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`NOTE: This disposition is nonprecedential.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.
`
`
`
`
`NOTE: This disposition is nonprecedential.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.
`
`
`
`Case: 19-2171 Document: 86 Page: 3 Filed: 04/14/2022
`
`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
`[𝑜𝑜𝑜𝑜𝑜𝑜𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟]
`
`
`
`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 Schlegl1 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.
`
`
`
`Case: 19-2171 Document: 86 Page: 4 Filed: 04/14/2022
`
`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
`
`
`
`Case: 19-2171 Document: 86 Page: 5 Filed: 04/14/2022
`
`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
`
`
`“In various embodiments the redox component has
`3
`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.
`
`
`
`Case: 19-2171 Document: 86 Page: 6 Filed: 04/14/2022
`
`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
`[𝑜𝑜𝑜𝑜𝑜𝑜𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟]
`
`
`
`
`
`Case: 19-2171 Document: 86 Page: 7 Filed: 04/14/2022
`
`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.
`
`
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