“Patent claims that would arguably provide the most protection by relying on portions of natural DNA may remain patent ineligible. Companies in this field facing such gaps in patentability will likely turn to trade secret protection in the short term.”
Since an international group of scientists first mapped the human genome in the early 2000s, the life sciences community has made rapid leaps in its understanding of our genetic makeup. Today, diagnostics companies can use recombinant DNA to detail a person’s ancestry. Doctors can predict a patient’s likelihood for certain cancers or personalize a patient’s treatment based on the presence of certain genetic markers. And biopharmaceutical manufacturers can develop life-saving drugs using exact DNA targets.
As the science has rapidly evolved, so too has the issue of patentability. In 2005, growing interest around the topic prompted researchers to further characterize gene patents and explain ethical concerns over them in the Journal of Community Genetics. The authors described how gene patents typically covered diagnostics, compositions of matter and functional uses, but they voiced concerns over whether the patents would hinder additional research.
Those concerns did not reduce interest in patenting genetic material—by 2013, more than 4,300 human genes had been patented, according to the U.S. National Library of Medicine. However, that same year, the U.S. Supreme Court issued a landmark decision limiting the patentability of genetic inventions, and in so doing provided new parameters that life sciences companies, universities, researchers and the courts are still grappling with today. Despite the limitations on patenting genetic inventions, with a careful analysis of that decision and the case law that has followed, certain claims remain patentable. But there are also important policy implications to consider as this area keeps evolving.
The U.S. Supreme Court’s 2013 ruling in Association for Molecular Pathology v. Myriad Genetics changed the landscape of what is considered patentable material in the context of genetic inventions. “The central dispute,” according to the U.S. Supreme Court, “… was whether the act of isolating DNA—separating a specific gene or sequence of nucleotides from the rest of the chromosome—is an inventive act that entitles the individual who first isolates it to a patent.” The justices ruled unanimously that the answer was no.
Writing for the Court, Justice Clarence Thomas noted that the Court has long held that “laws of nature, natural phenomena, and abstract ideas” are not patentable. Without those carve-outs, he explained, “There would be considerable danger that the grant of patents would ‘tie up’ the use of such tools and thereby ‘inhibit future innovation premised upon them.’” He wrote that just finding the location of the BRCA1 and BRCA2 genes on the chromosome “fell squarely” within the law-of-nature exception, noting that “[i]t is undisputed that Myriad did not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes.”
However, the court did not strike down all of the patent claims in question. Myriad also had claims related to synthetic cDNA it had created in a laboratory. The court ruled that “does not present the same obstacles to patentability as naturally occurring, isolated DNA segments.” After pointing out how the “creation of a cDNA sequence from mRNA results in an exons-only molecule that is not naturally occurring,” Justice Thomas concluded, “The lab technician unquestionably creates something new when cDNA is made.”
The Post-Myriad State of the Law
In the five years since Myriad, companies have pushed the boundaries of patenting certain types of genetic materials. Despite Myriad’s express statement that it was not considering “the patentability of DNA in which the order of the naturally occurring nucleotides has been altered,” the courts have not yet established the contours of how much nucleotide sequences need to be altered in order to “create something new” in order to be patentable. However, as we discuss in the next section, we expect the Court to address these questions as biotechnology companies increasingly invest resources into emerging, expensive technologies involving genes and seek to protect their investments through patents.
Roche Molecular Systems
It is clear post-Myriad that merely designing and isolating complementary primers for use to isolate or otherwise detect DNA in a sample does not pass muster. For example, in Roche Molecular Systems v. Cepheid, Roche sued a competitor for patent infringement over claims relating to the detection of an antibiotic resistant tuberculosis bacterium using primers that would hybridize, or bind, to certain nucleotides of the targeted bacterium’s DNA. In October 2018, the Federal Circuit issued an opinion affirming invalidity of certain asserted claims under Section 101. The Court held that because the specific nucleotide sequence of the primers was indistinguishable to that found in nature, the claims were unpatentable.
Roche argued, unsuccessfully, that the claimed primers were patent-eligible because they “are chemically and structurally distinct from any nucleic acid that occurs in nature or that can be isolated from naturally occurring DNA,” e.g., the naturally occurring DNA is circular, yet the primers were linear and contained a unique chemical “end.” Roche also argued for patent eligibility because the claimed primers could hybridize to “only one of eleven position-specific signature nucleotides” on the targeted gene of the bacterium. Relying on the Myriad case law, the Federal Circuit rejected both arguments since the operative nucleotide sequence was still naturally occurring.
