The Federal Circuit affirmed a district court’s finding this week that the claims of U.S. Pat. No. 8,399,514 (the ’514 patent) are invalid for lack of written description in Biogen v. Mylan. The ’514 patent claims a method of treating a subject for multiple sclerosis (MS) with a composition consisting essentially of a therapeutically effective amount of 480 mg/day of dimethyl fumarate (DMF), monomethyl fumarate, or a combination thereof, and one or more excipients.

In May 2006, Biogen’s Phase II clinical study showed that a 720 mg/day dosage of DMF effectively treated MS. The FDA suggested Biogen test a dosage of 480 mg/day, conceived of by Biogen’s Phase II lead scientist as early as 2003. During Phase III testing, both the 480 and 720 mg/day dosages were effective to treat MS. Biogen filed a provisional application in 2007, before the Phase III trials that tested the 480 mg/day dose. The Phase II lead scientist was not named as an inventor until 2011, when the title and claims of an application claiming priority to the provisional application, which resulted in the ’514 patent, were focused to treatment of MS. Mylan challenged the ’514 patent for lack of written description.

Written description requires the disclosure in the specification of the patent to show that the inventor was in possession of the invention. Written description is judged based upon the state of the art as of the priority date.

The Court reasoned that if the ’514 patent’s specification were “unambiguously focused on MS”, the skilled artisan might have understood that the use of DMF may be therapeutically linked to MS treatment. Then the skilled artisan would have looked for a DMF dosage range from the specification. However, the Court observed that the specification “casts a wide net for a myriad of neurological disorders…” and “does not focus on MS….” The “totality of the specification focuses primarily on drug discovery.” Only one of the five methods disclosed in the ’514 patent are relevant to the claimed method. Furthermore, only one paragraph in the disclosure contains dosages for DMF, but it is not linked to treatment of any specific disease. This paragraph discloses a DMF dosage range of, inter alia, 480-720 mg/day and is the only mention of a dosage of 480 mg/day. The 480 mg/day dosage “appears at the end of one range among a series of ranges, including DMF concentrations”. The specification’s “focus on basic research and broad DMF-dosage ranges show that the inventors did not possess a therapeutically effective DMF480 dose at the time of filing in 2007.” This was further confirmed by the original inventor named in the provisional application who testified that “his research could [not] be extrapolated to a clinical dose of DMF” and that it “was never the focus of [his] work to inform the clinical dosing of [DMF].”

Biogen asserted that a skilled artisan would have been drawn to the 480 mg/day dose of DMF because it was “anchored” to the effective 720 mg/day dose. The Court indicated that there are multiple DMF dose ranges in the specification including those that were known not to be effective for MS treatment (e.g., 250 mg/day) and that the specification includes DMF doses that are allegedly effective “without even identifying a target disease”, which the Court reasoned “is further indicative that the inventors were not in possession of a complete and final invention as of February 2007.”

Accordingly, the Court affirmed the district court’s finding, that a skilled artisan would not have recognized the 480 mg/day dose of DMF as being effective for treatment of MS. It based this conclusion on the specification’s single reference to the claimed dose, particularly because the specification’s only reference to it was a “part of a wide DMF-dosage range and not listed as an independent therapeutically efficacious dose.” Furthermore, Biogen’s later-established therapeutic efficacy of the claimed dose is irrelevant to the written description analysis.

Judge O’Malley dissented from the majority opinion. The Dissent would reverse and remand the case for reconsideration for three reasons. First, the Dissent disagrees with the district court’s finding that “Biogen was judicially estopped from drawing a distinction between clinical and therapeutic effects”. The Dissent notes a difference between therapeutic and clinical effects, which necessarily impacts how written description is evaluated vis-à-vis the claims of the ’514 patent. The Dissent indicates that the specification is concerned with the therapeutic efficacy of DMF to enhance expression levels of Nrf2 and, therefore, to “mitigate MS symptoms”, not whether it is superior to the current standard of care for MS. The district court prevented Biogen from raising this issue. The Majority responds that the specification’s definition of a therapeutically effective dose features both clinical and therapeutic insignia.

Second, the Dissent states that the district court conflated obviousness with written description. The district court inquired whether a person of ordinary skill in the art would have expected the DMF 480 mg/day dose to be clinically treat MS, rather than whether such a person would understand the inventor possessed the claimed invention.

Third, the Dissent indicates that the district court should not have required blaze marks regarding the claimed DMF dose. In some cases, the Federal Circuit has required “blaze marks,” or statements guiding the skilled artisan to a claimed compound from among a “laundry list” type disclosure in the specification. The Dissent does not believe that the blaze mark precedent applies in this case because the relevant disclosure in the ’514 patent does not provide a laundry list of therapeutically effective doses. Rather it begins with a range with the claimed dose of DMF.

Decisions like this week’s Biogen v. Mylan opinion may increase the burden on pharmaceutical companies to provide adequate written description, particularly for methods of treatment. Viewed in light of recent decisions on enablement and written description in pharmaceutical and biotech cases, this decision continues a trend that may cause difficulty for some life sciences patent owners.