Jazz Pharmaceuticals, Inc. v. Avadel CNS Pharmaceuticals, LLC

Sara W. Koblitz*

I. Why This Case Made the List

Patents listed in FDA’s List of Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”) play a critical role in maintaining the balance between access and innovation that underscores the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act” or “Hatch-Waxman”).[1] Indeed, each patent listed in the Orange Book requires a certification in any filed follow-on application—Abbreviated New Drug Applications (ANDA) or 505(b)(2) New Drug Applications (NDA)—seeking approval of a proposed drug referencing an innovator product.[2] Those listed patents are eligible for assertion prior to generic launch,[3] along with a thirty-month stay of follow-on approval,[4] preventing an onslaught of potentially infringing product from flooding the market during the pendency of litigation. Consequently, the patents that can be listed in the Orange Book are of significant concern, and industry has been asking FDA to opine on the proper patents for listing for many years. While FDA has asked for public opinion on the types of patents that should be listed in the Orange Book,[5] the agency itself has remained silent.[6]

With little guidance from FDA, companies have listed all sorts of patents in the Orange Book that could be asserted against a potential generic, including patents covering Risk Evaluation and Mitigation Strategies (REMS). However, because these patents do not necessarily cover the drug product itself, such listings have been controversial. In Jazz Pharmaceuticals, Inc. v. Avadel CNS Pharmaceuticals, LLC, the courts had the opportunity to address the listing of REMS patents in the Orange Book.[7] Ultimately, the court decided that the patent at issue in this case could not be listed in the Orange Book—and ordered the delisting of that patent—because the patent claimed a “system” rather than a “method” of using the drug.

Generally, Jazz v. Avadel addresses questions that have long gone unanswered related to listing patents in, and FDA’s role in administering, the Orange Book. While the court’s narrow interpretation of a method of use patent implicitly limits listable patents, it both stops short of limiting patent listings more generally and embraces FDA’s hands-off approach to listing decisions. But aside from the implications as to the propriety of listing REMS patents, this case is also notable because of the intervention of the Federal Trade Commission (FTC) and its strong amicus brief arguing that the listing of a REMS patent generally is anticompetitive. No government agency has taken that strong a position related to patent listings, even with industry prodding, making the filing of the FTC brief notable.

II. Discussion

A. Legal Background

The Federal Food, Drug, and Cosmetic Act (FDCA), initially enacted in 1938, provides statutory authority for FDA to oversee the safety of food, drugs, medical devices, and cosmetics.[8] Pursuant to 1962 amendments, the FDCA requires FDA to review and approve all new drugs for safety and efficacy prior to introduction into interstate commerce.[9] To that end, the FDCA establishes the procedure for obtaining FDA approval to sell pharmaceutical products through an NDA, which requires the submission of clinical trial data establishing the proposed new drug’s safety and efficacy for its intended use under the conditions of its proposed labeling.[10] Upon approval, the NDA sponsor must file with FDA “the patent number and the expiration date of each patent for which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture, use, or sale of the drug . . . .”[11] The statute then obligates FDA to “publish” and regularly “revise” a list of all such patent data.[12] That listing of patent data is published in FDA’s Orange Book alongside the NDA with which it is associated.

The FDCA also authorizes FDA to review and approve “abbreviated” or “follow-on” versions of approved drug products. A generic version of a previously approved drug may be approved under an ANDA so long as the ANDA includes data to establish that the proposed generic drug is “the same as” a previously approved Reference Listed Drug (RLD) in certain key respects.[13] The FDCA also provides for an additional type of abbreviated applicated—a 505(b)(2) NDA—which permits the submission of an NDA for a drug that is not a duplicate of a previously approved RLD, and where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference.[14] In practice, this enables the applicant to rely, in part, on FDA’s findings of safety and/or effectiveness for the RLD or on published literature reports of studies rather than re-conducting certain studies in support of its application.

Both ANDA and 505(b)(2) NDA applicants relying on FDA’s findings of safety or efficacy for an approved product must certify to any patents listed in the Orange Book for the RLD it is referencing.[15] Specifically, the applicant must certify to each patent in one of the following ways:

(i) the required patent information has not been filed;

(ii) the listed patent has expired;

(iii) the listed patent has not expired but will expire on a particular date and approval is sought after patent expiration; or

(iv) the listed patent is invalid or will not be infringed by the new product.

