New Drug Application/NDA Archives

If the Label Is Skinny Enough – No Inducement Under Hatch-Waxman

by Ian J. Howard | Dec 14, 2023 | Patents

The US Court of Appeals for the Federal Circuit made explicit what has long been considered implicit based on Warner-Lambert and its progeny, namely, that plaintiffs asserting an induced infringement theory to bar the entry of generic drugs in a Hatch-Waxman suit are subject to higher scrutiny than plaintiffs asserting the same theories outside of the Hatch-Waxman context. H. Lundbeck A/S v. Lupin Ltd., Case No. 22-1194 (Fed. Cir. Dec. 7, 2023) (Dyk, Prost, Hughes, JJ.)

Lundbeck owns the approved new drug application (NDA) for Trintellix®, a drug indicated for the treatment of major depressive disorder (MDD), as well as an expired compound patent for the associated active ingredient vortioxetine. Lundbeck also owns a patent that claims the use of vortioxetine as an antidepressant that can be prescribed in place of a traditional antidepressant to alleviate a patient’s negative sexual side effects, and another patent that claims the use of vortioxetine to treat cognitive impairment symptoms in patients with MDD.

Generic pharmaceutical companies filed abbreviated new drug applications (ANDAs) seeking approval to market generic versions of Trintellix® and asserting that Lundbeck’s unexpired patents listed in its NDA were invalid and would not be infringed by the generic companies. As required by the Hatch-Waxman Act (to prevent the entry of a generic on the market), Lundbeck sued the generic companies. At the district court, the defendants prevailed on the finding of noninfringement but lost on invalidity. Lundbeck appealed.

Lundbeck pressed its induced infringement and contributory infringement theories on appeal. Lundbeck argued that the generics infringed under the plain text of Hatch-Waxman (35 USC 271(e)(2)(A)) because they filed ANDAs seeking approval to market vortioxetine, and that “some uses of vortioxetine—for the treatment of patients that have previously taken other drugs but had to cease or reduce use due to sexually related adverse events and for the treatment of cognitive impairment—are covered by [Lundbeck’s listed] patents; and the labels do not prohibit prescribing vortioxetine for those uses, even though the defendants do not propose to market the drug for those patented uses.” In other words, Lundbeck argued that in terms of its inducement allegation, it made no difference whether a drug would be sold for a use not covered by Lundberg’s NDA-listed patents because the drug could be prescribed for those patented uses.

The Federal Circuit disagreed, explaining that “‘the use’ in § 271(e)(2)(A) refers to the use for which the FDA has granted an NDA” and for which the ANDA was submitted.” The Court emphasized that it is not “an act of infringement under . . . § 271(e)(2)(A) to submit an ANDA for a drug if just any use of that drug were claimed in a patent.” If it were, a brand could “maintain its exclusivity merely by regularly filing a new patent application claiming a narrow method of use not covered by its NDA,” which “would confer substantial additional rights on pioneer drug patent owners that Congress quite clearly did not intend to confer.” As the Court then held, “actions for [...]

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Patent Law Principles Apply to Claim Scope: Orange Book Delisting and Listing and Regulations

by Benjamin Ediger, Ph.D. | Mar 9, 2023 | Patents

The US Court of Appeals for the Federal Circuit ordered that the only Orange Book patent asserted in a lawsuit must be delisted since its claims were directed to the computer-implemented distribution system and not a method of use. Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, Case No. 23-1186 (Fed. Cir. Feb. 24, 2023) (Lourie, Reyna, Taranto, JJ.)

Jazz Pharmaceuticals holds a new drug application (NDA) for Xyrem, an oral sodium oxybate solution prescribed to help those with certain narcolepsies manage cataplexy. Sodium oxybate itself is no longer covered by patents because it has been used in relation to narcolepsy since the 1960s. For this reason, Jazz built its patent portfolio around Xyrem’s formulation, use and distribution.

Jazz uses a single-pharmacy distribution system for Xyrem, known as a risk evaluation mitigation strategy (REMS). Implementing REMS was a condition of Xyrem’s US Food & Drug Administration (FDA) approval because it mitigates safety risks of dangerous active pharmaceutical ingredients such as sodium oxybate. One of Jazz’s patents is directed to this REMS distribution system. Abbreviated New Drug Application (ANDA) 505(b)(2) NDA (Hybrid NDA) approval is similarly conditioned on implementing a REMS that is sufficiently comparable to any that the NDA holder must implement. The FDA eventually determined that single-pharmacy systems were unnecessary for Xyrem and potentially detrimental.

