  United States Court of Appeals
      for the Federal Circuit
               ______________________

                GENENTECH, INC.,
                    Appellant

                          v.

                  HOSPIRA, INC.,
                     Appellee

                 UNITED STATES,
                     Intervenor
               ______________________

                     2018-1933
               ______________________

    Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2016-
01837.
                 ______________________

              Decided: January 10, 2020
               ______________________

    THOMAS S. FLETCHER, Williams & Connolly LLP,
Washington, DC, argued for appellant. Also represented
by PAUL B. GAFFNEY, EDEN SCHIFFMANN, JONATHAN SIDHU.

   THOMAS J. MELORO, Willkie Farr & Gallagher LLP,
New York, NY, argued for appellee. Also represented by
ALEXANDRA AWAI, MICHAEL JOHNSON.

   COURTNEY DIXON, Appellate Staff, Civil Division,
2                             GENENTECH, INC. v. HOSPIRA, INC.




United States Department of Justice, Washington, DC, ar-
gued 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.
                ______________________

    Before PROST, Chief Judge, NEWMAN and CHEN, Circuit
                           Judges.
      Opinion for the court filed by Circuit Judge CHEN.
     Dissenting opinion filed by Circuit Judge NEWMAN.
CHEN, Circuit Judge.
    Genentech, 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 pa-
tent) unpatentable as anticipated or obvious. See Genen-
tech, 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 con-
stitutionality 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 affirm.
                         BACKGROUND
     Genentech owns the ’799 patent, which is directed to
methods of purifying antibodies and other proteins con-
taining a CH2/CH3 region from impurities by protein A af-
finity chromatography. ’799 patent at col. 7 ll. 50–54.
Protein A affinity chromatography is a standard purifica-
tion technique employed in the processing of therapeutic
proteins, especially antibodies, which involves “using pro-
tein A . . . immobilized on a solid phase.” Id. at col. 4 ll. 27–
30. “The solid phase may comprise a glass, silica,
GENENTECH, INC. v. HOSPIRA, INC.                             3



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 adsor-
bent for affinity chromatography of proteins, such as anti-
bodies” 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.
     In 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 chroma-
tography 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 pur-
poses after formulation. Id. at col. 19 ll. 51–63.
    While 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 puri-
fication steps are typically employed to remove leached
protein A from the antibody solution. See id. at col. 20 ll.
12–15.
    The invention of the ’799 patent “concerns a method for
reducing leaching of protein A . . . by reducing [the] tem-
perature” of the “composition that is subjected to protein A
affinity chromatography.” Id. at col. 1 ll. 16–21. The
4                            GENENTECH, INC. v. HOSPIRA, INC.




specification discloses that “[p]referably, . . . the tempera-
ture 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. Ac-
cording 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.
    Claim 1, the sole independent claim at issue, re-
    cites:
    1. A method of purifying a protein which com-
       prises 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).
    Hospira, 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 1 or van Som-
meren 2 as the primary reference.
    The 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



    1   International Patent Application Publication WO
95/22389 A1, J.A. 508–54 (WO ’389).
    2   van Sommeren et al., Effects of Temperature, Flow
Rate and Composition of Binding Buffer on Adsorption of
Mouse Monoclonal IgG1 Antibodies to Protein A Sepharose
4 Fast Flow, 22 PREPARATIVE BIOCHEMISTRY 135 (1992),
J.A. 555–74 (van Sommeren).
GENENTECH, INC. v. HOSPIRA, INC.                             5



*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.
    Genentech appeals. The Patent Office intervened pur-
suant to 35 U.S.C. § 143 to defend against Genentech’s con-
stitutionality 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).
                         DISCUSSION
    We review the Board’s legal determinations de novo,
and the Board’s factual findings underlying those determi-
nations 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).
     Anticipation is a question of fact that we review for sub-
stantial 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 con-
tent of the prior art, differences between the prior art and
the claims at issue, the level of ordinary skill in the perti-
nent 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)).
                I. ANTICIPATION BY WO ’389
    The Board determined that claims 1 and 5 are antici-
pated 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
6                            GENENTECH, INC. v. HOSPIRA, INC.




