Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-24-01664/USCOURTS-ca13-24-01664-0/pdf.json

Parties Involved:
Galderma Laboratories, L.P.
Appellant
Lupin Inc.
Appellee
Lupin Ltd.
Appellee
TCD Royalty Sub LP
Appellant

Document Text:

United States Court of Appeals 

for the Federal Circuit

______________________

GALDERMA LABORATORIES, L.P., TCD ROYALTY 

SUB LP,

Plaintiffs-Appellants

v.

LUPIN INC., LUPIN LTD.,

Defendants-Appellees

______________________

2024-1664

______________________

Appeal from the United States District Court for the 

District of Delaware in No. 1:21-cv-01710-SB, Circuit 

Judge Stephanos Bibas.

______________________

Decided: December 6, 2024

______________________

GERALD J. FLATTMANN, JR., Cahill Gordon & Reindel 

LLP, New York, NY, argued for plaintiffs-appellants. Also 

represented by ANDREW COCHRAN. 

 WILLIAM A. RAKOCZY, Rakoczy Molino Mazzochi Siwik 

LLP, Chicago, IL, argued for defendants-appellees. Also 

represented by KATIE BODA, JOSEPH THOMAS JAROS,

ADRIANNE C. ROSE.

 ______________________

Case: 24-1664 Document: 50 Page: 1 Filed: 12/06/2024
2 GALDERMA LABORATORIES, L.P. v. LUPIN INC.

Before MOORE, Chief Judge, LINN and PROST, Circuit 

Judges.

MOORE, Chief Judge.

Galderma Laboratories, L.P., TCD Royalty Sub LP 

(Galderma) appeals a decision from the United States 

District Court for the District of Delaware finding Lupin 

Inc. and Lupin Ltd.’s (collectively, Lupin) abbreviated new 

drug application (ANDA) does not infringe U.S. Patent 

No. 7,749,532 or U.S. Patent No. 8,206,740 (the Asserted 

Patents). Galderma Lab’ys L.P. v. Lupin Inc. & Lupin Ltd., 

No. 21-CV-1710, 2024 WL 1571686 (D. Del. Mar. 22, 2024)

(Decision). For the following reasons, we affirm.

BACKGROUND

Galderma owns and markets Oracea® (doxycycline 

USP) 40 mg capsules as a treatment for papules and 

pustules associated with rosacea. Following FDA approval, 

Oracea® was added to the Orange Book, which identified 

the Asserted Patents as encompassing Oracea®. The 

Asserted Patents share a common specification1 and are 

directed to a once-daily, oral pharmaceutical composition 

formulated as about 30 mg immediate release (IR), and 

about 10 mg delayed release (DR), doxycycline and 

methods of treatment using the composition. See ’532 

patent at claims 1, 15; ’740 patent at claims 1, 19. The 

claimed composition results in steady state blood levels of 

doxycycline between 0.1 μg/ml and 1.0 μg/ml. See ’532 

patent at claims 1, 15; ’740 patent at claims 1, 19.

Oracea® achieves the claimed steady state blood levels 

through this combination of IR and DR pellets in a once

daily dose. The IR portion is designed to “release 

substantially all of the active ingredient on administration 

1 Unless otherwise noted, we cite to only the ’532 

patent specification for brevity.

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GALDERMA LABORATORIES, L.P. v. LUPIN INC. 3

with no enhanced, delayed or extended release effect.” ’532 

patent at 4:5–8. The DR portion contains an enteric 

coating applied to the surface of the pellets such that “there 

is no substantial release of doxycycline in the acidic 

stomach environment of approximately below pH 4.5. The 

doxycycline becomes available when the pH-sensitive layer 

dissolves at the greater pH of the small intestine; after a 

certain delayed time; or after the unit passes through the 

stomach.” Id. at 7:47–52. In short, the IR portion is 

designed to release its doxycycline immediately upon 

ingestion in the fasted stomach, and the DR portion is 

designed to release its doxycycline at a delayed time when

it reaches an environment with a pH higher than 4.5.