A Paragraph IV certification also requires the ANDA or 505(b)(2) NDA sponsor to provide notice of the application and patent certification to the RLD holder within forty-five days so that the RLD holder has the opportunity to bring patent litigation prior to the approval of the application.[16] Should the RLD holder file an infringement suit against a follow-on applicant, approval of that ANDA is stayed for thirty months as the patent litigation is resolved.[17]

When an applicant believes that a patent has been wrongly listed in the Orange Book, the applicant can dispute the listing and ask the RLD sponsor, through FDA, to remove it from the Orange Book.[18] Should the RLD sponsor decline to remove or update the patent listing, the patent remains listed in the Orange Book, and any follow-on applicant must certify to that patent.[19] The only remaining remedy for the applicant to address an alleged improper listing is to file a counterclaim to the patent litigation initiated by the RLD sponsor “seeking an order requiring [the RLD sponsor] to correct or delete” from the Orange Book the relevant patent information.[20]

Importantly, FDA has enumerated—and thereby limited—the types of patents to be listed in the Orange Book and consequently the types of patents for which certifications are required upon submission of an ANDA or a 505(b)(2) NDA. Specifically, these patents are limited by FDA regulation to patents that claim the drug substance (active ingredient), drug product (formulation and composition), or methods of using the drug.[21] The scope of the limitations on patent listing are not entirely clear, however. FDA has not taken a position on whether certain patents should be listed, including drug delivery systems for combination products and patents covering REMS where FDA has determined such a REMS is necessary to ensure that the benefits of a drug outweigh its risks.[22] Absent FDA input, certain RLD sponsors have decided to list REMS patents in the Orange Book, requiring ANDA and 505(b)(2) sponsors referencing those products to certify to such patents.

Patents listed in the Orange Book as “method of use” patents do not necessarily require certification. Instead of a patent certification, an ANDA might include a “section viii statement” informing FDA that the proposed ANDA does not seek approval for the use covered by a listed method-of-use patent (and only a method-of-use patent), as detailed in the “use code” selected by the RLD sponsor.[23] In that situation, the ANDA applicant “carves-out” from its product labeling the language that the NDA sponsor lists in the “use code” for that patent. Because FDA’s role in administering patents is “ministerial,” FDA relies on the use code to assess the parameters of the patent claim that must be omitted (or “carved-out”) from the proposed product labeling to avoid infringement.[24]

B. Factual Background

Used for the treatment of cataplexy and excessive daytime sleepiness associated with narcolepsy, Jazz Pharmaceuticals, Inc. (“Jazz”) has marketed immediate release formulations of sodium oxybate in the United States since 2002. Given its potential for abuse, all sodium oxybate products are subject to a REMS that requires a limited distribution system involving a single, central pharmacy.[25] Jazz’s two sodium oxybate products, Xyrem and Xywav, are subject to its own REMS, and Jazz obtained a patent covering the REMS.[26] Jazz listed that patent, U.S. Patent Number 8,731,963 (“the ‘963 patent”), in the Orange Book with the associated use code U-1110, “method of treating a patient with a prescription drug using a computer database in a computer system for distribution.”[27]

Avadel CNS Pharmaceuticals, LLC (“Avadel”) developed its own sodium oxybate product, called Lumryz, that is dosed once nightly, in contrast to the Jazz products, which require a second dose in the middle of the night.[28] Avadel submitted a 505(b)(2) NDA referencing Xyrem in December 2020.[29] Because Avadel proposed to use its own REMS rather than Jazz’s patented system, Avadel did not certify to the ‘963 patent but instead submitted a section viii statement asserting that the patent “does not claim a use for such drug for which the applicant is seeking approval.”[30] Nonetheless, Jazz sued Avadel for infringement of the ‘963 patent, as well as infringement of other listed patents.

Notwithstanding Avadel’s section viii statement submitted with the 505(b)(2) NDA more than a year and a half earlier, FDA, in May 2022, ordered Avadel to certify to the ‘963 patent based on the conclusion that the Lumryz REMS’s use of four computer databases for distribution overlaps with the U-1110 use code.[31] Avadel certified to the ‘963 patent “under protest” in June 2022, and Jazz initiated a second lawsuit against Avadel for infringement of the ‘963 patent on July 15, 2022. Because Jazz timely sued Avadel, the lawsuit triggered a thirty-month stay, effectively barring Lumryz from coming to market until the June 2023 expiration of the ‘963 patent and its associated pediatric exclusivity.[32]

