Amgen Inc. v. Vidal

• Court: Court of Appeals for the Federal Circuit
• Decided: April 14, 2022
• Docket: 19-2171
• Status: Unpublished

Opinion

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NOTE: This disposition is nonprecedential.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

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 [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. Case: 19-2171 Document: 86 Page: 4 Filed: 04/14/2022

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

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. Case: 19-2171 Document: 86 Page: 6 Filed: 04/14/2022

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] 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

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.