Federal Circuit No. 2013-1306

The Federal Circuit affirmed a judgment by the United States District Court for the District of Delaware invalidating clam 8 of U.S. Patent No. 5,206,244 (the '244 patent), owned by Bristol-Myers Squibb Co. ("BMS").

Claim 8 of the '244 patent is directed to a nucleoside analog composed of a carbocyclic ring and a guanine base. One such nucleoside analog covered by claim 8 is entecavir, which BMS markets under the trade name Baraclude® as a treatment for hepatitis B. Teva Pharmaceuticals, Inc. ("Teva") filed an abbreviated new drug application ("ANDA") for a generic version of entecavir. BMS brought suit against Teva under 35 U.S.C. § 271(e)(2), alleging that Teva's ANDA filing constituted infringement. At trial, Teva’s invalidity argument was focused on whether it would have been obvious to select 2'-CDG (an antiviral carbocyclic nucleoside analog) as a lead compound from the prior art. The district court invalidated claim 8 of the '244 patent as obvious over several pieces of prior art that taught 2'-CDG would have been a natural choice for a lead compound in the field of antiviral pharmaceuticals. Furthermore, the prior art was found to teach that the substitution of an exocyclic methylene group on the carbocyclic ring of a nucleoside (or nucleoside analog) improves antiviral activity. Here, the inventors selected 2'-CDG as a starting point and substituted an exocyclic methylene group on the carbocyclic ring of 2'-CDG. In considering secondary considerations of non-obviousness, the district court found that some of these factors, such as commercial success, long-felt need, and evidence of unexpected properties, weighed in BMS's favor. However, the the district court concluded that the evidence of secondary considerations was insufficient to overcome Teva’s showing of obviousness.

BMS appealed the obviousness finding to the Federal Circuit. BMS argued that the selection of 2'-CDG would not have been obvious and that the district court erred by not considering that 2'-CDG was eventually discovered to have increased toxicity. The Federal Circuit rejected this argument, however, because the toxic nature of 2'-CDG was not yet known as of the date of invention. Rather, medicinal chemists were treating patients with 2'-CDG and using 2'-CDG as a lead compound as of the date of invention. Furthermore, there was nothing in any of the cited prior art publications that would have dissuaded a person of ordinary skill from pursuing 2'-CDG as a lead compound for developing antiviral compounds. On the contrary, the experts for both BMS and Teva agreed that 2'-CDG was a promising lead compound in the field of antivirals.

BMS further argued that a new chemical compound cannot, as a matter of law, be obvious when the claimed invention possess unexpected properties. BMS cited to entecavir's high potency against hepatitis B, its larger than expected therapeutic window, and a high genetic barrier to resistance. However, the Court was not persuaded, stating that while the degree of effectiveness was unexpected, the properties themselves were not unexpected. The Court further explained that they had already held that the existence of unexpected properties does not foreclose a finding of obviousness in the en banc Dillon decision. The Federal Circuit further rejected BMS's argument that the district court erred in its factual findings regarding the commercial success of entecavir and long-felt need for hepatitis B medication. Accordingly, the Federal Circuit affirmed the district court's judgment of invalidity.

Brennen Baylor