DEVELOPING TRANSGENIC RICE AT THE UNIVERSITYOF COSTA RICA: PERSPECTIVES AND CONSIDERATIONSFOR MANAGING INTELLECTUAL PROPERTY RIGHTS

Ana M. Espinoza, Ana Sittenfeld and Silvia Salazar

Ana M. Espinoza. B.S. in Agricultural Sciences and M.Sc. in Biology, Universidad de Costa Rica (UCR). PhD, University of East Anglia, England. Principal Investigator, the Rice Biotechnology Program, Centro de Investigación en Biología Celular y Molecular (CIBCM), UCR. Dirección: CIBCM, Ciudad de la Investigación, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, Costa Rica. e-mail: amespino@racsa.co.cr

Ana Sittenfeld. B.S. in Microbiology and Clinical Chemistry and M.Sc. in Microbiology, UCR. Associate Professor, CIBCM, UCR. Coordinator, Biodiversity Comisión, UCR. Address: CIBCM, Ciudad de la Investigación, Universidad de Costa Rica, UCR. San Pedro de Montes de Oca, San José, Costa Rica.

Silvia Salazar. Lawyer, UCR. Specialized in Intellectual Property and Techonology Transfer, Franklin Pierce Law Center, USA. PhD student in Agricultural Sciences, UCR. Researcher, Rice Biotechnology Program, CIBCM, UCR. Address: Vicerrectoría de Investigación, UCR. San Pedro de Montes de Oca, San José, Costa Rica.

Summary

    The Rice Biotechnology Program of the Center for Research in Cellular and Molecular Biology (RBP-CIBCM) at the University of Costa Rica (UCR) started in 1990 the molecular characterization of the rice hoja blanca virus (RHBV) genome, and the development of plant tissue culture protocols for regeneration of local Costa Rican indica rice varieties, aiming at the production of transgenic plants resistant to the virus. The next research phase focused on the development of resistant rice lines by means of genetic engineering of the Costa Rican varieties with RHBV sequences, in order to lend resistance to the virus and to the herbicide PPT, by expressing the bar gene. Transgenic lines produced were evaluated for their resistance to the RHBV and for PPT resistance under local field conditions, as well as for agronomic performance. Progress is currently leading to a shift from the testing of concepts and building up experience in production of transgenic plants, to field evaluation and deployment of modified rice varieties to farmers. For this purpose, the RBP-CIBCM is following a multi-step approach involving food and environmental safety assessment, and identifying and solving intellectual property rights (IPR) issues. The main goals are to design and implement IPR management and education policies, and to perform and audit the technologies and inputs used, and the ways in which these affect the commercialization of the final products. The Program is simultaneously exploring innovative ways to protect transgenic seeds and other research outputs.

Resumen

    El Programa de Biotecnología del Arroz del Centro de Investigación en Biología Celular y Molecular (RBP-CIBCM), de la Universidad de Costa Rica (UCR), inició en 1990 la caracterización molecular del genoma del virus de la hoja blanca del arroz (RHBV) y el desarrollo de protocolos para el cultivo in vitro y regeneración de variedades indica costarricenses, con la finalidad de producir plantas transgénicas resistentes al virus. La fase siguiente se enfocó en la producción, por medio de ingeniería genética, de líneas de arroz resistentes al RHBV y al herbicida PPT, mediante la expresión de secuencias del RHBV y del gen bar. Posteriormente se evaluó en ensayos de campo la resistencia al virus y al herbicida, y las características agronómicas de las plantas. Además de la experiencia acumulada durante el proceso de producción de las plantas transgénicas, se incursionó en evaluaciones de campo, para eventualmente liberar las variedades al mercado. Para este propósito, el RBP-CIBCM sigue actualmente una estrategia que incluye evaluar la inocuidad del nuevo alimento, realizar estudios de bioseguridad ambiental e identificar y resolver derechos de propiedad intelectual (DPI). Los objetivos principales de este trabajo contemplan diseñar e implementar políticas de educación y manejo de DPI para el RBP-CIBCM, efectuar una auditoría de las tecnologías e insumos utilizados, y determinar su efecto en la comercialización de los productos. Al mismo tiempo, el Programa explora formas innovativas para la protección de las nuevas variedades y de otros productos de la investigación.

Resumo

    O Programa de Biotecnologia do Arroz do Centro de Investigação em Biologia Celular e Molecular (RBP-CIBCM), da Universidade de Costa Rica (UCR), iniciou em 1990 a caracterização molecular do genoma do vírus da folha branca do arroz (RHBV) e o desenvolvimento de protocolos para o cultivo in vitro e regeneração de variedades indica costarriquenses, com a finalidade de produzir plantas transgênicas resistentes ao vírus. A fase seguinte se enfocou na produção, por meio de engenharia genética, de linhas de arroz resistentes ao RHBV e ao herbicida PPT, mediante a expressão de seqüências do RHBV e do gen bar. Posteriormente avaliou-se em ensaios de campo a resistência ao vírus e ao herbicida, e as características agronômicas das plantas. Ademais da experiência acumulada durante o processo de produção das plantas transgênicas, se incursionou em avaliações de campo, para eventualmente liberar as variedades ao mercado. Para este propósito, o RBP-CIBCM segue atualmente uma estratégia que inclui avaliar a inocuidade do novo alimento, realizar estudos de bio segurança ambiental e identificar e resolver direitos de propriedade intelectual (DPI). Os objetivos principais deste trabalho contemplam desenhar e implementar políticas de educação e direção de DPI para o RBP-CIBCM, efetuar uma auditoria das tecnologias e insumos utilizados, e determinar seu efeito na comercialização dos produtos. Ao mesmo tempo, o Programa explora formas de inovação para a proteção das novas variedades e de outros produtos da investigação.

