Federal Circuit Affirms PTAB's Final Written Decision that Merck's Claimed Inventions Were Not "At Once Envisaged" From the Prior Art

Sixty years ago, the Federal Circuit's predecessor court, the Court of Customs and Patent appeals, considered whether the prior art disclosure of a chemical genus anticipated species falling within the scope of that genus in In re Petering.

The Petering court explained that, based on the facts and circumstances before them, the prior art may be deemed to disclose each member of a genus when, reading the reference, a skilled artisan would "at once envisage each member of this limited class." See Application of Petering, 301 F.2d 676, 681 (C.C.P.A. 1962). Over the years, courts have questioned the proper application of In re Petering.

The Federal Circuit in Mylan Pharms., Inc. v. Merck Sharp & Dohme Corp. recently assessed the application of In re Petering in Mylan's appeal from the Patent Trial and Appeal Board's ("the Board") final written decision in inter partes review ("IPR") No. IPR2020-00040. The Board found that Merck's patent covering sitagliptin dihydrogenphosphate ("sitagliptin DHP") was not unpatentable as anticipated or obvious. Mylan Pharms., Inc. v. Merck Sharp & Dohme Corp., No. 2021-2121, 2022 WL 4541687 (Fed. Cir. Sept. 29, 2022).

Key Takeaways from Mylan v. Merck:

• The Board did not err in finding that a class of 957 salts that may result from the 33 compounds and eight preferred acids disclosed did not meet the "at once envisage" standard set forth in Petering.
• The Federal Circuit cannot provide a specific number defining the "limited class" a skilled artisan might "at once envisage" for anticipation of a member within the class—it depends on the circumstances and the facts before it.

Case Synopsis

Sitagliptin DHP can be used for treating non-insulin-dependent (i.e., Type 2) diabetes and is the active ingredient in Merck's Januvia® drug product. Merck's U.S. Patent No. 7,326,708 ("the '708 patent") describes and claims sitagliptin DHP. Claim 1 of the '708 patent recites a sitagliptin DHP salt with a 1:1 stoichiometry. The compound sitagliptin contains one asymmetric (or chiral) carbon, allowing for two enantiomers. Dependent claim 3 recites the (S)-configuration enantiomer. Dependent claim 4 recites a crystalline monohydrate form of the (R)-configuration enantiomer.

During the IPR, Mylan argued that claims 1—3, 17, 19, and 21—23 were anticipated by two Merck-owned publications, WO 2003/004498 and the equivalent U.S. Patent 6,699,871, collectively referred to as "Edmondson." Edmondson discloses a genus of dipeptidyl peptidase-IV inhibitors ("DP-IV inhibitors") useful for treatment of diseases such as Type 2 diabetes and 33 species of these inhibitors, one of which is sitagliptin. Edmondson further discloses that pharmaceutically acceptable salts can be formed using one of a list of eight "[p]articularly preferred" acids, including phosphoric acid. Mylan also argued that claims 1—4, 17, 19, and 21—23 were obvious over Edmondson and two additional publications: Brittain, describing the "pharmaceutical importance and prevalence of crystalline hydrates of pharmaceutical compounds," and Bastin, teaching "salt selection and optimization procedures during the development of pharmaceutical compounds."

The Board found that Mylan failed to show that the challenged claims were anticipated or obvious. The Board determined there was no anticipating disclosure of all of the limitations of the 1:1 sitagliptin DHP salt in Edmondson, and that Mylan could not fill in the gaps by arguing that a skilled artisan would "at once envisage" the missing limitations. Regarding obviousness, the Board determined, as a threshold issue, that Merck could successfully antedate the subject matter of claims 1, 2, 17, 19, and 21—23, and thus Edmondson was not a 35 U.S.C. § 102(a) reference, but instead a 35 U.S.C. § 102(e) (pre-AIA) reference. Because Merck did not assert a prior-reduction-to-practice argument for claims 3 and 4, the Board assessed the prior art obviousness combinations set forth by Mylan. For claim 3, the Board found that neither Edmondson nor Bastin disclosed anything related to (S)-sitagliptin or even a racemic mixture of any sitagliptin salt, thus claim 3 was not obvious. Regarding claim 4, the Board found that Mylan provided no rationale for why a skilled artisan would have been motivated to make the claimed crystalline monohydrate form of 1:1 sitagliptin DHP and have had a reasonable expectation of success in doing so.

