Cytiva Bioprocess R&dab v. JSR CORP., JSR LIFE SCIENCES, LLC, Cross-Appellants 2023-2074, 2023-2075,…

United States Court of Appeals
for the Federal Circuit
______________________
CYTIVA BIOPROCESS R&D AB,
Appellant
v.
JSR CORP., JSR LIFE SCIENCES, LLC,
Cross-Appellants
______________________
2023-2074, 2023-2075, 2023-2191, 2023-2192, 2023-2193,
2023-2194, 2023-2239, 2023-2252, 2023-2253, 2023-2255
______________________
Appeals from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in Nos. IPR2022-
00036, IPR2022-00041, IPR2022-00042, IPR2022-00043,
IPR2022-00044, IPR2022-00045.
______________________
Decided: December 4, 2024
______________________
DAVID M. KRINSKY, Williams & Connolly LLP,
Washington, DC, argued for appellant. Also represented
by ANDREW LEON HOFFMAN.
ERIC WILLIAM DITTMANN, Paul Hastings LLP, New
York, NY, argued for cross-appellants. Also represented by
ISAAC S. ASHKENAZI, KRYSTINA L. HO, CARL J. MINNITI, III;
PHILLIP W. CITROEN, STEPHEN BLAKE KINNAIRD, NAVEEN
MODI, MICHAEL WOLFE, Washington, DC; HIROYUKI
HAGIWARA, Tokyo, Japan.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 2
______________________
Before PROST, TARANTO, and HUGHES, Circuit Judges.
PROST, Circuit Judge.
In this consolidated appeal, Cytiva BioProcess R&D AB
(“Cytiva”) appeals the final written decisions from six inter
partes reviews (“IPRs”), determining that 79 claims of the
three challenged patents are unpatentable. JSR Corp. and
JSR Life Sciences, LLC (collectively, “JSR”) cross appeal
the final written decisions in four of these IPRs, which held
the remaining four challenged claims not unpatentable.
We affirm the Patent Trial and Appeal Board’s (“Board”)
determination that claims 1–7, 10–20, 23–26 of the ’765
patent,1 claims 1–3, 5–7, 10–16, 18–20, 23–30 of the ’142
patent,2 and claims 1–10, 12–14, 16–28, 30–32, and 34–37
of the ’007 patent3 are unpatentable (i.e., the 79 claims the
Board held are unpatentable), and we reverse the Board’s
determination that claims 4 and 17 of the ’142 patent4 and
claims 11 and 29 of the ’007 patent are not unpatentable.
1 U.S. Patent No. 10,213,765.
2 U.S. Patent No. 10,343,142.
3 U.S. Patent No. 10,875,007.
4 JSR’s briefing suggests that the cross-appeal
claims include claim 7 instead of claim 17 of the ’142
patent. E.g., Cross-Appellant’s Br. 58 n.12. Because the
Board found claims 4 and 17 not unpatentable, because
claims 4 and 17 mirror each other (and claim 7 is
substantively different), and because the limitation
disputed here appears in claims 4 and 17 (and not claim 7),
we interpret JSR’s dispute to apply to claims 4 and 17 of
the ’142 patent.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 3
BACKGROUND
I
JSR filed six IPRs challenging claims 1–7, 10–20, and
23–26 of the ’765 patent5; claims 1–7, 10–20, and 23–30 of
the ’142 patent6; and claims 1–14, 16–32, and 34–37 of the
’007 patent.7 Each of the challenged patents generally
relates to chromatography matrices and processes for
isolating target compounds using those matrices.
A
Chromatography is the process of separating
components in a mixture, which can be accomplished
through a variety of separation methods. The challenged
patents relate to a certain type of chromatography called
affinity chromatography. In affinity chromatography, a
biomolecule is separated from a mixture using molecular
binding. This is done by creating a chromatography matrix
(a solid support attached to a ligand), where the ligand
selected has a high affinity for binding to the target
biomolecule (e.g., a protein or antibody).8 The following
5 JSR Corp. v. Cytiva BioProcess R&D AB, IPR2022-
00036 and IPR2022-00043, Final Written Decision
(P.T.A.B. Apr. 19, 2023), J.A. 1–54; see also J.A. 177–230.
6 JSR Corp. v. Cytiva BioProcess R&D AB, IPR2022-
00041 and IPR2022-00044, Final Written Decision
(P.T.A.B. May 18, 2023), J.A. 55–115; see also J.A. 231–91.
7 JSR Corp. v. Cytiva BioProcess R&D AB, IPR2022-
00042 and IPR2022-00045, Final Written Decision
(P.T.A.B. May 18, 2023), J.A. 116–76; see also J.A. 292–352.
8 While affinity chromatography may be used to
isolate a variety of molecules, the challenged patents use
affinity chromatography to isolate certain antibodies. For
this reason, our discussion of affinity chromatography
focuses on the isolation of antibodies rather than other
types of molecules. Human antibodies are called
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 4
figure illustrates these parts of the chromatography matrix
inside a chromatography column:
Cross-Appellants’ Br. 6 (citing J.A. 2966).
