Mail call (ooph!)

A few weeks ago I came home to find someone had mailed me a phone book -- at least that was my first impression. The return address of the old shop suggested the explanation for the bulging package -- the full text of a newly issued patent on which I am listed as an inventor.

I've lost track of how many patents I have -- it's not a huge number, perhaps a dozen, and a few trickle out periodically. When I had to interview last year, I did go track them down to get the resume right. It could have been a deluge -- the paralegals once made a habit of booking me for an hour so I could autograph my way through a mountain of applications.

I non-chalant about it because the patents are part of that dubious flood of gene patents from the genome gold rush. Nobody knew whether they would be worth anything, but more importantly nobody wanted to be caught without one should they prove valuable -- so the lawyers made a fortune. On my end, in most cases my contribution was my development of the software which sieved the molecular databases -- I was more of a meta-inventor than inventor.

I'll never really know what, if anything, comes of most of them without a lot of work, as the patent titles are broad and vague. My notorious gene numbering system will be immortal though: many of the patent titles mention them. There is one major exception to this: one cluster of patents led to a compound currently in clinical trials. My contribution was clearly very small and very early, but it is nice to know that something good might come out of it.

I did somewhat expect the huge package -- not that I am claiming clairvoyance. No, I had advance warning, also by post. There are several companies which will put your patent number or title on a wide variety of knick-knacks, such as T-shirts, coffee mugs, plaques, etc., and their mailings spring forth as soon as the patent issues. That's how I've always known when a new patent came out -- because I got junk mail. Funny system.

Clearing the Gene Patent Thicket

The gene patent issue, which I addressed once before, continues to boil. Derek Lowe has two good back-to-back posts (with another anticipated) on the topic, triggered by a Michael Crichton OpEd piece in the NY Times. A few weeks back there was another opinion piece in the Sunday NY Times, which Hsien Hsien Lei has covered over at Genetics & Health(NY Times articles require free registration).

There are really two classes of concerns, and concern holders, in the debate. At the one end you have the Crichtons and many others who feel that any sort of patenting of genes is improper and immoral. At the other you have a lot of people (such as myself) who believe certain gene patents are appropriate, but that there is a lot of confusion generated by the legacy of past gene patents.

I can understand some of the concern of the Crichton camp. It is true that genes are natural monopolies -- in general, one can't invent around them easily if the goal is genetic testing. On the other hand, some of Crichton's complaints are simply those that are generally levied against any intellectual property protection in biomedicine: that it creates 'unnecessary' costs and unequal access to lifesaving information. But, as last weeks approval of the MammaPrint microarray-based breast cancer diagnostic test reminded, private companies do bring important health innovations to market. Without premiums for the investors to cover the very high risk of failure, such innovations might never reach market.

As an aside, the issue of failure in biotech is nicely covered in another of Lowe's postings, though Xoma? What pikers! Only 0.75B gone through in 25 years -- that's only 0.03B/year. I'm pretty sure a certain company in Cambridge that burned off closer to 1.5B in about 12 years, and Celera must have done even better than that in terms of bucks per year.

There are some other issues to consider in this space. If patent law is altered to exclude gene patents, will it exclude multigene tests? If I make a small change in a protein therapeutic, ala Aranesp, is that patentable? Are other purified preparations of natural products, such as natural-product derived pharmaceuticals, still patentable?

For those of us who feel that gene patents are appropriate, but under well defined restrictions, the current situation is clearly a mess. During the genomics gold rush, companies flooded the patent office with applications. The general assumption was that these patents would probably be worthless -- but that nobody could take the chance that the courts & Patent Office would decide otherwise. Until one was litigated, nobody knew how things stood -- and nobody felt they could afford to wait around and potentially find themselves naked. From the regulatory ambiguity of the time sprung a gazillion patents. The paralegals used to book me for an hour at a time just to sign patent forms -- since I wrote the software that tag things as 'worth' patenting, I was a co-inventor or sole inventor on many dozen applications. Most of my applications are dead, but there is a horrible mess out there.

Now these patents would just be irritating if they only gave fodder to writers, but there is a real cost to society of them. I was at a Celtics game recently with a friend and a bunch of his buddies, several from his law firm. One specialized in biotech law and was quite confident that none of those genome era patents would hold up under legal assault. But it is that very risk of litigation that hangs a cloud over everything. If you are working on these genes, prudence says that you must review all of those patents, and perhaps worry about them even though they are junk. The same sort of uncertainty that led to these patents continues to make them a problem.

So, I would like to make the following proposal. It won't interest the 'gene patents are evil' crowd, but I will claim it would make good public policy. An organization should be set up and funded with the goal of retiring mass numbers of the gold rush patents. At regular intervals, the organization would hold a Dutch auction to buy up blocks of patents. You couldn't sell them individual patents, only large batches. Once purchased, the organization would have the patents cancelled (if that isn't available in the current law, then that would require some legislation). Or, the organization would somehow be a legal black hole for the patents, forbidden to ever sell them or defend them in court. Not only would the regular auctions slurp in patents, but they would establish a market value for the patents -- and so profitable companies might just donate blocks of patents instead of selling them to reap tax benefits.

