Torrent Pharmaceuticals Ltd. / Apotex, Inc. / Mylan Pharmaceuticals Inc. (Petitioner) v. Novartis AG / Mitsubishi Pharma Corp. (Patent Owner)

IPR Case IPR2014-00784, IPR2015-00518
U.S. Pat. No. 8,324,283 B2
September 24, 2015

Brief Summary: Petitioner found to have shown by a preponderance of the evidence that prior art teaching compound (first reference) and use of mannitol in pharmaceutical compositions (second reference) renders obvious claims 1-32 of U.S. Pat. 8,324,283B2 (and proposed amended claims 33-64) relating to the multiple sclerosis treatment Gileyna. Proposed new claims not shown to be patentably distinct from the prior art.

Summary: The PTAB issued a Final Written Decision, finding Patent Owner’s (“Novartis”) claims 1-32 U.S. Pat. 8,324,283B2 (and proposed amended claims 33-64) relating to the multiple sclerosis treatment Gileyna (an orally administered composition of sphingosine-1 phospate (SIP) receptor agonist and a sugar alcohol) invalid as obvious, as requested by Petitioner (“Torrent”). The Board construed “solid pharmaceutical composition suitable for oral administration” essentially as it reads, “is stable” to mean “meets stability requirements of a test required by FDA for approval”, “has substantially uniform distribution…throughout the composition” as “meets content uniformity requirements for active ingredients in solid oral dosage forms as defined by the [United States Pharmacopeia]”, “rough particle surface” as “with higher surface area than a sphere of a diameter equal to the average diameter of the particle in question” (refusing Novartis’ request to define the term as “with higher surface area than a sphere” as it would “interpret the term as essentially unbounded”). The prior art considered were Chiba et al. (U.S. Pat. No. 6,004,565, teaching immunosuppressive compounds such as fingolimod) and Alton (a scientific publication teaching the use of mannitol and Mg stearate in tablets and capsules to administer drugs orally). Regarding claim 19, the Board agreed with Novartis that Torrent et al. bore “the burden of persuasion regarding a reason for the person of ordinary skill in the art to combine the teachings of Chiba and Aulton…by a preponderance of the evidence” (35 USC § 316(e)) “as part of their ‘proposition of unpatentability’”. It disagreed with Novartis’ position that “mere discovery of a new reason [“newly discovered low-dose instability”] to combine fingolimod and mannitol renders nonobvious an invention that was known in the prior art” (“a claim is not rendered patentable by virtue of being motivated in the inventors’ minds by a newly discovered advantage of the prior art combination…as long as there was some reason to combine the prior-art teachings” (In re Wiseman, CCPA 1979; Cross Med. Prods., FC 2005; “it does not matter that the prior art failed to recognize this advantage of a fingolimod-mannitol combination…[T]he motivation to combine the references does not have to be identical to that of the [patentee] to establish obviousness” (In re Kemps, FC 1996)). Novartis argued another prior art reference (Sakai, U.S. Pat. No. 6,277,888 B1) was not relevant as it only described “liquid-phase pharmaceutical compositions, as opposed to the claimed solid oral dosage forms” but the Board disagreed (based on part on an article written by Novartis’ declarant). At least three general references were also cited (e.g., Remington’s). Together, these were found to provide at least “an implicit motivation” (Dystar, FC 2006). And the Board did not find a teaching away as in Leo Pharm. (FC 2013). It also found a reasonable expectation of success in making the combination. “[E]vidence of unexpected results” was not found to be “commensurate in scope with the claims” (“claim 19 is not limited to any particular dose or dose range” and stability tests were “limited to a single, specified dose”). Evidence of a long-felt need, industry praise and commercial success were found to be “due to an element in the prior art” (e.g., “a need merely for a solid oral [MS] medication, not specifically for a medication of the form recited in claim 19”); therefore, “no nexus exists” (Tokai, FC 2011). The broader claims, including all the features of claim 19 (i.e., claims 1, 3, 4 and 32 including, e.g., “sugar alcohol” vs. “mannitol”), were also found obvious (Callaway, FC 2009). Claims requiring the hydrochloride salt, a lubricant, percentages by weight, micronized agonist, a particular form (tablet, capsule), use in treating various conditions, “mean particle size”/“bulk density” of mannitol (reason for using particular type not shown to be “unknown in the prior art”, or that the same was “critical in achieving the desired content uniformity”). Thus, each of claims 1-32 were found unpatentable. Novartis’ also proposed new claims 33-64; the burden for such is “on the patent owner to show patentable distinction over the prior art of record and also [the] prior art known to the patent owner” (Idle Free, IPR2012-00027). If the Patent Owner “sets forth a prima facie case of patentablity of narrower substitute claims over the prior art of record, the burden shifts to Petitioner” but the “ultimate burden of persuasion remains with the Patent Owner” (Id.) The Board concluded Novartis had not demonstrated the patentability of the proposed claims (directed, e.g., to “stable” composition, “substantially uniform distribution”, “made on automated equipment”, between 0.1 and 10 weight percent fingolimod, sugar alcohols having “a rough surface”). Various motions to exclude expert testimony and the like were also considered and discussed.

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