Anticipation of a claim generally requires that a single prior art reference explicitly discloses each and every claim element.[1] However, absent an express teaching in the prior art, a claim may also be anticipated if it is directed to a member of a limited class that a person of ordinary skill in the art would “at once envisage” from the teachings of the reference.[2] The U.S. Court of Appeals for the Federal Circuit recently provided more guidance on the bounds of its “at once envisage” standard in affirming a notable Patent Trial and Appeal Board (PTAB) decision.

In Mylan Pharms. Inc. v. Merck Sharp & Dohme Corp.,[3] Mylan appealed a PTAB decision finding the claims of Merck’s U.S. Patent No. 7,326,708 (’708 patent) novel over a single prior art reference. The claims at issue relate to a 1:1 sitagliptin dihydrogenphosphate (DHP) salt.[4] Claim 1 of the ’708 patent is directed to:

A dihydrogenphosphate salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine of structural formula I:

or a hydrate thereof.

During the inter partes review, Mylan argued that one of Merck’s prior art publications[5] – describing (R)-sitagliptin hydrochloride among 33 other exemplified compounds – anticipated the 1:1 sitagliptin DHP salt because the reference provides two closed lists containing both 33 compounds and eight preferred acids for forming the salts. Mylan asserted the prior art’s disclosure “collapse to form a single comprehensive list of all the compounds and salts.”[6] However, relying on the testimony of Merck’s expert, the PTAB disagreed, finding that Mylan’s position did not account for the numerous potential stoichiometric ratios of the salts, which could result in approximately 957 salts.[7] The PTAB also found that Mylan’s position was undermined by its own experts, who did not “at once envisage” each member of sitagliptin phosphate salts and whose testimony contradicted the evidence which “undeniably shows that non-1:1 sitagliptin phosphate salts do exist.”[8] As a result, the PTAB found that the claims directed to sitagliptin DHP were not anticipated due to both a lack of express disclosure and the inability of a person of skill in the art to envisage all the possible salts that could be generated from the prior art’s disclosure.

On appeal, the Court stated that in the context of anticipation where a skilled artisan may “at once envisage each member of [a] limited class” that “[t]he key term here is ‘limited.’”[9] The Court declined to provide a specific number that defines a “limited class” but stated that it would depend on the “class.”[10] However, the Court agreed with Merck that a class of 957 predicted salts resulting from 33 disclosed compounds, eight preferred acids, and various stoichiometric possibilities did not meet the “at once envisage” standard.

The Mylan case highlights the nuances of claiming different enantiomers and salt forms of the same small molecule and the ability to overcome references with such disclosure. In an art such as small molecules, reaction components and conditions cannot necessarily be substituted to obtain predictable results. Disclosure of a single salt form might not necessarily negate patentability of another salt form. In practice, the examiner bears the burden of establishing how a reference “at once envisages” a claim, yet applicants can provide evidence demonstrating why one of ordinary skill in the art would have considered the class to be much larger than what the examiner has proposed. Given the decision in Mylan, practitioners should consider the full implications and intricacies of combining compounds, components, or reaction conditions from disclosed lists when considering whether disclosure in a prior art reference forms a limited class and may be subject to the “at once envisage” standard for anticipation.

[1] Verdegaal Bros. v. Union Oil Co. of California, 814 F.2d 628, 631 (Fed. Cir. 1987).

[2] In re Petering, 301 F.2d 676, 681 (C.C.P.A. 1962).

[3] Mylan Pharms. Inc. v. Merck Sharp & Dohme Corp., 50 F.4th 147 (Fed. Cir. 2022).

[4] DHP is a dipeptidyl peptidase-IV inhibitor useful in treating diabetes.

[5] WO2003004498A1.

[6] Mylan Pharms. Inc. v. Merck Sharp & Dohme Corp., IPR2020-00040, 20 (PTAB May 7, 2021) (quotations and citations omitted).

[7] Id. at 29.

[8] Id. at 41.

[9] Mylan, 50 F.4th 147 at 153.

[10] Id. at 154.

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