IP Law Daily Patents for Indivior’s Suboxone sublingual opioid treatment products are valid and infringed by one competitor
Friday, July 12, 2019

Patents for Indivior’s Suboxone sublingual opioid treatment products are valid and infringed by one competitor

By Cheryl Beise, J.D.

Three Indivior patents for Suboxone sublingual opioid treatment films using a bottom drying heating method were valid and not infringed by two generic drug manufacturers’ products, but a product made by Watson Laboratories was properly held to infringe one asserted patent.

The federal district court in Wilmington, Delaware, did not err in determining that three patents covering Indivior’s Suboxone sublingual opioid treatment films—which were asserted against several drug manufacturers that had obtained FDA approval to market generic versions of Suboxone films—are valid and not infringed by all but one manufacturer, the U.S. Court of Appeals for the Federal Circuit has ruled. The district court correctly found that none of the prior art references disclosed all the drying process limitations and that a person of ordinary skill would not have been motivated to combine the prior art to achieve the requisite uniformity. In addition, the patents-in-suit expressly disclaimed the top air drying methods used by Dr. Reddy’s Laboratories and Alvogen Pine Brook in their generic products, making those products noninfringing. However, Watson Laboratories’ generic product met all of the limitations of one of the asserted patents, and the district court did not abuse its discretion in declining to reopen its infringement judgment after Watson amended its ANDA to remove the bottom heating source limitation. The court vacated as moot the district court’s judgment that a fourth asserted patent was valid, in view of an earlier Federal Circuit decision affirming a PTAB decision finding the patent unpatentable as obvious and anticipated. Circuit Judge Haldane R. Mayer filed a dissenting opinion to express his view that all of the patents were invalid as obvious (Indivior Inc. v. Dr. Reddy’s Laboratories, S.A., July 12, 2019, Lourie, A.).

Several generic drug companies filed Abbreviated New Drug Applications (ANDAs) with the Food and Drug Administration (FDA) to market generic versions of Suboxone® sublingual film ("Suboxone Film"), a quick-delivery opioid addiction treatment drug. Suboxone Film combines two active ingredients: the opioid buprenorphine and the opioid antagonist naloxone. Indivior Inc., Indivior UK Limited, and Aquestive Therapeutics, Inc. (collectively, "Indivior") brought several actions, asserting infringement of four patents listed in the FDA’s Orange Book as covering Suboxone Film.

Patents-in-suit. The patent-in-suit included U.S. Patent Nos. 8,017,150 (the ’150 patent), 8,603,514 (the ’514 patent), and 8,900,497 (the ’497 patent), which are owned by Aquestive and licensed to Indivior. Indivior’s ’514 patent is directed to sublingual films for uniform distribution and delivery of active ingredients. Generally, a film may be made by mixing an active compound with a solvent to form a flowable matrix, casting the mixture onto a planar surface, and then drying the film to produce a solid sheet. The ’497 patent is directed to film manufacturing methods, and on appeal, the parties did not distinguish it from the ’514 patent. The ’150 patent, like the ’514 patent, is directed to uniform pharmaceutical films, but rather than identifying process parameters relevant to film uniformity, as in the ’514 patent, the asserted claims of the ’150 patent claim pharmaceutical films by their components. The ’150 patent claims priority from an earlier provisional application, U.S. Patent Application 60/473,902 (the ’902 application). The fourth patent, U.S. Patent No. 8,475,832 (the ’832 patent), claims film formulations and is owned by Indivior.

Indivior accused Dr. Reddy's Laboratories, S.A. and Dr. Reddy's Laboratories Inc. (collectively, "DRL") of infringing the ’514 and ’150 patents; both DRL and Watson Laboratories Inc., Actavis Laboratories UT, Inc., and Watson (collectively, "Watson") of infringing the ’497 patent; and Alvogen Pine Brook, LLC ("Alvogen") of infringing the ’514 and ’497 patent. The district court held four bench trials and decided multiple issues of infringement and validity concerning the asserted patents.

