GAGELER AND NETTLE JJ. In this matter, the question for the judge at first instance (Nicholas J) and on appeal to the Full Court of the Federal Court of Australia (Allsop CJ, Dowsett, Kenny, Bennett and Middleton JJ) was whether "a valid patent may be granted for a claim that covers naturally occurring nucleic acid ... that has been 'isolated'". It was held that it may. For the reasons which follow, the appeal to this Court should be allowed and the claims should be held to be invalid.
The patent
The claims of the patent that were in suit were as follows:
"1. An isolated nucleic acid coding for a mutant or polymorphic BRCA1 polypeptide, said nucleic acid containing in comparison to the BRCA1 polypeptide encoding sequence set forth in SEQ.ID No:1 one or more mutations or polymorphisms selected from the mutations set forth in Tables 12, 12A and 14 and the polymorphisms set forth in Tables 18 and 19[].
2. An isolated nucleic acid as claimed in claim 1 which is a DNA coding for a mutant BRCA1 polypeptide, said DNA containing in comparison to the BRCA1 polypeptide encoding sequence set forth in SEQ.ID No:1 one or more mutations set forth in Tables 12, 12A and 14.
3. An isolated nucleic acid as claimed in claim 1 which is a DNA coding for a polymorphic BRCA1 polypeptide, said DNA containing in comparison to the BRCA1 polypeptide encoding sequence set forth in SEQ.ID No:1 one or more polymorphisms set forth in Tables 18 and 19."
It is common ground that the validity of claims 2 and 3 depended on the validity of claim 1.
"Nucleic acid" refers to two kinds of chemical compound: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the primary source of genetic information in a human cell. DNA is comprised of "nucleotides". Each nucleotide includes a nitrogenous base, of which there are four kinds (abbreviated as A, G, C and T). Nucleotides are linked end-to-end by covalent bonds to form a polynucleotide chain. The bases protrude from the chain at a perpendicular angle. In the nucleus of a cell, DNA almost always exists as a double helix formed by the intertwining of two polynucleotide chains with the bases lying on the inside of the helix, with each base forming a hydrogen bond with the base on the opposing chain.
The sequence of nucleotides in DNA encodes information which is used by the cell to produce, and regulate the production of, proteins. "Polypeptides" are proteins - large, three-dimensional molecules comprised of sequences of amino acids linked by peptide bonds. The mechanism by which proteins are produced is complex, but for present purposes it is sufficient to state that various three-base sequences of nucleotides in DNA correspond with the production of different kinds of amino acids. The sequence of nucleotides dictates the kind and sequence of amino acids produced and thus the composition of the resulting protein. For example, the protein in humans known as "BRCA1" is encoded by a DNA sequence which consists of approximately 6,000 nucleotides in a highly specific sequence.
In its natural state, the sequence coding for any particular polypeptide or protein is present as a series of "fragments" along the DNA molecular chain. Each fragment is called an "exon" and each exon is separated from its adjacent exons by sections of non-coding DNA called "introns". Although the introns do not encode a polypeptide or protein, they contain information which helps regulate and execute the cell's response to the information encoded in the exon. The 6,000 nucleotides which encode the BRCA1 polypeptide or protein are present as 24 exons separated by introns.
The word "gene" is used in a number of senses. For present purposes, the meaning which is relevant is the unit of DNA that encodes a specific protein. Thus, the BRCA1 gene consists of the 6,000 nucleotides comprised in 24 exons which encode the BRCA1 polypeptide or protein.
DNA is "packaged" within the nucleus of human cells as follows. DNA strands are wound around proteins called histones to form nucleosomes, which, in turn, are stacked on top of each other to form chromatin fibres. Chromatin fibres are organised into chromosomes. Production of proteins in a cell involves complex interactions between DNA and other factors together called the "committee", which includes the histones around which the DNA is wrapped; "regulatory proteins" present in the cell nucleus; other segments of DNA; and the three-dimensional structure of the DNA as packaged in the nucleus. The ultimate composition and structure of the proteins capable of being produced by a particular gene thus depend on several factors in addition to the sequence of nucleotides in the gene.
At conception, every human being inherits a half set of his or her mother's genetic information, consisting of 23 chains of DNA with 20,000 genes, and also a half set of his or her father's genetic information, consisting of another 23 chains of DNA with 20,000 genes. During gestation, that information is conveyed into every cell in the human being's body and thus results in two instances of every gene. The failure of one instance of a gene to operate normally can place the human being at a high risk of disease. For example, an abnormality in one instance of a woman's BRCA1 gene places her at high genetic risk of developing breast and ovarian cancer, even though the other instance of the BRCA1 gene may be functioning perfectly normally.
Medical genetic testing involves testing genetic material taken from a patient, inter alia, to identify abnormalities known to be indicative of disease. For example, genetic testing of a woman's DNA might identify an abnormal BRCA1 gene and thus reveal that she is at high genetic risk of developing breast and ovarian cancer. Treatment regimens are then structured accordingly.
Ordinarily, a test report includes details of any identified mutations of known clinical significance and also details of any variations of thus far unknown clinical significance. The latter are recorded to ensure that when and if the variation is later categorised as a mutation of clinical significance the clinician can inform the patient of its consequences.
The tools and techniques of genetic testing are long established and well understood by those who are skilled in the science. DNA is the most common target. A sample of DNA is removed from the patient's body and subjected to a range of processes to determine what if any variations there are between the sequence of nucleotides in the sample and what is known to be the normal sequence of nucleotides for the region of DNA the subject of examination. The variations, described as "mutations" or "polymorphisms", usually occur in exons and result in some abnormality in the protein derived from the gene. But they can also occur in introns. Some variations have been found to be present in a large number of patients and, as a result, have been classified as polymorphisms or mutations. There are also a number of other variations in the DNA sequence which have not yet been categorised as polymorphisms or mutations but which it may be expected will be so categorised as expert knowledge of a particular gene and familial genetic patterns continues to develop. The assignment of such variations is a major concern for all laboratories providing medical genetic testing services.
