Medical genetic testing

Access to medical genetic testing

20.3 Medical genetic tests are generally ordered by medical practitioners. Some genetic testing may involve referral of the patient to a clinical geneticist, as well as to a genetic counsellor for pre-test and post-test counselling. Genetic testing for research purposes may also be conducted in concert with medical practitioners, who liaise with participating patients.

20.4 Individuals generally cannot obtain direct access to medical genetic testing by laboratories in Australia. At present, most medical genetic testing is provided through state and territory clinical genetics services and the public sector laboratories associated with these services,[2] and a medical practitioner must refer individuals to them. However, the range of genetic testing available to the public is likely to expand in the future.[3]

20.5 The Human Genetics Society of Australasia (HGSA) maintains a register of medical genetic tests that are available in Australasia and a list of the laboratories that provide them. According to the HGSA, there are presently around 220 medical genetic tests available from 44 laboratories across Australia.[4] Some genetic tests offered overseas are not available in Australia. Likewise, some types of tests offered in Australia are not available, or not widely performed, in other countries.

20.6 A range of factors, other than patent laws and practices, affect access to medical genetic testing. These include the cost of the test; whether the test is listed under the Medicare Benefits Scheme (MBS); the level of funding provided for testing by state and territory governments; technical and ethical standards; laboratory protocols and accreditation; and regulation of testing provided direct to the public (rather than through a medical practitioner).[5] The availability of a genetic test in a particular laboratory may also reflect the research interests of that laboratory. For example, a laboratory that undertakes research into a particular genetic disease might also offer, as part of its research work, a diagnostic service for that disease

20.7 The availability of genetic testing in Australia may also depend on decisions about which tests are ethically acceptable,[6] and on a cost-benefit analysis of a particular test. Medical genetic testing is still a relatively slow and expensive process. However, the technology is advancing rapidly. The development of automated ‘DNA chip’ technology[7] may soon make it technically possible and financially practicable to test for numerous genetic mutations simultaneously in a single procedure.

Cost of medical genetic testing

20.8 As with other health services, access to medical genetic testing depends on the cost to consumers of testing procedures and on the rebates provided by public and private health insurers. The cost of genetic testing procedures varies, from less than $100 to more than $1,000, depending on a number of factors including the complexity and methodology of the testing procedure.[8]

20.9 In 2002, a report by the Organisation for Economic Co-operation and Development, Genetic Inventions, Intellectual Property Rights and Licensing Practices: Evidence and Policies (OECD Report) noted that while economies of scale may help reduce costs in the long term, other factors are likely to increase prices. These include the need for better epidemiological and genetic population data; increasing regulatory costs; laboratory certification costs; increased needs for counselling; and liability costs.[9]

20.10 In Australia, depending on the test and the laboratory, testing may be free to the patient or fees may be charged.[10] In some cases, Medicare funds genetic testing. However, the MBS currently funds medical genetic testing under only six MBS items (see Chapter 19).

Patents and medical genetic testing

20.11 Patents may be granted over isolated genetic material that has been separated from the human body or manufactured synthetically, provided the patent application satisfies the threshold tests for patentability.[11] Genetic sequences provide the basis for diagnostic tests—that is, mutations in genes can be detected by testing techniques based on knowledge of the genetic sequence. This may require the use of the genetic sequence of the normal gene, as well as that of the mutations.

20.12 Patents may also be granted over methods or products used in testing for mutations in a gene or genetic sequence. For example, a United States company, Myriad Genetics Inc (Myriad), holds patents internationally on isolated genetic materials associated with breast and ovarian cancer.[12] Myriad’s patents also cover methods for predictive testing[13] and products and processes involved in its breast cancer predisposition test, which is called ‘BRACAnalysis’. Similarly, another United States company, Bio-Rad Laboratories, holds gene patents associated with hereditary haemochromatosis, covering both isolated genetic materials and methods for testing.[14]

20.13 A patent that asserts rights to isolated genetic material per se may cover all uses of that material. These uses often include diagnostic or predictive testing for genetic conditions. For example, Myriad is said to have a dominant patent position covering the use of the BRCA1 genetic sequence for predictive testing relating to breast and ovarian cancer.[15] In other words, any technique for BRCA1 testing is likely to require use of Myriad’s patents.

