Patenting Genes

RAY SUAREZ: The race to map the human genome is over. Last week scientists announced that they had a rough draft of all human genes, but now, biotech companies and universities are filing for patent protection on human genes and their functions. They are a biological gold mine that may enable researchers to diagnose diseases and create new drugs.

Who can-- and who should-- own the information in a human gene? Have recent changes in patent law brought perplexing new challenges? To discuss the issue, we turn to: Jonathan King, a professor of molecular biology at MIT. He is also on the board of directors for the Council for Responsible Genetics, a public advocacy group on these issues; Randy Scott, president and chief scientific officer of Incyte Genomics, Incorporated; and Rebecca Eisenberg, a professor of law at the University of Michigan who specializes in biotechnology patent law. Professor Eisenberg, what does the law say in black and white about what you need in order to get a patent?

REBECCA EISENBERG: Well, in order to get a patent on any invention, you have to show that you have a new and useful invention that's nonobvious in light of what was known previously. Contrary to many people's belief, the patenting of genes is not really a new area for the patent system. Patenting of genes is at least as old as the biotechnology industry, which isn't all that old, but I suppose it's been going on for 20 years or so. And in the early days, it didn't really provoke much controversy. By now it's pretty well established that if you can show that a DNA sequence is new and useful and nonobvious, you can get a patent on it. The requirement that it be useful sometimes poses a problem in this era of identification of DNA sequences before their function is understood. That's the issue right now that the patent system is trying to work out. But this isn't really a new practice. This is a long-established practice.

RAY SUAREZ: Well, let's take a look at that term "nonobvious." When it used to be really hard to sequence a gene, weren't all genes, by definition, nonobvious. And now that machines can do it, aren't they less nonobvious?

REBECCA EISENBERG: That's a really good question. In the early days, the nonobviousness of the gene was... could well be established by the nonobviousness of the method of finding it. But at a certain point, it became a rather trivial matter to find the genes, and the court of appeals for the federal circuit, which decides many questions of patent law on appeal from rejections of patent applications, decided that we shouldn't confuse the nonobviousness of the method of identifying a gene with the nonobviousness of the gene itself. And so if there's nothing in the... in the state of prior knowledge in the field that would suggest the gene itself, the fact that the method by which the gene was found has become routine won't prevent the issuance of a patent on that gene.

RAY SUAREZ: Randy Scott, how many patents does Incyte Genomics have applications out for, and why is it important that you get this patent protection?

RANDY SCOTT: Right. Well, we have now about 500 issued and allowed U.S. patents and about another 7,000 patents filed on genes that we've discovered out of normal and diseased cells and tissues. For us, it's really been the cornerstone of our business, of discovering novel genes, associating them with disease and then providing that information broadly to the pharmaceutical industry, where 18 out of the top 20 major pharmaceutical companies now subscribe to Incyte databases and are actually already covered broadly under no, sir patents. So our feeling is that we're actually helping to enable the industry to have access to that intellectual property and to use that to cure and diagnose disease.

RAY SUAREZ: But in a lot of these cases, you haven't actually done anything to the gene or found a way to do something to the gene -- you've just described it, do I understand this right?

RANDY SCOTT: I think that's a bit of a misnomer. The approach that we plied going back to 1991 was actually starting from normal tissue and diseased tissue so, for example from either prostate cancer and normal prostate tissue and then randomly sequencing large newspaper numbers of genes out of both of those systems but then looking at the systems and trying to identify those genes that were associated where diseased prostate versus normal. So we actually started like any biological experiment. It's just the methodology now is really truly a paradigm shift for the whole field, that we can stand thousands of genes at a time in the search to discover novel genes, and we can now discover and process hundreds of genes that may be specifically associated with prostate tissue or prostate cancer. So simply the volume of information that's now coming out of this genomics revolution I think has really both excited everybody and of course taken some people aback in the speed at which this field is moving.

RAY SUAREZ: Professor King, a lot of the companies involved say, "look, you know, we did the digging. We figured out what was necessary to figure out about these genes. Why shouldn't we have the protection that the patent system has offered inventors for 1200--200 years?"

JONATHAN KING, The Council for Responsible Genetics: Well, you know, one of the major discoveries of modern genetics is that human genes are inherited, they're passed down to us from our parents and from all previous generations. The human genome is the kind of common biological heritage of all human beings, not the property of a corporation or an individual or a scientist. And these genes of course weren't invented by the people who sequence them. The notion that revealing the sequence of a gene should enable you to be granted a patent monopoly on it is like saying that the chemists who determined that graphite is made of lead atoms should get a patent on graphite - or that mapping the bottom of the ocean should allow you to own the ocean bottom.

It's really a profoundly flawed notion of transfer of biological comment into private property. In fact the genome... the sequence, which is an extraordinary step forward in, you know, human knowledge and human scientific history, this is the product of 50 years of public investment. So the American taxpayers, who financed this, thousands of scientists worked on this project. They were trained by thousands of scientists. All those people in general were financed by the public through the National Institutes of Health, National Science Foundation, Department of Energy. This is information that is absolutely part of the kind of human commons and really the notion that discovering of product of nature allows you to patent it is a profound kind of misappropriation of the commons.

