2016 ANNUAL REVIEW Ministry of Science and Technology

collaborative projects included the following: a. Drugs to treat severe thalassemia and sickle cell anemia: In this collaboration project involving the National Health Research Institutes and Academia Sinica, drugs were used to induce red blood cells to produce fetal hemoglobin in adults, which may be a very effective approach of treating sickle cell anemia and severe thalassemia. The current stage of the project has already been completed, and lead compound optimization, animal pharmacodynamics experiments, and animal pharmacology and pharmacodynamics research are currently underway. Furthermore, the Academia Sinica has signed a licensing contract with the PharmaEssentia Co. giving this company an exclusive global license to the "second- generation sickle cell anemia small molecular drug candidate molecule" developed by the Academia Sinica's research team. b. Drugs for treatment of Alzheimer's disease: This is a collaborative project involving National Health Research Institutes and Academia Sinica. Reports in the literature have indicated that glutaminyl cyclase depends on zinc ions for its enzymatic activity, and is responsible for catalyzing N-terminal pyroglutamate formation in many important proteins and polypeptides. This enzyme has been shown to be a new target for treatment of Alzheimer's disease. The project has entered the drug optimization stage, and it is expected that a candidate drug with development potential will be produced by the end of 2017. (3) Clinical group: Translational medicine and clinical trial projects a. In vitro diagnostic reagent for endometriosis: Endometriosis is common among women of childbearing age, and has a global prevalence of approximately 10%. Approximately 25-30% of infertile women have endometriosis. The research team designed a first-generation in vitro endometriosis diagnostic method employing one- step ELISA, collected approximately 300 new clinical serum samples, performed testing for the A1AT biological marker of endometriosis, and conducted validity assessment. The researchers also clarified the appearance of A1AT in other women's diseases (such as ovarian cancer) in order to determine whether the A1AT testing method might be confounded by the presence of other diseases, and assessed the specificity and accuracy of their diagnostic method. A US patent for relevant technology was obtained in November 2015, and a provisional patent application was completed in July 2016. Domestic and foreign companies are currently expressing interest in licensing the patented technology. b. Design and synthesis of functional nanoparticles for multi-level targeted therapy: The use of nanocapsules in drug transmission systems has recently become a trend. This drug transmission technology can allow the extension of product patent protection, and its use can benefit the public by facilitating the development of new applications from old drugs. The development of nano-carriers combined with sub-cellular drug transmission strategies targeting the molecular pathways of specific diseases can achieve more precise clinical treatments, greater therapeutic effectiveness, and reduced side effects. This project's research team is currently able to stably produce nano- carriers with a high yield; apart from reducing drug and transport costs, the product is suitable for industrial production. The nano-carriers produced in this project can serve as functional nano- carriers after modification, promote phagocytosis by immune cells, and achieve the goal of highly- specific targeted therapy. This targeted therapy approach has demonstrated very low toxicity in both in vitro and animal experiments, and has no significant toxic side effects. It can be seen from biological distribution charts that the nano-carriers are retained in living organisms longer than in the case of the control group drug delivery method, and are more likely to be used by the human body, rather than being quickly excreted from the body. The research team has successfully applied for a patent, and is in the midst of technology licensing negotiations. (4) Resource center: Providing technical services and consulting The program resource center chiefly strives to help find and confirm disease targets, perform drug screening and design, synthesize lead drugs, establish animal models, perform animal experiments, offer legal consulting, and conduct clinical trials of candidate drugs. As of October 2016, the resource center had earned service income of NT$310 million from over 3,300 paying service cases, and provided a total of more than NT$570 million worth of services, including service funding subsidies and industrial service fees, in over 4,800 service cases. This program established the Taiwan Clinical Trial Consortium (TCTC), which has accumulated the extensive implementation experience of Taiwan's medical centers. Many outstanding clinical trial-related Support for Academic Research Ministry of Science and Technology 53