Avadel submitted a hybrid NDA for a drug that requires only a single nightly dose, unlike Xyrem, which requires a patient to wake up during the night to ingest a second dose. Avadel’s application also proposed a more lenient REMS that utilizes multiple pharmacies. In view of these differences, Avadel believed that it could avoid a lengthy FDA approval process because all of Jazz’s Xyrem Orange-Book-listed patents seemed addressable without making any Paragraph IV certifications. As for the REMS patent, Avadel filed a statement under 21 U.S.C. § 355(b)(2)(B) because the patent was listed as claiming a method of use and Avadel was not seeking approval for the REMS system to which that patent’s claims were directed.

Jazz sued Avadel asserting seven patents, of which the REMS patent was the only Orange-Book-listed patent. Avadel asserted a counterclaim requesting that the district court order Jazz to delist the REMS patent from the Orange Book. The district court subsequently held a Markman hearing finding that the REMS patent’s claims were directed to a system and not a method. The district court granted Avadel’s motion for judgment on the pleadings, finding that the REMS patent did not claim “the drug for which the application was approved” and thus had to be delisted from the Orange Book. Jazz appealed.

Jazz argued that because the FDA permitted the REMS patent to be Orange Book listed, Avadel was prohibited from availing itself of the statutory delisting provision. The Federal Circuit disagreed, concluding that the language of the delisting provision was only concerned with whether a listed patent met the provisions’ conditions at the time of the triggering litigation.

Jazz also argued that there was no evidence that Congress imported patent-law [...]

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Material Information Submitted to FDA but Withheld from PTO Gives Rise to Inequitable Conduct

by Paul Devinsky | Sep 16, 2021 | Patents

The US Court of Appeals for the Federal Circuit found prior art submitted to the US Food and Drug Administration (FDA), yet withheld from the US Patent & Trademark Office (PTO) during prosecution of an asserted patent, sufficient evidence for a finding of inequitable conduct. Belcher Pharmaceuticals, LLC v. Hospira, Inc., Case No. 20-1799 (Fed. Cir. Sept. 1, 2021) (Reyna, J.)

The patent in issue relates to injectable formulations of l-epinephrine. Epinephrine is a hormone that has been on the market since approximately 1938 and is used for a variety of medical purposes. It is also known that l-epinephrine degrades into a more potent isomer known as d-epinephrine. L-epinephrine also degrades into an impurity known as adrenalone through a process called oxidation.

In 2012, Belcher first submitted a New Drug Application (NDA) for a 1 mg/mL injectable l-epinephrine formulation. The NDA was literature-based, meaning that Belcher did not perform any clinical or non-clinical studies on its epinephrine formulation to support its application. Among the materials submitted to the FDA was an article by Stepensky et al to support its statement that “racemization of the enantiomerically pure L-Epinephrine isomer in injectable formulations of epinephrine is a well-known process.” It also submitted data from Swiss pharmaceutical company Sintetica SA’s formulation that had a pH range of 3.1 – 3.3 and undetectable levels of adrenalone. Ultimately, Belcher pursued a formulation with a similar pH range of 2.8 – 3.3.

In 2014, Belcher filed a patent application that was ultimately issued as the asserted patent. The patent taught that increasing the in-process pH to 2.8 – 3.3 unexpectedly reduced the racemization of l-epinephrine to d-epinephrine at release by approximately two thirds. The asserted claims covered pharmaceutical epinephrine formulations having a pH between 2.8 – 3.3 and certain concentrations of l-epinephrine, d-epinephrine and adrenalone at the time of release and 12 months later.

The prosecution of the application involved a single office action in which the pending claims were rejected in view of Helenek. The examiner explained that Helenek taught 1 mg/ml of epinephrine injection that, among other things, had a pH range of 2.2 – 5.0. Belcher overcame this rejection by arguing that Helenek did not render obvious the claimed range of 2.8 – 3.3 because the claimed range was unexpectedly found to be critical to reduce racemization of l-epinephrine.

Hospiria also submitted an NDA seeking approval of an injectable l-epinephrine formulation, which included a certification under 21 U.S.C. § 355(b)(2)(A)(iv)(Paragraph IV) that the asserted patent’s claims were invalid, unenforceable and/or not infringed by Hospira’s NDA product. Belcher subsequently sued Hospira for patent infringement.

During trial, Darren Rubin, Belcher’s Chief Science Officer, testified that in his role at Belcher, he was involved in the drafting and development of the NDA and in the prosecution of the asserted patent—including drafting the claims and specification and responding to the examiner’s office action. Darren admitted he knew of Stepensky before the application was filed and that he possessed a label for a 1 mg/mL epinephrine product marked [...]

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