Technology Trend Analysis of R&D Strategy on IPS Cells: CASE STUDY ANALYSING TREND DIFFERENCES BASED ON PATENTS, ACCADEMIC PAPERS, OR NIH GRANT INFORMATION Takayoshi Hayashi LEAD ANALYST VALUENEX Seminar @ 21 September, 2017

Takayoshi Hayashi VALUENEX Japan Inc. Lead Analyst Self-introduction n Academic background Mar. 2013 Waseda University MS. Eng, Electrical and Electronics Engineering n Career Apr. 2013 Nippon Telegraph and Telephone Researcher on smart grid Jan. 2015 Recruit Data analyst on web service Apr. 2016 VALUENEX Lead analyst on R&D strategy n Specializations • Electric power engineering (Smart grid, renewable energy) • Machine learning / data science n Articles / International Conferences • Hayashi T, Wakao S. “Battery design optimization according to reversal PV power flow quantity from a distributing substation bank” Proceedings of 21st international Photovoltaic Science and Engineering Conference (2011) • Hayashi T, Wakao S. “Multi-objective design of battery operation in a photovoltaic system by means of PV output and load power forecasts” Proceedings of 27th European PV Solar Energy Conference and Exhibition (2012) • Hayashi T, Matsuyuki T, Wakao S, Inamori J, and Babasaki T. “Charge and Discharge Control of Electric Vehicle in PV System with PV Output and Load Power Forecast Information” Proceedings of 28th European Photovoltaic Solar Energy Conference and Exhibition (2013) • Hayashi T, Shimoo T, Wakao S. “Error Effect of PV Output and Load Power Forecast on Operation Design of PV System with Storage Battery” IEEJ Transactions on Power and Energy (2013) • Hayashi T, Shimoo T, Wakao S.” Error Effect of PV Output and Load Power Forecast on Operation Design of PV System with Storage Battery” Electrical Engineering in Japan (2014) • Hayashi T. “Research and Development Trend Analysis of Wellbeing AI Using Panoramic View Analytics” AAAI 2017 Spring Symposium (2017) VALUENEX ©2017 intellectual innovator 1

What is VALUENEX? We are a data analytics company focusing on strategy development and decision guidance, performing 100+ consultation projects per year to leading companies and public institutions, and licensing our analytics platform. VALUENEX ©2017 intellectual innovator 2

BIG DATA CLUSTERING VISUALISATION ANALYTICS What is Panoramic View Analytics? Proven scientific methods that allow the user to “see and understand” the entirety of large amounts of data rather than “search and reading” of individual pieces of data. 3 Clustering docs by calculating similarities among them Visualization of the similarity among docs Original indicators for mining and insight Patents / Research Papers / SNS News / Annual Reports, etc. VALUENEX ©2017 intellectual innovator

What is Panoramic View Analytics? You can get insight for strategy-making by analyzing output (distance, density, white space, distribution, etc.) of the radar chart. 4 The size of each cluster is proportional to the number of documents in it. The distance between clusters indicates the similarities between them. The axes have no particular meaning. Each circle is called a cluster. They contain similar documents. HIGH DENSITY LOW DENSITY TREND LINE VALUENEX ©2017 intellectual innovator CENTER OF GRAVITY

Our Services / Today’s Presentations 5 IP section R/D section Corporate planning section INDUSTRIAL COMPANY FINANCIAL ORGANIZATION Corporate sales/ CA M&A Start-up investment OTHERS (CONSULTING) Consulting (strategy) Consulting（M&A） New business development strategy R/D strategy Alliance strategy Technology due diligence IP portfolio strategy Open innovation strategy Proposal with additional value BUSINESS / JOB CATEGORY APPLICATION VALUENEX ©2017 intellectual innovator Takayoshi Hayashi Dr. Nakamura Dr. Liu

IMPORTANCE OF TECHNOLOGY INFORMATION ANALYSIS IN T R OD U C T ION

Importance of Technology Information Analysis IP / Technology information analysis can support management / business / R&D / IP strategies. 7 Ref: http://www.jpo.go.jp/shiryou/toushin/nenji/nenpou2004_pdf/honbun/3-1-2.pdf Business Strategy R&D Strategy Intellectual Property Strategy • Utilizing IP/technology information for making business strategies, such as new business development, business collaboration, etc. • Acquiring rights from view points of attack, defense, and prevention based on business strategy. • Utilizing IP/technology information for analyzing one’s technology capabilities and deciding R&D focus. • Utilizing IP/technology information for selecting partners for R&D collaboration. • Acquiring rights strategically for standardization of one’s technology. • Preliminary survey • Prior art search (R&D, filing, application for examination, etc.) • Other company trend survey (Making patent map etc.) • Acquiring rights (filing patent, trade secret) • Protection and utilization of rights (own monopoly, license, measures against counterfeit products and management of technology / know-how in foreign markets) IP / Technology Information Analysis Management Strategy VALUENEX ©2017 intellectual innovator Figure: Relationship among 3 types of management strategies

