Claims for Patent: 7,754,693

Summary for Patent: 7,754,693

Title:	Composition and method for the efficacious and safe administration of halopyruvate for the treatment of cancer
Abstract:	This invention provides compositions and methods for the treatment of cancer. An inhibitor cocktail buffer includes at least one sugar, a non-potassium containing buffer, and an inhibitor having the general formula: ##STR00001## Such an inhibitor cocktail buffer allows for the efficacious and safe delivery of various compounds, including halopyruvates and derivatives thereof, to human cancer patients.
Inventor(s):	Ko; Young Hee (Owings Mills, MD)
Assignee:
Application Number:	11/706,868
Patent Claims:	1. A method for the treatment of cancer, said method comprising the steps of: a) preparing a cocktail buffer having at least one sugar and a buffer; b) adding at least one inhibitor to said cocktail buffer having the following formula ##STR00006## wherein X is selected from the group consisting of: a halide, sulfonate, a carboxylate, an alkoxide, and amine oxide; and R is selected from the group consisting of: OR', N(R'').sub.2, C(O)R''', C1-C6 alkyl, C6-C12 aryl, C1-C6 heteroalkyl, a C6-C12 heteroaryl, H, and an alkali metal; where R' represents H, alkali metal, C1-C6 alkyl, C6-C 12 aryl or C(O)R''', R'' represents H, C1-C 6 alkyl, or C6-C12 aryl, and R''' represents H, C1-C20 alkyl or C6-C12 aryl; forming an inhibitor cocktail buffer; c) diluting said inhibitor cocktail buffer by adding said buffer to a saline solution; and d) administering said diluted inhibitor-cocktail buffer to a patient; wherein said cancer is a cancerous tumor that is positron emission tomography (PET) positive. 2. The method according to claim 1, wherein said buffer is a non-potassium containing buffer. 3. The method according to claim 2, wherein said non-potassium containing buffer is comprised of a sodium phosphate buffer. 4. The method according to claim 1, wherein said at least one sugar is two sugars. 5. The method according to claim 1, wherein said at least one sugar is three sugars. 6. The method according to claim 5, wherein at least one of the sugars is a five carbon sugar. 7. The method according to claim 6, wherein at least two of the sugars are a five carbon sugar. 8. The method according to claim 7, wherein said five carbon sugars are independently selected from the group consisting of mannitol, erytritol, isomalt, lactitol, maltitol, xyolitol, dulcitol, ribitol, inositol, sorbitol, and combinations thereof. 9. The method according to claim 5, wherein at least one of said sugars is glycerol. 10. The method according to claim 5, wherein each of said sugars may be added in a volume up to a maximum solubility of said sugar. 11. The method according to claim 5, wherein said sugars are glycerol, inositol, and sorbitol. 12. The method according to claim 11, wherein said cocktail buffer comprises said glycerol in a range from about 0.1% to about 3%, said inositol in a range from about 1% to about 5%, and said sorbitol in a range from about 30% to about 50%. 13. The method according to claim 1, wherein R of formula (I) is OH and X of formula (I) is selected from the group consisting of: a halide, a sulfonate, a carboxylate, an alkoxide, and an amine oxide. 14. The method according to claim 13, wherein X is a halide selected from the group consisting of: fluoride, bromide, chloride, and iodide. 15. The method according to claim 14, wherein the inhibitor is a 3-halopyruvate selected from the group consisting of: 3-fluoropyruvate, 3-chloropyruvate, 3-bromopyruvate, 3-iodopyruvate, and combinations thereof. 16. The method according to claim 13, wherein X is a sulfonate selected from the group consisting of: triflate, mesylate and tosylate. 17. The method according to claim 12, wherein X is an amine oxide. 