Warner-Lambert Company LLC v Apotex Pty Ltd

JUDGE: ALLSOP CJ, JAGOT & NICHOLAS JJ DATE OF ORDER: 19 may 2014 WHERE MADE: SYDNEY

The appellants by their Counsel give to the Court the following undertaking jointly and severally: (a) to submit to such order (if any) as the Court may consider to be just for the payment of compensation, to be assessed by the Court or as it may direct, to any person, whether or not a party, adversely affected by the operation of the interlocutory order set out below (with or without variation) thereof; (b) to pay the compensation referred to in (a) above to the person there referred to; and (c) to notify the respondent's solicitors promptly if the fifth appellant's accounts record a net asset position of less than $20 million.

1. The appeal be allowed.
2. Orders 2 and 3 made by the primary judge on 14 March 2014 be set aside.
3. Until the determination of proceeding number NSD 763 of 2013 between the appellants and the respondent (the proceeding) or further order of a Judge of the Court, the respondent, whether by it servants, agents or otherwise, be restrained from supplying or offering to supply in Australia any of the following products: (a) Apotex-Pregabalin pregabalin 300mg capsule blister pack (ARTG ID 193289); (b) Apotex-Pregabalin pregabalin 150mg capsule blister pack (ARTG ID 193286); (c) Apotex-Pregabalin pregabalin 75mg capsule blister pack (ARTG ID 193284); (d) Apotex-Pregabalin pregabalin 25mg capsule blister pack (ARTG ID 193280); (e) any other product containing pregabalin which is indicated for "adjunctive therapy in adults with partial seizures with or without secondary generalisation" (or any substantially similar indication) but is not indicated for the treatment of neuropathic pain (or any sub-category of neuropathic pain).
4. The costs of: (a) the interlocutory application heard by the primary judge; (b) the application for leave to appeal; and (c) the appeal, be the appellants' costs in the proceeding.
5. Order 4 hereof be suspended for a period of 21 days.
6. Any party wishing to apply for a costs order different to order 4 hereof may file and serve a written submission (limited to 2 pages in length) within 7 days.
7. Any party wishing to reply to any such written submission is to file and serve a written submission in reply (limited to 2 pages in length) within 14 days. Note: Entry of orders is dealt with in Rule 39.32 of the Federal Court Rules 2011.

IN THE FEDERAL COURT OF AUSTRALIA NEW SOUTH WALES DISTRICT REGISTRY GENERAL DIVISION NSD 287 of 2014

JUDGE: ALLSOP CJ, JAGOT & NICHOLAS JJ DATE: 19 may 2014 PLACE: SYDNEY

INTRODUCTION 1 This is an appeal against a judgment of a judge of this Court refusing the appellants' application for an interlocutory injunction restraining the respondent from infringing Australian Patent No 714980 (the pain patent) by (inter alia) supplying to pharmacists certain products the active ingredient of which is pregabalin. The pain patent relates to methods of use for pregabalin and related compounds in the treatment of pain including, but not limited to, neuropathic pain. There is no dispute that claim 1 catches the use of therapeutically effective amounts of pregabalin in the treatment of pain. The pain patent is due to expire on 16 July 2017. 2 The primary judge's reasons are at Warner-Lambert Company LLC v Apotex Pty Ltd [2014] FCA 241 (the interlocutory judgment). Leave to appeal against the primary judge's order refusing the interlocutory relief sought by the appellants was granted by order made on 9 April 2014. 3 Although his Honour refused an interlocutory injunction in the terms sought, he did grant an interlocutory injunction (the pain injunction) restraining the respondent from (inter alia) supplying any product containing pregabalin which is indicated for the treatment of neuropathic pain in adults or any substantially similar indication with or without any other indication. This order was not opposed by the respondent and was in a form proposed by it and to which it was apparently willing to submit, subject, of course, to the appellants providing the usual undertaking as to damages. 4 The primary judge was not satisfied that the appellants had demonstrated a prima facie case for the additional interlocutory relief they sought restraining the respondent from supplying any product containing pregabalin which is indicated for the treatment of seizures and that, even if they had, he considered that their case was at best a weak one. His Honour said that if he was wrong in concluding that the appellants had failed to establish a prima facie case or in holding that the case was at best weak, the balance of convenience in any event favoured the refusal of the application for the additional interlocutory relief. 5 We consider that the primary judge erred in his assessment of the existence and strength of the prima facie case, which necessarily affected his assessment of the balance of convenience. We have therefore considered for ourselves whether the additional interlocutory relief sought by the appellants should be granted. For reasons which follow, we consider that there should be an interlocutory injunction although not in the precise form sought by the appellants.