Once the chromatography matrices are prepared,
affinity chromatography generally isolates the target
antibody through the following steps: First, the
chromatography matrices are “packed into a
chromatography column.” Id. (citing J.A. 2967–70). Next,
“a fluid containing the target antibody is loaded into the
column.” Id. (citing J.A. 2970–71). The ligands in the
chromatography matrices then selectively bind to the
target antibody in the mixture—i.e., when the mixture is
poured into the column with the matrices, the antibody
attaches to the ligand, while the impurities do not. Next,
a washing step removes the unbound impurities from the
column, leaving behind the antibodies bound to the
matrices. Finally, a solution is poured into the column in
an elution step, which breaks the bond between the ligand
and the target antibody, thereby isolating the antibodies.
The following figure illustrates these steps:
immunoglobulins, of which one type is immunoglobulin G
(“IgG”). Here, we use the terms antibodies and
immunoglobulins interchangeably.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 5
Cross-Appellants’ Br. 7 (citing J.A. 2970–71). When the
process is complete, the columns are cleaned to remove
contaminants in the column. This procedure “typically
entails running an alkaline solution over the column, [and]
is called cleaning-in-place (‘CIP’).” Id.
Each of the patents here relates to chromatography
matrices comprising a ligand made from Protein A (also
called SPA) found in the bacterium staphylococcus aureus.
SPA has been the target of research in the field of
chromatography for decades due to its specific binding
properties to immunoglobulins. See, e.g., J.A. 3896–3902.
Protein A has “five highly homologous” natural domains:
Domains A, B, C, D, and E. J.A. 3815; ’765 patent col. 2
ll. 54–59. As early as the 1980s, researchers and scientists
had designed a synthetic SPA domain, referred to as
Domain Z, derived from a genetically altered Domain B.
J.A. 3898.
“Because CIP involves high-alkaline conditions, which
can degrade proteins, increased ligand stability in alkaline
environments is desirable.” Cross-Appellants’ Br. 8 (citing
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 6
J.A. 2972–73; J.A. 371; J.A. 3840–41). Thus, mutations to
SPA that improve ligand stability in alkaline environments
are also desirable—i.e., because they reduce the risk of
protein degradation when using CIP. Since at least the
1980s, the amino acid sequence asparagine-glycine, found
in each of the SPA domains, has been known to be sensitive
to alkaline environments. J.A. 3898. Additionally,
“[s]ubstituting the glycine at position 29 for alanine, also
called a ‘G29A’ modification, has been known since the
1980s to promote alkaline stability by avoiding this
problematic asparagine-glycine connection.” Cross-
Appellants’ Br. 8 (citing J.A. 2974–77; J.A. 3901;
J.A. 3816). Scientists made the G29A substitution when
creating Domain Z from Domain B, J.A. 3898; this
modification “improve[d] the domain’s alkaline stability.”
Appellant’s Br. 11 (citing J.A. 3911).
B
The independent claims of the challenged patents
recite making the same G29A modification to Domain C of
SPA as had already been made to Domain B in the prior
art. For example, claim 1 of the ’765 patent recites the
following, where SEQ ID NO. 1 is the amino acid sequence
for Domain C:
1. A chromatography matrix comprising:
a solid support; and
a ligand coupled to the solid support, the
ligand comprising at least two
polypeptides,
wherein the amino acid sequence of each
polypeptide comprises at least 55
contiguous amino acids of a modified SEQ
ID NO. 1, and
wherein the modified SEQ ID NO. 1 has an
alanine (A) instead of glycine (G) at a
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 7
position corresponding to position 29 of
SEQ ID NO. 1.
’765 patent claim 1 (composition claim). Claim 1 of the ’142
patent and claim 1 of the ’007 patent recite a process for
isolating a target compound with this chromatography
matrix. See ’142 patent claim 1 (process claim); ’007 patent
claim 1 (process claim).
In addition to the Domain C G29A mutation, the
challenged patents also claim certain antibody binding
properties. Antibodies are made up of different regions,
including an Fc region and a Fab region. “Fab regions
separated from antibodies are known as ‘Fab fragments’
. . . .” Appellant’s Br. 7 (citing J.A. 5802; J.A. 5874–79;
J.A. 6254). “Antigens can bind to either the whole antibody
or a fragment of an antibody.” Cross-Appellants’ Br. 5
(citing J.A. 5802–03). The following figure illustrates the
different regions of an antibody:
Cross-Appellants’ Br. 64 (citing J.A. 5802).
Certain challenged dependent claims recite binding “to
the Fab part of an antibody.” For example, claim 4 of the
’765 patent recites: “The chromatography matrix of claim
1, wherein the ligand is capable of binding to the Fab part
of an antibody.” See also ’765 patent claim 17. Claim 4 of
the ’142 patent and claim 11 of the ’007 patent both recite:
“The process of claim 1, wherein the ligand binds to the Fab
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 8
part of an antibody.” See also ’142 patent claim 17; ’007
patent claim 29.
