Horizon Medicines LLC v. Alkem Laboratories Ltd.

N OTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
HORIZON MEDICINES LLC,
Plaintiff-Appellant
v.
ALKEM LABORATORIES LTD.,
Defendant-Appellee
______________________
2021-1480
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:18-cv-01014-RGA, Judge
Richard G. Andrews.
______________________
Decided: November 16, 2021
______________________
CARYN B ORG -BREEN, Green, Griffith & Borg-Breen
LLP, Chicago, IL, argued for plaintiff-appellant. Also rep-
resented by J ESSICA T YRUS MACKAY , T IMOTHY O'BRIEN.
WILLIAM A. RAKOCZY , Rakoczy Molino Mazzochi Siwik
LLP, Chicago, IL, argued for defendant-appellee. Also rep-
resented by AMY D. BRODY , X IAOMEI CAI.
______________________
Before D YK, O’MALLEY , and HUGHES , Circuit Judges.
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 2
D YK, Circuit Judge.
Horizon Medicines LLC (“Horizon”) is the owner of U.S.
Patent Nos. 8,067,033 (“the ’033 patent”) and 8,067,451
(“the ’451 patent”). In response to Abbreviated New Drug
Application (“ANDA”) No. 211890 submitted by Alkem La-
boratories LTD. (“Alkem”), Horizon filed suit in the United
States District Court for the District of Delaware alleging
that Alkem’s ANDA infringed Horizon’s patents. After a
bench trial, the district court found that claims 1, 8, 11, and
14 of the ’033 patent were invalid for obviousness and not
infringed, and that claims 1–3 and 8–10 of the ’451 patent
were not infringed. We affirm the district court’s findings
that the asserted claims of the ’033 patent were invalid for
obviousness and that the asserted claims of the ’451 patent
were not infringed.
BACKGROUND
I
Patients with rheumatoid arthritis and osteoarthritis
may take high doses of non-steroidal anti-inflammatory
drugs (“NSAIDs”) to combat chronic pain and inflamma-
tion. NSAIDs may be selective or non-selective.1 Non-se-
lective NSAIDs, such as ibuprofen, can cause stomach
ulcers after prolonged use. Before 2004, doctors prescribed
1 Cyclooxygenase (“COX”) is an enzyme required to
create certain molecules responsible for inflammation and
pain. It comes in two varieties, COX-1 and COX-2. COX-1
enzymes also play a role in maintaining the mucus lining
of the stomach. Non-selective NSAIDs inhibit both COX-1
and COX-2. Selective NSAIDs only target COX-2, thereby
providing anti-inflammatory relief without compromising
the stomach lining. See Ida Ghlichloo & Valerie Gerriets,
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (May 12,
2021), https://www.ncbi.nlm.nih.gov/books/NBK547742/.
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 3
selective NSAIDs to relieve pain and inflammation while
causing fewer gastrointestinal complications. In 2004, se-
lective NSAID Vioxx was removed from the market be-
cause it created a risk of cardiovascular complications.
Anticipating a shift toward non-selective NSAIDs (such as
ibuprofen), Dr. George Tidmarsh and Barry Golombik
formed Horizon in September 2004 to develop a solution to
the problem created by taking non-selective NSAIDs.
The regular use of ibuprofen creates a risk of upper
gastrointestinal ulcers in patients with rheumatoid arthri-
tis and osteoarthritis. The ’033 and ’451 patents are di-
rected to a pharmaceutical composition wherein 800 mg
ibuprofen and 26.6 mg famotidine are combined in a tablet
product to treat pain while decreasing the risk of ulcera-
tion. The use of ibuprofen to treat pain and famotidine to
reduce the risk of ulceration was known in the art. Com-
bining ibuprofen and famotidine into a single dose was also
known in the prior art, thereby allowing patients to receive
both drugs concomitantly and avoiding the patient compli-
ance issues associated with a regimen consisting of two
separate dosage forms. However, due to the chemical in-
compatibility between ibuprofen and famotidine, such sin-
gle dose forms degraded over time, particularly in
conditions of elevated temperature and relative humidity.