In order to test a sample of naturally occurring DNA, it is necessary to break open human cells to expose the DNA. The goal is to remove the DNA from its normal cellular environment without corrupting the information contained in the DNA.
The DNA thus derived from the extraction process contains all of the DNA molecules from many cells, but the specific region of the DNA which is to be tested may account for only a small fraction of the DNA present in the sample. For example, the entire BRCA1 gene (exons plus introns) represents only 0.003 per cent of the total DNA obtained by such processes and the coding sequence of the BRCA1 gene accounts for an even smaller proportion (0.0002 per cent) of the DNA thereby obtained. Because isolated DNA has been removed from its cellular environment, and in particular from adjacent histones which support it and assist in the execution of its instructions, isolated DNA cannot survive unaided or reproduce. Isolated DNA is incapable of producing proteins as it would within the cell unless certain in vitro processes are performed upon it.
The isolation of the specific region of the DNA to be tested requires knowledge of the DNA sequences immediately flanking the target fragment. That information is available in medical databases and medical literature in the public domain. The isolation may be effected by a number of standard techniques but most often by making multiple copies of short fragments of the sequence of interest using a chemical process called PCR. Thus, for example, an exon of the BRCA1 gene may be amplified by the PCR process by ascertaining from the published literature the DNA sequence of a short segment (ordinarily between 50 and 100 nucleotides long) and the ends of the two introns which abut the exon. The amplification process is likely to result in millions of copies of the fragment and little other DNA.
The DNA sequence of the amplified fragment is then examined by a variety of methods for variations of established clinical significance as recorded in laboratory-based databases and, increasingly, as recorded in international reference sequences developed under the auspices of professional bodies and governmental agencies in the United States and Europe. As was earlier noticed, the sequence is also checked for variations of unknown significance.
Isolating DNA from a patient's cells using this process is useful for a number of purposes, including synthesis of recombinant protein, gene therapy, and as a "probe" to investigate whether particular genes are being expressed in a patient. None of these processes can be performed on DNA as it exists within a person's cells. But for the purpose of determining whether a patient possesses a mutation or polymorphism in one or both of her BRCA1 genes that could predispose her to a greater risk of breast or ovarian cancer, the utility of isolating the BRCA1 genes from her cells is that the nucleotide sequences in the isolated DNA represent the nucleotide sequences found in the BRCA1 genes in each cell of her body. For this purpose, it is essential that the nucleotide sequence in the isolated nucleic acid is identical to that found in the patient's cells; and the processes described above are designed to ensure that this is so.
The scope of claim 1
"Isolated nucleic acid" is defined in the patent as nucleic acid "which is substantially separated from other cellular components which naturally accompany a native human sequence or protein". It is, therefore, the sort of isolated nucleic acid which is routinely produced by pathologists when subjecting DNA to genetic testing as previously described. And, as has already been noticed, it may be created by first stripping the DNA from the cell, ordinarily by means of the application of detergents to release the hydrogen bonds which bind the DNA to the cell, and then isolating and amplifying the fragment of interest using the PCR process or something comparable.
The reference in claim 1 of the patent to "coding for a mutant or polymorphic BRCA1 polypeptide" is to an isolated nucleic acid molecule which, when compared to the standard reference sequence set forth in SEQ.ID No:1, exhibits one or more of the 54 mutations or polymorphisms delineated in Tables 12, 12A, 14 and 18.
The sequence set forth in SEQ.ID No:1 represents the sequence of A, G, C and T nucleotides that is known to code for the BRCA1 polypeptide. It represents the concatenation of the exons of the BRCA1 gene, and thus is presented as an uninterrupted sequence of nucleotides without introns.
The 54 mutations and polymorphisms delineated in Tables 12, 12A, 14 and 18 are claimed to be present in women with familial breast cancer and the claim is supported by evidence referred to in the patent that those mutations have been found to disrupt the function of the BRCA1 gene. As such, the 54 mutations and polymorphisms represent some three per cent of more than 1,600 mutations and polymorphisms of the BRCA1 gene which have now been identified as having clinical significance, and the catalogue continues to grow.
The only way of determining whether a patient has a mutation or polymorphism of the BRCA1 gene that is of clinical significance is for a pathologist to take a sample of the patient's DNA, isolate it from the cell in the manner already described, isolate and amplify the BRCA1 sequence by use of the PCR process, or by means of another comparable process or an analogous synthetic process, and compare the isolated sequence with known comparators recorded in the laboratory and other databases earlier described. It follows that the only means of determining whether a patient is afflicted by any of the mutations or polymorphisms delineated in Tables 12, 12A, 14 and 18 of the patent is for a pathologist to take and analyse a sample of the patient's DNA and compare its sequence to the sequences delineated in Tables 12, 12A, 14 and 18.
For convenience throughout the remainder of these reasons, the expression "BRCA1 gene" will be used to refer generally to isolated nucleic acid which codes for a BRCA1 polypeptide and the expression "mutated BRCA1 gene" will be used to refer to an isolated nucleic acid which codes for a BRCA1 polypeptide and which, in comparison to the BRCA1 sequence identified in SEQ.ID No:1, exhibits any of the mutations or polymorphisms identified in Tables 12, 12A, 14 and 18.
What is the product over which a monopoly is claimed?
