Patenting Opportunities For Synthetic Biology Products In India

While some are still fishing to find a suitable definition for the term "synthetic biology", we may be content to look for the patent eligibility of its application spanning everything from genetic engineering to synthetic chemistry. It is not surprising to find that the first most valuable patent that appeared on the landscape of synthetic biology was for the synthesis of 'Artemisinin' (an anti-malarial lactone) from yeast cells by turning up the controls on the yeast genes that make FPP (a precursor molecule) and turning down the genes that convert FPP into ergosterol. Jay Keasling, the inventor in the patent "Metabolic Engineering of The Shikimate Pathway", played a key role in inventing the synthesis of artemisinin.

Interestingly, the US Patent No. 9540652 for "Metabolic engineering of the shikimate pathway" is valued at $120,000. The second most highly valued patent in the area of synthetic biology is "US20160281113A1" for "Compositions and Methods for Producing Isoprene" (valued at $2,550,000). Curiously, Indian Patent IN284097 for this PCT application was also granted, but with only eleven claims. Originally, 105 claims were filed in India based on PCT applications.

However, the granted 1-6 claims in India were limited to recombinant microbial cells and claims 6-11 were for a method for producing isoprene using recombinant cells. The remaining claims for plant cells were deleted when the Section 3(j) objection was raised by the patent office. Another US10934226B2 patent for "Method and composition for improving plant traits" by Pivot Bio is revolutionising the nitrogen fixation process of non-leguminous crops by providing a microbial solution that enables crops to fix their own nitrogen from the atmosphere.

Synthetic Biology and Startups

Some of the synthetic biology inventions are disrupting traditional Industries. For example, new entrepreneur Ginkgo Bioworks is aspiring to produce high-quality fragrances by using the power of genetic engineering. Another synthetic biology entrepreneur, Zymergen, was not successful in launching Hyaline (bio-manufactured polyimide film made from diamine monomers). Hyaline, a polyimide film material, was transparent and flexible, and it was marketed for use in flexible smartphones and tablets. This product was withdrawn as Hyaline was not successful with customers, and its foldable screen did not have as large of a market as anticipated.

Ginkgo, in view of its drug and vaccine development potential, later acquired Zymergen. In the agriculture field, synthetic biology entrepreneur Pivot Bio provides a microbial solution that enables crops to fix their own nitrogen from the atmosphere, thereby eliminating the need for synthetic fertilisers. Another US10934226B2 patent for 'Method and composition for improving plant traits' by Pivot Bio is revolutionising the nitrogen fixation process of non-leguminous crops by providing a microbial solution that enables crops to fix their own nitrogen from the atmosphere.

In the leather industry a synthetic biology startup Modern Meadow is successful in production of lab-grown leather by using biofabrication techniques to grow collagen, the main component of leather, in the lab. Likewise, many other synthetic biology startups are pushing the boundaries of what is possible and creating a more sustainable and innovative future for synthetic biology. A list of the commercially available synthetic biotech products is given below.

Synthetic Biology Tool: CRISPR/Cas-9 System

The role of gene editing technologies in medicine has greatly impacted future therapies to treat debilitating conditions. Gene editing can modify genes of living organisms and help to improve our understanding of gene function. This would lead to the development of ways to use it to treat genetic or acquired diseases. One such gene editing tool is the CRISPR/Cas-9 system (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9). This tool allows for precision genome editing by cutting DNA in targeted locations for replacement. CRISPR Infographic would be the future of genome editing. The first gene editing therapy utilising CRISPR/Cas-9, named "Casgevy", got approval from the FDA in the US in December of 2023.

Casgevy is a potential treatment for patients suffering from sickle cell disease, known as genetically inherited blood disorder. The emergence of synthetic biology patents relating to CRISPR has led to much talk about the CRISPR-Cas9 battle between the Massachusetts Institute of Technology Broad Institute Inc. and the University of California and others. A quick glance at the litigation chart relating to synthetic biology patents reveals that much talked about the CRISPR-Cas9 patent battle does mark the realisation of the opportunities for synthetic biology innovators to commercialise their inventions in adjacent markets.

US patent US8697359B1 for "CRISPR-Cas systems and methods for altering expression of gene products" obtained by Massachusetts Institute of Technology Broad Institute Inc. was opposed by the University of California, Berkeley, and the University of Vienna with Emmanuelle Charpentier (CVC) on the ground that the patent (filed earlier) by CVC covers methods and compositions for use of CRISPR/Cas9 and chimeric Cas9 in all cell types including eukaryotic cells. Federal Circuit confirmed the PTAB's finding that the Broad Institute's claims were non-obvious regarding "the extent to which the art provided instructions for applying the CRISPRCas9 technology in a new environment".

The court upheld the Patent Trial and Appeal Board (PTAB) decision that Charpentier and Doudna's patent application of May 2012 demonstrated the use of this technology but did not go so far as to claim its use in eukaryotic cells (i.e. CRISPR/Cas-9 gene editing in human cells). Whereas the Broad Institute demonstrated the use of this technology specifically in eukaryotic cells in their December 2012 patent application. The Broad Institute's patent received its first patent on April 15, 2014, for a method of altering eukaryotic cells using technology.

It is interesting to know that both of the research groups have engaged in a continuous battle over many patents over the last 10 years. Both have appealed various patent decisions, with the Patent Trials and Appeals Board (PTAB) and the Federal Circuit continually ruling in favour of the Broad Institute. For instance, in 2017, in one appeal, the Federal Circuit confirmed the PTAB's finding that the Broad Institute's claims were non-obvious regarding "the extent to which the art provided instructions for applying the CRISPRCas9 technology in a new environment". In another decision on February 28, 2022, the Federal Court confirmed that the Broad Institute's team was the first to invent the technology for modifying genomes in human cells.

Under this ruling, Broad's thirteen patents and one application remain in force. At the same time, CVC's fourteen applications with claims directed to gene editing of eukaryotic systems were rejected for lack of priority. This decision favoured Broad as it was able to provide "sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as [University of California's] claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment."

Indian Patents on CRISPR/Cas9 and Chimeric Cas9

The ripple effect of synthetic biology patents was also felt in India, as many patent applications were filed in relation to CRISPR/Cas9 and chimeric Cas9 inventions. For instance, India Patent No. 397884 was granted for 'Methods and compositions for RNA directed target DNA modification and for RNA directed modulation of transcription' to the Regents of the University of California, University of Vienna and Charpentier, Emmanuelle (Assignee: ERS Genomics Limited) on May 27, 2022. This patent covered methods and compositions for the use of CRISPR/Cas9 and chimeric Cas9 in all cell types, including eukaryotic cells. It is interesting to note The Broad Institute Inc. is also actively pursuing granting patents on this synthetic biology field in India.

For instance, Indian patent 403134 for 'Delivery use and therapeutic applications of the CRISPR CAS systems and compositions for targeting disorders and diseases using viral components" (granted on August 5, 2022), Indian patent 479497 for 'Novel CAS13B orthologues CRISPR enzymes and systems' (granted on February 8,.2023), Indian patent 418414 for 'A composition for treating an ocular genetic disease comprising a CRISPR-Cas system' (granted on January 18, 2024) and Indian patent 508237 for 'A composition for treating an ocular genetic disease comprising a CRISPR-Cas system' (granted February 7, 2024) were obtained by The Broad Institute Inc. and others. It may be noted that all these PCT applications were examined under the scanner of Sections 3(J) and 3(i) of the Indian Patent Act, 1970, as amended in 2005.

List of a few more presentative patents granted in India for synthetic biology-related inventions

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