II
The Board, in its final written decisions, found all
challenged claims unpatentable as obvious in view of
Linhult,9 Abrahmsén,10 and Hober11 except for claims 4
and 17 of the ’142 patent and claims 11 and 29 of the ’007
patent, which the Board found were not unpatentable. See
J.A. 52–53; J.A. 112–13; J.A. 173–75.12 In holding most of
the challenged claims unpatentable, the Board first
determined it would have been obvious to make the G29A
mutation to Domain C based on express suggestions in the
prior art. With respect to certain dependent claims, which
claim the chromatography matrices’ capability of binding
or process of binding to the “Fab part of an antibody,” the
Board reached divergent results. The Board determined
that the Fab-binding composition claims (i.e., claims 4 and
17 of the ’765 patent) are unpatentable because they
claimed an inherent property. But with respect to the
parallel process claims (i.e., claims 4 and 17 of the ’142
patent and claims 11 and 29 of the ’007 patent), the Board
9 M. Linhult et al., Improving the Tolerance of a
Protein A Analogue to Repeated Alkaline Exposures Using
a Bypass Mutagenesis Approach, PROTEINS: Structure,
Function, and Bioinformatics, 55:407–16 (2004)
(“Linhult”); J.A. 3815–24.
10 U.S. Patent No. 5,143,844 (“Abrahmsén”);
J.A. 3825–38.
11 PCT App. No. WO 03/080655 (“Hober”);
J.A. 3839–92.
12 The substance of the final written decisions in each
of the six IPRs is substantively similar. Therefore, we rely
primarily on the Board’s Decision in IPR2022-00036 to
illustrate the Board’s factual findings or legal reasoning,
except where otherwise specified.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 9
determined that the claims were not shown to have been
unpatentable because even though Fab-binding was an
inherent property, JSR had failed to show a reasonable
expectation of success. The Board’s different results were
based, at least in part, on limiting the meaning of “Fab part
of an antibody” to Fab fragments.
Cytiva timely appealed, and JSR timely cross-
appealed. We have jurisdiction under 28 U.S.C.
§ 1295(a)(4)(A).
DISCUSSION
“Obviousness is a question of law that we review de
novo, but the Board’s underlying findings of fact are
reviewed for substantial evidence. Substantial evidence
means such relevant evidence as a reasonable mind might
accept as adequate to support a conclusion.” Liqwd, Inc. v.
L’Oreal USA, Inc., 941 F.3d 1133, 1136 (Fed. Cir. 2019)
(cleaned up).
Cytiva appeals the Board’s determination that claims
1–7, 10–20, 23–26 of the ’765 patent, claims 1–3, 5–7,
10–16, 18–20, 23–30 of the ’142 patent, and claims 1–10,
12–14, 16–28, 30–32, and 34–37 of the ’007 patent are
unpatentable. Cytiva first argues that the Board’s
determination as to all of these claims must be reversed
because the Board allegedly “failed to assess whether—and
JSR failed to present evidence that—[a person of ordinary
skill in the art] would have selected Domain C as a lead
compound over Domains B and Z.” Appellant’s Br. 20.
Cytiva also argues that the Board erred in its
determination that claims 4 and 17 of the ’765 patent are
unpatentable because “the Board failed to account properly
for the unexpected Fab-binding property recited in those
claims.” Id. at 21. JSR cross-appeals, arguing that the
Board erred in concluding that claims 4 and 17 of the ’142
patent and claims 11 and 29 of the ’007 patent were not
shown to have been unpatentable.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 10
We address each argument in turn and ultimately
conclude that the Board did not err in its determination
that claims 1–7, 10–20, 23–26 of the ’765 patent, claims 1–
3, 5–7, 10–16, 18–20, 23–30 of the ’142 patent, and claims
1–10, 12–14, 16–28, 30–32, and 34–37 of the ’007 patent
are unpatentable. But the Board did err in its
determination that claims 4 and 17 of the ’142 patent and
claims 11 and 29 of the ’007 patent were not shown to have
been unpatentable.
I
We start with Cytiva’s arguments regarding the lead-
compound analysis. Cytiva argues that (A) the Board
erred by failing to conduct this lead-compound analysis and
(B) a person of ordinary skill in the art would not have been
motivated to pick Domain C as the lead compound. We
disagree with both propositions.
“Our case law demonstrates that whether a new
chemical compound would have been prima facie obvious
over particular prior art compounds ordinarily follows a
two-part inquiry.” Otsuka Pharm. Co. v. Sandoz, Inc., 678
F.3d 1280, 1291 (Fed. Cir. 2012) (second emphasis added).
When it applies, the lead-compound analysis typically
proceeds with a two-part inquiry. “First, the court
determines whether a chemist of ordinary skill would have
selected the asserted prior art compounds as lead
compounds, or starting points, for further development
efforts.” Id. “A lead compound, as we have explained, is ‘a
compound in the prior art that would be most promising to
modify in order to improve upon its . . . activity and obtain
a compound with better activity.’” Id. (quoting Takeda
Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d
1350, 1357 (Fed. Cir. 2007)). “The second inquiry in the
analysis is whether the prior art would have supplied one
of ordinary skill in the art with a reason or motivation to
modify a lead compound to make the claimed compound
with a reasonable expectation of success.” Id. at 1292.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 11
A
We first address Cytiva’s argument that the Board
erred by not performing a lead-compound analysis. As a
preliminary matter, our case law has not suggested that
lead compound analysis is always required. Instead, we
have explained that the lead compound analysis is an
ordinary or generally applicable test that assists courts in
assessing obviousness for new compounds. See id. at 1291
(noting that the lead-compound analysis “ordinarily
follows a two-part inquiry” (emphasis added)); Eisai Co. v.
Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 1359 (Fed. Cir.
2008) (“[P]ost-KSR, a prima facie case of obviousness for a
chemical compound still, in general, begins with the
reasoned identification of a lead compound.” (emphasis
added)). The obviousness inquiry is a flexible one that
eschews rigid and formalistic rules. See KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 415 (2007) (“[O]ur cases have
set forth an expansive and flexible approach.”).
A lead-compound analysis is not required where the
prior-art references expressly suggest the proposed
modification. SIBIA Neurosciences, Inc. v. Cadus Pharm.
Corp., 225 F.3d 1349, 1359 (Fed. Cir. 2000) (“The express
teachings in the art provide the motivation and suggestion
to modify [the prior art] . . . .”). That is the situation here.
Specifically, the Board found that “Linhult and Abrahmsén
both expressly suggest that the glycine codon at position 29
can be mutated for an alanine codon in any one of the SPA
IgG binding domains E, D, A, B, or C.” J.A. 36 (emphasis
in original). For example, Abrahmsén states: “According to
still another aspect of the invention there is provided for a
recombinant DNA fragment coding for any of the E D A B
C domains of staphylococcal protein A, wherein the glycine
codon(s) in the Asn-Gly coding constellation has been
replaced by an alanine codon.” J.A. 3833 col. 2 ll. 32–37.
This teaching expressly discloses the proposed G29A
modification to Domain C—i.e., what is claimed in the
challenged patents. To require a separate justification for
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 12
starting with Domain C, when that starting point is
already taught in the prior art, would lead to the erroneous
“constricted analysis” that KSR criticized. KSR, 550 U.S.
at 421 (“Rigid preventative rules that deny factfinders
recourse to common sense, however, are neither necessary
under our case law nor consistent with it.”).
Cytiva argues that the Board erred by relying on KSR’s
obvious-to-try rationale, instead of the lead-compound test.
We disagree. “When there is a design need or market
pressure to solve a problem and there are a finite number
of identified, predictable solutions, a person of ordinary
skill in the art has good reason to pursue the known options
within his or her technical grasp. . . . In that instance the
fact that a combination was obvious to try might show that
it was obvious under § 103.” Id. Indeed, we have
previously indicated that the obvious-to-try inquiry is
similar to the lead compound inquiry—both effectively
require a finite number of proposed starting points. See
Eisai, 533 F.3d at 1359; Takeda, 492 F.3d at 1359; In re
Rosuvastatin Calcium Pat. Litig., 703 F.3d 511, 517–18
(Fed. Cir. 2012). The Board identified a design need of
“finding a SPA IgG binding domain that is resistant to
protein degradation.” J.A. 36 (cleaned up). The Board also
identified a finite number of identified, predictable
solutions:
The SPA IgG binding domains comprise a short list
of 5 members: E, D, A, B, or C. Of these 5 members,
the glycine at position 29 in Domain B has already
been mutated to an alanine to create a Domain Z
which has been shown to retain IgG binding
activity. . . . Linhult and Abrahmsén show that the
IgG binding domains of SPA – E, D, A, B, or C share
many structural similarities. . . . There is also an
express teaching in both Linhult and Abrahmsén
to mutate the glycine at position 29 to an alanine
in order to prevent degradation of the protein and
increase stability, which supports the obviousness
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 13
of incorporating the mutation into any IgG binding
domain that has the Asn-Gly dipeptide.
J.A. 36–37. Under these circumstances, we conclude that
no lead compound analysis was required and agree with
the Board that modifying Domain C with the G29A
mutation would have been obvious. J.A. 37.
B
Even if a formalistic lead-compound analysis was
required, we conclude that the Board’s findings and
application of those findings support the conclusion that
any one of the five homologous domains of SPA, including
Domain C, could serve as a lead compound here. See
Otsuka, 678 F.3d at 1293 (permitting the identification of
more than one lead compound).
Recall, the first step in the lead-compound inquiry is
“whether a chemist of ordinary skill would have selected
the asserted prior art compounds as lead compounds, or
starting points, for further development efforts.” Id.
at 1291 (emphasis added). The Board answered that
question affirmatively here by finding that the prior art
“suggests the use of any one of the SPA IgG binding
domains E, D, A, B, or C as the starting ligand.” J.A. 37
(emphasis added). “[I]t is sufficient to show that the
claimed and prior art compounds possess a sufficiently
close relationship to create an expectation, in light of the
totality of the prior art, that the new compound will have
similar properties to the old.” Eisai, 533 F.3d at 1357
(cleaned up). Here, the Board found that the prior art
(1) expressly suggested the G29A modification in any one
of the five natural SPA domains, (2) showed that the amino
acid sequences of each of the five domains were
homologous, and (3) “show[e]d that the IgG binding
domains of SPA – E, D, A, B, or C share many structural
similarities.” J.A. 36–37. Based on these facts, we see no
error in the Board’s conclusion that any one of the five
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 14
domains, including Domain C, could serve as the starting
point here.
