For Official Use DSTI/STP/BNCT(2016)2

Organisation de Coopération et de Développement Économiques Organisation for Economic Co-operation and Development 23-Feb-2016 ______English - Or. English DIRECTORATE FOR SCIENCE, TECHNOLOGY AND INNOVATION COMMITTEE FOR SCIENTIFIC AND TECHNOLOGICAL POLICY For Official Use DSTI/STP/BN

CT(2016)2

Working Party on , Nanotechnology and Converging Technologies

PROPOSAL FOR THE REVISION OF THE STATISTICAL DEFINITIONS OF BIOTECHNOLOGY AND NANOTECHNOLOGY

17-18 March 2016

OECD Conference Centre, 2 rue André Pascal, 75116 Paris

NESTI delegates are invited to review and discuss this document. This document is a shortened version of a Room Document presented at the 2nd BNCT Meeting, held on 03-04 December 2015.

Steffi Friedrichs (STI/STP); email: [email protected]

English English JT03390547

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DSTI/STP/BNCT(2016)2

PROPOSAL FOR THE REVISION OF THE STATISTICAL DEFINITIONS OF BIOTECHNOLOGY AND NANOTECHNOLOGY

TABLE OF CONTENTS

PROPOSAL FOR THE REVISION OF THE STATISTICAL DEFINITIONS OF BIOTECHNOLOGY AND NANOTECHNOLOGY ...... 2 EXECUTIVE SUMMARY ...... 3 Background and motivation ...... 4 Proposed revised OECD definition of biotechnology ...... 5 The biotechnology patent classification scheme ...... 6 Proposed revised definition of nanotechnology ...... 7 ANNEX A1: History and developments of the OECD statistical definition of biotechnology ...... 9 The basic definitions of biotechnology ...... 9 Definitions of biotechnology relevant for R&D data ...... 10 The proposed classification of biotechnology applications ...... 12 The basic definition of synthetic ...... 14 ANNEX A2: Proposed glossary of terms used in the OECD list-based definition of biotechnology ...... 19 ANNEX A3: Proposed changes to the IPC patent classification scheme of biotechnology ...... 22 Revisions of the IPC patent classification by WIPO ...... 24 New Developments in Biotechnology ...... 27 ANNEX A4: History and development of the OECD’s statistical definition of nanotechnology ...... 29 Definitions of nanotechnology ...... 29 The nanotechnology patent classification scheme ...... 34

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EXECUTIVE SUMMARY

Agreement on a harmonised application of clear statistical technology definitions are pertinent to the delineation of technology fields both with regard to each other and within context of wider economic developments.

The present document of the CSTP Working Party on Biotechnology, Nanotechnology and Converging Technologies (BNCT) reviews the OECD’s statistical definitions of biotechnology and nanotechnology, taking into consideration developments impacting the OECD’s statistical definitions led both by previous CSTP Working Parties (i.e. Working Party on Biotechnology, Working Party on Nanotechnology), and by organisations external to the OECD (i.e. ISO, IPC Committees at WIPO, international expert committees on synthetic biology, etc.).

NESTI delegates are invited to review and comment on the substance and the statistical implementation implications of the proposed changes to the OECD definitions of biotechnology and nanotechnology, giving specific consideration to the following recommendations:

 To revise the OECD statistical definition of biotechnology:

 Broadening of the OECD statistical definition on biotechnology to include the realm of marine biotechnology, by adding relevant terms to the list-based definition of biotechnology and adding Marine in the list of biotechnology applications, as already recommended and accepted by previous OECD Working Parties.

 Inclusion of the OECD description of synthetic biology into the OECD list-based statistical definition of biotechnology, providing explicit reference to the elements of orthogonality, hierarchy, and standardisation that experts deem to characterise synthetic biology as a complementary biotechnological technique.

 To note the review in progress of the list of International Patent Classification (IPC) biotechnology codes, currently conducted in collaboration with external experts:

 Specific attention should be given to the potential inclusion of the new codes.

 To review the proposal for an OECD statistical definition of nanotechnology:

 Adoption of the single and list-based definition of nanotechnology that resulted from the evidence-based research previously conducted by the OECD.

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Background and motivation

1. Biotechnology and nanotechnology are both enabling technologies, which find applications and give rise to innovations in many industry sectors, where they offer wide ranges of economic and societal impact.

2. Both technologies have raised the attention of policy makers in a wide spectrum of disciplines, ranging from ethics and governance to economic impact. At the OECD, the work in biotechnology and nanotechnology is shared between the Environment Directorate (ENV), which is concerned with aspects of biotechnology and nanotechnology in relation to human and environmental safety, biodiversity, ecosystems, resource efficiency and waste, and the Directorate for Science, Technology and Innovation (STI), which focuses on biotechnology and nanotechnology with regard to their scientific and economic impact, and their roles in public and private policies.

3. In January 2015, the OECD merged its Working Party on Biotechnology (WPB) and its Working Party on Nanotechnology (WPN) (both within the STI) into a new Working Party on Biotechnology, Nanotechnology and Converging Technologies (BNCT). The BNCT plans to conduct consolidated and harmonised analysis of indicators and statistics and impact assessment of both biotechnology and nanotechnology, in a comparative fashion. In order to enable this consolidated approach, which aims to ultimately identify the convergence of technologies, a clear delineation of both fields of technologies needs to be agreed, and NESTI delegates are expected to review the agreed definitions in the hope of adopting them into their future reporting of national data. This BNCT document represents a review of hitherto used statistical definitions of biotechnology and nanotechnology, and provides recommendations for the way forward regarding the improvement and application of these statistical definitions.

4. Biotechnology, as it is commonly understood in the public science and technology policy context and analysed in an economic context, is considered to have started in the 1970s with the first gene-splicing and –transfer experiments. Enabled by modern molecular biology, biotechnology is a field that is closely linked to biological sciences and fundamentally reliant on the involvement of biological material and systems in a technical process or application for it to be called ‘biotechnology’.

5. Nanotechnology, by contrast, is delineated only in that the underlying nanotechnology-based processes and applications are based on phenomena occurring on the nanometre scale (i.e. 1 and 100 billionth of a metre), independent of the materials involved or the scientific disciplines applied. Given nanotechnology’s strong dependence on instrumentation that makes the nanometre-scale accessible to targeted scientific experiments and exploitation of phenomena, the discipline of modern nanotechnology is understood to have commenced around the start of the millennium, enabled by the invention of the scanning tunnelling microscope in 1981.1

6. Following the context of the work on statistics and indicators of biotechnology and nanotechnology conducted by the WPB, the WPN and the Working Party of National Experts on Science and Technology Indicators (NESTI), this paper i) provides the statistical definitions of both technologies used by OECD to date, ii) summarises the work undertaken to date in reviewing and further developing these definitions, iii) illustrates the methodology and practical considerations applied in the review process, and iv) describes how the current definitions might be improved and should be applied, in order to provide a more reliable and uniquely relevant delineation of the two technologies with respect to each other and with a view to identifying areas of technology convergence.

1 . Binnig, G., and H. (1986). "Scanning tunneling microscopy". IBM Journal of Research and Development 30 (4): 355–69.

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7. The review process presented in this paper is based on three main objectives:

 The updating of the statistical definitions to take into account the latest advances in both the field of biotechnology and nanotechnology (e.g. the advent of synthetic biology and the invention of the CRISPR-Cas9 gene-editing technique in the former, and the increasing R&D activity on graphene in the latter),

 The adaptation of the OECD technology definitions to changes that have been applied to technology classifications, categories and codes (e.g. the International Patent Classification (IPC) codes identifying biotechnology patents has undergone annual reviews by topical IPC committees and changes since a list of IPC codes was agreed to delineate the field of biotechnology),2 and

 The alignment of all elements of a technology definition with regard to updates and additions that have been applied to specific elements only (i.e. in 2005, the terms “” and “nanobiotechnology” were added to the list-based definition of biotechnology, but the list of patent codes assigned to identify biotechnology patents has not yet been adapted).

Proposed revised OECD definition of biotechnology

8. At its 2nd Meeting in December 2015, the BNCT discussed and supported the detailed review of the definition of biotechnology, which had previously been conducted by the OECD Working Party on Biotechnology (WPB), but which was never operationalised, due to the termination of the WPB end of 2014.

9. The BNCT furthermore conducted a review of the definition of biotechnology with regard to updating the list-based definition by adding recognised keywords that reflect recent developments in biotechnology (e.g. the category ‘synthetic biology’, and the techniques ‘gene-editing’, etc.) (see ANNEX A1: History and developments of the OECD statistical definition of biotechnology).

10. The resulting proposed revised definition of biotechnology can be found in Box 1 below; proposed changes are highlighted in grey.

11. NESTI delegates are invited to discuss and approve the proposed changes to the list-based definition of biotechnology presented in Box 1 below, after giving consideration to the following criteria, and - if necessary – providing feedback on these considerations to the BNCT:

 Do the proposed changes to the definition represent a significant difference in the work conducted by the NESTI delegates (i.e. collection and reporting of data and indicators on biotechnology)? Is the list-based definition used in data collection as a survey item or as part of questionnaire explanatory notes/annexes?