As noted, claim 1 of the patent is a claim for an isolated nucleic acid which, compared to the known sequence of A, G, C and T nucleotides that codes for the BRCA1 gene, contains one or more of the mutations delineated in Tables 12, 12A and 14, or one or more of the polymorphisms set forth in Table 18 ("the specified mutations and polymorphisms"). Thus, as drafted, claim 1 presents as a claim by the first respondent that it has invented and thus is entitled to a monopoly over a manner of manufacture of isolated nucleic acid exhibiting any of the specified mutations and polymorphisms.
For reasons which will appear, it is significant that the first respondent does not and could not claim a monopoly over the process or method of manufacture of isolated nucleic acid per se, or for the process or method of manufacture constituted of the separation and amplification of the BRCA1 gene. As was earlier explained, the concepts and methods of manufacturing isolated nucleic acid and isolating and amplifying particular sequences of nucleic acid are long-established standard testing and diagnostic techniques. Presumably, it is for that reason that claim 1 is limited to a claim for a monopoly over the right to "manufacture" what the first respondent calls the "product" which results from isolating the BRCA1 gene when and if the nucleic acid so isolated contains any of the specified mutations and polymorphisms.
Patentable subject matter
As at the priority date, a "patentable invention" was defined in s 18(1) of the Patents Act 1990 (Cth) as follows:
"Subject to subsection (2), a patentable invention is an invention that, so far as claimed in any claim:
(a) is a manner of manufacture within the meaning of section 6 of the Statute of Monopolies; and
(b) when compared with the prior art base as it existed before the priority date of that claim:
(i) is novel; and
(ii) involves an inventive step; and
(c) is useful; and
(d) was not secretly used in the patent area before the priority date of that claim by, or on behalf of, or with the authority of, the patentee or nominated person or the patentee's or nominated person's predecessor in title to the invention."
The essential question in this case is whether the subject matter of claim 1 is an invention that so far as claimed is a manner of manufacture within the meaning of s 6 of the Statute of Monopolies as described in s 18(1)(a).
As was emphasised in National Research Development Corporation v Commissioner of Patents ("NRDC"), in relation to the Patents Act 1952 (Cth), the conception of a manner of manufacture is not limited to physical production but takes its meaning from the whole category under which all grants of patents which may be made in accordance with the developed principles of patent law are to be subsumed:
"It is of the first importance to remember always that the Patents Act 1952-1955 (Cth), like its predecessor the Patents Act 1903 (Cth) and corresponding statutes of the United Kingdom (see the Patents, Designs and Trade Marks Act 1883, s 46; the Patents Act 1907, s 93; and the Patents Act 1949, s 101), defines the word 'invention', not by direct explication and in the language of its own day, nor yet by carrying forward the usage of the period in which the Statute of Monopolies was passed, but by reference to the established ambit of s 6 of that Statute. The inquiry which the definition demands is an inquiry into the scope of the permissible subject matter of letters patent and grants of privilege protected by the section. It is an inquiry not into the meaning of a word so much as into the breadth of the concept which the law has developed by its consideration of the text and purpose of the Statute of Monopolies. One may remark that although the Statute spoke of the inventor it nowhere spoke of the invention; all that is nowadays understood by the latter word as used in patent law it comprehended in 'new manufactures'. The word 'manufacture' finds a place in the present Act, not as a word intended to reduce a question of patentability to a question of verbal interpretation, but simply as the general title found in the Statute of Monopolies for the whole category under which all grants of patents which may be made in accordance with the developed principles of patent law are to be subsumed. It is therefore a mistake, and a mistake likely to lead to an incorrect conclusion, to treat the question whether a given process or product is within the definition as if that question could be restated in the form: 'Is this a manner (or kind) of manufacture?' It is a mistake which tends to limit one's thinking by reference to the idea of making tangible goods by hand or by machine, because 'manufacture' as a word of everyday speech generally conveys that idea. The right question is: 'Is this a proper subject of letters patent according to the principles which have been developed for the application of s 6 of the Statute of Monopolies?'"
Threshold quality of inventiveness
In NRDC, it was also held that it was enough for a process to constitute a manner of manufacture that it resulted in an artificially created state of affairs of economic significance:
"Notwithstanding the tendency of these decisions, the view which we think is correct in the present case is that the method the subject of the relevant claims has as its end result an artificial effect falling squarely within the true concept of what must be produced by a process if it is to be held patentable. This view is, we think, required by a sound understanding of the lines along which patent law has developed and necessarily must develop in a modern society. The effect produced by the appellant's method exhibits the two essential qualities upon which 'product' and 'vendible' seem designed to insist. It is a 'product' because it consists in an artificially created state of affairs, discernible by observing over a period the growth of weeds and crops respectively on sown land on which the method has been put into practice. And the significance of the product is economic; for it provides a remarkable advantage, indeed to the lay mind a sensational advantage, for one of the most elemental activities by which man has served his material needs, the cultivation of the soil for the production of its fruits. Recognition that the relevance of the process is to this economic activity old as it is, need not be inhibited by any fear of inconsistency with the claim to novelty which the specification plainly makes. The method cannot be classed as a variant of ancient procedures. It is additional to the cultivation. It achieves a separate result, and the result possesses its own economic utility consisting in an important improvement in the conditions in which the crop is to grow, whereby it is afforded a better opportunity to flourish and yield a good harvest."
That holding is, however, to be understood as importing the Court's earlier observations as to the meaning of an "invention" and the idea that all that had come to be understood by that word, as used in patent law, is comprehended in the phrase "new manufactures". It should not be taken to suggest that an "artificial state of affairs" and "economic utility" are the only considerations relevant to whether an invention is "a manner of manufacture" for the purposes of s 18(1)(a) of the Act.
