feature PATENTS Ebola as a case study for the patent landscape of medical countermeasures for emerging infectious diseases A survey of patenting activity can facilitate coordination of R&D activities to fght emerging infectious diseases. ethods to combat Ebola virus a 200 196 2,000 disease (EVD) have gradually 175 improved since its discovery in Cumulative patent family number M 1–3 1976 (refs. ). EVD has caused over 33,000 150 infections and 14,000 deaths worldwide, 1,500 with most cases occurring in Africa. Ebola virus (EBOV)—named for the Ebola River, 114113 located near Yambuku, Democratic Republic 100 1,000 of the Congo (formerly Zaire)—is the cause 74 76 75 Patent families 73 4 of the disease . The discovery of the Reston 59 62 54 56 545557 Ebola virus in the Philippines in 1989 50 46 45 showed that EBOV is also present in Asia. 39 500 During the first outbreak, in 1976, 25 14 131614 9 9 9 12 improper nursing techniques such as 1 1 2 1 1 1 3 1 2 2 2 4 3 3 3 3 4 1 0 0 reuse of syringes for different patients and 6 4 7 9 1 3 5 7 8 9 1 2 3 5 7 9 1 3 5 7 9 0 3 4 5 7 9 7 2 4 6 0 4 6 8 0 2 4 6 8 11 2 6 8 0 close contact with infected blood were 195 196197 197197 198198 198198 198198198198 198199 199199 199 199199199 199199 199200 200200 200200 200200 200200 200201 20 201 201201 201201 201201 201202 the main source of human-to-human Year of first application transmission5. A better understanding of methods of virus transmission during b 133 133 the 1994 Cote d’Ivoire outbreak led to the Families with no granted applications use of personal protective equipment and Families with at least one granted application 104 single-use syringes, which helped in the 100 96 control of transmission. The international public health community helped contain 63 the disease by staffing local hospitals 60 51 53 and providing necessary equipment and Patent families 50 49 5 42 42 37 education for health care workers . 34 31 31 32 29 33 33 29 28 26 The 2014 outbreak of EVD caused more 23 23 25 24 23 20 21 17 17 18 18 16 14 than 28,000 cases and 11,000 deaths—more 11 77 7 8 8 8 9 9 6 54 45 6 5 5 than all previous EVD outbreaks combined . 1 1 2 1 1 1 21 1 2 2 2 22 3 21 21 3 31 3 3 2 1 0 Several factors contributed to the devastating 6 7 4 7 9 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 11 2 3 4 5 6 7 8 9 0 195 196 197 197 197 198 198 198 198 198 198 198 198 198 199 199 199 199 199 199 199 199 199 199 200 200 200 200 200 200 200 200 200 200 201 20 201 201 201 201 201 201 201 201 202 effects of this outbreak, such as the delay between identification of cases and reporting Year of first application to the World Health Organization (WHO), Fig. 1 | Analysis of patent application and granting frequencies. a, Number of patent families against the spread of the disease to urban areas, application years as a bar chart and cumulative chart. There were two peaks in the number of patent and the weak response of the international applications that coincide with two EVD outbreaks. b, Families that had at least one granted patent community7. The outbreak also highlighted were counted in the granted families group. The rest of the patent families were counted in no granted lack of proper medical countermeasures families group. The gap between granted and not granted patent applications widened with increase in (MCMs) in diagnosis of, vaccination against the number of patent applications. and treatment of the disease8. WHO has since included EVD on the list of priority pathogens with the potential of severe outbreaks for which to control an EVD outbreak forced WHO be more specific. However, the application few or no MCMs exist9 and has drafted an to call for “rapid, sensitive, safe and simple of rapid diagnostic tests in combination R&D roadmap to accelerate collaborative EBOV diagnostic tests” as a crucial MCM with PCR-based methods was suggested development of MCMs against the disease8. in