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.
    Claim 1, the sole challenged independent claim of the
’799 patent, requires “subjecting a composition . . . to pro-
tein 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.” In-
deed, Genentech’s own proposed construction for “about
18°C” embraces temperatures up to 19°C, which further re-
inforces the overlap with WO ’389’s disclosed temperature
range.
     A prior 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.
GENENTECH, INC. v. HOSPIRA, INC.                           7



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 chal-
lenge the Board’s finding as to criticality, and accordingly,
whether or not the claimed temperature range achieves dif-
ferent performance results than WO ’389’s disclosed tem-
perature range is not at issue on appeal. Appellee’s Br. at
15.
    Aside from the overlapping range issue, the Board con-
strued the limitation “subjecting a composition . . . to pro-
tein 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 pro-
tein 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 com-
ponents 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 col-
umn buffers are all within that temperature range. Id.
Based on WO ’389 Example 1’s disclosure of washing the
8                            GENENTECH, INC. v. HOSPIRA, INC.




composition with at least three column volumes of buffer,
the Board inferred that the composition would reach “18–
25°C” during the washing step, and thus be within the
claimed temperature range. Id.
     On appeal, Genentech argues that WO ’389’s statement
that “[a]ll steps are carried out at room temperature (18–
25°C)” refers only to the temperature of the laboratory
where each step was performed, and not to the temperature
of the HCCF composition applied to the chromatography
column. Appellant’s Br. at 33–34. Genentech contends
this statement cannot be referring to the temperature of
the HCCF composition because WO ’389 discloses some
“steps” being carried out where the composition was cold or
frozen. J.A. 523–24 (disclosing that after the viral inacti-
vation step “[t]he resulting solution is . . . held in sterile
containers at 4°C, or frozen and held at -70°C”). Both par-
ties’ experts testified that HCCF comes from a bioreactor
in which cells are typically cultured around 37°C. J.A.
1351–52 ¶ 77 (Dr. Cramer’s testimony); J.A. 1531 (Dr.
Przybycien’s testimony). Both parties’ experts also testi-
fied that WO ’389 does not specify how long the HCCF was
held before being subjected to protein A affinity chromatog-
raphy. J.A. 1352 ¶ 78 (Dr. Cramer’s testimony); J.A. 1554
(Dr. Przybycien’s testimony). According to Genentech’s ex-
pert, Dr. Cramer, efficiency is typically a goal of industrial
processes, and absent an instruction to wait to allow the
HCCF to cool to room temperature, a skilled artisan would
have interpreted WO ’389 as allowing the disclosed process
to be performed with HCCF that was potentially warmer
than room temperature. J.A. 1352 ¶ 78. Genentech con-
tends that even if the laboratory was at “room temperature
(18–25°C),” the HCCF composition need not have been.
Appellant’s Br. at 33. 3



    3  Although the dissent believes that WO ’389’s “room
temperature” would not be understood to encompass
GENENTECH, INC. v. HOSPIRA, INC.                             9



    Hospira responds that WO ’389 uses the term, “room
temperature (18–25°C),” to describe the temperature for
conducting protein A affinity chromatography, and all the
components involved in that process, including the compo-
sition to be purified. Appellee’s Br. at 29. According to
Hospira’s expert, Dr. Przybycien, in the field of antibody
purification, absent contrary language, a skilled artisan
would understand that experiments are being conducted at
ambient temperature with all materials equilibrated in or-
der to obtain robust scientific data. J.A. 946 ¶ 26. Based
on WO ’389’s disclosure that the composition was cold or
frozen after the viral inactivation step, Hospira contends
that WO ’389 specifically called out the temperature of the
composition when requiring it to be at a temperature other
than room temperature. Appellee’s Br. at 31–32 (citing
J.A. 523–24).
    Here, substantial evidence supports the Board’s finding
that the HCCF subject to protein A affinity chromatog-
raphy in WO ’389 is within the claimed temperature range
of claim 1. ’837 Decision, 2018 WL 1187484, at *9–10. The
Board reasoned that it would have been redundant to spe-
cifically call out the temperature of the HCCF during pro-
tein A affinity chromatography in light of WO ’389’s
blanket statement to carry out all steps at “18–25°C.” Id.
at *9. The Board considered, but disagreed with, Dr.
Cramer’s interpretation of WO ’389 as disclosing a process
with HCCF that was warmer than “18–25°C” because his
opinion was predicated on the view that the ’799 patent is
directed to large-scale, industrial processes, which it is not.
Id. Further, Dr. Cramer testified that even for large-scale,



temperatures as low as 18°C, WO ’389 expressly discloses
a temperature range that includes 18°C. Thus, the Board
reasonably read the temperature range of WO ’389 to en-
compass temperatures as low as 18°C. Genentech does not
contend otherwise.
10                          GENENTECH, INC. v. HOSPIRA, INC.




