United Therapeutics Corporation v. Liquidia Technologies, Inc.

Case: 23-1805 Document: 52 Page: 1 Filed: 12/20/2023 NOTE: This disposition is nonprecedential. United States Court of Appeals for the Federal Circuit ______________________ UNITED THERAPEUTICS CORPORATION, Appellant v. LIQUIDIA TECHNOLOGIES, INC., Appellee ______________________ 2023-1805 ______________________ Appeal from the United States Patent and Trademark Office, Patent Trial and Appeal Board in No. IPR2021- 00406. ______________________ Decided: December 20, 2023 ______________________ DOUGLAS H. CARSTEN, McDermott Will & Emery, LLP, Irvine, CA, argued for appellant. Also represented by ARTHUR PAUL DYKHUIS; ADAM WILLIAM BURROWBRIDGE, Washington, DC; WILLIAM COVINGTON JACKSON, Goodwin Procter LLP, Washington, DC; SHAUN R. SNADER, United Therapeutics Corporation, Washington, DC. SANYA SUKDUANG, Cooley LLP, Washington, DC, ar- gued for appellee. Also represented by BRITTANY CAZAKOFF, JONATHAN DAVIES. Case: 23-1805 Document: 52 Page: 2 Filed: 12/20/2023 2 UNITED THERAPEUTICS CORPORATION v. LIQUIDIA TECHNOLOGIES, INC. ______________________ Before LOURIE, PROST, and REYNA, Circuit Judges. LOURIE, Circuit Judge. United Therapeutics Corporation (“UTC”) appeals from the final written decision of the U.S. Patent and Trademark Office Patent Trial and Appeal Board (“the Board”) in an inter partes review (“IPR”) concluding that claims 1–8 of U.S. Patent 10,716,793 (“the ’793 patent”) are unpatentable. Liquidia Techs., Inc. v. United Therapeutics Corp., No. IPR2021-00406, 2022 WL 2820717 (P.T.A.B. July 19, 2022) (“Decision”). For the following reasons, we affirm. BACKGROUND UTC owns the ’793 patent, which is directed to meth- ods of treating pulmonary hypertension comprising inhala- tion of treprostinil. Claim 1 is the only independent claim. It reads as follows: 1. A method of treating pulmonary hypertension comprising administering by inhalation to a hu- man suffering from pulmonary hypertension a therapeutically effective single event dose of a for- mulation comprising treprostinil or a pharmaceu- tically acceptable salt thereof with an inhalation device, wherein the therapeutically effective single event dose comprises from 15 micrograms to 90 mi- crograms of treprostinil or a pharmaceutically ac- ceptable salt thereof delivered in 1 to 3 breaths. ’793 patent at col. 18, ll. 23–31. As relevant here, depend- ent claims 4, 6, and 7 include additional limitations di- rected to dry powders. Those claims read as follows: 4. The method of claim 1, wherein the inhalation device is a dry powder inhaler. Case: 23-1805 Document: 52 Page: 3 Filed: 12/20/2023 UNITED THERAPEUTICS CORPORATION v. 3 LIQUIDIA TECHNOLOGIES, INC. 6. The method of claim 4, wherein the formula- tion is a powder. 7. The method of claim 6, wherein the powder comprises particles less than 5 micrometers in di- ameter. Id. at col. 18, ll. 36–37, 40–43. Liquidia Technologies, Inc. (“Liquidia”) petitioned for IPR of all claims of the ’793 patent, asserting that they would have been obvious over, inter alia, U.S. Patent 6,521,212 (“the ’212 patent”), in view of Voswinckel JESC (“JESC”) 1 and Voswinckel JAHA (“JAHA”) 2 (collectively, “the Voswinckel abstracts”). The ’212 patent, an unrelated patent owned by UTC, is directed to methods of delivering benzindene prostaglandins, such as treprostinil sodium, to patients via inhalation to treat pulmonary hypertension. See ’212 patent at Abstract, J.A. 1207. JESC is an abstract that describes a study in which patients inhaled solutions of treprostinil in concentrations of 16, 32, 48, and 64 μg/mL via a nebulizer. See J.A. 1240. JAHA is an abstract that describes a study in which patients inhaled solutions of treprostinil sodium via a nebulizer in 3 single breaths. See id. at 1243. Before the Board, UTC challenged the prior art status of the Voswinckel abstracts, arguing that Liquidia had failed to adequately show that those references qualified as “printed publications” under pre-AIA 35 U.S.C. § 102(b). 