 Would the implementation of the proposed changes to the statistical definition of biotechnology, represent any significant challenges and – if yes – why? What actions by the BNCT and their national teams could facilitate the implementation of such proposals?

12. The BNCT is looking to adopt the resulting definitions at its 3rd Meeting in May 2016.

2. NOTE: the proposed changes to the International Patent Classification (IPC) Codes of biotechnology is work in progress; the full review process is illustrated in ANNEX A3: Proposed changes to the IPC patent classification scheme of biotechnology.

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Box 1. The OECD single and list-based definitions of biotechnology

The single definition of biotechnology:3 The application of science and technology to living organisms, as well as parts, products and models thereof, to alter living or non-living materials for the production of knowledge, goods and services.

The list-based definition of biotechnology:4 (find a proposed detailed glossary of the following terms in ANNEX A2: Proposed glossary of terms used in the OECD list-based definition of biotechnology)

· DNA/RNA: , pharmacogenomics, gene probes, genetic engineering, DNA/RNA sequencing/synthesis/amplification, gene expression profiling, and use of antisense technology.

· and other molecules: Sequencing/synthesis/engineering of proteins and peptides (including large molecule hormones); improved delivery methods for large molecule drugs; proteomics, isolation and purification, signalling, identification of cell receptors.

· Cell and tissue culture and engineering: Cell/tissue culture, tissue engineering (including tissue scaffolds and biomedical engineering), cellular fusion, vaccine/immune stimulants, embryo manipulation, marker assisted breeding technologies.

· Process biotechnology techniques: Fermentation using bioreactors, biorefining, bioprocessing, bioleaching, biopulping, biobleaching, biodesulphurisation, bioremediation, biosensing, biofiltration and phytoremediation, molecular aquaculture.

· Gene and RNA vectors: Gene therapy, viral vectors.

· Bioinformatics: Construction of databases on , protein sequences; modelling complex biological processes, including .

· Nanobiotechnology: Applies the tools and processes of nano/microfabrication to build devices for studying biosystems and applications in drug delivery, diagnostics, etc..

· Synthetic Biology: large-scale DNA synthesis, metabolic engineering, standard parts manufacture, gene- and -editing, gene-drive, protocells, computational design, xenobiology, DNA synthesis.

The biotechnology patent classification scheme

13. Patents are organised and indexed using patent classification systems, such as the International Patent Classification (IPC) or the US Patent Classification (for more information on the IPC system, see ANNEX A3: Proposed changes to the IPC patent classification scheme of biotechnology). As a part of the examination process, an examiner will assign patent classification codes to the patent specification under examination, so the assignment is usually considered to be reliable.5

14. There is no one section of the IPC system that cleanly equates to the field of biotechnology, so that the IPC codes assigned to patent documents in the field of biotechnology may cut across different Sections, Classes, Subclasses and Groups.

3. The provisional single definition of biotechnology is deliberately broad. It covers all modern biotechnology but also many traditional or borderline activities. For this reason, the single definition should always be accompanied by the list-based definition which operationalises the definition for measurement purposes.

4. The list of biotechnology techniques functions as an interpretative guideline to the single definition. The list is indicative rather than exhaustive and is expected to change over time as data collection and biotechnology activities evolve.

5 . OECD (2009), OECD Patent Statistics Manual, OECD Publishing, http://www.oecd.org/sti/inno/oecdpatentstatisticsmanual.htm

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15. In 2006, the OECD Working Party on Biotechnology adopted a list of refined IPC codes, developed in consultation with patent office experts through keyword searches, analysis of sample patents, and through preliminary testing with industry.6

16. The BNCT proposes to update the list of patent codes assigned to biotechnology, due to the many changes that happened since the classification was adopted by the WPB in 2006. The update of IPC codes ensures the consistence in the way statistics on biotechnology are produced. ANNEX A3: Proposed changes to the IPC patent classification scheme of biotechnology provides the full list of biotechnology- relevant changes identified by the BNCT Secretariat; the proposed changes are current reviewed by biotechnology patent expert. The OECD Working Party on Industry Analysis (WPIA) will be consulted on the proposed changes to the list.

Proposed revised definition of nanotechnology

17. The BNCT reviewed the detailed work previously conducted by the OECD Working Party on Nanotechnology (WPN), which adopted the introduction of a list-based definition of nanotechnology in addition to the hitherto used single definition of nanotechnology

18. NESTI delegates are invited to agree on the proposed single and list-based definitions of nanotechnology presented in Box 2 below, after giving consideration to the following criteria, and - if necessary – providing feedback on these considerations to the BNCT:

 Do the proposed changes to the definition represent a significant difference in the work conducted by NESTI delegates (i.e. collation and reporting of data on nanotechnology)?

 Would it be difficult to implement the proposed statistical definition of nanotechnology, and – if yes – why?

6 . OECD (2006), Validation of Biotechnology Patent Classes – Survey Questionnaire, OECD.

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Box 2. Proposed definition of nanotechnology

The single definition of nanotechnology:7 Understanding and control of matter and processes at the nanoscale typically but not exclusively below 100 nanometres in one or more dimensions where the onset of size-dependent phenomena usually enables novel applications utilizing the properties of nanoscale materials that differ from the properties of individual atoms molecules and bulk matter to create improved materials devices and systems that exploit these new properties.

The list-based definition of nanotechnology:8

- Nanomaterials

- Nanoelectronics

- Nanophotonics

- Nanobiotechnology

- Nanomedicine

- Nanomagnetics

- Nanomechanics

- Filtration and Membranes

- Nanotools (for manipulation, nanolithography and nanofabrication)

- Nanoinstruments or devices (for observation, analysis or control)

- Catalysis

- Software for modelling and

19. The detailed history and development of the OECD’s statistical definition of nanotechnology can be found in ANNEX A4: History and development of the OECD’s statistical definition of nanotechnology.

7 . OECD (2013), Considerations in moving towards a statistical Framework for Nanotechnology: Findings from a Working Party on Nanotechnology Survey of Business Activity in Nanotechnology, www.oecd.org/sti/biotech/statistical-framework-nanotechnology-business-activity-findings.pdf 8 . Based on the ISO Working Definition, ISO (2005).

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ANNEX A1: History and developments of the OECD statistical definition of biotechnology

The basic definitions of biotechnology

20. The OECD’s definition of biotechnology was developed in 2002;9 it consists of two parts: (i) a single definition, and (ii) a list-based definition.

21. In 2005, the list-based definition was revised to add the terms “bioinformatics” and “nanobiotechnology”,10 to result in the combination of single definition and list-based definition recommended for use since then. The combined definition is provided in Box 3 below.

22. At the sixth ad hoc meeting on biotechnology statistics, held in Paris in May 2008, there was an agreement to review the list-based definition. This review concluded that the fundamental categories in the definition were still stable and that the current definition was still valid.

Box 3. The OECD single and list-based definitions of biotechnology

The single definition of biotechnology:11 The application of science and technology to living organisms, as well as parts, products and models thereof, to alter living or non-living materials for the production of knowledge, goods and services.

The list-based definition of biotechnology:

· DNA/RNA: Genomics, pharmacogenomics, gene probes, genetic engineering, DNA/RNA sequencing/synthesis/amplification, gene expression profiling, and use of antisense technology.

· Proteins and other molecules: Sequencing/synthesis/engineering of proteins and peptides (including large molecule hormones); improved delivery methods for large molecule drugs; proteomics, protein isolation and purification, signalling, identification of cell receptors.

· Cell and tissue culture and engineering: Cell/tissue culture, tissue engineering (including tissue scaffolds and biomedical engineering), cellular fusion, vaccine/immune stimulants, embryo manipulation.

· Process biotechnology techniques: Fermentation using bioreactors, bioprocessing, bioleaching, biopulping, biobleaching, biodesulphurisation, bioremediation, biofiltration and phytoremediation.

· Gene and RNA vectors: Gene therapy, viral vectors.

· Bioinformatics: Construction of databases on genomes, protein sequences; modelling complex biological processes, including systems biology.

· Nanobiotechnology: Applies the tools and processes of nano/microfabrication to build devices for studying biosystems and applications in drug delivery, diagnostics, etc..

23. In 2015, the Working Party on Biotechnology concluded a 2-year-research project into marine biotechnology (including a Member State questionnaire) and recommended the broadening of the OECD

9 . OECD (2002), Frascati Manual 2002: Proposed Standard Practice for Surveys on Research and Experimental Development, The Measurement of Scientific and Technological Activities, OECD Publishing, Paris. Doi: http://dx.doi.org/10.1787/9789264199040-en.

10 . OECD (2005), A Framework for Biotechnology Statistics, www.oecd.org/sti/biotechnology/framework.

11. The provisional single definition of biotechnology is deliberately broad. It covers all modern biotechnology but also many traditional or borderline activities. For this reason, the single definition should always be accompanied by the list-based definition which operationalises the definition for measurement purposes.