The claimed invention of the patents in suit was to de-
velop a single dosage form comprising both ibuprofen and
famotidine that “exhibit[s] exceptional stability under
forced degradation conditions.” J.A. 223. The ’033 patent
achieves this stability by minimizing the surface area of di-
rect physical contact between the incompatible ingredi-
ents, as recited in claim 1 below:
1. A pharmaceutical composition comprising
a first portion that comprises 800 mg ibuprofen and
a second portion that comprises 26.6 mg fa-
motidine,
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 4
wherein the surface area of direct physical contact
between ibuprofen and famotidine does not exceed
130 mm 2,
wherein no more than about 1% sulfamide is pre-
sent when the composition is stored at 40° C. and
75% relative humidity for a period of one month,
wherein the composition is formulated so that re-
lease of both the ibuprofen and the famotidine oc-
curs rapidly at about the same time,
wherein none of the composition, the famotidine,
and the ibuprofen is enterically coated or formu-
lated for sustained or delayed release, and
wherein the composition is for use according to a
TID (three times per day) administration schedule
for reducing the risk of developing ibuprofen-in-
duced ulcers in a human patient requiring ibu-
profen for an ibuprofen-responsive condition.
Dependent claim 8 additionally recites a “barrier layer”
separating the ibuprofen and famotidine.
The ’451 patent discloses the use of Opadry® White YS-
1-7003 (“YS-1-7003”) as a barrier layer to further improve
stability. Claim 1 of the ’451 patent is reproduced in rele-
vant part below, reciting the use of the ingredients in YS-
1-7003 in a “barrier layer” limitation:
1. An oral dosage in tablet form comprising
a first portion that comprises 800 mg ibuprofen and
a second portion that comprises 26.6 mg fa-
motidine,
wherein a barrier layer comprising hydroxyl propyl
methyl cellulose 2910, polyoxyethylene glycol 400,
polysorbate 80, and titanium dioxide surrounds the
second portion completely separating it from the
first portion . . .
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 5
II
Horizon sells DUEXIS®, an FDA-approved tablet-in-
tablet product with a famotidine core, an ibuprofen shell,
and an Opadry® White barrier layer in between. In 2018,
Alkem submitted its ANDA seeking FDA approval for an
ibuprofen core, famotidine shell tablet product while also
making a Paragraph IV Certification under the provisions
of the Hatch-Waxman Act, 21 U.S.C. § 355(j)(2)(A)(vii)(IV),
asserting that its product did not infringe Horizon’s pa-
tents or that the patents were invalid. In response, Hori-
zon filed suit in the district court alleging infringement by
Alkem’s ANDA submission.
During claim construction, the district court found that
Horizon narrowed the claim scope of the ’451 patent by
specifying a barrier layer of YS-1-7003, describing it by list-
ing the ingredients. The district court accordingly con-
strued the “barrier layer” limitation in the ’451 patent to
mean “consisting essentially of” the ingredients in YS-1-
7003. Horizon apparently believed that claim 1 of the ’451
patent was not infringed under the district court’s claim
construction and did not present infringement evidence at
trial.
After trial, the district court found the asserted claims
of the ’033 patent invalid for obviousness and not infringed.
The district court also entered judgment in favor of Alkem
that its ANDA products did not infringe the claims of the
’451 patent. Horizon appeals. We have jurisdiction pursu-
ant to 28 U.S.C. § 1295(a)(1).
D ISCUSSION
We review the district court’s factual findings after a
bench trial for clear error and the court’s legal conclusions
de novo. See, e.g., Meds. Co. v. Mylan, Inc., 853 F.3d 1296,
1302 (Fed. Cir. 2017).
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 6
I. The ’033 Patent
A
In finding the asserted claims invalid for obviousness,
the district court relied in part on U.S. Patent Application
Pub. No. 2007/0043096 A1 (“the ’096 publication”). Hori-
zon argues that the district court committed legal error be-
cause the ’096 publication is not prior art to the ’033 patent.
We see no error in the district court’s finding that the ’096
publication is prior art.
Under pre-AIA 35 U.S.C. § 102(a), a reference is prior
art if it was “known or used by others in this country, or
patented or described in a printed publication in this or a
foreign country, before the invention thereof by the appli-
cant for a patent.” The court looks to “not merely the dif-
ferences in the listed inventors, but whether the portions
of the reference relied on as prior art, and the subject mat-
ter of the claims in question, represent the work of a com-
mon inventive entity.” Riverwood Int’l Corp. v. R.A. Jones
& Co., Inc., 324 F.3d 1346, 1356 (Fed. Cir. 2003). The ’033
patent claims the 800 mg ibuprofen and 26.6 mg fa-
motidine combination dosage form disclosed in the ’096
publication.
