Editor’s Note: Gene editing for a better (or worse) is coming to a store near you. Some of you may have followed the ongoing patent war on the ownership of CRISPR-Cas9 technology between University of California (Berkeley) and Broad Institute (MIT-Harvard). But there could be many who are wondering what is the fuss all about? At the Career Support Group (CSG) for STEM PhDs we might still continue the debate about CSG’s usefulness to biologists vs non-biologists, but as inventors we are always in unison about perfecting the art of claiming ownership. #ClubSciWri is always attempting to listen and respond to your expectations and we are pleased to present the “Battle of Wisdom:CRISPR-Cas9” from Dileep Vengasseri. Dileep has nicely deciphered the meshwork underlying this matrix of claims to the CRISPR invention. We hope this story helps make sure that the next big thing from your gray matter secures your rightful ownership to the intellectual property.- Abhinav Dey
My dear friend, this 60 minutes of my time and 1597 words are for you! As you rightly said, maybe we should discuss our opinion(s) in public at least for educating others on what we have learned during the due course of our time.
Disclaimer: All what is written/expressed here are my personal opinions, and are not to be construed in any manner as a reflection/opinion of the firm that I am associated with. My words are solely my words! I will try to be as generic as possible to ensure there is absolutely no conflicts of any interest. This is purely a personal blog, written within the constitutional freedom that my Country has offered me when I was born here.
Many great battles are won not in the battle fileds, but in the minds of the battle leaders. What we read, saw, and talked about were the after-effects of those battles won or lost inside those great minds. In the great epic Mahabharata, Arjuna was about to lose Kurukshetra battle even before it was fought. But, there was a Krishna to save him from that humiliation. Many may not be as lucky as Arjuna was.
Before I begin, with all due respect, let me remind all of us one trivia very clear. US is not the “World” … it is just one of the many countries [a privileged one, indeed] of this world. A larger population residing outside that privileged country, do not play a “World Cup” between their states or clubs. They don’t re-spell a word to make it look like they have invented it. For them, the metal “Al” is still aluminium and not aluminum.
We, living at the periphery of the world of modern(?) science, have got enough fuel from CRISPR-Cas, the game-changing method of gene editing, to satisfy our ego of being a part of a ‘privileged community’ who understands (?) the words like ‘gene editing’ and ‘CRISPR-Cas’. For all such ‘privileged souls’, the “IP Battle of CRISPR-Cas” is more than just another battle. Let me call it a “Battle of Wisdom”.
But, was this battle worth fighting?
Let me begin with disecting this IP battle to four main sections: (1) Technology (2) The Battle Field (3) The Win and (4) The Strategy. May be, in future, I can complete this article with “Lessons Learnt”.
- Technology: At least from what is publically available, we know that Doudna/Charpentier’s team made that beautiful gene editng system work in-vitro in prokaryotic cells, in a neater, simpler manner than what it was in the nature itself. Instead of using a 3-component system including tracrRNA, crRNA and Cas9, her team beautifully designed a 2-component system, including a key synthetic, single guided RNA (sgRNA), that effectively performed site specific genome editing along with Cas9 (It is interesting to note that in-vitro 3-component system is also IP protected!). What was the big deal? The big deal was its simplicity, efficiency, and marketability. It was not that gene editing methodologies never existed before… however, now the World has access to an elegant gene editing system that is much more easy to perform (no more protein engineering!) & predictable. We also know that Feng Zhang (don’t forget George Church’s back-to-back publication in Science along with Feng Zhang) made it work in the eukaryotic system.
- The Battle Field: No one (at least the majority of money makers) wants a gene editing system that works only in prokaryotic systems. So, the “Battle of Wisdom” eventually boiled down to the IP on gene editing in eukaryotic system with CRISPR-Cas. Duodna filed a US patent application (remember, US is not the World, more so when it comes to IP protection) first and Feng Zhang got the first granted patent in US (note that the USPTO could have provoked an interference at that time itself, but they didn’t!). Feng Zhang’s patent ‘claims’ to ‘cover’ eukaryotic CRISPR/Cas gene editing system (no comments on its “claims” and/or its “coverage” as the battle is still on…at least let the battle be fought under the belief that the land that is going to be conquered is still fertile!). Duodna had anyway made it easier for Feng Zhang to get his patent granted by ‘boasting about’ her team’s achievement in multiple forums and explaning ‘how difficult it is/was to make it work in a eukaryotic system’. Alas! enough of such wisdom on eukaryotic system was passed on to that Patent Attorney who filed her provisional applications, at least before the one on 19th October 2012 that is prior to the Feng Zhang’s priority date of 12th December 2012. Now, the battle of wisdom (what we call as “Interference Proceedings”) is to establish who invented (i.e., conceived and/or reduced-to-practice) the “eukaryotic CRISPR-Cas” first. Duodna will be fighting to make a point that porting CRISPR to eukaryotic system is just a non-inventive aspect. Feng Zhang is going to fight back at least on the ground that if it is that obvious why did it then take Doudna a good 6-9 months to achieve the same. I refrain from making any comments on how long or short is 6-9 months in a field like Molecular Biology. I know that my dear friend, who forced me (as usual) to write this long article, has wandered in the wilderness of IISc campus behind an elusive protein for a good 6 years :-)). And, I must admit that I have made the entire story of this Battle of Wisdom to a deeply abridged version as the facts of this case are much more than what this layman article can handle. But, I believe that this much background is good enough to make my “teaching moments” convincing.