9 DSTI/STP/BNCT(2016)2 statistics definition on biotechnology to include the realm of marine biotechnology, by adding relevant terms to both the single definition and the list-based definition of biotechnology, as outlined in Box 4 below.12

Box 4. WPB recommended definition of marine biotechnology (2015)

The single definition of marine biotechnology: The application of science and technology to living organisms from marine resources, as well as parts, products and models thereof, to alter living or non-living materials for the production of knowledge, goods and services.

List-based definition for biotechnology (new, recommended terms have a grey shading):13

- DNA/RNA: Genomics, pharmacogenomics, gene probes, genetic engineering, DNA/RNA sequencing/synthesis/amplification, gene expression profiling, and use of antisense technology.

- Proteins and other molecules: Sequencing/synthesis/engineering of proteins and peptides (including large molecule hormones); improved delivery methods for large molecule drugs; proteomics, protein isolation and purification, signalling, identification of cell receptors.

- Cell and tissue culture and engineering: Cell/tissue culture, tissue engineering (including tissue scaffolds and biomedical engineering), cellular fusion, vaccine/immune stimulants, embryo manipulation, marker assisted breeding technologies.

- Process biotechnology techniques: Fermentation using bioreactors, biorefining, bioprocessing, bioleaching, biopulping, biobleaching, biodesulphurisation, bioremediation, biosensing, biofiltration and phytoremediation, molecular aquaculture.

- Gene and RNA vectors: Gene therapy, viral vectors.

- Bioinformatics: Construction of databases on genomes, protein sequences; modelling complex biological processes, including systems biology.

- Nanobiotechnology: Applies the tools and processes of nano/microfabrication to build devices for studying biosystems and applications in drug delivery, diagnostics,etc.

Definitions of biotechnology relevant for R&D data

24. In 2005 the OECD introduced additional R&D-relevant statistical definitions of biotechnology, covering basic activities, actors, and investment in biotechnology. The definitions were based on work and recommendations by the Ad Hoc Meeting on Biotechnology Statistics, which reported to NESTI; the results were published in the OECD Framework for Biotechnology Statistics.14 The additional definitions are listed in Box 5 below. In 2008, the operational definition of dedicated biotechnology firm was revised, following the sixth ad hoc meeting on biotechnology statistics. The definition in the box presents the updated version.

12 . OECD (2015), Marine Biotechnology for Future Potential - Summary report 2013-2014, OECD.

13. The list of biotechnology techniques functions as an interpretative guideline to the single definition. The list is indicative rather than exhaustive and is expected to change over time as data collection and biotechnology activities evolve.

14 . OECD (2005), A Framework for Biotechnology Statistics, http://www.oecd.org/sti/biotechnology/framework.

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Box 5. Definitions of biotechnology relevant for R&D data assessment

Biotechnology product – defined as a good or service, the development of which requires the use of one or more biotechnology techniques per the list-based and single definitions above. It includes knowledge products (technical know-how) generated from biotechnology R&D.

Biotechnology process – defined as a production or other (e.g. environmental) process using one or more biotechnology techniques or products.

Biotechnology active firm (enterprise) – defined as a firm engaged in key biotechnology activities such as the application of at least one biotechnology technique (as defined above) to produce goods or services and/or the performance of biotechnology R&D (as defined below).

[NOTE: In the context of the definition of a biotechnology active firm, it should be noted that a firm is a single legal entity and is thus the smallest legal unit for which financial accounts are maintained. This is usually defined as an enterprise. It is not the group of legal units under common ownership, sometimes referred to as an enterprise group in statistical terms; nor is it a single physical location, sometimes referred to as an establishment.]

[NOTE: Within the statistical framework, the biotechnology active firm is the statistical unit for which statistical data are compiled. It is not necessarily the reporting unit, which is the entity that provides statistical information. While statistical units will generally be the same as reporting units, reporting units may be either lower level or higher level units within the firm or enterprise group.]

Dedicated biotechnology firm –defined as firms that devote at least 75% of their production of goods and services, or R&D, to biotechnology.

Innovative biotechnology firm – defined as a biotechnology active firm that applies biotechnology techniques for the purpose of implementing new or significantly improved products or processes (per the Oslo Manual (OECD, 1997) for the measurement of innovation). It excludes end users which innovate simply by using biotechnology products as intermediate inputs (for instance, detergent manufacturers which change their formulation to include enzymes produced by other firms via biotechnology techniques).

Biotechnology research and experimental development (R&D) – defined as R&D into biotechnology techniques, biotechnology products or biotechnology processes, in accordance with both the biotechnology definitions presented above and the Frascati Manual for the measurement of R&D (OECD, 2002).

Biotechnology sales/revenue – defined as the revenue generated from the sale (or transfer) of biotechnology products (including knowledge products) as defined above. It is thus generally a subset of the total revenue earned by biotechnology firms.

Biotechnology expenses – defined as an expense incurred in the generation of biotechnology revenue. It is thus generally a subset of the total expenses incurred by biotechnology firms.

Biotechnology employment – defined as the employment involved in the generation of biotechnology products as defined above. For ease of collection, it is suggested that employment be measured in terms of staff numbers rather than hours worked. However, where countries prefer, they can collect this information in terms of full-time equivalents, consistent with an R&D survey approach (as outlined in the Frascati Manual).

Biotechnology patent – defined as a patent belonging to a defined list of International Patent Classification codes.

25. Consequently, in 2005, and as a result of NESTI’s recommendations, the OECD adopted specific guidelines on the production of biotechnology R&D statistics.

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26. In 2007, NESTI revised the Field of Science and Technology Classification (FOS) Classification in the Frascati Manual, and newly introducing the terms ‘biotechnology’ and ‘nanotechnology’ into the ‘Engineering and technology’ field:15

 2.8 Environmental biotechnology o Environmental biotechnology; Bioremediation, diagnostic (DNA chips and biosensing devices) in environmental management; environmental biotechnology related ethics;  2.9 Industrial biotechnology o Industrial biotechnology; Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation; bioproducts (products that are manufactured using biological material as feedstock) biomaterials, bioplastics, biofuels, bioderived bulk and fine chemicals, bio-derived novel materials;  3.4 Medical biotechnology o Health-related biotechnology; Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction); Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions (pharmacogenomics, gene-based therapeutics); Biomaterials (as related to medical implants, devices, sensors); Medical biotechnology related ethics;  4.4 Agricultural biotechnology o Agricultural biotechnology and food biotechnology; GM technology (crops and livestock), livestock cloning, marker assisted selection, diagnostics (DNA chips and biosensing devices for the early/accurate detection of diseases) biomass feedstock production technologies, biopharming; agricultural biotechnology related ethics;  2.10 Nano-technology o Nano-materials [production and properties]; o Nano-processes [applications on nano-scale]; (biomaterials to be 2.9).

27. More recently, the 7th edition of the Frascati Manual (on The Measurement of Scientific, Technological and Innovation Action), revised the FOS Classification to create a Classification of Fields of R&D (FORD), maintaining for the time being the Codes for biotechnology and nanotechnology introduced in 2007.16

The proposed classification of biotechnology applications

28. Applications of biotechnology are detailed in the ‘Classifications for biotechnology applications’ (see Table 1 below), which had first been introduced in the Biotechnology Framework (2005).17

15. OECD (2007), Revised Field of Science and Technology (FOS) Classification in the Frascati Manual, http://www.oecd.org/science/inno/38235147.pdf

16. OECD (2015), Frascati Manual 2015: Guidelines for Collecting and Reporting Data on Research and Experimental Development, The Measurement of Scientific, Technological and Innovation Activities, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264239012-en

17 . OECD (2005), A Framework for Biotechnology Statistics, http://www.oecd.org/sti/biotechnology/framework.

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29. The BNCT proposes the addition of a separate category to cover ‘marine biotechnology’ applications. This means moving some of the keywords currently in Agriculture to this new category.

Table 1. Proposed classification for biotechnology applications

Broad Intermediate Detailed Large molecule therapeutics and monoclonal antibodies (MABs) produced using rDNA technology - Human Health Other therapeutics, artificial Other therapeutics, drug delivery technologies, etc. substrates, diagnostics and drug Substrates (artificial bone, skin etc.) delivery technologies, gene therapy, etc. Diagnostics, gene delivery For Veterinary Health: Large molecule therapeutics and monoclonal antibodies (MABs)

produced using rDNA Veterinary technology Health For Veterinary Health: Other For Veterinary Health: Other therapeutics, drug delivery therapeutics, artificial technologies, etc. substrates, diagnostics and drug For Veterinary Health: Substrates (artificial bone, skin etc.) delivery technologies, gene therapy, etc. For Veterinary Health: Diagnostics, gene delivery Marine Aquaculture GM fish, non-GM fish GM plants, incl. fruit trees, flowers, horticultural crops, grains, etc. New varieties of genetically GM animals for agriculture modified (GM) plants, animals, GM tree varieties for forestry and micro-organisms for use in GM micro-organisms for agriculture (including bio pest control) agriculture, and silviculture Non-GM plants, incl. fruit trees, flowers, horticultural crops, grains, etc. Agriculture Non-GM animals for agriculture New varieties of non-GM plants, Non-GM tree varieties for forestry animals, and micro-organisms Non-GM micro-organisms for agriculture (including bio pest for use in agriculture, control) silviculture, bio pest control and diagnostics developed using Diagnostics biotechnology techniques (DNA Using bioprocessing or improved crop varieties to improve food markers, tissue culture, etc.) quality and characteristics Mining: extraction using micro-organisms, etc. Food and Bioprocessing, functional beverages Petroleum/energy: extraction using micro-organisms foods/nutraceuticalsa processing Applications for mining, Other resource applications Natural petroleum/energy extraction, Diagnostics resources etc. Soil bioremediation, including phytoremediation Effluent treatment Diagnostics, soil bioremediation, Clean production processes treatment of water, air, and Environment industrial effluents using micro- organisms, clean production DNA/RNA/protein synthesis and databases for humans, plants, processes animals and micro-organisms. Gene identification, gene constructs etc.

