As shown in Table 1, Lacosamide General Information, Vimpat is available in three dosage forms: film coated tablets (50 mg, 100 mg, 150 mg and 200 mg), oral syrup (15 mg/mL) and intravascular injection solution (10 mg/mL). Vimpat injection for intravenous use is indicated when oral administration is not feasible.
Table 2, Lacosamide Key Patent Indicator, lists some of the most important data to consider for generic Lacosamide development. As shown, 3 patent families in the name of Research Corp are identified as representing key protection in the patent portfolio of Lacosamide.
Table 2: Lacosamide Key Patent Indicator
The first family with priority number US70219585A is a complex family protecting the molecule i.e. short peptide compounds with various substitution groups including 2-(acetylamino)-N-benzyl-3-methoxypropanamide (racemic Lacosamide) via a Markush formula. The members of this patent family that protect Lacosamide have mostly expired, except in the USA and Canada where the protection lasts until 2014 and 2017 respectively due to differences in calculating patent terms (data not shown). The second family with priority number US1352296P specifically claims substantially enantiopure N-benzyl-2-amino-3-methoxypropionamide with R-configuration (Lacosamide). The data for patent family US1352296P is extracted and tabulated in the bottom half of Table 2. The original term of protection of patents in this family lasts until 2017 in most territories; however patent term extensions have been applied for in many countries which, if granted, will extend protection for the Lacosamide product until 2022. So far, no SPC application has been published in Germany, however it is highly likely that one has been applied for and will be published soon, as the innovator would be interested in protecting their intellectual property rights for as long as possible in such a key European market. It is interesting to note that Research Corporation does not appear to have filed patent applications relating to this family in (or extended the EP applications to) any Central and Eastern European (CEE) countries, thus the launch of generic versions of Vimpat in those countries would be constrained by data exclusivity expiry, discussed later in this article (information on patent protection in these CEE countries and many more is available in the ‘Extended’ version of the Pipeline Selector report).
Two US patents (US5654301 and USRE38551) from these two families are listed in the FDA Orange Book for Lacosamide. The latter being more important for a generic developer because it claims the chiral Lacosamide specifically and has a later expiry date. However, four separate s156 patent term extension applications for these two patents have been identified, so attention should be paid to the new expiry data of these patents after the s156 applications have been reviewed.
The last patent family identified in the Key Patent Indicator with priority number US228232000P discloses the use of those Lacosamide derivatives for treatment of pain, which is not related to the approved indication of the Vimpat currently authorised. It is worthwhile to mention that UCB submitted a market authorisation application to the FDA and EMEA for Lacosamide for use in the treatment of diabetic neuropathic pain in early 2008. The FDA rejected the application in mid 2008 while the EMEA gave a warning about the quality of the clinical trial data for the application. UCB eventually withdrew the application voluntarily in September 2008.
Another obstacle to consider when developing a generic equivalent of Vimpat is the data exclusivity. Information related to this can also be found in the GenericsWeb Pipeline Selector Report alongside the patent expiry information (Table 2). Due to the filing of the application for authorisation of Vimpat in Europe after November 2005, Lacosamide benefits from the new 8+2+1 data/marketing exclusivity regime in Europe. Based on the approval date of 29th August 2008, approval for a generic equivalent of Vimpat may not be sought in any European country until 2016, and a further two years of Market Exclusivity will follow, preventing any regulatory authority from granting approval for a generic Lacosamide product. This would have a significant effect in delaying market entry of generic products in those CEE countries where patents do not protect the Lacosamide molecule until August 2018. If approved, the indication for treatment of diabetic neuropathic pain would have extended this protection for an extra year until 2019, however there is still opportunity for approval of a different indication for Lacosamide which would trigger the ‘+1’ protection of the new European Data Exclusivity provisions.
In contrast to the EU, the data exclusivity for Vimpat is not so important for developing a generic equivalent for the USA as only 5 years data exclusivity is available for the NCE. Protection for the Vimpat product will therefore expire in 2013 whereas the patents will still be in force until at least 17 March 2017, and even longer if an s156 extension is granted.
One of the recommendable features of GenericsWeb’s Pipeline Selector Report is that relevant patent data is subject to statistical analysis and presented graphically, which allows a clear and easy overview on the overall patent landscape. Figure 1 illustrates analytical results of Lacosamide patent categories based on comprehensive searching and analysis of patent filings for this molecule (full details of which are available in the corresponding Pipeline Developer Report). As shown, the patent distribution of Lacosamide is relatively simple for the time being, with over 90% of patents protecting various Lacosamide formulations and uses which may create a potential barrier for generic developers to market a bioequivalent formulation. Nowadays, innovator companies are becoming much more sophisticated in protecting their exclusive rights of their products by aggressive lifecycle management of intellectual property such as filing patent applications protecting other molecular forms or salts, formulations and new uses. Such patent-based strategies in the past couple of decades have been proven much more effective in extending market monopoly than just simply relying on the molecule patent. Compounded by patenting of work-arounds by generic competitors, it would not be surprising to see the patent landscape for Lacosamide become dramatically more complex over the years to come.
Figure 1: Lacosamide Patent Category Distribution
Figure 2 gives another dimension of patent analysis by examining the patent applicant distribution. So far, as always in the early stage of a lifecycle of a new drug, the innovator Schwarz still takes the number one position on the top applicant list in regards to Lacosamide patent applications – filing 23% of patents relevant to the drug. Research Corp and Alexza Molecular have filed 4% of the total patents respectively. Taking account the strategic partnership between Schwarz and Research Corp, the innovator is taking 27% share in total. This means that already, less than one year after launch of the product, a large part of the patent landscape is protected by companies other than the innovator.
Figure 2: Lacosamide Top Patent Applicants Analysis
Readers should keep in mind that many patents protecting Vimpat (e.g. formulation patents or preparation patents) may not be disclosed herein at present due to various factors, e.g. the normal lag of approximately 18 months between submitting a provisional application and an application based thereon being published for public inspection. Nevertheless, the information collected here still reflects an outline of the patent landscape surrounding Lacosamide. That is: the innovator still tightly controls the patent landscape of Lacosamide. However, the lifecycle management of the whole profile is still limited at this stage, perhaps due to the innovator relying on the indication for the treatment of diabetic neuropathy pain mentioned earlier. Now is a perfect time for generic companies to review the patent landscape of Lacosamide and take advantage of the weak points by filing patent applications which enable them to fill the gaps left and circumvent the patent applications filed by the innovator and block other generic competitors from doing the same. Generic players are strongly advised to have access to a comprehensive search of the patent landscape laid around the product well before any technical development takes place in order to avoid costly litigation. Obviously, this would not be possible without first comprehensively identifying the relevant patents for the development from the 50 million+ published patent documents worldwide, and keeping this information up to date.
Comprehensive data for patent families relating to Lacosamide, 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 z.he@genericsweb.com
Home
INNform