- The Win: Does it matter who wins this battle? Of course, YES! All battles are known after the leader who has won it (Aravind Kejriwal and Hilary Clinton are no where near their counterparts, as of today). Generally, the winner get the privilege to write the history that we all can read and study. But, is this Battle of Wisdom the same as any other great battles fought, lost and won? No. What is required to win this battle? It is required to show that who has invented the “eukaryotic CRISPR-Cas” first; it is required to show what is inventive/not inventive in this field; and it is required to show what constitutes an adequate written description/enablement in this field so that the “public disclosure function” (spirit and letter of any patenting system in the world) of the patenting sytsem is intact. But, as with any other battle, only one person can be the winner. But, what will they both win or lose? The loser will any way have a deep wound in ego that may take years to heal. But, will he/she lose everything? Need not be. It depends on what other IP portfolio or picket-fencing that he/she has done around this gene editing tool. For example, a good claim on the synthetic guide RNA, a good IP portoflio on a better Cas9 proteins, a better method for transfecting the cell, or an alternative to Cas9 itself… all these can make or break a commercial deal. Is the winner going to get everything? Need not be. During this entire process, it might open a pandora box and a myriad of avenues to potentially invalidate the patent claims that the winner can take home, to limit its claim scope, to limit its application coverage etc.
- Strategy: Isn’t it important for everyone in the field of IP to realize that most often a “hand shake” may do more good than “a fight”. Before taking the army to a battle, it is important to know if raisng a white flag will be more beneficial than a gruelling battle. It is important to understand for what one is fighting a battle. Does anyone fight for satisfying an ego or to make a point? It is imporant to understand that in a patent battle field, a wiser does not fight from their heart, but from their mind!. It is important for each of the fighting members to know “What will happen if we do not fight, but rather collaborate?”. Both Doudna/Charpentier and Feng Zhang could have been still partners in Editas, and they could have ruled the field. When you fight in public, you expose yourself…you expose more than what you wanted to. And, what you have exposed can kill you even if you win YOUR fight.
Three more points to ponder:
- IP protection of PCR technology made Roche the king of DNA amplificaiton for quite sometime. Why? It is true that PCR was a technology that literally transformed the world of Biotechnology. But, was the IP protection on PCR probes for important pathogens less important? Were Taqman probes for real time PCR less important? Were the chips that made thermal cycling easier less important? No. All of them “together” made PCR a “cult” technology. That’s what a strategy means.
- IP protection in the field of ESC took Thompson and Wisconsin Alumni Research Foundation (WARF) to the center of the scientific world. Many IP/Tech Transfer cells in the Universities across the world wanted to be like WARF. As far I know, WARF gave its rights for free to any academic instituties, but made any industry pay for the same. Great! What were the other things that were needed to sustain and progress that technology ? An environment that morally support ESC research, a completely synthetic media to grow ESC, a culture that is devoid of mouse fibroblasts … all these were essential for taking ESC to reach its maximum potential. In modern day science, it is unlikely that we will see a winner of a single battle emerging as the “real winner”. A real winner is going to be the one who knows the game and strategize accordingly.
- US is not the “World”, and IP rights are jurisdictional. So, make yourself open to strategize for the real world!
Another Disclaimer: While starting my blog in WordPress, I had promised that I will not proof-read what I have written. In the past, many times, I had become a victim of my perfectionism and my writings had never seen the light. So, please pardon any typographical, grammatical, or otherwise errors. I hope factual errors are not there. Please let me know if you find any errors so that I can correct the same.
Dr Dileep Vangasseri, PhD (Indian Institute of Science, IISc); Post-Doctoral research, University of Pittsburgh; Senior IP Professional, John F. Welch Technology Center, GE India Technology Center Pvt. Ltd., GE Global Research, Bangalore, India). Dileep has over ten years of in-house IP experience in Life Sciences, Healthcare and Medical Diagnostics industry after eight years of academic research experience in Bio-Organic Chemistry, Gene Therapy and Cancer Immunotherapy. He is well versed in all facets of patent analytics, techno-competitive intelligence, technology forecasting and business development.
This blog was originally posted here on December 7 (2016).
Featured image source: Pixabay
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