The last thing one would want to do is create more incentive for junk patents. The regular auctions would be capped so that these patents would be selling for cents on the dollar spent to get the patents in the first place. Only patents of a certain age range would be taken, perhaps nothing younger than 5 years old. Nobody's going to make a profit on this, but for companies stuck with lots of essentially worthless patents, this is free money. But because it is delivering a value to society, by reducing the overhead imposed by all those patents, I would argue it is a worthwhile expenditure.

This approach wouldn't solve the junk patent problem, and it clearly wouldn't address the patents that biotech executives think do have value. The controversial ones will all fall in that category, as they are controversial precisely because they can transfer money to entrepreneurs. Public debate about patenting is healthy & appropriate, but let's think carefully about unexpected consequences.

Gene Patents

Today's Parade magazine has an article titled "How Gene Patents are Putting Your Health at Risk". The topic of gene patents deserves public scrutiny & debate, but better coverage than this article.

Featured prominently (with a picture in the print edition) is Michael Crichton, whose new book has been touched on previously in this space. Crichton in particular makes a number of concrete statements, some of which are a bit dubious.

First, let's take the statement

A fifth of your genes belong to someone else. That’s because the U.S. Patent Office has given various labs, companies and universities the rights to 20% of the genes found in everyone’s DNA— with some disturbing results.

. The first sentence is just plain wrong, and given its inflammatory nature that is very poor journalism. Nobody can own your genes -- genes, as natural entities, are not themselves patentable. What can be patented are uses of information in those genes. That is a critical, subtle distinction which is too often lost. What can be patented are uses for genes, not the genes themselves, just as I could patent a novel use for water, but not water itself.

Time for the full disclosure: I am a sole or co-inventor on 11 issued gene patents (e.g. U.S. Patent 6,989,363) , many of which are for the same gene, ACE2. Many more gene patents were applied for on my behalf, but most have already been abandoned as not worth the investment. Those patents attempted to make a wide range of claims, but interestingly they missed what may be the key importance for ACE2 (we never guessed it), which is that it is a critical receptor for the SARS virus.

Many of the gene patents do illustrate a key shortcoming of current patent law. When filing a gene patent, we (and all the other companies) tried to claim all sorts of uses for the information in the gene. These sorts of laundry lists are the equivalent of being able to buy as many lottery tickets for free. A rational system would penalize multiple claims, just as multiple testing is penalized in experiment designs. The patent office should also demand significant evidence for each claim (they may well do this now; I am no expert on the current patent law).

Another one of Crichton's claims deserves at least some supporting evidence, plus it confuses two distinct concepts in intellectual property law

Plus, Crichton says, in the race to patent genes and get rich, researchers are claiming they don’t have to report deaths from genetic studies, calling them “trade secrets.”

First, just because some idiots have the chutzpah to make such claims doesn't mean they are believed or enforceable. Second, such claims have nothing to do with gene patents -- such claims could exist in any medical field. Finally, trade secrets and patents are two different beasts altogether. In a patent, the government agrees to give you a monopoly on some invention in return for you disclosing that invention so others may try to improve on it; a trade secret must be kept secret to retain protection and should someone else discover the method by legal means, your protection is shot.

The on-line version also includes a proposed "Genetic Bill of Rights". I would propose that before enacting such a bill, one think very carefully about the ramifications of some of the proposals.

Take, for example,

Your genes should not be used in research without your consent, even if your tissue sample has been made anonymous.

. What exactly does this mean? What it will probably mostly mean is that the thicket of consent hurdles around tissue samples will get thicker. Does this really protect individual privacy more, or is it simply an impediment which will deter valuable research? Will it somehow put genetic testing of stored samples on a different footing than other testing (e.g. proteomic), in a way which is purely arbitrary?

Another 'right' proposed is

Your genes should not be patented.

.
First, an odd choice of verb? "Should"? Isn't that a bit mousy? Does that really change anything? And what, exactly, does it mean to patent "your genes"?

On the flip side, I'm no fan of unrestricted gene patenting. All patents should be precise and have definite bounds. They should also be based on good science. Patents around the BRCA (breast cancer) genes are the most notorious, both because they have been extensively challenged (particularly in Europe) and because the patent holders have been aggressive in defending them. This has led to the strange situation in (at least part of) Europe where the patent coverage on testing for breast cancer susceptibility depends on what heritage you declare: the patent applies only to testing in Ashkenazi Jews.

In a similar vein, I can find some agreement with Crichton when he states

During the SARS epidemic, he says, some researchers hesitated to study the virus because three groups claimed to own its genome.

It is tempting to give
non-profit researchers a lot of leeway around patents. However, the risk is that some such researchers will deliberately push the envelope between running research studies and running cut-rate genetic testing shops. Careless changes to the law could also hurt companies selling patented technologies used in research: if a researcher can ignore patents for genetic tests, why not for any other patented technologies.

Gene patents, like all patents, are an attempt by government (with a concept enshrined in the U.S. Constitution) to encourage innovation yet also enable further progress. There should be a constant debate as to how to achieve this. Ideas such as 'bills of rights', research exemptions, the definitions of obviousness and prior art, and many other topics need to be hashed over. But please, please, think carefully before throwing a huge stone, or volley of gravel, into the pool of intellectual property law.