`
`
`
`NOTE: This disposition is nonprecedential.
`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`MERCK SHARP & DOHME CORP.,
`Appellant
`
`v.
`
`WYETH LLC,
`Appellee
`______________________
`
`2018-2133, 2018-2134
`______________________
`
`Appeals from the United States Patent and Trademark
`Office, Patent Trial and Appeal Board in Nos. IPR2017-
`00378, IPR2017-00380.
`______________________
`
`Decided: November 26, 2019
`______________________
`
`JEFFREY A. LAMKEN, MoloLamken LLP, Washington,
`DC, argued for appellant. Also represented by MICHAEL
`GREGORY PATTILLO, JR., BENJAMIN THOMAS SIROLLY; SARA
`MARGOLIS, New York, NY; ARLENE L. CHOW, Hogan Lovells
`US LLP, New York, NY; RYAN BOYD MCCRUM, Jones Day,
`Cleveland, OH; JENNIFER LORAINE SWIZE, Washington,
`DC.
`
` JOHN P. SCHEIBELER, White & Case LLP, New York,
`NY, argued for appellee. Also represented by DIMITRIOS T.
`
`
`
`Case: 18-2133 Document: 69 Page: 2 Filed: 11/26/2019
`
`2
`
`MERCK SHARP & DOHME CORP. v. WYETH LLC
`
`DRIVAS, DANIEL LEDESMA, STEFAN MENTZER, AMIT
`THAKORE.
` ______________________
`
`Before PROST, Chief Judge, DYK and WALLACH, Circuit
`Judges.
`
`DYK, Circuit Judge.
`Merck Sharp & Dohme Corp. (“Merck”) appeals deci-
`sions of the Patent Trial and Appeal Board (“Board”) de-
`clining to find claim 18 of U.S. Patent No. 8,562,999 (“the
`’999 patent”) unpatentable as obvious. We vacate and re-
`mand for further proceedings.
`BACKGROUND
`The ’999 patent, owned by Wyeth LLC (“Wyeth”), is di-
`rected to formulations for stabilizing polysaccharide-pro-
`tein conjugate vaccines. These vaccines are derived from
`the capsular polysaccharides present on the surface of cer-
`tain disease-causing bacteria. The human immune system
`can use these capsular polysaccharides to detect and iden-
`tify different serotypes (i.e., strains) of a species of bacteria.
`Polysaccharide vaccines can be monovalent (comprising a
`single serotype), or multivalent (comprising multiple sero-
`types). For example, a 13-valent vaccine would contain pol-
`ysaccharides from 13 different serotypes. Because these
`polysaccharides typically have low immunogenicity (i.e.,
`ability to provoke an immune response), it is desirable to
`enhance the effectiveness of these vaccines by conjugating
`(i.e., bonding) the polysaccharides to a carrier protein with
`high immunogenicity. However, as the ’999 patent ex-
`plains, polysaccharide-protein conjugate vaccines aggre-
`gate (i.e., clump together) when exposed to silicone oil, a
`common lubricant used in vaccine storage containers. The
`invention described in the ’999 patent is a formulation that
`inhibits silicone-induced aggregation by suspending the
`polysaccharide-protein conjugate in a mixture of (1) a pH-
`buffered saline solution and (2) an aluminum salt.
`
`
`
`Case: 18-2133 Document: 69 Page: 3 Filed: 11/26/2019
`
`MERCK SHARP & DOHME CORP. v. WYETH LLC
`
`3
`
`Claim 1, the sole independent claim of the ’999 patent, re-
`cites a formulation comprising of: (1) a pH-buffered saline
`solution, (2) an aluminum salt, and (3) one or more poly-
`saccharide-protein conjugates. Claim 18 recites a specific
`13-valent pneumococcal polysaccharide conjugate with
`CRM197 as the sole carrier protein for use with the formu-
`lation recited in claim 1.
