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Aug 06, 2023ADC Technology Market: Focus on ADC Linker and ADC Conjugation Technologies
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INTRODUCTION. The ADC technology market, comprising of ADC linker and antibody conjugation technologies is expected to grow at compounded annual growth rate (CAGR) of ~15% during the forecast period.
New York, July 31, 2023 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "ADC Technology Market: Focus on ADC Linker and ADC Conjugation Technologies - Distribution by Generation of ADC Technology, Type of Conjugation, Type of Linker and Key Geographical Regions: Industry Trends and Global Forecasts, 2023-2035" - https://www.reportlinker.com/p06481107/?utm_source=GNW Antibody drug conjugates have emerged as a promising alternative to the conventional anti-cancer therapies. Till date, around 14 ADCs have received the USFDA approval, while over 420 antibody drug conjugates are currently being evaluated under different stages of development. , Antibody drug conjugate is a complex and versatile class of biotherapeutics, in which linker moiety is attached to the cytotoxic payload. However, the complex structure and design of antibody drug conjugates poses a greater challenge in overall tolerability and efficacy of the molecule. , As a result, more advanced and efficacious antibody drug conjugate technology is required to generate the controlled assembly of antibody drug conjugates while maintaining tolerability and safety profiles. Antibody / ADC conjugation technologies generally involve modification / engineering of an antibody in order to conjugate it with a payload / linker-drug moiety. , On the other hand, ADC linker technologies involve development of a structural moiety to link the payload with an antibody in a reliable manner with desired payload delivery mechanics. , These technologies are optimized to produce homogenous antibody drug conjugate with high drug to antibody ratio (DAR). In fact, ADCs developed using these technologies have demonstrated improved stability and efficacy in tumor micro-environment. Homogenous ADCs with optimized linker technologies offer reduced immunogenicity, enabling the targeted delivery of linker-payload complex at the desired site without having any side effects. , , Owing to the aforementioned advantages, several start-ups and established players have entered the field of ADC linker and conjugation technologies, offering novel conjugation / bioconjugation technologies, more potent payloads and advanced linker chemistries. , These players have inked several licensing agreements to advance their ADC development programs. It is worth mentioning that researchers and antibody drug conjugate developers are actively relying on ADC linker and conjugation technology companies that offer technical expertise and experience in this market. Driven by the growing demand for antibody drug conjugates, the ADC linker and conjugation technologies market is anticipated to witness substantial growth during the forecast period.SCOPE OF THE REPORTThe market report features an in-depth analysis, highlighting the capabilities of various stakeholders engaged in this industry. Amongst other elements, the report includes: An executive summary of the key insights captured during our research, offering a high-level view on the current state of the ADC linker and antibody conjugation technologies market and its likely evolution in the short to mid and long term. A brief introduction to the concept of antibody drug conjugates, its various components, mechanisms of action and advantages over traditional targeted therapies. The chapter emphasizes the role of ADC linker and antibody conjugation technologies in the development of ADC therapeutics. Subsequently, it provides an overview of different types of linkers and conjugation technologies, listing their specifications. It also features a brief discussion on the challenges related to the development of associated technologies, offering insights on anticipated future trends. A detailed review of the overall landscape of ADC linker and conjugation technologies, based on a number of parameters, such as type of technology (antibody conjugation technology, linker technology, linker-payload technology, and antibody linker and conjugation technology), availability of licensing, generation of technology (first-generation, second-generation, third-generation and next-generation), site specificity (site specific, non-specific , and both, site specific / non-specific), type of conjugation (chemical, chemoenzymatic and enzymatic), drug antibody ratio, compatible linker (cleavable, non-cleavable, and both, cleavable / non-cleavable), conjugation chemistry (cysteine-based, click chemistry, lysine-based, transpeptidation using enzymes, maleimide-based, glycan conjugation and others), conjugation site (engineered, modified, endogenous and exogenous), type of linker (cleavable, non-cleavable, and both, cleavable / non-cleavable). It also includes information on ADC linker and antibody conjugation technology companies, based on several parameters, such as their year of establishment, company size (small, mid-sized and large) and location of headquarters (North America, Europe, and Asia-Pacific and rest of the world). An in-depth