3.2. Time Trends
The evolution of patent applications over time for plant-based vaccines (
Figure 2) can be deduced by first considering the variable first priority year, which is the year of the first request for protection of a given invention worldwide (
Figure 3, grey bars). At the global level, the data shows that this set of technologies began to develop in late 1990, and that the number of patent applications remained quite constant until the year 2015. Since then, patent applications have constantly grown and almost doubled from the 2011–2015 period (33 patent families) to the 2016–2020 period (60 families), even though data from 2020 must be considered incomplete (due to the time-lag between patent application and publication).
This growing trend is more evident when considering the data related to the last publication year (
Figure 3, dark area), which shows a dramatic increase in patent publications in the last five-year period.
Since the variable last publication year refers to the evolution of patent publication within each single patent family, which is composed of a set of patents referring to the same invention but protected in different patent systems, this data outlines that in recent years, there has also been a significant increase in the diffusion of innovation, in addition to the mere inventive activity revealed by the trend in the priority year. The dynamics of the patent diffusion are detailed in
Table 3, where the data shows that, in general terms, patent families evolved over time following a quite established development dynamic; more specifically, results show that every patent family had, on average, two patent publications in the five-year period when the priority was requested, then in the subsequent five-year period, the number of patent publications reached their maximum peak, while in the third five-year period, the number of publications declined. Notably, the evolution over time shows that the peak reached a growing number of patents counted (3.8 before 2006, 5.6 between 2006 and 2010, and 8.1 for the 2011–2015 period), so that it is possible to predict that the patent families published in the last period will generate a number of patents higher than the previous periods.
In summary, the results of the time trend analysis reveal that plant-based vaccines represent an innovation sector that has acquired increasing importance in recent years, and consequently a boost in the development and commercialization of new plant-based vaccines can be assumed in the near future.
3.3. Country Analysis
Country analysis based on the priority country reveals that the innovation activity in this field of research is not equally distributed worldwide. The United States is the leading country with 91 families, representing 50% of the total patenting production (
Figure 4). Far below, the Rep. of Korea and the EPO area are represented both with 28 patent families: the member states which mostly contribute to the European area activity are Great Britain (nine families) and Switzerland (six families). A minor role is played by Japan and China (nine and eight patent families, respectively), while the remaining countries account for only 8% of the total. A more detailed description of the trends in country-based patent production is provided by
Figure 5, where a set of four indices—total patent families, the average number of patents, average age, and average non-self forward citations—was developed. Results indicate that the United States is the leading patent system, not only for the number of patent families (meaning invention attractiveness), but also for the value of innovation, given that the average number of patents for each family is much higher than the Rep. of Korea and the EPO area (10.5 vs. 1.5 and 8.6, respectively).
In general, this latter index highlights huge differences in patenting strategy among countries: a group composed, inter alia, by the United States, Switzerland, Great Britain, and the Netherland have a clear propensity to protect inventions in a large number of patent systems worldwide (with index “average number of patents” higher than nine).
In contrast, other countries, and in particular eastern economies (China and the Rep. of Korea especially), though having a leading position for the number of patent families, show a quite minor attitude to disseminate their inventive activity; the index assumes that values below two indicate that inventions are often only protected in the domestic patent system.
As for the index “average age”, results show that among the countries that have started to develop innovation in plant-based vaccine production, some are not the current leaders in this technology; indeed, Australia and Brazil have the highest value for this index (20 and 18 years, respectively), followed by the Netherlands and Poland, whereas top countries like the US and the EPO area started to produce inventions in this field approximately ten years ago, with the exception being the Rep. of Korea where the research in this sector started some years later. As for the index “average non-self forward citation” the index reveals a quite uniform behavior, with all the countries ranging below the value of ten citations, except for Germany where a single patent family (EP262312, owned by the company Icon Genetics) received 62 non-self forward citations.
In summary, the country analysis shows the presence of one relevant innovation area, the United States, standing out as the most interesting market for plant-based vaccine production. Nevertheless, the future scenario will probably also include the European Union and some eastern economies like the Rep. of Korea.
3.4. Assignee Analysis
As for the analysis of the type of assignee, the results shows a quite balanced distribution among the different categories of players: globally, 49% of patent families belong to private assignees (or derive from private–private collaboration), 37% derive from public research activity (or public–public collaboration), while 12% of patent families come from public–private synergies (i.e., KR101732624 owned by the Korea Rural Development Administration and the Korean company Bioapplications or EP3167057 owned by Medicago together with the Canadian University of Laval), while the remaining 2% pertain to single inventors.