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Bioreactors to produce new products (chemicals, food, Industrial ethanol, plastics, etc.), - processing biotechnologies to transform inputs (bioleaching, biopulping, etc.) Genomics & molecular Bioinformatics - modelling

Non-specific Research tools, etc. applications

Other a. Nutraceuticals. Although nutraceuticals have been included with ‘Food and beverages processing’ this could also be included with ‘Human Health’ as they are foods that are altered to improve health benefits.

The basic definition of synthetic biology

30. In 2014 the OECD published a report entitled Emerging Policy Issues in Synthetic Biology.18 The report noted the many differing opinions on what constitutes synthetic biology and discussed a selected few that specifically outline the advancement and added value that synthetic biology represented in the wider field of Biology.

31. The report notes that the use of the terms “design”, “engineer” and “devices” sets synthetic biology apart from systems biology. A theme that is implicit in synthetic biology is that of rational design. Traditional biology, on the other hand, has always been a very descriptive science that does not lend itself to standardisation, a necessity in manufacturing. Moreover, synthetic biology relies on the ability to make gene sequences routinely. The fundamental difference with genomics is that gene synthesis is the ability to write the genetic code, not read it.19

32. A detailed list of different definitions of synthetic biology can be found in Table 2.

18 . OECD (2014), Emerging Policy Issues in Synthetic Biology, OECD Publishing . http://dx.doi.org/10.1787/9789264208421-en

19. Goldberg, M. (2013), “Catalyzing innovation. BioFab: Applying Moore’s Law to DNA synthesis”, Industrial Biotechnology Vol. 9, pp. 10-12.

14 DSTI/STP/BNCT(2016)2 Table 2. Collection of various definitions of the term ‘Synthetic Biology’

Definition of the Term ‘Synthetic Biology’ Source

Royal Academy of Engineering (2009), Synthetic Biology: Scope, applications and implications, Royal Academy of Engineering, London. https://www.cbd.int/doc/emerging-issues/UK-submission-2011-013- Synthetic biology aims to design and engineer biologically-based parts, novel devices and systems as Synthetic_biology-en.pdf well as redesigning existing, natural biological systems. OECD (2014), Emerging Policy Issues in Synthetic Biology, OECD Publishing. http://dx.doi.org/10.1787/9789264208421-en

Synthetic biology is the design and construction of biological systems guided by engineering principles, Bayer, T.S. (2010), “Using synthetic biology to understand the evolution with the aim of understanding biology or producing useful biological technologies. of gene expression”, Current Biology, Vol. 20, pp. R772–R779.

European Commission Scientific Committees (SCHER, SCENIHR, SynBio is the application of science, technology and engineering to facilitate and accelerate the design, SCCS): Opinion on Synthetic Biology I – Definition. manufacture and/or modification of genetic materials in living organisms. http://ec.europa.eu/health/scientific_committees/consultations/public_con sultations/scenihr_consultation_21_en.htm

Synthetic biology is advancing rapidly as biologists, physicists and engineers are combining their W. J. Blake, F. J. Isaacs, Synthetic biology evolves. Trends Biotechnol efforts to understand and program cell function. By characterizing isolated genetic components or 22, 321 (Jul, 2004). modules, experimentalists have paved the way for more quantitative analyses of genetic networks.

Synthetic biology is the engineering of biology: the synthesis of complex, biologically based (or inspired) systems which display functions that do not exist in nature. This engineering perspective may NEST - New and Emerging Science and Technology, “Synthetic Biology be applied at all levels of the hierarchy of biological structures – from individual molecules to whole Applying Engineering to Biology- Report of a NEST High-Level Expert cells, tissues and organisms. In essence, synthetic biology will enable the design of ‘biological systems’ Group” (2005). http://www.bsse.ethz.ch/bpl/publications/nestreport.pdf in a rational and systematic way.

Synthetic biology is the engineering of biological components and systems that do not exist in nature NEST – New and Emerging Science and Technology, “SYNBIOLOGY and the re-engineering of existing biological elements; it is determined on the intentional design of An Analysis of Synthetic Biology Research in Europe and North America artificial biological systems, rather than on the understanding of natural biology. (Output D3: Literature and Statistical Review)” (2005).

Synthetic biology is a new emerging scientific field where ICT, biotechnology and nanotechnology meet H. De Vriend, “Constructing Life. Early social reflections on the emerging and strengthen each other. Synthetic biology is a new trend in science and technology and a clear field of synthetic biology” (2006). example of converging technologies. 15 DSTI/STP/BNCT(2016)2

Definition of the Term ‘Synthetic Biology’ Source

Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological M. Heinemann, S. Panke, Synthetic biology--putting engineering into entities for novel applications. biology. Bioinformatics 22, 2790 (2006).

Synthetic biology is a new research field, combining elements of gene technology and sc | nat, “Synthetic Biology” (2006). nanotechnologies with elements of the engineering sciences.

Synthetic biology refers to a variety of experimental approaches that either seek to modify or mimic D. A. Drubin, J. C. Way, P. A. Silver, Designing biological systems. biological systems. Genes Dev 21, 242 (Feb 1, 2007).

Synthetic Biology (also known as Synbio, Synthetic Genomics, Constructive Biology or Systems Biology) – the design and construction of new biological parts, devices and systems that do not exist in ETC, “Extreme Genetic Engineering An Introduction to Synthetic Biology” the natural world and also the redesign of existing biological systems to perform specific tasks. (2007). Advances in nanoscale technologies – manipulation of matter at the level of atoms and molecules – are contributing to advances in synthetic biology.

Synthetic biology is an emerging area of research that can broadly be described as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing Royal Society, “Synthetic biology: Call for views” (2007). natural biological systems.

R. Entus, B. Aufderheide, H. M. Sauro, Design and implementation of Synthetic biology is a useful tool to investigate the dynamics of small biological networks and to assess three incoherent feed-forward motif based biological concentration our capacity to predict their behavior from computational models. sensors. Syst Synth Biol 1, 119 (Aug, 2007).

Synthetic biology aims to design and build new biological parts and systems or to modify existing ones S. Bunn, Synthetic biology Postnote 298, 1 (2008). to carry out novel tasks.

Most definitions of synthetic biology have two parts: synthetic biology is defined as the construction of IRGC, “Synthetic biology: risk and opportunities of an emerging field” completely novel biological entities, and the re-design of already existing ones. (2008).

A definition of synthetic biology should therefore include: 1. The design of minimal cells/organisms (including minimal genomes); 2. The identification and use of biological ‘parts’ (toolkit); 3. The EGE. (Publications Office of the European Union, Luxembourg, 2009). construction of totally or partially artificial biological systems.

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Definition of the Term ‘Synthetic Biology’ Source

UK Synthetic Biology Roadmap Coordination Group, “A synthetic biology Synthetic biology is the design and engineering of biologically based parts, novel devices and systems roadmap for the UK” as well as the redesign of existing, natural biological systems. (2012).http://www.synbioproject.org/topics/synbio101/definition/

Synthetic biology is the name given to an emerging field of research that combines elements of biology, PCSBI, “New Directions: The Ethics of Synthetic Biology and Emerging engineering, genetics, chemistry, and computer science. Technologies” (Washington DC, 2010).

Synthetic biology is a term used to cover areas of biochemistry research that is involved in the HSE, “Synthetic biology A review of the technology, and current and chemical synthesis of DNA, utilising biological agents or their components for potential application future needs from the regulatory framework in Great Britain” (2012). across a wide range of industrial sectors.

Synthetic biology aims to design and engineer biologically based parts, novel devices and systems as The Royal Academy of Engineering “ Synthetic Biology: scope well as redesigning existing, natural biological systems. Synthetic biology strives to make the applications and implications” (2009) engineering of biology easier and more predictable.

The fundamental idea behind synthetic biology is that any biological system can be regarded as a combination of individual functional elements — not unlike those found in man-made devices. These A. Danchin, ‘Synthetic biology: discovering new worlds and new words’, can therefore be described as a limited number of parts that can be combined in novel configurations to EMBO reports; doi:10.1038/embor.2008.159 (2008). modify existing properties or to create new ones.

