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Feature Article: Patent extensions for pharmaceutical substances: when do registered goods 'contain, or consist of' a pharmaceutical substance?
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Feature Article: Patent extensions for pharmaceutical substances: when do registered goods 'contain, or consist of' a pharmaceutical substance?

In brief: Partner Dr Trevor Davies (view CV) and Lawyer Jonathan de Ridder review recent decisions concerning the law relating to patent term extensions for pharmaceutical patents that may raise concerns for patentees seeking extension.

Summary
Background – extension of term for pharmaceutical patents
Merck & Co v Arrow Pharmaceuticals
Lundbeck v Alphapharm
Implications and discussion

Summary

In two patent decisions discussed in this article, it has been held that the 'first regulatory approval date' of a pharmaceutical substance is the first date on which goods were registered that contained any amount of the substance, in any form, regardless of the use of the goods.

The first regulatory approval date of a pharmaceutical substance is a crucial factor in determining entitlement to, and length of, any term extension for a patent claiming that pharmaceutical substance. In one of the cases discussed, a pharmaceutical substance was held to have received regulatory approval before the registration of the first product utilising the pharmaceutical substance as an active ingredient.

If this interpretation becomes settled, it could deprive some patentees of a claim to a term extension and may jeopardise term extensions already granted to other patentees.

This issue is currently before the Federal Court, which is hearing an appeal from one of the cases discussed below.

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Background – extension of term for pharmaceutical patents

Part 3 of Chapter 6 of the Patents Act 1990 (Cth) (the Act) allows for the term of patents claiming pharmaceutical substances to be extended by up to five years when certain conditions are met. Equivalent regimes are found in many other jurisdictions.

Pharmaceutical substances are seen to be a special case in patent law because their development process is often longer and more expensive than other categories of inventions. The extension of term regime is intended to provide an adequate economic incentive for businesses to invest in the development of pharmaceutical substances by extending the term of patents over substances that have taken a long time to achieve marketing approval.

The requirements for receiving an extension are set out in section 70 of the Act. An applicant must show the following.

The patent specification in substance discloses and claims either (a) a pharmaceutical substance per se or (b) a pharmaceutical substance when produced by a process using recombinant DNA technology (ss 70(2)).
Goods containing, or consisting of, the pharmaceutical substance must be included on the Australian Register of Therapeutic Goods (ARTG) (ss7 0(3)(a)), or have otherwise received regulatory approval (ss 70(3)(b)).
The period from the date of the patent to the 'first regulatory approval date' of the pharmaceutical substance must be at least five years (ss 70(3)(b)).
The patent's term must not have been previously extended (ss 70(4)).

If the above conditions are met, the patentee is entitled to a term extension of its patent. The longer it has taken to bring the pharmaceutical substance to market, the longer the available extension, subject to the five-year maximum. For a development period of 10 years or longer, the maximum five-year extension applies. For development periods of between five and 10 years, a sliding scale applies.

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Merck & Co v Arrow Pharmaceuticals

In this case¹, Merck sought a term extension for its patent over the pharmaceutical substance lovastatin β-hydroxy acid (LHA), which acts as a cholesterol-lowering agent.

In its request for an extension, Merck submitted that the requirement in ss 70(3)(a) that goods be included on the ARTG which 'contain, or consist of' the pharmaceutical substance in question – LHA – was satisfied by its cholesterol-lowering drug MERVACOR®. This was an unusual submission because the active ingredient of MERVACOR® was not LHA, but the related substance lovastatin, originally patented by a third party.

Lovastatin does not have the cholesterol-lowering properties of LHA. However, when lovastatin is ingested, the body's metabolism converts most of it into LHA. Lovastatin is therefore a 'prodrug' – an active ingredient consisting of one compound that is converted in the body to a second compound (or 'metabolite') that produces the desired medical effect. The cholesterol-lowering effect of ingesting lovastatin is greater than that of ingesting LHA due to differences in the way the body absorbs and metabolises the two substances.

Importantly, while the active ingredient in MERVACOR® is lovastatin, MERVACOR® also contained small amounts of LHA as an impurity. In opposition proceedings, the delegate of the Commissioner of Patents refused to grant Merck the term extension, finding that ss 70(3)(a) of the Act was not satisfied. The delegate found that MERVACOR® did not 'contain, or consist of' LHA as required by the Act, holding that 'the requirements of ss 70(3)(a) are not met if the relevant substance is only included in goods on the ARTG as an impurity.'²

In its Federal Court appeal of the decision of the Commisioner, Merck filed uncontested evidence that, of the 20 mg of active ingredient in MERVACOR® tablets, 0.2 per cent or 0.04mg is LHA.

Justice Wilcox allowed Merck's appeal and allowed its request for a term extension on the basis that ss 70(3)(a) was satisfied by MERVACOR®. His Honour held that:

LHA is present in Mervacor only in minute quantities. But I do not think that matters; ss70(3)(a) does not stipulate for any particular quantity or proportion of the substance in the registered goods.³

While the Merck decision was a win for the patentee, the construction of ss 70(3)(a) (and, by implication, of ss 70(5)(a)) adopted in that case could turn out to have unwelcome effects for many patentees, as became clear following a decision of the Commissioner of Patents earlier this year.

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Lundbeck v Alphapharm

This case⁴ concerned Lundbeck's patent over the pharmaceutical substance escitalopram, a selective serotonin reuptake inhibitor (SSRI), a class of drugs used to treat depression and other mental illnesses.

