Looking Into The Crystal Ball – Protecting Polymorphs To Lengthen The Drug Patent Life Cycle

Innovative pharmaceutical companies are increasingly attempting to patent improved forms of their original drug compound. Crystalline forms of a drug, called polymorphs, are one such improvement.1 A polymorph drug may provide benefits such as better efficacy, solubility, shelf life, or ease of manufacture, which can translate into increased adoption of the drug and higher sales. Patenting a polymorph also starts an additional 20-year patent term, which may help keep generic competition off the market longer.

Patentability of Polymorphs

Polymorphs are patentable subject matter in Canada and the U.S. The Federal Court of Canada dealt with the patentability of novel crystalline forms of known compounds in Abbott Laboratories v Canada.2 In this case, Ratiopharm sought approval to market Clarithromycin (6-O-methylerythromycin) in Canada. Although Abbott did not invent the Clarithromycin compound per se, they did own Canadian Patent No. 2,258,606, which claimed two different crystalline versions of the polymorphic drug. The claims covered two different crystalline forms of Clarithromycin that were distinguishable by their X-ray powder diffraction (XRPD) pattern: this effectively made the crystalline forms of the compound the patented invention. As a result, Canadian Patent No. 2,258,606 is a valid patent. Its American counterpart was also granted with claims by reference to the XRPD pattern.3

Although polymorphs are patentable in both Canada and the U.S., the patent strategy needs to precisely align with the properties of the claimed polymorph. For example, Abbott had originally patented the polymorph "or a pharmaceutically acceptable salt thereof". The salt of a polymorph would have a different XRPD pattern than the polymorph itself, so Abbott filed a disclaimer to delete the salt in order to make the claim accurately align with the claimed XRPD pattern.

Other cases have also upheld the patentability of a crystal form of a known compound. In Pfizer Canada Inc v Canada, the Federal Court had no difficulty in accepting that Canadian Patent No. 2,220,018 claims and protects specific and novel crystalline forms of atorvastatin calcium.4 The claims themselves identified the crystalline forms based on either their XRPD pattern or their solid-state carbon-13 nuclear magnetic resonance (13C NMR) pattern. This was important as the party asserting non-infringement showed only that their compounds did not share the same XRPD patternthey failed to show that...