The Case of the Disappearing Polymorph: ‘Inherent Anticipation’ and the Impact of SmithKline Beecham Corp. v Apotex Corp. (Paxil®) on Patent Validity and Infringement by Inevitable Conversion

Abstract

In two separate decisions, the United States Court of Appeals for the Federal Circuit invalidated the key patent protecting GlaxoSmithKline's (GSK) widely prescribed antidepressant drug Paxil®, generically known as paroxetine hydrochloride. The broadest claim of GSK's patent simply covered the chemical compound ‘crystalline paroxetine hydrochloride hemihydrate’, an allegedly new ‘polymorphic’ form of the drug. Generic challenger Apotex designed around the patent by making the old, off-patent ‘anhydrate’ polymorph of paroxetine that is the subject of the now-expired US Patent No. 4,007,196 (the ′196 patent). To prove infringement, GSK relied on the so-called ‘disappearing polymorph’ theory, under which the old polymorphic form of the drug effectively ‘disappears’ by ‘naturally’ converting into the new form. GSK thus argued that Apotex's non-infringing, prior art anhydrate form would ‘inevitably’ convert into GSK's new patented hemihydrate form. The Federal Circuit eventually invalidated the patent relying, in part, on the same conversion theory that GSK used to prove infringement. In the first decision, the Federal Circuit based its invalidity decision on GSK's early work and public use of the patented compound in US clinical trials. But after GSK petitioned for rehearing, the Panel modified its invalidity finding, basing it on the prior art disclosure of paroxetine in the expired ′196 patent that ‘inherently anticipated’ GSK's patent. The Court held that producing paroxetine anhydrate according to the expired ′196 patent inherently results — by a process of natural or inevitable conversion — in at least trace amounts of GSK's patented hemihydrate form, thus rendering GSK's patent invalid for lack of novelty. The Federal Circuit's decision strengthens the inherent anticipation doctrine, particularly for acts of infringement based on the so-called ‘disappearing polymorph’ or ‘natural’ conversion theories. Generics companies seeking to practise expired patents and prepare prior art products thus have added protection against charges of ‘inevitable infringement’.