The Australian pharmaceutical/biotechnology patent landscape is currently in a state of flux. Successfully navigating the terrain will be challenging as the sands shift on a number of fronts including:
- extension of term provisions for pharmaceutical patents – contraction and expansion in different directions;
- proposed legislative reform to align Australian patentability standards with those of other major jurisdictions; and
- a Senate Inquiry into the patentability of genes that could separate Australia from other major countries by more than its geography.
(a) Extension of patent term provisions – contracting to bypass enantiomers and expanding in the direction of devices?
H Lundbeck A/S and anor v Alphapharm Pty Ltd [2009] FCAFC 70
Summary
The Full Federal Court handed down its long-awaited decision in Lundbeck A/S and anor v Alphapharm Pty Ltd with mixed results for the patentee – a case of one step forward and two steps back.
The case relates to Lundbeck's patent for escitalopram, the (+)-enantiomer of citalopram, a pharmaceutical used in the treatment of depression. A number of issues of particular interest to the pharmaceutical sector were addressed. Specifically, it was found that:
- an enantiomer of a "known" racemate may be patentable;
- inclusion of a racemate on the Australian Register of Therapeutic Goods (ARTG) is considered inclusion of its constituent enantiomers – meaning that in many cases the patent covering the enantiomer may not be eligible for an extension of term; and
- a claim to a dosage form may be invalid if it specifies a range of quantities of active ingredient outside those shown by the evidence to be effective.
Enantiomer patent valid
Chemical compounds having the same atoms can exist in two (and sometimes many) different forms depending on the spatial arrangement of the atoms. When two forms of the compound are non-superimposable mirror images of each other (like a person's left and right hand), they are called enantiomers. A mixture of enantiomers is a racemate. In many cases only one enantiomer of a pharmaceutical compound is active.
Lundbeck's patent covering the racemate citalopram has expired. As indicated above, the present decision relates to Lundbeck's patent covering one of the two enantiomers of citalopram, the (+)-enantiomer, which is the active form.
The Court was required to determine whether claim 1, directed to the (+)-enantiomer, was anticipated by the disclosure of the racemate citalopram (which comprised both enantiomers). Bennett and Emmett JJ took different approaches to the construction of claim 1. Emmett J took a somewhat literal approach and found that nowhere in claim 1 was it specified that the enantiomer was "substantially pure" or "substantially separated from" the (-)-enantiomer. Moreover, he indicated that it would have been possible to include these qualifying words into claim 1. He went on to find that to read into claim 1 such qualifying words is impermissible as a matter of construing the clear and unambiguous words used by Lundbeck. Accordingly, he concluded, claim 1 does not require that the (+)-enantiomer, be separate from the (-)-enantiomer. In view of this construction, he found that the disclosure of citalopram anticipated claim 1 and dependent claims.
Bennett J (with whom Middleton J agreed) took a more purposive approach to the construction of claim 1. She noted that the patent is entitled "(+)-enantiomer of citalopram and process for the preparation thereof" and that it discloses a method for the preparation of the isolated (+)- enantiomer. Accordingly, Bennett J found that the skilled addressee would construe claim 1 as referring to the isolated (+)-enantiomer. However, she did not agree with the primary judge that claim 1 should be construed to limit the purity of the (+)-enantiomer to at least 95% purity.
In relation to determining the novelty of claim 1, Bennett J indicated that there is no anticipation unless the disclosure of the racemate citalopram was, to the skilled addressee, a disclosure of the (+)-enantiomer. In this regard, she indicated that there were no "clear and unmistakable directions" to obtain the enantiomers and, as such, the prior citalopram patent was found not to anticipate the claims of the escitalopram patent.
Extension of term revoked
Lundbeck's escitalopram patent had been extended for five years, until 13 June 2014, under the Australian provisions for extension of patent term.
A number of criteria must be fulfilled in order to render a patent eligible for an extension of term. One requirement is that the claims of the patent must define a pharmaceutical substance per se. Another is that goods containing, or consisting of, the pharmaceutical substance per se must be included on the ARTG. In addition, an application for an extension of term must be made within six months of (a) the date of first inclusion of the relevant product on the ARTG; or (b) the date of grant of the patent – whichever of the two dates is the later.
Lundbeck applied for an extension of term of their patent on 22 December 2003 based on the claims to escitalopram (a pharmaceutical substance per se) and inclusion of its product Lexapro (escitalopram) on the ARTG on 16 September 2003. However, the racemate Cipramil (citalopram) was included on the ARTG on 9 December 1997. As such, the critical issue was whether the registration of Cipramil could be considered the first inclusion of the enantiomer escitalopram on the ARTG for the purposes of the relevant section of the Patents Act (s70(3)).
The Court found that there is no requirement to consider either the effectiveness or the purity of the pharmaceutical substance contained in the goods included on the ARTG. Moreover, there is no suggestion from the words of s 70(3) that the relevant "goods" could, or must, include no more than one pharmaceutical substance. It was found that citalopram contains both (+) and (-) enantiomers in equal proportions and, as such, satisfies s70(3) in relation to the inclusion of escitalopram on the ARTG. Accordingly, it was held that the Cipramil registration date was the date of first inclusion of escitalopram on the ARTG. Consequently, the application for extension of term was made out of time i.e. well beyond the six month deadline after registration of Cipramil, and the patent was not entitled to an extension of term. The expiry date of the patent was therefore constricted to 13 June 2009.