November 2014 (ref. 10). Following to be more effective11. Lack of data from The vital importance of rapid isolation this call, several tests, including various randomized controlled trials made it of infected patients based on the clinical rapid diagnostic tests, became available4. difficult to draw conclusions about the diagnosis that could be further confirmed PCR-based methods, which detected one or efficacy of therapeutics against EVD. To with the results of a readily available test two of the EBOV genes were considered to address this difficulty, WHO developed an NATURE BIOTECHNOLOGY | VOL 39 | JULY 2021 | 799–808 | www.nature.com/naturebiotechnology 799 feature a WO 609 US 482 AU 155 CN 142 EP 99 JP 37 RU 22 KR 12 UK 9 CA 4 TW 2 Jurisdiction DE 2 ZA 1 PH 1 NZ 1 FR 1 EA 1 CZ 1 AT 1 0 200 400 600 Publications b WO 1 1 1 1 3 6 1 8 16 36 16 39 22 18 32 23 21 19 14 17 20 73 63 53 64 41 US 2 3 1 2 3 2 4 10 18 25 23 24 19 14 24 23 29 17 16 21 20 64 59 30 16 13 AU 1 1 1 2 1 1 2 2 5 3 2 8 2 6 3 6 5 3 6 7 7 7 3 5 6 1 4 4 9 3 10 10 10 8 1 CN 1 1 2 1 3 1 3 4 3 24 30 29 15 18 7 EP 1 1 2 2 1 1 1 1 1 2 1 1 1 4 1 5 3 5 5 9 2 5 5 1 10 5 8 4 5 4 1 1 JP 2 2 1 3 4 3 1 2 3 2 3 1 2 1 1 1 1 2 1 1 RU 1 2 1 1 6 3 4 3 1 KR 2 1 3 3 2 1 UK 1 1 2 2 1 1 1 CA 1 1 2 TW 1 1 1 1 Jurisdiction DE ZA 1 PH 1 NZ 1 FR 1 EA 1 CZ 1 AT 1 19561967 19741977 1979 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 19921993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 20042005 2006 20072008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 20192020 Year Fig. 2 | Analysis of jurisdictions. a, Offices of the first patent application are grouped and counted. The number of families that were filed through the PCT is more than in other types of applications. b, Patent applications for each patent office plotted versus time in years. Applications in most patent offices are concentrated in the years after 2000. However, applications in some patent offices, such as AU, EP and JP, are more evenly distributed. WO, world (PCT); US, United States; AU, Australia; CN, China; EP, European Patent Office; JP, Japan; RU, Russia; KR, South Korea; UK, United Kingdom; CA, Canada; TW, Taiwan; DE, Germany; ZA, South Africa; PH, the Philippines; NZ, New Zealand; FR, France; EA, Eurasian Patent Organization; CZ, Czech Republic; AT, Austria. ethical framework to bridge compassionate which led to the approval of REGN-EB3, and European Medicines Agency (EMA) for access to investigational therapeutics and or Inmazeb (atoltivimab, maftivimab and the prevention of EVD14 and is being used clinical trials12. Following the development odesivimab), as the first drug to treat EVD13. in the Democratic Republic of the Congo of this guidance, a clinical trial was initiated For vaccine development, GP1,2 according to a ring vaccination strategy. in the Democratic Republic of the Congo protein was considered the major EBOV The EMA has also granted marketing to test the monoclonal antibodies ZMapp, immunogen. A recombinant vesicular authorization for a vaccine composed of mAb114 and REGN-EB3, as well as the stomatitis virus (VSV) pseudotyped a two-dose regimen of Zabdeno (Ad26. viral polymerase inhibitor remdesivir. In with Ebola Zaire glycoprotein, ZEBOV) and Mvabea (MVA-BN-Filo). this trial, patients who received REGN-EB3 rVSVΔG-ZEBOV-GP, was approved by the One of the lessons of the 2014 EVD or mAb114 showed higher survival rates, US Food and Drug Administration (FDA) outbreak was that collaborative development 800 NATURE BIOTECHNOLOGY | VOL 39 | JULY 2021 | 799–808 | www.nature.com/naturebiotechnology feature a 1. Univ California 27 b 1 3 2 3 2 2 1 1 1 3 2 4 1 1 2 c 1 3 15 10 2. Harvard College 23 2 1 1 1 1 1 1 1 2 1 3 7 3 2 5 1 3 14 3. Univ Emory 21 3 2 1 1 2 2 3 1 4 1 2 1 1 3 1 3 6 11 4. Massachusetts Inst Technology 20 4 1 2 1 1 1 2 1 10 1 4 4 1 15 5. US Gov Health & Human Serv 17 5 1 4 6 2 2 1 1 5 1 2 1 12 1 6.