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Panorama Inmunología Vol. 26 / Núm 1/ Enero-Marzo 2007: 55-61

Technological analysis of immunology in Spain, 2004-2005 E. Campos Jiménez1, A. Campos Ferrer1,2 División Inmunología. Depto. Medicina Clínica. Universidad Miguel Hernández. 2Servicio Inmunohematología. Centro de Transfusión de Alicante.

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ANÁLISIS TECNOLÓGICO DE LA INMUNOLOGÍA EN ESPAÑA, 2004-2005 Recibido: 15 Marzo 2007 Aceptado: 5 Abril 2007

RESUMEN Los indicadores bibliométricos son esenciales para evaluar la actividad científica, y en el campo de la Inmunología básicamente están limitados a las publicaciones en revistas científicas especializadas, en los que el “factor de impacto” –aunque cuestionable- se usa internacionalmente. La investigación científica debería favorecer el incremento de la productividad y el desarrollo socio-económico, más que ser una actividad casi exclusivamente académica. Las patentes no solamente protegen los descubrimientos, sino que también proporcionan a los investigadores una gran cantidad de información que no se encuentra en las publicaciones científicas. Este estudio muestra los resultados de la investigación española en Inmunología desde el punto de vista de la publicación de patentes en 2004 y 2005, así como su posición en el contexto internacional. Las patentes inmunológicas registradas por españoles representaron el 1,99% de las patentes mundiales en 2004, y el 1,75% en 2005. Los españoles figuraron como los primeros en la lista de inventores o de solicitantes en el 10% de sus patentes. En Madrid, la mayor parte de las patentes fueron solicitadas por organismos públicos de investigación, debido a que es la base del Consejo Superior de Investigaciones Científicas (CSIC), mientras que en Cataluña los solicitantes de patentes fueron instituciones privadas.

ABSTRACT Bibliometric indicators are essential to evaluate scientific activity and in the field of Immunology they are usually limited to publications in specialised scientific journals, in which the “impact” factor -although questionable- is used internationally. Scientific research should help to increase productivity and socio-economic development rather than being an almost exclusively academic activity. Patents not only protect inventions but also make available to researchers a whole wealth of information not found in scientific publications. This study presents the results of Spanish immunological research from the perspective of the publication of patents during 2004 and 2005, together with its position in the international framework. The immunological patents filed by Spaniards accounted for 1.99% of patents granted worldwide in 2004, and 1.75% in 2005. Spaniards were the first listed inventor or applicant in 10% of their patents. In Madrid most patents were filed by the PRIs (Public Research Institutions), due to the fact that the CSIC (Consejo Superior de Investigaciones Científicas, scientific research council) is based there, whereas in Catalonia most patentees were private enterprises. KEY WORDS: Bibliometry / Patents / Scientific policy.

PALABRAS CLAVE: Bibliometría / Patentes / Política científica.

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TECHNOLOGICAL ANALYSIS OF IMMUNOLOGY IN SPAIN, 2004-2005

INTRODUCTION Western societies have become very much aware of the fundamental role played by science in today’s world. In fact, science has been defined as the most important cultural and social phenomenon in recent centuries(1). Bibliometric indicators are tools employed in the management of technological and scientific policies, as shown by the fact that they are used in studies evaluating scientific activity(2). In science, contributions to knowledge are often only considered as such if they appear in a scientific journal. For this reason, a country’s scientific capacity is usually judged to be in accordance with the quantity and quality of its publications. However, measuring the quality or importance of a particular scientific contribution is no easy task. The so-called “impact” factor is based on the number of times an article is mentioned in other published articles. However, this “real impact” measurement is often replaced by the impact of the journal in which the article in question is published, since it is assumed, sometimes erroneously, that an article that appears in a high impact journal is a high impact article. This assumption is questionable, but for the sake of convenience and since it is difficult to find better parameters, it is widely used internationally. Scientific research should indeed facilitate the advancement of knowledge, and this should necessarily entail the emergence of innovative ideas that contribute to an increase in productivity and socio-economic development(3). As a result of our social culture, universities have become disconnected from society, and research has become almost exclusively academic. Analysis of patent indicators, in order to evaluate innovation and technological capacity, has gradually progressed in Spain from being something used only by researchers and analysts to being on a par with the indicators traditionally used for this purpose. The analysis of patents has some methodological limitations, as do scientometric and bibliometric analyses, which include the difficulties involved in the compilation of source data. Despite these limitations, the analysis of patents is extremely important in the field of competitive intelligence(4), since in addition to protecting inventions, patents make available to all researchers technological information that would not otherwise be published(5), not even in scientific publications. A patent specification provides information that is very often not found in specialised publications. This study presents the results of Spanish immunological research during 2004 and 2005, and its position in relation to other countries throughout the world, based on the publication of patents.