KEY WORDS / Costa Rica / Freedom to Operate / Intellectual Property Rights / Transgenic Rice /

Paper presented at the Symposium on Intellectual Property organized by Interciencia Association and CONICIT, San José, Costa Rica, August 2002.

 

Importance of Rice and the Rice Hoja Blanca Virus Disease in Tropical America

    Since Latin American population is expected to grow from 510 to 720 million from the year 2000 to 2020, the food production deficit will rise to critical levels. The total food deficit in Latin America and the Caribbean (LAC) has been estimated in 26.6 million tons by 2020. As a consequence, productivity per area needs to be increased by 41% in order to keep up with population growth (Pinstrup-Andersen et al., 1999).

    Rice is currently the most important grain crop for human consumption in tropical LAC. However, since demand exceeds production (Pinstrup-Andersen et al., 1999), a more efficient use of the limited land resources must be developed through crop improvement, pest and disease management and the breeding of new varieties with increased yield potential, while preserving natural habitats and biodiversity.

    In the case of Costa Rica, rice is a very important staple crop that provides approximately 25% of the daily caloric intake to the population. Rice production faces phytosanitary constraints that include the rice hoja blanca virus disease (RHBV) and weeds, among others. The distribution of this viral disease is limited to tropical America, and there is no natural resistance to RHBV among indica rice varieties. An alternative approach would be to use non-conventional strategies, such as genetic transformation of commercial rice varieties with RHBV antiviral genes for conferring resistance to the virus and to the herbicide PPT (ammonium glufosinate), in order to perform a more effective weed control in post-emergence. The production and deployment to farmers of transgenic rice with these traits are two of the main research activities at the Rice Biotechnology Program, Centro de Investigación en Biología Celular y Molecular (RBP-CIBCM), Universidad de Costa Rica (UCR). Since this is the first locally produced transgenic crop that addresses production constraints not considered by private and public research institutions in developed countries, the RBP-CIBCM has faced many challenges, including basic research leading to the transformation of local germplasm, while at the same time considering the regulatory and intellectual property (IP) issues necessary for a successful commercialization of the new variety. Transgenic rice varieties, resistant to RHBV and produced by RBP-CIBCM, represent the first transgenic crop to be deregulated for commercial release in the country that responds to phytosanitary constraints specific to tropical America. This paper describes the technology used, as well as some of the major aspects concerning intellectual property rights (IPR).

The Rice Biotechnology Program at the Universidad de Costa Rica

    In 1990, the RBP-CIBCM started the molecular characterization and sequencing of the RHBV genome (de Miranda et al., 1994, 1995, 1996), the development of plant tissue culture protocols for regeneration of Costa Rican indica rice varieties CR-1821 and CR-527 (Valdez et al., 1996-1997a, 1996-1997b) and epidemiological studies (Oliva, 1998) of RHBV and its insect vector, Tagosodes orizicolus (Homoptera: Delphacidae). The next phase of the program focused on the development of resistant rice lines through genetic engineering of the Costa Rican rice cultivars, with RHBV sequences in order to confer resistance to the RHBV and to the herbicide PPT, by expressing the bar gene (Espinoza, 2000). Transgenic calli, produced in collaboration with Cornell University (Muñoz, 2000), were regenerated and evaluated in Costa Rica for their resistance to the RHBV and PPT under local field conditions, as well as for their agronomic performance.

    Progress in the research program is leading to a shift from testing of concepts and building up experience in production of transgenic plants, to field evaluation and deployment of modified rice varieties to farmers (Espinoza 2002). Field testing is just one of the several steps required before the genetically engineered rice plants produced can be grown commercially. These steps range from health and environmental risk assessment and management of transgenic crops under tropical conditions, to the establishment of an IP management plan dealing with proprietary inputs and technologies used during the genetic modification of the lines, possible negotiations due to IPRs of third parties enforceable in the countries where commercialization will take place, and protection of inputs and technologies developed within the Program. Public opinion surveys to determine levels of acceptance (Sittenfeld and Espinoza, 2002), together with cost benefit analysis and negotiations with seed producers, are all important activities for the commercialization and distribution of the new varieties. The identified steps, which are part of an integrated strategy developed by RBP-CIBCM, are most probably common to those from other groups working with transgenic rice in tropical countries.