industrial processes, he was not aware of any process
where HCCF was applied directly into the chromatography
column after being removed from the bioreactor and fil-
tered. Id. at *10 (citing J.A. 1075 at 85:6–15). The Board
instead credited Dr. Przybycien’s testimony that no skilled
artisan would contact 37°C HCCF to the chromatography
column, and report having performed the step at “room
temperature (18–25°C)” because using HCCF that was
warmer than the chromatography column would raise the
temperature of the entire system, making it impossible to
conduct “[a]ll steps . . . at room temperature.” ’837 Deci-
sion, 2018 WL 1187484, at *10 (citing J.A. 947 ¶ 27). To
the extent that the experts disagreed with each other, the
Board reasonably chose to credit the testimony of Dr.
Przybycien over the testimony of Dr. Cramer. Id. at *9–10.
See Yorkey v. Diab, 601 F.3d 1279, 1284 (Fed. Cir. 2010)
(“[T]he Board was well within its discretion to give more
credibility to [one expert’s] testimony over [another’s] un-
less no reasonable trier of fact could have done so.”). We
discern no reversible error in that choice.
    We are not persuaded by Genentech’s arguments that
this result is contrary to the case law. Appellant’s Br. at
36. Nidec Motor Corp. v. Zhongshan Board Ocean Motor
Co., cited by Genentech, holds that a reference missing a
limitation cannot anticipate even if a skilled artisan would
“at once envisage” the missing limitation. 851 F.3d 1270,
1274–75 (Fed. Cir. 2017). We do not agree with Genen-
tech’s argument that there is a “missing limitation.” As
discussed above, the Board reasonably found that a skilled
artisan would have understood that WO ’389’s disclosed
composition is within the claimed temperature range prior
to or during protein A affinity chromatography. “Anticipa-
tion is established when ‘one skilled in the art would rea-
sonably understand or infer from the prior art reference’s
teaching that every claim [limitation] was disclosed in that
single reference.’” CRFD Research, Inc. v. Matal, 876 F.3d
1330, 1338 (Fed. Cir. 2017) (quoting Akamai Techs., Inc. v.
GENENTECH, INC. v. HOSPIRA, INC.                         11



Cable & Wireless Internet Servs., Inc., 344 F.3d 1186, 1192–
93 (Fed. Cir. 2003)). That is the case here.
    Genentech does not raise any arguments with respect
to any other claim limitation, nor does it separately argue
dependent claim 5. Thus, dependent claim 5 stands or falls
together with independent claim 1. See In re Kaslow, 707
F.2d 1366, 1376 (Fed. Cir. 1983). We therefore conclude
that substantial evidence supports the Board’s finding that
WO ’389 anticipates claims 1 and 5 of the ’799 patent.
        II. OBVIOUSNESS GROUNDS BASED ON WO ’389
    The Board determined that claims 1 and 5 would have
been obvious over WO ’389; claims 1–3 and 5 would have
been obvious in view of WO ’389, Balint, 4 and Potier 5; and
claims 2–3 and 6–11 would have been obvious in view of
WO ’389, Balint, Potier and/or U.S. Patent 6,127,526. As
with anticipation, Genentech challenges the Board’s deter-
mination that WO ’389’s disclosed temperature range ren-
ders the claimed temperature range obvious.
    If the relevant comparison between a disputed claim
limitation and the prior art pertains to a range of overlap-
ping values, “we and our predecessor court have consist-
ently held that even a slight overlap in range establishes a
prima facie case of obviousness.” In re Peterson, 315 F.3d
1325, 1329 (Fed. Cir. 2003). We have said such an overlap
creates a presumption of obviousness, and that the burden


    4   Joseph P. Balint, Jr. and Frank R. Jones, Evidence
for Proteolytic Cleavage of Covalently Bound Protein A from
a Silica Based Extracorporeal Immunoadsorbent and Lack
of Relationship to Treatment Effects, 16 TRANSFUS. SCI. 85
(1995), J.A. 578–87 (Balint).
    5   P. Potier et al., Temperature-Dependent Changes in
Proteolytic Activities and Protein Composition in the Psy-
chrotrophic Bacterium Arthrobacter Globiformis S155, 136
J. GEN. MICROBIOL. 283 (1990), J.A. 592–600 (Potier).
12                           GENENTECH, INC. v. HOSPIRA, INC.