In the interim, FDA tentatively approved the Lumryz 505(b)(2) NDA on July 18, 2022, and Avadel sued the agency in the District Court of the District of Columbia alleging that it violated the Administrative Procedure Act (APA) by requiring a certification to the ‘963 patent.[33] Avadel reasoned that the decision whether to file a patent certification or a section viii statement rests solely in the “opinion” of the new drug “applicant” under the plain language of the statute set forth in 21 U.S.C. § 355(b)(2), and FDA therefore lacked the statutory authority to “second-guess Avadel’s decision to file a patent statement rather than a patent certification.”[34] Accordingly, Avadel argued that FDA does not have legal basis to compel a patent certification to the ‘963 patent.[35] Thus, Avadel concluded its 505(b)(2) is entitled to final approval now—not after the pendency of the thirty-month stay or expiration of the ‘963 patent. However, because the APA authorizes review only when there is no adequate remedy for a plaintiff’s injury, the district court dismissed Avadel’s suit against FDA citing the pending delisting counterclaim as a potential remedy.[36]

After the dismissal, Avadel responded to both of Jazz’s infringement lawsuits with a counterclaim seeking an order that Jazz delist the ‘963 patent for failure to claim a drug or method of use. [37]

While litigation was ongoing, the FTC filed an amicus brief in the case detailing the abuse arising from improper listing of patents in the Orange Book.[38] Because FDA has no tools to “remove improperly listed patents,” the FTC explained that there is “no gatekeeper to prevent a company from inappropriately listing patents that do not meet the Orange Book criteria.”[39] A brand can therefore list a patent—even if it does not adhere to FDA listing regulations—and sue, triggering an automatic thirty-month stay, with no oversight.[40] This, FTC explained, is anticompetitive.[41] While the FTC took no position on Jazz’s specific patent, it argued that patents only covering drug distribution systems “do not meet the Orange Book listing criteria; to the extent they claim a method at all, it is a method of distributing a drug rather than a method of using one. This is an important distinction.”[42] The FTC also argued that listing REMS patents not only contravenes the plain text of the Orange Book listing statute, but it also may violate the REMS statute by blocking or delaying follow-on approval.[43]

C. Court Decision

Jazz and Avadel engaged in two separate sets of lawsuits; the first lawsuit proceeded to claim construction in which Avadel argued that the ‘963 patents are directed to systems—not methods—while Jazz argued that the terms systems and methods are interchangeable.[44] On November 18, 2022, the District Court of Delaware agreed with Avadel, construing the ‘963 patent claims to be directed to systems, not methods.[45] Because it does not cover a method of using the drug, the district court issued a second Memorandum Opinion on the same day ordering the delisting of the ‘963 system patent.[46] Jazz appealed.

On February 24, 2023, the Court of Appeals for the Federal Circuit upheld the district court’s decision that the patent should be delisted.[47] The Federal Circuit looked to both the adequacy of the claim construction and to the proper interpretation of the term “‘an approved method of using the drug’ under 21 U.S.C. § 355(c)(2) and § 355(c)(3)(D)(ii)(I).”[48]

Based on the description in the patent specification and prosecution history, the Federal Circuit determined that the ‘963 patent claimed a system rather than a method.[49] Specifically, the court explained, Jazz’s claims to a system comprising computer memory and a data processor are not method claims; that the system can be used to treat patients “does not alter the fact that these are system claims.”[50] The court therefore determined that the district court properly construed the claims as system—rather than method—claims.[51]

The court next looked at whether the system claimed in the ‘963 patent qualified as “an approved method of using the drug” under 21 U.S.C. § 355(c)(2) and § 355(c)(3)(D)(ii)(I).[52] Jazz argued that the FDA regulation 21 C.F.R. § 314.53(b)(1) requires a broader definition of the term “method” than permitted by the language of patent law and that this broader definition encompasses the claims of the ‘963 patent.[53] Because prescribing Xyrem required following a REMS, Jazz argued that the REMS computer system described in the ‘963 patent was a “condition of use” for which approval had been granted in the NDA.[54] The court rejected this argument, explaining that the patent still needed to claim a method of use to be eligible for listing.[55] And because the ‘963 patent does not claim a method of use, the court found 21 C.F.R. § 314.53(b)(1) inapplicable.[56]

