 Hello and welcome to NewsClick. Today we're going to discuss something which has come into much more prominence because finally the United States President Biden has accepted that intellectual property limited to patents at least will not be considered as a bar bar for manufacturing this in other countries. So essentially something that India and South Africa and a huge number of social groups in the world, public health groups, countries, I think more than 100 odd countries have also said this in WTO that they would like intellectual property rights to be waived for the period of the pandemic. Now, one thing and Satyajit, I would like you to tell us a little more about it that a lot of the groups have said it is not patents which is the problem. It is the know-how that it is also the diagnostic kits. So there's a whole bunch of things on which the issue was never the question of patents because after all trips 2001 itself settled the issue that during a pandemic or a health crisis emergency countries could break patents of any company and license it from the production internally. So this is really not what the global community or the public health community was asking. So how far does it help? That's really the question. And if it doesn't, what are the things that it still does not help in? What are the specific issues with respect to not just patents, but also the other, the gamut of other things which intellectual property rights cover? So let's think about this in three different related aspects. One is that it is true that it's not about one patent. And in part, that is because most big pharma, big IT once upon a time, even today big pharma, tend to build not one patent for one product, but a whole patent hedge of literally hundreds of patents, fitting overlapping between each other, covering the entire process of making the product formulation. So this is still admittedly a patent issue, but it is a point to say that we're not talking about one patent. And it's quite possible that some of these patents in the patent hedge are the specific patents for which a waiver is being discussed, but others are drawn from a far more general patent pool and have been fitted here. And oh, those are not about this particular vaccine, so they shouldn't be part of the waiver. It is quite plausibly an argument that may come up sooner rather than later. So that's one point, which is tactical. The second point is increasingly over the past centuries, ever since the patenting system has been put in place, where originally the whole point was to describe the invention in a way that anybody could reproduce it. In fact, that was the original intent of the patent itself. The original intention of the entire patent process itself to shift to that from a trade secret based practice. But increasingly, what has happened inevitably is that while lip service is paid to full disclosure in the patent, in reality, there is actually not sufficient information in the patent document itself. There is no replication and reproduction. And as a consequence, you need to know all the little tricks of the train, which effectively are then trade secrets in order to make the published patent work in somebody else's hands. And this then becomes an additional lever of effectively intellectual property over and above formal published filed accepted patents in order to restrict distribution and maintain control for, in this case, public farming. That's the second component. The third component of this restriction is the argument, most notably, apparently at least implicitly made by Mr. Bill Gates recently that it's also a matter of the manufacturing landscape in a particular place in a country. It's level of sophistication. It's level of sophistication both in terms of the benchmarking and the reliability of its supply chains for all the small products that go into the final product, as well as the skill levels and the new take capacity of the professionals of the human resources who are going to do this. And it's at these three interlocking but distinct levels that this entire argument is functioning about, oh, what are the many limitations and restrictions for the global south to be simply taking these miraculous vaccine technologies and implementing them in large scale manufacturing. So, two simultaneous arguments, one is they're stealing our intellectual property, which I think was made recently by the American pharmaceutical industry, that if we wave patents on these miraculous drugs or vaccines, then China and Russia might start making good medicines against other diseases or why that should be something we should be looked upon with a great deal of suspicion is another matter. But the idea is not very different from saying the third world countries like India are stealing our property. So it's really going hand in hand with that. And we actually saw that argument with the AIDS epidemic as well. And this was essentially the reason why American pharma companies sued South African government rather shamelessly that cheap generics from India does not reach the AIDS patients in South Africa. So that was the big AIDS battle. And it's interesting when you look at the profit margins, for instance, of Pfizer or Moderna. And this year, Moderna said they expect to make something like $19 billion. They never had profit before $19 billion this year. So you are really talking about astronomical level of profits from companies who have always been at a loss. Of course, that is what venture capital does. But coming back to the crux