small cell lung cancer, choriocarcinoma, rhabdomyosarcoma, Wilms' tumor, neuroblastoma, hairy cell leukemia, mouth/pharynx, oesophagus, larynx, kidney cancer and lymphoma cancer. 19. The method according to claim 1 wherein said patient or subject is a human and R.sup.1 and R.sup.2 are each independently H, a C.sub.2-C.sub.18 acyl group or a phosphate group. 20. The method according to claim 19 wherein R.sup.1 and R.sup.2 are each independently H or a C.sub.2-C.sub.18 acyl group. 21. The method according to claim 19 wherein R.sup.1 and R.sup.2 are each H. 22. The method according to claim 20 wherein said cancer is a cancerous tumor. 23. The method according to claim 18 wherein said additional anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent or a microtubule inhibitor. 24. The method according to claim 18 wherein said additional anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent or a microtubule inhibitor. 25. The method according to claim 20 wherein said additional anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent or a microtubule inhibitor. 26. The method according to claim 21 wherein said additional anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent or a microtubule inhibitor. 27. The method according to claim 22 wherein said additional anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent or a microtubule inhibitor. 28. The method according to claim 18 wherein said additional anti-cancer compound is selected from the group consisting of 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; Denileuldn 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; gemcitabine, gemtuzumab ozogamicin; gleevec; 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; plicarmycin; mithramycin; porfimer sodium; procarbazine; quinacrine; Rasburicase; Rituximab; Sargramostim; streptozocin; surafenib; talbuvidine (LDT); talc; tamoxifen; tarceva; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; and mixtures thereof. 29. The method according to claim 19 wherein said additional anti-cancer compound is selected from the group consisting of Aldesleukin; Alemtuzumab; alltretinoin; allopurinol; altretamine; amifostine; anastrozole; arsenic trioxide; Asparaginase; BCG Live; bexarotene capsules; bexarotene gel; bleomycin; busulfin intravenous; busulfan oral; calusterone; capecitabine; carboplatin; 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; gemcitabine, gemtuzumab ozogamicin; gleevec; goserelin acetate; hydroxyurea; Ibriturnomab 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-MLP); mesna; methotrexate; methoxsalen; mitomycin C; mitotane; mitoxantrone; nandrolone phenpropionate; Nofetumomab; LOddC; Oprelvekin; oxaliplatin; paclitaxel; pamidronate; pegademase; Pegaspargase; Pegifigrastim; pentostatin; pipobroman; plicarnycin; mithramycin; porfimer sodium; procarbazine; quinacrine; Rasburicase; Rituximab; Sargramostim; streptozocin; surafenib; talbuvidine (LDT); talc; tamoxifen; tarceva; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; and mixtures thereof. 30. The method according to claim 20 wherein said additional anti-cancer compound is selected from the group consisting of 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; gemcitabine, gemtuzumab, ozogamicin; gleevec; goserelin acetate; hydroxyurea; Ibritumomab Tiuxetan; idarubicin; ifosfamide; imatinib mesylate; Interferon alfa-2a; Interferon alfa-2b; irinotecan; letrozole; leucovorin; levamisole; lomustine (CCNU); mechlorethamine (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; surafenib; talbuvidine (LDT); talc; tamoxifen; taarceva; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; and mixtures thereof. 31. The method according to claim 21 wherein said additional anti-cancer compound is selected from the group consisting of 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; gemcitabine, gemtuzumab ozogamicin; gleevac; goserelin acetate; hydroxyurea; Ibritumomab Tiuxetan; idarubicin; ifosfamide; imatinib mesylate; Interferon alfa-2a; Interferon alfa-2b; irinotecan; letrozole; leucovorin; levamisole; lomustine (CCNU); mechlorethamine (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; surafenib; talbuvidine (LDT); talc; tamoxifen; tarceva; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; and mixtures thereof. 32. The method according to claim 22 wherein said additional anti-cancer compound is selected from the group consisting of 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; gemcitabine, gemtuzumab ozogamicin; gleevac; goserelin acetate; hydroxyurea; Ibritumomab Tiuxetan; idarubicin; ifosfamide; imatinib mesylate; Interferon alfa-2a; Interferon alfa-2b; irinotecan; letrozole; leucovorin; levamisole; lomustine (CCNU); mechlorethamine (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; surafenib; talbuvidine (LDT); talc; tamoxifen; tarceva; temozolomide; teniposide (VM-26); testolactone; thioguanine (6-TG); thiotepa; topotecan; toremifene; Tositumomab; Trastuzumab; tretinoin (ATRA); Uracil Mustard; valrubicin; valtorcitabine (monoval LDC); vinblastine; vinorelbine; zoledronate; and mixtures thereof. 33. The method according to claim 18 wherein said cancer is a cancerous tumor. 34. The method according to claim 33 wherein said cancer is selected from the group consisting of colon, rectal, pancreatic and melanoma. 35. The method according to claim 33 wherein said cancer is pancreatic. 36. The method according to claim 18 wherein said cancer is leukemia. 37. The method according to claim 33 wherein said cancer is colon. 38. The method according to claim 33 wherein said cancer is bladder. 39. The method according to claim 33 wherein said cancer is prostate. 40. The method according to claim 33 wherein said cancer is breast. 41. The method according to claim 33 wherein said cancer is lung or pancreatic. 42. The method according to claim 33 wherein said cancer is nasopharyngeal. 43. The method according to claim 33 wherein said cancer is ovarian. 44. The method according to claim 33 wherein said cancer is lymphoma. 45. The method according to claim 33 wherein said cancer is melanoma. 46. The method according to claim 33 wherein said additional anticancer agent is fluorouracil, oxaliplatin, gemcitabine or mixtures thereof.

Details for Patent 7,951,788

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2025-12-02
Merck Teknika Llc	TICE BCG	bcg live	For Injection	102821	06/21/1989		2025-12-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2025-12-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2025-12-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2025-12-02