research and development perspectives of transgenic cotton...

Journal of Intellectual Property Rights Vol 16, March 2011, pp 139-153

Research and Development Perspectives of Transgenic Cotton: Evidence from Patent Landscape Studies

Kalpana Sastry R†, H B Rashmi and Jyothi Badri

National Academy of Agricultural Research Management, Indian Council of Agricultural Research, Rajendranagar, Hyderabad 500 407, Andhra Pradesh, India

Received 19 January 2011, revised 25 January 2011

Rapid developments of technological tools in the development of transgenic cotton harbouring the Bacillus

thuringiensis (Bt) gene for conferring resistance to bollworm have played a major role in ushering an agri-biotechnology revolution at the global level and more so in Southeast Asian countries like India and China. The unprecedented increase in the use of these technologies and major investments by technology providers through strategic alliances or through agreements has brought the tools into a developing country like India. The objective of the present study is to assess patenting trends of this revolutionary technology in agriculture and its role in commercialization of the crop. Patent landscape analysis was deployed to map bibliographic patterns such as publication and priority year, country, assignees and technological analysis of major research areas with applications in technology development. The study illustrates the crowded domain of technology providers and the need to build strategic partnership platforms for effective use of the products.

Keywords: Bt cotton, transgenics, agri-biotechnology, patent landscape

The highly-effective, insect control solution through Bacillus thuringiensis (commonly known as Bt) was discovered in 1901 and first used commercially in 1958 (ref. 1). At present, the products involve over 30 subspecies and 800 different strains of the bacterium for a variety of control mechanisms for several insects and their larva that feed on fruits, vegetables, and other cash crops including corn and cotton. These insecticidal properties facilitated capture of over 90 per cent of the bio-pesticide market with 100 Bt product formulations being produced by nearly 30 companies at a global level.2 The wide applications make Bt technology one of the most revolutionizing technologies in agriculture from the perspective of farmers, researchers and policy makers.3 Research on developing insect resistant transgenic crops using Bt technology was initiated to offset some of the disadvantages of Bt based bio- pesticides experienced in areas of production, up-scaling technology and vulnerability to heat. During the late eighties4, cotton was one of the first crops where this feature was exploited for developing insect resistance crops. The toxin gene of the bacterium was isolated in 1981 and the first Bt protected cotton crop

was field tested in 1990 in USA. Research indicated that the genetic engineering innovation not only reduced the consumption of pesticides but also increased the productivity of cotton by protecting the crop effectively from bollworm attack.5 After the verification and examination of the safety and suitability of this crop by various government regulatory agencies of USA, Bt cotton was commercialized and cultivated on 1.8 million acres in 1995. In 1997, China took up the cultivation of Bt cotton, followed by 13 other countries. In March 2002, cultivation of Bt cotton was permitted in India on a large scale with certain conditions.6 Efforts of transnational companies like Monsanto to partner with an Indian company, Mahyco since late 1990s fructified the advent of transgenic cotton in India by 2002 (ref.7). This was the first-ever agricultural biotech product to receive official approval and triggered the entry of India into commercial agricultural biotechnology.8 The operationalization of a PVP regime through PPV&FR Act, 2001(ref. 9) in India is also creating new opportunities for protecting such transgenic cotton varieties legally and thereby setting platform for more investments by the industry. While as many as 522 cotton hybrids including a Bt cotton variety have been approved for planting by

___________ †Email: Corresponding author: [email protected]

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the regulatory agency during 2009, about 209 applications for Bt cotton10 (95 extant and 114 new) were received in the PPV&FR Authority.

It is also well documented that Bt cotton has revolutionized cotton production in India.8 In a short span of seven years (2002 to 2008), Bt cotton has generated economic benefits for farmers valued at US$ 5.1 billion, halved insecticide requirements, contributed to the doubling of yield and transformed India from a cotton importer to a major exporter. Socio-economic surveys confirm that Bt cotton continues to deliver significant and multiple agronomic, economic, environmental and welfare benefits to farmers and society.11 A 2009 survey projects doubling of the Indian biotech industry revenue in the next two years reaching US$ 5 billion compared with US$ 2.7 billion in 2008 with major contribution from biotech crops like Bt cotton.12

Patent analysis is a unique management tool for addressing strategic management of a technology and product or service development process. Analytical tools are used for searching patents and associated scientific literature to show the gap in research areas. Translating such data into competitive intelligence allows gauging its current technical competitiveness, to forecast technological trends, and to plan for potential competition based on new technologies. Patent documents are well structured external sources of information that can be mined to discover state-of-the-art technical developments to make strategic decisions to support next generation crops.13 The structured documentation in patents viz., citation, issue date, inventors, institutions and their locations, technology field classification, etc., gives valued insights for assessing promising technology developments and known potential commercial applications.14 Such analysis is especially useful for input intensive, emerging and frontier technologies including agri-biotechnologies.15