18. The method according to claim 17, wherein the amine oxide is dimethylamine oxide. 19. The method according to claim 1, further comprising the step of adding an anticancer drug to said saline solution before said inhibitor cocktail buffer has been added to said saline solution. 20. The method according to claim 1, further comprising the step of adding an anticancer drug to said saline solution after said inhibitor cocktail buffer has been added to said saline solution. 21. The method according to claim 1, further comprising the step of adding an anticancer drug to said cocktail buffer prior to adding said inhibitor to said buffer. 22. The method according to claim 1, further comprising the step of adding an anticancer drug to said inhibitor cocktail buffer after said inhibitor has been added to said buffer. 23. The method according to claim 1, further comprising the step of adding an additional anticancer agent to said cocktail buffer, said additional anticancer agent being selected from the group consisting of: platinum-based agents, nitrogen mustard alkylating agents, nitrosourea alkylating agents, antimetabolites, pyrimidine antimetabolites, hormonal antineoplastics, natural antineoplastics, antibiotic natural antineoplastics, vinca alkaloid natural antineoplastics, dactinomycin, daunorubicin HCI, docetaxel, doxorubicin HCl, epoetin alfa, etoposide (VP-16), ganciclovir sodium, gentamicin sulfate, interferon alfa, leuprolide acetate, meperidine HCl, methadone HCl, ranitidine,HCl, vinblastin sulfate, zidovudine, interleukins 1 through 18, mutants of interleukins 1 through 18, interferons, cytokines, hormones, growth factors, fibroblast growth factor (FGF), nerve growth factor (NGF), growth hormone releasing factor (GHRF), epidermal growth factor (EGF), fibroblast growth factor homologous factor (FGFHF), hepatocyte growth factor (HGF),insulin growth factor (IGF), tumor necrosis factor-.alpha. & .beta. (TNF-.alpha. & .beta.), invasion inhibiting factor-2 (IIF-2), bone morphogenetic proteins 1-7 (BMP 1-7), somatostatin, Lhymosin-.alpha.-1,.gamma.-globulin, superoxide dismutase (SOD), complement factors, anti-angiogenesis factors, antigenic materials, pro-drugs, altretamine, asparaginase, BCG, bleomycin sulfate, busulfan, carboplatin, carmusine, chlorambucil, cisplatin, claladribine, 2-chlorodeoxyadenosine, cyclophosphamide, cytarabine, dacarbazine imidazole carboxamide, dactinomycin, daunorubicin--dunomycin, dexamethosone, doxurubicin, etoposide, floxuridine, fluorouracil, fluoxymesterone, flutamide, fludarabine, goserelin, hydroxyurea, idarubicin HCL, ifosfamide, interferon alfa, interferon alfa 2a, interferon alfa 2b, interferon alfa n3, irinotecan, leucovorin calcium, leuprolide, levamisole, lomustine, megestrol, melphalan, L-sarcosylin, melphalan hydrochloride, MESNA, mechlorethamine, methotrexate, mitomycin, mitoxantrone, mercaptopurine, paclitaxel, plicamycin, prednisone, procarbazine, streptozocin, tamoxifen, 6-thioguanine, thiotepa, vinblastine, vincristine, vinorelbine tartrate, and combinations thereof. 24. The method according to claim 1, further comprising the step of adding an additional anticancer agent to said saline solution, said additional anticancer agent being selected from the group consisting of: platinum-based agents, nitrogen mustard alkylating agents, nitrosourea alkylating agents, antimetabolites, pyrimidine antimetabolites, hormonal antineoplastics, natural antineoplastics, antibiotic natural antineoplastics, vinca alkaloid natural antineoplastics, dactinomycin, daunorubicin HCl, docetaxel, doxorubicin HCl, epoetin alfa, etoposide (VP-16), ganciclovir sodium, gentamicin sulfate, interferon alfa, leuprolide acetate, meperidine HCl, methadone HCl, ranitidine HCl, vinblastin sulfate, zidovudine, interleukins 1 through 18, mutants of interleukins 1 through 18, interferons, cytokines, hormones, growth factors, fibroblast growth factor (FGF), nerve growth factor (NGF), growth hormone releasing factor (GHRF), epidermal growth factor (EGF), fibroblast growth factor homologous factor (FGFHF), hepatocyte growth factor (HGF),insulin growth factor (IGF), tumor necrosis factor-.alpha. & .beta. (TNF-.alpha. & .beta.), invasion inhibiting factor-2 (IIF-2), bone morphogenetic proteins 1-7 (BMP 1-7), somatostatin, Lhymosin-.alpha.