BACKGROUND 6 The appellants are members of the Pfizer group of companies (the Pfizer group). The first appellant (Warner-Lambert Co) is the owner of the pain patent. The fifth appellant (Pfizer Australia), said to be Warner-Lambert's exclusive licensee, markets and sells a pharmaceutical product called Lyrica™ (Lyrica) which contains pregabalin as its active ingredient. The primary judge accepted that Lyrica is one of the Pfizer group's leading pharmaceutical products and its second biggest product by revenue in Australia. For convenience, unless it is necessary to distinguish between the two, we shall refer to Warner-Lambert Co and Pfizer Australia collectively as Warner-Lambert. 7 Pfizer Inc, the ultimate parent of the Pfizer group, is a co-owner (with Northwestern University) of Australian Patent 677008 (the seizure patent) for (inter alia) the use of pregabalin in the treatment of seizures. The seizure patent is due to expire on 18 May 2018. 8 Since 13 April 2005 Lyrica has been registered on the Australian Register of Therapeutic Goods (ARTG) for use for the treatment of neuropathic pain in adults (neuropathic pain indication) and as adjunctive therapy in adults with partial seizures with or without secondary generalisation (seizure indication). Pfizer Australia is the sponsor of each of those registrations. Given the scope of the ARTG registrations, Lyrica cannot be advertised for any other indication: see s 22(5) of Therapeutic Goods Act 1989 (Cth). 9 Lyrica is manufactured and sold by Pfizer Australia in capsule form containing 25mg, 75mg, 150mg and 300mg dosages. Pfizer Australia promotes the sale of Lyrica in Australia for the neuropathic pain indication, but not for the seizure indication. 10 On 19 September 2012 Apotex obtained ARTG registrations for various pharmaceutical products containing pregabalin as the active ingredient. These registrations were limited to the neuropathic pain indication and the seizure indication, and were obtained on the basis that the products are bioequivalent to Lyrica. The ARTG registrations obtained by Apotex were for products referred to as Apotex-Pregabalin (Apotex-Pregabalin) and various other products referred to as APO-Pregabalin, Terry White Chemists Pregabalin and ChemMart Pregabalin. The registrations for Apotex-Pregabalin include (but are not limited to) 25 mg, 75 mg, 150 mg and 300 mg capsules. The registrations for APO-Pregabalin, Terry White Chemists Pregabalin and ChemMart Pregabalin also include (but are not limited to) 25 mg, 75 mg, 150 mg and 300 mg capsules. 11 On 1 March 2013 Lyrica was listed on the Schedule of Pharmaceutical Benefits (SPB) for the treatment of neuropathic pain refractory to treatment with other drugs. This means that Lyrica is only available under the Pharmaceutical Benefits Scheme (PBS) at subsidised prices if it is to be used in the treatment of neuropathic pain which is not satisfactorily controlled by other medications. 12 The seizure patent and the pain patent were the subject of a revocation proceeding (the revocation proceeding) commenced by Apotex on 8 May 2013. In so far as the challenge to the validity of the seizure patent was concerned, the proceeding was resolved on or about 23 October 2013 by a partial discontinuance which occurred by consent, and on terms that the parties (which included Northwestern University) agreed would be kept confidential. Since that time, the revocation proceeding has been solely concerned with the pain patent. 13 The registrations for Apotex-Pregabalin 75 mg, 150 mg and 300 mg were amended on 9 October 2013 at Apotex's request to confine the registration to the seizure indication. The registration for the 25 mg product was not amended until late February 2014. The sole indication for which Apotex-Pregabalin is now registered on the ARTG is as an "adjunctive therapy in adults with partial seizures with or without secondary generalisation". 14 Apotex served most of its evidence in chief in the revocation proceeding on 14 February 2014. On the same date Apotex wrote to Warner-Lambert indicating that Apotex intended to launch Apotex-Pregabalin in 25 mg, 75 mg, 150 mg, and 300 mg dosages for the seizure indication only on or after 14 March 2014. In giving one month's notice of the launch, Apotex was fulfilling the requirements of an undertaking that it had given to Warner-Lambert on 21 December 2012. 15 On 21 February 2014 Apotex served the balance of its evidence in chief in the revocation proceeding. On the same date Warner-Lambert commenced their proceeding (the infringement proceeding) against Apotex for infringement of the pain patent seeking both final and interlocutory relief. 16 On 25 February 2014 Apotex notified Warner-Lambert that Apotex intended to apply for PBS listing of its other pregabalin products (ie. APO-Pregabalin, Terry White Chemists Pregabalin, and ChemMart Pregabalin) and that it intended to start taking orders for such products in May 2014. According to the letter from its solicitors, Apotex had already filed an application to have the ARTG registrations for these products amended to cover the following indications: (i) neuropathic pain in adults that is associated with diabetic peripheral neuropathy and post-herpetic neuralgia; and (ii) seizures. In the same letter Apotex advised that it intended to apply for PBS listing of these products before 28 March 2014 with effect from 1 August 2014. The next day Warner-Lambert informed Apotex that they intended to seek interlocutory relief in relation to that conduct. 17 On 4 March 2014 Apotex notified Warner-Lambert that, subject to Warner-Lambert providing the usual undertaking as to damages, Apotex would not oppose an interlocutory injunction relating to any of the Apotex products referred to in Warner-Lambert's amended statement of claim apart from Apotex-Pregabalin. At the same time, Apotex made clear that it still opposed any injunction in relation to Apotex-Pregabalin. 18 The appellants' application for interlocutory relief was heard by the primary judge sitting as duty judge on 13 March 2014. As previously mentioned, the pain injunction was granted on 14 March 2014. Because APO-Pregabalin, Terry White Chemists Pregabalin and ChemMart Pregabalin are indicated for neuropathic pain, the pain injunction prevents Apotex from supplying any of these products unless the registrations for these products are amended to exclude the neuropathic pain indication. 19 Further, while Apotex remains bound by the pain injunction, it cannot obtain PBS listing of Apotex-Pregabalin for use in the treatment of neuropathic pain. This is significant because, in the absence of such a listing, Apotex-Pregabalin cannot be supplied to patients presenting a PBS prescription for pregabalin (whether referred to in the prescription as Lyrica or pregabalin) unless the PBS prescription is converted to a non-PBS prescription (ie. a private prescription) so that patients might be supplied with Apotex-Pregabalin outside the PBS. 20 The evidence before the primary judge indicated that if Apotex-Pregabalin is supplied to pharmacists at the price levels referred to in the evidence of Mr Millichamp (Apotex's managing director) there would be no financial incentive for pharmacists to supply Apotex-Pregabalin to patients presenting PBS subscriptions by converting them to private prescriptions. 21 The possibility that Apotex might at some point reduce its prices below the levels referred to by Mr Millichamp in order to capture a share of the PBS market for Lyrica is a matter that does not appear to have featured in Warner-Lambert's submissions to the primary judge. In the circumstances, the focus of attention at the hearing before the primary judge (at least by the time final submissions were made) was on the damage that might be suffered by Warner-Lambert if pharmacists supplied Apotex-Pregabalin in place of Lyrica when filling non-PBS prescriptions (ie. private prescriptions) for Lyrica for any pain related indication. 22 There was no issue raised before the primary judge as to the validity of the pain patent. Nor was there any issue before the primary judge that if a person administers a therapeutically effective amount of pregabalin for the treatment of pain then that person would infringe claim 1 of the pain patent.

SECTION 117 23 Section 117(1) and (2) of the Patents Act 1990 (Cth) (the Act) provides: (1) If the use of a product by a person would infringe a patent, the supply of that product by one person to another is an infringement of the patent by the supplier unless the supplier is the patentee or licensee of the patent. (2) A reference in subsection (1) to the use of a product by a person is a reference to: (a) if the product is capable of only one reasonable use, having regard to its nature or design - that use; or (b) if the product is not a staple commercial product - any use of the product, if the supplier had reason to believe that the person would put it to that use; or (c) in any case - the use of the product in accordance with any instructions for the use of the product, or any inducement to use the product, given to the person by the supplier or contained in an advertisement published by or with the authority of the supplier. The word "supply" is defined in Sch 1 of the Act to include (inter alia) supply by way of sale and offer to supply by way of sale. 24 Warner-Lambert's case for an interlocutory injunction was explicitly founded upon s 117(1) and s 117(2)(b) of the Act. No reliance was placed upon s 117(2)(a) or (c). The strength of Warner-Lambert's case had to be assessed on that basis. There are two other points that should be emphasised. 25 First, the application for interlocutory relief was essentially in the nature of an application for quia timet relief. It was not suggested that Apotex had in fact supplied or offered to supply any Apotex-Pregabalin, and there cannot be actual (as opposed to threatened) infringement under s 117 until there has been a supply or an offer to supply. Secondly, the interlocutory injunction sought by the appellants went much further than the pain injunction did and, if granted, would have prevented Apotex from making, importing or supplying, or keeping for the purposes of supply, Apotex-Pregabalin regardless of the particular indication for which it might be supplied. In particular, the interlocutory injunction sought by Warner-Lambert would have prevented Apotex from supplying Apotex-Pregabalin for the treatment of seizure related conditions (the seizure market) and any other uses which might not infringe the pain patent. 26 Before the primary judge and on appeal, Warner-Lambert relied upon the decision of the Full Court in Generic Health Pty Ltd v Otsuka Pharmaceutical Co Ltd (2013) 100 IPR 240. That decision related to an application for leave to appeal against the grant of an interlocutory injunction expressed in broad terms (much like the interlocutory injunction sought in this case) that restrained the respondent from supplying pharmaceutical products which were capable of both infringing and non-infringing uses. The Full Court concluded that the requirement under s 117(2)(b) that the supplier have "reason to believe" involved an objective test. Bennett J stated the effect of s 117(2)(b) succinctly at [83]: … If the supplier had reason to believe that the supplied product would be put to the infringing use, then supply for any use of the product, being a non-staple commercial product, is an infringement, even if the use for which it is actually supplied is a non-infringing use. 27 Because it was not suggested by Apotex that pregabalin is a "staple commercial product" within the meaning of s 117(2)(b), the question arising under s 117 was whether Warner-Lambert made out a prima facie case that Apotex has reason to believe that Apotex-Pregabalin would be supplied by pharmacists to patients for the treatment of pain. 28 In its submissions to the primary judge Warner-Lambert disclaimed any suggestion that Apotex was deliberately seeking to encourage pharmacists to substitute Apotex-Pregabalin for Lyrica as a pain indicated treatment. Rather, it was submitted that given the small size of the seizure market, which Senior Counsel for Warner-Lambert described as "practically non-existent", Apotex's pricing strategy, even if directed at capturing a share of the seizure market, would inevitably impact the rest of the non-PBS prescription market as well, with the result that Apotex would gain significant market share across the whole of the non-PBS market for pregabalin. Thus, Warner-Lambert's case for the additional interlocutory relief sought was that, given the seizure market is practically non-existent, Apotex should be taken to have reason to believe that pharmacists would supply Apotex-Pregabalin to patients for pain relief.

