-Shivani Kinniwadi, B.B.A. L.LB., School of Business & Law, Navrachana University
From Mendelian Genetics to completion of human genome project, the evolution of genetic technology has gone beyond what it was imagined to do at its inception. The genotype sequencing process has become extremely simplified. The patent regime faces enormous challenges, especially when it comes to patenting DNA. The major concerns around the grant of gene patents include the fear that patenting may impede future research and development and preempt future innovation in genetic advancement. This could also potentially have adverse effects on public health and access to healthcare.
This article analyses gene patentability of complementary DNA (an exon-only genetic sequence that is left after the introns have been removed from an isolated genomic DNA sequence by man) in the Indian Patent Guidelines for Examination of Patent Applications and IMPPP (Indian Manual of Patent Practice and Procedure). This article will address this issue by analyzing the exclusions set out in sections 3(c), 3(d), 3(e) and 3(j) of The Patent Act, 1970.
Introduction
The central dogma of life states that genetic information is passed first from DNA to the mRNA and it is then used for protein production. Reverse transcription and cDNA synthesis enables scientists to work backward, decoding vital information about proteins and protein mutations.. Researchers are able to use cDNA for RNA quantitation (method of assessing the RNA concentration and its purity, to determine the average nucleic acid concentration, done either by UV fluorescence tagging or spectrophotometric quantification), to protect the genetic makeup of an endangered species, by mere amplification and target analysis of a particular loci in the entire genome sequence, dive deeper into clinical research by way of deduction of gene expression and understanding the mRNA and protein involved during a given developmental stage. Complementary DNA (cDNA) is synthesized in the laboratory from messenger RNA. cDNA is not genomic DNA, because the transcript of genomic RNA has been processed (i.e., it lacks promoters and introns). The enzyme reverse transcriptase is used to synthesize double-stranded DNA that is a complimentary copy of the mRNA. The addition of linker sequences to the end of this DNA, which contain the restriction site, followed by treatment with a restriction enzyme, produces a cDNA preparation with cohesive ends ready for insertion into a vector.
In, 1980, the United States Supreme Court ruled that a living human made micro-organism was a patentable subject matter (Diamond Vs Chakrabarty, 447 U.S. 303 (1980)). Specifically, the decision hinged on an interpretation of the terms “manufacture” and “composition of matter” in section 101 of the Patent Act. Writing for the majority of the court, Chief Justice Burger noted that Congress expressly intended for the statutory subject matter “to include anything under the sun that is made by man." In his dissent, Justice Brennan urged restraint, noting that the Court’s decision “uniquely implicated matters of public concern.” Pointing to the Plant Patent Act of 1930 and The Plant Variety Protection Act of 1970, Justice Brennan argued that congress had already considered the basic notion of patenting animate inventions and had selected limited language granting protection to certain living things, but specifically excluding others.
· Analysis of Exclusions set out under the Indian Patent Act:
On a broad reading of section 3(c), it may be possible to argue that an artificially created exon-only sequence is no more than a “discovery” notwithstanding the human excision of the introns. After all, the precise arrangement of any nucleotide sequence of exon-only man-made cDNA has its equivalent in naturally occurring DNA sequences too. Indeed, the informational content encoded in the exon only genetic sequence of the man-made cDNA would be identical to another exon sequence found in its “natural state”. While that is true, it must be noted that there is considerable skill involved in identifying its function, location, and isolation. A strand of cDNA, is an artificially synthesized product which is distinct from a naturally occurring substance. Based on this interpretation, the excision of the introns can be said to have transformed the entire naturally occurring genome sequence which rather turns it into an “invention.” Hence this would certainly suffice, to keep cDNA in the scope of section 3(c). Also, the exclusion so given is silent on the discoveries on a molecular level/cellular level. Furthermore, it is silent about the requisite degree of modification.
Another provision which may be applicable in the context of the patent-eligibility of cDNA is section 3(d). It is pertinent to observe that cDNA is not a just a new form of known genomic DNA sequence as it varies in its function when incorporated into a vector/plasmid for the purpose of DNA cloning of a particular organism of interest, these fragments are thereby combined with the host’s DNA making it recombinant DNA. Also, the gene probes have various application from being used in diagnosis of a specific disease, to research aspects of gene mutations, this would certainly result in “enhanced efficacy” as it ultimately fulfills the standard of “inventive step” as discussed under paragraph 4 of the article and “industrial application” (cDNA used in microbial ecology: to determine presence of microbial species or genera) as per the interpretation of the word “efficacy” which was established by the Supreme Court of India in Novartis AG v. Union of India and Ors. and the exclusion under section 3(d) this would be unreasonable.
This provision deals, inter alia, with substances obtained by a “mere admixture resulting only in the aggregation of the properties of the components thereof” If this provision were to be applicable to human genes, then several issues are worth pondering over. First, it is unclear whether cDNA constitutes a substance that is obtained by a “mere admixture”. On a broad reading, it may be possible to consider the creation of an exon-only cDNA through the excision of the introns from the genetic sequence as a “mere admixture” of genetic sequences. Second, even if it can be regarded as a “substance obtained by a mere admixture”, it will only be excluded under section 3(e) if it results only “in the aggregation of the properties of the components thereof”. That is to say that, if the “mere admixture” results in some “synergistic properties”, then it may fall outside the section 3(e) exclusion. This interpretation is supported by Guidelines For Examination of Biotechnology Applications for Patents which provides that the “mere placing side by side of old integers so that each performs its own proper function independently of any of the others is not a patentable combination, but that where the old integers when placed together has some working interrelation producing a new or improved result, then there is patentable subject matter in the idea of the working inter relations brought about by the collocation of the integers.”
Equally challenging is the issue of whether cDNA will fall within the section 3(j) exclusion, if the provision applies to human genes. Similarly, although the IMPPP contains a reference to permissive claims directed at genetically modified sequences, there is no further guidance on what constitutes “genetic modification” or the extent of modification required.
It could be argued that “a part of an animal” under section 3(j) should be confined to a “part of an animal” as it exists in nature i.e., in its naturally existing or predominantly unaltered state. Under this narrow interpretation, man-made cDNA where the introns have been excised by man would no longer form a “part of an animal” since it does not exist in that state in nature
Conclusion
While cDNA patenting might be beneficial in terms of research as there are many companies which have achieved remarkable results by identifying the actual functionality of a gene, the mutation that might cause diseases etc., but monopolizing gene probes that have ultimately been obtained from a naturally occurring genomic sequence might raise some consequential questions. Ultimately the raw form of specific cDNA (i.e. a single stranded mRNA template) or gene probe doesn't radically differ from its natural form. However, certain aspects of functionality can be challenged and this can be a pathway to misuse or monopolize cDNA patentswhich may prove to be dangerous without proper legal protections in place.
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