The objective of the present study is to assess patent landscape of research and development (R&D) activities centring around the development of Bt technology for transgenic cotton. With rapid technological developments and innovations rising in deployment of Bt technology in cotton, the Bt stakeholders need to be aware of the usefulness and availability of patents associated with Bt technology. The analysis will provide documented information to the users in the Bt sector and Bt researchers more particularly in the Indian National Agricultural System

(NAS) for strategic planning, for building foresight mechanisms for R&D programmes and for adopting innovative approaches to create strategic partnerships between investors, users, growers, and farmers to improve the rural livelihoods in agri-value chain.

Methodology of the Study

To address the objective of this study the following strategies were adopted: Characterization of Framework of Bt technologies in

Development of Transgenic Cotton

The various steps involved in the development of a transgenics viz., genetic engineering, transformation, tissue culture, hardening and crossing of the so produced transgenic with an elite cultivar to evolve a transgenic variety are schematically represented in Fig.1. Using this as a base framework, six thematic areas of core technologies were identified. Patent Search Strategies from Databases

In the present study, patent data was collected through a specially designed strategy. Patents related to Bt cotton technology were searched, collected and analysed from three resources viz., freely available databases of international/national patent offices (USPTO, EPO and WIPO); non-charge providers (Google patents, FreePatentsOnline) and charge providers (Delphion, Derwent). A set of subject specific keywords and standardized search strings, was identified by domain experts and used to perform full text search of patents (patent titles, abstract, claims and descriptions). A set of 194 relevant patents related to various domains of Bt cotton technology as depicted were retrieved, after following the usual methods of filtering out the irrelevant patents and duplicates. Units of analysis and representations in text mining of patents include inventors, type of affiliations, country, technology field and timelines.

A specially designed search strategy was designed for utilizing the recently available patent search facility in the National Patent Office of Government of India (GOI).16 Based on the various options available in the Indian Patent Information Retrieval System (iPAIRS), keyword search (using words like ‘cotton, transgenic, Bacillus thuringiensis, genetic engineering, delta-endotoxins’) was done for both granted patents and published patent applications. Out of the 800 patents retrieved, only 35 patents were found relevant and analysed further to understand technology dissemination in the Indian context.

SASTRY et al.: R & D PERSPECTIVE OF TRANSGENIC COTTON: PATENT LANDSCAPE STUDIES

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Knowledge Mapping of Technology Landscape

Knowledge mapping of technology landscape of relevant patents was done based on the basic bibliographic analysis through patent timelines, assignees and geographical distribution; and technology trend analysis through various sets of Bt transgenic technology, International Patent Classification (IPC) category composition. Additional techniques like patent clustering and Aureka Themescape maps were used to

analyse trends of technology transfer using the information in the patent sets.

Analysis of Results

Basic Bibliometric Analysis

Patent Timeline Analysis using Reference Dates

Reference dates in patent documents reflects timing of invention, process and strategy of the applicant. In the present study, two indicators, namely, priority

Fig. 1 Framework for integration of events of Bt technologies for developing transgenic cotton


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year and publication year were used to gauge trends in inventive activities over a span of years. It is known that priority date/year is first date of filing of patent application anywhere in the world and considered closest to the invention date while publication year reflects the time the information is disclosed to the public from statutory offices. Using priority date is most often recommended as it reflects the inventive performance of technologies, while publication year reflects the rate at which statutory offices are working on these technologies and therefore the time from which it forms full prior art for other patent applications worldwide.

The quantum of patents on Bt technologies applicable to cotton (Fig. 2) show exponential increase in a periodic manner (at an approximate interval of four years) from 1996 onwards. It is known that this was the period when major chemical companies like Ciba-Geigy, Royal Dutch/Shell, Monsanto, Evogene, started their consolidation into seed industry using agri-biotechnology tools.17 The same trend was observed in publication years, though not coinciding with priority years. This difference may be due to the fact that patent offices need to examine filed applications in conjunction with relevant national laws and time taken for publication differs in each country.

