Form II: Anticipation And Obviousness Of Crystal Form Patents In The Federal Court Of Canada

• Published date: 27 September 2022
• Subject Matter: Intellectual Property, Patent
• Law Firm: Bereskin & Parr LLP
• Author: Mr Joshua W. Spicer and Bruna Kalinoski

Many substances exist in multiple solid crystal forms. Thus "polymorphism"'the tendency of solids to crystalize in different intermolecular arrangements'is commonly encountered in the development and manufacturing process of pharmaceuticals, herbicides and other specialty chemical products. In litigation involving patents that claim particular crystal forms, the prior art often includes different forms of the compound at issue or a genus of compounds from which it was selected for further investigation. Against this backdrop, the court is often faced with the question of whether, in light of the prior art, the steps of identifying, selecting, characterizing and making a substance in a particular form can lead to a "new" compound or requires inventive ingenuity. In this paper, we discuss how the Federal Court has considered allegations of anticipation and obviousness in the context of issues raised by the nature of polymorphic compounds. This paper follows on our earlier "Form I" paper in which we reviewed the Federal Court case law addressing the issue of claims construction for crystal form patents.

Anticipation

The unstable nature of some polymorphic compounds, and corresponding tendency for conversion from less to more stable forms, have proven significant to the issue of anticipation in at least two cases. In Abbott Laboratories et al. v. Minister of Health et al.,¹ the Federal Court of Appeal had to consider whether a claim to a previously unknown intermediate was anticipated when the intermediate was unknowingly created during the synthesis of a more stable prior art form of the antibiotic clarithromycin. The inventors had discovered and stabilized a new Form 0 of the compound. Following this invention, although previously unknown, it was recognized that Form 0 was inherently produced during the synthesis of the prior art Forms I and II, but Form 0 was so unstable that it quickly converted to the known forms and previously went undetected. The alleged infringement was Ratiopharm's preparation of Form II during which Form 0 was inherently produced. Abbott sued on its claim to Form 0 per se (not to stabilized Form 0). The court applied the long-standing principle of "what would infringe if later, anticipates if earlier" and found the claim to Form 0 was anticipated despite anyone actually knowing of its existence: "Because a person who makes Form I or Form II following the teaching of the prior art inevitably would make Form 0, that person would infringe the 274 patent as surely as Ratiopharm would infringe it by making the Form II for its product, as it proposes to do, by a method that results in the creation of Form 0."²

In GlaxoSmithKline Inc. et al. v. Genpharm Inc. et al., the respondent Genpharm led evidence to show that crystalline paroxetine hydrochloride was made by following a prior art patent.³ The applicant GSK's patent in issue related to crystalline paroxetine hydrochloride hemihydrate. GSK challenged the reliability of experiments conducted by Genpharm's expert based on the theory of disappearing polymorphs. The theory suggests that once a more stable form of a polymorph has been made, the environment becomes "seeded" with that form (even in microscopic amounts) such that it is no longer possible to isolate the less stable form because it immediately converts (disappears) to the more stable form in the seeded environment. Relying this theory, GSK argued that, prior to the discovery of the more stable hemihydrate form in 1984, following the prior art would have led to the less stable (and non-anticipatory) anhydrous form but, once the hemihydrate form was discovered, it was no longer possible to make the anhydrous form due to...