Biogen sued Mylan for infringement under the Hatch-Waxman Act after receiving Mylan’s paragraph IV certification related to a bioequivalent version of Biogen’s multiple sclerosis (MS) drug, Tecfidera®. As relevant here, Biogen’s U.S. Patent No. 8,399,514 (the “’514 patent”) is directed to methods of treating MS with dimethyl fumarate (DMF) or monomethyl fumarate (MMF) at the specific dose of 480mg/day.
At issue here is whether the claims of the ’514 patent were invalid for lack of written description. In particular, Mylan argued that nothing in the specification of the ’514 patent teaches that a 480mg/day dose of DMF could effectively treat MS. Mylan additionally argued that, viewed as a whole, the specification does not teach the claimed method. According to Mylan, the issued claims were “grafted . . . onto a specification” directed to different inventions, conceived by a different inventor and filed more than four years before Biogen’s clinical trials indicated that a 480mg/day dose of DMF could be used to treat MS. Biogen argued in response that the claimed elements are disclosed in the specification and that Mylan’s argument conflates evidence of obviousness with the requirements for written description.
Following a trial, the district court found the claims of the ’514 patent lacked adequate written description. First, the district court found that the description of a method of treatment in the specification was too limited. In particular, the specification disclosed a method of slowing or preventing neurodegeneration by administering a therapeutically effective amount of DMF or MMF. But the disclosure included a wide range of disorders, including—but not limited to—MS. Thus, there were no “blaze marks” in the specification to lead a person skilled in the art to specifically select MS as the disorder to be treated. And while the specification disclosed 480mg/day as a potential effective dose for treating neurodegeneration, nothing in that disclosure linked the 480mg/day dose to the treatment of MS. The absence of a link between the specific dose and the treatment of MS was particularly problematic in view of the broad range of possible effective doses: 0.1g to 1g per day, or 200mg to 800mg per day.
Biogen argued that because 480mg/day to 720mg/day was the narrowest range disclosed, it should be viewed as the preferred dosage range. The district court rejected that argument, finding it not credible based on: 1) clinical trial results performed around the filing date, which showed that a dose of 720mg/day was effective, but a dose of 360mg/day was not; and 2) testimony from Biogen’s expert, who indicated that he could not determine the most effective dose for treating MS solely from reading the specification.
Although the district court’s analysis focused on the disclosures in the ’514 patent, its reading of the ’514 patent was clearly influenced by the history around it. The ’514 patent claims priority to an application filed with a single inventor who focused on molecular signaling pathways. The claims of the application that led to the ’514 patent were later amended to methods of treating MS with a dose of 480mg of DMF per day after subsequent clinical trials showed efficacy at that dose. One of the clinical investigators was added as an inventor when the claims were amended. However, the specification was not amended to include new matter, thus preserving the original priority date. To the district court, the “disparity” between the written description and the issued claims was telling, as was the fact that the newly added inventor and the original inventor played disparate roles in the MS research program. In reaching its decision, the district court cited testimony from the original inventor who testified that his research—exemplified in three examples in the ’514 patent—was part of a separate preclinical project that was unrelated to the development of DMF to treat MS. He testified that his work had “nothing to do with the efficacy [of DMF] in clinical disease” and would not be “helpful in identifying a therapeutically effective amount of DMF.” With this history in mind, the district court found that Biogen could not show possession of the claimed invention by piecing together disparate disclosures in the ’514 patent.
As further support for its determination, the district court pointed to a separate patent application that was filed at the conclusion of the clinical trials and that similarly claimed methods of treating MS with 480mg/day of DMF. That application, in contrast to the ’514 patent, contained substantial discussion of the clinical trial results. And, according to the district court, it was these disclosures—showing the “unexpected” result that a 480mg/day dose of DMF would provide effective treatment—that would be needed to show possession of the claimed treatment methods under the circumstances of this case. In other words, because the result was unexpected, an adequate written description must teach a person of ordinary skill in the art that a 480mg/day dose of DMF is efficacious in treating MS. The generic disclosure of target diseases and broad ranges of doses in the ’514 patent was not enough.
Practice Tip: Intrinsic and extrinsic evidence, as well as inferences derived from that evidence, can be persuasive when attempting to determine whether generalized disclosures are sufficient to support written description. Actions taken during prosecution should be traced to pre-filing inventive activities and post-filing “unexpected” results, and should be assessed for any impact they may have on the adequacy of a particular disclosure.
Biogen Int’l GmbH v. Mylan Pharm. Inc., Case No. 1:17-cv-116 (N.D. W.Va. Jun. 18, 2020)