Case: 21-2121
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`Document:49
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`Page:1_
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`Filed: 09/29/2022
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`GAnited States Court of Appeals
`for the Federal Circuit
`
`MYLAN PHARMACEUTICALSINC.,
`Appellant
`
`Vv.
`
`MERCK SHARP & DOHME CORP.,
`Appellee
`
`2021-2121
`
`Appeal from the United States Patent and Trademark
`Office, Patent Trial and Appeal Board in No. IPR2020-
`00040.
`
`Decided: September 29, 2022
`
`ERIC THOMAS WERLINGER, Katten Muchin Rosenman
`LLP, Washington, DC, argued for appellant. Also repre-
`sented by JITENDRA MALIK, Charlotte, NC; DEEPRO
`MUKERJEE, LANCE SODERSTROM, NewYork, NY.
`
`JEFFREY A. LAMKEN, MoloLamken LLP, Washington,
`DC, argued for appellee. Also represented by CALEB
`HAYES-DEATS, MICHAEL GREGORY PATTILLO, JR.; LAUREN F.
`DAYTON, MARK W. KELLEY, New York, NY; STANLEY E.
`FISHER, BRUCE GENDERSON, DAVID M. KRINSKy, SHAUN
`PATRICK MAHAFFY, CHARLES MCCLOUD, Williams & Con-
`nolly LLP, Washington, DC.
`
`

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`MYLAN PHARMACEUTICALSINC. v.
`MERCK SHARP & DOHMECORP.
`
`Before LOURIE, REYNA, and STOLL, Circuit Judges.
`
`LOURIE, Circuit Judge.
`
`Mylan Pharmaceuticals Inc. (“Mylan”) appeals from
`the final written decision of the U.S. Patent and Trade-
`mark Office Patent Trial and Appeal Board (the “Board”)
`holding thatit failed to show that claims 1—4, 17, 19, and
`21-23 of U.S. Patent 7,326,708 (the “708 patent”) were an-
`ticipated or would have been obvious over the cited prior
`art at the time the alleged invention was made. See Mylan
`Pharms. Inc. v. Merck Sharp & Dohme Corp., No. IPR2020-
`00040, 2021 WL 1833325 (P.T.A.B. May 7, 2021) (“Deci-
`sion”). For the reasons provided below,weaffirm.
`
`BACKGROUND
`
`Merck Sharp & DohmeCorp. (“Merck”) owns the ’708
`patent, which describes sitagliptin dihydrogenphosphate
`(“sitagliptin DHP”). Sitagliptin DHP is a dihydrogenphos-
`phate
`salt
`of
`4-oxo-4-[3-(trifluoromethy]l)-5,6-dihydro
`[1,2,4]triazolo[4,3-a] pyrazin-7(8H)-yl]-1-(2,4,5-trifluoro-
`phenyl)butan-2-amine. Sitagliptin DHP belongs to the
`class of dipeptidyl peptidase-IV (““DP-IV”) inhibitors, which
`can be usedfor treating non-insulin-dependent(i.e., Type
`2) diabetes. Independentclaim 1 recites a sitagliptin DHP
`salt with a 1:1 stoichiometry, and readsas follows:
`
`1. A dihydrogenphosphatesalt of a 4-oxo-4-[8-
`(trifluoromethyl)-5,6-dihydro
`[1,2,4]tria-
`zolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-tri-
`fluorophenyl)butan-2-amine of Formula I:
`
`
`
`

`

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`MYLAN PHARMACEUTICALSINC. v.
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`or a hydrate thereof.
`
`’708 patentcol. 15 1. 64-col. 161. 15.
`
`Sitagliptin contains a single asymmetric carbon,indi-
`cated by the asterisk in the above chemical structure. The
`(R)-configuration and (S)-configuration of sitagliptin DHP
`are recited in dependent claims 2 and 3, respectively. A
`crystalline monohydrate form of the (R)-configurationis re-
`cited in dependent claim 4.
`
`Mylan petitioned for inter partes review (“IPR”) of
`claims 1—4, 17, 19, and 21—23 of the ’708 patent. J.A. 177.