of production falls upon the patentee to come forward with
pertinent evidence that the overlapping range would not
have been obvious in light of the prior art. E.I. DuPont de
Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006, 1008
(Fed. Cir. 2018) (collecting cases).
    One way in which the patentee may rebut the pre-
sumption of obviousness is by showing “that there is some-
thing special or critical about the claimed range.” Id. The
presumption of obviousness applies here, and the Board
found that Genentech failed to establish criticality for the
claimed temperature range. ’837 Decision, 2018 WL
1187484, at *18. On appeal, Genentech does not argue that
this Board finding lacks substantial evidence. Appellee’s
Br. at 15.
      Another way in which the presumption can be rebutted
is by showing that a process parameter, such as tempera-
ture, was not recognized as “result-effective.” DuPont, 904
F.3d at 1006 (citing Applied Materials, 692 F.3d at 1295).
“The idea behind the ‘result-effective variable’ analysis is
. . . that a person of ordinary skill would not always be mo-
tivated to optimize a parameter ‘if there is no evidence in
the record that the prior art recognized that [that] particu-
lar parameter affected the result.’” Id. at 1008 (quoting In
re Antonie, 559 F.2d 618, 620 (CCPA 1977)). But where the
prior art recognizes that the process parameter affects the
relevant property or result, then the process parameter is
“result-effective.” Id. at 1009.
     The Board found that a skilled artisan would have rec-
ognized that the temperature for conducting protein A af-
finity chromatography was a result-effective variable. ’837
Decision, 2018 WL 1187484, at *18. The Board found that
it was recognized in the prior art at the time of the inven-
tion that leaching was caused by proteolysis of matrix-
bound protein A (as illustrated in Balint and other prior art
references), and that proteolysis was affected by tempera-
ture (as illustrated in Potier). Id.; see id. at *19; J.A. 594,
GENENTECH, INC. v. HOSPIRA, INC.                          13



596 (Potier demonstrating that the extent of protein degra-
dation caused by proteolysis increased with temperature).
Moreover, the Board found that a skilled artisan would
have expected that lowering temperature would reduce
proteolysis of matrix-bound protein A, and consequently,
would reduce protein A leaching. Id. at *17; see id. at *19.
     “The normal desire of scientists or artisans to improve
upon what is already generally known provides the moti-
vation to determine where in a disclosed set of . . . ranges
is the optimum combination.” Peterson, 315 F.3d at 1330.
“Where the general conditions of a claim are disclosed in
the prior art, it is not inventive to discover the optimum or
workable ranges by routine experimentation.” In re Ap-
plied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012)
(citing In re Aller, 220 F.2d 454, 456 (1955)). The Board
reasonably found that a skilled artisan would have been
motivated to optimize the temperature given the teachings
of the prior art, and that given the ease with which tem-
perature can be varied, finding an optimal temperature
range would have been nothing more than routine experi-
mentation. ’837 Decision, 2018 WL 1187484, at *18–19.
    On appeal, Genentech does not appear to contest that
temperature is a result-effective variable in the claimed
process. Instead, Genentech argues that the desire to re-
duce protein A leaching applies only to the large-scale, in-
dustrial purification of therapeutic antibodies for clinical
applications, because non-clinical applications do not in-
volve concerns about product purity that require the elim-
ination of leached protein A. Appellant’s Br. at 41.
Genentech further contends that chilling HCCF for large-
scale, industrial processes would have been inconvenient,
costly, and impractical. Appellant’s Br. at 45.
    Hospira responds that it would be desirable to reduce
protein A leaching for non-clinical applications because
protein A leaching degrades chromatography columns, re-
ducing their usable capacity and life span. Appellee Br. at
14                          GENENTECH, INC. v. HOSPIRA, INC.




46 (citing J.A. 932). The Board correctly noted that neither
the challenged claims nor the disclosure of WO ’389 are
limited to large-scale, industrial processes. ’837 Decision,
2018 WL 1187484, at *9. The evidence in the record sup-
ports the Board’s finding that the temperature of the chro-
matography column could be readily controlled. We hold
that substantial evidence supports the Board’s conclusion
that it would have been routine experimentation to explore
the temperature dependence of protein A leaching. Genen-
tech has not shown that the Board’s factual findings are
unsupported by substantial evidence.
    The Board considered Genentech’s evidence of objective
indicia of nonobviousness but found it to be unpersuasive.
’837 Decision, 2018 WL 1187484, at *19. Genentech al-
leged industry praise and recognition by others in the field
based on the selection of a presentation relating to the
claimed method at the American Chemical Society’s Na-
tional Meeting in 2005. Genentech contends that the fact
that its research was selected for presentation undermines
the Board’s conclusion that the claimed method would have
been the obvious result of “routine optimization.” Appel-
lant’s Br. at 52–53. Hospira responds, and we agree, that
Genentech fails to establish a nexus between the objective
indicia and the claimed method because there was no evi-
dence that the presentation was selected due to the claimed
method. Appellee Br. at 53. Substantial evidence supports
the Board’s decision to accord little weight to Genentech’s
evidence of objective indicia.
   The Board next determined that claims 2–3 and 6–11
would have been obvious over WO ’389, Balint, Potier
and/or U.S. Patent 6,127,526. Genentech does not sepa-
rately argue the dependent claims and relies on the argu-
ments it raised for anticipation and obviousness over WO
’389. Thus, the dependent claims stand or fall together
with the independent claim 1. See Kaslow, 707 F.2d at
1376. We therefore conclude that the Board did not err in
concluding that claims 1–3 and 5–11 of the ’799 patent
GENENTECH, INC. v. HOSPIRA, INC.                           15