The district court summarized the in vivo absorption of 

Oracea®. Decision at *1. To obtain the steady state blood 

levels required by the claims, some doxycycline is released 

right away, the IR portion, and some is released later, the 

DR portion. Upon ingestion, the capsule travels quickly to 

the fasted stomach where a low pH causes the IR portion 

to release its doxycycline. Id. The DR portion, however, 

designed to not release doxycycline until a higher pH, 

remains intact. Id. The composition then leaves the 

stomach and enters the small intestine, starting with the 

duodenum. Id. The duodenum has a higher pH, resulting 

in the DR portion beginning to release its doxycycline. Id. 

Lupin filed an ANDA to market a 40 mg doxycycline 

product, claiming bioequivalence to Oracea®. Lupin’s 

ANDA product is labeled as containing 22 mg IR and 18 mg 

DR. J.A. 6624.2 The prescribing information also describes 

its product as a 40 mg capsule composed of 22 mg IR and 

18 mg DR enteric coated pellets. J.A. 6635. Lupin’s ANDA 

Product achieves its DR effect by coating a portion of the 

pellets with Eudragit L30-D55, the same polymer used in 

Oracea®, which is designed to dissolve at and above pH 5.5. 

2 “J.A.” refers to the joint appendix.

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4 GALDERMA LABORATORIES, L.P. v. LUPIN INC.

The ANDA also contains comparative dissolution testing 

results at pH 1.1 HCl (Acid) and pH 4.5 Phosphate (Buffer) 

of Lupin’s ANDA product and Oracea®. J.A. 6559. 

Lupin submitted certifications under 21 U.S.C. 

§ 355(j)(2)(A)(vii)(IV) that the Asserted Patents are invalid 

or will not be infringed by Lupin’s ANDA product. In 

response, Galderma sued Lupin under the Hatch-Waxman 

Act for infringement of the Asserted Patents. Decision at

*2. Before trial, Galderma narrowed the case to four 

asserted claims: claims 1 and 16 of the ’532 patent, and 

claims 1 and 20 of the ’740 patent (the Asserted Claims). 

Id. Claim 1 of the ’532 patent is representative:

An oral pharmaceutical composition of doxycycline, 

which at a once-daily dosage will give steady state 

blood levels of doxycycline of a minimum of 0.1 

μg/ml and a maximum of 1.0 μg/ml, the 

composition consisting of (i) an immediate release 

(IR) portion comprising a drug, wherein the drug 

consists of about 30 mg doxycycline; (ii) a delayed 

release (DR) portion comprising a drug, wherein 

the drug consists of about 10 mg doxycycline, in 

which the DR portion is in the form of pellets coated 

with at least one enteric polymer; and (iii) one or 

more pharmaceutically acceptable excipients.

The district court construed the term “immediaterelease portion” to be “a functional limitation meaning any 

part of the claimed composition that releases drug 

immediately upon administration, with no enhanced, 

delayed or extended release effect.” Decision at *2. The 

district court construed “delayed-release portion” to be “a 

functional limitation meaning any part of the claimed 

composition that delays release of a drug until a time other 

than immediately following oral administration, e.g., 

through coating, uncoated matrix, or other impediment to 

delay release.” Id.

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GALDERMA LABORATORIES, L.P. v. LUPIN INC. 5

Galderma argued Lupin’s ANDA Product infringed the 

30 mg IR, 10 mg DR limitations of the Asserted Claims, 

despite Lupin’s ANDA stating its product contained 22 mg 

IR and 18 mg DR, because about 8 mg of Lupin’s ANDA 

product’s DR portion was actually an IR portion, resulting 

in a 30 mg IR, 10 mg DR product. Id. Galderma posited 

this was due to a “weak enteric coat” in the DR portion of 

Lupin’s ANDA Product, resulting in early release of some 

of the supposedly DR doxycycline. Id. at *3. Galderma 

explained that, while both Oracea® and Lupin’s ANDA 

Product use the same enteric polymer to coat the DR 

portion of their products, Lupin’s ANDA Product only has 

a pellet weight gain of 18% due to enteric coating, whereas 

Oracea® uses a 30% weight gain. Id.; J.A. 4873 at 104:7–9. 

