Will the future of gene patents be "markedly different" after Myriad?

On October 22, 2010, Myriad Genetics, Inc filed a brief on appeal to the US Court of Appeals for the Federal Circuit in its widely watched ‘gene patenting’ case. While many patent attorneys speculated that the ruling would not stand on appeal, recent developments, including the US Department of Justice’s (DOJ) filing of an amicus brief taking the position that isolated genes are not patentable, and Judge Dyk’s dissenting opinion in Intervet Inc. v. Merial Limited and Merial SAS, are providing room for doubt.

An affirmation would have a tremendous impact on the biotechnology community because the decision turns on whether isolated DNA and methods that require assessing its sequence are eligible for patent protection. The US Patent and Trademark Office (USPTO) has taken the position that this subject matter is patent-eligible, and thousands of US patents include such claims.

Myriad’s position is that the US District Court of the Southern District of New York improperly held invalid patent claims related to the BRCA1 and BRCA2 genes and to methods of using nucleotide sequences within those genes to assess susceptibility to cancer. The district court held that the isolated DNA was a product of nature and the methods constituted nothing more than a mental process, neither of which are eligible for patent protection.

To analyse Myriad’s DNA claims, the district court asked whether the isolated DNA possessed markedly different characteristics to the same DNA in vivo.

Despite the fact that the DNA must be isolated in order to be used, and despite Myriad’s arguments that the inventors were the first to discover that the genes could be used to assess risk for breast and ovarian cancers, the court found that “the purification of native DNA does not alter its essential characteristic—its nucleotide sequence—that is defined by nature and central to both its biological function within the cell and its utility as a research tool in the lab”.

Accordingly, the court concluded that the isolated DNA claimed was not markedly different from native DNA as it exists in nature and, therefore, constituted unpatentable subject matter under 35 USC § 101.

On appeal, Myriad argues that “markedly different” is not the appropriate legal standard. The district court relied heavily on two Supreme Court cases: Diamond v. Chakrabarty, which held that a genetically modified bacterium was patent-eligible, and the earlier case of Funk Bros Seed Co v. Kalo Inoculant Co, which held that a mixture of different types of bacterial cells was not (even though the mixture was agriculturally beneficial).

Myriad asserts that the district court “erroneously divined” a legal standard from Chakrabarty; that the court was not setting “markedly different” as the legal standard for patent-eligible subject matter but was, instead, simply contrasting Chakrabarty’s genetically modified bacterium with the mixtures of bacteria in Funk Bros. According to Myriad, the phrase “markedly different” appears nowhere else in Supreme Court precedent and is wholly unexplained in Chakrabarty.

This would invite subjective decisions and “surely was not meant as a legal standard to govern all future cases decided under the statute”. Instead, Myriad argues that the proper legal standard set out in Chakrabarty is “a non-naturally occurring manufacture or composition of matter—a product of human ingenuity ‘having a distinctive name, character and use’”.

Myriad further argues that this standard would be met by their claims as “[i]solated DNA molecules are ‘products of human ingenuity’”. In this portion of its brief, Myriad concludes that the “inventors’ work yielded a new composition of matter with substantial societal benefit, which added to the body of human knowledge” and that this “is enough to demonstrate that these compositions of matter are patent-eligible”.

Myriad also specifically addresses Judge Dyk’s dissent in Intervet. Judge Dyk wrote that it is “far from clear” that an “isolated DNA sequence is qualitatively different from the product occurring in nature” and further, that “[i]t would be difficult to argue, for instance, that one could patent the leaves of a plant merely because the leaves do not occur in nature in their isolated form”. According to Myriad, both the analogy to leaves and the conclusion Judge Dyk drew from it were flawed.

A plucked leaf does not qualify as “a product of human ingenuity” nor does it have properties that are markedly different from a leaf still attached to the plant. There is no new product nor any non-obvious invention in a plucked leaf.