RAY SUAREZ: But is there the possibility that certain discoveries simply won't be made if there isn't the profit motive to do the kind of expensive up-front work we're talking about?

JONATHAN KING: No. No. All of the major breakthroughs that enabled the genome to be sequenced, all of the wonderful discoveries of biotechnology and genetic engineering were developed by scientists working as public servants. They were motivated by the desire to kind of improve human welfare, to get credit for it. But they didn't do it for profit. The notion... the reason there was a race around the Human Genome project is there were thousands and thousands of scientists who were working very hard and very energetically to share this information with the public, to make it freely available. Cellera had a business plan that said, "all right, we're going to privatize this information. If we get the see sequences first, we'll try patent claims on it and then we'll sell back to the public what the public itself originally financed." It's really a profound misuse of the patent system and the congress ought to act and say no patents on human genes.

RAY SUAREZ: Professor Eisenberg, you've been able to patent living things for, what, about 20 years out?

REBECCA EISENBERG: Yes.

RAY SUAREZ: Is this a big change in patent law, the difference between a development and simply finding something and mapping it or identifying it?

REBECCA EISENBERG: Well, you can't patent something that... If you simply find something in nature and describe it, that's not a sufficient... You won't be able to get a pat enter on that thing as such. In order to get a patent, you have to claim the invention in a form that is distinct from what exists in nature. And that's been the way these patents on DNA sequences have been issued. They've claimed, you know, isolated and purified DNA sequences that are apart from the chromosomes in which they reside in nature. They've claimed genes that have been spliced into bacteria so that they can be used by a biotechnology firm to produce large quantities of a protein that, in nature, is made in smaller quantities by cells using their own DNA. If you were to claim a gene in a form that's infringed by ourselves doing cells doing what they've been doing for generations, that would be an invalid patent. But that's not what's going on.

RAY SUAREZ: Haven't there been cases, though, of companies sort of putting down markers where they aren't quite sure what a gene does, but they patent the sequence and subsequently it's found that they do something quite else or provide some other road but it's walled off now - you have to pay them in order to continue your research.

REBECCA EISENBERG: That's a very serious concern, that you can get a patent issued before you really know what it is that you're holding. And that raises the possibility that a patent will be held by someone who's done... who happens to have been first to identify a sequence and that that's going to cut into the future prospect of...... future researchers that have done more substantial work in order to actually understand the role of that particular gene in a disease pathway and figure out some sort of a therapeutic intervention that's possible. So I think what's new maybe is that we've seen the industry move further upstream in the course of research and product development to the point that now you're seeing a lot of patent applications being filed on discoveries that are primarily valuable as inputs into further research, rather than as products themselves.

The first generation of gene patents were issued on genes that provided the blueprint for therapeutic proteins and a patent on the gene looked pretty close to a patent on a drug. Now what we're seeing is patents on thousands of genes, where the primary value of knowing what these genes are is that it gives you a resource for further research, for future discovery. And that raises a very real concern about how those discoveries are going to be licensed. Randy Scott described Incyte's strategy of not exclusively licensing genes very broadly. I think when that happens, it's a lot less worrisome than when you see companies trying to exploit the genes that they've identified on an exclusive basis and not making them available to other researchers.

But I think we still have to worry about access by researchers who were not working in industry, who are working for universities perhaps. I know here at the University of Michigan, we're preparing to launch with a major life sciences initiative, a lot of universities are interested in exploring the tremendous potential of the genome, and are worried that a proliferation of patents in the hands of different owners might complicate the task of gathering the necessary licenses.

RAY SUAREZ: Well, let me quickly go to Randy Scott. I want to finish up with Randy Scott. Just to see whether, in your view, there needs to be some refinements to the pat enter law in order to wrap their arms around this new world where you can file phone book-sized applications and sort of put a brick on something while you're still figuring it out.

RANDY SCOTT: Right. I think in our view, the U.S. Patent Office has actually done a very add admirable job at sort of looking at the technology, looking at the state-of-the-art and adapting to that. One of the primary uses for genes these days is in diagnosis of finding genes as markers. One of the best known markers of all time, prostate-specifically antigen, or PSA is now the primary test for prostate cancer, and people don't really need to understand much about what that gene does functionally in the body, but when it shows up in the bloodstream, it's a good sign that prostate cancer has begun its course.

And so that's a great marker. A lot of this race is really about identifying new diagnostics, new therapeutics, and I think Rebecca raises some great points. You can't patent a gene as it exists in nature, so there's no danger that we can patent a gene as it's walking around in a person. In fact, you can only get it in a commercially viable form as it's useful for diagnostics and therapeutics. And historically in our industry, having a patent has actually meant that most holders of patents would encourage people to do basic research -

RAY SUAREZ: Randy Scott, I'm going to have to end it there.

RANDY SCOTT: Okay.

RAY SUAREZ: Thank you very much, all.