Prima facie case 29 The primary judge provided three reasons why in his view Warner-Lambert had not established a prima facie case for the additional interlocutory relief they sought. 30 The first reason was that Warner-Lambert had not made good the claim that there was essentially no market in Australia for pregabalin for the seizure indication. In support of this his Honour pointed to the following: Pfizer Australia's 2005 application for a PBS listing for Lyrica in relation to seizures; ambiguity in the prescribing data relied upon by Mr Dimopoulos (the head of Pfizer Australia's cardiovascular and pain therapy unit) in support of his evidence that Lyrica is rarely prescribed for seizures; the approved product information for Lyrica which "goes to some lengths to describe the seizure indication"; Apotex's own assessment that there is a viable non-PBS market for the use of pregabalin in the treatment of seizures. 31 The second reason why the primary judge considered that Warner-Lambert had not made out a prima facie case was that Warner-Lambert had not provided any evidence that shows the extent, if any, of pain indications that are outside the neuropathic pain indication refractory to treatment with other drugs (ie. the only indication for which Lyrica is listed on the PBS) that are also within the claims of the pain patent. His Honour referred to this as the "non-PBS pain market" and said (at [71]) that "[o]n the current evidence, the Court cannot reliably assess the size of the non-PBS pain market." 32 The third reason referred to by the primary judge related to what his Honour called "the Apotex promotional materials" which is the expression used by Mr Millichamp to describe such materials. These materials were: A pro forma letter to prescribers (which we were told Apotex proposed sending to all medical practitioners in Australia) headed "IMPORTANT INFORMATION WHEN PRESCRIBING pregabalin" (the letter to doctors). A pro forma letter to pharmacists (which we were told Apotex proposed sending to retail pharmacists) headed "IMPORTANT INFORMATION WHEN DISPENSING pregabalin" (the letter to pharmacists). A circular headed "APOTEX PRODUCT LAUNCH APOTEX-pregabalin" (the Apotex-Pregabalin circular). 33 The primary judge said of the Apotex promotional material at [72]-[73] of his reasons: [72] Thirdly, I consider that the Apotex promotional materials, including the revised letters to be sent to medical practitioners and pharmacists, contradict the applicants' claim that Apotex has the requisite belief for the purposes of ss 117(1) and (2)(b). These materials give particular prominence to the fact that the Apotex Products are not indicated for the treatment of neuropathic pain and are not listed on the PBS. The letters expressly state that, unlike Lyrica, the Apotex Products are not indicated for the treatment of neuropathic pain. Moreover, prescribers will be informed that, when prescribing the Apotex Products for the treatment of seizure disorders, that indication should be shown on the prescription. And pharmacists will be informed that, if the prescription does not specify the indication for which pregabalin has been prescribed, or if it includes a PBS authority indication, they should not offer the Apotex Products to patients. It should also be noted the approved product information for the Apotex Products deals exclusively with their use for the treatment of epilepsy and seizures, not pain. [73] Relying on Dr Jackson's evidence to the effect that the letters would have no impact on potential brand substitution, the applicants argued that the Court should find that pharmacists will not be deterred from substituting the Apotex Products based upon their knowledge of their bioequivalence with Lyrica. I do not accept that argument, which is unsupported by any evidence and is based on mere speculation and assertion ... 34 His Honour's conclusion on what he referred to as the "critical issue" appears most clearly at [74] of the reasons. His Honour said: [74] The critical issue for the purposes of ss 117(1) and (2)(b) is whether the applicants have established a prima facie case that Apotex has the requisite reason to believe. In my opinion, the contents of the promotional materials and proposed letters, when coupled with the narrowed ARTG registered indication and approved product information, provide strong evidence which is inconsistent with the applicants' claims. The in principle significance of such "emphatic instructions" was emphasised in Sanofi at [304] per Crennan and Kiefel JJ in the context of s 117(2)(b). In my opinion, in this particular context, any general knowledge which pharmacists have about the bioequivalence of the relevant products will not be sufficient to displace such express and emphatic statements. The position might be different if there was evidence indicating that, despite those materials, Apotex was taking steps to encourage substitution of the Apotex Products in circumstances which would infringe the Pain Patent. But that is not the case at present.

The balance of convenience 35 On the balance of convenience the primary judge said at [77] and following that it favoured Apotex essentially because: it would be easier to calculate Pfizer Australia's loss in an action for damages for infringement of the pain patent rather than to calculate Apotex's loss on the usual undertaking as to damages; Apotex had sought to "clear the way" of both the pain patent and the seizure patent; many of the matters raised by Mr Dimopoulos in his affidavits as to the harm that Pfizer Australia would suffer if the interlocutory relief sought was not granted turned on the likelihood that infringement would occur; restraining Apotex from supplying Apotex-Pregabalin would deprive seizure patients of a choice of products and at a potentially cheaper price which would be contrary to the public interest. 36 On the question of whether it was desirable to maintain the status quo pending final determination of the proceeding, the primary judge said that he did not consider this was a factor that should be given much weight, particularly given the weakness of Warner-Lambert's case under s 117(1) and (2)(b) and the currently available evidence.

THE NOTICE OF APPEAL 37 The notice of appeal includes 12 grounds. Ground 1 asserts that the primary judge erred in concluding that there was no prima facie case or, alternatively, at best a weak case. Grounds 2-10 identify particular errors which the primary judge is said to have made that led to this conclusion. Grounds 11 and 12 are concerned with the balance of convenience. They assert: 11. The primary judge erred in failing to find that the balance of convenience strongly favoured the grant of an injunction. The primary judge should have found: (a) that there was a strong prima·facie case; (b) that preservation of the status quo was appropriate; (c) that it was inappropriate for the Respondent to try to launch its product before successfully concluding its claim for revocation; (d) that the Applicants would suffer irreparable harm were an injunction not to be granted; (e) that the loss of sales to the Respondent as a result of an injunction would be insignificant and in any event quantifiable; (f) that the Respondent's preparedness to submit to an injunction against supplying its "pain" product suggested the appropriateness of the further injunction sought; and (g) that the public interest favoured the grant of the injunction. 12. The primary judge erred in finding that Generic Partners Pty Ltd would be unable to enter the pregabalin market. Generic Partners Pty Ltd is, like Apotex, a supplier of generic medicines.

THE EVIDENCE 38 There was a large volume of evidence before the primary judge given by affidavit. There was no cross-examination. Having regard to the way in which the hearing before the primary judge developed (focusing on the non-PBS market for Lyrica) much of that evidence was of limited relevance. Some evidence of particular relevance to the primary judge's ultimate conclusions is referred to below.

