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Drug In Focus: Rabeprazole
The following data is extracted from GenericsWeb Pipeline Patent Intelligence and is intended to give a brief outline of factors affecting the potential launch of generic equivalents of Janssen, Johnson & Johnson and Eisai’s proton pump inhibitor Rabeprazole (Pariet® and Aciphex®). Rabeprazole products global sales dropped 7.5% in 2011 to ¥136.9 billion.
Rabeprazole is currently available as an enteric-coated delayed release oral tablet in 10 and 20 mg strengths. Although originally discovered by Eisai, branded products are also marketed by Janssen and Johnson & Johnson.
Figure 1: General Information table for Rabeprazole
INN Constraint Comment
Whilst patent protection for the Rabeprazole molecule expired in Canada at the end of 2007, protection extends to May 2013 in the US (see Figure 3) courtesy of a granted 1708 days 156 patent term extension. The validity and enforceability of the US patent was upheld after challenges from Dr Reddy’s and Teva. Maximum 5 year extensions have been granted in Australia as well as most major markets in Europe, extending protection on these patents to November 2012. Data exclusivity is generally not considered to be a constraint as it expired prior to the normal expiry of patents in the constraining family.
Patent families JP12123388A and ES9500181A claim oral preparations consisting of a core containing an acid-unstable benzimidazole compound and two coating layers, the outer being an enteric polymer film. Patent family SE9600071A claims a multiple unit tablet comprising pellets of an acid susceptible proton pump inhibitor covered with an enteric coating layer which separates it from the other components. Family DK39798A claims an oral formulation comprising granules having an inert core coated with a benzimidazole, then with an outer enteric coating layer which is separated from the inner later by ingredients preventing degradation of the enteric coating. Patents within these families are not considered to be a constraint to generic competition because the protected technology is likely to be circumvented, especially given the prior market saturation of generic versions of other proton pump inhibitors, which also suffer the same instability.
Family with priority JP24404292A protects one of the approved indicated uses for Rabeprazole so is considered to be constraining for that indicated use only.
Figure 2: Key Patent Indicator; the most significant patents protecting products containing Rabeprazole
Figure 3: Patent Family View priority application JP27053686A
Figure 4: Marketing Authorisations for products containing Rabeprazole in Key Countries
Amongst the US approvals, tentative FDA approvals have been identified for generic Rabeprazole Sodium, awarded to Teva and Mylan. In the UK, generic authorisations have been awarded to Actavis, Caduceus, Chemo Iberica, CT Arzneimittel, KRKA, Ratiopharm, Teva, Torrent and Winthrop is indicative of the likely competition Rabeprazole will face across Europe upon SPC expiry.
Figure 5: Top Patent Applicants
This chart shows a representation of patentees who have filed the most patent families for this INN. Note the prominence of relevant applications filed by manufacturers of competing proton pump inhibitors, Takeda (Lansoprazole, Dexlansoprazole) and AstraZeneca (Omeprazole, Esomeprazole); as well as the diversity of applicants represented by the significant portion outside the top five.
Figure 6: Patent Filing Trend
This chart represents the timing of the earliest priority filing date for each patent family identified for this molecule as well as the type of claims found in the applications. Note the strong responsive patenting by generic companies post-launch, particularly in the area of formulations. The large numbers of filings prior to launch of Rabeprazole products relate to similar proton pump inhibitors and are filed by generic and innovator companies, these allow generic competition onto the market immediately after molecule patent expiry for this later ‘me-too’ product.
Figure 7: Patent Category Distribution
The types, number and relative distribution of patents that have been filed for Rabeprazole obtained via a comprehensive patent search (Pipeline Developer report). Note the dominance of formulation patent families, the majority of which relate to a wide range of oral formulations. The use patent families identified relate to a wide range of indications in addition to the currently approved indications.
In summary, the API patent remains in force in most major territories and means there still exists a significant barrier to generic competition. The number of generics available in Canada, the first of which were authorised immediately after Canadian molecule patent expiry, the significant number of marketing authorisation holders identified in the UK and the presence of Paragraph IV filings observed in the US is indicative of the interest shown by generic companies for Rabeprazole generics. Although this compound is difficult to formulate and the innovator has some patents protecting specific marketed formulations, these are not difficult to circumvent given the prior art landscape that exists as a result of development of other, similar compounds. Generic competition for Rabeprazole is therefore likely to be very strong upon molecule patent expiry.