    RBP-CIBCM has used proprietary technology in third world countries for the development of transgenic plants. However, none of these patents or any other kind of rights are granted in Costa Rica due to restrictions on the protection of biotechnological innovations, in place until year 2000. Nevertheless, the RBP-CIBCM is not legally risk free. Although patents are territorial, it is very likely that in the current global economy, rice produced in one country in Latin America would be exported to a second market, which may include countries where patents are either registered or pending. Latin American rice breeders are targeting the Caribbean Basin, Central America and the northern region of South America as potential markets for improved seed. In some of these countries the protection of biotechnological innovations is possible. Consequently, any rice lines developed by genetic engineering may end up as parental lines for different varieties. Furthermore, rice seed production and its distribution in Latin America are carried out mainly by private companies, and consequently, there is a required reassurance that the materials be propagated and sold in compliance with patent rights and plant breeders rights.

    Even though commercialization of the transgenic lines in Costa Rica is problem free, it is possible that, should the rice be exported, negotiations for commercial licenses with rightful holders of proprietary inputs and technologies will be needed. At the same time, companies investing in commercialization and distribution of seeds would rather enjoy the advantage of having exclusive rights on the new varieties. Studies are being conducted to determine the best avenues for the commercialization and transfer of the new varieties to the market, according to the best interest of farmers in the country.

How Were the Transgenic Lines Obtained?

    Transgenic plants were produced by using the RHBV coat protein sequences. First, RHBV cDNA library using pBluescript II/SK in E. coli JM83 was obtained and sequenced at CIBCM (de Miranda et al., 1994). Sub-cloning of the coat protein gene into plant expression vector pBY505 was used for rice transformation at Cornell University. The plasmid pRCP/S had two linked cassettes, the first contained the coat protein sequences of the rice hoja blanca virus (RHBVcp) and was driven by the rice actin I promoter, whereas the second cassette contained the bar gene as a selection marker gene, driven by the 35S CaMV promoter. Cell suspensions of the Costa Rican indica rice varieties CR-5272 and CR-1821 were bombarded using a Biolistic device (PDS/1000/He or the Helios™Gene Gun, Bio-Rad Laboratories, California), and in vitro selection of transformation events were performed in the presence of PPT.

    As part of the international activities of the Rockefeller Foundation Rice Biotechnology Program (RF-RBP), the transformation process was performed by a Costa Rican student at Cornell University, who used RHBV viral sequences (produced by CIBCM) and Costa Rican public domain rice germplasm. Once transgenic calli were obtained, all research processes and further developments were carried out at CIBCM. In Costa Rica, calli were regenerated and seedlings were adapted to greenhouse conditions. For herbicide resistance tests, PPT was applied to the terminal position of the youngest leaf of four-week-old plants. Eight days after herbicide testing, none of the transformed plants showed symptoms of toxicity, whereas the non-transformed control showed extensive damage starting 2-3 days after the exposure to PPT.

    Biological tests were conducted using viruliferous Tagosodes orizicolus (Homoptera: Delphacidae) to demonstrate resistance against the disease. The progeny, containing a single copy of the transgene cassette, was evaluated for herbicide and virus resistance at CIBCM greenhouses. Plants were challenged with viruliferous planthoppers and those that did not develop hoja blanca symptoms, even after two or three inoculation tests, were selected. Coat protein could not be detected in T1 plants using specific polyclonal antibodies in Dot blots, Western blot and DAS-ELISA. RHBV coat protein transgene transcripts were not detected by Northern blot analyses of T1 plants, whereas bar gene transcripts were detected in PPT-resistant plants, suggesting the transcriptional silencing of the cpRHBV gene driven by the rice actin 1 promoter (Muñoz, 2000).

    Primary transformed lines were shown to tolerate toxic concentrations of the herbicide, while T1 progeny segregates 3:1 as a dominant locus. T2 homozygous lines turned out to be herbicide resistant under field conditions. In addition, T2 lines were evaluated for morphology, phenology and agronomic performance under field conditions. Currently, T3 lines are being evaluated at two locations, and promising lines will be crossed with Costa Rican elite lines developed by conventional breeding, with the intention of sending new and improved varieties to the market. All experiments were conducted under the supervision of the Costa Rican National Biosafety Committee (NBC). The NBC has developed regulations and granted permits for transgenic seed increases for nearly a decade, but no genetically modified products have yet been deregulated and released for commercial purposes.

    At present, new transgenic lines using other RHBV genes and bar are under development at CIBCM. Preliminary experiments indicate that some of the To lines are resistant to the herbicide. The RBP-CIBCM research agenda is constantly searching for scientific and IPR improvement, including studies on the genetic diversity and reproductive biology of wild rice relatives (Zamora, 2001; Quesada et al., 2002) and weedy rice (Espinoza, 2002), aiming at the development of gene flow experiments. At the same time, prospecting for new genes from wild rice relatives and other sources is also being conducted.

IPR Legal Framework in Costa Rica

    As in most developing countries, IPR has received little attention from research institutions in Costa Rica. Until 1980, IPR laws dated from the previous century. The situation changed after the announcement of the Agreement on the World Trade Organization (WTO), as part of the Uruguay Round. Trade-Related Aspects of Intellectual Property Rights (TRIPs) of this agreement compel member countries to provide protection for plant varieties either by means of patents; by an effective sui generis system of unique, individual arrangements; or by a combination of both. Many Latin American countries, including Costa Rica, became members of the World Intellectual Property Organization (WIPO) and the WTO, and had to modify their existing IPR laws. The first challenge for the Costa Rican IP system was to amend laws in accordance to the TRIPs. Central American countries will also have to address IPR issues and negotiations, in order to create the Free Trade of the Americas (FTAA) region by 2005. Another area where IPR issues could be important is the bilateral free trade negotiation between the United States and Central America.