In contrast, according to Myriad, isolating the specific BRCA1 and BRCA2 DNA sequences from the hundreds of thousands of base pairs in the human genome required significant human endeavour based on the realisation that those particular sequences had a direct relationship to human disease.

In contrast to Judge Dyk, Chief Judge Rader has reportedly publicly expressed views that suggest he disagrees with the district court holding in Myriad, and the ACLU has filed a motion to request that he recuse himself from any involvement in the case. According to Dennis Crouch’s patent blog, Patently-O, Judge Rader was asked at a conference at Fordham Law School whether a commercially produced bottle of water was patent-eligible.

He reportedly replied by asking how many people, over the course of human events, had been killed by drinking polluted water. He then answered his own question: probably billions.

Thus, it appears, in Judge Rader’s opinion, that recognising a link between bacterial contamination and fatal illness and purifying the water required ingenuity and imparted distinctive characteristics, making the water safe for drinking (should that be determined to be the standard) or rendering it markedly different from naturally occurring water (should that be upheld as the standard) merits patent protection.

The analogy between “isolated” water and “isolated” DNA is all too clear. If the former is patent-eligible, surely the latter would be as well.

In a surprising move that reversed long-standing policy, the DOJ submitted a brief of amicus curiae on behalf of the US in the Myriad appeal, taking the position that isolated but otherwise unmodified genomic DNA is not a human-made, patent-eligible invention under 35 USC § 101.

The US also advocated, however, that “humanengineered” DNA molecules, such as cDNAs, are patent-eligible subject matter under § 101. It remains to be seen whether the government’s position sways the Federal Circuit to affirm the Myriad decision in part and/or influences a change in USPTO policy.

Under either the district court’s test or Myriad’s proffered standard, a key aspect of the Federal Circuit’s decision may be its articulation of the defining characteristics of naturally occurring DNA, against which a claimed DNA will be measured to determine if it is “markedly different” or “non-naturally occurring” and “a product of human ingenuity” having a “distinctive name, character and use”.

For example, if the Federal Circuit focuses on the informational properties of DNA, it may make it more difficult for Myriad to argue that isolated DNA has been given a distinctive character or use through ingenuity (should that standard be adopted) or that it differs markedly from naturally occurring DNA.

Looking at the evolution of the Federal Circuit’s characterisation of DNA in the context of analysing whether a patent properly describes a claim to a genus of DNA may be instructive.

For example, in its 1997 decision in University of California v. Eli Lilly and Co, the Federal Circuit characterised DNA as a type of chemical compound, which could only be described by reciting the sequence of a representative number of DNAs falling within the scope of the claim or by reciting structural features common to a substantial portion of the DNA molecules falling within the claim.

However, by 2004, in In re Wallach, the Federal Circuit noted than an amino acid sequence supports a claim to a genus of DNA sequences, because advances in the state of the art made it routine to convert a protein sequence to a nucleic acid sequence encoding the protein. If these cases reflect the Federal Circuit’s shift in focus from the chemical nature of DNA to its informational properties, it may increase the possibility that the court will affirm the Myriad district court decision, at least in part.

If the district court’s judgement is affirmed, the validity of any claim directed to a nucleic acid sequence that is simply isolated from the genome in which it occurs would be jeopardised. It seems unlikely that the Federal Circuit will comment directly on other subject matter, but the industry will no doubt be anxious for clarity on other gene-based products and processes.

It seems that modified sequences, particularly those with different or improved activities and sequences encoding non-naturally occurring products, such as fusion proteins and humanised antibodies, are certainly on more solid ground than completely naturally occurring sequences or DNA sequences encoding naturally occurring protein sequences, as the modified compositions are even more markedly different than wholly natural products and require even more human ingenuity.

Lee Crews, PhD, is a partner at Duane Morris LLP. She can be contacted at: llcrews@duanemorris.com

Vicki Norton, PhD, is a partner at Duane Morris LLP. She can be contacted at: vgnorton@duanemorris.com