Protection of phage applications in crop production: a patent landscape

Abstract

In agriculture, the prevention and treatment of bacterial infections represents an 10 increasing challenge. Traditional (chemical) methods have been restricted to ensure public health 11 and limit the occurrence of resistant strains. Bacteriophages could be a sustainable alternative. A 12 major hurdle towards the commercial implementation of phage-based biocontrol strategies 13 concerns aspects of regulation and intellectual property protection. Within this study, two datasets 14 have been composed to analyze both scientific publications and patent documents and to get an 15 idea on the focus of R&D by means of an abstract and claim analysis. 137 papers and 49 patent 16 families were found searching public databases, their numbers increasing over time. Within this 17 dataset, the majority of the patent documents were filed by non-profit organizations in Asia. There 18 seems to be a good correlation between the papers and patent documents in terms of targeted 19 bacterial genera. Furthermore, granted patents seem to claim rather broad and cover methods of 20 treatment. This review shows that there is indeed a growing publishing and patenting activity 21 concerning phage biocontrol. Targeted research is needed to further stimulate the exploration of 22 phages within integrated pest management strategies and to deal with bacterial infections in crop 23 production. 24 25 26 29 the first applications of phages focused on human medicine [3], other fields including agriculture 30 soon began to explore the potential of bacteriophages as biocontrol agents [4]. The first isolation of 31 phages infecting plant pathogenic bacteria (PPB) dates back to 1924, when it was shown that 32 Xanthomonas campestris pv. campestris, causing black rot in Brassicaceae, could be lysed by the filtrate 33 of diseased cabbages [4,5]. The following years, interest in phages as biocontrol agents remained 34 relatively high [4]. However, the discovery of broad-spectrum antibiotics and other bactericidal 35 chemicals resulted in a dwindling interest in phage therapy research in general [6].36 Within the agricultural sector, the prevention and treatment of bacterial infections represents an 37 increasing challenge. For farmers, devastating losses by bacterial pathogens are generally estimated 38 to reach 10% of the total production [7] and for some bacterial species like Xanthomonas campestris pv.39 campestris crop yield can be reduced by 25% [8]. Other major threats include Ralstonia solanacearum, 40 Xylella fastidiosa and Pseudomonas syringae pathovars [9]. In recent years, general antibiotics like 41 streptomycin as well as copper-based chemicals have been restricted in crop production to ensure 42 public health and limit the occurrence of resistant strains [10-13]. Because of these restrictions, the 43 search for sustainable, natural biocontrol of PPBs has come to a critical stage, especially considering 44 the increased food production needs [14]. Governments have decided to implement Integrated Pest 45 Management strategies (IPMs) as the stan...

The future of phage biocontrol in integrated plant protection for sustainable crop production

“…However, as chemical biocides became readily available and had a broader range of applicability, were simpler to use and more reliable at that time, the interest in phage biocontrol waned [12]. Since the beginning of the 21st century, phage biocontrol has regained an interest, driven by advances in biotechnology, as shown by the increasing numbers of publications, patents and patent applications [9 ]. Table 1 presents an overview of the most recent phage biocontrol studies in the field of phage biocontrol describing bioassays and/or large-scale trials.…”

“…Moreover, due to an increased awareness of their environmental and human health impact, the general public and governments demand that chemicals are restricted or, preferentially, are replaced by alternatives (EU Directive 2009/128/EC). In this regard, bacteriophages have received renewed attention from academia and industry as biological control agents for plant protection [8,9 ].…”