By Magdalina Gugucheva

On October 29, the United States Department of Justice filed an amicus brief in the Myriad gene patenting case. While the brief supported neither party, it was lauded in the media as weighing on the side of plaintiffs in opposing Myriad's breast cancer gene patents. The White House recently announced its support of DOJ's position, stating that patenting isolated genes would hinder innovation, delay advances toward the "revolution of personalized medicine," and prevent the proliferation of diagnostic tests like the one at issue in this case. Unfortunately, these statements misrepresent DOJ's actual position and the consequences stemming from it, and, like much of the discussion of Myriad, inaccurately gloss over the complications of gene patenting.

DOJ supported the district court's invalidation of some of the challenged Myriad patents but not others. The 15 challenged claims, covered by seven patents, roughly fall into two categories. One category of the challenged claims covers actual molecules of DNA, or "compositions of matter," while the other category is comprised of "method" claims, where Myriad has claimed the process of comparing a patient's DNA sequence to known mutations in order to determine whether she had a predisposition for breast cancer. Both categories of claims were invalidated by the district court.

The DOJ supported the invalidation of the method claims, but with respect to the composition of matter claims it took a different stance. The DOJ brief drew a distinction between the patents claiming natural, isolated DNA that came from a human cell, and "synthetic" DNAs called cDNAs that are made from the gene in a test tube. The DOJ took the position that the first kind of composition claims, the isolated human DNA, was a product of nature and therefore unpatentable. The second form of composition of matter patents, however, were patentable according to the DOJ. Because they were purely man-made versions of the naturally occurring gene, and because they were slightly different in structure and form, the DOJ argued these molecules were wrongly invalidated by the district court.

The distinction drawn by DOJ takes too formalistic an approach to both patent law and the nature of DNA. cDNAs, while different molecules than their corresponding DNAs, are different in ways irrelevant to the intellectual property Myriad has claimed. Genes in the form of DNA in our cells, in order to make the protein they encode, are first transcribed into mRNA. The mRNA, which is a perfect complement to the gene, then has certain portions of sequence, called the introns, chopped out by an enzyme in order to create a mature mRNA that only contains the nucleotide sequences coding for the protein in question. This chopping process is called splicing. To make things more complicated, the mRNA can be spliced in many alternate ways to produce sequences coding for slightly different but related proteins. Once isolated from a human tissue sample in a test tube, these mRNAs can be converted back into complementary DNA strands with the help of a viral protein called reverse transcriptase. This is how cDNA, which stands for complementary DNA, is produced. cDNAs are essentially identical to the naturally occurring, isolated mature mRNAs, except they have a different molecular "backbone" which makes them more stable. The code-the thing that is valuable, the information that Myriad through its patents has prevented others from using in diagnosing and treating genetic predispositions to breast cancer-is almost exactly the same. Thus, while in form these are different molecules, in substance and information, they are identical.

The value of gene patents, whether in cDNA, DNA, or mRNA form, is informational content. As Judge Sweet pointed out in his opinion for the district court decision, DNA is a unique and special molecule because it is the "physical embodiment of information," and, more specifically, "the physical embodiment of laws of nature-those that define the construction of the human body." The difference between cDNA and isolated DNA is like the difference between patenting a mathematical equation (not patentable under other patent law doctrines) saved on a computer and that printed out in a book. Saved on a computer it is perhaps "more stable" or permanent, can be transmitted by email, can be integrated into software. Yet while the physical embodiment is different when appearing on your screen or in a printed book, the thing that one might (unsuccessfully) try to patent, in either form, is the same. It is purely informational.

Importantly, by maintaining the validity of Myriad's patent on cDNAs, the DOJ's position would effectively do very little to alter the current status quo with respect to both gene patenting and the state of breast cancer diagnostics. Currently, any commercial diagnostic test must use cDNA. Isolated DNA in its natural form is not usable for these purposes. Furthermore, any research into the BRCA1/2 genes requires the use of cDNAs. By allowing Myriad to retain patents over these cDNAs, diagnostic tests for the purposes of promoting personalized medicine would remain equally hindered, and nothing would change with respect to the market for breast cancer gene testing.

DOJ has likely adopted its position with biotechnology products, rather than medical diagnostics, in mind. In order to make any transgenic organism-genetically modified crops, bacteria that produce important medicines from naturally occurring genes, and oil-eating bacteria, etc.-cDNAs must be used. Thus, firms who discover genes with useful commercial biotechnology applications-for example, those genes inserted into crops to make them herbicide-resistant-would want to patent the cDNAs used to make those crops. This intellectual property is, especially in the initial stages of product development, the only asset that biotech startups can use to attract investors. Without this intellectual property, the claim goes, biotech innovation would be stifled.

The claim that a prohibition on cDNA patents would deprive biotech startups of their only property is false, yet it highlights much of the problem with a binary approach to the patentability of genes. The question we should ask is not, "are genes patentable?" but "at what point from the location of the sequence in the genome to the development of a final, marketable product should we grant exclusive intellectual property rights to an inventor?" Once cDNAs are made, researchers can quickly make more complicated molecules, called vectors. Vectors integrate the cDNA into a larger, more complicated molecule that can be used to insert the gene into other cells in order to make the transgenic organisms at the heart of biotechnology. Myriad has patents out on many such vectors, and as the DOJ importantly points out, plaintiffs in this case never challenged those patents. The vector, unlike the cDNA itself, incorporates many elements that are functionally, not just formally, different than what one can find in nature, and truly combines naturally occurring genes with non-naturally occurring inventions. The vector is the starting point for all biotechnology products arising out of gene discoveries.

Myriad might counter that vectors can't be used for diagnostic tests, that only cDNAs can, and therefore cDNAs must be patentable to encourage the development of diagnostic technology. Yet the cDNA by itself cannot be used diagnostically either; it must be integrated into a platform that will allow the researcher to actually see if the patient's sample binds to and compliments the cDNA. The cDNA needs some sort of further alteration, creating an invention that does markedly differ from the naturally occurring gene in both form and function. Myriad's diagnostic technology integrating cDNA into a usable platform, like its vectors, are also not challenged in the current case. Not only does this diagnostic technology squarely fall within patent law, but more importantly, patents claiming it don't prevent others from working with the naturally occurring information in the genes as integrated into other platforms. Patents on diagnostic technology merely prevent others from using the same exact machinery-rather than information-in testing a patient for which version of the BRAC1/2 gene it contains. Thus, invalidating cDNA patents may prevent Myriad from charging absurdly high prices for BRAC1/2 testing by virtue of its monopoly on the gene, but will still allow the company to retain enough intellectual property in the form of technology integrated with the gene to maintain its valuable position as the leader in the BRAC1/2 testing market.

Unfortunately, the DOJ brief has missed an opportunity to highlight these important, consequential distinctions between various "kinds" of gene patents, instead arguing difference where it does not really exist. The DOJ position would do very little for women currently unable to undergo breast cancer gene testing, and would fail to solve the anti-commons effect currently resulting from exclusively held gene patents. In order to strike the best balance of encouraging innovation and preserving public access to natural phenomena and information, patents on naturally occurring genetic sequences in the form of cDNA, as well as DNA and mRNA, should be invalidated.         


Magdalina Gugucheva is a Fellow of CRG.

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