Amgen Inc. v. Amneal Pharmaceuticals LLC ( 2020 )

United States Court of Appeals
for the Federal Circuit
______________________
AMGEN INC.,
Plaintiff-Appellant
v.
AMNEAL PHARMACEUTICALS LLC, AMNEAL
PHARMACEUTICALS OF NEW YORK LLC,
PIRAMAL HEALTHCARE UK LIMITED,
Defendants-Appellees
ZYDUS PHARMACEUTICALS (USA) INC., CADILA
HEALTHCARE LTD., DBA ZYDUS CADILA,
Defendants-Cross-Appellants
______________________
2018-2414, 2019-1086
______________________
Appeals from the United States District Court for the
District of Delaware in Nos. 1:16-cv-00853-MSG, 1:16-cv-
00925-MSG, 1:17-cv-00183-MSG, 1:17-cv-00713-MSG,
Judge Mitchell S. Goldberg.
______________________
Decided: January 7, 2020
______________________
BRADFORD J. BADKE, Sidley Austin LLP, New York,
NY, argued for plaintiff-appellant. Also represented by
SONA DE; LAUREN CRANFORD KATZEFF, JOSHUA JOHN
FOUGERE, RYAN C. MORRIS, Washington, DC; ERIC
MICHAEL AGOVINO, LOIS KWASIGROCH, WENDY A.
2 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
WHITEFORD, Amgen Inc., Thousand Oaks, CA; ALICIA
ALEXANDRA ROSE RUSSO, Fitzpatrick, Cella, Harper &
Scinto, New York, NY; JOHN DENNIS MURNANE, JOSHUA
ROTHMAN, Venable LLP, New York, NY.
JACOB M. HOLDREITH, Robins Kaplan LLP, Minneap-
olis, MN, argued for defendants-appellees Amneal Phar-
maceuticals LLC, Amneal Pharmaceuticals of New York
LLC. Also represented by BRENDA L. JOLY, KELSEY
MCELVEEN; OREN D. LANGER, New York, NY.
AARON BARKOFF, McAndrews, Held & Malloy, Ltd.,
Chicago, IL, argued for defendant-appellee Piramal
Healthcare UK Limited. Also represented by ALEJANDRO
MENCHACA.
STEVEN ARTHUR MADDOX, Maddox Edwards, PLLC,
Washington, DC, argued for defendants-cross-appellants.
Also represented by JEREMY J. EDWARDS, MATTHEW C.
RUEDY, KAVEH SABA; CHRISTOPHER CASIERI, McNeely Hare
& War LLP, Princeton, NJ; WILLIAM HARE, RENITA SYBIL
RATHINAM, Washington, DC.
______________________
Before NEWMAN, LOURIE, and TARANTO, Circuit Judges.
LOURIE, Circuit Judge.
Amgen appeals from the district court’s judgment that
Amneal Pharmaceuticals LLC and Amneal Pharmaceuti-
cals of New York LLC (collectively, “Amneal”) does not in-
fringe claims 1, 2–4, 6, 8–12, and 14–18 of U.S. Patent
9,375,405 (“the ’405 patent”), Piramal Healthcare UK Ltd.
(“Piramal”) does not infringe claims 1–6 and 8–20. Zydus
Pharmaceuticals (USA) Inc. and Cadila Healthcare Ltd.
(collectively, “Zydus”) cross-appeals from the court’s judg-
ment that they infringe claims 1–4, 6, 8–9, 15–17, and 19
of the ’405 patent. Amgen Inc. v. Amneal Pharm. LLC, 328
F. Supp. 3d 373 (D. Del. 2018) (“Decision”). We conclude
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 3
that the district court construed the claims incorrectly and
erred in its analysis of infringement by Amneal. However,
the court properly applied prosecution history estoppel to
Amgen’s arguments regarding Piramal and otherwise did
not err in its fact findings for Zydus. Thus, we vacate and
remand the district court’s judgment as to Amneal and af-
firm with respect to Piramal and Zydus.
BACKGROUND
Amgen holds approved New Drug Application
No. 21688 for Sensipar®, a formulation of cinacalcet hydro-
chloride used to treat secondary hyperparathyroidism in
adult patients with chronic kidney disease who are on di-
alysis and to treat hypercalcemia in patients with parathy-
roid cancer and primary and secondary
hyperparathyroidism. Amneal, Piramal, and Zydus each
filed an Abbreviated New Drug Application (ANDA) seek-
ing to enter the market with a generic version of Sen-
sipar®, and Amgen brought suit against each ANDA filer
in the District of Delaware alleging that the proposed
ANDA products would infringe the ’405 patent.
The ’405 patent is directed to a rapid dissolution for-
mulation of cinacalcet. Amgen asserted different claims
against each defendant, but the parties stipulated that the
infringement findings for claim 1 would extend to the ma-
jority of the remaining claims. 1 Stipulation and Proposed
Order Regarding Infringement, Amgen Inc. v. Aurobindo
1 Four claims asserted below are absent from the
stipulation: claims 6, 8, 18 and 20. For claims outside of
the stipulation, the court provided specific reasoning for its
noninfringement or infringement conclusions. Because
each party in this appeal argues only about claim 1 and in
view of the stipulation, we treat claim 1 as dispositive for
all claims at issue.
4 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
Pharma Ltd., No. 1:16-cv-00853-MSG (D. Del. Mar. 23,
2018); J.A. 2805–08. Claim 1 recites:
A pharmaceutical composition comprising:
(a) from about 10% to about 40% by weight
of cinacalcet HCl in an amount of from
about 20 mg to about 100 mg;
(b) from about 45% to about 85% by weight
of a diluent selected from the group consist-
ing of microcrystalline cellulose, starch,
dicalcium phosphate, lactose, sorbitol,
mannitol, sucrose, methyl dextrins, and
mixtures thereof,
(c) from about 1% to about 5% by weight of
at least one binder selected from the group
consisting of povidone, hydroxypropyl
methylcellulose, hydroxypropyl cellulose,
sodium carboxymethylcellulose, and mix-
tures thereof; and
(d) from about 1% to 10% by weight of at
least one disintegrant selected from the
group consisting of crospovid[o]ne, sodium
starch glycolate, croscarmellose sodium,
and mixtures thereof,
wherein the percentage by weight is relative to the
total weight of the composition, and wherein the
composition is for the treatment of at least one of
hyperparathyroidism, hyperphosphonia, hyper-
calcemia, and elevated calcium phosphorus prod-
uct.
