Patenting the human genome
BUSINESS IN THE POST GENOMICS ERA: CHAIRED BY: Dr Romeo Paioni, Head Scientific and External Affairs, Novartis Pharma
By on May 17, 2001BUSINESS IN THE POST GENOMICS ERA:
CHAIRED BY: Dr Romeo Paioni, Head Scientific and External Affairs, Novartis Pharma
Okay, welcome back to the second part of the morning session on genomic products and patent protection. As I mentioned before the break we have now a very specific topic namely patenting the human genome. Before we start I have been asked to make a short announcement with respect to those participants who have a 3-day pass which means they will be here also tomorrow. They are kindly asked to sign up for the workshops which take place tomorrow morning. There are I think one or two or three in parallel and the organizers should know which one will be attended by whom. So if those participants who have a 3-day pass please sign up, it is a workshop in the exhibition hall or at the registration desk of eyeforpharma.
The next speaker is Tim Powell from Bristow. Tim has a MA Natural Science in Biochemistry from Cambridge University and then the xxxxx in Intellectual Property Law and Practice from Bristol University. He is a specialist in patent litigation in the pharmaceutical and in particular biotechnology fields. Many names you know xxxx the company have been involved in issues he has dealt with, Kyron, Adiba, SmithKline, Monsanto Searle xxxx and so on and Tim also sits on the Intellectual Property Advisory Committee in the UK by industry association. He is today a partner in Intellectual Property Department at Bristow and he will talk on patenting the human genome. Tim, please.
10.25 Patenting the human genome
Dr Tim Powell, Partner, Intellectual property Department, Bristows
Obtaining effective patent protection in the pharmaceutical and biotech fields has always been absolutely essential to commercial success for the actual patenting activity has taken place largely outside the public gaze, that is until recently. Patenting in bio-technology and patenting of gene sequence in particular is now the subject of heated debate on both sides of the Atlantic. Now the various strands of the debate, legal, commercial and ethical have become somewhat entangled and in the UK at least the patenting of genes has become linked in the public mind with the other perceived evils of letting commercial interests into science. To many Mad Cow Disease, GM crotes, gene patenting and even the recent Foot and Mouth disease outbreak are all aspects of the same underlying problem.
In this process the debate on gene patenting, even in the so-called quality media has bordered on the hysterical at times. This is a quote from the UK national newspaper The Guardian, they had a special supplement, 20-page supplement on gene patenting in November of last year: Patenting of gene sequences is revolting to most people on two grounds. It is an invasion of personal privacy and it threatens xxxxx of almost every country in the world except the US. Strong stuff indeed.
Now the editorial of the newspaper even called for the European Patent Office to be barricaded in the same way that environmental activists took the World Trade Organization by storm in Seattle and in fact the last biotech conference I spoke at was unfortunately timed to coincide with the May Day anti capitalist protest and we had a police presence which actually outnumbered the delegates to protect us against incursions by anarchists.
It is easy to dismiss these reactions as extreme and ill informed but concerns about gene patenting have also been voiced by eminent scientists. For example Professor Lewis Walpert a Fellow of the Royal Society and eminent developmental biologist said this in a recent seminar which we held on the subject. The very idea that someone can patent a gene is totally incomprehensible and wrong, I believe it is simply sense that a patent must involve novelty, it must be an invention and it must have commercial value. Some of the current patent activity seems to fly in the face of this logic and I am extremely concerned.
Not too many quotes the last one just to show that the debate is also heating up on this side of the Atlantic. Much of the debate on this side of the Atlantic is centered around the exercise by certain biotech companies who have broad patent coverage of gene related inventions. Unfortunately I think Myriad Genetics has been on the receiving end of quite a lot of controversy because of their robust patent enforcement strategy on their BRCA 1, BRCA2 patent on to the associated breast cancer diagnostics. This is a quote actually relating to the pending patent application on the related to the BT secretase which I understand is in association with Alzheimer's disease: The company that wins enough money to buy the Palace of Versailles and the company property didn'st even exist when Clinton was elected president. So these are the sort of media concerns.
