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Battle of Wisdom: CRISPR-CAS9

in Sci-IP/SciBiz/SciWorld by
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”.

  1. 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.
  2. 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.
  3. 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.
  4. 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:

  1. 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.
  2. 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.
  3. 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.

Authored by

 

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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This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Finding antibodies in the haystack…

in Entrepreneurship by

Face to Face with Thomas Leung, CSO, BenchSci.

 

The first day I started my postdoc in the Bremner lab, I remember talking to Tom, a graduate student working in the “Epigenetics” wing of the lab. Being fun-loving and most importantly coffee loving, we instantly bonded and formed a team…doing Science and talking non-sense. I witnessed the BenchSci growth closely…it is amazing how Tom took his idea forward, pursued relentlessly and now successfully launched his startup, raising money from both angel investors and VCs. Within a short span, the BenchSci team won University of Toronto Banting and Best Centre for Innovation and Entrepreneurship (BBCIE) Fellowship 2016, Ontario Centre of Excellence (OCE) Smart Seed 2016 and the Brightlane Entrepreneurship Award (BEA) 2016. To inspire potential start up seekers in CSG, I interviewed Tom recently about his journey with BenchSci.

 

ME: Tell me about BenchSci?

TL: BenchSci is a machine learning software that analyzes and decodes scientific papers to extract antibody usage data in the form of figures. These figures are then further indexed and aggregated to make them easily accessible to the research community.

ME: So, how did the idea get started?

TL: During my PhD, one day I was planning a new experiment, which required a lot of new antibodies for this huge Western blot. I was sitting in front of my computer, using conventional search engines and looking through PubMed to search for antibodies that have been validated in peer reviewed papers. After many hours, I thought to myself, “wouldn’t it be nice if there was a database somewhere that I can just input my favorite protein and I will be able to see all papers produced with different commercial antibodies against that protein?”. I started looking online and realized that such database does not exist, so I decided to build one on my own.

ME:  How did you go about it? What’s the process involved and how did you form a team?

TL:  To build this massive database, I know that I am going to need someone with superb programming expertise. My whole academic career was in Life Science and I do not know many people in Computer Science. I know that UofT is a great place with awesome ComSci talents, so I logged into my LinkedIn account and typed in “UofT, programming”. The first result was David Chen, who became our Chief Technology Officer. Amazingly, David is both an adept programmer and a PhD researcher in Neuroscience. I invited him out for a drink and we chatted for many hours and that’s how the team got started. I continue to look around UofT and assembled an awesome team right here, including our Chief Executive Officer, Liran Belenzon, MBA from Rotman, our Chief Database Officer, Elvis Wianda, PhD from Medical Biophysics, and our Community Architect, Maurice Shen, PhD from Pharmacology.

ME: How did your exposure in University of Toronto (U of T) help you in this pursuit, from a lab to a startup?

TL: UofT has many incubators aiming to nurture and support new ideas. We took advantage of this great opportunity and went to a few of these wonderful incubators such as the Hatchery at the Department of Engineering, the Creative Destruction Lab at Rotman Business School, and H2i at the Faculty of Medicine. Also, being a research scientist myself means I was able to talk to many professors and researchers to get valuable feedbacks and comments. For instance, our scientific advisors Dr. Jim Woodgett, Director of Research at Mount Sinai Hospital, Dr. Ruth Ross, Chairwoman of the Pharmacology Department and Dr. Ioannis Prassas, Staff Scientists at Mount Sinai, gave us many great suggestions that helped us develop and improve the BenchSci platform to better serve the scientific community.

ME: How is your platform different from the several antibody validation websites that already exist, like Antibodyreview, Biocompare, etc…?

TL: We are a true validation platform, meaning that we directly showcase experimental usage validation of antibodies in peer-reviewed journals. As a researcher, I realize the importance of seeing a figure more than anything, that’s why BenchSci is designed to show scientists antibody evidence-of-use directly in the form of figures, and not just a mere citation number.

ME: So right now what’s the design of your BenchSci website?