1 R. Voswinckel et al., Inhaled treprostinil is a potent pulmonary vasodilator in severe pulmonary hypertension, 25 EUROPEAN HEART J. 22 (2004), J.A. 1234–1240. 2 Robert Voswinckel et al., Inhaled Treprostinil So- dium (TRE) For the Treatment of Pulmonary Hypertension, in Abstracts from the 2004 Scientific Sessions of the Amer- ican Heart Association, 110 CIRCULATION III-295 (Oct. 26, 2004), J.A. 1241–43. Case: 23-1805 Document: 52 Page: 4 Filed: 12/20/2023 4 UNITED THERAPEUTICS CORPORATION v. LIQUIDIA TECHNOLOGIES, INC. Decision at *3. Specifically, UTC argued that, because in its petition Liquidia relied on those abstracts having been stored in libraries, it was required to establish that the ab- stracts would have both been available at the library and sufficiently indexed or categorized by priority date. Id. at *4. The Board observed, however, that Liquidia had not relied solely on the availability of those references in librar- ies to establish their prior art status. Id. Rather, Liquidia had also asserted that each abstract had been presented at a public conference and that they were both cited in other documents dating from before the priority date of the ’793 patent. Id. On the second of these two theories, the Board concluded that Liquidia had shown by a preponderance of the evidence that each of the Voswinckel abstracts was prior art because it had been cited in a “research aid,” i.e., a publicly accessible article that provided a “sufficiently definite roadmap leading to” the abstract. Id. at *5 (quot- ing Blue Calypso, LLC v. Groupon, Inc., 815 F.3d 1331, 1350 (Fed. Cir. 2016)). Having found the Voswinckel abstracts to be prior art, the Board concluded that a person of ordinary skill in the art would have been motivated to combine those abstracts with the ’212 patent to arrive at the claimed invention. See id. at *5–9. This, the Board found, was true despite UTC’s evidence of objective indicia of nonobviousness, such as un- expected results, copying, and long-felt and unmet need. Id. at *9–13. Accordingly, the Board found all claims of the ’793 patent unpatentable as obvious. See id. at *15. UTC requested rehearing of the Board’s decision, and included a request for rehearing by the U.S. Patent and Trademark Office’s Precedential Opinion Panel (“the Panel”) on the issue of whether or not the Voswinckel ab- stracts were prior art. See Liquidia Tech., Inc. v. United Therapeutics Corp., IPR2021-00406, Paper 81 (Oct. 26, 2022) at 2, J.A. 885. The Panel denied UTC’s request but determined that the Board had failed to consider whether the “research aids” in which the abstracts were cited were Case: 23-1805 Document: 52 Page: 5 Filed: 12/20/2023 UNITED THERAPEUTICS CORPORATION v. 5 LIQUIDIA TECHNOLOGIES, INC. themselves available prior to the critical date of the ’793 patent, i.e., May 15, 2005. Id. It also determined that the Board had not adequately addressed whether the Voswinckel abstracts “were publicly accessible by way of their presentation and/or inclusion in distributed materi- als, such as at a conference or library.” Id. Accordingly, the Panel directed the Board to, in its consideration on re- hearing, “clearly identify whether the [Voswinckel ab- stracts] qualify as prior art.” Id. at 3, J.A. 886. In its decision on rehearing, the Board maintained that the Voswinckel abstracts were prior art. See Liquidia Tech., Inc. v. United Therapeutics Corp., IPR2021-00406, Paper 82 (Feb. 2, 2023) (“Rehearing Decision”), J.A. 50–67. Conceding that it had overlooked the fact that the research aids did not pre-date May 15, 2005, see id. at 5–7, J.A. 54–56, the Board nevertheless found that Liquidia had ad- equately shown that the abstracts