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You had the Right to Remain Silent

in Sci-IP by
Editor’s Note: Silence is Golden, isn’t it? After reading #ClubSciWri’s Sunday Blog from Syam Anand, you will realize how the complications in the patent war on CRIPSR-Cas9 have resulted from the statements made by parties whose vested interests are at stake. So next time when you have a plan to cash your intellectual crop, look before you speak! –Abhinav Dey 

The patent system adopted by the constitution of the United States of America, is a pursuit to protect the rights and liberties of the individual vis-à-vis the interests of the state and the community it serves. It puts down common sense rules and laws to bestow privileges called patents to rightful inventors for a limited amount of time. Is it perfect? No. Is it good? Yes. Can it be improved? Certainly! Are the concerned people working to improve it? Yes.

Before the patent system, one should understand that we mostly had monopolies bestowed upon individuals based on the whims and fancies of the royals or whoever ruled. That was hardly democratic. The idea of the patent system (Venice had one of the oldest) was to put in place a democratic setup with weights and balances. Further, it meant to incentivize inventions and spur economic activity by stating rights and liabilities in commerce. From time to time, weights piling up on one side upset the balance. That is a natural consequence and the system usually adapts. It is a pursuit and not a static state.

One of the ways the changes for the better (at least that is the idea) happen is through amendments to old laws and passing new laws that replace old ones. Most of the wisdom that drives changes is derived from case law. Patent rights are often fought hard in the USPTO after a patent is granted and beyond that in the judicial system. Why? Because the outcomes have huge economic consequences- real jobs, real lives and real advancements in science and technology are at stake. There are aspects of the patent law that the USPTO can rely on to decide rights. For the aspects of the law beyond the USPTO’s gambit, the judicial system helps to decide rights and liabilities.

The title is a quote taken from Miranda rights, legally required to be read to any person in the United States of America by law enforcement personnel before they are interrogated to preserve the admissibility of their statements against them in criminal proceedings. The full version is

“You have the right to remain silent.

Anything you say will be used against you in a court of law.

You have the right to an attorney during interrogation;

if you cannot afford an attorney, one will be appointed to you”.

Much like criminal law, things that you say and do before and after filing a patent can affect your case. This could be anything- interviews, opinions, articles, conference talks, abstracts, emails…anything of which there is a record that can be accessed. Having a record can be as good or as bad as having no record. To top it all, you do not have a right to an attorney, when it comes to patent law. You will have to afford one yourself. Many of these aspects are technology-neutral. That is the key here- the technology and the finer details matter, but not in the way one would normally think.

In that sense, the CRISPR patent war that is going on currently in the USPTO (United States Patents and Trademark Office) is not unique. There are many cases prior to this that asked whether inventive step(s) were involved in taking something from one system and making it work in another?

The tests are simple:

  • Can an ordinary person skilled in the art (in this case a molecular biologist) have taken the system that Doudna disclosed in her patent application be practiced in the system that Zhang ALSO disclosed in his application without further experimentation?
  • Are there admissions that Doudna made (anywhere in any form of which there is a record) that incriminates herself in the sense that the invention was just an idea and the enablement (guarantee that it will work as described) was not present at the time of application?
  • Did Zhang enable the invention before Doudna did although she described the idea first?

If Doudna incriminated herself, making statements that it is not easy to move the system from prokrayotes to eukaryotes, but still has proof that she none the less did this successfully in eukaryotes, before Zhang did, she wins.

Does this mean that everyone has to license from the winner in this case? Not really. They have to license only in the countries were Broad Institute or UC Berkeley has pursued patents and obtained rights. Elsewhere, everyone can have fun with CRISPR-Cas9 and make money or go broke. Probably, even more so in countries where patent protection is lax.

About the author:

Syam

Authored by Dr Syam Anand, PhD (Indian Institute of Science, IISc; Post-Doctoral research, University of Pittsburgh School of Medicine; Faculty, University of Pittsburgh School of Medicine, Founder and US Patent Agent, Mainline Intellectual Property LLC, Ardmore, Philadelphia USA). Syam has over 20 years experience in diverse areas of Science with domain knowledge in Life Sciences and Intellectual Property. Dr. Anand is also an inventor and budding entrepreneur. A rationalist, Dr. Anand enjoys science at all levels and advocates the use of scientific methods for answering all questions and solving all problems and make common people curious and interested in understanding their worlds.

https://www.linkedin.com/in/syamprasadanand

About the illustrator:

Ipsa Jain is a Ph.D. student at IISc. She wants to gather and spread interestingness. She prefers painting and drawing over writing.

