Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 1 of 22 PageID #: 9096
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OFDELAWARE
`
`COSl\在o TBCHNOLOGIBS LINIITBD,
`VALBANTPHA去MACBUTICALS
`INTBRNATI0NAL, and VAL丑ANT
`PHARMACBUTICALS LUXBIv.1BOURG
`sλR.L.量
`
`REDACTED PUBLIC VERSION
`
`Plainti酶，
`
`C.A. No. 15-164-LPS
`
`飞v.
`
`ACTA VIS LABORATORIBS FL, INC.,
`
`Defendant.
`
`COSMO TBCHNOLOGIES L队tfITBD，
`VALEANTPHA去且在ACBUTICALS
`INTBRNATIONAL, and VALBA到T
`PHARMAC主UTICALS LUXEMBOURG
`sλ 孔L量
`
`Plain'往能F
`
`C.A. No. 15唰193-LPS
`
`飞v.
`
`ALVOG自 P时E BROOK, LLC,
`
`Defendant.
`
`Jack B. Blumenfeld, M旧yellen Noreika, MORRIS，边ICHOLS， ARSHT & TUNNELL L曰，
`Wi1mington, DB
`
`David.M. Conc缸， Melar出乱 Rupert， and Nicholas A. T泸在oczko， P AUL HASTINGS LLP, New
`York, NY
`
`Gary Frischling and Yite John Lu, IRELL & MANELLA LLP, Los A吨eles， CA
`
`Attomeys for Plainti岱.
`
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`Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 2 of 22 PageID #: 9097
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`John C. Phi1lips, Jr. and Dæ村d A. Bi1son, PHILLIPS GOLDMAN MCLAUGHLIN & HALL,
`P 儿， Wi1mington, DE
`
`Elizabeth J. Hol1and and Naomi L. Birbach, GOODWIN PROCTER LLP, New York, NY
`
`John T. Bennett, Samuel E. Sher巧， and Todd Mærabel1a, GOODW时 PROCTER LLP, Boston,
`MA
`
`Attomeys for Defendant Actavis Laboratories FL, Inc.
`
`Kæren E. Kel1er, J ef丘ey T. Castellano, and David M. F厅， SHA W KELLER LLP, Wi1mington,
`DE
`
`Matthew J. Becker imd Jason T. Murata, AXINN, VELTROP & HARKRIDER LLP, Hærtford,
`CT
`
`Delphine W. Knight Brown, AXll恼， VELTROP & HARKRIDER LLP, New York, NY
`
`Brett G缸rison， AX卧oIN， VELTROP &HARKRIDERLLP, Washington, DC
`
`Attomeys for Defendant Alvogen Pine Brook, LLC.
`
`MEMORANDUM OPINION
`
`October 27, 2017
`Wi1mington, Delawære
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`Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 3 of 22 PageID #: 9098
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`Cosmo Technologies Limited, ValemtPhannacmticals InteEZlationa1, aIldValeant
`
`Pharmaceuticals Luxembourg S.àr.L (collectively, "Plainti即') brought this patent infringement
`
`action under the Hatch附Waxman Act, 21 U.S.C. ~ 355(j), against DefendantsActavis
`
`Laboratories FL; Inc. ("Actavis") and Alvogen Pine Brook, LLC ("Alvogen勺， which eacli
`
`submitted an Abbreviated New Drug Application ("ANDA") to market a generic versiori of
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`Uωris⑧， which are ora1 tablets containing 9 mg ofbudesonide for 仕ea恤lent of mild to moderate
`
`ulcerative colitis. (C.A. No. 15国 164-LPS D.1. 118 at 咱 23; C.A. No. 15.193-LPS D.1. 116 at
`
`们的 1 Plainti他 assert Orange Book-listed U.S. Patent No. 8,784,888.2 Specifica1ly, Plainti能
`
`ass町t claim 9 against Actavis and claim 6 against Alvogen. (0.1. 221 , 223) As relevant here, the
`
`'888 p创ent genera1ly claims budesonide tablets having a macroscopically homogeÌlous
`
`∞mposition.
`
`The Court held a claim construction hearing oÌl July 11, 2016 to construe disputed claim
`
`terms and issued a claim construction opinion and order on September 7, 2016. (0.1. 183, 184)
`
`In May 2017，也e Court held a bench 创a1. (See D.1. 241 , 243 ("Tr.")) At the close of
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`P肌la划础ain讪n削nti性圳tif岱丑B旨s' cωas岱巳萨e-i也i
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`Federa1 Ru叫』址l巳 ofCαi忖ivi叽i证1 Procedure 52(φωc吩). The Court grant巳d Defendants' motions 企om the bench.
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`1All references to the Docket Index 缸eto C.A. No. 15-164, unless otherwisenoted.
`
`2In也eir second amended complaint, Plainti岱a1so asserted U.S. Patent Nos. 7,410,651;
`8 ，293 ，273; 阳 43万9; and 9,320,716 againstActavis (D.1. 118 at 们) and U.S. Patent Nos.
`7,410,651; RE 43,799; and 9,320,716 against Alvogen (C.A. No. 15-193 D.1. 118 at 咱匀， but
`吐ley narrowed 也e ass回ed patents and claims before tria1. (See D.1. 221) At trial, Plainti岱a1so
`asse此巳:d claim 3 ofthe '273 patent against Actavis. After tria1, Plaintiffs dropped their
`allegatjons ofinfringement ofthe '273 patent. (See D.I. 230 Ex. 1)
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`Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 4 of 22 PageID #: 9099
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`(See Tr. at 332) The C.ourt subsequently a1I.ow巳:d the parties t.o submit briefs t.o assist the C.ourt
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`in issuing written findings .offact and c.onclusi.ons .oflaw (D.I. 232; 234), and the p'arties a1s.o
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`submitted a j .oint Statement .ofUnc.ontested Facts ("SUF") (D.I. 233).