A. Prosecution History
The prosecution history is particularly relevant to the
instant appeal. The ’405 patent issued from U.S. Patent
Application 12/942,646 (“the ’646 application”). As origi-
nally filed, the ’646 application contained only one claim,
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 5
which recited a “pharmaceutical composition comprising
an effective dosage amount of a calcium receptor-active
compound and at least one pharmaceutically acceptable ex-
cipient, wherein” the composition achieved a specific disso-
lution profile. J.A. 9171. Amgen filed a Preliminary
Amendment, which cancelled claim 1 and added new
claims 2–24. Newly filed claim 2, which ultimately issued
as claim 1, recited a pharmaceutical composition compris-
ing specific ranges, by weight, of cinacalcet and various ex-
cipients:
A pharmaceutical composition comprising:
(a) from about 10% to about 40% by weight
of cinacalcet HCl;
(b) from about 45% to about 85% by weight
of a diluent selected from the group consist-
ing of microcrystalline cellulose, starch,
dicalcium phosphate, lactose, sorbitol,
mannitol, sucrose, methyl dextrins, and
mixtures thereof,
(c) from about 1% to about 5% by weight of
at least one binder; and
(d) from about 1% to 10% by weight of at
least one disintegrant,
wherein the percentage by weight is relative to the
total weight of the composition.
J.A. 9382 (emphasis added).
The Examiner rejected the claims under 35 U.S.C.
§ 103 over U.S. Patent 6,211,244 (“Van Wagenen”) “as evi-
denced by” U.S. Patent 6,656,492 (“Kajiyama”) in view of
U.S. Patent 6,316,460 (“Creekmore”) and U.S. Patent App.
2005/0147670 (“Hsu”). J.A. 9417. According to the Exam-
iner, Van Wagenen disclosed a calcimimetic “acting on a
parathyroid cell calcium receptor” that “can be used to
treat diseases such a primary hyperparathyroidism and
6 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
secondary hyperparathyroidism,” J.A. 9417–18, and, while
Van Wagenen failed to disclose the required amounts of
various excipients, Creekmore and Hsu taught those limi-
tations.
In response to this Office Action, Amgen filed an
amendment narrowing the cinacalcet limitation to recite
“from about 10% to 40% by weight of cinacalcet HCl in an
amount of from about 20 mg to about 100 mg” (“Cinacalcet
Amendment”). J.A. 9433. In support of this amendment,
Amgen explained that the now narrower range of ci-
nacalcet would not have been obvious in view of the teach-
ings of Van Wagenen, which taught a broader range that
“would translate to 0.62 mg to 3100 mg for an average hu-
man.” J.A. 9438–40.
After the Cinacalcet Amendment, the Examiner con-
ducted a telephone interview with Amgen’s counsel, and
Amgen accepted an amendment proposed by the examiner
(“Examiner’s Amendment”). J.A. 9464. The Examiner’s
Amendment revised the binder and disintegrant limita-
tions into their current, Markush group format. The Ex-
aminer then allowed the claims, stating that the closest
prior art did not disclose or render obvious the “combina-
tion of components . . . in the amounts . . . set forth in claim
2.” J.A. 9462.
Following the Notice of Allowance, Amgen filed a num-
ber of Requests for Continued Examination providing var-
ious additional references and updating the U.S. Patent
and Trademark Office on the revocation of a related patent
after opposition proceedings in the European Patent Office,
J.A. 9472–509, 9643–659. The Examiner issued a Notice
of Allowance after each Request. While the second of the
Requests was pending, Amgen submitted a “Preliminary
Amendment.” J.A. 10701. This amendment recited the
claims exactly as they were allowed but underlined the lan-
guage that had been proposed by the Examiner in the Ex-
aminer’s Amendment. In accompanying documentation,
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 7
Amgen remarked that “[t]hese amendments have not been
made in response to a prior art rejection but rather to place
the claims in proper format and to better define the claimed
subject matter, including equivalents.” J.A. 10707.
B. District Court Proceedings
In the district court litigation, the construction of the
binder and disintegrant Markush groups was a key issue.
Oddly, neither party sought construction of the binder and
disintegrant groups during claim construction. But the
proper construction of the Markush groups was placed at
issue in the context of pretrial preparations. In its pro-
posed pretrial order, Amgen argued that the Markush
groups should be open to unrecited elements, but the dis-
trict court disagreed. Relying on Multilayer Stretch Cling
Film Holdings, Inc. v. Berry Plastics Corp., 831 F.3d 1350(Fed. Cir. 2016), the court held that “Amgen ha[d] not over-
come the very strong presumption that the Markush
groups for the binder and disintegrant elements are closed
to unrecited binders and disintegrants.” Amgen Inc. v. Au-
robindo Pharma, Ltd., No. 16-cv-853, 2018 WL 1061369, at
*3 (D. Del. Feb. 27, 2018) (“Pretrial Order”). Amgen sought
reargument on this claim construction issue, but the court
again rejected its positions. Amgen Inc. v. Amneal Pharm.
LLC, No. 16-cv-853, 2018 WL 1885664, at *7–8 (D. Del.
Apr. 19, 2018) (“Reargument Order”).
The district court held a bench trial on the issue of in-
fringement. 2 The court held that Amneal and Piramal do
2 While Amneal, Piramal, and Zydus each asserted
counterclaims that the ’405 patent is invalid, the court bi-
furcated the infringement and invalidity issues, and trial
on the infringement issue proceeded first. Decision, 328 F.
Supp at 377; Reargument Order, 2018 WL 1885664, at *1
n.2.
8 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
not infringe any claim of the ’405 patent but found that Zy-
dus infringes claims 1–4, 6, 8–9, 15–17, and 19.