technology competitiveness analysis of ADC linker and conjugation technologies, segmented into three categories, namely small (2-50 employees), mid-sized (51-500 employees) and large (>500 employees) players. Within the respective peer groups, technologies were ranked based on various relevant parameters, such as portfolio strength (based on the years of experience), technology competitiveness (based on parameters, such as status of technology, availability of licensing, generation of technology, site specificity, type of conjugation, drug antibody ratio, compatible linker, conjugation chemistry, conjugation site and drugs developed using a technology), as well as partnership activity (in terms of number of partnerships). The analysis was designed to enable stakeholder companies to compare their existing capabilities within and beyond their respective peer groups and identify opportunities to achieve a competitive edge in the industry. Tabulated profiles of prominent companies that are currently engaged in offering ADC linker and ADC conjugation technologies. Each profile features a brief overview of company (with information on year of establishment, number of employees, location of headquarters and key members of the leadership team), details related to their respective technology portfolio, recent developments and an informed future outlook. A detailed review of the patents that have been filed / granted for ADC linker and ADC conjugation technologies during the time period 2018-2023, based on important parameters such as, type of patent, publication year, application year, number of granted patents and patent applications, patent jurisdiction, focus area, CPC symbols, patent age, type of applicant (on the basis of number of patents), and individual patent assignees (in terms of size of intellectual property portfolio). It also features a detailed patent benchmarking analysis and an insightful patent valuation analysis, highlighting the leading patents (in terms of number of citations). An analysis of the partnerships inked between various stakeholders in this industry, during the period 2014-2023, featuring a detailed set of analysis based on various parameters, such as year of partnership, type of partnership, type of partner, generation of technology, type of linker, type of conjugation, target therapeutic area(s), most popular technologies, most active players and geographical location of the companies. An insightful analysis on business models adopted by various technology providers engaged in this industry along with the information on parameters, such as year of partnership, purpose of partnership (merger / acquisition, product commercialization, product development, product distribution, research, research and development, technology / product integration, technology transfer), type of business model adopted (technology-out licensing, technology-in licensing, product out-licensing, product in-licensing, collaborative research and others), type of investment (upfront payments and milestone payments), amount invested and most active players. An in-depth analysis of over 85 antibody drug conjugate therapeutics developers that are likely to partner with ADC linker and conjugation technology companies in the near future, based on several relevant parameters, such as developer score (based on year of establishment and company size), portfolio score (based on type of linker and antibody structure), pipeline score (based on stage of development of a drug and number of pre-clinical molecules) and therapeutic area. An insightful brand positioning analysis of prominent antibody conjugation technology providers (shortlisted based on the number of conjugation technologies developed), highlighting the current perceptions regarding their proprietary technologies by taking into consideration several relevant aspects, such as experience of the technology provider, number of technologies offered, product diversity, number of patents and number of partnerships. A detailed case study on overall landscape of the antibody drug conjugates market, based on a number of parameters, such as stage of development, target disease indication, therapeutics area, line of treatment, dosing frequency, type of therapy, target antigen, antibody isotype, payload / cytotoxin / warhead, payload type, type of linker, type of linker (cleavable / non-cleavable). It also features details on antibody drug conjugate developers, including information on their year of establishment, company size and location of headquarters and most active players. A detailed market forecast analysis to estimate the existing market size and the future opportunity for ADC linker and antibody conjugation technologies supporting ADC development, during the given forecast period, 2023-2035. The overall opportunity has been distributed across various segments, such as generation of technology (third-generation, second-generation, and next-generation), type of conjugation (chemical, chemoenzymatic and enzymatic), type of linker (cleavable and non-cleavable), and key geographical regions (North America, Europe, Asia-Pacific and rest of the world). In order to account for future uncertainties and to add robustness to our model, we have provided three forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industry’s growth.The