The written description requirement has had a twenty-five year renaissance, particularly in the chemical and biotechnology arts as a way of restricting claim scope to what an inventor has actually invented (seeRegents of the University of California v. Eli Lilly & Co. and Ariad Pharmaceuticals Inc. v. Eli Lilly & Co.). In view of the unpredictability of these arts, the same evidence that supports non-obviousness (due to the skilled worker not having the requisite reasonable expectation of success) can also restrict the scope of what has been described (because there can be much less reliance and supplementation of what the person of ordinary skill would know for disclosures that fail to satisfy the possession test of written description due to that unpredictability). These conflicting rubrics were part of a recent District Court's decision that Biogen failed to provide adequate written description in ANDA litigation styled Biogen Int'l GmBH v. Mylan Pharmaceuticals Inc.
The case arose over Mylan's attempt to get regulatory approval of a generic equivalent of Biogen's Tecfidera® (dimethyl/monomethyl fumarate) multiple sclerosis drug. Biogen asserted several Orange Book-listed patents but the parties dismissed their causes of action on all patents except U.S. Patent No. 8,399,514 patent; claim 1 is representative:
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.
While this litigation was proceeding, Mylan successfully petitioned the Patent Trial and Appeal Board to institute an inter partes review proceeding, on the grounds that the asserted claims of the '514 patent were obvious. The Board found Mylan had failed to show the ‘514 patent claims were obvious and accordingly Mylan was collaterally estopped from asserting obviousness against the ‘'514 patent in the litigation. Accordingly, the only ground Mylan pursued before this Court was that the specification of the '514 patent did not satisfy the written description requirement of 35 U.S.C. § 112(a).
Mylan's arguments on its written description defense were grounded on certain characteristics of the '514 specification and its prosecution history. The '514 patent reflected Biogen's more general research goal of finding treatments for neurological disorders, including but not limited to multiple sclerosis (MS). Specifically, the research underlying the '514 patent disclosure showed that DMF could activate a particular metabolic pathway (the Nrf2 pathway). As originally filed, the claims of the application that matured into the '514 patent did not recite methods of treatment but rather were drawn to methods for identifying compounds that affected the Nrf2 pathway. However, in April 2011, Biogen received the results of a Phase III clinical study showing that a 480mg/day dose of DMF was effective in treating MS (specifically). Biogen replaced the then-pending claims with claims that eventually issued, changed the title of the application, and added as an inventor the scientist who posited that this dosage would be particularly effective as an MS treatment. In addition, Biogen filed a stand-alone provisional application expressly directed to MS treatment with 480mg/day of DMF. Biogen subsequently abandoned this application when the '514 patent was allowed.
Mylan's argument was simple: the invention described in the specification filed in 2007 "bears no resemblance to the invention claimed in 2011." Mylan argued, first, that "a POSA [person of skill in the art] would not have expected the claimed invention—a 480mg/day dose of DMF (BID)—to effectively treat MS" and "that nothing in the specification of the '514 Patent teaches otherwise." Second, Mylan argued that "when viewed as an integrated whole, the combination of selectively-plucked disclosures in the specification of the '514 Patent fails to sufficiently describe the claimed invention—a method of treating MS with a therapeutically effective amount of DMF, i.e., 480mg/day of DMF (BID)." According to Mylan, the reason for this situation is that "Biogen grafted the '514 claims onto a specification written to cover an entirely different set of inventions, conceived of by an entirely different inventor, and filed more than four years before Biogen's 2011 Phase III trial results demonstrated the effectiveness of the 480[mg/day] dose."
Biogen, for its part, asserted that Mylan was relying on arguments it had asserted for obviousness, and that the '514 specification contained express disclosure -- in Method 4 provided in an Example -- that linked each of these three recited elements of the claims ("(1) a method of treating MS with (2) DMF and/or MMF (3) at a dose of 480 mg per day") in a way sufficient to satisfy the written description requirement.
The District Court held that the '514 specification did not show that the inventors possessed the invention on its earliest claimed priority date. The Court noted that, although the '514 specification "[s]pan[s] 30 columns," with the first column focusing on MS, the specification is then directed to disclosure of "how 'the Nrf2 pathway may be activated in neurodegenerative and neuroinflammatory diseases as an endogenous protective mechanism,' and how '[e]merging evidence suggests that [plant-derived] compounds may exert their neuroprotective effects by activating cellular stress-response pathways, including the Nrf2 pathway, resulting in the upregulation of neuroprotective genes."
Biogen argued that the specification disclosed a method that provided the linkage between the elements of the asserted claims. The opinion is blunt, saying plainly "[t]his simply is not so." The Court understands this specification to "broadly describe[] treating neurological diseases with a therapeutically effective amount of DMF; MS is merely one such disease 'among a slew of competing possibilities.'" The Court also cites recitation of "an exhaustive list of 'diseases suitable for the [five] methods described' in the '514 Patent." In view of this listing of a "plethora of neurological diseases," the Court held that there were no specific disclosure that would teach the skilled worker to treat MS with DMF at this dosage. The Court particularly rejected Biogen's contention that the specification would teach the POSA that the '480 mg/day dosage was the preferred dosage,, focusing on the fact that the specification mentions the 480mg/day dosage only once, as part of a preferred range ("from about 480 to about 720mg/day"). The Court found "neither credible no persuasive" Biogen's argument that a POSA would understand that using the lowest effective dose of the narrowest range was preferred. The Court found it more consistent with what was known at the time the application was filed that dosages of 720 mg/day were effective in treating MS, and 120 and 360 mg/day were ineffective.
These decisions illustrate the dangers in relying on less than definitive disclosure in the specification that relies on written description support on the understanding of the POSA to “fill in the blanks” to achieve the claimed invention (as Biogen argued before the district court), while at the same time arguing that the invention is not obvious because the skilled worker would not have a reasonable expectation of success based on the prior art (as Biogen argued before the PTAB in the IPR).
Kevin Noonan is a partner with the law firm McDonnell Boehnen Hulbert & Berghoff LLP and represents biotechnology and pharmaceutical companies on a myriad of issues. A former molecular biologist, he is also the founding author of the Patent Docs weblog, https://patentdocs.typepad.com/.