of the issue that if we want to scale up production to the level that we need, that which is really 14, at least 12 billion doses this year, which means at least 12 to 13 billion will get into people's bodies. Then we are really talking about scaling up the capacity of the world very significantly, otherwise we'll not probably exceed 7-8 billion doses this year. And of course, India and China have a big role to play. And interestingly enough, South Korea as well, because these have all looks like capacities for producing vaccines at a scale. Now, if I look at the three major vaccine, shall we say processes that are being followed? One is the inactivated virus vaccine that is being used, which is Sinovac, Sinofarm, as well as Bharat Biotech. The second is the adenovirus platform, which is, again, it is AstraZeneca. Of course, Serum Institute India is following that. And then you have the Malia Russian Sputnik vaccine. You have also a CanSino vaccine, which is available. And there are also the other vaccines that come from the U.S., for instance, Johnson & Johnson Janssen's vaccine, which all of them seem to be variants of the adenovirus vector vaccine. And of course, the two which have become the star of the show at the moment, at least in advanced countries, economically advanced countries, which is the Pfizer Biotech and the Moderna vaccine. Now, can we separate them into the three groups? Say, the inactivated virus vaccine, vector virus vaccines, and the mRNA vaccines. And look at what are the scales involved? And can we start with the inactivated virus vaccines? And what could the world do? And are there any intellectual property rights issues involved in this? So I seriously doubt that for inactivated virus vaccines, any substantively restrictive patent or intellectual property rights would be available. At most, if you're using as a biotech in its co-vaccine is using, if you're using a particularly new adjuvant, the adjuvant may be under patent rights. But adjuvant patent rights typically are given non-exclusively because the whole point in adjuvant is that it should be used as widely as possible. So I don't think that an adjuvant patent right is ever going to be a restrictive matter. Also in the biotech got access to it fairly easily. As far as the technology itself is concerned, an inactivated virus vaccine technology. On the one hand, it's simple. Let's all keep in mind that every year we make and distribute worldwide influenza vaccines, every year a new set of influenza vaccines, all of which are essentially inactivated virus vaccines. Now, admittedly, they're still grown in chicken eggs because influenza viruses do grow in chicken eggs. But whether you grow them in chicken eggs or you grow them in human cell lines in industrial scale by reactors, essentially all you're doing is growing the original virus. That's just a wild organism. There's nothing to patent in it. That it grows in a cell line is common knowledge. So there's nothing to patent in that. All you're going to do is in at bioreactor scale, at commercial manufacturing scale, you're going to, you're going to culture cell line. You're going to infect it with the virus. You're going to harvest the virus. You're going to clean up the virus. You're going to inactivate the virus. The commonest method of inactivation is a chemical inactivation, such as beta propiolactone, which is what, for example, biotech uses for its co vaccine inactivated and formulated either formulated by itself, which I think is how for example, the vaccine is formulated or add for good measure a little adjuvant to it and formulate it. These are all very straightforward technologies. Mammalian cell culture at a manufacturing scale is a technology that any pharma manufacturer who is manufacturing so-called biologic drugs is familiar with and is competent to execute. As far as growing virus is concerned, clearly Bharat Baitech has shown the capacity to do so. A whole range of others have shown the capacity to do so. In fact, India has been making virus grown like that for polio vaccine, for this, that and other. In fact, ICMR many, many decades ago made an antiviral vaccine for what is now an obscure disease called Casanoog forest disease, which was exactly the same. They grow the virus, inactivate the virus and immunize with it. So that's a technology, the technological capacity for which is very widely available. Intellectual property restrictive regimes are likely to be very lax if at all present and therefore that's a technology that's very easily implemented across the world. The only catch there is that because you're growing infectious virus in large amounts, industrial amounts, and this is an infectious virus that causes disease. Now that as you scale up, the amount of infectious virus that you're carrying in any one place becomes larger and larger and therefore your biosafety, containment, security, provisions and technologies become more and more demanding, more and more robust and so on and so forth. Another way to think about that is, but if many people were growing it in small scale, many small manufacturers were growing it in small scale, it would be feasible. Absolutely. Yes, it would be feasible. There's a point I would like to make about this before we move on to the end viruses and that is, given these circumstances, given the fact that the government of India is along with the government of South Africa, one of the major layers in this demand for intellectual property waiver for COVID-19 vaccines. I find it incomprehensible