Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc., Amgen USA, Inc., Biocon Biologics Inc., Celltrion, Inc.,…

United States Court of Appeals
for the Federal Circuit
______________________
REGENERON PHARMACEUTICALS, INC.,
Plaintiff-Appellant
v.
MYLAN PHARMACEUTICALS INC., AMGEN USA,
INC., BIOCON BIOLOGICS INC., CELLTRION,
INC., FORMYCON AG, SAMSUNG BIOEPIS CO.,
Defendants
AMGEN INC.,
Defendant-Appellee
______________________
2024-2351
______________________
Appeal from the United States District Court for the
Northern District of West Virginia in Nos. 1:22-cv-00061-
TSK-JPM, 1:23-cv-00089-TSK-JPM, 1:23-cv-00094-TSK-
JPM, 1:23-cv-00097-TSK-JPM, 1:23-cv-00106-TSK-JPM,
1:24-cv-00039-TSK-JPM, 1:24-cv-00053-TSK, 1:24-md-
03103-TSK-JPM, Chief Judge Thomas S. Kleeh.
______________________
Decided: March 14, 2025
______________________
DAVID I. B ERL, Williams & Connolly LLP, Washington,
DC, argued for plaintiff-appellant. Also represented by
A RTHUR J OHN ARGALL, III, T HOMAS S. F LETCHER ,
C HRISTIAN GLADDEN-SORENSEN, KATHRYN SCHLECKSER
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REGENERON PHARMACEUTICALS , INC. v.
MYLAN PHARMACEUTICALS INC.
2
KAYALI, R HOCHELLE KRAWETZ , SHAUN P ATRICK MAHAFFY,
C HARLES MCC LOUD, ADAM PAN, ANDREW V. TRASK; J ACOB
HARTMAN, Kellogg, Hansen, Todd, Figel & Frederick,
PLLC, Washington, DC; P RIYATA PATEL, Paul, Weiss,
Rifkind, Wharton & Garrison LLP, Washington, DC;
E LIZABETH WEISWASSER , New York, NY.
J EFFREY A. LAMKEN, MoloLamken LLP, Washington,
DC, argued for defendant-appellee. Also represented by
KAYVON GHAYOUMI, R OBERT KRY, L UCAS M. WALKER ; E RIC
MICHAEL A GOVINO, C HANSON CHANG, PAULINE P ELLETIER ,
WENDY A. WHITEFORD, Amgen Inc., Thousand Oaks, CA;
T HOMAS B URNS, KEVIN M. F LOWERS, JOHN LABBE , Mar-
shall, Gerstein & Borun LLP, Chicago, IL; E DWARD
A NTHONY F IGG, J OSEPH A. HYNDS, JENNIFER NOCK, B RETT
A LAN P OSTAL, Rothwell, Figg, Ernst & Manbeck, P.C.,
Washington, DC.
______________________
Before MOORE , Chief Judge, L OURIE and STARK, Circuit
Judges.
L OURIE , Circuit Judge.
Regeneron Pharmaceuticals, Inc. (“Regeneron”) ap-
peals from a decision of the United States District Court
for the Northern District of West Virginia denying Regen-
eron’s motion for a preliminary injunction. In re Aflibercept
Pat. Litig., No. 1:24-md-3103, 2024 WL 4958308 (N.D. W.
Va. Oct. 1, 2024) (“Amgen Decision”).1 For the following
reasons, we affirm.
1 The case generating this appeal is Regeneron Phar-
maceuticals, Inc. v. Amgen, Inc., No. 1:24-cv-39 (mistak-
enly identified as 1:23-cv-39 in the district court case
caption), which is part of a consolidated multi-district liti-
gation, No. 1:24-md-3103.
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B ACKGROUND
The district court denied Regeneron’s motion because
it failed to establish a likelihood of success in showing that
Amgen Inc. (“Amgen”) infringed its U.S. Patent 11,084,865
(“the ’865 patent”). Regeneron’s ’865 patent is directed to
pharmaceutical formulations of a fusion protein known as
aflibercept, claimed by its amino acid sequence. The ’865
patent is asserted to cover a vial containing Regeneron’s
biologic product EYLEA ® (“Eylea”) and is listed in the
FDA’s Purple Book2 under Regeneron’s Biologic’s License
Application (“BLA”) 125387 for Eylea.
