Novartis v. Torrent

By Adrian SanchezShumaker & Sieffert, P.A.

Introduction: In Novartis v. Torrent,[1] the Court of Appeals for the Federal Circuit affirmed a decision by the Patent Trial and Appeal Board finding that all the claims of U.S. Patent No. 8,324,283 (the ’283 patent) were obvious and unpatentable in view of the cited references.  Among other issues, this decision explains how the Court applies standards for obviousness and, in particular, the “secondary” considerations to rebut an obviousness finding.

Background: This article focuses on the features of the ‘283 patent for a solid pharmaceutical (e.g. a tablet) with an active ingredient (fingolimod) that is useful for autoimmune diseases such as multiple sclerosis.  The ‘283 patent explains that properties of fingolimod make it difficult to create a solid form suitable for oral administration, and a solid form has advantages over a liquid form, including storage properties.  The ‘283 patent includes claims combining the active ingredient with an excipient, mannitol, to create the solid tablet.  An excipient is an inactive ingredient used as a carrier, filler, or to dilute (a diluent) the active ingredient.  The ‘283 patent claims a “solid pharmaceutical composition suitable for oral administration comprising mannitol,” and fingolimod. 

Standard of review:  The Court reviews the Board’s legal conclusions de novo and reviews factual determinations under the more deferential substantial evidence standard. The Court explained that obviousness is “a mixed question of fact and law.”  The conclusion that the claims are obvious is a legal determination.  However, motivation to combine and whether the secondary considerations support nonobviousness is a factual determination.

Prima facie obviousness: The petitioners filed a petition for an inter partes review (IPR) challenging the patentability of all the claims of the ‘283 patent.  The Board found that the combination of the Chiba[2] and Aulton[3] references “strongly suggested the claimed two-ingredient combination,” and further found, “additional evidence of the reason to combine fingolimod and mannitol.”   The Board explained, “Chiba teaches that a person of ordinary skill in the art would have been able to identify or easily determine excipients that would have been compatible with fingolimod…. Second, Aulton teaches that mannitol is not only a known diluent for direct compression manufacturing, but also commonly used in wet granulation, which Aulton teaches is ’the most widely used method for pharmaceutical materials.’”

As additional evidence of the reason to combine, the Board pointed to an article by a Novartis expert, “describing how “solution studies can be very helpful” in understanding drug degradations in the solid state.”  Further, the Board referenced Sakai,[4] which teaches the combination of fingolimod and mannitol for a liquid formulation.  Although the “Board found Sakai to be an improper anticipatory reference because the reference does not describe a solid composition…the Board concluded that ‘a suggestion to combine ingredients in the liquid phase would have been relevant to the determination of a person of ordinary skill in the art to combine the same ingredients in the solid phase.’” The Board cited additional references showing that mannitol was known to be useful for creating tablets.  The Court agreed that the additional evidence, such as Sakai, supported the finding that the references would have provided a person skilled in the art a reason to combine mannitol with fingolimod to create a solid tablet form.

Objective indicia of non-obviousness: Objective indicia of non-obviousness (also referred to as “Objective Evidence of Nonobviousness” in the MPEP[5]) may include “unexpected results,” “long-felt but unsolved need,” “industry praise,” and “commercial success.” These, and other objective indicia of non-obviousness are often referred to as secondary considerations.  The term “secondary” is not meant to imply “less important” but instead to mean second in time.  As noted by MPEP § 2142, “[i]f the examiner does not produce a prima facie case, the applicant is under no obligation to submit secondary evidence to show nonobviousness.”

The Court rejected the “unexpected results” argument by Novartis “that the combination of fingolimod and mannitol solved the problem of fingolimod’s unexpected low dose instability.”  The Court rejected the argument because Novartis only presented the unexpected results argument on appeal to the Court.  There was no evidence in the record of proceedings before the Board that Novartis presented an argument of unexpected results in the combination of fingolimod and mannitol. Therefore, whether or not the unexpected results argument was valid, the Court found that because the Board had no evidence of unexpected results to consider, Novartis had waived the argument.

The Court affirmed the Board’s analysis of the “nexus” requirement that “the identified objective indicia must be directed to what was not known in the prior art.” Novartis argued that its drug, which received FDA approval as Gilenya, “enjoyed commercial success, industry praise, and met a long-felt but previously unsolved need.” Novartis further argued that the nexus between its ‘283 patent and the commercial success, etc., was because Gilenya was the first commercially available drug of fingolimod and mannitol in tablet form.  However, the Court cited other case law establishing that “if the feature that creates the commercial success was known in the prior art, the success is not pertinent.”  As described above, the features that made Gilenya a commercial success, i.e., the combination of fingolimod and mannitol, were known in the prior art. The Court found that the Board had evidence that several prior art references disclosed “treating multiple sclerosis using a solid oral form of fingolimod.”  Therefore, the commercial success was a result of features that could be found in the prior art and thus “no nexus exists.”

For patent practitioners, objective indicia of nonobviousness need not be introduced until after the USPTO establishes a prima facie case of obviousness.  When introducing objective indicia of nonobviousness, the assignable cause of the one or more identified objective indicia must be unknown in the prior art in order to be compelling.  The assignable cause, “may well be the novel combination or arrangement of known individual elements.”  Finally, introducing all reasonable objective evidence of nonobviousness early in the process may be valuable.  First, because it supports “the goals of compact prosecution, which encourages the early submission of such evidence.[6]” Second, because “evidence submitted after final rejection may be denied entry into the record.”  Finally, as in Novartis, such evidence if attempted to be first introduced on appeal may be waived.

 

[2] U.S. Patent No. 6,004,565

[3] "Pharmaceutics: The Science of Dosage Form Design"

[4] U.S. Patent No. 6,277,888 (Sakai)

[5] MPEP § 716.01(a).

[6] MPEP ​§ 2142.