[MUSIC] Welcome to the last lecture on patent searching where we will also wrap up a bit and try to relate patent searching to freedom to operate, analysis, and in general why we consider patent searching so important in this course. We will today cover material that you should read in the textbook in chapter 3.3 about the American patent office and also chapter 5.3 on searching genetic sequences. Now why would we try to search for patent based on genetic sequences? Well, think about it this way. When does a genetic sequence, a gene, a protein get its name for the first time? [COUGH] That will usually happen when it's published in a scientific paper. Whereas, in patents it will be listed as sequence listing ID1 or ID47 or whatever. It doesn't have a name at that point in time. And also, if you discover a new sequence, it doesn't have a name, at least not if it is truly new as you think it is. So, therefore, you need to be able to search for patents based on the genetic sequence itself, and that is one of the things that we will cover today. And as usual, we need some invention to explore. And in this case, we will assume that you have developed a method of persuading your favorite host cell into producing and secreting galactans, pectin galactans that you also have a intended use for. And now you want to explore the patent landscape around your new invention. And we will not cover all aspects of your new inventions, it's an unknown invention, by the way. But you discovered that the funneling enough carbon through the circulatory pathway is an issue that is limiting to the production of the desired product. So therefore, you have come up with the idea and you have provided proof of concept that the over-expressing a nucleotide sugar transporter that ensures that the donor substrate is funneled in to the secretory pathway in increased amount is actually very beneficial to the rate of production of the desired product. So it is this small aspect of your invention that we are going to figure out whether other people have patent activity in this area in such a way that it could create problems for you. >> Let's us go straight to the USPTO, here is the link. [BLANK AUDIO] And look here, in USPTO we search patents and applications separately. Firstly, look, we have a little guide to how to phrase the boolean expression just like in. A list of the field codes as long as we saw it in pattern score. And what we're interested in here is this here ACLM claim search filter. We use the slash just like in pattern score, and here we have the UDP Galactose Transporter with various synonyms. So let's give that a try. Okay, we get 10 hits. If you look at them, they look like being about protein. All of them, the only one that could be about carbohydrates in more general sense could be this one. And let us scroll down and see what claim number one speaks about. And here it is. A method for producing recombinant glycoprotein in Pichia pastoris. So this, too, is a glycoprotein patent. Let us just take a look at where do we find the UDP galactose transporter that we are interested in. And that happens down here in claim number 17 where it speaks of equipping the cells with additional transporters to ensure that the UDP sugar nucleotide pools are not limiting for the desired. And that is incidentally the same motivation that we have for our production of galactin with polysaccharides in a host cell. So let's go and take a look at the applications because there might be younger ones that speak of the same thing. And so we repeat the same search string. And we get 20, twice as many. And many of them are, of course, the applications that are associated with the patents that we looked at before. And trust me, they all speak about protein glycosylation. None of them are concerned with the polysaccharide production that we are in this hypothetical case. So can we find a way of being more general to take a look at polysaccharides? And I think that we can. So let us now replace the UDP transporters and so on, with simply nucleotide sugar transporters, and then combine it with galactidyl polysaccharides. These are not likely to appear in a claim, but they will turn up the application of the technology will probably turn up in the abstract. And that's where we put these two, and using a dollar sign for plural of polysaccharide as a singular form. And now we get but a single application. It's from 2015, so we don't bother going back to see whether there's an issue patent corresponding to this one. Let's just look at what it is all about. And here it is. Cell modified in the expression of a nucleotide sugar transporter. That seems like being close to what we are interested in. And here you have the nucleotide transporter mentioned in the abstract. And also polysaccharide is mentioned and that's why we found this application. Glycopeptides are, by the way, also mentioned The cleanable one is phrased very much like the abstract, something about over expression or knockout of nucleotide sugar transporters in a host cell. Let's take a look at it anyway, to see what we will find. Note when we scroll by that there are quite a number of sequence listings here, and here are the claims. As said, claim number one is very similar to the abstract. Claim number two specifies that the nucleotide transport of the is from a plant, animal, or fungal cell. And number three that it is also a plant, animal, fungal cell that is to be engineered. And you can see here in claim number ten that saccharification is mentioned as an application. So they're probably more interested in biofuel production, compared to production of a polysaccharide like we are. So it's curious, there are no sequence claims down here, as fallback positions for these more general claims. So let's go up and see in the patent text whether a collection or UDP galactose transporter is actually known or specified. And indeed, here's a table of relevant genes, and down here you have UDP galactose UDP transporters mentioned, and they actually continue on the next page. Pay attention to the one called GALT2, because we will use that for something in a minute. Here under the heading, The Role of GalT2 in Plants, the inventors investigate mutants that are knocked out or transformers that are overexpressing GalT2. So it appears that it is these authors who have discovered what it actually does. I'm now making my way into the NCBI website, and you can see that I've entered the locus code under protein. And that's because I am looking up the NCPI record of the UDP-galactose transporters. Why do I do that, I do that because I want to run a blast on it. Not a completely standard blast, but rather a blast against patented protein sequences, why do I want to do that? I want to do that because I suspect there are patents claiming this sequence, but the claims originated at a time when it was not yet discovered what the role of this protein is. You can see here that there are quite many hits, and you can see that this particular patent, 7569389, comprises many, many sequences. Note that they are