had been publicly dis- tributed at conferences prior to that date, id. at 7–12, J.A. 56–61. Specifically, the Board concluded that JESC was distributed at the European Society of Cardiology Congress that was held from August 28, 2004, to September 1, 2004, in Munich, Germany, and that JAHA was distributed at the American Heart Association’s Scientific Sessions that occurred from November 7, 2004, to November 10, 2004, in New Orleans, Louisiana. Id.; see J.A. 1241. Both parties’ experts agreed that a person of ordinary skill in the art would have been one of over 20,000 attendees at each of those conferences and that an “abstract book” from which each of the abstracts was excerpted would have been pro- vided to all attendees. Rehearing Decision at 10, 12, J.A. 59, 61. Accordingly, the Board maintained that the ab- stracts were prior art and denied UTC’s rehearing request. UTC timely appealed. We have jurisdiction under 28 U.S.C. § 1295(a)(4)(A) and 35 U.S.C. § 141(c). Case: 23-1805 Document: 52 Page: 6 Filed: 12/20/2023 6 UNITED THERAPEUTICS CORPORATION v. LIQUIDIA TECHNOLOGIES, INC. DISCUSSION We review the Board’s legal determinations de novo, In re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), and its fac- tual findings for substantial evidence, In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000). A finding is sup- ported by substantial evidence if a reasonable mind might accept the evidence as adequate to support the finding. Consol. Edison Co. v. NLRB, 305 U.S. 197, 229 (1938). Moreover, we review the Board’s determination whether, under the Board’s own regulations, a party exceeded the scope of a proper reply for abuse of discretion. Axonics, Inc. v. Medtronic, Inc., 75 F.4th 1374, 1380 (Fed. Cir. 2023). UTC raises three challenges on appeal. First, it argues that the Board erred in determining that the Voswinckel abstracts are prior art. Second, it argues that, even if those abstracts are prior art, the Board erred in finding that the claimed dose would have been obvious over the ’212 patent in combination with the Voswinckel abstracts. And finally, it argues that the Board legally erred in its treatment of dependent claims 4, 6, and 7, and that its obviousness de- termination as to those claims was not supported by sub- stantial evidence. We address each argument in turn. I UTC contends that the Board’s prior art analysis as to the Voswinckel abstracts suffered from two errors. First, it argues that the Board’s analysis improperly exceeded the prior art theories set forth in Liquidia’s petition. Second, it argues that the Board’s determination that the abstracts were publicly accessible as of the critical date was not sup- ported by substantial evidence. A By statute, the scope of an IPR is limited to the grounds set forth in the initial petition. 35 U.S.C. § 312(a)(3); see SAS Inst. Inc., v. Iancu, 138 S. Ct. 1348, 1357 (“[T]he stat- ute tells us that the petitioner’s contentions, not the Case: 23-1805 Document: 52 Page: 7 Filed: 12/20/2023 UNITED THERAPEUTICS CORPORATION v. 7 LIQUIDIA TECHNOLOGIES, INC. Director’s discretion, define the scope of the litigation all the way from institution through to conclusion.”). It is therefore improper for the Board to deviate from the grounds in the petition and raise its own theories of un- patentability. Sirona Dental Sys. GmbH v. Institut Strau- mann AG, 892 F.3d 1349, 1356 (Fed. Cir. 2018). UTC argues that the Board violated this principle when it con- cluded that the Voswinckel abstracts were prior art based on an “abstract book” theory. In UTC’s view, this theory was not advanced by Liquidia until its Reply before the Board, and that it was therefore untimely. See Appellant’s Br. at 33. We disagree. As the Board recognized, Liquidia’s IPR petition as- serted that each of the Voswinckel abstracts was publicly presented or published at