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Tertiary patenting on drug–device combination products in the United States

Drug–device combination products are becoming increasingly prevalent, with many lasting years beyond the expiration date of primary and secondary patents on the drug itself.

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Figure 1: Changes in prevalence of primary, secondary, and tertiary patents over time.
Figure 2: Duration of unexpired primary, secondary, and tertiary patents for drug–device combination products in 2000 and 2016 (relative to FDA approval date).


  1. Rubin, R. Lancet 388, 1266 (2016).

    Article  Google Scholar 

  2. Duhigg, C. Outcry over EpiPen prices hasn't made them lower. The New York Times (4 June 2017).

  3. Kasperkevic, J. New York investigates EpiPen maker Mylan after price hike of medication. The Guardian (6 September 2016).

  4. Cha, A.E. US lawmakers demand investigation of $100 price hike of lifesaving EpiPens. The Washington Post (23 August 2016).

  5. US Food and Drug Administration. Approved Drug Products with Therapeutic Equivalence Evaluations 2017 (FDA, 2017).

  6. Beall, R.F., Nickerson, J.W., Kaplan, W.A. & Attaran, A. PLoS One 11, e0148939 (2016).

    Article  Google Scholar 

  7. AstraZeneca. Health Canada endorsed important safety information on Pulmicort Turbuhaler (budesonide) powder for oral inhalation, 200 μg per metered dose (23 July 2012).

  8. Rosenthal, E. The soaring cost of a simple breath. The New York Times (12 October 2013).

  9. Rosenthal, E. Even small medical advances can mean big jumps in bills. The New York Times (5 April 2014).

  10. Mahn, T.G. et al. Pharm. Law Industry Report 9 PLIR 1500 (2 December 2011).

    Google Scholar 

  11. Luo, J. & Kesselheim, A.S. Lancet Diabetes Endocrinol. 3, 835–837 (2015).

    Article  Google Scholar 

  12. Hunter, N.L. & Sherman, R.E. Nat. Rev. Drug Discov. 16, 513–514 (2017).

    CAS  Article  Google Scholar 

  13. Grabowski, H.G. & Kyle, M. Manage. Decis. Econ. 28, 491–502 (2007).

    Article  Google Scholar 

  14. The GoodRx Pharmacist. FDA recalls Ventolin HFA for asthma. GoodRx (14 April 2017).

  15. Herbert, G. Asthma inhaler recall: GSK says nearly 600,000 may have defect. The Post-Standard (6 April 2017).

    Google Scholar 

  16. Palmer, E. AstraZeneca again recalling inhalers. FiercePharma (24 March 2016).

    Google Scholar 

  17. US Food and Drug Administration. Enforcement Report (FDA, 2017).

  18. Government of Canada. Guidance Document: Patented Medicines (Notice of Compliance) Regulations (27 October, 2016).

  19. US Food and Drug Administration. Combination Products (FDA, 2017).

  20. Greene, J.A. & Riggs, K.R. N. Engl. J. Med. 372, 1171–1175 (2015).

    CAS  Article  Google Scholar 

  21. US Food and Drug Administration. Phase-out of CFC metered-dose inhalers (2013).

Download references


A.S.K.'s work is supported by the Laura and John Arnold Foundation and Harvard Program in Therapeutic Science, with additional support from the Engelberg Foundation. The authors are grateful to J.W. Nickerson, W.A. Kaplan, and A. Attaran for their feedback on developing this idea, as well as to J.J. Darrow and M.S. Sinha for their insights on earlier drafts.

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Correspondence to Aaron S Kesselheim.

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Supplementary information

Supplementary Table 1

Products listing tertiary patents in 2000, 2005, 2010, and/or 2016 (XLSX 19 kb)

Supplementary Table 2

Products listing tertiary patents in 2000, 2005, 2010, and 2016 (XLSX 74 kb)

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Beall, R., Kesselheim, A. Tertiary patenting on drug–device combination products in the United States. Nat Biotechnol 36, 142–145 (2018).

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