First, the district court found that Amneal does not in-
fringe the asserted claims because its product does not
meet the binder and disintegrant limitations. As a binder,
Amneal uses Opadry Clear YS-1-7006, a product that con-
tains hydroxypropyl methylcellulose (“HPMC”), polyeth-
ylene glycol 400, and polyethylene glycol 8000. Decision,
328 F. Supp. 3d at 383. Although HPMC is a listed binder,
the court found that Opadry itself is not, so Amneal does
not literally meet the binder limitation. Id. at 384.
As a disintegrant, Amneal’s product uses crospovidone,
which is listed in the disintegrant Markush group. Id. Re-
lying on its claim construction, however, the court found
that Amneal’s product does not meet the disintegrant lim-
itation. Id. at 385.
Next, the district court found that Piramal does not in-
fringe because it does not meet the binder limitation. Pi-
ramal uses pregelatinized starch, id. at 392, and Amgen
argued that the cold-water soluble fraction of the starch is
equivalent to povidone, a listed binder. The court rejected
this argument as barred by prosecution history estoppel.
Id. In the court’s view, Amgen had narrowed its claims by
accepting the Examiner’s Amendment to exclude binders
different from those listed in the Markush group. The
court found the Examiner’s reliance on the “combination of
components” in the notice of allowance underscored that
the Markush groups were added for patentability. Id. at
393.
In contrast, the district court found that Zydus’s ANDA
product infringes the asserted claims. At issue for Zydus
was the function of the pregelatinized starch in its formu-
lation. Zydus’s ANDA states that the formulation uses pre-
gelatinized starch as a diluent, and starch is listed in the
diluent Markush group of claim 1. Zydus relied on testi-
mony from Dr. Davies, Amgen’s expert, that the cold-water
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 9
soluble fraction of pregelatinized starch could function as
an unlisted binder, but the court disagreed, rejecting Dr.
Davies’s fraction opinion as lacking credibility. The court
ultimately found that Zydus’s ANDA product literally in-
fringes claim 1. Id. at 399.
DISCUSSION
Amgen appealed from the district court’s judgment
that Amneal and Piramal do not infringe the ’405 patent.
Zydus cross-appealed from the district court’s judgment
that it infringed. When Zydus filed its notice of appeal,
however, its defense and counterclaim that the ’405 patent
is invalid had not been resolved. As a preliminary matter,
we consider whether we have jurisdiction over Zydus’s ap-
peal.
“This court’s jurisdiction is governed by the final judg-
ment rule.” Robert Bosch, LLC v. Pylon Mfg. Corp., 719
F.3d 1305, 1308 (Fed. Cir. 2013) (en banc). The rule “as
applied to patent disputes arising under 28 U.S.C. § 1338,
is set forth at 28 U.S.C. § 1295.” Nystrom v. TREX Co., 339
F.3d 1347, 1350 (Fed. Cir. 2003). We review “final deci-
sions” from district courts, which are decisions that end lit-
igation on the merits and leave nothing for the court to do
but execute the judgment. Id. (quoting Catlin v. United
States, 324 U.S. 229, 233 (1945) and citing Coopers &
Lybrand v. Livesay, 437 U.S. 463, 467 (1978)). The district
court expressly conditioned its infringement judgment here
on the claims being found “valid and enforceable.” Trial
Order, Amgen Inc. v. Amneal Pharm. LLC., No. 1:16-cv-
00853-MSG (July 27, 2018), ECF No. 376; J.A. 2. Accord-
ing to its own terms, the judgment did not resolve the par-
ties’ dispute and was thus not a “final decision.” See Final
Judgment, Amgen Inc. v. Amneal Pharm. LLC., No. 1:16-
cv-00853-MSG (Oct. 9, 2018), ECF No. 405; J.A. 5059–60.
However, when questioned at oral argument about the
jurisdictional defect in Zydus’s appeal, Zydus represented
that it would “give up” its invalidity defense and claim even
10 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
if infringement was affirmed. Oral Arg. at 20:23–33,
http://oralarguments.cafc.uscourts.gov/default.aspx?fl=20
18-2414.MP3. Zydus’s representation effectively cures the
jurisdictional defect in its notice of appeal because the con-
tingency identified by the district court—Zydus’s potential
invalidity defense and claim—is nullified. Thus, the
court’s judgment resolves all claims for all parties and is a
final decision within our jurisdiction. Accordingly, we have
jurisdiction over both the appeal and cross-appeal under
28 U.S.C. § 1295(a)(1).
We now turn to the merits. In its appeal, Amgen chal-
lenges the district court’s construction of the binder and
disintegrant Markush groups in claim 1 and alternatively
argues that even under the district court’s constructions,
the court’s findings for Amneal and Piramal were in error.
For its part, Zydus agrees with the court’s claim construc-
tions but challenges the court’s factfinding that Zydus’s
ANDA product infringes the ’405 patent claims. We first
address the overarching claim construction issue and reach
the other issues in turn.
A. Legal Standard
On appeal from a bench trial, we review a district
court’s conclusions of law de novo and its findings of fact
for clear error. Braintree Labs., Inc. v. Novel Labs., Inc.,
749 F.3d 1349, 1358 (Fed. Cir. 2014) (citing Brown & Wil-
liamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120,
1123 (Fed. Cir. 2000)). “A factual finding is clearly errone-
ous when, despite some supporting evidence, we are left
with a definite and firm conviction that the district court
was in error.” Alcon Research Ltd. v. Barr Labs., Inc., 745
F.3d 1180, 1186 (Fed. Cir. 2014) (citing Alza Corp. v. Mylan
Labs., Inc., 464 F.3d 1286, 1289 (Fed. Cir. 2006)). “The
burden of overcoming the district court’s factual findings
is, as it should be, a heavy one.” Polaroid Corp. v. Eastman
Kodak Co., 789 F.2d 1556, 1559 (Fed. Cir. 1986). “Where
there are two permissible views of the evidence, the
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 11
factfinder’s choice between them cannot be clearly errone-
ous.” Anderson v. City of Bessemer City, 470 U.S. 564, 574
(1985) (citing United States v. Yellow Cab Co., 338 U.S.