would have been obvious over WO ’389 alone or in combi-
nation with other prior art references.
                     IV. OTHER ISSUES
    Genentech also argues that because the Board erred in
construing “about 18°C,” the claims are not anticipated by
van Sommeren nor obvious over grounds that include van
Sommeren. Because we have determined that the Board
did not err in concluding that all of the challenged claims
are unpatentable on grounds based on WO ’389, we need
not reach the arguments involving van Sommeren. See
Oral Arg. at 2:01–2:50, Genentech, Inc. v. Hospira, Inc., No.
2018-1933 (Fed. Cir. Aug. 5, 2019), http://oralargu-
ments.cafc.uscourts.gov/default.aspx?fl=2018-1933.mp3.
     Finally, we address Genentech’s challenge that retro-
active application of IPR to a patent issued prior to passage
of the AIA constitutes a violation of the Fifth Amendment’s
Takings Clause. 6 We recently addressed this issue in
Celgene Corp. v. Peter, 931 F.3d 1342, 1356–63 (Fed. Cir.
2019). As we explained, pre-AIA patents were issued sub-
ject to both district court and Patent Office validity pro-
ceedings. Id. at 1359. Though IPR differs from district
court and pre-AIA Patent Office reexamination proceed-
ings, we held that those differences were not sufficiently
substantive or significant such that a “constitutional issue”
is created when IPR is applied to pre-AIA patents. Id. at
1362; see also id. at 1358 & n.13 (affirming that our prior
decisions ruling that retroactive application of reexamina-
tion does not violate the Fifth Amendment, the Seventh




    6    To the extent Genentech intends to separately
raise a due process challenge, the limited conclusory asser-
tions it presented are “insufficient to preserve the issue for
appeal.” See Trading Techs. Int’l, Inc. v. IBG LLC, 921 F.3d
1378, 1385 (Fed. Cir. 2019).
16                          GENENTECH, INC. v. HOSPIRA, INC.




Amendment, or Article III “control the outcome” of similar
challenges to IPR).
    Like the patent at issue in Celgene, when the ’799 pa-
tent issued, patentees already expected that their patents
could be challenged in district court and “[f]or forty years”
had expected that “the [Patent Office] could reconsider the
validity of issued patents on particular grounds, applying
a preponderance of the evidence standard.” Id. at 1363.
Accordingly, application of IPR to Genentech’s patent, on
grounds that were available for Patent Office reconsidera-
tion when the patent was issued and under the same bur-
den of proof, does not create a constitutional issue, and we
reject Genentech’s constitutional challenge.
                       CONCLUSION
     We have considered Genentech’s remaining arguments
but find them unpersuasive. For the foregoing reasons, we
affirm the decision of the Board.
                       AFFIRMED
  United States Court of Appeals
      for the Federal Circuit
                  ______________________

                  GENENTECH, INC.,
                      Appellant

                             v.

                     HOSPIRA, INC.,
                        Appellee

                    UNITED STATES,
                        Intervenor
                  ______________________

                        2018-1933
                  ______________________

    Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2016-
01837.
                 ______________________
NEWMAN, Circuit Judge, dissenting.
    I respectfully dissent, for the court finds the claims of
U.S. Patent 7,807,799 (“the ’799 patent”) invalid for antici-
pation or obviousness, although no prior art shows the
claimed method, or suggests that it should be attempted or
that it might be successful. The court presents a hindsight
determination that this apparently simple solution to a dif-
ficult problem is anticipated and obvious, although it was
not known or obvious to the scientists who were attempting
to solve the problem of leaching contamination, and the ex-
perts for both sides agreed that the solution presented in
the ’799 patent was new to them.
2                            GENENTECH, INC. v. HOSPIRA, INC.




