Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-23-02074/USCOURTS-ca13-23-02074-0/pdf.json

Parties Involved:
Cytiva Bioprocess R&D AB
Appellant
JSR Corp.
Cross-Appellant
JSR Life Sciences, LLC
Cross-Appellant

Document Text:

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.

Case: 23-2074 Document: 53 Page: 1 Filed: 12/04/2024
2 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

 ______________________

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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4 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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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6 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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.” CrossAppellants’ 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 

Case: 23-2074 Document: 53 Page: 7 Filed: 12/04/2024
8 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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 crossappealed. 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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10 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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 leadcompound 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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12 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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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14 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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-artobviousness 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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16 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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 ‘Fabbinding 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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18 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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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20 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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.” CrossAppellants’ 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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22 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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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24 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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 reasonableexpectation-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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26 CYTIVA BIOPROCESS R&D AB v. JSR CORP.

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.

Case: 23-2074 Document: 53 Page: 26 Filed: 12/04/2024