[MUSIC] Before we move on to other topics on these lectures, I want to quickly mention about what we call selection patent or selection invention. Which has to deal with basically when you patent a chemical structure. As we saw before, you can describe a chemical structure in a patent or in a document with a very generic formula where you basically describe a general structure, or a general backbone, on which you can add things, you can manipulate things. So for example, from the previous example for the drug from a lily, we had this Formula A that describes these rings and the structure with groups. And we have this R1 and R2 symbols here or elements here which means that we can attach any kind of element or structure or compound from particular list to generate different molecules. It would be kind of wild cards or jolly positions. By putting this on the patent, it becomes very broad. So if you remember from the previous section of the course, of the lecture, this particular structure here can describe about 10th to the 19th number of elements which is a very big range, a very big number. And it sometimes might become even unpatentable because it just covers too much. So let's say, you're in your lab, you're in a company, and you want to kind of find out which of these structures might be the most performing. And you might identify a particular structure or a particular element that you can add to the R1 position, that makes your compounds deriving from there, are really outperforming anything else. What you want to do with this, what you might want to release is to actually, change that into the formula and block that position with a particular compound. So that will be your selection, you select this particular structure here to be added on position R1 and then you can play around with your formula. So basically, you're limiting your scope of your compound. You clearly show that this particular addition at the R1 position makes it better on everything, and therefore you can focus on that particular structure. So basically, you're locking this position on R1 with that particular element, so that will be your selection. Now, let's move to the doctrine of equivalents, which is a very important concept especially for chemical compounds. Because as you can imagine, a chemical compound is a very complex structure and any kind of little change in the structure could be seen as novelty as we've seen before. And as we have seen the previous lecture, for a patent or for an invention being novel, any little change that makes it different, is important. For compounds and for chemicals, this becomes even more tricky because you can make a molecule novel without actually changing anything. Or you can basically change something in the structure without changing the properties of the compound and that becomes kind of chicken. So what is the deduction of equivalents? So as you remember, novelty and invention is different. So an invention is novel if the invention is different from whatever is there. So it is not a subjective thing, it is actually different or not, is it identical or not? So that would be novel if it is not identical. However, this novelty element should also bring something new. Should bring an improvement or an extra property to the existing prior art. So you cannot just change something and nothing happens. You have to change something to make it better or to change the properties. So for example, in a chemical structure, you could add a couple of neutral chemical groups to a patented molecule. So, couple of hydrogens here and there or CS3s here and there. The structure is different, the formula is different, but no change in activity or properties happen. So, I can take a structure, add some little neutral groups. There is no change in activity, there is no change in properties, there is no change in function of the compound, but technically speaking, that molecule will be different. However, because of this doctrine of equivalents on this, are we having chemical structures, it has been decided that if nothing is added to the compound, that new molecule will be infringing on the previous one. Okay, so the best way to describe this is to look at a real life example, what really happen in the course. So there is this case of Graver Tank versus Linde Air, which was maybe the first case where this deduction was used, which basically kind of was a landmark. So we have this company, Linde Air, that generated or invented a novel electronic welding process to weld things. And they had this very nice system and they found out that there is a competing company, Graver Tank that created and patented something or tried to patent something which was very similar but different. So where was it different? So the first company, Linde Air, their process was composed by an alkaline earth metal silicate that was used for the welding process and the company that was sued, Graver Tank, the defendants, they were using a non-alkaline one. So the idea was, if the first company used alkaline, we'll use something non-alkaline and that would be different and that would be grounds for novelty and patenting. However, even though they really thought they were novel, the judges, in this case, decided that Graver was infringing on Linde Air because they understood and they came up with the point that using the non-alkaline compound did not bring any change to the reaction. Most importantly this lack of change was known from the literature. So basically was known from previous literature that using a non-alkaline reagent for this reaction would not change the efficiency or the properties of the whole reaction. And finally, Graver never really tested their invention. So they never really went into the lab and tested it. So they just kind of changed from one to the other and tried to bind it. So they were found guilty of infringement and they had to drop their case and they had to drop their patent and they were guilty. So this case resulted in the definition of the rules for equivalents. So in that situation, the US Supreme Court made two definitions or two tests to define whether you're infringing or not on equivalents base. So, first of all, is the triple identity test, which is used to determine equivalence. We says that something is deemed equivalent or the same or therefore infringing, if it performs substantially the same function, in substantially the same way, to yield substantially the same result. So basically, nothing changes, I have changed