ASTRAZENECA AB et al v. DR. REDDY'S LABORATORIES INC. et al

Filing 498

REDACTED AMENDED MEMORANDUM OPINION filed. Signed by Judge Mary L. Cooper on 7/10/2017. (mps)

UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY
HORIZON PHARMA, INC. and POZEN :
INC.,
:
Case No. 11-2317 (MLC) (DEA)
REDACTED
:
Plaintiffs,
: AMENDED MEMORANDUM OPINION :
v.

:
:
DR. REDDY’S LABORATORIES,
:
INC., et al.,
:
:
Defendants.
:
__________________________________ :
COOPER, District Judge
I. Background.............................................................................................................................. 2
II. Legal Standards ....................................................................................................................... 6
A. Infringement ......................................................................................................................... 6
B. Written Description.............................................................................................................. 7
C. Enablement / Utility ............................................................................................................. 8
D. Obviousness ......................................................................................................................... 9
III.

Infringement and Related § 112 Challenges to the ’285 Patent ...................................... 10

A. Written Description (Uncoated Naproxen) ...................................................................... 11
B. Written Description (Sustained Release Formulations) ................................................... 23
C. Infringement ....................................................................................................................... 27
IV.

Obviousness and Related § 112 Challenges ..................................................................... 31

A. Obviousness ....................................................................................................................... 31
B. Enablement......................................................................................................................... 59
C. Written Description (Uncoated PPI) ................................................................................. 62
V. Conclusion ............................................................................................................................. 65

I.

Background
This is a patent dispute between Plaintiffs Horizon Pharma, Inc. and Pozen Inc.

(together, “Horizon”) and two groups of generic drug manufacturers: (1) Dr. Reddy’s
Laboratories, Inc. and Dr. Reddy’s Laboratories, Ltd. (“DRL”); and (2) Mylan, Inc.; Mylan
Pharmaceuticals Inc.; and Mylan Laboratories Ltd. (“Mylan,” and together with DRL,
“Defendants”). Horizon holds New Drug Application (“NDA”) No. 022511 for Vimovo, a
branded drug product whose active pharmaceutical ingredients are naproxen and
esomeprazole magnesium. (Dkt. 421 at 6.)1
This case arises out of Defendants’ submission of Abbreviated New Drug
Applications (“ANDAs”) to the FDA pursuant to the Hatch-Waxman Act, 21 U.S.C.
§ 355(j), for the purpose of obtaining FDA approval for the commercial manufacture, use,
import, offer for sale, and sale of a generic version of Vimovo. Specifically, DRL filed
ANDA No. 202461 (“DRL ANDA I”) and ANDA No. 204206 (DRL ANDA II”). Mylan
filed ANDA No. 204920 (“Mylan ANDA”). Based on submissions by the parties in the pretrial order, all three ANDAs relate to tablets containing 375 mg or 500 mg of naproxen and 20
mg esomeprazole magnesium. (Dkt. 421 at 7–8.)2 All three ANDAs included so-called
“Paragraph IV” certifications that the products would not infringe Horizon’s patents and/or
that those patents are invalid or unenforceable. (Id.) The Paragraph IV certifications covered
U.S. Patent No. 6,926,907 (“the ’907 patent”) and No. 8,557,285 (“the ’285 patent”)
1

The Court will cite documents filed on the Electronic Case Filing System (“ECF”) by referring to
the docket entry numbers as “dkt.” Pincites reference ECF pagination.
2

Lupin Pharmaceuticals, Inc. and Lupin Ltd. (“Lupin”) submitted an ANDA filing (No. 202654).
Horizon’s case against Lupin (Case No. 11-4275) has been stayed pending the outcome of this case.
(Dkt. 455.)

2

(together, the “Asserted Patents”). In response to those Paragraph IV certifications,
Horizon asserted infringement of claims 5, 15, 52, and 53 of the ’907 patent.3 Horizon
has also asserted claims 1 through 4 of the ’285 patent.4
Mylan has stipulated that its ANDA product would infringe the Asserted Patents.
(Dkt. 421 at 8.) DRL has admitted that its DRL ANDA I Product would infringe the Asserted
Patents. (Id.) We previously granted summary judgment in DRL’s favor that its ANDA II
3

The asserted claims of the ’907 patent (together with claim 1 for context) are:
1. A pharmaceutical composition in unit dose form suitable for oral administration to a
patient, comprising:
(a) an acid inhibitor present in an amount effective to raise the gastric pH of said patient
to at least 3.5 upon the administration of one or more of said unit dosage forms;
(b) a non-steroidal anti-inflammatory drug (NSAID) in an amount effective to reduce or
eliminate pain or inflammation in said patient upon administration of one or more of
said unit dosage forms; and wherein said unit dosage form provides for coordinated
release such that:
i) said NSAID is surrounded by a coating that, upon ingestion of said unit dosage form
by said patient, prevents the release of essentially any NSAID from said dosage form
unless the pH of the surrounding medium is 3.5 or higher;
ii) at least a portion of said acid inhibitor is not surrounded by an enteric coating and, upon
ingestion of said unit dosage form by said patient, is released regardless of whether the
pH of the surrounding medium is below 3.5 or above 3.5.
5. The pharmaceutical composition of claim 1, wherein said acid inhibitor is a proton pump
inhibitor selected from the group consisting of: omeprazole, esomeprazole, lansoprazole,
pantoprazole and rabeprazole.
15. The pharmaceutical composition of . . . claim[] 1 . . . wherein said acid inhibitor is a
proton pump inhibitor.
51. A method of treating a patient for pain or inflammation, comprising administering to
said patient the pharmaceutical composition of claim 15.
52. The method of claim 51, wherein said pain or inflammation is due to either
osteoarthritis or rheumatoid arthritis.
53. The pharmaceutical composition of any one of claims 5-11 wherein said unit dosage form
is a multilayer tablet comprising a single core and one or more layers outside of said single core,
wherein:
i) said NSAID is present in said core;
ii) said coating that does not release said NSAID unless the pH of the surrounding medium is
3.5 or higher surrounds said core; and
iii) said acid inhibitor is in said one [or] more layers outside said core.
(’907 patent at col. 20, line 9 to col. 24, line 6.)

3

Product does not infringe the ’907 patent. (Dkt. 380). Accordingly, the only infringement
dispute at trial was whether DRL’s ANDA II Product infringes the ’285 patent. Most of the
trial was focused on Defendants’ contentions that claims in the Asserted Patents are invalid
under 35 U.S.C. § 103 and/or § 112.
We held a six day bench trial on those issues from January 12–20, 2017 and heard
closing arguments on May 17, 2017.5 We heard live testimony from seven witnesses. Dr.
John Plachetka, called by Horizon, was the named inventor on the Asserted Patents. (Tr. 15–
192.) Dr. David Metz, called by Defendants, was qualified as an expert in gastroenterology,
including the treatment of acid peptic disorder. (Tr. 260–396.) Dr. Arthur Kibbe, called by
Defendants, was qualified as an expert in pharmaceutical formulation and development. (Tr.

4

The asserted claims of the ’285 patent are as follows:
1. A pharmaceutical composition in unit dosage form comprising therapeutically effective
amounts of:
(a) esomeprazole, wherein at least a portion of said esomeprazole is not surrounded by an
enteric coating; and
(b) naproxen surrounded by a coating that inhibits its release from said unit dosage form unless
said dosage form is in a medium with a pH of 3.5 or higher;
wherein said unit dosage form provides for release of said esomeprazole such that upon
introduction of said unit dosage form into a medium, at least a portion of said esomeprazole
is released regardless of the pH of the medium.
2. The pharmaceutical composition of claim 1, wherein naproxen is present in said unit dosage
form in an amount of 200-600 mg.
3. The pharmaceutical composition of claim 1, wherein esomeprazole is present in said unit
dosage form in an amount of from 5 to 100 mg.
4. The pharmaceutical composition of claim 1, wherein naproxen is present in said unit dosage
form in an amount of between 200-600 mg and esomeprazole in an amount of from 5 to 100
mg per unit dosage form.
(’285 patent at col. 22, lines 8–28.)
5

The trial transcript is separated into seven volumes, but the pages are numbered consecutively. (See
dkt. 458 (Vol. 1), dkt. 461 (Vol. 2), dkt. 463 (Vol. 3), dkt. 466 (Vol. 4), dkt. 468 (Vol. 5), dkt. 471
(Vol. 6), and dkt. 491 (Vol. 7).) We will cite to the trial transcript using the designation “Tr.” without
indicating the specific volume.

4

408–565.) Dr. Michael Mayersohn, called by Defendants, was qualified as an expert on
pharmacokinetics and pharmacodynamics. (Tr. 569–603; Tr. 610–707.) Dr. Robert
Williams, III, called by Horizon, was qualified as an expert in pharmaceutical formulation.
(Tr. 716–842; Tr. 849–1017.) Dr. David Taft, called by Horizon, was qualified as an expert
in pharmacokinetics. (Tr. 1018–1102.) Dr. David Johnson, called by Horizon, was qualified
as an expert in gastroenterology. (Tr. 1108–1266.) The parties also submitted designated
deposition testimony from Brian Ault (DTX-1393); Mark Sostek (DTX-1396); Jeff Sherman
(DTX-1397); Dennis McNamara (DTX-1398); Abhijit Desmukh (PTX-581); John Horn
(PTX-582); T. Sudhakar Koudinya (PTX-583); Snehalatha Movva (PTX-584); and Badri
Viswanathan (PTX-585).6
This opinion follows the parties’ division of the relevant legal issues raised at trial and
addresses the interrelated infringement and § 112 issues in Section III, infra, and the
interrelated obviousness and § 112 issues in Section IV, infra. In support of their arguments,
Horizon and Defendants submitted separate post-trial briefs on the issues addressed in Section
III (dkt. 489-2; dkt. 489-3) and Section IV (dkt. 489; dkt. 489-1).
For the reasons below, we conclude that DRL’s ANDA II Product infringes the ’285
patent and that the asserted claims are not invalid under 35 U.S.C. § 103 and/or § 112.
Accordingly, we will grant judgment in Horizon’s favor and issue an appropriate order.

6

Defendants object to Dr. Horn’s deposition testimony as inadmissible hearsay. (Dkt. 472.) We
conclude that Dr. Horn’s testimony is admissible because it satisfies the requirements of the hearsay
exception in Federal Rule of Civil Procedure 32(a) for deposition testimony of an unavailable witness.
See Novozymes A/S v. Genencor Int'l, Inc., No. 05-160, 2006 WL 318936, at *1 (D. Del. Feb. 10,
2006). We note, however, that the exclusion of Dr. Horn’s testimony would not have changed any of
our conclusions in this opinion.

5

II.

Legal Standards
A.

Infringement

The standard for patent infringement is set forth in 35 U.S.C. § 271, which states that
“whoever without authority makes, uses, offers to sell, or sells any patented invention, within
the United States or imports into the United States any patented invention during the term of
the patent therefor, infringes the patent.” 35 U.S.C. § 271(a). The burden to prove
infringement rests with the patentee who must prove infringement by a preponderance of the
evidence. Medtronic, Inc. v. Mirowski Family Ventures, LLC, 134 S. Ct. 843, 846 (2014).
To prove infringement, the patentee must show that an accused product is within the claim
limitations of the patent-in-suit either literally or under the doctrine of equivalents. See
Warner Jenkinson Co., Inc. v. Hilton Davis Chem. Co., 520 U.S. 17, 21 (1997); Amgen Inc.
v. F. Hoffman La Roche Ltd., 580 F. 3d 1340, 1374 (Fed. Cir. 2009). In a Hatch-Waxman
case, the actual act of infringement is the filing of an ANDA to obtain approval to engage
in the commercial manufacture, use, or sale of a patented drug or method of use. 35
U.S.C. § 271(e)(2). Specifically, § 271(e)(2)(A) provides that it shall be an act of
infringement to submit an ANDA “if the purpose of such submission is to obtain
approval . . . to engage in the commercial manufacture, use, or sale of a drug . . . claimed
in a patent or the use of which is claimed in a patent before the expiration of such patent.”
The infringement analysis is a two-step process in which we must: (1) determine the
scope and meaning of the disputed patent claim terms; and (2) compare the properly
construed claims to the allegedly infringing product or device. Advanced Steel Recovery,
LLC v. X-Body Equip., Inc., 808 F.3d 1313, 1316 (Fed. Cir. 2015).
6

B.

Written Description

A patent specification must contain “a written description of the invention.”
35 U.S.C. § 112(a). To satisfy that requirement, “the specification must describe an
invention understandable to [a] skilled artisan and show that the inventor actually
invented the invention claimed.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
1351 (Fed. Cir. 2010). “The purpose of the written description requirement is to prevent
an applicant from later asserting that he invented that which he did not.” Amgen Inc. v.
Hoechst Marion Roussel, 314 F.3d 1313, 1330 (Fed. Cir. 2003). The requirement thus
mandates that the applicant “recount his invention in such detail that his future claims can
be determined to be encompassed within his original creation.” Vas-Cath Inc. v.
Mahurkar, 935 F.2d 1555, 1561 (Fed. Cir. 1991).
The “hallmark of written description is disclosure,” and the test for its sufficiency
is “whether the disclosure . . . reasonably conveys to those skilled in the art that the
inventor had possession of the claimed subject matter as of the filing date.” Ariad, 598
F.3d at 1351. “It is the specification itself that must demonstrate possession” and
analysis of the adequacy of the written description “requires an objective inquiry into the
four corners of the specification from the perspective of a person of ordinary skill in the
art.” Id. at 1351–52. The disclosure must “allow one skilled in the art to visualize or
recognize the identity of the subject matter purportedly described.” Enzo Biochem, Inc.
v. Gen-Probe Inc., 323 F.3d 956, 968 (Fed. Cir. 2002).
“There is no rigid requirement that the disclosure contain ‘either examples or an
actual reduction to practice.’” Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1308 (Fed.
7

Cir. 2015) (quoting Ariad, 598 F.3d at 1352). Rather, “the proper inquiry is whether the
patentee has provided an adequate description that ‘in a definite way identifies the
claimed invention’ in sufficient detail such that a person of ordinary skill would
understand that the inventor had made the invention at the time of filing.” Id. at 1308.
Moreover, “an applicant is not required to describe in the specification every conceivable
and possible future embodiment of his invention.” See Cordis Corp. v. Medtronic AVE,
Inc., 339 F.3d 1352, 1365 (Fed. Cir. 2003). The challenging party must show lack of
adequate written description by clear and convincing evidence to rebut the patent’s
presumption of validity. Alcon Research Ltd. v. Barr Labs., Inc., 745 F.3d 1180, 1188–
91 (Fed. Cir. 2014).
C.