Dosage form invalid for want of utility
At first instance, Lindgren J had held that a claim to a dosage form comprising escitalopram in an amount of 0.1 to 100 mg was invalid for want of utility since the evidence showed that 5 to 40 mg was the minimum to maximum effective range. His Honour accepted that 100 mg was not harmful. The Full Federal Court found that Lundbeck had not established any error on the part of the primary judge and, consequently, his ruling on this point stood.
Ramifications for patentees
In light of this decision, patentees holding rights to Australian patents covering enantiomers may feel secure in the knowledge that their patents are not going to be held invalid based only on disclosure of the racemate. It should be noted, however, that whether an enantiomer patent is ultimately found to be valid will depend on the precise nature of the disclosure of the racemate and whether all other criteria for patentability – including inventive step – are fulfilled.
Further, patentees holding enantiomer patents should note that any patent term extensions already obtained may be vulnerable (see below re appeal). This is likely to lead to generic manufacturers attempting to enter the market immediately upon expiry of the original term of the enantiomer patent. On the other hand, this increased vulnerability may be a point of negotiation for licensees considering terms and conditions.
Claims to dosage forms should be carefully drafted to ensure that they cover only useful dosages or, at the very least, a dependent claim should be included which is restricted to a narrow range of doses which the patentee can confidently argue are effective.
Next
Lundbeck have applied for a stay of the order, pending an application for special leave to the High Court. This may provide an interesting sequel.
NV Organon [2009] APO 8 (29 May 2009) and LTS Lohmann Therapie-Systeme AG and Schwarz Pharma Limited (2009) APO 16 (21 August 2009)
Summary
In the past, the case law very clearly indicated that patents covering medical devices are not eligible for an extension of term (Boehringer Ingelheim International GmbH v Commissioner of Patents (No 2) 2001 FCA 647). Recently, however, the Courts have been interpreting the legislation to include patents protecting inventions that look increasingly like medical devices. In NV Organon, the Court concluded that a patent covering a vaginal ring was eligible for an extension of term.
The Decision in NV Organon
One of the conditions required for a patent to be eligible for an extension of term is that the patent must include a claim to a pharmaceutical substance per se. The value of pharmaceutical patents has resulted in applications for extension of term that push the boundaries of what is encompassed by the term "pharmaceutical substance per se". This recent Patent Office decision appears to indicate that certain drug delivery devices are now eligible for an extension of term – a significant shift in direction.
The patent in question relates to NUVARING, a vaginal ring adapted for the slow release of steroidal mixtures for the purpose of contraception or hormone replacement therapy. Specifically, a steroidal mixture is contained in a thermoplastic polymer core over which is laid a permeable thermoplastic skin. The question considered was whether NUVARING is a pharmaceutical substance per se.
In arriving at the decision, the deputy Commissioner was cautious in interpreting the term "substance" in a way that would exclude innovations in the pharmaceutical sector. Account was also taken of the purpose of the extension of term scheme i.e. to compensate patentees that were unable to take advantage of the monopoly conferred by the patent due to regulatory approval requirements.
Expert witness testimony indicated that the steroidal components are mixed with, and necessarily diffuse through, the thermoplastic materials in the core and the skin regions of the device. As such, it was held that the product as a whole exhibits a level of integration between the component parts. Such an arrangement was considered to be a characteristic of a pharmaceutical substance rather than a substance combined with another element. Accordingly, the extension of term was allowed.
This decision suggests (or confirms) that eligibility for an extension of term depends on a degree of "interaction" between component parts. While that might have appeared to open the extension of term door for devices such as impregnated polymer implants and possibly transdermal patches, the decision contrasts with that in the more recent case, LTS Lohmann and Schwarz, referenced above.
In this latter case, a request for an extension of term of the patent covering a transdermal patch for delivery of a receptor agonist to treat Parkinson's syndrome was rejected. The patch comprised a polymer matrix containing the active ingredient, an inert backing layer and a protective layer. The Patent Office found that the product as claimed did not fall within the definition of a "pharmaceutical per se" since the protective layer had to be removed before use and the product was consequently a pharmaceutical substance in combination with a separate integer.
Thus, the battle for extensions of term for patents covering medical devices continues.
(b) Proposed legislation reform to align Australian patentability standards with those in other major jurisdictions
In March 2009 IP Australia, the Australian Patent Office, issued a discussion paper entitled: "Getting the balance right" ( http://www.ipaustralia.gov.au/pdfs/news/ip_reforms_balance.pdf) in which it called for submissions in relation to patentability standards in Australia.
Specifically, it is suggested that current Australian patentability standards are set lower than our major trading partners. Accordingly, the proposed reforms are directed at raising patentability standards to better align Australian standards with standards in other major jurisdictions.