Dr Jackson 39 Dr Jackson is an experienced pharmacist who gave evidence for Warner-Lambert. He said he was well aware of Lyrica and that he had dispensed it frequently in the past. He said that in his experience medical practitioners (except those working in hospitals) mostly prescribed pregabalin using the brand name Lyrica and that the overwhelming majority of prescriptions for Lyrica are PBS prescriptions indicated for neuropathic pain. Dr Jackson said that he could not recall ever seeing a prescription for Lyrica for seizures. 40 In his first affidavit Dr Jackson gave evidence that Schedule 4 medicines (which include pregabalin) can be prescribed for a non-ARTG registered indication (ie. "off-label") so long as the prescription is made by a medical practitioner or any other health professional legally capable of making a prescription. He said that medical practitioners commonly rely on other sources of information and their own clinical experience when prescribing medicines for off-label uses. Dr Jackson also said: If a medical practitioner writes a prescription, whether PBS or non-PBS, for a particular pharmaceutical substance (whether or not a particular brand is specified), and the pharmacist is aware that there is an alternative brand of the same pharmaceutical substance registered on the TGA and available to the pharmacist, the pharmacist is entitled to supply that alternative brand. In doing so, the pharmacist would be expected to satisfy himself or herself that, as well as having the same active pharmaceutical ingredient, the medicine is the same dosage and that there is no evidence of a lack of bioequivalence to the prescribed brand. The active ingredient and dosage are recorded on the label and ordinarily also in the pharmacist's dispensing software. Pharmacists are regularly visited by representatives of generic suppliers who inform them when bioequivalent products are available, and most pharmacists also have dispensing software that specifically identifies bioequivalent products. It is a requirement under professional guidelines that patient consent is gained when generic substitution occurs. 41 Dr Jackson went on to state that a pharmacist may legally dispense and supply a generic medicine to a patient holding a private prescription for the originator product. He added that in his experience pharmacists usually do so only after having consulted with the patient by, for example, asking whether the patient would like a cheaper or alternative brand. 42 In his second affidavit, responding to evidence of Mr McEvoy (discussed below), Dr Jackson reiterated that it was his belief that there was no professional or legal obligation preventing a medical practitioner from prescribing, or a pharmacist dispensing, a medicine that is ARTG listed for an "off-label" indication if the medicine is registered on the ARTG. He sought to support his opinion by reference to relevant professional standards including the "Guidelines for dispending of medicines" issued by the Pharmacy Board and the National Competency Standards Framework for Pharmacists in Australia issued by the Pharmaceutical Society of Australia (the Competency Standards). Dr Jackson is the former chair of the committee which developed the Competency Standards. Dr Jackson said: [i]f a product is bioequivalent with a prescribed brand, and there are no contraindications, substitution is completely acceptable within the Competency Standards without any need to have reference to the TGA approved indications. 43 Dr Jackson also gave evidence concerning the letter to pharmacists. The version of the letter to pharmacists upon which he was asked to comment was slightly different to a later version produced by Mr Millichamp but in all relevant respects the documents are to the same general effect. 44 The effect of Dr Jackson's evidence was that the letter to pharmacists would not deter pharmacists from substituting Apotex-Pregabalin for Lyrica. In particular, Dr Jackson stated that nothing in the letter to pharmacists would suggest to a pharmacist that substitution of Apotex-Pregabalin for Lyrica is not legal. 45 Dr Jackson said that in his opinion, if Apotex-Pregabalin is supplied to pharmacists at a significantly cheaper price compared to Lyrica, that would be the driving factor, and that the letter to pharmacists would do little if anything to prevent substitution of Apotex-Pregabalin for Lyrica for neuropathic pain. Clearly, Dr Jackson's opinion on this question was founded upon his view that a pharmacist could legally supply Apotex-Pregabalin in place of Lyrica if the pharmacist was aware that Apotex-Pregabalin was a bioequivalent pharmaceutical listed on the ARTG (ie. a product which contains the same API and is available in the same dosage).

Professor Schug 46 Professor Schug is a medical specialist who gave evidence for Warner-Lambert. He is Director of Pain Management at Royal Perth Hospital. Professor Schug gave evidence that he was very familiar with pregabalin, and that it is useful in the treatment of pain, including neuropathic pain, and that it is widely used for that purpose. He also said that pregabalin is presently very widely (and increasingly) prescribed in relation to a variety of pain states. His evidence was that pregabalin is rarely if ever used in the treatment of seizures. Professor Schug said: I am aware that pregabalin was originally identified as an anti-seizure medication. To my knowledge and in my experience, it is rarely used for that purpose. I am aware that Pfizer's Lyrica product is only indicated as an adjunctive medicine (ie a medicine to be used in conjunction with another medicine) for the treatment of partial epileptic seizures, which are not satisfactorily controlled by other anti-epileptic drugs. The use of pregabalin in this indication is to the best of my knowledge minimal. That is because there are well established seizure medicines and there is rarely a clinical need for use of pregabalin in this context. In addition, the occurrence of partial epileptic seizures is rare compared with the occurrence of pain generally or neuropathic pain. To the best of my knowledge, Lyrica has not been promoted by Pfizer for use in relation to seizures. 47 Professor Schug also gave evidence concerning the off-label prescribing of medicines. He said that he is aware that medical practitioners are not limited to ARTG approved indications when prescribing medicines and that they can rely on medical publications and their own clinical experience when making prescribing decisions.

Mr Dimopoulos 48 Mr Dimopoulos has worked in the pharmaceutical industry for 19 years and for Pfizer Australia for the last 15 years. He has held a variety of positions at Pfizer Australia including, since January 2014, his present position as Cardiovascular & Pain Therapy Lead. In his present position Mr Dimopoulos is responsible for managing those of Pfizer Australia's cardiovascular and pain products covered by patents in Australia. This includes Lyrica. 49 Mr Dimopoulos explained in his affidavit that Pfizer Australia began selling Lyrica in Australia in 2005. He said Lyrica (as we have already mentioned) is indicated on the ARTG for the treatment of neuropathic pain, and as adjunctive therapy in adults with partial seizures with or without secondary generalisation, and that it is also listed on the PBS but only if prescribed for treatment of neuropathic pain refractory to treatment with other drugs. 50 Mr Dimopoulos described Lyrica as one of the Pfizer group's "flagship products" and by far the fastest growing of the Pfizer group's products by both revenue and number of prescriptions. A confidential exhibit to Mr Dimopoulos' first affidavit provides details of Pfizer Australia's revenue from Lyrica over the last three years, and the amounts spent by Pfizer Australia in promoting Lyrica over the same period. The figures for both revenue and expenditure are substantial including in the years prior to Lyrica being listed on the PBS. The revenue figures do not take account of sales of Lyrica to hospitals but a separate figure for hospitals shows that the hospital market is quite small compared to the retail pharmacy market. 51 Mr Dimopoulos also exhibited to his affidavit confidential data provided by IMS Health to Pfizer Australia (the IMS Retail Sales Data). He said that the pharmaceutical market data provided by IMS Health is considered by him to be reliable and accurate, that it is the industry standard for market data in Australia and, in his experience, is treated as such within the pharmaceutical industry. The IMS Retail Sales Data, which relates to the month of December 2013, shows that Lyrica held 32.7% of the Australian market for pharmaceuticals suitable for the treatment of neuropathic pain. The comparable figure for each of the other drugs referred to in the IMS Retail Sales Data is in every case significantly less than that attributed to Lyrica. 52 Mr Dimopoulos gave evidence relevant to the size of the market in Australia for the use of pregabalin in the treatment of seizures. Mr Dimopoulos said that, to the best of his knowledge, doctors (other than some specialists) rarely prescribe Lyrica to patients as a treatment for partial seizures. He also gave evidence that Pfizer had not commercialised or promoted Lyrica for treatment of seizures because there are other cheaper and more effective treatments available. And he said that Pfizer had never applied for PBS listing of Lyrica for the seizure indication. The latter statement was shown by other evidence to be incorrect. 53 Mr Dimopoulos also gave evidence based upon two surveys of prescribing data which he relied upon in support of the proposition that doctors only prescribe Lyrica for the treatment of seizures in rare cases. 54 In one survey of prescribing data (the Beach data), referred to in Mr Dimopoulos' first affidavit, Lyrica was shown to have been prescribed by participating general practitioners on 319 occasions (out of a total of approximately 100,000 consultations). According to Mr Dimopoulos, the Beach data showed that of the 319 prescriptions written for Lyrica, none was for epilepsy (including partial seizures). In his affidavit in reply Mr Dimopoulos added: In my experience, a patient's first prescription (or few prescriptions) for the treatment of seizures is commonly written by a specialist and then continued by a general practitioner (so that the patient does not need to return to the specialist simply to obtain a repeat prescription). I therefore consider the absence of any recorded prescriptions of Lyrica for the treatment of epilepsy (including partial seizures) in the BEACH data is also illustrative of the prescribing practices of specialists treating that condition. 55 The second survey of prescribing data (the IMS Prescribing Data) relied upon by Mr Dimopoulos was first referred to by him in his affidavit in reply. According to Mr Dimopoulos, the IMS Prescribing Data supported his opinion as to the prescribing practices of specialists treating epilepsy. He said that the IMS Prescribing Data showed that of the total number of prescriptions written by the 420 doctors contributing to the IMS Health database over a 12 month period to December 2013, prescriptions of Lyrica for epilepsy comprised only 0.23% of the total.

