By Abhishek Parmar

Biomedicine has undergone major transformational changes over the past few decades, from personalized medicine to evidence-based and targeted therapies which is a result of amounts of investments in the field of Genomics and molecular biology. Gene therapy is one such area of biomedicine that has shown great potential for the treatment of ‘rare diseases in the coming years. “Gene Therapy refers to the process of introduction, removal or change in the content of an individual’s genetic material with the goal of treating the disease and a possibility of achieving long term cure”^[1], and with the advent of CRISPR gene editing technology many new possibilities have emerged for its applicability and utility in gene therapy for treatment of various diseases. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a tool based on a bacterial CRISPR-associated protein-9 nuclease (Cas9) from Streptococcus pyogenes that has generated considerable excitement within the researchers’ community.

CRISPR technology is in its nascent stages in India, whereas in western countries it has already proven its worth, therefore, it’s imperative that CRISPR should be introduced and must be regulated in India and hence in November 2019 ICMR, the topmost health research authority in India released ‘National Guidelines’ that must be followed while developing, performing or indulging in any activity related to gene therapies in India. “The aim of the document is to ensure that gene therapies can be introduced in India and clinical trials for gene therapies can be performed in an ethical, scientific and safe manner,” the ICMR said.

Gene Therapy Products (GTPs) has been defined as a ‘new drug’ and shall always be deemed to be a ‘new drug’ as identified under section 2(w) of New Drugs and Clinical Trial Rules (2019). Thus as per these rules ‘academic trials’ are not applicable to clinical trials using GTPs¹, and the new guidelines defines gene therapy product (GTPs) as “any entity which includes a nucleic acid component being delivered by various means for therapeutic benefit”, and has clearly stated that “Modifications resulting from the use of CRISPR and other similar technologies would also be considered as GTP” under sub-section 2.2.1.5 of the guidelines. It has also classified CRISPR as a somatic cell gene therapy under section 4.2, and under the sub-section 11.1.1.6 of the guidelines it has been stated that “For complex diseases, the natural history of the disease must be taken into context when selecting the suitable GTP – CAR-T, CRISPR, gene augmentation or others.”

CRISPR & Patenting Process

Patenting in the field of CRISPR technology can be a subject of various debates, Section 3(b) of the Patents Act, 1970 poses a hurdle of morality which seems to be extremely relevant in the case of CRISPR technology, especially after the infamous Lulu and Nana controversy also known as the He Jiankui Affair, which led to widespread criticism of a well-renowned researcher for making the first genome-edited babies, that led to many legal & ethical controversies after he publicly announced the birth of babies in November 2018. This led various governments to regulate such types of activity.

Methods and inventions related to CRISPR technology will have to go through Section 3(b) of the Act, which states, “an invention the primary or intended use or commercial exploitation of which could be contrary to public order or morality or which causes serious prejudice to human, animal or plant life or health or to the environment” and the ‘Guidelines for Search and Examination of Patent Applications’ released by the ‘Indian Patent Office’ has listed a few non-limiting examples to clarify the bar posed by Section 3(b) of the Act,

1. a process for cloning human beings or animals;
2. a process for modifying the germline of human beings;
3. a process for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical or other benefits to man or animal, and also animals resulting from such process;
4. a process for preparing seeds or other genetic materials comprising elements that might cause adverse environmental impact;
5. uses of human embryos for commercial exploitation.

However, Germline and in utero gene therapy is prohibited in India, due to ethical and social considerations.

Another statutory provision that should be considered is Section 3(c) of the Act. Cas9 (CRISPR associated nuclease) is a protein that occurs naturally inside many different bacteria and other prokaryotes and therefore it fails to qualify the barrier posed by Section 3(c) of the Act, which clearly states that,” the mere discovery of a scientific principle or the formulation of an abstract theory or discovery of any living thing or non-living substance occurring in nature”, hence it’s not patentable. But, since this machinery is of prokaryotes it can’t be used directly in human beings or any other animal, it would require considerable alterations of the components. And therefore, the methods and the engineered components or their sequence which are substantially different from their naturally occurring counterpart can be a subject of the patenting process.

Another provision that should be taken care of is Section 3(i) which restricts “any process for the medicinal, surgical, curative, prophylactic diagnostic, therapeutic or other treatment of human beings or any process for a similar treatment of animals to render them free of disease or to increase their economic value or that of their products” from being patented. Since CRISPR has also demonstrated its ability in fighting many genetic disorders, it will also be scrutinized under Section 3(i) of the Act. The ‘Guidelines for Search and Examination of Patent Applications’ states that “The term “therapy’’ includes prevention as well as treatment or cure of disease. Therefore, the process relating to therapy may be considered as a method of treatment and as such not patentable”. 

Perspective and Future of CRISPR in India

Currently, India is in its nascent stage in the development of personalized treatment and precision medicine, both of which are developing rapidly. Therefore, the guidelines have been released at just the right time; as gene therapy technologies like CRISPR gene editing have many ethical and moral issues associated with them like in the case of designer babies.

These guidelines are in line with their US, FDA, and EU counterparts, and were framed while considering the existing rules and regulation at the same time.  These guidelines are necessary for driving the research & development in the area of Gene Therapy Products, especially when every year millions of Indians are affected by inherited genetic diseases or disorders or rare diseases that have very limited or no treatment, many of which can result in life-long disability.

This is a welcoming step taken by the authorities that will surely impact the development of drugs or therapies against a vast number of rare diseases that will stimulate the research of personalized treatment using these highly sophisticated technologies and made a very mature balance between ethics, morality, public interest, and technological development.