Case Law on Small-Molecule Obviousness:
Takeda Chemical Industries, Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350 (Fed. Cir. 2007).
- Takeda sued Alphapharm after Alphapharm filed an ANDA for a generic version of ACTOS® (pioglitazone).
- The CAFC agreed that Takeda’s claims were not-obvious.
- Differences from prior art compound: Pioglitazone has an ethyl group at 5-postion of a pyridine ring while the prior art “compound-b” had a methyl group at the 6-position of the pyridine.
- CAFC concluded that the case did not present a situation like that of KSR in which an invention may be “obvious-to-try.” It was not obvious-to-try because the closest prior art disclosed a broad selection of compounds that would not have been selected as lead compounds because of the prior art’s teaching away.
Otsuka Pharmaceutical Co. v. Sandoz, Inc. (Fed. Cir. 2012) (No. 11-1126)
- ANDA applicants contended that the compound claimed in Patent No. 5,006,528, aripiprazole (marketed under the brand name Abilify®) was obvious in light of three prior art carbostyril derivative compounds.
- Examining the two steps, the CAFC concluded that the district court did not err when it found that a PHOSITA would not have selected the prior art compounds for use as lead compounds for further antipsychotic research or made the modifications necessary to arrive at the claimed compound.
Fustibal LLC [Petitioner] v. Bayer Healthcare, LLC [Patent Owner] (IPR 2016-01490)
- As expected, the PTAB applied the two-prong inquiry [“lead compound analysis”] from Otsuka Pharm. Co. v. Sandoz, Inc., 678 F.3d 1280, 1291–93 (Fed. Cir. 2012) for determining whether a claimed compound would have been obvious over prior art compounds. First, the PTAB determined whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds, or starting points, for further development efforts. Second, the PTAB analyzed whether there was a reason to modify a lead compound to make the claimed compound with a reasonable expectation of success.
Regorafenib (API of STIVARGA®) Patent 8,637,553 B2
Prior art compound = Sorafenib (Nexavar®) for Patients with Inoperable Liver Cancer
- The PTAB noted that Fustibal’s petition did not include a “mandatory” lead compound analysis. Fustibal merely
- assumed – without explanation – that a person of ordinary skill in the art would select sorafenib as a lead compound for modification.
- The PTAB did not discern a reason to select from Sorafenib from the prior art Riedl reference because the reference does not highlight any of the vast number of disclosed compounds is having particularly beneficial properties or present any enzymatic or biological data.
- No reason to modify Sorafenib by adding one fluorine to arrive at Regorafenib.
- Fustibal’s petition did not provide the necessary reasons why a chemist would modify the prior art in that particular manner. Even though the prior art discloses potential benefits of adding one or more fluorine atoms, the prior art merely indicates that the prior art compound can be halogenated.
- The PTAB did not read the prior art to suggest that any fluorine substitution will result in improved pharmacological properties. The PTAB agreed with the patent owner that if improvements by adding fluorine were always true, then “all pharmaceutical compounds would be fluorinated, which is plainly not the case.” Meanwhile, the compound already had a trifluoromethyl group on it. The petitioner could not explain why a chemist would add multiple additional fluorine atoms