`Mylan argued that claims 1—3, 17, 19, and 21—23 were an-
`ticipated
`by
`International
`Patent
`Publication
`WO 2003/004498 (the “498 publication”), a Merck-owned
`publication, and the equivalent U.S. Patent 6,699,871 (the
`“871 patent”) (collectively, “Edmondson”).1
`
`Edmondson“is directed to compounds whichare inhib-
`itors of the dipeptidyl peptidase-IV enzyme (‘DP-IV inhibi-
`tors’) and which are useful in the treatment or prevention
`of diseases in which the dipeptidyl peptidase-IV enzymeis
`involved, such as diabetes and particularly type 2 diabe-
`tes.” Decision, 2021 WL 1833325, at *6. Specifically, Ed-
`mondson discloses a genus of DP-IV inhibitors and
`33 species, one of which is sitagliptin. 498 publication
`col. 54 1. 16—-col. 60 1. 5. Edmondson further discloses that
`pharmaceutically acceptable salts can be formed using one
`of eight “[p]articularly preferred” acids.
`Jd. at col. 10
`ll. 14-15. Phosphoricacidis in thelist of “particularly pre-
`ferred” acids. Edmondsonalso discloses that the salts may
`
`The parties agree that the ’498 publication and the
`1
`’°871 patent are identical in relevant part. Appellant’s
`Br. 1; Appellee’s Br. 5, n.1. The Board also treated them as
`identical in relevant part. Decision, 2021 WL 1833325, at
`*1,n.4.
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`exist in crystalline forms, including as hydrates. Id. at col.
`9 ll. 832-34.
`
`Mylan also argued that claims 1—4, 17, 19, and 21-23
`would have been obvious over Edmondson and two addi-
`tional publicationstitled “Structural Aspects of Hydrates
`and Solvates” (“Brittain”)? and “Salt Selection and Optimi-
`sation Procedures for Pharmaceutical New Chemical Enti-
`ties” (“Bastin”).3
`
`Brittain describes the pharmaceutical importance and
`prevalence of crystalline hydrates of pharmaceutical com-
`pounds.
`J.A. 438-94. Specifically, Brittain teaches that
`approximately one third of studied pharmaceutical active
`ingredients could form crystalline hydrates, and half of
`those one-third were monohydrates.
`J.A. 441.
`In other
`words, Brittain illustrates that approximately one sixth of
`the analyzed pharmaceutical compounds formed crystal-
`line monohydrates. Brittain also cites various challenges
`that arise during the manufacturing and development of
`hydrates, including lower solubility, chemical instability,
`and discoloration. J.A. 440.
`
`Bastin teaches salt selection and optimization proce-
`dures during the development of pharmaceutical com-
`pounds. J.A. 495-97. Specifically, Bastin teaches that a
`rangeof possible salts should be prepared for each new sub-
`stance to compare adequately the properties of each salt
`during the development process.
`J.A. 495. Bastin also
`
`2 Kenneth R. Morris, Structural Aspects of Hydrates
`and Solvates, in Polymorphism in Pharmaceutical Solids
`125-181 (Harry G. Brittain ed., 1999).
`3 Richard J. Bastin, Michael J. Bowker, & Brian J.
`Slater, Salt Selection and Optimisation Procedures for
`Pharmaceutical New Chemical Entities, 4 Organic Process
`Rsch. & Dev. 427 (2000).
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`discloses disadvantages of certain salts used in drug for-
`mulations, including hydrochloric acid (“HCI”). J.A. 496.
`
`First, the Board determined that there was no express
`disclosureofall 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 en-
`visage” what is missing. Decision, 2021 WL 183833825, at
`*10, *12. The Board also concluded that Mylan had not
`proven an inherent disclosure of the 1:1 sitagliptin DHP
`salt in Edmondson, and that evidence, both experimental
`and from the technical literature, undeniably showed that
`1:1 sitagliptin DHP does not form every timesitagliptin
`and DHP were reacted.
`Id. at *15-16. The Board con-
`cluded that claims 1—3, 17, 19, and 21—23 were neither ex-
`pressly nor inherently anticipated by Edmondson.
