By Kevin E. Noonan --
One of the most notable consequences (intended or not, for good or ill) of the Leahy-Smith America Invents Act (AIA) has been the possibility (now likelihood, if only in frequency) that the decisions of the Patent Trial and Appeal Board and district courts will be different (typically to the detriment of patent holders). This outcome Is at least in part the result of differences in the burdens of proof between the two fora, specifically the preponderance of the evidence before the Board and the clear and convincing evidence in court. These circumstances have raised concerns (most notably by now-suspended, Federal Circuit Judge Pauline Newman) regarding the constitutional propriety of an Article I court being able to overrule an Article III court on separation of powers grounds (see "XY, LLC v. Trans Ova Generics, L.C. (Fed. Cir. 2018)"). Another example of such an outcome arose in the Federal Circuit's affirmance of the PTAB decision that the claims of an asserted patent that had already been held not invalid in litigation were invalidated by the Board, in United Therapeutics Corp. v. Liquidia Technologies, Inc.
The case arose in litigation between NDA holder United Therapeutics Corp. ("UTC") and Liquidia, who filed its own NDA (under § 505(b)(2) of the Food, Drug, and Cosmetic Act). Both regulatory approval applications were directed towards inhaled formulations of treprostinil for treating pulmonary hypertension (UTC's Tyvaso®, Liquidia's Yutrepia™). UTC asserted two Orange Book-listed patents, U.S. Patent Nos. 9,593,066 and 10,716,793 in the litigation. The District Court found that the '066 patent claims were invalid albeit infringed and are not at issue here. For the '793 patent, the District Court found the asserted claims not to be invalid and that Liquidia's competing product would infringe (having not yet obtained FDA approval), and enjoined Liquidia from marketing its version of the drug until after expiration of the '793 patent (expected on May 14, 2027). However the District Court noted that Liquidia had challenged the validity of the '793 patent in an ongoing IPR (No. IPR2021-00406) and that, should the PTAB hold the asserted claims of this patent to be invalid Liquidia would be able to seek having the injunction lifted (for further details, see "United Therapeutics Corp. v. Liquidia Technologies, Inc. (Fed. Cir. 2023)").
All claims of the '793 patent were challenged in the IPR, with claim 1 being representative:
1. A method of treating pulmonary hypertension comprising administering by inhalation to a human suffering from pulmonary hypertension a therapeutically effective single event dose of a formulation comprising treprostinil or a pharmaceutically acceptable salt thereof with an inhalation device, wherein the therapeutically effective single event dose comprises from 15 micrograms to 90 micrograms of treprostinil or a pharmaceutically acceptable salt thereof delivered in 1 to 3 breaths.
The opinion also sets forth relevant dependent claims 4, 6, and 7:
4. The method of claim 1, wherein the inhalation device is a dry powder inhaler.
6. The method of claim 4, wherein the formulation is a powder.
7. The method of claim 6, wherein the powder comprises particles less than 5 micrometers in diameter.
Liquidia's IPR petition asserted obviousness of all '793 claims based on U.S. Patent No. 6,521,212 ("the '212 patent") in combination with two scientific abstracts to Voswinckle (termed "JESC" and "JAHA"). The '212 patent described methods for delivering benzindene prostaglandins (of which treprostinil sodium is one) by inhalation to treat pulmonary hypertension, while the Voswinckle references described studies using various amounts of treprostinil (16, 32, 48, and 64 μg/mL) (JESC) and wherein patients in the study were administered the drug in three breaths (JAHA). UTC responded to Liquidia's obviousness allegation by challenging the status of the Voswinckle references as prior art. The basis for this assertion was that Liquidia had not established that the Voswinckle references were printed publications under pre-AIA 35 U.S.C. § 102(b). Liquidia relied upon the Voswinckle references having been stored in libraries but it had not (according to UTC) shown that "both [had] been available at the library and sufficiently indexed or categorized by priority date" (see In re Hall, 781 F.3d 897, 898–99 (Fed. Cir. 1986)). In rejecting this challenge, the Board noted that each of the Voswinckle references were presented at a public conference attended by 20,000 people (including "scientists, physicians, and nurses, as well as journalists") (emphasis in opinion). In addition, the Board recognized that the Voswinckle references were cited in other documents available to the public prior to the '793 priority date. On these bases the Board concluded that the combination of the Voswinckle references and the '212 patent rendered obvious the invention claimed in the '793 patent. The Board also held that the objective indicia asserted by UTC ("unexpected results, copying, and long-felt and unmet need") did not overcome their prima facie obviousness determination.