Regeneron obtained FDA approval to commercially
market Eylea for administration in a vial presentation on
November 18, 2011.3 Amgen Decision, at *1. Eylea is an
ophthalmic drug product used to treat angiogenic eye dis-
orders, associated with uncontrolled blood vessel growth in
the retina, that can cause vision loss or even blindness. Id.
When administered intravitreally, it controls excessive
blood vessel growth by inhibiting a growth factor known as
vascular endothelial growth factor (“VEGF”). Id. at *2.
The Eylea formulation contains 40 mg/ml aflibercept (the
active ingredient), 10 mM sodium phosphate, 40 mM so-
dium chloride, 0.03% polysorbate 20, and 5% sucrose, and
has a pH of 6.2. Id. Examples 3 and 4 of the ’865 patent
disclose that formulation. Id.
Amgen filed abbreviated Biologics License Application
761298 (“Amgen’s aBLA”) at the FDA on August 23, 2023,
seeking to market ABP 938, a biosimilar of Eylea now
branded as “Pavblu.” Id. at *2–3; see also J.A. 26703-09.
Amgen’s aBLA, approved a year later, states that ABP
2 The FDA’s Purple Book is a searchable online da-
tabase that lists all FDA-approved biological products.
3 Regeneron received FDA approval for its pre-filled
syringe presentation in August 2019. Amgen Br. 9.
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938’s formulation is different from Eylea’s formulation. Id.
at *3. Relevant here, while ABP 938’s formulation con-
tains a version of the fusion protein aflibercept, it does not
contain a separate buffer component. Id. That is because
Amgen had discovered a way to prepare and formulate the
active ingredient, aflibercept, in a manner that eliminates
the need for a separate buffer component—i.e., the afliber-
cept itself provides sufficient buffering capacity to stabilize
the formulation. See id.; Amgen Br. 2. Unlike Amgen’s bi-
osimilar ABP 938, other aBLA filers, including Mylan,
Formycon, Samsung Bioepis, and Celltrion, proposed bio-
similar versions of Eylea that do contain a separate buffer
component. Amgen Decision, at *3.
On January 10, 2024, Regeneron filed an action
against Amgen in the U.S. District Court for the Central
District of California, alleging infringement of various Re-
generon patents based on Amgen’s aBLA for ABP 938. Id.
at *4. After Regeneron’s action was consolidated with
other aBLA-filer actions by the Joint Panel on Multidistrict
Litigation (“JPML”), Regeneron filed a motion for a prelim-
inary injunction against Amgen, based on allegations that
Amgen’s filing of its aBLA for ABP 938 infringed claims 2,
3, 27, and 28 (“the asserted claims”) of the ’865 patent. Id.
at *1.
The asserted claims depend from claims 1 and 26 of the
’865 patent. Claim 1 is representative and recites:
1. A vial comprising an ophthalmic formulation
suitable for intravitreal administration that com-
prises:
a vascular endothelial growth factor
(VEGF) antagonist,
an organic co-solvent,
a buffer,
and a stabilizing agent,
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wherein said VEGF antagonist fusion pro-
tein is glycosylated and comprises amino
acids 27-457 of SEQ ID NO:4; and
wherein at least 98% of the VEGF antago-
nist is present in native conformation fol-
lowing storage at 5° C. for two months as
measured by size exclusion chromatog-
raphy.
’865 patent col. 19 ll. 29–41 (emphases added). Because we
have held that “[t]here can be no literal infringement
where a claim requires two separate structures and one
such structure is missing from an accused [product],” Bec-
ton, Dickinson & Co. v. Tyco Healthcare Grp., LP, 616 F.3d
1249, 1255 (Fed. Cir. 2010), the primary dispute before the
district court was “whether the asserted claims require
that the ‘VEGF antagonist’ [i.e., aflibercept] and the ‘buffer’
be separate and distinct components of the claimed formu-
lation.” Amgen Decision, at *8 (cleaned up).
Amgen opposed the motion for a preliminary injunc-
tion, arguing that “the asserted claims require that the
claimed ‘VEGF antagonist’ and the claimed ‘buffer’ be sep-
arate components” and therefore that ABP 938 could not
infringe the asserted claims. Id. at *9 (cleaned up). Regen-
eron disagreed and argued that “the VEGF antagonist can
also satisfy the limitation of the claimed buffer.” Id. Spe-
cifically, Regeneron argued that the asserted claims were
not so limited by pointing to two passages from the specifi-
cation allegedly explaining that (1) the claimed formula-
tion’s components could embody multiple functions, and
(2) all scientific terms should retain their ordinary mean-
ings. Id. at *15. To support the latter allegation, Regen-
eron relied on extrinsic evidence, including various
references and expert testimony, to show that “using
aflibercept as a buffer was so ‘well known in the art’ such
that no description in the specification was necessary for a
[person of ordinary skill in the art] to understand that the
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claimed VEGF antagonist can serve as the separately
claimed ‘buffer.’” Id. at *17.