“The second inquiry in the analysis is whether the prior
art would have supplied one of ordinary skill in the art with
a reason or motivation to modify a lead compound to make
the claimed compound with a reasonable expectation of
success.” Otsuka, 678 F.3d at 1292. Cytiva does not appear
to dispute that, once Domain C is selected as the lead
compound under step one, a person of ordinary skill in the
art would have been motivated to make the G29A
modification. See Appellant’s Br. 26–34. Regardless, we
conclude that the Board did not err in finding that
“Abrahmsén . . . provides motivation for making [the
G29A] mutation in any one of the IgG binding domains of
E D A B C domains of SPA.” J.A. 34 (emphasis in original).
We see no error in the Board’s finding that a skilled artisan
would have been motivated to modify Domain C with the
G29A mutation.
Therefore, we affirm the Board’s determination that
claims 1–7, 10–20, 23–26 of the ’765 patent, claims 1–3,
5–7, 10–16, 18–20, 23–30 of the ’142 patent, and claims
1–10, 12–14, 16–28, 30–32, and 34–37 of the ’007 patent
are unpatentable.
II
Cytiva separately argues that the Board erred in
concluding that claims 4 and 17 of the ’765 patent (“the
composition claims”) are unpatentable. And relatedly, JSR
argues on cross-appeal that the Board erred in concluding
that claims 4 and 17 of the ’142 patent and claims 11 and
29 of the ’007 patent (collectively, “the process claims”)
were not shown to have been unpatentable. Both the
composition and process claims relate to binding to the
“Fab part of an antibody.” Cytiva argues, with respect to
the composition claims, that the Board erred by relying on
inherency to avoid consideration of whether a skilled
artisan would have a reasonable expectation of success and
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 15
by relying on inherency to avoid secondary considerations.
JSR, with respect to the process claims, argues that the
Board misconstrued the claims to be limited to Fab
fragments and that, under the proper construction, the
process claims are unpatentable for the same reason as the
composition claims—i.e., that they claim only the inherent
feature of Fab binding.13
We address each of these arguments below. First, we
explain that there is no material difference between the
composition and process claims for the purposes of this
appeal and conclude that these claims must rise or fall
together. See Section II.A., below. Second, we conclude
that the Board erred in limiting the construction of the
term “Fab part of an antibody” to Fab fragments when
analyzing the process claims. See Section II.B., below.
Third, we address the parties’ arguments regarding
inherency and conclude, as we have before, that “[i]f a
property of a composition is in fact inherent, there is no
question of a reasonable expectation of success in achieving
it.” Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d
1322, 1332 (Fed. Cir. 2020). See Section II.C., below.
Finally, we reject Cytiva’s argument that the Board failed
to properly consider the alleged unexpected results of Fab
binding. See Section II.D., below. We therefore conclude
that both the composition and process claims are
unpatentable.
13 In its petition and on appeal, JSR raised two
primary theories of unpatentability with respect to the
Fab-binding claims: an inherency theory and a prior-art-
obviousness theory. See J.A. 443–45; J.A. 521–23;
J.A. 587–89; J.A. 660–62; J.A. 750–52; J.A. 819–21.
Because we reverse based on JSR’s inherency-based theory,
we do not address the prior-art obviousness theory here.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 16
A
We start with our conclusion that the composition and
process claims should be treated the same in this appeal.
The composition and process claims are nearly identical
and contain no substantive distinction relevant to this
appeal. While the composition claims recite that “the
ligand is capable of binding” and the process claims recite
that “the ligand binds,” these differences are immaterial to
assessing the obviousness of the claims. That is because,
on the facts here, binding is not disputed. Thus, if the
ligand binds, the ligand is capable of binding.
Despite the similarity of these claims, the Board held
the composition claims unpatentable (claims 4 and 17 of
the ’765 patent) and the process claims not unpatentable
(claims 4 and 17 of the ’142 patent and claims 11 and 29 of
the ’007 patent). J.A. 44–49; J.A. 101–05; J.A. 162–66.
But both parties, throughout these proceedings have
treated the composition and process claims the same. For
example, in its petitions, JSR argued for each of these
claims that the limitation “binding to the Fab part of an
antibody” “is an inherent property of the claimed C(G29A)-
based SPA ligand.” See J.A. 443–44; J.A. 521–22; J.A. 587–
88; J.A. 660–61; J.A. 750–51; J.A. 819–20. And in its
patent owner responses, Cytiva made nearly identical
responses to the petition for both sets of claims. J.A. 1428–
32; J.A. 1493–97; J.A. 1559–62. Even on appeal, both
parties cross-reference the arguments made between the
composition and process claims. See, e.g., Appellant’s
Br. 48–49; Cross-Appellants’ Br. 58.
Because the composition and process claims have no
material differences, and because the parties relied on the
same arguments before the Board for each of these claims,
we see no basis for treating the claims differently here and
for finding one set of claims unpatentable and the other not
unpatentable.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 17
B
We next address the Board’s construction of “Fab part
of an antibody.” JSR alleges that the Board misconstrued
“Fab part of an antibody” when it determined that the
process claims were not shown to have been unpatentable.