Jazz also argued that the patent was permissibly listed in 2014 because the patent was neither required nor forbidden from listing.[57] Thus, Jazz argued, Avadel could not compel Jazz to delist it.[58] The Federal Circuit again disagreed, explaining that whether the patent was eligible for listing when it was initially listed does not control whether a court could order delisting now.[59] Thus, the Federal Circuit concluded that the district court was correct in ordering the ‘963 patent delisted.[60]

III.   Impact of the Decision

While limited to the delisting of the ‘963 patent, this case has significant implications as to the listing of certain patents in the Orange Book. Because FDA historically has declined to opine on the propriety of listing certain patents in the Orange Book, including REMS patents, RLD sponsors have taken a broad approach to Orange Book listing by including patents that do not reference specific drug products.[61] The decision in Jazz v. Avadel implicitly limits the types of patents listable by narrowly interpreting a “method” of use.[62] Indeed, that a condition of use is recited in the patent does not render the patent a “method of use” patent covering the drug product eligible for Orange Book listing; consequently, RLD sponsors will need to carefully draft claims so that they undeniably claim a method of using the drug, which can be challenging since REMS typically involve strategies for educating patients and practitioners or limiting distribution of drug products rather than an actual use of the drug product. Whether this means that the patent must include a claim covering use of the drug itself is still unclear, leaving unanswered the question of whether other types of patents, like device patents, can be properly listed in the Orange Book even if they do not expressly claim the drug.

Additionally, that both the district court and the Federal Circuit determined that the listability of the ‘963 patent in the Orange Book hinged on claim construction legitimizes FDA’s position that its role in administering the Orange Book is merely ministerial.[63] Because claim construction is squarely within the purview of the courts and the U.S. Patent and Trademark Office,[64] the decision allows FDA to avoid any responsibility for monitoring and administering the Orange Book with an eye toward improper listings. In other words, FDA can continue to avoid intervening in patent listing disputes by directing applicants to the delisting counterclaim provisions in the Hatch-Waxman Amendments, leaving all Orange Book listing concerns to the discretion of the courts.

With the procedural history of this case and the delay in approval of the Lumryz 505(b)(2) NDA, this case suggests that FDA’s refusal of responsibility for proper Orange Book listing can cause a significant roadblock for applicants. It took Avadel several years to get to the point where a court finally made a delisting decision, delaying market entry for reasons that were ultimately baseless. Admittedly, claim construction clearly is not in the purview of FDA, but because there is no mechanism by which FDA can or will interpret a patent or compel its removal from the Orange Book without a sponsor undertaking costly and lengthy litigation—and because FDA had refused to address the question of listability of REMS patents—Avadel was forced to certify to a questionably listed patent. In turn, and even though Lumryz was ready for approval, the compelled certification triggered a second round of patent litigation and an automatic thirty-month stay of approval that theoretically would block Avadel from marketing until the expiration of the relevant patent. A clever—and completely legal—listing strategy consumed significant time, money, and court resources. And importantly, this was not even a direct copy of the Jazz product, which means that such a listing strategy prevented innovation rather that encouraged it.

It is also notable that FTC took a strong position in its amicus brief that the listing of certain patents in the Orange Book is anticompetitive. While neither court expressly agreed with the FTC, it is clear that the reasoning presented in the FTC’s brief permeated the courts’ decision. Indeed, the FTC argued that patents claiming a method of distributing a drug do not cover the drug itself or a method of using the drug, which is similar to the reasoning the Federal Circuit used in holding that the Jazz system of distribution was not listable; the court stopped just short of the pronouncement made by the FTC. The FTC further argued that listing REMS patents not only contravenes the plain text of the Orange Book listing statute, but it also may violate the REMS statute by blocking or delaying follow-on approval. While the courts may not have addressed that point, that the enforcer of the antitrust statutes believes that listing REMS patents in the Orange Book is anticompetitive is significant and may serve as the impetus for FDA to announce its perspective on listing REMS patents in the Orange Book.