    The ’799 patent describes the complexities of obtaining
and purifying biological products such as antibodies, in the
purity and on the scale needed for medicinal use. The pa-
tent describes a procedure called “protein A affinity chro-
matography,” and its known use with biological materials.
The patent describes the problem that the inventors en-
countered due to leaching of the protein A. The inventors
described their discovery of the cause of the leaching, and
the solution they found. This solution is not shown or sug-
gested in the prior art—yet is deemed anticipated or obvi-
ous by my colleagues.
    The ’799 invention
     The ’799 patent is directed to the separation and puri-
fication of specified antibodies from the harvested cell cul-
ture fluid. Protein A affinity chromatography was a known
tool for purifying antibodies. ’799 patent col. 20, ll. 6–7.
Protein A has “the ability to bind proteins which have a
CH2/CH3 region.” Id. at col. 4, ll. 20–25. In protein A affin-
ity chromatography, the antibody containing “a CH2/CH3
region may be reversibly bound to, or adsorbed by, the pro-
tein A,” the protein A extracts the antibody from its cell
culture fluid, and the pure antibody is eluted. Id. at col. 4,
ll. 27–47; Id. at col. 1, ll. 56–66. “Dynamic capacity” of pro-
tein A affinity chromatography “depends on many factors,
including the type of protein A affinity chromatography
media, the antibody concentration in the load, the column
temperature and column length, the buffer, conductivity,
and pH of the load, and the flow rate.” J.A. 1312. 1




    1   This scientific article, authored by an inventor of
the ’799 patent, discusses protein A affinity chromatog-
raphy for purification of biologicals. Fahrner et al., The
Optimal Flow Rate and Column Length for Maximum
GENENTECH, INC. v. HOSPIRA, INC.                         3



    Genentech states that in its commercial-scale process
for preparing specified antibodies, it was found that small
but unacceptable amounts of protein A had leached from
the column and contaminated the eluted antibody. Alt-
hough the prior art describes possible procedures for re-
moving any contaminating protein A, the Genentech
inventors testified, and the experts for both sides agreed,
these procedures were not effective for these antibodies.
The Genentech research team “spent months trying to
solve the leached protein A problem, under significant com-
mercial pressure.” J.A. 1436. “The research team eventu-
ally observed that . . . leaching might be caused by
proteolysis” leading to “a series of experiments using re-
duced temperature and protease inhibitors.” J.A. 1435.
    Thus the inventors found the solution of temperature
reduction, as described and claimed in the ’799 patent. The
retrospective simplicity of the solution apparently led the
Board to find it obvious to them, despite the undisputed
testimony that no reference suggests this solution to the
contamination problem here encountered, as the experts
for both sides acknowledged. On this appeal, Hospira of-
fers no contradictory evidence, prior art, or argument.
    Nonetheless, the Board held this novel method to be
anticipated and obvious, although not described or sug-
gested in the prior art; and my colleagues agree.
    The prior art temperature range does not
    show or suggest the ’799 invention
    Claim 1 of the ’799 patent states the temperature and
other limitations for conduct of the claimed method:
    1. A method of purifying a protein which com-
       prises a CH2/CH3 region, comprising subjecting


Production Rate of Protein A Affinity Chromatography, 21
Bioprocess Engineering 287 (1999)), J.A. 1312–17.
4                             GENENTECH, INC. v. HOSPIRA, INC.




        a composition comprising said protein to pro-
        tein A affinity chromatography at a tempera-
        ture in the range from about 10 º C. to about
        18 º C.
’799 patent col. 35, ll. 44–47.
     The ’799 patent specification describes the invention as
“a method of purifying a protein which comprises a
CH2/CH3 region, comprising reducing the temperature of a
composition comprising the protein and one or more impu-
rities subjected to protein A affinity chromatography in the
range from about 3º C. to about 20º C., wherein protein A
leaching is reduced.” Id. at col. 2, ll. 22–27. The specifica-
tion further states: “Preferably, the method comprises re-
ducing the temperature of the composition subjected to the
protein A affinity chromatography, e.g. where the temper-
ature of the composition is reduced below room tempera-
ture, for instance in the range from about 3º C. to about
20º C., e.g. from about 10º C. to about 18º C.” Id. at col. 18,
ll. 4–9.
    The Board discarded this description, stating that it
was merely a “preferred embodiment,” whereby the Board
“decline[d] to rewrite claim 1.” Hospira, Inc. v. Genentech,
Inc., No. IPR2016-01837, 2018 WL 1187484, at *6 (P.T.A.B.
Mar. 6, 2018) (“Board Op.”). The Board stated that “under-
standing the claim language may be aided by the explana-
tions contained in the written description, [but] it is
important not to import into a claim limitations that
[which is] not a part of the claim,” quoting SuperGuide
Corp. v. DirecTV Enters., Inc., 358 F.3d 870, 875 (Fed. Cir.
2004)), the Board apparently ignoring that claim 1, and all
the claims, explicitly require “a temperature in the range
from about 10 º C. to about 18 º C.” See Board Op. at *6.
The Board’s statement that it “decline[d] to rewrite claim
1” is puzzling, for claim 1 as written is limited to the pre-
ferred embodiment.
GENENTECH, INC. v. HOSPIRA, INC.                            5