Enablement / Utility

35 U.S.C. § 112 requires applicants to describe the manner of making and using
the invention “in such full, clear, concise, and exact terms as to enable any person skilled
in the art . . . to make and use the same . . . .” The Federal Circuit has explained that “the
how to use prong of section 112 incorporates as a matter of law the requirement of 35
U.S.C. § 101 that the specification disclose as a matter of fact a practical utility for the
invention.” Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1323 (Fed. Cir.
2005) (citing In re Cortright, 165 F.3d 1353, 1356 (Fed. Cir. 1999)). As a result, “an
applicant’s failure to disclose how to use an invention may support a rejection under . . .
section 112 . . . when there is a complete absence of data supporting the statements which set
forth the desired results of the claimed invention.” Id. (internal quotations omitted).
Conversely, “a specification disclosure which contains a teaching of the manner and
8

4

process of making and using the invention . . . must be taken as in compliance with the
enabling requirement of the first paragraph of [section] 112 unless there is reason to
doubt the objective truth of the statements contained therein which must be relied on for
enabling support.” Id. The challenging party bears the burden of showing by clear and
convincing evidence that the specification lacks adequate enablement. ALZA Corp. v.
Andrx Pharms., 603 F.3d 935, 940 (Fed. Cir. 2010).
D.

Obviousness

Under 35 U.S.C. § 103, a “patent may not be obtained . . . if the differences between
the subject matter sought to be patented and the prior art are such that the subject matter as a
whole would have been obvious at the time the invention was made to a person having
ordinary skill in the art to which said subject matter pertains.” “Obviousness is a question of
law, which depends on several underlying factual inquiries.” See Senju Pharm. Co. v. Apotex
Inc., 717 F. Supp.2d 404, 418 (D. Del. 2010), aff’d, 485 Fed. App’x 433 (Fed. Cir. 2012).
Those inquiries include the scope and content of the prior art, differences between the prior art
and the claims at issue, and the level of ordinary skill in the pertinent art. KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 406 (2007) (quoting Graham v. John Deere Co., 383 U.S. 1, 1718 (1966)). We also consider as part of the obviousness analysis “secondary considerations,”
including commercial success, long felt but unsolved needs, and failure of others. Id. “A
nonmovant may rebut a prima facie showing of obviousness with objective indicia of
nonobviousness.” Ormco Corp. v. Align Tech., Inc., 463 F.3d 1299, 1311 (Fed. Cir.
2006). “Although secondary considerations must be taken into account, they do not

9

necessarily control the obviousness conclusion.” In re Huai–Hung Kao, 639 F.3d 1057,
1068 (Fed. Cir. 2011).
“[A] patent composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently, known in the prior art.” Id. at
418; see also Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011).
Instead, proof of obviousness requires proof that a person of ordinary skill in the art
(“POSA”) “would have been motivated to combine the teachings of the prior art references to
achieve the claimed invention, and . . . would have had a reasonable expectation of success in
doing so.” Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989, 994 (Fed. Cir.
2009). A POSA would interpret prior art references “using common sense and appropriate
perspective.” Unigene Labs., 655 F.3d at 1361. The party challenging the validity of the
patent must prove obviousness by clear and convincing evidence. See Novo Nordisk A/S v.
Caraco Pharm. Labs., Ltd., 719 F.3d 1346, 1352 (Fed. Cir. 2013)
III.

Infringement and Related § 112 Challenges to the ’285 Patent
The only infringement question at trial was whether DRL’s ANDA II Product

infringes claims 1, 2, 3, and 4 of the ’285 patent. See Section I, supra. Horizon submitted
evidence that DRL’s ANDA II Product satisfies each limitation of the asserted claims. In
response, Defendants offer a pair of arguments in the alternative. One argument (and, per
Defendants, the “better decision” for us to reach) is that the asserted ’285 patent claims are
invalid for lack of written description on two distinct grounds. The other is that DRL’s
ANDA II Product cannot infringe the ’285 patent if we construe the claims such that they

10

survive the written description challenges. In this section, we reject both written description
challenges and conclude that DRL’s ANDA II Product infringes the ’285 patent.
A.

Written Description (Uncoated Naproxen)

Defendants’ first written description challenge involves two primary contentions.
First, Defendants contend that claim 1 of the ’285 patent encompasses formulations that
include naproxen that is released immediately. Second, they contend that the ’285 patent
specification discloses a coordinated release product that does not permit the immediate
release of naproxen. This purported disconnect between the scope of the claims and the
specification forms the basis of the written description challenge. This section consequently
proceeds in two parts. First, we review the parties’ evidence and arguments related to the
scope of the ’285 patent claims and the written description of the invention in the ’285 patent
specification. Second, we assess whether the ’285 patent claims are adequately described by
the patent specification under the applicable legal standards.
1.

Parties’ Evidence and Arguments
(i)

Scope of the ’285 patent claims

Claim 1 of the ’285 patent reads:
A pharmaceutical composition in unit dosage form comprising
therapeutically effective amounts of:
(a) esomeprazole, wherein at least a portion of said esomeprazole
is not surrounded by an enteric coating; and
(b) naproxen surrounded by a coating that inhibits its release from
said unit dosage form unless said dosage form is in a medium
with a pH of 3.5 or higher;
wherein said unit dosage form provides for release of said
esomeprazole such that upon introduction of said unit dosage form
11

into a medium, at least a portion of said esomeprazole is released
regardless of the pH of the medium.
(’285 patent at col. 22, lines 8–14.)
Any product alleged to infringe claim 1 must, of course, satisfy the enteric coated
naproxen claim limitation set forth in subsection (b). The question before us is the scope of
claim 1 as it pertains to uncoated naproxen that may be released into the body immediately
regardless of pH level.7 The plain language of claim 1 does not explicitly restrict the amount
of uncoated naproxen that may be present in the claimed formulation and indeed the parties
agree that the claim encompasses formulations that have at least some uncoated naproxen.
The real dispute between the parties is whether claim 1 limits how much uncoated naproxen
may be present in the claimed formulation. Broadly, Defendants urge us to adopt the “plain
meaning” of the claim, which “imposes no limitation on the amount of naproxen that may be
outside the enteric coating.” (Dkt. 489-2 at 12.) Horizon argues that the claim covers
formulations that contain uncoated naproxen so long as it is less than a “therapeutically
effective amount.”8 (Dkt. 489-3 at 16–17.)
Defendants’ proposed reading of claim 1 is straightforward: the plain language of the
claim imposes no limitation on the amount of uncoated naproxen that may be present in
claimed formulations, and it would be improper to read in such a limitation. (Dkt. 489-2 at

7

We follow the parties in using the phrase “enteric coating” as shorthand to describe the pH-sensitive
coating used to satisfy the limitation in claim 1, subsection (b). We use the term “uncoated naproxen”
to mean naproxen without an enteric coating that may be released immediately regardless of pH.
Because the enteric coating in Vimovo is applied around a naproxen “core” of the tablet, the term
“uncoated naproxen” can also refer to the naproxen outside the (enteric coated) core.
8

The parties appear to use the term “therapeutic amount” and “therapeutically effective amount”
interchangeably.

12

12–14.) Defendants argue that a POSA “would recognize that any amount of naproxen
outside the enteric coating (and that could fit in a “unit dosage form”) would be covered
by the ’285 patent claims.” (Id. at 12.) They note that Horizon expert Dr. Williams
testified that a POSA would understand the term “comprising” to permit the inclusion of
additional elements. (Id.; Tr. 821:6-25.) Dr. Williams also explained, in his infringement
analysis, that he could “ignore” uncoated naproxen given the “comprising” language. (Tr.
855:12-24.)
Defendants submit that their interpretation is consistent with the history of the ’285
patent because Horizon deliberately removed the claim limitation related to uncoated
naproxen. (Dkt. 489-2 at 8–9.) As Defendants explain, the ’285 patent differs somewhat
from the earlier-issued ’907 patent. Claim 1 of the ’907 patent restricts the amount of
uncoated naproxen that may be present by requiring NSAID surrounded by a coating that
prevents the release of “essentially any NSAID . . . unless the pH of the surrounding medium
is 3.5 or higher.” (’907 patent at col. 20, lines 8–32.) Allegedly to avoid infringement of the
’907 patent, DRL formulated its ANDA II Product with some naproxen outside of the enteric
coated core of the tablet. (Dkt. 489-2 at 7.) As part of this litigation, we previously construed
the term “essentially any NSAID” to mean “the minimum amount of NSAID released by an
enteric coated dosage form, or tablet.” (Dkt. 380 at 18–22.) Because DRL’s ANDA II
product redacted

, we

concluded that DRL’s ANDA II Product does not infringe the ’907 patent. (Id. at 22–23.)
Horizon was later granted the ’285 patent, which does not contain the “essentially any
NSAID” language that formed the basis of our non-infringement finding for the ’907 patent.
13

Horizon disagrees with Defendants’ proposed reading of claim 1 of the ’285 patent,
and urges us to interpret the claim to limit the amount of permissible uncoated naproxen to
less than a “therapeutic amount.”9 Dr. Williams testified that a POSA would understand
the claim to allow only “less than a therapeutic amount” of uncoated naproxen. (Tr.
821:15–822:7.) Horizon also points to a decision from the Patent Trial and Appeal Board
(“PTAB”) denying Inter Partes review of the ’285 patent and purportedly supporting
Horizon’s “therapeutic amount” limitation.10 The PTAB concluded that claim 1 of the
’285 patent “does not exclude the presence of additional naproxen outside of the coating”
and “does not exclude a unit dosage form that has an amount of naproxen outside the
coating that is not therapeutically effective.” (PTX-351 at 13.) Consequently, the PTAB
rejected the argument that claim 1 “encompass[ed] a composition where the vast majority
of the naproxen, i.e., a therapeutically effective amount, would be outside the coating.”
(PTX-351 at 12.)
Defendants argue that Horizon’s proposed therapeutic amount limitation is
inconsistent with an FDA Citizen’s Petition filed by Horizon. (Dkt. 489-2 at 26–27;
DTX-1248.) In that petition, Horizon argued to the FDA that “locating any naproxen

9

The ’285 patent states that the “most preferred NSAID is naproxen in an amount of between 50 mg
and 1500 mg, and more preferably, in an amount between 200 mg and 600 mg.” (’285 patent at col.
4, lines 11–14.) The parties accordingly appear to agree that the smallest “therapeutic amount” of
Naproxen would be 50 mg. The distinction is irrelevant for infringement purposes in this case
because DRL’s ANDA II Product redacted
.
10

See Dr. Reddy’s Laboratories, Inc. v. Pozen Inc., IPR2015-00802, Paper No. 28 (P.T.A.B. Oct. 9,
2015). For ease of reference, we will cite this PTAB decision by its trial exhibit number, PTX-351.
We acknowledge Defendant Mylan’s concern that it was not a party to the PTAB proceeding. (Tr.
547:23–459:19.) None of our conclusions depend on the PTAB’s decision but, as discussed below,
we are mindful of instances where the PTAB rejected arguments comparable to those made at trial.

