Addressing the issue of obviousness of a chemical compound over a structurally similar prior art compound in a post-KSR world, the U.S. Court of Appeals for the Federal Circuit upheld a district court decision that the patented invention—the blockbuster diabetes drug ACTOS®—was unobvious. Takeda Chem. Indus. et al. v. Alphapharm et al., Case No. 06-1329 (Fed. Cir., June 28, 2007) (Lourie, J.).
Thiazolidinediones (TZDs) are a class of drugs that act as insulin sensitizers. The TZD compound pioglitazone is the active ingredient in Takeda’s ACTOS®, which is used to control blood sugar in patients who suffer from Type 2 diabetes. Takeda owns U.S. Patent No. 4,687,777 (the ’777 patent), entitled "Thiazolidinedione Derivatives, Useful As Antidiabetic Agents." Claim 1 of the ’777 patent claims a genus of compounds, while claim 5 claims pharmaceutical compositions containing that genus of compounds. The critical portion of the claimed compound structure is a ring structure referred to as an ethyl-substituted pyridyl ring. The claimed formula covers four possible compounds with an ethyl substituent located at the four available positions on the pyridyl ring. The formula includes the 3-ethyl compound, 4-ethyl compound, 5-ethyl compound (pioglitazone) and 6-ethyl compound. Claim 2 of the ’777 patent covers the single compound pioglitazone.
Alphapharm, a generic drug manufacturer, filed an Abbreviated New Drug Application (ANDA) for a generic version of pioglitazone along with a Paragraph IV certification asserting that the ’777 patent is invalid as obvious under 35 U.S.C. § 103. In response, Takeda brought an infringement action against Alphapharm to market generic pioglitazone. Alphapharm advanced its invalidity argument, asserting that the claimed compounds would have been obvious at the time of the alleged invention. Alphapharm’s obviousness contention rested entirely on a prior art TZD compound that was referenced in Table 1 of the ’777 patent as compound b, a compound structurally similar to pioglitazone. After a bench trial, the district court concluded that Alphapharm failed to make a prima facie case that compound b rendered pioglitazone obvious.
On appeal, Alphapharm argued that the Supreme Court’s recent decision in KSR v. Teleflex, as well as the Federal Circuit’s recent decision in Pfizer v. Apotex, mandated reversal. Alphapharm contended that the district court had erred as a matter of law (relating to the obviousness of chemical compounds) in holding that the ethyl-substituted TZDs were non-obvious in light of the closest prior art compound, compound b. The Federal Circuit rejected this contention, noting that in chemical cases "normally a prima facie case of obviousness is based upon structural similarity, i.e., an established structural relationship between a prior art compound and the claimed compound," but additionally requires "a showing that the prior art would have suggested making the specific molecular modifications necessary to achieve the claimed invention." The Federal Circuit noted that its test for prima facie obviousness for chemical compounds is consistent with the legal principles enunciated in KSR.
The Court acknowledged that in situations involving a need to solve a problem that has a finite number of predictable solutions, a skilled person has good reason to pursue these known options. In such circumstances, the Court noted, the fact that a combination may be obvious to try can be sufficient to show it was obvious. The Court distinguished the present case, noting that rather than identify predictable solutions for diabetes treatment, the prior art disclosed a broad selection of compounds any one of which could have been selected as a lead compound for further investigation.
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