TL: It is very straightforward. All you need to do is go to our platform, type in the protein you are interested in and press, “enter”. We will show you a list of figures produced by commercial antibodies that target your protein of interest. You can continue to narrow down your search to fit your experimental criteria by applying multiple layers of filter including technique, tissues, cell lines, and disease models. We have a demo video on our website at www.BenchSci.com. For one minute of your time you will immediately realize how simple it is to use BenchSci.

ME: Do you plan to move to other reagents, other than antibodies?

TL: Yes for sure. BenchSci is a powerful software that can decode scientific papers, and we are also planning to target other experimental reagents that require validation information before making a purchasing decision.

ME: Is the software the end product that you will sell, if so, what is your future direction after that?

TL: We are offering BenchSci free to use for all research scientists. We truly believe that BenchSci would be helpful for researchers around the world. Many PhD students that we talked to had one recurring comment: “oh how I wish I have something like this earlier in my career!”.

ME: You mentioned to me that you are the CSO, but not the CEO of the company, although the idea is yours. For scientists like me who do know much about startups, can you describe how these titles work out? What or who decides these things?

TL: Each of our founders plays very specific role in the company. As the Scientific Officer, I am responsible for all things life science and biology related during product development, from backend data collection logic to frontend user interface search mechanics. I am not directly involved in the coding (which is done by David and Elvis), I design the scientific reasoning behind the code. Our CEO Liran is responsible for all things on the business side of our company. It is a triangle: Science, Technology and Business, each of the founder’s specialties in each of these components makes the team strong.

ME: There are two types of people who are getting into startups. One kind, like you, start with your own idea. On the other hand, I was attending a talk recently and the guy wanted to start a startup and he did some research on what’s hot right now and came up with an idea and went about it. According to you, which type is more sustainable? Or do you think both will work the same?

TL: The story that you build from the idea is the important element. A good story will resonate with people and bring more impact to the idea. However, the idea can either be something that took place in your dream, or something that was triggered after hearing another person’s seminar. The only difference is that, if you are creating a solution to a problem close to yourself, it is easier to convince others the value of your solution. It is more credible for a cell biology scientist to create a solution for the reagent problem than, for instance, an outsider from mechanical engineering. Let’s say I realized this terrible traffic problem on the highway and wanted to build a transportation system to solve this problem. This idea itself might be very good, but since I have no computer or engineering background, it would be more difficult for me to convince people about this idea.

ME: Finally, do you have any advice for beginners, who want to start a startup?

TL: Imagine a road parked full of cars, looking for a parking space is not going to be possible. If your car is your idea and the road is the market, with so many other solutions already out there, it would be tough for your idea and product to develop and grow. To build a startup, good “product-market” fit is important. Do not try to find parking space on a road already filled with cars. Instead, create solutions for problems that do not yet have a good solution. Maurice, our Community Architect, wrote a very good article for students who are thinking about startup, you can read more here.

 

 

You can find more information about BenchSci, see the following:

Company info: http://www.benchsci.com/about/.

Demo/Introduction video on www.benchsci.com

Company statement: http://blog.benchsci.com/2016/09/15/the-benchsci-story/ “The BenchSci Story”

http://www.theglobeandmail.com/report-on-business/small-business/science-startups-make-research-faster-cheaper-more-accurate/article32270645/ “Science startups make research faster, cheaper, more accurate”

 

About Thomas Leung:

 

Tom Leung completed his MSc in Virology and PhD in Epigenetics at the University of Toronto. For his PhD thesis, he investigated the molecular mechanism of repressive genetic bookmarking during cellular division and the potential application of reversing these bookmarks as alternative cancer therapeutic approaches. As a molecular biology research scientist, Tom experienced first hand the inefficient organization of biomedical publications.

Tom is very passionate about the development of a solution to better organize the vast amount of data in scientific literature in order to bring the most relevant information to scientists to facilitate the next big biomedical breakthrough.