We interpret a claim in view of the claim language, the
specification, the prosecution history, and, where relevant,
extrinsic evidence. Phillips v. AWH Corp., 415 F.3d 1303,
1314 (Fed. Cir. 2005) (en banc). Here, we examine the
meaning of “Fab part of an antibody” in both the process
and composition claims together because the same term in
different claims generally means the same thing unless
context indicates otherwise. PODS, Inc. v. Porta Stor, Inc.,
484 F.3d 1359, 1366 (Fed. Cir. 2007).
Recall, a whole antibody has a Fab region. When that
Fab region is separated from the whole antibody, it is called
a Fab fragment. The specification14 asserts that “a ‘Fab-
binding ligand’ is capable of binding to either full
antibodies via Fab-binding; or to antibody fragments which
includes the variable parts also known as Fab fragments.”
’765 patent col. 4 ll. 39–58. Additionally, both parties agree
that the “Fab part of an antibody” may refer to either the
Fab portion of the full antibody or the Fab antibody
fragment. Appellant’s Reply Br. 49–50; Cross-Appellant’s
Br. 62. We therefore conclude, in line with the
specification, that the term “Fab part of an antibody” may
refer to either a Fab part of a full antibody or a Fab
fragment.
Turning to the Board’s decisions, we agree with JSR
that the Board’s analysis with respect to the process claims
14 The patents here are part of the same family and
share substantively similar specifications. For simplicity,
we cite only the ’765 patent’s specification, except where
otherwise indicated.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 18
was focused on the ligand’s ability to bind to a Fab
fragment. See, e.g., J.A. 102 (“Petitioner needs to establish
that a mutated SPA domain would reasonably bind a Fab
fragment.” (emphasis added)). Indeed, this appears to be a
part of the reason for the Board’s conclusion that the
process claims were not unpatentable. For example, the
Board explained that the composition claims were
unpatentable because binding to Fab was an inherent
feature of the claimed structure. J.A. 104 n.12. But with
respect to the process claims, according to the Board,
“isolating Fab . . . requires prior knowledge that the ligand
binds Fab. . . . [T]here would be no elution of Fab because
the fragments are not present in an IgG containing
sample.” Id. (emphasis added). The Board believed that a
person of ordinary skill in the art would need to be aware
that the ligand binds to Fab fragments (or have a
reasonable expectation of success of binding) to take the
step of separating those fragments from the full antibody
before the claimed process could be performed. But
because we and the parties agree that the claims are not
limited to Fab fragments and instead also include the Fab
part of the full antibody, the Board erred in requiring that
JSR separately demonstrate that a person of ordinary skill
in the art would have a motivation or prior knowledge
concerning Fab fragments to show obviousness of the
process claims.
C
Having determined that the composition claims and
the process claims only contain immaterial differences
relevant to the inquiry here and concluded that “Fab part
of an antibody” means either a Fab fragment or the Fab
part of a whole antibody, we next turn to whether a skilled
artisan would have a reasonable expectation of success of
arriving at the claimed invention. We conclude, as we have
before, that if a limitation of a claim is inherent, “there is
no question of a reasonable expectation of success in
achieving it.” Hospira, 946 F.3d at 1332.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 19
1
A prima facie case of obviousness requires “evidence
that a person of ordinary skill would have selected and
combined and modified the subject matter of the references
in the manner of the claimed invention, with a reasonable
expectation of success.” Orexo AB v. Actavis Elizabeth
LLC, 903 F.3d 1265, 1271 (Fed. Cir. 2018). “The reasonable
expectation of success requirement refers to the likelihood
of success in combining the references to meet the
limitations of the claimed invention.” Intelligent Bio-Sys.,
Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed.
Cir. 2016).
“[I]nherency may supply a missing claim limitation in
an obviousness analysis.” PAR Pharm., Inc. v. TWI
Pharms., Inc., 773 F.3d 1186, 1194–95 (Fed. Cir. 2014). “It
is long settled that in the context of obviousness, the ‘mere
recitation of a newly discovered function or property,
inherently possessed by things in the prior art, does not
distinguish a claim drawn to those things from the prior
art.’” Persion Pharms. LLC v. Alvogen Malta Operations
Ltd., 945 F.3d 1184, 1190 (Fed. Cir. 2019) (quoting In re
Oelrich, 666 F.2d 578, 581 (C.C.P.A. 1981)); see also In re
Wiseman, 596 F.2d 1019, 1023 (C.C.P.A. 1979) (explaining
it “is not the law” that “a structure suggested by the prior
art, and, hence potentially in the possession of the public,
is patentable . . . because it also possesses an Inherent, but
hitherto unknown, function which [patent owners] claim to
have discovered); In re Pearson, 494 F.2d 1399, 1403
(C.C.P.A. 1974) (concluding a compound was undisputedly
taught in the prior art and then determining that
additional limitations that merely “set forth the intended
use for, or a property inherent in, an otherwise old
composition . . . do not differentiate the claimed
composition from those known to the prior art”).
