Claims for Patent: 7,759,367

Summary for Patent: 7,759,367

Title:	Pharmaceutical compositions and their uses
Abstract:	The present invention relates to compositions comprising 1,2-dihydropiridin-2-one compounds and an immunoregulatory or anti-inflammatory agent. The compositions are useful for the prevention or the treatment of neurodegenerative diseases, for example demyelinating disorders.
Inventor(s):	Smith; Terence (Truro, GB)
Assignee:	Eisai R&D Management Co., Ltd. (Tokyo, JP)
Application Number:	10/497,518
Patent Claims:	1. A pharmaceutical composition comprising I) a compound represented by the following formula or a salt thereof: ##STR01297## wherein, Q indicates O; R.sup.1 indicates X.sup.1-A.sup.1; R.sup.2 indicates X.sup.2-A.sup.2; R.sup.3 indicates hydrogen; R.sup.4 indicates X.sup.3-A.sup.3; and R.sup.5 indicates hydrogen, wherein X.sup.1, X.sup.2, and X.sup.3 each indicates a single bond and A.sup.1, A.sup.2, and A.sup.3 are the same as or different from each other and each indicates a C.sub.6-14 aromatic hydrocarbocyclic group or a 5 to 14 membered aromatic heterocyclic group, wherein each of A.sup.1, A.sup.2, and A.sup.3 is optionally substituted with a hydroxyl group, a halogen atom, an amino group, or a nitrile group; and II) .beta.-interferon. 2. A composition as claimed in claim 1, wherein the compound is one or more of: 3-(2-cyanophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-on- e, 3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one, 3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one, 3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-o- ne, 3-(2-cyanophenyl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one, 3-(2-cyanophenyl)-1-(3-pyridyl)-5-(2-pyrinidinyl)-1,2-dihydropyridin-2-on- e, 3-(2-fluoropyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-- 2-one, and 3-(2-cyanopyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydrop- yridin-2-one. 3. A composition, as claimed in claim 1, wherein the .beta.-interferon is IFN-beta-1a or IFN-beta-1b. 4. A composition, as claimed in claim 3, wherein the IFN-beta-1a is Rebif or Avonex and the IFN-beta-1b is Betaseron or Betaferon. 5. A pharmaceutical composition for the treatment of a demyelinating disorder comprising a therapeutically effective amount of a composition for treating said demyelinating disorder according to claim 1 in combination with a pharmaceutically acceptable carrier or excipient. 6. The pharmaceutical composition according to claim 5, wherein the demyelinating disorder is encephalitis, acute disseminated encephalomyelitis, acute demyelinating polyneuropathy (Guillain Barre syndrome), chronic inflammatory demyelinating polyneuropathy, multiple sclerosis, Marchifava-Bignami disease, central pontine myelinolysis, Devic syndrome, Balo disease, HIV-myelopathy, HTLV-myelopathy, progressive multifocal leucoencephalopathy, or a secondary demyelinating disorder. 7. The pharmaceutical composition as claimed in claim 6, wherein the demyelinating disorder is a secondary demyelinating disease which is CNS lupus erythematodes, polyarteritis nodosa, Sjoegren's syndrome, sarcoid granuloma or isolated cerebral vasculitis. 8. A method for the treatment of a demyelinating disorder, the method comprising administering to a patient a composition as claimed in claim 1. 9. A method for the treatment of a demyelinating disorder, the method comprising administering to a patient a composition comprising I) a compound represented by the following formula or a salt thereof: ##STR01298## wherein, Q indicates O; R.sup.1 indicates X.sup.1-A.sup.1; R.sup.2 indicates X.sup.2-A.sup.2; R.sup.3 indicates hydrogen; R.sup.4 indicates X.sup.3-A.sup.3; and R.sup.5 indicates hydrogen, wherein X.sup.1, X.sup.2, and X.sup.3 each indicates a single bond and A.sup.1, A.sup.2, and A.sup.3 are the same as or different from each other and each indicates a C.sub.6-14 aromatic hydrocarbocyclic group or a 5 to 14 membered aromatic heterocyclic group, wherein each of A.sup.1, A.sup.2, and A.sup.3 is optionally substituted with a hydroxyl group, a halogen atom, an amino group, or a nitrile group; and II) .beta.-interferon wherein the compound and the .beta.-interferon are administered separately, simultaneously or sequentially. 