The district court began its claim construction analysis
by reciting well-established claim construction principles,
including that “[t]he construction that stays true to the
claim language and most naturally aligns with the patent’s
description of the invention will be, in the end, the correct
construction.” Id. at *11 (quoting Phillips v. AWH Corp.,
415 F.3d 1303, 1316 (Fed. Cir. 2005) (en banc)). Consistent
with such principles, the district court applied our prece-
dent in Becton and its progeny to assess the claims. Amgen
Decision, at *11 (citing Becton, 616 F.3d at 1254). Specifi-
cally, the district court evaluated the applicability and ef-
fect of the claim construction principle, reiterated in
Becton, that explains “[w]here a claim lists elements sepa-
rately, the clear implication of the claim language is that
those elements are distinct components of the patented in-
vention.” Id. (emphasis added); see Becton, 616 F.3d at
1254 (quoting Gaus v. Conair Corp., 363 F.3d 1284, 1288
(Fed. Cir. 2004)).
The district court acknowledged that the “parties d[id]
not dispute that the asserted claims separately list the
claimed ‘VEGF antagonist’ and the ‘buffer.’” Amgen Deci-
sion, at *12 (citing the ’865 patent at claims 1 and 26)
(cleaned up). It therefore determined that there was no
dispute that “the separate listing of these elements estab-
lishes a presumption the claimed ‘VEGF antagonist’ and
‘buffer’ are distinct components.” Id.
The district court next considered whether the evi-
dence overcame “the clear implication” of separateness un-
der Becton. See id. at *12–23. It determined that it did
not. Specifically, the district court determined that neither
the intrinsic nor extrinsic evidence rebutted the implica-
tion of separateness and, in fact, only reinforced the impli-
cation that the “VEGF antagonist” and “buffer” must be
separate components of the claimed formulation. Id. at *17
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(“Here, neither the claims nor the specification of the ’865
patent explain or suggest that the VEGF antagonist can
serve as the buffer, or vice versa, or that these components
can overlap in function. Rather, the claims and the speci-
fication further support and confirm that they cannot be
one and the same.”); id. at *19 (considering the extrinsic
evidence).
As part of its analysis, the district court explained that
the claim construction issue in this case had yet to be de-
termined, notwithstanding the district court’s earlier con-
struction of the term “buffer,” in separate Regeneron
litigation asserting the same ’865 patent, as “a substance
that resists changes to pH upon addition of an acid or base
within an optimal pH range through a proton-donating
component and/or a proton-accepting component, includ-
ing, for example, histidine, phosphate, and proteins like
aflibercept.” Id. at *8; see In re Aflibercept Pat. Litig.,
No. 1:23-cv-97, 2024 WL 3423047, at *15–17 (N.D. W. Va.
July 9, 2024) (“the Formycon Decision”).4 Because the
claim construction issue before the district court in this
case was different from the issue presented in the
Formycon Decision, the district court explained that its
earlier decision “did not address the claim construction is-
sue that Amgen raises in this case” and proceeded to
4 Prior to its decision in this case, the district court
granted Regeneron’s motion for a preliminary injunction
against Formycon based on Formycon’s biosimilar product,
FYB203, which contains a separate histidine buffer.
Amgen Decision, at *8. Formycon had argued that it did
not infringe the ’865 patent because, in its view, the term
“buffer” was limited to a phosphate buffer. Formycon De-
cision, at *15. The district court rejected that construction.
Id. That issue was not raised on appeal, and we otherwise
affirmed. See Regeneron Pharms., Inc. v. Formycon AG,
No. 2024-2009, 2025 WL 324288 (Fed. Cir. Jan. 29, 2025).
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determine whether the “buffer” was a distinct component
of the claimed formulation under Becton and its line of
cases. Id. at *8.
Ultimately, the district court “construe[d] the asserted
claims to require that the claimed ‘VEGF antagonist’ be a
separate component from the claimed ‘buffer.’” Id. at *9
(cleaned up). And because Amgen’s ABP 938 product does
not contain a separate buffer, the district court determined
that Amgen had raised a substantial question of nonin-
fringement and thus that Regeneron had not demonstrated
a likelihood of success on the merits for its infringement
action. Id. The district court therefore denied Regeneron’s
motion for a preliminary injunction. Id. at *27.