Finally, Avadel made interesting arguments in the APA litigation that the District Court for the District of Columbia did not have an opportunity to address. Avadel argued that FDA does not have the authority to compel a patent certification rather than a section viii statement based on the plain language of 21 U.S.C. § 355(b)(2), which calls for certification based on “the opinion of the applicant and to the best of his knowledge.”[65] This language seems to delegate decision-making authority regarding the proper patent certification to the applicant. This raises an interesting question—whether the applicant alone can determine the proper certification—a decision on which could upend the patent certification process. Additionally, Avadel explained that FDA’s review of the Lumryz REMS document to assess the use code overlap—rather than the Prescribing Information alone—violated FDA regulations. Avadel argues that FDA regulations state that a patent certification is necessary “[i]f the labeling of the drug product for which the application is seeking approval includes an indication or other condition of use that, according to the patent information submitted under section 505(b) or (c) of the Federal Food, Drug, and Cosmetic Act and § 314.53 or in the opinion of the applicant, is claimed by a method-of-use patent,” which thereby limits FDA to review of the labeling for use code overlap.[66] This is an important question because FDA frequently assesses the propriety of use code carve-outs in Citizen Petitions by looking at the impact of the labeling carve-out on doctors’ prescribing decisions. If FDA is not permitted to look beyond the confines of the Prescribing Information to assess a carve-out, FDA likely could not rely on the implications of the omission of that carved-out language beyond the actual instructions for use in the labeling to the foreseeable use of those instructions. Of course, no court has reached these questions yet.

Ultimately, the Federal Circuit decision stands, and in March 2023, Jazz delisted the ‘963 patent at the direction of the Federal Circuit.


* Sara W. Koblitz is a Director at Hyman, Phelps & McNamara, P.C., where she advises drug and device manufacturers on applicable regulatory requirements under the Federal Food, Drug, and Cosmetic Act and Public Health Service Act, with a specific focus on the Hatch-Waxman Act, the Orphan Drug Act, and the Biologics Price Competition and Innovation Act.

[1]   Pub. L. No. 98-417, 98 Stat. 1585 (1984).

[2]   21 U.S.C. § 355(b)(2)(A); 21 U.S.C. § 355(j)(2)(A)(vii).

[3]   35 U.S.C. § 271(e)(2).

[4]   21 U.S.C. § 355(c)(3)(C); 21 U.S.C. § 355(j)(5)(B)(iii).

[5]   Listing of Patent Information in the Orange Book; Establishment of a Public Docket; Request for Comments, 85 Fed. Reg. 33,169, 33,170 (June 1, 2020).

[6]   See Request for Advisory Op. by GlaxoSmithKline, Docket No. FDA-2005-A-0476 (formerly 2005A-0015) (Jan. 10, 2005); Request for Advisory Op. by AstraZeneca, Docket No. FDA-2006-A-0063 (formerly 2006A-0318) (Aug. 10, 2006); Request for Advisory Op. by AstraZeneca, Docket No. FDA-2007-A-0099 (formerly 2007A-0261) (June 21, 2007); Request for Advisory Op. by Forest Lab’ys, Inc., Docket No. FDA-2011-A-0363 (May 12, 2011); Request for Advisory Op. by Novo Nordisk Inc., Docket No. FDA-2012-A-1169 (Nov. 26, 2012); see also Letter from Douglas C. Throckmorton, CDER, to James Ford, GlaxoSmithKline, et al., Docket Nos. FDA-2005-A-0476, FDA-2006-A-0063, FDA-2007-A-0099, FDA-2011-A-0363, and FDA-2012-A-1169 (June 1, 2020).

[7]   Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, No. 1:21-cv-00691 (D. Del. 2021); No. 1:21-cv-01594 (D. Del. 2021); No. 1:22-cv-00941 (D. Del. 2022); No. 23-1186 (Fed. Cir. 2022).

[8]   Kefauver Harris Drug Amendments Act of 1962, Pub. L. No. 87-781, 76 Stat. 780 (1962); Federal Food, Drug, and Cosmetic Act, Pub. L. No. 75-717, 52 Stat. 1040 (1938).

[9]   See 21 U.S.C. § 355.

[10]  Id.

[11]  21 U.S.C. § 355(b)(1); see also 21 C.F.R. § 314.50(h).

[12]  21 U.S.C. § 355(j)(7)(A)(i)–(iii); see also id. § 355(c)(2).

[13]  Id. § 355(j)(2)(A).

[14]  Id. § 355(b)(2).

[15]  Id. § 355(b)(2)(A); id. § 355(j)(2)(A)(vii).

[16]  Id. § 355(c)(3)(C); id. § 355(j)(5)(B)(iii).

[17]  Id.

[18]  21 C.F.R. § 314.53(f).

[19]  Id. § 314.53(f)(1)(i).

[20]  21 U.S.C. § 355(c)(3)(D)(ii)(I); id. § 355(j)(5)(C)(ii)(I).

