Durgesh Mukharya Sneha Menon September 15 2021 Untapped potential of CRISPR in India: IP perspective K&S Partners | Healthcare & Life Sciences - India Durgesh Mukharya, Sneha Menon Healthcare & Life Sciences IntroductionGlobal CRISPR patent trendsCRISPR in IndiaOpportunities that lie aheadIntroductionClustered regularly interspaced short palindromic repeats (CRISPR), one of the most talked-about technologies of the decade whose developers were awarded the Nobel Prize in Chemistry in 2020, is essentially a product of the efficient adaptation of a bacterial immune mechanism against invading viruses into a gene-editing tool in higher organisms. CRISPR enables alterations at genomic level with high specificity and accuracy. From healthcare and agriculture to the energy sector, the applications of CRISPR have made it one of the most promising gene-editing technologies to date, with further applications being constantly explored by scientists to achieve new heights in scientific innovation.Surprisingly, unlike other contemporary technologies, CRISPR has reached the vocabulary of individuals even outside the scientific community over the years. The merits of the technology aside, what has also garnered a lot of attention are the ethical concerns pertaining to its in vivo applications and the long-fought patent disputes over its application in eukaryotes.Global CRISPR patent trendsWhile these debates around the technology continue, worldwide patent filing trends in this domain, based on published data, indicate that several organisations have jumped on the CRISPR bandwagon in the past few years. While the top players in this domain in terms of patent filings have primarily remained the same over the years, the emergence of newer players, including pharma giants, further highlights the spurt of interest in the technology (Figure 1). This is not surprising since its high degree of precision makes CRISPR an obvious choice in the field of gene editing.Figure 1: key players in terms of CRISPR patent filings(1)While patent filings on the gene-editing applications of CRISPR seem to have gained real momentum from 2012 onwards, 2017 saw a peak in worldwide filings. This spurt in filings appears equally applicable even to the relatively smaller subsets such as Patent Cooperation Treaty (PCT) filings and filings at the IP5 patent offices (ie, those of Europe, Japan, South Korea, China and the United States) (Figures 2–4).Figure 2: worldwide filings of CRISPR patentsFigure 3: PCT filings of CRISPR patentsFigure 4: filings of CRISPR patents in IP5 countriesCRISPR in IndiaWith all the excitement surrounding CRISPR, a similar trend in terms of technology development as well as patent filings might have been expected in India, which could, in particular, be a potential market for applications of CRISPR in sectors such as healthcare and agriculture. However, developments around intellectual property on CRISPR are yet to gather momentum in India, with the overall number of patent filings forming a very small fraction of what is seen abroad (Figure 5). This is not particularly surprising since jurisdictions such as the United States, Europe, China and Japan are known for their heavy investments in research in upcoming technologies and strong emphasis on intellectual property. Moreover, patents in these jurisdictions often have a heavy bearing on the licensing opportunities that follow.Figure 5: number of patent filings in India compared with IP5 countriesFurther, while foreign entities form the major share of patent applicants in India, there have been relatively fewer filings by them as well in this domain in India (Figure 6).Figure 6: key players in terms of CRISPR patent filings in IndiaAs to why the numbers do not match up to global standards, while this could partly be in view of India only slowly emerging as a potential market, it could also be due to factors such as apprehension surrounding patent protection possibilities and the regulatory environment for CRISPR-related inventions in India. For instance, the Indian patent system has been subject to intense scrutiny over the years for its provisions that determine the patent ineligible subject matter, potentially creating a negative impression about the patenting environment in the country.While some provisions under section 3 of the Patents Act bar certain types of claims, an important aspect to consider here is that the Act does not pose serious impediments to claimable subject matter, especially in the context of CRISPR technology. Feasible claims include those relating to CRISPR/guide ribonucleic acid (gRNA) sequences – which would be of prime significance, given the design-oriented nature of the technology – and the methods employing the sequences in in vitro applications such as methods of modifying cells or genetic elements through CRISPR. Also realisable are claims relating to new non-naturally occurring endonucleases such as variants or alternatives of the existing Cas enzymes that facilitate CRISPR mediated cleavage.Aspects excluded from patentability in India are fewer and less significant, such as those that could raise ethical concerns surrounding the in vivo applications of the technology – for example, gene editing in human embryos, stem cells and germ-line stem cells or gametes (section 3(b) of the Patents Act) – or those that could potentially prohibit a medical practitioner and involve methods of treatment (section 3(i) of the Patents Act). These limitations would not restrict a patentee from commercialising inventions such as those based on CRISPR sequences or accompanying endonucleases that together confer flexibility of target recognition and cleavage – aspects which form the