The CRISPR-Cas9 Decision in a nutshell

CRISPR-Cas9 is more than a quick and inexpensive method for editing genes; it is a revolutionary genetic engineering technique with enormous potential in healthcare, agriculture and industrial biotechnology (not to mention the ‘resurrection’ of woolly mammoths). 

As reported below, a major decision was handed down this week by the USPTO’s Patent Trial and Appeal Board, ending (for now) a dispute over who was the first to invent a key application of the CRISPR-Cas9 technology. 

The Patents: 

The first complete patent application to the CRISPR-Cas9 system was filed on 15th March 2013 by the University of California (UoC). US 13/842,859 exemplifies the use of CRISPR-Cas9 to alter DNA in bacteria. The claims of the patent application do not specify the environment in which the method is performed. This means that the patent application covers the use of the CRISPR-Cas9 system in any cell type. 

On 15th October 2013 the Broad Institute (Broad) filed a complete patent application (US 14/054,414), which exemplified and claimed gene editing methods using CRISPR-Cas9 in eukaryotic cells in particular. Despite Broad’s patent application being filed later than UoC’s, it was the first to grant because Broad’s patent attorney filed a successful request for expedited examination. The patent (US 8,697,359) granted on 15th April 2014 with claims limited to the methods performed in eukaryotic cells. 

The Dispute:

UoC submitted to the USPTO that this (and other) Broad patents were “interfering” with their patent application. In short they argued that both their application and the Broad patents claimed the same invention, and that they, rather than Broad, invented it first so Broad’s patents should be removed. 

The case was decided on the issue of whether or not the two groups’ patents did cover the “same invention’. The legal test was whether or not Broad’s methods in eukaryotic cells were obvious over UoC’s general disclosure of the CRISPR-Cas9 technique and its exemplification in bacteria. If the eukaryotic methods were obvious in light of the demonstrated methods in bacteria, then they would be considered to be the same invention. This is because a patentable invention must be inventive (non-obvious) as well as new. 

This issue was addressed by both sides at a Hearing in December last year. Eukaryotic cells are more complex than bacteria (prokaryotic cells) and as evidence of eukaryotic methods being non-obvious over UoC’s bacterial methods, Broad’s lawyers presented quotes from UoC’s co-lead inventor, Jennifer Doudna, in which she admitted the difficulty her lab had experienced when trying to use CRISPR-Cas9 in eukaryotic cells. UoC’s lawyers argued in response that the difficulties were insignificant and that Doudna had not published the idea of using CRISPR–Cas9 in eukaryotic cells because she simply expected it would work (i.e. it was obvious). 

In this week’s Decision, the PTAB stated that there was no interference. In other words, they agreed with the Broad Institute that getting the CRISPR technique to work in eukaryotic cells was not obvious and the two groups’ patents and applications relate to different inventions. 

What does this mean?

Various reports that circulated immediately after the Decision stated that the Broad Institute has “won ownership” of CRISPR-Cas9 technology. This isn’t quite accurate. It is true that Broad retain their patents and applications to methods of gene editing using CRISPR-Cas9 in eukaryotic cells. However, the University of California also retain their original broader applications claiming the CRISPR-Cas9 technology in any cell type. 

If UoC’s applications proceed to grant with that scope of claim, then both parties would need to obtain licenses from each other to commercialise the technique in eukaryotic cells. Third parties would need to license both UoC and Broad patents to do the same. 

Nevertheless, the result is a significant blow for UoC and their licensees. The Decision is expected to be appealed and further proceedings may follow if another of UoC’s applications directed to eukaryotic systems is granted. In the meantime, UoC has tried to put a positive spin on the results. Doudna stated:

 “They [Broad] have a patent on green tennis balls. We [likely] will have a patent on all tennis balls”. 

While this is logically true (UoC’s patents cover the CRISPR-Cas9 system in general and Broad’s patents cover its use in eukaryotic cells specifically), the analogy doesn’t reflect the fact that uses of CRISPR-Cas9 in eukaryotic cells - plants, fungi, animals and humans - represent by far the most lucrative applications of the technology.