UTC petitioned for rehearing (including an appeal to the PTO's Precedential Opinion Panel) on the question of whether the Voswinckle references were prior art. While the Panel did not deign to review the decision, it did direct the Board to reconsider because in its judgment the Board had failed to determine whether the "other publications" (identified as "research aids") that purportedly disclosed the Voswinckle references had themselves had been available to the public before the critical date. In addition, the Panel determined that the Board had not "adequately addressed" whether the Voswinckle references "were publicly accessible by way of their presentation and/or inclusion in distributed materials, such as at a conference or library." The Board dutifully reconsidered the evidence and maintained its decision that the references were prior art. Admitting it had not recognized that the research aids had not been publicly available before the priority date, the Board nevertheless found that the Voswinckle references had been distributed at conferences prior to that date (including in an "abstract book" provided to attendees). Having dispensed with any deficiencies in its reasoning on this issue, the Board held the asserted claims of the '793 patent to be invalid for obviousness and UTC appealed.
The Federal Circuit affirmed in an opinion by Judge Lourie joined by Judges Prost and Reyna. With regard to the prior art status of the Voswinckle references, the Court first addressed whether the Board's analysis "improperly exceeded the prior art theories set forth in Liquidia's petition" under 35 U.S.C. § 312(a)(3) as interpreted by the Supreme Court in SAS Inst. Inc. v. Iancu, 138 S. Ct. 1348, 1357 (2018). UTC argued that the Board's reasoning regarding the prior art patency of the Voswinckle references that depended on their inclusion of the abstract books at conferences exceeded Liquidia's arguments in its petition. The panel held that Liquidia's position in its petition was that the Voswinckle references were prior art because they had been publicly disclosed, and that the Board properly found Liquidia's later arguments in its Reply to be timely under the statute because they were asserted "in direct response" to UTC's contrary arguments first raised in its Response. This reasoning was not an abuse of discretion, according to the panel, under inter alia Anacor Pharms., Inc. v. Iancu, 889 F.3d 1372, 1380–82 (Fed. Cir. 2018), because Liquidia's arguments in its Reply were not inconsistent with its position in its Petition (i.e., that the Voswinckle references were prior art under pre-AIA 35 U.S.C. § 102(b)).
The panel also agreed with the Board's substantive determination that the Voswinckle references were prior art. UTC argued that the Board's reasoning regarding the references was entirely "hypothetical" and only supported by "conclusory expert testimony." In this regard, the Court rejected UTC's assertion that "evidence of actual existence or dissemination" was required, saying this was "not the proper standard" (emphasis in brief). Rather, the opinion asserts that "[o]ur 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," citing Samsung Elecs. Co. v. Infobridge Pte. Ltd., 929 F.3d 1363, 1374 (Fed. Cir. 2019) (emphasis in brief). But once such public accessibility has been established "there is no requirement to show that particular members of the public actually received the information," according to the opinion citing Jazz Pharms., Inc. v. Amneal Pharms., LLC, 895 F.3d 1347, 1356 (Fed. Cir. 2018), quoting Constant v. Adv. Micro-Devices, Inc., 848 F.2d 1560, 1569 (Fed. Cir. 1988) (emphasis added). On this basis, the panel held that the Board relied on substantial evidence that the Voswinckle references were prior art.
Turning to the ultimate question of obvious for sole independent claim 1, the Court held that the Board had relied on substantial evidence in concluding that, while no one reference explicitly taught the recited administered range of a therapeutically effective single event dose that comprises from 15 micrograms to 90 micrograms of treprostinil, the skilled worker would have understood that the JESC reference disclosed solutions within this range. This reference taught administration of treprostinil in various concentrations (16, 32, 48, and 64 μg/mL) but did not disclose explicitly recited administered dosage volumes. However, according to the Federal Circuit the Board properly relied on expert testimony regarding such volumes (ranging from at least 1 mL and up to 5 mL of solution), which would deliver 16–80, 32–160, 48–240, or 64–320 μg, each of which contained a value falling within the dose recited in claim 1. The panel considered UTC's challenges to these calculations on technical grounds, finding that the Board had heard and rejected these same arguments. Accordingly, the panel accepted the Board's conclusions to be supported by substantial evidence on the obviousness question.
Regarding the objective indicia of non-obviousness, the panel found that the Board's rejection of UTC's arguments was also supported by substantial evidence (noting that UTC's assertions regarding unexpected results were included in "only a single paragraph in UTC's opening brief, [which] borders on waiver"). On the merits the Court held that UTC provided assertions but not evidence of any such unexpected results.
Finally, the Federal Circuit upheld the Board's obviousness determination of dependent claims 4, 6, and 7. UTC's arguments regarding these claims were that the recitation therein of dry power administration of treprostinil was a "separated invention" not disclosed in any of the asserted prior art references. Thus, UTC argued that the Board failed to explain how the ordinarily skilled worker would have had any reasonable expectation of success in administering treprostinil as a dry powder. The panel first held that UTC had waived this argument because it had not raised it (at least in this form) before the Board. And on the merits, the panel held that as with independent claim 1 the Board's decision on these dependent claims was supported by substantial evidence (including the unrebutted testimony of Liquidia's experts) and thus affirmed.
United Therapeutics Corp. v. Liquidia Technologies, Inc. (Fed. Cir. 2023)
Nonprecedential disposition
Panel: Circuit Judges Lourie, Prost, and Reyna
Opinion by Circuit Judge Lourie
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