Regeneron timely appealed and we have jurisdiction
under 28 U.S.C. §§ 1292(a)(1) and 1292(c)(1).
DISCUSSION
Regeneron’s appeal challenges the district court’s claim
construction, and specifically whether the district court
erred in applying Becton. In Regeneron’s view, Becton is
inapplicable here and, even if it were applicable, the evi-
dence overcomes the clear implication, recited in Becton,
that separately listed components of a claimed invention
are distinct. We address each argument in turn.
I
We first address the applicability of Becton. As ex-
plained below, because the plain language of the claim re-
cites a formulation comprising four separately listed
components, Becton applies.
“We review claim construction based on intrinsic evi-
dence de novo and review any findings of fact regarding ex-
trinsic evidence for clear error.” Promptu Sys. Corp. v.
Comcast Corp., 92 F.4th 1372, 1377 (Fed. Cir. 2024). Claim
terms are generally given their plain and ordinary mean-
ing, which is the meaning that one of ordinary skill in the
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art would ascribe to a term when read in the context of the
claims, specification, and prosecution history. See Phillips,
415 F.3d at 1313–17.
We have held that “where a claim lists elements sepa-
rately, the clear implication of the claim language is that
those elements are distinct components of the patented in-
vention.” Becton, 616 F.3d at 1254 (quoting Gaus, 363 F.3d
at 1288) (cleaned up); see, e.g., Kyocera Senco Indus. Tools
Inc. v. Int’l Trade Comm’n, 22 F.4th 1369, 1382 (Fed. Cir.
2022) (“The asserted claims list those elements separately”
and “there is, therefore, a presumption that those compo-
nents are distinct.”); see also Schindler Elevator Corp. v.
Otis Elevator Co., 593 F.3d 1275, 1282 (Fed. Cir. 2010) (ex-
plaining that “the term ‘information transmitter’ itself sug-
gests that the transmitter is a thing, separate and apart
from an ‘elevator user’”).5
Here, claim 1 plainly recites a pharmaceutical formu-
lation, comprising four separately listed components,
which include a “VEGF antagonist” and “a buffer.” ’865
patent col. 19 ll. 29–34. As we determined in Becton, the
plain language of the claim therefore establishes a “clear
implication” that the VEGF antagonist and buffer
5 As we recently reiterated in Google LLC v. Ecofactor,
Inc., 92 F.4th 1049, 1058 (Fed. Cir. 2024):
[Our] cases do not create a per se rule that
separately listed claim elements are distinct
components, regardless of the intrinsic rec-
ord. . . . Rather, we have explained that there
is a “presumption” that separately listed
claim limitations may indicate separate and
distinct physical structure, but that presump-
tion may always be rebutted in the context of
a particular patent.
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components are distinct components of the claimed formu-
lation. Becton, 616 F.3d at 1254. Becton therefore applies.
Regeneron’s arguments otherwise are misplaced. Re-
generon argues that “[t]he district court fundamentally
erred in applying the Becton line of precedent.” Regeneron
Br. 35; see also Regeneron Reply Br. 2–8. Regeneron ar-
gues that “claim construction must ‘begin’ with, not evade,
the claim language’s ordinary meaning,” Regeneron Reply
Br. 12 (citing Phillips, 415 F.3d at 1313), and that the dis-
trict court failed to heed that established principle of claim
construction, see id. (“The fundamental error in the district
court’s construction is that it failed to address what ‘buffer’
means.”). Specifically, Regeneron argues that because the
district court in Formycon had previously construed the
term “buffer” in a way that “encompasses what the patent
recites in a different limitation, the implication of separate-
ness under Becton is simply inapplicable.” Regeneron
Br. 35–37 (relying on Formycon Decision, 2024 WL
3423047, at *16–17). Stated otherwise, Regeneron argues
that because the district court previously construed the
claimed buffer as covering “proteins like aflibercept,” Bec-
ton does not apply. Amgen Decision, at *39. We disagree.
First, contrary to Regeneron’s arguments, the district
court did properly engage with the claims, consistent with
Phillips and established claim construction principles. It
did so by evaluating, under Becton, whether the implica-
tion of separateness applied, which necessarily requires a
review of the claims themselves. See id. at *11 (“The
claims separately list ‘a VEGF antagonist’ and ‘a buffer,’
giving rise to a presumption that they are separate and dis-
tinct components of the claimed formulation.”). Addition-
ally, as discussed in Section II, infra, the district court also
considered whether the surrounding context, including
other claims of the ’865 patent, overcomes the implication
of separateness. Id. at *12–15.