`Id. at
`*16.
`
`Next, the Board determined that claims 1—4, 17, 19,
`and 21—23 would not have been obviousin view of Edmond-
`son, Bastin, or Brittain. First, the Board considered the
`threshold issue whether Merck could antedate Edmondson
`with evidence that it had reduced to practice the subject
`matter of claims 1, 2, 17, 19, and 21—23 before Edmondson
`had been published on January 16, 2008.
`Id. at *16—20.
`The Board concluded that Merck had reduced to practice at
`least as much,and in fact more, of the claimed subject mat-
`ter than was shown in Edmondson.
`Id. at *20. Thus,
`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 merely a 35 U.S.C.
`§ 102(e) (pre-AIA) reference.
`Jd. Because it was undis-
`puted that the inventions claimed in the ’708 patent and
`the subject matter of Edmondson were commonly owned by
`Merck, or underobligation of assignment to Merck, at the
`time of the invention,
`the Board determined that the
`35 U.S.C. § 103(c)(1) (pre-AIA) exception applied to claims
`1, 2, 17, 19, and 21-28. Id. Merck did not assert a prior-
`reduction-to-practice argument for claims 3 and 4. Jd.
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`The Board considered whether claim 3, which recites
`the (S)-configuration of sitagliptin DHP, and claim 4, which
`recites the crystalline monohydrate form of (R)-sitagliptin,
`would have been obvious in view of Edmondson, Bastin,
`and Brittain. The Board found that neither Edmondson
`nor Bastin disclosed anything related to (S)-sitagliptin or
`even a racemic mixture of any sitagliptin salt. Id. at *21.
`The Board thus concluded that Mylan did not show that
`claim 3 would have been obvious to a skilled artisan at the
`time the invention was made. Id. at *22. The Board also
`found that Mylan provided no rationale to explain why a
`person of ordinary skill would have been motivated to
`make the claimed crystalline monohydrate form of 1:1
`sitagliptin DHPof claim 4 andfailed to show that a skilled
`artisan would have had a reasonable expectation of success
`in making the crystalline monohydrate form of the 1:1
`sitagliptin DHPsalt. Id. at *24, *26. The Board thus con-
`cluded that Mylan failed to show that claim 4 would have
`been obvious to a person of ordinary skill at the time the
`invention was made. Id. at *26.
`
`In summary, the Board concluded that Mylan had not
`demonstrated that claims 1—4, 17, 19, and 21—23 were an-
`ticipated or would have been obviousat the time the inven-
`tion was made. Mylan appealed. We have jurisdiction
`under 28 U.S.C. § 1295(a)(4).
`
`DISCUSSION
`
`Mylan raises three challenges on appeal. First, Mylan
`contends that the Board erred in determining that a 1:1
`stoichiometry of sitagliptin DHP was not anticipated, ei-
`ther expressly or inherently, by Edmondson.
`Second,
`Mylan contends that the Board erred in determining that
`the ’708 patent antedates Edmondson.4 Third, Mylan
`
`The ’498 publication was published on January 16,
`4
`2003, and the ’871 patent was published on May 29, 2003.
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`contends that the Board erred in determiningthatit failed
`to prove that claims 3 and 4 of the ’708 patent would have
`been obvious over Edmondson, Brittain, and Bastin. We
`address each argumentin turn.
`
`Wereview the Board’s legal determinations de novo, In
`re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), but we re-
`view the Board’s factual findings underlying those deter-
`minations for substantial evidence.
`In re Gartside,
`203 F.3d 1305, 1816 (Fed. Cir. 2000). A finding is sup-
`ported by substantial evidence if a reasonable mind might
`accept the evidence as adequate to support the finding.
`Consol. Edison Co. v. NLRB, 305 U.S. 197, 229 (1938). And
`“lilf two ‘inconsistent conclusions may reasonably be drawn
`from the evidence in the record, [the PTAB]’s decision to
`favor one conclusion over the otheris the epitome of a de-
`cision that must be sustained upon review for substantial
`evidence.” Elbit Sys. of Am., LLC v. Thales Visionix, Inc.,
`881 F.3d 1354, 1356 (Fed. Cir. 2018) (alteration in original)
`(quoting In re Cree, Inc., 818 F.3d 694, 701 (Fed. Cir.
