Alphapharm Pty Ltd v H Lundbeck A/S - [2006] APO 18

ABSTRACTS OF DECISIONS
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No. 623144 in the name of H.Lundbeck A/S

Title: (+)-Enantiomer of citalopram and process for the preparation thereof

Action: Request to amend the Register under reg 10.7(1) by Alphapharm Pty Ltd; and an amendment of the Register under reg 10.7(7)

Decision: Issued 19 May 2006.
Abstract

Regulation 10.7(7): The Merck decision has taken a broad construction of what it means for goods to “contain” a substance. It is not necessary for the substance contained in the goods to be the substance that gives the goods their pharmaceutical activity. It follows that escitalopram is contained in citalopram, and the Commissioner must amend the Register under reg 10.7(7) to insert the correct extension of the term of the patent, i.e. 9 December 2012.
Merck & Co Inc v Arrow Pharmaceuticals Ltd [2003] FCA 1344; 59 IPR 226 followed.
Regulation 10.7(1): It is possible to invoke reg 10.7(1) to correct mistakes that appear on the Register as a direct result of an obvious mistake elsewhere.
Behringwerke Aktiengesellschaft’s Application (1986) 7 IPR 59 applied.
In the present case it is necessary to consider the specification, and the entries in the ARTG, in the light of the Act and decisions of the Federal Court, in order to appreciate that an error exists. The depth of consideration that is necessary is antithetical to the notion of the mistake being obvious. Obvious mistake was not established.
PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re:Patent Application No. 623144 by H.Lundbeck A/S and a request to amend the Register under reg 10.7(1) by Alphapharm Pty Ltd, and an amendment of the Register under reg 10.7(7)