Synthetic biology uses nucleic acid elements or complex systems that are predefined and chemically synthesised in the laboratory by a modular approach. This approach aims to: 1. engineer and study website of the EU Project ‘Towards a European Strategy for Synthetic biological systems that do not exist as such in nature, and 2. use this approach for i) achieving better Biology’ (TESSY, 2007-2008): http://www.tessy-europe.eu/ understanding of life processes, ii) generating and assembling functional modular components, iii) developing novel applications or processes.

[Synthetic biology] attempts to recreate in unnatural chemical systems the emergent properties of living systems … [the] engineering community has given further meaning to the title…to extract from living Benner SA and Sismour AM, Synthetic Biology Nat Rev Genet 6:533-43 systems interchangeable parts that might be tested, validated as construction units, and reassembled (2005) to create devices that might (or might not) have analogues in living systems.

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Definition of the Term ‘Synthetic Biology’ Source

To advance knowledge and create products that can promote human welfare, synthetic biologists seek to create biological systems that do not occur naturally as well as reengineer biological systems that do Hastings Center, USA occur naturally. [Synthetic biology] describes research that combines biology with the principles of engineering to design and build standardised, interchangeable biological DNA building-blocks. These have specific functions and can be joined to create engineered biological parts, systems and, potentially, organisms. UK Parliamentary Office of Science and Technology, POST (2008). [Synthetic biology] may also involve modifying naturally occurring genomes… to make new systems or by using them in new contexts. Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems. Synthetic biology builds on the advances in molecular, cell, and systems biology and seeks to transform biology in the same way that synthesis transformed chemistry and integrated circuit design transformed computing. The element that distinguishes synthetic biology from traditional molecular and cellular biology is the focus on the design and construction of core components (parts of enzymes, genetic circuits, metabolic pathways, etc.) that can be modeled, understood, and tuned to meet specific performance criteria, and the assembly of these smaller parts and devices into larger integrated systems to solve specific problems. Just as http://www.synberc.org/what-is-synbio engineers now design integrated circuits based on the known physical properties of materials and then fabricate functioning circuits and entire processors (with relatively high reliability), synthetic biologists will soon design and build engineered biological systems. Unlike many other areas of engineering, biology is incredibly non-linear and less predictable, and there is less knowledge of the parts and how they interact. Hence, the overwhelming physical details of natural biology (gene sequences, protein properties, biological systems) must be organized and recast via a set of design rules that hide information and manage complexity, thereby enabling the engineering of many-component integrated biological systems. It is only when this is accomplished that designs of significant scale will be possible.

This community defines ‘synthetic biology’ as: 1. the design and construction of biological parts, devices andsystems, and; http://syntheticbiology.org/ 2. the redesign of existing, natural biological systems for useful purposes.

Synthetic biology is a further development and new dimension of modern biotechnology that combines science, technology and engineering to facilitate and accelerate the understanding, design and UNEP CBD Syn Bio redesign, manufacture and/or modification of genetic materials, living organisms and biological systems.

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ANNEX A2: Proposed glossary of terms used in the OECD list-based definition of biotechnology

33. The detailed glossary of terms used in the OECD list-based definition of biology was first introduced in the Biotechnology Framework (2005), and subsequently updated in 2008.20 The BNCT proses the addition of a detailed description of synthetic biology (highlighted in the table in grey).

Box 6. Proposed glossary of terms used in the list-based definition of biotechnology

DNA/RNA: Genomics, pharmacogenomics, gene probes, genetic engineering, DNA/RNA sequencing/synthesis/amplification, gene expression profiling, and use of antisense technology.

- Genomics/pharmacogenomics: The study of genes and their function. Advances in genomics due to the Human Genome Project and other genome research into plants, animals and micro-organisms are enhancing our understanding of the molecular mechanisms of genomes. Genomics stimulates the discovery of health care products by revealing thousands of new biological targets for the development of drugs and by identifying innovative ways to design new drugs, vaccines and DNA diagnostics. Genomic-based therapeutics includes both protein drugs and small molecule drugs. Genomics is also used in plant and animal breeding programmes.

- Gene probes/DNA markers: A section of DNA of known structure or function which is marked with a radioactive isotope, dye or enzyme so that it can be used to detect the presence of specific sequences of bases in another DNA or RNA molecule.

- Genetic engineering: Altering the genetic material of cells or organisms in order to make them capable of making new substances or performing new functions.

- DNA/RNA sequencing: Determination of the order of nucleotides (i.e. the base sequence) in a DNA or RNA molecule.

- DNA/RNA synthesis: The linking together of nucleotides to form DNA or RNA. In vivo, most synthesis involves DNA replication, but incorporation of precursors also occurs in repair. In the special case of retroviruses, an RNA template directs DNA synthesis.

- DNA/RNA amplification: The process of increasing the number of copies of a particular gene or gene- derived sequence.

- Other: There are several fields of research on RNA, including RNAi and siRNA, based on the use of recombinant technology to generate RNA sequences to inhibit gene function. Expression profiling analyses expressed genes using microarrays or gene chips.

Proteins and other molecules: Sequencing/synthesis/engineering of proteins and peptides (including large molecule hormones); improved delivery methods for large molecule drugs; proteomics, protein isolation and purification, signaling, identification of cell receptors.

- Peptide/Protein sequencing: Determination of the order of amino acids in a protein or peptide.

- Peptide synthesis: A procedure which links two or more amino acids in a linkage called a peptide bond.

- Protein engineering: The selective, deliberate (re)designing and synthesis of proteins. This is done in order to cause the resultant proteins to carry out desired (new) functions. Protein engineering is accomplished by changing or interchanging individual amino acids in a normal protein. This may be done via chemical synthesis or recombinant DNA technology (i.e. genetic engineering). “Protein engineers” (actually genetic engineers) use recombinant DNA technology to alter a particular nucleotide in the triplet codon of the DNA of a cell. In this way it is hoped that the resulting DNA codes for the different (new) amino acid in the desired location in the protein produced by that cell.

- Proteomics: Analysis of the expression, functions and interactions of all proteins of an organism.

20 . OECD (2005), A Framework for Biotechnology Statistics, http://www.oecd.org/sti/biotechnology/framework.

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- Signaling: Analysis of signaling molecules such as cytokines, chemokines, transcription factors, cell cycle proteins, and neurotransmitters.

- Cell receptors: Structures (typically proteins) found in the plasma membrane (surface) of cells that tightly bind specific molecules (organic molecules, proteins, viruses etc.). Some (relatively rare) receptors are located inside the cell (e.g. free-floating receptor for Retin-A). Both (membrane and internal) types of receptors are a functional part of information transmission (i.e. signalling) of the cell.

Cell and tissue culture and engineering: Cell/tissue culture, tissue engineering (including tissue scaffolds and biomedical engineering), cellular fusion, vaccine/immune stimulants, embryo manipulation.

- Cell/tissue/embryo culture and manipulation: Growth of cells, tissues or embryonic cells under laboratory conditions.

- Tissue engineering: Refers to the technologies used to induce:

- (Injected) liver, cartilage, etc., cells to grow (within a recipient organism's body) and form replacement [integral] tissues.

- (Extant) cells within the body encouraged to grow and form desired tissues, via precise injection of relevant compounds (e.g. certain growth factors, growth hormones, stem cells, etc.).

- Laboratory grown tissue or organs to replace or support the function of defective or injured body parts (an example is skin tissue culture for grafts).

- Cell fusion: The combining of cell contents of two or more cells to become a single cell. Fertilisation is such a process.

- Vaccines/immune stimulants: A preparation containing an antigen consisting of whole disease-causing organisms (killed or weakened), or parts of such organism is used to confer immunity against the disease that the organisms cause. Vaccine preparations can be natural, synthetic or derived by recombinant DNA technology.

Process biotechnology techniques: Fermentation using bioreactors, bioprocessing, bioleaching, biopulping, biobleaching, biodesulphurisation, bioremediation, biofiltration and phytoremediation.

- Bioreactor: A vessel in which cells, cell extracts or enzymes carry out a biological reaction. Often refers to a fermentation vessel for cells or micro-organisms.

- Bioprocessing: A process in which living cells or components are used to produce a product, especially a biological product involving genetic engineering for commercial use.

- Bioleaching: The conversion of metals to a soluble form by live organisms such as bacteria or fungi.

- Biopulping: Use of micro-organisms to break down wood fibres for the purpose of producing pulp.

- Biobleaching: Use of micro-organisms to bleach pulp.

- Biodesulphurisation: Use of specific micro-organisms to transform hazardous sulphurs into less hazardous compounds.

- Bioremediation/biofiltration/phytoremediation: The process by which living organisms act to degrade hazardous organic contaminants or transform hazardous inorganic contaminants to environmentally safe levels in soils, subsurface materials, water, sludge, and residues.

- Bioremediation: The use of micro-organisms to remedy environmental problems rendering hazardous wastes non-hazardous.

- Biofiltration: The use of a support containing specific bacteria to capture by filtration hazardous substances from a gas stream.

