The interplay (or perhaps utilization) of inter partes review (IPR) in ANDA litigation was illustrated by the Federal Circuit in last month's Dr. Falk Pharma GmbH v. Generico, LLC nonprecedential decision.

The case arose over U.S. Patent No. 8,865,688 owned by Dr. Falk Pharma GmbH and exclusively licensed to Salix.  The claimed invention relates to a method for treating ulcerative colitis using extended-release, granulated mesalamine formulations, sold by Salix as 375 mg capsules under the brand name Apriso®.  The claimed method addressed known deficiencies in the art, particularly premature release of mesalamine, which prevented the drug from reaching the colon where it must act.

Claim 1 of the '688 patent is representative:

1.  A method of maintaining the remission of ulcerative colitis in a subject comprising
    administering to the subject a granulated mesalamine formulation comprising four capsules each comprising 0.375 g of granulated mesalamine once per day in the morning, without food, wherein:
    said method maintains remission of ulcerative colitis in a subject for a period of at least 6 months of treatment;
    remission is defined as a DAI score of 0 or 1;
    the granulated mesalamine formulation is not administered with antacids; and
    wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon.

Generico, LLC; Flat Line Capital LLC; and Mylan Pharmaceuticals Inc. each successfully petitioned for inter partes review of the '688 patent.  Before the Patent Trial and Appeal Board (PTAB), Mylan, Generico, and Flat Line Capital LLC argued that the claims of the '688 patent were obvious over two separate press releases by Salix and a scientific journal reference, in view of either of two other scientific journal references.

In parallel litigation, Mylan filed its ANDA having a Paragraph IV certification and Salix filed suit; the District Court dismissed without prejudice Defendants' affirmative defenses and counterclaims in favor of the outcome of the IPR before the PTAB.

In the IPR, the PTAB in a Final Written Decision determined that claims 1 and 16 were invalid for obviousness.  The PTAB construed the claim language, wherein the first ("administering to the subject a granulated mesalamine formulation comprising four capsules each comprising 0.375 g of granulated mesalamine once per day in the morning, without food") and fourth ("the granulated mesalamine formulation is not administered with antacids") limitations recited steps in the method while the other limitations ("said method maintains remission of ulcerative colitis in a subject for a period of at least 6 months of treatment"; "remission is defined as a DAI score of 0 or 1"; and "wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon") recited the results of the practice of the method.

Important to the PTAB's decision, the specification expressly defined "the DAI score":

Ulcerative colitis disease activity was assessed using a modified Sutherland Disease Activity Index1 (DAI), which is a sum of four subscores based on stool frequency, rectal bleeding, mucosal appearance on endoscopy, and physician's rating of disease activity.  Each subscore can range from 0 to 3, for a total possible DAI score of 12.

The asserted prior art taught the following:

• Press release: Salix's own announcement regarding successful Phase III results with their mesalamine formulations

• "Endonurse": another Salix press release regarding successful Phase III trial results

• Davis: an academic paper showing that the presence of food in the stomach can increase acid and retard release from stomach, compromising mesalamine delivery to colon

• Marakhouski: another academic paper comparing pellets vs tablet administration of 5-acetylsalacylic acid, and that pellets are more advantageous

• Brunner: similar disclosure showing pellets advantageous over tablets

The PTAB found the claims obvious in view of this prior art, considering Marakhouski as the primary reference, based on construction of the term "DAI score" to mean "remission is defined as a DAI score of 0 or 1, where the DAI score is a sum of four subscores."  As explained by the Federal Circuit:

Specifically, the Board found that a skilled artisan would have been motivated to combine the method of the September 2007 Press Release and Endonurse with the teachings of either Marakhouski or Brunner that the granulated mesalamine formulation could be administered without food.  The Board cited as its rationale the fact that all four prior art references pertain to the same or similar granulated mesalamine formulation for treatment of the same disease and because Marakhouski and Brunner teach that an advantage of a granulated mesalamine formulation is the ability to administer the drug independent of food.

The PTAB also found the required reasonable expectation of success from Salix's press releases, wherein the absence of teaching that the drug must be administered with food was interpreted to support the claim term affirmative requiring that the drug not be administered with food; this conclusion was also supported by other asserted art (Davis) and expert testimony.  The Board also rejected Dr. Falk's contention that the art was deficient for not teaching a comparative food study, i.e, comparing the results of administration of mesalamine with and without food.  Finally, the Board rejected Dr. Falk's assertion of objective indicia of non-obviousness, characterizing this evidence as Salix's own failures which did not satisfy the "failure of others" secondary consideration.

In the parallel litigation, the District Court construed the term "wherein 85% to 90% of the mesalamine formulation reaches the terminal ileum and colon" to provide both lower and upper limits on delivery percentages and found noninfringement based on the delivery performance of Mylan's generic drug and whether its formulation was a granulated mesalamine formulation.

The Federal Circuit affirmed the PTAB's obviousness determination in the IPR and vacated as moot the District Court decision (and thus did not reach the correctness of the District Court's noninfringement determination), in an opinion by Judge O'Malley, joined by Judges Lourie and Reyna.

Regarding the PTAB, the Court held that the Board correctly construed the DAI score limitation based on the express definition in the specification, using either the broadest reasonable interpretation test or the Phillips v. AWH test.  This conclusion was also supported by the patentee conceding that the DAI score was "ordinarily understood" to be the sum of four subscores.  In addition, the opinion notes that in patentee's specification, "when the DAI score was identified as being the sum of only two subscores [in the '688 specification] it was called a 'revised Sutherland Disease Activity Index' which is not a term used in the claims."  (This raises the possibility that Dr. Falk could file a narrowing reissue to amend the claims for validity, but the PTO might correctly determine that such an amendment would be broadening rather than narrowing.)

Turning to the "without food" limitation, the Federal Circuit disagreed with Dr. Falk's contention that in this case the PTAB had changed the basis for its obviousness determination from institution to final written decision, contrary to SAS Institute, Inc. v. ComplementSoft, LLC, 825 F.3d 1341 (Fed. Cir. 2016).  Here, the Court explained that what was prohibited was failing to give a patentee the opportunity to address the "new" grounds for the Board's decision.  This was not the case here, in the Federal Circuit's opinion, because Dr. Falk (in the Court's view) had sufficient notice and opportunity and did in fact address the question of whether drug administration without a "food effect" was recognized in the prior art (where the food effect is "that taking the formulation without food is preferable to taking it with food").  The panel also held that the skilled worker had a reasonable expectation of success of achieving the invention set forth in the claims (requiring that the patient not take food) even without the art teaching this feature (typically by containing a "food effect" study), based on "other rationales" for avoiding food, not specified in the opinion.

Finally, the Court also affirmed the PTAB conclusion that, despite there being an affirmative limitation that administration occur "without food" the art did not need a food study to establish this effect because the specification taught that the formulation could be administered with or without food, and that the Board correctly did not find its obviousness conclusion contradicted by the asserted secondary considerations.

This outcome shows that even under circumstances where the district court conducts a trial on infringement under 35 U.S.C. § 271(e)(2), an ANDA defendant can benefit by moving its invalidity case to the PTAB and avoid the cost of putting on affirmative defenses and counterclaims before a lay judge not having the PTAB's purported expertise (or apparent anti-patent bias).

Dr. Falk Pharma GmbH v. Generico, LLC (Fed. Cir. 2019)
Nonprecedential disposition
Panel: Circuit Judges Lourie, O'Malley, and Reyna
Opinion by Circuit Judge O'Malley