Comparative Strength of Countries in Bt Cotton Technology

The trends in R&D activity are also associated with geographical scope of patent protection, which reflects the market coverage of an invention. It is known that where patent protection is sought, it reflects the expectations of inventors or the companies for good market diffusion.18 This also indicates the country’s intellectual property (IP) and technology

transfer environment including costs, policies and more users of the technology. Hence, comparative strength of countries in the present study was analysed based on the location of assignees and inventors. USA topped the list of assignee countries with highest share of patents (70 per cent) followed by European Union (10 per cent), including Belgium (6 per cent), Switzerland (3 per cent), and France (1 per cent); Mexico (2 per cent), Germany (1 per cent) and India (1 per cent). USA (76 per cent) also was major among the inventor countries followed by European Union countries (12 per cent)–{Belgium (6 per cent), France (2 per cent), Spain (2 per cent), Netherlands (1 per cent) and United Kingdom (1 per cent)}; India (4 per cent), and Mexico (1 per cent). Priority country is defined as the country (jurisdiction) in which the earliest filing of a patent application is claimed. USA, Europe, Germany, China, India, United Kingdom and New Zealand are in the list of priority countries in the set of patents studied. Designated countries for regional patents are cited in a subsequently published search report. Top most designated countries were Austria, Belgium, France, Germany, Italy, Luxembourg, Netherlands, Sweden, Switzerland and United Kingdom.

A patent family is ‘a set of patents taken in various countries to protect a single invention’; when a first application in a country - the priority - is then extended to other patent offices.19 This is also used as a tool for assessment of patents as it indicates the scope of technology and its marketability. Complete patent family countries of the 194 patents studied, is as follows USA, WIPO, European patent office, Australia, China, Canada, Germany, Brazil, Japan, Argentina, Mexico, South Africa, Austria, Israel, New Zealand, Turkey, Hungary, Colombia, Spain, Portugal, African Regional IPO, Chile, Indonesia, Russian Federation, Czech Republic, Republic of Korea, Bulgaria, Denmark, Ukraine, Republic of Slovenia, Eurasian PO, Uruguay, United Kingdom, Poland, Romania, Slovak republic, Singapore, Taiwan, Costa Rica, India, El Salvador and Greece. This wide geographical range indicates the expected markets for product and the initiatives of inventors/assignees to file in several jurisdictions.

Comparative Strength of Assignees in Bt Cotton Technology

In the present study, the patent data was classified into the following categories of assignees: Corporate sector comprising of industrial organizations and corporate bodies, institution sector comprising

Fig. 2 Patent timeline analysis (n=194)


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academic institutions, government sector and public funding agencies, individuals with no institutional affiliation and collaborations between either public–private or public-public and private-private. The analysis indicated that industrial organizations registered maximum patents (86 per cent) followed by independent investors (7 per cent), institutes in public domains including universities, R&D centres etc., (4 per cent), and collaborations between private-private organizations (3 per cent, limited to joint applications of institutions as assignees), and public-public organizations (1 per cent). Interestingly, there was no collaboration between public-private organizations in the data set studied. Pioneer Hi-bred international Inc was the leading assignee with maximum patents (24 per cent) followed by Monsanto Technology LLC (23 per cent), Athenix Corporation (13 per cent), Bayer Bioscience N V (4 per cent), Ecogen Inc (3 per cent) and Syngenta Participations AG (3 per cent). A further detailed analysis of assignees against a timeline with major periods (at five yearly intervals) from 1991 was done. Data revealed the existence of technology providers like Agracetus (bought by Monsanto20 in 1995), Dowlanco, Ciba, Mycogen, etc. Distinct shift patterns were observed, starting late nineties: Monsanto & Ecogen as major assignees and rise of Syngenta,

Pioneer Hi-Bred as major holders. An earlier study21 done in 1996 pointed clearly that major players in transgenic Bt technology were Monsanto, Novartis, AgrEvo, Mycogen with their technologies and DeKalb Genetics Corporation and Pioneer Hi-Bred International through strategic alliances. Nineteen major companies were reported to work on advanced products of Bt based technologies in a variety of crops including cotton. It was further indicated that 57 per cent of patents (numbering 410 in OECD countries) during 1986 to 1996 were owned by eight companies21, some of which have figured in the present data set too. Aggressive patenting stance by US based transnational corporations like Agracetus22 for instance, led to protests and reexamination of some patents in several jurisdictions and revocation in some countries like India. Many life sciences firms namely, Monsanto (which has acquired DeKalb Plant Genetics, the international seed business of Cargill and Plant Breeding International and many other smaller firms), Aventis Crop Science (now taken over by Bayer), Syngenta (the agriculture arm of the merger between Novartis and AstraZeneca), Dow Agro Sciences (which acquired Cargil Hybrids) and DuPont (which acquired Pioneer Hi-Bred) are major input supplying agricultural businesses with interests in agri-biotechnologies. The presence of such high profile companies as assignees in this study (Fig. 3) indicates

* CINVESTAV|EMBRAPA|Univ of Brasilia|Univ of Costa Rica Fig. 3 – Assignee and time frame analysis of Bt cotton technology patents (n=194)


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the entry of many new players23 who either own several enabling patents or are operating through major licensing agreements. Considering this large proliferation of technology providers with patent rights, the R&D sector using Bt technology should be apprised of the patent profile and rights of the asset holders before taking steps to deploy Bt technologies in cotton. This is more pertinent especially in several developing countries in Asia24 where potential markets are being forecasted. Concurrently, most of these countries have liberalized their trade regimes, have become TRIPS compliant and are envisaging on building stronger IP regimes (than the system prior to 2005) in their jurisdictions.