least one year before the priority date of the ’793 patent, making each of them printed pub- lications within the meaning of § 102(b). See Decision at *4; see also Petition at 22, 24, J.A. 133, 135. UTC first chal- lenged the sufficiency of those grounds in its post-institu- tion Patent Owner Response. See Patent Owner Response at 11–18, J.A. 372–79. Thereafter, in its Reply, Liquidia asserted, with additional evidence, that both Voswinckel abstracts were publicly presented and sufficiently dissem- inated at conferences prior to the critical date such that they qualified as printed publications. See J.A. 471, 474–75. The Board found that Liquidia’s arguments and evi- dence raised in its Reply were not untimely as they were made in direct response to UTC’s attack on the prior art status of the abstracts first raised in its post-institution Pa- tent Owner Response. Decision at *4, J.A. 10. This conclu- sion was not an abuse of the Board’s discretion. See Anacor Pharms., Inc. v. Iancu, 889 F.3d 1372, 1380–82 (Fed. Cir. 2018) (explaining that the petitioner “may introduce new evidence after the petition stage if the evidence is a legiti- mate reply to evidence introduced by the patent owner”); see also Axonics, 75 F.4th at 1380 (explaining that a Case: 23-1805 Document: 52 Page: 8 Filed: 12/20/2023 8 UNITED THERAPEUTICS CORPORATION v. LIQUIDIA TECHNOLOGIES, INC. petitioner’s entitlement to respond to new arguments made in a patent owner response is consistent with SAS). As the Board observed, Liquidia’s arguments were not incon- sistent with, and therefore not new over, the grounds raised in its IPR petition—that the Voswinckel abstracts were publicly accessible prior to the critical date. Ericsson Inc. v. Intell. Ventures I LLC, 901 F.3d 1374, 1380 (Fed. Cir. 2018) (“[T]he Board has discretion to determine whether a petition for inter partes review identified the specific evidence relied on in a reply and when a reply con- tention crosses the line from the responsive to the new.”). Accordingly, we conclude that the Board did not abuse its discretion in considering the arguments and evidence raised in Liquidia’s Reply. B UTC next argues that, even if timely, the Board erred in finding that the Voswinckel abstracts were publicly ac- cessible because its “abstract book” theory was entirely “hypothetical” and supported only by “conclusory expert testimony.” Appellant’s Br. at 37. In its view, the Board’s theory would have been adequately supported only if Liquidia had provided “evidence of actual existence or dis- semination” of the books. Id. (emphasis added). But that is not the proper standard. Public accessibility is the “touchstone in determining whether a reference constitutes a ‘printed publication.’” Blue Calypso, 815 F.3d at 1348 (quoting In re Hall, 781 F.3d 897, 898–99 (Fed. Cir. 1986)). “Our cases have consistently held that the standard for public accessibility is whether a person of ordinary skill in the art could, after exercising reasonable diligence, access a reference.” Sam- sung Elecs. Co. v. Infobridge Pte. Ltd., 929 F.3d 1363, 1374 (Fed. Cir. 2019). Once accessibility is proved, “there is no requirement to show that particular members of the public actually received the information.” Jazz Pharms., Inc. v. Amneal Pharms., LLC, 895 F.3d 1347, 1356 (Fed. Cir. Case: 23-1805 Document: 52 Page: 9 Filed: 12/20/2023 UNITED THERAPEUTICS CORPORATION v. 9 LIQUIDIA TECHNOLOGIES, INC. 2018) (quoting Constant v. Adv. Micro-Devices, Inc., 848 F.2d 1560, 1569 (Fed. Cir. 1988)) (emphasis added). Contrary to UTC’s position then, Liquidia had no obliga- tion to produce, for example, a declarant testifying to hav- ing received the abstract books in which the Voswinckel abstracts appeared, let alone the abstract books them- selves. We find that the Board’s conclusion that the Voswinckel abstracts were sufficiently