Importance of Technology Information Analysis There are various technology information analyses according R&D and IP cycles. 8 Basic / Application Research Development Design Production Commercialization Marketing Sales Technology trend analysis Collection search Prior art search (Pre-filing search) Invalidity search Clearance search, FTO Technology assessment R&D cycle Technology Information Research / Analysis Figure: Relationship among IP, R&D and technology information research / analysis Ref: Atsushi Nozaki: Patent Research and Search Technique (2015) [Japanese] Creating inventions Making IP strategy Protecting inventions Filing, Rights, Patent portfolio Utilizing inventions One’s usage, Licensing IP cycle VALUENEX ©2017 intellectual innovator

How do you perform technology information analyses? 9 Simply reading? VARIOUS TYPES OF INFORMATION • Patents • Academic papers • Research grants • Cloud funding • Start-up information, etc. VALUENEX ©2017 intellectual innovator HUGE VOLUMES • Doc number: thousands ~ millions • Length: long…

Volume of Technology Information on “Stem and iPS cells” • Volume: Technology information volume on stem / iPS cells is enormous. • Time: It takes an excessive amount of time to get insight by simply reading. • Difficulty: It is difficult to classify by keywords, inventors, etc. because there are various research themes. • Risk: If you set keywords for classification in advance, you may miss new research opportunities. 10 * The number of documents including “stem cell” or “ips cell” Patents Academic papers Research grants Volume 10,000 (Title, Abstract, Claim) 50,000 (Full text) 245,000 60,000 Source US application (DB: PatentSquare) PubMed NIH Table: Volume of patents, academic articles, and research grants on Stem / iPS cells* VALUENEX ©2017 intellectual innovator

Technology Information Features There are many differences among features of patents, academic papers, and research grants. 11 Patents Academic papers Research grants Overview Patent is for protecting one’s R&D achievements and manufacturing / selling products. Academic article is for informing others of one’s R&D achievements. Thus, it is sometimes not with the intention to sell achievements as products. Research grant is for gathering R&D from organizations. It is published by the funding organization unlike patent and academic research. Player Company > University, Research institution University, Research institution > Company University, Research institution > Company Sentence characteristics ˚: Patent should be written concretely because the other engineers must be able to implement it. However, patent has the legal and strategic perspectives. Thus, it is sometimes not easy to read. ˓: Academic article is written for easy reading because it is intended for the general public. ˓: Research grant is written for easy reading because it is intended for the general public. Bibliographic information Format ˓: Unified globally (INID) ˚: Depend on the journal ˚: Depend on the funding organization Classification ˓: Unified globally (IPC) ˚: Depend on the journal ˚: Depend on the funding organization Citation ˚: Citation by applicant includes arbitrariness. In the case of citation by examiner, arbitrariness is small. ˓: Arbitrariness is less than patent. - Others Number, Inventor, Assignee, Date, etc. Author, Organization, Impact Factor, etc. Researcher, Organization, Earned amount, etc. Availability ˓: You can get full text easily and free or with minimal cost because patent is open data, and there are many database options. ˚: There are many free / paid database options. You can get “Title” and “Abstract” easily for free or with minimal cost. Full text might be expensive. In the case of publication on web, data processing might be necessary. ˚: Funding organization may provide search database. However, it depends on the funding organization. You can get research overviews and achievements (academic articles, patents, technical reports, etc.) VALUENEX ©2017 intellectual innovator

TECHNOLOGY TREND ANALYSIS ON STEM/iPS CELLS C A S E S T U D Y

Technology Development Overview: Patents There are various R&D areas from stem cells to medicine, disease (cancer) and body repair. 13 Medicine / Compound Cancer Mesenchymal stem cell Hair follicle stem cell Fat Hydrogel Figure: Radar chart of patents Extracellular Matrix Gene Nuclease Hematopoietic cell Reprogramming of iPS cell Oocyte microRNA Tooth Recombination Human ES cell NSC Placenta Disease (Cancer) Body Repair etc. Control of Stem Cells Research on Cells Figure: Technology area position Medicine / Compound Plerosis using scaffold VALUENEX ©2017 intellectual innovator