Other Federal Circuit cases have similarly struck down patents claiming exact copies of nucleotide sequences found in nature, for example, claims directed to the genetic makeup of a cloned animal. Thus, while it is clear that something must be done to alter the genetic material from what is found in nature, the leading post-Myriad Federal Circuit cases have not fully analyzed how far removed a nucleotide sequence must be from a natural sequence to be patent eligible.
The Myriad opinion specifically did not rule on method claims, stating that the opinion did not address patentability of “new applications of knowledge” about genes such as BRCA1 and BRCA2. This issue was addressed in the U.S. Supreme Court’s Mayo Collaborative Servs. v. Prometheus Labs ruling in 2012, which held that neither a natural law nor a routine application of a natural law is patentable, and the court later expanded on that ruling in Alice Corp. v. CLS Bank Int’l. Two recent Federal Circuit opinions provide additional guidance on the patentability of method claims relating to genes and the operation of the human body, requiring some type of inventive step to transform the invention from claiming the result of a natural relationship between the genetic material and its use in nature to something inventive.
First, in Vanda Pharm. Inc. v. W.-Ward Pharm. Int’l Ltd., the Federal Circuit evaluated the patentability of asserted claims relating to the treatment of schizophrenia patients with iloperidone, an FDA-approved antipsychotic drug. In particular, the inventors discovered that certain genotypes correlated with poor metabolism that could lead to “serious cardiac problems” during treatment. The claimed methods covered treating patients with an iloperidone dosage based on the patient’s genotype. In contrast to Myriad, the claims in Vanda utilized a human gene, but did “not claim naturally occurring DNA segments.” Moreover, the method claims were sufficiently narrow and tied to a limited application of the gene, enabling them to pass the Mayo test for § 101 eligibility. The court emphasized that “the claims here are directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” In contrast to Mayo, the Federal Circuit determined that the claims in Vanda “recite more than the natural relationship between . . . genotype and the [cardiac] risk . . . Instead, they recite a method of treating patients based on this relationship that makes iloperidone safer . . . . Accordingly, the claims are patent eligible.”
Second, in Athena Diagnostics, Inc. v. Mayo Collaborative Services, LLC, the Federal Circuit evaluated asserted claims relating to a method “for diagnosing neurotransmission or developmental disorders” associated with a protein known as “MuSK”. The inventors had discovered for the first time that the immune systems of a subset of patients suffering from a condition known as myasthenia gravis (MG) generated autoantibodies to MuSK (seemingly largely because of genetics). The claimed method involved detecting such autoantibodies in a patient through chemical or radioactive labeling of MuSK in the body, immunoprecipitation of antibody/MuSK complexes, and subsequent detection of the label in the resulting precipitate. The Federal Circuit concluded that the “claims at issue here involve both the discovery of a natural law and certain concrete steps to observe its operation.”
However, the method was patent ineligible because the “claimed advance” was the discovery of the natural law, and the concrete steps applying it were “conventional techniques to detect that natural law.” The patentee presented an argument for eligibility on the grounds that its claims “recite an inventive concept because they use a man-made molecule, i.e., labeled MuSK.” The patentee analogized the claimed methods involving such labeled MuSK “to the composition claims involving cDNA held eligible in [Myriad].” The Federal Circuit rejected this argument because the claims at issue were for a method – not a composition – and for such a method claim, “appending labeling techniques to a natural law does not provide an inventive concept.”
Both Vanda and Athena represent the evolving life sciences patent case law following Mayo and Myriad as industry and practitioners continue to test the grounds of Section 101 eligibility of various new applications of genetic knowledge. The takeaways are twofold: Patent practitioners should not shy away from utilizing genes in method claims—if the claims are sufficiently narrow and targeted as in Vanda. However, the tenets of Mayo are still very much alive in the Federal Circuit as indicated by the Vanda opinion—and characterizing a naturally occurring condition using man-made molecules (without further limitations on the applicability or scope of the natural law) is insufficient for patent eligibility.