Analysis of Indian Patent Data

An attempt was also made to use the recently provided services through iPAIRS.25 This is only a representative analysis in this technology, not a complete picture of the present Bt technology patenting activity. Published patent applications26 could be browsed through title and abstracts only as full text of the applications were not available. Granted patents were browsed with the help of complete specification, available in html format. A total of 35 relevant documents (applications and granted) were finally retrieved. Keeping in view the restricted platform of the retrieval system and small number of documents retrieved, this set was not used for further analysis with the first set of 194 patents. Rather, a stand-alone analysis on this small set was done to get preliminary evidence on the type of assignees filing in India.

Patent timeline of these patents shows that filing of patents started from the year 2000 and remained progressive till date. However, majority of the patent filings were seen in the year 2001 and 2005 followed by 2006. With the changes operationalized in Indian Patent Act since 2005 for full compliance with TRIPS provisions in subjects of provisions for patenting for microbes, biotechnological tools, it is expected that filing in these technology areas may increase. This surmise is further strengthened by the fact that WIPO (World Intellectual Property Organisation) recently recognized the Indian Patent Office as an International Searching Authority (ISA) and International Preliminary Examining Authority (IPEA) under the Patent Cooperation Treaty (PCT)27 affording a suitable platform for foreign based inventors/assignees to file in India.

The analysis showed an increasing interest of big players including MNCs and also universities from

India and abroad (Table 1). Almost 69 per cent of the patents were from private sector and 31 per cent were from public sector. It was observed that public sector organizations both from India [Indian Council of Agricultural Research (ICAR), Tamil Nadu Agricultural University] and abroad (The University of Chicago, Texas Tech University and Protein Research Trust) filed for Bt cotton technology patents. Further, a public–private partnership from Australia collaborating Benitec Australia Ltd, and Commonwealth Scientific and Industrial Research Organization (CSIRO) was observed. In case of MNCs, major players like Monsanto Technology LLC, Bayer Bioscience NV, Syngenta Participations AG, Temasek Life Sciences Laboratory Limited, Cropdesign NV, LTA Resource Management, M/S Toyota Jidosha Kabushiki Kaisha, Meristem Therapeutics and Nippon Paper Industries Co Ltd, showed growing interest in filing of patents in India. This trend of filing in India although from a small sample set, indicates the recognition of the Indian market by foreign investors in this technology and advocates the need for building a positive business investment environment including biosafety regulatory systems in the country. Upscaling of R&D activities by public sector organizations and domestic companies singly or in strategic partnerships can also be expected in future.

In recent years, however, the private sector has become an important supplier of varietal technology in agriculture. Although the trend is most prominent in the developed countries, the retreat of the public sector from seed distribution and seed production is becoming evident in recent years in most developing countries including India. The rise of private seed companies in this sector is associated with the development of improved or hybrid varieties in Bt cotton where it encompasses both seed market and technology markets. Till 2005, the technology market consisted only one supplier – Monsanto Mahyco Biotech (MMB) that has licensed its Bt gene to almost all the leading cotton seed companies (about 20 firms)

Table 1 Analysis of patents retrieved from iPAIRS

Assignee category Number of patents (applications)

Public sector institutions-India 3 (2) Public sector institutions-Foreign 5 Public-private collaborations 1 Public-private collaborations 16 (8)

Data based on available search tools in iPAIRS


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who became contractually bound to pay royalties to MMB, setting a basic price for Bt seed despite competition among these firms.28 The results in this study indicate a possible shift from the present model of single platform provider to platform of multiple technology providers as new assignees including public sector organizations that joined in the fray of developing IP assets in this technology. It is now reported that nearly 34 indigenous companies and one public sector institution in India are involved as developers for the 522 Bt hybrids/variety approved by the regulating agency during 2009.

Technology Trend Analysis

IPC Analysis

A more detailed assessment (Table 2) on the fields of technology was made by analysing the distribution pattern of the patents in various subfields of categories under IPC.29 The patents were found in about 16 IPC classes (till sub class level or the third hierarchical level of classification) covering a large domain of sectors. It is well known that a patent application can be associated with more than one IPC class and one patent may occupy more than one subclass. IPC code analysis was restricted to the

fourth hierarchical level of the classification that is ‘group’ level. It was found that maximum number of patent records were in IPC group C12N 15/82 which covers mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors. The other prominent IPC codes under which the data studied were classified are listed in Table 2.

