In the last two weeks, the PTAB has invalidated three patents covering Copaxone®, a multiple sclerosis drug marketed by Teva with annual sales of over $3 billion. Challenged by generic manufacturers Mylan and Amneal, the patents specifically covered a long-acting form of Copaxone®, known as “3-times-a-week COPAXONE® 40 mg/ml,” which Teva developed when the original version of Copaxone® was coming off patent protection.
These IPR decisions highlight the usefulness of post-grant proceedings for generic and biosimilar manufacturers, particularly for challenging follow-on patents, such as those covering specific dose regimens, as we discussed in earlier posts.
All three patents contained claims directed to methods of treating multiple sclerosis by administering three 40 mg injections of Copaxone® over seven days. The Board found this dose regimen was obvious over prior art that disclosed administering 40 mg doses of Copaxone® every other day, corresponding to one additional injection every two weeks compared to the claimed dose regimen.
The Board was also unconvinced by evidence of secondary considerations. While Teva tried to establish unexpected results for the claimed dose relative to the originally approved dose of 20 mg daily, the Board found this comparison irrelevant because it was not a comparison with the closest prior art, which the Board determined disclosed a dose of 40 mg every other day.
On commercial success, the Board acknowledged a presumption of a nexus between the drug’s success and the claimed dose regimen. However, the Board found that the petitioner overcame this presumed nexus by showing that, rather than being attributed to superior properties of the claimed invention, commercial success was largely a result of brand recognition combined with aggressive marketing and substantial price discounts aimed at outcompeting generics of the original version of COPAXONE®.
The Board also disregarded arguments based on long-felt but unmet need, finding there was insufficient evidence of failure by others, and that solutions to the problem already existed in the art given the minimal difference between the art and the claimed invention.
While these IPR decisions start to clear a path for generics of 3-times-a-week COPAXONE® 40 mg/ml, several other factors will prevent immediate generic market entry. A 30-month stay of FDA approval resulting from ANDA litigation is still in effect. Also, a petition for post-grant review of a fourth Orange Book patent covering the product was denied institution based on ineligibility. This patent is currently in litigation and will likely be challenged in an IPR.
Given that disputes over the original COPAXONE® patents went all the way to the Supreme Court, it is expected that all avenues of appeal will be pursued to stave off competition to 3-times-a-week COPAXONE® 40 mg/ml. However, these IPR decisions provide momentum to generic manufacturers and reveal a vulnerability in patent strategy that attempts to extend brand-name exclusivity by relying on minor adjustments to dose regimens.