Applicability to Today’s Technology
The current legal framework for gene patents has important implications across the life sciences industry, and in particular for drug manufacturers and universities. We always advise clients to create layers of patent protection for commercial technologies and products—for biopharmaceutical clients, two main layers of patentable protection intersect with gene patenting: (1) patent protection for nucleotide sequences, and (2) patent protection for biologic molecules. In the next few years we expect that the courts will increasingly need to apply Myriad to gene patents covering altered, non-naturally occurring nucleotide sequences and biologics as the industry trends towards further advances in biopharmaceutical manufacturing and gene editing technology.
For the patent protection of the relatively new class of drugs known as biologics, biopharmaceutical companies may seek to patent the isolated molecules themselves. One potential legal challenge is whether active sites, or residues of novel proteins or the nucleotides encoding them, are the same or substantially similar as those found in nature and thus, may be found ineligible for patentability. Even if the portions of the protein surrounding the active sites are non-natural, or made from non-natural amino acids, if the active site or residue is the same as that expressed in natural proteins, then is the protein still eligible for patentability?
Further cases could potentially arise where a company patents a synthetic protein and the nucleotides encoding it, or discovers a synthetic active site configuration but it is later discovered to exist in nature. This synthetic protein or active site configuration and the nucleotides that encode it could be vulnerable, not only to invalidity arguments of anticipation or obviousness under Sections 102 or 103, but also claims that the subject matter is patent ineligible under Section 101.
One emerging technology for manufacturing biologics is cell-free protein synthesis, where lab technicians isolate ribosomes and other machinery from cells and use them outside of living organisms to construct proteins. In other words, the cellular machinery reads the DNA code and utilizes it to construct biologic molecules such as proteins. There are a variety of advantages to cell-free protein synthesis, including manufacturing proteins in higher concentrations because they wouldn’t be toxic to the cell that’s creating them. Manufacturers could also add an amino acid that isn’t found in nature to the resulting protein. Many aspects of the process may be patentable such as the equipment, settings and operations, and in certain cases even the cellular machinery.
But patent claims that would arguably provide the most protection by relying on portions of natural DNA, such as those used in a manufacturing process, may remain patent ineligible. Companies in this field facing such gaps in patentability will likely turn to trade secret protection in the short term while continuing research efforts to develop patent eligible synthetic DNA. Yet, because patents are still the gold standard for protection in the famously R&D-intensive pharmaceutical industry, we expect companies to continue to push the envelope in engineering patent-eligible inventions. For example, in certain cases companies may design synthetic nucleotide sequences for biologics, even if such innovation may be associated with increased R&D outlays as compared to simply using the patent-ineligible natural sequences.
In addressing the issue of whether synthetic DNA may be patent eligible, it is crucial to follow the Court’s guidance in Roche: any patent protection of underlying DNA must claim a sufficiently different molecule than that occurring in nature. The Federal Circuit will likely resolve nuanced related legal challenges, in particular (1) whether non-nucleotide portions of a DNA sequence can render patentable a molecule containing a natural nucleotide sequence, and (2) how close a nucleotide sequence may be to a naturally occurring sequence for patentability.
We expect to see more cases from the Federal Circuit in the coming years defining the boundaries of Mayo that will enable a clearer path for life sciences practitioners to patent method claims for genetic material. Until then, we would advise practitioners to draft a set of “safe” claims following Federal Circuit case law having known eligibility, and also to draft a second set of claims in continuation applications to explore broader protection with riskier enforceability.
Policy Considerations as Gene Patents Evolve
As those in the life sciences community—as well as judges and lawmakers—continue working through what genetic inventions should be patentable, there are a variety of policy considerations to keep in mind. The underlying threat ultimately is the possibility of private companies patenting people, or even parts of people. No one should be able to patent something that belongs to humanity. But there has been passionate debate in the research community on where to draw the line of what is found in nature and the ethical dilemmas that can result from the shifting of that line.
At the same time, it is critical to maintain incentives for new medical breakthroughs, and the patent system is a primary driver of those incentives when correctly applied—as Justice Thomas recognized in Myriad, basic science research tools should not be heedlessly “tie[d] up” with patents that could risk “inhibit[ing] future innovation premised upon them.” If there is too much uncertainty about what is patentable, companies will be less likely to invest millions of dollars searching for the next advancement in gene technology. For that reason, some in the biopharmaceutical industry who disagreed with the ultimate result of Myriad were at least grateful for its clarity. As the case law continues evolving, it can be valuable to partner with outside counsel to track the latest decisions and consider how they impact each organization’s strategy.
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