Mylan raised three challenges on appeal. First, Mylan asserted that the Board erred in determining Edmondson did not expressly or inherently anticipate a 1:1 stoichiometry of sitagliptin DHP. Second, Mylan contended that the Board erred in determining that the relevant '708 patent claimed subject matter antedated Edmondson. And third, Mylan argued that the Board erred in determining that it failed to prove that combinations of Edmondson, Brittain, and Bastin rendered claims 3 and 4 obvious. The Federal Circuit affirmed the Board's findings on all three grounds.

On anticipation, the Federal Circuit agreed with Merck and the Board that Edmonson did not expressly disclose a 1:1 sitagliptin DHP salt, crediting testimony from Mylan's own expert that nothing in Edmondson directs a skilled artisan to choose sitagliptin from among the 33 listed DP-IV inhibitors. The court further found nothing in Edmondson singles out phosphoric acid or any phosphate salt of any DP-IV inhibitor supporting an express disclosure of a 1:1 sitagliptin DHP salt. As to inherent disclosure, the Federal Circuit considered the "at once envisage" standard set forth in In re Petering relied upon by Mylan. The Court emphasized that the "key term" in the Petering standard is "[a] limited class." See 2022 WL 4541687, at *4 (quoting 301 F.2d at 681) ("a skilled artisan may at once envisage each member of [a] limited class, even though the skilled person might not at once define in his mind the formal boundaries of the class.'") (emphasis in original). It found that, here, Edmondson provided no direction to select sitagliptin from among the listed 33 compounds, plus the eight "pharmaceutically preferred" acids and various stoichiometric possibilities, which resulted in 957 salts, some of which may not exist. Id. The court further found the Edmonson genus "a far cry from the 20 compounds 'envisaged' by the narrow genus in Petering." Id. Testimony from Mylan's own expert that salt formation is an unpredictable art that requires a "trial and error process" further supported the court's finding that a skilled artisan could not "at once envisage" 1:1 sitagliptin DHP salt from the Edmonson genus. Id. Notably, the Federal Circuit expressed that it could not provide a specific number defining "a limited class," rather "[i]t depends on the 'class.'" Id.

As for Mylan's first challenge relating to obviousness, the Federal Circuit agreed with the Board that Merck reduced to practice "more . . . than what is shown in [Edmondson] for the claimed subject matter." 2022 WL 4541687, at *5 (markup in original). So while Edmondson was available as prior art under pre-AIA § 102(e), application of the reference was prohibited under a pre-AIA § 103(c) obviousness analysis because Edmondson and the '708 patent were commonly owned.

Lastly, the Federal Circuit agreed with Merck and the Board that Mylan failed to show that claim 3 ((S)-configuration) and claim 4 ((R)-configuration as a crystalline monohydrate) of the '708 patent were obvious. The court credited the Board's reliance on Mylan's expert's testimony that that the (S)-enantiomer was not disclosed in Edmondson, and that a skilled artisan "couldn't predict with any degree of certainty" hydrate formation. 2022 WL 4541687, at *6-7. The Federal Circuit also noted that Mylan advanced no expected or theoretical benefit to making the (S)-enantiomer of 1:1 sitagliptin DHP, and the general disclosure on diastereomers in Edmondson encompasses millions of potential compounds and salts with no motivation to make the (S)-enantiomer with a reasonable expectation of success, particularly in an unpredictable activity like salt formation. Finally, the Federal Circuit noted the Board's consideration of teaching away evidence presented by Merck's expert, notably that a skilled artisan would have sought to avoid hydrates and that forming crystalline salts, including hydrates, is, again, a highly unpredictable process.

The Federal Circuit concluded that, overall, the Board's decision was supported by substantial evidence and not erroneous as a matter of law.