crux of the technology. Those familiar with this field would understand that obtaining protection on the CRISPR RNA sequences or the enzyme for genetic modification, delivery vectors, in vitro methods of gene manipulation and potential optimisation techniques and applications arising therefrom would provide sufficient leverage to a patentee to safeguard its interest and prevent trespassing by infringers in India.These possibilities around intellectual property relating to CRISPR also do not seem to be sufficiently recognised by the Indian entities, as the number of Indian applicants filing CRISPR-related patent applications remains extremely low. While this may be reflective of lesser work on this front in India, the lower number of filings may also be attributable to research work that is yet to be published or preference towards literature over patents. Further deterrents could include:significant upfront research and development costs;long incubation time;the existence of fewer and younger deep tech companies willing to invest in the technology; andpotential licensing obligations towards the original inventors.While most of these deterrents are universally applicable, some inspiration may be drawn from the manner in which young companies in the West have been able to carve their niche in this space, with entities such as CRISPR Therapeutics, Editas Medicine, Intellia Therapeutics, Poseida Therapeutics and Beam Therapeutics going public over the past few years.In a sense, CRISPR has been a catalyst in bringing back the biotech boom. Recognising the potential applications of gene editing, India is taking measures to make the ecosystem more conducive for the ethical exercise of technologies such as CRISPR. One such example lies in the issuance of the draft National Guidelines for Gene Therapy Product Development & Clinical Trials in early 2020 by the Indian Council of Medical Research (ICMR), the Department of Biotechnology (DBT) and the Central Drugs Standard Control Organisation (CDSCO), which provides general principles for the development and applications of genome-editing technologies such as CRISPR, while laying down guidelines to address the safety and security concerns surrounding this field. Further, the DBT is also promoting and prioritising research and development in the field of genome engineering technologies such as CRISPR and their applications.(2)Opportunities that lie aheadWhile many Indian institutes have been active with projects on CRISPR and its related applications, and with those such as Institute of Genomics and Integrative Biology (CSIR-IGIB) and InStem being recognised globally for their research in this domain, if the patent filing trends were to qualify as a yardstick, there appears to be a fair degree of untapped potential.A success story in the present context has been the approval of the commercial launch of "Feluda", the Tata CRISPR covid-19 test, by the Drugs Controller General of India, on which corresponding patent applications have also been filed. The test is reported to be significantly faster, cheaper and uncomplicated in comparison to a reverse transcription polymerase chain reaction diagnosis, showcasing marked improvement in sensitivity and specificity of detection. While this addresses the need of the hour, applications such as these, eligible for IP protection, also serve as a push for continued innovation around CRISPR towards solving real-world problems, many potentially being indigenous to India. Such applications could include:enhancing the agricultural yield, drought tolerance and nutritional value of crops;engineering mosquitos for eliminating diseases such as malaria;diagnosing and treating cancers, diabetes and population-specific disorders such as sickle cell anaemia; anddetecting the effect of pollutants on human health.Specifically in the field of agriculture, improving the awareness and public perception of applications of gene editing (ie, modification of existing genes) as opposed to conventional genetically modified products (ie, those which contain foreign genes) may also help open avenues in terms of research and commercial opportunities. With the projected value of the worldwide CRISPR market reaching close to $5 billion by 2027, the expectation is for CRISPR technology to be increasingly worked on. Moreover, with the evolution of the patent system in India, and with the government's focus on making the Indian IP system stronger by the day, it is hoped that there will be innovation in this domain translating into higher volumes of patent filings in the Indian jurisdiction.CRISPR therefore clearly holds the potential to foster a stronger culture of research and innovation in India to generate cutting-edge solutions across multiple sectors. Researchers and organisations must be encouraged to view this potential through the prism of intellectual property to leverage their inventions in this domain strategically.For further information on this topic please contact Durgesh Mukharya or Sneha Menon at K&S Partners by telephone (+91 80 4042 7900) or email ([email protected] or [email protected]). The K&S Partners website can be accessed at www.knspartners.com.Endnotes(1) The graphs and trends referred to in this article have been derived from a keyword-based search on Derwent Innovation restricted to the text fields of title, abstract and claims for the purposes of relevance, for patent applications having earliest priority date between 1/1/2012-27/08/2021. The graphs reflect data based on published patent applications. Since recently filed applications may be awaiting publication, there could be a change in trends from 2019 onwards.(2) For further information please click here.