Essentially, precedent law in Australia has developed such that only one example of an invention falling within the scope of the claims is sufficient to provide basis for a claim covering significantly more subject matter than the example. Unlike other countries, eg. the US, there is no requirement to show examples of the invention across the whole scope of the claim.
Moreover, under Australian law, the judicially affirmed test for inventive step is: "would the skilled person be led directly as a matter of course to try a particular approach with a reasonable expectation of success?" In contrast, in Europe, the question to be asked in determining obviousness is: "would the invention have been obvious to try with a reasonable expectation of success?". It is clear that the difference in these tests means that in Australia an invention is more likely to be deemed inventive than in Europe and consequently more patents, and patents with broader scope, will be granted. Interestingly, while the threshold for inventiveness falls in Australia, it has been raised in the US (KSR International Co v Teleflex Inc – (2007) 75 IPR 434).
In addition, in order for a document to be considered when assessing inventive step in Australia, it must be a document that the skilled addressee could reasonably be expected to have "ascertained, understood and regarded as relevant". In some cases, and in one controversial case in particular, Commissioner of Patents v Emperor sports Pty Ltd (2006) 225 ALR 407, this test can result in a document being excluded that would otherwise have been highly relevant to the case.
It is proposed to:
Amend s40 of the Act to:
introduce descriptive support requirements analogous to those applied in other jurisdictions including that the whole scope of the claimed invention be enabled and that the description provide sufficient information to allow the skilled addressee to perform the invention without undue experimentation.
Amend s40 and s102 and of the Patents Act to:
explicitly indicate that the requirement for full description is met if the description of the claimed invention was sufficient at the filing date to allow the skilled addressee to perform the invention without undue experimentation.
Amend reg 3.12(1)(b) of the Patent Regulations to:
replace the 'fair basis' requirement for establishing the priority date of claims with a descriptive support requirement analogous to those applied in other jurisdictions, and to that proposed for s40
Amend s7(3) of the Patents Act to:
remove the requirement that prior art information for the purpose of inventive step must be such that a person skilled in the art could be reasonably expected to have been ascertained, while retaining the requirements that prior art be understood and regarded as relevant.
Revise the inventive step test to a test where the claimed invention is obvious if it was 'obvious for the skilled person to try a suggested approach, alternative or method with a reasonable expectation of success'.
Needless to say, the introduction of any major legislative changes could significantly alter the Australian patent landscape. Moreover, history tells us that legislation is not always interpreted by the Courts as apparently intended and, as such, it would be wise to brace oneself for a period of much uncertainty should the changes proceed.
(c) Senate Inquiry into gene patenting
It is somewhat ironic that, on the one hand the proposed IP legislation reform aims to align Australian standards with standards of our major trading partners, while a current Senate inquiry into the patenting of genes potentially threatens to alienate Australian patent practice from the rest of the world (isolating us in more than just the geographic sense). The inquiry raises substantial issues for the pharmaceutical and medical technology sectors.
The inquiry resulted from anxiety raised last year when a Melbourne-based company, Genetic Technologies, which held an exclusive license to conduct tests for determining susceptibility to breast cancer based on identification of mutations in the BRCA-1 and BRCA-2 genes, decided to assert their rights and charge licensing fees. The resulting potential increase in breast cancer testing costs resulted in a "front-page outcry". Although Genetic Technologies, ultimately backed down, the scare motivated Senator Bill Heffernan to secure an inquiry by the Senate's community affairs committee into the patentability of genes.
The terms of reference for the inquiry are very broad and cover the impact of granting patents in Australia over human and microbial genes and non-coding sequences, proteins, and their derivatives (including these materials in an isolated form). In particular, the inquiry will:
(a) consider the impact that granting of such patents has had, is having, and may have had, on:
(i) the provision and costs of healthcare,
(ii) the provision of training and accreditation for healthcare professionals,
(iii) the progress in medical research, and
(iv) the health and wellbeing of the Australian people;
(b) identifying measures that would ameliorate any adverse impacts arising from the granting of patents over such materials, including whether the Patents Act 1990 should be amended; and
(c) consider whether the Patents Act 1990 should be amended so as to expressly prohibit the grant of patent monopolies over such materials.
Perhaps predictably, submissions to the inquiry appear to follow one of two arguments: (a) that genes are naturally occurring substances and should not be patented; and (b) that without sufficient return on a research investment, there would be no identification of the use of genes that would lead to, for example, diagnostic tests and treatment of disease - in other words the argument is that there is a link between patenting and innovation.
There are some that would argue that the inquiry is focused on the wrong area and that it is the use and enforcement of patent rights rather than the patent rights themselves that create the barriers to, for example, the use of gene sequences for healthcare purposes.
The Committee reports in November and their recommendations will no doubt be eagerly awaited.
Conclusion
In some areas, the Australian patent landscape is becoming as unpredictable as our weather patterns. As can be seen from the examples provided above, careful crafting of patent claims will be required to ensure that the pitfalls we are aware of, and potentially those yet to become apparent, are avoided.
We look forward to reporting further developments in this region.
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