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Second, Regeneron’s argument that Becton does not ap-
ply conflates two independent claim construction inquiries.
The claim construction inquiry relevant here, under Bec-
ton, is directed to whether a formulation is claimed in a
way that clearly implies it requires distinct components. In
contrast, Regeneron’s proposed inquiry, relevant in the
Formycon Decision, asks whether the claimed “buffer” com-
ponent overlaps in scope with the claimed “VEGF antago-
nist” component. Formycon Decision, 2024 WL 3423047, at
*15–17. Because the district court’s Formycon Decision
“did not address the claim construction issue that Amgen
raises in this case,” id. at *8, the district court properly
viewed itself as not bound by its earlier construction. Thus,
we find Regeneron’s related arguments regarding overlap-
ping claim scope unpersuasive.6
Because the asserted claims plainly recite a pharma-
ceutical formulation comprising four separately listed com-
ponents, including a “VEGF antagonist” and “a buffer,” we
conclude that “the clear implication of the claim language
is that those elements are distinct components of the pa-
tented invention.” Becton, 616 F.3d at 1254 (cleaned up).
The district court therefore correctly applied Becton.
II
We next address whether the evidence overcomes the
implication of separateness under Becton, such that a for-
mulation comprising a self-buffering VEGF antagonist,
like Amgen’s ABP 938, may infringe the claims even in the
absence of a separate buffer component. Because the
claims and specification of the ’865 patent only reinforce
that the claimed components are distinct, we agree with
6 We note that the Formycon construction was also
preliminary in nature and non-binding, as it was deter-
mined at the preliminary injunction stage of a separate lit-
igation to which Amgen is not a party.
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the district court that the implication of separateness has
not been overcome, and the claimed “VEGF antagonist”
and “buffer” are distinct limitations.
A claim “can be defined only in a way that comports
with the instrument as a whole.” Markman v. Westview
Instruments, Inc., 517 U.S. 370, 389 (1996). Consistent
with this principle, to overcome Becton, there must be evi-
dence that shows that the impliedly distinct components,
instead, can be satisfied by a single component. Compare
Google, 92 F.4th at 1058 (overcoming the implication of
separateness in part because “the specification contem-
plates an embodiment in which one claimed input is calcu-
lated based on at least one other claimed input”), with
Becton, 616 F.3d at 1254 (not overcoming the implication
of separateness because “[t]he specification . . . confirms
that the spring means is a separate element from the
hinged arm, as the only elements disclosed in the specifica-
tion as ‘spring means’ for urging the guard forward are sep-
arate structures from the hinged arm and its hinges”)
(emphasis added). Such evidence may be intrinsic or ex-
trinsic, though it is difficult to envision Becton’s clear im-
plication of separateness being overcome without at least a
suggestion of non-separateness in the intrinsic evidence.
See generally Intel Corp. v. VIA Techs., 319 F.3d 1357, 1367
(Fed. Cir. 2003) (holding that extrinsic evidence may never
be used to alter meaning that is clear from intrinsic evi-
dence); see also Kyocera, 22 F.4th at 1382 (“The mere fact
that there is an alternative embodiment disclosed in [a] pa-
tent that is not encompassed by a claim construction does
not outweigh the language of the claim, especially when the
court’s construction is supported by the intrinsic evidence.”
(cleaned up) (emphasis added) (quoting TIP Sys., LLC v.
Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1373
(Fed. Cir. 2008))).
Having addressed the showing required to overcome
the implication of separateness under Becton, we now turn
to whether Regeneron has made such a showing. For the
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following reasons, the district court correctly determined
that the record evidence failed to overcome the implication
of separateness under Becton. See Amgen Decision, at *16
(“[T]he intrinsic evidence is clear and uniform that the
‘VEGF antagonist’ and the ‘buffer’ are separate compo-
nents.”).
