Taking care with CRISPR

17-04-2018

Cath Coombes

Taking care with CRISPR

Natali_Mis / iStockphoto.com

Attorneys drafting CRISPR patent applications in Europe may need to ensure there is relevant data to support the application if patentability relies on a specific technical effect associated with the CRISPR system used. Cath Coombes of HGF reports.

With more than 2,000 patent families related to CRISPR technology, we are seeing more follow-on patent applications being examined before the European Patent Office (EPO). Inventive step objections being raised generally fall into two categories: that a technical problem is not credibly solved in the patent application as filed, or that it would at least be obvious to try to use CRISPR over other known gene-editing techniques.

Determination of inventive step before the EPO is based on a problem and solution approach. This requires an analysis of a technical contribution achieved by the claimed invention which is not found in the closest prior art. The technical contribution is then considered in formulating the objective technical problem to be solved over the prior art.

A technical problem put before the EPO may be regarded as being solved only if it is credible that substantially all claimed embodiments exhibit the technical effects upon which the invention is based. As stated in a decision of the Boards of Appeal of the EPO (T1329/04): “The definition of an invention as being a contribution to the art, ie, as solving a technical problem and not merely putting forward one, requires that it is at least made plausible by the disclosure in the application that its teaching indeed solves the problem it purports to solve.”

Post-published data is allowable only to confirm that the claimed subject matter solves the problem where it is already credible from the disclosure in the patent that the problem is indeed solved (see T1329/4 and T415/11).

A one-way street

With regard to “obvious to try” inventive step objections, in a recent examination report (issued in October 2017) on EP 3 019 595 the examiner summarised the use of CRISPR instead of other genome-editing techniques to correct known mutations leading to sickle cell disease as follows: “Of course applicant will try and argue that it was not a one-way street situation because he could have chosen other options … However, where one option is akin to a motorway while the other is winding unpaved roads, the applicant is presented with a clear one-way street situation.”

"New applications of CRISPR technology with at least detailed methodology to support the new application are also considered patentable."

Follow-on patent applications will fare best before the EPO where they demonstrate an unexpected technical effect rendered plausible at the filing date, otherwise challenges regarding inventive step appear likely. 

Guide RNAs (gRNAs) are used to guide the endonuclease cas9 to make the appropriate “edit” to a target nucleic acid to achieve the desired technical result. Patent applications that focus on specific therapeutic applications such as sickle cell diseases, HIV, etc, often seek protection for gRNAs.

With various online databases available to design gRNAs, patent applications filed without data have encountered difficulties during prosecution. For a patent application disclosing thousands of sequences, is it credible that the skilled person would understand that the subset of sequences (or specific sequence) relied on during examination had the advantageous properties that the applicant is relying on for inventive step?

In contrast, in EP 3 036 327, the EPO considers claims to a single guide sequence which comprises DNA to be patentable, as the earlier patent applications and literature did not make it clear that DNA could be used within the guide sequence.

New applications of CRISPR technology with at least detailed methodology to support the new application are also considered patentable. For example, the EPO in EP 3 218 513 considers the use of CRISPR to amplify a target double-stranded nucleic acid to have an inventive step.

Patent applications relating to Cas9 fusion proteins to improve efficiency of cleavage, reduce off-target effects, etc, with accompanying data demonstrating the technical effect have also been viewed favourably by the EPO, whereas adaption of known fusion proteins from other gene-editing systems have been met with “obvious to try” objections.

In EP 3 277 805 the EPO argues that a fusion protein comprising inactive Cas9 and a retroviral integrase lacks an inventive step; a fusion protein of a zinc finger protein and HIV-1 integrase was known and it is common general knowledge that Cas9 is a superior alternative to zinc finger proteins.

In summary, when drafting CRISPR patent applications care may need to be taken that there is relevant data to support the application if patentability relies on a specific technical effect associated with the CRISPR system used.

Cath Coombes is a patent director at HGF. She has more than a decade of experience in the life sciences field and can be contacted at: ccoombes@hgf.com

CRISPR, Cath Coombes, HGF, European Patent Office, EPO

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