BACKGROUND

Patent number 623144 (‘the patent’) is recorded in the name of H.Lundbeck A/S (‘Lundbeck’). The term of the patent has been extended under s 76 of the Patents Act 1990 (Cth) (‘the Act’), and the Register of Patents (‘the Register’) records that the term has been extended until 13 June 2014.
The Commissioner has been advised by Alphapharm Pty Ltd (‘Alphapharm’) of facts that would lead to the extension of term being recalculated to 9 December 2012. If these facts are established, then the Commissioner must amend the Register under reg 10.7(7) of the Patents Regulations 1991 (Cth) (‘the Regulations’). On the basis of the same facts, Alphapharm have requested that the Commissioner amend the Register under reg 10.7(1) (to correct an obvious mistake).
A hearing was held in Canberra on 13 April 2006 in relation to both matters. Lundbeck was represented by Ms Katrina Howard of counsel and Mr Matthew Swinn of Corrs Chambers Westgarth. Alphapharm was represented by Mr Stephen Burley of counsel and Ms Lynne Peach of Mallesons Stephen Jaques. Mr Barry Spencer of Alphapharm attended.
FACTS
The relevant facts in this case are straight forward. Citalopram is a compound belonging to the therapeutic category of selective serotonin re-uptake inhibitors. Citalopram is a racemate, meaning that its molecules exists as two mirror-image forms in equal amounts. Citalopram hydrobromide is marketed by Lundbeck under the brand name Cipramil. Cipramil was first registered on the Australian Register of Therapeutic Goods (ARTG) on 9 December 1997.
The present patent relates to the (+)-enantiomer of citalopram, commonly known as escitalopram. Claim 1 of the patent reads:
(+)-1-(3-dimethylaminopropyl)-1-(4’-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile and non-toxic acid addition salts thereof.
It is not in dispute that escitalopram is an alternative name for the compound named in full in claim 1. The specification provides a list of “exemplary” acids that form addition salts in the passage bridging page 1a and page 2. The list includes oxalic acid, hydrochloric acid and hydrobromic acid.
Escitalopram oxalate was registered on the ARTG on 16 September 2003, and is marketed under the brand name Lexapro. Escitalopram is over 100 fold more potent than citalopram.
ALPHAPHARM’S SUBMISSIONS
Alphapharm’s submissions revolve around a simple proposition: citalopram is a mixture of two enantiomers, one of which is escitalopram. Consequently, citalopram contains escitalopram, and so the goods known as Cipramil contain escitalopram.
LUNDBECK’S SUBMISSIONS
Lundbeck’s submissions were very complex, but at their core was the proposition that citalopram is a pharmaceutical substance, and that escitalopram is a different pharmaceutical substance. As a consequence citalopram is not merely a mixture of escitalopram and R-citalopram. It then follows that Cipramil does not contain escitalopram. Ms Howard also made submissions on the proper construction of s 70(5), that I will address later.
DECISION
It is necessary to understand the overall scheme of the extension of term provisions. The relevant provisions are found in ss 70 - 79A of the Act. Extensions under these provisions are limited to standard patents relating to pharmaceutical substances. Pharmaceutical substance is defined in Schedule 1 of the Act:
pharmaceutical substance means a substance (including a mixture or compound of substances) for therapeutic use whose application (or one of whose applications) involves:
(a)a chemical interaction, or physico-chemical interaction, with a human physiological system; or
(b)action on an infectious agent, or on a toxin or other poison, in a human body;
but does not include a substance that is solely for use in in vitro diagnosis or in in vitro testing
Importantly, a pharmaceutical substance can be either a single substance or a mixture of substances. The relationship between the pharmaceutical substance and the patent is specified in s 70(2)(a):
(2)Either or both of the following conditions must be satisfied:
(a) one or more pharmaceutical substances per se must in substance be disclosed in the complete specification of the patent and in substance fall within the scope of the claim or claims of that specification; …
Thus, the pharmaceutical substance must be both described and claimed in the specification. The meaning of “in substance be disclosed” was considered Bennett J in Pfizer Inc v Commissioner of Patents [2005] FCA 137; 64 IPR 547. For present purposes, it is not necessary to consider that decision.
The relationship between the pharmaceutical substance and the ARTG is specified in s 70(3):
(3)Both of the following conditions must be satisfied in relation to at least one of those pharmaceutical substances:
(a) goods containing, or consisting of, the substance must be included in the Australian Register of Therapeutic Goods;
(b) the period beginning on the date of the patent and ending on the first regulatory approval date for the substance must be at least 5 years.
This provision uses the term “the substance”. It seems clear that “the” substance is a pharmaceutical substance. Thus, the pharmaceutical substance must be contained in goods included in the ARTG. The meaning of “containing, or consisting of” was considered by Wilcox J in Merck & Co Inc v Arrow Pharmaceuticals Ltd [2003] FCA 1344; 59 IPR 226 (‘Merck’). I will return to this decision later.
Ms Howard placed weight on the fact that s 70(2) refers to the pharmaceutical substance “per se”. This has been considered by the Federal Court in a series of cases: Boehringer Ingelheim International GmbH v Commissioner of Patents [2001] FCA 647; 112 FCR 595 (‘Boehringer’), Prejay Holdings Ltd v Commissioner of Patents [2003] FCAFC 77; 57 IPR 424 (‘Prejay’) and Pharmacia Italia SpA v Mayne Pharma Pty Ltd [2006] FCA 305 (‘Pharmacia’). It is clear that for a substance to fall within s 70(2)(a) it must itself be the subject of a claim of the patent. In the present case, compliance with s 70(2) is not in dispute. Rather it is s 70(5) that is significant. I note that s 70(5) does not use the expression “per se”. It would be inappropriate to read the words “per se” into s 70(5) when they are not there, given the significant impact that these words have (as noted in Boehringer). The proper approach to the interpretation of s 70(5) is discussed below.
Where it is determined that these requirements have been satisfied, the term of the patent is extended (subject to the opposition process). The term of an extended patent is determined by s 77, and is related to the “first regulatory approval date (as defined by section 70)”. This term is defined in s 70(5) as follows:
(5)For the purposes of this section, the first regulatory approval date, in relation to a pharmaceutical substance, is:
(a) if no pre-TGA marketing approval was given in relation to the substance- the date of commencement of the first inclusion in the Australian Register of Therapeutic Goods of goods that contain, or consist of, the substance; or
(b) if pre-TGA marketing approval was given in relation to the substance- the date of that first approval.
This provision also uses the term “the substance”. Similarly to the situation with s 70(3), this also refers to a pharmaceutical substance (which satisfies both ss 70(2) and 70(3)). The first regulatory approval date relates to both registrations and listing in the ARTG (Re Pfizer Corp [2005] APO 41). Where there are several pharmaceutical substances in a patent, the relevant date for determining the extension of term is the earliest first regulatory approval date in relation to any of the pharmaceutical substances (see s 77(1)(a)).
Looking at the provisions as a whole, the approach called for is quite simple. A typical specification will disclose and claim many pharmaceutical substances (i.e. substances that satisfy s 70(2)). Of these pharmaceutical substances, several may be included in the ARTG, and some may be included in the ARTG several times (i.e. they also satisfy s 70(3)). Each of these pharmaceutical substances will have a first regulatory approval date (calculated according to s 70(5)). It is the earliest of these dates that determines the extension of term (see s 77(1)(a)).
Ms Howard submitted that for the purposes of s 70(5) it is necessary to determine the pharmaceutical substance per se that is contained in the goods included in the ARTG. To my mind this reverses the test laid down in the Act. The structure of Act shows that the term “pharmaceutical substances” is consistently used in relation to the patent, i.e. the substance must be both described and claimed in the specification. When the Act refers to the ARTG, the term used is “goods”. Goods are included in the ARTG. The relationship between the substances in the patent and the goods in the ARTG is consistently expressed in ss 70(3) and 70(5): the goods must contain, or consist of, the substance. The sole question to be determined is whether those goods contain or consist of the substance. I will return to this point later, as it is the key to the present matter.