the formulation, I have changed the structure, I have changed the way I produce it, but the end result is the same. And therefore it's equivalent, and therefore you're infringing on that product. The second test says, something that you can use, is that something is deemed equivalent if there is only an insubstantial change between each of the features of the accused device or process and the patent claim. So basically there is nothing, you change a lot, not to change anything. That's kind of an old Italian saying but it basically explains clearly here. I might reshuffle the whole thing, but I don't change anything in the output or in the performance of my invention and therefore I'm infringing and I have copied. So this is very important to remember and is very important for small chemicals because you can imagine that you can put a lot of changes in a chemical structure without changing anything in the activity of the structure. So that's very important to remember. Now let's move to the more complicated part of the chemicals and their compounds, which is to do with pro-drugs, drugs and metabolites. This is the complicated one and I will put some text online to help you out to go to some more readings and some references because this is a very crucial part of the biopharma or the pharma companies or the pharma intellectual property and master in these, or understanding this properly is very important for your future. So what is the issue? So first of all, let's look at what a pro-drug is. So the IUPAC definition, also the official definition, for pro-drug is that a pro-drug is a compound that undergoes biotransformation Before exhibiting pharmacological effects. So, basically the way you can see that it is a pro-drug could be a wrapper or could be delivery system for the drug. So, let's say you have your active compound and you want to make it stable or you want to make sure that it get's activated in your body on the right place, you might wrap it or you might modify it in a way that it gets changed once you take your pill and it becomes active. So you might block it on yourself, on your little box, by adding some kind of cleavable elements. And that will be removed once it's in the stomach or in the belly or in the liver and by cleaning off that part you will release the active compound and that will be it. So basically it's a wrapper for a drug. So right here we have a pro-drug that you eat your pill, it gets modified, it gets metabolised, it gets cleaved and releases the drug, the active substance to stomach. So what's the point here, what's the relevant point here in terms of the property? So let's say you're company or you work as a seller and identify an active compound, you identify a small molecules, chemical compounds that you see has an effect. Or a therapeutic effect or beneficial effect in your organism. You eat, you give that to a little mouse or you take it yourself, and you feel better. So you have the active compound, you have the structure, you know how you produce it, you know how you make it. You know that it has an effect on your body. You can that. You write your patent for your active compound, and you can go up in the business. Let's say that your neighbor, your competitor modifies such large compound because he can look at the patent publication after 18 months and modifies a traffic compound in a way that your compound is still present, but he adds a little ph-sensitive cleavable unit. So takes your compound, let us write it down here and let's say, I have my compound like this. This is my compound and your competitor comes in and puts a link here and puts an element. This linker can be removed by an acidic pH. Gets removed and you separate it. And the competitor shows that by adding these little pH cleavable element, the life shelf of the compound trebles, becomes way more stable. So that's an improvement. So he can go out and try to patent his modification. But the problem here is that yes he has made another compound which shows a different activity or a better activity, an improvement of activity which would be the shelf life of the compound. But the problem we get there is that the moment I take that drug, and it goes down into my belly, and the pH of my belly or my stomach cleaves off the linker, The active compound is mine. The one that actually gives the benefit to the patient is my compound. So what's going on here? So you have something new that gives a better half life or shelf life to the compound or to the active compound, or to the drug. But when actually I eat it, what gives me the benefit, what gives me the good thing is my compound that is actually having an effect. So therefore, I would say here the modification will get novelty over your invention, because of the improvement and the change in structure. However, once the unit is cleaved, that invention will be infringing on my pattern or your pattern, as you active compound will have the pharmacological effect in the body. So, basically the competitor, the neighbor that has come up with this guy, if he tries to sell it as a drug, will be infringing on my patent, even though his molecule is different and his activity is different. Because, he's selling it as a drug with a pharmacological effect, and that pharmacological effect is only caused because my compound is there, not his. So this is very important to remember. He can sell it that way but he's infringing on my patent because of the pharmacological effects. So I hope this is clear. And now let's move to the second part of the equation which is drug to metabolite. So I still have my compound as before, I know it is not a very important compound but just let's make it simple. And let's imagine that the other neighbor who is working on the same thing finds out that actually it's not that particular structure that is having pharmacological effect, is the result of that particular compound being modified or being cleaned or being processed by the stomach or by your organism into a different molecule. Let's call it metabolite has been metabolized into a different molecule and that different molecule is why it's actually having the pharmacological action. So let's say this guy gets then transformed into this guy. Very simple. It's modified into a different thing. So this is the metabolite resulted from this drug processed in the liver, for example, and that is the real active compound. So at this point my drug is not the active compound anymore, my drug is not the drug anymore, my