338, 342 (1949)).
An infringement analysis requires two steps. Clare v.
Chrysler Grp., LLC, 819 F.3d 1323, 1326 (Fed. Cir. 2016).
First, the court construes the asserted claims. Claim con-
struction is a question of law that may involve underlying
factual questions. Teva Pharm. USA, Inc. v. Sandoz, Inc.,
574 U.S. 318, 332 (2015). Here, the court’s constructions of
Markush limitations are based solely on the intrinsic evi-
dence, so we review them de novo. HTC Corp. v. Cellular
Commc’ns Equip., LLC, 877 F.3d 1361, 1367 (Fed. Cir.
2017). Second, the court determines whether the accused
product meets each limitation of the claim as construed,
which is a question of fact that we review for clear error.
Wright Med. Tech., Inc. v. Osteonics Corp., 122 F.3d 1440,
1443 (Fed. Cir. 1997).
“Whether prosecution history estoppel applies to limit
the doctrine of equivalents is a question of law which we
review de novo.” Pharmacia & Upjohn Co. v. Mylan
Pharm., Inc., 170 F.3d 1373, 1376 (Fed. Cir. 1999) (citing
Wang Labs., Inc. v. Mitsubishi Elecs. Am., Inc., 103 F.3d
1571, 1578 (Fed. Cir. 1997)).
B. Claim Construction
Amgen first challenges the district court’s construction
of the binder and disintegrant Markush groups in, respec-
tively, elements (c) and (d). The district court held both of
these Markush groups to be closed. Pretrial Order, 2018
WL 1061369, at *3. In reaching this result, the court first
compared claim 1 to that at issue in Multilayer, which sim-
ilarly recited “comprising,” followed by “consisting of” ter-
minology. The court explained that, as in Multilayer, there
was a “very strong presumption” that the Markush groups
were closed to unrecited constituents. Id. at *2. At this
point in the litigation, Amgen pointed the court only to the
12 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
use of the word “comprising” in the preamble to support its
position, and the court found this insufficient to overcome
the presumption of closure.
Amgen later moved for reargument, contending that
the district court misunderstood its claim construction po-
sition. Reargument Order, 2018 WL 1885664, at *3–4. In
that motion, Amgen focused on the claim’s recitation of “at
least one” disintegrant and binder before the “consisting of”
terms in each claim. Relying on this language, it argued
that “[s]o long as the weight percentage is met by one of the
listed binders or disintegrants, the presence of an addi-
tional excipient that functions as a binder or disintegrant
does not take Defendants’ products outside the literal scope
of the claims.” J.A. 2585.
The district court first rejected Amgen’s arguments as
untimely raised. Reargument Order, 2018 WL 1885664, at
*4. The court still considered the merits, however, and
found Amgen’s construction to be inconsistent with the
prosecution history. Particularly noteworthy was the fact
that, before the claims even contained the Markush group
limitations, Amgen claimed “from about 1% to about 5% by
weight of at least one binder” and “from about 1% to about
10% by weight of at least one disintegrant.” Id. at *5. Con-
sidering the prosecution history, it found that the percent-
age amounts of binder and disintegrant were “critical to the
invention and, therefore, not subject to a construction that
results in their vitiation.” Id.
In this appeal, Amgen argues that the district court
erred in construing the binder and disintegrant Markush
groups because neither group forecloses the use of unlisted
binders or disintegrants. Amgen Br. 29. As it did before
the district court, Amgen again cites the “comprising” and
“at least one” language in the claim to support its position.
According to Amgen, the “comprising” term renders the
claim open-ended, even when other language restricts the
scope of particular claim elements, and the “consisting of”
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 13
term here only applies to the group from which “at least
one” binder or disintegrant must be selected. Id. at 30.
Amgen also contrasts the binder and disintegrant lim-
itations with the diluent limitation, which lacks the “at
least one” language. Amgen maintains that the “at least
one” language would be meaningless if the groups are
closed to additional binders and disintegrants and mean-
ingless in view of the claim’s recitations of “mixtures
thereof” within the Markush groups. Id. at 32 (citing Bi-
con, Inc. v. Straumann Co., 441 F.3d 945, 951 (Fed. Cir.
2006)).
For additional support, Amgen argues from the specifi-
cation and trial testimony that the lists of excipients in the
Markush groups are not exhaustive and that excipients can
have different functions in different formulations. As for
the district court’s reliance on Multilayer and similar cases,
Amgen argues that its claims here are distinguishable from
the claims at issue in those cases because of the “at least
one” limitation.
In response, Amneal, Piramal, and Zydus argue that
the district court’s construction was correct. Each of these
parties argues that the district court properly applied Mul-
tilayer and that Amgen failed to overcome the strong pre-
sumption that a claim term set off with “consisting of” is
closed to unrecited elements. Amneal & Piramal Br. 34
(quoting Shire Dev., LLC v. Watson Pharm., Inc., 848 F.3d
981, 984 (Fed. Cir. 2017)); Zydus Br. 23–24. Each party
also argues that Amgen’s claim construction would require
the court to ignore the criticality of the weight ranges for
the binder and disintegrant elements as evidenced by the
prosecution history. Amneal & Piramal Br. 29; Zydus Br.
29.
We conclude that Amneal, Piramal, and Zydus read
more into Multilayer and Shire than is properly found
there. Multilayer and Shire did not hold broadly that,
whenever “consisting of” Markush group language is
14 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
present in a particular claim limitation, even when the lim-
itation follows a general claim transition phrase of “com-
prising,” all components of an accused product that
perform the general function of the particular limitation
must meet the requirements of that limitation, thus pre-
cluding components outside the Markush group. No such
issue was presented in those cases. Rather, each decision
held only that the terms of a particular claim limitation
that used “consisting of” Markush group language were re-
stricted to members of the Markush group. Those decisions
do not apply in this case, where the question is whether the
“binder” or “disintegrant” claim limitations are written to
preclude other binders and disintegrants in the claimed
composition. We conclude that they are not.