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- Phytoremediation: Refers to the use of specific plants to remove contaminants or pollutants from either soils (e.g. polluted fields) or water resources (e.g. polluted lakes).

Gene and RNA vectors: Gene therapy, viral vectors.

- Gene therapy: Gene delivery, the insertion of genes (e.g. via retroviral vectors) into selected cells in the body in order to:

- Cause those cells to produce specific therapeutic agents.

- Cause those cells to become (more) susceptible to a conventional therapeutic agent that previously was ineffective against that particular condition/disease.

- Cause those cells to become less susceptible to a conventional therapeutic agent.

- Counter the effects of abnormal (damaged) tumour suppressor genes via insertion of normal tumour suppressor genes.

- Cause expression of ribozymes that cleave oncogenes (cancer-causing genes).

- Introduce other therapeutics into cells.

- Viral vectors: Certain (retro-) viruses that are used by genetic engineers to carry new genes into cells.

Bioinformatics: Construction of databases on genomes, protein sequences; modelling complex biological processes, including systems biology.

- The use of computers in solving information problems in the life sciences; mainly, it involves the creation of extensive electronic databases on genomes, protein sequences, etc. Secondarily, it involves techniques such as the three-dimensional modelling of biomolecules.

- The generation/creation, collection, storage (in databases), and efficient utilisation of data/information from genomics (functional genomics, structural genomics, etc.), combinatorial chemistry, high-throughput screening, proteomics, and DNA sequencing research efforts in order to accomplish a (research) objective (e.g. to discover a new pharmaceutical or a new herbicide, etc.). Examples of the data/information that is manipulated and stored include gene sequences, biological activity/function, pharmacological activity, biological structure, molecular structure, protein- protein interactions, and gene expression products/amounts/timing.

Nanobiotechnology: Applies the tools and processes of nano/microfabrication to build devices for studying biosystems and applications in drug delivery, diagnostics etc.

- Covers the interface between physics, biology, chemistry and the engineering sciences and which, among other things, aims to develop completely new measuring technologies for the biosciences.

- Nanotechnology develops or makes materials that function on a very small scale, typically between 1 and 100 nanometers. Nanobiotechnology uses these particles and materials as tools to improve the performance and sensitivity of several life science technologies e.g. biosensing, medical devices and medical implants.

Synthetic Biology:21 SynBio is the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms.

21. European Commission Scientific Committees (SCHER, SCENIHR, SCCS): Opinion on Synthetic Biology I – Definition. http://ec.europa.eu/health/scientific_committees/consultations/public_consultations/scenihr_cons ultation_21_en.htm

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ANNEX A3: Proposed changes to the IPC patent classification scheme of biotechnology

34. The current patent classification of biotechnology is based on a 2006 version of the IPC Scheme (more information on the IPC Scheme can be found in Box 7).

Box 7. Background Information on the International patent Classification System (IPC)

The IPC is based on an international multilateral treaty administered by WIPO (World Intellectual Property Organization).22

The IPC is a hierarchical classification system used primarily to classify and search patent documents according to the technical fields to which they pertain. The classification scheme contains about 70,000 entries, i.e. classification symbols that can be allotted to patent documents. These different classification places are arranged in a hierarchical, tree-like structure. The classification consists of several hierarchical levels:

• Sections - 1st level

• Classes - 2nd level

• Subclasses - 3rd level

• Main groups - 4th level

• Subgroups - 5th and lower levels

Sections are subdivided into 120 classes in the eighth edition of the IPC (IPC-8 (IPC-2006)). Class C21, for example, deals with the "Metallurgy of iron".

Classes are further subdivided into more than 600 subclasses. Subclass A21B, for example, deals with "Bakers' ovens; Machines or equipment for baking". Subclasses are divided into main groups and subgroups.

Main group symbols always end with "/00". For example, main group A21C 5/00 deals with "Dough-dividing machines". The hierarchy of the subgroups under main groups is designated by dots preceding the titles of the entries. IPC-2006 contains about 70,000 groups. Ten percent of the groups are main groups. Subgroups can be on different hierarchical levels; this hierarchical level is indicated by a certain number of dots with a lower level corresponding to a higher number of dots.

A complete classification symbol comprises the combined symbols representing the section, class, subclass and main group or subgroup.

Example:23

22 . http://www.wipo.int/classifications/ipc/en/

23 . Guide to the IPC (2015), WIPO; http://www.wipo.int/export/sites/www/classifications/ipc/en/guide/guide_ipc.pdf

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35. The current list of (refined) patent codes identifying biotechnology patents is provided in Table 3 below.

Table 3. Refined List of Patent Codes identifying Biotechnology Patents (2006)

IPC Code Title A01H 1/00 Processes for modifying genotypes. A01H 4/00 Plant reproduction by tissue culture techniques. A61K 38/00 Medicinal preparations containing peptides. A61K 39/00 Medicinal preparations containing antigens or antibodies. A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy. C02F 3/34 Biological treatment of water, waste water, or sewage: characterised by the micro-organisms used. C07G 11/00 Compounds of unknown constitution: antibiotics. C07G 13/00 Compounds of unknown constitution: vitamins. C07G 15/00 Compounds of unknown constitution: hormones. C07K 4/00 Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof. C07K 14/00 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof. C07K 16/00 Immunoglobulins, e.g. monoclonal or polyclonal antibodies. C07K 17/00 Carrier-bound or immobilised peptides; Preparation thereof. C07K 19/00 Hybrid peptides. C12M Apparatus for enzymology or microbiology. C12N Micro-organisms or enzymes; compositions thereof. Fermentation or enzyme-using processes to synthesise a desired chemical compound or C12P composition or to separate optical isomers from a racemic mixture. Measuring or testing processes involving enzymes or micro-organisms; compositions or test C12Q papers therefore; processes of preparing such compositions; condition-responsive control in microbiological or enzymological processes. Processes using enzymes or micro-organisms to liberate, separate or purify a pre-existing C12S compound or composition processes using enzymes or micro-organisms to treat textiles or to clean solid surfaces of materials. G01N 27/327 Investigating or analysing materials by the use of electric, electro-chemical, or magnetic means: biochemical electrodes. G01N 33/53* Investigating or analysing materials by specific methods not covered by the preceding groups: immunoassay; biospecific binding assay; materials therefore. G01N 33/54* Investigating or analysing materials by specific methods not covered by the preceding groups: double or second antibody: with steric inhibition or signal modification: with an insoluble carrier for immobilising immunochemicals: the carrier being organic: synthetic resin: as water suspendable particles: with antigen or antibody attached to the carrier via a bridging agent: Carbohydrates: with antigen or antibody entrapped within the carrier. G01N 33/55* Investigating or analysing materials by specific methods not covered by the preceding groups: the carrier being inorganic: Glass or silica: Metal or metal coated: the carrier being a biological cell or cell fragment: Red blood cell: Fixed or stabilised red blood cell: using kinetic measurement: using diffusion or migration of antigen or antibody: through a gel.

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IPC Code Title G01N 33/57* Investigating or analysing materials by specific methods not covered by the preceding groups: for venereal disease: for enzymes or isoenzymes: for cancer: for hepatitis: involving monoclonal antibodies: involving limulus lysate. G01N 33/68 Investigating or analysing materials by specific methods not covered by the preceding groups: involving proteins, peptides or amino acids. G01N 33/74 Investigating or analysing materials by specific methods not covered by the preceding groups: involving hormones. G01N 33/76 Investigating or analysing materials by specific methods not covered by the preceding groups: human chorionic gonadotropin. G01N 33/78 Investigating or analysing materials by specific methods not covered by the preceding groups: thyroid gland hormones. G01N 33/88 Investigating or analysing materials by specific methods not covered by the preceding groups: involving prostaglandins. G01N 33/92 Investigating or analysing materials by specific methods not covered by the preceding groups: involving lipids, e.g. cholesterol. * Those IPC codes also include subgroups up to one digit (0 or 1 digit). For example, in addition to the code G01N 33/53, the codes G01N 33/531, GO1N 33/532, etc. are included.

Revisions of the IPC patent classification by WIPO

36. Since the OECD Working Party on Biotechnology adopted the list of refined biotechnology patent codes, the World Intellectual Property Organization (WIPO) has revised the IPC Scheme every calendar year, resulting in changes concerning the biotechnology patent code list; the full list of the resulting biotechnology-relevant changes is currently under review by biotechnology patent experts.

37. WIPO adopted a number of changes to the IPC; while some changes fall within Subclasses that are already fully counted as biotechnology patent classes, other changes have direct statistical impact on the identification of biotechnology patents. The changes that are most relevant to the statistical biotechnology definition are:

 The creation of new biotechnology-relevant groups under Subclass C40B (‘Combinatorial Chemistry; Libraries, e.g. Chemical Libraries, in silico Libraries’): Groups on ’Libraries [of] arrays, [and] mixtures’ were introduced (i.e. Groups C40B 40/00 – C40B 40/18), including titles on ‘Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries’. These Subclasses were introduced both for subject matters of ‘Organic or Organic Macromolecular Compounds’ and their ‘Methods of preparation’ (C07), and for subject matters of ‘Biochemistry; Mutation or Genetics Engineering’ (C12).