Additionally, Galderma theorized Lupin’s use of methylene 

chloride in the coating process resulted in a weaker coat. 

Decision at *3; J.A. 4860 at 71:14–16. To prove its theory, 

Galderma relied mainly on the testimony of its expert, Dr. 

Rudnic, a two-stage in vitro dissolution test taking place at 

pH 1.1 and pH 4.5 from Lupin’s ANDA showing release of 

some doxycycline from its DR portion at pH 4.5, and 

bioequivalence data between Oracea® and Lupin’s ANDA 

Product. Decision at *3; J.A. 6559, 6520–21. Dr. Rudnic 

testified the two-stage dissolution test was relevant to the 

claims because pH 4.5 is found in the stomach, and the test 

showed some of the DR portion of Lupin’s ANDA Product 

would release its doxycycline immediately upon ingestion, 

resulting in a product with about 30 mg IR portion and 10 

mg DR portion. J.A. 4901 at 132:7–19.

Lupin argued its ANDA Product did not infringe. 

Decision at *3–4. Lupin’s Executive Vice President of 

Research and Development, Mr. Avachat, testified that any 

methylene chloride used in the manufacturing process 

evaporates away, J.A. 5115 at 346:17–18, and was not used 

to make the coating weak, J.A. 5113 at 344:14–19. Lupin’s 

dissolution expert, Ms. Gray, testified the two-stage 

dissolution test was unreliable because the percentage of 

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6 GALDERMA LABORATORIES, L.P. v. LUPIN INC.

dissolved doxycycline in the Oracea® tablets decreased over 

time and the results for Lupin’s ANDA Product had a high 

relative standard deviation. Decision at *4; J.A. 5167 at 

398:14–18, 5168 at 399:12–16. Ms. Gray also testified 

about a single-stage test Lupin performed during trial on a 

small batch of capsules (the “rebuttal batch”) that showed 

Lupin’s DR pellets did not dissolve at pH 4.5. Decision at 

*4; J.A. 5177 at 408:19–20. Lupin also presented testimony 

from Dr. Buckton, who disagreed with Dr. Rudnic’s 

conclusions regarding Lupin’s ANDA Product’s coating 

weakness due to an 18% weight gain and the two-stage 

dissolution test results. Decision, at *4; J.A. 5306 at 

537:16–18, 5294–95 at 525:5–526:20.

The district court, after a three-day bench trial, found 

Lupin did not infringe the Asserted Patents.3 Decision at 

*8. Specifically, the district court found Dr. Rudnic did not

provide any evidence of how many pellets would get a 

lighter coating or how Lupin’s ANDA showed insufficient 

coating of the DR pellets. Id. at *5. The district court 

credited the testimony of Dr. Buckton, Lupin’s expert, that 

the two-stage dissolution test was not representative of the 

in vivo behavior of Lupin’s ANDA Product. Id. at *6. The 

district court also found that, even if the test did reflect in 

vivo behavior, evident flaws in the data called the 

reliability of the results into question. Id. This was 

confirmed by the single-stage test using a batch of capsules 

produced with a rebuttal expert report of capsules, which 

showed no release of doxycycline from the DR pellets at pH 

4.5. Id. 

The district court found Galderma had not shown 

infringement via the doctrine of equivalents under either 

the function-way-result test or the insubstantial 

differences test. Id. at *8. Finally, the district court held 

3 Lupin did not present any validity challenges in 

the district court. J.A. 222–41.

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GALDERMA LABORATORIES, L.P. v. LUPIN INC. 7

Galderma did not show contributory or induced

infringement, because there was no finding of direct 

infringement. Id. Galderma appeals. We have jurisdiction 

under 28 U.S.C. § 1295(a)(1). 

DISCUSSION

Galderma argues on appeal the district court erred in 

four ways: (1) disregarding controlling data in Lupin’s 

ANDA, specifically the two-stage dissolution test, (2) 

allowing into evidence the results of the single-stage test 

using the rebuttal batch, (3) imposing limitations not 

present in the claims, and (4) not finding infringement 

under the doctrine of equivalents. We do not agree.

