CRISPR Interference Update

Two weeks ago I wrote about the interference proceedings that have been instituted by the US Patent and Trademarks Office (USPTO) in order to determine who is rightfully entitled to fundamental patent rights in relation to CRISPR gene-editing technology, under the former ‘first-to-invent’ priority rules.  The contest is between a team led by Berkeley Professor of Chemistry Jennifer Doudna and her collaborator Emmanuelle Charpentier, and a team at the Broad Institute, Inc and MIT led by Feng Zhang.  In that article, I explained generally how interference proceedings work, the distinction between ‘senior’ and ‘junior’ parties in an interference, and what it means to be ‘first-to-invent’.

Kevin Noonan has now written about the CRISPR interference over at the Patent Docs blog.  Being both a US patent attorney, and having a background in molecular biology, Kevin is far better qualified than I to write about this topic!  Obviously, therefore, you should read his article in full, if this subject is of particular interest to you. 

I was also recently contacted by Lee McGuire, who is the Chief Communications Officer at the Broad Institute, drawing my attention to a CRISPR IP information page that is being maintained on the Broad’s website.  You will appreciate, of course, that this is not a source of unbiased information.  It is, however, a useful resource with a lot of interesting content and links covering the CRISPR ‘story’ from Broad’s perspective.  As far as I have been able to determine, Berkeley is not (at this stage) providing any similar resource.

So, what will you learn if you take the time to read these additional sources?

The Patent Docs article provides a full list of the 12 Broad/MIT patents (all examined and granted under the USPTO’s ‘Track One’ prioritised examination process), all of which are implicated in the interference proceedings, along with a number of representative claims.  The article also reveals the ‘count’, which is a kind of ‘notional claim’ established by the USPTO to define the subject matter of the interference.  The interfering claims of both parties are those which fall within the scope of the count.

There may be multiple counts in an interference, however only one has (thus far) been established for the CRISPR claims, as follows:

A method, in a eukaryotic cell, of cleaving or editing a target DNA molecule or modulating transcription of at least one gene encoded thereon, the method comprising:
    contacting, in a eukaryotic cell, a target DNA molecule having a target sequence with an engineered and/or non-naturally-occurring Type II Clustered Regularly lnterspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) (CRISPR-Cas) system comprising:
    a) a DNA-targeting RNA comprising
        i) a targeter-RNA or guide sequence that hybridizes with the target sequence, and
        ii) an activator-RNA or tracer sequence that hybridizes with the targeter-RNA to form a double-stranded RNA duplex of a protein-binding segment, and
    b) a Cas9 protein,
    wherein the DNA-targeting RNA forms a complex with the Cas9 protein, thereby targeting the Cas9 protein to the target DNA molecule, whereby said target DNA molecule is cleaved or edited or transcription of at least one gene encoded by the target DNA molecule is modulated.

The Patent Docs article also provides additional detail about the interference proceedings, including:

1. an initial stage in which the parties can seek to have the count modified, to have particular claims excluded from the interference, and/or request a finding that some or all of the disputed claims are invalid; and
2. the mechanisms for private settlement of the interference (which I am inclined to believe would be the best outcome for all concerned).

Perhaps the most interesting aspect of the Broad Institute’s coverage (and an issue that is not addressed by Patent Docs) is its contention that it expects to turn the tables on team Doudna, and have itself declared the senior party.  As I have already indicated, I do not consider this information to be unbiased, but I think it reasonable to assume that we can expect Zhang to challenge Doudna’s status as senior party in the interference.  Broad explains its position as follows:

When an interference is first declared, the parties are temporarily designated as “Senior” or “Junior” parties according to the date of a particular filing date designated by the Patent Office (in this case, March, 2013 for UC Berkeley and December, 2013 for Broad/MIT). The initial designations were based on dates for completed applications as published rather than the underlying provisional applications that were filed in 2012 and through March 15, 2013.
 
Each party then has an opportunity to request that its priority date be pushed back to the first patent filing that is pertinent to the question before the administrative law judge--in this case, the use of CRISPR in a eukaryotic cell. After the parties present evidence as to whether their earlier patent filing demonstrated the use of CRISPR to achieve genome editing in a eukaryotic cell, a final determination will be made as to who is the “Senior” and “Junior” party. ….
 
In this case, Broad/MIT’s first [provisional] filing demonstrating the use of CRISPR to achieve genome editing in a eukaryotic cell considerably predates the Berkeley filing.

In the absence of a settlement, there is a long road ahead for this patent interference!

Tags: Biotechnology, CRISPR, Genetic technology, Interference, US