Now it is clear that many of the concerns which are voiced in public and in the media are based on fundamental misconceptions about the reality of the patent system. So in this thought I am just going to go right back to basics about the nature of the patent system and then look at how that can be applied to inventions arising from (cough) sequencing the human genome, then I'sll look briefly at the differential approaches in the US and Europe trying to tackle the issues which have been raised by patenting in this new technology. Then I will look briefly at the enforcement of genomics patents and the flipside of that, freedom to operate issues for a company that is involved in research in fields which are dominated by upstream gene patents.
Okay, so what is a patent and apologies to people, I mean this is extremely familiar already? A common held misconception is that a patent when someone gives a positive for the patent holder to practice an invention, may seem strange to people in the industry but that is a widely held view. Now of course a patent is not that, a patent is a negative right, it simply allows the patent holder to prevent the unauthorized commercial exploitation of his invention for a limited duration, could be twenty years and of course if you are a patent holder you still have to clear all the regulatory hurdles and you may actually be completely barred by national legislation from practicing your invention and of course you may also need to take a license from owner of a prior patent right in order to commercialize your own invention.
The essence of the patent and this is something which I think is sometimes forgotten even by industry insiders is that the contract between the patentee and the public at large and theis a monopoly which is given in exchange for putting a technical advance into the public domain. The rationale for that is that in the absence of this encouragement published technical advances, commercial concerns may be tempted to keep their advance a secret as confidential information. I actually understand just talking to a speaker from Oxford GlycoSciences for example that there are certain aspects of the algorithms they are using which are so sensitive that they don'st want to take the risk of publishing and putting into the patent domain and they would rather it as confidential information.
Okay, the basic criteria to obtain patent protection, xxxx patented invention must be new and that means it must (cough) xxxxx part of the state of the art, perhaps the date the invention is made, that is the US test or the date on which the patent application is filed which is basically the test in the rest of the world and that means that anything published anywhere even in the Mongolian Journal of Enzymology that nobody ever reads, it is still state of the art. Secondly and critically it must involve an inventive step, that means it is not simply an obvious progression over that which is already known in the art. Thirdly, it must be fully described in the text of the patent application and this again goes back to the idea of the patent being a contract. You need to be able to describe your invention sufficiently clearly that somebody skilled in the art can then go and put it into effect without undue effort. And finally it must be capable of industrial application, that is the European test, or show some utility, which is the equivalent American approach. In other words it is something which can actually be made in industry and something for which there is a purpose for it to be made.
Now there are important exceptions to patentability which are quite topical in the biotech field. The first of all, a discovery as such is not patentable although the technical exploitation of a discovery may be. Now many critics of biotech patents say xxxxx or gene patents in particular say well, it is really nothing more than a discovery xxxxx something which exists in nature, how on earth can that be patented. Secondly inventions that are contrary to morality are unpatentable and again and for some people the biotechnology industry in general is immoral and therefore anything that comes out of it should not be patentable and that is one extreme view. This is actually come into the fore and the patenting of the Harvard Oncomass where a number of groups opposed the patenting of the Onco mass on ethical grounds and in fact that application is still bogged down in the European Patent Office. I think it has become politically safe, sensitive that it is just sort of lost in the xxx process but in the patent has issued in the US and Canada and obviously the ethical issues did not get in the way of that.
Okay looking more generally .. end of tape
And in Europe there is also a database right, which is basically a right to stop unauthorized utilization and extraction of the substantial part of a database and that is limited for US companies, it is only available to EU residents and residents of countries that have a similar type of protection and that doesn'st extend to the US, so it is something a bit different there. Also confidential information, elements of these databases are kept as proprietary by the database holders and access is allowed on restrictive terms but again that is a useful thing to bear in mind but it is not really clear how long there is money to be made out of proprietary databases, after all there is an enormous amount of information which is now coming into the public domain either by the action of the human genome projects, SMP Consortia, etc, etc. and this is really a shrinking asset and it may be because of this or it may just because genomic companies are hedging their bets that so many patent applications are being filed.
Human Genome Sciences recently said that they had filed over ten thousand patent applications on gene related inventions and as at April this year the US, they had 169 US patents on human gene related inventions and Insight Genomic said at the end of last year that they had patent applications covering portions of more than 50 000 genes. I just noticed in passing that's more genes than they currently estimate to be in the human genomes, so they are doing quite well.