    In Costa Rica, IPRs are protected by the Constitution. Article 47 establishes that every author, inventor or producer will be granted temporary exclusive rights in his or her creation, invention, trademark or commercial name. Based on it, Costa Rica has implemented laws and subscribed international conventions related to IPR protection (Palacios and Salazar, 1995). The rights being protected include patents, utility models, industrial models and designs, trademarks, commercial names, origin denominations and copyrights. The Patent Law dates from 1983 but has been recently amended (Law 7979 of Jan 2000). Other important laws related to IPR include the Trademark Protection Law and the Law for Special Procedures for the Enforcement of IPR. The Law for Undisclosed Information protects trade secrets. Costa Rica, as a member of WIPO, continuously receives technical assistance and training. The country is also a member of the 1916 Buenos Aires Convention and, more recently, of the Paris Convention and the Patent Cooperation Treaty.

    Costa Rican law excludes from patentable subject matter some inventions or fields, such as discoveries, scientific theories, mathematical methods and software by itself. Esthetic and literary works are excluded, as well as plant varieties (which are expected to receive special protection by another law), animals and the biological processes used to obtain them, plans and principles, economic or business methods, original methods, intellectual activities, game rules, therapeutic and surgical methods, methods of diagnosis applicable to humans and animals, and inventions contrary to the public health, security, public order or morals.

    In accordance with standard patenting principles, the requisites for patentability are novelty; non-obviousness and utility. Patent period is 20 years starting from the filing date in the country of origin. Other characteristics of the Costa Rican patent system are the obligation to exploit the invention in Costa Rica within three years from the date of issue; compulsory licensing in special cases (as an anti-competitive measure, in case of dependent patents, or in case of public need); patent examinations are not performed by the Registry but by professionals from professional associations and universities; a first-to-file system; publication after fulfilling the formality examination, no maintenance fee, and pre-grant opposition system after publication.

    The 1978 Seeds Law (6289) establishes that the Seeds Office is compelled to create a protected variety registry and establish the procedures for the control of plant breeders’ rights. However, at present there is no plant variety protection in Costa Rica. Over the last five years, the Seeds Office has been working on a draft for the promotion of regulations to protect plant varieties by means of a system in accordance with the International Union for the Protection of New Varieties of Plants (UPOV). The draft is being discussed in Congress, subject to analyses and consultations, and has been criticized by certain sectors. Yet, a political decision on this matter was reached when Congress stated in the Patent Law that plant varieties will have to be protected by a special law. It remains to be decided if Costa Rica will join UPOV. The draft was written to fulfill UPOV requirements, but it does not mention if Costa Rica will become a UPOV member.

    In relation to biotechnological inventions, it should be mentioned that for Costa Rican law purposes, scientific discoveries are not considered inventions and, thus, they are not subjects of patents. Neither are plant varieties, animal breeds and essentially biological processes considered. In accordance to TRIPs, microbiological processes and genetically transformed microorganisms are patentable. A transgenic plant or a transgenic animal, being the result of a biological process, would not be patentable. The rule in the past stated that nothing that implicated biological material could be patented, and the Patent Law is unclear as to whether an isolated gene is patentable. Would the way in which a gene is located be considered a biological process? The question addresses the possibility of rejecting the idea of patenting it, under the premise that it is not clear whether gene isolation and location will qualify as a biological or microbiological process.

    The Biodiversity Law 7788 must be added to this Costa Rican panorama. The law specifically regulates biodiversity issues, but also contains regulations on IP. Since the law is very recent (1998), it is not clear yet on how to solve legal problems that may potentially arise from conflictive articles present in both the Biodiversity and Patent Laws, which regulate the same matter, without being abolished or modified. The Biodiversity Law indicates that IPR should not be granted for nucleic acid sequences per se, plants and animals, non-genetically modified microorganisms, essentially biological processes for the production of plants and animals, the natural processes or cycles themselves or inventions essentially derived from knowledge associated with traditional or cultural biological practices in the public domain. Monopolized commercially exploited inventions that may affect basic agricultural processes or products for the nutrition and health of the inhabitants are also excluded. In addition, in conformity with articles 62 and 69, every investigation program or bioprospecting on genetic material collected in Costa Rican territory requires access permission, unless covered by the exceptions foreseen by the law. Moreover, public universities can establish their own controls and regulations in the case of non-profit investigations requiring access to biodiversity. The UCR complied with this provision, and has its own regulations under the supervision of the Institutional Commission for Biodiversity. Previous reported consent is one of the conditions required for access permits, according to the Convention on Biological Diversity (CDB).

