How Orange Book patent listings get challenged, from FDA's dispute form to the FTC's letters

FDA keeps a running list of every formal challenge to a patent listed in its Orange Book. The version current through Oct. 9, 2026, has 122 entries, by GxRadar's count of the agency's Patent Listing Dispute List¹. In 80 of them, the brand company that listed the patent answered the challenge and nothing in the Orange Book changed. In 40, the patent listing was updated. Two were still pending.

That ratio says a good deal about how the system is built. FDA publishes the patents brand companies submit, does not judge whether they belong there, and changes a listing only if the company agrees to. Since 2023, the most persistent challenger has been another federal agency, the Federal Trade Commission, which has disputed hundreds of listings and warned that improper ones may break federal competition law.

Listings matter because a listed patent can delay a generic. If a generic applicant challenges it and the brand sues in time, FDA approval is generally paused for up to 30 months, as GxRadar's explainer on the 30-month stay describes. This piece covers which patents may be listed, how a dispute works, what the FTC has done, and how courts have drawn the line.

What may be listed, and what may not

Federal law, as tightened by the Orange Book Transparency Act of 2020⁵, requires a brand applicant to submit two kinds of patents: those that claim the drug and are drug substance (active ingredient) or drug product (formulation or composition) patents, and those that claim a method of using the drug for which approval is sought or granted. Patent information "that is not the type of patent information required" may not be submitted, the FTC noted in its 2023 policy statement⁹, quoting the law.

FDA's regulation at 21 CFR 314.53³ fills in the details.

Timing rules are strict too. Patent information is due on Form FDA 3542 within 30 days of approval, and within 30 days of issuance for later patents, and the signer must "verify under penalty of perjury" that the submission complies, the regulation says³. Device components, such as inhaler dose counters or autoinjector mechanisms, are not on either list, and that gap is where most recent fights have taken place.

Why FDA does not referee

FDA settled its own role two decades ago. In its June 2003 rule on patent listings, the agency wrote that "we have long observed that we lack expertise in patent matters" and that, although it would keep relaying questions to application holders, "our patent listing role remains ministerial," according to the published rule⁶. It noted that courts had upheld that view. A 2016 rule repeated that "FDA's role in listing patents remains ministerial," in the Federal Register text⁷.

In practice, FDA "lists the patent information provided by drug companies in the Orange Book without independently verifying that it meets the statutory and regulatory requirements," the Congressional Research Service wrote in its January 2026 update on Orange Book listings⁸. GxRadar's Orange Book explainer covers the rest of the publication.

How a 314.53(f) dispute works

Anyone can start one. A challenger writes to FDA under the heading "314.53(f) Patent Listing Dispute," with a statement of the specific grounds; for method-of-use disputes the statement is limited to a short narrative, the rule says³. FDA forwards it to the application holder, which has 30 days to confirm the listing with a signed verification or to withdraw or amend it. "Unless the NDA holder withdraws or amends its patent information in response to the patent listing dispute, the Agency will not change the patent information in the Orange Book."

A dispute does not excuse the generic applicant from the usual paperwork. An abbreviated application "must contain an appropriate certification or statement for each listed patent, including the disputed patent, during and after the patent listing dispute," under the same section. Those certifications are explained in GxRadar's piece on Paragraph IV certifications.

FDA posts each dispute and its outcome on the Orange Book page². GxRadar tallied the entries by the year the holder's response was due.

Source: GxRadar analysis of FDA's Patent Listing Dispute List¹, current through Oct. 9, 2026. An entry can cover several patents for one product. The list records how a holder answered the dispute; a company can also withdraw a patent separately, which the list does not necessarily capture.

The FTC's three rounds

On Sept. 14, 2023, the FTC voted 3-0 to issue a policy statement saying it would scrutinize improper listings as potential "unfair methods of competition in violation of Section 5 of the FTC Act," according to its announcement¹⁰. The statement says a brand may benefit from a 30-month stay "regardless of whether a court ultimately finds the patent at issue is valid or infringed by the competing product," and points to the agency's 2002 study, which "identified numerous instances in which the 30-month stay was used to block competition," the policy statement says⁹.

Sources: FTC announcements of November 2023¹¹, April 2024¹² and May 2025¹³.

Rather than sue, the FTC chose FDA's dispute process, while saying it retained "the right to take any further action as needed in the public interest," its November 2023 release says¹¹. FDA's commissioner reminded application holders at the time that they "are obligated to ensure that patent listings comply" and to "substantively respond" to disputes.

The first two rounds "led to the delisting of patents across 22 different brand-name products," the FTC said in May 2025¹³. "Several hundred patents have been removed from the Orange Book following FTC's actions," CRS reported in 2026⁸. A May 2024 analysis by the American Action Forum¹⁴, a policy research group, found that FDA's dispute list at that point showed updated listings for 17 patents from the first round, with the rest unchanged.

Courts and the active-ingredient test

Generic applicants have a second route. Since 2003, a generic company sued for infringement may counterclaim for an order requiring the brand to correct or delete patent information on the ground that the patent does not claim the drug or an approved use, under 21 U.S.C. 355(j)(5)(C)(ii)⁴. Under the Orange Book Transparency Act⁵, when a final Patent Trial and Appeal Board or court decision cancels listed claims and the brand company concludes the patent no longer qualifies, it must notify FDA within 14 days and ask for the listing to be amended or removed. FDA then acts, except while a 180-day exclusivity that depends on the patent is running. That board's review is covered in inter partes review and drug patents.

In December 2024, the US Court of Appeals for the Federal Circuit affirmed an order requiring a brand company to delist five patents on an inhaler's device components, holding that to be listed a patent must claim at least the active ingredient of the approved product, the National Law Review¹⁵ reported. CRS pairs that ruling with an earlier appeals court decision that a patent on a device for injecting a drug should not have been listed, and a Federal Circuit decision against listing a patent on a computerized drug-safety program system. The FTC cited the inhaler ruling in its May 2025 letters.

Whether Congress steps in is open. CRS lists options including more responsibility for FDA or the FTC and whether "the 30-month stay should apply only to certain patent types (e.g., active ingredient patents)," its report says⁸. GxRadar's piece on patent thickets and evergreening covers the wider debate. On the regulatory side, FDA issued a draft guidance in June 2026, "Forms FDA 3542a and FDA 3542: Questions and Answers," under docket FDA-2026-D-2698, covering the forms brand companies use to submit patents¹⁶. The two dispute entries still marked pending on FDA's list have response dates of Sept. 24 and Nov. 7, 2026.