Losartan Potassium (Cozaar) and Losartan +HCTZ (Hyzaar/Cozaar Plus): Interesting decisions in US and EU

The generic players for Angiotensin Receptor Blocker (ARB) medicine Losartan Potassium (Cozaar) and Losartan + Hydrochlorthiazide (Hyzaar/Cozaar Plus) in the last 8-9 months have witnessed various interesting decisions in the courts, patent offices and regulatory agencies of US and Europe.

In US, generic player Teva secured First To File (FTF) 180 days exclusivity by challenging innovator Merck’s patent US5608075 (Expiry: Sep 4, 2009), which covers various polymorphic forms of Losartan Potassium. After Teva's ANDA filing, innovator Merck filed patent delisting request to USFDA on '075 patent. However, Teva opposed this delisting and after a long legal battle with USFDA in the court, Teva got exclusivity on this product. Also, generic players Roxane and Apotex challenged USFDA decision of grant of FTF 180 day’s exclusivity to Teva. The decision of US court and regulatory agency USFDA's decision has interesting discussion on patent delisting, Medicare Modernization act and FTF exclusivity forfeiture events.

In EU, the patent on Losartan (Cozaar) was supposed to expire in Sep, 2009. However, the Paediatric extension to the Losartan Potassium (Cozaar) at the last moment (before SPC expiry) delayed the generic launch date of various generic players to March, 2010. Earlier, in Sep, 2009 there was uncertainty on Paediatric extension status in some EU countries including UK, where patent office first rejected Paediatric extension, however, higher court granted the Paediatric extension in UK.

Now, Kluverpatentblog (http://kluwerpatentblog.com/2010/04/28/the-losartan-case-in-belgium-one-spc-too-far/) has reported interesting case of Losartan +HCTZ (Hyzaar/Cozaar Plus) launch date issues in Belgium and France. The highlights of the issues are as follows:

1) EP 0253310 (Expiry: March, 2010): the patent covers Losartan as product. The patent has got SPC in major EU countries like Belgium and France, which expired on 2 September 2009. Also, innovator Merck got Paediatric extension of 6 months for monotherpay, which expired in March, 2010.

2) EP0733336 (Expiry: February 15, 2010): This patent covers combination of Losartan and diuretic like Hydrochlorthiazide as product. The patent has got SPC in major EU countries like Belgium and France, which expired on 15 February 2010.

The various generic players were ready to launch Cozaar plus after the expiry of ‘336 patent (as no Paediatric extension was granted to this patent). However, innovator Merck opposed generic version based on the argument that paediatric extension granted to ‘310 would also covers combination of Losartan with diuretic, so generic players can not launch generic version till March, 2010.

The President of the Brussels Commercial Court on February 12, 2010 sided with generic players and opined that paediatric extension will not be applicable to Cozaar Plus. Also, Brussels Court of Appeal on February 23, 2010 upheld the commercial court’s decision.

Conversely, in France, the court opined that Paediatric extension granted to Cozaar will also cover Cozaar plus.

Overall, the patent disputes, exclusivity disputes and Paediatric extension disputes on this molecule have provided clarity to various generic players for the future generic launches in EU and US. Also, the techno-legal discussions and facts on various issues will serve as a training material for IP professionals.