Chinta & Fratangelo LLP

Obviousness in prodrugs — Daiichi Sankyo Co. v. Mylan

The drug was olmesartan, similar in structure to losartan. Mylan filed ANDA’s w/ PIV certs challenging the olmesartan patents as obvious in view of losartan. The issue in front of the Federal Circuit panel was whether claim 13 of the ‘599 patent was invalid as obvious.   Daiichi Sankyo Co., Ltd. v. Mylan, Inc., No. 2009-1511 (Fed. Cir. 9/9/2010). Dist ct found for Daiichi, holding that

Mylan failed to show by clear and convincing evidence that one skilled in the art would have chosen the ’902 ARBs [angtiotensin receptor blockers] as lead compounds over other better-studied ARBs with greater potency and thus had failed to establish a prima facie case of obviousness. The district court went on to find that, even assuming that Mylan had shown the ’902 ARBs to be leads, the structure of the ’902 compounds differed significantly from olmesartan medoxomil, and that, even assuming structural similarity, Mylan had failed to prove that one of skill in the art would have been motivated to modify the 4- and 5-positions of the ’902 ARBs to obtain olmesartan medoxomil.

Slip op. at 9.  Secondary considerations also mitigated against a prima facie case of obviousness. Slip. op. at 9. Discussion of law on appeal:

When a patent claims a chemical compound, a prima facie case of obviousness under the third Graham factor frequently turns on the structural similarities and differences between the compounds claimed and those in the prior art. In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990) (en banc) (“This court . . . reaffirms that structural similarity between claimed and prior art subject matter, proved by combining references or otherwise, where the prior art gives reason or motivation to make the claimed compositions, creates a prima facie case of obviousness.”); see also Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 1356-57 (Fed. Cir. 2008). Proof of obviousness based on structural similarity requires clear and convincing evidence that a medicinal chemist of ordinary skill would have been motivated to select and then to modify a prior art compound (e.g., a lead compound) to arrive at a claimed compound with a reasonable expectation that the new compound would have similar or improved properties compared with the old. Eisai, 533 F.3d at 1357; Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1356 (Fed. Cir. 2007). In keeping with the flexible nature of the inquiry after KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the motivation to select and modify a lead compound need not be explicit in the art. Eisai, 533 F.3d at 1357; Takeda, 492 F.3d at 1356-57.

Slip op. at 11. Mylan had to prevail on each step in the Dist Ct decision to prevail.

Selection of lead compound: The “analysis still requires the challenger to demonstrate by clear and convincing evidence that one of ordinary skill in the art would have had a reason to select a proposed lead compound or compounds over other compounds in the prior art.” Slip op. at 15.  The Dist ct found that a medicinal chemist of ordinary skill would not have been motivated to select the ’902 compounds over other second-generation ARBs, because many of the latter ARBs demonstrated greater potency and all had been more thoroughly studied than the ’902 ARBs.  Id. at 13. The case law is that one of skill in the art would not have chosen the structurally closest prior art compound, compound b, as the lead compound in light of other compounds with more favorable characteristics. Id. at 14.  In this analysis pharmacological activity trumps “mere structural relationships.” Id. at 15.

Motivation to modify: The Dist ct found that a POSA “would not have been motivated to modify the ARBs disclosed in the ’902 patent to obtain olmesartan medoxomil.” Slip op. at 15. The prior art taught away from the use of a hydrophilic substitute at the 4-position, so there was no motivation to modify. Id. at 15–16.

Conclusion: the claim at issue, claim 13 of the ‘599 patent, was valid and not obvious.