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

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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From cloning genes to directing X-rays: Face to Face with Nishant Kumar Varshney

in Face à Face by

Dr Nishant Kumar Varshney is working as a Beamline Scientist on an Indo-Italian Macromolecular Crystallography beamline XRD2 at Elettra Sincrotrone, Trieste, Italy, which will be open to Users in start of the 2017. The Career Support Group (CSG) for STEM PhDs caught up with him about his career and experience while working in an unconventional postdoctoral career of a Beamline Scientist after a PhD in Structural Biology.

He did his bachelors in Chemistry from DU and Masters in Marine Biotechnology from Goa University in 2005. Completed his PhD in 2013 from Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India on structure-function relationship of three enzymes that has industrial and therapeutic applications. During his PhD, he received Commonwealth Split-Site Scholarship to work for an year in York Structural Biology Laboratory, University of York, UK, where he developed his interest in the field of Structure Based Drug Discovery field.

me_2

In Nishant’s (NKV) words, “First, I would like to thank Abhinav Dey (AD) for adding me to CSG group and now giving me this opportunity to share my thoughts about new Indo-Italian joint venture at Elettra Synchrotron, Trieste, Italy which we Inaugurated last month.”

14711082_1239623179443730_8023412272330443242_o

(XRD2 Beamline; Picture source: NKV)

AD: During your graduate school, when did you realize you wanted to try a different research-based career than conventional postdoc?

NKV: Actually the thought and the opportunity came after the PhD, when I was working as Research Associate (RA) in National Center for Cell Science (NCCS), Pune. During my PhD, I was working both at the bench (cloning, expressing, purifying and setting up protein for crystallization) as well as collecting data at our home source for my proteins and sometimes helping other collaborators. Like most of the graduate students, I dreamt of getting a conventional post doc position abroad and coming back after few years for some decent permanent position in India. It was during RA-ship, that I saw the ad for a Beamline Scientist position at the new Indian beamline at Elettra. I thought of it as a good opportunity to not only learn about the working of beamlines but also having plenty of time to play and learn with data collection strategies to get best out of your protein crystals. Moreover, the idea of helping different users with different projects and, if possible, making some worthy contribution to their projects excited me too.

AD: What is your typical work day like?

NKV: Most often our day starts with a black filter coffee at 9 🙂 and ends around 6pm. Currently, we are at the final stages of commissioning the beamline and implementing an automated instrument on the experimental table. Since working at the beamline is a first time for me, my work schedule usually revolves around my local supervisor and Head of our group, Maurizio. We help our supervisors with the work and learn out of it. Everyday there is something new to learn. We set small targets with deadlines and sometimes we work till late to meet those deadlines. Also being an industry, there are many other usual administrative/non administrative appointments also to be taken care of.

AD: Do you think having a PhD was an advantage for you in the current job?

NKV: Yes. Experience and a degree in structural biology were the essential educational qualifications for this job. I was brought into the field of X-ray diffraction, protein crystallization, three-dimensional structures etc. in practice during my PhD only. Having hands-on experience with these techniques and a visit to a Beamline in Diamond, UK during my Commonwealth Scholarship tenure gave me experience and confidence to apply for this job. Some technical terms and what’s behind the walls of Experimental Hutch was totally new to me in the beginning but I think I am getting better day-by-day.

AD: How was the transition from a bench to a synchrotron?

NKV: I would say transition was not that easy. Coming from enjoying a mostly wet lab, handling buffers/proteins and transitioning to the technical aspects of a synchrotron where I was expected to understand as well as install beamline components, alignments, installing vacuum etc. was initially too much technical for me. Mathematics has not been my strongest subject so I am still trying to get better with the numbers.

AD: What would you recommend as first steps for students/postdocs interested in pursuing a fellowship in handling this kind of job?

NKV: If one is coming to synchrotron as a user, I would say, apart from having familiarity with data processing programs and knowing your proteins, you need not to worried about what’s behind the walls of Experimental Hutch. Beamline staff should teach you how things work at the Experimental table and how to collect data. But if someone wants to be a Beamline Scientist or a Beamline Postdoc, first step is to develop your love for the technical aspects of a beamlines. Brushing up your Physics or say Biophysics will also help you to understand your work. It is also important to keep in mind that it is not a 9-5 job and you should be ready to devote long days sometimes.

