Can an individual claim ownership of “life’s instructions” – a human gene?

20 September 2012 by Rosalind English

Yes, says the US Court of Appeals for the Federal Circuit, upholding the validity of human gene patents related to breast and ovarian cancer (Association for Molecular Pathology and others v the Patent Office and Myriad Genetics – read judgment) UPDATED

The three judge panel ruled in a 2-1 decision that the biotechnology company Myriad was entitled to its patents on the molecules because each of them represented “a non-naturally occurring composition of matter”. The court also upheld Myriad’s patent on a technique for identifying potential cancer therapies by monitoring effects on cell growth, but denied their claim on assessing cancer risk by comparing DNA sequences because the method is based on “abstract, mental steps” of logic that are not “transformative”.

This fascinating judgment is a model of clarity and fluency in this difficult area. But what does this intellectual property tussle have to do with human rights? Well, there is nothing unfamiliar to human rights lawyers in litigation over the availability of life-saving treatment  (patient B, the Herceptin case and the antiretroviral litigation in South Africa are three examples that spring to mind). And much of it begins in the laboratory, with the critical allocation of exclusivity rights.

Make no mistake, this is ethically charged litigation involving sharp conflicts of rights and incentives –  commerce, health, innovation, education and research.  The American campaigning  organisation Breast Cancer Action as well as a number of representative cancer patients were among the plaintiffs (although not ultimately granted standing – see below).

Nevertheless, we have become accustomed to a range of intellectual property rights granting exclusivity to genes, stem cells, animals with human genes, and a host of non-biological products used by humans. Since a landmark US Supreme Court decision in 1980 it has been accepted wisdom that an artificial life form can be patented.  Each time one of these rulings takes root, there is a tiny shift from what we deem to be nature’s creation to one of ours. Inventions that must have seemed miraculous at the time are increasingly becoming, well, second nature. So the line between “natural” and “non-natural” for the purpose of patent law is ever changing, patrolled by the courts in cases like this.

James Watson, co-discoverer of the structure of the DNA molecule, was amongst those who put in a brief, arguing that “Life’s instructions ought not be controlled by legal monopolies created at the whim of Congress or the courts”.  But, as Judge Moore warns in her partially concurring opinion, the courts should avoid disturbing

 settled industry expectations for no reason other than a gut feeling that DNA is too close to nature to be patentable, an arbitrary decision based on a judge-made exception.

Biotechnology, unlike industry or financial services, depends on the lifeblood of the patent system. Without it most research for therapeutic treatments for breast cancer or anything else would grind to a halt. As the Public Health Genomic foundation observes

A ruling against Myriad could potentially have rendered thousands of similar gene patents invalid. It would have left many biotech companies in an uncertain and vulnerable position, since investors would be reluctant to become involved with enterprises lacking the security of patent protection.

Background facts

Myriad holds patents on variants of the genes BRCA1 and BRCA2 that are linked to inherited breast and ovarian cancer.  Diagnostic genetic testing for the existence of BRCA mutations is therefore an important step in clinical care for breast or ovarian cancer patients. These patents give Myriad exclusive rights on this testing, which provides information about hereditary risk and in turn helps patients to decide whether to undertake preventive options such as surgery. Diagnostic results can also be an important factor in structuring an appropriate course of cancer treatment, since certain forms of therapy are more effective in treating cancers related to BRCA mutations.

The inventors of the patents under attack had isolated the BRCA genes in the human genome and determined their exact nucleotide sequences. They were granted three categories of patents.  The first category covered BRCA1 and BRCA2 (“BRCA”) and certain mutations in these genes associated with a predisposition to breast and ovarian cancers. The second category covered methods of comparing a patient’s BRCA sequence with the normal, or “wild-type”, sequence to identify the presence of cancer-predisposing mutations. The third category covered a method for screening potential cancer therapeutics which involved growing a host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, then growing that transformed host cell in the absence of that compound,  and then comparing the growth rate of those host cells.

The litigation behind this challenge germinated when a rival outfit  at the University of Pennsylvania (“GDL”) started providing BRCA diagnostic services to women.  Myriad launched into battle, hotly defending its patents and forcing GDL’s  to stop providing such services. As a result, consultants started sending patient samples for BRCA genetic testing to Myriad, which became (and remains today) the only provider of such services in the United States.

The challenge

The US Council for Civil Liberties coordinated this challenge. The group included directors of GDL as well as a number of representative patient plaintiffs  who stated that they have been unable to obtain any BRCA genetic testing or their desired BRCA testing covered by their insurance or at a price that they can afford, because of Myriad’s patent protection. Their main contention was that Myriad’s claims offended patent law because they were “products of nature”. But they also argued that the patents on human genes stemmed the free flow of information and thus violated the First Amendment.  They were successful in the Disctrict Court, which  held that isolated DNA molecules fell within the “products of nature” exception to patent eligibility  because such isolated DNAs are not “markedly different” from native DNAs.  That court also held the method claims patent ineligible.  As for the one method claim to “comparing” the growth rate of cells was also held to be patent ineligible because it amounted to only preparatory data gathering.

The Federal Appeal Court’s judgment

The Court upheld Myriad’s appeal, in part, against the District Court’s ruling.

