On February 24, 2023, the Federal Circuit held that Jazz Pharmaceuticals, Inc. (Jazz) must delist U.S. Patent No. 8,731,963 (the ’963 Patent) from the U.S. Food and Drug Administration’s (FDA’s) “Orange Book” because the claims in the ’963 Patent to a method of Risk Evaluation and Mitigation Strategies (REMS) to control access of Jazz’s Xyrem® did not qualify as “a method of using [the] drug for which approval is sought” under 21 U.S.C. § 355(b). Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, 60 F.4th 1373 (Fed. Cir. 2023).
Background
Jazz manufactures and sells sodium oxybate under the brand name Xyrem®, an FDA-approved drug for treating cataplexy and excessive daytime sleepiness associated with narcolepsy. Sodium oxybate is the sodium salt of gamma-hydroxybutyric acid (GHB). Because of known abuse of GHB, the FDA conditioned its approval of Xyrem® on the implementation of a REMS to control the access and distribution of Xyrem®. Jazz subsequently pursued and was granted patent claims to the REMS. The relevant claim in Jazz’s ’963 Patent recites:
1. A computer-implemented system for treatment of a narcoleptic patient with a prescription drug that has a potential for misuse, abuse, or diversion, comprising:
one or more computer memories for storing a single computer database having a database schema that contains and inter- relates prescription fields, patient fields, and prescriber fields…
a data processor configured to…
said identifying that the narcoleptic patient is a cash payer by said second database query being an indicator of a potential misuse, abuse, or diversion by the narcoleptic patient and being used to notify the physician that is interrelated with the narcoleptic patient through the schema of the single computer database.
Jazz listed the ’963 Patent in the Orange Book on the basis that it claims a method of using Xyrem® under 21 U.S.C. § 355(b)(1)(A)(viii). FDA has not opined on whether REMS patents are properly listed in the Orange Book and has historically taken the position that its duties with respect to Orange Book listings are purely ministerial.
Jazz v. Avadel
In May 2021, Jazz initiated a patent infringement action against Avadel CNS Pharmaceuticals (Avadel) following Avadel’s submission of a new drug application (NDA) pursuant to Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA), asserting five patents, including the ’963 Patent. Avadel counterclaimed, seeking a declaration pursuant to 21 U.S.C. § 355(c)(3)(D)(ii)(I) to order Jazz to remove the ’963 Patent from the Orange Book. Avadel filed a motion for judgement on the pleadings seeking delisting of the ’963 Patent from the Orange Book, which was granted by the U.S. District Court for the District of Delaware and affirmed by the Federal Circuit on February 24, 2023. Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, No. CV 21-691-GBW, 2022 WL 17084371, at *4 (D. Del. Nov. 18, 2022), aff'd, 60 F.4th 1373 (Fed. Cir. 2023).
Under the Hatch-Waxman Act, an NDA filer must submit to the FDA information on each patent “for which a claim of patent infringement could reasonably be asserted” if the patent claims “a method of using such drug for which approval is sought or has been granted in the application.” 21 U.S.C. § 355(b)(1)(A)(viii). For “patents that claim a method of use, the applicant must submit information only on those patents that claim indications or other conditions of use for which approval is sought or has been granted in the NDA.” 21 C.F.R. § 314.53(b)(1). The FDA publishes that information in the “Approved Drug Products with Therapeutic Equivalence Evaluations” (also known as the “Orange Book”), which provides the NDA filer with the ability to initiate a 30-month suspension of the FDA’s approval of a competitive product.
Central to the Federal Circuit’s decision was the fact that the ’963 Patent claimed systems rather than methods. The Federal Circuit disagreed with Jazz’s argument that § 355(b)(1)(A)(viii) yields a broader definition of “method” because using Xyrem® was conditioned on prescribers of Xyrem® following the REMS recited in the claims of the ’963 Patent. Instead, the Federal Circuit concluded that § 355(b)(1) “narrows that category of listable patents to those that (1) claim methods of use, wherein (2) those methods of use are directly relevant to the NDA in question.” According to the Court, “claims to a system comprising computer memories and a data processor are not claims to a method.”
The Federal Circuit also disagreed with Jazz’s argument that 21 U.S.C. § 355(c)(3)(D)(ii)(I) is not available to provide Avadel with a delisting remedy for the ’963 patent. Instead, the Court found that § 355(c)(3)(D)(ii)(I) provides that an accused infringer of a listed patent may request an order requiring the patent holder to correct or delete listings for patents that do not claim the drug or a method of using the drug.
Practice Tips
NDA filers wishing to take advantage of the Orange Book should pursue patent claims directed to a method of using a drug or to the drug itself.
NDA holders who previously listed REMS patents or distribution-related patents in the Orange Book should review this decision carefully.
505(b)(2) and ANDA applicants should review all Orange Book patents listed for each reference listed drug product to confirm that they are properly listed in the Orange Book. Improper listing may impact patent expiration dates and any remaining exclusivities in preparing approval strategy.
