The curious incident of the Supreme Court in Myriad Genetics.

• Author: Burk, Dan L.

Often what is not said is as significant as what is said. In its recent Myriad Genetics decision, the United States Supreme Court is curiously silent about the relationship between its holding in that case and the holding in its immediately previous patent subject matter case, Mayo v. Prometheus. This reticence is all the more puzzling given that the Court initially remanded Myriad to the lower courts for reconsideration in light of the Mayo holding. The Court's silence regarding Mayo leaves uncertain the relationship between the "products of nature" doctrine that serves as the basis for the Myriad decision, and the "laws of nature" doctrine that has been the basis of nearly all of its other subject matter cases. In this Article I assemble the clues in the laws of nature cases to suggest what the Court might have said or might still say regarding products of nature.

INTRODUCTION

This is an essay about something not said. In its recent gene patenting opinion in Association for Molecular Pathology v. Myriad Genetics, Inc., the United States Supreme Court held that genomic DNA sequences (gDNA) that had been extracted and purified from human cells fell outside of patentable subject matter. (1) It further held that claims to another type of nucleotide sequence, complementary DNA (cDNA) that had been replicated in the laboratory, did fall within patentable subject matter. (2) And the Court squarely held that there exists a judicially created doctrine on products of nature that distinguishes between the two types of molecules. (3)

But what is not said is often as important as what is said. In Sir Arthur Conan Doyle's mystery story, Silver Blaze, Sherlock Holmes announces that the critical clue to solving the mystery presented is the "curious incident of the dog in the night-time." (4) When the ever-hapless Scotland Yard Inspector Gregory observes that the dog did nothing in the nighttime, Holmes responds, "[t]hat was the curious incident." (5)

Despite all that it did say in its Myriad opinion, the Supreme Court said not a word explaining the relationship of the products of nature doctrine to the holding in its previous opinion in Mayo Collaborative Services v. Prometheus Laboratories, Inc., decided only a year before. (6) Mayo was also a case about patentable subject matter. In the Mayo opinion, the Court declared claims to a medical diagnostic test to be excluded from patentable subject matter, because they read on a law or principle of nature. Mayo concerned the disposition of natural processes; Myriad involved the disposition of natural substances. (7) The Court is prone to mention both in the same breath, (8) but their relationship remains unarticulated.

The Court's deafening silence on this relationship is particularly odd given the procedural history of the Myriad decision. It began conventionally enough with a district court decision that was affirmed in part and reversed in part by the Court of Appeals for the Federal Circuit. (9) The parties petitioned the Supreme Court for certiorari. But while the Myriad petition was pending, the Supreme Court decided the Mayo case and remanded Myriad to the Federal Circuit for reconsideration in light of the Mayo opinion. (10)

One might think, given its earlier instruction to the intermediate court to reconsider Myriad in light of Mayo, that the Court might have expressed some view on the connection between the cases. Indeed, the Myriad opinion begins by citing Mayo regarding the patentability of natural law. (11) But it quickly moves on to discuss unpatentable products rather than unpatentable principles without a word about the relationship between the two. (12) The ultimate holding regarding Myriad's claims to DNA molecules is as silent on the subject as Holmes's dog in the nighttime.

A good deal has been written about Mayo and the Court's laws of nature jurisprudence. (13) No doubt a good deal will be written about the implications of the Supreme Court's decision in Myriad. (14) But my brief here is to trace the connections between the two that the Court left unarticulated in the latter opinion. I begin by reviewing salient features of the Myriad decision itself and the somewhat dubious history of the "product of nature" doctrine. I then turn to the parallel line of cases regarding laws of nature, tracing the conceptual threads that culminate in the Mayo decision. I conclude by looking for some consonance or point of contact between the two lines of cases and by suggesting the work that remains to be done, probably by lower courts, to articulate the connections that the Supreme Court left unspoken.