10. A kit comprising, a first container comprising a compound represented by the following formula or a salt thereof: ##STR01299## wherein, Q indicates O; R.sup.1 indicates X.sup.1-A.sup.1; R.sup.2 indicates X.sup.2-A.sup.2; R.sup.3 indicates hydrogen; R.sup.4 indicates X.sup.3-A.sup.3; and R.sup.5 indicates hydrogen, wherein X.sup.1, X.sup.2, and X.sup.3 each indicates a single bond and A.sup.1, A.sup.2, and A.sup.3 are the same as or different from each other and each indicates a C.sub.6-14 aromatic hydrocarbocyclic group or a 5 to 14 membered aromatic heterocyclic group, wherein each of A.sup.1, A.sup.2, and A.sup.3 is optionally substituted with a hydroxyl group, a halogen atom, an amino group, or a nitrile group, and a second container comprising .beta.-interferon, optionally with instructions for use. 11. A kit comprising: a first container comprising therein a compound represented by the following formula or a salt thereof: ##STR01300## wherein, Q indicates O; R.sup.1 indicates X.sup.1-A.sup.1; R.sup.2 indicates X.sup.2-A.sup.2; R.sup.3 indicates hydrogen; R.sup.4 indicates X.sup.3-A.sup.3; and R.sup.5 indicates hydrogen, wherein X.sup.1, X.sup.2, and X.sup.3 each indicates a single bond and A.sup.1, A.sup.2, and A.sup.3 are the same as or different from each other and each indicates a C.sub.6-14 aromatic hydrocarbocyclic group or a 5 to 14 membered aromatic heterocyclic group, wherein each of A.sup.1, A.sup.2, and A.sup.3 is optionally substituted with a hydroxyl group, a halogen atom, an amino group, or a nitrile group; and a second container comprising therein .beta.-interferon, optionally with instructions for use, wherein one or both of the first container and the second container further comprise a pharmaceutically acceptable carrier or excipient. 12. A kit, as claimed in claim 10, for use in the treatment of a demyelinating disorder. 13. A kit, as claimed in claim 10, wherein the compound and the .beta.-interferon, are administered separately, simultaneously, or sequentially. 14. A pharmaceutical composition comprising: 3-(2-cyanophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one or a salt thereof; .beta.-interferon; and at least one pharmaceutically acceptable carrier or excipient. 15. The pharmaceutical composition of claim 14, wherein 3-(2-cyanophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one or a salt thereof and .beta.-interferon are formulated for separate, simultaneous, or sequential administration. 16. A method of treating a demyelinating disorder which comprises administering to a patient in need thereof a pharmaceutically effective amount of a composition of claim 14 or 15. 17. The method of claim 16, wherein 3-(2-cyanophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one or a salt thereof and .beta.-interferon are administered sequentially. 18. A composition as claimed in claim 1, wherein the compound and the immunoregulatory or anti-inflammatory agent are for separate, simultaneous, or sequential administration. 19. A combination comprising: 3-(2-cyanophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one or a salt thereof; and .beta.-interferon. 20. The combination of claim 19, wherein 3-(2-cyanophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one or a salt thereof and .beta.-interferon are for separate, simultaneous, or sequential administration. 21. The method of claim 8, wherein the demyelinating disorder is encephalitis, acute disseminated encephalomyelitis, acute demyelinating polyneuropathy (Guillain Bane syndrome), chronic inflammatory demyelinating polyneuropathy, multiple sclerosis, Marchifava-Bignami disease, central pontine myelinolysis, Devic syndrome, Balo disease, HIV-myelopathy, HTLV-myelopathy, progressive multifocal leucoencephalopathy, or a secondary demyelinating disorder. 22. The method of claim 8, wherein the demyelinating disorder is a secondary demyelinating disease which is CNS lupus erythematodes, polyarteritis nodosa, Sjoegren's syndrome, sarcoid granuloma or isolated cerebral vasculitis.

Details for Patent 7,759,367

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bayer Healthcare Pharmaceuticals Inc.	BETASERON	interferon beta-1b	For Injection	103471	07/23/1993		2021-12-06
Biogen Inc.	AVONEX	interferon beta-1a	For Injection	103628	05/17/1996		2021-12-06
Biogen Inc.	AVONEX	interferon beta-1a	Injection	103628	05/28/2003		2021-12-06
Biogen Inc.	AVONEX	interferon beta-1a	Injection	103628	02/27/2012		2021-12-06
Emd Serono, Inc.	REBIF	interferon beta-1a	Injection	103780	03/07/2002		2021-12-06
Emd Serono, Inc.	REBIF	interferon beta-1a	Injection	103780	12/17/2004		2021-12-06