CRISPR patents: guidance from US courts

The CRISPR gene manipulation system—an adaptive immune system used by microbes to defend against viruses, which has been repurposed into an efficient and reliable gene-editing technique in mammalian cells—has taken the genome engineering world by storm and has attracted much attention for its immense promise in the development of innovative diagnostic tools and therapies.

Since the filing of the first patent claiming CRISPR as a gene-editing tool in 2012, the US Patent and Trademark Office (USPTO) has granted more than 1,000 patents pertaining to CRISPR in some form, and over 600 applications with claims pertaining to CRISPR remain pending.

Building on the original CRISPR patents, which modestly claimed methods of sequencing certain CRISPR regions, and similarly narrow applications encompassing strain typing, phage resistance and uses in bacteria, the current CRISPR patent landscape appears enormously varied, both in terms of the patentees and applicants involved and the types of claims sought.

Pending claims include, for example, methods for editing DNA, methods of treating a neurodegenerative disease, methods for producing RNA compositions, compositions for treating a lysogenic virus, CRISPR assays, and kits for the treatment or prophylaxis of HIV infections.

Court challenges

Because CRISPR claims are fundamentally based on a naturally occurring phenomenon—a DNA sequence that helps bacteria recognise and fend off viruses—they may be susceptible to patent eligibility challenges under 35 USC §101. The Supreme Court’s seminal decision in Mayo Collaborative Services v Prometheus Labs set the stage for the application of patent eligibility challenges to the biotechnology field.

In Mayo, the court struck down claims pertaining to the use of thiopurine drugs in the treatment of autoimmune diseases and articulated a framework for §101 analysis. The Supreme Court subsequently elucidated the Mayo test in Alice Corp v CLS Bank (2014), arriving at what has become known as the two-step Alice/Mayo test: (1) determine whether the claims are directed to a patent-ineligible concept (ie, a law of nature, a natural phenomenon, or an abstract idea); and, if so, (2) consider whether additional elements “transform the nature of the claim” into a patent-eligible application, such that there is an “inventive concept” that is “sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the [ineligible concept] itself.”

Since Alice, courts have applied the Alice/Mayo test in a number of cases spanning diverse technologies. In the biotechnology field, Ariosa Diagnostics v Sequenom (2015) appeared to signal the US Court of Appeals for the Federal Circuit’s hostility to method claims premised on the recognition of a natural phenomenon.

In Ariosa, the Federal Circuit struck down claims directed to a method of using cell-free foetal DNA (cffDNA) in non-invasive prenatal testing. Although agreeing that “the patent does not claim cffDNA” but rather “certain methods of using cffDNA” and noting that the claimed method “reflects a significant human contribution in [combining] man-made tools of biotechnology in a new way that revolutionised prenatal care,” the panel ultimately found that the method at issue “amounts to a general instruction to doctors to apply routine, conventional techniques when seeking to detect cffDNA” that does not provide an “inventive concept” sufficient to render the claims patent-eligible. The Supreme Court declined to revisit the issue.

In Rapid Litigation Management v CellzDirect (2016), however, the Federal Circuit appeared to change course. At issue in CellzDirect were claims directed to an improved process of preserving hepatocytes, stemming from the discovery that some hepatocytes could survive repeated freeze-thaw cycles. In finding that the claims were directed to patent-eligible subject matter, the court held that, although ostensibly based on a natural law, the claims were not directed to the natural law, but were rather “directed to a new and useful laboratory technique for preserving hepatocytes,” which “requires an artisan to carry out a number of concrete steps.”