His last bow – CRISPR/Cas9 and possibly the last famous Interference proceeding

The patent fight over the CRISPR/Cas9 system  between Dr. Jennifer Doudna with her employer and assignee UC Berkeley on the one side and Dr. Feng Zhang with MIT and the Broad institute on the other side has gained (almost) as much attention as the Sanders vs. Clinton race. Whereas the latter will be decided no later than July this year at the DNC convention, we may have to wait much longer to know the outcome of the patent fight.

The invention: The invention, a cheap and efficient tool for fine-tuned manipulation of genomes (including our own human genome), has already profoundly changed many fields of biomedical research. A Nobel Prize award is thought to be likely. With more than one billion dollars of backing from Venture capitals, Editas, the Startup based on CRISPR technique closed its IPO in January, during which it raised $97.8 million. Furthermore, there will be many other downstream techniques and patents based upon the original CRISPR/Cas9, and thus, even more money.

The dispute: The frenzy started in June 2012 when Doudna and coworkers published their Science paper describing the potential of the CRIPSR/Cas9 system in bacteria. Before publication, Doudna filed her first patent application on CRISPR/Cas9 with the patent office in May 2012. Meanwhile, Dr. Zhang independently filed his first application on the use of CRISPR/Cas9 in eukaryotic cells (those cells that have a nucleus, including all plants, animals, humans, but not bacteria) in Dec 2012. Although Zhang’s application was filed later, the patent was granted in April 2014 thanks to a fast-track program of the PTO, whereas Doudna’s application is still pending today. Sure enough, the Doudna group contested the Zhang patent, claiming that they, not Zhang and MIT/Broad should be awarded the patent on CRISPR/Cas9. On Jan 11 this year, the patent office declared an adjudication proceeding for this dispute.

The governing law: Since both parties’ effective filing dates are before the American Invents Act (AIA) transition date March 16th 2013, the pre-AIA, first-to-invent (FTI) regime will govern. Under this regime, a patent is awarded to the party who first invented, not the party who first filed the patent application. When two or more parties claimed that they are the first inventor, the pre AIA law provides an inter partes “interference” mechanism to resolve the dispute, where each party is required to prove—with lab record, affidavit, oral testimony, limited discovery and deposition—that they invented earlier and also that they did not “abandon, suppress, or conceal” their invention. In the CRISPR/Cas9 dispute, with both parties constantly working in the public eye, “abandon, suppress, conceal” doesn’t seem to be a concern. The dispute will come down to the invention date.

In an interference, the party with the earlier filing date is declared the “senior party” and the other the “junior party.” The senior party is given, prima facie, the presumption of being the first inventor and the junior party bears the initial burden of proof to overcome that presumption.  Furthermore, in the event of a tie, either because the parties actually invented at the same time, or the evidence is simply not sufficient to find for any party, the senior party wins. These rules favor the party who filed first (although technically the law is under a first-to-invent premise) and is in accordance with the policy consideration of the patent law to encourage early disclosure. Thus, the interference is not necessarily a great news for Zhang, who now is the junior party because of his later filing date. Not only is he facing a second round of scrutiny at his patent, he also has to do that from a suboptimal position. But interference is a legal battle, and MIT/Broad seems to be doing just fine with their legal counsel till now. A powerful NPE like MIT/Broad also has sufficient resource for a race of interference, which is notoriously long, complicated, tedious and unpredictable.

Precisely because of the long, tedious and unpredictable nature of interference, parties often prefer to settle. They can reach some cross-licensing agreements, share the licensing fee flowing out of the patent and avoid the risk and cost of a quasi-litigation. Would Dr. Zhang and MIT /Broad want to settle? Dr. Zhang has made a lot of progresses since the original CRISPR/Cas9, including, significantly, finding a potential replacement for Cas9. Also, Zhang’s company Editas already went public and is probably not in a desperate need to win this fight. As for the other side, Doudna and UC were said to have rejected  “repeated efforts and trips since the beginning of 2013 to resolve this situation outside the legal system” from MIT. And finally, even when the parties do come to an agreement, the agreement still has to be approved by the PTO. In any case, the outcome of this dispute is far from certain.

An AIA Hypo: Now, what if the filing dates were after the transition date March 16, 2013 and the AIA law governed? AIA changed the premise of the US patent law from first-to-invent to first-to-file (FTF), awarding patents to the party who filed the first application with the PTO— as long as they independently made the invention. If another party invented earlier but filed later, he is out of luck, although this party would have been awarded the patent pre AIA, if he didn’t “abandon, suppress or conceal” the invention. In the current case, it would be clear that Doudna should get the CRISPR/Cas9 patent because of her earlier filing date. Under AIA, Doudna would request a “post grant review” or “ex parte reexamination” at the PTO, asking for a review of the Zhang patent based on her earlier application. (If she didn’t find out about the Zhang patent until more than 9 months after issuance, she could still choose between inter parte review and ex parte reexamination.) Either way, the resolution will be quick and cheap because of the clear AIA rule of awarding the first filer, which obviates the complicated determination of who invented earlier. The parties would not have to go through the long and expensive interference proceeding, and the incentive for settlement will be much less because of the predictability of the outcome.

With or without you: By obviating the need to litigate invention date, FTF seems more efficient than FTI.

But it was often argued that FTF is less fair because it favors large corporations, which have the resources to win the race to file.  However, for the biomedical field, the reality today is such that very few (if any) truly high-impact inventions can be made in private garages. Research is very expensive, and those who were able to make inventions probably already have an assignee –be it corporations or universities—that is well equipped for the race to file.

Nevertheless, the intrinsic complexity and unpredictability of interference in FTI system encourages settlement, which dilutes the winner-take-all character of a priority fight under FTF. It can be argued that this is more consistent with the traditional collaborative spirit—and often also the reality—among scientists and is for this reason more fair than FTF.

In any case, FTF is the new law. While the applications filed before March 2013 are gradually disappearing, so are interferences, especially the kind of 102(g)(1) interference like the CRISPR/Cas9 dispute. The CRISPR/Cas9 fight may very well be the last high profile interference in the US history. Let’s enjoy the game and bid a fond farewell to interference and FTI.

 

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