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 20
2
Cytiva does not dispute that Fab binding in fact occurs
when the other limitations are met (i.e., that the claim
limitations at issue recite an inherent property). See
Appellant’s Br. 45–59. Instead, Cytiva asserts that “[t]he
issue before the Board here was whether [a person of
ordinary skill in the art] would have had a reasonable
expectation of combining the disclosures of the prior art to
achieve a C(G29A) ligand ‘capable of binding to the Fab
part of an antibody.’” Appellant’s Br. 46 (emphasis added).
The question we must resolve, therefore, is whether a claim
limitation that merely recites an inherent property of an
otherwise obvious combination requires additional
analysis to demonstrate that a person of ordinary skill in
the art would have a reasonable expectation of success. We
conclude that this additional showing is not required.15
To start, reasonable expectation of success is a question
about the expectation of success in “combining the
references to meet the limitations of the claimed
invention.” Intelligent Bio-Sys., 821 F.3d at 1367; see also
Appellant’s Br. 46. But for its inherency-based theory
addressed here, JSR’s obviousness argument concerning
the “Fab binding” limitation does not rely on any
combination or modification of prior-art references to
arrive at the property required by that limitation. Instead,
taking the obviousness of the combination of the other
claim limitations as established without regard to any Fab
binding property (as it has been), JSR asserts that “[t]he
15 Our holding today does not address the situation
where a claim contains a limitation that would require
prior knowledge of the inherent property. Further, a
petitioner must still meet its burden to demonstrate that
the claimed limitation is indeed inherent. Simply saying it
is so without sufficient evidence will not demonstrate
unpatentability.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 21
natural result of th[e] [C(G29A)] modification is the
capability to bind to the Fab part of an antibody.” Cross-
Appellants’ Br. 41; see also In re Oelrich, 666 F.2d at 581
(inherency may be demonstrated by “the natural result
flowing from the operation as taught would result in the
performance of the questioned function” (emphasis added)
(citation omitted)).
The parties each identify cases reaching back decades
that purportedly support their respective positions. Cytiva
relies heavily on cases that stand for the principle that
“unexpected properties may cause what may appear to be
an obvious composition to be nonobvious.” Appellant’s
Br. 50 (quoting Honeywell Int’l Inc. v. Mexichem Amanco
Holding S.A. DE C.V., 865 F.3d 1348, 1354–55 (Fed. Cir.
2017)); see also id. at 46 (“protein engineering is a
notoriously unpredictable art”); id. at 48 (“binding . . . was
unexpected”). JSR, in contrast, primarily relies on the
principle that, “[i]f a property of a composition is in fact
inherent, there is no question of a reasonable expectation
of success in achieving it.” Cross-Appellants’ Br. 44
(quoting Hospira, 946 F.3d at 1332); see also id. 40–45.
Both Honeywell and Hospira discuss inherency in the
context of composition claims. The claims in Honeywell
recited “a heat transfer composition for use in an air
condition system compromising [an HFO refrigerant] and
[a PAG lubricant].” 865 F.3d at 1350–51. There, HFO
refrigerants were disfavored and known to be reactive and
unstable, and PAG lubricants were also known to be
unstable—i.e., both components of the composition were
disfavored in the art for the intended purposes in the claim.
Id. at 1351. Unexpectedly, however, the combination of
these two components achieved a stable composition. Id.
at 1354. Yet, the Board held the claims unpatentable,
viewing the disadvantages as trade-offs and finding the
combination of the two compounds were inherently stable.
Id. at 1352. We concluded that the Board’s reasoning was
flawed in a number of ways, but relevant here is that the
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 22
claims in Honeywell did not attempt to claim the inherent
result—instead, they claimed a composition that itself was
not inherent, the combination of which had unexpected
properties. In other words, in Honeywell, a person of
ordinary skill in the art would not have been motivated to
combine the two compounds in the first place.
Conversely, the claims in Hospira contained a
limitation that stated the “composition when stored in the
glass container for at least five months exhibits no more
than about 2% decrease in the concentration of
dexmedetomidine.” Hospira, 946 F.3d at 1327, 1332.
There, the claim limitation recited the stability and
activity of the composition after storage—an inherent
property of the claimed composition. Id. at 1329. After
concluding the limitation was an inherent property of the
otherwise obvious composition, we turned to the district
court’s analysis of reasonable expectation of success and
determined the district court’s analysis was “unnecessary”
because, “[i]f a property of a composition is in fact inherent,
there is no question of a reasonable expectation of success
in achieving it.” Id. at 1332.
These two cases provide important guideposts between
claims which require knowledge of an inherent property to
arrive at the claimed invention and claims which simply
claim an inherent property or result. When claims require
prior knowledge of the inherent property—e.g., for
motivation to combine—then a petitioner would still
generally need to demonstrate a reasonable expectation of
success. As explained decades ago in In re Spormann,
unknown properties cannot be used as the basis for such a
motivation. 363 F.2d 444, 448 (C.C.P.A. 1966)
(“Obviousness cannot be predicated on what is unknown.”
(emphasis added)). But that situation is different from
simply claiming an inherent property of an otherwise
obvious composition or process—i.e., one obvious without
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 23
regard to the property at issue.16 In this latter context,
“there is no question of a reasonable expectation of
success.” Hospira, 946 F.3d at 1332. Any separate analysis
on this point is unnecessary. Id.