 Statistical analysis of the use to patent code C40B returns 3927 distinct patents filed.

 Creation of new Groups and Subgroups, and addition of new descriptive elements to existing Groups and Subgroups under the Groups of ‘Medicinal preparations containing inorganic active ingredients’(A61K 33/00) and ‘Medicinal preparations containing materials or reaction products thereof with undetermined constitution’ (A61K 35/00); the latter was significantly amended by addition of descriptive details on ‘Materials from mammals; Compositions comprising non- specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells […]’.

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 Statistical analysis of the use to patent codes A61K 33/00 and A61K 35/00 return 1368 and 521 distinct patents filed, respectively.

38. WIPO also deleted Subclass C12S (Processes using enzymes or micro-organisms to liberate, separate or purify a pre-existing compound or composition) between Version 2010.01 and Version 2013.01.24 Since Subclass C12S is part of a set of Subclasses (i.e. C12M, C12N, C12P, C12Q, C12S) in IPC Section C (Chemistry; Metallurgy), a statistical analysis of patent filing under all Subclasses of the sets was performed; the process and outcome of the analysis are described Table 4 below.

39. Statistical analysis of the specific use of individual biotechnology patent codes shows that the code C12S is indeed rarely assigned (i.e. the code C12S has been assigned to ca. 625 patents (until 2012), compared to the much more frequent assignment of C12M (ca. 10459 times), C12N (ca. 94575 times), C12P (30156 times), and C12Q (ca. 49291 times)). Furthermore, over 50% of all C12S-classified patents had also been assigned another biotechnology patent code of Class C12.

24 . According to WIPO (private conversation), their experts had recommended the deletion of Subclass C12S, because nobody had been using it.

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Table 4. Statistical overview of the use of biotechnology IPC codes (assigned and adopted in 2006)

Statistical analysis of the use of biotechnology-specific patent codes C12M, C12N, C12P, C12Q, and C12S, in order to determine how many patents would be lost to a biotechnology count subsequent to the abolition of IPC Code C12S.25

1st ICP Code (under AND search results PCT) 2nd ICP Code (under PCT) [distinct patent applications] A01H 1/00 - 1203 A01H 4/00 - 542 A61K 38/00 - 3542 A61K 39/00 - 11130 A61K 48/00 - 15761 C02F 3/34 - 932 C07G 11/00 - 53 C07G 13/00 - 3 C07G 15/00 - 1 C07K 4/00 - 208 C07K 14/00 - 4184 C07K 16/00 - 4735 C07K 17/00 - 643 C07K 19/00 - 4491 C12M - 10459 C12N - 94575 C12P - 30156 C12Q - 49291 C12S - 625 G01N 27/327 - 856 G01N 33/53* - 17090 G01N 33/54* - 8028 G01N 33/55* - 1988 G01N 33/57* - 9616 G01N 33/68 - 11625 G01N 33/74 - 1257 G01N 33/76 - 191 G01N 33/78 - 93 G01N 33/88 - 68 G01N 33/92 - 888 C12S C12M 30 C12S C12N 303 C12S C12P 153 C12S C12Q 28 any C12 Code C12S 390 (i.e. C12M OR C12N OR C12P OR C12Q)

25 . The search was performed using the OECD PATSAT Database; scope: all entries until December 2015.

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New Developments in Biotechnology

40. Enabling technologies, such as Biotechnology and Nanotechnology advance with a rapid pace; their advancement takes the shape of both breakthroughs in science, scale-up and commercial viability (e.g. the 100-fold drop in the cost of genome sequencing between 2008 and 2011),26 as well as in the broadening of applications into markets and industry sectors that have formerly not utilised processes or products enabled by the technology (e.g. the establishment of entire industries based on biofuels and bioplastics, enabled by the synthetic biology).27

41. The advancement in technologies leads to new discoveries and inventions, manifesting themselves in the creation of new names, keywords and abbreviations mentioned in publications and patents, which, in turn, refer to and describe the specific novelty, discovery or invention (i.e. the “technical subject matter” in patents).

42. Patent analysis is specifically supportive to identifying trends in science and technology, because the “technical subject matter” of a patent must be sufficiently described through the assignment of a limited number of IPC Code, which is limited to describing a process, a product, an apparatus, or a material (or the way these are used or applied). The assignment of “new” IPC Codes (i.e. IPC Codes that have previously not been part of the adopted list of Biotechnology IPC Codes) to patents that either feature certain keywords in their title (e.g. keyword: “omics”), or that have been identified to be key-patents for recent developments in biotechnology (e.g. Patent US 8,697,359 B1, entitled Crystal structure of a CRISPR system and uses thereof), thus provides an indication of patents codes that have become relevant to the field of biotechnology. The title of these “new” IPC Codes, in turn, may contain new keywords that might need to be considered to be included in the statistical combined definition of biotechnology.

43. Two independent searches were carried out:

 Individual keyword searches in the WIPO IPC Database, using the ‘stats-search’ function;28 the search terms entered were “gene-editing”, “gene-drive”, “bioinformatics”, “omics”, “shotgun”, and “CRISPR”. The full list of the resulting biotechnology-relevant changes is currently under review by biotechnology patent experts.

 Manual analysis of key-patents on recent biotechnology advances; the analysis looked for “new” IPC Codes assigned to the Key-Patents themselves, as well as “new” IPC Codes found in the Key-Patents backward- and forward-citations.29 The full list of the resulting biotechnology- relevant changes is currently under review by biotechnology patent experts.

44. The searches yielded the following main outcomes:

 Both search (a) and search (b) clearly identified Group A01K 67/00 (‘Rearing or breeding animals, not otherwise provided for; New breeds of animals’) as a newly frequented Group assigned to biotechnology patents. Several Subgroups of this group are also found in the IPC list of such patents.

26 . OECD (2014), Measuring the Digital Economy: A New Perspective, OECD Publishing. http://dx.doi.org/10.1787/9789264221796-en

27 . OECD (2014), Measuring the Digital Economy: A New Perspective, OECD Publishing. http://dx.doi.org/10.1787/9789264221796-en

28 . http://web2.wipo.int/classifications/ipc/ipcpub/search/stats/#version=20150101&lang=en

29 . The search was conducted using the ESPACENET Database: http://worldwide.espacenet.com/

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 Statistical analysis of the use to patent code A01K 67/00 returns 578 distinct patents filed.

 Group G06F 19/00 (‘Digital computing or data processing equipment or methods, specially adapted for specific applications’) and Subgroup G06F 17/30 (‘Digital computing or data processing equipment or methods, specially adapted for specific functions - ·Information retrieval; Database structures therefor’) were frequently returned in search (a), and once in search (b). The highest occurrence of search returns is found for Subgroup G06F 19/10 (‘·Bioinformatics, i.e. methods or systems for genetic or protein-related data processing in computational molecular biology (in silico methods of screening virtual chemical libraries C40B 30/02; in silico or mathematical methods of creating virtual chemical libraries C40B 50/02’) and its lower-level Subgroups. It should be noted that this Subgroup was introduced in 2011, and that it makes specific reference to Subclass C40B (see Section 0 above).

 Statistical analysis of the use to patent codes G06F 19/00 and G06F 17/30 return 12851 and 25497 distinct patents filed, respectively.

 Both search (a) and search (b) result in a frequent return of Group Code C07H 21/00 (and its Subgroups) (‘Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids’).

 Statistical analysis of the use to patent code C07H 21/00 returns 3138 distinct patents filed.

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ANNEX A4: History and development of the OECD’s statistical definition of nanotechnology

Definitions of nanotechnology

45. Since the coining of the term ‘nanotechnology’ in the context of science, technology and innovation, a diverse range of nanotechnology definitions has been proposed. The definitions differ depending of their context and scope: the context which ranges from technical specification and standardisation, such as the working definition of the term ‘nanotechnologies’ agreed by the International Organization for Standardization (ISO) in 2005 upon the creation of its Technical Committee (ISO/TC 229) on ‘nanotechnologies’,30 to regulatory definitions, such the definition of the term ‘nanomaterial’, passed in 2011 by the European Union.31 The scope of potential definitions of nanotechnology may vary with regard to the deliberate exclusion or inclusion of naturally occurring examples of nanotechnologies (e.g. nanomaterials).

46. No international consensus has been reached on a general or even statistical definition of nanotechnology, and to this date, statistical offices are collecting nanotechnology-specific data on the bases of statistical definitions of nanotechnology that differ between countries. Table 5 provides a list of the different nanotechnology definitions used by countries contributing to the OECD’s annual statistical publication of Key Nanotechnology Indicators (KNIs).32

47. Most countries use the following ISO definition as a basis for the collection of statistical data:

1. Understanding and control of matter and processes at the nanoscale, typically, but not exclusively, below 100 nanometres in one or more dimensions where the onset of size-dependent phenomena usually enables novel applications,

2. Utilizing the properties of nanoscale materials that differ from the properties of individual atoms, molecules, and bulk matter, to create improved materials, devices, and systems that exploit these new properties.