opinions and insights presented in the report were influenced by our discussions with senior stakeholders in the industry. The market research report features detailed transcripts of interviews held with the following industry stakeholders: Cedric Lizin (Board Member, Singzyme) Jiaqiang Cai (Co-Founder and Chief Scientific Officer, MedLink Therapeutics) Kai Uhrig (Head of Strategy and Business Development, Merck KGaA) Saptarshi Ghosh (Scientist II, Abzena) Mary Chaohong Hu (Chief Executive Officer, Miracogen) Floris van Delft (Chief Scientific Officer, Synaffix) Jan Modregger (Head of Research and Development, Eucodis Bioscience) Okuzumi-Tatsuya (General Manager, Research and Development, Ajinomoto) and Brian Mendelsohn (Director of ADC Process Development and Tech Transfer, Ajinomoto) Wouter Verhoeven (Former Chief Business Officer, NBE-Therapeutics)All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.KEY MARKET INSIGHTSThe Antibody Drug Conjugates: Focus on ADC Linker and Conjugation Technologies (2nd Edition) - Distribution by Generation of Technology (Third-Generation, Second-Generation and Next-Generation), Type of Conjugation (Chemical, Chemoenzymatic and Chemical), Type of Linker (Cleavable and Non-Cleavable), and Key Geographical Regions (North America, Europe, and Asia-Pacific and Rest of the World): Industry Trends and Global Forecasts, 2023-2035 report features an extensive study of the current market landscape, market size and future opportunities associated with the ADC linker and antibody conjugation industry, during the given forecast period. The report highlights efforts of several stakeholders engaged in this rapidly emerging segment of the pharmaceutical industry. Key takeaways of the ADC technologies market are briefly discussed below.Rising Interest in ADC linker and Antibody Conjugation Technology for the Development of Homogenous Antibody Drug ConjugateIn 2000, the USFDA approved the first ADC, Mylotarg . However, it was withdrawn voluntarily from the market due to safety concerns and poor clinical benefits of the product. With continued research in the area of ADCs, innovators have identified various factors that determine the success of an antibody drug conjugate; these include structure and design of an antibody drug conjugate, systemic toxicity, validation of tumor biomarkers, choice of antibody and potency of the payload. , The challenges associated with conventional drug products have led to the development of advanced ADC linker and ADC conjugation technologies. These technologies have the potential to develop antibody drug conjugates with improved stability and toxicity profile, while maintaining efficient release of the cytotoxic payload at the desired location. The most important characteristic of these technologies is the production of controlled, homogenous ADCs, which are site-selective and can be utilized as a targeted anti-cancer therapy. We anticipate that the growing demand for targeted, stable and non-toxic ADCs will continue to drive the adoption and growth of linker technology and antibody conjugation technologies for development of ADC during the forecast period.Current Market Landscape of ADC TechnologiesThe ADC technologies market landscape features an extensive list of over 65 large, mid-sized and small companies that offer more than 95 ADC linker and conjugation technologies. These platforms include linker technologies, linker-payload technologies and antibody conjugation technologies for the development of ADC. It has been observed that the majority of the antibody drug conjugates generated via these technologies are site specific, have high tolerability and precise DAR ratio. In addition, we believe that third-generation technologies are poised to play a significant role in shaping the future market landscape, by enabling the development of new therapeutic modalities that were previously considered unattainable. The constant evolution of ADC linkers and conjugation technologies will support the development of novel and more efficacious ADCs. In turn, the growing ADC therapy market will drive the demand for these technologies, contributing to substantial CAGR of ADC technology market during the forecast period.ADC Technology Market SizeThe ADC technology market, comprising of ADC linker and antibody conjugation technologies is expected to grow at a CAGR of ~15% during the forecast period. Driven by the growing interest of stakeholders in addressing the efficiency and safety related concerns with antibody drug conjugates, the ADC linker and conjugation technologies market is anticipated to witness tremendous growth in the foreseen future.Based on mechanism of drug release, the linkers are categorized as cleavable or non cleavable linkers. Majority of the approved ADCs use cleavable linkers and based on the current late-stage pipeline of ADCs, the global ADC technology market is anticipated to be driven by cleavable linkers in the short term.North America and Europe to Compete for the Largest Share of ADC Linker and Antibody Conjugation Technologies MarketClose to 80% of the market share is estimated to be captured by companies based in North America and Europe. This can be attributed to the escalating partnership activity in these regions. It is interesting to note that 78% of the total deals were inked by