Japan's Challenges to Streamline the Drug Discovery Process Based on Patent Application Trends in Biomarker-Related Research Fields
Yuji Toriyama (Former Senior Researcher, Pharmaceutical and Industrial Policy Research Institute)
(No. 46: Published October 2009)
This paper examines the challenges to improve the efficiency of the drug discovery process in Japan by analyzing the trends and structure of biomarker research, using the number of biomarker-related patent applications and the "number of patents cited per patent" as indirect indicators of the level of biomarker research activity and results, respectively, which are considered to be proxy indicators of patent quality. In addition, the study examined the challenges to improving the efficiency of the drug discovery process in Japan by analyzing the trends and structure of biomarker research. In addition, a questionnaire survey was conducted among pharmaceutical companies that are members of the Japan Pharmaceutical Manufacturers Association (JPMA) to find out what they think about the current status and issues of biomarker research related to the drug discovery process in their actual drug discovery research sites. By comparing the results of this survey with those obtained from the survey on biomarker-related patent application trends, we discussed the research environment in Japan that has become a bottleneck in biomarker development.
Based on the results of the survey and the patent trend survey, the following issues can be identified in the research environment for biomarkers in Japan. First, based on the results of the questionnaire survey, the bottlenecks in biomarker development can be summarized as follows.
First, although it is important to use human samples for biomarker development, it is difficult in practice due to the complicated procedures and costs required to obtain them. Second, biomarkers in the narrow sense are molecules that serve as indicators of biological changes in the body and consist of DNA, RNA, proteins, peptides, etc. These molecules can be quantified and quantified, and their quantitative changes in correlation with disease status have been confirmed in basic experiments using cultured cells and model animals, and finally verified in large-scale clinical trials. Only after this is verified in large-scale clinical trials can it be confirmed as a useful indicator. In this way, the initial stage of new drug development using biomarkers requires more labor and cost than conventional drug discovery-centered R&D, making it difficult to identify drug targets and conduct search and validation of surrogate markers in parallel from the initial stage of new drug development to clinical trials. Third, even if a surrogate marker has been explored and validated by a pharmaceutical company, unless the review authority recognizes it as a key indicator, the pharmaceutical company cannot use it as an evaluation tool for data used in an application for approval. To solve this problem, there is no system of collaboration between industry, academia, and government to establish regulatory science. Fourth, there are many unknowns in prognostic markers, and there is no national government initiative to explore and verify these unknowns through collaboration among universities and medical institutions. Fifth, while some companies are willing to conduct joint research with universities and medical institutions, many are generally reluctant to do so, and companies are not yet sufficiently committed to joint research.
The results of the first and fifth bottlenecks are consistent with the results of the biomarker-related patent survey. In order to improve the quality and quantity of pharmaceutical biomarker research and development, it is essential for pharmaceutical companies and bio-ventures to actively engage in joint research using human tissues and cells with university medical schools, as well as to promote the establishment of laws related to research using human tissues. The number of applications for surrogate marker patents from Japan is lower than those from the U.S. and Europe, but this survey revealed that the second and third bottlenecks are the cause. In order to promote the use of the results of biomarker research, the establishment of an industry-academia-government collaboration system and regulatory science for the verification and certification of surrogate markers on the initiative of the Japanese government are required.
The number of prognostic marker patent applications from Japan is also low, which may be due to the fourth bottleneck. Many pharmaceutical companies have expressed a desire to use prognostic markers that have been validated by the national government and medical institutions, if available, and the establishment of joint research and consortium-like partnerships with these institutions can be considered a challenge.