     The ’799 patent specification describes the protein A
affinity chromatography of 12,000 liters of cell culture
fluid, chilled to “15 +/– 3º C,” supporting the temperature
limit of “about 18 º C” in the claims. ’799 patent col. 21,
ll. 4–8.
     The Board cited the prosecution history of a related pa-
tent, and found that Genentech “limited the meaning of
‘about’ in the term ‘about 18 ºC’ to at least ±>2 ºC, but less
than ±4º C.” Board Op. at *7. Genentech amended the up-
per limit of its claims from “20ºC” to “about 18ºC” in view
of a reference that showed affinity chromatography at
“about 22ºC.” J.A. 733–43, 740. The Board recited that
“self-serving statements in the prosecution” are “accord[ed]
little weight.” Board Op. at *7. To the contrary, state-
ments during prosecution are a primary resource and rig-
orous commitment in construing patent claims. Phillips v.
AWH Corp., 415 F.3d 1303, 1317 (Fed. Cir. 2005) (en banc).
The Board’s construction that the range of “about 10 º C. to
about 18 º C.” reads on the prior art is not supported in fact
or law.
    The Board cited, and my colleagues discuss, two prin-
cipal references. The scientific article of van Sommeren 2
includes data for protein A affinity chromatography per-
formed at the standard of ambient temperature. The arti-
cle compares results at “ambient temperature (AT)
(20–25 ºC)” with results in a cold room at 4 ºC. J.A. 570.
Based on this reference, the Board reasoned that 20–25ºC
“overlaps with [its] construction of ‘about 18º C.’ as having
an upper bound of 21 ºC.” Board Op. at *12. Thus the



    2   van Sommeren et al., Effects of Temperature, Flow
Rate and Composition of Binding Buffer on Adsorption of
Mouse Monoclonal IgG1 Antibodies to Protein A Sepharose
4 Fast Flow, 22(2) Preparative Biochemistry 135 (1992),
J.A. 555–74 (“van Sommeren”).
6                           GENENTECH, INC. v. HOSPIRA, INC.




Board held the ’799 patent claims anticipated or obvious in
view of van Sommeren.
    The other principal reference, WO ’389, 3 shows protein
A chromatography in which “[a]ll steps are carried out at
room temperature (18–25 ºC).” J.A. 522. The WO ’389 ap-
plication recognizes that protein A may leach from the col-
umn, and states that its removal from the eluent may
require “hydrophobic interaction chromatography.”
J.A. 512–13 (“Although Protein A affinity column chroma-
tography is widely used, it is also appreciated that elution
of antibody from such columns can result in leaching of re-
sidual Protein A from the support. . . . It has now been
surprisingly discovered that HIC [hydrophobic interaction
chromatography] can be usefully employed to remove con-
taminating Protein A.”). Genentech points to the ad-
vantages of its method, in contrast with the WO ’389
teaching of the need to conduct another chromatographic
procedure to remove the contaminating Protein A.
    The experts for both sides agreed that the WO ’389 ap-
plication’s room temperature of 18–25ºC refers to the am-
bient temperature, not the temperature of the chilled
material in the column. J.A. 1350–53, 1547–48. Nonethe-
less, the PTAB and now my colleagues hold that this “room
temperature” range anticipates the ’799 patent’s chilled
range of 10ºC–18ºC, ignoring the significantly different re-
sults in the recited ranges. The general understanding of
room temperature is in the range of 21ºC–25ºC (69ºF
–77ºF), as the experts for both sides testified. J.A. 1346–
50, 1599–1600. The ’799 patent specification shows 15±3ºC
as the basis for the 18ºC limit in the claims. No reference
contemplates or suggests or hints that chilling below room
temperature for the affinity chromatographic process



