Drug In Focus: Rosiglitazone

This month’s Drug In Focus is an updated analysis of the patent landscape surrounding the hypoglycaemic agent Rosiglitazone, following our previous report in September 2006.  Based on analysis of information contained in the GenericsWeb Pipeline Selector report for Rosiglitazone, it appears that generic pharmaceutical manufacturers should proceed with caution.  

The General Information (Table 1) indicates that Rosiglitazone remains available in four strengths of oral, film-coated tablets and also in fixed combinations with Glimepiride and Metformin.  In all product forms, the active ingredient is present as the maleate salt.

The Key Patent Indicator confirms that the SPC extensions on the Rosiglitazone active ingredient patent expire in Europe in 2013, however it can be seen from Table 2 that a maleate salt patent for Rosiglitazone offers additional protection until 2014, also by virtue of SPC extensions.  Although one would be correct in thinking that Article 3(c) of the current EU regulation in regards to SPCs precludes an SPC from being granted if the product has already been the subject of a certificate, this rule appears to have been construed very differently to the common interpretation, at least in the UK where two distinct SPCs were applied for two days apart and granted more than six months apart.  The result is a confusing situation for generic competitors, both in terms of the timing of their prospective European launch and the nature of the product that may be launched at a given time. 

In the US, a number of patents offer protection of the compound per se, as well as the product’s indicated use until 2017 due to the patent term expiry rules applicable to patent applications filed prior to 1995. This expiry date gives the Rosiglitazone product an effective marketing life of around 18 years and seemingly removes any benefit of the maleate salt patent which was filed later, but expires earlier than the patents on the molecule per se and formulations containing it.  This differing situation between major US and European markets suggest that different products will need to be developed for different markets to capitalise on early launch opportunities.

The Key patent Indicator also highlights that additional protection is being sought by GSK in regards to the combination of Rosiglitazone with Metformin.  Not surprisingly, in Europe SPC extensions have been applied for which, if granted, would only offer a marginal extension over the normal expiry date of June 2018.  US equivalents would have similar expiry dates if granted.

Study of the Patent Risk Analysis section, based on comprehensive patent data (details of which is accessible in the corresponding Pipeline Developer subscription) indicates that patenting activity relating to this drug is heavily concentrated on molecular forms.  The Patent Category Distribution graph (Figure 1) shows that nearly 25% of the total patent filings for this active ingredient are in relation to polymorphs, salts and other specific molecular forms, with more applications being published every month.

he Patent Filing Trends graph further shows that most of these molecular form patents were filed around the time of product launch in 1999, highlighting GlaxoSmithKline’s intent to protect their market for this product by filing patents defensively and seeking to prevent generic competitors from circumventing their key patent protection.  Noteworthy are the significant numbers of filings in regard to formulation patents at this time, possibly indicating an intent by the innovator to extend the product line and possibly switch late in the key patent life as a further measure of defence.

n summary, the market for Rosiglitazone has been well protected by the GSK beyond the life of the active ingredient patents.  An extraordinarily high number of salt and polymorph patents are likely to cause concern for all but the most proactive generic competitors who have not yet considered their course of action for this product, as they may be forced to hold back launch until the maleate salt patent expires, at least in Europe.  Meanwhile other generic competitors may take advantage of their early patent analysis and subsequent patenting of their own work-arounds to gain earlier market entry.

Development of non-infringing Rosiglitazone generic pharmaceuticals should only be considered after an in-depth analysis of the results of a comprehensive patent search such as those found in the GenericsWeb Pipeline Developer report, which includes twelve monthly updates to keep you abreast of recently published patents and applications.  A raft of pending patent applications in the US and Europe to GlaxoSmithKline may see later expiring patents appearing in the portfolio of Rosiglitazone key patents, hence regular monitoring of the patent landscape is also essential for efficient generic development.

Comprehensive data for patent families relating to Rosiglitazone, based on professional patent searching, may be accessed by subscribing to GenericsWeb Pipeline Developer reports which include twelve monthly updates to keep you abreast of recently published patents and applications.  GenericsWeb Pipeline Selector reports are available for any active ingredient upon request.

 

For questions and comments about this article please contact the author [e-mail].

 

Leighton Howard
Managing Director
GenericsWeb
May 2008
[e-mail]

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