Patenting genes and diagnostics

A market is developing for the application of biomarker assays as clinical diagnostics. Moreover, at a time when the number of prospective blockbuster drugs is dwindling, pharmaceutical companies are investing heavily in the potential benefits of targeted medicine—such as delivering specific treatments to specific patient populations whose genetic profile may make them more receptive to particular treatments.

While there has been a pronounced downturn in the number of biotechnology patent applications in industrialised countries since 2002, possibly due to the declining number of new human genes to be identified since the Human Genome Project, patent filings for cancer diagnostics have apparently shown very little decline since 2001. Indeed, patent activity in the biotechnology area is becoming increasingly focused on diagnostic uses of genetic information.

One of the most important and sweeping challenges with biomarker-based therapies and diagnostics is how to develop intellectual property policies that will bring opportunity and entrepreneurship in balance with meeting unmet market needs and clinical value.

The challenges were emphasised by Alan Greenspan, the former Chairman of the Federal Reserve, who noted that “arguably the single most important economic decision our lawmakers and courts will face in the next 25 years is to clarify the rules of intellectual property”.

Gene and diagnostic patents in the US

Myriad Genetics is the owner or exclusive licensee of a series of patents claiming isolated DNA molecules (related to the genes known as BRCA1 and BRCA2) and methods for testing for the presence of mutations in these genes. Seven US patents had claims that sought protection for: isolated DNA containing all or portions of the BRCA1 and BRCA2 gene sequences, and methods for ‘comparing’ or ‘analysing’ BRCA1 and BRCA2 gene sequences to identify the presence of mutations correlating with a predisposition to breast or ovarian cancer.

The US patent law provides that, subject to meeting other patentability requirements: “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor....” For several decades, the US Supreme Court has construed this provision broadly: while laws of nature, physical phenomena and abstract ideas are not patentable, “anything under the sun that is made by man” is patentable.

The Patent and Trademark Office (USPTO) and lower federal courts have interpreted the law to mean that genes that have been isolated by man from their natural environment (isolated nucleic acids) are patent-eligible, and have issued or sustained the validity of many such patents.

This long-standing practice was called into question by a declaratory judgment challenge to the validity of selected claims in Myriad’s BRCA gene and diagnostic patents brought by several parties, including researchers who purportedly wanted to perform the patented genetic tests in their laboratories; various individuals, some of whom were breast cancer sufferers or survivors; as well as political and medical organisations.

On March 29, 2010, the US District Court for the Southern District of New York issued a decision in Association for Molecular Pathology v U.S. Patent & Trademark Office (Myriad) in which the patent claims at issue were declared invalid under 35 USC 101.

Patentability of isolated DNA

On motion for summary judgment, the US District Court decided that the claims to the isolated BRCA genes were not patentable because the claims encompass “products of nature”. The court reasoned that, to be patentable, a purified product must posses “markedly different characteristics” from the naturally occurring product.

The court concluded that the isolated DNA did not possess the requisite “markedly different characteristics”.

The court did not decide how much a patent applicant needs to have changed isolated DNA from the DNA that exists in nature in order to make it patentable. In fact, the plaintiffs declined to challenge numerous other claims in Myriad’s patents that might have shed light on this issue, including claims directed to nucleic acid probes, replicative cloning vectors that contain the isolated DNA, and pairs of DNA primers useful for DNA amplification experiments.

Thus, even if the court’s decision is sustained on appeal, these are issues that would need to resolved in the future. Stated differently, a variety of claim strategies will remain available to patent applicants who invent new and useful nucleic acids, even if the decision in the Myriad case is upheld.

In an unusual development, the US Department of Justice (DoJ) filed an amicus brief with the Federal Circuit, ostensibly representing the position of the executive branch of the Federal government, which includes the USPTO. In its brief, and again at oral argument, the DoJ urged the Federal Circuit to affirm the District Court’s holding of invalidity with respect to certain claims directed to isolated DNA (but urged reversal with respect to other claims directed to cDNA).

However, it is far from certain that the court’s decision will be sustained. In oral arguments before the Federal Circuit, the three-judge panel spent significant time questioning the parties as to whether the Federal Courts had jurisdiction to hear the litigation.

If the Federal Circuit determines that the collection of plaintiffs did not have a sufficiently immediate bona fide controversy with the patentee Myriad—e.g. caused by a legitimate threat of litigation from Myriad—it may dismiss the case on jurisdictional grounds without reaching the merits.

While it is often folly to predict the outcome of a case from questions posed at oral argument, it was clear that the judges appreciated the importance of the case to the biotechnology industry and its implications for thousands of existing patents. The questions posed to counsel for the patent challengers suggested to many pundits that the Federal Circuit may reverse the District Court’s holding on the merits.

For example, Judge Bryson questioned whether Myriad’s “isolated DNA” actually represents a product of nature, or whether a chemical distinction should be drawn by virtue of the breaking covalent chemical bonds during the isolation process. The judges also appeared to recognise that the BRCA1 and BRCA2 genes, when isolated, had practical uses—e.g. in medical diagnostics—that the naturally occurring DNA counterparts in the human genome did not have.

Patentability of diagnostic methods

In Myriad, the Southern District of New York held that certain of Myriad’s patent claims directed to diagnostic/prognostic methods that involved ‘analysing’ or ‘comparing’ BRCA1 or BRCA2 ‘sequences’ were invalid for failure to define patent-eligible subject matter. The court cited the Federal Circuit’s recent Bilski decision.

Although Bilski related to the patent-eligibility of a ‘business method’ patent, the Federal Circuit’s opinion provided an analytical framework for analysing the patent-eligibility of other method claims. Although phenomena of nature, mental processes or abstract intellectual concepts are not patentable, the court reasoned that a process may be patentable if it passes a ‘machine or transformation test’.