The Patentability of Human Genes: more developments

20 March 2013 by

Breast Cancer in DNA StrandsCancer Voices Australia v Myriad Inc 13 February 2013 – read judgment

Another battle in the war against gene patenting has been lost, this time in Australia.

The US litigation is still ongoing, with the US Court of Appeals for the Federal Circuit upholding Myriad’s patents on DNA sequenced in the laboratory: see my post on that judgment. On 30 November 2012, the US Supreme Court announced that it would hear an appeal in the Myriad case. The US law in relation to the patentability is therefore not likely to be settled until the Supreme Court reaches it own decision on the issue.

This Federal Court ruling in Australia has now endorsed the government’s rejection of calls for an outright ban on the patenting of genes  by ruling that  isolated nucleic acid (including isolated DNA and RNA) is patentable.  

Background

On 8 June 2010, Cancer Voices Australia (CVA) filed an application with the Federal Court seeking, amongst other things, declarations that claims of Myriad’s Australian patent directed to isolated nucleic acids coding for variations of a gene linked to various forms of cancer (the BRCA1 gene), were invalid. The charity argued that the invention claimed in the claims, namely isolated, naturally occurring DNA and RNA, was not patentable subject matter.

The issue before the court was  whether under the Australian Patents Act 1990 , a valid patent may be granted for a claim that covers naturally occurring nucleic acid – either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) – that has been “isolated”. In this context, the word “isolated” implies that naturally occurring nucleic acid found in the cells of the human body, whether it be DNA or RNA, has been removed from the cellular environment in which it naturally exists and separated from other cellular components also found there. The particular gene with which the patent is concerned (BRCA1) is a human breast and ovarian cancer disposing gene. Various mutations that may be present in this gene have been linked to various forms of cancer including breast cancer and ovarian cancer.

For an invention to be patentable in Australia, it must (in addition to being new, useful and not obvious) be a “manner of manufacture”. The leading Australian authority on this question is National Research Development Corporation v Commissioner of Patents (1959) 102 CLR 252 (the “NRDC case”).

Myriad contended that each of their patent claims was valid because it covered a product that consists of an artificial state of affairs, providing a new and useful effect that is of economic significance. This is all that was required, according to the respondents, to establish the existence of subject matter that satisfies the requirements of the Patents Act as interpreted in light of the NRDC case. The respondents relied on evidence said to show that nucleic acid found in a human cell differs chemically, structurally and functionally from the isolated nucleic acid of the disputed claims.

Background science

DNA resides in the nucleus of every cell in the body. This “native” DNA (genomic DNA) is an extremely long three-dimensional molecule consisting of a number of repeating chemical units called nucleotides. These are linked end to end to form a strand (chain) of nucleotides. These nucleotides form paired “bases” which lie on the inside of the double helix, perpendicular to the axis of the double helix. The nucleotide guanine bonds with cytosine, adenine with thymine. RNA has a slightly different chemical composition to DNA consisting of a single strand of the sugar group ribose instead of deoxyribose, and the nitrogenous base uracil instead of thymine. “Messenger” RNA (mRNA) strands pair with their complementary basis on the DNA, translating the sequence in the coding gene in order to create strings of amino acids that comprise the various proteins that make up the tissues of the whole organism.  Genetic information in DNA in other words forms of sequences of “codons” that translate to specific amino acid sequences, which has been tabulated in the genetic code.  This genetic information ultimately determines what particular protein will be synthesised in the cell.

The isolation of DNA sequences outside the body involves a complex series of steps in the laboratory to break down the cell wall, remove the DNA and RNA strands from the surrounding protein molecules. For present purposes, the technique which is most relevant is one for template-based DNA synthesis that involved the use of mRNA as a template to create complementary DNA (cDNA). This technique is called “reverse transcription” because it involves the use of a particular enzyme (not naturally found in humans) known as reverse transcriptase. The result of the reverse transcription technique is to create an RNA-cDNA hybrid molecule that can then be converted to a double stranded DNA molecule using several different approaches. These hybrid molecules are better suited than mRNA molecules for use in molecular biology applications because mRNA is less stable than DNA.

The isolated sequence that formed the subject of the patent claim was from the “BRCA1” gene, found on the long arm of chromosome 17. Mutations on this gene cause a number of types of cancer, most significantly breast and ovarian cancer:

The present invention provides an isolated polynucleotide comprising all, or a portion of the BRCA1 locus or of a mutated BRCA1 locus, preferably at least eight bases and not more than about 100 kb in length.

It was this invention that was the target of CVA’s challenge, who argued that it did not involve an artificially created state of affairs, since there was no material difference between the claimed isolated nucleic acids and the corresponding nucleic acids in their natural state within the human body.

The legal issues

Justice Nicholas emphasised that the subject of the patents claim was a thing, not just information:

the disputed claims are not to genetic information per se. They claim tangible materials. Much emphasis was placed by the applicants upon the informational character of DNA as a storehouse of genetic information. But the disputed claims are not to information as such. They could never be infringed by someone who merely reproduced a DNA sequence in written or digitised form.

