Cellectis patent surprises biopharma, could block CRISPR

09-Jan-2015 - Last updated on 09-Jan-2015 at 14:36 GMT

Cellectis says its patent could block rival gene-editing tools.

A patent issued to French biotech Cellectis threatens to block gene editing tools currently in use by several big pharma and service companies.

The broad patent covers all gene-editing technologies that depend on chimeric endonucleases to alter and repair DNA – providing the DNA sequence has at least 12 base pairs, and only for in vitro applications.

The company claims the IP could cover tools like CRISPR – which uses a short sequence of RNA (Cas-9) to guide endonucleases to cut genomes – and zinc-finger nuclease – enzymes used to perform knock-outs on mammalian cells.

The patent also “may result in severe IP constraints” to mega-TALE, transcription activator-like effector-nucleases, and meganucleases, other technologies based on chimeric endonucleases, said Cellectis.

The biotech this week announced plans for a US IPO in the near future.

Rivals ‘thought they were in the clear’

The US patent – No. 8,921,332 – was awarded on December 30th, 2014 to Boston Children’s Hospital and Institut Pasteur, which have licensed it exclusively to Cellectis. André Choulika, Cellectis CEO, and Richard Mulligan, Professor of Genetics at Harvard Medical School, are named as inventors.

Although tools like CRISPR-Cas9 have only recently been taken up by scientists, the document claims priority from 1999, when the technology was in its earliest stages.

“Scientists ask, ‘How can they issue this patent when we’ve been doing this science for 10 years?’” said an expert IP lawyer who spoke to BioPharma-Reporter.com. “People developing in vitro diagnostics may have thought they were in the clear but it was pending all along.”

Opposing the patent?

Rival companies reliant on these gene-editing methods “might have a difficult time invalidating this patent,” she told us, but added there are several possibilities open to litigants.

One is to find an example of the technology being used before February 1999, she said. An instance of this “prior art” would invalidate the patent.

The lawyer we spoke to believes the patent Examiner could have misunderstood the scientific issues involved in the case – application documents accuse him of “not understand[ing] much of what went on”– and have overlooked examples that opponents could seize on.

“The fact the Examiner may not have understood the technology means the Examiner may not have performed proper searches for the prior art, or if the Examiner found it, they didn’t apply it appropriately,” said the legal expert.

Another possibility is that other companies own “blocking” patents which would stop Cellectis from exercising its own intellectual property. In this case, the two patent holders could enter a licensing agreement allowing them both to use the technology.

Firms could also try to sue for infringement, said the lawyer.

Biopharma industry responds

Cellectis has already entered a licensing agreement with ThermoFisher, which uses the technology in its transcription activator-like effector-nucleases (TALE nucleases) to cut genes using enzymes.

BioPharma-Reporter.com approached other companies which Cellectis said could be affected by its IP claim to ask them if the patent infringed their techniques and whether they plan legal or licensing action.

Sangamo BioSciences, which uses zinc finger nucleases, told us it does “not believe that this patent reads on or will have any impact on our ZFP Therapeutic programmes.”

Precision BioSciences, which works with meganucleases, said its IP is not covered by the Cellectis patent and that it will therefore gain an advantage over competitors.

“We are very pleased to note that, to the best our knowledge, Precision BioSciences’ ARCUS genome editing platform is the only genome editing technology in use today that is not a chimeric nuclease.

“We believe that this patent further distances ARCUS as the leading genome-editing platform, both from a technical and intellectual property perspective,” a spokeswoman told us.

BioPharma-Reporter.com did not receive a response from Editas Medicines, Intellia or DuPont Industrial Biosciences (which work with CRISPR), BlueBird Bio (which uses Mega-TALE), Dow or Sigma-Aldrich (which work with zinc finger nucleases).

Cellectis is remaining quiet while it prepares for its US IPO and did not comment on its plans for any legal challenges or on speculation that it has filed a patent for in vivo use of the technology.