By Kevin E. Noonan —

Having been instructed once again by the Supreme Court that the Federal Circuit is not special when it comes to review of district court decisions (see, e.g., Teva Pharm. USA, Inc. v. Sandoz, Inc.), the Federal Circuit has increased the quantum of explanation it requires from district courts (and the Patent Trial and Appeal Board even more frequently) in reviewing questions of fact for clear error (see, e.g., Tris Pharma, Inc. v. Actavis Laboratories FL, Inc.).  This practice results in remand back to the district court for further explication of the lower court's reasoning (followed, in at least some cases, by another appeal to the Federal Circuit).  Regardless of the strain on already-overtaxed judicial resources, this trend shows no evidence of diminishing, and the latest case having this outcome was decided earlier this month in Forest Laboratories, LLC v. Sigmapharm Laboratories, LLC.

The case involved several ANDA applicants as Defendants*, each of whom had filed their ANDA over Forest Laboratories' antipsychotic drug Saphris, identified in the opinion as an "atypical antipsychotic containing asenapine maleate" (where asenapine is the trivial name for trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrole).  Known in the art for oral administration in a pill, this drug is administered sublingually or by buccal administration according to the specification and claims of the patent-in-suit, U.S. Patent No. 5,763,476 ("the '476 patent").

Asserted claims 1 and 4 of the '476 patent were set forth in the opinion as being relevant to its decision:

1.  A pharmaceutical composition comprising as a medicinally active compound: trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole or a pharmaceutically acceptable salt thereof; wherein the composition is a solid composition and disintegrates within 30 seconds in water at 37° C.

4.  A method for treating tension, excitation, anxiety, and psychotic and schizophrenic disorders, comprising administering sublingually or buccally an effective amount of a pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5- c]pyrrole or a pharmaceutically acceptable salt thereof.

In a bench trial, the District Court held that the ANDA Defendants had not shown by clear and convincing evidence than claims 1, 2, 4–6, 9, and 10 were invalid for obviousness or failure to provide an adequate written description of the claimed invention, and that Forest had not shown that claims 4, 9, and 10 were infringed as to the Alembic and Breckenridge Defendants.

The Federal Circuit vacated the District Court's judgment regarding invalidity and non-infringement, and remanded for reconsideration of infringement under the correct (i.e., the Federal Circuit's) claim construction, in an opinion by Judge Moore joined by Chief Judge Prost and Judge Dyk.  The panel first addressed the District Court's claim construction with regard to the District Court imbuing claim 1 with the limitation of sublingual and buccal routes of administration (which were expressly recited in claim 4) based on the claim 1 limitation that requires the formulation to comprise solid compositions that disintegrate within 30 seconds in water at 37° C.  The Federal Circuit found no error based on the claim construction rubric that claims must be construed in light of the specification.  Here, the '476 specification affirmatively recited that "[t]he invention relates to a sublingual or buccal pharmaceutical composition" as well as the benefits of these routes of asenapine administration.  The panel also relied on the title of the application itself ("Sublingual or Buccal Pharmaceutical Composition," citing UltimatePointer, L.L.C. v. Nintendo Co., 816 F.3d 816, 823 (Fed. Cir. 2016)) and that the properties and advantages of the recited dissolution profile as it was related to these administration routes "strongly suggest[ed]" that this language was intended to limit the claims to formulations for sublingual or buccal administration.

Having affirmed the District Court's claim construction, the opinion then reviewed its determination that the Defendants had not shown the claims to be invalid for obviousness.  The opinion notes that oral asenapine formulations, on the one hand, and these administration routes (for other drugs) on the other, were known in the prior art, but that there was no motivation to combine these teachings, and further that an observed reduction in cardiotoxicity was an unexpected result of the claimed formulation.  Finally, the District Court found that the claimed formulation satisfied a "long-felt need for a safe, effective, and tolerable atypical antipsychotic useful to treat schizophrenia and mania."  The District Court also considered testimony that sublingual and buccal administration routes posed more difficult compliance problems with schizophrenic patients and also require patients to refrain from drinking or swallowing until the medicine had dissolved, as evidence negating a motivation to combine.

The Federal Circuit did not find that these factual conclusions were clear error; instead the Court opined that "[s]ummarizing testimony, however, is not a clear finding.  Our review would be aided by an express finding regarding whether compliance concerns regarding patients with swallowing difficulties would provide a motivation to combine."