AD: Having gone through interviews as an applicant yourself, what are a couple of things that could help a PhD standout from the crowd?

NKV: Especially for a job at the Beamlines, working knowledge of the beamline, however little it may be, through regular visits to the synchrotron for data collection and processing the data on your own will make you stand out. Familiarity with different programs for data collection to structure deposition will help you for the job. Apart from that, one should enjoy working with the users and be ready to help them to sort out the technical as well as practical problems outside the normal office hours.

AD: Was there anything (positive or negative) that you were surprised about this job/profession that you didn’t expect until you were in it?

NKV: As a matter of personal opinion, anyone who starts the unconventional career, will wish to have a sense of stability in his/her tenure. As I am working in an Italian Industry, as a visiting Scientist on an India-funded project, there is always an insecurity regarding the length and timing of the next extension. Moreover, the absence of funds available for in-house research and for attending/presenting work in the conferences was not what I expected.

AD: Please tell us about the new Indo-Italian venture and what do you foresee of this collaboration for the development of science in India?

NKV: Till the date, India is either renting beamtimes for macromolecular crystallography e.g. BM14 beamline in ESRF or funding visits to other beamlines of the world. This is the first time when India is a partner right from the design, construction, commissioning and maintenance of two beamlines at synchrotron. The XRD2 and Xpress beamlines are a part of a scientific partnership between India and Italy under a project administered through the Indian Institute of Science (IISc) at Bangalore with financial support from Department of Science and Technology (DST), Govt. of India and Elettra Sincrotrone,Trieste. The Xpress experimental station has been constructed to study the structure of materials under high- pressure using the technique of X-ray diffraction of samples subjected to the action of two diamonds that can exert higher pressures to 50 GPa. In this way the researchers will be able to access the possibility of synthesizing new superconducting materials, harder and more resistant. This beamline will also be applied in other areas, such as mineralogy and geophysics. XRD2 is a dedicated beamline to determine three-dimensional structures of proteins and biological macromolecules with application in biology, medicine, pharmaceuticals and biotechnology. XRD2 is an highly automated and tunable beamline with state of the art instruments which will allow to collect faster X-ray diffraction data from protein crystals in highly automated way better than collected using home source. With 50% share in the project, now Indian crystallographers and High Pressure diffraction groups will have plenty of beamtime accessible to them. Once the proposal has been accepted, DST will provide the travel and daily cost funds.

AD: What are the career possibilities after being trained at the cutting edge of your field?

NKV: The field of macromolecular crystallography is still in a developing stage. There is lot to explore and develop in the field right from the data collection step to relate the structure to its function. With the experience at the synchrotron, prospects of developing your own research in the field are always open. Working in Pharmaceuticals Industries mainly involved in Structure based Drug Discovery is another option. With all the knowledge of the structural biology, a career in academics is also a possibility. Moreover, with the advent of Free-Electron lasers and new developments in alternative techniques, three-dimensional structure determination of macromolecules using serial crystallography and Cryo-Electron Microscopy and Cryo-Imaging techniques are the new open fields where experience in structural biology is a desirable qualification.
I hope, these facilities will be very beneficial to our Indian researchers.

 

 

Nishant Kumar Varshney was interviewed by Abhinav Dey. Abhinav is a postdoctoral fellow at Emory University and a Young Investigator Awardee from Alex’s Lemonade Stand Foundation for Childhood Cancer. He is also the co-founder of PhD Career Support Group (CSG) for STEM PhDs and ClubSciWri

(https://www.linkedin.com/in/abhinavdey)

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The different hats of technology transfer officers

in Entrepreneurship/Sci-IP by

business-561387_1920

With the establishment of Bayh Dole Act in 1983, US universities started establishing “Technology Transfer Offices”, whose main job was to evaluate inventions coming out of their laboratories. This helped universities to protect their intellectual property (IP) and license it out to startups or established companies. Technology transfer begins as soon as inventors disclose their technology to technology transfer offices. A technology transfer officer then wears different hats- an inventor’s, an attorney’s, an entrepreneur’s, an industrialist’s or a consumer’s to weigh various aspects of the technology before he/she consents to file a patent. As simple as it sounds, it requires a sound knowledge of the science involved and the rules and laws of patent prosecution. It also requires the business acumen needed to license a technology after filing a patent. Let us go through these steps one by one:

Determining prior art: The first and the most important hat worn by a technology manager is that of a patent agent. He/she asks the most important questions on the disclosed technology that a patent office will also ask: Does the technology have “utility” in the real world? Is the technology “novel”? Given all the previous knowledge or literature in the field, is the technology described by the inventor “obvious”? A patent will be granted by a patent office only if the answer to the first two questions is affirmative, and the answer to the third question is negative. Based on literature and patent database searches for the disclosed technology and judgment from experience, technology transfer officers decide whether to proceed forward with the technology and file a patent.

Freedom to operate (FTO): Wearing an attorney’s hat, the tech transfer officer asks another crucial question: Assuming that a patent is issued for the disclosed technology, can the owner or licensee of the patent practice the invention without infringing upon other patents? In other words, how much “freedom to operate” does the patent actually confer to its inventor/owner/licensee when compared with other patents that have been granted in the same area. A patent that cannot be practiced is as good as not having the patent. It is like investing in a dead technology. No business will buy or license out the technology. Patent prosecution being a very expensive process, a technology transfer officer evaluates the FTO very carefully to decide whether or not to invest university’s money to protect the technology. In my future blog, I will discuss FTO in detail.

Market: The next hat that a technology transfer officer wears is that of a marketing analyst. A tech transfer officer is not only involved in protecting the IP but is also instrumental in supporting the development of the technology. The whole idea of protecting the technology is to incentivize the companies to license out the technology from the university to make it useful to the society. To attract industries to invest in the technology many important questions are asked in advance: 1. What is the current market for the technology? 2. What is the market landscape (what other companies are involved in the technology space?) 3. If the technology enters the market, how much market penetrance will it get? In other words, will the industry see the return of investment if they license the technology from the university? Stage of development: A crucial factor in marketing university-owned technologies is to gauge the stage of development of the technology. Most of the university-based technologies are very embryonic or in other words, very early-stage technologies. Such technologies, especially in biotechnology, need a lot of investment from companies who are licensing it, both in terms of money and product development. Remember, an issued patent has a term of 20 years from the date of filing in

Stage of development: A crucial factor in marketing university-owned technologies is to gauge the stage of development of the technology. Most of the university-based technologies are very embryonic or in other words, very early-stage technologies. Such technologies, especially in biotechnology, need a lot of investment from companies who are licensing it, both in terms of capital and time investment. Remember, an issued patent has a term of 20 years from the date of filing in USA. A technology that requires a long incubation time will eat up the patent term (number of years of the patent rights). Losing the patent term means losing the competitive advantage. Therefore, the technology transfer officer needs to ascertain that there will be sufficient patent term remaining for the company, to recover its invested dollars and generate a considerable return of investment on the product.

Tradeoff analysis: One of the primary objectives of technology transfer offices, as I have already mentioned, is to see the university technology get developed into a product that is directly useful to the society. Therefore, the tech transfer officer evaluates pipeline products of companies, their business and development plans, their market share and capital as well as their past performance in developing the licensed technologies. The question whether the technology is suitable for a startup or an established companies is very crucial. A startup will have a vested interest in developing a technology. Therefore, it will have a focused approach towards the development of the product. In the case of established companies, they will have several products in their pipelines. Therefore, their focus, and hence, the development plan my change with changing priorities that is heavily shaped by the market. At the same time, startups are risky, and their product development pipelines are not as well charted out as an established enterprise. Therefore, an important challenge for tech transfer officers is to do a tradeoff analysis to narrow down the companies that will provide the best opportunity for the technology to get developed into a viable product.

Technology valuation: This is perhaps the most difficult part of the technology transfer process in the universities for which there are no easy answers. In general, the technology transfer officers rely on past deals (also known as comparable deals) for similar technologies and market analysis to come up with a value. There are complex quantitative ways to estimate the cost of the product 5-10 years from the present day for a thorough evaluation. One can easily imagine the difficulty in predicting the market a decade in advance. The two most important aspects of valuation are license issue fee and royalty. The latter is most important for universities, as it is their return of investment for their innovation. It is through royalties that universities can pump back money into the basic research and infrastructure. They can also incentivize inventors by giving them a part of the royalty.