disseminated such that each constituted a printed publication was supported by substantial evidence. Specifically, the Board deter- mined that the two 2004 conferences at which the abstracts were presented were attended by over 20,000 attendees. Rehearing Decision at 7–12, J.A. 58–61. And both Liquidia’s and UTC’s experts testified that every attendee of either conference would have received a copy of the ab- stract book in which each of the Voswinckel abstracts ap- peared. See id. Further still, the Board found that neither abstract book would have been disseminated with any ex- pectation of privacy, given that the conference attendees included scientists, physicians, and nurses, as well as jour- nalists. See id. at 59. Substantial evidence therefore sup- ports the Board’s conclusion that the Voswinckel abstracts qualify as prior art. II UTC’s next challenges pertain to the Board’s obvious- ness analysis as to independent claim 1. A Claim 1 requires the inhalation of a therapeutically ef- fective single event dose of 15 micrograms to 90 mi- crograms of treprostinil or a therapeutically acceptable salt thereof. ’793 patent at col. 18, ll. 28–30. The Board con- cluded that, although no reference explicitly taught this dose, the person of ordinary skill in the art would have un- derstood the solutions in JESC to have delivered an Case: 23-1805 Document: 52 Page: 10 Filed: 12/20/2023 10 UNITED THERAPEUTICS CORPORATION v. LIQUIDIA TECHNOLOGIES, INC. amount of treprostinil within the claimed range. Decision at *6–7. That finding was supported by substantial evi- dence. JESC discloses the administration of treprostinil solu- tion via a nebulizer to patients in concentrations of 16, 32, 48, and 64 μg/mL. J.A. 1240. As the Board recognized, JESC does not disclose the volume of solution adminis- tered, which is necessary to calculate the amount (in μg) of treprostinil administered. Decision at *6. Accordingly, the Board looked to the declarations of Liquidia’s two experts, each of which testified that, at the time of the invention, nebulizers delivered at least 1 mL and up to 5 mL of solu- tion. Id. (citing J.A. 1054, 1166). Based on those delivery volumes, the Board concluded that the amounts of trepros- tinil delivered in JESC would have been from 16–80, 32– 160, 48–240, or 64–320 μg, each of which has at least one endpoint that falls within the claimed range of 15–90 μg. Id. UTC argues that the Board’s conclusion was error be- cause the experts’ testimony related only to fill volume, not volume actually delivered. Appellant’s Br. at 43. Because no nebulizer can be 100% efficient, UTC argues it was error to rely on the experts’ testimony without accounting for other factors, such as patients’ breathing volume and pat- terns, and individual nebulizer characteristics (e.g., resid- ual volume, nebulization rate, etc.). Id. But the Board considered, and rejected, those same arguments. Specifi- cally, it concluded that, “[t]o the extent that something less than the entire fill volume was delivered to the patient, . . . the preponderance of the evidence still supports actual delivered solution volume being at least one milliliter.” De- cision at *7. And, to be sure, UTC’s own expert testified that, in 2006, he had not administered treprostinil via a nebulizer that utilized less than one milliliter of drug solu- tion. Id. (citing J.A. 3185). Case: 23-1805 Document: 52 Page: 11 Filed: 12/20/2023 UNITED THERAPEUTICS CORPORATION v. 11 LIQUIDIA TECHNOLOGIES, INC. Accordingly, the Board’s finding that the combination of the ’212 patent, JESC, and JAHA would have rendered obvious claim 1 was supported by substantial evidence. B UTC further challenges the Board’s consideration of its evidence of objective indicia of nonobviousness, arguing that the Board “clearly erred” by concluding that UTC had failed to even allege