I.

Following a bench trial, we review a district court’s 

conclusions of law de novo and its factual findings for clear 

error. Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1303 

(Fed. Cir. 2015). Infringement is a question of fact we 

review for clear error. Alza Corp. v. Mylan Labs., Inc., 464 

F.3d 1286, 1289 (Fed. Cir. 2006). Under the clear-error 

standard, we defer to the district court’s findings “in the 

absence of a definite and firm conviction that a mistake has 

been made.” Scanner Techs. Corp. v. ICOS Vision Sys. 

Corp. N.V., 528 F.3d 1365, 1374 (Fed. Cir. 2008) (cleaned 

up). 

It is an act of infringement to submit an ANDA seeking 

FDA approval to make and sell a patented drug. 35 U.S.C. 

§ 271(e)(2); Warner-Lambert Co. v. Apotex Corp., 316 F.3d 

1348, 1358 (Fed. Cir. 2003). Because the characteristics of 

a proposed ANDA product may not be established until the 

ANDA is approved, to determine infringement under 

§ 271(e)(2), courts must conduct an inquiry to determine 

whether the probable ANDA product would infringe once it 

is made, used, or sold. Glaxo, Inc. v. Novopharm, Ltd., 110 

F.3d 1562, 1569 (Fed. Cir. 1997). The “ANDA specification 

directly resolves the infringement question” if “it defines a 

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8 GALDERMA LABORATORIES, L.P. v. LUPIN INC.

proposed generic product in a manner that either meets the 

limitations of an asserted patent claim or is outside the 

scope of such a claim.” Ferring B.V. v. Watson Labs., Inc.-

Fla., 764 F.3d 1401, 1408–09 (Fed. Cir. 2014). If the ANDA 

specification does not speak clearly and directly to the 

question of infringement, courts may look to other relevant 

evidence, such as data or samples the ANDA filer has 

submitted to the FDA, to assess whether a proposed 

product will infringe. Id. at 1409.

Galderma argues the district court clearly erred in 

disregarding the two-stage dissolution test in Lupin’s 

ANDA. Galderma argues the two-stage dissolution test

proves Lupin’s ANDA Product releases about 8 mg of 

doxycycline from the labeled DR portion at pH 4.5. 

J.A. 6559. For example, the test results show capsule 1 

released 78% doxycycline at time 150 minutes in pH 4.5. 

Id. This translates to 78% of a total of 40 mg of doxycycline 

released, or about 30 mg. Galderma asserts pH 4.5 is 

relevant to infringement because evidence at trial showed 

pH 4.5 is present in the stomach at the time of 

administration of Lupin’s ANDA Product. Therefore, any 

product released at pH 4.5 is functionally immediate 

release. Additionally, the specification of the Asserted 

Patents notes the claimed DR portion should not release at 

pH 4.5, making any release at pH 4.5 necessarily a 

component of the IR portion. Opening Br. 15 (citing ’532 

patent at 7:47–53). 

Lupin responds the district court did not disregard the 

two-stage dissolution test. Instead, the district court 

considered Galderma’s arguments, but found the secondstage pH of 4.5 in the test was not physiologically relevant 

for a fasted stomach. Decision at *6. Therefore, the district 

court correctly found “Galderma cannot draw valid 

conclusions about in vivo behavior by looking to the secondstage results at pH 4.5.” Id. We see no clear error in the 

district court’s findings. 