So US PTO, what's been going on? Well as we said they have been deluged with patent applications relating to gene inventions and by the sounds of it now they are being deluged with proteomics related applications as well, not just inventions on full length genes but also applications relating to express sequence tags or EST's which are simply fragments of full length genes which are actually expressed by the organism rather than being dormant. Now my understanding is that techniques for identifying EST's have actually been around for a number of years now and it is a largely robotic process to generating EST information. This really came to the fore first when the National Institutes of Health and the UK Medical Research Council filed patent applications in the early l990's relating to EST's and there was a public outcry then about publicly funded bodies trying to monopolize basic scientific knowledge and in fact those applications were withdrawn but since then as we have seen a number of companies have applied for patents on EST's and the first one was actually granted by the Patent Office in the US in 1998. Much of the debate has been centered around these so-called utility of these types of invention.
In 1995 the US PTO published utility guidelines and provided that one specific credible utility must be shown for these gene related inventions but in practice that wasn'st a very high hurdle and a number of patent applicants got by with so called throw away utilities. You could imagine if you were applying for a patent for an expressed sequence tag, then you could say if it has got the utility it could be a probe for the human DNA. Well, you know, sure but so what, but these were the sort of things which were going through the process and there was a lot of debate in the US Patent Office about whether that was really the right way to go and recently, January of this year they published a revised guidelines and saying that the utility for these sort of inventions should not just be specific and credible but should also be substantial. Now that obviously raises as many questions as it answers but it is a clear indication of this trend towards showing functionality when you'sre applying for a patent, it is not simply good enough to come along just saying I'sve found a gene sequence, I don'st know what it does but I'sd like a patent.
Secondly, they have published adequacy of description guidelines which say that again with gene related inventions it is not good enough simply to describe the invention by relation to function, you need also to have some physical characterizing information, sequence information or other physical characterized information.
So that's briefly where they have got to over here. In Europe as many of you probably know there has been a biotech directive relating to patenting in this field. That took some ten years to be passed after a lot of political argument. It was finally approved by the European Parliament in 1998 and it should have been incorporated into national laws in July of last year but it has not actually been universally been implemented. The UK has actually implemented the main provisions but the Netherlands, France and Italy are still maintaining objections to it and they have not implemented it into the national law yet so we still have to see how that one plays out.
The object of the directive is simply to harmonize the approach throughout Europe to patentability of biotech inventions but just looking at a couple of provisions; this is the main article which says what you can and cannot get a patent for. Basically it confirms that the position which I think has always been the case that you can'st just simply get a patent for the simple discovery of an element of the human body, even if that is a gene or a partial sequence, that is not patentable but if you actually isolate that element, take it to the laboratory, characterize it, that does bring you into the realm of patentability, that's point two there.
And thirdly, and this is again going towards the issue utility, the industrial application of a sequence or a partial sequence of a gene must be disclosed in the patent application.'s So it shows a similar view in Europe, you need to give functional information.
Briefly looking at some of the morality provisions. I said earlier that inventions could not be patentable if they are contrary to morality. This is the compromise which was thrashed out: you can'st patent processes for cloning humans, no patents for modifying the germ line identity and thirdly which is quite an interesting one, you can'st patent uses of human embryos for industrial or commercial purposes. This is quite interesting because recently in the UK members of parliament voted to relax the law to allow the use of early stage human embryos in stem cell research which really shows the difficulty of trying to codify these sort of morality objections across a number of countries that may have their own particular views on what is or is not immoral.
So what in practice has been the approach of the European Patent Office? Well they have already indicated that they will object to the patenting of express sequence tag type inventions where no function is given or if a postulating function is given but no real technical backup. Industrial application as we have seen is an important test and the fact that because of the biotech directive you must disclose that in your patent application.
Going onto inventive steps, in Europe the approach I think in the biotech world is stricter than in the US. There is a focus on the methods by which you make your invention. If you simply use very routine methods, you know robotic sequences in pursuit of an obvious goal, you may well have difficulty with patentability I mean in the contrast in the US the emphasis is much more on whether the sequence information was obvious in, you know, could it have been written down before you actually went and found it, which obviously is a much lower threshold to being found, invented.
Finally on sufficiency of disclosure and breadth of claim issues, the scope of the monopoly must correspond to the technical advance. It is not much good if you make a small advance in the field and then try and claim everything downstream from that, you may run into difficulties.
