Author: Soundarya Mathavan, School of Excellence in Law, TNDALU
Introduction:
The emergence of science and technology in genetic engineering and biomedicine coupled with the rising possibilities of identifying and manipulating birth defects has heralded in an age of immense development. One such technology is CRISPR-Cas9. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a variant of DNA sequences that are found in bacteria and prokaryotic cells. CRISPR-Cas9 is used in genetic engineering to modify the gene codes. However, there is a long patent dispute over this technology which also won the Noble Prize in Chemistry in October 2020 This article discusses the uncertain future for this invention in commercial world. Despite the growth in science and technology, the capacity to edit genes precisely had always been limited. But with the emergence of CRISPR-Cas9, site specific and precise gene editing has become possible.
Using CRISPR, researchers can modify the gene sequence in organisms and can potentially create a permanent solution for complex and autoimmune diseases like sickle cell anemia and beta thalassemia. This technology is used to engineer and produce probiotics cultures and is also applied in agriculture in order to increase yield turnover, nutritional values of crops.
The Dispute
The first application for patent was filed by University of California on 15th March 2013. The patent was filed by Emmanuelle Charpentier from the Max Planck Unit for the Science of Pathogens and Jennifer Doudna of the University of California (hereinafter referred to as ‘UC’). In the June 2012 issue of Science, Doudna and Charpentier published solid evidence that bacteria derived CRISPR tool can cut down targeted DNA. This marked the beginning of CRISPR’s future and the battle for patent rights.
After eight months since the filing of the first application, the Broad Institute (Broad Institute, Inc., Massachusetts Institute of Technology and the President and Fellows of Harvard College (hereinafter referred to as ‘Broad’) led by Feng Zhang filed a complete patent application for the use of CRISPR in eukaryotic cells in particular. Broad Group had managed to claim patents for genome editing in eukaryotic cells that also included site specific genome editing in the cells of animals, plants and humans as well. On the other hand, UC’s patent was not site specific to be put to use in eukaryotic cells, but instead derived the applicability of CRISPR Cas9 solely through the efforts catered through test tubes and not through the support of any environment like eukaryotes. This gave an upper hand to the claims made by Broad since they were certainly patently distinct and showed sufficient evidence claimed in eukaryotic environment. UC did not file the claim for employing this technology in eukaryotic cells unlike the Broad group did in its report, which again gave an upper hand to the Broad institute for patent rights. Broad Group had managed to claim patents for genome editing in eukaryotic cells that also included site specific genome editing in the cells of animals, plants and humans as well.
In 2014, Broad was granted a patent with a limited claim that allowed for the use of CRISPR-Cas9 in eukaryotic cells by The U.S. Patent and Trademark Office (USPTO). This led to the beginning of a legal battle in 2016 on the supposed interference of the patent. The interference caused a claim of irregularity whether the patents granted by the USPTO to the Broad for use of CRISPR Cas9 in eukaryotes had overlapped or interfered with patent claims filed by the UC group. The UC group had then equivalently argued that both claims by the groups contented the same invention and the patent must be given to UC Group for inventing it before the broad group.
The legal test that was applied in this case was the question of “same invention”. Eukaryotic cells are complex than prokaryotic cells and it was held that eukaryotic methods are non-obvious use over the claims of UC, thus the application relate to different inventions.
Verdict
The PTAB trials seemed to have a mixed verdict. They held that the use of CRISPR on eukaryotic cells is patentable by the Broad group and the other uses of the tool is patentable by the UC group. Unsatisfied by the decision of the PTAB, the UC group approached the Federal Court where the appeal was denied.
After the first PTAB trial, the UC group filed a new claim with the PTAB to decide a second interference. The Board compared the claims and held that a direct declaration on the use of the tool in Eukaryotic cells, nevertheless gave the priority edge to Broad group. In September 2018, the Federal Circuit affirmed the PTAB’s decision, holding that the invention at issue was not obvious but an evidence adduced in respect of simultaneous invention.
Analysis of Simultaneous Invention And Secondary Evidence of Obviousness:
A secondary invention subsequent to the prior invention could be a result of introducing a foundational technology and many other researches working on the progress of the issue at hand. It is not common, but is of great significance to ascertain & reach a conclusion of obviousness.
The relevant foundational technology in UC v. Broad is CRISPR-Cas9. In Noelle v Leaderman, it was held that, “These simultaneous inventions adduce as evidence of obviousness when it is considered in the light of all of the facts and circumstances” The Federal circuit also held that simultaneous invention may influence the analysis of obviousness in two ways (relying on the decision in Monarch Knitting Mach. Corp. v. Sulzer Morat Gmbh)
1) If it is evidence of the level of skill in the art.