The parties appealed various adverse judgments, and the Federal Circuit consolidated the appeals. Indivior challenged the district court’s judgments that DRL and Alvogen did not infringe the ’514 patent. Watson appealed from the court’s separate judgment that it did infringe the ’514 patent. The generic manufacturers appealed from the court’s judgments that the ’514, ’497, and ’150 patents are not invalid as obvious and that the ’514 patent is not invalid as indefinite. Indivior cross-appealed the findings that DRL did not infringe either the ’514 or the ’150 patent and that Alvogen did not infringe the ’514 patent. Indivior also challenged the district court’s judgment that certain claims of the ’832 patent would have been obvious over the cited prior art.

’514 patent infringement. The Federal Circuit first affirmed the district court’s judgments that DRL and Alvogen did not infringe the ’514 patent, and that Watson did infringe the ’514 patent.

Indivior’s challenges to the district court’s judgments of noninfringement largely turned on construction of the drying limitation. The district court concluded that the patentee disclaimed drying wet cast films using solely conventional convection air drying from the top. The Federal Circuit agreed with the district court’s construction. In an earlier case involving a related patent (U.S. Patent No. 9,931,305) sharing a specification with the ’514 patent, the Federal Circuit affirmed the district court’s ruling that the inventors expressly disclaimed use of conventional top air drying methods. According to the Federal Circuit, the specification "repeatedly disparages conventional top air drying because such drying does not produce uniform films, the central object of the claimed invention." Moreover, contrary to Indivior’s assertion, the court found that the specification’s disclosure of "zone drying" did not qualify its disclaimer of conventional top air drying. The patent nowhere suggests that zone drying achieves uniform films by using solely conventional top air drying.

Consequently, DRL’s ANDA product—where the sole source of heat in its drying process is hot air coming from above the film—did not infringe any of the asserted claims of the ’514 patent. Similarly, the district court did not err in concluding that Alvogen’s ANDA product was noninfringing. Alvogen’s expert testified that Alvogen’s product used nozzles above the film supply all the hot air to dry the films and that any bottom drying in Alvogen’s process was insubstantial and not within the reach of the asserted claims.

Watson’s appeal did not fare as well. After the district court entered judgment of infringement against Watson, Watson amended its ANDA process to remove bottom heating sources. It then moved under Rule 59 to reopen the court’s judgment. The district court did not abuse its discretion in denying the request. Watson was fully aware of the drying issue prior to trial, and it had never requested the claim construction it sought on appeal. "Furthermore, Watson acknowledges that it can still seek a judgment of noninfringement based on the amended ANDA process even if it fails to secure Rule 59 relief," the court said. The Federal Circuit found no manifest injustice under these circumstances. Watson next argued that the district court clearly erred in finding that Watson’s ANDA product met the viscosity limitation of the ’514 patent claims. The claims require that the viscosity of the matrix be "sufficient to aid" in maintaining uniformity. The district court correctly Watson’s ANDA product plainly encompassed by the most preferred range disclosed in the ’514 patent.

’514 patent validity. The appeals court agreed with the district court that the generic manufacturers failed to prove that the ’514 patent is invalid. Watson and Teva argued that the asserted claims are indefinite because they recite a physical impossibility—a flowable yet solid cast film. The Federal Circuit agreed with Indivior that the claims are not indefinite. The only sensible reading of the cited claim (claim 62) was that the cast film is made from a matrix that is flowable before drying and is not simultaneously dry and flowable.

DRL argued the asserted claims were obvious over U.S. Patents 4,849,246 ("Schmidt"), 6,552,024 ("Chen"), and 5,881,476 ("Strobush"). Schmidt discloses processes for making pharmaceutical films using a roll-coating process with temperature-controlled rollers and a drying tunnel that is controllable in sections. Chen teaches pharmaceutical films made by a casting process and a drying oven that included top air drying nozzles and that have controllable temperature and air speed. Strobush discloses a method for drying photographic and other non-pharmaceutical films without introducing a surface defect called "mottle." The district court found that none of the references disclosed all drying process limitations and that a person of ordinary skill in the art (POSA) would not have been motivated to combine the prior art to achieve the requisite uniformity. The district court determined that a POSA would have one to three years’ experience and would be on a team with an engineer or scientist with experience in manufacturing films. The Federal Circuit discerned no clear error in the district court’s findings. The POSA definition was not unreasonable; Schmidt only discloses a uniform wet film; Chen’s discussion of uniformity involved films lacking an active compound; and a POSA would not have been motivated to modify either Schmidt or Chen in light of Strobush with a reasonable expectation of success because Strobush did not address the uniformity of either pharmaceutical films or non-pharmaceutical films, but rather a surface defect called mottle.

