Intellectual Property/Ownership Issues

• Author: Robert Wells
• Position: J.D., V.P. Government Affairs
• Pages: 69-78

Page 69

J.D., V.P. Government Affairs, Affymetrix. This work is based upon a live presentation made on February 5, 2004, and does not necessarily reflect events and changes thereafter.

Affymetrix 1

A review of the agenda for this conference is a reminder of the tremendous challenge before all of us who are trying to build an ethical, legal, social, and economic bridge as we cross into this next era of genomics and proteomics, and all the other "...omics" buzzwords that seem to be coming out of biotechnology. I notice there is a question mark after "Revolution" in the program title. I have to object to that question mark, because I think there is no question; there is a revolution. But I also appreciate the fact that there is not an exclamation mark up there, because there is an awful lot of hype that runs through all of this. I think it is good to, on the one hand, think about all of these tough questions we are going to confront, but on the other hand, we should be grounded in reality and think about where we are today. We should contemplate how we need to literally put one legal, ethical, and social foot in front of the other to move forward responsibly.

Publication of the human genome, and the realization that we are all 99.9 percent the same, that we essentially share those three billion base pairs,² is a significant rite of passage. And yet, so much of this is about that one-tenth of one percent that we are all trying to figure out-the small percentage of DNA variation that differentiates us and makes most of us susceptible to some diseases.

Affymetrix is in the business of making a tool that, we think, is one of the fundamental points in understanding how to catalogue, how to decipher, how to interpret, and how to use this information. Our existing technology includes fitting the human genome on a chip the size of a postage stamp. Page 70

There are two great dimensions to the genome, and you can think of them as micro and macroeconomic if you will. On the bottom is DNA analysis, and that is sort of macroeconomic-for example, looking across an entire population to understand the differences among people within that population. And this gets back to the point that Michael was making about biobanks. A dimension above that, we ask the microeconomic question. We look out and we ask Michael, "What, specifically, is happening in your genome that would tell us if you have a certain condition, how you'll respond to certain medication, what your prognosis might be?" And so on and so forth. How do we take that understanding of you and reduce it to a molecular level? The word "reduce" is a misnomer because "reduce" sounds like there is less of something. But, in fact, by taking things down to a molecular level, the amount of information we are getting is so much more powerful that we are actually exponentially expanding our understanding of the human condition.

Affymetrix's founder's great idea was to take the principles of combinatorial chemistry and marry them to the principles of semiconductor manufacturing in Silicon Valley.³ And this really predates, by almost a decade, the publication of the genome because, even as early as 1991 when our founder's paper was published in Science,⁴ people were starting to understand that completion of a map of the genome would bring an abundance of information. It would bring all of those As and Cs and Gs and Ts, which could stretch between Portland and Chicago fifty times over, or between here and the moon, or fill up 9,000 newspapers. We use a bunch of these wonderful illustrations to capture how much information is involved.

Affymetrix was founded with a focus on moving from fusing transistors on a chip to fusing DNA and RNA on a chip.⁵

Increasingly, foremost for developing pharmaceuticals with genomics, including drug discovery, is the notion of looking across a population to understand genetic variance and how that might impact a condition. Secondly, drug validity must be understood on a genetic level-meaning understanding what will and will not work based on genetic insight for what drug targets would be valid, Page 71 rather than based on the outcome of a winding process of clinical trials involving some 5,000 people. The goal is to be smarter, more selective.

Our whole paradigm of what constitutes success, or lack thereof, in drugs is changing. In the old days, we said, "Well, this drug works for sixty-five to seventy percent of the people. That means it is a pretty good drug." If you are in the thirty percent that it did not work for, you are not going to be very happy about it. But on the other hand, there may be a drug for which people said, "Well, it is not all that effective, it only works thirty percent of the time." If you are in that thirty percent, it is one hundred percent effective. So, being able to stratify patients and the kinds of pharmaceuticals we develop is a powerful application of the technology.

And at last, clinical genomics. Today, most of this technology is what the Food and Drug Administration ("FDA") calls "research use only" (RUO) technology. But Affymetrix can move quickly, as can others in the industry and the FDA, and there are the folks in the clinic who would like to take this technology today and be able to say with great definition from what types of conditions people suffer.

I will tell you one quick, anecdotal story from a friend of mine, Terry, who is the Medical Curator of the Smithsonian in Washington, D.C. It is a story about Ulysses S. Grant, our only president to have died from cancer.⁶ A series of biopsies were taken, before and after he died, of the tumor that had lodged in his throat.⁷ Those were kept at Walter Reed Army Hospital over the many years that followed. In 1999, the Army decided to bring in a group of pathologists to look at Ulysses S. Grant's tumor slides and to try to discern what we would know today that we did not know when Grant died in the 1880s.⁸

The results were interesting, which Terry reported in "What's in Grant's Tumor?," which I think is a great pun.⁹ They brought all of these great pathologists in, and they all looked at a slide.¹⁰

And more than one hundred...