Court Opinion

ID: 6334954
Source: CourtListenerOpinion
Date Created: 2022-04-26 15:02:15.635334+00
Date Added: 2024-06-11T09:23:45.262871
License: Public Domain

Case: 19-2171   Document: 86     Page: 1   Filed: 04/14/2022

        NOTE: This disposition is nonprecedential.

   United States Court of Appeals
       for the Federal Circuit
                 ______________________

      AMGEN INC., AMGEN MANUFACTURING,
                   LIMITED,
                    Appellants

                            v.

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

                       2019-2171
                 ______________________

     Appeal from the United States Patent and Trademark
 Office, Patent Trial and Appeal Board in No. IPR2016-
 01542.
                  ______________________

                 Decided: April 14, 2022
                 ______________________

    ARLENE L. CHOW, Latham & Watkins LLP, New York,
 NY, for appellants. Also represented by JON STEVEN
 BAUGHMAN, Paul, Weiss, Rifkind, Wharton & Garrison
 LLP, Washington, DC; JENNIFER GORDON, NICHOLAS P.
 GROOMBRIDGE, New York, NY.
Case: 19-2171     Document: 86      Page: 2     Filed: 04/14/2022

 2                                          AMGEN INC.   v. VIDAL

     THOMAS W. KRAUSE, Office of the Solicitor, United
 States Patent and Trademark Office, Alexandria, VA, for
 intervenor. Also represented by AMY J. NELSON; MAUREEN
 DONOVAN QUELER.
                  ______________________

      Before CHEN, SCHALL, and STOLL, Circuit Judges.
 CHEN, Circuit Judge.
      Appellants Amgen Inc. and Amgen Manufacturing Ltd.
 (collectively, Amgen) appeal a Final Written Decision and
 reconsideration of the same by the Patent Trial and Appeal
 Board (Board) in an inter partes review proceeding involv-
 ing U.S. Patent No. 8,952,138 (’138 patent). The Board de-
 termined that claims 1–24 of the ’138 patent are
 unpatentable under 35 U.S.C. § 103(a). Amgen appeals the
 Board’s construction of the claim term “final thiol-pair ra-
 tio” and determination that claims 1–24 are unpatentable.
 For the following reasons, we reverse.
                         BACKGROUND
      The ’138 patent explains that when recombinant pro-
 teins are formed in non-mammalian expression systems
 (e.g., bacterial cells), they can precipitate into limited-solu-
 bility aggregates of misfolded proteins called “inclusion
 bodies.” ’138 patent at col. 1 ll. 20–24. To obtain properly
 folded proteins from inclusion bodies, practitioners devel-
 oped various methods to accomplish refolding. Id. at col. 1
 ll. 36–38. Such methods generally include steps of (1) ex-
 tracting the inclusion bodies from the expression system;
 (2) solubilizing the inclusion bodies in a solubilization
 buffer, which disassembles the inclusion bodies into indi-
 vidual protein chains and unfolds the proteins; and (3) di-
 luting or washing the unfolded proteins in a refolding
 buffer, which causes the proteins to refold in the proper
 manner. Id. col. 1 ll. 38–51.
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 AMGEN INC.   v. VIDAL                                           3

     The ’138 patent claims methods for refolding proteins
 at high concentrations using a controlled reduction-oxida-
 tion (redox) reaction. See ’138 patent at claims 1–24; see
 also id. at col. 1 ll. 11–14, col. 2 ll. 52–61. Claim 1 is the
 only independent claim, and claims 2–24 depend there-
 from.
      In its Final Written Decision, the Board construed “fi-
 nal thiol-pair ratio,” recited in claim 1, to mean “the rela-
 tionship of the reduced and oxidized redox species used in
 the redox component of the refold buffer as defined by the
 [following] equation”:
                         [𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟]2
                            [𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜]
 Apotex Inc. v. Amgen Inc., IPR2016-01542, 2018 WL
 935620, at *4 (P.T.A.B. Feb. 15, 2018) (Final Written Deci-
 sion). Based on this construction of “final thiol-pair ratio,”
 the Board determined that Petitioners Apotex Inc. and
 Apotex Corp. (collectively, Apotex) had demonstrated that
 claim 1 is unpatentable over Schlegl 1 in view of Hevehan. 2
 J.A. 40–47, 62. Since Amgen did not separately argue the
 patentability of dependent claims 2–17 and 19–24, the
 Board concluded claims 2–17 and 19–24 are also unpatent-
 able. J.A. 47–55, 58–60. Although the Board was initially
 unpersuaded that Apotex had demonstrated that claim 18
 was unpatentable, the Board later reconsidered and
 amended its Final Written Decision to find claim 18 un-
 patentable. Apotex Inc. v. Amgen Inc., No. IPR2016-01542,
 2019 WL 2180042, at *5–6 (P.T.A.B. May 20, 2019); see also
 Final Written Decision, at *18.