2) Constitutes evidence that a person of skill in the art understands the problem & solution.
When two parties claim patentably indistinct subject matter under pre-AIA, 35 U.S.C. § 102(g), the patent is granted to the first inventor and the occurrence of interference is determined by comparing the entailed claims. The Board here applied a two-way test questioning if the patent claim and subject matter of one party would have rendered obvious the patent claim of the opposite party and vice versa. If the two-way test is not met with, in such a case interference-in-fact doesn’t exist. In Graham v. John Deere Co. the US Supreme Court set forth factors for assessing obviousness. These factors were:
(1) Scope of the prior art,
(2) Difference between the claims & prior art,
(3) Level of standard skill in the art,
(4) Objective considerations of non-obviousness.
It was also held that the assessment of these factors is the question of fact that has to be reviewed for substantial evidence.An obviousness determination requires assessing whether a person of customary skill in the art would be able to modify the ideology in the prior art.
Reasonable Expectation of Success:
For the purpose of determination of obviousness in a case, it is vital to ascertain if a person of ordinary skill in the art would have the essentiality to modify or even combine the teachings and ideology in the prior art and would have had the slightest and reasonable expectation of success by doing so. The Federal court in re Stepan company emphasized on the fact that reasonable expectation of success would require more motivation to attain success other than simply try all possible choices.
The fact that there were 6 groups that succeeded in application of this technology in eukaryotic cells provides enough evidence that there persists a motivation to combine the prior art. The PTAB also found that a person of ordinary skill in the art would not possess a reasonable expectation of success to apply CRISPR-Cas9 tool in a eukaryotic cell. It concluded that substantial evidence supports it’s finding that there would not have been a reasonable expectation of success for a person of ordinary skill. It also pointed out the necessity to deal each case with respect to its state of advance, characteristics of the technology, the generality of the prior art and the consistency of results in the area of specificity. The United States Court of Appeal for the Federal Circuit held that the Board did not error in no interference-in-fact and considered the Broad group’s invention as a simultaneous one supported by substantial evidence.
The long-running patent battle may have fetched a Noble Prize to the team led by the UC group, but it has taken a new twist and complicated the claims. The PTAB on 10 September ruled that the Broad Institute group has “priority” over patents that were already granted for the use of CRISPR in eukaryotic cells. However, the ruling also favors the UC group thereby guaranteeing a priority on the invention of a major component in the CRISPR tool.
Indian Law on Patenting of Genes
One of the key requirements for an invention to satisfy the grant for patent in Intellectual Property is the detailed disclosure of credible utility, practical and moral ways of utilizing the invention.
For patenting biotechnological inventions in India like CRISPR, apart from ascertaining the requirements of Novelty, inventive step and capability of Industrial application, the said invention has to overcome the possibility of falling under S. 3 of The Indian Patents Act,1970. Inventions like methods for Cloning humans violate ethical, social and principles and are these are not considered as inventions under S. 3(b) of the Act. A few other inventions relating to cloning of humans, commercially exploiting human embryos, inventions relating to process of manufacturing seeds that might contain potentially harmful substances indirectly & adversely affecting the environment are held violative and are not considered as patentable subject matter.
Also under the purview of Section 3(c), products like microorganisms, enzymes compounds, proteins etc., that are isolated from nature are not regarded as patentable subject matter. The processes of isolation of the same compounds can be regarded under the requirements of S 2(i). Section 3(c) prohibits inventions relating to living things occurring in nature. Hence only modified microorganisms are patentable.
Regarding patentability of inventions under Section 3(d), inventions which result in discovery of new/known substances without enhancement in efficacy and modifications in existing or known substances like enzymes, compounds etc. are not patentable unless & until the efficacy of the modified substance is established. Patent applications relating to inventions involving two or more biological products should disclose the combinative effects of the components in order to overcome objections based on Section 3(e).
Apart from the above-mentioned hurdles in patenting biotechnology in India, what lies ahead is the question of fair, reasonable and non-discriminating terms of licensing of inventions like CRISPR-Cas9.
CRISPR in India has already made a huge breakthrough, with the recent CRISPR invoked rapid COVID-19 Testing and Indian scientists paving way for gene editing in Indian corps to improve crop varieties. But the ethical and legal issues pertaining to regulate a technology like CRISPR-Cas9 in and their regulation needs to strike a balance between public interest, principles of medical ethics and technological advancement.
Conclusion:
The battle for the patent is still going on. There have been varied opinions on the subject of granting of the patent and the interference. The results of this technique could set the tone for the development of this technique for the US, and the world. The PTAB hasn’t set a date for the next hearing but if a settlement is reached, it will be a major breakthrough in genetic engineering and enable researchers to curate solutions and provide a cure to many diseases which are so far, incurable.
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