Mr Millichamp 56 Mr Millichamp is the managing director of Apotex. He said that he was ultimately responsible for making the decision to launch any new "generic" product. He gave evidence of various matters that he has considered before deciding to launch a new Apotex product. These have included the market opportunity for the product in question, including market size based upon published PBS and IMS data, product price to consumer, costs of goods and profitability, including an estimate of market share that the product will achieve on entry and over time. 57 Mr Millichamp also gave evidence of the marketing and selling of Apotex products. He said that Apotex does not directly market its prescription products to either doctors or patients and that: [a] significant aspect of the marketing and selling of Apotex's products, and of the marketing and selling carried out by other generic pharmaceutical companies, in my experience, is to offer discounts directly to pharmacists … this provides an incentive to pharmacists to substitute an approved generic product for the originator brand for a prescribed pharmaceutical substance where substitution is possible. Other evidence given by Mr Millichamp indicated that Apotex plans to supply Apotex-Pregabalin to retail pharmacies at prices that are 20% less than what Pfizer Australia presently charges for Lyrica. 58 Mr Millichamp provided a detailed response to Mr Dimopoulos' first affidavit. Significantly, he did not raise any issue in relation to the proper interpretation of the Beach data or whether the conclusion drawn by Mr Dimopoulos was correct. 59 However, Mr Millichamp did give some evidence relevant to the size of the seizure market. He said with reference to a confidential IMS wholesale sales report (the IMS Wholesale Report) for Lyrica exhibited to his affidavit and the publicly available PBS data available at an Australian government website (www.medicareaustralia.gov.au) that he was able to draw a number of conclusions as to the extent to which Lyrica was being sold outside the PBS. Most relevantly, having drawn attention to large differences between the figures appearing in the IMS Wholesale Report (Exhibit Confidential RM-10) and the PBS data (Exhibit RM-11), Mr Millichamp said: As prescriptions for LYRICA for neuropathic pain are now reimbursed via the PBS, the large difference in these figures indicates to me that LYRICA is being prescribed privately for other indications, including seizures. I have also compared the value data in the IMS Report for the month of January 2014 with the "benefits" data in the report in RM-11 for the month of January 2014. The IMS Report shows that almost $6.5 million was paid by pharmacists for units of LYRICA supplied to retail pharmacies in January 2014, but the Medicare report shows that only $5.6 million was reimbursed in the same time period. This also indicates to me that LYRICA is being prescribed privately for other indications, including seizures. His evidence suggested that for the month of January 2014, approximately $6.5 million was paid by retail pharmacists for Lyrica supplied through their outlets while only $5.6 million was reimbursed to them. This was said by Mr Millichamp to support the proposition that Lyrica is being prescribed privately for other indications including seizures. 60 There are a number of other matters on which Mr Millichamp gave evidence relevant to the issues on appeal. 61 First, Mr Millichamp produced a copy of Pfizer Australia's 2005 application to have Lyrica listed on the SPB for the treatment of partial seizures. He said that this indicated to him that in 2005 Pfizer Australia considered that there was a market for Lyrica as a treatment for partial seizures. 62 Secondly, Mr Millichamp said that he was aware from regular discussions with pharmacists, hospitals and medical practitioners that Lyrica is used as a seizure treatment in Australia. However, he did not purport to give any evidence as to the extent to which Lyrica is used as a seizure treatment nor did he take issue with Mr Dimopoulos' evidence suggesting that it is only rarely prescribed for that indication. 63 Thirdly, he referred to various documents relevant to the use of Lyrica in the treatment of seizures including an assortment of documents published by various bodies, such as Epilepsy Australia, which refer to Lyrica as a seizure treatment. He also referred to a copy of Pfizer Australia's own Consumer Medicine Information (CMI) for Lyrica which includes a statement that "Lyrica is also used to control epilepsy." 64 Fourthly, Mr Millichamp also stated that, in his experience, even if retail pharmacists had a price incentive to substitute Apotex-Pregabalin for Lyrica, they would not do so for "ethical reasons" because they will have been informed by Apotex that Apotex-Pregabalin is not approved by the Therapeutic Goods Administration (TGA) for the treatment of neuropathic pain. However, he did not provide any explanation as to why it would be unethical for a pharmacists to substitute in such circumstances notwithstanding that the products are bioequivalent, nor did he specifically answer Dr Jackson's evidence to the effect that the letter to pharmacists would do little, if anything, to prevent substitution if Apotex-Pregabalin was supplied to pharmacists at a significantly cheaper price compared to Lyrica. 65 Fifthly, Mr Millichamp stated that he did not accept, and had no reason to believe, that Apotex would obtain any share of Lyrica's "neuropathic pain market". However, it is clear from the context in which this statement appears that Mr Millichamp was referring to the PBS pain market. This is significant because the PBS pain market is narrower than its name implies. The PBS listing is limited to the use of Lyrica for the treatment of neuropathic pain refractory to other treatment. It follows that the PBS does not cover the use of Lyrica as a first line neuropathic pain treatment.

Mr McEvoy 66 Mr McEvoy is an experienced pharmacist who gave evidence for Apotex. He is the National Merchandise Manager, for Health, for the Terry White chain of pharmacies. Relevantly, Mr McEvoy gave evidence as to whether a pharmacist would dispense a medicine to a patient for an indication in respect of which the medicine is not registered. He said: In the context of offering an alternative bioequivalent product to a patient instead of the brand specified on a valid script issued by a prescriber, in my experience, a pharmacist cannot, and would not, dispense a medicine to a patient for an indication when the pharmacist knows that that medicine is not approved for that indication on the ARTG … In my opinion, it is not sufficient that a medicine is registered on the ARTG for 'something'; a product must be approved for a particular use in order for that product to be dispensed for that use … If the TGA has registered a medicine on the ARTG as only being approved for a given indication, than I would consider the TGA only to have approved that medicine (which includes an assessment of the medicine's relevant safety and efficacy data) to be used in the treatment of humans for that specific indication. In my opinion, a pharmacist is not entitled to, and would not risk their professional standing and registration by proceeding to, dispense a substituted product that they know is not approved on the ARTG for the treatment of the same condition as the product which the prescriber has issued the script for. 67 This evidence from Mr McEvoy is expressly directed to a situation in which the script issued by the prescriber specifies a particular brand of drug. Whether or not the ethical issue to which he alluded in this evidence would also arise if the prescriber used the generic name of the drug (eg. pregabalin) is not clear. In any event, the effect of this evidence (which is directly contrary to that given by Dr Jackson) is that a pharmacist would not be entitled to substitute Apotex-Pregabalin for Lyrica for the treatment of pain even with the patient's consent.