For a claimed invention to qualify as a manner of manufacture it must be something more than a mere discovery. The essence of invention inheres in its artificiality or distance from nature; and thus, whether a product amounts to an invention depends on the extent to which the product "individualise[s]" nature. As Professors Sherman and Bently wrote:
"What then was required in order to move from the realm of discovery to that of invention? The simple answer was that it was necessary to show that abstract principles had been reduced to practice, that Nature had been individualised or activated. ... While philosophical or abstract principles could not on their own be patented, their embodiment in a material or practical form could. In these circumstances it was clear that in law it was the artificial or created nature of the final product, its distance from Nature, which ensured that an object became an invention rather than a mere discovery."
The question then is whether the subject matter of the claim is sufficiently artificial, or in other words different from nature, to be regarded as patentable.
Relevantly, the artificiality of a product may be perceived in a number of factors, including the labour required to create it and the physical differences between it and the raw natural material from which it is derived. Regardless, however, of the amount of labour involved or the differences between the product and the raw natural material from which it is derived, it is necessary that the inventive concept be seen to make a contribution to the essential difference between the product and nature.
Admittedly, it has occasionally been doubted that there is any longer a threshold requirement of inventiveness as opposed to the specific requirements of inventive step and novelty for which s 18(1)(b) provides. It has also been suggested that it would be desirable to collapse the subject matter requirement into the specific inquiries of inventive step and novelty. The Advisory Council on Intellectual Property concluded that it would make sense for "questions of newness to be dealt with under the specific provisions for novelty and inventive step, rather than under the general umbrella of manner of new manufacture".
But for present purposes, the law on the point appears to be tolerably clear. In Commissioner of Patents v Microcell Ltd, the Full Court held that the subject matter of a claim as disclosed in the specification must possess a quality of inventiveness or, in other words, the use of ingenuity that adds to the sum of human knowledge. In N V Philips Gloeilampenfabrieken v Mirabella International Pty Ltd, the majority recognised that the quality of inventiveness must appear on the face of the specification. In Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd ("Ramset"), the majority held that whether claimed subject matter is an invention for the purposes of s 100(1)(d) of the Patents Act 1952 (Cth) is distinct from inquiries as to inventive step, obviousness and novelty under s 100(1)(e) and (g), and that the court below had erred in considering "inventive merit" in light of prior art for the purposes of s 100(1)(d). The majority distinguished Philips on the basis that it was decided under the Patents Act 1990 (Cth). But, at a later point in the judgment, the majority also acknowledged that, where the subject matter of a claim as disclosed in the specification is plainly not an invention, the claim should be dismissed.
Notwithstanding that Microcell did not establish a discrete "threshold" test, each of those decisions is consistent with the requirement, essential to the concept of a "manner of manufacture", that the subject matter of a claim have about it a quality of inventiveness which distinguishes it from a mere discovery or observation of a law of nature. That requirement is separate and distinct from the other requirements of inventive step and novelty. As Brennan, Deane and Toohey JJ stated in Philips, an alleged invention will:
"remain unsatisfied if it is apparent on the face of the relevant specification that the subject matter of the claim is, by reason of absence of the necessary quality of inventiveness, not a manner of new manufacture for the purposes of the Statute of Monopolies. That does not mean that the threshold requirement of 'an alleged invention' corresponds with or renders otiose the more specific requirements of novelty and inventive step (when compared with the prior art base) contained in s 18(1)(b). It simply means that, if it is apparent on the face of the specification that the quality of inventiveness necessary for there to be a proper subject of letters patent under the Statute of Monopolies is absent, one need go no further."
Naturally occurring phenomena
As counsel for the first respondent stressed repeatedly in the course of argument, the appellant's only basis of objection is lack of patentable subject matter; in particular that, because the mutated BRCA1 gene was a naturally occurring substance, it was incapable of being a patentable invention. It follows, as the first respondent contended, that other possible grounds of invalidity such as lack of inventive step, lack of novelty and lack of utility are irrelevant.
But the fact that the appellant objected on the sole basis of lack of patentable subject matter does not exclude the threshold requirement of inventiveness. For the reasons already given, the threshold requirement of inventiveness is part of the inquiry into whether the subject matter of the claim is a patentable invention.
Here, the essence of claim 1 is the correlation between the incidence of cancer and the presence of the specified mutations and polymorphisms in the mutated BRCA1 gene. Such ingenuity as that entails consists in the idea of examining an isolated fragment of a patient's naturally occurring DNA constituted of the BRCA1 gene for the presence or absence of the specified mutations and polymorphisms. The subject matter of the claim does not make any contribution to the inclusion of the specified mutations and polymorphisms in the mutated BRCA1 gene. Their presence or absence in or from it is the result of the isolated BRCA1 gene being part of the naturally occurring DNA from which the sequence is isolated. To adopt and adapt the reasoning in NV Philips' Gloeilampenfabrieken Application, it is "the inevitable result of that which is inherent in the [DNA]".
In this case, the courts below concluded that, despite the presence or absence of the specified mutations and polymorphisms being the result of naturally occurring phenomena, the subject matter of the claim was a patentable invention. The Full Court held so because, as their Honours put it:
"In Australia, there is no statutory or jurisprudential limitation of patentability to exclude 'products of nature'. To the contrary, the High Court has specifically rejected such an approach. A mere discovery is not patentable and an idea is not patentable, but a 'manner of manufacture', as that term has been developed, is.
...
In our view the products the subject of claim 1 are different to the gene comprising the nucleic acid sequence as it exists in nature."
But in fact, there are limits on the patentability of products of nature inasmuch as products of nature do not involve human intervention and therefore are lacking in the necessary quality of inventiveness to qualify as a manner of manufacture. As Professor Sherman observed in his recent article on the subject:
"The US product of nature doctrine and the Australian test of artificially created state of affairs are the same question asked from different perspectives. In both cases, they build on an (implicit) image of what it means to invent something; ... nature and artifice are flip sides of the same coin."
