Pemetrexed pops up in Milan

This GuestKat was delighted to get her paws on a recent decision handed down by the Court of Milan which forms part of the long running multi-jurisdictional battle concerning Eli Lilly's patent protecting its pemetrexed (Alimta) product.  She is doing her best to digest this month's decision of Fresenius Kabi Oncology Plc and Ors v Eli Lilly & Company and Ors (N.R.G. 54470/2016) (available on darts-ip) by reference to an automated online translation of the decision, and so asks that readers bear with her. The gist of the Court of Milan's judgment is as follows.  

Background

Magnifico Milano

Fresenius issued proceedings in the Court of Milan in Oct 2016 for precautionary measures (interim relief).  In its application, Fresenius sought a declaration from the Court that Fresenius' generic product - based on pemetrexed diacid (with tromethamine) - did not infringe the Italian designation of Eli Lilly's patent EP 1313508, which specifies pemetrexed disodium in the claims. By way of reminder, pemetrexed is an oncology treatment, the damaging side-effects of which can be mitigated if given together with vitamin B12.  The applicant argued inter alia that:

1. the claims of EP '508 are limited to only pemetrexed disodium, because of the unambiguous wording of the claims; 
2. infringement on the basis of equivalents was excluded in this case, because the file history of EP '508 showed that the patentee had limited the scope of protection to the salt pemetrexed disodium; 
3. use of pemetrexed diacid (with tromethamine) was not suggested even implicitly in EP '508.  

Eli Lilly counterclaimed, seeking an injunction on the basis of direct and indirect infringement of its patent.

Court of Milan's analysis and decision

The Court examined the EPO file history in detail.  In the text of the original patent application, the claims extended to the entire class of antifolates.  It was subsequently limited by the patentee to 'pemetrexed', and finally to 'pemetrexed disodium'.  These changes to the claims were consistent with changes to the EP '508 description.  The Court noted that these changes were a 'clear delineation of patent protection', for only pemetrexed disodium.  Other compounds, such as pemetrexed diacid were therefore excluded from the scope of the EP '508 claims.  Further, while Fresenius' product has the same therapeutic effect as Alimta, the association of pemetrexed disodium associated with tromethamine could not also be considered an obvious substitution of the expression pemetrexed disodium in combination with vitamin B12.   Any form of direct infringement, including on the basis of equivalents was excluded.  Further, there was no indirect infringement - the SmPC of the generic product indicated that reconstitution and dilution would happen in a glucose solution, rather than a saline solution as specified in the claims of EP '508.

Consideration of UK decision 

Eli Lilly drew the recent decision of the UK Supreme Court in Eli Lilly v Actavis to the Court of Milan's attention.  The UK judgment considered whether the Actavis generic pemetrexed products, which used (a) pemetrexed diacid, (b) pemetrexed ditromethamine, or (c) pemetrexed dipotassium, directly infringed the UK, Italian, Spanish or French designations of the patent claims, which specify pemetrexed disodium. 

Arnold J. had found at first instance in the UK proceedings that under Italian law "the patent clearly demonstrated a conscious intention of the patentee to limit the claims to pemetrexed disodium” and that this was "amply confirmed by the prosecution history". However, both these conclusions were rejected by the Supreme Court which found direct infringement of the Italian designation of the patent by the Actavis variants.  The Court of Milan noted that it was not bound by the UK Supreme Court decision in relation to the Italian designation, because those proceedings concerned different parties, and the generic products in the UK proceedings were not identical in their excipients, ratios, and licensed indications to Fresenius' product. (For anyone in need of a quick recap, Stephen's series of posts on the UK Supreme Court decision can be found here (equivalence), here (EPO file history) and here (consideration of French, Italian and Spanish designations)).   

Although the facts of the Italian and UK cases differ in certain respects, the Court of Milan judgment is an interesting juxtaposition against the UK Supreme Court decision.   Should a doctrine of equivalents go hand in hand with some form of file wrapper estoppel?  Any insights (particularly from Italian patent enthusiasts) are welcome.