Technology Development Overview: Academic Papers • Overall structure is similar to patents. • Compared to patents, cancer stem cell and HSC (hematopoietic stem cell) transplantation areas are active. 14 Neural Stem Cell Heart Cancer stem cell Musculoskeletal Treatment Bone regeneration / Reconstruction Spermatogonial stem cell Mesenchymal stem cell (Transplant) Hematopoietic stem cell (Mouse experiment) Cornea SCF Interleukin Hematopoietic Stem Cell Transplantation / Graft Versus Host Disease (GVHD) Body Repair Cancer Stem Cells Control of Stem Cells Research on Cells Mesenchymal stem cell (Culture) Transplantation Therapy (HSC: Hematopoietic Stem Cell) Figure: Radar chart of academic articles Figure: Technology area position Reprogramming VALUENEX ©2017 intellectual innovator

Technology Development Overview: Research Grants • Overall structure is similar to patents and academic papers. • There are various areas on diseases and body repair. 15 Fanconi Anemia Acute Myelogenous Leukemia Chronic Myelogenous Leukemia GVHD HIV β-globin Liver cell Education Program (Noise) Blood vessel Heart Muscle Regeneration Tendon care Cartilage Repair Myeloid Stem Cell HSC Liver Disease Diabetes Breast Cancer Glial Tumor Intestinal Stem Cell Lung Generative Cell (Male) Scalp Hair, Skin Cornea Retina Neuron cell Alzheimer's disease Epigenetics Disease (Leukemia, HIV, Diabetes etc.) Body Repair (Bone, Heart, Cartilage, Tendon, Neuron cell, Retina etc.) Control of Stem Cells Research on Cells Figure: Radar chart of research grants Figure: Technology area position Reprogramming VALUENEX ©2017 intellectual innovator

Technology Development Overview: Summary • In particular, there is a big difference regarding disease and treatment among the information sources (Research grants > Academic articles > Patents). These areas were studied in the past, but the effectiveness was not confirmed. Or, they might be waiting for, or expecting, new fields to emerge. • In the case of patents, there are several compounds and medicines (mainly used for culturing stem cells). 16 Cell Disease / Treatment Others Patents Oocyte, Human ES cell, NSC, Mesenchymal stem cell, Hair follicle stem cell, Placenta, Hematopoietic cell, Adipocyte Cancer, Tooth, Plerosis using scaffold Reprogramming, Gene, Compounds / Medicine Academic papers Hematopoietic cell (Transplant, Culture), Hematopoietic stem cell, Neural stem cell, Cancer stem cell Bone regeneration / reconstruction, Musculoskeletal treatment, Cornea, Hematopoietic stem cell transplantation (GVHD) Reprogramming, Interleukin, SCF, etc. Research Grants Liver cell, HSC, Generative cell, Intestinal stem cell, Myeloid stem cell, Neuron cell Fanconi anemia, (Acute, Chronic) myelogenous leukemia, Liver disease, Diabetes, Glial tumor, Scalp hair / skin, Retina, Cornea, Alzheimer‘s disease, Cartilage repair, Tendon care, Muscle regeneration, Heart, Blood vessel, HIV, GVHD Reprogramming, Epigenetics, etc. Table: Comparison among insights from information sources VALUENEX ©2017 intellectual innovator

Time Series Evolution Analysis • Patents: (1) “Recombination” is active. (2) “Reprogramming of iPS cell” and “Extracellular Matrix” are active. • Academic papers: (1) “Reprogramming” and “HSC (Hematopoietic stem cell) transplantation” are active. (2) R&D spread to many areas close to “Cancer stem cell” • Research grants: (1) “GVHD with HSC (Hematopoietic stem cell) transplantation” and “Diabetes” are active. (2) R&D spread around areas. 17 (1) Past (2001 – 2004) PATENTS ACADEMIC PAPERS RESEARCH GRANTS Figure: Time series change Recombination (HSC) Hematopoietic Stem Cell Transplantation Reprogramming GVHD With Hematopoietic Stem Cell Transplantation Diabetes (2) Recent (2013 – 2017) Extracellular Matrix Reprogramming of iPS Cell R&D Areas Spread R&D Areas Spread Cancer Stem Cell VALUENEX ©2017 intellectual innovator

