CRISPR/Cas9 technology
ToolGen’s patent application, AU2013335451, concerns the now well-known CRISPR/Cas9 system, a platform technology used to edit DNA sequences. In our article, CAR-T cell therapy's unique legal considerations, we discussed the legal considerations around CAR-T cell therapy which involves genetically modifying a patient’s T cells to treat cancer. CRISPR/Cas9 technology has provided a significant advance for CAR-T cell therapy, because it can be used to generate CAR-T cells with particular precision, enhancing safety and efficacy. But this is just one of the many applications of CRISPR/Cas9 technology. ToolGen’s patent application for example suggests using CRISPR/Cas9 technology to develop enhanced crops and animals.
ToolGen’s patent application claims compositions and methods involving a DNA-editing system comprising a Cas9 protein and a “guide RNA”. Together, they introduce a precise break in the DNA strand. Cas9 is a protein used in nature in the immune defence systems of certain bacteria. It is now widely used in genetic engineering applications. The independent claims (claims 1 and 10, to a composition and method respectively) do not limit the source of the Cas9, however certain dependent claims require the Cas9 to be derived from a species of bacteria known as Streptococcus pyogenes (S. pyogenes).
ToolGen and its patent battles
Korean company ToolGen focuses on genome-editing products and services and promotes itself as leveraging its original CRISPR gene-editing patent and funnelling research and development resources into the development and commercialisation of gene-editing based therapeutics and plant and animal products. ToolGen has 10 granted patents in Australia, but none have as early a priority date as the earliest claimed priority date of the patent application in this proceeding (23 October 2012). ToolGen is one of a number of parties involved in US patent actions concerning who first invented the CRISPR/Cas9 system.
Grant Fisher, a lawyer and patent attorney, opposed ToolGen’s application before the Patent Office as a “strawman”. In the opposition, 19 of the 21 claims were found invalid on grounds including lack of novelty, inventive step, and clarity. When he moved to a different law firm, Mr Fisher assigned his rights in the opposition to a shell company, which became the second respondent in the Federal Court proceeding. In an earlier procedural decision, the respondents, being Mr Fisher and the shell company, were ordered to pay ToolGen security for costs (Toolgen v Fisher [2019] FCA 2158).
ToolGen’s application found invalid
ToolGen appealed the Patent Office decision to the Federal Court, and the respondents cross-appealed. The key issue, was whether the patent was entitled to its earliest claimed priority date of 23 October 2012, based on a US provisional patent application. Justice Nicholas found against ToolGen, concluding that (ToolGen v Fisher (No 2) [2023] FCA 794):
- none of the claims were entitled to the earliest claimed priority date, because the provisional application did not disclose or enable the claims (Patents Act s 43(2A));
- all of the claims lacked novelty and/or an inventive step;
- the specification did not provide an enabling disclosure of the invention (Patents Act s 40(2)(a));
- none of the claims were supported by the specification (Patents Act s 40(3)); and
- claim 19 lacked clarity (Patents Act s 40(3)).
ToolGen indicated in its closing submissions that it may apply to amend the application to avoid invalidity. Justice Nicholas suggested that ToolGen could narrow the scope of the claims to align them with the disclosure of the provisional application. At the time of this article's publication, ToolGen has yet to apply to amend the application, but has until 1 September 2023.
ToolGen not entitled to earlier priority date
It was crucial for ToolGen to establish that certain claims were entitled to the earliest priority date based on the provisional application, because ToolGen had accepted that most of the claims would otherwise lack novelty and inventive step over intervening prior art. However Justice Nicholas ultimately disagreed with ToolGen on the priority date issue.
The priority date of a claim is usually the filing date of the patent application, unless other circumstances entitle the patentee to claim an earlier priority date (Patents Act s 43(2A)). An earlier priority date may be the filing date of an earlier provisional application, if the provisional application “clearly disclose[s] the invention in the claim” in the sense that it “discloses the invention in a manner that is clear enough, and complete enough, for the invention to be performed by a person skilled in the relevant art” (emphasis added) (Patents Regulations 1991 (Cth) regs 3.12 and 3.13C). Those provisions were introduced by the Raising the Bar Act in April 2013, and few judgments have considered them since.
