Court Opinion

ID: 9839490
Source: CourtListenerOpinion
Date Created: 2023-09-13 15:01:44.400907+00
Date Added: 2024-06-11T09:40:12.266645
License: Public Domain

Case: 19-2011   Document: 117     Page: 1   Filed: 08/22/2023

         NOTE: This disposition is nonprecedential.

    United States Court of Appeals
        for the Federal Circuit
                  ______________________

    SUN PHARMACEUTICAL INDUSTRIES, INC.,
    F/D/B/A CONCERT PHARMACEUTICALS, INC.
                    Appellant

                             v.

                INCYTE CORPORATION,
                       Appellee

   KATHERINE K. VIDAL, UNDER SECRETARY OF
   COMMERCE FOR INTELLECTUAL PROPERTY
     AND DIRECTOR OFTHE UNITED STATES
       PATENT AND TRADEMARK OFFICE,
                   Intervenor
             ______________________

                        2019-2011
                  ______________________

     Appeal from the United States Patent and Trademark
 Office, Patent Trial and Appeal Board in No. IPR2017-
 01256.
                  ______________________

                 Decided: August 22, 2023
                  ______________________

    WILLIAM M. JAY, Goodwin Procter LLP, Washington,
 DC, argued for appellant. Also represented by GERARD
 JUSTIN CEDRONE, EMILY L. RAPALINO, DARYL L. WIESEN,
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 2                  SUN PHARMACEUTICAL INDUSTRIES, INC. v.
                                     INCYTE CORPORATION

 DAVID ZIMMER, Boston, MA.

     MARK J. FELDSTEIN, Finnegan, Henderson, Farabow,
 Garrett & Dunner, LLP, Washington, DC, argued for ap-
 pellee. Also represented by DREW CHRISTIE, C. COLLETTE
 CORSER, JASON LEE ROMRELL; J. DEREK MCCORQUINDALE,
 Reston, VA; TRENTON A. WARD, Atlanta, GA.

     ROBERT MCBRIDE, Office of the Solicitor, United States
 Patent and Trademark Office, Alexandria, VA, for interve-
 nor. Also represented by THOMAS W. KRAUSE, FARHEENA
 YASMEEN RASHEED; SCOTT R. MCINTOSH, MELISSA N.
 PATTERSON, Civil Division, Appellate Staff, United Depart-
 ment of Justice, Washington, DC.

     JOHN C. KAPPOS, O'Melveny & Myers LLP, Dallas, TX,
 for amicus curiae Bald Girls Do Lunch. Also represented
 by CAITLIN P. HOGAN, New York, NY.
                  ______________________

      Before HUGHES, LINN, and STARK, Circuit Judges.
 STARK, Circuit Judge.
     Sun Pharmaceutical Industries, Inc. (“Sun”) 1 appeals
 the Final Written Decision of the Patent and Trial Appeal
 Board (“Board”) in an inter partes review (“IPR”) in which
 Petitioner, Incyte Corporation (“Incyte”), challenged all
 claims of Sun’s U.S. Patent No. 9,249,149 (“’149 patent”).
 The Board concluded that the claims were invalid as obvi-
 ous. Sun sought review by the Director of the Patent and
 Trademark Office, which was denied, and then timely filed
 an appeal to this court. We have jurisdiction pursuant to

     1    The original appellant was Concert Pharmaceuti-
 cals, Inc. (“Concert”), which merged with Sun on March 31,
 2023. We granted Sun’s motion to replace Concert as the
 appellant on April 26, 2023.
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 INCYTE CORPORATION

