Tavaborole - USA

On May 14, 2018, Federal Circuit affirmed PTAB’s decision & held patent covering toenail fungus treatment Kerydin® invalid for obviousness.

The patent in suit, U.S. Patent No. 7,582,621 is entitled “Boron-containing Small Molecules.” The patent is directed to the use of 1,3-dihydro-5- fluoro-1-hydroxy-2, 1-benzoxaborole, also known as tavaborole, to treat fungal infections. In particular, the patent teaches the use of tavaborole as a topical treatment for fungal infections that develop under fingernails and toenails (Onychomycosis). In its final written decision, the Board observed that Austin teaches that tavaborole is a known fungicide with particular potency against C. albicans. The Board also found that another prior art, Brehove taught the treatment of onychomycosis with boron heterocycles and, in particular, that Brehove’s compounds were effective against C. albicans, which Brehove characterized as a common cause of onychomycosis. In light of Brehove’s test results, the Board concluded that a person of ordinary skill in the art would have used Austin’s tavaborole in Brehove’s topical treatment of onychomycosis with a reasonable expectation of success. Anacor appealed.

On appeal, Anacor first argued that the Board violated due process and the procedural requirements of the Administrative Procedure Act (“APA”) by failing to provide Anacor with adequate notice of, and an opportunity to respond to, the grounds of rejection ultimately adopted by the Board. Anacor argued that the Board’s decision violated the APA and due process in two related ways. First, Anacor contends that the petitioner abandoned one prior art reference in its reply (Brehove) and shifted to a new theory of invalidity (relying on Austin in light of Segal and Mertin), and that the Board adopted that new theory without giving Anacor proper notice or an opportunity to respond to it. Second, Anacor argued that, in bolstering this new theory of obviousness, the petitioner impermissibly relied on new evidence, not included in the petition, to satisfy its burden of showing a prima facie case of obviousness. Court, however, rejected Anacor’s argument that the Board violated the APA or due process by adopting a new theory of obviousness not presented in the petition. Court held that the Board did not materially deviate from the theory of obviousness set forth in the petition, and Anacor had ample notice of and an opportunity to respond to the Segal and Mertin references, which in any event were properly offered in reply to arguments made by Anacor and for the purpose of showing the state of the art at the time of the patent application.

Anacor next argued that the Board improperly shifted the burden of proof by requiring the patent owner to disprove obviousness. In substance, Anacor’s argument was not that the Board shifted the burden of proof to Anacor, but that the Board improperly relaxed the burden on the petitioner to prove its case. Austin disclosed the use of oxaboroles, a subset of boron heterocycles, as fungicides that were effective against five different species of fungi, including C. albicans. It stated that compounds containing an oxaborole ring, such as tavaborole, are particularly effective against fungi. The compounds of Brehove, also boron heterocycles, were shown through in vitro testing to be effective against C. albicans. The results of Brehove’s in vivo testing showed that Brehove’s compounds were effective against onychomycosis in each of the patients suffering from that condition. Also approximately 90 percent of all onychomycosis cases are attributable to dermatophytes. In light of the full record before the Board, court concluded that substantial evidence supports the Board’s findings that a person of ordinary skill in the art would have been motivated to combine the pertinent teachings of Austin and Brehove and would have had a reasonable expectation of success in doing so.

In its third argument, Anacor challenged what it refers to as the Board’s “conclusion that the compounds of Austin are ‘structurally similar’ to the compounds of Brehove.” Anacor contended that the compounds are structurally dissimilar, and that a person of ordinary skill in the art would have expected that even small structural differences between tavaborole and the Brehove compounds would result in significant differences in their chemical and biological properties. Court said that the Board correctly acknowledged that there “are obviously structural differences between the dioxaborinanes of Brehove and the benzoxaboroles of Austin,” but it concluded that “the combination of the structural similarities and the similar fungicidal activity against C. albicans would have led a person of ordinary skill in the art to combine Brehove’s method of treating onychomycosis using Austin’s tavaborole instead of [Brehove’s compounds]. The obviousness inquiry often depends on whether there is evidence demonstrating a nexus between structural similarities (or dissimilarities) and functional similarities (or dissimilarities). In this case, although there is only limited structural similarity between the compounds disclosed in Austin and Brehove, we conclude that, in light of the combination of the structural and functional similarities between the compounds, substantial evidence supports the Board’s findings.

Thus, court rejected Anacor’s challenges to the Board’s reasoning and upheld the Board’s conclusion that claim 6 of the ’621 patent is invalid for obviousness.