On 29 June 2018 Justice Fothergill of the Federal Court granted Shire's application under the pre-amended Patented Medicines (Notice of Compliance) (PMNOC) Regulations for an order prohibiting the minister of health from issuing a notice of compliance to Apotex for its lisdexamfetamine (LDX) product (Shire's Vyvanse) until the expiry of Canadian Patent 2,527,646 (the 646 patent).(1) The prohibition application had been consolidated with Apotex's action seeking a declaration of invalidity and non-infringement and was decided on the basis of the evidence adduced in that action. In addition to granting the prohibition order, the court dismissed both Apotex's action for impeachment of the 646 patent and Shire's counterclaim for infringement based on Apotex's experimental/regulatory use defence. Under the current PMNOC Regulations, which took effect on 21 September 2017, such dual litigation no longer exists.
LDX is a prodrug of amphetamine. The 646 patent:
- claims LDX, compositions containing LDX and uses of LDX; and
- addresses the need for a sustained release dosage form of amphetamine that is resistant to abuse.
Shire's Vyvanse is approved for the treatment of attention deficit hyperactivity disorder and binge eating disorder in adults.
Foreign proceedings not instructive
Shire encouraged the court to view proceedings in other jurisdictions addressing the validity of patents corresponding to the 646 patent as instructive. The judge declined to rely on these decisions, accepting Apotex's view that the court must decide the issues "in accordance with the factual record and Canada's own laws".
The validity analysis below applies equally to Apotex's action for impeachment of the 646 patent and Shire's application for a prohibition order.
Anticipation The court found that the claims at issue were not anticipated by Australian Patent 54168/65, which disclosed a "very large class of d-, l-, and dl-amphetamine amino acid conjugates", including LDX. LDX fell within the 'advantageous' sub-group, but not the 'especially advantageous' sub-group of compounds in the Australian patent. It was unclear whether the skilled person would understand the compounds in the Australian patent to be prodrugs; they were never manufactured or tested and the patent did not address how they would function. No manufacturing process for LDX was disclosed. The advantageous properties of LDX (sustained release and reduced potential for abuse) were not discussed in relation to the compounds in the Australian patent.
The court held that while it was "left in some doubt" whether the patent was a selection patent, nothing turned on this point.
Obviousness The court concluded that the claims at issue were not obvious.
The judge determined the inventive concept of the claims at issue, expressly declining the opportunity to construe the claims instead (as suggested by the Federal Court of Appeal in Ciba Specialty Chemicals Water Treatments Limited v SNF Inc).(2) The judge found that Ciba did not overturn the Supreme Court's decision in Apotex Inc v Sanofi-Synthelabo Canada Inc(3) by discarding 'inventive concept'. Instead, the Federal Court found that the inventive concept of the claims at issue could be "grasped without difficulty": "a sustained release formulation of a therapeutically useful dose of amphetamine that is resistant to abuse".
The court concluded that the key difference between the state of the art and the inventive concept was the compound LDX and its advantageous properties. At the relevant time, "no prodrug had yet been developed as a means of reducing abuse potential", and there was no suggestion in the prior art that prodrugs could solve this problem. Even to the extent that prodrugs were known, "use of prodrugs to achieve sustained release was unpredictable and complex". Prodrug development was "expensive and time-consuming", consistent with the "extensive work" performed by the inventors. LDX was not obvious to try because its properties could not be known without testing, regardless of whether such testing was routine.
Insufficiency Apotex argued that the 646 patent was insufficient for failing to state that only certain forms of the hydrochloride salt of LDX could be isolated, and that only the mesylate salt was likely to be useful for solid oral dosage forms. The court disagreed, finding that the compounds captured by the claims at issue could be made by the skilled person following the 646 patent. It held that the invention "does not relate to scale-up synthesis or to a particular crystal form of LDX", and that the skilled person would be capable of making the compounds simply by following the patent.
While not affecting the prohibition application, Shire's counterclaim for infringement was dismissed on the basis that Apotex had satisfied the exception for experimental or regulatory use. The court accepted Apotex's evidence that it had obtained LDX for experimental or regulatory purposes, despite the large number of capsules made by Apotex and the fact that it had retained an inventory of close to 1 million capsules. According to Apotex's witness, the remaining inventory would be used for research and demonstration batches and, per an internal policy, not sold commercially.
Apotex may appeal, as of right.
For further information on this topic please contact Brandon Heard at Smart & Biggar/Fetherstonhaugh by telephone (+1 416 593 5514) or email ([email protected]). The Smart & Biggar/Fetherstonhaugh website can be accessed at www.smart-biggar.ca.
Endnotes
(1) Apotex Inc v Shire LLC, 2018 FC 637.
(2) 2017 FCA 225.
(3) 2008 SCC 61.
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