Molecular IP
Intellectual Property for Life Sciences, Chemistry and Biotechnology
Patent for Novartis MS Drug Found Invalid in Win for Generics
April 18, 2017

By: Steven M. Kellner

In Novartis AG v. Torrent Pharms. Ltd., No. 2016-1352, 2017 U.S. App. LEXIS 6245 (Fed. Cir. Apr. 12, 2017), the Federal Circuit affirmed the Patent Trial and Appeal Board’s (“Board”) determination that all original claims of U.S. Patent No. 8,324,283 (“283 patent”) and Novartis’ proposed substitute claims were unpatentable as obvious.

The 283 patent relates to a solid pharmaceutical composition suitable for oral administration, comprising a sphingosine-1 phosphate (S1P) receptor agonist (‘fingolimod”) and a sugar alcohol (“mannitol”), which the patent explains is useful for the treatment of certain autoimmune diseases, such as multiple sclerosis (“MS”). The drug is sold by Novartis under the trade name Gilenya®, and is globally a top selling MS drug. It was the first oral disease-modifying drug approved by the Food and Drug Administration (“FDA”) to reduce relapses and delay disability progression in patients with relapsing forms of MS.

During inter partes review, Torrent argued that the claims of the 283 patent were unpatentable as obvious over a combination of U.S. Patent No. 6,004,565 (“565 patent”) and non-patent literature on drug dosing. The 565 patent teaches the use of immunosuppressive compounds with fingolimod as the preferred species. The non-patent literature teaches the use of tablets and capsules using mannitol to administer drugs orally. Neither of the references disclosed the formulation of fingolimod and mannitol in a “solid pharmaceutical composition” as required by the claims. However, the Board found that the combination of references would have led a person skilled in the art to arrive at the invention claimed in the 283 patent.

The Federal Circuit reviews review the Board’s legal conclusions, such as the ultimate question of obviousness, de novo. However, the underlying factual determinations are reviewed for substantial evidence, which is “such relevant evidence as a reasonable mind might accept as adequate to support a conclusion.” Consol. Edison Co. v. NLRB, 305 U.S. 197, 229, 59 S. Ct. 206, 83 L. Ed. 126 (1938); see In re Applied Materials, Inc., 692 F.3d 1289, 1294 (Fed. Cir. 2012).

Giving this deference to the Board’s conclusion on the motivation-to-combine, a factual determination, the Federal Circuit found substantial evidence to support the Board’s finding on the motivation to combine the 565 patent and the non-patent literature. The court was not persuaded by Novartis’s arguments that the Board erred in its motivation to combine analysis because it failed to read the prior art as a whole and overlooked critical evidence of mannitol’s known disadvantages as an excipient for solid compositions. Novartis went further to say that because the Board did not expressly state that it was weighing all of these negatives against mannitol’s positives, Novartis contends that the Board’s motivation to combine analysis was legally flawed.

Although the court previously stated in Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157 (Fed. Cir. 2006), that prior art must be considered as a whole and the disadvantages of a reference must be considered in addition to the benefits, it clarified that there is no requirement that the Board expressly discuss each and every negative and positive piece of evidence lurking in the record to evaluate a cursory argument.

Ultimately, the court held that substantial evidence supports the Board’s finding that, despite mannitol’s potentially negative characteristics, it was nevertheless a valid consideration as an excipient for solid oral pharmaceuticals and a person of skill in the art would have been motivated to combine fingolimod and mannitol in the manner claimed by the 283 patent.

While the 283 patent is only one of four patents listed by the FDA for Gilenya, the Federal Circuit’s decision chips away at Novartis’s exclusivity for its lucrative MS drug.