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November 21, 2025
The tension between regulatory compliance and antitrust exposure in Orange Book patent listings reached a dramatic inflection point this fall. In late October, Teva Pharmaceuticals agreed to pay $35 million to settle a class-action antitrust lawsuit alleging that its ProAir HFA inhaler patents were improperly listed in the FDA’s “Approved Products with Therapeutic Equivalence Evaluations” (the “Orange Book”), delaying generic entry and inflating inhaler prices.1 The settlement marks the first major monetary resolution of a private antitrust claim predicated on over-inclusive Orange Book filings.
Orange Book listing is a prerequisite to asserting a patent in a Hatch-Waxman suit, so a brand-name manufacturer that fails to list an eligible patent is barred from enforcing that patent through the Hatch-Waxman framework. For decades, brand pharmaceutical manufacturers have tended to err on the side of caution and include patents in FDA’s “Approved Drug Products with Therapeutic Equivalence Evaluations” list, also known as the Orange Book, to put the market on notice about patent protection associated with a drug, specifically with an active pharmaceutical ingredient, formulation, or delivery system. But that strategy, once thought prudent, has flipped. Since late 2023, the FTC and private litigants have reframed over-inclusive listings as an anti-competitive tactic, and courts have begun to agree.2 The FTC has argued that improperly listed patents in the Orange Book undermine fair competition because the costs associated with challenging those patents can disincentivize investments in developing generic drugs.3 The agency warned that delays in generic competition, even if brief, can reduce or foreclose patient access to more affordable alternatives. These concerns prompted the FTC to submit an amicus brief in Teva v. Amneal in 2023.4
This enforcement climate has left some stakeholders scratching their heads. The following situates the Teva settlement within that broader enforcement shift, offering context for how Orange Book strategy has evolved and why precision matters now more than ever.
Under 21 C.F.R. § 314.53 and FDA practice, NDA holders must list only patents that claim the drug substance (active ingredient), the drug product (its formulation/composition), or an approved method of use to the Orange Book.5 Listing a patent that does not “claim the drug” is improper; FDA’s 2022 guidance reiterated these limits.6
Historically, brand firms often erred on the side of inclusion, motivated by two features of Hatch-Waxman: (1) listing serves a notice function, forcing ANDA applicants to certify against each listed patent, thereby raising entry costs even if a patent does not actually claim the API or approved drug, and (2) only listed patents are subject to Paragraph IV notification and may be included in a potential suit.7 A particular focal point has been drug-device combinations (e.g., inhalers and autoinjectors), as many patents covering these spaces deal primarily with mechanical device tweaks rather than drug substance, yet appear in the Orange Book and, purportedly, chill generic entry.8
In 2020, the United States District Court for the District of Massachusetts held in In re Lantus that improper Orange Book listing can support antitrust claims, denying Defendant Sanofi-Aventis’s motion to dismiss for lack of Article III standing.9 In so doing, the court emphasized the stay-inducing power of Orange Book listings and rejected arguments that listing could not be a material cause of competitive harm.10
In November 2023, enforcement accelerated after the FTC challenged over one hundred device-centric patents as improperly or inaccurately listed in the Orange Book.11 This action followed a policy statement12 that warned the agency would be scrutinizing the improper submission of patents for listing in the Orange Book, which the FTC said can “disincentivize investments in developing generic drugs, which risks delaying or thwarting competitive generic alternatives.”13
The resulting enforcement sentiment led to the most consequential case to date in the debate over listing device-related patents in the Orange Book, Teva Branded Pharm. Prods. R&D, Inc. v. Amneal Pharms. of N.Y., LLC. Armed with an amicus brief from the FTC, the Federal Circuit affirmed the district court’s delisting order of five Teva ProAir HFA inhaler patents, holding that the phrase “claims the drug for which the application was submitted” requires a patent to particularly point out and distinctly claim the substance itself which renders the “product regulatable and approvable as a drug.”14 Merely covering a device used to deliver the drug, or a feature that might infringe when embodied in the approved product, does not suffice.15
The growing prospect of private antitrust enforcement has amplified the consequences of improper Orange Book listings beyond regulatory correction. Bolstered by recent FTC enforcement, generic manufacturers now have another incentive (and the evidentiary foundation) to argue that inaccurate listings were part of a deliberate scheme to delay competition. This has changed the calculus for brand sponsors, whose routine listing strategies have turned into potential antitrust liabilities.
Before Teva v. Amneal, brand-name sponsors often took a more inclusive approach to Orange Book submissions. FDA’s neutral administrative role coupled with the inability to sue on unlisted patents as well as the strategic value of a 30-month stay encouraged listing anything related to the NDA products’ formulation, device, or method of delivery. But listing, what once availed their products of regulatory exclusivity, now invites scrutiny.
Brand sponsors are rapidly delisting their own products from the Orange Book in order to avoid these dual risks of FTC enforcement and private antitrust suits. Other than conducting a careful re-audit of their Orange Book portfolios to ensure each patent claims the associated active ingredient or finished dosage form, brand pharmaceutical companies should maintain thorough documentation of the legal rationale for any listing decision, as contemporaneous good-faith reasoning may mitigate antitrust exposure. This is especially important for combination product patents that toe the line of Orange Book propriety. As always, companies should monitor FDA and FTC updates for new information,and consult regulatory and antitrust counsel to understand how developments may impact them.
The Federal Circuit’s interpretation of 21 C.F.R. § 314.53 in Teva v. Amneal restored textual discipline to a system blurred for decades by practice, and has transformed the Orange Book from a defensive registry to an antitrust target catalogue. The October 2025 Teva settlement underscores how quickly that theoretical risk has become economic reality, signaling that listing practices once viewed as routine now carry material liability. In this climate, pharmaceutical manufacturers must focus on the accuracy and defensibility of each listed patent, rather than the breadth of their portfolios, to stay ahead of the next wave of scrutiny.