THE RELEVANT PRINCIPLES 68 There was no dispute between the parties as to the test that the primary judge was required to apply in deciding whether to grant or withhold the interlocutory relief sought by Warner-Lambert. There are two inquiries that must be undertaken when determining whether an applicant should be granted an interlocutory injunction. The first relates to the strength of the applicant's claim to final relief. The second relates to the balance of convenience or, as it is sometimes expressed, the balance of the risk of doing an injustice by either granting or withholding the interlocutory relief sought. 69 The principles to be applied in determining whether or not to grant interlocutory relief were considered by the High Court in Australian Broadcasting Corporation v O'Neill (2006) 227 CLR 57, including by Gummow and Hayne JJ at [65]-[72]. Gleeson CJ and Crennan J agreed at [19] with the explanation of the relevant principles in those paragraphs. In O'Neill Gummow and Hayne JJ stated at [65]: The relevant principles in Australia are those explained in Beecham Group Ltd v Bristol Laboratories Pty Ltd [(1968) 118 CLR 618]. This Court (Kitto, Taylor, Menzies and Owen JJ) said that on such applications the court addresses itself to two main inquiries and continued [(1968) 118 CLR 618 at 622-623]: "The first is whether the plaintiff has made out a prima facie case, in the sense that if the evidence remains as it is there is a probability that at the trial of the action the plaintiff will be held entitled to relief ... The second inquiry is ... whether the inconvenience or injury which the plaintiff would be likely to suffer if an injunction were refused outweighs or is outweighed by the injury which the defendant would suffer if an injunction were granted." By using the phrase "prima facie case", their Honours did not mean that the plaintiff must show that it is more probable than not that at trial the plaintiff will succeed; it is sufficient that the plaintiff show a sufficient likelihood of success to justify in the circumstances the preservation of the status quo pending the trial. That this was the sense in which the Court was referring to the notion of a prima facie case is apparent from an observation to that effect made by Kitto J in the course of argument [(1968) 118 CLR 618 at 620]. With reference to the first inquiry, the Court continued, in a statement of central importance for this appeal [(1968) 118 CLR 618 at 622]: "How strong the probability needs to be depends, no doubt, upon the nature of the rights [the plaintiff] asserts and the practical consequences likely to flow from the order he seeks." 70 Whether an applicant for an interlocutory injunction has made out a prima facie case and whether the balance of convenience favours the grant of such relief are related questions. It will often be necessary to give close attention to the strength of a party's case when assessing the risk of doing an injustice to either party by the granting or withholding of interlocutory relief especially if the outcome of the interlocutory application is likely to have the practical effect of determining the substance of the matter in issue or if other remedies, including an award of damages, or an award of compensation pursuant to the usual undertaking, are likely to be inadequate. 71 It is also not in dispute that the decision of the primary judge to grant or withhold the interlocutory relief sought by Warner-Lambert required the primary judge to exercise a judicial discretion. As the High Court explained in House v The King (1936) 55 CLR 499 at 504-505: The manner in which an appeal against an exercise of discretion should be determined is governed by established principles. It is not enough that the judges composing the appellate court consider that, if they had been in the position of the primary judge, they would have taken a different course. It must appear that some error has been made in exercising the discretion. If the judge acts upon a wrong principle, if he allows extraneous or irrelevant matters to guide or affect him, if he mistakes the facts, if he does not take into account some material consideration, then his determination should be reviewed and the appellate court may exercise its own discretion in substitution for his if it has the materials for doing so. 72 Warner-Lambert referred us to the decision of the New South Wales Court of Appeal in Shercliff v Engadine Acceptance Corporation Pty Ltd [1978] 1 NSWLR 729 (Shercliff). That was a case in which it was held that, in granting an interlocutory injunction, the primary judge had failed to consider the evidence as a whole, a requirement which, it was accepted by the Court, appeared from Beecham Group Limited v Bristol Laboratories Pty Limited (1968) 118 CLR 618 at 622-623. However, Mahoney JA (with whom Glass and Samuels JJA agreed) made some further observations as to the nature of the task which is to be undertaken by a judge hearing such a case where there is a conflict of evidence. His Honour said at 734: But there are limitations upon the extent to which a judge is to take into account such evidence as the defendant may tender upon an interlocutory application. It is not his function to conduct a preliminary trial of the action, nor is it, in general, to resolve the conflict between the parties' evidence, and grant or refuse the application upon the basis of such findings. Where there is conflict of evidence, the use which may be made of the defendant's evidence in determining whether the plaintiff has made out a prima facie case is a limited one. For example, the plaintiff's evidence, considered alone, may be such a prima facie case as would be acceptable if submitted to a jury in a trial. But, when considered in the light of the defendant's evidence, it may be explained away so as no longer to be such. Or the defendant's evidence, when juxtaposed to that of the plaintiff may show that there is in reality no such case, no real question between the parties, appropriate to warrant preserving the status quo until the hearing. 73 One of the complaints made by Warner-Lambert in the present appeal is that the primary judge in effect conducted a preliminary trial of the proceeding at least in so far as he rejected the evidence of Dr Jackson on a key issue. We will say more about his Honour's evaluation of Dr Jackson's evidence later in these reasons. We first turn to consider a number of other issues that directly relate to the matters dealt with in [70] of the primary judge's reasons.

ISSUE 1: THE SEIZURE MARKET 74 Warner-Lambert argued that the primary judge erred in principle in his assessment of the strength of their case by rejecting (in the sense of discounting entirely) relevant evidence. In particular, it submitted that there was clear evidence that the seizure indication for which Lyrica is registered could account for a very small percentage of the total market for pregabalin only and that it was likely that Apotex-Pregabalin would be dispensed by retail pharmacists for the treatment of pain much more often than it would be dispensed by them for the treatment of seizures. 75 As to Pfizer Australia's 2005 application for PBS listing for Lyrica in respect of the seizure indication (see 70 of the primary judge's reasons), it was submitted that his Honour's reliance upon this evidence was misplaced. Warner-Lambert submitted that the 2005 application did not contain any market or prescribing data, that the forecasts included in the application were nearly 10 years old, and that they were given on the assumption that Lyrica would be listed on the PBS with a seizure indication and be promoted by Pfizer Australia accordingly. Warner-Lambert also relied on the fact that the Pharmaceutical Benefit Advisory Committee (PBAC) rejected the claim, apparently advanced in support of the application for PBS listing, that pregabalin was significantly more effective than a comparable treatment for seizures which was already listed on the PBS. 76 As to the primary judge's reliance on the CMI and the API for Lyrica (see 70 of his reasons), Warner-Lambert submitted that his Honour was wrong to give any weight to the fact that the CMI and the API describe the seizure indication. Warner-Lambert submitted that these documents say nothing about the extent to which Lyrica is used for that indication. 77 As to the primary judge's reliance upon Apotex's sales forecasts, and his conclusion (see 70 of his reasons) that there was no "demonstrated reason to doubt the genuineness of Apotex's own assessment that there is a viable non-PBS market for the use of pregabalin in the treatment of seizures", Warner-Lambert submitted that there was no evidence to indicate that Apotex had undertaken such an assessment or at least not one based upon any identified information or experience as to the size of the seizure market. In particular, it was submitted the assessment referred to by the primary judge reflected no more than an unsupported and, in any event, erroneous assumption made by Mr Millichamp as to the size of the seizure market. 78 Apotex submitted that it was open to the primary judge to conclude that Warner-Lambert had not made good their claim that there was essentially no market in Australia for pregabalin for the seizure indication. In support of this submission particular reliance was placed on Pfizer Australia's 2005 PBS application which Apotex submitted was cogent evidence, on which the primary judge was entitled to rely, that directly contradicted the argument that there was no market for Lyrica for the treatment of seizures. Apotex also placed considerable reliance on Apotex's three year sales forecasts exhibited to Mr Millichamp's affidavit, the genuineness of which was not put in issue by Warner-Lambert at the interlocutory hearing. 79 In our view the evidence before the primary judge provided strong support for Warner-Lambert's argument that Lyrica is only rarely prescribed for the treatment of seizures and that the seizure market is very small even to the point where it might be said (with sales quite possibly accounting for less than 0.25% of the market) that there was essentially no market for pregabalin in Australia as an anti-seizure medication. 80 As is apparent from our summary of the evidence, Mr Dimopoulos' evidence, supported by evidence from Professor Schug and Dr Jackson, provided strong support for Warner-Lambert's argument that there was essentially no market, or at least only a very small market for pregabalin in the treatment of seizures. None of the witnesses called by Apotex directly contradicted Mr Dimopoulos' evidence on this issue. In particular, Mr McEvoy was conspicuously silent on the issue. He did not respond in his affidavit to Dr Jackson's evidence that he (Dr Jackson) had never seen a prescription for Lyrica for use in the treatment of seizures. We do not know, for example, whether Mr McEvoy has ever knowingly dispensed Lyrica for treatment of seizures. 81 As to Pfizer Australia's 2005 PBS application, we do not consider that it demonstrates the existence of a significant market for the use of Lyrica in the treatment of seizures. In particular, we do not understand it to contradict the clear evidence given by Mr Dimopoulos in 2014 to the effect that Lyrica is only rarely prescribed for the treatment of seizures. Apart from the fact that Pfizer Australia's 2005 application was almost 10 years old, it is important to recognise that the projected market referred to in the document was based upon two implicit assumptions, first, that Lyrica would receive a PBS listing for the seizure indication, and second, that Pfizer Australia would promote the sale of Lyrica to doctors for that particular indication. Another relevant fact is that Pfizer Australia's 2005 PBS application was put forward on the basis that pregabalin (600 mg) was significantly more effective than gabapentin (1800 mg) (the relevant comparator), a claim that the PBAC did not accept. 82 Nor do we think the Apotex forecasts upon which the primary judge relied should have been given any weight. We say this in circumstances where neither the relevant document (Exhibit Confidential RM-12) nor Mr Millichamp's evidence indicated the basis for the assumption made as to the size of the seizure market. This is not a matter of questioning the genuineness of the Apotex's forecasts, but merely recognising that the evidence does not disclose any basis for this key assumption. If it was based on empirical evidence of some description, one would still need to know whether it was further assumed that there would be a PBS listing for Apotex-Pregabalin for the seizure indication. The primary judge's reasons suggest that the forecast was not predicated on a PBS-listing for the seizure indication but whether or not it was prepared on that basis is not apparent from the evidence. 83 In our view, Warner-Lambert's submissions on this issue should be accepted. In particular, we consider the primary judge erred in finding that the evidence relied upon by Warner-Lambert was insufficient to demonstrate, on a prima facie basis, that the market for pregabalin for the treatment of seizures was virtually non-existent or (as we would prefer to express it) extremely small. In our view the evidence from Mr Dimopoulos, which found support in the prescribing data upon which he relied, as well as Dr Jackson's and Professor Schug's evidence, was sufficient to establish, to a prima facie level, that the seizure market for pregabalin was indeed extremely small. It is important to note that none of the evidence relied upon by Apotex contradicted Mr Dimopoulos' evidence, supported by the other witnesses to whom we have referred, that Lyrica was rarely prescribed for seizures. We include here not only the evidence from Mr Millichamp but also the evidence of Mr McEvoy who might reasonably be expected to have at least some knowledge as to the extent to which Lyrica is dispensed for the treatment of seizures by pharmacists working in the Terry White group of pharmacies.