that the government of India licensed an Indian Council of Medical Research generated inactivated virus technology vaccine to one single private sector company. That means true even now. And it might be worthwhile asking the government, why is this, has it done this? No, that's something which is very interesting because we have at least 20 officially registered vaccine manufacturers in the country, all of whom have the ability to do what exactly you talked about. That's what routinely they do. This includes seven public sector undertakings which have actually, most of them seem to have stopped making anything. And out of that one of that was of course the famous Havkin Institute's derivative which is the vaccine biopharmaceutical company, which is again Maharashtra public sector undertaking as of now, which has restarted doing this COVID vaccine, hopefully with ICMR technology. And it still is one of the largest suppliers of the oral polio vaccine in India. In fact, I think it has a 9% global share of vaccines by volume. So we have, apparently we have a large number of companies in India who can do it. China is actually the Sinovac vaccine and the Sinofarm vaccine have been farmed out to a number of producers. And they seem to be scaling up exactly the way you suggested that it has been developed in the public sector, in the universities and in the public sector. And this has been the technology has been found out to a number of vaccine manufacturers, and they're scaling up. And that's why China has been able to scale up production quite rapidly, not having the kind of serum institute facility. And they have adopted the strategy Satyajit was talking about. So this is for our viewers, that this is a technology which is which is being used. Unfortunately, India decided to go only with modern biotech. And this, as he says, is not explicable not only from Indian come point of view because you could have really ramped up manufacture much faster, but also from the point of view globally, sharing the knowledge so that others could produce instead of becoming a bottle. Satyajit coming back to the adenovirus vector vaccines, the vector virus vector vaccines, which are used. And the next popular ones at the moment, which are in use. Looking at it from the point of view of global amount of actions being produced is seems to be the adenovirus vector vaccines as to Zenka being of course a leading amount in volume. But we also have CanSino, which is also seems to have developed an adenovirus vector, vector based vaccine. They also had an Ebola vaccine earlier. So this is not something they have done for the first time. And we also have the Sputnik 5, Gamalaya vaccine. So all of them, how difficult are they to scale up considering Gamalaya tied up it seems now with at least five Indian bio biologic manufacturers, they're not per se the vaccine manufacturers but the biologic manufacturers and they seem to be also willing to produce large amounts. China has signed up with Gamalaya and so has South Korea and if all of them come to the market we're really talking about 1.5 billion doses of vaccine probably in the next 6 to 10 or 12 months. So was that a route possible for India to take and was intellectual property a major issue over here? So let's get something clear about the technologies involved. We discussed the inactivated virus vaccine and we pointed out that if you had human cell lines growing in bioreactors, you could infect those cell lines with the original virus, that's the COVID-19 SARS-CoV-2 virus, it will grow in those cell lines, it will come out and you can take out the liquid from the reactors and you can purify the virus. The adenoviral technology is at the manufacturing level pretty much the same. The difference is rather than putting the dangerous original infectious virus on to human cell line, what you're putting is a relatively harmless adenovirus into which you've engineered a piece of the SARS-CoV-2 virus. Essentially the spike protein gene of the SARS-CoV-2 virus. Now the adenovirus will infect and the adenovirus will generate therefore large numbers of adenovirus is carrying the target of interest. So that's in manufacturing terms it's exactly the same technology. Now keep in mind the additional wrinkle that all these adenoviral vector vaccines, the AstraZeneca one, the Gamalaya one, the Sinovac one, the Janssen-Jonsen-Jonsen one, all of them are non-replicating vectors. And what that means is from this cell line the new adenoviruses that come out, they can infect target cells but they cannot make new viruses in those target cells. They can simply express proteins in those target cells which is how it will function as a vaccine but they in turn can't make infectious virus. So then how did they make infectious virus in the bioreactor in the first place? That got made because the genes that the viruses are lacking for making infectious virus in an ordinary cell have been engineered into this cell line. But that's at the laboratory scale. Once you have done that, once you have created this pair of an engineered cell line and a defective virus, then manufacturing technology-wise it becomes the exact same technology. Take the cell line, grow the cell line in a bioreactor, infect it with your virus of choice, this time an adenovirus, harvest large amounts of freshly produced virus, don't even inactivate it because this is an adenovirus. It's not dangerous, it's not going to replicate, it's just going to go in once and create the protein for the immune response to happen and therefore