     1   U.S. Patent Pub. No. 2007/0238860. J.A. 248–60.
     2   Diane L. Hevehan & Eliana De Bernardez Clark,
 Oxidative Renaturation of Lysozyme at High Concentra-
 tions, 54 Biotechnology & Bioengineering 221 (1997).
 J.A. 261–270.
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 4                                        AMGEN INC.   v. VIDAL

     Amgen appeals the Board’s construction of “final thiol-
 pair ratio” and unpatentability determinations based on
 the same. Apotex informed this Court that it would not
 participate in the appeal, ECF No. 2, and the U.S. Patent
 and Trademark Office (Patent Office) intervened to defend
 the Board’s decision, ECF No. 11. We have jurisdiction un-
 der 28 U.S.C. § 1295(a)(4)(A).
                         DISCUSSION
                              A
     Because Apotex filed its petition for inter partes review
 before November 13, 2018, we apply the broadest reasona-
 ble interpretation claim construction standard. Valve
 Corp. v. Ironburg Inventions Ltd., 8 F.4th 1364, 1380 n.14
 (Fed. Cir. 2021). There being no dispute here about find-
 ings or evidence of facts extrinsic to the patent, we conduct
 a de novo review of the Board’s determination of the broad-
 est reasonable interpretation of the claim language. See In
 re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1279–80 (Fed.
 Cir. 2015); Microsoft Corp. v. Proxyconn, Inc., 789 F.3d
 1292, 1297 (Fed. Cir. 2015).
     Obviousness is a question of law based on underlying
 factual determinations. Facebook, Inc. v. Windy City Inno-
 vations, LLC, 973 F.3d 1321, 1339 (Fed. Cir. 2020). We re-
 view the Board’s legal conclusions de novo and its factual
 findings for substantial evidence. ACCO Brands Corp. v.
 Fellowes, Inc., 813 F.3d 1361, 1365 (Fed. Cir. 2016).
                              B
      Amgen argues the Board misconstrued “final thiol-pair
 ratio” because claim 1’s “language makes clear that the re-
 dox component is a distinct volume from the refold buffer,
 and it is that redox component [rather than the refold
 buffer] that comprises the claimed ‘final thiol-pair ratio.’”
 See Appellant’s Br. 41–42, 43. Since the thiol-pair ratio
 (TPR) equation is volume-dependent, the TPR value will be
 different when calculated in the redox component versus
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 AMGEN INC.   v. VIDAL                                           5

 the refold buffer. Id. at 40–41, 43–44. The Patent Office
 responds that redox component is not, and need not be, a
 separate volume from the refold buffer. Intervenor’s Br.
 36–37. The Patent Office assumes that the only way to give
 meaning to the word “final” in “final thiol-pair ratio” and
 make sense of the ’138 patent’s claims and specification is
 to understand “final thiol-pair ratio” in the context of the
 ultimate solution—i.e., the refold mixture—rather than
 specific ingredients therein—e.g., the redox component. Id.
 at 38–39. We agree with Amgen.
      Claim 1 recites “contacting the protein with a refold
 buffer comprising a redox component comprising a final
 thiol-pair ratio. . . . to form a refold mixture.” ’138 patent
 at claim 1. A straightforward reading of the claim lan-
 guage indicates that the “final thiol-pair ratio” is an attrib-
 ute of the redox component. Id. Additionally, the ’138
 patent specification distinguishes between “final thiol-pair
 ratio,” 3 “buffer thiol-pair ratio,” 4 and “system thiol-pair ra-
 tio,” 5 which respectively correspond to TPR values calcu-
 lated in the “redox component,” “refold buffer,” and “refold

     3     “In various embodiments the redox component has
 a final thiol-pair ratio.” ’138 patent at col. 2 ll. 62–64 (em-
 phasis added); see also id. at col. 8 ll. 37–43, col. 9 ll. 20–22,
 col. 10 ll. 22–26, col. 11 ll. 9–13 & 40–42 & 54–63, col. 13
 ll. 29–35.
      4    “As used herein, the term ‘buffer thiol-pair ratio’ is
 defined by the relationship of the reduced and oxidized re-
 dox species used in the refold buffer as defined in Equation
 1[.]” Id. at col. 6 ll. 20–28 (emphasis added); see also id. at
 col. 4 ll. 39–42 & ll. 46–48, col. 10 ll. 45–56.
      5    “The buffer thiol-pair ratio is, however, only one
 component in determining the total system thiol-pair ratio
 in the total reaction.” Id. at col. 4 ll. 46–48 (emphasis
 added); see also id. at col. 4 ll. 48–51 & 55–58, col. 9 ll. 3–
 13.
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 6                                               AMGEN INC.   v. VIDAL