Justice Nicholas referred to the Explanatory Memorandum for the Raising the Bar Act, which stated that: “since an enabling disclosure will be required, the amendment will also align the requirements for securing a priority date with most other major patent jurisdictions”. His Honour referred to decisions of the UK Courts, which cited the European Patent Office's Technical Board of Appeals and held that a claim is only entitled to an earlier priority date if the “same invention” is disclosed in the priority document, and said that “the position under Australian law is not materially different”. This is the first time an Australian Court has applied this principle of strict alignment.
Justice Nicholas agreed with the respondents that the provisional application was not an enabling disclosure of a number of aspects of the claims, one of which was a system for cleaving DNA using Cas9 derived from a bacterial species other than S. pyogenes. The claims that covered a CRISPR/Cas9 system other than a system using Cas9 derived from S. pyogenes were therefore not entitled to priority based on the provisional application.
His Honour disagreed with ToolGen that even if the provisional application did not disclose the use of Cas9 derived from a bacterial species other than S. pyogenes, it was enough that the provisional application enabled the use of Cas9 derived from a bacterial species other than S. pyogenes by the skilled person without undue burden. According to Justice Nicholas, both disclosure and enablement were required for ToolGen to claim the deferred priority date, but neither was satisfied by the provisional application.
While the provisional application disclosed, in a general sense, the existence of Cas9 proteins derived from other bacterial species and the possibility that they may be used to mediate DNA cleavage, this was raised as a mere possibility. There was no further discussion, evidence, commentary, or encouragement (“whether by the elucidation of a general principle or a series of working examples”), to suggest that a skilled person would reasonably expect Cas9 proteins derived from other bacterial species to work to cleave DNA. Regardless of whether the skilled person was a molecular biologist alone or working in a team with a microbiologist, the disclosure in the provisional application would not enable a skilled person to determine whether, and if so what, other bacterial species would work without undue burden.
The proper approach to determining the priority date under s 43(2A) was also raised by Allied Pumps in Allied Pumps v LAA Industries, in which the trial was heard in March 2023 and judgment is reserved. MinterEllison acted for Allied Pumps in that proceeding.
Claims invalid for lack of enabling disclosure and support
Justice Nicholas concluded that for the same reasons as for the provisional application, the specification of ToolGen’s patent application did not provide an enabling disclosure of the claims that were not limited to a system comprising Cas9 derived from S. pyogenes. Those claims were therefore invalid.
Section 40(2)(a) requires that a “complete specification must disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art” (emphasis added). This is referred to as the “enabling disclosure” or "sufficiency” requirement. As Justice Nicholas pointed out, "the language used in s 40(2)(a) and s 43(2A)(b) is essentially the same”. Justice Nicholas again referred to the Explanatory Memorandum, to support his observation that s 40(2)(a) was similarly intended to align the Australian law of sufficiency with UK and European law.
Having already found that ToolGen’s specification did not provide an enabling disclosure of certain claims (ie, it failed the sufficiency requirement), Nicholas J concluded that the claims also did not meet the “support” requirement, again because those claims were not limited to the use of Cas9 derived from S. pyogenes.
The support requirement is imposed by s 40(3), which requires that claims “must be clear and succinct and supported by matter disclosed in the specification” (emphasis added). Justice Nicholas held that “it is difficult to see how a claim to an invention for which there was no enabling disclosure could meet the support requirement. In such circumstances, the scope of the monopoly defined by the claim could not be justified by the technical contribution to the art. The two requirements are closely interrelated and not wholly distinct in their fields of operation.” His Honour noted that while it is possible for a claim to meet the sufficiency requirement in s 40(2)(a), but not the support requirement in s 40(3), that was not the case here.
The MinterEllison Intellectual Property team specialises in patent law in the biotechnology field, and continues to monitor CRISPR and CAR-T developments closely.