20.14 Patents may be granted on general methods for identifying genetic sequences, mutations or deletions in an individual’s genetic sequence. For example, United States patents for the process known as polymerase chain reaction (PCR), which enables the DNA from a genetic sample to be reproduced in large quantities for testing, were granted to Cetus Corporation in 1989, and assigned to Roche Diagnostics in 1991.[16]

20.15 The subject of most concern has been patents that assert rights over isolated genetic material and the use of genetic sequences in diagnostic or predictive genetic testing. The ALRC understands that these patents generally include claims over isolated genetic materials containing sequences that code for proteins. Patents over methods for using so-called ‘junk’ or non-coding genetic sequences are also relevant to medical genetic testing. The use of non-coding genetic sequences is integral to medical genetic testing because they are used to design primers for PCR assays. An analysis of Australian patents relating to medical genetic testing conducted by Dr John Abbott reveals a wide divergence in the scope of patent claims.

At one extreme are patents which contain very broad claims, which may include all mutations within a gene (including those in intron, exons and regulatory sequence regions) … At the other extreme are patents which have only narrow claims, to include a specific mutation or a relatively small well-defined mutation set.[17]

20.16 As noted above, there are about 220 medical genetic tests available in Australia.[18] Many of these medical genetic tests, particularly the common ones, are likely to be subject to patents on isolated genetic materials. Dr Abbot’s analysis, which correlated patent applications and granted patents with genetic tests available in Australia, identified 60 genetic tests that are subject to patent rights. This was said to suggest that ‘at least 30% of the genetic tests offered are, or may be in the future, subject to patent protection’.[19]

Enforcement of patents and medical genetic testing

20.17 The most publicised instance of a patent holder seeking to enforce rights to isolated genetic materials used in medical genetic testing is that of Myriad and the BRCA1 and BRCA2 patents associated with testing for pre-disposition to breast and ovarian cancer.[20] Myriad has sought to enforce its patent rights against Canadian provincial health authorities.[21] In the United Kingdom, the Department of Health entered into an agreement with Rosgen Limited, the exclusive licensee of the Myriad patents in the United Kingdom. However, Rosgen went into liquidation and the Department of Health commenced negotiations with Myriad.[22] Myriad’s patents led to calls for patent law reform in France and Canada.[23] As discussed in Chapter 19, in May 2004, an opposition division of the European Patent Office decided to revoke Myriad’s BRCA1 patent in Europe, in view of relevant prior art.[24]

20.18 In the United States, research indicates that gene patent holders are actively enforcing their rights against laboratories.[25] In contrast, the results of a survey of Australian laboratories that perform medical genetic testing found that there was ‘little indication that holders of patents related to disease genes were actively enforcing their patents against Australian genetic test laboratories’.[26]

20.19 Consultations confirmed that, while there is a high degree of concern about the potential impact of patents over isolated genetic materials on public sector laboratories, enforcement by patent holders has been limited.[27] The ALRC understands that Australian public sector laboratories currently do not pay licence fees for the use of isolated genetic materials in medical genetic testing, and generally have not been approached by patent holders seeking to enforce their rights over such materials. The situation is different with respect to gene patents over genetic technologies, such as PCR, where royalties are commonly paid, often as part of the purchase price of equipment or consumables.[28]

20.20 There has been much conjecture about the future enforcement of gene patents against public sector laboratories. Much of this conjecture has concerned patents held by Australian biotechnology company Genetic Technologies Limited (GTG). There are two sets of patents involved. The first set is associated with testing for pre-disposition to breast and ovarian cancer (the BRCA patents). The second set of patents relates to methods of using non-coding DNA polymorphisms (the non-coding patents).[29]

20.21 In May 2003, Myriad granted GTG an exclusive licence in Australia, New Zealand and South East Asia relating to predictive genetic testing for breast and ovarian cancer using the BRCA patents.[30] GTG has stated publicly that the rights it has obtained from Myriad for breast cancer testing ‘will not be enforced against other health service providers in Australia and New Zealand’.[31] In July 2003, GTG reiterated that it did not intend to enforce the BRCA patents and confirmed that it has allowed the existing public hospital cancer genetics laboratories in both Australia and New Zealand to continue to perform tests on the BRCA genes unhindered.[32]

