On February 6, 2019, the US Patent Trial and Appeal Board (PTAB) announced that it has instituted Mylan Pharmaceuticals, Inc.’s inter partes review (IPR) proceeding against Biogen MA Inc’s multiple sclerosis drug, Tecfidera® (IPR2018-01403). Tecfidera® sales exceed $4 billion a year and account for nearly 48% of Biogen’s sales, but there are now questions about its long-term value since it may face generic competition sooner than expected.
The focus of the IPR is on U.S. Patent No. 8,399,514 (the ‘514 patent) which is directed to a method of treating multiple sclerosis in a subject by administering a specific daily dosage, namely 480 mg, of fumarates, specifically dimethyl fumarate (DMF) and/or monomethyl fumarate (MMF). Claim 1 below is reproduced below:
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.
The IPR will focus specifically on the 480 mg per day dosage amount. To win, Mylan will have to prove that it would have been obvious to one skilled in the art to administer a dosage of 480 mg per day. Biogen has already shown that a 720 mg dose was efficacious but a 320 mg dose was not statistically significant. Biogen has previously argued that the magnitude of the clinical efficacy of the 480 mg dose was unexpected and therefore, not obvious. Therefore, a key issue is whether it would have been obvious to a person of ordinary skill in the art to optimize the effective dose and arrive at a dosage of 480 mg per day.
The ‘514 patent is at the heart of the Tecfidera® patent portfolio because it has an expiration date of 2028. Other patents protecting Tecfidera® have expiration dates in April 2019, October 2019, and June 2020, according to the Orange Book. The ‘514 patent is, therefore, critical to protecting Tecfidera’s long-term value beyond 2020.
The new IPR, however, threatens that long-term value. A final decision in an IPR is typically announced 12 months after the IPR has been instituted. In this case, it means that we will probably have a final decision around February of 2020, not accounting for any appeals. If Mylan wins the IPR, it would have to wait until at least the June 2020 patent expires before launching a generic competitor drug. Again, this does not account for any appeals in the IPR. Nevertheless, the earliest possible launch for Mylan could occur in June 2020 which significantly cuts into Tecfidera’s market exclusivity.
The important question now is whether the ‘514 patent can withstand an IPR challenge by Mylan Pharmaceuticals, Inc. While Biogen’s stock dropped more than 7% when it was announced that the IPR was instituted, just because an IPR is instituted by the PTAB does not necessarily mean that a patent will be revoked. Around 60% of petitions are instituted in the pharma space. Once instituted, the likelihood that a patent claim will be cancelled is around 46%, which is a lower percentage compared with other technological areas.
Moreover, the ‘514 patent has already faced an IPR and won. In 2017 it successfully overcame a challenge from Kyle Bass and the Coalition for Affordable Drugs (IPR2015-01993). That IPR was also based on a Section 103 obviousness argument. In that IPR, the PTAB held that the petitioner failed to present any evidence that refuted Biogen’s claims that the magnitude of the clinical efficacy of the 480 mg dose was unexpected and thus, not obvious.
While the new Mylan IPR will also rely on prior art to prove whether the 480 mg dose was obvious or not, Mylan relies on at least one new prior art reference, Schimrigk 2004. The new reference, according to Mylan, shows that “doses of 720 mg/day, 360 mg/day, and those in between, such as 480 mg/day, were likely to be efficacious to treat MS.” In instituting the IPR, the PTAB acknowledged that there was a factual dispute regarding whether Schimrigk 2004 does in fact establish efficacy at 360 mg/day but decided to leave that question for trial. Also to be determined in the IPR will be the question of whether knowledge of efficacy of dimethyl fumerate (DMF) for the treatment of MS at the 720 mg/day dose and/or 360 mg/day dose would have provided sufficient motivation to a person of ordinary skill in the art to optimize the dose of DMF in the treatment of MS and arrive at a 480 mg dose.
Whether Mylan can succeed where the Coalition of Affordable Drugs has failed remains to be seen. We will keep you informed of any new developments in this case.
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