drug becomes a pro-drug and the metabolite that I have identified becomes the drug. So now we've got a situation. What happens here? My drug is at the pro-drug, can the metabolite be patented? Am I infringing on the metabolite? And the answers are, yes, my drug is a pro-drug. Yes, in my patent, I already have my patent because the final patent order from pharmacological body, I never mentioned how it works in the organism, what are the physiological and pharmacological process going through in the body. So I don't describe what has actually happened with my compound, once it's there I just show that my drug is actually having a health benefit on the patient but I don't say how because I didn't do all the physiology. And I do not know what are the metabolites deriving from my drug. So I cannot list what are the metabolites because I don't know what is going on with my drug once its gets into the organism. So therefore, the metabolites can be patented by the inventor because he shows a new molecule, with an activity, he knows how it works, he knows what it's doing physiologically. So they can patent that as a metabolite generating something. But my drug will not infringe in the metabolite, because we don't know about that metabolite. So we don't know what it is, we didn't know how it works, we don't know what it was, we just described a compound that gives a process, and gives an output in terms of health benefit, in terms of curing or giving benefit to the patient. But we never mentioned the metabolite, and we don't know about it, so basically we're not infringing on that metabolite, and therefore we can have both patents being there without infringing. This is a very, very, very tricky part of this part of patenting chemicals. It is very complicated, it has a lot of literature, lots of books describing because it has a lot of grey areas. So as I said before I will put some links and some directions on where to find more information to read about this if you want it. If you don't want to get into the complete areas, just remember that you have big difference between pro-drugs and drugs and drugs and metabolites and how you can patent it and how we can deal with it. So to conclude this lecture on small chemicals and compounds, we're going to quickly touch on natural products. So why is this important? They're important because we know from kind of a lot of cultures and a lot of places that People use plants or fungi or mushrooms or different kind of elements from nature as a therapeutic effect or alleviating effect. So, we know for example in the cases of coca leaves in South America or other spices in India that in various combinations they say to have some therapeutic effects. China has also a lot of medicine which is based on plants and animals. The point is kind of what can we do with natural products? What can we do with this? Can we patent? What can we patent? What can we use it for, in terms of our business? Natural products will fall into the category of Discovery versus Invention. Let's say that you are working around in the forest, and you have a horrible headache, and you decide to eat a particular leaf or particular mushroom, and your headache disappears. Great. My headache disappears because I've eaten these things, beautiful. Let's take it to the business, let's make a business out of it. And the problem you will have there is that that leaf or that fungus that you have just eaten would not be an invention. Would be a discovery. You have discovered a natural element or a natural product which has the property of killing your headache. In order to patent that or in order to kind of go in through the line of interaction property and making a headache cure from that particular natural products, you will have to first of all identify which compound in that leaf is actually removing your headache. You had to show how you purify it, how you extract it from your plant. You had to show how it's worth. Ideally you will have to show what the structure of it is. Basically you had to really scheme down from leaf to that particular compound and to show that is the compound that kills my headache, and that is how I produce it, identify, isolate it, produce it, prepare it, and how it works in terms of pharmacological values. That's what you can patent from natural product, the particular single element. As an example, I would like to kind of mention the case of cyclosporine which was, this is a very important drug in the grafting, surgery. When we graft an organ into a patient. The cyclosporine has the property or stopping the rejection reaction between the host and the organ after transplantation. This was first observed from a Norwegian fungus that was shown to have properties to stop this interaction, this immune response of an organ into a host. And the scientists of in the 60s and 70s when they were working on this, started from this Norwegian fungus trying to understand what was the element that was actually having these reaction or this effect on the immune response between these two species, these two elements. And starting from the food fungus, they started screening all possible metabolites and compounds in that fungus until they identify the cyclosporine was the one that was actually, giving the best, the strongest effect and that was the one that was being responsible for this pharmacological effect. Therefore, from the complete fungus, there were able to identify cyclosporine, they should how to purify from the fungus, how to prepare it, what was the action? And they were able to patent it and come up this, the biggest blockbusters in the pharmacological industry. This was the last part of this lecture about small chemicals and compounds. As we have seen is a quite complicated topic, it is changing a lot, it's very, there are many areas that are in them, there are many grey areas. I would recommend to go through these slides a few times. I would say that we put some literature in there to get some better reading and to better understanding. But it's a very important element to understand and to get the grasp on before moving forward. Because if you want to go into the pharma industry or you want to work with chemistry and chemical compounds, as we can see there are very subtle yet very important differences from a normal biotech patent. I hope this was clear for you all, and please do not hesitate to send me an email or to drop me a line if you have more questions about it. And, thank you for your attention. [MUSIC]
