CRISPR (an acronym for clustered regularly interspaced short palindromic repeats) is a technology derived from a bacterial immunity system for altering chromosomal sequences in situ in a cell in combination with a bacterially derived protein called Cas9, that is expected to have a game-changing effect on next-generation genetic engineering efforts in a wide variety of fields (hailed as the “Breakthrough of the Year” for 2015).
CRISPR provides a mechanism for inserting or deleting specific DNA sequences using CRISPR-associated targeting RNAs and the Cas9 RNA-guided DNA endonuclease enzyme. It provides for the first time the type of specificity for altering DNA that the polymerase chain reaction (PCR) provided a generation ago for amplifying specific DNA.
Accordingly, patent ownership is a valuable commodity, and while there are now several groups of inventors developing the technology, there were two principal players at its inception. One group represents inventors from the University of California, Berkeley (Jennifer Doudna) and the University of Vienna (Emmanuel Charpentier), and the other group is The Broad Institute/MIT and Harvard University (Zhang and colleagues). In the United States, an expensive and hotly contested proceeding before the U.S. Patent and Trademark Office termed an interference determined that the Broad/Harvard inventors were entitled to embodiments of the invention directed to eukaryotic cells (including human cells), and the Berkeley/Vienna inventors were entitled to embodiments with no restrictions as to cells in which the modifications are made. This determination remains on appeal.
On Jan. 17, the European Patent Office (EPO) came to a different decision, based in part on the more stringent priority rules applied under the European Patent Convention. The Opposition Division (OD) of the EPO revoked in its entirety The Broad’s European Patent No. EP 2771468, which had been opposed by Novozymes A/S, CRISPR Therapeutics GG, and several other entities anonymously.
The revoked claims were directed to a CRISPR system comprising chimeric RNA polynucleotides made up of a guide sequence of between 10 to 30 nucleotides in length, capable of hybridizing to a target sequence in a eukaryotic cell, as well as additional helper sequences having a particular arrangement, and a Type II Cas9 protein that complexes with the polynucleotide sequences to effect intracellular genetic engineering (replacement or deletion of specific gene sequences).
The basis for this decision (which was released only as a preliminary opinion last year) is that the European Patent was not entitled to the earliest claimed priority date, to a U.S. provisional application naming not only MIT and Harvard inventors but also inventors from The Rockefeller University. In the United States, in contrast, these provisional applications were filed in the name of the inventor.
Under European law, in situations like these, the application that is the basis for the granted European patent must be filed in the name of all assignees, or at the time of filing the right must be transferred by assignment to the named applicants. Neither provision of European priority law was satisfied by the Broad, and thus the OD held that the European patent was not entitled to this priority claim. This made available prior art that precluded patentability of the granted claims, and they were thus revoked.
The Broad argued that this was a misapplication of the law and that priority should be determined based on the national law of the priority document. Here, the earlier provisional applications (in the Broad’s view) disclosed more than one invention, and the invention pursued in the granted European patent was invented by the Harvard, MIT and Broad inventors, and not by the Rockefeller inventor. Accordingly, those inventors through their assignees properly claimed the priority right to what was disclosed in those provisional applications and contained in the granted European patent. The Broad filed a notice of appeal based on these arguments.
Paradoxically, just two days before the OD’s decision, the Broad won an arbitration against Rockefeller, wherein U.S. patents claiming priority to some of the same provisional applications were determined to properly exclude the Rockefeller inventor and to quiet title to these patents with the Broad et al. and not Rockefeller. This occurrence was not considered by the OD (who deemed its submission two days prior to oral proceedings to be untimely) and may not be particularly relevant to the Broad’s appeal, insofar as it is another example of the differences between U.S. law and the EPC regarding a priority determination. But in view of the financial interests at stake, the answer to this question will be extremely significant to the Broad and the development of this technology in Europe.
Kevin Noonan is a partner with the law firm McDonnell Boehnen Hulbert & Berghoff LLP and represents biotechnology and pharmaceutical companies on a myriad of issues. A former molecular biologist, he is also the founding author of the Patent Docs weblog, https://patentdocs.typepad.com/.