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MATERIAL AND METHODS The SCOPUS database was used to obtain world patents, since it uses the key words as the search criterion, and the search was limited to patents published in 2004 and 2005. The search for Spanish patents was done using the database of the Spanish Patent and Trademark Office (OEPMPAT: “Patentes de la Oficina Española de Patentes y Marcas”). We selected patents belonging to the technological sub-classes of the International Patent Classification (IPC) in which ESPACENET includes the area of immunology. In descending order of importance these subclasses are: A61K39, C07K14, C07K16, A61K38, G01N33, A61K31, A61K47, C12N15, C12N9, C07D215, and any duplication were eliminated. The database of the U.S. Patent and Trademark Office (USPTO) was used to find Spanish patents in the United States. The patents granted were taken from the PatFT base of the USPTO. This base allows a selection to be made by year and key words. As in the case of the patents obtained through SCOPUS and the USPTO, the results were ordered alphabetically. With this list a new database was created using Access and the data relevant to our study were introduced therein. The software package SPSS 14.0. was used for statistical analysis of the data.

RESULTS The search carried out in the SCOPUS database, using the terms that cover the area of immunology, gave as a result a total of 28196 patents, of which 1206 correspond to 2004 and 1312 to 2005. Analysis of these patents indicates that: • Of the 2518 patents, 2028 involved the work of researchers from a single country and 490 were generated by researchers from various countries. • The patents published in 2004 corresponded to researchers from 35 countries and those published in 2005 to researchers from 41 countries. The total number of countries in the two years was 44 and the mean number of researchers per patent was 3.67±2.56. • Researchers came mainly from the United States, the United Kingdom, Germany, France, Switzerland, the Netherlands, Canada, Israel, Denmark and Italy (Fig. 1A). • Of the 2518 patents, 2036 were filed by one single country and 482 by various countries. • The applicants for the patents published in 2004 were from 36 different countries and for those published in 2005 from 43. The total number of countries applying

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Figure 1. Countries from which the researchers (A) and applicants (B) for patents come, indicating whether they come from the same or various countries.

for patents in the two years was 49 and the mean number of applicants per patent was 4.51±2.78. • Applicants were mainly from the following countries: the United States, the United Kingdom, Germany, Switzerland, France, the Netherlands, Canada, Israel, Denmark and Australia (Fig. 1B). Of the patents filed jointly by various countries, the first listed inventors were mainly from the United States, the United Kingdom, Germany, the Netherlands and Australia (Fig. 2A), and the first listed applicants were mainly from the United States, Switzerland, Germany, the United Kingdom, the Netherlands and Belgium (Fig. 2B). In the two years, 117 immunological patents were published in which Spaniards figured as inventors or as applicants. Seventy came from the 211 patents obtained from the OEPMPAT database in which Spaniards were involved either as inventors or as applicants; 43 were obtained from the ESPACENET-WIPO database, and 14 from the USPTO database. Of the 117 patents, (62 in 2004 and 55 in 2005), in which Spanish researchers participated, 69 were the work of Spanish researchers exclusively, 5 patents were applied for in Spain

but neither the inventors nor the applicants were Spanish, so these were not taken into account. The mean number of inventors per patent was 4.24±2.53. Likewise, 47 of the 112 patents (24 in 2004 and 23 in 2005) were the work of Spanish inventors who patented jointly with inventors from other countries: the United States (32), United Kingdom (11), Germany (3), France (3), Italy (2), the Netherlands (2), Australia (1), Austria (1), Canada (1), Ireland (1), Israel (1), Mexico (1), Sweden (1) and Switzerland (1). In only 6 of the patents obtained by Spanish researchers in conjunction with researchers from other countries was the first listed inventor Spanish (1 in 2004 and 5 in 2005). In 107 patents, (59 in 2004 and 48 in 2005), some of the applicants were Spanish and in 69 of these patents all the applicants were Spanish. The mean number of applicants per patent was 3.51±3.17. Thirty eight of the 107 patents, (20 in 2004 and 18 in 2005) were applied for by Spaniards in conjunction with applicants from other countries: the United States (27), United Kingdom (10), Germany (5), France (3), Australia (1), Austria (1), Canada (1), Ireland (1), Italy (1), Japan (1),

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Figure 2. Country of origin of the first listed inventor (A) or applicant (B) for patents held jointly by various countries.