3
Turning to the merits, we conclude that both the
composition and process claims would have been obvious.
With respect to the composition claims, the claims’
undisputed Fab-binding ability is dispositive. No
reasonable expectation of success argument or analysis is
required where the sole disputed limitation was an
inherent property of the claimed composition already
determined to be obvious. See id. As explained above, the
independent claims here recite obvious chromatography
matrices. The dependent composition claims recite only a
natural result of the obvious composition recited in the
independent claims. Therefore, the Board did not err in
determining that these dependent claims would have been
obvious.
With respect to the process claims, we likewise
conclude that the claims recite an inherent property of an
otherwise obvious composition. Based on the erroneous
construction we discussed above, the Board assumed that,
unless a skilled artisan first had a reasonable expectation
of success of Fab fragment binding, such an artisan would
not have prepared the Fab fragments for elution in the
chromatography process to begin with. But we disagree
that the Board should have limited the claims to Fab
fragments. As explained above, the term “Fab part of an
16 While much of our case law on inherency in the
chemical and biological fields discusses composition claims,
we see no reason that these same guideposts do not apply
equally to claims for processes of making those
compositions.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 24
antibody” refers both to a Fab fragment and the Fab
portion of the full antibody. Thus, demonstrating
inherency that the ligands would bind to the Fab part of
the full antibody does not require separate showing that a
person of ordinary skill would first prepare Fab fragments
for elution. And because the dependent process claims
recite only the property of Fab binding and Fab binding
under the proper construction is an undisputedly inherent
property on this record, “there is no question of a
reasonable expectation of success in achieving [the claimed
invention].” Hospira, 946 F.3d at 1332. Therefore, with
respect to the cross-appeal, we reverse the Board’s
determination that the process claims were not shown to
have been unpatentable.
D
Turning back to the main appeal, Cytiva argues that the
Board also erred by failing to address secondary
considerations—here, that “the claimed chromatography
matrices unexpectedly retained their ability to bind to the
Fab part of an antibody,” J.A. 1434. See Appellant’s Br. 59
(“Objective indicia of non-obviousness must be considered
if present.”); id. at 63 (“The Board’s dereliction of its duty
to consider objective indicia of nonobviousness here was
error . . .”). But the Board did in fact address this
argument. J.A. 48–49. It simply was “not persuaded by
Cytiva’s unexpected-results argument.” J.A. 48.
Cytiva also argues that the Board conflated reasonable
expectation of success with unexpected results. Appellant’s
Br. 62. While we agree that reasonable expectation of
success and unexpected results are separate inquiries, we
disagree that the Board here conflated these concepts.
Instead, the Board appears to have found, based on the
facts here, that the reasonable expectation of success
included expecting that modifying Domain C with the
G29A mutation would “result[] in a product that binds at
least IgG.” J.A. 48 (emphasis added). In other words, the
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 25
Board found that binding to an antibody was not
unexpected. It is also not unusual that the reasonable-
expectation-of-success and unexpected-results inquiries
may contain similar underlying factual inquiries. In fact,
we have previously stated that reaching different results
on these two inquiries may be “internally inconsistent” in
certain circumstances. Honeywell, 865 F.3d at 1354
(determining that the Board was inconsistent by
dismissing evidence of “unpredictability and unexpected
properties of the claimed combination by characterizing
them as ‘inherent’” on the one hand and simultaneously
crediting the same evidence as persuasive of unexpected
results on the other hand).
While the Board could have been more specific that
Fab-binding was not unexpected, rather than explaining
that antibody binding was not unexpected, we find that any
error in the Board’s analysis on this point is harmless
because “[t]here is no requirement that the inherent
characteristic of the Fab binding needed to be recognized
. . . .” J.A. 48–49. In In re Couvaras, “Couvaras
attempt[ed] to claim a mechanism of action that naturally
flows from the co-administration of two known
antihypertensive agents.” 70 F.4th 1374, 1380 (Fed. Cir.
2023). “According to Couvaras, even if the recited
mechanism of action is, effectively, inherent . . . the [result]
was unexpected.” Id. We concluded that “results that
naturally flow from the administration of a given
compound or mixture of compounds . . . cannot overcome a
prima facie case of obviousness, even if the nature of that
mechanism is unexpected.” Id. The same analysis applies
to the facts here: Having determined that the independent
claims would have been obvious, the recitation of a
naturally flowing property of those obvious claims “cannot
overcome a prima facie case of obviousness.” Id.
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CYTIVA BIOPROCESS R&D AB v. JSR CORP. 26
CONCLUSION
We have considered the parties’ remaining arguments
and find them unpersuasive. For the foregoing reasons, we
affirm the Board’s determination that claims 1–7, 10–20,
23–26 of the ’765 patent, claims 1–3, 5–7, 10–16, 18–20,
23–30 of the ’142 patent, and claims 1–10, 12–14, 16–28,
30–32, and 34–37 of the ’007 patent are unpatentable. We
reverse the Board’s determination that claims 4 and 17 of
the ’142 patent and claims 11 and 29 of the ’007 patent are
not unpatentable.
AFFIRMED-IN-PART AND REVERSED-IN-PART
COSTS
No costs.
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