“[T]he claims themselves provide substantial guidance
as to the meaning of particular claim terms.” Phillips, 415
F.3d at 1314. Moreover, “[o]ther claims of the patent in
question, both asserted and unasserted, can [] be valuable
sources of enlightenment as to the meaning of a claim
term.” Id. For instance, “[d]ifferences among claims can []
be a useful guide in understanding the meaning of partic-
ular claim terms.” Id. Here, the district court identified
that all of the claims of the ’865 patent treat the “VEGF
antagonist” as separate from the “buffer.” Amgen Decision,
at *13. Specifically, as the district court explained, “[t]he
components are listed with different concentrations and
different units of measurement.” Id. (emphasis added). The
district court therefore concluded that “[t]he clear implica-
tion of the claims’ use of different units of measurement for
these two components is that the components are separate
and distinct.” Id. We agree.
Certain dependent claims use different units of meas-
urement to recite the claimed concentrations of each com-
ponent, respectively. For example, where claim 2 recites a
“concentration of said VEGF antagonist fusion protein
[that] is 40 mg/ml,” claim 7 recites a concentration of
buffer that is “5-25 mM.” Compare ’865 patent col. 19 ll.
21–43 (claim 2), with id. at col. 19 ll. 53–54 (claim 7) (em-
phases added). Put simply, one component is measured in
milligram per milliliter (mg/ml) units and the other in mil-
limolar units (mM). The dependent claims therefore pro-
vide “a useful guide in understanding the meaning of
particular claim terms,” Phillips, 415 F.3d at 1314, and
such context reinforces that the two components are differ-
ent.
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We next consider whether the specification overcomes
the implication that the claimed buffer and VEGF antago-
nist are separate components. And again, we agree with
the district court that “[l]ike the claims, the specification of
the ’865 patent uniformly describes the ‘VEGF antagonist’
and the ‘buffer’ as separate and distinct components of the
formulation.” Amgen Decision, at *14.
“The importance of the specification in claim construc-
tion derives from its statutory role,” requiring that “the
specification describe the claimed invention in ‘full, clear,
concise, and exact terms.’” Phillips, 415 F.3d at 1316 (cit-
ing 35 U.S.C. § 112, para 1). The specification is therefore
“always highly relevant to the claim construction analysis,”
“is the single best guide to the meaning of a disputed term”
and can “make[] plain what the [patentee] did and did not
invent.” Id. at 1315 (cleaned up). “Thus claims must be
construed so as to be consistent with the specification, of
which they are a part.” Merck & Co., Inc. v. Teva Pharms.
USA, Inc., 347 F.3d 1367, 1371 (Fed. Cir. 2003).
The specification explains that a “VEGF antagonist is
a compound capable of blocking or inhibiting the biological
action of [VEGF], and includes fusion proteins capable of
trapping VEGF.” ’865 patent col. 6 ll. 27–30. The specifi-
cation further describes how “the buffering agent, may be,
for example, phosphate buffer.” Id. col. 2 ll. 45–48. And as
the district court correctly identified, “[t]he specification
does not suggest that the VEGF antagonist can be a buffer
or vice versa,” and “Regeneron has not identified any such
disclosure.” Amgen Decision, at *14. More to the point, the
specification explains that “[p]referably, the liquid formu-
lation comprises a pharmaceutically effective amount of
the VEGF antagonist . . . [and] can also comprise one or
more pharmaceutically acceptable carriers, buffers, tonic-
ity agents, stabilizers, and/or excipients.” ’865 patent col.
6 l. 65–col. 7 l. 2 (emphases added). That is, the specifica-
tion describes a formulation containing a VEGF antagonist
plus a distinct buffer component. And that understanding
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is reinforced consistently throughout the specification,
which “includes eight example formulations and twenty-
two (22) embodiments, each of which describes the VEGF
antagonist (aflibercept) plus a buffer.” Amgen Decision,
at *14 (cleaned up) (citing ’865 patent col. 2 l. 33–col. 4 l.
62, col. 8 l. 32–col. 12 l. 26).
Regeneron does not seriously dispute the overwhelm-
ing evidence from the specification reinforcing the implica-
tion that the claimed “VEGF antagonist” and “buffer” are
distinct components of the claimed formulation. Instead,
Regeneron argues that “[t]he patent did not need to list
known or unknown buffers in order for ‘a buffer’ to overlap
with the ‘VEGF antagonist’ limitation and rebut any pre-
sumption from Becton.” Regeneron’s Br. 51. Regeneron ex-
plains that is so because there is no “requirement to repeat
what is known.” Id. To support that argument, Regeneron
relies on the Formycon construction, arguing that it proves
that “proteins like aflibercept . . . were known buffers or
categories of buffers.” Id. (citing Formycon Decision, 2024
WL 3423047, at *16). It continues, “[j]ust as the patent un-
disputedly did not have to list ingredients like histidine in
order for them to be within the scope of ‘buffer,’ . . . it also
did not have to list proteins as buffers where, as the experts
agreed, proteins like aflibercept that contain histidine res-
idues were understood to act as buffers.” Id. at 51–52 (cit-
ing Formycon Decision, 2024 WL 3423047, at *16). We
disagree.