    3 International Patent Application Publication No.
WO 95/22389 A1, J.A. 508–54 (“WO ’389”).
GENENTECH, INC. v. HOSPIRA, INC.                          7



would eliminate the contaminating leaching of the pro-
tein A.
     WO ’389’s lower edge of 18ºC does not anticipate the
chilled range of 10ºC–18ºC. The abutment at 18ºC between
the claimed chilled temperature range and room tempera-
ture does not produce anticipation of the lower range. An-
ticipation requires that the same invention, including all
claim limitations, was previously described. Nidec Motor
Corp. v. Zhongshan Broad Ocean Motor Co., 851 F.3d 1270,
1274–75 (Fed. Cir. 2017) (holding that precedent “does not
permit the Board to fill in missing limitations simply be-
cause a skilled artisan would immediately envision
them.”). Neither party’s expert testified that the prior art
showed that lowering the temperature below the norm of
protein A affinity chromatography would eliminate leach-
ing of protein A.
    It was conceded that no reference showed or suggested
the solution that was here discovered, and no expert wit-
ness acknowledged this practice. Hospira’s expert testi-
fied:
    Q. . . . Are you aware of anyone prior to July of
    2003 doing protein A chromatography at a reduced
    temperature using a jacketed column and/or a
    chilling tank?
    A. I have not seen that.
J.A. 1667–68.
    The ’799 patent specification describes that by conduct-
ing the affinity chromatography in the range of 10ºC–18ºC,
substantially all of the leaching of protein A is prevented.
However, my colleagues hold that the mention of 18ºC as
the lower boundary of room temperature anticipates the
claimed range of 10ºC–18ºC—and that this ends the in-
quiry. That is not the law of anticipation. An anticipating
reference must describe the entirety of the claimed subject
matter. “Anticipation is established when ‘one skilled in
8                            GENENTECH, INC. v. HOSPIRA, INC.




the art would reasonably understand or infer from the
prior art reference’s teaching that every claim [limitation]
was disclosed in that single reference.’” CRFD Research,
Inc. v. Matal, 876 F.3d 1330, 1338 (Fed. Cir. 2017) (quoting
Akamai Techs., Inc. v. Cable & Wireless Internet Servs.,
Inc., 344 F.3d 1186, 1192–93 (Fed. Cir. 2003)).
    My colleagues nonetheless find the mention of a “room
temperature” lower edge of 18ºC in the 18–25ºC range to be
a fatal anticipation of the claimed 10ºC–18ºC range, despite
the absence of identity of these ranges, despite the different
results at the lower range, and despite the significance of
the purity of the eluted antibody.
    Precedent does not support my colleagues’ finding of
anticipation, for precedent requires that to anticipate, the
prior art must describe the same invention. See id.; King
Pharm., Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1274 (Fed.
Cir. 2010) (“[A] claim is anticipated if each and every limi-
tation is found either expressly or inherently in a single
prior art reference.” (internal quotation marks omitted)).
The prior art does not show the 10ºC–18ºC range, and the
specification supports the distinction with description of
the different characteristics of the cooled material. Noth-
ing in the prior art suggested that the leaching of protein
A could be prevented by lowering the temperature, with no
adverse effect on the efficacy of the affinity purification,
and no loss of the purified antibody.
     The experts for both sides agreed that the prior art does
not show or suggest that this 10ºC–18ºC temperature range
would produce the favorable results that were achieved.
Contrary to my colleagues’ reasoning, this is not simply a
matter of selecting the optimum temperature within a
taught temperature range for conducting a known proce-
dure. Neither the cooled temperature range nor the result
of cooling the material subjected to protein A affinity chro-
matography is shown or suggested in the prior art.
GENENTECH, INC. v. HOSPIRA, INC.                           9



    Nor is the question whether it would be easy to experi-
ment at varying temperatures, as my colleagues suggest.
Maj. Op. at 13 (“The Board reasonably found that a skilled
artisan would have been motivated to optimize the temper-
ature given the teachings of the prior art, and that given
the ease with which temperature can be varied, finding an
optimal temperature range would have been nothing more
than routine experimentation.”). However, the question is
not whether it would have been easy to cool the material to
the 10ºC–18ºC range; the question is whether it would have
been obvious to do so. Contrary to the Board’s and the
court’s view, this is not a matter of optimizing a known pro-
cedure to obtain a known result; for it was not known that
cooling the material for chromatography would avoid con-
tamination of the purified antibody with leached protein A.
     The Board’s holding that the ’799 method is anticipated
by van Sommeren and WO ’389 is devoid of support by sub-
stantial evidence, for the only evidence was that these are
different procedures conducted under different conditions
to achieve different purposes.
    The Board and this court err in holding the ’799 patent
claims invalid on the grounds of anticipation and obvious-
ness, for no prior art shows or suggests the claimed proce-
dure.
