Of Mice and Men
John Burke and his knockout practice
Published in 2006 Colorado Super Lawyers magazine
By Rebecca Boever on March 9, 2006
Mice: pesky, disease-ridden rodents leaving droppings in your kitchen cupboards, or benevolent, life-saving creatures? John Burke says the latter. He has seen firsthand the potential of a mouse to predict prescription-drug side effects, treat osteoporosis and prevent obesity.
With an undergrad degree in biochemical engineering and a stint as a high school chemistry teacher, Burke would seem a natural for donning a lab coat and playing scientist with these mice. Instead, this Greenberg Traurig IP attorney is working on patenting them — 750 of them, to be exact. He holds the world’s largest patent portfolio covering these mice. He’s patenting these pint-sized creatures for Deltagen, a company that primarily creates these mice, called “knockout mice.” Their purpose? “We all have these genes and really don’t know what their function is,” says Burke. By deleting a gene in a mouse — “knocking it out” — researchers can determine the gene’s function by monitoring the behavior of the mouse without the gene.
This is especially interesting to pharmaceutical companies because many drugs interfere with the normal function of a gene, and if they know exactly what a specific gene’s function is, they have not only information into potential drugs but also insight into what the side effects will be. “Deltagen has a mouse, for example, that is an obesity model, where when you take a normal mouse and feed it a high-fat diet, the mouse gets obese,” says Burke. “You take the knockout mouse and give it the same diet and it doesn’t gain any weight.” Now Deltagen knows the gene to target to block the absorption of fat — music to a pharmaceutical company’s ears. “If you took this drug — if they were to develop it — it would effectively block the absorption of fat. So someone taking that, it wouldn’t matter how much fat they took in, they wouldn’t gain weight.” Pharmaceutical companies throughout the world have snatched up the mice — every single mouse developed by Deltagen has been ordered by companies including Pfizer, Merck and GlaxoSmithKline. The National Institutes of Health has realized the value of these helpful rodents and is calling for the creation of knockout mice for approximately 30,000 genes. But it won’t be easy or cheap. It costs around $100,000 to create and study each mouse. “But everybody recognizes the value of these models,” says Burke. “For $100,000, if you can predict the side effects of a drug, think about the number of lives and the money you’ll save before you do your clinical trials.”
Remember fen-phen? The tragic side effects of that drug potentially could have been avoided with the knockout mice technology. “Fen-phen interacts with a particular gene, that if you knocked it out in a mouse, it leads to embryonic death because of heart defects,” says Burke. “If someone had done the knockout mouse first on that gene, they would have seen that the drug caused heart defects. It’s not just time and money, but a lot of lives can be saved.”
This month marks Burke’s one-year anniversary at Greenberg Traurig; before that, he worked in-house with Deltagen for three and a half years. He had access to the facilities and scientists working on the knockout project, so he got to observe the mice. One in particular stands out to Burke. Researchers targeted a particular protein, and the knockout mouse became a runt with poorly developed bones. When they overexpressed that gene in a normal mouse, the mouse’s bones became healthier and stronger. “It’s things like that that make it worthwhile, because now you have a potential drug on your hand and treatment for osteoporosis,” says Burke. “I think it’s just a matter of time before pharmaceutical companies develop something that results from these mice that’s really beneficial for human health.”
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