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-cv00925-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, Minneapolis, MN, argued for defendants-appellees Amneal Pharmaceuticals 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 Pharmaceuticals of New York LLC (collectively, “Amneal”) does not infringe 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 judgment 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 affirm with respect to Piramal and Zydus. 

BACKGROUND

Amgen holds approved New Drug Application 

No. 21688 for Sensipar®, a formulation of cinacalcet hydrochloride used to treat secondary hyperparathyroidism in 

adult patients with chronic kidney disease who are on dialysis and to treat hypercalcemia in patients with parathyroid cancer and primary and secondary 

hyperparathyroidism. Amneal, Piramal, and Zydus each 

filed an Abbreviated New Drug Application (ANDA) seeking to enter the market with a generic version of Sensipar®, 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 formulation of cinacalcet. Amgen asserted different claims 

against each defendant, but the parties stipulated that the 

infringement findings for claim 1 would extend to the majority 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 consisting 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 mixtures 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, hypercalcemia, and elevated calcium phosphorus product. 

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 originally 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 excipient, wherein” the composition achieved a specific dissolution 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 comprising specific ranges, by weight, of cinacalcet and various excipients:

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 consisting 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 evidenced 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 Examiner, 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 limitations. 

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 cinacalcet would not have been obvious in view of the teachings of Van Wagenen, which taught a broader range that 

“would translate to 0.62 mg to 3100 mg for an average human.” J.A. 9438–40.

After the Cinacalcet Amendment, the Examiner conducted 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 limitations into their current, Markush group format. The Examiner then allowed the claims, stating that the closest 

prior art did not disclose or render obvious the “combination of components . . . in the amounts . . . set forth in claim 

2.” J.A. 9462. 

Following the Notice of Allowance, Amgen filed a number of Requests for Continued Examination providing various 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 language that had been proposed by the Examiner in the Examiner’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 proposed pretrial order, Amgen argued that the Markush 

groups should be open to unrecited elements, but the district 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 overcome the very strong presumption that the Markush 

groups for the binder and disintegrant elements are closed 

to unrecited binders and disintegrants.” Amgen Inc. v. Aurobindo 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 infringement.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 bifurcated 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 Zydus infringes claims 1–4, 6, 8–9, 15–17, and 19. 

First, the district court found that Amneal does not infringe 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 contains hydroxypropyl methylcellulose (“HPMC”), polyethylene 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. Relying on its claim construction, however, the court found 

that Amneal’s product does not meet the disintegrant limitation. Id. at 385.

Next, the district court found that Piramal does not infringe because it does not meet the binder limitation. Piramal 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 formulation. Zydus’s ANDA states that the formulation uses pregelatinized starch as a diluent, and starch is listed in the 

diluent Markush group of claim 1. Zydus relied on testimony 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 infringes 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 appeal. 

“This court’s jurisdiction is governed by the final judgment 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 decisions” from district courts, which are decisions that end litigation 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-cv00853-MSG (July 27, 2018), ECF No. 376; J.A. 2. According to its own terms, the judgment did not resolve the parties’ 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 contingency 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 challenges 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 constructions 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 & Williamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120, 

1123 (Fed. Cir. 2000)). “A factual finding is clearly erroneous 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 erroneous.” 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 construction 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 evidence, 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, respectively, 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 similarly recited “comprising,” followed by “consisting of” terminology. 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 position. 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 additional 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. Considering the prosecution history, it found that the percentage 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 limitations 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 meaningless in view of the claim’s recitations of “mixtures 

thereof” within the Markush groups. Id. at 32 (citing Bicon, Inc. v. Straumann Co., 441 F.3d 945, 951 (Fed. Cir. 

2006)). 