ISSUE 2: USE FOR PAIN OTHER THAN NEUROPATHIC PAIN 84 We have already referred to Professor Schug's evidence that pregabalin is widely and increasingly prescribed for the treatment of a variety of pain states, including, but not limited to, neuropathic pain. He was eminently qualified to give that evidence. Moreover, Professor Schug's evidence was not contradicted by any expert evidence called by Apotex. In our view it provided strong support for the conclusion, at the prima facie level, that pregabalin is widely used for a variety of pain states not limited to neuropathic pain. 85 However, the primary judge accepted Apotex's submission that Warner-Lambert had not provided any evidence to show the extent, if any, of pain indications that are outside the neuropathic pain indication but still within the claims of the pain patent. His Honour added at [71] that "[o]n the current evidence, the Court cannot reliably assess the size of the non-PBS pain market." 86 The primary judge was correct in finding that he could not reliably assess the size of the non-PBS pain market. On the evidence before his Honour, it was simply not possible to determine, even approximately, what percentage of the total market for pregabalin might be attributed to other indications apart from its PBS listed indication (ie. neuropathic pain refractory to treatment with other drugs). The evidence certainly established that the vast majority of prescriptions for Lyrica (or pregabalin) are PBS prescriptions. However, the evidence from Professor Schug suggested that there is also a significant market for Lyrica for pain related indications that fall outside the PBS indication, including (we infer) any use of Lyrica as a first line (ie. non-refractory) pain medication. This view of the evidence also finds support in Mr Millichamp's analysis of the figures appearing in the IMS Wholesale Report and the PBS data which seems to confirm that a significant number of private prescriptions for Lyrica are written by prescribers. It is reasonable to infer that many of these private prescriptions are for pain related indications of the kind referred to by Professor Schug. 87 Apotex drew our attention to evidence (the seizure patent specification and the prescribing data exhibited to Mr Dimopoulos' affidavit) in support of its submission that Lyrica is, or at least may be, prescribed "off-label" for a variety of other indications (eg. depression, anxiety and bipolar disorders) apart from pain and seizure related indications. However, the evidence to which we were referred on this topic was slight. No witness gave evidence to suggest that Lyrica is or has been prescribed other than for pain or seizure related indications. Whether or not there is substance to Apotex's argument is a matter that may need to be revisited at final hearing in light of any further evidence. It is sufficient for us to observe that the evidence before the primary judge did not provide a basis for inferring, even at a prima facie level, that any such off-label prescribing was likely to occur on any significant scale.

ISSUE 3: THE APOTEX PROMOTIONAL MATERIALS 88 We have already set out the passages from the primary judge's reasons ([72]-[73]) which explain the significance which his Honour attached to the Apotex promotional materials. At [72] of his reasons, the primary judge noted that prescribers will be informed (by the letter to doctors) that Apotex-Pregabalin is not indicated for the treatment of neuropathic pain and that when prescribing Apotex-Pregabalin for the treatment of seizures, that indication should be shown on the prescription. Specifically, the letter to doctors states under the heading "Action Required" that "[w]hen prescribing Apotex-Pregabalin for the treatment of seizure disorders, please ensure that you include the indication on the prescription." There was no evidence at all to indicate what notice, if any, doctors would pay to such a direction from Apotex, a company with which, as we understood the evidence, doctors have little, if any, direct contact. There was evidence before the primary judge to show that many doctors who prescribe drugs (including pregabalin) routinely do so without specifying any indication on the prescription. Moreover, there does not appear to us to be any reason to think that doctors are likely to write prescriptions for Apotex-Pregabalin (as opposed to Lyrica or pregabalin) unless perhaps they are prompted to do so by the letter to doctors itself. 89 The primary judge also found that pharmacists were to be informed (by the letter to pharmacists) that if a prescription does not specify the indication for which pregabalin has been prescribed, or if it is a PBS prescription, then they should not offer Apotex-Pregabalin to patients. His Honour did not make any explicit finding that pharmacists would comply with Apotex's requests although it is implicit in his Honour's reasoning that he considered a pharmacist who had read and considered the letter would not supply Apotex-Pregabalin unless the relevant prescription indicated that the medication was to be used in the treatment of seizures. 90 The primary judge dealt expressly with the argument by Warner-Lambert based upon Dr Jackson's evidence that pharmacists would not be deterred from substituting Apotex-Pregabalin based upon their knowledge that it is bioequivalent to Lyrica. As is apparent from [73] of his reasons, the primary judge rejected this argument on the ground that it was "unsupported by any evidence and is based on mere speculation and assertion". In our respectful opinion, this was an error by the primary judge. Dr Jackson's evidence included his reasoned expert opinion (apparently admitted into evidence without objection) as to why a pharmacist would not be deterred for legal or ethical reasons from substituting Apotex-Pregabalin for Lyrica. In particular, his evidence included a detailed response to Mr McEvoy's evidence to the contrary effect, in which Dr Jackson referred to the Competency Standards which he considered supported his opinion that if Apotex-Pregabalin is bioequivalent to Lyrica, it would not be unethical for a pharmacist to substitute one for the other with the patient's consent. 91 The primary judge was confronted with a clear conflict of expert evidence from Dr Jackson and Mr McEvoy on what seems to us to be a critical matter. In our opinion, it was not a conflict that could be resolved on the basis that Dr Jackson's evidence was "mere speculation and assertion". Consistent with the reasoning in Shercliff, the conflict was one that could be resolved at a final hearing only. 92 Apotex relied on the recent decision of the High Court in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd (2013) 304 ALR 1 in support of a submission that Apotex is entitled to sell Apotex-Pregabalin indicated for a condition outside the "limited novelty" possessed by the pain patent. We were referred in particular to the reasons of Hayne J at [169]-[172] and Crennan and Kiefel JJ at [293]-[304]. For present purposes it is sufficient for us to refer to the reasons of Crennan and Kiefel JJ (with whom French CJ and Gageler J agreed at [51] and [316] respectively). Their Honours said at [304]: For the purposes of the application of s 117(2)(b), it was not shown, nor could it be inferred, that Apotex had reason to believe that the unpatented pharmaceutical substance, which it proposes to supply, would be used by recipients in accordance with the patented method, contrary to the indications in Apotex's approved product information document. 93 The finding recorded in [304] involved a question of fact. In that case, the High Court was not satisfied that Apotex had the requisite "reason to believe". The matters relied on by their Honours in support of that conclusion included the fact that the approved production information document for the relevant pharmaceutical product (Apo-Leflunomide) disclosed that it was not indicated for the method of treatment to which the claims of the patent in suit were directed. Whether or not the absence of a pain related indication for Apotex-Pregabalin from the relevant ARTG registrations, the API and the CMI, coupled also with the information and directions given to doctors and pharmacists by means of the Apotex promotional material, should lead to the same result in this case is not something that can be resolved before trial.