Of course, as NRDC implies, the application of naturally occurring phenomena to a particular use may be a manner of manufacture if it amounts to a new process or method of bringing about an artificially created state of affairs of economic significance. Even so, the inventor cannot claim to have invented the naturally occurring product as opposed to the process of application. In NRDC, the patentee could not claim to have invented, and therefore there was no suggestion of it laying claim to a monopoly over, the commonplace herbicides which were used in the course of the patentable process. Similarly, in Shell Oil Co v Commissioner of Patents, the patentee could not claim to have invented, and therefore there was no suggestion of laying claim to a monopoly over, the known compounds which were applied as part of the patentable process to a new use of plant growth regulation. So too here, insofar as the invention consists in the application of a naturally occurring phenomenon to a particular use, the inventor cannot claim to have invented the naturally occurring phenomenon as opposed to the method of use and has no claim to a monopoly over the naturally occurring phenomenon as opposed to the method of use.
The scope of the invention
Certainly, as the Full Court recognised, the substance of the claimed invention consists not only in the discovery of the BRCA1 gene but also in the development of a process or method of detecting the increased likelihood of certain kinds of malignancy by using known techniques to isolate the BRCA1 gene and examining it by the use of known techniques for the presence of the specified mutations and polymorphisms. On that basis, it might fairly be said that a pathologist who isolated a fragment of a patient's DNA comprising the BRCA1 gene and examined it for the presence of the specified mutations and polymorphisms, with the object of identifying the likelihood of malignancy of which the specified mutations and polymorphisms are claimed to be indicia, would make use of the claimed invention. But, equally on that basis, the pathologist would only infringe claims 1 to 3 if the patient's DNA happened to possess one or more of the specified mutations and polymorphisms.
Moreover, what if a pathologist had no interest in looking for the specified mutations and polymorphisms - indeed let it be assumed that the pathologist vehemently rejected the conclusion that the specified mutations and polymorphisms were clinically significant - and was concerned with isolating the fragment of a patient's DNA comprising the BRCA1 gene in order only to examine it for different mutations and polymorphisms which the pathologist's independent research had led him or her to conclude were of clinical significance? In those circumstances, the only aspect of the claimed invention of which the pathologist could be said to make any use would be the discovery of the BRCA1 gene; and as has been seen, the BRCA1 gene is not patentable as such because it is a naturally occurring phenomenon which lacks the quality of inventiveness necessary to qualify as a manner of new manufacture.
Of course, that does not mean that an intention to infringe a patent is an essential element of infringement. If an inventor patents a product and another inventor later reinvents it in ignorance of its earlier invention, the subsequent inventor's ignorance is clearly no defence to a claim of infringement. Nor is it to deny that it is permissible in a proper case to define the physical characteristics of an article by reference to the result which the article may achieve or that, in cases where such a method of definition is appropriate, it is no objection to that method of definition that a person skilled in the art may need to experiment to ascertain whether an article made by that person infringes the patent. But, in the former case, there is infringement because the subsequent inventor has employed the manner of manufacture which the earlier inventor invented and, in the latter case, the definition of an article by reference to what it is able to achieve is permissible because the article is patentable in itself.
By contrast, a pathologist who employs established technology to isolate a fragment of naturally occurring DNA comprising the BRCA1 gene does not employ any method invented by the first respondent and, as has been seen, because the BRCA1 gene is a naturally occurring phenomenon, it is not patentable in itself. Nor does it assist the first respondent to point to the inventiveness involved in the combination of its discovery of the BRCA1 gene with the first respondent's system for isolating and examining the gene for the presence of the specified mutations and polymorphisms; for as Sir Wilfrid Greene MR said in Mullard Radio Valve Co Ltd v British Belmont Radio Ltd:
"an article which is not in itself patentable cannot be made the subject of a good ... claim merely by pointing out that, if it is used in a particular way or in a particular collocation, it will produce novel and useful results."
The substance and effect of claim 1
That invites the question of whether the wording of claim 1 properly reflects the substance of the claimed invention.
The judge at first instance held it was enough to uphold claim 1 on the basis that isolated nucleic acid containing the specified mutations and polymorphisms "constitutes an artificial state of affairs in the sense those words should be understood in the present context". The Full Court emphasised that claim 1 is drafted as a claim for a compound - an isolated nucleic acid - as opposed to a claim to information, and that the product the subject of claim 1 is different from the gene comprising the nucleic acid sequence as it exists in nature:
"Claim 1 is not to the genetic code. What is claimed is an isolated nucleic acid, a chemical molecule characterised in a certain way, which is chemically, structurally and functionally different to what occurs in nature. There is a distinction between a claim to an isolated nucleic acid comprised in part of a sequence of nucleotide bases and a claim to a written sequence of nucleotides which may be identical to the corresponding sequence in the natural cell. The claim is to be construed according to the normal principles of claim construction. To identify the invention as lying in the concept of information said to be embodied in a sequence of nucleotides ignores the language of the claim."
The way in which a claim is drafted cannot, however, transcend the reality of what is in suit. As Lord Loreburn LC observed in British Vacuum Cleaner Company Ltd v London and South Western Railway Company, albeit in dissent in the result, "[i]t is an abuse, which cannot be too sedulously watched and prevented by Courts of law, when a patentee, even if he is really an inventor, so shapes his claim that it may cover what he has not invented at all". Monopolies are granted for inventions, not for the inventiveness of the drafting with which applicants choose to describe them. Hence, as was observed in Eli Lilly & Co's Application, where an alleged invention is based on the discovery of the particular properties of known compounds, care must always be taken to examine the form of claim actually made. Whatever words have been used, the matter must be looked at as one of substance and effect must be given to the true nature of the claim.