…  because each of the claims is to an isolated chemical composition, naturally occurring DNA and RNA as they exist in cell are not within the scope of any of the disputed claims and could never, at least not until they had been isolated, result in the infringement of any such claim.

The claimants referred to Lord Hoffmann in Kirin-Amgen which they said supported the proposition that a naturally occurring protein (and, a fortiori, naturally occurring DNA) was not patentable subject matter even if it was isolated. What  Lord Hoffman said was this:  (para [132]):

Standing back from the detail, it is clear that Amgen have got themselves into difficulties because, having invented a perfectly good and ground-breaking process for making [the protein] EPO and its analogues, they were determined to try to patent the protein itself, notwithstanding that, even when isolated, it was not new.(emphasis added)

However, it is clear that Lord Hoffmann did not say that an isolated protein was inherently non-patentable. He was referring to the validity of  a claim which was to something ”not new”  and therefore not patentable under section 1(1)(a) of the UK Patents Act 1977.  The question before the Australian court, on the patentability of isolated strands of nucleic acids, had to be decided in accordance with the principles set out in the NRDC case. It followed that a composition of matter may constitute patentable subject matter if it consists of an artificial state of affairs, that has some discernible effect, and that is of utility in a field of economic endeavour.

 The real problem lies in knowing, or rather not knowing, what degree of human intervention is necessary before it can be concluded that the requisite artificial state of affairs exists. It is an especially difficult problem in the present case, not so much because the authorities provide no clear solution to it, but because the problem has an almost metaphysical dimension to it. (para 102)

In Justice Nicholas’ view, the patentability of the isolated nucleic acids referred to in the disputed claims did not turn upon what changes have been made to the chemical composition of such substances as a result of them having been isolated. The disputed claims did not require that the isolated nucleic acids they describe differ from those found in the cell in this or any other respect so far as their chemical composition is concerned.

Accordingly, the issue in this case turns upon whether an isolated nucleic acid, which may be assumed to have precisely the same chemical composition and structure as that found in the cells of some human beings, constitutes an artificial state of affairs in the sense those words should be understood in the present context.

In the absence of human intervention, the judge continued, naturally occurring nucleic acid does not exist outside the cell, and “isolated” nucleic acid does not exist inside the cell. Isolated nucleic acid is the product of human intervention involving the extraction and purification of the nucleic acid found in the cell. Extraction of nucleic acid requires human intervention that necessarily results in the rupture of the cell membrane and the physical destruction of the cell itself. And purification of the extracted nucleic acid requires human intervention that results in the removal of other materials which were also originally present in the cell.

It would lead to very odd results if a person whose skill and effort culminated in the isolation of a micro-organism (a fortiori, an isolated DNA sequence) could not be independently rewarded by the grant of a patent because the isolated micro-organism, no matter how practically useful or economically significant, was held to be inherently non-patentable.

The judge therefore ruled that there was no rule in principle or law which prevented patents extending to naturally occurring DNA and RNA which have been extracted from cells obtained from the human body and purged of other biological materials with which they were associated.

Comment

Until this case there had been no judicial decisions in Australia considering directly the patentability of isolated DNA or RNA sequences.Like all patent systems in the world, Australian law provides that “human beings, and biological processes for their generation” are not patentable. It has nothing to say on components, or indeed essential components, of what make us human, such as DNA. In the UK, the law is governed by the EU Directive on the Legal Protection of Biotechnological Inventions, implemented by section 76A of the Patents Act. Schedule A2 to that Act provides that

An invention shall not be considered unpatentable solely on the ground that it concerns –

(a) a product consisting of or containing biological material; or
(b) a process by which biological material is produced, processed or used.
…An element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element.

It is clear from these provisions that in the UK, as in many other parts of Europe, isolated DNA and isolated RNA may be patentable even though they are identical in their chemical composition to DNA and RNA found in the cell. The US position is reflected in the long-standing practice and guidelines of the US Patent Office in granting patents for isolated DNA molecules that have the same sequence as a naturally occurring gene on the basis that the DNA molecule does not occur in nature in isolated form.

There is no doubt that this practice has given rise to exceedingly valuable property rights, and it is highly unlikely that the challenge to Myriad’s claims will succeed, in the US Supreme Court or anywhere else. Until genetic manipulation has reached the sophistication and extent that it truly challenges the rule against patenting human beings, these challenges to isoloated biological material need not unsettle the expectations of the biotechnology industry. But the moment will come: our demands on science for own health are on a collision course with our instinctive revulsion against what science, ultimately, can offer. Chemical sequences of nucleotides mean nothing to most of us, and the objections to their patentability are social, not visceral. But when human brain tissue (cultured from stem cells) is first transferred to a pig for drug trials, the issue may seem less esoteric.

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