CONCLUSIONS ABOUT PRIMA FACIE CASE 94 We consider that the primary judge erred in rejecting important aspects of Warner-Lambert's evidence in circumstances where the factual disputes to which the evidence gave rise could not properly be resolved before final hearing. Once that evidence is taken into account as required for the purpose of assessing whether interlocutory relief should be granted, it becomes apparent that his Honour's conclusion that Warner-Lambert had not established a prima facie cannot be accepted. His Honour's alternative assumption that, if he was wrong about no prima facie case being established, then the case was a weak one, is inseparable from his primary conclusion that there was no prima facie case established at all. Accordingly, and as explained below, that assumption undermines his Honour's assessment of the balance of convenience.

THE BALANCE OF CONVENIENCE 95 Apotex submitted that the primary judge found, independently of his Honour's assessment of the strength of Warner-Lambert's case, that the balance of convenience favoured the refusal of Warner-Lambert's application for the additional interlocutory relief sought. 96 We do not accept this submission. As the primary judge recognised at [82] of his reasons, the fact that the patentee's trade in its product is old, established and still growing, and that the proposed trade in the putative infringer's product is new, is a matter that is given particular weight in some cases. However, his Honour said that this was not a matter that should be given much weight in this case, particularly having regard to the weakness of Warner-Lambert's case based on s 117(1) and (2)(b) on the evidence then before him. 97 For the reasons given, we respectfully differ from the primary judge on this point. In our view, Warner-Lambert made out a prima facie case under s 117(1) and (2)(b) for the additional interlocutory relief they seek. We do not consider that prima facie case to be weak. Nor do we consider it either necessary or desirable to say anything further concerning the strength of the prima facie case. The additional interlocutory injunction sought by Warner-Lambert, if granted, will not have the effect of determining the substance of the matter and (as discussed below) the usual undertaking as to damages is likely to provide Apotex with an adequate remedy should it prevail at the final hearing. 98 The fact that Pfizer Australia enjoys a well-established market for pregabalin as a treatment for pain which Apotex is threatening to disrupt, is a matter to which we give considerable weight. In our view the following matters are also of particular significance when it comes to assessing the balance of convenience: (a) There is no evidence to suggest that the pain patent, including, in particular, claim 1, is or might be invalid. Nor is it suggested by Apotex that any patient who uses Apotex-Pregabalin for the treatment of pain would not thereby infringe claim 1 of the pain patent. (b) Apotex's stated position is that it does not wish to see Apotex-Pregabalin supplied to any patient who intends to use the product for any indication apart from the seizure indication (at least not for so long as the pain patent remains in force). So much is apparent from the letter to doctors and the letter to pharmacists. (c) On the basis that the market for pregabalin for the treatment of seizures is very small (on the evidence presently before us we think that is most likely the case) then the loss of revenue that would be suffered by Apotex in the event that it was kept out of that market prior to the determination of the revocation and infringement proceedings is likely to be comparatively small. (d) However, if the interlocutory relief sought is not granted and there is widespread substitution of Apotex-Pregabalin for Lyrica for pain related indications, then there is a substantial risk that this could significantly reduce Pfizer Australia's sales of Lyrica and also force it to reduce its prices in order to match the discounts offered by Apotex to pharmacists who choose to supply Apotex-Pregabalin. If a permanent injunction is granted against Apotex following the final hearing, then it may be extremely difficult for Pfizer Australia to increase its prices back to their existing levels. (e) Apotex gave an undertaking to the primary judge not to supply pregabalin to hospitals until the determination of the infringement proceeding. No doubt this undertaking was given without admissions, but the willingness of Apotex to "stay its hand" in relation to trade in pregabalin in the hospital market is in our view a relevant consideration. We think the preferable approach is to maintain the status quo in the retail pharmacy market as well until a decision has been made as to whether the supply of Apotex-Pregabalin by Apotex or its distributors to retail pharmacies would be an infringement of the pain patent. (f) The revocation and infringement proceedings (which have now been consolidated) are to be heard in October of this year (a development that occurred after the primary judge's decision was given and not until the application for leave to appeal was heard). The length of any restraint to be imposed by reason of the grant of the interlocutory relief sought by the appellants is therefore relatively modest. 99 We accept that there may be some difficulties in calculating Apotex's entitlements under the usual undertaking as to damages, should that become necessary, and that it may be simpler to calculate Warner-Lambert's entitlements to a monetary remedy for patent infringement. Whether or not that is so may depend on whether Pfizer Australia is forced to reduce its prices for Lyrica in response to Apotex's entry into the market. In our view, Apotex will be adequately protected by the undertaking as to damages in the event Warner-Lambert fails to obtain a permanent injunction. 100 Taking all these matters into account, we think that the overall balance of convenience favours the grant of the additional interlocutory relief sought by Warner-Lambert.

DISPOSITION 101 In the result, the appeal should be allowed. The primary judge's order that the interlocutory application heard by him otherwise be dismissed (order 3) should be set aside together with his Honour's costs order (order 2). There is no application before us to set aside or vary the pain injunction (order 1). We propose to grant an additional interlocutory injunction substantially in the form sought by the appellants in their notice of appeal but limited to acts of "supply" and "offer to supply". 102 On the question of costs, we consider that the appropriate order is that the costs of the proceeding before the primary judge, the application for leave to appeal, and the appeal, should be the appellants' costs in the substantive proceeding. However, we will suspend the costs order for a period of 21 days to enable any party who wishes to argue for a different order to file a short written submission on the issue. 103 Orders accordingly. I certify that the preceding one hundred and three (103) numbered paragraphs are a true copy of the Reasons for Judgment herein of the Honourable Chief Justice Allsop and Justices Jagot and Nicholas.