For additional support, Amgen argues from the specification 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 Multilayer and that Amgen failed to overcome the strong presumption 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 limitation follows a general claim transition phrase of “comprising,” all components of an accused product that 

perform the general function of the particular limitation 

must meet the requirements of that limitation, thus precluding 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 restricted 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 homopolymers, copolymers, or terpolymers, of 

ethylene and alpha-olefins; and

(b) five identifiable inner layers, with each 

layer being selected from the group consisting 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 alpha-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 lexicographer to give “consisting of” an alternative, less restrictive 

meaning, “[b]ut to overcome the exceptionally strong presumption that a claim term set off with ‘consisting of’ is 

closed to unrecited elements, the specification and prosecution 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 concluded 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 “comprising” 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 layers. The only issue was whether element (b) by itself declared that each layer among the five inner ones was 

restricted to the listed resins. The Multilayer claim limitation required, in terms, that “each layer” among the identified 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 compositions containing as an active ingredient 5-aminosalicylic acid, comprising:

a) an inner lipophilic matrix consisting of 

substances selected from the group consisting 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 compounds selected from the group consisting 

of polymers or copolymers of acrylic or 

methacrylic acid, alkylvinyl polymers, hydroxyalkyl celluloses, carboxyalkyl celluloses, 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 explained 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 element (b), without any reliance on the “comprising” 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 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 composition “consists of” the compounds in the Markush group. 

The court considered the component of the appellee’s product that was alleged to meet that outer matrix limitation. 

That component, by the terms of element (b), had to “consist 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 component 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 formulation are subject to the specific binder or disintegrant limitations. 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 inconsistent with the overall composition containing other 

binders or disintegrants. The plain language of this claim 

requires “at least one” of the Markush members and certainly does not indicate that the only binders and disintegrants 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 follow. 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 recited in the Markush group may be included in the claimed 

formulation.

In short, this case involves a claim that uses a “comprising” transition phrase and one of the following limitations requires a component that “consists of” items listed in 

a Markush group and that meets the limitation’s requirements 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 limitation’s requirements for the component. It does not forbid 

infringement of the claim if an additional component is present 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 precluding 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 ingredients—binders, disintegrants, or otherwise—those constructions 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 disintegrant rendered Amneal’s product non-infringing. Because we have reversed the claim construction, we vacate 

and remand this finding. On remand, the court should consider 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 noninfringement 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 findings 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 undisputed below that Opadry is a composite product comprised 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, including 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 granulation 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 accurately 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 present in Amneal’s formulation. There will of course be differences 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 Amneal’s formulation, even if it was added as a component of 

another commercially available product. The claim requires only that HPMC be present, not that HPMC’s physical 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 consider 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 application 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 pregelatinized 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 instead 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 [patentee] 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 equivalents 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 [Cinacalcet] 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 understood these statements in the prosecution history to indicate 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. Instead, 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 Examiner 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 patentability. 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 argues 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 amendment could not have distinguished Creekmore or Hsu because those references already disclosed the excipients in 

the Markush groups. 

Piramal responds that Amgen’s acceptance of the Examiner’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 amendment. Piramal also argues that the addition of the 

Markush groups overcame the obviousness rejection. Piramal reads Creekmore to disclose 152 binder-disintegrant 

combinations and Hsu discloses 120 combinations. Thus, 

Piramal submits that the narrowed range of excipient combinations in the Examiner’s Amendment—which would include 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 equivalents argument is barred by prosecution history estoppel. 

Amgen amended its claims in two ways during prosecution—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 Cinacalcet 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 secure 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 Request for Continued Examination that the Examiner’s 

Amendment was added “to place the claims in proper format 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 statement provides into the reasons for the Examiner’s Amendment.

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 tangential exception to prosecution history estoppel applies. However, 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 patent. At issue here is the starch in Zydus’s formulation. As 

the district court noted, Zydus’s ANDA states that the pregelatinized starch in Zydus’s formulation functions as a diluent. But starch is listed in the diluent Markush group of 

claim 1, so, if the starch in Zydus’s formulation truly functions as a diluent, Zydus infringes claim 1. 

Before the district court, Amgen argued that pregelatinized 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 functions 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 Aurobindo3 and Piramal, Dr. Davies provided his fractions opinion regarding the function of pregelatinized 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 Aurobindo were tried alongside its claims against Amneal, Piramal, 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 hydroxypropyl cellulose as a binder, also includes 3.97% of pregelatinized 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 testimony because, while he consistently asserted that the function 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 testimony 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, contrary to this court’s precedent. Zydus further contends that 

the court’s consideration of testimony from other defendants’ 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 infringement. 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 Zydus’s product functions as a diluent. Zydus thus is an infringer. 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 pregelatinized starch in Zydus’s product functions only as a diluent. 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 diluent. 

Zydus’s argument that the district court incorrectly 

compared the accused products is unfounded. In evaluating 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.