Gene-ius at stake: who really cracked CRISPR in plants and animals?

3 June 2025

Many of our readers will have first heard of CRISPR-Cas9 a number of years ago. This is the revolutionary gene-editing technology that allows scientists to make precise alterations to DNA, which Jennifer Doudna of the University of California and Emmanuelle Charpentier, who was then at Umeå University in Sweden, first developed in 2012 and were awarded the Nobel Prize in Chemistry for in 2020. However, there have been questions hanging over who invented the single guide RNA (sgRNA) version of the CRISPR-Cas9 system to edit genes in eukaryotic cells, like those of plants and animals since 2012. In June 2025, that question is still unresolved.

In 2022 the US Patent and Trademark Office’s Patent Trial and Appeal Board (PTAB) decided that the Broad Institute, Massachusetts Institute of Technology, and the President and Fellows of Harvard College (collectively, Broad) were the first to invent CRISPR-Cas9 gene editing which uses an sgRNA to cleave DNA in eukaryotic cells. However, the Regents of the University of California, University of Vienna, and Emmanuelle Charpentier (collectively, Regents) challenged this decision. They argued that the PTAB had misapplied the law and overlooked key evidence.

(Slowly) fast forward to May 2025: the US Court of Appeals for the Federal Circuit has now agreed with Regents in part, finding that the PTAB had used the wrong legal standard for determining who was first to invent. The Court has sent the case back to the PTAB for reconsideration, leaving the true inventor of sgRNA CRISPR-Cas9 gene editing in eukaryotes still up in the air.

The legal issue: conception

The dispute centres on one of the oldest doctrines in US patent law, ‘conception’.[1] That doctrine plays a pivotal role in United States patent law, particularly in the context of inventorship and priority disputes. Under US patent law, there are three stages to the inventive process: (1) conception, (2) reasonable diligence, and (3) reduction to practice. Generally, priority will go to the first party to reduce an invention to practice, unless the other party can show that it was the first to conceive of the invention and that it exercised reasonable diligence in later reducing that invention to practice.

The concept of conception is largely absent from Australian patent law, which takes a fundamentally different approach to determining inventorship and priority: in Australia, the first to file secures the rights. In 2013, the US changed to a first-to-file approach. But the recent decision in the CRISPR-Cas9 patent saga has thrown a spotlight on the complexities of the old system, and just how different the conception and first first-to-file systems are.

Before looking at the law on ‘conception’, we will take a CRISPR-inspired break to set out the relevant facts and claims.

A ‘crisp’ refresher on the CRISPR-Cas9 claims

CRISPR systems are natural genome editing mechanisms found in prokaryotic (single-celled) organisms. Broad and Regent claim that by 2011 or early 2012, they knew that a particular type of CRISPR system could be used to edit DNA using three components: a protein called Cas9, mature tracrRNA, and mature crRNA. This combination is known as the ‘CRISPR-Cas9 complex’ or the ‘CRISPR-Cas9 system’.

Regents claim that they believed then that the CRISPR-Cas9 complex could be used to edit eukaryotic DNA and that, by 2012, they had combined the two RNA sequences into a single guide RNA (sgRNA). This sgRNA, together with Cas9, could edit DNA in vitro. From March 2012, Regents planned experiments to show that that the sgRNA CRISPR-Cas9 system could edit eukaryotic DNA.

*Key dates:*
1 March 2012: Regents’ scientist Martin Jinek documents experiments and exchanges emails with another Regents’ scientist, Jennifer Doudna, about using the system in mammalian cells to test if the system could successfully edit eukaryotic DNA. This is Regents’ earliest asserted date of conception. 11 April 2012: Jinek drafts an invention disclosure form relating to in vitro tests that Regents claims confirmed that an sgRNA CRISPR-Cas9 system could cleave targeted DNA. This is an alternative date of conception asserted by Regent. 25 May 2012: Regents files the first provisional patent application. 28 May 2012: Regents constructs sgRNAs for programming CRISPR-Cas9 systems to target genes in human cells. This is an alternative date of conception asserted by Regent. 28 June 2012: Regents’ scientists, including Charpentier, discuss via email plans to inject the sgRNA CRISPR-Cas9 system into zebrafish embryos. This is an alternative date of conception asserted by Regent. June 2012: Regents publicly announces the sgRNA CRISPR-Cas9 system. July 2012: Broad claims one of their scientists used Regents’ sgRNA with a Cas9 system to edit mouse DNA. 9 August 2012: Regents’ scientists conduct experiments showing some success in editing embryos and describe those experiments as *‘[p]otentially good news’* because additional changes to the tests *‘might work but we shouldn’t be overexcited now.’* This is Regents’ earliest asserted date of actual reduction to practice. 5 October 2012: Broad submits results of the July 2012 experiments on mice to the journal Science. October 2012 and January 2013: Regents files additional provisional patent applications.