 28 U.S.C. § 1295(a)(4) and 35 U.S.C. §§ 141(c) and 319. We
 affirm.
                              I
                              A
      The ’149 patent, entitled “Deuterated Derivatives of
 Ruxolitinib,” “relates to novel heteroaryl-substituted pyr-
 rolo[2,3-d]pyrimidines, and pharmaceutically acceptable
 salts thereof,” including the compounds and their use “in
 methods of treating diseases and conditions that are bene-
 ficially treated by administering an inhibitor of Janus-as-
 sociated kinase with selectivity for subtypes 1 and 2
 (JAK1/JAK2).” ’149 patent 3:25-32. Ruxolitinib is a known
 JAK1/JAK2 inhibitor and is “currently approved for the
 treatment of patients with intermediate or high-risk
 myelofibrosis.” Id. at 2:53-67. Common adverse reactions
 associated with ruxolitinib include thrombocytopenia, ane-
 mia, bruising, dizziness, and headache. Id. at 3:15-18.
     Deuteration involves replacing one or more hydrogen
 atoms of a drug with deuterium, an isotope of hydrogen, “to
 slow” the “CYP-mediated metabolism” (i.e., cytochrome
 P450 enzyme) “of a drug or to reduce the formation of un-
 desirable metabolites.” Id. at 2:7-10. The bonds formed
 between deuterium and carbon are stronger than carbon-
 hydrogen bonds; this stronger bond “can positively impact
 the ADME [absorption, distribution, metabolism, and/or
 excretion] properties of a drug, creating the potential for
 improved drug efficacy, safety, and/or tolerability” without
 “affect[ing] the biochemical potency and selectivity of the
 drug as compared to the original chemical entity that con-
 tains only hydrogen.” Id. at 2:12-20. These measures of
 how a human body processes a drug, ADME, are also re-
 ferred to as the drug’s pharmacokinetic properties.
 J.A. 8225-46.
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                                        INCYTE CORPORATION

     The ’149 patent has two independent claims, 1 and 9.
 Claim 1 claims deuterated variations of Formula A and is
 reproduced below:
     1. A compound of Formula A:

     or a pharmaceutically acceptable salt thereof,
     wherein:
     Y1 is hydrogen;
     each Y2 is selected from hydrogen and deuterium,
     and each Y2 is the same;
     each Y3 is selected from hydrogen and deuterium,
     and each Y3 is the same;
     Y4 is selected from hydrogen and deuterium;
     each Y5 is the same and is selected from hydrogen
     and deuterium; and
     Y6, Y7, Y8, Y9, and Y10 are each independently se-
     lected from hydrogen and deuterium; provided
     that:
     each Y2 is deuterium; or
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     each Y3 is deuterium; or
     each Y2 and each Y3 is deuterium.
 Id. at 36:17-53.
      The IPR focused primarily on three compounds, pic-
 tured below, all of which are within the scope of claim 7,
 which depends from claim 1: an “octo-deuterated” rux-
 olitinib analog, in which every Y2 and Y3 hydrogen is deu-
 terated,

 and two “tetra-deuterated” ruxolitinib analogs,

 in which either Y2 hydrogens or Y3 hydrogens are deuter-
 ated. Id. at 36:66-40.
     Sun named the octo-deuterated analog with a high iso-
 topic purity CTP-543. Sun contends that CTP-543 has the
 potential to be a desirable treatment for alopecia areata.
 The FDA has given “Fast Track” and “Breakthrough Ther-
 apy” designations to CTP-543, which means the FDA will
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                                       INCYTE CORPORATION

 expedite its review of CTP-543 as a new drug. See, e.g., J.A.
 10102.
                               B
     In its IPR petition, Incyte presented two obviousness
 grounds, but the Board only considered one: the combina-
 tion of Rodgers, Shilling, and the Concert Backgrounder. 2
 We summarize these prior art references below.
      Rodgers is a U.S. patent directed to “heteroaryl substi-
 tuted pyrrolo[2,3,-b]pyridines and heteroaryl substituted
 pyrrolo[2,3-b]pyrmidines that modulate the activity of Ja-
 nus kinases.” J.A. 1747. Rodgers’ claimed compounds all
 depend on “Formula I,” reproduced below, and include rux-
 olitinib. J.A. 1749, 1933.

      Shilling discloses a study of the “metabolism, excretion,
 and pharmacokinetics” of ruxolitinib and teaches that rux-
 olitinib is a “potent, selective inhibitor” of JAK1/JAK2.
 J.A. 1729.      It adds that ruxolitinib was the “first