No doubt the motive consideration in Eli Lilly was that methods of treatment of illness or disease of human beings were at that time not regarded as patentable. That is no longer the case in this country. But the point remains that care must be taken to examine the form of claim actually made to see if it is in fact an attempt to establish a monopoly for the manufacture of a substance for a purpose for which a monopoly cannot be claimed. More generally, an "invention is to be understood as a matter of substance and not merely as a matter of form". If a claim drafted as a product claim is in truth a "'disguised' process claim", it will be treated as such.
As already noticed, the first respondent did not invent and cannot claim to have invented the process of isolating nucleic acid or the process of amplifying for genetic testing the fragment comprising the BRCA1 gene. The technologies for each are longstanding and well known to those who are skilled in the science. Nor did the first respondent invent a method for infusing any such fragment of isolated DNA with the specified mutations and polymorphisms. Nor would there have been the slightest utility in doing so. The only relevant clinical significance of the presence of the specified mutations and polymorphisms in an isolated fragment is that the fragment has been extracted from the naturally occurring DNA in the cell and thus that the specified mutations and polymorphisms were present in the cell before being so extracted.
It was not disputed that the first respondent might justly lay claim to the discovery that, if an isolated fragment comprising the BRCA1 gene is found upon examination to exhibit the specified mutations and polymorphisms, their presence is or may be indicative of particular kinds of malignancy in the cell. Nor was it disputed that a process or method of using known technology to isolate a sequence of nucleic acid comprising the BRCA1 gene and examining it for the presence of the specified mutations and polymorphisms for the purpose of detecting or predicting malignancy might be patentable. But, as has been observed, the discovery of a natural correlation is not patentable as such and its discovery does not entitle the first respondent to patent the BRCA1 gene as a product, whether or not afflicted by the specified mutations and polymorphisms.
The fair basis cases provide an analogy which assists in illuminating the point. As they show, a claim for a new use of an old product does not confer a monopoly over the old product (just the new use). Parity of reasoning dictates that application of a method of detecting the increased likelihood of certain kinds of cancer by isolating the BRCA1 gene and comparing it to the reference sequence does not confer a monopoly over the mutated BRCA1 gene.
In Mullard Radio Valve Co Ltd v Philco Radio and Television Corporation of Great Britain Ltd, the claim in suit was for a "discharge tube having at least three auxiliary electrodes between the cathode and the anode, characterised in that the auxiliary electrode nearest to the anode is directly connected to the cathode so as to be maintained continuously at the cathode potential". It was, however, established by the evidence that the discharge tube was a triode of known construction in which the anode was connected to the cathode and could only achieve its avowed object of maintaining the anode at the cathode potential if the three electrodes were connected in a particular sequence. The patentee's inventive idea thus consisted only in the discovery that in that particular juxtaposition the tube achieved that object. Accordingly, the claim was not fairly based on the invention because it went beyond the ambit of the patentee's inventive step. As Lord Macmillan said:
"If an inventor claims an article as his invention but the article will only achieve his avowed object in a particular juxtaposition and his inventive idea consists in the discovery that in that particular juxtaposition it will give new and useful results, I do not think that he is entitled to claim the article at large apart from the juxtaposition which is essential to the achievement of those results."
Similarly, in Adhesive Dry Mounting Company Ltd v Trapp & Co, Parker J held that:
"The first question which arises on this Claim is, whether it claims the pellicle therein described, or merely the use of this pellicle in the process claimed in the first Claiming Clause. If the former, the Letters Patent would entitle the Patentees to prevent the use of such a pellicle by others, whatever might be the purpose for which it was used. If the latter, the Letters Patent would only entitle the Patentees to restrain the use of such a pellicle in any process substantially the same as the process referred to in the first Claiming Clause. ... The idea of using an old material for an entirely new purpose, not being analogous to purposes for which it has theretofore been used, may be good subject-matter, but such idea, however ingenious, can hardly justify a claim for the material itself."
So too, in Wellcome Foundation Ltd v Commissioner of Patents, where the claim in suit was for a known chemical substance together with a set of instructions for its use for a previously unknown purpose of treating anaplasmosis in cattle, the Court said that:
"What the applicant seeks is a monopoly in an old substance limited to its use in the process which is the subject of claims 17 to 28. It is one thing to say that the inventor of a process is entitled to a monopoly, albeit limited, in the product of that process. It is quite another and different thing to say that the inventor of a process is entitled to a monopoly in a substance which is used merely as an ingredient in that process. In the latter case the invention claimed makes no contribution to the manufacture of the substance. At best, it takes advantage of properties in the substance hitherto unknown or unsuspected.
A further answer to the appellant's submission is that there is no distinction between the claim to the process and the claim to the substance when the substance claim is limited to its use in the process. So much appears from the judgment of Parker J in Adhesive Dry Mounting Company Ltd v Trapp & Co".
In the same way here, it is one thing to say that the first respondent has invented a process which consists in isolating and examining the fragment comprising the BRCA1 gene for the presence of the specified mutations and polymorphisms as an indicium of malignancy. It is quite another and different thing to say that the first respondent, as inventor of that process, is entitled to a monopoly over the mutated BRCA1 gene, which is used merely as an ingredient in that process. The invention claimed makes no contribution to the manufacture of the substance. At best, it takes advantage of properties in the substance hitherto unknown or unsuspected. Just as there was no difference between the process and the product in Wellcome Foundation, there is no distinction between a claim to the process of isolating the BRCA1 gene for the purpose of examining it for the presence of the specified mutations and polymorphisms and the claim to the BRCA1 gene itself.