’510 patent infringement. The Federal Circuit affirmed the court’s judgment that DRL did not infringe the ’150 patent under the doctrine of equivalents. Claim 1 recites that the film includes a hydrophilic cellulosic polymer (HCP). DRL substituted polyvinyl pyrrolidone (PVP) for HCP in its ANDA product. The district court held that DRL’s product did not infringe under the doctrine of equivalents because the ’150 patent discloses PVP as an alternative to HCP but did not claim it, thereby dedicating it to the public. The Federal Circuit agreed that the disclosure-dedication rule applied and that the disclosures teaching PVP as an unclaimed embodiment could not be recaptured through the doctrine of equivalents.

’510 patent validity. In challenging the district court’s conclusion that the ’510 patent was not obvious,DRL argued that the district court erred in finding that the ’902 application provided written description support for the asserted claims of the ’150 pa- tent. According to DRL, the application failed to describe the claimed composition with the specificity of the ’150 patent claims. While the specification does not recite the claimed invention in the exact words, the Federal Circuit found that the specification does disclose films with varying amounts of L-PEO, H-PEO, and HCP, describes films with 60% L-PEO as having desirable properties, and states that the remainder of the polymer component apart from L-PEO may include H-PEO and HCP. These disclosures sufficed to convey to a skilled artisan the films claimed in the ’150 patent, according to the court.

’832 patent. In light of prior PTAB decision finding claims 15–19 of the ’832 unpatentable as anticipated and obvious, which the Federal Circuit affirmed in a summary order, the appeals court vacated as moot the district court’s decision that claims 15–19 of the ’832 patent are invalid.

Dissenting opinion. Circuit Judge Haldane R. Mayer filed a dissenting opinion to express his view that the’497, ’514, and ’150 patents are invalid as obvious. According to Judge Mayer, Schmidt and Chen both taught how to obtain uniform distribution of pharmacological active ingredients on a film, and Schmidt disclosed a film having drug content uniformity. Although Indivior suggested that Schmidt only measured weight uniformity rather than drug content uniformity, Indivior’s own patents acknowledge that weight uniformity is a proxy for active ingredient uniformity, Judge Mayer said. In addition, Strobush teaches the precise bottom drying methods that the ’497 and ’514 patents rely upon to achieve uniform dried films. Judge Mayer would have found that the identified skilled artisan would have been motivated to dry films from the bottom rather than from the top, as explicitly disclosed in Strobush. "Indeed, any person having basic familiarity with a kitchen oven would certainly appreciate that, since hot air rises, heating an item from the bottom rather than the top facilitates uniform baking," Judge Mayer said.

Judge Mayer also opined that the ’150 patent is invalid as obvious because the district court erred in concluding that the ’150 patent was entitled to rely on the priority date of the ’902 application. "Nothing in the ’902 application even arguably suggests possession of a polymer component including at least 60% low molecular weight PEO and at most 25% HCP as required by claim," Judge Mayer said.

The case is Nos. 2018-1949 and 2018-2045.

Attorneys: Jeffrey B Elikan (Covington & Burling LLP) for Indivior Inc., Indivior UK Limited, and Aquestive Therapeutics, Inc. Kevin Paul Martin (Goodwin Procter LLP) for Dr. Reddy's Laboratories, S.A., and Dr. Reddy's Laboratories Inc. Stephen R. Smerek (Winston & Strawn LLP) for Watson Laboratories Inc., Actavis Laboratories UT, Inc., and Teva Pharmaceuticals USA, Inc. Steven H. Sklar (Leydig, Voit & Mayer, Ltd.) for Alvogen Pine Brook, LLC.

Companies: Indivior Inc.; Indivior UK Limited; Aquestive Therapeutics, Inc.; Dr. Reddy's Laboratories, S.A.; Dr. Reddy's Laboratories Inc.; Watson Laboratories Inc.; Actavis Laboratories UT, Inc.; Teva Pharmaceuticals USA, Inc.; Alvogen Pine Brook, LLC

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