 mixture.” In other words, the specification clearly and ex-
 clusively describes “final thiol-part ratio” as an attribute of
 the redox component. If claim 1 covered a TPR calculated
 in the refold buffer—as the Board construed and analyzed
 claim 1—claim 1 would have recited a “buffer thiol-pair ra-
 tio” rather than “final thiol-pair ratio.” Moreover, the spec-
 ification confirms that the redox component is a chemical
 or solution that is independent of the refold buffer by ex-
 pressly defining “‘redox component’ [to] mean[] any thiol-
 reactive chemical or solution comprising such a chemical
 that facilitates a reversible thiol exchange with another
 thiol or the cysteine residues of a protein.” Id. at col. 6 ll.
 63–66 (emphasis added).
     Accordingly, claim 1 requires a redox component with
 concentrations of reductant and oxidant optimized using
 the TPR equation disclosed in the ’138 patent. The Board’s
 construction, which treats the claimed “final thiol-pair ra-
 tio” as an attribute of the redox component in the refold
 buffer rather than of the redox component independent of
 the refold buffer, is inconsistent with the plain language of
 claim 1 and the specification and is therefore unreasonably
 broad. See In re Smith Int’l, Inc., 871 F.3d 1375, 1382–83
 (Fed. Cir. 2017) (stating that “the Board cannot construe
 the claims so broadly that its constructions are unreasona-
 ble under general claim construction principles,” and that
 giving claim terms “a strained breadth in the face of the
 otherwise different description in the specification [is] un-
 reasonable” (internal quotation marks and emphasis omit-
 ted)). As such, the correct construction of “final thiol-pair
 ratio” in claim 1 under the broadest reasonable interpreta-
 tion standard is “the relationship of the reduced and oxi-
 dized redox species used in the redox component,” as
 defined by the following equation:
                         [𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟]2
                            [𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜]
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 AMGEN INC.   v. VIDAL                                        7

 See ’138 patent at col. 8 ll. 37–43 (“Thiol-pair ratio [is] de-
 fined in Equation[] 1[.]”); see also id. at col. 10 ll. 22–26
 (stating that “the redox component has a final thiol-pair
 ratio (as defined herein)”) (emphasis added), col. 11 ll. 9–13
 (same). We therefore hold that the Board misconstrued “fi-
 nal thiol-pair ratio.”
                               C
     On the evidence and arguments presented to the
 Board, 6 there is only one possible evidence-supported find-
 ing regarding patentability: Apotex failed to demonstrate
 that claims 1–24 are unpatentable under § 103(a). No-
 where in the record did Apotex present argument or evi-
 dence that Schlegl or Hevehan discloses calculating a final
 thiol-pair ratio in a redox component independent of the
 refold buffer. See, e.g., J.A. 124–25 (Petition arguing that
 claim 1’s “final thiol-pair ratio” is disclosed in Schlegl and
 Hevehan’s respective refold buffers or mixtures). It is not
 necessary or appropriate to remand for the Board to deter-
 mine whether claim 1 is unpatentable over the Schlegl-He-
 vehan combination under the correct construction of “final
 thiol-pair ratio” because the only conclusion supported by
 substantial evidence is that neither Schlegl nor Hevehan
 disclose a “final thiol-pair ratio.” See Owens Corning v.
 Fast Felt Corp., 873 F.3d 896, 902 (Fed. Cir. 2017) (explain-
 ing that in circumstances “where only one answer is sup-
 ported by substantial evidence and there is neither a
 request nor an apparent reason to grant a second record-
 making opportunity, reversal is warranted”). That conclu-
 sion requires reversal of the Board’s finding that claim 1

     6   The Patent Office argues for the first time on ap-
 peal that Schlegl or Hevehan teaches optimizing thiol con-
 centrations of a redox component within a refold mixture.
 Intervenor’s Br. 26–32. We do not consider this theory as
 it was not presented to the Board.
Case: 19-2171    Document: 86     Page: 8   Filed: 04/14/2022

 8                                      AMGEN INC.   v. VIDAL

 and claims 2–24 depending therefrom are unpatentable
 under § 103(a). 7
                       CONCLUSION
     For the foregoing reasons, we hold that Apotex failed
 to demonstrate that claims 1–24 of the ’138 patent are un-
 patentable under § 103(a). The Board’s decision is re-
 versed.
                       REVERSED
                          COSTS
 No costs.

     7   Amgen also appeals the Board’s reconsideration of
 claim 18. Appellant’s Br. 58–71. Since we reverse the
 Board’s patentability determination with respect to
 claim 1, we need not reach any additional issues raised
 with respect to claim 18, which depends from claim 1.