Abstract
IMPORTANCE: Manufacturers of drug-device combinations, such as inhalers and injectable medications, often obtain patents not just on the active pharmaceutical ingredients of these products (primary patents) but also on other features, such as their formulations and methods of use (secondary patents) and delivery devices (tertiary patents). Courts, policymakers, and regulators have recently begun scrutinizing whether manufacturers may be improperly listing tertiary patents with the Food and Drug Administration (FDA) that lack claims on active pharmaceutical ingredients and whether such patents may be delaying generic competition. However, the full scope of patenting practices on drug-device combinations remains unknown. OBJECTIVE: To analyze patent protection on small-molecule drugs approved by the FDA from 1986 to 2023 with 1 or more tertiary patents. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study of patenting practices on drug-device combinations, all patents listed in the FDA's Approved Drug Products With Therapeutic Equivalence Evaluations (Orange Book) were categorized (primary, secondary, or tertiary), and products with at least 1 tertiary patent were included. Analyses were performed between May 2024 and October 2025. MAIN OUTCOMES AND MEASURES: The primary outcome of the study was the duration of expected patent protection on each product, measured from the time of approval until expiration of the last-to-expire patent. Added protection from tertiary patents that went beyond protection afforded by primary or secondary patents was also analyzed. RESULTS: The FDA approved 331 products from 1986 to 2023 with 1 or more tertiary patents; 137 of 3241 patents (4.2%) listed on these products were primary patents, 1353 of 3241 were secondary patents (41.7%), and 1751 of 3241 were tertiary patents (54.0%). Among tertiary patents, 1047 of 1751 (59.8%) lacked claims making any mention of active pharmaceutical ingredients. The median (IQR) duration of expected patent protection among products in the cohort was 17.6 (14.4-21.2) years. There were 180 products (54.4%) that had tertiary patents extending periods of expected protection beyond other patents, and the median (IQR) duration of added protection was 7.5 (2.8-13.9) years. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that policymakers and regulators should take steps to ensure that tertiary patents are not improperly listed in the Orange Book and that generic competition occurs in a timely fashion.