Claim not defined by chemical composition
Counsel for the first respondent stressed more than once in argument that claim 1 was for a discrete chemical molecule achieved by the breaking of chemical covalent bonds in the course of the extraction and amplification processes employed in deriving isolated nucleic acid from the source DNA. According to the first respondent, that significantly distinguished claim 1 from the first respondent's claim for patent protection in respect of the BRCA1 gene simpliciter which the Supreme Court of the United States rejected in Association for Molecular Pathology v Myriad Genetics Inc. As the plurality of the Supreme Court of the United States observed in that case:
"[The first respondent's] claims [are not] saved by the fact that isolating DNA from the human genome severs chemical bonds and thereby creates a nonnaturally occurring molecule. [The first respondent's] claims are simply not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA."
As counsel for the first respondent ultimately conceded, however, because of the variable length once isolated of the fragments which may comprise the BRCA1 gene, in truth the claim made in relation to the BRCA1 gene relates to a very large if not infinite number of isolated nucleic acids with different molecular structures according to, inter alia, the number of exons isolated, the degrees of purification achieved in the extraction and amplification processes, and the presence of mutations and polymorphisms in the consequent extraction. Nor is there any conceivable way in which the processes could be adjusted by reference to any disclosed chemical formula to avoid the presence of the specified mutations and polymorphisms and thereby infringement of the patent. It follows that, in reality, the claim in suit is no more expressed in terms of a chemical formula than was the claim in respect of the BRCA1 gene simpliciter which was rejected in the United States.
The reasoning of the courts below
The judge at first instance considered that it followed from what was said in NRDC about a process being patentable when it results in an artificially created state of affairs of economic significance that the artificially created state of affairs of economic significance which results from isolating and amplifying the BRCA1 gene and discovering that it is afflicted by one or more of the specified mutations and polymorphisms is a patentable product. His Honour added that three considerations fortified him in that view. The first was that NRDC was "deliberate in its use of very expansive language" and emphasised "the 'broad sweep' of the concept involved". The second was that "[e]xtraction 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 the third was that:
"It would lead to very odd results if a person whose skill and effort culminated in the isolation of a [DNA sequence] could not be independently rewarded by the grant of a patent because the isolated [DNA sequence], no matter how practically useful or economically significant, was held to be inherently non-patentable."
The Full Court adopted a generally similar approach but with greater emphasis on the artificiality of isolated nucleic acid. Their Honours said that:
"What is being claimed is not the nucleic acid as it exists in the human body, but the nucleic acid as isolated from the cell. The claimed product is not the same as the naturally occurring product. There are structural differences but, more importantly, there are functional differences because of isolation. As Lourie J explains, 'the ability to visualise a DNA molecule through a microscope, or by any other means, when it is bonded to other genetic material ... is worlds apart from processing an isolated DNA molecule that is in hand and usable'.
...
The isolation of the nucleic acid also leads to an economically useful result - in this case, the treatment of breast and ovarian cancers. This is surely what was contemplated by a manner of new manufacture in the Statute of Monopolies."
With respect, there are problems with the reasoning at both levels. First and foremost, claim 1 is not a claim for a monopoly over nucleic acid isolated from the cell. Nor could it be. The process of isolating nucleic acid from the cell for the purposes of genetic testing is a matter of longstanding practice and diagnostic technique. Pathologists have long routinely isolated fragments of nucleic acid by the PCR process of amplification, and the DNA sequences of the BRCA1 exons by which pathologists are guided in that process are well described in medical literature. Other things being equal, they are free (without fear of contravention of any patent to which the first respondent might lay claim) to "manufacture" isolated nucleic acid in order both to check it against known reference comparators and to check it for variations of unknown clinical significance.
Secondly, and for the same reason, the fact that isolated nucleic acid is a product which is "chemically, structurally and functionally different" from the naturally occurring DNA from which it is isolated - essentially because the isolation process consists of chemically stripping away the histones which control and execute the function of the exons in the cell and separating the fragment intended for examination - is for all intents and purposes beside the point. It would be to the point if the first respondent had invented and was claiming a new method for isolating nucleic acid; but claim 1 does not disclose any such method.
Thirdly, although claim 1 is restricted to isolated nucleic acid comprising the mutated BRCA1 gene, claim 1 does not disclose any method of infusing the isolated BRCA1 gene with the specified mutations and polymorphisms or otherwise facilitating their presence. As was earlier noticed, a pathologist has no way of knowing whether a patient's DNA, and therefore isolated nucleotides coding for the BRCA1 polypeptide, are afflicted by the specified mutations and polymorphisms until and unless the pathologist first isolates the patient's DNA, amplifies the fragment of it and examines it for the presence of the specified mutations and polymorphisms.
Consequently, so far from being a claim for a manner of manufacture of isolated nucleic acid constituted of the mutated BRCA1 gene, claim 1 is in truth a claim for a monopoly over the right to apply long-established methods for the isolation and amplification of specific nucleotide fragments to the isolation and amplification of a patient's naturally occurring BRCA1 gene, where and if it is found upon subsequent examination that the patient's BRCA1 gene happened to be afflicted by any of the specified mutations and polymorphisms.
That is not a valid claim of a manner of manufacture of a product. By definition, a manner of manufacture is an artificial thing or state of affairs which involves an element of inventiveness. Although the isolation of nucleic acid comprising the BRCA1 gene is a man-made process, it does not involve any element of inventiveness. It is no more than the application of a recognised diagnostic technique to a known purpose of examining fragments of human DNA.
The selection of the fragment which comprises the BRCA1 gene is novel, in the sense that it reflects the first respondent's discovery of the significance of the SEQ.ID No:1 sequence. But the first respondent does not and cannot claim to be entitled to a monopoly over the right to isolate the fragment which codes to the SEQ.ID No:1 sequence, or indeed to isolate any other fragment of the DNA polymer. The presence of the specified mutations and polymorphisms in the isolated nucleic acid is also of critical importance inasmuch as it reflects the first respondent's discovery of the correlation between their presence and the heightened probability of cancer. But nothing that is done in the course of isolating the BRCA1 gene has any effect on whether the specified mutations and polymorphisms will be present. Their presence or absence in or from the isolated nucleic acid is entirely dependent upon whether they were present in or absent from the DNA of the patient from whom the isolated nucleic acid was extracted, and in effect that is the antithesis of a man-made artificial state of affairs.
