In the wake of Anurag Chaurasia’s (paywalled) Nature piece cautioning Indian scientists to conduct due diligence before using CRISPR gene editing tools, Prashant Reddy T looks closely at the patent issues raised by Chaurasia in his paper. Prashant Reddy T is one of our most prolific bloggers (his posts can be accessed here). He is also the co-author of two books- “Create, Copy, Disrupt: India’s Intellectual Property Dilemmas” (OUP, 2017) and “The Truth Pill: The Myth of Drug Regulation in India” (Simon and Schuster India, 2022).
Do Indian Scientists Need to Worry about CRISPR Licences?
By Prashant Reddy T
Last month, Nature published this paywalled piece, by Anurag Chaurasia, a scientist with the Indian Council for Agricultural Research (ICAR), cautioning Indian scientists to conduct their due-diligence before using CRISPR gene-editing tools. In pertinent part, Chaurasia states that the Indian Patent Office has granted a patent for the CRISPR tool to the Dublin based ERS Genomics and that the company can control the terms of use of the tool, including over potential innovations created with the help of its tool.
Some of these issues raised by Chaurasia require closer scrutiny before the government adopts his solution of purchasing a CRISPR licence for all research institutes in the country, on the lines of the government’s ‘one nation one subscription’ policy for journals.
But first, let me begin with some basics about CRISPR, which expands into “clustered regularly interspaced short palindromic repeats”. While many scientists in India’s public sector are busy burning public money pursuing pseudoscience projects in pursuit of political objectives, scientists in the West discovered that immunological defence systems of some bacteria have enzymes/proteins with the ability to modify genes of other organisms. In effect these enzymes can operate like a pair of “genetic scissors” capable of “editing” specific genes. One such bacterial enzyme discovered, around ten years ago, by scientists Emmanuelle Charpentier and Jennifer Doudna, is Cas9. They won a Noble Prize for the discovery in 2020, although there has been bitter litigation in the United States and European Union, between scientists at Broad Institute etc. and the University of California, on who exactly is entitled to the patents for Cas9.
Theoretically, Cas9 opens the door to a whole world of applications in medicine and agricultural research. By editing genomes of different organisms, scientists can silence or express specific genes to create specially tailored products, including ‘designer babies’ or fruits and vegetables with specific traits such as taste, colour or resistance to pests. Long story short, it is one of the most consequential inventions for the biotech industry and will have a profound impact on all of our lives within less than a decade.
With this background, let us delve into the patent issues raised in the Nature piece.
Does ERS Genomics have a Patent for Cas9 Technology?
To begin with I tried examining the claim that ERS Genomics which is co-founded by Charpentier, has been granted a patent for the Cas9 technology in India. The company on its website has claimed that it was granted Indian patent number 397884 on May 27, 2022 by the Indian Patent Office. Deciphering claims in biotech patents is never easy but per my reading of ‘884, it covers a toolkit that can be used to deploy Cas9 for research on organisms other than animals. A patent for the Cas9 enzyme is different from a patent for a toolkit to deploy Cas9 in the laboratory for experiments. I do not think ERS Genomics has a patent for Cas9 but I am open to correction.
More pertinently though, I should point out that ERS Genomics is not the registered owner of the ‘884 patent in the electronic Patent Register. It is also not mentioned as a licensee of the patent. As per Section 69 of the Patent Act, any licensing agreements need to be registered with the Patent Office (which is supposed to evaluate whether stamp duty etc. is paid and if not impound the document until the penalty is paid). It is not clear if ERS Genomics simply failed to register itself with the Patent Office or whether the Patent Office failed to update the online register. In any event, per the Patent Office website, this patent is currently facing a post-grant opposition from ToolGen Inc, a South Korean company which has claimed that it developed CRISPR before the Broad Institute and University of California.
So, is Cas9 Patented in India?
I do not have an answer to the question of whether Cas9 is patented in India. Deciphering patent claims in biotech patents is time consuming and difficult. Further, the patent landscape for this technology is complicated by the dispute between Broad Institute et. al. and the University of California et. al. in Europe and the United States. Long story short, somebody in the government should commission a patent landscape study to figure out just how many patent applications have been filed for Cas9, as well as toolkits to deploy Cas9 in laboratories, before making any decisions to spend public money on a “one nation, one licence” option, as proposed in the Nature piece.
Can Cas9 be Patented in India?