Lundbeck's patent on escitalopram was granted on 13 June 1989. On 16 September 2003 (or 14 years later) Lundbeck was able to begin selling a drug product containing escitalopram as the active ingredient when its drug LEXAPRO® was registered on the ARTG. Lundbeck received a five-year extension for its escitalopram patent, granted on the basis that the first regulatory approval date of escitalopram was the date that LEXAPRO® had been registered.

Alphapharm wrote to the Commissioner of Patents and submitted that the first regulatory approval date of escitalopram was not 16 September 2003, but 9 December 1997, the date on which another Lundbeck product called CIPRAMIL® had been registered on the ARTG.

The active ingredient of CIPRAMIL® is citalopram, another SSRI closely related to escitalopram. Citalopram is a racemate, a chemical consisting of two forms of molecule that are mirror images of each other, with equal amounts of each form. Escitalopram is one of the two enantiomers of the racemate citalopram, known as 'S-citalopram' (hence 'escitalopram'). The other enantiomer of citalopram is known as 'R-citalopram'.

The Delegate of the Commissioner of Patents, Dr Barker, upheld Alphapharm's submission and reduced the term of Lundbeck's escitalopram patent pursuant to Regulation 10.7(7) of the Patents Regulations 1991. Dr Barker held that the first regulatory approval date of escitalopram was the date that CIPRAMIL® had been registered. Even though the active ingredient of CIPRAMIL® was not escitalopram but citalopram, the delegate held that CIPRAMIL® 'contained, or consisted of' escitalopram in the manner required by ss 70(5)(a) of the Act because citalopram was a mixture of escitalopram and R-citalopram.

Lundbeck had argued for a different construction of the Act by submitting that escitalopram was a different pharmaceutical substance than citalopram and had different properties. The registration of CIPRAMIL® did not give the registrant the right to market escitalopram. No one could use escitalopram therapeutically until LEXAPRO® had been included on the ARTG.

Consequently, for the purposes of ss 70(5)(a) the Act, Lundbeck argued, CIPRAMIL® could not be said to 'contain, or consist of' the pharmaceutical substance escitalopram. Dr Barker quoted the following passage from Second Reading Speech for the patent term extension regime of the Act, stating that it supported Lundbeck's construction.

A new chemical entity, from which a pharmaceutical is derived, is patented early in the process. However, considerable research and testing is still required before the product can enter the market.⁵

Nevertheless, Dr Barker felt bound by Merck, summarising the construction of ss 70(5)(a) in that case as follows:

...provided that the pharmaceutical substance is present (to some extent) in the goods that are included on the ARTG, then the requisite link has been established. In particular, I note that it is not necessary for the substance contained in the goods to be the substance that gives the goods their pharmaceutical activity.⁶

Dr Barker concluded that 'Merck represents the law on this point, and it is not open to me to come to any other construction'.⁷

Lundbeck has appealed the decision of the Commissioner and the case is currently before Justice Lindgren in the Federal Court. A claim by Alphapharm for revocation of Lundeck's escitalopram patent and a cross-claim by Lundebeck alleging infringement of the same patent by Alphapharm will be heard together with Lundbeck's appeal against the Commissioner's decision on the term of its patent. The Federal Court has stayed the orders of the Commissioner and a trial is expected in April or May 2007. We await the outcome of this case with interest.

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Implications and discussion

There may be implications if the Merck and Lundbeck decisions becoming settled law. Many new medicines developed today are close chemical relatives of existing medicines. If the construction of the Act in Merck and Lundbeck becomes settled, pharmaceutical patentees should be careful when requesting an extension of a patent whenever the pharmaceutical substance claimed in that patent could be said to be 'contained' in an older medicine, even as an insignificant impurity, or as an element of another chemical that has an entirely different effect.

The construction of the Act that was adopted in Merck and followed in Lundbeck is open to a reasonable reader, and may be seen as the most direct way of reading the legislation. At this stage, it is unclear in the Lundbeck appeal whether the Federal Court will reconsider that construction. An argument can be made that the Act should be interpreted in the manner urged by Lundbeck before the Patent Office. That is, reading ss 70(3)(a) and ss 70(5)(a) in the context of the term extension regime as a whole, and in the light of Parliament's stated intentions in enacting that regime, goods registered on the ARTG only 'contain, or consist of' a pharmaceutical substance if they utilise that substance as an active ingredient.

The Federal Court decision of Lundbeck will be of interest to many players in the pharmaceutical area.

Footnotes

Merck & Co., Inc v Arrow Pharmaceuticals Ltd (2003) 59 IPR 226
Merck & Co., Inc v Arrow Pharmaceuticals Ltd [2002] APO 13 (17 April 2003) at paragraph [46]. (AAR acted for Arrow).
Merck & Co., Inc v Arrow Pharmaceuticals Ltd (2003) 59 IPR 226 at 232.
H. Lundbeck A/S v Alphapharm Pty Ltd [2006] APO 18 (19 May 2006).
Ibid at paragraph [25].
Ibid at paragraph [27].
Ibid at paragraph [29].

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Avandia® more effective than other medications for type 2 diabetes

4 December – Results from the 'A Diabetes Outcome Progression Trial' (ADOPT) demonstrated that initial treatment with Avandia® reduced the risk of monotherapy failure in people compared to other medications, including metformin and glyburide. The results were published in the New England Journal of Medicine and presented at the 19th World Diabetes Congress of the International Diabetes Federation. Avandia® was more effective in delaying the progressive loss of blood sugar control, as measured in the study by fasting plasma glucose and glycosylated haemoglobin levels. ADOPT also demonstrated that Avandia® significantly improved insulin sensitivity and reduced the rate of loss of beta-cell function.