30 . ISO (2005), http://www.iso.org/iso/home/standards_development/list_of_iso_technical_committees/iso_technical_com mittee.htm?commid=381983

31 . EU (2011), COMMISSION RECOMMENDATION of 18 October 2011 on the definition of nanomaterial, Official Journal of the European Union, http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32011H0696

32 . OECD, Key nanotechnology Indicators, http://www.oecd.org/sti/nanotechnology-indicators.htm

29 DSTI/STP/BNCT(2016)2 Table 5. List of statistical Definitions of Nanotechnology used in OECD’s annual KNIs

The following table provides a list of nanotechnology definitions used by countries contributing to the OECD's annual publication of Key Nanotechnology Indicators (KNIs).

Country Definition of Nanotechnology

Belgium ISO 1 Nanotechnology is a set of technologies that enables the manipulation of the matter until the limits of the atom with the purpose of Brazil incorporating nanostructured materials or nanoparticles to existing products to improve their performance, or to create and/or develop new materials and new products. Canada Revenue Agency, Field of Science Codes - 2.10.01 - Nano-materials (production and properties) 2.10.02 - Nano-processes Canada (applications on nano-scales)

Nanotechnology is the set of technologies that enables the manipulation, study or exploitation of very small (typically less than 100 Czech Republic nanometres) structures and systems. Denmark The science and technology involving work at the nanometer scale. Public data: OECD Field of Science 2007 classification on the 2-digit level Finland 1 Private (i.e. firms): ISO France All technologies for manipulating, studying or using very small structures and systems (less than 100 nanometers). Nanotechnology is concerned with the controlled creation, analysis and use of materials and components with functionally relevant structure Germany sizes between approx. 1 and 100 nanometers in at least one dimension. The nanoscale results in new functionalities and properties which are able to contribute to the improvement of existing products or to the development of new products and applications. Ireland Nanotechnology refers to the manipulation of matter on an atomic scale to develop materials and devices with novel properties By nanotechnology is meant the ability to observe, measure and manipulate matter at the atomic and molecular scale. For the purposes of this questionnaire should be considered both nanotechnologies based on the approach so-called "top-down" i.e. aimed at reducing the size Italy of structures, by means of physical methods, to nano levels, and those nanotechnologies based on the 'bottom-up' method, i.e. the use of small components, usually molecules or aggregates of molecules, to achieve nanostructures, either of inorganic or organic / biological nature. Nanotechnology R&D is defined as: R&D that enables new functions based on the specific properties of nanoscale materials, by manipulating and controlling atoms and molecules at the nano(10^-9)meter order. For example, it includes nano-materials, which have novel functions, such as hyper high intensity, hyper light weight, hyper high efficiency light-emitting, by controlling material structures at the nano Japan level; nano-information devices, which enables next-generation hyper high speed telecommunications and hyper high speed information processing, by utilizing hyper miniaturization technology and quantum effect; medical technology that is used to diagnose and treat by directly transmitting extremely small system to affected parts of the body; nano-biotechnology, which observes various biological phenomena at the nanometer level and utilize and control the mechanism. Korea ISO 1

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Country Definition of Nanotechnology

Mexico The science and technology involving work at the nanometer scale. Norway None Poland ISO 1 Field of Science (FOS-2007) classification definition of nanotechnology: 2.10 Nano-technology • Nano-materials [production and properties]; Portugal • Nano-processes [applications on nano-scale]. Other (based on ISO): Nanotechnologies – a set of methods and techniques, related to analysis & control of elemental composition of the Russian Federation matter and processes at the nanoscale level (100 nm or less by one or several dimensions) and providing new properties of the matter to create improved materials, devices or systems which utilize those new properties 1 Nanotechnology is a technology dealing with the smallest particle of matter, which can be manipulated. For example development of nano- transistors, diodes, and the like to minimize the size of the computers, further optoelectronics - optoelectronic properties of semiconductors, Slovak Republic receptor surfaces of biosensors for biological systems, new microscopic techniques. Nanotechnology can be interdisciplinary field, it may merge physics, computer science, electronics, biology, biotechnology, chemistry, and so on. Field of Science (FOS-2007) classification definition of nanotechnology: 2.10 Nano-technology • Nano-materials [production and properties]; Slovenia • Nano-processes [applications on nano-scale]. South Africa ISO 1 Nanotechnology refers to research, development and eventually the production of products which use materials engineered at the atomic, molecular or macromolecular levels, in the length scale of approximately 1–100 nanometre range. Switzerland Nano-science refers to the fundamental understanding of phenomena and materials at the nanoscale. On a larger scale, nanotechnology research and development includes the controlled manipulation of nanoscale structures and their integration into larger material components, systems and architectures. United States The science and technology involving work at the nanometer scale.

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48. The OECD acknowledges the widespread adoption of the ISO definition, and thus applies it as a ‘default’ definition in its annual R&D survey for KNIs. Nevertheless, for its own statistical analysis the OECD uses the nanotechnology definition introduced by the European Patent Office (EPO):33

The term nanotechnology covers entities with a controlled geometrical size of at least one functional component below 100nm in one or more dimensions susceptible to make physical, chemical or biological effects available which are intrinsic to that size. It covers equipment and methods for controlled analysis, manipulation, processing, fabrication or measurement with a precision below 100nm.

49. The EPO’s definition of nanotechnology also underpinned the creation of the patent tagging system Y01N, developed in 2003, and since then revised into a set of IPC Subclasses, and has consequently since 2007 been used for statistical patent analysis in the biennial OECD Science, Technology and Industry Scoreboard.34

50. In 2014, the OECD Working Party on Nanotechnology (WPN) published Considerations in moving towards a statistical Framework for Nanotechnology: Findings from a Working Party on Nanotechnology Survey of Business Activity in Nanotechnology,35 which reviewed the various basic definitions of nanotechnology used and recommended the addition of a ‘list-based’ definition of nanotechnology to an agreed ‘single definition’ (i.e. the ISO definition, see above) , in order to allow the collection of statistical data on a sub-area level. Such a statistical definition of nanotechnology in two parts would follow the example of the statistical definition of biotechnology.

51. In 2013, the WPN applied the feedback received during the piloting of a Questionnaire on Business Activity in Nanotechnology in 2010-2011, resulting in the proposed Definition of Nanotechnology provided in Box 8 below.

33 . Scheu, M., V. Veefkind, Y. Verbandt, E. Molina Galan, R. Absalom W. and Förster (2006), “Mapping nanotechnology patents: The EPO approach”, World Patent Information, 28, 204-211.

34 . OECD (2007), OECD Science, Technology and Industry Scoreboard 2007, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/sti_scoreboard-2007-en

35 . OECD (2013), Considerations in moving towards a statistical Framework for Nanotechnology: Findings from a Working Party on Nanotechnology Survey of Business Activity in Nanotechnology, http://www.oecd.org/sti/biotech/statistical-framework-nanotechnology-business-activity-findings.pdf

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Box 8. Proposed single and list-based Definition of Nanotechnology

The single definition of nanotechnology:36 Understanding and control of matter and processes at the nanoscale typically but not exclusively below 100 nanometres in one or more dimensions where the onset of size- dependent phenomena usually enables novel applications utilising the properties of nanoscale materials that differ from the properties of individual atoms molecules and bulk matter to create improved materials devices and systems that exploit these new properties.

The list-based definition of nanotechnology:

- Nanomaterials

- Nanoelectronics

- Nanophotonics

- Nanobiotechnology

- Nanomedicine

- Nanomagnetics

- Nanomechanics

- Filtration and Membranes

- Nanotools (for manipulation, nanolithography and nanofabrication)

- Nanoinstruments or devices (for observation, analysis or control)

- Catalysis

- Software for modelling and simulation

36. Based on the ISO Working Definition , ISO (2005).

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The nanotechnology patent classification scheme

52. In 2003, the European Patent Office (EPO) developed a patent tagging system Y01N,37 which was advanced into a set of IPC Subclasses in 2011.38 The full list of IPC Codes uniquely assigned to nanotechnology patents is given in Table 6 below.

Table 6. List of IPC Patent Codes uniquely assigned to Nanotechnology Patents

IPC Patent Code Title

B82Y5 Nanobiotechnology or nano-medicine B82Y10 Nanotechnology for information processing, storage and transmission B82Y15 Nanotechnology for interacting, sensing and actuating B82Y20 Nanotechnology for optics B82Y25 Nanomagnetism B82Y30 Nanotechnology for materials and surface science B82Y35 Methods or apparatus for measurement or analysis of nanostructures B82Y40 Manufacture or treatment of nanostructures

37 . Scheu, M., V. Veefkind, Y. Verbandt, E. Molina Galan, R. Absalom W. and Förster (2006), “Mapping nanotechnology patents: The EPO approach”, World Patent Information, 28, 204-211.

38. EPO (2013), Nanotechnology and Patents, http://documents.epo.org/projects/babylon/eponet.nsf/0/623ECBB1A0FC13E1C12575AD0035EFE6/$File/ nanotech_brochure_en.pdf

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