Dimethyl fumarate- USA

IPR decision: Feb. 05, 2020

AIA Review #	Filing Date	Institution Date	Petitioner	Patent	Respondent	FINAL WRITTEN DECSION
IPR2018-01403	07/13/2018	02/06/2019	Mylan Pharmaceuticals Inc.	8,399,514	Biogen Idec MA Inc.	Claims 1-20 are patentable

On US’514 patent, Coalition for Affordable Drugs previously filed IPRs (IPR2015-01136 & IPR2015-01993) on 05/01/2015 & 09/28/2015. IPR2015-01136 was terminated & in IPR2015-01993, Final Written Decision was issued by PTAB finding claims 1-20 patentable. Sawai also filed IPR (IPR2019-00789) which was instituted on 09/12/2019.

US 8,399,514 (Biogen Idec; Exp: Feb 07, 2028) – OB listed

1. A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.

11. A method of treating a subject in need of treatment for multiple sclerosis consisting essentially of orally administering to the subject about 480 mg per day of dimethyl fumarate, monomethyl fumarate, or a combination thereof.

15. A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate is about 480 mg per day.

20. A method of treating a subject in need of treatment for multiple sclerosis comprising treating the subject in need thereof with a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.

PTAB analysis:

Mylan filed IPR petition citing different prior arts essentially disclosing different dosage ranges (360 mg/day and 720 mg/day) of dimethyl fumarate (DMF) for treatment of multiple sclerosis (MS). None of the prior art disclosed specific 480 mg dose for the treatment of MS. The central question before PTAB was whether discovery of the 480 mg/day dose of DMF in a method of treating multiple sclerosis was obvious because of dose optimization within an established effective range. PTAB said that “discovery of an optimum value of a variable in a known process is usually obvious.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368 (Fed. Cir. 2007); see also In re Aller, 220 F.2d 454, 456 (CCPA 1955) (“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”)

PTAB said that most of the prior arts cited by petitioner cast doubt on lower range, ie 360 mg/day dose. However, there is teaching in the arts about 720 mg/day dose of DMF. In absence of the specific lower range it would not have been routine dose optimization. In one of the ground, PTAB agreed with petitioner & said that prior arts (Kappos 2006 and WO ’342) disclose each claim limitation in the combination of references & POSA would have been motivated to optimize the daily dose of DMF with a reasonable expectation of success. But the patent owner’s evidence of unexpected result overcomes the obviousness challenge. Specifically, 480 mg/day dose was found in fact as efficacious as 720 mg/day dose. Additionally both USFDA & EMA have considered the results & allowed marketing application with 480 mg/day dose. PTAB thus concluded that weight of the evidence on this record sufficiently establishes that the comparable efficacy between the 480 mg/day and 720 mg/day doses would have been unexpected. Therefore, challenged claims 1-20 are not unpatentable.