Case No. IPR2015-01993 (US 8,339,514 B2)
Final Written Decision
March 21, 2017
Brief Summary: Board found CAD V failed to show obviousness by a preponderance of the evidence as Biogen presented persuasive evidence of unexpected results (“the magnitude of the clinical efficacy” of the claimed dose “would have been unexpected”).
Summary: CAD V’s petition for IPR of Biogen’s US 8,399,514 (relating to Biogen’s multiple sclerosis (MS) drug Tecfidera® (dimethyl fumarate (“DMF”))) claiming methods for treating MS on the basis of a reasonable likelihood that it would prevail on obviousness grounds was granted based on three different combinations of prior art (Kappos, Clinical Trials, Joshi ‘999 and ICH for claims 1-6, 8-16 and 20; the same four references plus Joshi ‘992 for claim 7; and the initial four references plus Begleiter for claims 17-19). “Claim 20, the broadest” includes the limitation “wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day”. The Decision explained that “[t]he parties disagree on the level of skill of the person ordinarily skilled in the art” but the Board wrote that that person “is a hypothetical person that is presumed to be aware of all the relevant prior art” (Custom Accessories, FC 1986) and that “[g]eneralities that the person of ordinary skill in, for example, an M.D. with three years experience in some field or another, provides little help in establishing what that person knows or doesn’t know” (“As long as the art relied upon is from the same or analogous fields the hypothetical person is presumed to be aware of it.” In re Gorman, FC 1991). It held “that the cited references are representative of the level of ordinary skill in the art.” Kappos describes results of a MS Phase II trial using 120, 360 and 720 mg/day of DMF. Joshi ‘999 is a US patent publication describing methods of treating MS using an effective amount of DMF. “Clinical Trials” describes a clinical study using DMF for MS. “ICH” is a technical publication presenting general guidance for determining drug doses. Biogen argued that even in view of these references, “[t]he magnitude of the clinical efficacy exhibited by administering the 480 mg/day dose was unexpected”, relying on “post-filing date Phase III trials” (the “DEFINE study” and the “CONFIRM study” (480 and 720 mg/day DMF)) to show “‘surprisingly-that a 480 mg/day dose of DMF proved to have similar efficacy’ to the 720 mg/day taught by Kappos”. Expert testimony of Dr. Thisted, Dr. Brundage and Dr. Rudick was also submitted as evidence of unexpected results. The Board reviewed their backgrounds and found them to be “qualified by knowledge, skill, experience, training and education that is sufficiently related to the claimed invention that they may provide opinion testimony”. The Decision explains that “[a]ll three experts testif[ied] that one skilled in the art would have expected the efficacy of 480 mg/day to be closer to that of 360 mg/day, a dose which did not have a statistically significant effect, than to 720 mg/day dose described by Kappos” and “Drs. Thisted and Rudick further testif[ied] that the reported similar efficacy…would have been unexpected.” The Board found that “the degree of efficacy of the 480 mg/day dose of DMF would have been unexpected” (“the magnitude of the clinical efficacy…would have been unexpected”). This was found to be so even though “one having ordinary skill in the art would have had ample reason to use routine experimentation, including appropriate clinical trials, to determine the optimum doses for MS treatment” since “obviousness is not established when the results of optimization are shown to result in a propery or benefit that a person of ordinary skill in the relevant art would have found to be unexpected” (Antonie, CCPA 1977; Proctor & Gamble, FC 2009). Thus, the Board concluded the claims were not shown to be unpatentable by a preponderance of the evidence. It is also noted that FN1 of the Decision explains that Biogen was allowed to file a motion to antedate the Kappos reference and argued that another (Joshi) was not eligible prior art under § 103(c), but “[b]ecause post-filing date evidence demonstrates unexpected results, [it] did not reach” those issues.