Generics Successful at Invalidating Novartis Gilenya Patent

by Dennis Crouch

Novartis v. Torrent Pharma, Apotex, and Mylan (Fed. Cir. 2017)

At the conclusion of its Inter Partes Review (IPR) Trial, the Patent Trial & Appeal Board (PTAB) found all claims of Novartis U.S. Patent No. 8,324,283 invalid as obvious.  The PTAB had allowed Novartis to include substitute claims as well, but found those also unpatentable as obvious.  On appeal here, the Federal Circuit affirms.

The ‘283 patent covers a solid combination of a sphingosine-1 phosphate (S1P) receptor agonist (fingolimod) and a sugar alcohol (mannitol). The drug – sold under the trade name Gilenya – is used to treat multiple sclerosis.  This is the first oral disease modifying MS drug approved by the FDA and is a big drug with billions in sales each year.

The particular ingredients were already known in the art, and the active ingredient – fingolimod – was already known as useful for treating autoimmune diseases such as MS.  However, none of the references brought-together the entire combination in a “solid pharmaceutical composition” as required by the claims.  However, the Board found that the combination of references would have led an ordinary skilled artisan to the invention claimed here.

On appeal, the Federal Circuit reviews the Board’s factual findings for substantial evidence – a liberal and forgiving standard that only requires “such relevant evidence as a reasonable mind might accept as adequate to support a conclusion.”  Conclusions of law, however, are reviewed de novo on appeal.  In patent law, the ultimate question of obviousness is deemed a question of law.  However, that ultimate conclusion must be based upon a set of predicate factual conclusions as outlined in Graham v. John Deere.

Perhaps of most relevance for many obviousness cases – the existence of a motivation-to-combine references is deemed a question of fact and thus deference is given to the PTO’s conclusion.  Here, the court noted that the board considered the negative properties of using mannitol (teaching-away), but was not convinced, and sufficient evidence supported the Board’s decision.  The patentee also focused on the fact that the Board’s written decision did not expressly consider all of the patentee’s teaching-away arguments.  On appeal, the Federal Circuit rejected that argument – holding 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.” On this point, the court recognized the tension with Medichem‘s holding that the disadvantages of a reference must be considered, but held that Medichem does not create a bright-line rule requiring express discussion of all disadvantages.  Rather, the Board is “not require[d] . . . to address every argument raised by a party or explain every possible reason supporting its conclusion.” Synopsys, Inc. v. Mentor Graphics Corp., 814 F.3d 1309, 1322 (Fed. Cir. 2016).

Novartis also raised an APA challenge – arguing that the Board did not provide the required notice and an opportunity since the Board included a new reference (Sakai) in its final decision.  Sakai was raised in the IPR petition, but institution was denied for the particular grounds raising Sakai.  On appeal, the Federal Circuit sided with the PTAB holding that – although institution decision rejected Sakai as anticipatory or the primary obviousness reference – the Board did not exclude Sakai from consideration since it is clearly a relevant reference.  “The Board’s discussion of Sakai in the Final Written Decision was not inconsistent with its review of Sakai in the Institution Decision.”  With this explanation, the court was able to justify the PTAB approach and find that the agency did not “change theories in midstream without giving respondents reasonable notice of the change.”   and ‘the opportunity to present argument under the new theory.” Rodale Press, Inc. v. FTC, 407 F.2d 1252, 1256–57 (D.C. Cir. 1968).

What next: I’ll note here that the ‘283 patent is only one of four patents listed in the Orange Book covering Gilenya, one of which is also currently being challenged at the PTAB.


9 thoughts on “Generics Successful at Invalidating Novartis Gilenya Patent

  1. 2

    The following part of this decision on p.19 sounds like the Fed. Cir. is saying that if you fail to adequately brief something to the PTAB in the IPR they are not going to give it much weight on appeal?
    “In a lengthy brief, Novartis’ discussion was relegated to one passing, unsupported sentence, stating that “[w]hile mannitol has some positive properties, it also has negative ones, including expense, poor machinability and possible impurities.” J.A. 7354. Novartis did not direct the Board to the expert declarations it now highlights on appeal, nor did it direct the Board to any record evidence at all. And there is no indication in the record that Novartis elsewhere meaningfully advanced these suggested negatives or developed them in such a fashion as to necessarily overcome the numerous advantages of mannitol identified by Petitioners and discussed in the Final Written Decision.”

    1. 2.1

      “[w]hile mannitol has some positive properties, it also has negative ones, including expense

      So glad you brought this up, Paul. This raises an issue that’s been on my mind for a while now.

      Can the assertion that a component of a claimed invention was deemed in the art to be “too expensive” ever represent a bona fide teaching away from an otherwise acceptable technical solution? I can’t see a policy reason or a legally sensible reason for a doctrine that would lead to such a result.

      Let’s see you figure out a business deal that gives you access to cheap platinum. Does a platinum pencil holder in a form otherwise obvious in view of the art become patentable because of that? Consider the same question in the situation where you have become aware (by polling or some other means) that there is a market out there for this very expensive thing. That realization (or that business insight) represents a non-obvious “innovation” meriting patent protection?

      1. 2.1.1

        “Let’s see you figure out a business deal that gives you access to cheap platinum.”

        Funny you should ask for just that. Here’s a business deal that literally gives everyone access to super cheap platinum:

        link to

        Might happen in our lifetime.

  2. 1

    the court noted that the board considered the negative properties of using mannitol

    Ah, yes: mannitol. Surely one of the most dangerous and destabilizing additives out there.

    1. 1.1

      Mannitol is nasty stuff. It causes explosive diarrhea among other things. Even the source of all knowledge (Wikipedia) has some questions about it:

      “Common side effects from medical use include electrolyte problems and dehydration.[4] Other serious side effects may include worsening heart failure and kidney problems.[4][2] It is unclear if use is safe in pregnancy.”

      Whether it would act this way in pill form, I’m not sure. But I avoid mannitol at all costs.

      1. 1.1.1

        It causes explosive diarrhea among other things

        That’s true of just about every sugar if you eat enough of it.


          And saccharine causes cancer in rats if you feed them enough of it in a short enough period of time. Do you have any other non-sequiturs for us, Malcolm?



            The point is that mannitol is a ubiquitous stabilizer/”bulking agent”/additive. The odds that you consume some mannitol with one or more meals/snacks every day are close to 100%.

            There is no “teaching away” from using mannitol, in general, in any consumable product. Likewise, given the alternatives out there, there is no “teaching away” from not using it.

            Where does that leave the world’s “innovators” who choose mannitol in their combinations (or not)? Answer: It leaves them relying on unexpected results.


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