Publisher Analysis • There is a high number of universities. (Companies usually make up most of the patent ranking in other fields.) • Californian Universities are top in class of every information source. • Almost all publishers are North American organizations, but Kyoto University (Japan) appears in Patent and Academic Papers, as well as A*Star (Singapore) in Patents. 18 Figure: Main publishers of each information source 0 20 40 60 80 100 120 140 Univ of California IMMUNOMEDICS, INC. THE GENERAL HOSPITAL CORP. AGENCY FOR SCI., TECH. & RES (A-STAR) KYOTO UNIV. JOHNS HOPKINS UNIV. MIT ANTHROGENESIS CORP. UNIVERSITY OF MICHIGAN Univ. of Southern California 0 200 400 600 800 1,000 STANFORD Univ. BASIC SCIENCES JOHNS HOPKINS Univ. Univ. OF PENNSYLVANIA Univ. OF WASHINGTON FRED HUTCHINSON CANCER RESEARCH CENTER MASSACHUSETTS GENERAL HOSPITAL Univ. OF CALIFORNIA LOS ANGELES Univ. OF CALIFORNIA, SAN FRANCISCO Univ. OF MICHIGAN 0 50 100 150 200 Univ. of California Stanford Univ. Kyoto Univ. Univ. of Washington Univ. of Toronto Univ. of Cambridge Univ. of Michigan Baylor College of Medicine Harvard Medical School Massachusetts General Hospital ■ - 2012 ■ 2013 - ■ - 2012 ■ 2013 - ■ - 2012 ■ 2013 - PATENTS ACADEMIC PAPERS RESEARCH GRANTS VALUENEX ©2017 intellectual innovator

Publisher Analysis You can get insight from the differences among publishers by combining various technology information sources. 19 Figure: R&D fields of Kyoto Univ. and Univ. of California UNIV. OF CALIFORNIA KYOTO UNIV. PATENTS ACADEMIC PAPERS RESEARCH GRANTS Heart Neural Stem Cell Spermatogonial Stem Cell Reprogramming Spermatogonial Stem Cell Heart Reprogramming HSC (Hematopoietic Stem Cell) Transplantation / GVHD Musculoskeletal Treatment They focus on reprogramming of iPS cell. Are these fundamental patents? HIV Education Program (Noise) Alzheimer's Disease Reprogramming of iPS cell are few. However, they file patents widely. 1 2 3 4 n Insights 1. Kyoto Univ. has fundamental patents on reprograming of iPS cells? 2. In academic articles, you can see R&D fields that do not appear in the patents landscape. 3. The characteristic field of Kyoto Univ. is “HSC (Hematopoietic stem cell) transplantation / GVHD”. The Univ. of California’s is “Neural stem cell”. 4. Research grants for Univ. of California are concentrated in HIV and Alzheimer’s disease fields. VALUENEX ©2017 intellectual innovator

Growing Area Analysis • Red squares show growing areas. These are extracted by counting documents in each mesh of the radar. • The growing areas are different among information sources as shown below. 20 Application of Adipose Stem Cell Extracellular Matrix Scaffold (Manufacturing Method of Electro Spinning Process) Cancer Treatment using Chimeric Antigen Receptor CRISPR CAS9 Effect of Inorganic Substances to Cells (cancer etc.) Relationship between Autophagy, Metabolism, and Cancer Application of Hematopoietic Stem Cells Clarification and Repair of Heart Disease Utilization and Control of Human ES Cell Reproduction Signal Transmission in Retina Genea Biocells (relationship with gene) Leukemia Inhibitory Factor (LIF) Reprogramming of iPS cell Synthesis of Hydrogel Glioblastoma Multiforme Figure: Growing areas of each information source VALUENEX ©2017 intellectual innovator PATENTS ACADEMIC PAPERS RESEARCH GRANTS

CONCLUSION

Conclusion • Technology information is an important element for strategy development. There are huge volumes and various kinds, like patents, academic papers, and research grants. • In this presentation, we went over a macro analysis of R&D trends on “Stem / iPS cells”. The obtained insights are different among information sources. • The features of information sources vary. Therefore, you should apply them according to the individual analyses objectives. For example, research grants are the most basic and patents are the most practical. Moreover, sentence characteristics and bibliographic information, etc., are different. • If you want find application fields where your technology can be applied in the near future: Patent > Academic paper > Research grant • If you want find novel R&D focuses and application fields in the long term: Research grant > Academic paper > Patent • For a data fusion analysis, you can find the next R&D theme and collaborators with the flow below. 22 Panoramic view analytics of research grant information • Earned amount from research grant • Research achievements assessment from academic papers and patents of researchers (Impact Factor, Position and synergy analysis by panoramic view analytics, etc.） • Next R&D themes • Potential collaborators EXTRACTION OF GROWING AREAS ASSESSMENT OF EACH AREA OUTPUT VALUENEX ©2017 intellectual innovator

Contact US VALUENEX ©2017 intellectual innovator 23 Takayoshi Hayashi Lead Analyst, VALUENEX Japan Inc. [email protected] Navigate the Ocean of Big Data Harness the power of Panoramic View Analytics