14

outside the enteric coated core will result in the immediate release of at least some
portion of the naproxen at the same time as esomeprazole is released. Any portion of the
generic product’s naproxen that is released prematurely in the stomach will act both
topically and systemically without the benefit of the raised gastric pH produced by the
esomeprazole component.” (DTX-1248 at 7 (emphasis added).) In the same petition,
Horizon argued that esomeprazole/naproxen combination tablets with uncoated naproxen
“could subject patients to significantly increased risk of potentially fatal side effects.”
(DTX-1248 at 7; Tr. 436:19–437:5.) Because Horizon has separately argued to the FDA
that any amount of uncoated naproxen might pose a safety risk, Defendants claim that
Horizon’s therapeutic amount limitation is not credible. Defendants further argue that a
therapeutic amount limitation does not make sense because the FDA rejected the notion
that the sequential release of esomeprazole and naproxen in Vimovo is clinically
significant. (DTX-1250 at 7; Tr. 358:11-23; Tr. 462:10-23.)
Defendants also ask us to reject Horizon’s proposed therapeutic amount limitation
because it was not raised during discovery. (Dkt. 489-2 at 18.) Dr. Williams did not
explicitly propose a therapeutic amount limitation in his deposition. Instead, Dr.
Williams testified at his deposition that some amount of naproxen outside of an enteric
coating might pose a safety issue but did not quantify how much. (Tr. 855:19–858:11.)
Moreover, Defendants claim that Horizon “admitted” that the “plain meaning of the ’285
patent claims applied and they had no limitation on the amount of naproxen that could be
outside of an enteric coating.” (Id. at 15.) They point to statements in Horizon’s

15

invalidity contentions that “the disclosed dosage forms [in the ’285 patent] may include
additional naproxen outside the coating.” (DTX-1333 at 48–49.)
Horizon in turn rejects the relevance of its Citizen’s Petition to understanding the
scope of the ’285 patent claims. They argue that the relevant time period for our analysis
is the priority date, and that any statements made in the Citizen’s Petition (which was
submitted years later) should not bear on our analysis. (Dkt. 489-3 at 25.) Horizon also
notes that its Citizen’s Petition merely “requested that the FDA require testing to ensure
that products containing non-enteric coated naproxen were as safe as those that contained
only enteric coated naproxen.” (Id.; DTX-1248 at 2.)
(ii)

Invention as described

Defendants submit that the ’285 patent specification discloses a “coordinated release”
product that does not immediately release any NSAID (e.g., naproxen). The first part of
Defendants’ argument—that the ’285 patent specification discloses a coordinated release
product—is not particularly controversial. The title of the ’285 patent is “Pharmaceutical
Compositions for the Coordinated Delivery of NSAIDS” and the patent itself notes that the
invention is directed to “pharmaceutical compositions that provide for the coordinated release
of an acid inhibitor and an [NSAID] . . . .” (’285 patent at col. 1 lines 20–23.) As explained
by defense expert Dr. Kibbe, “coordinated release” is the mechanism by which a formulation
achieves “coordinated delivery.” (Tr. 420:11–422:12.)
Evidence from both sides also indicates that coordinated release refers here to
sequential delivery. The ’285 patent itself discloses “the coordinated release of therapeutic
agents, i.e., for the sequential release of acid inhibitor followed by analgesic.” (’285 patent at
16

col. 6, lines 23–35.) Dr. Kibbe and Horizon expert Dr. Williams both described coordinated
release as sequential release. (Tr. 420:20–421:7; Tr. 861:9-12.) The description of the
invention offered by the named inventor, Dr. Plachetka, also supports this view. Dr.
Plachetka explained that the coordinated delivery is the immediate release of the proton
pump inhibitor followed by the release of the NSAID when the pH rises to a certain level.
(Tr. 43:22–44:10.) According to Dr. Plachetka, “[t]he whole point of the idea here is to
get acid inhibition before the administration of the NSAID . . . .” (Tr. 134:4-5.)
The parties disagree on Defendants’ second contention—namely, that the ’285 patent
specification does not describe formulations where some naproxen is released immediately.
Dr. Kibbe testified that there were no teachings in the ’285 patent specification related to
formulations where naproxen is released before esomeprazole. (Tr. 431:19–432:5.) He also
said that “[t]here is no support for any release of naproxen until the enteric coat comes off.”
(Tr. 437:11-17.) In Dr. Kibbe’s view, a product that releases even some naproxen early
cannot have a coordinated release within the meaning of the patent specification. (Tr.
422:14–423:16.)
Defendants point to our previous statements regarding the ’907 patent specification as
evidence of the nature of the invention disclosed in the ’285 patent specification. Both Dr.
Kibbe and Dr. Williams noted that the specifications of the two patents are essentially the
same. (Tr. 419:9-22; Tr. 856:14-17.) We did observe earlier in this litigation discussing the
’907 patent:
The ‘907 patent’s distinction from prior art is the “coordinated
drug release . . . [and reduction of] intragastric acid levels to a nontoxic level prior to the release of NSAID.” The specification does
not contemplate an embodiment that releases a small amount of
17

NSAID before the GI tract reaches a pH of 3.5 or above, nor does
the specification state that releasing a small amount of NSAID
would be “acceptable or part of the invention.”
(Dkt. 380 at 19) (internal citations omitted).11
Defendants also point to Horizon’s FDA Citizen’s Petition as evidence that the
invention disclosed in the ’285 patent does not extend to formulations that immediately
release some naproxen. In that petition, Horizon told the FDA that a formulation with
some uncoated naproxen (i.e., DRL’s ANDA II Product) “obviates VIMOVO’s careful
design and allows release of a measureable amount of naproxen before the
gastroprotective benefits of esomeprazole can take effect” and “that VIMOVO’s design is
intended to produce a sequential delivery of gastroprotective esomeprazole before
systemic (or local) exposure to naproxen.” (DTX-1248 at 2, 5.) In Defendants’ view,
these statements are evidence that Horizon viewed any early release of naproxen as
antithetical to the key aspect of the invention—that is, delaying the release of naproxen
until after the esomeprazole can take effect. (Dkt. 489-2 at 25–26.) In sum, Defendants
argue that coordinated release is the “central feature” of the invention disclosed in the
specification and that formulations with uncoated naproxen are “not the invention and
even . . . contrary to it.” (Dkt. 489-2 at 19.)
To illustrate how the ’285 patent claims encompass formulations that do not have
a coordinated release, Defendants offered an example of a hypothetical product
containing a 50 mg naproxen core surrounded by an enteric coating, an esomeprazole

11

Horizon disagrees that our previous statements on the ’907 patent are useful in characterizing
the invention and notes that the statements were made in the context of construing “essentially
any NSAID,” a claim term that does not appear in the ’285 patent. (Dkt. 489-3 at 23–24.)

18

layer immediately above, and an outer layer with 49 mg of naproxen. Defendants submit
that this product cannot be considered to have a “coordinated release” because nearly half
of the naproxen is released immediately. (Dkt. 489-2 at 23.) They argue that such a
formulation is fundamentally at odds with what Dr. Plachetka says he invented. (Tr.
134:4-5.)
Dr. Williams disagreed with Defendants and testified that a formulation with some
uncoated naproxen would still have a coordinated release. (Tr. 884:4-12.) Horizon
likewise rejects Defendants’ use of a hypothetical formulation, which, in their view, “in
no way represent[s] any of Defendants’ ANDA products” and for which there is no
evidence “that a person of skill in the art exercising any sort of reason would actually
contemplate making or using them.” (Dkt. 489-3 at 15.) Horizon argues that “even if
Defendants’ unrealistic, hypothetical embodiments fell within the literal scope of the
claims, one of skill in the art would understand them to be unreasonable and inoperable
embodiments and would not pursue them.” (Id.)
2.

Analysis

We turn now to the question of whether the ’285 patent claims are adequately
described by the ’285 patent specification. As summarized above, the parties dispute both
the scope of the claimed invention and the adequacy of the written description. As to the
scope of the claims, we agree with Defendants that claim 1 of the ’285 patent—whose only
naproxen-related limitation relates to enteric coated naproxen—does not limit the amount of

19

uncoated naproxen that may be present in claimed formulations.12 It is well understood in
patent law that the term “comprising” does not exclude additional elements in addition to the
elements named in the claim. See Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d
1313, 1344–45 (Fed. Cir. 2003) (“Comprising is a term of art used in claim language
which means that the named elements are essential, but other elements may be added and
still form a construct within the scope of the claim.”). The language of the claim itself
does not preclude uncoated naproxen. We are not persuaded by Horizon’s argument that
we should read in a “therapeutic amount” limitation on uncoated naproxen, particularly as that
interpretation finds little support in the claim language, specification, or anywhere else. See
Omega Eng’g, Inc, v. Raytek Corp., 334 F.3d 1314, 1323 (Fed. Cir. 2003) (noting “heavy
presumption that claim terms carry their full ordinary and customary meaning” (internal
quotations omitted)).
We disagree with Defendants, however, that the ’285 patent specification precludes
the inclusion of uncoated naproxen in the formulations it describes. The specification itself is
silent on whether the formulation can include uncoated naproxen in addition to the enteric
coated naproxen present in the claimed formulation. Defendants point out, fairly, that the
’285 patent specification describes a product whose embodiments “preferably” provide
for coordinated drug release such that “the acid inhibitor is released first and the release
of NSAID is delayed until after the pH in the GI tract is risen.” (’285 patent at col. 4,
lines 45–51.) It is likewise true that the specification explains that the invention is at

12

Any such uncoated naproxen would necessarily be in addition to the therapeutic amount of enteric
coated naproxen required by subsection (b) of claim 1.

20

least in part directed toward resolving injuries associated with NSAIDs being released
“before the pH of the gastrointestinal tract can be raised . . . .” (Id. at col. 1, lines 60–64.)
We agree that these and other statements in the specification might counsel a POSA
against incorporating uncoated naproxen when formulating the described invention.
Indeed, Horizon expert Dr. Williams expressed skepticism about a hypothetical
formulation that contained uncoated naproxen because he did not “know why someone
would want to do this” when the patent was “about preventing the release of . . . of the
therapeutic amount of NSAID from that enteric coating until the pH is above 3.5.” (Tr.
883:12-24.)
That the specification can be read to convey a preference for formulations without
uncoated naproxen, however, does not warrant invalidating the claims under § 112(a).
To hold otherwise would be to invalidate the claims simply because they encompass less
preferable embodiments—a reading of § 112(a) that we find incompatible with patent law
principles. See, e.g., Cordis Corp. v. Medtronic AVE, Inc., 339 F.3d 1352, 1365 (Fed.
Cir. 2003) (“an applicant is not required to describe in the specification every conceivable
and possible future embodiment of his invention”); Gillette Co. v. Energizer Holdings,
Inc., 405 F.3d 1367, 1371 (Fed. Cir. 2005) (“a patentee typically claims broadly enough
to cover less preferred embodiments as well as more preferred embodiments, precisely to
block competitors from marketing less than optimal versions of the claimed invention”);
Golight, Inc. v. Wal-Mart Stores, Inc., 355 F.3d 1327, 1331–32 (Fed. Cir. 2004) (“An
applicant is not necessarily required by 35 U.S.C. § 112 . . . to describe more

21

embodiments than its preferred one, and . . . [it has] outright rejected the notion that
disclosure of a single embodiment necessarily limits the claims.”)
We note that Defendants have offered an unusual written description challenge here
that appears to have little support in the law. Rather than allege that a specific element of the
claim lacks support in the specification, Defendants argue that the claim is invalid for merely
allowing the possibility of the addition of uncoated naproxen in view of the specification.
The question of whether a POSA would view the ’285 patent specification (and Defendants’
other extrinsic evidence) as limiting the plain language of the claim to preclude the presence
of uncoated naproxen would seem a more natural fit for claim construction proceedings. The
law of written description requires us to evaluate whether the four corners of the specification
“reasonably convey[] to those skilled in the art that the inventor had possession of the
claimed subject matter as of the filing date.” Ariad, 598 F.3d at 1351–52. Our inquiry is
therefore whether the ’285 patent specification would reasonably convey to a POSA that
Dr. Plachetka had possession of the “invention”—here a combination drug product
featuring enteric coated naproxen and an uncoated proton pump inhibitor (“PPI”). As Dr.
Williams explained at trial, those elements are indeed present and described in the
specification. (Tr. 812:17–824:10.) Whether there is extrinsic evidence, such as
Horizon’s FDA Citizen’s petition, suggesting that the presence of uncoated naproxen was
against the spirit of the invention does not bear on our written description analysis.
Because Defendants have not demonstrated by clear and convincing evidence that any
element of the claimed invention lacks written description support, we decline to
invalidate the ’285 patent on those grounds.
22

B.

Written Description (Sustained Release Formulations)

Defendants’ second written description challenge arises out of the use of the term
“inhibits” in claim 1 of the ’285 patent. In their view, the use of the word “inhibits”
extends the scope of the claim to include “sustained release” formulations while the
specification discloses only “delayed release” formulations. As above, we first review the
parties’ evidence and arguments related to the scope of the claims and the description in the
patent specification. We then analyze whether the claims satisfy the written description
requirement of § 112(a) on this issue.
1.

Parties’ Evidence and Arguments
(i)

Scope of the ’285 patent claims

Claim 1 of the ’285 patent requires, inter alia, “naproxen surrounded by a coating
that inhibits its release from said unit dosage form unless said dosage form is in a medium
with a pH of 3.5 or higher.” (’285 patent claim at col. 22, lines 12–14 (emphasis added).)
Defendants submit that the term “inhibits” should be given its plain meaning, “to slow
down.” (Dkt. 489-2 at 12; Tr. 887:1-7.) They highlight a previous filing in this case
where Horizon agreed that the plain meaning of “inhibit” was “slow down or stop” and
that “inhibit” in the ’285 patent claims takes on this plain meaning. (DTX 1333 at 51.)
Defendants also contend that the term “inhibits” should be understood to be broader
than the term “prevents” because the term was consciously selected by the inventor to
expand the scope of the ’285 patent claims beyond what was claimed in the ’907 patent.
(Dkt. 489-2 at 30.) Claim 1 of the earlier-issued ’907 patent requires an “NSAID . . .
surrounded by a coating that . . . prevents the release of essentially any NSAID from said
23

dosage form unless the pH of the surrounding medium is 3.5 or higher.” (’907 patent at
col. 20, lines 22–27 (emphasis added).) Horizon expert Dr. Williams agreed that a POSA
might presume that “inhibits” in the ’285 patent means something different than
“prevents” in the ’907 patent because the language is different in the two claims. (Tr.
892:20-24; see also Tr. 885:8-17.) Per defense expert Dr. Kibbe, the term “inhibits”
(understood as “slows down”) extends the scope of the claim to “sustained release”
formulations. (Tr. 416:4-23; 438:12–441:14.) A sustained release product, as described by
Dr. Kibbe, is one that “begins releasing right away, but it does so at a slower rate than you
would see if you were comparing it to an immediate-release product.” (Tr. 441:10-13.) Dr.
Kibbe contrasted sustained release products, which allow for immediate (albeit slowed)
release of the active ingredient, with formulations that “stop” drug release, meaning that “for a
fixed period of time, no drug will come out until the dosage form migrates into an area where
the pH is above the pH of the enteric coat.” (Tr. 441:6-9.)
Horizon argues that a POSA “would recognize that the term ‘inhibit’ in the ’285
patent describes the same goal as the term ‘prevent’ in the context of the ’907 patent.”
(Dkt. 489-3 at 27.) As Dr. Williams testified, “inhibit” would be understood by a POSA “to
accomplish the goal of no release in the stomach, in acid, or until the pH is 3.5 or higher.”
(Tr. 814:21–815:2.) That understanding, according to Horizon, would arise out of a
POSA’s reading of the specification (discussed below). Horizon also urges us to reject
Dr. Kibbe’s trial testimony as incredible in light of previous statements in his expert