Again, Regeneron unduly relies on the preliminary
claim construction in Formycon. Regardless, Regeneron’s
avoidance of the specification’s disclosures, or lack thereof,
is telling and is an apparent concession that the “specifica-
tion, moreover, confirms that the [buffer] is a separate ele-
ment from the [VEGF antagonist], as the only elements
disclosed in the specification as [being a buffer] are sepa-
rate structures from the [VEGF antagonist].” Becton,
616 F.3d at 1254. Further, like the patent at issue in Bec-
ton, “[n]othing in the specification indicates” that the
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VEGF antagonist “might” also satisfy the distinct “buffer”
component. Id. at 1255. In fact, all eight examples and
twenty-two other embodiments disclose a VEGF antago-
nist “plus” a separate buffer. Amgen Decision, at *14 (em-
phasis in original) (citing ’865 patent col. 2 l. 33–col. 4 l. 62,
col. 8 l. 32–col. 12 l. 26). And every embodiment either de-
scribes the buffer as a phosphate buffer or provides a con-
centration range for a buffer that does not overlap with the
converted concentration range for the VEGF antagonist.
Id.
Despite acknowledging that the specification nowhere
gives an example of a single component performing both
functions (e.g., a self-buffering protein), Regeneron argues
that “[t]he patent does not disavow the ordinary meaning
of ‘buffer.’” Regeneron Br. 67 (“Although the specification
only explicitly discloses phosphate buffer, it contains no
‘expressions of manifest exclusion or restriction’ as to non-
excipient buffers.”). It adds that “[t]he patent did not need
to list known or unknown buffers,” id. at 51, and that “[t]he
evidence was unequivocal that proteins containing histi-
dine were known buffers,” id. at 52.
But here, the claims recite the “VEGF antagonist” and
“buffer” as distinct components, and the specification only
reinforces that understanding. The specification makes
clear what “the inventors actually invented and intended
to envelop,” Phillips, 415 F.3d at 1316, and that is, a for-
mulation containing a VEGF antagonist plus a distinct
buffer. While Regeneron argues “that the [person of ordi-
nary skill] would have understood in the context of the ’865
patent that proteins containing histidine were buffers,”
like Amgen’s ABP 938 product, it says so without identify-
ing any support from the specification. Regeneron Br. 63.
That lack of specification-based support is revealing be-
cause the claims “do not have meaning removed from the
context from which they arose.” Netword, LLC v. Centraal
Corp., 242 F.3d 1347, 1352 (Fed. Cir. 2001). And the
claims here “arose” from a specification that clearly and
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repeatedly describes the “VEGF antagonist” and “buffer”
as distinct components and does not explain or suggest that
one can stand in as the other. See ’865 patent col. 2 l. 33–
col. 4 l. 62, col. 8 l. 32–col. 12 l. 26.
Similarly, the fact that the term “buffer” was left unde-
fined in the specification without any clear disavowal, does
not mean that the term is divorced from what is so clearly
implied by the claims and the specification alike. See Se-
quoia Tech., LLC v. Dell, Inc., 66 F.4th 1317, 1324 (Fed.
Cir. 2023) (“[T]he use of a term denoting a non-exhaustive
list does not eviscerate our obligation to construe terms in
the context of the entire patent.”). Accordingly, and be-
cause the Becton presumption applies, the district court
correctly concluded that the only reasonable construction
of the claim language, in light of the specification (which
does nothing to rebut the presumption of separateness), is
that the “VEGF antagonist” and “buffer” are distinct com-
ponents.
We turn next to the district court’s consideration of ex-
trinsic evidence and Regeneron’s argument that the dis-
trict court clearly erred by “concluding that extrinsic
evidence was irrelevant to whether claim terms could over-
lap under Becton.” Regeneron Br. 53. For the following
reasons, we conclude that the district court did not clearly
err in finding that “none of the extrinsic evidence discloses
that aflibercept can function as a buffer in a pharmaceuti-
cal formulation” as of the effective filing date of the ’865
patent. Amgen Decision, at *19.