Thematic Areas of Bt Technologies for Transgenic Cotton

A detailed study of whole text patent documents with reference to the thematic areas of transgenic development (Fig. 1) and associated transgenic features was further made. Patents were analysed both for processes and products of Bt transgenic technology (Table 3). In the first event, genetic engineering (Fig. 1), process patents describing the methods for gene construct preparation/gene design, its use and development of diagnostic kits were analysed which were related to the thematic area of procedural description (Class V). Further, product patents encompassing the event of genetic engineering were found in the areas of DNA, RNA sequences and amino acid sequence of the polypeptide. These were applicable in the areas of Class I and II. The second event, i.e., transformation,

Table 2 Distribution of patents in top 10 IPC groups*

IPC Code Description Patents (%)

C12N 15/82 Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; use of eukaryotes as host- for plant cells

11

C07K 14/195 Peptides having more than 20 amino acids; gastrins; somatostatins; melanotropins; derivatives thereof from bacteria

9

C07K 14/325 Peptides having more than 20 amino acids; gastrins; somatostatins; melanotropins; derivatives thereof Bacillus thuringiensis crystal peptide (deltaendotoxin)

9

A01H 5/00 New plants or processes for obtaining them; plant reproduction by tissue culture techniques: products- flowering plants, i.e. angiosperms

8

C12N 1/21 Microorganisms, e.g. protozoa; compositions thereof; processes of propagating, maintaining or preserving microorganisms or compositions thereof; processes of preparing or isolating a composition containing a micro-organism; culture media therefore modified by introduction of foreign genetic material

4

C12N 15/32 Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; use of hosts It covers processes wherein there is a modification of the genetic material which would not normally occur in nature without intervention human produces a change in the gene structure that is passed on to succeeding generations. Bacillus crystal proteins

3

A01H 1/00 New plants or processes for obtaining them; plant reproduction by tissue culture techniques, processes for modifying genotypes

3

C07H 21/00 Sugars; derivatives thereof; nucleosides; nucleotides; nucleic acids- compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

3

C07H 21/04 Sugars; derivatives thereof; nucleosides; nucleotides; nucleic acids - compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups with deoxyribosyl as saccharide radical

3

A01N 63/00 Biocides, pest repellants or attractants, or plant growth regulators containing micro-organisms, viruses, microbial fungi, animals, e.g. nematodes, or substances produced by, or obtained from microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates

3

* IPC version 2009; Relevant patent records: 194; Data set for analysis limited to categories with more than 30 records; totaling to 55 %.


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process patents for site of transformation (Class III) and product patents for target species/applicability were studied (Class IV). For site of transformation, mitochondria or plastids form possible areas of research. Hence, process patents related to transformation activities at these sites were studied (Class III). Process describing delayed resistance development, products of the transgenic like insecticidal activity, and use of gene construct/protein type are the various other aspects of the transgenic technology irrespective of the transgenic event were considered in the thematic area of procedural description (Class V) transgenic features (Class VI) and in. Patents with claims for insecticidal activity with specificity to a particular insect order (e.g. coloeptera or lepidoptera) or species were grouped under host specific/narrow range category and if applicable for two or many insect orders, were grouped under broad range category.

Maximum patents were both for nucleic acid sequence and amino acid sequence of polypeptide (65 per cent of Class I), broad applicability (69 per cent of Class IV), methods of preparation and using of nucleic acids and polypeptides (28 per cent of Class V), either narrow (49 per cent) or broad range

(37 per cent) and utilization of gene construct both for transgenic development and preparation of pesticidal composition (34 per cent) (Class VI). Interestingly, patents that claimed both nucleic acid and polypeptide also claimed pesticidal compositions. If the target of transformation was an organelle like plastid or mitochondria, the type of molecule was RNA.

A further attempt was made to identify the major assignees across the thematic areas. Results indicated the presence of major players like Pioneer Hi-Bred International Inc, Monsanto technology LLC in all the areas and Athenix Corporation, Bayer Bioscience in few areas (Table 4).

