The interference between the Broad Institute and the University of California/Berkeley has been in the spotlight over the past year (see "PTAB Decides CRISPR Interference -- No interference-in-fact"; "PTAB Decides CRISPR Interference in Favor of Broad Institute -- Their Reasoning"; "University of California/Berkeley Appeals Adverse CRISPR Decision by PTAB"; and "Berkeley Files Opening Brief in CRISPR Appeal").  But there have been other skirmishes between the parties, each of which has recently been (for now) resolved.

The more significant one is the decision on January 17 by the Opposition Division (OD) of the European Patent Office to revoke in its entirety Proprietors The Broad Institute, MIT, and Harvard College's European Patent No. EP 2771468, which had been opposed by Novozymes A/S, CRISPR Therapeutics GG, and several strawmen).  Representative claims revoked by the OD are as follows:

1.  A non-naturally occurring or engineered composition comprising:
    a Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) (CRISPR-Cas) system chimeric RNA (chiRNA) polynucleotide sequence, wherein the polynucleotide sequence comprises
        (a) a guide sequence of between 10 - 30 nucleotides in length, capable of hybridizing to a target sequence in a eukaryotic cell,
        (b) a tracr mate sequence, an
        (c) a tracrRNA sequence
        wherein (a), (b) and (c) are arranged in a 5' to 3' orientation,
    wherein when transcribed, the tracr mate sequence hybridizes to the tracrRNA sequence and the guide sequence directs sequence-specific binding of a CRISPR complex to the target sequence,
    wherein the CRISPR complex comprises a Type II Cas9 protein complexed with (1) the guide sequence that is hybridized to the target sequence, and (2) the tracr mate sequence that is hybridized to the tracrRNA sequence,
    wherein the tracrRNA sequence is 50 or more nucleotides in length.

2.  A Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) (CRISPR-Cas) vector system comprising one or more vectors comprising
    I. a first regulatory element operably linked to a nucleotide sequence encoding a CRISPR-Cas system chimeric RNA (chiRNA) polynucleotide sequence as defined in claim 1, and
    II. a second regulatory element operably linked to a nucleotide sequence encoding a Type II Cas9 protein comprising one or more nuclear localization sequences, of sufficient strength to drive accumulation of said Cas9 protein in a detectable amount in the nucleus of a eukaryotic cell;
    wherein components I and II are located on the same or different vectors of the system.

12.  Use of the composition of claim 1, or the vector system of claim 2 or any claim dependent thereon for genome engineering, provided that said use is not a method for treatment of the human or animal body by surgery or therapy, and provided that said use is not a process for modifying the germline genetic identity of human beings.

17.  Use of the composition of claim 1, or the vector system of claim 2 or any claim dependent thereon, in the production of a non-human transgenic animal or transgenic plant.

The OD has not yet issued its formal opinion (which can be expected in the next month or so), but last year it did issue a preliminary opinion prior to summoning Proprietor Broad Institute and the opponents to oral hearing earlier this month.  In that opinion the OD "preliminarily and non-bindingly" set forth its opinions, on novelty, inventive step, sufficiency of disclosure, and entitlement to priority; the latter ground for opposition apparently formed the basis for the OD's decision to revoke.

The preliminary opinion found claims 1 and 2 did not satisfy Article 123(2) EPC, because the claim limitation "one or more of the guide, tracr and tracr mate sequences are modified in order to preserve stability" went beyond the disclosure of the application as filed.  Similar deficiencies of disclosure were found for claims 14 and 15 but not for claim 16.  In view of the OD's preliminary priority determination (see below), claims 1-6 and 9-17 were invalid on novelty grounds and claims 7 and 8 invalid on inventive step grounds.

The priority issue was raised based on the earliest two provisional applications (U.S. Provisional Application Nos. 61/736,527 and 61/748,427), as well as U.S. Provisional Application Nos. 61/791,409 and U.S. 61/835,931, which named Luciano Marraffini as an inventor, and which were owned by Rockefeller University.  The priority documents and their named inventors are as follows:

• U.S. 61/736,527 named Zhang, Cong, Hsu, Ran, Habib, Cox, Lin and Maraffini as inventors
• U.S. 61/748,427 named Zhang, Cong, Hsu, Ran, Habib, Cox, Lin and Maraffini as inventors
• U.S. 61/758,468 named Zhang, Cong, Hsu, and Ran as inventors
• U.S. 61/769,046 named Zhang, Cong, Hsu, and Ran as inventors
• U.S. 61/791,409 named Zhang, Cong, Hsu, Ran, Habib, Cox, Lin and Maraffini, Bikard and Jian as inventors
• U.S. 61/802,174 named Zhang, Cong, Hsu, Ran, and Platt as inventors
• U.S. 61/806,375 named Zhang, Cong, Hsu, Ran, and Platt as inventors
• U.S. 61/814,263 named Zhang, Cong, Hsu, Ran, and Platt as inventors
• U.S. 61/819,803 named Zhang, Cong, Hsu, Ran, and Platt as inventors
• U.S. 61/828,130 named Zhang, Cong, Hsu, Ran, and Platt as inventors
• U.S. 61/835,931 named Zhang, Cong, Hsu, Ran, Cox, Lin, Maraffini, Platt, Santjana, Bikard and Jian as inventors
• U.S. 61/836,127 named Zhang, Cong, Hsu, and Ran as inventors

In Europe, under Article 87 EPC and Paragraph IV of the Paris Convention, priority to an earlier-filed application can be validly claimed by the prior applicant or by her successor in interest.  In either case, the applicant must be someone having the right to claim priority.  In the U.S., provisional applications are filed in the name of the inventor and the EPO requires that there be an assignment of the invention on or before a European or PCT application is filed.  (Of course, a PCT can always be filed naming the inventors as applicants.)  In this case, proper application of the applicable rules required both the named applicants (The Broad Institute, MIT and Harvard College) and the Rockefeller to have been named as applicants when the application was filed.  Rockefeller was not named as an applicant.  Accordingly, the OD determined that the named Proprietors could only validly claim priority to the third provisional application, and by the filing date of that application there had published prior art that invalidated the granted claims.  In this regard, the preliminary opinion may provide guidance on the OD's thinking, where that opinion states that "In both the EPC and the Paris convention systems the decisive fact for a valid claim of priority is the status of applicant, rather than the substantial requirement [] to the subject matter of the first application" (emphasis in opinion).  The OD determined (preliminarily) that "neither the requirement of the applicant's identity nor the proof of a valid success in title [had] been fulfilled" for the claimed invention, and stresses that these were requirements to promote legal certainty that would protect third parties' interests, and that these requirements were not subject to the national law of the priority document.  Nor, according to the preliminary opinion could the granted European patent properly claim priority to U.S. 61/758,468 because that document failed to disclose the length of the guide sequence as claimed.

The Broad argued that this was a misapplication of Article 87 and the Paris Convention, 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 Dr. Marraffini.  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 and in a press release evinced an intention to make some of these arguments before the Technical Boards of Appeal (although many believe that the decision is consistent with how the EPO has administered their law of priority and that the Broad faces a difficult task in seeking to overturn the OD's decision).

Paradoxically, just two days before the OD's decision, the Broad won its arbitration against the Rockefeller and Dr. Maraffini, wherein U.S. patents claiming priority to some of the same provisional applications were determined to properly exclude Dr. Maraffini as an inventor and to quiet title to these patents with the Broad et al. and not the 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.