`2016)).
`
`Anticipation is a question of fact. Genentech, Inc. v.
`Hospira, Inc., 946 F.3d 1333, 1837 (Fed. Cir. 2020). The
`prior art may be deemedto disclose each memberof a ge-
`nus when,reading the reference, a person of ordinary skill
`can “at once envisage each memberof this limited class.”
`In re Petering, 301 F.2d 676, 681 (C.C.P.A. 1962).
`
`Obviousnessis a “mixed question of law and fact,” and
`we review “the Board’s ultimate obviousness determina-
`tion de novo and underlying fact-findings for substantial
`evidence.” Hologic, Inc. v. Smith & Nephew, Inc., 884 F.3d
`1357, 1861 (Fed. Cir. 2018).
`
`Since the ’498 publication was published earlier, we con-
`sider Edmondson,for purposes of antedation, to have been
`published on January 16, 2003.
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`MYLAN PHARMACEUTICALSINC. v.
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`I
`
`Wefirst consider Mylan’s challenge to the Board’s de-
`termination that it failed to prove that Edmondsonantici-
`pates claims 1—3, 17, 19, and 21-23. Mylan argues that
`Edmondson anticipates the claims because it discloses
`sitagliptin in a list of 833 compounds. Mylan further asserts
`that Edmondsondisclosesacids forming “pharmaceutically
`acceptable salts,” including phosphoric acidin a list of eight
`“particularly preferred” acids. Mylan, therefore, asserts
`that sitagliptin DHPis effectively disclosed in Edmondson,
`and Edmondsonthusanticipates the challenged claims.
`
`Mylan further asserts that a skilled artisan would “at
`once envisage” a 1:1 stoichiometry of the sitagliptin DHP
`salt for two reasons. First, Example 7 of Edmondsondis-
`closes a sitagliptin hydrochloride salt (“sitagliptin HCl”)
`having a 1:1 stoichiometry. Second, experimental data pre-
`sented by Mylan’s expert Dr. Chorghade illustrate that
`only a 1:1 sitagliptin DHP stoichiometry forms under con-
`ditions allegedly similar to those disclosed in Edmondson.
`Mylan contends that the Board thus erred in holding that
`a 1:1 stoichiometry was not anticipated by Edmondson.
`
`Merck responds that the Board’s holding that the
`claims are not anticipated by Edmondson was supported by
`substantial evidence. Merck asserts that a skilled artisan
`would not “at once envisage” all membersof the entire ge-
`nus of DP-IV-inhibitor salts disclosed in Edmondson.
`Merck further contends that the combinedlist of 33 com-
`poundsandeight preferred salts, taking into accountvari-
`ous stoichiometric possibilities, would result in 957 salts,
`some of which may not even form under experimental con-
`ditions. That, Merck asserts, does not meet the standard
`set by the “at once envisage” theory. Merck argues that
`Mylan seeksto expandthe theory inappropriately, improp-
`erly focusing on whetherskilled artisans could have envis-
`aged 1:1 sitagliptin DHP among the membersoftheclass
`instead of envisaging each memberof the disclosed class.
`
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`In essence, Merck asserts that Mylan uses hindsightto sin-
`gle out one compound from the large class. Merck further
`argues that Mylan’s own expert conceded that Edmondson
`does not direct a skilled artisan to sitagliptin from among
`the 33 DP-IVs, nor does it disclose a phosphate salt of any
`DP-IV inhibitor.
`
`We agree with Merck that the Board’s decision was
`supported by substantial evidence. The Board did not err
`in determining that Edmondsondoesnot expressly disclose
`a 1:1 sitagliptin DHPsalt. The Board groundedits finding
`in the testimony from Mylan’s own expert, Dr. Chorghade,
`stating that nothing in Edmondsondirects a skilled artisan
`to sitagliptin from among the 33 listed DP-IV inhibitors.