Patent Text Clustering

Patent text clustering, a powerful visualization tool in linguistic and relational technology is used to analyse the patent documents in the result set to extract key terms from the titles and abstracts. This tool transforms obscure, textual information into science based clusters of useful knowledge. With an objective to understand the technology diffusion processes, the set of 194 Bt cotton patents were evaluated using text clustering feature in Delphion. This allows large number of documents having

Table 3 Classification of relevant patent set* into thematic areas of Bt technologies

Class Bt cotton thematic areas % Patents

Nucleic acid 15 Polypeptide 2 Both nucleic acid and polypeptide 65

I Type of molecule

RNA 3

Cry 27 VIP 2 TIC 5 AXMI 4

II Type of gene construct/Protein type

Combination 10

III Site of transformation Organelle (plastid/mitochondria) 3

Species specific 3 Narrow applicability 3

IV Target species

Broad applicability 69

Gene construct preparation 9 Use of the gene construct in transformation 6 Both for preparation and use of gene construct 28 Diagnostic kit 3

V Procedural description

All 6 49 Insecticidal activity

Host specific/narrow range Broad range 37 Delayed resistance development 2 Transgenic technology commercialization 1

VI Transgenic features

Gene construct/protein type used both in transgenic development and in the preparation of pesticidal composition

34

* Total set of 194 patent records; full patent document studied and percent patents in each thematic area mapped into framework as in Fig. 1


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common concepts to a large extent, to be organized into clusters and visualized graphically with a map to provide an overview of the clusters and an indication of the relationship among them.30 There were 10 classified groups of clusters from the basic set of 194 patents. Table 5 summarizes the features of the cluster areas along with distribution of years and major technologies in each cluster. It is interesting to note that distribution of years in all clusters is broad, ranging from 1989 to 2010. This clearly indicates a continuous and evolving pattern across all the clusters in the entire set of 194 patents and relates to the earlier observation on increasing trend in filing of patents.

In terms of numbers of patents in each cluster, the maximum (21 per cent) were in cluster 1 which comprised of technologies related to isolation of nucleic acid molecule from strains of Bacillus thuringiensis with insecticidal activity for very short period between 2008 and 2010. Almost 12 percent of the patents were found bunched into cluster 2 highlighting patents on coding sequence for delta-

endotoxin genes, polypeptides, nucleic acids through DNA construct or expression cassettes for transformation, which are AXMI genes specific, Cluster 3 comprised of 11 per cent of 194 patents with technologies involving synthetic Bt chimeric crystal proteins with broad-spectrum activity and these are Cry 1 genes specific. This was followed by the cluster 4 (10 per cent) containing patents with methods of expressing Cry 2 Bacillus thuringiensis δ-endotoxins in plants. There were about 7 per cent of the unclustered patents due to unavailability of enough textual information to perform this operation.

Further, similarity analysis between each cluster was worked out (Fig. 4). It was found that utmost similarity was between clusters 3 and 4 (22 per cent), 19 per cent between clusters 1 and 2, clusters 3 and 6, clusters 4 and 6 at first level represented by thick line in the map, followed by second level percent similarity (17 per cent) between the clusters 4 and 5, 16 per cent between clusters 3 and 7, clusters 3 and 5 and clusters 4 and 8, 15 per cent between clusters 1 and 4, clusters 2 and 4, clusters 5 and 7, clusters 5 and

Table 4 Major assignees* of Bt cotton technologies vs thematic areas

Bt cotton thematic areas Major assignee(s) **

Nucleic acid Pioneer Hi-bred International Inc (39%), Athenix corporation (19%)

Type of molecule

Both nucleic acid and polypeptide

Monsanto technology LLC (31%) Pioneer Hi-bred International Inc (30%) Athenix corporation (18%)

TIC Monsanto technology LLC (71%)

Cry genes Monsanto technology LLC (43%), Pioneer Hi-bred International, Inc (13%)

Type of gene construct/protein type

AXMI Athenix corporation (100%)

Target species Broad applicability Pioneer Hi-bred International Inc (36%), Monsanto technology LLC (24%), Athenix corporation (18%), Syngenta Participation AG (5%)

Gene construct preparation Monsanto technology LLC (35%)

Both for preparation and use of gene construct

Monsanto technology LLC (44%), Athenix corporation (22%)

Procedural description

For preparation of gene construct, usage of gene construct and diagnostic kit

Monsanto technology LLC (73%)

Pioneer Hi-bred International Inc (46%), Monsanto technology LLC (26%), Bayer Bioscience NV (6%)

Insecticidal activity Host specific/narrow range Broad Range

Athenix corporation (34%), Monsanto technology LLC (31%), Pioneer Hi-bred International Inc (10%)

Transgenic features

Combination of insecticide and transgenic

Pioneer Hi-bred International Inc (54%), Monsanto technology LLC (17%), Athenix corporation (6%)

* Assignees identification restricted to those with more than 5 patents, ** Figure in parenthesis indicates per cent patents owned by an assignee in a specific thematic area of Bt technology