Mexico (1), the Netherlands (1) and Switzerland (1). In only 4 of the patents filed jointly by Spanish and foreign applicants were Spaniards the first listed applicant (2 in 2004 and 2 in 2005). The distribution of the 117 Spanish patents by researcher and institutional sector shows that researchers in the private sector patent the most, followed by public research institutions (PRIs), universities, private applicants and hospitals (Fig. 3). Most of the applicants for the patents published in Spain come from the provinces of Madrid and Barcelona (Fig. 4). The distribution by institutional sector of patents obtained in the Autonomous Regions of Madrid and Catalonia show that in Madrid the PRIs (mainly CSIC) obtain over half the patents, whereas in Catalonia, most patents are applied for by private entities (Fig. 5). The scientific-technical production in immunology during 2004-2005 accounts for 1.11% of the total number of patents published in this period in Spain. In 2004 and 2005, 5233 and 4876 patents were published respectively, of which 62 (1.18%) and 50 (1.03%), respectively, were considered immunological.

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Private aplicants 8% Public Research institutions 25%

Hospitals 2%

Universities 24%

Private entities 45%

Figure 3. Distribution of Spanish patents by researcher and institutional sector.

DISCUSSION Biomedical research is a good example of the “boom” in science that has taken place in many countries, including Spain, in the last century. Likewise, the publications by Spanish authors indicate the great importance of hospital research, which accounts for 20% of all publications(6,7). Spain

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Figure 4. Spanish patents by Provinces.

occupies the fourth position in the European Union in terms of scientific production in biotechnology, with approximately 4.05% of the total worldwide production, coming after Germany (8.79%), the United Kingdom (8.09%) and France (6.06%), according to the data from Genoma Spain in 2003. Around 40% of Spanish publications deal with biomedicine(8). Spanish researchers are very active, but they probably do not make the most of their research. The international projection of research is something that the scientific community is fully aware of, and researchers generally prefer to publish in international journals. However, the number of patent applications filed is a minimum, much lower than would be expected. Only 0.16% of patents granted by the European Patent Office deal with biotechnology(9), and this seems to be the case in many other fields, including immunology. Spanish immunologists have not adopted the habit of patenting; we prefer to publish rather than patent, and in most cases we do not even think about the option of patenting. In Spain, investment in R&D - the amount of money companies dedicate to research and development - and the number

Figure 5. Distribution by institutional sector of patent applications filed in Madrid and Catalonia.

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of patents applied for is far below the level not only of the United States but also of the European Union. Spain, with 8% of the PIB of the European Union and almost 3% of all publications worldwide, has only 1% of the patents in the European Union, and only 5 researchers per 1,000 inhabitants, which places our country ahead of only Greece, Portugal and Italy(10). Research in Spain is basically aimed at preparing university graduates and publishing scientific articles. This is considered the genuine contribution made by scientific activity, and only a very small percentage of researchers consider the possibility of obtaining patentable technology. In the same way, clinical researchers focus their efforts on resolving healthcare problems, developing new protocols or techniques and training new healthcare staff. This marked tendency of researchers to give priority to the publication of their research in journals, especially foreign ones, is the result of the present policy for promoting scientists based almost exclusively on the number of articles they publish. The tremendous recognition given to publications by the scientific community means that they are a decisive factor in the promotion of researchers and in granting of resources by public institutions. This seems to have been the case for many years, since Benjamin Franklin stated that his indifference to worldly things allowed him to give free rein to all his creative capacity and for that reason he made no effort to patent or derive any benefit from his inventions(11). The results of university research may be embodied in “unrestricted processes” such as publications in scientific journals, but these give no financial benefit to either the institution or the researcher. When the results of research are embodied in “restricted processes” such as patents, copyright, and know-how agreements, they become more profitable. The scant number of Spanish immunological patents and the limited economic resources offered to carry out research in immunology at universities and research centres are the reason for the poor financial return obtained by these institutions and researchers. In this respect, companies complain that universities do not take into account whether the knowledge gained by their students will be of practical use in the “real world”. Salvador Ordóñez, ex-Secretary of State for Research, claimed that Spain is a country that neither creates entrepreneurs nor foments constructive criticism(12). Spain is making an enormous investment in R&D, although less than other European countries, and so an awareness exists that there is a direct relationship between investment in science and results in the medium-term(13), but this effort has not been related enough to business. In Spain, this is