In Multilayer, we considered a claim to multilayer
stretch films:
1. A multi-layer, thermoplastic stretch wrap film
containing seven separately identifiable polymeric
layers, comprising:
(a) two identifiable outer layers, at least
one of which having a cling performance of
at least 100 grams/inch, said outer layer
being selected from the group consisting of
linear low density polyethylene, very low
density polyethylene, and ultra low density
polyethylene resins, said resins being ho-
mopolymers, copolymers, or terpolymers, of
ethylene and alpha-olefins; and
(b) five identifiable inner layers, with each
layer being selected from the group consist-
ing of linear low density polyethylene, very
low density polyethylene, ultra low density
polyethylene, and metallocene-catalyzed
linear low density polyethylene resins; said
resins are homopolymers, copolymers, or
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 15
terpolymers, of ethylene and C3 to C20 al-
pha-olefins;
wherein each of said two outer layers and each of
said five inner layers have different compositional
properties when compared to a neighboring layer.
831 F.3d at 1353 (quoting U.S. Patent 6,265,055 col. 1 l.
43–col. 2 l. 3).
In construing this claim, we held that a product, to
come within element (b), with its Markush group listing
particular resins, could not have other resins in the five
identified inner layers of such a product. Id. at 1358–61.
This construction was dictated by the transitional phrase
“consisting of,” which “creates a very strong presumption
that that claim element is ‘closed’ and therefore ‘exclude[s]
any elements, steps, or ingredients not specified in the
claim.’” Id. at 1358 (quoting AFG Indus., Inc. v. Cardinal
IG Co., 239 F.3d 1239, 1245 (Fed. Cir. 2001)). We further
recognized that a patentee could act as its own lexicogra-
pher to give “consisting of” an alternative, less restrictive
meaning, “[b]ut to overcome the exceptionally strong pre-
sumption that a claim term set off with ‘consisting of’ is
closed to unrecited elements, the specification and prosecu-
tion history must unmistakably manifest an alternative
meaning.” Id. (citing Conoco, Inc. v. Energy & Envtl. Int’l,
L.C., 460 F.3d 1349, 1359 n.4 (Fed. Cir. 2006)). We con-
cluded that the presumption was not overcome. Id. at
1359–61. As a result, we held that dependent claim 10,
which added a requirement that “at least one said inner
layer” of claim 1’s element (b) contain a resin not listed in
element (b), was invalid because it was inconsistent with
the independent claim. Id. at 1361–62.
The issue was framed by Multilayer solely in terms of
interpreting element (b), without any reliance on the “com-
prising” language of the general transition phrase of
claim 1. This court thus had no occasion to, and did not,
consider the effect of that transition phrase. Nor was there
16 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
a question presented or decided about whether element (b)
applied to all layers in the claimed film, even all inner lay-
ers. The only issue was whether element (b) by itself de-
clared that each layer among the five inner ones was
restricted to the listed resins. The Multilayer claim limita-
tion required, in terms, that “each layer” among the iden-
tified inner layers be “selected from” the Markush group.
The only question was the meaning of the “consisting of”
language applicable to “each layer.”
Shire presented this court with a similar construction
issue, but for a pharmaceutical claim:
1. Controlled-release oral pharmaceutical composi-
tions containing as an active ingredient 5-amino-
salicylic acid, comprising:
a) an inner lipophilic matrix consisting of
substances selected from the group consist-
ing of unsaturated and/or hydrogenated
fatty acid, salts, esters or amides thereof,
fatty acid mono-, di- or triglycerides, waxes,
ceramides, and cholesterol derivatives with
melting points below 90° C., and wherein
the active ingredient is dispersed both in
said [sic] the lipophilic matrix and in the
hydrophilic matrix;
b) an outer hydrophilic matrix wherein the
lipophilic matrix is dispersed, and said
outer hydrophilic matrix consists of com-
pounds selected from the group consisting
of polymers or copolymers of acrylic or
methacrylic acid, alkylvinyl polymers, hy-
droxyalkyl celluloses, carboxyalkyl cellu-
loses, polysaccharides, dextrins, pectins,
starches and derivatives, alginic acid, and
natural or synthetic gums;
c) optionally other excipients . . .
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 17
848 F.3d at 983 (quoting U.S. Patent 6,773,720 col. 6 ll. 7–
30). In construing the (a) and (b) Markush groups, we ex-
plained that the “consisting of” language defined the
groups and created a “very strong presumption” that the
Markush groups were closed to additional elements not
specified in the claim. Id. at 984 (citing Multilayer, 831
F.3d at 1358). We then focused on element (b), determined
that the presumption was not overcome, and found that the
presence of magnesium stearate in the outer hydrophilic
matrix, an excipient not recited in the (b) Markush group,
rendered the appellee’s product noninfringing. Id. at 985–
86.
As in Multilayer, the issue presented to and decided by
this court was framed solely in terms of interpreting ele-
ment (b), without any reliance on the “comprising” lan-
guage of the general transition phrase of claim 1. This
court thus had no occasion to, and did not, consider the ef-
fect of that transition language. Nor was there a question
presented or decided about whether element (b) applied to
all matrices or outer matrices in the claimed composition.
Element (b) states that an outer matrix of the claimed com-
position “consists of” the compounds in the Markush group.
The court considered the component of the appellee’s prod-
uct that was alleged to meet that outer matrix limitation.
That component, by the terms of element (b), had to “con-
sist of” of those compounds to meet that limitation. The
court’s reiteration of the normal restrictive meaning of the
“consist[ing] of” language settled the infringement issue:
the product did not meet element (b) because the compo-
nent alleged to meet that limitation contained compounds
other than the listed ones.
The decisive issue in this case is critically different
from any issue decided in Multilayer or Shire. The issue is
whether all binders or disintegrants in the claimed formu-
lation are subject to the specific binder or disintegrant lim-
itations. The answer, we conclude, is no. There is no
language in Amgen’s claim indicating that every binder or
18 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
disintegrant in the claimed formulation must be within the
Markush groups. Instead, the claim recites “at least one”
binder or disintegrant “selected from the group consisting
of” various excipients. And the limitations merely require
that those particular binders or disintegrants meet the
specified weight-percentage requirements, which is not in-
consistent with the overall composition containing other
binders or disintegrants. The plain language of this claim
requires “at least one” of the Markush members and cer-
tainly does not indicate that the only binders and disinte-
grants in the claimed formulation are those listed in the
groups. And we do not see a sufficient basis for a different
conclusion in the specification or in the prosecution history
we have recited.