all four digit numbers, we'll need that in a second. And, you can see here on the right that the e values for the sequences here are perfect zero, so these are indeed very closely related. So let's look up the patent number in the question, here it is, we are back in USPTO. Is one of the very few shared field text, and here it is. Let us scroll down and take a look at claim number one. A method of introducing an isolated nucleic acid molecule into a host cell comprising, and then only one sequence ID, a five digit number, not what we were looking for. And the application is increased leaf number, increased in florescence, meaning biomass production, very different from what we are after. How come that the four-digit sequences that are single unto the team that we're interested in are not here? Well, one thing that we could do is to take a look at the real application, note here, DN, document number, is the replacement for PN. And lo and behold, it didn't get anything, and I can assure you, I typed in the number correctly. But, databases disagree on how many digits are there so use patent serials now and then to make the individual database happy. And that's what I did here, and here is the corresponding application. So let's take a look at claim number one, Here again, and you can see here that this is a claim that refers to sequence listing, with all the different sequences. However, the issued pattern only regards one of these, the one with a five-digit number. I trust that you can come up with a good case as to why this is so. So, this was a long and tortuous path, and there are a number of things that were not sufficiently covered in what you have seen so far. And that is because I will leave that for you to think about and to also do something about in this week's quiz. And this is the number one here, to look into this Ceres application with the long sequence listing. And find out using an appropriate database, I hope you can immediately guess which one. Why the issued patent only claims one of these hundreds of sequences that were in the original application from Ceres, and that's left for you to do in this week's quiz. And also we probably cut some corners, now and then, I made a very strict discrimination between patterns that regarded protein isolation, and those that regarded polysaccharide production. And I think that was maybe overstating the case a little bit. And I want you to think about where the line should be drawn in reality. Now if you think about this whole example, and maybe also some of the previous ones, as being a bit contrived or reverse engineered from the answers back to the questions, then you are not mistaken. And the issue here is that the verve to invent does not exist in the imperative, you cannot tell people to invent. Although scientists come up with novel things all the time. And in this case the invention itself is unknown and that's Part of the reason why the whole thing seems a little bit arbitrary, but look upon it this way. Here we have the core of the invention, the galactan production in your favorite host cell. And here you have the unknown invention. And what it comprises, I don't know. I suggested that galactan synthases and galactosyltransferases probably unneccessary components, but certainly not sufficient to make your invention fly. And that aspect because it's unknown to us, we have not explored at all. What we have explored is donor substrate provision the UDP- galactose where we have investigated a topic expression of transporters to increase the funneling of UDP-galactose into the secretory pathway. Are these the only domains of interest to your invention? I think not. Because when you engineer your cell, you will probably use some promoters or signal sequences and whether your cell is an animal or fungal or plant cell makes a difference in this case. But if some of these promoters or signal sequences are very suitable or optimal, maybe people have product links on these sequencers for completely unrelated applications. But remember that product claims are application independent. So patents in this area is certainly part of your patent landscape and therefore it's important that you investigate this domain for your invention as well. And then there are the end users. I said in the introduction that you also had an intended end use for the galactans that your cell could produce. It could be food ingredients, surface functionalization of advanced materials. It could be materials for wound dressing. I don't know. But if somebody else has patents on the use of galactans for either of these purposes, then you can certainly be a provider of galactans but you cannot control the entire value chain until the end users because you need agreements with people who have patents in the end use area. So this is also [COUGH] A part of your patent landscape. And then finally in addition to the promoters, there might be more generic tools that you have used, vectors or imagine for the sake of argument that you have knocked out a competing use of carbon in your cell using the Crisp/Cas9 system, that's an area of intense patent warfare at the moment. And if you have done any such thing, I would certainly advise you to look into the patent landscape of such a tool before you declare that you have freedom to operate for your invention. So, in this regard I hope that you can see that searching for patents is an intrical part of freedom to operator analysis. And the diagram that you saw before if you think of that, as a mind map, I'm sorry to say that you are mistaken. Mind maps is a central concept where you're inspiration meanders away from it. The plot diagram that you saw is a directed graph that depicts technology domains that impinge on the central concept of your invention. And therefore, in order to tie patent searching into freedom to operate analysis you should draw this blob diagrams and you encrypt them perhaps with search terms or sequences or molecular structures or whatever, so that you can do a thorough search on each technology domain separately. And [COUGH] When you have gone that, then you know to what extent you might be dominated by other people's patent, people you need to have equipments with. It's very rare that an interesting invention these days will be completely independent of other people's invention and activities. However, one thing is dominance. That's not the same thong as patenting opportunities. In order to assess the patenting opportunities for your own invention, then you cannot limit yourself to searching the patent literature, because of course the scientific literature is just as novelty destroying or dismantle to inventive step pf what you come up with as anything that is there in the patent literature. So it's a comprehensive activity to map the patent landscape around your invention. But without it, freedom to operate analysis is shallow and it doesn't hold true. I hope that I have convinced you that clever and thorough patent searching is a very important aspect of innovation and making biotechnology valuable. [MUSIC]