    Authorities are reluctant to protect products and processes related to agriculture with patents, due to lack of studies on the possible impact this could have on this sector, especially on price increases in developing countries. Currently, there is a debate about the convenience of strong intellectual property regimes in less developed countries. (IPR Commission, 2002). In Costa Rica there are several projects on genetic improvement of plant varieties, including transgenic varieties as shown by the RBP-CIBCM. The country’s efforts in this field are recognized in Latin America, due to the high level of human resources and research facilities available. Investigators conducting these projects were the first to point out the consequences of not protecting their research activities.

IPR Framework at the Universidad de Costa Rica

    According to DaSilva (2001) universities in industrialized and developing countries are producing scientific knowledge and, consequently, face IP protection. Concerns today focus on the relationships between academy and industry, on how to generate, share and own knowledge, and to consequently translate it into marketable products. Understanding IPR is important for such cooperation. The problem lies on the fact that academics in developing countries are not sufficiently aware of the commercial value of their knowledge, and often give it away for the profit of companies, without assuring that part of this profit will benefit university research (Devon, 2001). On the other hand, patents and the exercise of IPRs might lead to restricted access to proprietary knowledge and germplasm, and to control over the research process.

    The scope for innovations is growing considerably and researchers at universities have powerful tools to work with, but they must learn how to manage the highly complex IPR procedures that control their access, in order to exploit them (Erbisch and Velásquez, 1998; Uchida, 2001). Costa Rican universities are no exception concerning the delay observed in developing countries for building the necessary capacity to deal with IPR issues (Solleiro and Castañón, 1999). IPR was not a concern at UCR until the last decade, when the University began a closer relationship with the private sector, with the purpose of accessing private funds supplementary to public support. The transfer of technology and research products to the private sector catalyzed the concern for IPR and the creation of the Technology Transfer Unit (UTT). Although concerns were raised, actions took longer to implement. There is no institutional culture promoting the protection of IP. Investigators favor the publication of results to upgrade their positions, rather than applying them for patents, as there are no incentives for IPRs. UCR has not established norms and policies leading to IP protection, and regulations do not contain clear indications concerning this matter. Moreover, study plans in Biotechnology and Plant Genetic Improvement do not consider specific IPR related courses, although IP issues are mentioned. References to IPR are part of the curriculum for Commercial Law, and only two courses at the Law School offer IPR training.

    Only recently an IPR lawyer was hired as staff at the UTT, to assist researchers on IP issues, access to technologies, technology transfer or ways to protect their inventions. Therefore, the challenge for RBP-CIBCM was to start and develop on its own the expertise and capacity on IPR related issues, in view of the limited institutional capacity at UCR.

IPR Issues Implemented by the RBP-CIBCM

    Agricultural scientists are clearly affected by globalization trends and IP regimes. Many of them need to become more strategic and systematic concerning their collaborative research programs, and to acquire a clearer understanding of the institutional application of their work (Cohen, 2000). Beyond access to knowledge and materials, there is also an increased complexity in managing IPR for some biotechnological work. It is not unusual that the development of a single product may require to solve 15 to 30 different proprietary technology issues. For example, there are 31 private and public institutions holding 70 patents related to Golden Rice (Kryder et al., 2000).

    Public research organizations need to develop specific capacities and strategies to access knowledge and technologies, but this involves a drastic departure from the organizational cultures of most universities and research centers (Cohen, 2000). In this respect, and in view of the limited institutional capacity and qualified assistance at UCR, RBP-CIBCM has to develop its own expertise required for sorting through IPR issues and complex negotiation schemes. CIBCM staff has been directly responsible for the implementation of IPR audits, internal IPR policies (IPR management), and negotiations related to freedom to operate, with the assistance of a knowledgeable IPR lawyer. Some of the advances in IPR management and freedom to operate at CIBCM are described hereunder, including comments on what remains to be done and the lessons learned along the process.

IPR Management at CIBCM

    The application of IP to biotechnology is changing the way in which scientists exchange ideas, techniques and materials, and has great impact on the way in which scientific research is performed. The RBP-CIBCM has established working procedures and ways to ensure the safekeeping and management of proprietary knowledge, according to good scientific practices that ensure the safekeeping of proprietary knowledge. For example, ownership and confidentiality agreements, and material transfer agreements (MTAs), are signed to protect results and assign rights on a project team. Laboratory notebooks have clear guidelines (Garabedian, 1997), and are signed and witnessed to establish a date for the invention. Even though preliminary, accomplishments in IPR management include:

    Confidential Agreements. Confidential Agreements are signed by researchers, and also by undergraduate and graduate students working on their thesis as part of the RBP-CIBCM. The agreements are applied to all participants in the research process, in order to obtain adequate protection of confidential results. In view of the open conditions observed at UCR, confidential documents and information are labeled as such; in this way, researchers and students are aware of the level of confidentiality pertaining to a particular document or information. Confidentiality Agreements are also signed before disclosing confidential information to companies or investigators in other research units in the early stages of discussion. In some cases, visitors are also requested to sign confidential agreements in advance.

