Claims for Patent: 8,492,441

Summary for Patent: 8,492,441

Title:	Dosage regimen of an S1P receptor agonist
Abstract:	S1P receptor modulators or agonists are administered following a dosage regimen whereby during the initial days of treatment the daily dosage is lower than the standard daily dosage.
Inventor(s):	Eric Legangneux
Assignee:	Novartis Pharmaceuticals Corp
Application Number:	US12/655,049
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,492,441
Patent Claims:	1. A method of administering to a subject in need thereof a medication comprising a S1P receptor agonist, whereby said S1P receptor modulator or agonist is given at a dosage lower than the standard daily dosage of said S1P receptor modulator or agonist during the initial period of treatment and then the dosage is increased, up to the standard daily dosage of said S1P receptor agonist. 2. The method according to claim 1, wherein the medication is for the treatment of an autoimmune condition. 3. The method according to claim 2 wherein the autoimmune condition is multiple sclerosis. 4. The method according to claims 1, wherein the S1P receptor agonist is a compound of formula Ia or Ib wherein Ak is —COOR5k, —OPO(OR5k)2, —PO(OR5k)2, —SO2OR5k, —POR5kOR5k or 1H-tetrazol-5-yl, R5k being H or C1-6alkyl; Wk is a bond, C1-3alkylene or C2-3alkenylene; Yk is C6-10aryl or C3-9heteroaryl, optionally substituted by 1 to 3 radicals selected from halogen, OH, NO2, C1-6alkoxy; halo-substituted C1-6alkyl and halo-substituted C1-6alkoxy; Zk is chosen from wherein the asterisks of Zk indicate the point of attachment between —C(R3k)(R4k)—and Ak of Formula Ia or Ib, respectively; R6 is chosen from hydrogen and C1-6alkyl; and J1 and J2 are independently methylene or a heteroatom chosen from S, O and NR5k; wherein R5k is chosen from hydrogen and C1-6alkyl; and any alkylene of Zk can be further substituted by one to three radicals chosen from halo, hydroxy, C1-6alkyl; or R6 can be attached to a carbon atom of Yk to form a 5-7 member ring; R1k is C6-10aryl or C3-9heteroaryl, optionally substituted by C1-6alkyl, C6-10aryl, C6-10arylC1-4alkyl, C3-9heteroaryl, C3-9heteroarylC1-4alkyl, C3-8cycloalkyl, C3-8cycloalkylC1-4alkyl, C3-8heterocycloalkyl or C3-8heterocycloalkylC1-4alkyl; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R1k may be substituted by 1 to 5 groups selected from halogen, C1-6alkyl, C1-6 alkoxy and halo substituted-C1-6alkyl or —C1-6alkoxy; R2k is H, C1-6alkyl, halo substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl: R2k is in particular methyl; and each of R3k or R4k, independently, is H, halogen, OH, C1-6alkyl, C1-6alkoxy or halo substituted C1-6 alkyl or C1-6alkoxy; and the N-oxide derivatives thereof or prodrugs thereof, or a pharmacologically acceptable salt, solvate or hydrate thereof. 5. The method according to claim 4, wherein the S1P receptor agonist is Compound A or a pharmaceutically acceptable salt thereof. 6. The method according to claim 1, wherein a sub-therapeutic dose of the S1P receptor agonist that is 80 fold less, 40 fold less, 10-fold less or 4-fold less than the standard daily dosage is administered during the initial period of treatment. 7. The method according to claim 1 wherein, during the initial period of treatment, the administered dosage is increased stepwise. 8. The method according to claim 7, wherein the administered dosage is increased stepwise such that the dosage administered on a specific day during the initial period of treatment is the sum of the dosages administered on the previous two days within a range of ±40%. 9. A method for treating a subject in need thereof comprising administering a S1P receptor agonist which induces a negative chronotropic effect in heart rate, to the subject at a daily dosage which is lower than the standard daily therapeutic dosage during an initial period of treatment and thereafter commencing the administration of said S1P receptor modulator or agonist at the required standard daily therapeutic dosage. 10. The method of claim 9, wherein the patient is suffering from an autoimmune condition. 11. The method of claim 10 wherein the autoimmune condition is multiple sclerosis. 12. The method of 9, wherein the S1P receptor agonist is Compound A or a pharmaceutically acceptable salt thereof or prodrug thereof. 13. A method of ameliorating or preventing a negative chronotropic side effect associated with a treatment using an S1P agonist of a subject suffering from an autoimmune disease, comprising administering to the subject in need thereof, said S1P receptor agonist at a daily dosage which is lower than the standard daily dosage during an initial treatment period and raising the daily dosage stepwise up to the standard daily dosage. 14. The method of 13, wherein the S1P receptor agonist is Compound A or a pharmaceutically acceptable salt thereof or prodrug thereof. 15. The method according to claim 9, comprising administering to the subject, a S1P receptor agonist at a daily dosage which is lower than the standard daily dosage during the first 10 days and raising the daily dosage stepwise up to the standard daily dosage. 16. The method according to claim 13, comprising administering to the subject, a S1P receptor agonist at a daily dosage which is lower than the standard daily dosage during the first 10 days and raising the daily dosage stepwise up to the standard daily dosage.