Drug In Focus May 09

       
 
The second patent family, US10779998P, also has multiple patents filings per territory generally derived from two separate PCT applications in the family. The first, based on WO0027828 relates to triazines and so does not protect the Etravirine product. However, the second, based on WO0115221 claims the use of substituted pyrimidine and triazines in a solid dispersion particle, and specifically claims the use of Etravirine in such particles.  The second patent family can therefore be considered to be a ‘formulation’ patent in respect of Etravirine.

As such the first patent family, US10779298P appears to be the one that will prevent generic competition until expiry of all of the patents it contains, hence SPC applications in France, Great Britain and Spain (Table 2) have been applied for and published to date only on patents in this family (US ‘298 priority).  SPC applications in respect of other countries can be expected to be published in the near future, and the applied-for SPC expiry date of 2023 seems to be fairly based on the circumstances so should not meet with much objection from the national patent offices that approve the SPCs. However, any corresponding US patent term extension under 35 U.S.C. 156 would be limited to 14 years from FDA approval, thus would likely expire early in 2022, more than 18 months prior to corresponding European patent protection.

Interestingly, when comparing the patent families in the KPI of the Pipeline Selector Report with the data obtained from the ‘Orange Book’, the Orange Book only identifies one of these familes, containing US patents 6878717 and 7037917 as being relevant to Etravirine.  As the Key Patent Indicator uses multiple data sources from many countries to identify key patents, it allows a much more reliable view of the patents constraining the production and launch of a generic equivalent for the drug, so that critical patent families not represented in the Orange Book are not missed.

Data Exclusivity is based upon the first market authorisation of a drug product in a particular country and therefore poses another barrier to filing an application for a authorisation of a generic product. The KPI shows data exclusivity expiry for the molecule in January 2013 in the US and August 2018 in Europe (this date being the Market Exclusivity date under the more recent European 8+2+1 rule). In Canada Etravirine is also subject to new data exclusivity laws. Active ingredients contained in products first authorised on or after 17 June 2006 are protected by the law for a six-year period where applications for authorisation of a generic are not permitted to be submitted (Data Exclusivity), followed by a no-marketing period of two years during which a notice of compliance will not be granted to the generic manufacturer (Marketing Exclusivity). Thus if no patent or other protection were in place, generic versions of Etravirine would be able to be approved on March 2016 following submission of applications for authorisation of a generic in March 2014. An exception to this provision is required to allow for the filing of drug submissions within the framework of the Jean Chrétien Pledge to Africa Act (JCPA Act). The Act makes exception to patent law for generic equivalents manufactured for developing nations, specifically targeted at allowing generic production of drugs that can help fight HIV/AIDS. In each country covered by the ‘Core’ Pipeline selector report, the most significant patent expires long after any data or marketing exclusivity, hence the data exclusivity becomes a rather obselete form of protection for this molecule, unless the patents are successfully challenged.

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 Etravirine are highly focused on formulations and combinations, with 65% of the total patent families falling into one of these two categories (Figure 1). 

Antiretroviral therapies often use a combination antiretroviral drugs regime to maximise suppression of HIV. This usually means patients take large numbers of individual drug tablets, so a move to fixed-dose combination formulations reduces the number of individual tablets which increases patient compliance.  The trend of a few patent application filings by many small stake innovator and generic companies and the high percentages of formulation and combination patents overall could be attributed to companies taking the initiative and filing patents covering the use of multiple antiretrovirals and fixed-dose combinations for the treatment of HIV.

Unfortunately for Janssen, with the second formulation patent family identified in the KPI not benefitting from any kind of extension in most countries, it will expire before the molecule patent and should provide freedom to use the disclosed solid dispersion particle formulation in a generic product immediately after molecule patent expiry.