Table 4 outlines the results for the assignee classification based on their strategic positioning and productivity over time; more specifically, considering the variables average age of patent families, number of patent families, number of non-self forward citations, and number of patents after 2016, assignees have been classified into three main groups: pioneers, leaders, and newcomers. Pioneers are characterized by having the highest value for the variable average age of patent families and the lowest value for the variable number of patents after 2016; this means that this group of assignees worked in plant-based vaccine production in the earliest years of development of this innovation sector, though they do not occupy a dominant position in the current period. The group of assignees defined as leaders is characterized by a lower value for the average age of patent families (between 16 and 8 years) and higher levels of patent productivity after 2016 (greater than 10%). The last group of assignees is classified as newcomers because it is defined by the lowest value for average patent age (lower than 8 years) and the highest productivity in the last five-year period.
Table 4 outlines the results of patent-based indices elaboration for each of the assignee groups identified. The pioneers group of assignees is fully composed of US players, both public and private. Among the public institutions can be found one university (Ohio State, strongly focused on veterinary vaccines) and a non-profit institute (Boyce Thompson Institute for Plant Research). For the private sector, the most significant player is represented by the firm Kentucky Bioprocessing, the biotech subsidiary of the company British American Tobacco; this firm has announced the development of a COVID-19 vaccine candidate, which is currently in phase 1/2 of clinical testing. In 2014, the company produced an anti-Ebola monoclonal antibody cocktail, and more importantly, a vaccine platform technology developed for pandemic flu, which was then exploited as the core of their COVID-19 vaccine development. Moreover, amongst leaders, there is the presence of only one agbiotech firm (Corteva) of the so called “Big Six” (recently turned to be “Big Four” due to mergers and acquisitions), which have historically played a leading role in the research and development of agbiotech innovations. The remaining two players are Advanced Bionutrition, specializing in veterinary vaccines, and Pfenex (rebranded in 2021 to Pelican Expression Technology), which inherited part of the patents developed by DowAgroSciences.
The structure of the patenting activity of the leaders group of assignees (
Table 5) confirms the US leadership already evidenced in the country analysis, given that among the nine top players identified, six originated in the United States. Nevertheless, the first assignee in terms of the number of patent families is the Canadian firm Medicago, with 21 families corresponding to the impressive amount of 466 single patents. This data can certainly explain the fact that Medicago was the first company to develop a COVID-19 plant-based vaccine candidate since the Canadian company had already developed the experience and the technologies for vaccine production, and subsequently had the opportunity to adapt existing solutions for the case of COVID-19. Medicago, since 2013, has been owned by a subsidiary of Mitsubishi Tanabe Pharma (67%) and Phillip Morris International (33%), and has been very active in the fields of antiviral vaccines and antibody therapeutics.
A further leader player is represented by a US public institute, the Arizona State University, with six patent families, has a considerably smaller portfolio in terms of the number of patents when compared to Medicago (19 patents), confirming a very common behavior of the public sector, which is the ability to innovate and produce inventions paired with the lack of attitude and capacity to exploit the inventions and disseminate them. Notably, a second company that has already announced the development of a COVID-19 vaccine candidate is on the list of the leader assignee: this is the US firm iBio, which is highly specialized in plant-based biologics manufacturing and owns four patent families composed of forty single patents. This company has already produced a plant-based animal vaccine against swine fever and is working on the development of a second-generation vaccine, which they have announced will be able to overcome some of the limitations inherent in the currently available products: cold chain, cost, and protection against variants.
A further point of interest regarding this group of players is related to the patenting strategy and can be recognized by the variable percent of families patented in US-EP, which show a clear attitude to protect inventions in major patent systems, even when they do not coincide with the domestic one, as the Spanish firm Zip Solutions (100% of patent families in the US) and the Canadian firm Medicago (20 patent families out of 21 patented in the US). The public institute Fraunhofer, though headquartered in Germany, has several research centers in the United States and has developed patents for a plant-based vaccine, and has been consequently been classified as US assignee. A further firm belonging to this group of assignees is the Spanish biotech company Zip Solutions, which specializes in recombinant vaccines for human and animal health and in research on virus-like particles.