 

About Manoja Eswara:

Manoja did her PhD from University of Guelph, Canada, where she worked on unraveling nuclear cytoplasmic transport pathways for transfer RNAs (tRNAs). Currently, she is doing Postdoctoral fellowship at LTRI, Canada, on Cancer Molecular biology and Epigenetics. Her work is focused on understanding the epigenetic factors involved in regulating replication and gene expression in Cancer cells and the potential use of small molecule inhibitors targeting them as Cancer therapeutics.

 

Featured image source: Pixabay

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This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Med-Ness-JPM meeting, Epipen and more…..

in SciBiz by

Hi all, its our second week and co-incidentally this week SciWri turned one. Happy Birthday SciWri and may the members continue to spread the light of wisdom through their blog sections!

MedRecap

35th Annual JP Morgan Healthcare Conference (JPMHC17)

The annual JPMHC17 took place in San Francisco from Jan9-13. This conference boasts to be one of the largest healthcare conference wherein pharmaceutical companies and small-scale biotech companies present their most recent innovation technology and share their future goals. The major highlights of this year’s conference are as follows:

  • Major focus on Oncology as leading pharmaceutical companies presented their innovative ideas at the pipeline stage or approval stage. CAR-T therapy presentations stole the show.
  • Genomics was another hot topic that was discussed and new therapies and technological advancements were presented. Illumina’s $100 genome was one of the most successful presentations. Illumina’s latest baby NovaSeq was unveiled at JPMHC17. This new machine (available as 5000 or 6000 system) is expected to expedite the experimental plan while reducing the over all cost, although, the real “$100 genome” deal is still far. The introduction of NovaSeq is definitely good for the company’s rising stock.

Head turning business deal: $5.2 billion bid by Takeda Pharmaceutical Co Ltd for Ariad Pharmaceuticals Inc. Ariad Pharmaceuticals, specializing in oncology drugs, developed drugs like Iclusig (Ponatinib for chronic myeloid leukemia); AP32788- kinase inhibitor for NSCLC and now Brigatinib for Alk positive NSCLC patients resistant to or who experienced drug progression on Pfizer Inc’s Xalcori (Crizotinib). The deal is expected to close by end of February.

 MedNess

Do we have an alternative to Mylan’s EpiPen?

2016’s most controversial product, EpiPen’s alternative is expected to hit the market with a list price of $4500. Kaleo’s Auvi-Q allergic device will be available for as low as $360 in cash for uninsured patients. However, the company has agreed to cover the full cost for those with a high deductible insurance plan or with household income less than $100,000.

MedPharm

Biosimilar for AbbVie’s Humira accepted for Review

Abbvie’s Humira (adalimumab), indicated for multiple inflammatory conditions including rheumatoid arthritis, psoriatic arthritis, adult and pediatric Crohn’s disease, ulcerative colitis, pulls in annual sales of nearly $15 billion. This drug was approved in US and EU. Boehringer Ingelheim introduced their biosimilar to Humira and has been accepted for review by both FDA and EMA.

In September last year, FDA also approved Humira’s first biosimilar version- Amgen’s Amjevita.

MedPol

Joe Biden’s Cancer Moonshot Future

Cancer Moonshot- an initiative by Joe Biden was a ray of hope for the scientists focusing on cancer research. However, researchers all over the US have feared the thwarting of research after the successful fulfillment of Barak Obama’s presidential term. In one of the last initiative, National Cancer Institute (NCI) is designing a new plan wherein the scientists can pursue new combination therapies. NCI will act as a mediator between the drug makers and the outside researcher’s thus enabling scientists to access new drugs for research.

At the present, six companies including Bristol-Myers Squibb, Eli Lilly, Genentech, Kyowa Kirin, Loxo Oncology and Xcovery have participated in the program.

Francis Collins to stay as NIH Director under Trump’s administration

Francis Collins has been asked by the president-elect Donald Trump to stay on his position as National Institute of Health Director. The duration of his stay is still unknown. He has been serving at NIH since last eight years under Obama’s administration.

 

This was the succinct version of MedRecap, MedNess, MedPol and MedPharm..more to follow next week. Have a great weekend.

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