Importantly, we also have the “comprising” language.
The term “comprising” is the standard transition term used
to make clear that the claim does not preclude the presence
of components or steps that are in addition to, though not
inconsistent with, those recited in the limitations that fol-
low. See Wis. Alumni Research Found. v. Apple Inc., 905
F.3d 1341, 1348 n.8 (Fed. Cir. 2018); Multilayer, 831 F.3d
at 1358. Here, for the reasons just stated, the language of
the binder and disintegrant limitations is not inconsistent
with the presence of binders and disintegrants beyond
those identified in those limitations. Amgen’s use of the
“comprising” transition phrase reinforces the conclusion
that the language of those limitations is best construed not
to foreclose such additional binders and disintegrants.
Thus, optional additional binders and disintegrants not re-
cited in the Markush group may be included in the claimed
formulation.
In short, this case involves a claim that uses a “com-
prising” transition phrase and one of the following limita-
tions requires a component that “consists of” items listed in
a Markush group and that meets the limitation’s require-
ments for the component. Without more, such language is
satisfied when an accused product contains a component
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 19
that is from the Markush group and that meets the limita-
tion’s requirements for the component. It does not forbid
infringement of the claim if an additional component is pre-
sent functionally similar to the component identified in the
Markush group limitation, unless there is a further basis
in the claim language or other intrinsic evidence for pre-
cluding the presence of such additional components. There
is no such basis here.
Because the district court’s claim constructions in this
case excluded formulations with additional unlisted ingre-
dients—binders, disintegrants, or otherwise—those con-
structions are incorrect. The district court relied on its
construction for the disintegrant Markush group to find
that Amneal’s product did not meet this limitation. The
court held that the presence of an additional, unlisted dis-
integrant rendered Amneal’s product non-infringing. Be-
cause we have reversed the claim construction, we vacate
and remand this finding. On remand, the court should con-
sider whether Amneal’s product meets the disintegrant
limitation applying the corrected construction.
The court’s remaining findings regarding Amneal and
the other defendants do not depend on its constructions of
the Markush groups and are separately addressed below.
C. Amneal’s Product
Amgen next challenges the district court’s specific non-
infringement finding for both Amneal and Piramal. We
consider its arguments for each appellee in turn.
Amgen asks us to reverse the district court’s fact find-
ings that Amneal’s ANDA product does not meet the binder
limitation. The literal infringement question for the binder
limitation is straightforward: does Amneal’s formulation
contain “from about 1% to about 5% by weight of at least
one binder selected from the group consisting of povidone,
hydroxypropyl methylcellulose [“HPMC”], hydroxypropyl
20 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
cellulose, sodium carboxymethylcellulose, and mixtures
thereof”? ’405 patent col. 13 ll. 26–30.
Amneal’s ANDA states that its product uses “Opadry”
as a binder. Decision, 328 F. Supp. 3d at 383. It was un-
disputed below that Opadry is a composite product com-
prised of HPMC, polyethylene glycol (“PEG”) 400, and PEG
8000. J.A. 3770:14–22; 3977:5–3978:13. By containing
Opadry, Amneal’s formulation necessarily contains HPMC.
HPMC is a binder listed in the binder Markush group of
claim 1, so, provided that Amneal’s formulation contains
from about 1% to about 5% HPMC, irrespective of whether
PEG is present, the formulation literally meets the binder
limitation of claim 1.
The district court’s analysis was more complex. The
district court considered whether Opadry was “literally
HPMC.” Decision, 328 F. Supp. 3d. at 383. The court then
identified differences between Opadry and HPMC, includ-
ing that “HPMC is a single molecule, whereas Opadry is a
molecular dispersion” of HPMC, PEG 400 and PEG 8000;
that HPMC is a powder while the “three ingredients in
Opadry make a ‘slurry’”; and that Opadry is “manufactured
by a single company, Colorcon, using a proprietary method,
whereas HPMC is not.” Id. at 383–84. The court also found
that Opadry acts as a wet granulation binder by “spreading
and surrounding the drug and excipient particles, forming
a granule from the outside, in,” but HPMC, also a wet gran-
ulation binder, acts “by sticking different types of particles
together, forming a granule from the inside, out.” Id.
These factual findings may be sound and perhaps ac-
curately recite the differences between HPMC and HPMC
in the presence of PEG. But they are not relevant to the
question here—whether Amneal’s formulation contains a
listed binder. HPMC is a listed binder, and HPMC is pre-
sent in Amneal’s formulation. There will of course be dif-
ferences between HPMC alone as compared to Opadry,
which is HPMC combined with PEG. But those differences
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 21
cannot alter the conclusion that HPMC is present in Am-
neal’s formulation, even if it was added as a component of
another commercially available product. The claim re-
quires only that HPMC be present, not that HPMC’s phys-
ical characteristics or function be unaffected by additional
ingredients.
Because the district court erred in its analysis of the
binder in Amneal’s formulation, we vacate its finding that
Amneal does not infringe the asserted claims because of
the identity of Opadry. On remand, the court should con-
sider whether Amneal’s formulation contains “from about
1% to about 5% by weight” of HPMC, irrespective of the
HPMC’s pairing with PEG.
D. Piramal’s Product
Amgen challenges the district court’s noninfringement
finding for Piramal for a different reason: the court’s appli-
cation of prosecution history estoppel. Piramal’s product
uses pregelatinized starch as a binder, which is not listed
in the binder Markush group of claim 1. Amgen therefore
argues under the doctrine of equivalents that pregelati-
nized starch has a native starch fraction that functions as
a diluent and a cold water soluble fraction that functions
as a binder.