The ’096 publication published on February 22, 2007,
listing both Golombik and Tidmarsh as inventors. The ’033
patent has a priority date of November 30, 2007, listing
Tidmarsh but not Golombik as an inventor.2 Horizon
2 We note that the ’096 publication lists Tidmarsh,
Golombik, and Lii as inventors and that the ’033 patent
lists Tidmarsh and Xu as inventors. In view of our dispo-
sition regarding Golombik’s inventorship on the ’033 pa-
tent, we need not consider the impact of the additional
inventors Lii and Xu as to whether the ’096 publication is
prior art.
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 7
sought to correct the inventorship of the ’033 patent by add-
ing Golombik as an inventor pursuant to 35 U.S.C. § 256
so that Golombik and Tidmarsh would be listed as inven-
tors on both the ’033 patent and the ’096 publication. The
district court denied the request. Horizon argues that be-
cause the district court determined that Tidmarsh and
Golombik invented the dosage amounts and dosing regi-
men disclosed in the ’096 publication, which appear in
claim 1 of the ’033 patent, then Golombik must have also
invented this subject matter in the ’033 patent and Horizon
should be allowed to add Golombik to the list of inventors
on the ’033 patent.
We see no error in the district court’s decision declining
to add Golombik as an inventor on the ’033 patent. The
general rule is that the inventors named in an issued pa-
tent are presumed to be correct, and “a district court must
find clear and convincing evidence that [an] alleged un-
named inventor was in fact a co-inventor before correcting
inventorship.” Caterpillar Inc. v. Sturman Indus., Inc., 387
F.3d 1358, 1377 (Fed. Cir. 2004). “[I]nventor[] testimony,
standing alone, is insufficient to prove conception—some
form of corroboration must be shown” to safeguard against
inventors who might otherwise “be tempted to remember
facts favorable to their case.” EmeraChem Holdings, LLC
v. Volkswagen Grp. of Am., Inc., 859 F.3d 1341, 1346 (Fed.
Cir. 2017). In the related context of analyzing corrobora-
tion for priority of invention, this court has held that “tes-
timony of one co-inventor cannot be used to help
corroborate the testimony of another.” Medichem, S.A. v.
Rolabo, S.L., 437 F.3d 1157, 1171 (Fed. Cir. 2006).
Our cases are clear that inventing something in an ear-
lier patent or patent application does not automatically
make one an inventor of patents that incorporate the ear-
lier invention. See, e.g., Eli Lilly and Co. v. Aradigm Corp.,
376 F.3d 1352, 1358, 1362 (Fed. Cir. 2004) (“A contribution
of information in the prior art cannot give rise to joint
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 8
inventorship because it is not a contribution to concep-
tion.”). Otherwise, as the district court pointed out, “the
inventors of ibuprofen and famotidine would be properly
named inventors of the ’033 patent, as the patent claims
build on the prior art by using those two ingredients.” J.A.
143–44.
Horizon relies on Pannu v. Iolab Corp., 155 F.3d 1344
(Fed. Cir. 1998) to argue that Tidmarsh and Golombik were
engaged in a collaborative enterprise and thus their disclo-
sure in the ’096 publication should not prevent Golombik
from being included as an inventor on the ’033 patent.
However, Pannu is inapt because the court declined to find
sole inventorship in a situation where it was “undisputed
that [the individuals] collaborated in the development and
production of one-piece prototype embodiments of the in-
vention.” Id. at 1351. The only support for Golombik’s con-
tribution to the ’033 patent is testimony by Tidmarsh and
Golombik. The district court discounted these testimonies
as “non-specific,” “convenient, uncorroborated, and not
very credible,” and concluded that “there was no proof that
Mr. Golombik made even the slightest contribution to the
’033 patent.” J.A. 143. We see no clear error in these de-
terminations. There is also no corroborated collaboration
with respect to the invention of the ’033 patent. Indeed,
Golombik minimized his own involvement in its conception
and admitted that Tidmarsh came up with the idea of sep-
arating the ibuprofen and famotidine into two portions.
B
With respect to the issue of obviousness, Horizon ar-
gues that the district court committed legal error in finding
that a person of ordinary skill in the art would have had a
reasonable expectation of success to achieve the claimed
degree of stability in the ’033 patent. Contrary to Horizon’s
argument, the district court did not place the burden on
Horizon to establish a reasonable expectation of success.