24

report that “[a] person of ordinary skill in the art would understand the word ‘inhibit’ to
mean ‘prevent’ based upon the specification of the ’285 patent.” (Tr. 556:7-12.)
(ii)

Invention as described

Defendants submit that the ’285 patent specification does not contain any
disclosure related to “sustained release” products—i.e., formulations that slowly but
immediately release the active ingredient. Instead, Dr. Kibbe pointed to various instances
in the ’285 patent specification that refer specifically to “prevent[ing]” the release of
naproxen. (Tr. 439:14–440:17; see, e.g., ’285 patent at col. 4, lines 64–67; id. at col. 5,
lines 34–39; id. at col. 9, lines 30–33.) As he explained, the term “inhibits” is not used in
the specification to refer to the release of naproxen; to the extent it is used at all, it
describes proton pump inhibition. (Tr. 438:15–439:2.) Horizon expert Dr. Williams
agreed that the specification does not “talk[] about” sustained release formulations. (Tr.
890:19-24.)
Horizon submits that the specification does disclose what it means to “inhibit” in
the context of a coating. (Dkt. 489-3 at 27; Tr. 814:18-20.) The ’285 patent describes
two types of coatings that may be used to surround the NSAID. (Dkt. 489-3 at 28.) One
is the pH-sensitive enteric coating that does not dissolve until the pH of the surrounding
medium is 3.5 or higher. (See, e.g., ’285 patent at col. 4, lines 54–59.) The other coating
described “controls the release of NSAID by time, as opposed to pH, with the rate
adjusted so that NSAID is not released until after the pH of the gastrointestinal tract has
risen to at least 3.5.” (Id. at col. 4, lines 59–67.) In Horizon’s view, these alternatives

25

describe coatings that either prevent the release of naproxen at low pH or delay its release
until sufficient time has passed to allow the pH to rise. (Dkt. 489-3 at 28.)
2.

Analysis

Defendants argue that claim 1 of the ’285 patent fails the written description
requirement of 35 U.S.C. § 112(a) because the claim encompasses sustained release
formulations and the patent specification does not describe sustained release
formulations. (Dkt. 489-2 at 29–30.) Their argument primarily rests on the assertion by
defense expert Dr. Kibbe that the use of the term “inhibits” in claim 1 broadens the claim
to encompass “sustained release” formulations. (Tr. 438:15–439:2.)13
We note that the PTAB recently rejected a similar argument from DRL. In that
proceeding, as here, the parties argued over whether “inhibits” should be afforded its
ordinary meaning or interpreted to mean something akin to “prevents.” (PTX-351 at 13.)
DRL argued then that claim 1 of the ’285 patent “encompass[es] formulations that release
all of its naproxen slowly at any pH, instead of preventing release until the formulations
are in a medium with a pH of 3.5 or higher.” (Id. at 14.) The PTAB declined to provide
an explicit definition of “inhibits” because it did not “discern a significant difference
between the definitions offered by the parties.” (Id.) The PTAB, however, “disagree[d]
with [DRL]’s interpretation of the difference in breadth between ‘inhibit,’ ‘prevent,’ and
‘delay,’ [which] would lead to the conclusion that the claims of the ’285 patent
encompass a formulation that releases all of its naproxen slowly at any pH.” (Id. at 14–

13

As with Defendants’ written description challenge in Section III.A, supra, the question of whether
use of the claim term “inhibits” broadens the scope of the claim appears more properly considered a
claim construction issue than a written description challenge.

26

15.) Accordingly, the PTAB concluded that the claims of the ’285 patent, including the
term “inhibits,” were adequately supported by the relevant specification. (Id. at 19.)
We conclude that Defendants have failed to meet their burden to show by clear
and convincing evidence that claim 1 of the ’285 patent lacks written description support.
We are not convinced that use of the term “inhibits” in claim 1 expands the scope of the
claim to include sustained release formulations. A POSA reading the specification would
understand that the term “inhibits” in the context of the patent refers back to the enteric
coatings described in the patent specification that encompass both preventing and
delaying the release of naproxen. (See, e.g., ’285 patent at col. 4, lines 54–67.) Put
another way, given the description in the specification of coatings that “inhibit” the
release of an NSAID in specific ways, (Tr. 815:6–9), we are unconvinced that a POSA
would understand that claim 1 of the ’285 patent encompasses sustained release
formulations. Because we conclude that the claim does not encompass sustained release
formulations, we need not reach the question of whether the specification adequately
describes such formulations.
C.

Infringement

Horizon alleges that DRL’s ANDA II Product infringes claims 1– 4 of the ’285 patent.
Having evaluated the scope and meaning of the pertinent claim terms above, we now compare
those claims against the allegedly infringing product. Advanced Steel Recovery, LLC v. XBody Equip., Inc., 808 F.3d 1313, 1316 (Fed. Cir. 2015). DRL’s ANDA II Product red
act

(PTX-234 at 25.) DRL’s “500
27

mg/20 mg” dose ANDA II Product redacted
. (Id.) DRL’s “375 mg/20 mg” dose ANDA II Product redacted
redacted

. (Id.)

redacted

. (Id.) In addition, redacted

redacted

r
e

(PTX-014 at 15.) We now turn

redacted

to whether the product satisfies the various claim limitations of the asserted claims.14
1.

Claim 1 of the ’285 patent
(i)

“a pharmaceutical composition in unit dosage form”

Horizon provided unrebutted testimony that the DRL ANDA II Product is “a
pharmaceutical composition in unit dosage form.” (Tr. 833:18-834:1.)
(ii)

“therapeutically effective amounts of: (a) esomeprazole, wherein
at least a portion of said esomeprazole is not surrounded by an
enteric coating”

Horizon provided unrebutted testimony that the DRL ANDA II Product includes a
“therapeutically effective amount[] of esomeprazole.” (Tr. 834:5–835:5.) Further, the
esomeprazole in the DRL ANDA II Products is not surrounded by an enteric coating.
(Tr. 835:6-20; PTX-234 at 25.)
(iii)

“therapeutically effective amounts of: (b) naproxen surrounded
by a coating that inhibits its release from said unit dosage form
unless said dosage form is in a medium with a pH of 3.5 or
higher”

Horizon provided unrebutted testimony that the DRL ANDA II Product redacted
, both of which are therapeutically

redacted

14

Mylan takes no position on whether DRL’s ANDA II Product infringes the ’285 patent. (Dkt. 4892 at 6.)

28

effective amounts. (Tr. 835:22–836:12.)

redacted

DRL II ANDA

Products redacted
. (Tr. 838:8-21.)

redacted

(iv)

“wherein said unit dosage form provides for release of said
esomeprazole such that upon introduction of said unit dosage
form into a medium, at least a portion of said esomeprazole is
released regardless of the pH of the medium”

Horizon provided unrebutted testimony that DRL’s ANDA II Product redacted

(Tr. 838:22–839:15.)
Because DRL’s ANDA II Product satisfies each limitation of claim 1 of the ’285
patent, we find that Horizon has proven by a preponderance of the evidence that DRL’s
ANDA II Product infringes that claim.
2.

Claim 2 of the ’285 patent

Claim 2 of the ’285 patent reads: “The pharmaceutical composition of claim 1,
wherein naproxen is present in said unit dosage form in an amount of 200-600 mg.” (’285
patent at col. 22, lines 19–21.) Horizon provided unrebutted testimony that DRL’s ANDA
II Product redacted
(Tr. 840:1-8.)
Because DRL’s ANDA II Product satisfies each limitation of claim 2 of the ’285
patent, we find that Horizon has proven by a preponderance of the evidence that DRL’s
ANDA II Product infringes that claim.

29

3.

Claim 3 of the ’285 patent

Claim 3 of the ’285 patent reads: “The pharmaceutical composition of claim 1,
wherein esomeprazole is present in said unit dosage form in an amount of from 5 to
100 mg.” (’285 patent at col. 22, lines 22–24.) Horizon provided unrebutted testimony
that DRL’s ANDA II Product redacted
(Tr. 840:9-15.)
Because DRL’s ANDA II Product satisfies each limitation of claim 3 of the ’285
patent, we find that Horizon has proven by a preponderance of the evidence that DRL’s
ANDA II Product infringes that claim.
4.

Claim 4 of the ’285 patent

Claim 4 of the ’285 patent reads: “The pharmaceutical composition of claim 1,
wherein naproxen is present in said unit dosage form in an amount of between 200-600
mg and esomeprazole in an amount of from 5 to100 mg per unit dosage form.” (’285
patent at col. 22, lines 25–29.) Horizon provided unrebutted testimony that the naproxen
in DRL’s ANDA Product redacted
(Tr. 840:1-8.)

redacted

DRL’s

ANDA II Products redacted
(Tr. 840:9-15.)
Because DRL’s ANDA II Product satisfies each limitation of claim 4 of the ’285
patent, we find that Horizon has proven by a preponderance of the evidence that DRL’s
ANDA II Product infringes that claim.

30

IV.

Obviousness and Related § 112 Challenges
Defendants at trial offered a second line of interrelated invalidity challenges under 35

U.S.C. § 103 and § 112. These issued were briefed separately from the infringement and
§ 112 issues argued in Section III, supra, and are consequently considered together in this
section. Section IV.A addresses the Defendants’ obviousness challenge under § 103.
Sections IV.B and IV.C address the Defendants’ related enablement and written description
challenges under § 112.
A.

Obviousness

We undertake several factual inquiries to determine whether the Asserted Patents are
invalid under § 103, including determining the scope and content of the prior art, differences
between the prior art and the claims at issue, and the level of ordinary skill in the pertinent
art. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). In this section, we recount the
parties’ evidence at trial pertaining to the prior art as well as so-called secondary
considerations of nonobviousness. We then assess that evidence and ultimately conclude
that the Defendants have failed to meet their burden to show that the Asserted Patents are
invalid under § 103.
1.

Parties’ Evidence and Arguments on Prior Art

Defendants maintain that a POSA would have been “motivated to combine the
teachings of the prior art references to achieve the claimed invention, and . . . would have had
a reasonable expectation of success in doing so.” Procter & Gamble Co. v. Teva Pharm.
USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009). They submit two theories as to why the
invention disclosed in the Asserted Patents (the “Invention”) was obvious under the prior
31

art.15 (Dkt. 489 at 15–27.) Those theories primarily involve prior art pertaining to
existing combination drug products and other art describing NSAID/PPI co-therapies,
and are discussed in Section IV.A.1.i, infra. Horizon’s primary defense is that the
invention cannot be considered obvious because the invention uses an “uncoated” PPI.
The parties’ extensive dispute over the prior art as it relates to uncoated PPIs is discussed
in Section IV.A.1.ii, infra.
(i)

Defendants’ obviousness theories

Defendants offer two theories of why the Invention was obvious under the prior
art. The first theory is that it would have been obvious to a POSA to improve upon the
combination product described in U.S. Patent No. 5,601,843 (the ’843 patent) (DTX1063) and commercialized as Arthrotec. (Dkt. 489 at 25.)16 Arthrotec is a branded drug
product that combines an NSAID (diclofenac) with misoprostol (a synthetic
prostaglandin). (DTX-1095 at 2.) Arthrotec is used to treat conditions such as
osteoarthritis and rheumatoid arthritis in patients with a high risk of developing NSAIDrelated injuries such as gastric and duodenal ulcers. (Tr. 322:15-20.) The misoprostol in
Arthrotec was designed to reduce the risk of NSAID-related injury by: (1) replacing
prostaglandin in the stomach to protect the stomach from acid exposure; (2) inhibiting

15

We undertake our obviousness analysis from the perspective of a POSA as of June 1, 2001, the
date on which Provisional application No. 60/294,588 was submitted. Horizon expert Dr. Williams
stated at trial that he used a priority date of May 31, 2002 but later agreed to use the earlier 2001
priority date. (Tr. 729:8–731:8; dkt. 489 at 18.)
16

Horizon argues that some of Defendants’ arguments at trial constituted new (and therefore
impermissible) combinations of prior art. (Dkt. 489-1 at 23–24.) Because we conclude that the
Invention was nonobvious under Defendants’ proffered combinations, we do not reach the
question of whether Defendants waived particular combinations during discovery.