20.22 The position is different with regard to enforcement of the non-coding patents. In March 2003, GTG advised public sector laboratories in Australia and New Zealand that they would need to negotiate licences in relation to its non-coding patents.[33] GTG claimed that its non-coding patents may be infringed by medical genetic testing for a range of genetic conditions, including cystic fibrosis, Duchenne muscular dystrophy, Friedreich’s ataxia, fragile X syndrome, haemophilia, myotonic dystrophy and prothrombin (Factor II). In the United States, Applera Corporation, is facing an infringement action for refusing to obtain a licence to use GTG’s non-coding patents for, among other things, a diagnostic test for cystic fibrosis.[34]

20.23 There is growing concern in Australia about the possibility that gene patent holders and licensees might enforce their patents against medical genetic testing laboratories. However, actual enforcement activity remains more limited than in the United States. Dr Dianne Nicol and Jane Nielsen comment:

Could Australian testing laboratories face demands for licence fees from a number of different patent holders in the future? The small size of the Australian market suggests that it may not be worthwhile for foreign companies to pursue Australian laboratories. In addition, most laboratories are in public hospitals and many do not charge for their services, further suggesting that there may be little financial incentive in targeting them.[35]

[2] Of those laboratories listed on the HGSA’s website as offering diagnosis of genetic disorders, 81% were located in public hospitals (as at November 2002): D Nicol, ‘The Impact of Patents on the Delivery of Genetic Tests in Australia’ (2003) 15(5) Today’s Life Science 22, 25.

[3] See Australian Law Reform Commission and Australian Health Ethics Committee, Essentially Yours: The Protection of Human Genetic Information in Australia, ALRC 96 (2003), [11.50]–[11.63].

[4] J Brasch, DNA Diagnosis of Genetic Disorders in Australasia, Human Genetics Society of Australasia, <www.hgsa.com.au/labs.html> at 16 June 2004. Not all tests are available from all laboratories. The register does not include newborn screening laboratories.

[5] The ALRC and the Australian Health Ethics Committee (AHEC) have made a number of recommendations with implications for the future availability of medical genetic testing. These included recommendations: for the enactment of new legislation to require laboratories that conduct genetic testing to be accredited; to amend the Therapeutic Goods Act 1989 (Cth) and related regulations to enable the Therapeutic Goods Administration to regulate more effectively genetic testing products provided directly to the public; and for the development of genetic testing and counselling practice guidelines, which identify genetic tests, or categories of genetic tests, requiring special treatment in relation to procedures for ordering, testing and ensuring access to genetic counselling. See Australian Law Reform Commission and Australian Health Ethics Committee, Essentially Yours: The Protection of Human Genetic Information in Australia, ALRC 96 (2003), rec 11–1, 11–5, 23–3.

[6] For example, predictive testing of minors for late onset disorders (such as Huntington’s disease) may be considered unethical.

[7] Also known as ‘gene chips’, ‘biochips’ and ‘DNA microarrays’.

[8] See Australian Law Reform Commission and Australian Health Ethics Committee, Essentially Yours: The Protection of Human Genetic Information in Australia, ALRC 96 (2003), [10.20]–[10.21].

[9] Organisation for Economic Co-operation and Development, Genetic Inventions, Intellectual Property Rights and Licensing Practices: Evidence and Policies (2002), 71.

[10] See D Nicol, ‘The Impact of Patents on the Delivery of Genetic Tests in Australia’ (2003) 15(5) Today’s Life Science 22, Table 2.

[11] See Ch 6.

[12] In the United States: US 5753441; in Australia: AU 691958, AU 686004 and AU 691331. As discussed below, Myriad has granted an exclusive licence in Australia and New Zealand relating to predictive genetic testing for breast and ovarian cancer to Australian biotechnology company Genetic Technologies Limited.

[13] See M Rimmer, ‘Myriad Genetics: Patent Law and Genetic Testing’ (2003) 25 European Intellectual Property Review 20, 21–23.

[14] In the United States: US 5705343; US 5712098; US 5753438; in Australia AU 733459. A list of United States and equivalent Australian patents associated with medical genetic testing can be found in D Nicol and J Nielsen, Patents and Medical Biotechnology: An Empirical Analysis of Issues Facing the Australian Industry (2003) Centre for Law and Genetics Occasional Paper No 6, Table 1.