    Material Transfer Agreements. MTAs are standard documents defining the conditions for the exchange of germplasm, microorganisms and DNA sequences with scientists within and outside UCR. All MTAs are done according to the Costa Rican Biodiversity Law and the CDB. Basic aspects of MTAs prepared by RBP-CIBCM include transfer conditions, provisions for materials location (to facilitate tracking down results), use of materials and associated information (usually, restrictions for research purposes only are included, as well as confidentiality of results and materials), reporting and conditions for any research results conductive to publication. The policy of RBP-CIBCM is to carry out previous evaluations on the convenience and consequences of future commercialization and use of technologies and materials acquired through MTAs containing restricting clauses related to research purposes.

    Of particular interest is the Germplasm Transfer Agreement signed between the International Rice Research Institute (IRRI) and UCR for the inventory, collection and ex situ conservation, at the International Rice Genebank, of wild rice relatives present in Costa Rica (Zamora, 2001; Quesada et al., 2002). Species and accessions transferred from RBP-CIBCM to IRRI will not be assigned to a system based on free exchange of materials. However, RBP-CIBCM will permit IRRI to exchange samples on a worldwide basis for research and non-commercial purposes only, provided that IRRI obtains a previous written permission from RBP-CIBCM. In the case of recipients who wish to commercialize research products that originate from the wild rice germplasm supplied by RBP-CIBCM, direct and written approval from RBP-CIBCM must be obained. By incorporating these conditions to the MTA, the RBP-CIBCM complies with rights and obligations for the access of genetic resources, as stipulated in the Costa Rican Biodiversity Law. At the same time, the signed transfer agreement allows for convenient direct negotiations of the RBP-CIBCM with third parties.

    Prior informed consent for accessing biodiversity. RBP-CIBCM has obtained all permits from the Ministry of the Environment and Energy (MINAE) for accessing biological and genetic resources, according to the Biodiversity Law and the Biodiversity Convention. All collectors have licenses, and research results are reported back to MINAE.

    Laboratory notebooks. The establishment of clear rules on how the laboratory notebook should be handled and written is part of the policies implemented by the Program. In this way, all results could be documented. Records must be signed periodically by the research group leader and validated by a notary in order to establish a date for the invention. By the same token, researchers must disclose any inventions and discoveries.

    Thesis results at UCR are public by definition. The RBP-CIBCM has tried to persuade university authorities of the importance of restricted access when students are defending and presenting the results of their thesis. Confidential agreements are proposed to be signed by thesis boards, and access to the written document is restricted for a period of time before being released to the university libraries. These procedures intend to protect any information potentially capable of patent applications or any other IP protection procedures. However, there is a controversy between the Confidential Agreements signed by students at the Program and the obligation for information disclosure in UCR bylaws. This conflict remains one of the most important challenges for IP protection at RBP-CIBCM as there are ethical dimensions related to the balance between communicating results from research, as part of the mission of UCR, and the need of confidentiality for IP protection.

    Conflict of interest policy. Disclosing conflicts of interest with donors and partners is part of the new rules and regulations at RBP-CIBCM, and a requirement for the incorporation of new personnel. A conflict of interest may arise when a member of RBP is able to influence administrative, academic, business or any other kind of decisions for personal gain or advantages of any kind, or to interfere with obligations and commitments of RBP-CIBCM. Disclosure should be made to the Coordinator of the RBP and the issues involved discussed. This is an area of concern for RBP-CIBCM, since UCR does not have clear policies and regulations in this connection.

    Training and capacity building at all levels. Seminars and workshops are frequently conducted by RBP-CIBCM to create awareness on IPR issues among students and staff. Understanding of the importance of IPRs is part of the Program’s culture, and state-of-the-art update for senior staff is considered.

    Terms and conditions with donors. Several national and international institutions have financed RBP-CIBCM. However, the support of the Rockefeller Foundation (RF) and the Fundación Costa Rica-Estados Unidos de America para la Cooperación (CRUSA), has been crucial for the development of research activities at RBP-CIBCM. Several research contracts between these foundations and the UCR were signed.

    The RBP-CIBCM was part of the RBP-RF for more than a decade. The main goal was to develop new technologies for the genetic improvement of rice by genetic engineering, and the transfer of these new technologies to laboratories of developing countries. The policy of RF in the early 90s included free exchange of genes, plasmid vectors for rice transformation and technologies among the laboratories participating in the Program. No MTAs were signed. RF initially established that if commercial products were derived from the research, UCR could not grant exclusive licenses to industry. However, more recently, RF is funding a project that specifically considers IPR issues, so that transgenic rice varieties produced by RBP-CIBCM could be commercialized and, if necessary, exclusive licenses awarded to the private sector. In addition, the contract between CRUSA and RBP-CIBCM indicates that if products of research are commercialized, 5% of net revenues will be transferred to CRUSA, to support further research.

Freedom to Operate

    The concept of freedom to operate is fundamental to the effective development and commercialization of any innovation, and is particularly important in agricultural biotechnology. If a research program or commercialization is conducted under the assumption that its implementation will ultimately be allowed, future negotiations may be seriously affected. Research licenses may be relatively easy to obtain, but licenses for the commercialization of research products can be more difficult to acquire (Binenbaum et al., 2000).

