Amgen Inc. v. Vidal

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NOTE: This disposition is nonprecedential.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

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
[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
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

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]
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.