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GALDERMA LABORATORIES, L.P. v. LUPIN INC. 9

The district court found Galderma improperly drew 

conclusions about in vivo behavior from the two-stage in 

vitro dissolution test. Decision at *5. Specifically, the 

district court found “the pH of a fasted stomach is between 

1 and 2, though it could be slightly higher for a short time 

right after drinking water.” Id. at *6. The district court 

credited the testimony of Dr. Buckton and a paper 

submitted by Galderma. Id. (citing J.A. 5255 at 486:8–13

(“1 to 2 is a fasting figure.”); J.A. 5592 (“Median pH value 

was 2.4 twenty minutes after administration of water and 

stabilized to 1.7 at later time points.”)). The district court 

also credited Dr. Buckton’s testimony that pH 4.5 better 

approximates the pH of the duodenum, where the DR

portion is supposed to release its doxycycline. Id. While

Dr. Rudnic testified that upon ingestion of the water 

required with Lupin’s ANDA Product the pH of a fasted 

stomach will rise to pH 4.5, J.A. 4839:10–22, the district 

court did not clearly err in crediting Dr. Buckton over Dr. 

Rudnic. Anderson v. City of Bessemer City, N.C., 470 U.S. 

564, 575 (1985) (“When findings are based on 

determinations regarding the credibility of witnesses, Rule 

52(a) demands even greater deference to the trial court’s 

findings.”). Dr. Rudnic relied on a paper which explicitly 

states “[m]edian pH value was 2.4” after administration of 

water. J.A. 5592. The district court did not clearly err in 

finding Galderma did not prove the two-stage dissolution 

test represented in vivo behavior of Lupin’s ANDA Product, 

and therefore Galderma did not prove its theory of 

infringement.

Galderma also disputes the district court’s alternative

finding that even if the two-stage dissolution test results 

represented in vivo conditions, “evident flaws” in the data 

show it is unreliable. Decision at *6–7. Because we find no 

clear error in the district court’s finding that Galderma did 

not prove the two-stage dissolution test represented in vivo

behavior of Lupin’s ANDA Product, we need not reach the

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10 GALDERMA LABORATORIES, L.P. v. LUPIN INC.

district court’s analysis regarding the reliability of the 

test’s data. 

II.

Galderma argues the district court abused its 

discretion in admitting evidence regarding the rebuttal 

batch and legally erred in relying on the evidence to find 

noninfringement. The district court, to the extent it relied 

on rebuttal batch evidence at all,

4 did so to support its 

finding that the data from the two-stage dissolution test 

was unreliable. Decision at *6. Because we affirm the 

district court’s finding Galderma did not prove the twostage dissolution test represented in vivo behavior of 

Lupin’s ANDA Product, we need not reach this issue.

III.

Galderma argues the district court imposed limitations 

during its infringement analysis not required by the 

Asserted Claims. Lupin responds the district court did not 

impose any additional claim limitations, and Galderma

merely takes issue with the district court’s factual findings. 

We agree with Lupin. 

Galderma argues the court imposed a pH limitation, 

based on the testimony of Dr. Buckton, and used this 

limitation to improperly differentiate between the IR and 

DR portions of Lupin’s ANDA Product. The district court’s 

reliance on pH ranges was limited to its analysis of 

whether the two-stage dissolution test represented in vivo 

behavior of Lupin’s ANDA Product in its evaluation of 

Galderma’s infringement theory. See Decision at *6. As 

4 As the district court noted in its denial of 

Galderma’s emergency-injunction motion “even if it were 

error for me to consider the small batch, the testing on that 

batch merely reinforced the lack of patent infringement.” 

J.A. 31.

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GALDERMA LABORATORIES, L.P. v. LUPIN INC. 11

already discussed, the district court’s finding on this issue

was not clearly erroneous. 

For temporal limitations, Galderma argues the district 

court required an exact thirty-minute cutoff between the 

IR and DR portions. The district court did not impose this 

requirement. Instead, the district court used thirty 

minutes as an example of a possible distinction between 

immediate and delayed release, noting “if release is 

‘delayed’ after thirty minutes, it is ‘immediate’ before then.” 

Decision at *2. The district court also took issue with 

Galderma’s explanation of the relevance of the time 

capsules spent at the different pH levels in the two-stage 

dissolution test. It explained “the first stage is not just a 

stress test: it represents the capsule’s arriving in the 

stomach and spending time at pH 1.1.” Decision at *6. 