[15] Australian Health Ministers’ Advisory Council Working Group on Human Gene Patents, Final Draft Report of the AHMAC Working Group on Human Gene Patents (2001), 33.

[16] A division of F Hoffmann-La Roche Ltd: Roche Diagnostics, Roche Molecular Diagnostics Patents Portfolio, <www.roche-diagnostics.com/ba_rmd/patent_list.html> at 16 June 2004. PCR is discussed further in Ch 3.

[17] J Abbot, Submission P83, 16 April 2004.

[18] J Brasch, DNA Diagnosis of Genetic Disorders in Australasia, Human Genetics Society of Australasia, <www.hgsa.com.au/labs.html> at 16 June 2004.

[19] J Abbot, Submission P83, 16 April 2004. See also M Cho and others, ‘Effects of Patents and Licenses on the Provision of Clinical Genetic Testing Services’ (2003) 5 Journal of Molecular Diagnostics 3; D Nicol and J Nielsen, Patents and Medical Biotechnology: An Empirical Analysis of Issues Facing the Australian Industry (2003) Centre for Law and Genetics Occasional Paper No 6, Table 1.

[20] In Australia, Cancer Research Centre Technologies Limited and Duke University have filed for patent protection on the BRCA2 genetic sequence. This patent application has been challenged by Myriad: M Rimmer, ‘Myriad Genetics: Patent Law and Genetic Testing’ (2003) 25 European Intellectual Property Review 20, 23.

[21] As of mid-2002, all but one Canadian province (British Columbia) had decided to continue to provide genetic testing that might infringe the patents granted to Myriad: R Gold, ‘Gene Patents and Medical Access’ (2000) 49 Intellectual Property Forum 20, 23. British Columbia resumed testing in February 2003: British Columbia Government Decision to Ignore Myriad Patent’, CanWest News Service, 16 February 2003.

[22] M Llewelyn, Intellectual Property Rights on Public Healthcare: A UK Response (2003).

[23] See R Gold, ‘Gene Patents and Medical Access’ (2000) 49 Intellectual Property Forum 20, 23.

[24] European Patent Office, ‘“Myriad/Breast Cancer” Patent Revoked after Public Hearing’, Press Release (Munich), 18 May 2004.

[25] M Cho and others, ‘Effects of Patents and Licenses on the Provision of Clinical Genetic Testing Services’ (2003) 5 Journal of Molecular Diagnostics 3.

[26] D Nicol and J Nielsen, Patents and Medical Biotechnology: An Empirical Analysis of Issues Facing the Australian Industry (2003) Centre for Law and Genetics Occasional Paper No 6, 201.

[27] Department of Human Services Victoria, Consultation, Melbourne, 3 September 2003; New South Wales Genetics Service, Consultation, Sydney, 9 September 2003; South Australian Clinical Genetics Service, Consultation, Adelaide, 16 September 2003; Western Australian Department of Health and others (healthcare issues), Consultation, Perth, 17 September 2003.

[28] Issues relating to the enforcement and licensing of gene patents are also discussed in Ch 22.

[29] Sometimes referred to as GTG’s ‘intron sequence patents’.

[30] Genetic Technologies Limited, ‘Genetic Technologies and Myriad Genetics Announce Strategic Licensing Agreement’, Press Release, 28 October 2002, <www.gtg.com.au/Announcements2002.html>. As part of this arrangement GTG granted Myriad a non-exclusive licence for the use of GTG’s non-coding patents.

[31] Genetic Technologies Limited, ‘Genetic Susceptibility Testing: A Third Progress Report’, Press Release, 22 May 2003, <www.gtg.com.au/Announcements.html>.

[32] Genetic Technologies Limited, ‘Letter from GTG to Medical and Scientific Colleagues’, Press Release, 21 July 2003, <www.gtg.com.au/Announcements.html>.

[33] See also Genetic Technologies Limited, ‘Licensing the “Non-Coding” Patents: A Third Report to the ASX’, Press Release, 2 April 2003, <www.gtg.com.au/Announcements.html>.

[34] Z Moukheiber, ‘Junkyard Dogs’, Forbes Magazine, 29 September 2003.

[35] D Nicol and J Nielsen, Patents and Medical Biotechnology: An Empirical Analysis of Issues Facing the Australian Industry (2003) Centre for Law and Genetics Occasional Paper No 6, 203.