`J.A. 23842, 2373-74; Chorghade Dep. 61:7-62:9, 188:6—
`189:8. Further, nothing in Edmondson singles out phos-
`phoric acid or any phosphate salt of any DP-IV inhibitor,
`andthelist of “pharmaceutically preferred” salts comes 44
`pages earlier in the specification. The Board reasonably
`concluded that Edmondson does not expressly disclose the
`1:1 sitagliptin DHPsalt.
`
`Wealso agree with Merck that the Board did not err in
`determining that Edmondson does not inherently disclose
`a 1:1 sitagliptin DHP salt.
`In re Petering stands for the
`proposition that a skilled artisan may “at once envisage
`each memberof [a] limited class, even though the skilled
`person might not at once define in his mind the formal
`boundariesof the class.” 301 F.2d at 681 (emphasis added).
`The key term hereis “limited.” As Merck asserted, and as
`the Board considered, thelist of 33 compounds, with no di-
`rection to select sitagliptin from among them, plus the
`eight “pharmaceutically preferred” acids and various stoi-
`chiometric possibilities, results in 957 salts, some of which
`may not exist. That is a far cry from the 20 compounds
`“envisaged” by the narrow genusin Petering. Id. Mylan’s
`own expert, Dr. Chorghade, even stated that salt formation
`is an unpredictable art that requires a “trial and error
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`process.” Decision, 2021 WL 1833325,at *8; J.A. 2855-56;
`Chorghade Dep. 116:22—117:3.
`
`Wecannot provide a specific number defining a “lim-
`ited class.” In re Petering, 301 F.2d at 681. It depends on
`the “class.” But we agree with Merck and hold that the
`Board did not err in finding that a class of 957 predicted
`salts that may result from the 33 disclosed compounds and
`eight preferred acids, some of which maynot even form un-
`der experimental conditions,is insufficient to meet the “at
`once envisage” standardset forth in Petering.
`
`II
`
`Wenext consider Mylan’s challenge to the Board’s de-
`termination that Mylanfailed to prove that claims 1—4, 17,
`19, and 21—23 would have been obvious to a person of ordi-
`nary skill in the art at the time the invention was made.
`
`A
`
`We mustfirst consider the threshold issue of Mylan’s
`antedation challenge and application of the 35 U.S.C.
`§ 108(c)(1) exception. Under 35 U.S.C. § 102(a) (pre-AIA),
`“[a] person shall be entitled to a patent unless the inven-
`tion was knownor used by others in this country, or pa-
`tented or described in a printed publication in this or a
`foreign country, before the invention thereof by the appli-
`cant for a patent.” But a party can overcomethe § 102(a)
`barrier if it can antedate a reference “by showing that the
`invention wasconceived before the effective date of theref-
`erence, with diligence to actual or constructive reduction to
`practice.” In re Steed, 802 F.3d 1311, 1320 (Fed. Cir. 2015).
`To prove antedation, the patent owner must show that it
`reduced to practice at least as much as “the reference
`showsof the claimed invention” before the reference’s pub-
`lication date.
`In re Clarke, 356 F.2d 987, 991 (C.C.P.A.
`1966).
`
`Mylan does not dispute that Merck reduced 1:1 (R)-
`sitagliptin DHP salt to practice before Edmondson was
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`published, nor does it dispute that Merck commonly owned
`Edmondson and the ’708 patent. Mylan, instead, argues
`that the Board erred in finding that Merck’s reduction to
`practice of the 1:1 (R)-sitagliptin DHP salt antedates Ed-
`mondson, because Edmondson discloses sitagliptin hy-
`drates, and Merck had not made hydratesof 1:1 sitagliptin
`DHPuntil March 2008, about two monthsafter the Janu-
`ary 16, 2003 Edmondson publication date. Mylan also ar-
`gues that the Board erred in finding that Edmondson does
`not disclose hydratesof sitagliptin phosphate.
`
`Merck responds that the Board did not err in finding
`that Merck’s work on the subject matter in claims 1, 2, 17,
`19, and 21—23 of the ’708 patent antedated Edmondson.