1. PATENT ELIGIBILITY OF DNA

   Even without its strange silence regarding the Mayo decision and principles of nature, the Myriad opinion would be something of a puzzle. The case presented to the Supreme Court involved patents over two types of genetic molecules: genomic DNA, or "gDNA" that was extracted from human cells, and complementary DNA or "cDNA" that was synthesized in the laboratory using a process called reverse transcription, and which would generally not occur in the normal course of human cellular function. (15) In a unanimous opinion written by Justice Thomas, the Court found the gDNA not patent eligible, but the cDNA to fall within patentable subject matter. (16)

   The principal opinion from the intermediate Court of Appeals for the Federal Circuit also held that the cDNA was the patent eligible product of human manipulation. (17) But it additionally held that the gDNA was patentable subject matter, because extraction from the cell separated the gene sequence from the larger chromosome in which it was embedded, changing the chemical structure of the molecule. (18) The Supreme Court rejected that logic, opining that because the sequence of nucleotides in the extracted molecule was the same as that found in the native chromosome, the extracted molecule was for subject matter purposes a product of nature. (19)

   This reasoning is at best incoherent. (20) Thomas's opinion tells us that the Myriad genomic DNA is unpatentable, because it is for subject matter purposes identical to what is found in nature. How is it identical? The identity between the native molecule and the extracted gDNA, he tells us, is found in the coding information--never mind that the extracted molecule has a different chemical structure than what one finds in the human chromosome. (21) It is the nucleodde sequence that counts.

   I have previously criticized the characterization that Thomas adopts here of DNA as "information," (22) but, very well then, one would think--and the petitioners certainly argued (23)--if the Court is going to adopt this rationale, it should also preclude the Myriad patent claims drawn to the cDNA, since such molecules code for exactly the same gene product as the gDNA. Indeed, the cDNAs are reverse transcribed from mRNA molecules produced in the cell using the gDNA as a template. But no, Justice Thomas tells us, the Myriad cDNA is patent eligible because it is for subject matter purposes distinct from what is found in nature. (24) What is the distinction? The distinction between the native molecule and the cDNA is found in the structural difference between the reverse transcribed molecule and what one finds in the human chromosome. (25) Because it was produced by a process of reverse transcription, the cDNA lacks intervening nucleotide sequences or "introns" found in the native gene--never mind that it carries the same coding information. (26) It is the chemical structure that counts.

   Reading Thomas's opinion, one is therefore forced to conclude that molecules that differ structurally from a native molecule are both excluded from and included within patentable matter, while molecules with the same coding information as a native molecule are also both excluded from and included within patentable subject matter. It is, in short, quite impossible to logically determine from the opinion whether a given macromolecule meets the criterion for patent eligibility. The Patent Office initially adopted the most simplistic reading of the case, instructing its examiners that extracted genomic DNA is not patent eligible. (27) But this reading gives no guidance as to the patent eligibility of a wide range of other molecules that may or may not be precluded from [section] 101 (28) by the Myriad opinion's reasoning. (29)

   The problem is perhaps most starkly illustrated by a molecule known as a peptide nucleic acid, or PNA. (30) The molecule's title is a bit of a misnomer, as it is not a nucleic acid at all; it is rather a synthetically created polymer in which the natural sugar-phosphate chain "backbone" of a nucleic acid is replaced by peptide backbone, but maintains the same nucleotide side structures as found in a nucleic acid--in other words, the PNA combines features of a protein and a nucleic acid. (31) It is, therefore, an entirely artificial molecule that would never occur in the wild, but which is capable of carrying the same sequence information as a nucleic acid.

   Consider a PNA with the nucleotide sequence from a particular gene, such as BRCA1. What could one tell a client about the patentability of such a molecule? The molecule is entirely a synthetic creation and would never be synthesized by cells in the wild. Thus, under the structural rationale of the second half of the Myriad opinion, it seems to be patentable. Certainly it differs structurally from any naturally occurring molecule more than does a cDNA molecule. But at the same time, the PNA carries the same base sequence information as the native gDNA molecule. Thus, under the informational rationale of the first half of the Myriad opinion, it seems to fall outside patentable subject matter.

   This logical discontinuity throws into doubt the patent eligibility of a wide range of macromolecules, not necessarily used in diagnostic testing, but in a range of industries from chemical manufacturing to agriculture...