Patent thickets, evergreening and the Orange Book

As of October 9, 2026, FDA's Orange Book listed 148 separate patents against a single brand application, an extended-release tablet that combines two long-marketed medicines, bupropion and dextromethorphan. Across all 1,348 brand applications with any patents listed, the median was four. The figures come from GxRadar's analysis of FDA's Orange Book data files¹.

Long lists like that one are what critics mean by a patent thicket, many overlapping patents on one product covering formulations, dosing, uses and delivery devices, often issued years after first approval. Evergreening is the related practice of adding newer patents to an old product so that protection outlasts the original patent. Since 2023 the Federal Trade Commission has formally disputed hundreds of Orange Book listings it considered improper, and in December 2025 one manufacturer removed more than 200 of them.

A listed patent matters because of what it sets in motion for generic competitors. Every generic applicant must answer it, and a timely lawsuit over it can hold up generic approval for 30 months. The FTC, a federal appeals court and the patent office have each pushed on that system since 2023. Patents are not the only lever; brand owners can also file citizen petitions that FDA must answer before acting on some generics.

Which patents a brand may list with FDA

FDA's patent listing rule, 21 CFR 314.53², allows three kinds of patents: drug substance (active ingredient) patents, drug product (formulation and composition) patents, and method-of-use patents. The rule also names what does not qualify: "Process patents, patents claiming packaging, patents claiming metabolites, and patents claiming intermediates are not covered by this section, and information on these patents must not be submitted to FDA." Brands file patent information on a declaration form within 30 days of approval, or within 30 days of a new patent issuing.

FDA publishes what it receives without checking whether the patent claims match those categories. In a 2022 Federal Register notice³, the patent office put it this way: "The FDA has a ministerial role with regard to the patent listing provisions." A drug can therefore accumulate listings over its whole life, and each one carries legal weight.

A generic applicant has to file a certification for each listed patent, and the riskiest choice, a Paragraph IV certification that the patent is invalid or not infringed, invites a lawsuit. Under FDA's rules, a suit filed within 45 days over a patent that was listed before the generic application was submitted blocks FDA from making approval effective for 30 months. Patents listed later can still be litigated, but they do not trigger that automatic stay. Our explainer on the Orange Book covers the rest of the publication, and the glossary defines its terms.

Congress tightened one part of the system in the Orange Book Transparency Act of 2020⁴, signed January 5, 2021. When a court or the Patent Trial and Appeal Board issues a final decision cancelling or invalidating a listed patent's claims, the brand must notify FDA within 14 days and ask that the listing be amended or withdrawn.

What the patent list looks like in 2026

GxRadar counted every patent-application pair in FDA's October 9, 2026, patent file and found 8,861 listings of 7,134 distinct patents across 1,348 brand applications. A small group of products carries a large share of them. The 262 applications with 10 or more patents account for 4,844 listings, or 55 percent of the total.

FDA's file flags each listing by the type of claim the brand declared. Of the 8,861 listings, 1,574 (18 percent) were flagged as claiming the drug substance. Another 3,029 (34 percent) were flagged as drug product patents without a substance flag, and 3,251 (37 percent) carried only a method-of-use code. The remaining 1,007 had no flag; FDA's data documentation explains that the flags apply to patents submitted on the current declaration form and listed after August 18, 2003. More than half of the applications on the list, 749 of 1,348, had no patent flagged as covering the active ingredient at all.

None of that proves a listing is improper. Formulation and use patents are legitimate when they meet the rule, though they are the ones usually called secondary because they tend to issue after the compound patent. A 2018 study in the Journal of Law and the Biosciences⁵ that examined all drugs on the market from 2005 to 2015 found that "78 percent of the drugs associated with new patents in the FDA's records were not new drugs coming on the market, but existing drugs."

The FTC's challenges to improper listings

Its recent campaign began with a September 2023 policy statement⁶. It warned that a brand that improperly lists a patent "may benefit from a 30-month stay of FDA approval of generic drug applications," regardless of whether a court ultimately finds the patent valid or infringed, and that the practice "may constitute an unfair method of competition in violation of Section 5 of the FTC Act." The statement said the FTC could use FDA's own dispute procedure under 21 CFR 314.53(f).

That procedure lets anyone challenge a listing. As the FTC has described it⁸, FDA forwards the dispute to the brand, which has 30 days to withdraw or amend the listing or to certify, under penalty of perjury, that it is correct. FDA does not decide who is right, and a brand that certifies its listing keeps it.

FTC staff then used the process in waves. Its first round, in November 2023, covered more than 100 patents. In April 2024⁷ it disputed more than 300 listings across 20 brand products, among them injectable diabetes and weight-loss drugs, inhalers and a glucagon nasal spray, and said four entities had delisted patents after the first round. The May 2025 round challenged more than 200 device patent listings on 17 products and said earlier efforts had led to delistings across 22 brand products.

On December 20, 2024, the Federal Circuit affirmed⁹ an order requiring a brand to delist inhaler patents. "To claim that drug, the patent must claim at least the active ingredient," the court wrote, so "patents claiming just the device components of the product approved in an NDA do not meet the listing requirement." In December 2025, the FTC announced that a manufacturer had requested removal of more than 200 listings covering more than 30 asthma, diabetes and COPD drugs and epinephrine autoinjectors.

What the patent office and FDA have done

Patent office and FDA officials started formal talks after a July 2021 executive order on competition. FDA sent the patent office a letter in September 2021, the patent office replied in July 2022, and a November 2022 notice³ announced a joint public listening session, held January 19, 2023, on ways to keep the patent system from "unjustifiably" delaying generic and biosimilar competition.

Next the patent office took aim at a building block of many thickets. Patents on obvious variants of an earlier invention are often allowed only if the owner files a terminal disclaimer, which ties the later patent's term to the earlier one. A May 2024 proposed rule¹⁰ would have made patents tied together this way unenforceable if any one of them had a claim finally held invalid as anticipated or obvious. The office said the change was meant "to prevent multiple patents directed to obvious variants of an invention from potentially deterring competition." It withdrew the proposal¹² in December 2024 after receiving more than 300 comments.

On FDA's side, a March 2023 GAO report¹¹ found no consensus among 15 stakeholders on whether device patent listings delay generic drug-device products, though 13 of them said it would help for FDA to clarify which device-related patents belong on the list. GAO reported that FDA planned a workgroup to consider that question. Device-heavy products such as inhalers are a large part of why some complex generics still have few or no copies.

Patent disputes over these products often end in settlements, covered in our piece on pay-for-delay settlements. Exclusivity periods such as 180-day first-filer exclusivity layer on top of the patent list. Generics that clear FDA review while listed patents remain in force get tentative approval instead of final approval.

FDA posts a refreshed patent file¹ every month. The question GAO raised in 2023 is only partly settled. The 2024 ruling established that a patent claiming only device parts cannot be listed; the court said it did not need to reach a further argument about drug substance and drug product patents, leaving open the status of patents that claim a device together with its drug.