all you have to do is to purify the virus and package it. If you can make biologics, this is how we've been making biologics. If you can make biologics, if you can make inactivated vaccines, you can make the adenoviruses vaccines. So in that sense, this is again a technology that is only incrementally different if at all from well established technologies that as you point out manufacturers of biological drugs and of relatively recent vaccines have been using widely for the past few decades. Except the number of such vaccines still are very few before the present upsurge as we might note because otherwise the couple of Ebola vaccines and I think a couple of more vaccines were using the adenovirus vector as the So, just as a footnote to that, let us all keep in mind that one of the largest, most protracted vaccination campaigns in our history, global history, has been with a tissue culture grown virus, the injectable polio virus vaccine. That's how we made the polio virus vaccine. We took cell lines. That's what you're not stuck to the cell line grew polio virus attenuated it by growing it a few times and then harvested the virus inactivated it. What you're saying is that technology again is relatively well known. And in technology terms whether you're growing and the virus or the actually the virus itself for manufacturing, it makes no difference. So, this again, therefore, the whole argument about know how etc. Well, I will not use the sharp word bogus, but it's basically much more of an overkill in order to sell the idea that people don't have the technology of the capacity, unless as you pointed out about Mr. He says that there are dates on what he said, where he actually send it and so many words that Indians don't really have the capacity, till we give them the money, and we teach them how to do it. I'm not paraphrasing him this were almost his exact words. This is the sky TV interview that he did. And the interesting part about all of this is again, India has a part of the 20 vaccine manufacturing companies. or the biologic companies who all have the capacity of doing it and scaling this up to the level required again as you say it is not as difficult as scaling up for the inactivated virus because you are really not doing, you're not growing live viruses you're really growing viruses which are in that sense are not going to be dangerous. So that's that's the second part of it again here the know how is not the major issue if IP is an issue well that of course is something that we can still discuss. The third part and this is where I think there is an argument regarding patents, because this is relatively the first time the mRNA vaccines have come into emergency use authorization we never had a successful mRNA vaccine till date. These are really platforms we have built and whether it's an adenovirus vector platform or an ever in a virus ever in a vaccine platform, what it means is the ability to switch essentially from one virus to another, and that is relatively not that difficult as a platform itself. Now this is a chemical really platform, and therefore scaling it up theoretically is simpler than scaling up a biological process. So what is the intellectual property, not patents intellectual property involved here, because I don't think the mRNA can be patented, even in the US, but that's a part of what our body has or what the virus has so it's available in nature. So what is the exact technology know how that in the first place, the mRNA used in the mRNA vaccine design is actually patentable I suspect because it is chemically modified. Okay, it's not entirely native mRNA it's changed to so that it's not it's sensed a little less by certain cellular processes, its secondary structures are tweaked a little so so it's a tailor made modified mRNA. Okay, that creates both a substantive technical advantage and an intellectual property protection opportunity. But it also does something else. It makes it a somewhat of an overstatement when people say oh we can the mRNA technology allows us to change vaccines to just to change the sequence and make a new vaccine and just to change. But if you're going to have to worry about secondary structures if you're going to have to tweak them, then there's a fair amount of technological modification to be tried and tested. So it's not as flexible as the hype might suggest. But as I said, despite all that, there is some opportunity for protection, number one, number two, mRNAs are extremely fragile molecules even these engineered mRNAs are extremely fragile molecules. And as a result, for them to after injection to be protected and to get into cells of the body where they can be used to make the target proteins. It requires the mRNA requires packaging. All the viruses that we've been talking about there's no packaging you just put them in fluid and inject them and they will do their thing. The mRNA needs to be packaged so the mRNA these designs that we are talking about the Pfizer design or the or the Moderna design or more correctly the NIH design and the bio and tech designs are really essentially creating a precisely formulated layer bubble of fat inside which the mRNA nanoparticles as they are called and they carry the nanoparticles makes it sound like high technology. That's that's exactly why I guess the name is given and also just for our viewers who may not be aware of this the mRNA essentially is the information which makes the our cell produce the spike protein itself, but only produce it once so it's not that the cell is turned