-1,.gamma.-globulin, superoxide dismutase (SOD), complement factors, anti-angiogenesis factors, antigenic materials, pro-drugs, altretamine, asparaginase, BCG, bleomycin sulfate, busulfan, carboplatin, carmusine, chlorambucil, cisplatin, claladribine, 2-chlorodeoxyadenosine, cyclophosphamide, cytarabine, dacarbazine imidazole carboxamide, dactinomycin, daunorubicin--dunomycin, dexamethosone, doxurubicin, etoposide, floxuridine, fluorouracil, fluoxymesterone, flutamide, fludarabine, goserelin, hydroxyurea, idarubicin HCL, ifosfamide, interferon alfa, interferon alfa 2a, interferon alfa 2b, interferon alfa n3, irinotecan, leucovorin calcium, leuprolide, levamisole, lomustine, megestrol, melphalan, L-sarcosylin, melphalan hydrochloride, MESNA, mechlorethamine, methotrexate, mitomycin, mitoxantrone, mercaptopurine, paclitaxel, plicamycin, prednisone, procarbazine, streptozocin, tamoxifen, 6-thioguanine, thiotepa, vinblastine, vincristine, vinorelbine tartrate, and combinations thereof. 25. The method according to claim 1, wherein the inhibitor cocktail buffer retains at least 50% of the inhibitor in active form after 2 hours. 26. The method according to claim 1, wherein the inhibitor cocktail buffer retains at least 95% of the inhibitor in active form after 2 hours. 27. A composition for the treatment of cancer, wherein said composition is an inhibitor cocktail buffer formed by a method comprising the steps of: a) preparing a cocktail buffer having at least one sugar and a buffer; and b) adding at least one inhibitor to said cocktail buffer having the following formula ##STR00007## wherein X is selected from the group consisting of: a halide, sulfonate, a carboxylate, an alkoxide, and amine oxide; and R is selected from the group consisting of: OR', N(R'').sub.2, C(O)R''', C1-C6 alkyl, C6-C12 aryl, C1-C6 heteroalkyl, a C6-C12 heteroaryl, H, and an alkali metal; where R' represents H, alkali metal, C1-C6 alkyl, C6-C12 aryl or C(O)R''', R'' represents H, C1-C6 alkyl, or C6-C 12 aryl, and R''' represents H, C1-C20 alkyl or C6-C 12 aryl; forming said inhibitor cocktail buffer; and wherein said cancer is a cancerous tumor that is positron emission tomography (PET) positive. 28. The composition according to claim 27, wherein said buffer is a non-potassium containing buffer. 29. The composition according to claim 28, wherein said non-potassium containing buffer is comprised of a sodium phosphate buffer. 30. The composition according to claim 27, wherein said at least one sugar is two sugars. 31. The composition according to claim 27, wherein said at least one sugar is three sugars. 32. The composition according to claim 31, wherein at least one of the sugars is a five carbon sugar. 33. The composition according to claim 32, wherein at least two of the sugars are a five carbon sugar. 34. The composition according to claim 33, wherein said five carbon sugars are independently selected from the group consisting of mannitol, erytritol, isomalt, lactitol, maltitol, xyolitol, dulcitol, ribitol, inositol, sorbitol, and combinations thereof. 35. The composition according to claim 31, wherein each of said sugars may be added in a volume up to a maximum solubility of said sugar. 36. The composition according to claim 31, wherein at least one of said sugars is glycerol. 