players based in North America and Europe during the time period, 2014-2023. Further, some of the companies based in these developed regions, such as Mersana Therapeutics, Seattle Genetics and Zymeworks offer several antibody conjugation and ADC linker technology / platforms. These platforms are either second-generation or third-generation technologies that offer chemical site specific conjugation. Moreover, all these players have in-house ADC portfolio for testing the potential of their technologies and resulting in the development of innovative cancer therapies.Adoption of Different Business Models by the ADC Linker and Antibody Conjugation Technology CompaniesThe growing demand for antibody drug conjugates for the treatment of various forms of cancer, especially breast cancer, has paved the way for continued innovation in antibody conjugation technologies. In order to access these advanced technologies for the development of antibody drug conjugate, several business deals have been inked over the past few years. It is interesting to note that technology out-licensing and collaborative research are the most popular type of business models adopted by stakeholders in this industry. It is worth highlighting that Synaffix has received / is likely to receive close to USD 5.5 billion from out licensing their ADC conjugation platform. In June 2023, Lonza acquired Synaffix, getting access to the latter’s ADC technologies for payload and site-specific linkers. Another company, Mersana Therapeutics expects to receive nearly USD 2 billion in total payments from their collaborative research efforts with several stakeholders engaged in ADC development. Substantial investments like these, along with ongoing technological innovations, will act as the key driver behind the evolution of ADC linker and antibody conjugation technologies market during the forecast period.Partnership Activity in ADC linker and ADC Conjugation Technologies MarketIn recent years, several partnerships have been inked by various stakeholders in order to consolidate their presence and enhance their capabilities and product portfolio to meet the growing demand for antibody drug conjugates. In fact, the partnership activity has witnessed a CAGR of ~30% in the past three years. Licensing agreements, product development agreements, and research and development agreements are the most common types of partnerships that have been inked in this industry.In March 2022, Seattle Genetics entered into a research and development agreement with Sanofi for the development of three targets, focused on targeting cancer. In addition, it was observed that Mersana Therapeutics has signed several deals over the past few years for the development of various ADC candidates, targeting a wide array of cancers, including breast cancer, gastric cancer and non-small cell lung cancer. The growing interest in novel antibody drug conjugates and rising number of deals focused on advancing conventional therapies for targeting various oncological indications will continue to drive the ADC technology market over the coming years.Key Players in the ADC Conjugation Technologies MarketExamples of key players engaged in this industry (which have also been profiled in this report) include (in alphabetical order), Alteogen, Ambrx, Antikor, Catalent Biologics, Heidelberg Pharma, Iksuda Therapeutics, LegoChem Biosciences, Mersana Therapeutics, NBE-Therapeutics, Seattle Genetics and Sutro Biopharma.RESEARCH METHODOLOGYThe data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market will evolve across different regions and technology segments. Wherever possible, the available data has been checked for accuracy from multiple sources of information.The secondary sources of information include: Annual reports Investor presentations SEC filings Industry databases News releases from company websites Government policy documents Industry analysts’ viewsWhile the focus has been on forecasting the market over the coming 12 years, the report also provides our independent view on various technological and non-commercial trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant markets, gathered from various secondary and primary sources of information.FREQUENTLY ASKED QUESTIONSQuestion 1: What is antibody conjugation technology?Answer: Antibody conjugation technology refers to a technology that is designed to increase the absorption of cytotoxic drug molecules at the desired location, resulting in the formation of site specific homogenous antibody drug conjugates.Question 2: What is an ADC linker?Answer: Linker is one of the components of an ADC. It helps in connecting antibody with the cytotoxic payload.Question 3: What types of linkers are used in antibody drug conjugates?Answer: Two types of linkers are used in ADCs; cleavable linkers, which release the cytotoxic payload near the desired location resulting in killing of the tumor and neighboring cells and non-cleavable linkers, which release the potent payload at the desired site minimizing off-site toxicity.Question 4: What is site specific conjugation of ADC?Answer: Site specific conjugation of ADC refers to attaching the linker to a defined site on an antibody resulting in the production of homogeneous and controlled structures of antibody drug conjugate.Question 5: What are the technologies used