Key dates:

1 March 2012: Regents’ scientist Martin Jinek documents experiments and exchanges emails with another Regents’ scientist, Jennifer Doudna, about using the system in mammalian cells to test if the system could successfully edit eukaryotic DNA. This is Regents’ earliest asserted date of conception.
11 April 2012: Jinek drafts an invention disclosure form relating to in vitro tests that Regents claims confirmed that an sgRNA CRISPR-Cas9 system could cleave targeted DNA. This is an alternative date of conception asserted by Regent.
25 May 2012: Regents files the first provisional patent application.
28 May 2012: Regents constructs sgRNAs for programming CRISPR-Cas9 systems to target genes in human cells. This is an alternative date of conception asserted by Regent.
28 June 2012: Regents’ scientists, including Charpentier, discuss via email plans to inject the sgRNA CRISPR-Cas9 system into zebrafish embryos. This is an alternative date of conception asserted by Regent.
June 2012: Regents publicly announces the sgRNA CRISPR-Cas9 system.
July 2012: Broad claims one of their scientists used Regents’ sgRNA with a Cas9 system to edit mouse DNA.
9 August 2012: Regents’ scientists conduct experiments showing some success in editing embryos and describe those experiments as ‘[p]otentially good news’ because additional changes to the tests ‘might work but we shouldn’t be overexcited now.’ This is Regents’ earliest asserted date of actual reduction to practice.
5 October 2012: Broad submits results of the July 2012 experiments on mice to the journal Science.
October 2012 and January 2013: Regents files additional provisional patent applications.

The PTAB decided Broad is entitled to priority, rejecting Regents’ asserted dates of conception. The PTAB also rejected Regents’ earliest asserted date of reduction to practice. Since all of Regents’ other asserted dates of actual reduction to practice postdated 5 October 2012, the PTAB did not need to consider Broad’s claimed dates of conception (26 June 2012) or actual reduction to practice in July and August 2012. The PTAB concluded that Broad had reduced the invention to practice by 5 October 2012, when the relevant results were submitted to the journal Science.

‘Edits’ from the Appeal Court: conception is a tricky concept

The Court sent the case back to the PTAB that it found had misunderstood the law on conception. The PTAB had wrongly insisted that Regents needed to prove they knew the invention would work in eukaryotic cells to prove conception. The Court made clear that inventors do not need to be certain their invention will work to satisfy the requirement of conception. Inventors need only have a ‘definite and permanent idea’ which only requires the exercise of ordinary skill to reduce it to practice.

The Court also criticised the PTAB for relying almost exclusively on Regents’ uncertainty about whether the experiments had succeeded and perceived experimental difficulties, without considering whether these doubts led to any real changes in the original inventive concept or whether routine materials and techniques were used to achieve success during subsequent experimentation.

Next steps

PTAB will re-reconsider the issue of conception. However, as PTAB’s decision on reduction to practice remains undisturbed, Regents will only have priority if it can prove it was first to conceive of the invention and that it either exercised reasonable due diligence in later reducing that invention to practice or communicated the conception to Broad. The next steps for Regents are, as outlined by the Court:

‘On remand, [Regents] will have the opportunity to show, under a conception date established by the correct standard, either (1) it was ‘the first to conceive of the invention and that it exercised reasonable diligence in later reducing that invention to practice,’ […], or (2) it had ‘prior conception of the claimed subject matter and communication of the conception to the adverse claimant.’

As to Regents’ prospects, it is worth noting that the Court upheld the PTAB’s decision that Regents’ 2012 provisional applications lacked adequate written description – Regents cannot rely on those applications to establish reduction to practice. Regents has said that the decision:

‘creates an opportunity for the PTAB to reevaluate the evidence under the correct legal standard and confirm what the rest of the world has recognised: that the Doudna and Charpentier team were the first to develop this groundbreaking technology for the world to share.’

Protecting investment in CRISPR

As CRISPR continues to transform medicine and agriculture around the globe, the real winners may be those who can navigate the patent landscape as deftly as they do the lab. In the race to protect innovation, knowing the intricacies of the positions in different jurisdictions is crucial.

Featured image: ‘Breaking DNA Strand – Genetic Mutation Concept in High Detail‘ by SerenityArt, Pixabay, CC0.

[1] As the court notes on page 15 of its decision, conception is defined as ‘the formation in the mind of the inventor, of a definite and permanent idea of the complete and operative invention, as it is hereafter to be applied in practice’ but that conception ‘is complete only when the idea is so clearly defined in the inventor’s mind that only ordinary skill would be necessary to reduce the invention to practice, without extensive research or experimentation,’ citing Burroughs Wellcome Co. v. Barr Labs., Inc., 40 F.3d 1223, 1228 (Fed. Cir. 1994).

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