from the United States Patent and Trademark Office, Patent
Trial and Appeal Board in No. IPR2016-01837.
S. Fletcher, Williams & Connolly LLP, Washington, DC,
argued for appellant. Also represented by Paul B. Gaffney,
Eden Schiffmann, Jonathan Sidhu.
J. Meloro, Willkie Farr & Gallagher LLP, New York, NY,
argued for appellee. Also represented by Alexandra Awai,
Courtney Dixon, Appellate Staff, Civil Division,
States Department of Justice, Washington, DC, argued for
intervenor. Also represented by Katherine Twomey Allen, Scott
R. McIntosh, Joseph H. Hunt; Thomas W. Krause, Joseph Matal,
Farheena Yasmeen Rasheed, Office of the Solicitor, United
States Patent and Trademark Office, Alexandria, VA.
Prost, Chief Judge, Newman and Chen, Circuit Judges.
Inc. appeals from the final written decision of the United
States Patent and Trademark Office (Patent Office) Patent
Trial and Appeal Board (the Board) holding claims 1-3 and
5-11 of U.S. Patent 7, 807, 799 (the '799 patent)
unpatentable as anticipated or obvious. See Genentech,
Inc. v. Hospira, Inc., No. IPR2016-01837, 2018 WL
1187484 (P.T.A.B. Mar. 6, 2018) (the '837 Decision). The
Patent Office intervened in this appeal to defend the
constitutionality of inter partes review (IPR)
proceedings as applied to patents issued before the enactment
of the America Invents Act (AIA), Pub. L. No. 112-29, 125
Stat. 284 (2011). For the following reasons, we
owns the '799 patent, which is directed to methods of
purifying antibodies and other proteins containing a
CH2/CH3 region from impurities by protein A
affinity chromatography. '799 patent at col. 7 ll. 50-54.
Protein A affinity chromatography is a standard purification
technique employed in the processing of therapeutic proteins,
especially antibodies, which involves "using protein A .
. . immobilized on a solid phase." Id. at col.
4 ll. 27- 30. "The solid phase may comprise a glass,
silica, polystyrene, or agarose surface," such as a
chromatography column resin "to which the protein A can
. . . be covalently bound." Id. at col. 4 ll.
41-47. "Protein A is a useful adsorbent for affinity
chromatography of proteins, such as antibodies" because
protein A reversibly binds with high affinity to a specific
region common to most antibodies, the
CH2/CH3 region. Id. at col. 2 ll.
6-11, col. 4 ll. 20-25, 30- 31, col. 5 ll. 17-28.
protein A affinity chromatography, a composition comprising a
mixture of the target antibody and undesired impurities often
present in harvested cell culture fluid (HCCF) is placed into
the chromatography column. Id. at col. 18 ll. 47-51.
The target antibody binds to protein A, which is covalently
bound to the chromatography column resin, while the
impurities and rest of the composition pass through the
column. Id. at col. 18 ll. 47-51, col. 20 ll. 6-11.
Next, the antibody of interest is removed from the
chromatography column, typically with a low pH wash.
Id. at col. 19 ll. 45-51. The antibody is collected
as it is washed from the chromatography column, then
typically subjected to further purification steps, and used
for therapeutic purposes after formulation. Id. at
col. 19 ll. 51-63.
protein A affinity chromatography has been "a powerful
tool . . . for purifying antibodies," it was known to
have a downside. See id. at col. 20 ll. 6-12. Small
amounts of the protein A that are attached to the
chromatography column would "leach" (i.e., detach)
from the column and contaminate the otherwise-purified
antibody solution. See id. at col. 20 ll. 11-15,
col. 4 ll. 48-50. Thus, further purification steps are
typically employed to remove leached protein A from the
antibody solution. See id. at col. 20 ll. 12-15.
invention of the '799 patent "concerns a method for
reducing leaching of protein A . . . by reducing [the]
temperature" of the "composition that is subjected
to protein A affinity chromatography." Id. at
col. 1 ll. 16-21. The specification discloses that
"[p]referably, . . . the temperature of the composition
is reduced below room temperature, for instance in the range
from about 3°C to about 20°C, e.g. from about
10°C to about 18°C." Id. at col. 18 ll.
4-9. According to the patent, "[t]he temperature of the
composition may be reduced prior to and/or during protein A
affinity chromatography" and, in a preferred embodiment,
involves "lowering the temperature of the harvested cell
culture fluid (HCCF) which is subjected to
chromatography." Id. at col. 18 ll. 9-16.
1, the sole independent claim at issue, recites:
1. A method of purifying a protein which comprises
CH2/CH3 region, comprising subjecting a
composition comprising said protein to protein A affinity
chromatography at a temperature in the range from about
10°C to about 18°C.
Id. at col. 35 ll. 44-47 (emphasis added).
Inc. sought IPR of claims 1-3 and 5-11 of the '799
patent. The Board instituted trial on all eight grounds of
unpatentability, which all rely on WO '389 or van
Sommeren as the primary reference.
Board determined that all the challenged claims were
unpatentable as anticipated by WO '389 or rendered
obvious by WO '389 alone or in combination with other
prior art references. '837 Decision, 2018 WL
1187484, at *12, *19-20. Also, the Board construed
"about 18°C," and based on that claim
construction, it concluded that all the challenged claims
were unpatentable as anticipated by van Sommeren or rendered
obvious by van Sommeren alone or in combination with other
prior art references. Id. at *13, *22.
appeals. The Patent Office intervened pursuant to 35 U.S.C.