Salesman: A tech transfer officer also needs to be an excellent salesman. Like a prudent salesman the officer has to win the best possible deal (in terms of royalty from the sale of the technology (also known as consideration) and due diligence (DD) terms for the technology development) for the universities. This is the most challenging hat worn by a tech transfer officer. It starts when a company shows interest to license a technology for making, using and selling it as a product. The tug-of-war involved in coming to a perfect term for a licensing deal is a thesis on its own. It will be sufficient to stress that this step requires the wizardry of a technology transfer officer to win a profitable deal for the university to support everything that a tech transfer office stands for. During the negotiation process, the officer always makes sure that the interest of the university and its IP is given the supreme interest. Once, the negotiation is done, the deal is formalized in a license agreement and is then bound by the law of the state.

Police Officer: Following license agreements, tech transfer officers monitor the strict DD terms. DD is very crucial for technology transfer officers, because it acts as an instrument to make sure that the technology gets developed in a timely manner. Breaching DD leads to termination of the license agreement.

The final goal is to see that the technology gets developed and is transferred to the masses for their consumption, thereby advancing the society through cutting-edge science and technology.

Ananda Ghosh

https://www.linkedin.com/in/ananda-ghosh-3238a716

How to create and measure innovation?

in That Makes Sense by

“Innovation” is THE buzz-word of today!

Everyone wants to label their companies as innovative, hire innovative people, create processes to induce innovation and be the next big innovator! But how does one really ‘innovate’ and how do we quantify innovation?

Sarah Kaplan, professor at the Rotman School of Management at the University of Toronto came up with an interesting answer that you might not have expected.

It is generally thought that brain storming with people from diverse knowledge backgrounds is a great way to come up with new ideas. In their paper, Kaplan and colleagues show that while combining different disciplines does lead to novel ideas, there is another equally important way that innovation works. In-depth knowledge in a field is required to understand the anomalies within the field, which can then lead to novel ideas.

“We find that, counter to theories of recombination, patents that originate new topics are more likely to be associated with local search, while economic value is the product of broader recombinations as well as novelty.”

Interestingly, breakthrough innovations were more likely to result from searches within a domain but economic value was a result of novel innovations arising from a combination of diverse ideas. However, such patents were very rare making up only 1% of the dataset.

“Patents that were both novel and had economic value were the most valuable. And that was only about 1% of the total patents.”

At this point, most researchers must be nodding in agreement “I had thought so”. What was the most surprising thing for me, though, was the way they measured “novelty”. In scientific literature as well as the patent world, innovation is measured as a direct function of citations. Even though most of the scientific community has rejected the idea of the journal impact factor as a way to measure the quality of a scientific article, the next best measure employed is the number of citations for the article itself. Thus, a patent or scientific paper that get highly cited is considered superior and thus a breakthrough innovation.

“What we found in our study is, in fact, that most of the patents that do get highly cited are not necessarily novel.”

In this study, the authors used a different metric to examine patents from the field of nanotechnology. A computer science and natural language processing (NLP) method called topic modeling that uses “a bag of words, a body of text, …and it infers from that body of text by the co-location of all the different words, what are the key underlying topics in the data”  was employed to determine if novel ideas were being developed. Interestingly, the patents that had high level of citations were not necessarily novel.

This is an interesting revelation, and something that scientists should also consider while judging the quality of literature. The entire reward system in science is largely based on publications and the feedback from citations. This generates ‘hot’ topics that many scientists work on, read about and cite, thus creating a research bubble. In such an environment, other fields of potential interest have difficulty to gain exposure and citations. Researchers flock towards hot topics, which can hinder the overall progress of science.

This generates ‘hot’ topics that many scientists work on, read about and cite, thus creating a research bubble. In such an environment, other fields of potential interest have difficulty to gain exposure and citations.

Kaplan and her group plan to delve deeper into how innovation works by studying novel ideas in different fields. It would be interesting to see what insights they can bring!

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About the author: Czuee has a PhD from the University of Lausanne, Switzerland and Masters from IIT Bombay. She has previously worked at IISc-Monsanto collaboration and as a patent analyst at Evalueserve. Apart from her research on proteins involved in brain signalling and diabetes, she is interested in scientific communication (czuee.wordpress.com), entrepreneurship and runs a webcomic (http://gradschoolmuse-icals.thecomicseries.com/).

Photo source: Forbes.com

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