     2   U.S. Patent No. 7,598,257 (“Rodgers”) (J.A. 1744-
 933); Adam D. Shilling et al., Metabolism, Excretion, and
 Pharmacokinetics of [14C]INCB018424, a Selective Janus
 Tyrosine Kinase 1/2 Inhibitor, in Humans, 38 Drug Metab-
 olism & Disposition 2023 (2010) (“Shilling”) (J.A. 1729-37);
 Concert Pharmaceuticals, Inc., Precision Deuterium
 Chemistry Backgrounder (2007) (“Concert Backgrounder”)
 (J.A. 1738-43).
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 investigational drug of its class in phase III studies for the
 treatment of myelofibrosis.” Id. Importantly, Shilling also
 identifies ruxolitinib’s metabolic “hotspots,” which are the
 sites on a compound where oxidative metabolism occurs
 during in vivo metabolism. J.A. 154, 1734. The study iden-
 tifies that the majority of ruxolitinib’s metabolism occurs
 on its cyclopentyl ring at its four methylene carbons (the Y2
 and Y3 positions in Formulas A and I of the ’149 patent and
 the positions that are deuterated in octo-deuterated and
 tetra-deuterated ruxolitinib). See J.A. 1736.
      The Concert Backgrounder is a marketing publication
 issued by the original owner of the ’149 patent, Concert. It
 teaches that deuteration of compounds provides the poten-
 tial for improved safety, better tolerability, and enhanced
 efficacy. J.A. 1739 (“[S]ince deuterium is heavier than hy-
 drogen, it forms significantly stronger bonds with carbon
 resulting in differentiated ADME (Adsorption, Distribu-
 tion, Metabolism and Excretion). . . . [Hence,] [d]euterium
 substitution has the potential to create NCEs [new chemi-
 cal entities] with improved safety, tolerability and effi-
 cacy.”). The Concert Backgrounder observes that “the
 magnitude and nature of the deuterium benefit cannot be
 predicted a priori,” so it is necessary to first “test multiple
 compounds in a range of assays to identify those that are
 differentiated.” J.A. 1740. It further emphasizes, however,
 that “[d]euteration provides novel agents with the poten-
 tial for . . . [i]mproved safety[,] . . . [b]etter tolerability[,] . .
 . [and] [e]nhanced efficacy,” adding that Concert “is deploy-
 ing its product technology platform to rapidly assemble a
 pipeline of valuable new deuterated drugs.” J.A. 1740,
 1743 (emphasis omitted).
                                  II
     “Obviousness under 35 U.S.C. § 103 is a mixed ques-
 tion of law and fact. We review the Board’s ultimate obvi-
 ousness determination de novo and underlying fact-
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 8                    SUN PHARMACEUTICAL INDUSTRIES, INC. v.
                                       INCYTE CORPORATION

 findings for substantial evidence.” Hologic, Inc. v. Smith &
 Nephew, Inc., 884 F.3d 1357, 1361 (Fed. Cir. 2018). “A
 claimed invention is unpatentable if the differences be-
 tween the claimed invention and the prior art are such that
 the claimed invention as a whole would have been obvious
 to one of ordinary skill in the relevant art.” Intercontinen-
 tal Great Brands LLC v. Kellogg N. Am. Co., 869 F.3d 1336,
 1343 (Fed. Cir. 2017) (internal quotation marks omitted).
 The presence or absence of a motivation to combine prior
 art references, and a reasonable expectation of success in
 doing so, are questions of fact. See Intelligent Bio-Sys., Inc.
 v. Illumina Cambridge Ltd., 821 F.3d 1359, 1366 (Fed. Cir.
 2016).
     In an IPR, it is the petitioner’s burden to prove, by a
 preponderance of the evidence, that a person of ordinary
 skill in the art would have been motivated to combine the
 prior art references the petitioner is relying on in its obvi-
 ousness grounds. See 35 U.S.C. § 316(e) (“In an inter
 partes review instituted under this chapter, the petitioner
 shall have the burden of proving a proposition of unpatent-
 ability by a preponderance of the evidence.”). 3 Motivation