`On December 1, 2016, Merck filed two petitions for in-
`ter partes review with the Board, challenging claims 1–6,
`10, 11, 14, and 17–20 of the ’999 patent. The Board insti-
`tuted review of all challenged claims in two parallel pro-
`ceedings, IPR2017-00378 (“the 378 IPR”) and IPR2017-
`00380 (“the 380 IPR”). In each proceeding, the Board found
`all the challenged claims except one—claim 18—to be un-
`patentable as obvious. Claim 18 covers a 13-valent pneu-
`mococcal conjugate vaccine. In both proceedings, the Board
`rejected Merck’s argument that the formulation recited by
`claim 18 was obvious in light of the prior art. Merck ap-
`peals the Board’s decisions as to claim 18. We have juris-
`diction pursuant to 28 U.S.C. § 1295(a)(4)(A).
`DISCUSSION
`“We review the Board’s factual findings for substantial
`evidence and review its legal conclusions de novo.” In re
`Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1280 (Fed. Cir.
`2015). “The ultimate determination of obviousness un-
`der [35 U.S.C.] § 103 is a question of law based on underly-
`ing factual findings.” Id.1 “The presence or absence of a
`
`
`1 Congress amended § 103 when it enacted the
`Leahy-Smith America Invents Act (“AIA”). Pub. L. No.
`112-29, § 3(b)(1), 125 Stat. 284, 285–87 (2011). However,
`because the application that led to the ’999 patent has
`never contained (1) a claim having an effective filing date
`on or after March 16, 2013, or (2) a reference under 35
`U.S.C. §§ 120, 121, or 365(c) to any patent or application
`
`
`
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`4
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`MERCK SHARP & DOHME CORP. v. WYETH LLC
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`motivation to combine references in an obviousness deter-
`mination is a pure question of fact.” Intelligent Bio-Sys-
`tems, Inc. v. Illumina Cambridge, Ltd., 821 F.3d 1359, 1366
`(Fed. Cir. 2016) (quoting Par Pharm., Inc. v. TWi Pharms.,
`Inc., 773 F.3d 1186, 1196 (Fed. Cir. 2014)). “The presence
`or absence of a reasonable expectation of success is also a
`question of fact.” Id. (quoting Par Pharm., 773 F.3d at
`1196).
`
`I
`It is well established that “[t]he agency tribunal must
`make findings of relevant facts, and present its reasoning
`in sufficient detail that the court may conduct meaningful
`review of the agency action.” In re Lee, 277 F.3d 1338, 1346
`(Fed. Cir. 2002). “The [Board]’s own explanation must suf-
`fice for us to see that the agency has done its job and must
`be capable of being ‘reasonably . . . discerned’ from a rela-
`tively concise [Board] discussion.” In re NuVasive, Inc., 842
`F.3d 1376, 1383 (Fed. Cir. 2016) (quoting In re Huston, 308
`F.3d 1267, 1281 (Fed. Cir. 2002)).
`On appeal, Merck argues that the Board’s decisions
`here fail to provide a reasoned basis for upholding claim 18.
`For the reasons discussed below, we agree.
`Claim 18 depends on claim 1, which recites:
`A formulation comprising (i) a pH buffered saline
`solution, wherein the buffer has a pKa of about 3.5
`to about 7.5, (ii) an aluminum salt and (iii) one or
`more polysaccharide-protein conjugates, wherein
`the formulation is comprised in a siliconized con-
`tainer means and inhibits aggregation induced by
`the siliconized container means.
`
`
`that ever contained such a claim, the pre-AIA § 103 ap-
`plies. See id. § 3(n)(1), 125 Stat. at 293.
`
`
`
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`MERCK SHARP & DOHME CORP. v. WYETH LLC
`
`5
`
`’999 patent, col. 31, ll. 7–12.
