Risk Evaluation and Mitigation Strategy Patent Not listable in Orange Book

March 6, 2023

The Federal Circuit on February 24th affirmed the Delaware District order in Jazz Pharm., Inc. v. Avadel CNS Pharm., LLC., 2023-1186, that Jazz delist from the Orange Book its Patent 8,731,963 directed to a REMS to control access to its drug Xyrem, also known as gamma hydroxyl butyrate (GHB) which was misused to facilitate rape, the “date rape” drug.” The decision considered whether to list a drug in the Orange Book was proper.   Patents may be listed in the Orange Book if it either claims the drug or methods of using the drug. 21 U.S.C. § 355(b)(FDCA) and 21 C.F.R. § 314.53(b)(1). Jazz contended that patent law did not provide the correct framework determining whether a patent should be listed in the Orange Book. Both the statute and rule look to the patent claims to determine if a patent claims either the drug or a method of using the drug.  Here the issue was whether the ‘963 claims were directed to a method of using Xyrem.

The claims are:

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.



6. The system of claim 1 wherein the prescription drug comprises gamma hydroxyl butyrate (GHB). 

The district court had performed a claim construction deciding that the ‘963 patent was not a method of use patent under the FDCA which requires the patent “claims a method of using [the] drug for which approval is sought or has been granted in the application.” Jazz argued that the district court erred in not treating the claims as method claims which relate a REMS-based procedure. The Federal Circuit agreed with the district court that the claims are directed to a “system” and not a method.  Like the district court the Federal Circuit noted the claims recite an “assemblage of components.” Jazz did not point to anything in the patent or the prosecution history which contradicts this conclusion.

The Court then turned to Jazz’ second point that 21 C.F.R. § 314.53(b)(1) which describes listing patents that “claim conditions of use,” informs the analysis of whether a patent claims “an approved method of using the drug” under § 355. Jazz argued this allowed for a broader definition of “method” than permitted under patent law. Jazz also points to subsections of 21 U.S.C. § 355 that use the phrase “conditions of use,” to establish that this term is inclusive of all patents claiming elements of an approved REMS.  However, the conditions of use described in the rule describe conditions of use evaluated for efficacy, implicating “relevant science,” “clinical investigations,” and “establishing effectiveness” and determining whether a “new drug can be expected to have the same therapeutic effect as the listed drug when administered” according to the approved “conditions of use prescribed, recommended, or suggested in the labeling.”  The Court did not consider these provisions to expand the meaning of “method of using the drug” which must take its meaning from patent law.

Jazz’ final argument was that to delist a patent does not permit delisting a patent which falls into a category neither requiring nor forbidden to be listed.  Jazz argued that since it was permissive in 2014 to list the patent, § 355(c)(3)(D)(ii)(I) does not provide one with the power to request a delisting. The Federal Circuit affirmed the district court’s analysis that the provision does not require the listing to have violated law but 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. As the ’963 patent claims neither and has been asserted in a patent infringement action against Avadel, §355(c)(3)(D)(ii)(I) provides Avadel with a delisting remedy.


The key is to remember that the patent claims should be directed to a method of using the drug, here they were to a system for using the drug.  A better approach would have been to draft the claims to a method of using the drug using the claimed system. Here the claims could have been drawn to a patient selection scheme which may have avoided the Court’s criticisms.