The doctrine of equivalents is well-established in our
jurisprudence. See Eli Lilly & Co. v. Hospira, Inc., 933 F.3d
1320, 1329 (Fed. Cir. 2019) (collecting cases). While “[t]he
scope of a patent is not limited to its literal terms but in-
stead embraces all equivalents to the claims described,”
Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535
U.S. 722, 732 (2002), prosecution history estoppel acts as a
“legal limitation” on the doctrine, Warner-Jenkinson Co. v.
Hilton Davis Chem. Co., 520 U.S. 17, 30 (1997). “Estoppel
arises when an amendment is made to secure the patent
and the amendment narrows the patent’s scope.” Festo,
535 U.S. at 736. The burden falls on the patentee to
“demonstrate[] that an amendment required during
22 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
prosecution had a purpose unrelated to patentability.”
Warner-Jenkinson, 520 U.S. at 40–41. “Where the [pa-
tentee] is unable to establish such a purpose, a court should
presume that the purpose behind the required amendment
is such that prosecution history estoppel would apply.” Id.
at 41.
The district court rejected Amgen’s doctrine of equiva-
lents argument as barred by prosecution history estoppel.
During prosecution, the examiner rejected Amgen’s claims
for obviousness, and, in response, Amgen narrowed the
amount of cinacalcet in the claim in an attempt to overcome
the rejection. In the court’s view, Amgen tried but “failed”
to overcome the obviousness rejection. Decision, 328 F.
Supp. at 392. The court noted that the Examiner did not
allow the claims following this amendment, but, instead,
proposed the Examiner’s Amendment adding Markush
groups to the binder and disintegrant limitations. The
court opined that “[t]here would have been no need for the
Examiner to propose an amendment if Amgen’s [Ci-
nacalcet] Amendment was sufficient.” Id. Moreover, the
court noted that the Examiner stated that the claims were
being allowed because the closest prior art failed to disclose
or render obvious the “combination of components and in
the amounts” in the claim. Id. at 392–93. The court un-
derstood these statements in the prosecution history to in-
dicate that the Examiner’s Amendment was entered for
substantial reasons relating to patentability.
Amgen first argues that the presumption of estoppel
does not apply here because it did not narrow the binder or
disintegrant limitations for reasons of patentability. In-
stead, it submits that the Cinacalcet Amendment alone
was necessary to rebut the prior art. Amgen Br. 47.
Amgen points to the absence of any statements by the Ex-
aminer about the Markush groups in particular and
Amgen’s own later statement in the second Request for
Continued Examination that the language added by the
Examiner was not added in “response to a prior art
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 23
rejection but rather to place the claims in proper format
and to better define the claimed subject matter, including
equivalents.” Amgen Br. 49 (quoting J.A. 10707).
Even if the presumption of estoppel applies, however,
Amgen argues that it is overcome because the Markush
limitations were added for reasons other than patentabil-
ity. Amgen argues that the Examiner’s Amendment
simply explained in more explicit terms and clarified the
composition that the claims already covered. Because the
Markush groups and treatment limitations were already
present in previously rejected dependent claims, Amgen ar-
gues that a person of skill would have understood from the
intrinsic record that the Examiner’s Amendment was not
related to patentability. According to Amgen, the amend-
ment could not have distinguished Creekmore or Hsu be-
cause those references already disclosed the excipients in
the Markush groups.
Piramal responds that Amgen’s acceptance of the Ex-
aminer’s Amendment led directly to the allowance of the
claims. Amneal & Piramal Br. 49. According to Piramal,
Amgen’s statement during prosecution that its amendment
was not in response to a prior art rejection was self-serving
and is irrelevant to whether a claim amendment was made
for reasons of patentability. Id. at 50. In Piramal’s view,
the Examiner’s Amendment was substantial and narrowed
the claims, so it could not be considered a clarifying amend-
ment. Piramal also argues that the addition of the
Markush groups overcame the obviousness rejection. Pi-
ramal reads Creekmore to disclose 152 binder-disintegrant
combinations and Hsu discloses 120 combinations. Thus,
Piramal submits that the narrowed range of excipient com-
binations in the Examiner’s Amendment—which would in-
clude only 12 disintegrant-binder combinations—overcame
Creekmore and Hsu because the amended claim recited a
smaller set of members within the group. Id. at 54.
24 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
We agree with Piramal that Amgen’s doctrine of equiv-
alents argument is barred by prosecution history estoppel.
Amgen amended its claims in two ways during prosecu-
tion—first narrowing the amount of cinacalcet to a range
of 20 mg to 100 mg and second, accepting an Examiner’s
Amendment that revised the claim’s disintegrant and
binder limitations to be in Markush group format. Amgen
urges that only the first of these amendments, the Ci-
nacalcet Amendment, was adopted for a substantial reason
relating to patentability. But if Amgen is correct that its
narrowing of the cinacalcet limitation was sufficient to se-
cure allowance, the Examiner proposed the Examiner’s
Amendment for no purpose at all. Such a reading of the
prosecution history is at best unpersuasive.
Amgen also points to its statement in its second Re-
quest for Continued Examination that the Examiner’s
Amendment was added “to place the claims in proper for-
mat and to better define the claimed subject matter.”
Amgen Br. 49 (citing J.A. 10707). But this statement was
made over eight months after the Examiner’s Amendment
was accepted and the claims were allowed. It is unclear
what, if any, insight this conventional boilerplate state-
ment provides into the reasons for the Examiner’s Amend-
ment.
We therefore conclude that Amgen failed to carry its
burden to demonstrate that the Examiner’s Amendment
was made for a reason unrelated to patentability. We thus
agree that Amgen surrendered equivalent but unclaimed
binders and disintegrants. Warner-Jenkinson, 520 U.S. at
41. It is estopped to claim equivalence to remedy a failure
of the accused product to meet the Markush limitations.
As a final argument, Amgen suggests that the tangen-
tial exception to prosecution history estoppel applies. How-
ever, Piramal uses pregelatinized starch as a binder, a use
taught by Creekmore and Hsu. “[A]n amendment made to
avoid prior art that contains the equivalent in question is
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 25
not tangential.” Intervet Inc. v. Merial Ltd., 617 F.3d 1282,
1291 (Fed. Cir. 2010).
