Patent Battle over Modified Meganucleases Heats Up

Meganucleases are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs); as a result this site generally occurs only once in any given genome. For example, the 18-base pair sequence recognized by the I-SceI meganuclease would on average require a genome twenty times the size of the human genome to be found once by chance. Meganucleases are therefore considered to be the most specific naturally occurring restriction enzymes.

The high specificity of meganucleases gives them a high degree of precision and much lower cell toxicity than other naturally occurring restriction enzymes; they were identified in the 1990s as particularly promising tools for genome engineering.

However, the meganuclease-induced genetic recombinations that could be performed were limited by the repertoire of meganucleases available. Despite the existence of hundreds of meganucleases in nature, and the fact that each one is able to tolerate minor variations in its recognition site, the probability of finding a meganuclease able to cut a given gene at the desired location is extremely slim. Several research laboratories therefore soon began trying to engineer new meganucleases targeting the desired recognition sites.

Cellectis and Precision Biosciences are two competing biotechnology companies, both seeking to commercialize engineered meganucleases for use in genetic engineering.

On March 1, 2011, Cellectis sued Precision Biosciences in the District Court of Delaware for allegedly infringing US patent number 7,897,372, directed to "I-CreI Meganuclease Variants with Modified Specificity.” That case is presently proceeding with discovery, and trial is set for February 2013.

On September 20, 2011, the US patent office issued US patent number 8,021,867, which is directed towards "Rationally-Designed Meganucleases with Altered Sequence Specificity and DNA-Binding Affinity." The named assignee on the patent is Duke University, but according to Celectis the patent is actually owned by Precision.

On September 30, 2011, Cellectis filed another lawsuit against Precision Biosciences, again in the District Court of Delaware, and this time it is a declaratory judgment action seeking a declaration that the Duke/Precision patent is invalid and not infringed by Cellectis.

In the complaint, Cellectis does not allege that it has explicitly been threatened with a lawsuit by Precision. Instead, it argues that declaratory judgment is appropriate because: both patents-in-suit concern the same field of technology, i.e., "modified" or "altered" I-CreI meganucleases; the Cellectis patent is prior art to the precision patent, the parties in both cases are the same, and the discovery in both cases likely would substantially overlap.