1) Standing

American public law rules on locus standi are much stricter than they are in this country. Representative actions, such as the one brought by the medical organisations and patients, are generally not allowed. Under the US Constitution, a federal court cannot pass judgment on a case unless there is a “sufficient legal dispute” between the parties.  In this case the only plaintiff allowed standing was the researcher, Dr Ostrer, who was a target of patent enforcement and whose commercial activities were adversely affected by Myriad’s active patent protection. The other plaintiffs’ interests, including those of the patients and their representative organisation, were insufficient:

Simply disagreeing with the existence of a patent on isolated DNA sequences or even suffering an attenuated, non-proximate, effect from the existence of a patent does not meet the Supreme Court’s requirement for an adverse legal controversy of sufficient immediacy and reality to warrant the issuance of a declaratory judgment.

2) Merits

Under the US Patent Act,

Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improve- ment thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.35 U.S.C. § 101.

Although the US Supreme Court has interpreted this provision generously, it has created three exceptions to § 101’s broad patent-eligibility principles:

Laws of nature, natural phenomena, and abstract ideas

are not patentable. The plaintiffs (now plaintiff) framed their challenge under § 101 to Myriad’s composition patents covering “isolated” DNA molecules, its method patents directed to “analyzing” or “comparing” DNA sequences, and its patent on the above-mentioned method for screening potential cancer therapeutics.

The Court was at pains to stress that it was not adjudicating on the merits of the patent system itself, nor whether one company could own the exclusive right to a life saving treatment. Disapproving of patents on medical methods and novel biological molecules were policy questions best left to Congress.  The sole question before the three judges was whether the claims to isolated BRCA DNA, to methods for comparing DNA sequences, and to a process for screening potential cancer therapeutics met the threshold test for patent-eligible subject matter under 35 U.S.C. § 101 in light of various Supreme Court holdings.

The Court concluded that the composition claims and the screening claim involving growing a transformed host cell meet the standards for patent eligibility, while the claimed methods for “analyzing” or “comparing” did not.

The Court’s reasoning

1) The composition claims

The isolated DNA molecules before the court are not found in nature. They are obtained in the laboratory and are man-made, the product of human ingenuity. Judge Alan Lourie, writing for the majority in the ruling, said:

Everything and everyone comes from nature, following its laws, but the compositions here are not natural products. They are the products of man, albeit following, as all materials do, laws of nature….While they are prepared from products of nature, so is every other composition of matter. All new chemical or biological molecules, whether made by synthesis or decomposition, are made from natural materials.

Over the past thirty years the American patent office has taken the position  that isolated DNA molecules, ie ones artificially made up from native DNA via messenger RNA, are patent eligible. Nearly 3,000 patents have been granted for compositions whose nucleotide sequences exist because of man, not nature, and in the case of certain of Myriad’s isolated genes (called compound genes or cDNA), they are particularly distinctive because they have non-contiguous coding sequences which do not exist in the chromosomal DNA. These made up the second category of Myriads patents – those relating to cDNA – and were plainly eligible for patent protection even though they were made using biological tools and the naturally occurring mRNA as a template.

The District Court had wrongly focussed on the fact that both the isolated genes and native genes from which they were copied are identical because the genetic function of both is to transmit information. This was incorrect, said the appeal judges, because the distinctive nature of DNA molecules as isolated compositions of matter that determines their patent eligibility rather than their physiological use or benefit:

Whether its unusual status as a chemical entity that conveys genetic information warrants singular treatment under the patent laws as the district court did is a policy question that we are not entitled to address

In answer to the arguments that “adverse effects” that may occur if isolated DNAs are held to be patent eligible – one of these effects being the non-affordability of certain treatments or drugs – the Court reminds us that it is the adverse effects on innovation that a holding of ineligibility might cause.

Patents encourage innovation and even encourage inventing around; we must be careful not to rope off far-reaching areas of patent eligibility.

2) The method claims

The claimed methods of comparing or analyzing nucleotide sequences were only directed to the abstract mental process of comparing two nucleotide sequences. As such, the Court deemed them ineligible for patent protection.

3) Method of screening potential cancer therapeutics

This patent recites a method involving host cells that are transformed with an altered BRCA1 gene. Those cells are not naturally occurring. Rather, they are derived by altering a cell to include a foreign gene, resulting in a man-made, transformed cell with enhanced function and utility and as such are patent-eligible. Unlike the method claims, this patent thus includes more than the abstract mental step of looking at two numbers and “comparing” two host cells’ growth rates. As such, they are patentable.

In her partly concurring opinion Circuit Judge Moore did not agree with the majority that the first category of isolated DNA  (as opposed to the cDNA) was sufficiently different from the genomic material, simply because the covalent bonds had been broken. She did not accept that this was enough constitute patentable subject matter. However, in the light of the Patent Office’s longstanding and consistent policy of allowing patents for isolated natural products, she was inclined to resist expanding the judicial exceptions to patentable subject matter, particularly “where both settled expectations and extensive property rights are involved”. Judge Bryson filed a dissenting opinion, concurring with the majority only on the method claims and their patent ineligibility.

As expected when it came out in August, this decision has been welcomed by biotech and drug companies and condemned by patient groups and medical organisations. But the importance of protecting and supporting innovation generally outweighs the more ethics- based arguments about according due respect to what James Watson calls the “fundamentally unique nature of the human gene”.

17 October 2012:

The US Supreme Court has been asked to again examine the legality of patents held by the company Myriad Genetics on variants of the breast and ovarian cancer-linked genes BRCA1 and BRCA2. The request was filed by the American Civil Liberties Union (ACLU) and the Public Patent Foundation.The Court is not obliged to re-examine the case, and is expected to invite Myriad to respond before deciding whether to proceed.
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