Going on to enforcement issues and again it may seem crazy but it is a public misconception if not in industry that once you have actually got a patent that is automatically enforceable. That is not the case. If you are going after somebody you will have to submit to the scrutiny of the courts about whether your patent is actually valid, was validly granted or not and in the US my understanding from talking to lawyers over here is that there is quite a strong presumption of the validity, partly because that is the way that the law is set up but also because of the realities of the jury system over here, it may be difficult to convince, say a jury, that the US Patent Office examiners got it wrong in granting a patent. In Europe that is not necessarily the case. In many countries and certainly in the UK the courts will have a complete re-examination of whether the patent was validly granted or not.
These breadth of claim issues are particularly important when the patent gets anywhere near a court because the court has sort of policy considerations in its head as well but in practice, speaking for the UK at least, I think this being a fairly pragmatic view taken, inventions which genuinely open up huge fields of research can be accorded very xxxxx patent protection and an example of that was the Karon patent on Hepatitis C Virus which claims antigenic proteins from any strain of Hepatitis C Virus diagnostics generally, probes, PCR, the whole lot and that was upheld by the UK Court of Appeal because it was accepted that really that was a breakthrough invention. In contrast Biogen's patent on Hepatitis B virus vaccines was struck down because it was held that the claims had really been framed too broadly for the actual technical advance which Biogenic made even though it was a valuable advance.
In the US again broad biotech patents have been upheld, recent example is Allergan's Rethropertin patent when they were going against TKT and effectively the claims were to more naturally occurring Arethropeotin, very broad claims but they were still upheld buy the court. Having said that when looking at infringement the US courts have been prepared to construe some of these biotech patents relatively narrowly and an example of that was the Shearing and Biogen versus Amgen case where it was held that really the patent should be limited to one particular form of interferon rather than as contended by the patentees being interpreted more generally than that and there was a recent case which is causing a lot of comment among lawyers at least, the Festo case which has been limiting the doctrine of equivalents which is an adoption by which you can actually effectively blur the edges of your patent protection to catch equivalent inventions.
Okay, so that's enforcement. What about the opposite side, Freedom to Operate? This is of major interest considering the number of upstream patent applications which are out there. What happens if you are researching in the field and you know that somebody has got a patent on the base of the gene or EST. This is a, you know, hypothetical example. You have got company A with a patent on an expressed sequence tag and company B does some more work, finds the full length sequence, gets a patent for that. Company C does some more work, detects a disease associated polymorphism and then company D wants to actually make use of that and bring a diagnostic test based on that polymorphism to market. Well company D to get freedom to operate may have to approach all of those upstream companies and ask for licenses, so there is a real potential for royalties stacking here which could make some of these diagnostics, at least theoretically, very expensive but of course it's a commercial matter if you'sre company D, you have to ask yourself, ask your lawyers, how enforceable are some of these patents, do you take the risk or not?
QUESTION: (Can'st hear, sorry)
TIM: Well, I mean in theory, yes, they would still have to go back to A and B. I mean if you imagine that your test, I don'st know xxxx in manufacturing your test or actually incorporate some element using the genes directly, you know, so that you are actually, you'sre using the gene in your test I mean, so it's some sort of PCR or whatever and it just happens that in the process you are using the sequences, then in principle, yes, you have to go back and ask those royalties. I mean that's the real issue and I think that is why some people involved in the down stream product development get particularly exercised about having these patents on very basic genetic information out there, they just.they are wondering if they are going to be on the receiving end of the legal unpleasantness
Going onto other issues of Freedom to Operate. The research exemption to patent infringement, again passion stifle research, something which you hear in the public debate. In Europe, well and in the States although a different scope, there is a research exemption to patent infringement. Basically in Europe it is not an infringement of a patent to use a patented invention for experimental purposes relating to the subject matter of the invention and that is even if your experiment has a commercial xxxx. If it is a genuine experiment which is designed to actually look at the patented invention, pull it apart, see if there is ways to improve it, you'sre okay, in fact that's.there is a policy to actually encourage that in the interests of further development. Now in contrast my understanding at least of what the situation in the US is the Experimental Use Exemption is much more limited but even if you are doing that sort of genuine experiment into the patented invention, if you are doing it in a commercial context as opposed to a purely academic context that may still be patent infringement and that is something perhaps to bear in mind if you are setting up some research facilities, you know, do you start them over here or over there?
Finally