Association for Molecular Pathology et al v Myriad Genetics Inc, et al, United States Supreme Court 13 June 2013 – read judgment. The headlines are misleading. Myriad Genetics has lost some, but not all of its patent protection as a result of this final ruling in the long running litigation concerning the company’s BRCA 1 and BRCA 2 breast cancer gene patents. According to the American Council on Science and Health, the Court’s decision is
a groundbreaking moment in the history of biotechnology, and a case that will surely rank among the most noteworthy biomedical decisions of our time.
I have posted here, here and here on previous stages in the Myriad patent case, in the United States and Australia, so will not set out the facts again (although for anyone who is interested, the Supreme Court judgment provides a superbly clear explanation of the molecular biology underlying the issues). In essence, Myriad was seeking to protect the R&D it had invested in discovering the typical nucleotide sequence of the BRCA1 and BRCA2 genes, mutations of which can dramatically increase the risk of breast and ovarian cancer. This knowledge enabled the company to develop medical tests useful for detecting mutations in these genes in a particular patient to assess the patient’s cancer risk. The patents on these sequences would have given Myriad the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes. But the company went one step too far by claiming proprietary protection for the genes themselves. This the Supreme Court could not swallow, because such patent exclusivity would have prevented any other company from developing therapies from their own discoveries related to the BRCA genes. With rare unanimity, the Court ruled against Myriad on these claims. But what has not been so widely reported is the endorsement of Myriad’s other claim: the exclusive right to synthetically create the nucleotide sequence for BRCA in the form of “complementary”DNA or cDNA. This contains the same protein-coding information found in a segment of natural DNA but omits portions within the DNA segment that do not code for proteins. Only Myriad’s cDNA are eligible for patent protection, because it is truly an artificial creation. The Court therefore affirmed in part, and reversed in part the decision of the US Court of Appeal for the Federal Circuit below. The Myriad litigation highlights the tension at the heart of patent eligibility. Naturally occurring things should of course be excluded from patent protection, but all inventions at some level
embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas, …[and] too broad an interpretation of this exclusionary principle could eviscerate patent law. (Diamond v. Chakrabarty, 447 U. S. 303, 309 (1980))
– and this case encapsulates the very reason why the financial incentives provided by patent protection are so critical to scientific progress. Mutations – sub-microscopic changes in the genetic sequence – can involve nothing more than a change affecting only one letter in the genetic code. Such small-scale changes can produce an entirely different amino acid or can end protein production altogether, with catastrophic consequences for the host organism. To find the genes on which these mutations operate, let alone the nucleotide changes themselves, involves biochemical and financial investment on a massive scale. Which is why Myriad has come this far in fighting to protect their claim to patent eligibility on the genetic information found in the BRCA1 and BRCA2 genes. And they were successful in the court below. The US Court of Federal Appeals found that the act of isolating DNA—separating a specific gene or sequence of nucleotides from the rest of the chromosome—was an inventive act that entitled the individual who first isolates it to a patent. That court came to the conclusion (from very different routes) that chemical isolation of stretches of naturally occurring DNA were dispositive of the matter, because isolating a particular strand of DNA creates a non-naturally occurring molecule, even though the chemical alteration does not change the information transmitting quality of the DNA. But the Supreme Court disagreed. Discovery of this information, however innovative or groundbreaking, does not by itself satisfy the Patent Act inquiry. Myriad’s claims, in other words, were
not saved by the fact that isolating DNA from the human genome severs the chemical bonds that bind gene molecules together. The claims are not expressed in terms of chemical composition, nor do they rely on the chemical changes resulting from the isolation of a particular DNA section. Instead, they focus on the genetic information encoded in the BRCA1 and BRCA2 genes. Myriad found the location of the BRCA1 andBRCA2 genes, but that discovery, by itself, does not render the BRCA genes “new . . . composition[s] of matter,” §101, that are patent eligible.
What mattered was that the nucleotide sequences of the claimed molecules were the same as the nucleotide sequences found in naturally occurring human genes. The artificially sequenced cDNA was a different matter altogether. On the human chromosomes where they are found, BRACA1 and BRACA2 are about 80,000 nucleotides long. If just the protein-coding bases are counted, the BRCA1 gene is only about 5,500 nucleotides long; for the BRCA2 gene, that number is about 10,200. The cDNA created by Myriad represents those radically reduced molecules. Even though their sequences of cDNA did nothing more than mimic the information that messenger RNA conveys to the protein-making machinery once it leaves the nucleus of the cell, it was sufficiently separated from the naturally occurring sequences of nucleotide bases to pass the test for patent protection. Comment The news focus on this case suggests that the Supreme Court unanimously found against Myriad on all their claims. On the contrary, the important point about this decision is not that the court ruled against Myriad on the naturally occurring DNA claims but that it upheld the patent eligibility of cDNA. This is entirely in line with its approach to genetically engineered organisms, which, whilst using natural sequences, represent something that is created by man. As long ago as 1980 the Court upheld a patent claim on bacteria driven by artificially inserted genes to degrade oil. It explained that the patent claim was “not to a hitherto unknown natural phenomenon, but to a non-naturally occurring manufacture or composition of matter—a product of human ingenuity having a distinctive name, character and use, “with markedly different characteristics from any found in nature” (447 U. S., at 310). What is truly fascinating about this judgment is the rapidly dissolving line between nature and artifice. Even cDNA has not escaped the attention of some micro-organisms; as noted in a footnote to the ruling, there are viruses out there that can “read” messenger RNA to produce their own, convenient protein-coding-only strips of cDNA. Unlike Myriad’s artificial cDNA, this viral effort amounts to little more than scraps of useless “pseudo-gene” inserted into the host DNA. Whilst nature may replicate at random what has been achieved in the laboratory, a line has to be drawn somewhere:
The possibility that an unusual and rare phenomenon might randomly create a molecule similar to one created synthetically through human ingenuity does not render a composition of matter nonpatentable
As molecular science and synthetic biology closer towards the boundaries of what we consider “natural” we can only rely on what we know and understand now, in the world about us. The Supreme Court has endorsed that approach without getting in the way of scientific endeavour. The petitioners argued that Myriad’s cDNA was not patent eligible because the nucleotide sequence of cDNA “is dictated by nature, not by the lab technician.” That may be so, said the court, going along with the white-coat theme, but the lab technician
unquestionably creates something new whence DNA is made. cDNA retains the naturally occurring exons of DNA, but it is distinct from the DNA from which it was derived. As a result, cDNA is not a “product of nature” and is patent eligible under §101, except insofar as very short series of DNA.
Finally, anyone looking to this judgement for a stick with which to beat genetic engineering will be disappointed. The Court expressly declined any view on the patentability of DNA in which the order of the naturally occurring nucleotides has been altered. Scientific alteration of the genetic code presents a different inquiry, and they expressed no opinion about the application of the Patent Act to such endeavors. Sign up to free human rights updates by email, Facebook, Twitter or RSS