Upholding the validity of Bayer’s patent covering orally disintegrating tablet (ODT) formulations of vardenafil hydrochloride trihydrate, the US District Court for the District of Delaware rejected Defendant’s arguments that the claims were invalid as obvious. Notwithstanding, the court also held the secondary objective indicia points to non-obviousness. Bayer Pharmaceuticals AG et al. v. Watson Laboratories, Inc. et al., C.A. No. 12-cv-517, 2016 WL 1703281(D. Del. April 27, 2016)

At issue was Bayer’s US Patent No. 8,613,950, directed to particular orally disintegrating tablet formulations of vardenafil hydrochloride trihydrate. Specifically, Claim 9 is directed to a drug formulation wherein the sugar alcohols are a mixture of sorbitol and mannitol. Claim 11 is directed to a drug formulation wherein at least one sugar alcohol is sorbitol. Bayer received approval from the US Food and Drug Administration (FDA) to market vardenafil hydrochloride orally disintegrating tablets (ODT), 10 milligrams, under the trade name Staxyn® for the treatment of erectile dysfunction. Watson sent Bayer a Paragraph IV notice letter indicating it submitted an abbreviated new drug application (ANDA) seeking approval for 10 milligram vardenafil hydrochloride orally disintegrating tablets, prior to the expiration of the Orange Book-listed patents.

Bayer brought suit against Watson alleging infringement under the Hatch-Waxman Act. It filed two separates lawsuits—one on April 25, 2012, alleging infringement of the US Patent Nos. 6,362,178 and 7,696,206 and the second on March 21, 2014, for infringement of the ‘950 patent. Both actions were consolidated for trial. The parties stipulated to infringement of the asserted claims of the ‘178 and ‘206 patents, provided the claims are valid and enforceable. After a six-day bench trial, the court rejected Watson’s indefiniteness defense and ruled that the asserted claims of the ‘178 and ‘206 were not obvious. During post-trial briefing, the parties stipulated to infringement of the ‘950 patent, leaving the only remaining issue, Watson’s obviousness defense with respect to the ‘950 patent.

Watson argued that the asserted claims for the ‘950 patent are obvious for two reasons: (1) combining vardenafil hydrochloride trihydrate with the sugar alcohol excipients mannitol and sorbitol into a known ODT dosage form was taught by the prior art and would have be obvious to a person of ordinary skill in the relevant art (POSA); and (2) competitive pressure would have motivated a POSA to derive the claimed subject matter. Relying on Bayer’s expert, the court determined that absent hindsight, there was no motivation in the prior art to develop vardenafil ODT because of the rarity of ODT formulations. The court found significant that prior art references from 2004 listing ODTs on the market, and likely to come to market in the next few years, did not include any drugs for the treatment of erectile dysfunction.

The court also considered whether a POSA would have been motivated to make an immediate-release ODT, rather than a delayed release ODT focusing on concerns related to increased bioavailability and taste. Bayer contended that immediate release ODT results in increased bioavailability of vardenafil, a major concern in older men. Additionally, a POSA would have expected vardenafil would have a bitter taste and therefore taught away from developing an ODT. Both of these concerns taught away from the claimed subject matter. Finally, the court determined that there was nothing in the prior art that would have given a POSA reason to use sorbitol and mannitol in an ODT, and that the tableting properties of mannitol and sorbitol mixtures are not obvious. The court relied on Bayer’s evidence that every ODT on the market in the relevant time frame contained only a single sugar alcohol—mannitol.

The court was further persuaded by several secondary considerations that weigh against a finding of obviousness, holding the bioavailability profile would have been unexpected by a POSA at the time. Specifically, a POSA making an ODT formulation of vardenfil would have wanted to formulate the ODT similar to Levitra® (another vardenfil formulation for the treatment of erectile dysfunction). Bayer states that a POSA would not have expected the bioavailability curves for Staxyn compared to Levitra to have an increase in bioavailability and no increase in the maximum concentration of vardenafil in the bloodstream. Staxyn’s results lead to a longer duration of action without added side effects. The court also agreed that Watson’s copying is evidence of non-obviousness. Typically, copying is not relevant in the ANDA context, however here, Bayer demonstrated that Watson did not simply copy in order to bring the Paragraph IV challenge, but desired the claimed subject matter. In support, Bayer proffered evidence that Watson considered design-arounds, but instead copied Bayer’s formulation.

Watson’s request for attorneys’ fees was denied having held the in favor of Bayer on the issue of obviousness.