[21]  21 C.F.R. § 314.53(b)(1).

[22]  See 85 Fed. Reg. at 33,172, 33,173 (soliciting comments on the types of patents that should be listed in the Orange Book).

[23]  21 U.S.C. § 355(b)(2)(B), (j)(2)(A)(viii); 21 C.F.R. § 314.94(a)(8)(iv); 21 C.F.R. § 314.53(f)(1)(i)(B).

[24]  85 Fed. Reg. at 33,170; see 21 C.F.R. § 314.53(f)(1)(i)(B).

[25]  Op. at 2–3, Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, No. 23-1186 (Fed. Cir. Feb. 24, 2023), ECF No. 59.

[26]  Id.

[27]  U.S. Dep’t of Health & Hum. Servs., Prescription and OTC Drug Product Patent and Exclusivity List, in Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, at ADA 369 (43rd ed., 2023).

[28]  Jazz v. Avadel, No. 23-1186, at 6 (Fed. Cir. Feb. 24, 2023).

[29]  Id.

[30]  Mem. of P. & A. in Supp. of Pl.’s Mot. for a Prelim. Inj. or in the Alternative Summ. J. at 3, Avadel CNS Pharms., LLC v. Becerra, Docket No. 1:22-cv-2159 (D.D.C. July 21, 2022), ECF No. 2-1; 21 U.S.C. § 355(b)(2)(B).

[31]  Compl. for Declaratory and Injunctive Relief at 4, Avadel CNS Pharms., LLC v. Becerra, No. 1:22-cv-2159 (D.D.C. July 21, 2022), ECF No. 1.

[32]  Id. at 5.

[33]  Id.; id. at 24.

[34]  Id. at 24.

[35]  Id.

[36]  Mem. Op., Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, No. 1:21-cv-00691 (D. Del. Nov. 18, 2022), ECF No. 231.

[37]  Id. at 2.

[38]  Federal Trade Commission’s Br. as Amicus Curiae, Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, No. 1:21-cv-0691 (D. Del. Nov. 10, 2022), ECF No. 222-3.

[39]  Id. at 13.

[40]  Id. at 13–14.

[41]  See id. (“An improper listing harms competition and consumers: By listing a patent in the Orange Book and then filing an infringement suit, a brand can block competition for up to two-and-a-half years regardless of the scope or validity of the patent and regardless of whether it meets the statutory listing criteria.”).

[42]  Id. at 2 (emphasis added).

[43]  Id. at 20.

[44]  Mem. Op., Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, No. 1:21-cv-01594 (D. Del. Nov. 18, 2022), ECF No. 146.

[45]  Id.

[46]  Jazz v. Avadel, No. 1:21-cv-00691 (D. Del. Nov. 18, 2022).

[47]  Jazz v. Avadel, No. 23-1186 (Fed. Cir. Feb. 24, 2023).

[48]  Id. at 11.

[49]  Id. at 10.

[50]  Id.

[51]  Id.

[52]  Id. at 11.

[53]  Id.

[54]  Id. at 12.

[55]  Id. at 11–12.

[56]  Id.

[57]  Id. at 14.

[58]  Id.

[59]  Id.

[60]  Id.

[61]  See In re Lantus Direct Purchaser Antitrust Litigation, No. 18-2086 (1st Cir. 2020) .

[62]  Jazz v. Avadel, No. 23-1186, at 11–12 (Fed. Cir. Feb. 24, 2023).

[63]  85 Fed. Reg. at 33,170 (“We note that FDA has a ministerial role with regard to the listing of patent information.”).

[64]  Small Business Assistance: Frequently Asked Questions on the Patent Term Restoration Program, U.S. Food & Drug Admin. (Feb. 4, 2020), https://tinyurl.com/FDAPTE (“FDA defers to PTO on all matters involving the construction and validity of patent claims.”).

[65]  Complaint for Declaratory and Injunctive Relief, Avadel CNS Pharms., LLC v. Becerra, No. 1:22-cv-2159 (D.D.C. July 21, 2022) (Doc. 1), at 10.

[66]  Mem. of P. & A. in Supp. of Pl.’s Mot. for a Prelim. Inj. or in the Alternative Summ. J. at 3, Avadel CNS Pharms., LLC v. Becerra, Docket No. 1:22-cv-2159 (D.D.C. July 21, 2022), ECF No. 2-1 (citing 21 C.F.R. § 314.50(i)(1)(iii)(B)) (emphasis added).