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particularly true in the field of biochemistry, microbiology and immunology. In the field of immunology, the United States is the country with by far the greatest number of researchers and patent applicants; likewise, when American researchers and/or applicants patent their inventions jointly with those of other countries, they usually appear as the first listed inventor or applicant. As mentioned above, Great Britain, Germany and France are the European countries with the greatest production of patents, including immunological patents, and there was an increase in the number of patents published by the Czech Republic and Holland in 2005. Of the 49 countries that filed immunological patent applications, Spain occupies the twelfth place in terms of publication of patents by researchers, and the fifteenth in terms of applicants. The United States is the country with which Spain shares the greatest number of joint patents, but in very few of them do Spaniards appear as the first listed inventors or applicants. Furthermore, unlike what happens in other countries, only very seldom do researchers figure as patent applicants. The interaction between immunology and the solution of practical problems is an aspect that has been never clearly solved, neither by researchers nor by the institutions responsible for financing research projects, even though both believe that the solution of practical problems, that is, applicable rather than academic immunology, is their main objective. The unsatisfactory conditions in many university laboratories, the limited capacity of researchers to carry out productive research other than for academic publication and the very few systems of evaluation that exist imply a scant financial return that is far below what would be desirable. In today's globalised setting, we are at a disadvantage compared to other countries that are better prepared technologically, since we make much less efficient use of unrestricted knowledge. The countries that are better prepared take unrestricted knowledge and give it back to those that are less prepared in the form of patented products, on which substantial royalties must be paid. Companies demand immediate results, which are rarely possible in immunology, since in applied immunology any potential benefit is totally uncertain. At the same time, the institutions financing research seek results that are easy to measure (i.e. articles/impact factor), and for this reason the publication of academic results ends up being the main aim of research. It is true that the publication of patents also implies certain risks. The priority for many companies, in particular large ones that invest in research is to obtain profits and as a result,

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research may be stifled. Very often, industry favours research into what is profitable rather than what is necessary(14,15). It is therefore essential to promote collaboration between the private and the public sector, increasing not only the material resources provided by private and public institutions but above all human resources. A critical mass is vital. In order to design the university of the future and evaluate researchers we need to know what type of research we wish to encourage. Basically, we evaluate publications, but there are many other indicators that should figure among the evaluation criteria, for example, agreements, contracts with private agents, and patents(16). It is a mistake to favour only a few large companies or important research centres. The current trend is to create “networks” intended to solve the problems of Spanish research. However, one might wonder if this is not merely another strategy to allow just a few to obtain the lion's share of research financing. Small research centres and companies have a lot to offer in many aspects of research. Globalisation tends to result in concentrations that appear to be beneficial, but perhaps we are forgetting how important it is to motivate researchers. In this respect, the institutional sectors to which Spanish researchers and/or applicants for the patents analysed belong vary depending on the Autonomous Region in question. Overall, the private sector is seen to be more active in patenting, whereas hospitals and private applicants account for only a small proportion of the patents published. A detailed analysis of the publication of patents in the Autonomous Regions of Madrid and Catalonia also shows that there is a big difference between these two regions. Whereas in Madrid the PRIs participate most in patenting, since the CSIC has its headquarters there, in Catalonia the private sector is a clear example of the innovative character of this region.

ABBREVIATIONS IPC: International Patent Classification; OEPMPAT: Patentes de la Oficina Española de Patente y Marcas; PRIs: Public Research Institutions; USPTO:US Patent and Trademark Office.

CONFLICT OF INTEREST The authors declare no financial conflict of interest.

E. CAMPOS JIMÉNEZ, A. CAMPOS FERRER

CORRESPONDENCE TO: Dr. Adolfo Campos Ferrer Centro de Transfusión de Alicante. Ctra. Nacional 332, Km 87 03550 San Juan de Alicante Phone number: 0034.659.461.861. E-mail: [email protected]

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