CRISPR

A synthetic biology perspective

A subset of SynBio - CRISPR related patents were identified during the hybrid topic modelling stage applied to SynBio EPO patents. The publication year trends are shown in figure 10.1, together with the subset related to recombinant proteins and nucleic acids based patents within the CRISPR topic. Publication trends discussed below are based on EP A1/A2 applications.

In figure 10.1, the peak publication figures for SynBio CRISPR occurred in 2023 (651 publications), with a compound annual growth rate (CAGR) of 68.3% during 2014-2023. The CRISPR subset related to recombinant proteins and nucleic acids also peaked in 2023 (432 publications) with a CAGR of 64.1% during 2014-2023. The recombinant proteins and nucleic acids related subset accounted for 69.2% of the total CRISPR topic publications during 2004-2023. The recent evidence suggests explosive growth amongst SynBio CRISPR related publications.

The INPADOC legal status breakdown of the SynBio CRISPR subset published during 2014-2023 is shown in figure 10.2.

The INPADOC based legal status stats in figure 10.2 revealed 70% of patents are pending with approx. 15% already granted. The legal status data suggests the topic has a large proportion of alive patents (85%) and the high pending proportion (70%) indicating the potential for further growth.

Publication year subtrends

The publication trends for further subtopic areas within the CRISPR topic were investigated; gene expression regulation, genetically modified microorganisms, fusion proteins & engineered cells e.g. stem cells, shown in figure 10.3.

All subtrend areas exhibited fast growing publication trendlines for CRISPR technology in gene expression regulation, genetically modified microorganisms, fusion proteins & engineered cells e.g. stem cells. However, there was a levelling off for fusion proteins and engineered cells in 2023. Publications related to genetically modified microorganisms engineered by CRISPR grew at 50.7% CAGR during 2014-23.

The filing trends for the SynBio CRISPR subset and subtrend areas are shown in figure 10.4. Here we explore the filing or application date of published applications, data is restricted to 2021 due to the potential for an 18 month delay between filing and publication.

In figure 10.4, the increasing trendline for SynBio CRISPR filings have grown rapidly peaking in 2021 for CRISPR generally, and the subsets including recombinant proteins & nucleic acids, gene expression regulation and genetically modified microorganisms. However there is a slight drop-off in 2021 for fusion proteins and engineered cells which has influenced the levelling off seen in the publication subtrends (figure 10.3).

The distribution of the top 20 CPC classification codes is skewed towards genetic engineering in figure 10.5. For example, C12N15/113 – Non-coding nucleic acids modulating gene expression, e.g. antisense, C12N15/11 – DNA/RNA fragments, and C12N15/102 – mutagenizing nucleic acids and C12N15/907 – genetic engineering in animal cells, amongst others. The class descriptors are manually refined for readability, the counts are cumulative publications and publication year based.

Overall the SynBio CRISPR publication trend is rapidly growing, numerous classification codes have also peaked either during 2023 or relatively recently, reflecting the rapid growth in this topic, shown in figure 10.5. The diversity of the genetic engineering related classifications are apparent including a variety organisms from animals to viruses (C12N15 codes, etc.) plus the therapeutic influence within immunotherapy (A61K35/117), anti-cancer agents (A61P35/00) and gene therapy (A61K48/00 & A61K48/005). Genetic engineering in viral vectors via CRISPR increased by 44.1% year-on-year to 147 publications in 2023.

Growing areas within SynBio - CRISPR: compound annual growth rate (CAGR)

The SynBio CRISPR related CPC classifications were further investigated to identify areas with a positive compound annual growth rate (CAGR) to identify trending areas, shown in figure 10.6. The selected classes have a cumulative total above 200 publications (due to the number of candidates) during the publication period and are relevant for SynBio subject matter.

In figure 10.6, a large number of genetic engineering classification codes have high CAGR rates during 2014-2023 which is unsurprising given the explosive overall growth of the CRISPR topic. There are also CRISR subtopics such as therapeutic applications involving antineoplastic agents growing at 63.8% CAGR, fusion polypeptides at 55.1% CAGR and medicinals for gene therapy at 44.4% CAGR. Notable patent examples within the classes identified using citing patent counts, top assignees, etc. include EP4286403 (BROAD INSTITUE, ETC.) disclosing CRISPR-CAS component systems and compositions for sequence manipulation. EP3611263 (SIGMA ALDRICH) disclosing CRISPR based genome modification and regulation. From a UK perspective, Tropic biosciences via EP3684929, disclosing modifying the specificity of non-coding RNA molecules for silencing gene expression in eukaryotic cells.

Growing areas within SynBio - CRISPR: average growth rate

The average number of publications during two 5 year publication periods; 2014-18 & 2019-23 are contrasted in figure 10.7. The CPC classification codes within the CRISPR topic, related to SynBio and with sufficient publication totals are analysed.

In figure 10.7, the use of CRISPR with non-coding nucleic acids modulating gene expression e.g. antisense (C12N15/113) grew more than 5 times to 291 publications on average per year during 2019-23. There are numerous genetic engineering related classifications which exhibit solid growth when contrasting average publications during 2014-18 with 2019-23. For example, genetic engineering in mammalian cells (162 publications), viral vectors (99 publications) and animal cells (88 publications). From a therapeutic perspective, gene therapy (106 publications) antineoplastic agents (79 publications) and fusion polypeptides with 42 publications on average per year during 2019-2023. CRISPR related vectors or expression systems specifically adapted for E.coli grew to 20 publications on average per year during 2019-20, representing a niche area of innovation.

SynBio - CRISPR: top 30 applicants

The total number of publications for the top 30 SynBio CRISPR related applicants are shown in figure 10.8, contrasting the overall publication period (2004-23) with a more recent perspective during 2014-2023.