37. The composition according to claim 31, wherein said sugars are glycerol, inositol, and sorbitol. 38. The composition according to claim 37, wherein said cocktail buffer comprises said glycerol in a range from about 0.1% to about 3%, said inositol in a range from about 1% to about 5%, and said sorbitol in a range from about 30% to about 50%. 39. The composition according to claim 27, wherein R of formula (I) is OH and X of formula (I) is selected from the group consisting of: a halide, a sulfonate, a carboxylate, an alkoxide, and an amine oxide. 40. The composition according to claim 39, wherein X is a halide selected from the group consisting of: fluoride, bromide, chloride, and iodide. 41. The composition according to claim 40, wherein the inhibitor is a 3-halopyruvate selected from the group consisting of: 3-fluoropyruvate, 3-chloropyruvate, 3-bromopyruvate, 3-iodopyruvate, and combinations thereof. 42. The composition according to claim 39, wherein X is a sulfonate selected from the group consisting of: triflate, mesylate and tosylate. 43. The composition according to claim 39, wherein X is an amine oxide. 44. The composition according to claim 43, wherein the amine oxide is dimethylamine oxide. 45. The composition according to claim 27, further comprising the step of adding an anticancer drug to said saline solution before said inhibitor cocktail buffer has been added to said saline solution. 46. The composition according to claim 27, further comprising the step of adding an anticancer drug to said saline solution after said inhibitor cocktail buffer has been added to said saline solution. 47. The composition according to claim 27, further comprising the step of adding an anticancer drug to said cocktail buffer prior to adding said inhibitor to said buffer. 48. The composition according to claim 27, further comprising the step of adding an anticancer drug to said inhibitor cocktail buffer after said inhibitor has been added to said buffer. 49. The composition according to claim 27, further comprising the step of adding an additional anticancer agent to said cocktail buffer, said additional anticancer agent being selected from the group consisting of: platinum-based agents, nitrogen mustard alkylating agents, nitrosourea alkylating agents, antimetabolites, pyrimidine antimetabolites, hormonal antineoplastics, natural antineoplastics, antibiotic natural antineoplastics, vinca alkaloid natural antineoplastics, dactinomycin, daunorubicin HCl, docetaxel, doxorubicin HCl, epoetin alfa, etoposide (VP-16), ganciclovir sodium, gentamicin sulfate, interferon alfa, leuprolide acetate, meperidine HCl, methadone HCl, ranitidine HCl, vinblastin sulfate, zidovudine, interleukins 1 through 18, mutants of interleukins 1 through 18, interferons, cytokines, hormones, growth factors, fibroblast growth factor (FGF), nerve growth factor (NGF), growth hormone releasing factor (GHRF), epidermal growth factor (EGF), fibroblast growth factor homologous factor (FGFHF), hepatocyte growth factor (HGF),insulin growth factor (IGF), tumor necrosis factor-.alpha. & .beta. (TNF-.alpha. & .beta.), invasion inhibiting factor-2 (IIF-2), bone morphogenetic proteins 1-7 (BMP 1-7), somatostatin, Lhymosin-.alpha.-1,.gamma.-globulin, superoxide dismutase (SOD), complement factors, anti-angiogenesis factors, antigenic materials, pro-drugs, altretamine, asparaginase, BCG, bleomycin sulfate, busul fan, carboplatin, carmusine, chlorambucil, cisplatin, claladribine, 2-chlorodeoxyadenosine, cyclophosphamide, cytarabine, dacarbazine imidazole carboxamide, dactinomycin, daunorubicin-dunomycin, dexamethosone, doxurubicin, etoposide, floxuridine, fluorouracil, fluoxymesterone, flutamide, fludarabine, goserelin, hydroxyurea, idarubicin HCL, ifosfamide, interferon alfa, interferon alfa 2a, interferon alfa 2b, interferon alfa n3, irinotecan, leucovorin calcium, leuprolide, levamisole, lomustine, megestrol, melphalan, L-sarcosylin, melphalan hydrochloride, MESNA, mechlorethamine, methotrexate, mitomycin, mitoxantrone, mercaptopurine, paclitaxel, plicamycin, prednisone, procarbazine, streptozocin, tamoxifen, 6-thioguanine, thiotepa, vinblastine, vincristine, vinorelbine tartrate, and combinations thereof. 