`Merck argues that it had reduced to practice the subject
`matter of these claims before Edmondson had been pub-
`lished on January 16, 2003. As a result, Merck asserts,
`Edmondson could not serve as 35 U.S.C. § 102(a) prior art
`and would merely be a 35 U.S.C. § 102(e) reference. Be-
`cause it is undisputed that the invention claimed in the
`"708 patent and the subject matter of Edmondson were
`commonly owned by Merckat the timeof the invention, the
`exception in § 103(c)(1) applies. Section 103(c)(1) (pre-AIA)
`provides that “[s]ubject matter developed by another per-
`son, which qualifies as prior art only under one or more
`subsections(e), (f), and (g) of section 102, shall not preclude
`patentability under this section where the subject matter
`and the claimed invention were, at the time the claimed
`invention was made, owned by the same person or subject
`to an obligation of assignmentto the same person.” Merck
`therefore argues that Edmondson cannot serve as an obvi-
`ousnessreferencefor claims 1, 2, 17, 19, and 21-23. With-
`out Edmondson,the obviousnesschallenge to these claims
`fails. Decision, 2021 WL 18333285, at *20.
`
`We agree with Merck that the Board’s antedation de-
`termination was supported by substantial evidence. As
`Merck asserts, and as the Board considered, Merck showed
`that it developed a 1:1 sitagliptin DHP salt in December
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`2001 with experimental confirmation in early 2002. As
`Merck highlights, Mylan did not argue that claim 4, di-
`rected to a crystalline monohydrate, was anticipated by Ed-
`mondson, which it could have done had it believed that
`Edmondson disclosed a crystalline monohydrate. The
`Board’s finding that Edmondson does not disclose 1:1
`sitagliptin DHP was supported by substantial evidence;
`thus, the Board’s finding that it does not disclose a hydrate
`of that salt was likewise supported by substantial evidence.
`Wetherefore agree with the Board that Merck reduced to
`practice “more .. . than what is shown in [Edmondson] for
`the claimed subject matter.” Decision, 2021 WL 18383325,
`at *18.
`
`B
`
`Wenext turn to whether the Board erred in holding
`that Mylan failed to prove that claims 3 and 4 of the ’708
`patent would have been obvious to a skilled artisan at the
`time the invention was made.
`
`Mylan argues that the Board erred in holding that it
`failed to prove that claim 3, which recites the (S)-configu-
`ration of 1:1 sitagliptin DHP, would have been obvious.
`Mylan argues that Edmondson, in combination with Bas-
`tin, would have allowed a skilled artisan to envisage and
`create 1:1 (S)-sitagliptin DHP. According to Mylan,Bastin,
`which cites disadvantages of hydrochloric acid in pharma-
`ceutical formulations, would encouragea skilled artisan to
`replace the hydrochloric acid in Example 7 of Edmondson.
`Furthermore, Mylan states that sitagliptin has one asym-
`metric carbon, and a skilled artisan would thus havea rea-
`sonable expectation of success in creating both (R)-
`sitagliptin and(S)-sitagliptin.
`
`Mylan further argues that the Board erred in holding
`that it failed to prove that claim 4, which recites the crys-
`talline monohydrate form of (R)-sitagliptin, would have
`been obvious. Mylan asserts that a skilled artisan would
`have had a reasonable expectation of success in creating a
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`crystalline monohydrate in view of Edmondson in combi-
`nation with Brittain. First, Mylan argues that Edmondson
`states that the described salts exist in more than onecrys-
`tal structure and in the form of a hydrate. Second, Mylan
`argues that Brittain’s discussion of hydrates would have
`provided motivation for a skilled artisan to explore hy-
`drates in the developmentprocess.
`
`Merck argues that the Board did not err in holding that
`claim 3 would not have been obvious, and that the Board’s
`underlying factual findings were supported by substantial
`evidence. As the Board considered, Bastin does not provide
`a specific motivation, including any screening or optimiza-
`tion protocol that, combined with Edmondson, would lead
`to 1:1 sitagliptin DHP,the (S)-configuration, or even a ra-
`cemic mixture.
