Curbing Patent Thickets Will Reduce High Drug Prices
Luis Gil Abinader
Policy Director, Generation Patient
luis@generationpatient.org
Drug patent policy must strike a balance between incentivizing genuine biomedical innovation and enabling competition after limited exclusive rights expire. Achieving this balance is crucial for ensuring affordable access to medicines for young adults with chronic conditions, many of whom rely on high-cost therapeutics. However, brand companies typically exploit gaps in the patent system to disrupt that balance and delay generic competition long beyond the expiration of foundational exclusive rights. One of the primary mechanisms that drug companies use to delay competition is filing patent applications claiming inventions that are patentably indistinct from earlier patents filed by the same applicant. When these overlapping patent applications are detected, examiners at the U.S. Patent and Trademark Office (USPTO) reject the later claims under double patenting grounds because they are too similar to one or more earlier patents.
Applicants can overcome these rejections by agreeing to shorten the term of the later-filed patent so that it expires on the same date as the earlier patent. These agreements are formalized through terminal disclaimers. When a terminal disclaimer is entered, the USPTO withdraws the double patenting rejection, and the patent is cleared for issuance if other office actions have been resolved. With terminal disclaimers, the applicant does not extend the length of exclusive protection but does increase the number of patents that can be asserted against competitors.
Terminally disclaimed patents surge around the first generic
challenge and continue long after
Terminal disclaimer status is based on the patent front page. First generic challenge is based on the date of the earliest Hatch-Waxman case filing per active ingredient. Universe is 5,494 patents in the Orange Book across 529 active ingredients.
New research by Generation Patient shows that drug companies ramp up patent filings as generic competition approaches. Generation Patient reviewed the Orange Book patent listings for 529 active ingredients with at least one Paragraph IV Abbreviated New Drug Application (ANDA) filed from 2010 to 2025. Our analysis shows that a third of Orange Book patents filed a decade before the first generic challenge have a terminal disclaimer. In the years immediately surrounding and following the first challenge, the share of Orange Book patents that have terminal disclaimers increases sharply. More than 80 percent of patents filed after the first generic challenge carry a terminal disclaimer. Drug companies probably secure these patents to increase litigation costs and discourage generic challenges. The large share of disclaimers after the first ANDA challenge also suggests that drug companies adjust their thickets in response to how the first case unfolds.
Young adults with chronic and rare conditions rely on innovation and strong incentives to promote meaningful research and development. However, thickets of late-stage patents with terminal disclaimers reflect something entirely different. Brand drug companies file overlapping applications to expand their patent arsenal and deter competition. Each of these patents can be asserted independently against prospective competitors, deterring some generic manufacturers from challenging the thicket altogether and forcing others to endure years of costly litigation before they can enter the market. Young adult patients who are balancing finances, education, and employment while living with a chronic condition face the impossible reality of paying high prices for medications they need or risking serious health consequences by going without them.
Rifaximin illustrates the mechanics of patent thickets in practice and how they delay affordable access for young adult patients. Rifaximin (Xifaxan) was discovered by Italian scientists over four decades ago and licensed to Salix Pharmaceuticals in 1996 [1]. The Food and Drug Administration (FDA) has approved rifaximin for various indications since 2004, including the treatment of irritable bowel syndrome (IBS) with diarrhea in 2015. The earliest Orange Book patent associated with rifaximin expired in 2019. However, Salix built a thicket with more than 34 patents, 25 with terminal disclaimers, to assert against prospective competitors seeking to enter the U.S. market.
When Norwich filed an ANDA to market generic rifaximin in 2020, Salix asserted 26 patents, including 19 with terminal disclaimers [2]. Judge Richard Andrews presided over the case and, in 2022, issued an order invalidating four of the seven patents that reached trial, including two that claimed methods of treating IBS. In 2023, the USPTO granted Salix two new terminally disclaimed patents claiming methods of treating IBS in females. Salix then asserted the newer patents claiming methods of treating IBS against Norwich in 2024, delaying generic competition for several more years while Americans pay among the highest prices in the world for rifaximin.
The bipartisan and bicameral ETHIC Act will curb anticompetitive patent thicket gamesmanship and reduce high drug prices for young American patients
Each box represents a patent asserted in court litigation. Red boxes represent patents with terminal disclaimers. Reduced counts are based on terminal disclaimer linkages.
Symbravo similarly illustrates the magnitude of drug patent thickets and how they impact Hatch-Waxman litigation today. Axsome Therapeutics has listed 94 patents in the Orange Book entry for Symbravo, a drug combination approved by the FDA in 2025 for treating migraines. Symbravo combines meloxicam and rizatriptan, two active ingredients first patented decades ago. Research by Generation Patient shows that 82 of the 94 patents listed in the Orange Book entry for Symbravo carry terminal disclaimers in their front pages. Although most are interconnected through a complex linkage that traces back to a dosage form patent issued in 2017 and are therefore expected to expire in 2036 together with their earlier filed references, Axsome can assert each one of them individually against generic challengers seeking to enter the U.S. market.
Court documents show that Axsome has already asserted 1,856 claims across 75 patents from their thicket against Apotex, a generic manufacturer seeking to enter the market [3]. That case was filed in September 2025 and is still ongoing as of May 2026. Apotex has sought to narrow the scope of this case, arguing that litigating 1,856 claims at once “will become a cost-prohibitive endeavor” instead of a “reasonable inquiry” into whether their ANDA infringes legitimate patent rights [4]. Apotex has argued that litigating all the asserted claims at once would subject them to a “Kafkaesque and cost-prohibitive nightmare requiring it to expend enormous amounts of money and resources to defend against what can only be described as a ‘patent thicket.’” [5] Public records indicate that Apotex’s motion to narrow the scope of this case is still pending as of May 2026.
Seventy of the 75 patents asserted by Axsome against Apotex are interlinked thought disclaimers. Under Eliminating Thickets to Increase Competition Act (ETHIC) (S. 2276; H.R. 3269), Axsome would have been able to assert no more than five patents against Apotex in this ANDA litigation. [6]
Applied to the Symbravo scenario, Axsome would have been able to assert no more than five patents against Apotex instead of 75. Applied to the rifaximin scenario, Salix would have been able to assert no more than seven patents against Norwich instead of 26. The ETHIC Act would also neutralize follow on litigation involving patents from a terminally disclaimed group previously asserted in court against the same generic challenger. This provision of the ETHIC Act would have prevented the second lawsuit filed by Salix against Norwich in 2024, which alleges ANDA infringement based on a newer set of method of treatment claims from one of the terminally disclaimed patent families that was already invalidated in the 2020 case.
References:
[1] BioWorld, “Licensing agreement signed for rifaximin,” BioWorld, Aug. 9, 1996
[2] Generation Patient, Rifaximin Patents, https://generationpatient.org/rifaximin-patents (last visited May 27, 2026).
[3] Ibid.
[4] U.S. Patent No. 9,821,075
[5] Axsome Therapeutics, Inc. v. Apotex Inc., No. 2:25-cv-16038 (D.N.J. filed Sept. 26, 2025).
[6] Generation Patient, Symbravo Patents, https://generationpatient.org/symbravo-patents