     3   The parties disagree as to whether our case law
 limits the reasonable expectation of success inquiry to only
 those properties that are actually claimed in the patent be-
 ing challenged. Compare, e.g., Appellee Resp. Br. at 51
 (“Although an unclaimed property may be relevant to the
 motivation-to-combine inquiry where it is the reason prof-
 fered for the motivation, unclaimed properties are ‘of no
 moment’ to the separate ‘reasonable expectation of success’
 inquiry directed to ‘success in meeting the claims.’”) (inter-
 nal emphasis omitted; quoting Intelligent BioSystems, 821
 F.3d at 1367-68), with Appellant Reply Br. at 18-19 (re-
 sponding “that has never been this Court’s approach to
 compound patents” and citing Takeda Chem. Indus., Ltd.
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 to combine “need not be [based on] an explicit teaching that
 the claimed compound will have a particular utility; it is
 sufficient to show that the claimed and prior art com-
 pounds possess a sufficiently close relationship to create an
 expectation, in light of the totality of the prior art, that the
 new compound will have similar properties to the old.”
 Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499
 F.3d 1293, 1301 (Fed. Cir. 2007) (internal quotation marks
 and alterations omitted). “[T]he greater the structural sim-
 ilarity between the compounds, the greater the motivation
 to combine and reasonable expectation of success.” Anacor
 Pharms. Inc. v. Iancu, 889 F.3d 1372, 1385 (Fed. Cir. 2018).
     In evaluating an obviousness claim, we also consider,
 where present, the objective indicia of nonobviousness. See
 Apple Inc. v. Samsung Elecs. Co., 839 F.3d 1034, 1048 (Fed.
 Cir. 2016). These can include “commercial success enjoyed
 by devices practicing the patented invention, industry
 praise for the patented invention, copying by others, and
 the existence of a long-felt but unsatisfied need for the in-
 vention.” Id. at 1052. A patentee’s evidence of objective
 indicia can rebut a petitioner’s prima facie showing of ob-
 viousness. See WMS Gaming, Inc. v. Int’l Game Tech., 184
 F.3d 1339, 1359 (Fed. Cir. 1999).
                                A
     For new chemical compounds, we apply a two-step test
 for determining obviousness. “First, the court determines

