The Penciclovir Key Patent Indicator (KPI, Table 2) identifies five patent families protecting the authorised Penciclovir products currently on the market, one molecule patent, two formulation patents and two relating to its current authorised indications. Exploring the KPI confirms that the patent protection on the Penciclovir molecule family, having priority GB8322199A, has expired firstly in Spain and Canada in 2006 with no SPC or term extension being available in these two countries. The term of equivalent patents was extended by a maximum five years in other European countries and Australia to expire in August 2009. In contrast, patent protection on the Penciclovir active ingredient per se remains in force in the US until September 2010 due to a section 156 extension of the US5075445 patent term. Notably, the latest expiring patent obstacle for developing a generic Penciclovir product in the US appears to result from a later equivalent patent US6579981 which protects a pharmaceutical composition of Penciclovir (or a salt thereof) and a carrier or excipient. This patent, although benefitting from the same 1983 priority date as the molecule, expires in 2020 – nearly 24 years after the product was first launched in the US and 11 years after it’s (extended) equivalents worldwide due to the patent deriving its term of 17 years from the issue (grant) date. Although this method of determining US patent term has been changed for patents filed after June 1995, such unusually long patent protection still exists for those patents filed prior to this date, such as US6579981. This patent will therefore prevent a launch of a generic version of Penciclovir product until 2020 in the US.
Table 2: Penciclovir Key Patent Indicator
In addition to the molecule patent family, four other patent families, identified in the KPI, significantly constrain the development of generic Penciclovir. These patent families relate to the current authorised formulations and indications of Penciclovir.
Specifically, families GB9001886A and GB9114939A comprise granted patents for cream compositions for topical use. These patents will expire in 2011 and 2012 in all territories discussed except the US where the Orange Book patent US6469015 is not due to expire until October 2019 for similar reasons to those described above for US6579981. The claims of these patents are specific to the use of propylene glycol in Europe, so could possibly be circumvented with some R&D effort by a generic competitor, should the market size support such an investment.
Patent family GB9320485A protects the use of Penciclovir for treatment of Post Therapeutic Neuralgia, and Herpes Zoster-associated pain. Although the claims of the patents in this family do not appear to protect the approved indications in Europe, it should be noted that the Expiry date for US5866581 is incorrectly stated under the Penciclovir product in the US Orange Book – a good reason to use third party products such as Pipeline Selector or Pipeline Scope when researching and planning launch opportunities.
Patent family GB9425012A provides patent protection for the use of Penciclovir for the reduction of establishment or reactivation of latent herpes virus infection and expires in late 2015 in Europe. Because the claims of these patents seems to protect the authorised indications of the Penciclovir product currently on the market, generic developers will probably not be able to launch a generic Penciclovir product before expiry of this patent in all territories. Given that the US composition patent in the earliest identified patent family remains valid until 2020 as discussed previously, it is interesting to note that European countries will probably have the generic Penciclovir as early as 2015 whereas patients in the US will not benefit from generic versions of this product until nearly five years later.
Interestingly, all of these key patent families provide parallel protections to Penciclovir and its prodrug, Famciclovir, by either claiming a general structural formula with functional groups varied at the diol end and the purine ketone or having an equivalent in the same family. While several litigation proceedings in relation to paragraph IV applications for generic Famciclovir are under way in US, no such legal challenges for Penciclovir have been identified in key markets.
Generally, data exclusivity is another potential barrier for developing a generic product. Data exclusivity laws provide that, for a specified period, the drug regulatory agency must not, without the consent of the innovator, access the innovator’s data when considering an application from a generic competitor seeking approval to sell a generic equivalent product. Information in relation to data exclusivity for Penciclovir can also be found in GenericsWeb Pipeline Selector reports. As seen in Table 2, data exclusivity for Penciclovir in all European countries expired in February 2006 or February 2002. Data exclusivity in the US, Australia and Canada has also expired due to the innovator only being offered 5 years data protection in these territories. Therefore, this issue should not be a concern for generics developers in obtaining approval for a bioequivalent Penciclovir product.
Study of the Patent Risk Analysis section of the Penciclovir Pipeline Selector report, based on comprehensive patent information (details of which are available by subscribing the corresponding Pipeline Developer report from GenericsWeb), indicates that the patenting activity relating to this drug is heavily focused on methods of API synthesis and formulation, with around 80% of the total patent families falling into these two categories. (Figure 1) Readers should be aware that these statistics may contain some of patents also protecting Famciclovir. Given that process patents are generally not Orange Book-listed or subject to pharmaceutical patent term extensions, it is highly likely that active ingredient synthesis is a major constraint in launching a generic Penciclovir product. Generic players are therefore strongly advised that a significant amount of attention should be paid to identifying and evaluating such patents to ensure that a generic product does not contain any active ingredient manufactured by a protected process at the time of commercialisation.
Figure 1: Penciclovir Patent Category Distribution
Furthermore, analysis of the Patent Filing Trends for Penciclovir (Figure 2) also reveals some interesting information. The patent filing activity for Penciclovir can be divided into two periods: before and after 1996 where Novartis were first launching their Penciclovir product to the marketplace. The patent filing trends clearly shows that the patent filing activity prior to the product launch mainly focused on molecule, process and formulation, thus indicating the innovators' attempts at managing the lifecycle of Penciclovir. Traditionally, post launch patent activity is attributed to generic development which has more attention to API manufacturing. However, few process patents for synthesis of Penciclovir are found after 1996 as shown in Figure 2. This is a rare case considering the fact that generic developers generally like to have their own synthetic routes to circumvent the innovator patent protection on API manufacture. Therefore, it may be fair to say that the activity for developing generic Penciclovir products is still not very vigorous at the moment.
Figure 2: Penciclovir Patent Filing Trends Analysis
In summary, the market for Penciclovir has been reasonably well protected by the innovator with a proactive patenting strategy. However, data exclusivity for Penciclovir in all territories has expired. The innovator therefore mainly relies on patent protection to safeguard its market share for Penciclovir. The Penciclovir molecule patents have expired in Canada, Australia and Europe. The patents protecting the cream formulations are probably circumventable but patent protection of the use of Penciclovir in treating and preventing cold sores may protect European generic entry until 2015, providing non-infringing active ingredient can be identified prior to this date. The US market is currently protected from generic entry until 2020 due to differing patent term regulations. Even with this in mind, there are a great many patent families protecting products containing the Penciclovir active ingredient which are not easily found using simple patent research resources such as the Orange Book.
Now is a golden period for generic developers to review the patent landscape of Penciclovir and develop strategies to fill any possible gaps and circumvent the patent applications filed by the innovator and block other generic competitors from doing the same. Generic developers are strongly advised that a comprehensive search of the patent landscape laid around Penciclovir is a crucial step 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 Penciclovir, 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
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