Takeda Pharm. Co. Ltd. v. Torrent Pharms. Ltd.

Nesina® (alogliptin)

February 16, 2021

GENERICally Speaking: A Hatch Waxman Litigation Bulletin

Case Name: Takeda Pharm. Co. Ltd. v. Torrent Pharms. Ltd., No. 2020-1552, -1598, 2021 WL 560763 (Fed. Cir. Feb. 16, 2021) (Circuit Judges Dyk, Mayer, and Chen presiding; Opinion by Chen, J.) (Appeal from D.N.J., Chesler, J.) 

Drug Product and Patent(s)-in-Suit: Nesina® (alogliptin); U.S. Patent No. 7,807,689 (“the ’689 patent”)

Nature of Case and Issue(s) Presented: The ’689 patent claimed alogliptin and it salts, a uracil-containing DPP-IV inhibitor useful for treating type II diabetes. Following a two-day bench trial where the trial court heard testimony from three experts, the district court found that defendants had failed to prove by clear and convincing evidence that the asserted claims were invalid for either statutory obviousness or non-statutory obviousness-type double patenting. Defendants appealed, challenging several different fact findings by the district court. Holding that the district court did not commit clear error in its finding that a skilled artisan would not have been motivated to make defendants’ proposed scaffold and isosteric replacements with a reasonable expectation of success, the Federal Circuit affirmed.

Why Takeda Prevailed: The Federal Circuit opinion began presenting, as a backdrop to its opinion, one undisputed factual finding relevant to its analysis of expectation of success: “in the relevant art of pharmaceutical development, very small changes in molecular structure can have dramatic effects on the properties of the molecule.”

Torrent argued two obviousness-type double patenting theories using Feng’s F162 compound as the lead compound for further modification. First, a skilled artisan would replace F162’s pyrimidinone scaffold with uracil, citing the Böhm and Kim references. The Federal Circuit found that those references did not demonstrate that uracil was known to possess DPP-IV inhibitory activity or other characteristics desirable in a scaffold for DPP-IV inhibition as of the relevant priority date. The second argument: a skilled artisan would have replaced a fluoro-olefin unit in F162’s pyrimidinone scaffold with an amide unit because fluoro-olefin and amide were known isosteres in the prior art. The Federal Circuit did not discern clear error in the district court’s contrary holding because Torrent did not identify anything in the prior art that would have motivated a skilled artisan to dispose of F162’s fluoro-olefin unit, let alone replace it with an amide, given myriad more conservative and predictable modifications that were available for transforming F162 into a “novel” compound. Indeed, Torrent’s expert conceded at trial that he was unaware of any prior art disclosing this specific modification, despite citing references that taught the opposite modification: replacing an amide unit with a fluoro-olefin unit.

Next, Defendant Indoco argued that a skilled artisan would have been motivated to use DCAX as a lead compound and to replace DCAX’s xanthine scaffold with uracil because xanthine and uracil are “interchangeale” naturally occurring nitrogenous bases. But the Federal Circuit agreed with the district court that Indoco failed to show that a skilled artisan who did so would have had a reasonable expectation of success with this particular scaffold replacement. The “interchangeability” references on which Indoco relied did not pertain to DPP-IV inhibitors or diabetes, nor did they teach substituting an existing xanthine scaffold for uracil. Moreover, the Federal Circuit relied on the district court’s observation that Indoco’s expert did not present any testimony or evidence as to the predictability of the resulting properties from replacing DCAX’s scaffold with uracil.

Finally, the Federal Circuit disagreed with Defendants’ argument that the district court improperly ignored the parties’ dispute over whether a skilled artisan must have specific experience developing DPP-IV inhibitors and/or type II diabetes drugs-experience, experience Takeda’s expert did not have. The Federal Circuit found that rather than ignore the dispute, the district court considered the prior art from both perspectives—that of a skilled artisan with and without specific experience with DPP-IV inhibitors or type II diabetes drugs—and concluded that Defendants had failed to prove invalidity under either definition of a skilled artisan.

Oren D. Langer

Partner

Managing Partner, New York Office
Member of Executive Board

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