This is a factual finding regarding Galderma’s 

infringement theory, and not an imposition of any claim 

limitations. Finally, the district court stated that “if [it]

credited that Capsule 1’s behavior at [thirty] minutes into 

the second stage reflects in vivo behavior at that time in 

the stomach, Galderma would have shown infringement.” 

Decision at *7. But the district court did not find a 

capsule’s behavior thirty minutes into the second stage of 

the dissolution test reflected in vivo behavior. It found 

Galderma did not prove the two-stage dissolution test 

represented in vivo behavior. This finding, which was not 

clearly erroneous, foreclosed the use of the two-stage 

dissolution test at pH 4.5 to show infringement. The 

district court’s statement did not, as Galderma argues, 

impose a strict thirty-minute cutoff between IR and DR.

Finally, Galderma argues the district court imposed

unspecified structural limitations. Galderma takes issue 

with the district court’s finding that Galderma “never 

explained how [the district court] can infer that a certain 

percentage of pellets will leak based on a certain 

percentage of capsules leaking.” Decision at *7. The 

district court did not impose any structural claim 

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12 GALDERMA LABORATORIES, L.P. v. LUPIN INC.

limitations, but was, again, explaining a factual issue with 

Galderma’s theory of infringement based on the two-stage 

dissolution test. 

IV.

Galderma also raises several factual disputes 

regarding the district court’s analysis of infringement 

under the doctrine of equivalents. We see no clear error in 

the district court’s findings.

The doctrine of equivalents is “limitation specific, not 

focused only on the claim as a whole.” VLSI Tech. LLC v. 

Intel Corp., 87 F.4th 1332, 1342 (Fed. Cir. 2023). The 

doctrine asks “whether a substitute element matches the 

function, way, and result of the claimed element,” or 

whether there are only “insubstantial differences.”

Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 

520 U.S. 17, 40 (1997). 

The district court found Galderma did not show 

infringement under the doctrine of equivalents under 

either test. Decision at *7–8. Under the “function, way, 

result” test, the district court found Galderma did not show 

Lupin’s ANDA Product released either 30 mg immediately 

or 10 mg after a delay. Id. at *8. The district court noted 

Galderma argued bioequivalence was enough, but that 

only went to the result portion of the test. Id. Under the 

“insubstantial differences” test, the district court found the

evidence showed Lupin’s ANDA Product has a 22 mg IR 

and 18 mg DR portion, which is substantially different 

from the Asserted Claims. Id. We see no clear error in 

these findings.

Galderma argues the two-stage in vitro dissolution test 

in combination with the in vivo bioequivalence data 

satisfies both tests. For the “function, way, result” test,

Galderma argues the two-stage dissolution test shows at 

pH 4.5 Lupin’s ANDA Product functions as a 30 mg IR, 10 

mg DR product by releasing doxycycline from the DR 

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GALDERMA LABORATORIES, L.P. v. LUPIN INC. 13

portion at pH 4.5, and performs in substantially the same 

way by having a Eudragit L30-D55 coating. For 

substantially the same result, Galderma argues this is 

satisfied because the FDA deemed Lupin’s ANDA Products 

bioequivalent to Oracea®. Galderma argues this same data 

also satisfies the “insubstantial differences” test. Finally, 

Galderma argues the mean data from the two-stage 

dissolution test at pH 4.5 show Lupin’s ANDA Product will 

result in IR and DR portions equivalent to the Asserted 

Claims. 

We see no clear error in the district court’s findings that 

this evidence does not prove infringement under the 

doctrine of equivalents. As discussed, supra, the district 

court did not clearly err in finding Galderma did not prove 

the two-stage dissolution test represented relevant in vivo 

conditions such that the data correlated to the Asserted 

Claims’ requirements. That leaves only Galderma’s

evidence of bioequivalence, which at most showed 

substantially the same result. This is insufficient to meet 

either the “function, way, result” test or the “insubstantial 

differences” test.

CONCLUSION

We have considered Galderma’s other arguments and 

find them unpersuasive. Because the district court did not 

clearly err in finding Lupin’s ANDA Product does not 

infringe the Asserted Patents, we affirm.

AFFIRMED

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