Claims for Patent: 6,747,036

Summary for Patent: 6,747,036

Title:	Methods of treating leukemia
Abstract:	The present invention provides a novel method for treating leukemia and more particularly acute myelogenous leukemia (AML) in a host comprising administering to the host a therapeutically effective amount of a compound having the formula I: ##STR1## wherein B is cytosine or 5-fluorocytosine and R is selected from the group comprising H, monophosphate, diphosphate, triphosphate, carbonyl substituted with a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-10 aryl, and ##STR2## wherein each Rc is independently selected from the group comprising H, C.sub.1-6 alkyl, C.sub.2-6 alkynyl, C.sub.2-6 alkynyl and an hydroxy protecting group; and wherein said compound is substantially in the form of the (-) enantiomer.
Inventor(s):	Gourdeau; Henriette (Montreal, CA), Giles; Francis J. (Houston, TX)
Assignee:	BioChem Pharma Inc. (Laval, CA)
Application Number:	10/046,289
Patent Claims:	1. A method for treating leukemia in a host comprising administering to the host having leukemia synergistically a therapeutically effective amount of doxorubucin and at least one compound of general formula I ##STR8## wherein B is cytosine or 5-fluorocytosine and R is selected from the group comprising H, monophosphate, diphosphate, triphosphate, carbonyl substituted with a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-10 aryl, and ##STR9## wherein each Rc is independently selected from the group comprising H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl and hydroxy protecting groups, and wherein said compound is substantially in the form of the (-) enantiomer. 2. A method according to claim 1, wherein the leukemia is chronic myelogenous leukemia. 3. A method according to claim 1, wherein the leukemia is acute myelogenous leukemia. 4. A method according to claim 1, further comprising the step of administering a multidrug resistance reversing agent or a biological response modifier. 5. A method according to claim 4, wherein the multidrug resistance agent is PSC 833. 6. A method according to claim 4, wherein the biological response modifiers are selected from the group consisting of monoclonal antibodies and cytokines. 7. A method according to claim 4, wherein the cytokines are selected from the group consisting of interferons, interleukins and colony-stimulating factors. 8. A method according to claim 4, wherein the biological response modifiers are selected from the group consisting of Rituxan, CMA-676, Interferon-alpha recombinant, Interleukin-2, Interleukin-3, Erythropoetin, Epoetin, G-CSF, GM-CSF, Filgrastim, Sargramostim and Thrombopoietin. 9. A method according to claim 1, wherein the compound of formula I and the doxorubicin are administered sequentially. 10. A method according to claim 1, wherein the compound of formula I and the doxorubicine are administered simultaneously. 11. A method according to claim 1, wherein said compound of formula I is (-)-.beta.-L-Dioxolane-Cytidine (.beta.-L-oddC) or a pharmaceutically acceptable salt thereof. 12. A method according to claim 1, wherein the step of administering comprises administering to a patient that has been previously treated with Ara-C. 13. A method according to claim 1, wherein said patient is suffering from a leukemia which is non-responsive to treatment with other chemotherapeutic agents. 14. A method according to claim 1, wherein said compound is at least 95% free of the corresponding (+) enantiomer. 15. A method according to claim 1, wherein said compound is at least 97% free of the corresponding (+) enantiomer. 16. A method according to claim 1, wherein said compound is at least 99% free of the corresponding (+) enantiomer. 17. A method according to claim 11, wherein .beta.-L-OddC is administered in an amount of at least 1 mg/kg and doxorubicin is administered in an amount of at least 2 mg/kg. 18. A pharmaceutical composition comprising a synergistically effective amount of doxorubicin and at least one compound of formula I ##STR10## wherein B is cytosine or 5-fluorocytosine, R is H, monophosphate, diphosphate, triphosphate, carbonyl substituted with a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-10 aryl, or ##STR11## Rc is in each case independently H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or a hydroxy protecting group, and wherein said compound is substantially in the form of the (-) enantiomer. 