The CRISPR Patent Dispute – No interference upheld by the US Court of Appeals

The CRISPR Patent Dispute – No interference upheld by the US Court of Appeals

The CRISPR Patent Dispute – No interference upheld by the US Court of Appeals

In a decision handed down on 10 September 2018, the US Court of Appeals for the Federal Circuit has unanimously upheld the decision of the Patent Trial and Appeal Board (PTAB) of the US Patent and Trademark Office to terminate the interference between the University of California, the University of Vienna, and Emmanuelle Charpentier (collectively “UC”) and the Broad Institute, Massachusetts Institute of Technology and the President and Fellows of Harvard College (collectively “Broad”) in relation to pending applications and granted patents relating to the CRISPR-Cas9 gene editing technology.

 

Background to the Dispute

Under the pre-America Invents Act (AIA) first-to-invent system, a patent may only be granted to the first inventor. Therefore, where any two of more parties claim the same subject matter, interference is determined by comparing the claims to determine whether the claims are distinct, according to a two-way test. Specifically, whether the subject matter of a claim of one party would, if prior art, have anticipated the subject matter of a claim of the other party and vice versa. If the two-way test is not met, there is no interference-in-fact.

UC sought to establish interference between the claims of UC’s Patent Application No 13/842,859, directed to CRISPR-Cas9, and the claims of twelve patents and one application owned by the Broad, each of which relate to the adaptation of CRISPR-Cas9 gene editing for use in eukaryotic systems.

At first instance, the PTAB determined that there was no interference because, given the differences between eukaryotic and prokaryotic cells, the skilled person would have no reasonable expectation of applying the technique developed in prokaryotic cells to eukaryotic cells (see our previous article here).

UC appealed this decision to the Court of Appeals on the basis that the PTAB:

a)    improperly adopted a rigid test for obviousness that required the prior art to contain specific instructions; and

b)    erred in dismissing evidence of simultaneous invention as irrelevant.

 

Obviousness

 An obviousness determination requires a finding that the person skilled in the art would have been motivated to combine or modify the prior art and would have had a reasonable expectation of success in doing so.

The claims of UC’s pending patent application (US Patent Application No. 13/842,859) are not limited to a particular cell type (i.e., eukaryotic or prokaryotic cells). By contrast, the claims of the Broad’s patent and applications are limited to eukaryotic cells. Therefore, the key question in the interference proceeding was whether a skilled person would have a reasonable expectation of success in applying the CRISPR-Cas9 system in a eukaryotic cell.

In upholding the decision by the PTAB that a skilled person would not have any such reasonable expectation of success, the Court considered expert evidence from the Broad, suggesting that the application of the CRISPR-Cas9 system in eukaryotic cells would be “unpredictable”. In particular, the differences in cellular conditions between prokaryotic and eukaryotic cells may impact on the conformational folding of the Cas9 protein. Furthermore, eukaryotic ribonucleases and mechanisms for the degradation of double-stranded RNA were also provided as issues impacting on the translation of the CRISPR-Cas9 system to eukaryotic cells. Interestingly, this position was strengthened by a 2012 article authored by UC’s expert witness, which recognised the same issues, such as the effect of nucleases and the unpredictability of Cas9 working effectively on the chromatin target.

While the Court indicated that the Broad’s expert evidence and previous publications of UC’s expert witness were, in themselves, substantial evidence that a skilled person would consider the implementation of the CRISPR-Cas9 system in eukaryotes to be problematic, the Court also considered evidence that one of the key inventors of the UC patent application, Dr Jennifer Doudna, had acknowledged that she was not sure if the CRISPR-Cas9 system would work in eukaryotes. For example, evidence was led that she had expressed her “many frustrations” in getting the CRISPR-Cas9 to work in human cells. This evidence appears to be particularly compelling to both the PTAB and the Court in arriving at the conclusion that the skilled person would have no reasonable expectation of success in applying the CRISPR-Cas9 technology to eukaryotic cells.

 

Specific Instructions

 UC argued that the obviousness test applied by the PTAB required that there be specific instructions in the prior art to establish the reasonable likelihood of success. In particular, UC contended that the PTAB had ignored “the inferences and creative steps that a person of ordinary skill in the art would employ” in the absence of specific instructions.

In dismissing UC’s argument, the Court held that the PTAB had correctly acknowledged that certainty in the art was not required and that it “looked to whether or not there were instructions in the prior art that would be specifically relevant to CRISPR-Cas9” as well as “whether there are examples in the prior art of the success or failure of similar systems”.

 

Simultaneous Invention

 UC also argued that the PTAB dismissed their evidence of simultaneous invention as irrelevant. In particular, UC contended that simultaneous invention is evidence of obviousness, as it demonstrates that the claimed invention “was the product of ordinary skill and engineering skill”, rather than an invention. To support this argument, UC submitted evidence to establish that six independent research groups applied CRISPR-Cas9 in eukaryotic cells within months of its initial disclosure of the technology.

The Court was of the opinion that the PTAB did, in fact, recognise the relevance of simultaneous invention to the question of obviousness. In this context, the Court held that while simultaneous invention may be used as evidence of the level of a skilled person and that the skilled person understood the problem and a solution to the problem, evidence of simultaneous invention cannot alone render a claim obvious. Accordingly, the fact that six independent research groups succeeded in applying the CRISPR-Cas9 technology to eukaryotic cells in a short period of time after UC had disclosed the technology provided strong evidence to support the conclusion that the skilled person would be motivated to combine the prior art, this did not necessarily indicate that the skilled person would have a reasonable expectation of success before the necessary experiments had been conducted. 

 

Implications of the Decision

 By upholding the decision of the PTAB to terminate the interference, examination of the pending UC application will continue. As outlined in our previous article, UC needs to overcome a number of formalities objections, a written description objection directed to the breadth of Cas9 modifications encompassed by the claims and a statutory double patenting objection in order to allow their pending application to proceed to acceptance. No objections have been raised against the claims encompassing any cell.

Therefore, assuming that the UC application proceeds to grant with the present claim scope, it is likely that the commercial use by third parties will require licences from both UC and the Broad. Furthermore, in the event that the dual-licencing scenario eventuates, UC and the Broad will also require licences from each other to commercialise the CRISPR-Cas9 technology.

Further developments in the CRISPR dispute and related patents and application will be reported as it comes to hand. If, however, you have any questions about commercialisation or licencing of CRISPR-Cas9 related technologies, our experts at DCC and DCCL will be glad to assist

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