Fourthly, whether or not the processing of an isolated molecule is "worlds apart" from the ability to visualise a DNA molecule through a microscope or by other means is also beside the point. Claim 1 is not a claim for a monopoly over the right to isolate and amplify the fragment of the BRCA1 gene.
Fifthly, it is not the isolation of nucleic acid, or even the isolation and amplification of the fragment comprising the BRCA1 gene, which leads to the "economically useful result" of treating breast and ovarian cancers. It is rather the first respondent's discovery of a naturally occurring correlation between the presence of the specified mutations and polymorphisms in such a fragment (and thus in the DNA in the cell from which the fragment is derived) and an increased probability of actual or potential malignancy.
Sixthly, the discovery of a naturally occurring correlation between the presence of the specified mutations and polymorphisms in an isolated fragment comprising the BRCA1 gene and an increased likelihood of actual or potential malignancy in the cell from which the fragment is derived is not what was contemplated by a "manner of new manufactures" in the Statute of Monopolies. As was observed in Ramset, although discovery of a naturally occurring phenomenon or a correlation between naturally occurring phenomena adds to the sum of human knowledge, s 6 of the Statute of Monopolies was concerned with a manner of new manufacture; and neither naturally occurring phenomena, nor the correlation between naturally occurring phenomena, is a manner of new manufacture. A manner of new manufacture necessitates invention and, as Buckley J said in Reynolds v Herbert Smith & Co Ltd:
"Invention ... adds to human knowledge, but not merely by disclosing something [not previously known]. Invention necessarily involves also the suggestion of an act to be done, and it must be an act which results in a new product, or a new result, or a new process, or a new combination for producing an old product or an old result."
Finally, much of the judgment at first instance and of the judgment of the Full Court appears to attribute misplaced significance to the conclusion reached in NRDC earlier set out that it was sufficient to render patentable the process or method of production there in suit that it had as its end result an artificially created state of affairs of economic significance. The judge at first instance concluded, and the Full Court appears to have taken a similar view, that: "It is apparent from this passage that a product that consists of an artificially created state of affairs which has economic significance will constitute a 'manner of manufacture'."
With respect, that is not apparent and it is not the case. The passage of the judgment in NRDC in question was explicitly directed to whether a process or method of applying a known product to a new application qualified as a manner of manufacture within the meaning of s 6 of the Statute of Monopolies. It was sufficient, to conclude that it did, that the process resulted in "some product whereby the validity of [the process] can be tested". It was held that, by reason of the direction of development in patent law since the 17th century and the direction which it must take in modern society, the notion of a manner of manufacture comprised of the result of a method or process is not confined to a tangible product but extends to an artificially created state of affairs of economic significance. But it does not follow that it is enough to found a claim for a monopoly in relation to a product, as opposed to a process by which the product is created, to demonstrate that an artificially created state of affairs of economic significance results from the application of a process to the product for which product no claim for a monopoly has been or could be made.
It is not disputed that a process or method of detecting the increased likelihood of certain kinds of malignancy by isolating the BRCA1 gene and examining it for the presence of any of the specified mutations and polymorphisms may be patentable subject matter as a process (subject to considerations of novelty and inventive step when compared to the prior art base). But, to repeat, claim 1 is not a claim for any such process. It is a claim for a monopoly over such isolated fragments of naturally occurring DNA as comprise the BRCA1 gene as are found upon examination to contain the (naturally occurring) specified mutations and polymorphisms.
In the result, the claim extends too far. The difficulty for the first respondent is that, having discovered a presumably good and perhaps ground-breaking process for detecting the probability of certain kinds of malignancy by reference to the presence of particular mutations and polymorphisms in the BRCA1 gene, the first respondent has attempted to patent those sequences of the gene themselves notwithstanding that, even when isolated, they are naturally occurring and therefore not new.
Contemporary contextual considerations
Both parties to the appeal sought to support their positions by reference to contemporary practice in the European Union. The course of argument highlighted a controversy between them as to whether claim 1 would meet the requirements for patentability prescribed by the applicable Directive. That is not a controversy which needs to be resolved. The structure and prescriptive detail of European patent legislation in its application to biotechnology and genetic engineering are such that the resolution of the controversy could provide little assistance in determining whether the claim is a proper subject for letters patent according to the principles which have been developed for the application of s 6 of the Statute of Monopolies.
The first respondent also sought to support its position by reference to the practice of the Australian Patent Office since 1995 of accepting the patentability of isolated nucleic acid sequences as well as to the history of executive consideration and legislative amendment of the Patents Act since 2002, both of which were explained in sufficient detail by the trial judge. The legislative history does not go so far as to demonstrate a legislative endorsement of the Patent Office practice. Nor has the Patents Act been amended in a way which necessarily assumes the patentability of isolated nucleic acid sequences. The most that can legitimately be drawn from the legislative history is a repeated legislative acceptance that, unlike the position in the European Union, issues of patentability in biotechnology and genetic engineering in Australia will continue to be resolved, consistently with NRDC, according to the principles which have developed for the application of s 6 of the Statute of Monopolies, except as otherwise specifically provided in s 18(2) and (3) of the Patents Act. That is to highlight the critical question, not to answer it.
Conclusion and orders
The appeal should be allowed. We agree with the orders proposed in the judgment of French CJ, Kiefel, Bell and Keane JJ.