The Abatacept Key Patent Indicator (KPI, Table 2) lists two patent families. The first family (displayed) contains multiple patent filings per territory as a result of several different groups of priority applications. This patent family covers, amongst other things, the Abatacept molecule claiming an isolated soluble CTLA4 fusion protein having the extracellular domain of CTLA4 which binds a B7 antigen expressed on activated B cells.
Although, at first, this patent family looks overwhelming it is clear to see which patent in each territory is considered by the patentee to be the most important in terms of protection, by the filing for an extension of term on that particular patent.
The KPI shows that a full five-year extension has been granted to AU661854 which subsequently will remain in force until June 2017. The US patent 5,851,795 has been extended by 1413 days via the provision of USC s156 to expire in November 2017. Applications for extensions have also been filed in Great Britain, France, Germany and Spain which extend the expiry of EP0606217 in these territories until June 2017 when granted (at present the UK and Germany patent offices have not published a decision despite more than two years passing since the SPC application date). It is also important to remember that an additional 6 months SPC extension is available in Europe for conducting approved pediatric studies in accordance with a PIP, hence SPC expiry dates could also be extended further.
Table 2: Key Patent Information for Abataceptat
When reviewing the variation between patent filings within this patent family, attention must also be paid to patents/applications EP0610046 and EP1746162 and direct equivalents, which claim the expression vectors encoding bi-specific fusion proteins and methods of producing the proteins and could be potential barriers for generics developers in manufacturing Abatacept until early 2014 in countries where no extension has been granted, e.g. Canada. In contrast, EP1666498 and EP0613944 are less important because they claim the use of the CLTA-4 fusion proteins in regulating immune response which is not a currently authorised indication in any territory. The patent family view in Pipeline Selector therefore highlights important information to assist with planning litigation and assessing other patent related risks beyond which is possible when looking simply at a single, extended patent.
Patents of the second identified family, predominantly based on WO0202638, claim the use of a soluble CTLA4 molecule for treatment of rheumatic diseases. The patent protection in all territories share the same expiry date of July 2021, with some exceptions. In certain EU countries (available in the 'Extended' version of the Selector report) it can be seen that SPCs have been granted to further extend this date to 2022. Based on a cursory review, this patent family appears to be a major obstacle for developing a generic Abatacept product in Europe where it protects the sole indicated use, since the expiry dates in this family are much later than those of other patents protecting the Abatacept molecule. However, in the US, it is arguable that the claims of US 7,455,835 do not protect the indicated use and the broader equivalent application has been rejected only last month.
In addition to patent exclusivity, to launch a generic version of Abatacept, generic developers have to also consider the Data and Market Exclusivity in each territory. Data exclusivity laws prevent, for a specified period, a generic competitor from filing an application for a generic product and/or marketing a generic product. These exclusivity dates are shown alongside the patent expiry dates in the Patent Family View (Table 2), an indicating that the date represents Market Exclusivity with a data exclusivity period expiring prior.
The data does not show an expiry date for data exclusivity in the US since the legislation does not appear to have been finalised for biosimilar molecules. This is rather problematic when planning a generic development since proposals range from 7 to 12 years data exclusivity and could significantly affect the generic launch date. As a worst case scenario, potential generic filers could be looking at an earliest filing date of December 2017, resulting in possible approval anywhere from 2019 onwards.
In the European community, the product benefits from the new 8+2+1 data/marketing exclusivity regime. Based on the first market authorisation approval date of May 2007, approval for a generic equivalent of Orencia may not be sought in any European country until May 2015, and a further two years of Market Exclusivity will follow, preventing any regulatory authority from granting approval for a generic Abatacept product. In addition, the new data protection directive (2004/27/EC) also provides that an additional one year period of data exclusivity is allowed in respect of new indications with ‘significant clinical benefit’ over the existing indications. Last year, Bristol Myers Squibb extended the indication to cover treatment of juvenile idiopathic arthritis. However, no announcement for the “+1” data exclusivity has been reported although the new indication has been approved, presumably, since the new indication cannot be assessed as ‘significant clinical benefit’ over the existing indication. Even with this extended period of data exclusivity, it is unlikely to affect a generic competitor who would need to wait until expiry of the rheumatoid arthritis indication patent in 2021 (or 2022) in Europe.
GenericsWeb's Pipeline Selector report also provides statistical analysis of all patents identified that protect Abatacept and gives a clear and easy overview of the overall patent landscape surrounding the molecule. Figure 1 illustrates analytical results of patents protecting Abatacept (full details of which are available in the corresponding Pipeline Developer report) based on six major patent categories. The statistical result shows that the patenting area of greatest activity for this drug is related to use, with close to 40% of the total patent families falling into this category. This is not uncommon in the drug development arena as innovators are always trying to find new uses for this class of drug which could possibly extend the data/market exclusivity and block other drug development players from the potential market in the future (see discussion above). Figure 1 also show that those patents filed for protecting the manufacturing process of Abatacept comes second with over 35% of total patents in the whole patent portfolio. The high percentage of this patent category may reflect the complexity in manufacturing the biologic Abatacept active ingredient. Generic players are strongly advised that a significant amount of attention should be paid to identifying and evaluating these patents to ensure that a generic product does not contain any active ingredients manufactured by a protected process at the time of commercialisation.
Figure 1: Abatacept Patent Category Distribution
Analysis of the Top Patent Applicants (Figure 2) suggests that innovator Bristol Myers Squibb is still the most active player in filing patents to protect the intellectual property rights on Abatacept, having about one third of patents filed for the drug. Figure 2 further shows that all top five patent applicants are innovators in nature. No prominent generic developers can be identified in this early stage in the products lifecycle, however some are present amongst the 50% in the 'Others' category.
Figure 2: Abatacept Top Patent Applicants Analysis
In summary, the present time is still an early stage for developing a generic version of Abatacept, and indeed it is very difficult to predict with any certainty when the earliest opportunity exists to break this monopoly with many opportunities to apply effective lifecycle management. In Europe the constraint appears to be based on the later indication patent expiring in 2021 or 2022 in some countries. In the US, the need for a decision on data exclusivity for biogenerics is very prominent as this will affect the availability of generics on the market. The patent landscape surrounding Abatacept has been well protected by the innovator through standard patent terms, pharmaceutical patent extensions where available and data/market exclusivities. As time progresses the lifecycle management of Abatacept products by the innovator will likely be challenged by action from generic players, demonstrated by own patent filings, challenges to innovator filings and lobbying for legislative changes. The complex nature of developing a biologic and the uncertainties of approval legislation and regulations surrounding follow-on biologics may cause generics companies to hesitate whether to invest valuable resources in the development of Abatacept products. Given these difficulties and uncertainties it is even more essential to understand and monitor the patent landscape of a future generic product to ensure that a suitable IP strategy is adopted and to avoid being locked out from a potentially profitable market by other generic players.
For those generics companies with follow-on biologics capabilities this is a great opportunity to start the development of Abatacept in your generics pipeline, and with professionally searched and easily accessible GenericsWeb patent products, the process is made easier for you. Comprehensive data for patent families relating to Abatacept and many other drugs, including biological drugs, which is based on professional patent may be accessed by subscribing to the GenericsWeb Pipeline Developer report. Subscriptions include twelve monthly updates to keep you abreast of recently published patents and applications. GenericsWeb Pipeline Selector reports are also available in 'Core' and 'Extended' formats for any active ingredient upon request.
For questions and comments about this article please contact me at z.he@genericsweb.com
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