    Determining freedom to operate requires technical knowledge, business skills, detailed understanding of patent claims in the relevant countries, understanding markets and market dynamics, national jurisdictions and knowledge of litigation and negotiation procedures in different countries (Binenbaum et al., 2000). Some accomplishments of this project in IPR issues concerning freedom to operate involve:

    IPR audit. A preliminary inventory of the appropriate materials and technologies of third parties used by RBP-CIBCM, and of their relation to freedom to operate, was conducted. These included vectors for DNA transformation, promoters, selectable marker genes and DNA transformation technologies. The audit led to the analyses and scope of third party rights over research results at CIBCM, including potential IPR infringement and other legal conflicts. However, many of the components used have to be negotiated in a more realistic context, in view of the territorial application of patents. As previously mentioned, none of the technologies and materials used in the production of the transgenic rice lines is patented in Costa Rica. Concerns relate to exports of transgenic seeds or products to third countries, where proprietary inputs and technologies used are protected and require commercial licenses with rightful holders. Recent changes in Costa Rican Patent Law introduced after 2000 might affect the use of new research tools. Also, future negotiations in this area, including the FTAA and a possible free trade agreement with the US might affect patentability of biotechnological innovations.

    Contractual arrangements. Patents might not represent the complete spectrum of IP concerning agricultural biotechnology. Other restrictions to freedom to operate might be imposed through contracts. As an example, RBP-CIBCM signed a contract with Bio-Rad as a requirement for purchasing the Biolistic device used in plant transformation procedures. The contract clearly stated that the use of the biolistic gun is only for research purposes. In the event of commercial applications for agricultural purposes, a license is required from E.I. Dupont de Nemours & Co. Although Dupont and its licensor do not hold any patents in Costa Rica claiming the Biolistic® technology, in view of the restrictions for potential applications, negotiations were conducted regarding the right of UCR over the transgenic lines developed at RBP-CIBCM.

    Collaboration with other research institutions. There were no MTAs signed between Cornell University and UCR in relation to the transformation of rice germplasm, and materials and knowledge from both institutions were freely exchanged. Within the context of RF-RBP, a PhD thesis of a Costa Rican student was developed at Cornell, as a collaboration that started in the early 90s, when IPR issues were not yet considered. As a result of the collaboration, transgenic rice calli were obtained by the student at Cornell, using the CIBCM cpRHBV gene, Costa Rican rice germplam, and technology and genes provided by Cornell. Negotiations were initiated to clarify and define the scope and rights of each institution, according to the degree of participation and the research outcome of each institution. It is clear that early phase research on the characterization of the RHBV was conducted at CIBCM (de Miranda et al., 1994; 1995 and 1996), and the transformation process at Cornell. The following steps regarding biological and agronomic evaluation of the transgenic rice lines, environmental and food safety, were or are being conducted at CIBCM.

What Remains to be Done?

    RBP-CIBCM must investigate opportunities for technology protection and licensing, since at present there is no protected technology derived from its own research activities. The Program is currently evaluating which research outputs might be subject to protection, which inventions should be freely released or brought to the farmers through the private sector or the Ministry of Agriculture, and how the process could be implemented in a transparent and equitable manner. An ex ante cost-benefit study is needed in order to determine which inventions and/or discoveries will merit the cost of IP protection, and which could be used as "bargaining chips" for cross licensing.

    There is a need to promote the development of an institutional IP policy strategy related to internal and external use of proprietary assets. A comprehensive IPR management strategic plan, procedures for tracking terms and conditions, rights and responsibilities established through MTAs and contracts should be developed concerning this issue.

    The creation of institutional IP units at UCR level to be promoted, to handle technology transfer, licensing, institutional negotiations, training, and protection of assets, research processes and products (Salazar et al., 2000). It is also necessary to promote a more proactive strategy by taking steps to find institutional mechanisms for addressing the complexity of IP challenges. At the same time, the establishment of an IPR Committee at CIBCM, with clear instructions and mandates, should provide first-hand and on-the-job training to key personnel at the institutional level.

What Have We Learned?

    We have learned about the importance of developing expertise in IPR and negotiation at the Program level, particularly when and where IPRs represent a real constraint; how to design our own IPR policies and how to obtain favorable conditions for using existing technologies and developing new technologies. It is also important to carefully consider IPR management strategies and freedom to operate, prior to embarking on new research projects.

    Costa Rica is potentially capable of obtaining benefits from biotechnology, especially from agricultural biotechnology. The country is privileged in terms of biodiversity and genetic resources, the raw materials for biotechnology. These facts have to be taken into account when making decisions regarding IPR protection in agriculture. When dealing with protecting agricultural biotechnology in countries like Costa Rica, some concerns arise. Developing countries are beginning to understand that innovation is crucial for development, and that protection of IP is a basic step. However, they do not want their farmers to pay high prices and limit their access to agricultural goods (Couzin and Bagla, 2002). Within this context, the decision to be made by RBP-CIBCM, in terms of how to protect transgenic rice varieties, remains a difficult one.