`Claim 18 recites:
`The formulation of claim 1, wherein the one or
`more polysaccharide-protein conjugate comprises
`[13 different S. pneumoniae serotype polysaccha-
`rides conjugated to a CRM197 polypeptide].
`’999 patent, col. 32, ll. 24–45.2
`In the 378 IPR, Merck challenged claim 1 as obvious in
`light of International PCT Application No. WO 03/009869
`(“Chiron”); Edward J. Smith, Siliconization of Parenteral
`Drug Packaging Components (1988) (“Smith”); and Inter-
`national PCT Application No. WO 2004/071439 (“Elan”).
`In the 380 IPR, Merck challenged claim 1 as obvious in
`light of Chiron and Annex I of the European Medicines
`Agency’s European Public Assessment Report for Prevenar
`(“Prevenar”). In both proceedings, the Board made de-
`tailed findings that claim 1 was obvious in light of the cited
`references.3 The Board also found that a skilled artisan
`“would have found it obvious to prepare Chiron’s formula-
`tion [according to claim 1 and also] comprising the seven
`
`2 The 13 serotypes are 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14,
`18C, 19A, 19F, and 23F.
`3 The Board found that “Chiron teaches a formula-
`tion comprising the ingredients [pH-buffered saline solu-
`tion, aluminum salt, and one or more polysaccharide-
`protein conjugate] recited in independent claim 1,” J.A. 21,
`that “a person of ordinary skill in the art would have had
`reason to provide Chiron’s formulation in a siliconized con-
`tainer means, and would have had a reasonable expecta-
`tion of successfully doing so, as had been done with other
`. . . conjugate vaccines [identified by Chiron],” J.A. 29, and
`that “a person of ordinary skill in the art would have ap-
`preciated that Chiron’s formulation inhibits aggregation
`induced by a siliconized container means,” J.A. 32.
`
`
`
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`6
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`MERCK SHARP & DOHME CORP. v. WYETH LLC
`
`valent conjugate recited in claim 17.” J.A. 37. Wyeth does
`not challenge either of these determinations on appeal.
`In each proceeding, Merck also challenged dependent
`claim 18 as obvious in light of the previously cited refer-
`ences and in combination with an additional reference,
`Peña et al., Present and Future of the Pneumonia Vaccina-
`tion, 24 Pediatrika 47 (2004) (“Peña”). Peña disclosed a
`study involving a 13-valent conjugate, but did not disclose
`conjugating with the CRM197 protein as required by claim
`18.
`
`The Board found that although Peña disclosed a “13-
`valent pneumococcal conjugate vaccine with the same sero-
`types recited by claim 18 that is described as being in an
`‘advanced phase of study,’” Merck failed to “direct [the
`Board] to any disclosure in Peña, or other evidence of rec-
`ord, further characterizing the vaccine or the study.”
`J.A. 44 (citing J.A. 272, 992), see also J.A. 86. The Board
`stated that it was “unable to assess whether the study in-
`volved a formulation comprising each of the thirteen
`known serotypes conjugated to a CRM197 polypeptide, [the
`carrier protein] required by the claim, or if such an attempt
`was even considered, tried, and successful.” Id. The Board
`concluded that Merck “ha[d] not provided a reason that a
`person of skill in the art would have modified Chiron’s for-
`mulation to comprise a thirteen valent conjugate,” and that
`“[Merck] ha[d] not provided sufficient evidence for [the
`Board] to determine whether a skilled artisan who endeav-
`ored to modify Chiron’s formulation to yield a 13-valent
`pneumococcal conjugate vaccine with the same serotypes
`as in Peña would have had a reasonable expectation of suc-
`cessfully doing so.” Id. at 44.