The last group of assignees, classified as newcomers, is characterized by the largest variety of players, with an increased role of public institutions: six assignees belong to universities and public research centers, and also the Swiss firm Saiba AG, founded in 2012, is a spin-off of the University of Zurich. This company also announced that it is working on a future COVID-19 vaccine candidate, focusing on the implementation of a second-generation vaccine product be developed in the coming years. Saiba AG and the University of Zurich present high values for the number of patents (24 and 18, respectively) together with the highest values for patents/family, and consequently can be recognized as the most promising players among the newcomers group. Finally, Plantform, is a biotechnology company that produce vaccines and antibodies in tobacco plants using a technological platform developed at the University of Guelph.
Table 6 summarizes the main features of patent production for each type of assignee. In general terms, the nine players identified as leaders own 26.7% of the inventions; thus, it is possible to say that this specific innovation sector is characterized by a quite low concentration. Nevertheless, the concentration level significantly increases and reaches a value of 52.3% when considering single patent count. By contrast, the role of the group of assignees classified as newcomers shows an opposite trend, since their relevance significantly decreases from patents families (26.7%) to single patents count (10.9%).
Figure 6 condenses the different profiles of assignees according to three main variables: age, count of non-self forward citations, and number of patents. The map shows that the intense development of this innovative sector generated one leading player, the company Medicago, which detaches itself from the rest of the assignees for the number of patents and citations. Data suggest that this firm is the one characterized by the most intense research background and these results could partially explain the current position of Medicago having the most advanced COVID-19 plant-based vaccine candidates. In a similar position was the company Corteva, though its share of patents after 2016 decreased to 1.5%, meaning that after an intense phase of innovation production, in the last period, the company decided to invest in different fields of research. Of the COVID-19 plant-based vaccine candidates, one was developed by a pioneer assignee (Kentucky Bioprocessing), while two of them belong to leader assignees (Medicago and iBio); albeit results outline a clear leading position for the company Medicago, some similarities can be found between the profile of the firms Kentucky Bioprocessing and iBio for the variables considered (average age and count of non-self forward citations). The bottom-left area of the map is crowded by a huge number of new players who recently entered this innovation sector with potential future development in the coming years.
In brief, the assignee analysis revealed the dominance of the public sector and the presence of a high variety of players, led by a few, specialized companies focused more on the protection of plant-based inventions, and also are connected to COVID-19 vaccine candidate development.
3.5. Object of the Invention
The CPC codes analysis (
Figure 7) reveals a quite consistent technical profile of inventions, which mainly fall in the domain of medicinal preparation (A61K codes) and plant biotechnology (C12N codes). It can be seen that the most used technical code is the C12N 27, which describes inventions related to viruses, while one-third of the inventions also contains the code for virus-like particles. Nevertheless, when analyzing technical code distribution, it is important to consider that the attribution of codes is highly dependent on the patent examiner and consequently highly variable. The time evolution of codes for plant-based vaccines (
Appendix A and
Appendix B) adds some relevant details about the pattern of CPC used in the considered period.
Figure 8 provides the radar plot of the CPC distribution by typology of assignees. Results show that the process of innovation production—reflected by the selection of CPC codes—present some differences depending on the type of assignee considered; more specifically, leaders (yellow line) are characterized by intense use of the code C12N 15/8258 regarding the development of genetically modified plants for the production of vaccines. This aspect highlights the leading role of this group of players as they are highly specialized in applied research for the realization of new potential commercial products.
The second point of interest related to the leaders’ group is their expertise in the field of virus-like particles implementation (codes A61K 2039/5258 and C12N 27xx/xxx23), which is one of the most promising technologies for plant-based vaccine production. By contrast, pioneers firms (red line) have a tendency to be more specialized in medicinal preparations comprising whole cells, viruses, or DNA/RNA (codes A61K 2039/(51–53) and C12N 27).
A more detailed scenario is provided by
Figure 9, where the general CPC distribution (black line) is compared to the ones of the three companies having announced their obtainment of a COVID-19 vaccine candidate. The company Medicago (blue line) shows a very balanced pattern of technological development, with the highest percentages in the key codes for virus-like particles. The company Kentucky Bioprocessing shows quite a different profile, which is more focused on virus research, while the codes for plant biotech applications are almost absent. Finally, the firm iBio is characterized by the intense use of the code C12N 15/8258, which is present in 100% of the patent families registered, whereas the research on virus-like particles does not seem to be the focus of this company. Nevertheless, its activity is not only dedicated to viruses, since two of the four patent families owned by this company focus on the treatment of Plasmodium and Trypanosoma diseases. Further information about CPC distribution by type of assignee is in
Appendix B.
In summary, the analysis of CPC technical classification shows the emergence of virus-like particle technology for vaccine production, and a greater specialization in biotechnology applications for those firms who have already developed a COVID-19 vaccine candidate.