32

acid production in the stomach. (Tr. 456:10–15; Tr. 495:4–9; Tr. 501:18–21.) Of these
mechanisms, the prostaglandin replacement mechanism was the “primary” mechanism by
which misoprostol would help reduce the risk of NSAID-related injury. (Tr. 502:16–
503:10.) In Defendants’ telling, the only significant difference between Arthrotec and the
Invention is the choice of “acid inhibitor” (a PPI instead of misoprostol) and NSAID
(naproxen instead of diclofenac). (Tr. 456:23–457:17; Tr. 461:12-24.)
Defendants submit that the Invention was obvious because a POSA would have
been motivated to replace the misoprostol in Arthrotec with a PPI, and particularly
esomeprazole. They argue that a POSA would have replaced misoprostol with
esomeprazole because: (1) misoprostol was understood to have harmful side effects; and
(2) misoprostol was understood to be less effective than esomeprazole for treating
NSAID-related injuries. As to the first point, experts from both sides testified that
misoprostol carried significant side effects, including diarrhea, flatulence, and even
spontaneous abortion. (Tr. 311:7-10, Tr. 330:12-23; Tr. 463:17-23; Tr. 1180:11–
1182:14; DTX-1095 at 2.) These side effects were well documented in the prior art.
(’907 patent at col. 2, lines 52–56.) As to the second point, Defendants submit that it was
understood in the prior art that PPIs, and especially esomeprazole, were superior to other
acid inhibitors, including misoprostol, for treating NSAID-related injuries. (Tr. 309:11–
317:9; Tr. 464:4-10.)
Defendants highlight academic literature indicating that PPIs were understood to
be a better treatment option for NSAID-related injuries than other available acid
inhibitors such as H2-receptor antagonists and prostaglandins. Much of the literature
33

relies on two studies comparing PPIs with alternative treatments. The Omeprazole versus
Misoprostol for NSAID-Induced Ulcer Management (or “OMNIUM”) study compared
the PPI omeprazole to misoprostol. (DTX-1077; Tr. 312:19-25.) The Acid Suppression
Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer treatment (or
“ASTRONAUT”) study compared omeprazole with the H2-receptor antagonist
ranitidine. (DTX-1069.)
Subsequent articles reviewing the safety and efficacy of treatments for NSAIDrelated injuries cite the OMNIUM and ASTRONAUT studies. As recounted in Brown
(DTX-1080), the OMNIUM study reported that use of omeprazole resulted in a reduction
in the reoccurrence of NSAID-related ulcers and increased compliance compared with
misoprostol. (DTX-1080 at 7; Tr. 316:5-25; Tr. 1207:3–1209:12.) Per Brown, “[PPIs]
have demonstrated efficacy in the prevention of the adverse gastrointestinal effects of
NSAIDs” and have “clear benefits” over alternatives. (DTX-1080 at 8.) Another article,
Wolfe (DTX-1089), explained that the “more potent inhibition of gastric acid secretion
provided by PPIs enhances their healing properties.” (DTX 1089 at 10; Tr. 310:20–
311:10.) Citing the ASTRONAUT study comparing omeprazole with H2-agonist
ranitidine, Wolfe and Brown both recommended the use of PPIs over H-2 antagonists.
(Tr. 316:6-11.) Relying in part on these articles, defense expert Dr. Metz testified that
PPIs were understood to be the best acid inhibitor as of the priority date for both
effectiveness and tolerability. (Tr. 309:22-24.) Moreover, Dr. Metz testified that a
POSA would have been motivated to replace the misoprostol in Arthrotec with
esomeprazole in particular because it was understood to be the most potent PPI. (Tr.
34

331:19–332:13; Tr. 337:13-17.) Dr. Kibbe testified that it would have been a routine
modification to use a PPI instead of misoprostol in formulating the product. (Tr. 461:21–
462:4.)
Defendants argue that a POSA would have had additional motivation to replace
the misoprostol in Arthrotec with a PPI because NSAID/PPI combination therapies were
already known in the prior art. (Tr. 332:8-13.) For example, International Patent Pub.
No. WO 97/25064 (“Depui”) (DTX-1064) disclosed a combination dosage form of a PPI
with an NSAID for treatment and prevention of NSAID-related injury. (Tr. 325:23–
327:1; Tr. 464:11–466:6.) Acceptable PPIs in Depui included omeprazole and
esomeprazole, while acceptable NSAIDs included naproxen. (Tr. 326:19–327:1.)
Defendants also point to U.S. Patent No. 6,544,556 (the ’556 patent) (DTX-1118), which
disclosed a combination dosage form of a PPI with an NSAID to prevent NSAID-related
injury. (’556 patent at col. 1, lines 7–14.)17 Specifically, the ’556 patent discloses the
use of a PPI combined with diclofenac (the same NSAID found in Arthrotec). (Id. at col.
4, lines 51–54; Tr. 1216:17–1219:4.) They also cite U.S. Patent No. 5,204,118 (’118
patent) (DTX-1051), which discloses combination dosage forms of an “[NSAID] or
acetaminophen and a histamine receptor blocker and/or a proton pump inhibitor
composition.” (’118 patent at col. 1, lines 13–16.)

17

There is some dispute as to whether the ’556 patent is prior art. (Dkt. 489-1 at 22 n.4.) The ’556
patent issued on April 8, 2003, from a patent application filed on September 11, 2000.
Accordingly, it is prior art under former 35 U.S.C. § 102(e), which includes as prior art “a patent
granted on an application for patent by another filed in the United States before the invention by
the applicant for patent.” Our finding of nonobviousness, however, does not turn on whether the
’556 patent is considered prior art.

35

Horizon disputes that a POSA would have been motivated to replace the
misoprostol in Arthrotec with a PPI such as esomeprazole. Horizon rejects the notion
that a PPI and a synthetic prostaglandin, such as misoprostol, would be seen as
interchangeable because they have different mechanisms of action. Misoprostol helps
replace prostaglandins, the depletion of which makes the stomach more susceptible to
NSAID-related injury. (Tr. 1138:15–1139:4; PTX-292.) In contrast, PPIs act as “acid
suppressants” or “acid inhibitors” that do not replace the loss of prostaglandins due to
NSAID use. (Tr. 503:16–25; Tr. 1259:20–1260:4.) Dr. Plachetka, the named inventor of
the Asserted Patents, similarly explained that “the only thing that a proton pump inhibitor
will do is inhibit the secretion of acid . . . , whereas misoprostol will repair or replace the
gel coat.” (Tr. 40:4-13.) In light of these differences, Horizon argues that a POSA would
not have been motivated to swap the two ingredients. (Dkt. 489-1 at 47.)
Horizon argues further that a POSA would not have been motivated to replace the
misoprostol in Arthrotec with uncoated esomeprazole. Although we discuss the prior art
related to uncoated PPIs in detail below, Horizon expert Dr. Williams testified that a
POSA would not have chosen to replace misoprostol, which is not acid labile, with a PPI
that is acid labile. (Tr. 773:22–774:5; Tr. 774:8-17.) The distinction also matters, in
Horizon’s view, because much of the prior art discussing the efficacy of PPIs analyzed
enteric coated PPIs. The OMNIUM and ASTRONAUT studies, for example, were
conducted using enteric coated PPIs. (Tr. 384:12–386:1.)
The second obviousness theory proffered by Defendants relies on essentially the same
references but in a different logical progression. Whereas their first theory is that a POSA
36

would have been motivated to replace the ingredients in a combination drug product (e.g.,
Arthrotec) with an NSAID/PPI combination, the second theory is that a POSA would have
been motivated to take existing NSAID/PPI co-therapies and put them into a combination
drug product . (Dkt. 489 at 15–27.) As discussed above, NSAID/PPI co-therapies were
known in the prior art. (See, e.g., Depui (DTX-1064); ’556 patent (DTX-1118); Tr. 325:23–
327:1; Tr. 464:11–466:6.) At the same time, it was understood that administering
medications separately “can be difficult to achieve and can be difficult for a patient to
faithfully follow.” (Tr. 319:17–321:19.) Requiring patients to take multiple tablets per
day can lead to patients forgetting or declining to take both tablets. (Tr. 319:17–321:7;
Tr. 458:7-23.) Defense expert Dr. Metz testified that a POSA would have sought to
address potential compliance issues by combining drug components into a single tablet.
(Tr. 321:16-19.) As an example, he highlighted the ’843 (Arthrotec) patent, which
disclosed that combination tablets could improve patient compliance. (’843 patent at col.
12, lines 10–14; Tr. 321:24–324:17.)18
Defendants explain that the prior art also disclosed combination drug therapies
with “coordinated release” (i.e., the sequential release of an acid inhibitor and an
NSAID). U.S. Patent No. 6,319,519 (’519 patent) (DTX-1112) discloses a tablet
comprised of an NSAID (to treat arthritis pain and inflammation) and misoprostol (to
prevent NSAID-related injury). (Tr. 913:7-915:23; ’519 patent at col. 1, lines 9–34.)
According to the ’519 patent, “[i]t has been found experimentally that it is necessary for

18

Defendants also argue that the dependent claims (e.g., claim 52 of the ’907 patent) would be
obvious because it was understood that an NSAID in conjunction with a PPI could be used to treat
osteoarthritis or rheumatoid arthritis. (Tr. 88:23–89:4; Tr. 333:21–334:2; Tr. 338:10-24.)

37

the prostaglandin to be released before the NSAID so as to protect the stomach from the
effects of the NSAID. It is therefore preferable that the NSAID is coated to delay
release.” (’519 patent at col. 1, lines 21–25.) Horizon expert Dr. Williams conceded at
trial that the coordinated release structures described in the ’519 patent and the ’843
Arthrotec patent are similar to the coordinated release mechanism of the Invention. (Tr.
915:20–917:3; see also Tr. 454:2–457:17.)
(ii)

Uncoated PPIs

Horizon’s primary response to Defendants’ obviousness arguments is that the
Invention was nonobvious because it uses an uncoated PPI and the prior art taught away
from using uncoated PPIs.19 (Dkt. 489-1 at 27–43; 45–49.) Horizon argues that it was
widely understood—and reflected in the prior art—that PPIs must be enteric coated
because they are susceptible to acid degradation in the stomach. Defendants disagree that
the prior art taught away from using uncoated PPIs and offered testimony at trial why a
POSA would have had a reasonable expectation of success using an uncoated PPI. We
summarize below the parties’ evidence on these subjects.
Horizon’s experts testified that a POSA would not have been motivated to use an
uncoated PPI. Dr. Williams explained that, as of the priority date, all commercially
available PPIs were formulated with an enteric coating. (Tr. 733:2-13; Tr. 735:8-23; see
also Tr. 372:23–373:5.) He testified that PPIs were enteric coated because they are acid
labile and dissolve much more quickly in acidic pH environments. (Tr. 733:16–735:1.)

19

We use “uncoated PPI” in this section as shorthand to refer to a PPI that does not have a pHsensitive enteric coating.

38

In Dr. Williams’ view, this understanding was reflected in prior art that affirmatively
discouraged the use of non-enteric coated PPIs. (Tr. 737:1-18.) For example, Pilbrant
1985 (PTX-325) evaluated the use of enteric coated and uncoated omeprazole solid
dosage formulations, and concluded that the uncoated dosage form was “ruled out in a
pilot bioavailability study . . . where it was shown that more than half of the omeprazole
in a rapidly dissolving dosage form degrades in the stomach.” (PTX-435 at 2; Tr.
738:16–740:1.) In contrast, Pilbrant 1985 stated that an enteric coated solid dosage form
“offer[ed] the best possibilities.” (PTX-435 at 3; Tr. 740:15-22.) Per Dr. Williams, a
POSA would conclude from Pilbrant 1985 that a non-enteric coated PPI would not work
and would be discouraged from pursuing such a formulation. (Tr. 740:2-14.) Although
he did not discuss each in detail, Dr. Williams testified that 25 additional prior art
references supported his contention that PPIs must be enteric coated.20 (Tr. 747:20–
748:12.)
Horizon notes that Defendants’ own experts have acknowledged the need to
enteric coat PPIs because of their acid lability. (Tr. 502:5-15.) Dr. Metz co-authored an
article stating that “[p]roton pump inhibitors are inactivated by gastric acid and thus must
be given as enteric coated granules in gelatin capsules or enteric coated tablets.” (PTX73 at 8 (emphasis added); Tr. 365:6–369:5.) Dr. Metz testified at trial that it was the

20

See (PTX-77 at 3); (PTX-78 at 4); (PTX-79 at 3); (PTX-80 at 2); (PTX-242 at 3); (PTX-243 at 2);
(PTX-244 at 2); (PTX-245 at 2); (PTX-246 at 4); (PTX-247 at 9); (PTX-248 at 5); (PTX-249 at 6);
(PTX-250 at 2); (PTX-251 at 2); (PTX-252 at 2); (PTX-253 at 3); (PTX-254 at 4); (PTX-255 at 10);
(PTX-256 at 2); (PTX-257 at 1); (PTX-258 at 6); (PTX-337 at 5); (PTX-570 at 4–5); (PTX-573 at 5–
6); and (DTX-1117 at 13). We recognized at trial that PTX-79 cannot be considered prior art. (Tr.
528:19–529:16.)