`The Board found—and there is no dispute—that Peña
`discloses each of the 13 serotypes in claim 18. Merck’s ex-
`pert testified (without contradiction from Wyeth’s expert)
`that early pneumococcal polysaccharide vaccines included
`14-valent and 23-valent unconjugated vaccines which,
`
`
`
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`MERCK SHARP & DOHME CORP. v. WYETH LLC
`
`7
`
`together, included all 13 serotypes, and that it would have
`been obvious to combine them. At oral argument in this
`court, Wyeth made little effort to counter Merck’s conten-
`tions that each of the 13 serotypes was disclosed in the
`prior art and that there was motivation to combine the 13
`serotypes into a single vaccine. Furthermore, Wyeth was
`unable to identify any expert testimony in the record sug-
`gesting that the 13-serotype combination was not obvious.
`On this record, Merck established that it was obvious to
`combine the 13 serotypes into a single vaccine.
`Instead, the question was whether it was obvious to
`conjugate the 13 serotypes to the CRM197 protein in a single
`vaccine. The Board’s decision rests on its finding that the
`study discussed in Peña did not show that “a formulation
`comprising each of the thirteen known serotypes conju-
`gated to a CRM197 [protein] . . . was even considered, tried
`and successful.” J.A. 44. Standing alone, this finding is
`insufficient to support a lack of motivation or a reasonable
`expectation of success. Obviousness, unlike anticipation,
`does not require a prior art successful formulation. See Par
`Pharm., 773 F.3d at 1198. Here, there was conflicting evi-
`dence as to motivation and reasonable expectation of suc-
`cess—evidence not discussed by the Board.
`Even if we assume that the Board found that Peña it-
`self did not suggest conjugating the 13-valent combination
`with CRM197, the Board found that Chiron identified
`CRM197 as a “particularly preferred” carrier protein.
`J.A. 19. Merck’s expert testified that “[o]ne of the studies
`cited in [Peña] describes the 9-valent version of the vaccine
`as being conjugated to only the single CRM197 carrier,”
`J.A. 697, and Wyeth’s expert conceded that the prior art
`disclosed “Wyeth’s 9-valent conjugate vaccine in which the
`carrier protein is CRM197,” J.A. 6098. But the parties’ ex-
`perts differed as to the 11-valent conjugate vaccine.
`Merck’s expert testified that that “it had been reported in
`the literature that, prior to 2004, Wyeth’s . . . 11-valent
`conjugate vaccine[] used only CRM197 as a carrier protein.”
`
`
`
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`8
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`MERCK SHARP & DOHME CORP. v. WYETH LLC
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`J.A. 697. On the other hand, Wyeth’s expert stated that
`none of the references “provide any citations or references
`to describe or even confirm the existence of the 11-valent
`pneumococcal CRM197 conjugate vaccine allegedly being
`developed by Wyeth,” and that “[i]n fact, the two 11-valent
`vaccines in development at the time were Sanofi’s mixed
`carrier vaccine and GSK’s protein D carrier vaccine.”
`J.A. 6098–99. Merck’s expert testified that “as of April 26,
`2006, [the priority date of the ’999 patent,] a [skilled arti-
`san] would have found it obvious to select the 13 conjugates
`recited in [Peña] (each conjugated to CRM197) for a polysac-
`charide-protein conjugate vaccine.” J.A. 698. Wyeth’s ex-
`pert testified to the contrary that Peña “would not have
`lead a [skilled artisan] to conclude that the 7-valent conju-
`gate vaccine . . . could be expanded to the 13-valent pneu-
`mococcal polysaccharide single-carrier CRM197 conjugate
`vaccine of claim 18 with a reasonable expectation of suc-
`cess.” J.A. 6098.
`Merck’s expert, relying on a memorandum purportedly
`drafted by Ireland’s Environmental Protection Agency, tes-
`tified that “Wyeth applied for a facility license to produce
`the 13-valent conjugate vaccine . . . around 2003,” and that
`the memorandum noted that “CRM197 would be the only
`carrier protein for the . . . 13-valent version[] of the vac-
`cine.” J.A. 698 (citing J.A. 1253). However, the Board de-
`clined to rely on that memorandum, stating that it was
`“cumulative to previously submitted evidence, or related to
`issues disposed upon other bases.” J.A. 48.