that the invention demonstrated un- expected results over the ’212 patent, JESC, and JAHA. Appellant’s Br. at 49–50 (citing Decision at *10). This ar- gument, only a single paragraph in UTC’s opening brief, borders on waiver. See SmithKline Beecham Corp. v. Apo- tex Corp., 439 F.3d 1312, 1320 (Fed. Cir. 2006). But even if given due consideration, we conclude that the Board’s de- termination was supported by substantial evidence. Before the Board, UTC only provided evidence that the claimed compositions exhibited unexpected results over in- haled iloprost, intravenous epoprostenol, and intravenous treprostinil. See Decision at *10. But, as the Board recog- nized, the claims require inhaled treprostinil, which is taught by each of the ’212 patent, JESC, and JAHA, mak- ing those references the closest prior art. And the only ar- gument made by UTC that the claimed invention was unexpected over those references was a conclusory state- ment that “the ability to administer treprostinil at high doses in only 1–3 breaths and with fewer side effects was unexpected.” J.A. 585. With no other evidence to consider, we see no error in the Board’s conclusion that UTC failed to satisfy its burden in establishing unexpected results. III Finally, we turn to UTC’s challenge to the Board’s treatment of dependent claims 4, 6, and 7, which are di- rected to the inhalation of dry powder formulations of treprostinil. UTC argues that the Board failed to consider each claim as a separate invention and that none of the ’212 Case: 23-1805 Document: 52 Page: 12 Filed: 12/20/2023 12 UNITED THERAPEUTICS CORPORATION v. LIQUIDIA TECHNOLOGIES, INC. patent, JESC, or JAHA discloses any dry powder dosages. Specifically, it argues that the Board failed to explain why a person of ordinary skill in the art would “reasonably ex- pect to succeed in preparing a therapeutically effective dry powder formulation” using concentrations prepared only for solutions. Appellant’s Br. at 55. But, as Liquidia explains, UTC never raised this par- ticular argument before the Board. Instead, it argued that claims 4, 6, and 7 were not obvious “because the prior art lacks disclosure of a single event dose of 15–90 μg delivered in 1–3 breaths, regardless of the form of administration (liquid or powder).” Patent Owner Response at 41, J.A. 401 (emphases added). We therefore find UTC’s argument for- feited. Fresenius USA, Inc. v. Baxter Int’l, Inc., 582 F.3d 1288, 1296 (Fed. Cir. 2009) (explaining that this court may decline to consider an argument “[i]f a party fail[ed] to raise [that] argument before the trial court, or present[ed] only a skeletal or undeveloped argument to the trial court.”). In any event, the Board’s conclusion that dependent claims 4, 6, and 7 were obvious was supported by substan- tial evidence. Namely, as the Board observed, the ’212 pa- tent, which is also owned by UTC, discloses the use of an “inhaler,” and that “solid formulations, usually in the form of a powder, may be inhaled in accordance with the present invention.” ’212 patent at col. 5, ll. 30, 37–39, J.A. 1228. It also teaches that such formulations have particle sizes of preferably “less than 5 micrometers in diameter.” Id. at col. 5, ll. 39–41, J.A. 1228. The Board relied not only on these disclosures, but also on the unrebutted testimony of Liquidia’s expert that a person of ordinary skill in the art would have had a reasonable expectation of success in ar- riving at the claimed dry powder formulation based on the combined teachings of the ’212 patent, JESC, and JAHA. Decision at *14. Case: 23-1805 Document: 52 Page: 13 Filed: 12/20/2023 UNITED THERAPEUTICS CORPORATION v. 13 LIQUIDIA TECHNOLOGIES, INC. CONCLUSION We have considered UTC’s remaining arguments and find them unpersuasive. For the reasons provided above, we affirm the Board’s unpatentability determination. AFFIRMED