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8 represented by dotted lines. Third level of per cent similarity was 14, 13, 12, 11 and 10 found between set of clusters represented by thin lines. Further analysis was done by correlating these patent clusters with Bt cotton thematic areas as projected in Fig. 1. Cry/VIP/AXMI/TIC are the different types of genes from Bacillus thuringiensis with specificity to a particular insect order.31-32 The type of gene construct/protein type (Class II) is the product resulting from the process involved in the preparation of gene construct (Class V). Ultimately insecticidal activity (Class VI) is the function of gene construct/protein type. The results in this study clearly indicate interdependency of these related technologies (Class II, V and VI). Interestingly, the transgenic feature, delayed resistance development (Class VI) claimed in four patents (US 20070028324A33, US 20090313717A134, WO2009132850A135 and WO2009149787A136), is closely related to a combination of two or more genes which is termed as ‘combination’ in the class type of gene construct (Class II). Delayed resistance development in Helicoverpa armigera to the transgene due to the presence of two or more genes was also reported as early as 1999 in a laboratory scale experiment.38

Upscaling such research would be essential to develop technology product(s) in these areas. It may be mentioned that in view of better performance of multigene Bt cotton hybrids during the last 2-3 years in India, it has been reported that there is marked preference for such multiple gene Bt cotton hybrids by the end users. It is also projected that such hybrids are likely to occupy 90 per cent of the total Bt cotton area in India.39 Considering the research advancements being currently made use of in technologies with two or more genes to confer delayed resistance development in the target pests which is expected to enhance performance of the crop, it may be practical to invest R&D programmes in these new areas of research. Aureka Themescape Maps

Visual maps creation using Aureka themescape was done to create content maps of the set of 194 patents (Fig. 5). The results generated through common conceptual terms are displayed in a two- dimensional map with peaks representing a concentration of documents and showing the relative relationship of one record to another topographically. Large concentration of documents is denoted by a

Table 5 Overview of Bt cotton technology patent cluster

Cluster First issued date Last issued date Major technologies % Patents Bt thematic areas*

1 24-01-2008 21-10-2010 Isolation of nucleic acid molecule from strains of Bt gene with insecticidal activity

21 Class V & VI

2 21-10-2004 12-08-2010 Coding sequence for delta-endotoxin genes, polypeptides, nucleic acids through DNA construct or expression cassettes for transformation, AXMI genes specific

12 Class II

3 28-05-1998 04-12-2007 Synthetic Bt chemeric crystal proteins with broad spectrum activity, Cry 1 genes specific

11 Class VI

4 11-05-2000 15-06-2010 Methods of expressing Cry2 Bt δ-endotoxins in plants

10 Class V

5 10-12-1992 15-07-2010 DNA/nucleotide/ amino acid sequences encoding insecticidal proteins derived from Bt

9 Class I

6 19-03-1998 03-06-2010 Plant transformation methods 7 Class III

7 21-12-1995 12-10-2010 Methods and compositions for controlling pest infestation by feeding one or more different recombinant RNA to pest through suppression of gene expression

7 Class VI

8 11/22/2001 5/13/2010 Transgenic plant event detection 6 Class VI

9 10/30/1997 5/27/2010 Developing transgenic crop for insecticidal activity with any other traits

5

10 6/1/1989 12/25/2008 Methods for the commercial production of transgenic plants

4 Class VI

*As defined in Fig. 1


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*Thick line represents 1st level of similarity with close proximity between 2 clusters of patents, dotted line represents 2nd level (moderate proximity), thin line represents 3rd level (distant proximity), numerals in parentheses represent number of patents in that cluster and those on the lines indicate per cent similarity between 2 clusters

Fig.4 Patent cluster

Fig. 5 Aureka themescape map based on title and abstract


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peak, with the whitest part, the top, representing the highest concentration of documents related to the listed topic. The dots in the map are examples of specific patents. Valleys reflect a lack of similarity or lack of concentration of documents related to that theme. The blue ‘ocean’ represents areas of low patent activity. The topics shown are automatically identified by a themescape algorithm before being topographically displayed.1

The content map based on title and abstract of the set of 194 patents showed top three areas of genes, polypeptides, embodiments and sequence ids of

transformed bacteria, cells, tissues and seeds. Tight clustering within documents in each of these topic areas was seen. These findings substantiate the trends observed earlier from basic bibliographic data and technology analysis through IPC codes.

Creation and Analysis of Groups

Drilling the data within the top four highly cited groups such as delta-endotoxins, nucleic acids, host cells and seeds and seed tissues were drafted on the Aureka themescape map to know where these technologies are distributed (Fig. 6). Delta-endotoxins

Fig. 6 Bt Cotton technology thematic area representation through Aureka themescape maps


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(49) is the leading group with more number of patent documents (represented by dots) spread across the ontent map, followed by nucleic acids (42), host cells (39) and seeds and seed tissues (32).