39

“general party line” and belief in the industry that “proton pump inhibitors are inactivated
by gastric acid and thus must be given as enteric coated granules in gelatin capsules or
enteric coated tablets.” (Tr. 369:11-21; Tr. 370:16-20; Tr. 371:16-21.) Dr. Mayersohn
likewise testified in a sworn expert declaration in another case that “[b]ecause PPIs are
chemically unstable in the acidic environment of the stomach, they must be protected
from stomach acid. Drug manufacturers accomplish this by combining the PPI with
various stabilizers and coatings, resulting in a drug formulation that has an outer layer
(referred to as the ‘enteric coat’) that protects the PPI from stomach acid.” (PTX-434 at
6; Tr. 686:4–689:12.) In light of the prevailing understanding about uncoated PPIs,
Horizon argues that a POSA would have understood that using an uncoated PPI in a
formulation would fail because of acidic gastric pH levels. (See, e.g., Tr. 737:1-18;
1029:9-22; 1163:10–1164:3.)
Defendants disagree with Horizon’s characterization of the prior art, which they
see as, at most, expressing a general preference for enteric coated PPIs. (Dkt. 489 at 48.)
They criticize Horizon’s 25 “teaching away” references that purportedly counsel against
using an uncoated PPI on several grounds. Defense expert Dr. Mayersohn explained that
one of Horizon’s references merely states that omeprazole is acid labile and enteric
coated, and does not discuss uncoated PPIs. (Tr. 613:5–614:13 (discussing PTX-256).)
Dr. Mayersohn testified that some of the other references were “repetitive and
duplicative,” (Tr. 611:20-23) while Dr. Kibbe explained that “often the same thing is
repeated and repeated in articles because it’s easier to do that than to actually test it.”
(Tr. 527:16-19.) Defendants criticized ten of the references for being AstraZeneca
40

publications, who they argue had an interest in promoting “the benefits of AstraZeneca’s
own, patented, enteric coated PPI formulation.” (Dkt. 489 at 49; Tr. 939:5–945:4.)
Defendants criticized another six references as lacking original research or analysis on
the efficacy or usefulness of uncoated PPIs. (Tr. 968:13–970:2.)
Defendants also submitted that a POSA would have been motivated to use
uncoated PPIs and would have had a reasonable expectation of success in doing so
because: (1) the PPI could be administered with an alkalizing agent to help protect it from
stomach acid; (2) the dose of the PPI could be increased to offset acid degradation; (3)
the repeated dosing of the PPI would create a “feedback loop” that would increase
bioavailability for the uncoated PPI over time; and (4) an uncoated PPI would have
certain advantages over an enteric coated PPI.
Alkalizing Agent
Defendants argue that a POSA would have a reasonable expectation of success
using an uncoated PPI because the formulation could include an alkalizing agent, such as
sodium bicarbonate, that would protect the PPI from degradation by stomach acid. (Dkt.
489 at 43–44.) Dr. Kibbe testified that an alkalizing agent could raise the pH of the
stomach around the tablet and protect the PPI from degradation. (Tr. 485:1-16.) He
explained that Pilbrant 1985 teaches that an omeprazole-sodium bicarbonate combination
could be used to improve bioavailability. (Tr. 489:15-23; PTX-435 at 4–5.) Other prior
art, including U.S. Patent No. 6,489,346 (the ’346 patent) (DTX-1117), eventually
commercialized as Zegerid, disclosed an omeprazole and sodium bicarbonate
formulation. (Tr. 345:1-20; Tr. 483:11–484:10.) Although Horizon submitted the ’346
41

patent as one of its “teaching away” references, Defendants submit that it would have
taught a POSA to account for PPI’s acid lability by co-administering an alkalizing agent.
(Dkt. 489 at 49; Tr. 977:16–980:21.)
Horizon expert Dr. Williams disagreed that sodium bicarbonate could feasibly be
added to the formulation to prevent acid degradation. He testified, citing Pilbrant 1993
(PTX-262), that the resulting tablet would be too large because of the amount of sodium
bicarbonate needed. (Tr. 758:3–760:16.)21 Dr. Williams also argued, citing International
Patent Publication WO 00/026185 (DTX-1102), that sodium bicarbonate would be
incompatible with the enteric coated naproxen also present in the formulation because it
could dissolve that enteric coat. (Tr. 753:21–755:16.)
Increased PPI Dosage
Defendants also argue that a POSA would have a reasonable expectation of
success using an uncoated PPI because a POSA could increase the dosage level to
account for the PPI’s acid lability. Dr. Mayersohn cited Clissold (DTX-1036) for the
proposition that about 50% of an uncoated PPI remains bioavailable despite acid
degradation. (Tr. 620:7–621:6; DTX-1036 at 19 (citing Pilbrant 1985).) As some of the
uncoated PPI remains available to the body (or “bioavailable”), Dr. Mayersohn explained
that a POSA could account for acid degradation by increasing the amount of PPI in the
formulation—in this case by essentially doubling the dose to account for the PPI’s 50%
bioavailability. (Tr. 621:23–622:7; Tr. 704:18–705:2.) Dr. Metz likewise testified that

21

Defendants argue that Horizon’s “tablet size” arguments do not account for the possibility of
multiple dosages nor mechanisms such as the “feedback loop” discussed below that might make
smaller amounts of PPI effective. (Dkt. 489 at 44–45.)

42

the PPI dose could be doubled to account for acid degradation. (Tr. 390:2-6.) Dr.
Mayersohn added that a POSA would have further reason to believe that increasing the
dosage would be effective because Regårdh (DTX-1029) taught that a comparatively
higher percentage of PPI would be bioavailable at higher dosage levels. (Tr. 635:23–
636:22.)
Horizon rejects the idea that a POSA would have been motivated to increase the
dose of PPI to account for its acid lability. First, Dr. Taft questioned whether the 50%
bioavailability figure from Pilbrant 1985 (PTX-432), which explicitly related to
suspensions of omeprazole, could be used as a proxy for the bioavailability of a drug in
tablet form. (Tr. 1060:5–1061:10.) Dr. Williams added that a subsequent study, Pilbrant
1993 (PTX-262), indicates that as much as 84% of a PPI may be lost due to acid
degradation.22 (Tr. 778:12–780:7.) Second, even assuming a 50% bioavailability, Dr.
Taft testified that a POSA would not have simply doubled the dose to address the acid
lability of PPIs. (Tr. 1067:9–1068:3.) On cross-examination, Defendants’ experts could
not provide any examples of situations where low bioavailability was addressed through
doubling the dosage form. (Tr. 393:6-9 (Metz); Tr. 514:4–515:25 (Kibbe); Tr. 692:24–
695:10 (Mayersohn).)
PPI Feedback Loop
Defendants also believe that a POSA would have had a reasonable expectation of
success using uncoated PPIs because the prior art described a “positive feedback loop”

22

Defendants dispute the relevance of the data in Pilbrant 1993 because the study reported the
bioavailability of a PPI after a meal and commercially available PPIs, even enteric coated ones, are
typically administered with food. (Tr. 964:15–965:21.)

43

that would increase the bioavailability of an uncoated PPI. As explained by both Dr.
Kibbe and Dr. Mayersohn, the feedback loop occurs because the first PPI dose inhibits
stomach acid production and raises gastric pH, which consequently causes less acid
degradation of the second dose, which further inhibits acid production, and so on. (Tr.
492:25–494:18; Tr. 589:9–590:4; 620:18–627:11; DTX-1396 at 6–7.) Dr. Kibbe pointed
to Clissold (DTX-1036) as support for this feedback mechanism. (Tr. 492:25–493:25.)
Dr. Mayersohn cited Tolman (DTX-1061) as additional evidence of the feedback effect.
(Tr. 625:16–627:7.)
Horizon disputes the relevance of Clissold (DTX-1036) and Tolman (DTX-1061),
arguing that those references do not assert that an uncoated PPI would increase its own
bioavailability over time or reach therapeutically effective levels. (Dkt. 489-1 at 38–39.)
Horizon expert Dr. Taft explained that Clissold and Tolman would not provide a POSA
with a reasonable expectation of success for an uncoated PPI because those articles
evaluated enteric coated or otherwise buffered PPI formulations. (Tr. 1067:9–1068:3.)
Disadvantages of Enteric Coated Formulations
Defendants also submitted evidence that a POSA would have been motivated to
use an uncoated PPI because of known disadvantages of enteric coated PPI formulations.
(Dkt. 489 at 46–47.) International Patent Pub. No. WO 00/78293 states that
“[o]meprazole should preferably not be in contact with the enteric coating” because the
enteric coating can cause “discoloration and degradation of omeprazole.” (DTX-1105 at
4–5.) On cross-examination, Dr. Williams was presented with U.S. Patent 6,077,541
(’541 patent) (PTX-242) describing how the potential need to provide a protective layer
44

between PPIs and their enteric coating can “increase[] the length of the manufacturing
process and the cost of the product.” (Tr. 971:24–973:20.) He agreed that one “wouldn’t
have that problem” if one “ha[d] a delayed release coat that’s not pH-dependent.” (Tr.
973:11-16.) The ’541 patent also discloses that “[e]nteric coated formulations are
expensive and time consuming to manufacture, and requires [sic] elaborate technology
and equipment.” (Tr. 973:21–974:9.)
2.

Secondary Considerations of Non-Obviousness

We also consider the significance and relevance of so-called “secondary
considerations” such as commercial success, long felt but unsolved needs, and the failure
of others. See AstraZeneca LP v. Breath Ltd., 88 F. Supp. 3d 326, 382 (D.N.J.), aff’d,
603 F. App’x 999 (Fed. Cir. 2015).
(i)

Unexpected results

Horizon submits that the nonobviousness of the Invention is evidenced by the fact that
its Vimovo product had surprising and unexpected results in treating NSAID-related
gastrointestinal injury. Dr. Williams and Dr. Johnson testified that the success of a
formulation with an uncoated PPI in Vimovo was an unexpected result. (Tr. 782:24–
783:6; Tr. 1169:16–1170:1.) In designated deposition testimony, Dr. Sostek of
AstraZeneca testified that “it was unexpected that a completely unprotected form of a
proton pump inhibitor could result in effective acid suppression.” (DTX-1396 at 10.) Dr.
Johnson also highlighted statements from certain clinical studies involving Vimovo. (Tr.
1170:2-7.) One such study, Goldstein (DTX-1135), noted “a striking and highly
statistically significant difference between the patients that received Vimovo” compared
45

to other formulations, including those who received enteric coated naproxen alone. (Tr.
1170:22–1172:3.) Another publication, Hawkey (DTX-1142) characterized Vimovo by
noting that “Impressively—and surprisingly, in view of the instability of PPIs in gastric
acid—a clinical trial has shown a reduction . . . in the proportion of patients developing
NSAID-associated gastric ulcers on [Vimovo] compared with similar doses of naproxen
alone.” (DTX-1142 at 3; Tr. 1087:22–1088:10.)
Defendants dispute the relevance of the Goldstein study because it compared Vimovo
against formulations without a PPI component. (Tr. 1170:20–1171:14.) They submit that
the study cannot be considered an “unexpected result” because it does not show the
effectiveness of Vimovo against the closest prior art, which they assert would be a
Naproxen/PPI co-therapy. (Tr. 350:18–354:8; Tr. 641:5–643:17; DTX-1396 at 10; DTX1398 at 10–11.)
(ii)

Skepticism

Horizon argues that the nonobviousness of the Invention is supported by evidence
that there was skepticism that the Invention would work. As with its evidence of
unexpected results, Horizon’s skepticism evidence at trial focused on the Invention’s use
of an uncoated PPI. Dr. Plachetka, the inventor, testified that potential marketing
partners for Vimovo were skeptical about whether an uncoated PPI would work in the
formulation. (Tr. 65:5-22; 68:23–70:9.) In one email from a prospective partner (TAP),
an employee asked what steps Pozen had taken to address the degradation of a PPI that
might be predicted from using an uncoated PPI. (PTX-267 at 1.) Dr. Plachetka testified
that some TAP employees “didn’t believe” the data presented about the formulation and
46

thought it would “never work . . . because everybody knows that [PPIs] have to be enteric
coated.” (Tr. 66:13–67:23.) In another example, a Pozen employee summarized a call
with a potential marketing partner (Purdue) and wrote that Purdue “need[ed] a better
understanding of why we do not enteric coat the PPI. They feel this is an ‘enigma’ vs. all
the prior art and they are ‘not convinced’ it is necessary or beneficial to not enteric coat
the PPI.” (PTX-085 at 1.) In the same email, the employee asked: “How could all the
PPI experts be so wrong for so long?” (PTX-085 at 1; Tr. 796:14–797:18.)
Scientists at AstraZeneca, who had developed the PPIs omeprazole and
esomeprazole, similarly appeared to express skepticism regarding the use of an uncoated
PPI. (See, e.g., PTX-273; PTX-271; PTX-102; PTX-269.) In one internal email chain,
AstraZeneca’s Dr. Sostek wrote: “I think it is clear, that the current formulation is NOT
optimal from an acid suppression standpoint (because of PPI is degradation [sic] in the
stomach), but they characterize it as a good first attempt. . . . It could be difficult to
explain to physicians why PPI ‘protection’ is not necessary for this product unlike all
other PPIs.” (PTX-273 at 4.) At his deposition, Dr. Sostek explained why he thought it
would be difficult to explain to physicians why PPI protection is not necessary for
Vimovo:
Well, for years since 2000 and before, since omeprazole was
really first approved in ’89, so that at this time was over 25
years. And then by this year, Nexium had been around for five
years, Prevacid has been around for 10, 15 years. All of the PPI
manufacturers had consistently educated physicians that a
critical component of proton pump inhibitors was the enteric
coat and that you had to protect the PPI from acid degradation.
So I guess that I was saying that in light of all that education
effort about the importance of an enteric coat the Pozen
47

platform does not have an enteric coat, and so that might create
an educational challenge for physicians.
(DTX-1396 at 9.)
Horizon submitted a number of other examples of skepticism about the use of
uncoated PPIs. One Pozen memo recounted a conversation in which a doctor stated he
was “of the school” that PPIs need to be enteric coated. (PTX-266 at 1.) Another email
from Novartis asked Pozen to “[p]lease explain the rationale for the PPI in a non-enteric
coated form (since PPIs are acid labile).” (PTX-268 at 1.) A due diligence assessment
by Pozen questioned whether “unprotected esomeprazole 20 mg BID [will] produce
sufficient acid suppression to meet primary endpoint of Phase II study.” (PTX-271 at 2.)
The FDA appeared to express skepticism that an uncoated PPI would be effective, and
asked Horizon to “clarify if immediate release or delayed release esomeprazole will be
used” because “[e]someprazole is acid labile . . . [and] therefore, without a proper
delivery system it is not clear if the product will result in an intended pharmacological
effect.” (PTX-84 at 1; Tr. 789:17-23.)
Defense expert Dr. Mayersohn characterized much of Horizon’s skepticism
evidence as requests for more information rather than skepticism. (Tr. 650:1–662:16.)
Regarding Horizon’s AstraZeneca documents, Defendants argue that AstraZeneca was
actually concerned about a marketing problem because AstraZeneca had spent years
telling physicians that an enteric coating was important. (Dkt. 489-1 at 58; DTX-1396 at
9.) AstraZeneca, as Defendants point out, was the patent holder of a combination of
enteric coated esomeprazole with an NSAID and had other patents related to enteric
coated esomeprazole. (Tr. 939:5–945:4.) More broadly, Defendants contest the
48

admissibility of Horizon’s skepticism evidence on the basis that the documents are from after
the priority date. (Dkt. 489 at 56–57.)
(iii)