§ 143 to defend against Genentech's
constitutionality challenge to IPRs as applied to the
'799 patent because it issued on October 5, 2010, which
is before the enactment of the AIA in 2011. We have
jurisdiction under 28 U.S.C. § 1295(a)(4)(A).
review the Board's legal determinations de novo, and the
Board's factual findings underlying those determinations
for substantial evidence. Belden Inc. v. Berk-Tek
LLC, 805 F.3d 1064, 1073 (Fed. Cir. 2015). A finding is
supported by substantial evidence if a reasonable mind might
accept the evidence to support the finding. Consol.
Edison Co. v. NLRB, 305 U.S. 197, 229 (1938).
is a question of fact that we review for substantial
evidence. In re Rambus, Inc., 753 F.3d 1253, 1256
(Fed. Cir. 2014). Obviousness is a question of law based on
underlying factual findings, including "the scope and
content of the prior art, differences between the prior art
and the claims at issue, the level of ordinary skill in the
pertinent art, and any objective indicia of
non-obviousness." Randall Mfg. v. Rea, 733 F.3d
1355, 1362 (Fed. Cir. 2013) (citing KSR Int'l Co. v.
Teleflex Inc., 550 U.S. 398, 406 (2007)).
Anticipation by WO '389
Board determined that claims 1 and 5 are anticipated by WO
'389. '837 Decision, 2018 WL 1187484, at *8.
WO '389 teaches a method for purifying certain antibodies
of the IgG class, which are proteins comprising the
CH2/CH3 region, including a step wherein
HCCF is subject to protein A affinity chromatography. J.A.
511 at 2:37, 522 at 13:9-13. WO '389 Example 1 discloses
a washing step after HCCF is applied to the chromatography
column, whereupon the HCCF composition is washed with at
least three column volumes of buffer before the antibody is
eluted. J.A. 523 at 14:20-23. WO '389 teaches that
"[a]ll steps are carried out at room temperature
(18-25°C)." J.A. 522 at 13:13.
1, the sole challenged independent claim of the '799
patent, requires "subjecting a composition . . . to
protein A affinity chromatography at a temperature in the
range from about 10°C to about 18°C." '799
patent at claim 1. The temperature range disclosed in WO
'389, "18-25°C," overlaps with the claimed
range of "about 10°C to about 18°C,"
regardless of the construction of "about 18°C."
Indeed, Genentech's own proposed construction for
"about 18°C" embraces temperatures up to
19°C, which further reinforces the overlap with WO
'389's disclosed temperature range.
art reference that discloses an overlapping but different
range than the claimed range can be anticipatory, even where
the prior art range only partially or slightly overlaps with
the claimed range. See Ineos USA LLC v. Berry Plastics
Corp., 783 F.3d 865, 870-71 (Fed. Cir. 2015) (affirming
summary judgment of anticipation of patent claims for
composition with "0.05 to 0.5% by weight of at least one
saturated fatty acid amide" lubricant in view of a prior
art reference disclosing the same class of lubricant in an
overlapping range of "0.1 to 5 parts by weight,"
and the parties agreed that a measurement in "% by
weight" was equivalent to one in "parts by
weight"). Once the patent challenger has established,
through overlapping ranges, its prima facie case of
anticipation, "the court must evaluate whether the
patentee has established that the claimed range is critical
to the operability of the claimed invention."
Id. at 871; see also E.I. DuPont de Nemours
& Co. v. Synvina C.V., 904 F.3d 996, 1008 (Fed. Cir.
2018) ("'where there is a range disclosed in the
prior art, and the claimed invention falls within that range,
the burden of production falls upon the patentee to come
forward with evidence' of . . . criticality")
(quoting Galderma Labs., L.P. v. Tolmar, Inc., 737
F.3d 731, 738 (Fed. Cir. 2013)). Here, the Board found that
Genentech failed to establish that the claimed temperature
range of "about 10°C to about 18°C" is
critical to performing protein A chromatography. '837
Decision, 2018 WL 1187484, at *10-11. Genentech does not
challenge the Board's finding as to criticality, and
accordingly, whether or not the claimed temperature range
achieves different performance results than WO '389's
disclosed temperature range is not at issue on appeal.
Appellee's Br. at 15.
from the overlapping range issue, the Board construed the
limitation "subjecting a composition . . . to protein A
affinity chromatography at a temperature in the range from
about 10°C to about 18°C" as referring to the
temperature of the composition prior to and/or
during protein A affinity chromatography. '837
Decision, 2018 WL 1187484, at *8 (emphasis added). The
Board found that WO '389's disclosed temperature
range applies to all components used in the purification
process, including the HCCF composition being purified.
'837 Decision, 2018 WL 1187484, at *10. In that
way, it found WO '389 discloses that prior to
protein A affinity chromatography, the HCCF composition is at
a temperature within the claimed range of "about
10°C to about 18°C." Additionally, the Board
found that WO '389's disclosed composition's
temperature reaches the claimed temperature range
during protein A affinity chromatography.
'837 Decision, 2018 WL 1187484, at *10. The
Board read WO '389's teaching that "[a]ll steps
are carried out at room temperature (18-25°C)" to
mean that the apparatus of the chromatography column and
column buffers are all within that ...