Court Opinion

ID: 5132218
Source: CourtListenerOpinion
Date Created: 2021-12-07 00:01:38.959381+00
Date Added: 2024-06-11T08:23:28.894714
License: Public Domain

Case: 21-1480     Document: 38    Page: 1   Filed: 11/16/2021

        NOTE: This disposition is nonprecedential.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 BORG-BREEN, Green, Griffith & Borg-Breen
 LLP, Chicago, IL, argued for plaintiff-appellant. Also rep-
 resented by JESSICA TYRUS MACKAY, TIMOTHY O'BRIEN.

     WILLIAM A. RAKOCZY, Rakoczy Molino Mazzochi Siwik
 LLP, Chicago, IL, argued for defendant-appellee. Also rep-
 resented by AMY D. BRODY, XIAOMEI CAI.
                  ______________________

    Before DYK, O’MALLEY, and HUGHES, Circuit Judges.
Case: 21-1480     Document: 38      Page: 2    Filed: 11/16/2021

 2        HORIZON MEDICINES LLC    v. ALKEM LABORATORIES LTD.

 DYK, 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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 4        HORIZON MEDICINES LLC   v. ALKEM LABORATORIES LTD.

     wherein the surface area of direct physical contact
     between ibuprofen and famotidine does not exceed
     130 mm2,
     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).
                          DISCUSSION
     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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 6        HORIZON MEDICINES LLC    v. ALKEM LABORATORIES LTD.

                      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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 8        HORIZON MEDICINES LLC   v. ALKEM LABORATORIES LTD.

 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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 10       HORIZON MEDICINES LLC    v. ALKEM LABORATORIES LTD.

                      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