Licensing

Horizon argues in its post-trial brief that the licensing of the ’907 and ’285 patents
by AstraZeneca (and the subsequent acquisition of that license by Horizon) is evidence
that the asserted claims are not obvious. (Dkt. 489-1 at 53–54.) Defendants contest the
relevance of AstraZeneca’s license in view of how quickly AstraZeneca sold the rights to
Horizon, and disputes that either license “arose out of recognition and acceptance of the
patent.” See Stratoflex, Inc. v Aeroquip Corp., 713 F.2d 1530, 1539 (Fed. Cir. 1983).
Defendants also note that many potential marketing partners declined the opportunity to
license and develop the invention. (Tr. 65:14–68:12.) Moreover, AstraZeneca’s interest
may have had incentives to license the product because of its existing esomeprazole
product; as Dr. Plachetka explained, AstraZeneca had requested to use its own
esomeprazole product in the formulation. (Tr. 74:5-13.)
(iv)

Long-felt need

Horizon argues that the prevalence of NSAID-related gastrointestinal injury is
additional evidence of non-obviousness. (Dkt. 489-1 at 55.) Horizon expert Dr. Johnson
explained that NSAID-induced gastric injury was a significant medical problem at the
time of the invention. (Tr. 1118:22–1120:23; PTX-572.) He also testified that various
efforts to create safer NSAID therapies (using, e.g., sucralfate, misoprostol, and acid
suppression therapies) had not resolved the problem of NSAID-related injuries. (Tr.
1138:4–1139:4.)
49

Defendants argue that Horizon did not offer any evidence at trial that the Asserted
Patents or Vimovo addressed a long-felt but unmet need of reducing the risk of gastric
injury associated with long-term NSAID use. Dr. Johnson conceded that he had not
opined on whether NSAID-related injuries had declined following the invention. (Tr.
1227:18–1228:18.) Defense expert Dr. Metz testified that the standard of care remains
the same today after the release of Vimovo and that he had not seen any reduction in the
incidence or severity of NSAID-induced gastropathy. (Tr. 350:4-15.) Defendants also
highlighted designated deposition testimony from Dennis McNamara that Vimovo had
not been demonstrated as superior to other available co-therapies. (DTX-1398 at 10–14.)
3.

Analysis

We turn now to the overarching inquiry of whether Defendants have demonstrated
“by clear and convincing evidence that a skilled artisan would have been motivated to
combine the teachings of the prior art references to achieve the claimed invention, and
that the skilled artisan would have had a reasonable expectation of success in doing so.”
Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009).
Answering that question requires us to address: (1) the level of ordinary skill in pertinent
art; (2) the scope and content of prior art; (3) differences between the claims and the prior
art; and (4) secondary considerations. See KSR Int’l Co., 550 U.S. at 406.
We note preliminarily that the level of ordinary skill in the art was not a
significant area of contention between the parties. The parties submitted proposed
definitions of a POSA in the pretrial order:

50

Horizon’s Proposed Definition
(Dkt. 421 at 10)
A person of ordinary skill in the art
for the inventions of the asserted
claims is a person with at least a
graduate degree in pharmacy,
chemistry, chemical engineering,
pharmaceutics, or a comparable field,
and some relevant pharmaceutical
formulation work experience in
industry. Other aspects of the claimed
subject matter, such as those aspects
relating to the amounts of active
ingredient in the unit dosage form,
would implicate a person skilled in
the art of dosage, administration, and
intended clinical use and effect of an
acid inhibitor. The development of
new formulations or dosage forms can
require people with different areas of
expertise, including, for example,
those with familiarity of the dosage
and administration of the relevant
active ingredients, as well as those
with familiarity or experience in drug
formulation.

Defendants’ Proposed definition
(Dkt. 421 at 130–31)
A person of ordinary skill in the art (POSA) is a
pharmaceutical scientist having a Ph.D. degree,
or equivalent training or degree, and at least 2
years of practical experience in pharmaceutical
formulations. A POSA would have collaborated
with a medical doctor having at least 2 years of
practical experience treating patients in the
gastroenterology field and a pharmacologist /
pharmacokineticist having a Ph.D. degree, or
equivalent training or degree, and at least 2 years
of practical experience in pharmacology and
pharmacokinetics. A POSA has a general
understanding and knowledge of basic principles
of formulation development. A POSA is familiar
with the general strategies, procedures and tools
of pharmaceutical formulation development,
including pre-formulation studies, formulation
screening and optimization, and experimental
design. A POSA is also generally familiar with
the commonly used textbooks in the field of
formulation development, and has a general
knowledge of the relevant references and/or
printed publications in the field of
pharmaceutical formulation.

Witnesses at trial, to the extent they testified about the definition of a POSA,
offered largely similar definitions. (See, e.g., Tr. 268:4–269:8; Tr. 444:15-23; Tr. 574:28; Tr. 721:8–722:5; Tr. 1028:14-19.) Importantly for our purposes, experts from both
sides testified that differences between the proposed definitions of a POSA did not affect
their opinion. (See Tr. 270:13-17 (Dr. Metz); Tr. 574:14-20 (Dr. Mayersohn, noting “they’re
virtually identical descriptions of persons of ordinary skill”); Tr. 723:13-23 (Dr. Williams);
Tr. 1144:23–1145:18 (Dr. Johnson).) We will formally adopt Defendants’ definition of a
POSA (Tr. 444:13-23), but note that our analysis would be the same under either definition.

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The relevant prior art presented by the parties at trial fell broadly into two
categories. The first category pertained to drug therapies designed to reduce NSAIDrelated injury and NSAID/PPI co-therapies. The second pertained to the use and efficacy
of coated and uncoated PPIs.23 We briefly review the key disclosures in the prior art
guiding our obviousness analysis.
The ’843 (Arthrotec) patent (DTX-1063) disclosed a pharmaceutical composition
with an enteric coated NSAID core (i.e., diclofenac or piroxicam) surrounded by a
prostaglandin. (’843 patent at col. 12, lines 19–62.) The ’519 patent (DTX-1112)
disclosed the coordinated release of a prostaglandin and an enteric coated NSAID
designed to delay the release of the NSAID in order to protect the stomach. (’519 patent
at col. 1, lines 21–30.) The prior art includes studies comparing various treatment
options for NSAID-related injuries, including misoprostol, omeprazole, and ranitidine.
(DTX-1077; DTX-1069.) Based on these studies, a POSA would have understood that
omeprazole compared favorably in at least some ways to misoprostol and ranitidine in
preventing NSAID-related injuries. (DTX-1080; DTX-1089.) The prior art also
disclosed co-therapies that included PPI and NSAID components. (DTX-1051; DTX1064; DTX-1118.) Indeed, the ’907 patent acknowledges that “others have disclosed
strategies for combining” PPIs and NSAIDs for therapeutic purposes. (’907 patent at col.
2, lines 20–27.)

23

It is undisputed that some features of the Invention were well-known in the prior art, including:
(1) use of an NSAID to treat arthritis; (2) use of PPIs to inhibit acid; and (3) use of an enteric coated
NSAID. (Tr. 82:13–93:24.)

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There is much discussion in the prior art on the importance of protecting PPIs
because of their acid lability. The ’346 patent (DTX-1117) discloses the use of an
uncoated PPI together with a buffering agent designed to protect the PPI from acid
degradation. (’346 patent at col. 11, lines 13–23.) One review article states that PPIs are
“acid-unstable, requiring protection against gastric acidity.” (PTX-337 at 5.) U.S. Patent
No. 6,013,281 (PTX-573) notes that “it is obvious that a proton pump inhibitor in an oral
solid dosage form must be protected from contact with the acidic reacting gastric juice”
and that a dosage of PPIs “is best protected from contact with acidic gastric juice by an
enteric coating layer.” (’281 patent at col. 4, line 63 to col. 5, line 11.) Another reference
discloses that PPIs “are all acid-labile, so when administered orally they must be
formulated in an enteric coating to protect them from rapid degradation in the stomach.”
(PTX-077 at 3 (emphasis added).)
The prior art also discusses the bioavailability of uncoated omeprazole. Pilbrant
1985 states that a suspension of uncoated PPI had a bioavailability of about 50%. (PTX435 at 1.) A subsequent study, Pilbrant 1993 analyzed omeprazole absorption after a
meal and indicated that bioavailability might be as low as 16%. (PTX-262 at 7–8.)
Clissold cites the 44% bioavailability total from Pilbrant 1985 but also explains that the
PPI might increase its own bioavailability over time “by decreasing gastric acid secretion
and enhancing the extent of its absorption.” (DTX-1036 at 19.) Regårdh offers some
evidence that the bioavailability of omeprazole might increase as the dosage amount
increases. (DTX-1029 at 10–11.)

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The prior art contains at least some support for the notion that the use of an enteric
coat in a PPI formulation can have some disadvantages, as the enteric coat itself can
degrade the PPI. (DTX-1105; PTX-242.)
We find that the Invention departs from formulations disclosed in the prior art in
essentially two ways. First, the Invention differs from other coordinated release drug
formulations in the prior art for treating NSAID-related gastric injuries (e.g., the ’843
patent) because it used a PPI (e.g., esomeprazole) instead of a prostaglandin (e.g.,
misoprostol) as the agent to prevent or treat NSAID-related gastric injury. Second, the
Invention differs from other therapies in the prior art that used PPIs (including
NSAID/PPI co-therapies) by virtue of using an uncoated PPI.
We conclude that Defendants have failed to demonstrate that a POSA would have
been motivated to combine the teachings of the prior art references and would have had a
reasonable expectation of success in doing so. Specifically, based on the evidence
presented at trial, we conclude that a POSA would not have been motivated to use an
uncoated PPI given numerous prior art references reflecting a widely-held understanding
that the acid lability of PPIs, particularly in a solid dosage form, would generally require
an enteric coating. See KSR Int’l Co., 550 U.S. at 416 (noting “principle that when the
prior art teaches away from combining certain known elements, discovery of a successful
means of combining them is more likely to be nonobvious”).
Defendants contend that the prior art demonstrated, at most, that enteric coated
PPIs were a superior alternative to uncoated PPIs. (Dkt. 489 at 52.) These arguments
understate the language used in the prior art when discussing the need to enteric coat
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PPIs. One reference cited the “obvious” need to protect a PPI from acidic gastric juice,
and noted that a PPI is “best protected . . . by an enteric coating layer.” (DTX-573 at 5–
6.) Another explained that “PPIs are highly acid labile and hence oral formulations are
enteric coated.” (PTX-244 at 2.) Pilbrant 1985—a reference heavily relied upon by
Defendants to argue that an uncoated PPI might be expected to work—affirmatively
“ruled out” the use of uncoated omeprazole given its relatively low bioavailability.
(PTX-435 at 2.) Indeed, the Federal Circuit has previously concluded that Pilbrant 1985
“would discourage a [POSA] from pursuing conventional oral dosage forms such as
tablets, capsules, or granules with non-enteric coated PPIs, and thus teaches away from
such formulations.” Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1355 (Fed. Cir.
2012). Although Defendants’ experts argued that a POSA would have been motivated to
use an uncoated PPI, prior statements by those same experts undercut the credibility of
their testimony. (See, e.g., Tr. 365:6–369:5; Tr. 686:4–689:12.)
In light of the expert testimony and prior art references submitted at trial, we
disagree that a POSA would have been motivated to use an uncoated PPI in a new
combination drug product. See In re Chapman, 595 F.3d 1330, 1337 (Fed. Cir. 2010)
(“A finding that a reference teaches away can preclude a finding that the reference
renders a claim obvious.”) We acknowledge Defendants’ various objections to particular
references (Dkt. 489 at 48–50), but conclude that the references in their entirety would
have counseled a POSA against the use of an uncoated PPI.
We are not persuaded by Defendants’ evidence that a POSA would have had a
reasonable expectation that an uncoated PPI would be successful. Defendants base much
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of their argument on the 44% bioavailability figure from Pilbrant 1985 and the assertion
that a POSA would simply double the dosage to account for acid degradation of the PPI.
But Pilbrant 1985 itself ruled out the possibility of using an uncoated PPI given its low
bioavailability. (PTX-435 at 2.) Tellingly, in our view, Defendants’ experts could not
recall examples where a formulator simply increased the dosage to compensate for low
bioavailability caused by acid degradation. (Tr. 393:6-9; Tr. 514:4–515:25; Tr. 692:24–
695:10.) And notably, a POSA would be aware that other disclosures, such as Pilbrant
1993, suggest that bioavailability might be even lower than the 44% figure from Pilbrant
1985. (PTX-262 at 7–8.)
Nor are we persuaded by Defendants’ contention that a POSA would have had a
reasonable expectation of success by virtue of other mechanisms that might serve to
increase the bioavailability of uncoated PPI. Although there is some indication from
Clissold (DTX-1036) and Tolman (DTX-1061) that there may be a “feedback loop” that
might eventually increase the bioavailability of an uncoated PPI, those references did not
evaluate whether uncoated PPIs would be effective. The ’346 (Zegerid) patent disclosed
that an uncoated PPI could be administered with an alkalizing agent such as sodium
bicarbonate. But as explained by Horizon’s experts, a POSA would have had concerns
that the addition of an alkalizing agent would raise new challenges related to tablet size
and the possibility that the alkalizing agent would interfere with the enteric coated
naproxen also present in the Invention. (Tr. 753:21–760:16.) Indeed, the ’346 patent
itself describes how sodium bicarbonate can dissolve an enteric coating. (’346 patent at
col. 14, lines 32–37.) These drawbacks would have undermined, if not precluded, a
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POSA’s motivation to use an uncoated PPI or any expectation of success in doing so.
See Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358, 1365 (Fed. Cir.
2008) (noting that challenges associated with the inventive process that “would have
prevented one of ordinary skill in this art from traversing the multiple obstacles to easily
produce the invention”).
The PTAB has similarly rejected the argument that it would have been obvious to use
an uncoated PPI in view of Pilbrant 1985. (PTX-351 at 23–26.) Although the PTAB did not
analyze all of the references raised at trial, the thrust of the obviousness argument (there made
by Defendant DRL) was similar. Consequently, we are mindful that Defendants’ evidence
must be scrutinized carefully. See Sciele Pharma Inc. v. Lupin Ltd., 684 F.3d 1253, 1260
(Fed. Cir. 2012) (“[I]t may be harder to meet the clear and convincing burden when the
invalidity contention is based upon the same argument on the same reference that the
PTO already considered.”).
Our conclusion is somewhat strengthened by Horizon’s evidence of so-called
“secondary considerations” of non-obviousness, although we find that the Defendants have
failed to satisfy their burden of showing invalidity even without that evidence. For the most
part, Horizon’s secondary consideration evidence flows from the Invention’s use of an
uncoated PPI. There is at least some evidence in the record that the success of a formulation
with an uncoated PPI was surprising. Indeed, Hawkey explicitly noted that “Impressively—
and surprisingly, in view of the instability of PPIs in gastric acid—a clinical trial has
shown a reduction . . . in the proportion of patients developing NSAID-associated gastric
ulcers on [Vimovo] compared with similar doses of naproxen alone.” (DTX-1142 at 3.)
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Defendants reject the relevance of Hawkey, noting that unexpected results “must be
shown to be unexpected compared with the closest prior art.” In re Baxter Travenol
Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). We agree that “naproxen alone” is not the
closest prior art, but also note that the reference is commenting on the unexpected result
of an uncoated PPI compared, at least implicitly, against PPI formulations in the prior art
protected from gastric acid (i.e., through an enteric coat).
Horizon also presented a substantial amount of evidence that industry participants
were skeptical that an uncoated PPI would work at all. One potential development
partner wrote that they “need[ed] a better understanding of why we do not enteric coat
the PPI. They feel this is an ‘enigma’ vs. all the prior art and they are ‘not convinced’ it
is necessary or beneficial to not enteric coat the PPI . . . How could all the PPI experts be
so wrong for so long?” (PTX-085 at 1.) These documents, as well as others outlined
above and presented at trial, evince skepticism that a formulation with an uncoated PPI
would work. Defendants object to the applicability of these documents because they
post-date the Invention and therefore “fail[] as a matter of law.” (Dkt. 489 at 56–57.)
See In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998) (identifying “skepticism of
skilled artisans before the invention” as a secondary indicium (emphasis added)). We
disagree that controlling case law prohibits our consideration of documents created after
the priority date when evaluating evidence of industry skepticism. While the relevant
inquiry may be whether there was skepticism before or at the time of the invention, we
see no reason why post-invention documents cannot be considered as evidence of preexisting industry skepticism. Accordingly, although we may discount the weight of
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skepticism evidence created some time after the invention, documents evincing
longstanding skepticism (e.g., an industry participant asking “[h]ow could all the PPI
experts be so wrong for so long?”) still support our finding of nonobviousness.24
Other secondary indicia cited by Horizon do not similarly support a finding of
nonobviousness. We do not find that evidence of “licensing” supports a finding of
nonobviousness here, in part because the minimal evidence presented by Horizon does not
demonstrate that the “licenses arose out of recognition and acceptance of the patent.”
Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1539 (Fed. Cir. 1983). Likewise, Horizon
did not present evidence at trial that the introduction of Vimovo satisfied a “long-felt, but
unmet need” by meaningfully reducing the number of injuries associated with NSAID use.
(Tr. 1227:18–1228:18) Indeed, Defendants presented unrebutted testimony that the standard
of care has remained essentially unchanged. (Tr. 350:4-15.) It is also well-established that
filing of an ANDA does not constitute “copying” for obviousness purposes. Bayer
Healthcare Pharms., Inc. v. Watson Pharms., Inc., 713 F.3d 1369, 1377 (Fed. Cir. 2013).
For the reasons above, we conclude that the Defendants have failed to satisfy their
evidentiary burden to demonstrate that the Asserted Patents are invalid as obvious.
B.