`
`Merck also argues that the Board did not err in holding
`that claim 4 would not have been obvious, and that the
`Board’s underlyingfactual findings were supported by sub-
`stantial evidence. Merck argues that the Board wascorrect
`in finding that Mylan did not provide a persuasive motiva-
`tion for making the crystalline monohydrate form of
`sitagliptin. Merck asserts evidence that skilled artisans
`would avoid making hydrates dueto solubility and stability
`challenges during the drug-production process. Merck also
`contends that the monohydrate has unexpectedly favorable
`properties, and that these properties are objective indicia
`of nonobviousness.
`
`Weagree with Merck that the Board’s decision that
`Mylan failed to show that claims 3 and 4 of the ’708 patent
`would have been obviousto a skilled artisan at the time the
`invention was made was supported by substantial evi-
`dence.
`
`Withrespect to claim 3, the Board found that there was
`no motivation to combine Edmondson and Bastin to make
`sitagliptin DHP, that the two cited references did not pro-
`vide motivation to make (S)-sitagliptin, and that there was
`
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`Case: 21-2121 Page: 14_Filed: 09/29/2022 Document:49
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`14
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`MYLAN PHARMACEUTICALSINC. v.
`MERCK SHARP & DOHMECORP.
`
`no reasonable expectation of success in combiningtheref-
`erences. The Board adequately credited Dr. Chorghade’s
`testimony, which stated that the (S)-enantiomer was not
`disclosed in Edmondson. Decision, 2021 WL 1838325, at
`*21. The Board further highlighted that Mylan advanced
`no expected or theoretical benefit to making the (S)-enan-
`tiomer of 1:1 sitagliptin DHP, and that the general disclo-
`sure on diastereomers in Edmondson encompasses millions
`of potential compounds and salts with no motivation to
`makethe (S)-enantiomer with a reasonable expectation of
`success, particularly in an unpredictable activity like salt
`formation. Id. at *22. We thus agree with Merck that the
`Board’s decision was supported by substantial evidence.
`
`Withrespect to claim 4, the Board found that there was
`no motivation to combine Edmondson, Bastin, and Brit-
`tain, and that a person of ordinary skill would have had no
`reasonable expectation of success in doing so. The Board
`credited Dr. Chorghade’s testimony, which stated that a
`skilled artisan “couldn’t predict with any degree of cer-
`tainty” hydrate formation.
`Jd. at *21; Chorghade Dep.
`238:8-18. The Board also addressed the numerous down-
`sides of hydrates reported in the literature, including those
`stating that a skilled artisan would have several reasons
`for avoiding hydrates. Decision, 2021 WL 18383838285,at *23.
`The Boardalso credited Merck’s expert, Dr. Myerson, who
`stated that a skilled artisan would have sought to avoid
`hydrates, Decision, 2021 WL 1833325, at *22; Myerson
`Decl., 127-88, and that formingcrystalline salts, includ-
`ing hydrates, is highly unpredictable. Decision, 2021 WL
`1833325, at *24; Myerson Decl., | 146-49. We thus agree
`with Merck that the Board’s decision was supported by
`substantial evidence.
`
`Finally, the Board did not err in its evaluation of pur-
`ported objective indicia of nonobviousness. Although the
`Board did not consider in detail the alleged unexpected
`properties of the claimed crystalline monohydrate of
`claim 4, the Board stated that such unexpected results
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`Case: 21-2121 Page:15_Filed: 09/29/2022Document:49
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`MYLAN PHARMACEUTICALSINC. v.
`MERCK SHARP & DOHME CORP.
`
`15
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`served as further evidence undermining Mylan’s challenge
`to claim 4. See Hamilton Beach Brands,Inc.v. freal Foods,
`LLC, 908 F.3d 1328, 1348 (Fed. Cir. 2018) (holding that
`there is no need to reach objective indicia of nonobvious-
`ness where the petitioner has not made a showing neces-
`sary to prevail on threshold obviousness issues).
`
`CONCLUSION
`
`Wehave considered Mylan’s remaining arguments, but
`wefind them unpersuasive. The Board’s decision was sup-
`ported by substantial evidence and not erroneous as a mat-
`ter of law. For the foregoing reasons, the decision of the
`Boardis affirmed.
`
`AFFIRMED
`
`