The panel also did not find clear error in the District Court rejecting Defendants' arguments that "having multiple treatment options available would provide a motivation to combine," holding that this was "a generic need for more antipsychotic treatment options [that] did not provide a motivation to combine these particular prior art elements."  Nor was there clear error in the District Court not finding support for a motivation to combine in "general suggestions in the prior art indicating a growing interest in sublingual and buccal formulations at the time of filing."  And the Federal Circuit did not disagree with the District Court's holding that the patentee (originally, inventors working for the patent assignee, Organon) had recognized and solved an unmet need, reducing cardiotoxicity caused by prior art asenapine formulations.

While finding no basis in the District Court's opinion for concluding there was clear error, the Federal Circuit also found insufficient evidence that there was no error, based on "the district court's failure to make an express finding as to whether compliance concerns for patients with trouble swallowing would provide a motivation to combine," and accordingly remanded, presumably to obtain such express findings.

The Federal Circuit was able to decide that the District Court's determination that there was a long-felt but unmet need in the art for the claimed formulations was not error, based on evidence that "there were a variety of existing antipsychotics, they had debilitating negative side effects, which evidence indicates are reduced in Saphris."  On the other hand, the panel held that there was insufficient evidence of unexpected results because the cardiotoxicity of asenapine formulations was not recognized at the time the invention was made and thus the capacity for the claimed formulations to reduce this side-effect could not have been unexpected for being completely unknown to the person of ordinary skill in the art (a curious conclusion but one on its face consistent with prior precedent; see, In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995), and In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997)).

With regard to infringement of claim 4, the District Court found that generic formulations produced by the Alembic and Breckenridge Defendants did not infringe, literally or under the doctrine of equivalents.  This determination was based on these Defendants claiming bipolar disorder as the indication, which the District Court found was not recited in claim 4 (which recites "tension, excitation, anxiety, and psychotic and schizophrenic disorders").  The Federal Circuit was not convinced by the District Court's construction and remanded; as construed by the panel:

The claim language and the specification indicate that "excitation" refers to a symptom rather than a "disorder."  The use of the conjunction "and" before "psychotic and schizophrenic disorders" indicates that "psychotic and schizophrenic disorders" is a distinct item on the list, and that unlike the terms "psychotic" and "schizophrenic," the words "tension," "excitation," and "anxiety" are not describing "disorders."  This is consistent with how "excitation" is used elsewhere in the specification.  '476 patent at 5:55–58.  Moreover, experts for both parties agree that there is no such thing as an "excitation disorder," . . . further indicating the claim covers treatment of the symptom "excitation" rather than treatment of an "excitation disorder."  Although excitation may be a symptom of bipolar I disorder, the district court nevertheless carved bipolar I disorder out of its construction because it concluded that the "language of the '476 patent is directed to 'diseases' and 'disorders,' not to symptoms of such."  . . .  This misreads the plain language of the claims and specification [citations to the record omitted].

Thus, the case returns to the District Court to develop the factual record for its non-obviousness determination with sufficient completeness for (almost assuredly) further review, as well as reconsideration of infringement by Alembic's and Breckenridge's generic formulations.  Whether the current insistence on a crystal clear record by the Federal Circuit is necessary or beneficial to its jurisprudence may be questionable, but it can be expected that district courts will quickly conform their practices (or at least how they write their opinions) to comply with the Federal Circuit's recent mandates, if only to avoid yet further backlogs in their dockets.

* Defendants/ANDA filers:  Sigmapharm Laboratories; Hikma Pharmaceuticals, LLC; Hikma Pharmaceuticals, PLC; Hikma Pharmaceuticals USA Inc., fka West-Ward Pharmaceuticals Corp.; Breckenridge Pharmaceutical Inc.; Alembic Pharmaceuticals LTD; Alembic Global Holdings SA; Alembic Pharmaceuticals Inc.; Amneal Pharmaceuticals LLC; Amneal Pharmaceuticals of New York LLC; and Amneal Pharmaceuticals Co. India Pvt. Ltd.

Forest Laboratories, LLC v. Sigmapharm Laboratories, LLC (Fed. Cir. 2019)
Panel: Chief Judge Prost and Circuit Judges Dyk and Moore
Opinion by Circuit Judge Moore