Yesterday, a judge in New York issued a sweeping decision that, if upheld following a seemingly inevitable appeal, may put most gene patents on shaky ground. The ACLU, various researchers, and medical advocacy groups had sued Myriad genetics and the University of Utah, which held patents that covered tests for mutations in the BRCA genes, which predispose their carriers to breast and ovarian cancers (the US Patent and Trademark Office was also sued, for good measure). Just about everyone involved requested summary judgement, and the ruling grants it in favor of the plaintiffs, invalidating Myriad's patents in the process.

Summary judgment requires that there be little dispute over the basic facts of the matter. And, not surprisingly, all of the parties agree on the history of modern genetics, which the decision recites, starting with Mendel and moving through Watson and Crick to the biotechnology era.

The are a number of disputed issues, however, mostly focused on whether gene patents are a public good. The plaintiffs argue that Myriad's patents block the option of second opinions, while Myriad points out that it has licensed the patents to other groups. The two sides disagree about whether gene patents foster research, with Myriad arguing that the lure of profits does, while the plaintiffs suggest that the fear of running afoul of intellectual property ends up intimidating researchers.

To a large extent, however, the judge in this case, Robert Sweet, has indicated that the public good disputes aren't central to the decision, which largely hinges on the facts that aren't disputed. Precedent indicates that laws of nature or natural substances can't be patented, although significant transformations to natural products can lead to a patentable process or product. The USPTO grants patents to isolated DNA based on the conclusion that they are "distinctly different in character" from the DNA that is present in human cells.

The court has chosen to essentially reanalyze the USPTO's decision in that regard, noting that it sees no reason to defer to the organization, given that roughly 40 percent of the patents challenged in court are ruled to be invalid. To do so, it divides Myriad's patents into two features: the patent on the genes themselves, and the analysis process by which an individual's genes are scanned for potential mutations.

DNA as an information carrier

Sweet's analysis of the former focuses heavily on a Supreme Court decision called Funk Brothers, in which the court overturned a patent that was granted to a specific mix of bacterial species that doesn't occur naturally. In contrast, a single species of naturally occurring bacteria that was transformed with a combination of genes that don't occur naturally was ruled patentable, because the addition of foreign DNA was transformative. So, the question becomes one of whether the isolation of the BRCA genes as part of the genetic test involves some sort of transformative process.

It doesn't, according to Sweet, but he uses a very novel bit of reasoning to get there. Chemically, he notes, DNA is rather inert, and the process of testing performed by Myriad doesn't really rely on any chemical properties that are distinct to the BRCA genes. (It does rely on chemical behaviors, like base pairing, as part of procedures like PCR, but those properties are common to all DNA molecules.) Instead, the BRCA patents rely on the second aspect of what the decision terms the "dual nature" of DNA: its role as a carrier of information.

To draw an analogy, the chemical nature of DNA can be thought of as akin to the magnetic nature of the surface of a hard disk. The patent doesn't deal with that aspect; instead, it deals with the information encoded by the DNA/disk.

Sweet considers both biology and the patents themselves to reach this conclusion. For example, there's what's termed a pseudogene copy of one of the BRCA genes, which has inactivating mutations in it, and no longer produces any protein. Nevertheless, chemically, large stretches of the pseudogene are identical to the active form—it's only the complete informational context that distinguishes the two. Myriad's patents also regularly switch among different versions of the genes—the full genomic sequence, the processed RNA transcript, even small fragments of the gene—suggesting, in Sweet's view, that it's the informational context that matters.

From this perspective, it's clear that Myriad doesn't rely on anything that transforms the BRCA genes—it's simply relying on their sequence as generated by evolution. It does isolate the DNA from cells, but that's not transformative, and simply involves "techniques well known to those skilled in the art." So, that aspect of the patents fails the test of precedent as defined in Funk Brothers.

Sequence comparisons and the scientific method

The decision then turns to the other aspect of the patents, the process of comparing the sequences obtained to determine whether they contain mutations that might predispose their carriers to cancer. Myriad claimed that the Prometheus decision applies to its patents; this indicated that a common lab technique for isolating chemicals from blood was sufficiently transformative that the process of analyzing the levels of those chemicals could be patented. Purifying DNA from cells, then, is a similarly transformative step during the process of DNA analysis.

Unfortunately, the patents themselves don't include a description of the process of isolating the DNA for sequencing. As such, obtaining the sequences is a generic data-gathering process, and not central to Myriad's claims. Prometheus doesn't apply as precedent, and the patent is invalid.

Sweet wasn't done with Myriad yet. The patents also covered a process by which BRCA mutations could be engineered into a cell line, and chemicals tested for therapeutic activity. Again, this is a fairly generic lab technique, and the ruling is very dismissive, stating, "this claimed 'process' is, in fact, the scientific method itself."

About the only defendant that comes out well is the USPTO, which was sued on constitutional grounds, under the claim that it stifled free speech by granting a patent that restricted discussions of diagnostic information to licensees of Myriad's patents. Since the patents are invalid, the court could avoid considering constitutional issues, so it did.

The state of biotech patents

Although this ruling is sweeping, there are certainly grounds for appeal. The decision also cites the Bilski case, which is currently before the Supreme Court; depending on the court's ruling, some of the reasoning may end up being invalid.

Nevertheless, it's difficult not to be intrigued by the court's reasoning here, namely that it's the information content of a gene that's valuable, and that information is a strict product of nature, and can't be patented. That would seem to put most gene patents (which cover roughly 20 percent of the human gene complement) at risk, and the logic clearly is not limited to patents on human genes. It might be possible to use the Prometheus decision as a guide to write narrower patents that would work around this ruling, but this would seem to require narrower, more focused genetic tests, ones that wouldn't block diagnoses based on different technologies, like the impending arrival of cheap whole-genome sequencing.

It's also difficult not to be reminded of the concluding paragraph of our coverage of last week's Appeals Court decision of another biotech patent. In both cases, the patents appeared to cover processes that are fundamental to biological research; in both cases they were struck down. These decisions can be seen as an indication that biotech is now sufficiently mainstream that doing what's obvious to biologists is no longer considered sufficiently inventive by the courts to warrant patent protection.

A copy of the decision is being hosted by the Genomics Law Report, which has extensive analysis of it.