Where the term of a patent is extended, the extended date is recorded on the Register. The power of the Commissioner to amend the Register is quite limited, and does not extend to the correction of any error in relation to extensions of term. Amendment of the Register is governed by reg 10.7, the relevant sub-regulations of which are (1) and (7):
(1)The Commissioner may, on a request being made in the approved form, amend:
(a) an entry in the Register for the purpose of:
(i)correcting a clerical error or an obvious mistake …
(7)If:
(a) an extension of the term of a standard patent for a pharmaceutical substance has been granted under section 76 of the Act; and
(b) the Commissioner becomes aware that the first regulatory approval date in relation to the pharmaceutical substance is earlier than:
(i)the date of commencement of the first inclusion in the Australian Register of Therapeutic Goods that was supplied, under subregulation 6.9(2), with the application for the extension of term; or
(ii)the date of the first approval that was supplied, under subregulation 6.10(2), with the application for the extension of term;
the Commissioner must amend the relevant entry in the Register to insert the correct extension of the term of the patent.
Lindgren J has recently found that reg 10.7(7) is valid (H.Lundbeck A/S v Commissioner of Patents [2006] FCA 163). The errors that are capable of correction under reg 10.7(7) relate to “the first regulatory approval date in relation to the pharmaceutical substance” (emphasis added). The pharmaceutical substance can only be the substance that was the basis of the extension of term (analogous to the interpretation of “the substance” above). Significantly reg 10.7(7) does not contain an equivalent to s 77(1), allowing amendment if there is an earlier date in relation to “any” pharmaceutical substance. Consequently, an amendment is required only if there is an earlier first regulatory approval date in relation to the substance which was used as the basis of the extension of term.
Regulation 10.7(7)
Regulation 10.7(7) authorises the Commissioner to amend the Register in limited circumstances. Two questions that immediately arise are:
(a)what is the pharmaceutical substance, and
(b)what is the first regulatory approval date of that substance.
In the present case the extension of term is based on the substance escitalopram. This substance is specified on the Request for Extension of Term form filed on 10 December 2003. It is not in dispute that escitalopram is described and claimed in the specification of the patent, and that it is contained in the goods known as Lexapro. The parties did not disagree that escitalopram is the relevant substance for the extension of term.
Turning to my second question, the definition of the first regulatory approval date that is given in s 70(5) is expressly limited to “for the purposes of this section”, i.e. s 70. No alternative definition is provided for the purposes of reg 10.7. Given the technical nature of this term, it is hard to see how any other definition could justifiably be used. I believe that the same definition must apply for the purposes of reg 10.7.
At this point the parties take a markedly different view of the way that the Act should be interpreted. Mr Burley argued that citalopram is a mixture of two enantiomers, one of which is escitalopram. Consequently, citalopram contains escitalopram, and so the goods known as Cipramil contain escitalopram. Ms Howard argued that escitalopram is a different substance to citalopram. Evidence was presented showing that R-citalopram has pharmaceutical effects in its own right, acting as an inhibitor of the S-enantiomer. The consequence of this submission is that citalopram is not merely a mixture of escitalopram and R-citalopram.
It is true that escitalopram is a new chemical entity, having properties different to those of citalopram. The registration of citalopram in the ARTG does not give the right to market escitalopram (except as part of the racemic mixture). It was not until goods containing escitalopram per se had been included in the ARTG that compounds of the present patent could be commercially exploited. I also recognise that the Second Reading Speech provides support for Ms Howard’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.”
However, the alternative argument advanced by Mr Burley is supported by the authority of the Federal Court in Merck. In that case a pharmaceutical substance called Mevacor was included in the ARTG. Mevacor contains the substance lovastatin, and a small amount of an impurity called lovastatin beta-hydroxy acid (LHA). Merck sought to extend the term of their patent to LHA based on the registration of Mevacor. The key to the case was whether s 70(3)(a) had been satisfied, that is whether “goods containing, or consisting of, the substance” were included in the ARTG. Wilcox J concluded (at [26] to [28]) that:
“Subsection (3)(a) of s 70 makes it a condition of extension of a patent that ‘goods containing, or consisting of, the substance must be included in the [ARTG]’. Mevacor is included in the ARTG. And the undisputed evidence of Dr Brenner is that Mevacor contains LHA. … it is irrelevant whether or not LHA itself is included in the ARTG. For s 70(3)(a) purposes, it is enough that it is contained in some other good (Mevacor) that is included in the ARTG. … LHA is present in Mevacor only in minute quantities. But I do not think that matters; s 70(3)(a) does not stipulate for any particular quantity or proportion of the substance in the registered goods.”
It is clear that the ratio derived from Merck is that provided the pharmaceutical substance is present (to some extent) in the goods that are included in 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.
Ms Howard submitted that I should not follow Merck because that case was undefended, so the judge did not have the benefit of counter submissions. Instead, the decisions of the Federal Court in Boehringer, Prejay and Pharmacia should be preferred. None of these cases directly addressed the same point as Merck. In Boehringer, a Full Court (Wilcox, Whitlam and Gyles JJ) had to consider a patent where the pharmaceutical substance was contained in a container. The court concluded that as the pharmaceutical substance, in itself, was not a thing claimed in the patent sense, it did not fall within the scope of a claim. In Prejay, another Full Court (Wilcox, Cooper and Allsop JJ) considered a patent where the claims were to a method of treatment by administering a pharmaceutical substance. The court concluded that the substance was not itself the subject of such a claim. In Pharmacia, Weinberg J considered claims to a composition of a pharmaceutical substance. The court concluded that the claim was not a method, and that the mixture was a pharmaceutical substance. It is clear from these cases that the patent must claim a pharmaceutical substance in itself, not in combination with other integers or as a part of a process. These cases did not have to deal with the question of whether the goods in the ARTG contained that substance. I consider that Merck is the most relevant decision.
My conclusion is that Merck represents the law on this point, and it is not open to me to come to any other construction. The Merck decision has taken a broad construction of what it means for goods to “contain” a substance. I cannot find support for a narrower construction in the other cases. The facts of the present case are much simpler than in Merck: citalopram is a mixture of the R and S enantiomers in equal proportions. Applying the ratio in Merck, it is immaterial that escitalopram is not responsible for all of the activity of citalopram. It is a fact citalopram is a mixture that contains escitalopram, and consequently Cipramil is goods that contain escitalopram. The first regulatory approval date for Cipramil is the first regulatory approval date for escitalopram. It follows that escitalopram has an earlier first regulatory approval date than that supplied with the application for the extension of term, and the Commissioner must amend the Register under reg 10.7(7) to insert the correct extension of the term of the patent, i.e. 9 December 2012.
Regulation 10.7(1)
Alphapharm have requested that the Commissioner amend the Register under reg 10.7(1). The Commissioner has declined to advertise that amendment (under reg 10.7(3)). The present hearing relates to whether that decision is correct. If Alphapharm are successful in this action, the amendment will be advertised and there will be the opportunity for Lundbeck to oppose the amendment. Consequently, the present action is not formally an opposition to the amendment. However, in deciding whether to advertise the amendment I must have regard to whether the amendment is allowable, since the amendment must be made if there is no opposition (reg 10.7(5)).