in ADC?Answer: Antibody drug conjugate industry conventionally use three technologies; first-generation, second generation and third generation. However, now-a-days, next generation technologies are also emerging, offering development of site specific ADCs.Question 6: What are the key factors driving the ADC linker and antibody conjugation technologies market?Answer: The ADC linker and antibody conjugation technologies market is currently driven by the growing prevalence of oncological disorders, ageing population and increased interest of researchers in novel therapeutic interventions.Question 7: Which types of partnerships are forged by ADC linker and ADC conjugation technology providers?Answer: Licensing agreements, product development and R&D agreements are the most common partnership models adopted by stakeholders engaged in the ADC linker and conjugation technologies market.Question 8: Which are the leading technology providers in the ADC conjugation market?Answer: Leading technology providers include Alteogen, Ambrx, Antikor, Catalent Biologics, Heidelberg Pharma, Iksuda Therapeutics, LegoChem Biosciences, Mersana Therapeutics, NBE-Therapeutics, Seattle Genetics and Sutro Biopharma.Question 10: Which region has the highest market share in ADC linker and conjugation technologies market?Answer: North America and Europe capture around 80% share in the global ADC linker and conjugation technologies market. Emerging regions, such as Asia-Pacific, are likely to grow relatively fast in the long term.Question 11: What is the likely growth rate (CAGR) of ADC linker and conjugation technologies market?Answer: The global market size for ADC linker and ADC conjugation technologies is anticipated to grow at a compound annualized growth rate (CAGR) of ~15% during the forecast period 2023-2035.CHAPTER OUTLINESChapter 1 is a preface providing an introduction to the full report, ADC linker and Conjugation Technologies Market (2nd Edition), 2023-2035.Chapter 2 is an executive summary of the key insights captured in our research. It offers a high-level view on the current state of ADC linker and conjugation technologies market and its likely evolution in the short to mid and long term.Chapter 3 provides a general overview of the concept of ADC, its various components, mechanisms of action and advantages over traditional targeted therapies. The chapter emphasizes the role of linker and conjugation technologies in the development of ADCs. Subsequently, it provides an overview of the different types of linkers and conjugation technologies, listing their specifications. It also features a brief discussion on the challenges related to the development of associated technologies, offering insights on anticipated future trends.Chapter 4 includes a detailed review of the overall landscape of the ADC linker and conjugation technologies, based on a number of parameters, such as type of technology (antibody conjugation technology, linker technology, linker-payload technology, and antibody linker and conjugation technology), availability of licensing, generation of technology (first-generation, second-generation, third-generation and next-generation), site specificity (site specific, non-specific , and both, site specific / non-specific), type of conjugation (chemical, chemoenzymatic and enzymatic), drug antibody ratio, compatible linker (cleavable, non-cleavable, and both, cleavable / non-cleavable), conjugation chemistry (cysteine-based, click chemistry, lysine-based, transpeptidation using enzymes, maleimide-based, glycan conjugation and others), conjugation site (engineered, modified, endogenous and exogenous), type of linker (cleavable, non-cleavable, and both, cleavable / non-cleavable). It also includes information on ADC linker and antibody conjugation technology companies, based on several parameters, such as their year of establishment, company size (small, mid-sized and large) and location of headquarters (North America, Europe, and Asia-Pacific and rest of the world).Chapter 5 provides in-depth technology competitiveness analysis of ADC linker and ADC conjugation technologies, segmented into three categories, namely small (2-50 employees), mid-sized (51-500 employees) and large (>500 employees) players. Within the respective peer groups, technologies were ranked based on various relevant parameters, such as portfolio strength (based on the years of experience), technology competitiveness (based on parameters, such as status of technology, availability of licensing, generation of technology, site specificity, type of conjugation, drug antibody ratio, compatible linker, conjugation chemistry, conjugation site and drugs developed using a technology), as well as partnership activity (in terms of number of partnerships). The analysis was designed to enable stakeholder companies to compare their existing capabilities within and beyond their respective peer groups and identify opportunities to achieve a competitive edge in the industry.Chapter 6 includes tabulated profiles of prominent companies that are currently engaged in offering ADC linker and ADC conjugation technologies. Each profile features a brief overview of company (with information on year of establishment, number of employees, location of headquarters and key members of the leadership team), details related to their