E. Zydus’s Product
In its cross-appeal, Zydus asks us to reverse the district
court’s finding that Zydus’s product infringes the ’405 pa-
tent. At issue here is the starch in Zydus’s formulation. As
the district court noted, Zydus’s ANDA states that the pre-
gelatinized starch in Zydus’s formulation functions as a dil-
uent. But starch is listed in the diluent Markush group of
claim 1, so, if the starch in Zydus’s formulation truly func-
tions as a diluent, Zydus infringes claim 1.
Before the district court, Amgen argued that pregelat-
inized starch in Zydus’s formulation functions as a diluent,
but Zydus argued that the starch functions as a binder. To
support its position, Zydus adopted the testimony of Dr.
Davies, Amgen’s expert, that Amgen had proffered for its
argument about Piramal’s formulation. Dr. Davies opined
that pregelatinized starch’s native starch fraction func-
tions as a diluent but that its cold water soluble fraction
functions as a binder.
The district court did not find Dr. Davies’s testimony
credible for several reasons. For example, the court first
found that Dr. Davies’s opinion was inconsistent between
defendants. For Aurobindo 3 and Piramal, Dr. Davies pro-
vided his fractions opinion regarding the function of prege-
latinized starch, but for Zydus, Dr. Davies simply accepted
Zydus’s identification in its ANDA that pregelatinized
starch functions as a diluent. At trial, Dr. Davies modified
his opinion and testified that he was also applying his
3 Amgen also accused Aurobindo Pharma Ltd. and
Aurobindo Pharma USA, Inc. (collectively, “Aurobindo”) of
infringing the ’405 patent, and Amgen’s claims against Au-
robindo were tried alongside its claims against Amneal, Pi-
ramal, and Zydus but are not at issue in this appeal.
26 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
fractions opinion to Zydus. As a result, Dr. Davies testified
that Zydus’s product, which already uses 4.98% of hydrox-
ypropyl cellulose as a binder, also includes 3.97% of prege-
latinized starch as a binder. Dr. Davies thus opined that
Zydus’s formulation contains 8.95% by weight of binder,
which exceeds the “about 5%” binder limitation in claim 1.
When this opinion was challenged, Dr. Davies provided a
third opinion that was inconsistent with the court’s claim
construction.
The district court also discounted Dr. Davies’s testi-
mony because, while he consistently asserted that the func-
tion of pregelatinized starch was context-specific and could
vary based on the amount of pregelatinized starch, other
excipients present, and the manufacturing process, he did
not provide testimony applying those contextual factors to
each ANDA product. The court contrasted Dr. Davies’s tes-
timony with that of Aurobindo’s expert, Dr. Fassihi, and
Amneal’s expert, Dr. McConville, who did provide such
analysis.
Because the district court ultimately did not credit Dr.
Davies’s fraction opinion concerning pregelatinized starch,
it rejected Zydus’s noninfringement argument. The court
thus found that Zydus’s ANDA product infringed claim 1.
Zydus now argues on appeal that Amgen failed to prove
that pregelatinized starch is a listed binder in Zydus’s
product. Zydus again cites Dr. Davies’s fraction opinion
and testimony that pregelatinized starch functions as a
second binder in Zydus’s product. According to Zydus, the
district court required Zydus to disprove infringement, con-
trary to this court’s precedent. Zydus further contends that
the court’s consideration of testimony from other defend-
ants’ experts in evaluating Zydus’s products was improper
because it amounts to comparing the accused products to
one another. Zydus Br. 42.
Amgen responds that it met its burden to show in-
fringement. According to Amgen, it presented the district
AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC 27
court with Zydus’s ANDA, which explicitly discloses that
Zydus’s product uses pregelatinized starch as a diluent.
Amgen points further to Dr. Davies’s testimony that the
starch in Zydus’s product functions as a diluent. Amgen
suggests that the court was free to credit some aspects of
Dr. Davies’s testimony and reject others, which it chose to
do here.
We agree with Amgen that the district court did not
clearly err in finding that the pregelatinized starch in Zy-
dus’s product functions as a diluent. Zydus thus is an in-
fringer. Dr. Davies undoubtedly provided a wide range of
opinions regarding the starch in Zydus’s product. But the
district court repeatedly identified problems in Dr. Davies’s
“fractions opinion,” but not in his opinion that the prege-
latinized starch in Zydus’s product functions only as a dil-
uent. And the court was not required to reject all of Dr.
Davies’s testimony once finding any individual part of it
incorrect. See Bluebonnet Sav. Bank, F.S.B. v. United
States, 466 F.3d 1349, 1359 (Fed. Cir. 2006) (quoting White
Mountain Apache Tribe of Arizona v. United States, 11 Cl.
Ct. 614, 663 (1987)). Thus, the court was permitted to rely
on Dr. Davies’s initial opinion that the pregelatinized
starch in Zydus’s product functions as a diluent. See J.A.
3433:23–3434:5. And, expert testimony aside, the court
was certainly permitted to credit the statements in Zydus’s
own ANDA that the starch in its product functions as a dil-
uent.
Zydus’s argument that the district court incorrectly
compared the accused products is unfounded. In evaluat-
ing whether Dr. Davies’s testimony was credible, the court
was entitled to consider the record, including testimony
from other experts regarding the multifunctional nature of
excipients, before reaching its conclusion. At no point,
however, did the court compare Aurobindo’s or Piramal’s
products to Zydus’s in its analysis.
28 AMGEN INC. v. AMNEAL PHARMACEUTICALS LLC
CONCLUSION
We have considered the parties’ remaining arguments
but find them unpersuasive. Accordingly, the district
court’s judgment that Amneal does not infringe claims 1,
2–4, 6, 8–12, and 14–18 of the ’405 patent is vacated and
remanded for further proceedings consistent with this
opinion. The district court’s judgment that Piramal does
not infringe claims 1–6 and 8–20 of the ’405 patent and that
Zydus infringes claims 1–4, 6, 8–9, 15–17, and 19 of the
’405 patent is affirmed.
AFFIRMED-IN-PART, REVERSED-IN-PART,
VACATED-IN-PART, AND REMANDED
COSTS
No costs.