Andrea Berenbaum May 18 2022 Merck's Januvia crystalline monohydrate DHP salt patent found valid Smart & Biggar | Healthcare & Life Sciences - Canada Andrea Berenbaum Healthcare & Life Sciences FactsDecisionIn a patent infringement action brought under subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, in relation to sitagliptin phosphate monohydrate (Merck's Januvia), Justice Furlanetto of the Federal Court found Canadian Patent No. 2,529,400 (the 400 patent) to be valid and granted a declaration of infringement.(1)FactsThe 400 patent is directed to:the dihydrogen phosphate (DHP) salt of sitagliptin and its crystalline monohydrate form;a process for its preparation;its formulation as a pharmaceutical composition; andits use to treat diseases affected by the inhibition of dipeptidyl peptidase-4 (DPP-4) (an enzyme that degrades one of the peptides that stimulates the secretion of insulin), such as type 2 diabetes.The 400 patent asserts that the crystalline DHP salt of sitagliptin has pharmaceutical advantages over the sitagliptin free base and hydrochloride salt of Merck's earlier Patent Cooperation Treaty Patent Application No. 03/004498 (WO498), such as enhanced chemical and physical stability. The DHP salt of sitagliptin and its monohydrate are generically encompassed within WO498 but not specifically exemplified or claimed.DecisionWhile accepting that a finding that the characteristics of a selection patent have or have not been met would not constitute an independent basis upon which to attack the validity of the patent, the Court assessed whether the 400 patent was a selection patent to put the 400 patent in context. The Court considered the 400 patent to be a selection patent on the basis that there has been a selection of a particular salt and crystalline form of a particular compound from the genus of compounds, salts and crystalline forms encompassed within WO498, and that the particular salt and crystalline form were said to have advantages over sitagliptin free base and its hydrochloride salt, which are disclosed in WO498.ObviousnessThe Court found that the inventive concept of claim 4 (which is directed to the R-enantiomer of the DHP salt of sitagliptin in its crystalline monohydrate form) is the identification of the compound sitagliptin DHP monohydrate with its enhanced chemical and physical properties over sitagliptin free base and the hydrochloride salt. This was found to underlie the inventive concept of the remaining dependent claims, including:process claims 19, 20 and 24;Swiss-style medical use claim 22 (which was held to be directed to the enhanced ability to formulate the crystalline monohydrate into a medicament); anddirect medical use claim 26 (which was held to recognise the therapeutic efficacy of the crystalline monohydrate to treat type 2 diabetes).It was not necessary for the Court to determine whether the additional elements of these claims imparted their own inventiveness.Following a lengthy analysis, including a consideration of factors relating to the "obvious to try" test, the Court held that there was insufficient motivation to focus on the particular crystalline form of a salt of sitagliptin over the other compounds disclosed in WO498, including as there was no differentiation between the activity of any of the compounds of WO498. Further, the Court held that the work and effort required to obtain the crystalline monohydrate was extensive and not predictable. The Court further concluded that the compound and a process for making it would not have been self-evident to explore or arrive at, nor would its suitability for making medicaments or its capability of being used as a therapeutic. Accordingly, the claims were held not to be obvious.InsufficiencyPharmascience also argued that the process details disclosed in the 400 patent for making the crystalline monohydrate were insufficient. However, Pharmascience did not identify any evidence to suggest that, as of the filing date of the 400 patent, the crystalline monohydrate could not be made following the methods set out in the patent.The Court held that there was no basis to conclude that the person skilled in the art would not have been able to make the crystalline monohydrate at the filing date following the methods set out in the 400 patent and, similarly, no basis to conclude that the public would not be able to make the same successful use of the teachings of the patent when it expires in 2024. The 400 patent was therefore held not invalid for insufficiency.InfringementAs Pharmascience did not dispute infringement beyond its validity attacks, the Court issued judgment in favour of Merck. Pharmascience has appealed the decision.For further information on this topic please contact Andrea Berenbaum at Smart & Biggar by telephone (+1 416 593 5514) or email ([email protected]). The Smart & Biggar website can be accessed at www.smartbiggar.ca.Endnotes(1) Merck Sharp & Dohme Corp v Pharmascience Inc, 2022 FC 417.