Vardenafil – USA

On Nov. 01, 2017, Federal circuit reversed the Delaware court’s decision of non-obviousness in Staxyn® (Vardenafil) & found that Bayer’s patent is invalid as obvious handing a win to generics maker Teva (Actavis). Federal circuit held that Delaware federal judge “clearly erred” when he found that the patent was not invalid.

Watson Laboratories, Inc. appealed the District of Delaware’s final judgment holding Watson failed to prove by clear and convincing evidence that claims 9 and 11 of U.S. Patent No. 8,613,950 (“the ’950 patent”) would have been obvious. The US’950 patent is directed to a formulation of vardenafil “in the form of an uncoated tablet which disintegrates rapidly in the mouth comprising vardenafil hydrochloride trihydrate, and at least two sugar alcohols.” Two sugar alcohols are a mixture of sorbitol and mannitol.  The parties agree that claim 8’s requirement that the formulation “releases the drug in the mouth” means it is an immediate-release formulation.

The district court held a six-day bench trial to consider the validity of the ’950 patent. Watson argued the claimed formulation of vardenafil would have been obvious to a person of ordinary skill in the art based on multiple exemplary references showing a motivation to: (1) create an ODT formulation of vardenafil; (2) select mannitol and sorbitol as sugar alcohols; and (3) make the ODT formulation immediate-release. The district court rejected each of Watson’s arguments. It found a person of ordinary skill in the art would not have been motivated to create an ODT formulation of vardenafil and would not have used mannitol and sorbitol as excipients. It found the prior art taught away from formulating vardenafil ODT as immediate-release. The district court also addressed Bayer’s objective evidence of nonobviousness and found it supported its conclusion that Watson failed to prove by clear and convincing evidence that claims 9 and 11 would have been obvious. This determination rested largely on the court’s finding the testimony of Bayer’s expert, Dr. Wicks, more persuasive than the testimony of Watson’s expert, Dr. Jacobs.

Federal circuit on appeal said that the clear error in the district court fact finding that there was no motivation to formulate ED drugs in ODTs & that the record did not contain an indication that ED drugs would be good candidates for ODT formulations. Watson relied on nine prior art references to support its assertion that there would have been a motivation to create an ODT formulation of vardenafil. Dr. Jacobs testified that the Chang reference states “drugs for [ED] would be good candidates for ODT formulation.” He testified the Boolell and Fryburg references each disclose formulating vardenafil as an ODT. He testified that numerous companies had already begun formulating ODT versions of ED drugs: Pfizer filed the Bell-Huff patent application directed to sildenafil ODT; Eisai filed the Furitsu patent application claiming an ODT formulation of phosphodiesterase inhibitors; and Lavipharm filed the Chen international patent application, identifying ODT versions of sildenafil. These six references—Chang, Boolell, Fryburg, BellHuff, Furitsu, and Chen—are absent from the district court’s decision. These references are highly relevant to whether a person of ordinary skill in the art would have been motivated to formulate ODT vardenafil. And their express disclosures cause the district court fact finding regarding motivation to combine to be clear error.

Bayer argued that Watson’s arguments concerning many of its references, such as Chang, Boolell, and Fryburg, were insignificant and the district court did not clearly err by failing to address them. It argued that while Watson asserted on appeal that the district court ignored its key prior art, Watson flooded the district court with references without adequately addressing them. Federal circuit however disagreed. Court held that while it may at times be unwise for a party to rely on numerous prior art references when challenging a patent on obviousness grounds, Watson’s approach were not untenable here. Watson produced these nine references to support a narrow point: they each “disclosed formulating vardenafil and other approved ED drugs into ODTs.” Also Dr. Wicks’ testimony does not cast doubt on the weight of Watson’s evidence regarding the vardenafil ODT limitation. Many of the references Watson relied on for this limitation were unchallenged by Dr. Wicks. Therefore the district court’s finding that ODTs were not considered applicable to ED drugs is clearly erroneous in light of Watson’s evidence.

The remainder of the district court’s findings underlying the motivation to formulate vardenafil ODT focused too heavily on the commercial availability of ODT formulations of ED drugs as of the ’950 patent’s priority date. It is unclear why the district court found it important that no ODT ED drug had gained FDA approval as of ’950 patent’s priority date. The motivation to combine inquiry is not limited to what products are forthcoming or currently available on the market. Particularly given the lengthy FDA approval process, the pharmaceutical industry is no exception. Any motivation, “whether articulated in the references themselves or supported by evidence of the knowledge of a skilled artisan, is sufficient.” Here, the motivation to formulate an ODT version of vardenafil is plainly evident from the face of multiple prior art references disclosing ODT formulations of ED drugs. No further rationale for developing vardenafil ODT was necessary. Therefore here also district court clearly erred when it found there would not have been a motivation to formulate vardenafil ODT.

With respect to combination of mannitol & sorbitol in a formulation District court found Dr. Wicks’ testimony persuasive that “every ODT on the market in the relevant prior art time frame contained only a single sugar alcohol: mannitol,” and that “there were no known problems with the use of mannitol in the existing ODTs.” It found “there was nothing in the prior art that would have given the [person of ordinary skill in the art] a reason to use sorbitol in addition to mannitol in an ODT. Federal circuit held that we do not question the district court’s credibility determinations. However, the district court’s analysis for the sorbitol and mannitol limitation again focused on the commercial availability of products while failing to address relevant prior art. Upon consideration of the entire record and under a proper analysis, we conclude that the district court clearly erred in finding a person of ordinary skill in the art would not have been motivated to formulate an ODT with sorbitol and mannitol.

Federal circuit further held that the district court did not clearly err in its fact finding that a person of ordinary skill in the art would have had concerns using an immediate-release formulation due to vardenafil’s expected bitter taste and bioavailability; however, it clearly erred when it concluded that those findings taught away from the immediate release. The fact that there may be reasons a skilled artisan would prefer one over the other does not amount to a teaching away from the lesser preferred but still workable option. The district court’s finding that a person of ordinary skill in the art would have first pursued a delayed-release formulation over an immediate-release formulation is insufficient to support a finding of teaching away.

Federal circuit held that Bayer presented evidence of copying and unexpected results that weigh in favor of a conclusion of nonobviousness. But weighing all four Graham factors, court concluded that claims 9 and 11 of the ’950 patent would have been obvious & reversed the district court’s holding.