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Dae Oh joined Genericsweb in August 2006 as a patent searcher/analyst to provide quality patent information for generic pharmaceutical companies. Before joining Genericsweb, Dae worked as a Korean patent attorney specialised in biotechnology and biochemistry for Zenith Patent & Law Firm in Korea, drafting patent specification and investigating registration possibility of patents. Dae’s educational background is in microbiology, plant pathology, biotechnology and natural product chemistry. During his Master of agricultural biotechnology in Seoul National University, he researched new molecules isolated from fungal metabolites and new genes related to producing fungal toxins. |
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Drug In Focus: Gefitinib
Gefitinib (Iressa) was launched by AstraZeneca in the US during May 2003, as an oral anti-cancer agent, which is indicated for treating locally advanced or metastatic non-small lung cancer. Gefitinib selectively inhibits epidermal growth factor (EGFR) tyrosine kinase therefore there is a possibility that it may be used in the future for treating other cancers where EGFR is over-expressed.
Based on information contained in the GenericsWeb Pipeline Selector report for Gefitinib, this month’s Drug In Focus analyses the patent landscape surrounding the Iressa product with a view to launching generic equivalents.
Table 1: Gefitinib General Information
The first challenge that generic developers need to consider is data exclusivity existing in major territories. The Regulatory Data (Table 2) indicates that the data exclusivity has recently expired in Australia in November 2007 and in the US in May 2008, but is still in force in Canada until December 2008. Due to the withdrawal of a European marketing authorisation application for Iressa, no data exclusivity is applicable in European countries. The range of dates here differs due to the difference of the first authorisation date and the method of calculating the expiry of data exclusivity in each country.
Table 2: Gefitinib First Marketing Authorisation Dates
At this stage two patent families claiming the Gefitinib active ingredient have been identified in the Key Patent Indicator (KPI) (Table 3). This occurs occasionally where an active ingredient is claimed as one of many possible structures in a first patent, then a second patent (often called ‘selection patent’) is applied for claiming specific compounds from within these structures, based on them having superior properties. Recently, the Supreme Court of Canada has reaffirmed the validity of ‘selection patents’, when the Court upheld the validity of a patent claiming a single isomer despite the existence of an earlier patent claiming a broad genus that included the isomer (Apotex Inc. v Sanofi-Synthelabo Canada Inc., 2008 SCC 61).
Currently, all the patents from all the major territories in the first family are due to expire in 2013, whilst the AU and US patents in the second family are due to expire in May 2017 and in November 2017 respectively because of the grant of an extension under USC s156 in the US and under s70 of the Australian Patent Act 1990 to the original expiry date of 2016. Due to an absence of pharmaceutical patent extension provisions in Canada, the patent protecting the active ingredient will expire there in April 2016. No application for an SPC has been lodged in Europe because Iressa was not approved there.
Table 3: Gefitinib Key Patent Indicator
Only two patent families being recognised in the KPI could be due to a number of reasons. Firstly, there may be key patent applications that have been filed and are still awaiting grant and are therefore yet to appear in databases such as the Orange Book, which is one method for identifying key patent families. Secondly, patent applications may not have even been published yet, due to the normal lag of approximately 18 months between lodging a provisional application and it being gazetted.
Over time, there is a very strong possibility that more patents will be added to the KPI, as this is based on patents which appear in the US Orange book and the Canadian patent register, or which have had extension of terms applied for in major territories. Innovator companies are becoming much more diligent in protecting their monopoly by life cycle management activities such as filing patent applications protecting other molecular forms or salts, formulations and new uses. Such patent-based strategies in the past have been proven very successful in extending market share much further than simply relying on the molecule patent.
Indeed, according to the information accessed by subscribing to the GenericsWeb Pipeline Developer report, there are indications of some life cycle management being performed by AstraZeneca. There are several patent families filed by the innovator in a range of categories, including oral formulations, which could pose potential problems for generics companies relying only on basic patent information. Examining the Patent Risk Analysis section of the Pipeline Selector report, which gives a graphical window into these comprehensive patent filings, provides further insight into the likely obstacles that will be encountered.
The Patent Filing Trends graph (Figure 1) shows a significant rise in patenting activity just prior to the drug’s launch. Most of these can be assumed to be innovator patents, which indicate the innovator’s attempt to manage the life cycle of Iressa. The relatively even spread of molecule, process, formulation and use patent applications filed in this period shows that the innovator is attempting to gain the maximum protection across as many facets of the Iressa product as possible. These patents are likely to contain broad claims, thus provide strong protection and, if granted, will expire long after the patent on the active ingredient, thereby extend the monopoly on this molecule.
Figure 1: Gefitinib Patent Filing Trends
The Top Patent Applicants graph (Figure 2) reveals some weak points in the patent protection, characterised by AstraZeneca filing only 9 % of the published applications on this API while other firms or institutions occupy more than 90 % of the applications. This might suggest that the life cycle management activities of AstraZeneca have not been so vigorous or that the limited market size in European countries, where Iressa was not approved, has curtailed R&D investment of the innovator. In contrast, the activities of other innovators with other tyrosine kinase inhibitors such as Dasatinib (Sprycel) or Sorafenib (Nexavar) are much more vigorous. For these other products the innovators occupy more than 20% of the total applications. This might be a great opportunity for generic competitors to review the situation early and take advantage of the weak points by filing patent applications which enable them to circumvent the patent applications filed by the innovator and block other generic competitors from doing the same.
Figure 2: Gefitinib Top Patent Applicants Analysis
These analyses bring us to the question: why do we need this information now if the expiry of the molecule patent is not for another 8 years or more? The answer is to maximise benefits from research and development activities. A generics company should have their product on the market first, preferably with as few competitors as possible. This is only possible in the situation where a generic company is selecting a drug that fits in with their pipeline, assessing the patent landscape immediately after launch therefore being able to file their own patents to “fill in the holes” left by the innovator.
Comprehensive data for patent families relating to Gefitinib, based on professional patent searching, may be accessed by subscribing to the GenericsWeb Pipeline Developer report 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 at d.oh@genericsweb.com.
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