 v. Alphapharm Pty., Ltd., 492 F.3d 1350 (Fed. Cir. 2007)).
 This case does not call on us to resolve this dispute. In-
 stead, we conclude that the Board had substantial evidence
 to support its conclusion of obviousness even assuming
 (without deciding) that a skilled artisan would have needed
 to have reasonably expected success in obtaining the bene-
 ficial (though possibly unclaimed) properties Sun posits for
 it claimed compounds.
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  whether a chemist of ordinary skill would have selected the
  asserted prior art compounds as lead compounds, or start-
  ing points, for further development efforts.” Otsuka
  Pharm. Co. v. Sandoz, Inc., 678 F.3d 1280, 1291 (Fed. Cir.
  2012). “The second inquiry in the analysis is whether the
  prior art would have supplied one of ordinary skill in the
  art with a reason or motivation to modify a lead compound
  to make the claimed compound with a reasonable expecta-
  tion of success.” Id. at 1292.
       The parties do not dispute that a person of ordinary
  skill would have selected ruxolitinib as the lead compound.
  Rather, Sun argues that the Board erred, in three respects,
  in connection with the second portion of this test. Specifi-
  cally, Sun contends the Board failed to (1) ask whether a
  person of ordinary skill would have been motivated to deu-
  terate ruxolitinib to alter its pharmacokinetic properties,
  (2) determine whether the skilled artisan would have been
  motivated to make the specific molecular modifications
  claimed in the ’149 patent, and (3) consider whether the
  person of ordinary skill would have reasonably expected
  success in modifying ruxolitinib. We review each of these
  arguments in turn.
                                1
      Sun asks us to reject the Board’s finding of obviousness
  because the Board purportedly failed to consider whether
  a person of ordinary skill would have been motivated to
  deuterate ruxolitinib to modify its pharmacokinetic prop-
  erties, including its ADME. We conclude that the Board
  had substantial evidence, including the testimony of In-
  cyte’s expert, Dr. Guengerich, to find that the combined
  teachings of Shilling, Rodgers, and the Concert Back-
  grounder would have provided a skilled artisan with moti-
  vation to deuterate ruxolitinib, at its metabolic hotspots, in
  order “to achieve the potential benefits that the Concert
  Backgrounder disclosed, e.g., improved safety, tolerability,
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  and efficacy.” J.A. 23-24; see also J.A. 1472-87 (Dr.
  Guengerich testifying to deuteration’s effect on compound’s
  ADME, including improved safety, tolerability, and effi-
  cacy), J.A. 1491-92 (Dr. Guengerich stating that Concert
  Backgrounder teaches deuteration has “substantially re-
  duced R&D risk, time and expense”). The close structural
  similarity between prior art ruxolitinib and the deuterated
  ruxolitinib analogs of the ’149 patent is undisputed and
  was reasonably found by the Board to have motivated a
  skilled artisan to modify ruxolitinib to retain its potency
  and selectivity, but improve the pharmacokinetic proper-
  ties identified in the Backgrounder. This conclusion is fur-
  ther supported by Sun’s own expert, Dr. Harbeson, J.A.
  6016, and Concert’s chief executive officer, who added
  “we’ve never seen any biologically relevant differences in
  target selectivity or potency of a drug when we deuterate
  it,” J.A. 2406; see also J.A. 2919 (“The attraction of specific
  deuterium substitution as a parameter in drug design is
  based on the facts that not only is the replacement of one
  or a few hydrogens in a drug molecule by deuterium the
  smallest structural change that can be made but also such
  a change will have negligible steric consequences or influ-
  ence on physicochemical properties . . . .”).
                                2
      Sun argues that the Board erred in failing to ask
  whether a person of ordinary skill would have pursued the
  specific modifications claimed in the ’149 patent, particu-
  larly those that would have resulted in the tetra- and octo-
  deuterated analogs of ruxolitinib. But the combination of
  the Concert Backgrounder, Shilling, and Dr. Guengerich’s
  declaration provides substantial evidence for the Board’s
  finding that a person of ordinary skill would have been mo-
  tivated to modify ruxolitinib at its metabolic hotspots on its
  cyclopentyl ring. J.A. 23-24; see also J.A. 1736 (Shilling
  identifying ruxolitinib’s metabolic hotspots as four meth-
  ylene carbons on its cyclopentyl ring); J.A. 1739-42
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  (Concert Backgrounder teaching that “[m]etabolic
  ‘hotspots’” are deuterated to improve compound’s efficacy,
  safety, and tolerability). Dr. Guengerich testified that a
  skilled artisan “would have deuterated at the site corre-
  sponding to Y2 and/or Y3 in Formula A or Formula I . . . at
  every Y2 and/or every Y3,” meaning that the “most reason-
  able deuterated analogs” would be the tetra- and octo-deu-
  terated analogs of dependent claim 7. J.A. 1500-02
  (emphasis omitted). Hence, there is substantial evidence
  that an ordinarily skilled artisan would have been moti-
  vated to make the specific modifications necessary to mod-
  ify ruxolitinib to its deuterated analogs.
                                3
        Sun argues that, in finding Incyte had proven a reason-
  able expectation of success, the Board erred by ignoring the
  unpredictable effects of deuterating ruxolitinib and by not
  considering how that unpredictability would have deterred
  a skilled artisan. “The reasonable expectation of success
  requirement refers to the likelihood of success in combining
  references to meet the limitations of the claimed invention.
  . . . [O]ne must have . . . a reasonable expectation of achiev-
  ing what is claimed in the patent-at-issue.” Intelligent Bio-
  Sys., 821 F.3d at 1367.
      The Board had substantial evidence to conclude that a
  person of ordinary skill would have had a reasonable ex-
  pectation that she could succeed in modifying ruxolitinib to
  arrive at its tetra- and octo-deuterated analogs, which she
  would expect to display “superior ADME properties.” J.A.
  32; see also J.A. 1491-92, 1495-96 (Dr. Guengerich Decl.).
  Dr. Guengerich opined that a person of ordinary skill would
  have viewed the deuteration strategy as predictable, would
  have been able to synthesize the claimed compounds of the
  ’149 patent, and would also have expected the resulting
  compounds to demonstrate metabolic stability. J.A. 1503-
  22.     The Board acknowledged that the Concert
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  Backgrounder discloses that the “magnitude and nature of
  the deuterium benefit cannot be predicted a priori,” J.A.
  14, 31, 1740, but found, nonetheless, that an ordinarily
  skilled artisan would have reasonably expected – based on
  the overall teachings of the Backgrounder and the opinions
  of Dr. Guengerich – that deuterium modification could “re-
  sult[] in differentiated ADME,” including potential
  “[r]educed Cmax-driven side effects” and “[i]mproved effi-
  cacy, convenience and compliance,” J.A. 1739; see also J.A.
  1491-92 (Dr. Guengerich explaining that deuteration “sub-
  stantially reduce[s] R&D risk, time, and expense,” notwith-
  standing lack of a priori predictability). “[O]bviousness
  cannot be avoided simply by a showing of some degree of
  unpredictability in the art so long as there was a reasona-
  ble probability of success.” Pfizer, Inc. v. Apotex, Inc., 480
  F.3d 1348, 1364 (Fed. Cir. 2007).
      Thus, the Board had substantial evidence to support its
  findings that a person of ordinary skill in the art would
  have been motivated to modify ruxolitinib to create the ’149
  patent’s deuterated analogs to alter its pharmacokinetic
  properties and would have reasonably expected that such
  modifications would lead to the beneficial changes sug-
  gested by the Concert Backgrounder.
                                B
       Sun further argues the Board erred in its evaluation of
  two objective indicia of nonobviousness: unexpected results
  and long-felt need. We disagree. Nothing about Sun’s ob-
  jective indicia evidence rebuts Incyte’s prima facie showing
  of obviousness. 4