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 9
Rather, the district court found that a prior art reference
(“the ’671 publication”) disclosed tablet-in-tablet separa-
tion methods, like those recited in the ’033 patent, “to
achieve greater stability” in pharmaceutical formulations
containing drugs similar to ibuprofen and famotidine, un-
der the same stability conditions claimed in the ’033 pa-
tent. J.A. 159. The district court’s analysis is also
supported by testimony from Alkem’s expert witness. For
example, in response to a question about what the stability
data in the ’671 publication disclosed to a skilled person,
Alkem’s expert stated the following:
Well, they put the embodiment in the room temper-
ature and elevated accelerated temperature condi-
tions. The same 40 degrees C, 75 relative humidity
that's in claim 1 of the ’033 patent. And they stored
it, not only for one month as required in the [’]033
limitation, but for one, two, three to six months.
And what they found was that the ranitidine which
was the compound they were stabilizing by struc-
ture small core, barrier layer, larger shell, was sta-
ble at that 40 degrees, 75 percent humidity for up
to six months.
J.A. 11101. We see no clear error in the district court’s
findings regarding expectation of success.
C
Horizon also appeals the district court’s noninfringe-
ment finding with respect to the ’033 patent. Because we
affirm the district court’s finding that the asserted claims
of the ’033 patent are invalid for obviousness, the infringe-
ment issue is moot, and we do not reach it. TypeRight Key-
board Corp. v. Microsoft Corp., 374 F.3d 1151, 1157 (Fed.
Cir. 2004) (“[A] judgment of invalidity necessarily moots
the issue of infringement.”).
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 10
II. The ’451 Patent
Horizon argues that the district court erred in constru-
ing “comprising” in the “barrier layer” term in the ’451 pa-
tent to mean “consisting essentially of,” and that the
construction and subsequent finding of noninfringement
should be vacated. However, in its briefing before this
court, Horizon makes no effort to show how the alleged er-
ror in interpreting “comprising” was prejudicial. Accord-
ingly, Horizon has failed to establish harmful error
warranting reversal. See Ecolab, Inc. v. Paraclipse, 285
F.3d 1362, 1374 (Fed. Cir. 2002) (“[T]o warrant a new trial,
Ecolab must show that the erroneous jury instruction was
in fact prejudicial. When the error in a jury instruction
‘could not have changed the result, the erroneous instruc-
tion is harmless.’”) (citations omitted); see also Omega Pa-
tents, LLC v. CalAmp Corp., 920 F.3d 1337, 1343 (Fed. Cir.
2019).
In any case, the prosecution history of the ’451 patent
supports the district court’s construction. Across multiple
exchanges with the examiner, Horizon explained that it
was amending the claims to “focus on an embodiment of the
invention that uses Opadry® White (YS-1-7003) as a bar-
rier layer,” acknowledged that the claims specified that
“the barrier layer is Opadry White (YS-1-7003),” and dis-
tinguished prior art based on current claims with “the lim-
itation that the barrier layer be Opadry White (YS-1-
7003).” J.A. 123. For example, Horizon argued in an office
action response that “[t]he [p]rior [a]rt, [e]ither [a]lone or
[i]n [c]ombination, [p]rovides [n]o [r]ationale for a [b]arrier
[l]ayer of Opadry White (YS-1-7003).” J.A. 2425. Horizon
eventually amended its claims to include the “comprising”
language at issue, but this was only at the Examiner’s sug-
gestion “to combine the method claims with the specific
composition comprising OP[A]DRY-WHITE (YS[-]1-7003)
for a favorable consideration.” J.A. 124. Considering the
intrinsic record, the district court concluded that “the
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HORIZON MEDICINES LLC v. ALKEM LABORATORIES LTD. 11
amendment resulted in no increase in scope regarding the
barrier layer.” Id. We do not see any error in the district
court’s determination that Horizon unambiguously nar-
rowed its claim scope to a barrier layer of YS-1-7003.
CONCLUSION
We affirm the district court’s findings that claims 1, 8,
11, and 14 of the ’033 patent are invalid for obviousness
and that claims 1–3 and 8–10 of the ’451 patent are not
infringed by Alkem’s ANDA.
AFFIRMED
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