50. The composition according to claim 27, further comprising the step of adding an additional anticancer agent to said saline solution, said additional anticancer agent being selected from the group consisting of: platinum-based agents, nitrogen mustard alkylating agents, nitrosourea alkylating agents, antimetabolites, pyrimidine antimetabolites, hormonal antineoplastics, natural antineoplastics, antibiotic natural antineoplastics, vinca alkaloid natural antineoplastics, dactinomycin, daunorubicin HCl, docetaxel, doxorubicin HCl, epoetin alfa, etoposide (VP-16), ganciclovir sodium, gentamicin sulfate, interferon alfa, leuprolide acetate, meperidine HCl, methadone HCl, ranitidine HCl, vinblastin sulfate, zidovudine, interleukins 1 through 18, mutants of interleukins 1through 18, interferons, cytokines, hormones, growth factors, fibroblast growth factor (FGF), nerve growth factor (NGF), growth hormone releasing factor (GHRF), epidermal growth factor (EGF), fibroblast growth factor homologous factor (FGFHF), hepatocyte growth factor (HGF),insulin growth factor (IGF), tumor necrosis factor-.alpha. & .beta. (TNF-.alpha. & .beta.), invasion inhibiting factor-2 (IIF-2), bone morphogenetic proteins 1-7 (BMP 1-7), somatostatin, Lhymosin-.alpha.-1,.gamma.-globulin, superoxide dismutase (SOD), complement factors, anti-angiogenesis factors, antigenic materials, pro-drugs, altretamine, asparaginase, BCG, bleomycin sulfate, busulfan, carboplatin, carmusine, chlorambucil, cisplatin, claladribine, 2-chlorodeoxyadenosine, cyclophosphamide, cytarabine, dacarbazine imidazole carboxamide, dactinomycin, daunorubicin-dunomycin, dexamethosone, doxurubicin, etoposide, floxuridine, fluorouracil, fluoxymesterone, flutamide, fludarabine, goserelin, hydroxyurea, idarubicin HCL, ifosfamide, interferon alfa, interferon alfa 2a, interferon alfa 2b, interferon alfa n3, irinotecan, leucovorin calcium, leuprolide, levamisole, lomustine, megestrol, melphalan, L-sarcosylin, melphalan hydrochloride, MESNA, mechlorethamine, methotrexate, mitomycin, mitoxantrone, mercaptopurine, paclitaxel, plicamycin, prednisone, procarbazine, streptozocin, tamoxifen, 6-thioguanine, thiotepa, vinblastine, vincristine, vinorelbine tartrate, and combinations thereof. 51. The composition according to claim 27, wherein the inhibitor cocktail buffer retains at least 50% of the inhibitor in active form after 2 hours. 52. The composition according to claim 27, wherein the inhibitor cocktail buffer retains at least 95% of the inhibitor in active form after 2 hours. 53. The method according to claim 1, wherein the cancerous tumor is in a tissue selected from the group consisting of brain, colon, urogenital, lung, renal, prostate, pancreas, liver, esophagus, stomach, hematopoietic, breast, thymus, testis, ovarian, skin, bone marrow, and uterine. 54. The composition according to claim 27, wherein the cancerous tumor is in a tissue selected from the group consisting of brain, colon, urogenital, lung, renal, prostate, pancreas, liver, esophagus, stomach, hematopoietic, breast, thymus, testis, ovarian, skin, bone marrow, and uterine.

Details for Patent 7,754,693

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2026-02-16
Amgen, Inc.	EPOGEN/PROCRIT	epoetin alfa	Injection	103234	06/01/1989		2026-02-16
Amgen, Inc.	EPOGEN/PROCRIT	epoetin alfa	Injection	103234			2026-02-16
Amgen, Inc.	PROCRIT	epoetin alfa	Injection	103234			2026-02-16