      4   Incyte argues that none of Sun’s objective indicia
  evidence is probative of nonobviousness because it all re-
  lates solely to CTP-543, which is a single embodiment and
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       Sun argues that CTP-543, the highly pure octo-deuter-
  ated embodiment of claim 7 of its ’149 patent, displays two
  unexpected results: (1) a flatter pharmacokinetic curve,
  which increases the time of the drug in the therapeutic
  window, and (2) a greater relative increase in half-life for
  patients who metabolized ruxolitinib most quickly. The
  record contains substantial evidence to support the Board’s
  contrary finding that CTP-543’s results were “an increase
  in the same clinical activity observed with ruxolitinib, and
  therefore represent merely a difference in degree and not
  in kind.” J.A. 35; see Bristol-Myers Squibb Co. v. Teva
  Pharms. USA Inc., 752 F.3d 967, 977 (Fed. Cir. 2014)
  (“While a ‘marked superiority’ in an expected property may
  be enough in some circumstances to render a compound pa-
  tentable, a ‘mere difference in degree’ is insufficient.”).
  That is, the Board reasonably concluded that CTP-543’s in-
  creased time in the therapeutic window and increased clin-
  ical response at a given dose were differences in degree that
  did not indicate a marked superiority in these properties.
  See J.A. 6636-37, 6745-55 (Incyte’s experts testifying that
  therapeutic differences between CTP-543 and ruxolitinib
  were not “clinically meaningful” or “clinically impactful”).
      “The existence of a long-felt but unsolved need that is
  met by the claimed invention is further objective evidence
  of non-obviousness.” Millennium Pharms., Inc. v. Sandoz
  Inc., 862 F.3d 1356, 1369 (Fed. Cir. 2017). “Evidence of a
  long-felt need is particularly probative of obviousness when
  it demonstrates both that a demand existed for the

  not commensurate with the scope of any claim of the ’149
  patent. It is sufficient for our purposes, as it was for the
  Board, see J.A. 35, to assume without deciding that Sun has
  met its burden to show that CTP-543 is representative of
  all embodiments within the scope of a challenged claim, as
  Sun’s evidence lacks significant probative value for other
  reasons that we explain.
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  patented invention, and that others tried but failed to sat-
  isfy that demand.” Id. (internal quotation marks omitted).
  Assuming, without deciding, that the need for an effective
  and safe alopecia areata treatment existed, the Board had
  substantial evidence for its finding that CTP-543 had not
  actually satisfied this long-felt need, but only had the “po-
  tential” and “likelihood” to do so. J.A. 36-37; see also J.A.
  9385-86 (Dr. Mackay-Wiggin Decl.). While we agree with
  Sun (and amicus Bald Girls Do Lunch) that FDA approval
  is not a prerequisite to showing that a long-felt need has
  been met, and FDA’s designation of CTP-543 for “Break-
  through Therapy” and “Fast-Track” approval are probative
  of nonobviousness, here Sun expressly framed its objective
  indicia argument as “CTP-543 satisfies the long-felt need
  for an FDA-approved, evidence-based alopecia areata
  treatment,” J.A. 465 (emphasis added), and the Board rea-
  sonably found that CTP-543 had not met this need because
  it lacked FDA approval, see J.A. 1366. 5 Thus, substantial
  evidence supports the Board’s conclusion that Sun did not
  prove that CTP-543 has satisfied this long-felt need.
                               III
      We have considered Sun’s remaining arguments and
  find them unpersuasive. For the foregoing reasons, we af-
  firm.
                         AFFIRMED

      5   Evidence provided by the amicus, Bald Girls Do
  Lunch, but not otherwise in the record cannot be consid-
  ered on appeal. See In re Watts, 354 F.3d 1362, 1367 (Fed.
  Cir. 2004).