on forever and is going to produce continuously spike proteins. No, that's correct. So, but but that's perhaps a component of a discussion on vaccine misconceptions at some other stage, but so the mRNA is packaged in an extremely empirically precisely formulated nano minute fat bubble. So here's the kind of manufacturing technology related know how issues involved, what are the fats, what is their relative composition to each other, how pure are they, how purely have they been manufactured and supplied to the vaccine manufacturer. Exactly what are the steps of the process in which they are to be mixed so that they will form the right size bubble bubbles around the mRNA and having gotten these bubbles, how do you stabilize them in solution in the in the injection liquid. All of these as you can imagine, provide opportunity for proliferating empirical meaning data driven, meaning trial and error optimization that you can then pretend is intellectual property. I have never quite understood how trial and error optimization becomes an intellectual property, but never mind. I think that there is at least a little more ground for the mRNA vaccine technology to say, there are not too many manufacturers generic manufacturers across the world, who can smoothly easily and in a very short time absorb the technology and start producing the scale. And, and that's because of these multi component features. Once the technology is absorbed and assimilated by the manufacturer scale up becomes easy because it's a much more chemistry heavy technology. But I think that the initial learning process, there is some basis to saying that's going to take a little conveying of skill and what amounts to trade secrets tricks of the tree. Just for our users that just for our viewers that there are these words buzzwords or in IP words which are circulating, that when you come to patents you have to write it down, even if you write it down opaque, if you want to claim a patient. But you can have trade secrets which are by definition secrets, which you never write down, and you don't share with anybody. And unless you can claim theft, you really cannot go against somebody who might duplicate what you have done and said, Well, it's a trade secret. I don't know what he has done but I haven't done it this way. And that will have actually the full property rights, you would not be able to contest it, because you never really paid it. How much is patented, what's a trade secret is still not known. And again, here, the mRNA technologies are new. So yes, a lot of it is not known. But as Satish points out, they're really chemical engineering secrets, and they're not in that sense very secrets. They are not very, very secretive in that sense because they are something you can duplicate you can try and do again your own trial and error, and give it give or take one or two years. It would be in the public domain how these are done. So when American companies claim that this is something which the Russians and Chinese women steal from us. So this is exactly the 1940s debate that nuclear bombs are with us. They're not going to be allowed. They'll not be with anybody else over the next 10 15 years. This is the time to dominate over the world, and get rid of this red Soviet Soviet dash dash ones. It took really about two to three years before this bubble was broken. So this is come out again and again, that even the technological edge to somebody in the world doesn't stay for too long, maybe a year and two, and there are enough companies in the world who would be able to duplicate it, given the fact that we now know broadly how it is being done. I think that's a matter of time. So till that point of time, yes, some companies would have an edge. Unfortunately, or unfortunately, the product of these vaccines are really they require ultra cold chain. So as of now, it is not of interest to large parts of the world, or large parts of the global population, who do not have the requisite ultra cold chain to really give it on a white scale. And here, because I think we have spent something more than half about, we have spent about half an hour discussing it, and relatively an esoteric topic for most people, but the real bottom line that something is shared with us is as none of this is really something which is secret, which cannot be duplicated, and taking away the protection would allow this to be shared much more widely. Secondly, the governments, including the government of India, and the government of the United States, if they could actually help in sharing this knowledge, rather than in talking about it and this time including the government of India as well, because we have talked about it but not done it. And the Biden administration saying will support patents being withdrawn for the time of the pandemic, but that's not the issue. Issue is sharing the knowledge, which is there with the companies, pay them some money, that's not the point, but help to share the knowledge, because that's what the world needs, if it has to get to 14 billion doses. This year, which should be the target for getting rid at least of the pandemic. We'll not get rid of the COVID-19 disease, what we'll get rid is of the pandemic, and that's what we need. Thank you Satyajit for being with us and sharing with us this rather difficult knowledge of how we can build vaccine processes, vaccine manufacturing in the world at a scale which can defeat the pandemic. This is all the time we have today. Thank you for watching NewsClick. Do visit our website as well.