The larger patent law question is whether enzymes like Cas9, derived from a microorganism, can be patented under Indian patent law? The answer I think comes down to whether Cas9 is classified as a “microorganism” or “microbiological process”. I have written on the importance of this distinction earlier for SpicyIP but let me summarise the argument once again.
When the Patents Act was originally enacted in 1970, Section 3(j) prohibited the patenting of plants and animals as well as essentially biological processes. When India signed the WTO Agreement, these prohibitions in Indian law became a problem because Article 27 of TRIPs requires all WTO members to ensure that “microorganisms” as well as “microbiological processes” are patentable under national law. As a result, in 2002, India amended Section 3(j) to create an exception for microorganisms. Ideally, it should have also introduced an exception for microbiological processes in the same provision. Instead, it did something strange by clarifying the definition of “process” in Section 5 by inserting an “Explanation” clarifying that the definition of “chemical process” included microbiological process.
Now, Section 5 was basically the provision that allowed for the patenting of chemical processes but not chemical products, which had applications in medicine or agriculture. This provision was the reason that Big Pharma launched the TRIPs project in the eighties. When in 2005, India amended its patent law once again, to meet the final deadline for complying with TRIPs it simply deleted Section 5 without realising that the provision also contained the exception for microbiological processes. I know this sounds crazy but the entire process around the amendments in 2005 was mired in secrecy and confusion, as I have discussed earlier over here. As a result, there is currently no exception in Indian law for microbiological processes which means that the bar in Section 3(j) against the patenting of “essentially biological process for the production or propagation of plants and animals” is absolute.
Thus, if Cas9 is classified as a “microbiological process”, as opposed to a “microorganism”, it may not be granted a patent due to Section 3(j), especially since it is being use to modify genes, which may qualify as “production or propagation of plants and animals”.
Can Scientists Claim the Experimental Use Exception under Section 47 of the Patents Act?
Presuming that my argument above is incorrect and CRISPR technologies like Cas9 are granted patents by the Patent Office, does it necessarily mean that Indian scientists cannot use these tools without purchasing a licence?
The Nature piece claims that the patentees for this technology are allowing the non-commercial use of Cas-9 for academic purposes without the requirement for a licence. While that may be true, there is also the matter of Section 47 of the Patents Act which makes the grant of all Indians patent conditional on the patentee agreeing to allow for the patented technology to be used for “for the purpose merely of experiment or research including the imparting of instructions to pupils”.
Around 15 years ago, I had written a longish paper with Shamnad, on this experimental use provision in Section 47. It was published in the IDEA journal and can be accessed here. While we conclude that the experimental use exception in Indian law is quite broad, we also concluded that an Indian court will likely read the experimental use exception in S. 47 narrowly when it comes to “research tools” (e.g. microscopes) whose primary purpose is to be used only in the course of research. A broad reading of the experimental use exception would end up destroying the incentive to produce research tools going against the objections of patent law. While experimenting “on” a research tool may still be permissible under S. 47, it may not be permissible to conduct research “with” the research tool.
Since CRISPR technology like Cas9, is primarily a “research tool”, I doubt an Indian court would interpret S. 47 broadly to allow anybody to use it for the purpose of conducting research on other organisms without a licence. How if the aim is to research Cas9 itself, it should be possible to do so under S. 47 without the need of a licence.
Can the Owner of CRISPR Patents Control the Use of the Technology by Other Scientists?
One of the interesting points made in the Nature piece is that the patent licences for CRISPR technologies can impose terms on the use of CRISPR. This to say, that whoever ends up patenting Cas9 in India, may require all Indian licensees to share royalties of all inventions created by the licensee with the help of Cas9. There is precedent for these “reach through” royalty clauses in the gene-splicing patent licences that covered the break-through invention of Cohen-Boyer that gave birth to the biotech industry in the eighties. Stanford and Berkeley which owned that patent earned $255 million dollars.
The question however is whether Indian law permits such clauses. The answer lies in how one interprets S. 140 of the Patents Act. This provision basically regulates the manner in which patents can be licensed, prohibiting certain restrictive conditions from being imposed by patentees in their licences. For example, “exclusive grant back” clauses (what-ever it means in the Indian context) are prohibited and will be considered void. So, if public sector laboratories are purchasing licences for research tools, it may be advisable to seek a legal opinion prior to agreeing to the licence. If a licensing clause appears to be particularly oppressive it is always open to approach the Competition Commission of India requesting for an investigation into whether the patentee is in effect abusing its dominant position in the market. The mere threat of a complaint can also be used as leverage in negotiations for a licence.