Time Slicing of Bt Cotton Technology Patents

The additional feature in Aureka themescape, of progress through time slices was used and analysed for three periods namely; 1980-89, 1990-99 and 2000-09. Time slices display documents on the map for a specific slice of time. While only 1 per cent of patents were found in the eighties’, 22 per cent of patents were found in the nineties and 77 per cent reported from the time slice of 2000-09 (Fig. 7), substantiating the observation in the bibliometric analysis.

In terms of technology areas, more patents were found in the areas of Bacillus thuringensis chimeric crystal, helices domain crystal, sequences of nucleotides, proteins, infestation of endotoxin segments, optimized recombinant expression, and optimized hybrid promoters during the 1990s. There was migration to several more areas in addition to the areas concerned in the nineties and documents were found distributed in several areas in between 2000 and 2009. Trends of R&D in areas of Bt cotton technology such as Bacillus thuringiensis gene expression, embodiments, sequence ids of transformed bacteria, cells, tissues and seeds, tolerance resistance and delta-endotoxins codage were found to be intensifying as evidenced by more valleys (Fig. 7). Some of the patents in 2000-2009 claimed both insecticidal and herbicidal activity substantiating results obtained earlier.

Conclusion Patent analysis methods are attempts to retrieve

most relevant set of patents describing various tools and products for deploying this technology in cotton. Using a multi-pronged strategy to locate maximum information from patents in this wide area, an attempt was made to understand trends of research activities through patents. The results obtained through various strategies were found to be in agreement. However, it is acknowledged that though this strategy is exhaustive, the set of 194 relevant patents may not be complete keeping in view the drawbacks encountered in patent analysis methodology. The study provided indicative trends of this rapidly evolving technology at multiple platforms by multiple agencies for multiple sets of technologies as listed below:

Fig. 7 Time slicing of Bt cotton technology patents in Aureka themescape map


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• Research and development activities in these technologies are on upward trajectory with involvement of several agencies, majority being private companies. Public sector organizations and universities since 2000 at a global level and from 2006 in India, form a component of the set of patent owners. This is a significant development as these institutions can also become major focal points for negotiations for users engaged in deployment processes of Bt based tools in genetically improving cotton.

• Increasing trends were observed in tactics available for deployment of insect resistance genes in cotton in areas viz., gene strategies, gene promoters, gene expression and building of transgenic features including detection processes. In terms of technology assessment, there appears to be more focus on Bacillus thuringiensis gene expression, embodiments, sequence ids of transformed bacteria, cells, tissues and seeds, tolerance resistance and delta-endotoxins codage for both insecticidal and herbicidal properties. Recent reports of better performance of multiple gene stacked transgenics of cotton and preferences exhibited by farmers in India for such hybrids confirm the need to focus R&D programmes towards these areas.

• Several technology providers are emerging at the global level. The level of knowledge base in development of these technologies is particularly multi-layered, with involvement of multiple players. With restrictive legal property ownership issues in place in most countries as part of TRIPS compliance processes, it can be expected that costs for deployment of such Bt technologies may get enhanced and thereby increase transactional budgets of the technology developers and deployment agencies. Possibilities of overlaps and less ‘white’ spaces in various domains may hinder R&D processes. Creation of patent pools or sharing platforms (open access models like Cambia) or enabling models (like African Agricultural Technology Foundation (AATF) is suggested.

• It is encouraging to see that several transnational players are venturing into developing countries by filing in local jurisdictions or forming partnerships (through equity or through licensing agreements with royalties) with local companies. Such developments can be expected to trigger enhanced incomes for local rural communities if proper policies including effective regulatory mechanisms

are set in place. Therefore, such steps infuse a strong competitive ability for research and development efforts in transgenic cotton variety/hybrid production cycles, which are essential to build capacities and capabilities in R&D sector, not only in the core technology areas, but, also in the area of technology management tools including prospecting, acquisition, and deployment of technologies.

• Equally significant is the entry of public research institutions as technology builders and holders indicating need of infusion of more professionalism in public R&D systems of developing countries like India. Thus, it becomes imperative to plan for creation of new models of public-private research or public-public collaborations and partnerships with focused goals of product development. Public policies fostering such activities would be essential to create such an integrative environment.

Acknowledgement The authors gratefully acknowledge financial

support for this work under the XI Plan Scheme ‘Intellectual Property Management and Transfer/ Commercialization of Agricultural Technology Scheme’ by ICAR, New Delhi, India. Grateful thanks are also expressed to Dr P K Joshi, Director, NAARM and Dr N H Rao, Joint Director, NAARM for constant support and encouragement. The technical inputs from Dr M Sujatha, Principal Scientist, Directorate of Oilseeds Research on biotechnology events were critical in developing the search methodology.

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