As the district court correctly noted, “while extrinsic
evidence can shed useful light on the relevant art, it is less
significant than the intrinsic record in determining the le-
gally operative meaning of claim language.” Id. at *18
(cleaned up) (citing Phillips, 415 F.3d at 1317). The district
court also correctly recognized that “it need not consider
this extrinsic evidence for claim construction where, as
here, the intrinsic evidence is clear and unambiguous.” Id.
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at *19 (citing Seabed Geosolutions (US) Inc. v. Magseis FF
LLC, 8 F.4th 1285, 1287 (Fed. Cir. 2021) (“If the meaning
of a claim term is clear from the intrinsic evidence, there is
no reason to resort to extrinsic evidence.”)). The district
court accordingly determined that “the claims and specifi-
cation are clear and uniform in supporting that the as-
serted claims require separate components such that the
buffer must be separate and distinct from the VEGF antag-
onist.” Id. (cleaned up). Nevertheless, the court considered
the extrinsic evidence “for completeness” and found “that
the evidence supports the construction that the claims re-
quire the VEGF antagonist and buffer to be separate and
distinct components.” Id. We see no clear error in the dis-
trict court’s analysis.
Regeneron argues that “the court erred in disregarding
the . . . extrinsic evidence.” Regeneron Br. 54; see also Re-
generon Reply Br. 23–28. In Regeneron’s view, “[t]he [ex-
trinsic] evidence was unequivocal that proteins containing
histidine were known buffers,” and that “[t]here was no dis-
pute that proteins have been known for decades to be buff-
ers or have buffering capacity.” Regeneron Br. at 52. It
also contends the district court, “in alternatively consider-
ing the extrinsic evidence, . . . legally erred in disregard-
ing [International Patent Application Publication
WO 2006/138181 (“Gokarn”)] as irrelevant to claim con-
struction.” Id. at 55. Gokarn, it argues, “undisputedly pre-
dated the filing of the ’865 patent, and so it unquestionably
confirmed to the [person of ordinary skill in the art] that
‘biopharmaceutical proteins’ could ‘be formulated in self-
buffering compositions.’” Id.
We are unpersuaded. Indeed, as already noted, the dis-
trict court did not need to consider the extrinsic evidence
given the overwhelming evidence in the intrinsic record.
But the district court nevertheless considered both experts’
testimony as well as the references submitted by Regen-
eron and found that evidence too “supports the construc-
tion that the claims require the VEGF antagonist and
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buffer to be separate and distinct components.” Amgen De-
cision, at *19. Additionally, it was reasonable for the dis-
trict court to determine that, given the proximity of
Gokarn’s publication date to the ’865 patent’s filing date,
the reference actually supports Amgen’s contention that
self-buffering proteins were not well known and that “Go-
karn advanced the art over the ’865 patent precisely by dis-
closing certain buffer-free formulations in which the
therapeutic protein is itself capable of maintaining pH sta-
bility.” Amgen Br. 51. We therefore conclude that the dis-
trict court’s findings regarding the extrinsic evidence are
not clearly erroneous. See Genentech, Inc. v. Sandoz Inc.,
55 F.4th 1368, 1376 (Fed. Cir. 2022) (“Where there are two
permissible views of the evidence, the fact-finder’s choice
between them cannot be clearly erroneous.”).
In light of the foregoing, and given the undisputed fact
that Amgen’s ABP 938 product does not contain a buffer
separate from the VEGF antagonist, there is at least a sub-
stantial question of noninfringement. Regeneron has
therefore not established a likelihood of success on the mer-
its of its infringement allegations and the district court did
not abuse its discretion in denying its motion for a prelim-
inary injunction. See Genentech, Inc. v. Novo Nordisk A/S,
108 F.3d 1361, 1364 (Fed. Cir. 1997) (holding that if an al-
leged infringer “raises a ‘substantial question’ concerning
validity, enforceability, or infringement (i.e., asserts a de-
fense that [the patentee] cannot show ‘lacks substantial
merit’)[,] the preliminary injunction should not issue”).
III
Amgen, during oral argument, waived its right to a re-
mand for a calculation of damages from the temporary in-
junction. See Oral Arg. at 25:13–48, Appeal No. 24-2351,
available at https://oralarguments.cafc.uscourts.gov/de-
fault.aspx?fl=24-2351_01142025.mp3.
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C ONCLUSION
We have considered Regeneron’s remaining arguments
and find them unpersuasive. For the foregoing reasons, we
affirm.
AFFIRMED
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