19. A composition according to claim 18, further comprising a pharmaceutically acceptable carrier. 20. A composition according to claim 19, further comprising a multidrug resistance reversing agent or a biological response modifier. 21. A composition according to claim 20, wherein the multidrug resistance agent is PSC 833. 22. A composition according to claim 20, wherein said biological response modifier is a monoclonal antibody or a cytokine. 23. A composition according to claim 22, wherein said cytokine is an interferon, an interleukin or a colony-stimulating factor. 24. A composition according to claim 20, wherein the biological response modifier is Rituxan, CMA-676, Interferon-alpha recombinant, Interleukin-2, Interleukin-3, Erythropoetin, Epoetin, G-CSF, GM-CSF, Filgrastim, Sargramostim or Thrombopoietin. 25. A composition according to claim 19, wherein said compound is (-)-.beta.-L-Dioxolane-Cytidine (.beta.-L-oddC) or a pharmaceutically acceptable salt thereof. 26. A composition according to claim 19, wherein said compound is (-)-.beta.-Dioxolane-5-fluoro-Cytidine (5-FddC) or a pharmaceutically acceptable salt thereof. 27. A composition according to claim 25, wherein said compound is (-)-.beta.-L-Dioxolane-Cytidine (.beta.-L-oddC). 28. A composition according to claim 26, wherein said compound is (-)-.beta.-Dioxolane-5-fluoro-Cytidine (5-FddC). 29. A composition according to claim 19, wherein said compound is at least 95% free of the corresponding (+) enantiomer. 30. A composition according to claim 19, wherein said compound is at least 97% free of the corresponding (+) enantiomer. 31. A composition according to claim 19, wherein said compound is at least 99% free of the corresponding (+) enantiomer. 32. A composition according to claim 19, wherein said composition is in unit dosage and contains 10 to 1500 mg of said compound per unit dosage form. 33. A composition according to claim 19, wherein said composition is in unit dosage and contains 20 to 1000 mg of said compound per unit dosage form. 34. A composition according to claim 19, wherein said composition is in unit dosage and contains 50 to 700 mg of said compound per unit dosage form. 35. A composition according to claim 19, wherein said compound of formula I is (-)-.beta.-L-Dioxolane-Cytidine (.beta.-L-oddC) or a pharmaceutically acceptable salt thereof. 36. A composition according to claim 19, wherein said compound of formula I is (-)-.beta.-L-Dioxolane-Cytidine (.beta.-L-oddC) or a pharmaceutically acceptable salt thereof. 37. A pharmaceutical combination comprising a synergistically effective amount of doxorubicin and at least one compound of formula I ##STR12## wherein B is cytosine or 5-fluorocytosine, R is H, monophosphate, diphosphate, triphosphate, carbonyl substituted with a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-10 aryl, or ##STR13## Rc is in each case independently H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or a hydroxy protecting group, and wherein said compound is substantially in the form of the (-) enantiomer. 38. A combination according to claim 37, wherein said compound and said chemotherapeutic agent are in separate pharmaceutical formulations. 39. A combination according to claim 37, wherein said compound of formula I is (-)-.beta.-L-Dioxolane-Cytidine (.beta.-L-oddC) or a pharmaceutically acceptable salt thereof. 40. A composition according to claim 35, wherein said composition contains doxorubicin and .beta.-L-OddC at a ratio of at least 1:2. 41. A combination according to claim 39, wherein the ratio of doxorubicin to .beta.-L-OddC is at least 1:2.

Details for Patent 6,747,036

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2019-03-29
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2019-03-29
Partner Therapeutics, Inc.	LEUKINE	sargramostim	For Injection	103362	03/05/1991		2019-03-29
Partner Therapeutics, Inc.	LEUKINE	sargramostim	Injection	103362	03/05/1991		2019-03-29
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2019-03-29
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2019-03-29