Regulation 10.7(1) does not limit the classes of people who may request amendment of the Register. Consequently, I accept that Alphapharm have standing under reg 10.7(1).
Obvious mistakes have often been considered in the context of mistakes in a patent specification. In this context, it has been established that
“the natural meaning of the expression ‘obvious mistake’ is that: what must be obvious is not simply that there has been some mistake but also what the mistake is and what is the correction needed”
Holtite Limited v. Jost (Great Britain) Ltd [1979] RPC 81 per Lord Diplock
Initially it must be noted that there is no obvious mistake on the face of the Register itself. However, it is possible to invoke reg 10.7(1) to correct mistakes that appear on the Register as a direct result of an obvious mistake elsewhere. In this regard I drew both parties attention to the decision in Behringwerke Aktiengesellschaft’s Application (1986) 7 IPR 59, where the hearing officer decided that the Register could be amended under reg 76 of the former Patents Regulations (the equivalent of the present reg 10.7(1)) to correct a clerical error in a document filed in connection with an application. The reasoning of that decision is equally applicable to obvious mistakes.
In the present case it is necessary to consider the specification, and the entries in the ARTG, in the light of the Act and decisions of the Federal Court, in order to appreciate that an error exists. The depth of consideration that is necessary is antithetical to the notion of the mistake being obvious. I am not satisfied that there was an obvious mistake in the request for extension of time. I refuse to advertise the amendment.
Conclusion
I direct that the Register be amended to insert the correct extension of the term of the patent, i.e. 9 December 2012.
The situation in relation is costs is unusual. Alphapharm are a party to the action under reg 10.7(1), and Lundbeck are a party to the action under reg 10.7(7). Although both actions rely on the same facts, they are separate actions proceeding ex parte. For convenience, both parties were allowed to make submissions on each action, but that does not make them parties to each action (they are more akin to an amicus curiae in relation to the other action). Given that both actions are proceeding ex parte, it is not appropriate to make an award of costs.
Dr S.D.Barker
Delegate of the Commissioner of Patents
19 May 2006
Representatives for H.Lundbeck A/S : Corrs Chambers Westgarth
Representatives for Alphapharm Pty Ltd : Mallesons Stephen Jaques