REFERENCES

1. Binenbaum E, Nottenburg C, Pardey PG, Wright BD, Zambrano P (2000) South-North trade, intellectual property jurisdictions, and freedom to operate in agricultural research on staple crops. Discussion paper Nº70. Environment and Production Technology Division, International Food Policy Research Institute. Washington DC. 83 pp.         [ Links ]

2. Cohen JI (2000) Managing intellectual property. Challenges and responses for agricultural research institutes. In Persley GJ, Lantin MM (Eds) Agricultural Biotechnology and the Poor. Consultative Group on International Agricultural Research. pp. 209-217.        [ Links ]

3. Couzin J, Bagla P (2002) Report urges leeway for developing world. Science 297: 1791.        [ Links ]

4. Da Silva E (2001) Intellectual property rights, biotechnology and developing countries. In Biotechnological Intellectual Property at Universities: scientific, technological, economic, legal and ethical aspects. ICCS. Ljubljana. Slovenia. pp. 10-16.        [ Links ]

5. de Miranda JR, Hernández M, Hull R, Espinoza AM (1994) Sequence analysis of rice hoja blanca virus RNA-3. J. Gen. Virol. 75: 2127-2132.        [ Links ]

6. de Miranda JR, Hull R, Espinoza AM (1995) Sequence of the PV2 gene of rice hoja blanca virus tenuivirus RNA-2. Virus genes 10: 205-209.        [ Links ]

7. de Miranda JR, Muñoz M, Wu R, Espinoza AM (1996) Sequence of rice hoja blanca tenuivirus RNA-2. Virus genes 12: 231-238.        [ Links ]

8. Devon TK (2001) The importance of patents as intellectual property to the pharmaceutical industry. In Biotechnological Intellectual Property at Universities: scientific, technological, economic, legal and ethical aspects. ICCS. Ljubljana. Slovenia. pp. 48-51.        [ Links ]

9. Erbisch FH, Velázquez C (1998) Introduction to intellectual properties. In Erbisch FH, Maredia KM (Eds) Intellectual property rights in agricultural biotechnology. Biotechnology in Agriculture Series Nº 20. CAB International. New York. pp. 3-18.        [ Links ]

10. Espinoza AM (2000) Transgenic rice in Costa Rica: A study case for biosafety considerations. Abstr. Int. Cong. Perspectives and limitations of biotechnology in developing countries. University of Costa Rica / European Community. San José, Costa Rica.        [ Links ]

11. Garabedian TE (1997) Laboratory record keeping. Nature Biotechnology 15: 799-800.        [ Links ]

12. IPR Commission (2002), Report of the Commission on Intellectual Property Rights. London. www.iprcommission.org.        [ Links ]

13. Kryder R, Kowalski S, Krattiger A (2002) The Intellectual and Technical property components of pro-Vitamin A Rice (Golden Rice): A preliminary freedom-to-operated review. ISAAA Briefs Nº20. Ithaca, NY. 56 pp.        [ Links ]

14. Muñoz M (2000) Sequences of hoja blanca virus and attempts to develop viral-resistant Costa Rican rice. Thesis. Cornell University. Ithaca, New York. 199 pp.        [ Links ]

15. Oliva M (1998) Fluctuación poblacional de delfacidos y su ámbito de poaceas hospederas asociadas al arroz en Liberia, Guanacaste. Tesis. Universidad Nacional. Costa Rica. 61 pp.        [ Links ]

16. Palacios MA, Salazar S (1995) Diagnosis of situation of intellectual property in Central America. SIECA. Guatemala. 502 pp.        [ Links ]

17. Pinstrup-Andersen P, Pandya-Lorch R, Rosengrant M (1999) World food prospects: Critical issues for the early twenty-first century. International Food Policy Research Institute. Washington, DC. 32 pp.        [ Links ]

18. Quesada T, Lobo J, Espinoza AM (2002) Genetic diversity and mating system of the wild rice species Oryza Latifolia Desv. Genetic Resources and Crop Evolution. 49: 633-643.        [ Links ]

19. Salazar S, Falconi C, Komen J, Cohen J (2000) The use of proprietary biotechnology research inputs at selected Latin American NAROs. ISNAR Briefing Paper Nº 44. 8pp.        [ Links ]

20. Sittenfeld A, Espinoza AM (2002) Costa Rica: Revealing data on public perception of GM crops. Trends Plant Sci. 7: 468-470.        [ Links ]

21. Solleiro JL, Castañón R (1999) Technological strategies of successful Latin American biotechnological firms. Electronic J. Biotechnol. 2: 26-35.        [ Links ]

22. Uchida H (2001) University-Industry-Government cooperation in Japan. In Biotechnological intellectual property at universities: Scientific, technological, economic, legal and ethical aspects. ICCS. Ljubljana. Slovenia. pp 52-54.        [ Links ]

23. Valdez M, Garro G, Espinoza AM (1996-1997a) Establishment of morphogenic rice cell suspension cultures (Oryza sativa) in Costa Rica. Revista Biología Tropical 44/45: 593-595.        [ Links ]

24. Valdez M, Muñoz M, Vega GR, Espinoza AM (1996-1997b) Plant regeneration from embryo derived callus of several Costa Rica indica rice (Oryza sativa L.) cultivars. Revista Biología Tropical 44/45: 13-21.        [ Links ]

25. Zamora A (2001) Diversidad morfológica y genética de las especies de oryza (Poaceae) nativas de Costa Rica. Thesis. Universidad de Costa Rica. 178 pp.        [ Links ]