respective technology portfolio, recent developments and an informed future outlook.Chapter 7 provides a detailed review of the patents that have been filed / granted for ADC linker and conjugation technologies during the time period 2018-2023, based on important parameters such as, type of patent, publication year, application year, number of granted patents and patent applications, patent jurisdiction, CPC symbols, patent age, type of applicant (on the basis of number of patents), and individual patent assignees (in terms of size of intellectual property portfolio). It also features a detailed patent benchmarking analysis and an insightful patent valuation analysis, highlighting the leading patents (in terms of number of citations).Chapter 8 presents an in-depth analysis of the partnerships inked between various stakeholders in this domain, during the period 2014-2023, featuring a detailed set of analyses based on various parameters, such as year of partnership, type of partnership, type of partner, generation of technology, type of linker, type of conjugation, target therapeutic area, most popular technologies, most active players and geographical location of the companies.Chapter 9 provides an insightful analysis on business models adopted by various technology providers engaged in this domain along with the information on parameters, such as year of partnership, purpose of partnership (merger / acquisition, product commercialization, product development, product distribution, research, research and development, technology / product integration, technology transfer), type of business model adopted (technology-out licensing, technology-in licensing, product out-licensing, product in-licensing, collaborative research and others), type of investment (upfront payments and milestone payments), amount of investment and most active players.Chapter 10 presents an in-depth analysis of over 85 antibody drug conjugate therapeutics developers that are likely to partner with ADC linker and conjugation technology companies in the near future, based on several relevant parameters, such as developer score (based on year of establishment and company size), portfolio score (based on type of linker and antibody structure), pipeline score (based on stage of development of a drug and number of pre-clinical molecules) and therapeutic area(s).Chapter 11 includes a detailed brand positioning analysis of prominent antibody conjugation technology providers (shortlisted based on the number of conjugation technologies developed), highlighting the current perceptions regarding their proprietary technologies by taking into consideration several relevant aspects, such as experience of the technology provider, number of technologies offered, product diversity, number of patents and number of partnerships.Chapter 12 presents a detailed case study on overall landscape of the ADC therapeutics market, based on a number of parameters, such as stage of development, target disease indication, therapeutics area, line of treatment, dosing frequency, type of therapy, target antigen, antibody isotype, payload / cytotoxin / warhead, payload type, type of linker, type of linker (cleavable / non-cleavable). It also features details on ADC therapeutics developers, along with the information on their year of establishment, company size and location of headquarters and most active players.Chapter 13 presents an insightful market forecast analysis, highlighting the likely growth of ADC linker and conjugation technologies market till 2035. We have segmented the market across various segments, such as generation of technology (third-generation, second-generation and next-generation), type of conjugation (chemical, chemoenzymatic and enzymatic), type of linker (cleavable and non-cleavable), and key geographical regions (North America, Europe, Asia-Pacific and rest of the world). In order to account for future uncertainties and to add robustness to our model, we have provided three forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industry’s growth.Chapter 14 is a collection of interview transcripts of our discussions with various key stakeholders in this industry. The chapter provides a brief overview of the companies and details of interviews held with Cedric Lizin (Board Member, Singzyme), Jiaqiang Cai (Co-Founder and Chief Scientific Officer, MedLink Therapeutics), Kai Uhrig (Head of Strategy and Business Development, Merck KGaA), Saptarshi Ghosh (Scientist II, Abzena), Brian Mendelsohn (Director of ADC Process Development and Tech Transfer, Ajinomoto), Mary Chaohong Hu (Chief Executive Officer, Miracogen), Floris van Delft (Chief Scientific Officer, Synaffix), Jan Modregger (Head of Research and Development, Eucodis Bioscience), Okuzumi-Tatsuya (Associate General Manager, Research and Development, Ajinomoto) and Wouter Verhoeven (Ex-Chief Business Officer, NBE-Therapeutics)Chapter 16 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.Chapter 17 is an appendix, which contains the list of companies and organizations mentioned in the report.Read the full report: https://www.reportlinker.com/p06481107/?utm_source=GNWAbout ReportlinkerReportLinker is an award-winning market research solution. 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SCOPE OF THE REPORTRESEARCH METHODOLOGYCHAPTER OUTLINES