In Takeda Chemical Industries Ltd. v. Alphapharm Pty. Ltd., 83 U.S.P.Q.2d 1169 (Fed. Cir. 2007), Takeda developed the drug ACTOS®, which is used to control blood sugar in patients who suffer from Type 2 diabetes. ACTOS® uses a specific TZD compound that is covered by U.S. Patent 4,687,777 (the “’777 patent”). Alphapharm filed an Abbreviated New Drug Application (“ANDA”) pursuant to the Hatch-Waxman Act in order to manufacture a generic version of ACTOS®. As such, Takeda filed suit against Alphapharm for infringement of the ‘777 patent.
As a defense, Alphapharm asserted that the ‘777 patent was obvious under 35 U.S.C. §103 as the patented TZD compound would have been obvious to try in light of an existing compound admitted to be in the prior art and which is structurally similar to the patented TZD compound: compound b,. The District Court found that Alphapharm had not provided sufficient evidence to maintain a prima facie obviousness defense as there was insufficient evidence as to why compound b would have been modified to meet the requirements of the claimed compound. The District Court further noted that the prior art taught away from the use of the compound b. Lastly, the District Court found that there was unrebutted evidence of unexpected results, which further supported a finding of non-obviousness.
On appeal, the Federal Circuit affirmed the findings of the District Court. In reviewing the Supreme Court’s decision in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 82 U.S.P.Q.2d 1385 (2007), the Federal Circuit affirmed that mere structural similarity is not sufficient to make out a prima facie obviousness defense as set forth in In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed. Cir. 1995). As characterized by the Federal Circuit, In re Deuel stands for the proposition that “close or established ‘[s]tructural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds.’” However, while “a known compound may suggest its homolog, analog, or isomer because such compounds ‘often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties’ … in order to find a prima facie case of unpatentability in such instances, a showing that the ‘prior art would have suggested making the specific molecular modifications necessary to achieve the claimed invention’ was also required.”
The Federal Circuit held that such evidence of suggestion remained after KSR since the Supreme Court in KSR “acknowledged the importance of identifying ‘a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does’ in an obviousness determination.” As such, the Federal Circuit found that there needs to be evidence as to “some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound.”
Since Alphapharm did not provide any such evidence, the District Court was correct in finding nonobviousness based solely on compound b. Specifically, the District Court noted that the evidence of record indicated that there were “hundreds of millions of TZD compounds” and the prior art “specifically identified fifty-four compounds, including compound b, that were synthesized according to the procedures described in the patent, but did not disclose experimental data or test results for any of those compounds.” Further, the District Court relied upon a prior art article which reviewed 101 TZD compounds, including compound b, recommended three other compounds for use instead of compound b, and specifically criticized compound b. Lastly, testimony from witnesses, including Alphapharm’s head of intellectual property department, admitted that, especially in light of the prior art article, there was no suggestion as to why compound b would be investigated as opposed to the three more promising TZD compounds identified in the article. As such, based upon the record as a whole, there was insufficient evidence as to why, out of the TZD compounds, compound b would have been used or why a chemist would have investigate compound b to obtain the claimed TZD compound in the ‘777 patent.
Moreover, the Federal Circuit rejected Alphapharm’s argument that adjusting compound b to achieve the claimed TZD compound would have been “obvious to try.” Specifically, the Federal Circuit found that the Supreme Court, in analyzing whether a combination would be obvious to try, limited such a situation to “'[w]hen there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions [such that] a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.’” In applying the factors outlined in KSR, the Federal Circuit noted that the prior art identified more than a few predictable solutions since there were “a broad selection of compounds” and “any one of which [of the broad selection of compounds] could have been selected as a lead compound for further investigation.”
Lastly, the Federal Circuit found that, even if compound b were chosen, there was insufficient evidence that one skilled in the art would typically make modifications to the TZD compounds to achieve the patented TZD compound. There was no evidence that there would have been an expectation of success in making a specific substitution or structural change to compound b to achieve the patented TZD compound, and the prior art article actually suggested that other changes should be made instead. Thus, the Federal Circuit also found that the art was not predictable and that the number of solutions was more than finite, as would be required to find obviousness under the Supreme Court’s test in KSR.