Enablement

Defendants argue that the asserted claims are invalid under 35 U.S.C. § 112
because the ’907 and ’285 patents do not adequately disclose the utility of using an

24

Defendants also lodged a standing objection at trial to Horizon’s skepticism evidence as
inadmissible hearsay, but did not elaborate in their post-trial brief. (Dkt. 489 at 57 (submitting only
that Horizon’s “vague, after-the-fact, and anecdotal claims derived from hearsay do not salvage the
patents”).) We deny this objection, but, as noted above, our ultimate conclusion on invalidity would
remain the same even without Horizon’s evidence of secondary considerations of nonobviousness.

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uncoated PPI. (Dkt. 489 at 69.) They highlight that the patents do not contain any
experimental testing data regarding the use of uncoated PPIs, and argue that the
inventor’s unsupported “suspicion” that the invention would work is insufficient to
satisfy the utility prong of enablement. (Id.) Horizon responds that the utility of the
invention was self-evident to a POSA and that enablement does not require the disclosure
of experimental test results. (Dkt. 489-1 at 67.)
There appears to be no serious dispute between the parties that the Asserted
Patents disclose how to make and use the claimed invention. Horizon expert Dr.
Williams testified that making the claimed formulations would be routine. (Tr. 809:24–
819:13.) Defense expert Dr. Mayersohn agreed that the patent specification teaches how
to make the claimed tablets. (Tr. 680:18-21.) The patents themselves disclose their
intended use. (See, e.g., ’907 patent at col. 4, lines 18–27 (“The invention includes
methods of treating a patient for pain, inflammation and/or other conditions . . . Although
the method may be used for any condition in which an NSAID is effective, it is expected
that it will be particularly useful in patients with osteoarthritis or rheumatoid
arthritis . . . .”).)
Defendants’ specific enablement challenge focuses on whether the patents disclose
sufficient evidence to support the Invention’s claimed utility for treating various medical
conditions. (Dkt. 489-2 at 69–70.) They rely primarily on Rasmusson v. SmithKline
Beecham Corp. to argue that the disclosures in the ’90 7 and ’285 patents are inadequate.
413 F.3d 1318, 1324 (Fed. Cir. 2005). Rasmusson involved an enablement challenge to a
patent claiming the use of finasteride to treat prostate cancer. Id. at 1322. The Federal Circuit
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upheld a finding by the Board of Patent Appeals and Interferences25 that the claim was not
enabled because “a person of ordinary skill in the art would have had no basis . . . for
believing that finasteride could be used to treat prostate cancer in light of the state of the art
and in light of [the patentee’s] failure to provide any data to demonstrate the effects of
finasteride in treating prostate cancer.” Id. The Federal Circuit cited the Board’s review of
the scientific articles and expert testimony, and noted that the patentee “did not make any
contrary showing that a [POSA] . . . would have recognized that a selective 5αR inhibitor in
general, or finasteride in particular, would be effective in treating prostate cancer.” Id. at
1324.
The stated utility in the Asserted Patents of using an NSAID and a PPI to treat
pain and NSAID-related gastric injury rests on far firmer evidentiary ground than the
novel cancer treatment in Rasmusson. Testimony from both sides at trial indicated that a
POSA at the time of the invention would have accepted that a combination of an NSAID
and a PPI would be effective for treating pain and conditions like arthritis. (Tr. 562:14–
563:4; Tr. 1172:12–1173:5.) Given the understood utility of the invention, we disagree
with Defendants that the asserted claims constitute “little more than respectable guess”
that must be invalidated under the enablement requirement. Rasmusson, 413 F.3d at
1325. We also do not find that a lack of testing data on the efficacy of uncoated PPIs
renders the claims invalid. While it may often be true that “patent applications claiming
new methods of treatment are supported by test results,” it is also “clear that testing need not

25

The Board of Patent Appeals and Interferences was replaced by the PTAB under the terms of the
Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284 (2011).

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be conducted by the inventor.” In re ’318 Patent Infringement Litig., 583 F.3d 1317, 1324
(Fed. Cir. 2009). Indeed, were testing data required to obtain patents, “the associated costs
would prevent many companies from obtaining patent protection on promising new
inventions, thereby eliminating an incentive to pursue . . . potential cures.” Id. (citing In
re Brana, 51 F.3d at 1568). Consequently, we conclude that Defendants have failed to
meet their evidentiary burden to show by clear and convincing evidence that the patents
should be invalidated for lack of enablement.
C.

Written Description (Uncoated PPI)

Defendants mount a separate written description challenge based on the alleged failure
of the ’907 and ’285 patents to adequately describe the use of uncoated PPI. They believe
they have caught Horizon in a catch-22:
According to [Horizon], the claimed formulation is novel
because a POSA would not have expected an uncoated PPI to
be effective. Against this background, Plaintiffs argue that a
POSA reading the asserted patents’ formulation recipes would
immediately understand that an uncoated PPI is effective—
even though the specifications disclose no data, reasoning, or
other information in support. But both cannot be true.
Fundamentally, because the patents lack any disclosure of an
uncoated PPI’s efficacy, the claims are either obvious (if the
POSA understands that uncoated PPIs work), or lacking
description (if the POSA believes uncoated PPIs would not
work).
(Dkt. 489 at 69.)
As Defendants point out, the Asserted Patents do not address the efficacy of
uncoated PPIs through experimental testing data or other statements in the specification.
(Tr. 666:16–677:14; Tr. 1004:16–1005:11.) Instead, Defendants characterize the
specification as “parroting claim language,” which they view as insufficient given
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Horizon’s position that the prior art had taught away from the use of uncoated PPIs.
(Dkt. 489 at 66.)
Horizon responds that the specifications of the Asserted Patents adequately
describe the use of uncoated PPIs, and that the law does not require the specification to
“present data or an explanation of why the prior art was wrong to refute the teaching the
in the prior art.” (Dkt. 489-1 at 65.) Instead, Horizon cites Allergan, Inc. v. Sandoz Inc.,
for the proposition that “[a] claim that recites a property that is necessarily inherent in a
formulation that is adequately described is not invalid as lacking written description
merely because the property itself is not explicitly described.” 796 F.3d 1293, 1309 (Fed.
Cir. 2015).
Our inquiry is whether the lack of information regarding the efficacy of uncoated PPIs
means that the patent specification does not “reasonably convey[] to those skilled in the art
that the inventor had possession of the claimed subject matter as of the filing date.”
Ariad, 598 F.3d at 1351. The ’285 patent specification contains various disclosures
describing the immediate release of an acid inhibitor as a component of the invention.26
For example, the specification describes that “[t]he acid inhibitor is in one or more layers
outside of the core which do not contain any NSAID. These layers are not surrounded by
an enteric coating and, upon ingestion of the tablet or capsule by a patient, release the
acid inhibitor into the patient’s stomach.” (’285 patent at col. 4, lines 37–41.) This early
release of the acid inhibitor is repeatedly described, with the specification similarly

26

As noted above, the ’285 and ’907 patents contain virtually identical specifications and our analysis
applies equally to both patents.

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disclosing that: “the acid inhibitor is released first and the release of NSAID is delayed
until after the pH in the GI tract has risen.” (Id. at col. 4, lines 45–51; see also id. at col.
5, lines 12–16.) The immediate release of an uncoated acid inhibitor is explicitly
distinguished in the specification from enteric coated PPI formulations that delay the
absorption of the acid inhibitor: “[t]he effect [of PPIs] may be diminished towards the
end of the usual dosing interval. Intragastric pH rises particularly slowly with the first
dose in a course of treatment since this class of drugs is enteric coated to avoid
destruction by stomach acid. As a result, absorption is delayed for several hours.” (Id. at
col. 2, lines 3–8.) In contrast, the examples in the specification describe, e.g., the “rapid[]
release” of uncoated omeprazole. (Id. at col. 16, lines 33–49.)
Particularly in light of disclosures in the specification describing the immediate
release of an uncoated PPI and the potential disadvantages of enteric coated PPI
formulations, we conclude that Defendants have not shown by clear and convincing
evidence that the Asserted Patents should be invalidated for failing to meet the written
description requirement. The lack of experimental testing data or detailed analysis on
why an uncoated PPI might prove effective does not require us to find otherwise. We
reject, however, Horizon’s suggestion that the efficacy of uncoated PPIs need not be
described because it is “necessarily inherent” in a formulation. (Dkt. 489-1 at 65.)
Horizon relies without elaboration on Allergan, 796 F.3d at 1309, a case which we have
previously noted does not provide clear guidance on what qualifies as an inherent
property of a formulation nor how that determination bears on the written description

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analysis. See Helsinn Healthcare S.A. v. Dr. Reddy's Labs., Ltd., No. 12-2867, 2017 WL
631899, at *26 n.43 (D.N.J. Feb. 14, 2017).
V.

Conclusion
For the reasons discussed in Section III, we find that the DRL ANDA II Product

infringes claims 1, 2, 3, and 4 of the ’285 patent and that those claims are not invalid
under 35 U.S.C. § 112. For the reasons discussed in Section IV, we find that the claims
of the ’907 and ’285 patents are not invalid under 35 U.S.C. § 103 or § 112. We will file
this memorandum opinion under temporary seal and order the parties to submit a
proposed form of Judgment in accordance with this opinion.
s/ Mary L. Cooper
MARY L. COOPER
United States District Judge
Dated: July 10, 2017

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