`The parties’ differences primarily concerned whether a
`skilled artisan would have been dissuaded from using a
`single carrier protein (i.e. CRM197) due to “immune inter-
`ference,” a phenomenon that may result in decreased im-
`munogenicity in multivalent vaccines with a sole carrier
`protein. Merck argues that the immune interference issue
`is irrelevant, quoting the Board’s claim construction of the
`term “polysaccharide-protein conjugate[]” as not requiring
`“any specific level of immunogenicity for the composition.”
`
`
`
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`MERCK SHARP & DOHME CORP. v. WYETH LLC
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`9
`
`J.A. 10. However, this issue is relevant to whether a
`skilled artisan would have been motivated to conjugate the
`13 serotypes with CRM197 as a sole carrier protein. “If all
`elements of a claim are found in the prior art, as is the case
`here, the factfinder must further consider the factual ques-
`tions of whether a person of ordinary skill in the art would
`be motivated to combine those references . . . .” Dome Pa-
`tent L.P. v. Lee, 799 F.3d 1372, 1380 (Fed. Cir. 2015); see
`also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418
`(2007) (“[I]t can be important to identify a reason that
`would have prompted a person of ordinary skill in the rel-
`evant field to combine the elements in the way the claimed
`new invention does.”).
`On the issue of immune interference, Wyeth’s expert
`testified that “[a] [person of ordinary skill in the art] would
`have had significant concerns expanding the formulation of
`[the 7-valent] Prevenar [prior art reference] because of the
`possible loss of immunogenicity due to ‘immune interfer-
`ence’ when developing a 13-valent conjugate vaccine,” and
`that “[v]accine development researchers believed that
`mixed-carrier [i.e., multiple different] conjugates provided
`the most reasonable technical solution for increasing the
`number of polysaccharide serotypes in a multivalent conju-
`gate vaccine.” J.A. 6090–91. On the other hand, Merck’s
`expert testified that he “strongly disagree[d]” with the as-
`sertion that “concerns over ‘immune interference’ would
`have dissuaded a [person having ordinary skill in the art]
`from pursuing a 13-valent formulation in which each poly-
`saccharide is conjugated to [only] CRM197.” J.A. 699.
`Despite these clearly disputed factual issues, the Board
`simply did not address the evidence as to whether someone
`skilled in the art would have been motivated to combine
`the 13 serotypes into a CRM197 conjugate or whether the
`potential loss of immunogenicity would have dissuaded
`someone skilled in the art from making such a combina-
`tion. The fact that Peña did not disclose such a combina-
`tion fails to answer this central question, and an
`
`
`
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`10
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`MERCK SHARP & DOHME CORP. v. WYETH LLC
`
`explanation was particularly necessary given the Board’s
`finding that the use of CRM197 was obvious with the 7-va-
`lent conjugate in claim 17—which also uses CRM197 as a
`sole carrier protein. We conclude that the Board’s decision
`is too cryptic to survive judicial review.
`Under these circumstances, “we have consistently va-
`cated and remanded for further proceedings.” In re Van
`Os, 844 F.3d 1359, 1362 (Fed. Cir. 2017). We therefore va-
`cate the Board’s obviousness findings with respect to claim
`18, and remand for further consideration of the parties’ ar-
`guments and evidence as to (1) motivation to combine and
`(2) reasonable expectation of success and, if the Board finds
`a sufficient motivation to combine and reasonable expecta-
`tion of success, other issues such as secondary considera-
`tions.4 We do not reach Merck’s remaining arguments.
`VACATED AND REMANDED
`COSTS
`
`No Costs.
`
`
`4 The Board in its decision did not consider the Ire-
`land Environmental Protection Agency memorandum. On
`remand, the Board should consider these documents and
`their probative value.
`
`