Genetically Modified Microorganisms

A synthetic biology perspective

A subset of SynBio - genetically modified microorganisms (GMOs) related patents were identified during the hybrid topic modelling stage applied to SynBio EPO patents. The publication year trends are shown in figure .1, together with the subset of GMOs related to recombinant proteins and nucleic acid production, etc. Publication trends discussed below are based on EP A1/A2 applications.

In figure 7.1, the peak publication figures for SynBio genetically modified microorganisms occurred in 2023 (1918 publications), with a compound annual growth rate (CAGR) of 14% during 2014-2023. The subset related to the production, etc. of recombinant proteins & nucleic acids also peaked in 2023 (654 publications) with a CAGR of 13.6% during 2014-2023. The recombinant proteins & nucleic acids related subset accounted for 37.8% of the total genetically modified microorganisms topic publications during 2004-2023. The recent evidence suggests strong growth of SynBio based applications for genetically modified microorganisms.

The INPADOC legal status breakdown of the genetically modified microorganisms subset published during 2014-2023 is shown in figure 7.2.

The INPADOC based legal status stats in figure 7.2 revealed approx. 57% of patents are pending with 23% already granted, reflecting an established and growing field. The legal status data suggests the topic has a large proportion of alive patents (80%) and the high pending proportion (57%) indicates the potential for further growth.

Publication year subtrends

The publication trends for further subtopic areas were investigated in the genetically modified microorganisms topic; Enzyme (compositions & genetic engineering, etc.), Vaccine related, CRISPR and gene expression regulation, shown in figure 7.3.

The subtrends reveal how genetically modified microorganisms (GMOs) are engineered via CRISPR with explosive growth since 2014 (50.7% CAGR). The regulation of gene expression within microorganisms has also exploded with 283 publications in 2023 (28.8% CAGR). There exists similar growth for vaccine related applications (18.3% CAGR). The recent publication trends for enzyme related applications has more than doubled when comparing 2017 with 2023 (323 publications).

The filing trends for the genetically modified microorganisms subset and subtrend areas are shown in figure 7.4. 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 7.4, there exists strong growth for genetically modified microorganisms (GMOs) and the subtrend areas identified. Overall, GMOs filings increased by 10.4% year-on-year in 2021. The recombinant proteins and nucleic acids accounted for approx. 36% of the identified GMOs patent filings during 2004-2021. There is further evidence the innovation of genetically modified microorganisms plus the bioproducts produced and engineered are increasing, based on recent trends in figures 7.3 & 7.4.

In figure 7.5, the distribution of top 20 CPC classification codes is skewed towards genetic engineering, in particular viral vectors (C12N15/86), which peaked in 2023 with 1089 publications, more than double the next classification area. The class descriptors are manually refined for readability, the counts are cumulative publications and publication year based.

The top 20 analysis reveals therapeutic applications such as medicinals comprising genetic material, antineoplastic agents and gene therapy, etc. Viral vectors such as E.coli (C12N15/70) is a prominent microorganism peaking in 2022 along with Dependovirus in particular adeno-associated virus (AAV) (C12N2750/14143) which peaked in 2023 (520 publications). Innovation is also occurring outside of viral vectors, etc. with bacterial isolates (C12N1/205) positioned in the top 10.

Growing areas within SynBio - genetically modified microorganisms: compound annual growth rate (CAGR)

The SynBio genetically modified microorganisms related CPC classifications were further investigated to identify areas with a positive compound annual growth rate (CAGR) to identify trending areas, shown in figure 7.6. The selected classes have a cumulative total above 500 publications (due to the number of candidates) during the publication period and are relevant for SynBio subject matter.

Citing patent counts and prominent assignees were used to identify influential patents within the classification codes and highlight specific areas identified in figure 7.6, as follows:

  • T-cell receptor & Chimeric antigen receptors
    The therapeutic classification codes in these areas were found to be growing at high CAGR rates (published 2014-23). For example, immunotherapy related e.g. chimeric antigen receptors grew at 70.1% CAGR. Example patents include EP3660029A1 (UNIV PENNSYLVANIA) disclosing a t-cell transfected with a retroviral vector expressing an anti-CD19 chimeric antigen receptor to treat cancer. EP4026909A1 (NOVARTIS) disclosing a chimeric antigen receptor (CAR) specific to mesothelin, vectors encoding the same, and recombinant T cells comprising the mesothelin CAR.

  • Escherichia coli (E.coli)
    The specific E.coli genetic engineering classification code grew at 9.3% CAGR and were found to be used for recombinant protein, fusion protein and antibody production, vaccine applications etc. amongst others. Whilst E.coli is an important microorganism / vector for therapeutic uses, it is also important for biofuels. For example, EP3591056 (GENOMATICA) discloses a bacteria such as E.coli having a 1,3-butanediol pathway for biofuels. EP4296364A2 (GENOMATICA) discloses microorganisms such as E.coli for improving product yields in methanol using acetyl-COA synthesis.

  • Yeasts – genetic engineering
    The specific yeast genetic engineering classification code growing at 6.1% CAGR was also allocated to patents for recombinant protein / nucleic acids production, etc. plus enzyme composition and genetic engineering, amongst many other topics. An important non-therapeutic area includes biofuels; EP3752626A1 (NOVOZYMES) discloses improved yeast for ethanol production from starch-containing material and EP3551759A1 (NOVOZYMES) discloses producing ethanol from xylose-containing cellulosic substrates using engineered yeast strains. There exists a small portfolio related to waste processing such as EP3483279A1 (LALLEMAND) disclosing recombinant microorganism comprising a deletion of one or more native enzymes that function to produce glycerol and/or regulate glycerol synthesis using a carbohydrate source which can include lignocellulosic biomass such as agricultural wastes, etc.

  • Bacterial isolates
    Multiple topic areas were identified, of specific interest are: Probiotic bacteria applications including the UK company EP3713642A2 (OPTIBIOTIX) disclosing a Lactobacillus spp. selective prebiotic composition. Biofuels such as EP3623465A2 (GENOMATICA) disclosing genetically engineered bacteria, producing products from the fatty acid biosynthetic pathway. EP3693468 (LANZATECH) disclosing improved capturing of carbon by microbial fermentation of a gaseous substrate comprising CO, which could be used in processes for producing alcohols, particularly ethanol, from industrial waste streams. Processing of industrial wastes such as EP3728614 (LANZATECH) which discloses genetically engineered microorganisms and methods for the biological production of ethylene glycol.

Growing areas within SynBio - genetically modified microorganisms: average growth rate

The average number of publications during two 5 year publication periods; 2014-18 & 2019-23 are contrasted in figure 7.7. The CPC classification codes within the genetically modified microorganisms topic, related to SynBio and with sufficient publication totals are analysed.

In figure 7.7, the use of viral vectors and engineering viral genomes have exhibited the fastest average growth rates when contrasting 2014-18 with 2019-23. The specific genus Dependoparvovirus (formerly Dependovirus or Adeno-associated virus group) which can be engineered for gene therapy and the species Escherichia coli, a SynBio workhorse across therapeutics and biofuels, have increased rapidly. The Dependoparvovirus publications, almost increasing by 4.5 times during 2019-2023 to 358 publications per year on average and E.coli roughly doubling to 219 publications on average per year. These figures could likely be higher if further specific classification codes were grouped but act as a sufficient proxy to measure average rate of growth.

SynBio - genetically modified microorganisms: top 30 applicants

The total number of publications for the top 30 SynBio genetically modified microorganisms related applicants are shown in figure 7.8, contrasting the overall publication period (2004-23) with a more recent perspective during 2014-2023.