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`Pursuant t.o Rule 52(吟， after having c.onsidered 也een甘rerec.ord in 也is case and the
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`applicable law, and c.onsistent with the C.ourt's ruling after the cl.ose .ofPlainti邸， case, the C.ourt
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`c.oncludes that Plainti岱 have failed t.o pr.ove by a prep.onderance .of the evidence that (1) Actavis
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`in企i，nges claim 9 .ofthe '888 patent and (2) Alv.ogen infringes c1aim 6 .oftl窟 '888 patent.
`
`FINDINGS OF FACT
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`ηIÌs secti.on ∞ntains 出 C.ourt's findings .offact ("FF") .on disputes raised by the partiω
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`during 甘ial， as well as facts t.o 'which the parties have stipulated. Certain 岛ldings .of fact 町eals.o
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`provided in c.onnωti.on with the C.ourt's c.onclusi.ons .oflaw.
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`1.
`
`The Parties
`
`1. .
`
`Plaintiff C.osm.o τechn.ol.ogies Limited ("C.osm.o") is an lrish c.orp.orati.on, havirig
`
`its prin巳ipal place .ofbusiness at Riverside II, Sir J.ohn R.ogers.on's Quay, Dublin 2, Ireland. (SUF
`
`咱 1)
`
`2;
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`PlaintiffVale明t Pharmaceuticals Intemati.onal 问PI") is a c.orp.orati.on .organized
`
`and existing under the laws .ofthe State .ofDelaware, having a principal place .ofbusiness at 400
`
`S.omerset C.orp.orate Blvd., Bridgewater, New Jersey 08807. (σSUF 咱 2)
`
`3.
`
`Plaintifì贸fValeant Pha且rmac臼eu旧叫It创ticωals Luxemb.ou町.rrg S.à r.1. ("Valeant S.à r.l.'乃，
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`Lux阻X巳mb.o∞>ur鸣gc∞or甲p.o町rati甘.on民1， having a princ比ci协P且alp抖lace .ofbus囚sine田ss a创t 1η3町 15 Avenue de la Lib刷品，
`
`L-1931 Luxemb.ourg, Grand Duchy .of Luxemb.ourg. Valeant S.à r.l. is a wh.olly-.owned
`
`subsidiary .ofVPI. (SUF 咱 3)
`
`2
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`Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 5 of 22 PageID #: 9100
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`4.
`
`Defendant Actavis Laboratories FL, Inc. ("Actavis") is a corporation organized
`
`and existing under the laws of the State of Florida, having a pla∞ ofbusiness at 400 Interpace
`
`Parkway, Parsippany, New Jersey 07054. (SUF 咱 4)
`
`5.
`
`Defendant Alvogen Pine Brook, LLC ("Alvogen") is a limited liabili1y company
`
`organized and existing under the laws of the State of Delaware, having à. principal place of
`
`businωs at 10 Bloomfield Av巳:nue， Pine Brook, New Jersey 07058. (SUF 咱 5)
`
`11.
`
`Uceris⑧
`
`6.
`
`VPI holds New Drug Application ("NDA'丁 No. 203634 for oral tablets containing
`
`9 mg of the active ingredientbudesoni巾， which are sold in the United States under the brand
`
`name Uceris@, (SUF 节的
`
`7.
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`Uceris@ is indicatedfor the induction ofremission in patients with active, mild to
`
`moderate u1cerative ∞litis. (SUF 咱 7)
`
`8.
`
`Uc町is⑧ was launched on February 14, 2013 by Santarus, Inc. (SUF 咱 8)
`
`111. Defendants' ANDAs
`
`9.
`
`Actavis submitted ANDA No. 205457 to 也巳 FDA under ~ 505(j) ofthe Federal
`
`Food, Drug, and Cosme位c Act (21 U.S.C. ~ 355(j)) seeking FDA approval to engage in the
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`commercial manufactnre, use, sale, or offer for sale of extended release tablets containing 9 mg
`
`ofbudesonide ("Actavis ANDA product") prior to the expitation ofthe patentscin-suit. The
`
`Actavis ANDA product is a pharniaceutical composition for oral administration. Actavis'
`
`ANDA describes amanufacturing process for the production ofthe Actavis ANDA product.
`
`(SUF 啊 21-23)
`
`10.
`
`Alvogen submitted ANDA No. 205556 to the FDA under 21 U.S.C. ~ 355(j)
`
`3
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`Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 6 of 22 PageID #: 9101
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`seeki且g FDA approval to engage in the commercial manufacture, use, sale, or offer for sale of
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`extended-release tablets containing 9 mg ofbudesonide ("Alvogen ANDA product") prior to the
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`expiration ofthe patents-in-suit. 四e Alvogen ANDA product is a pharmaceutical composition
`
`for oral administration. Alvogen' s ANDA describes a manufacturing process for the production
`
`of the Alvogen ANDA product. (SUF 啊 24-26)
`
`IV. The '888 Patent
`
`1 L
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`U.S. Patent No. 8,784,888 was issued by the USPTO on July 22， 2014.η邸 '888
`
`patent will expire on June 20, 2020. The patent n缸nes Roberto Vi11a, Massimo. Pedrani, Mauro
`
`Ajani, and Lorenzo Fossati as inventors, and lists Cosmo as assign四. (SUF 啊 11 ， 14cI5)
`
`12.
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`Cosmoowns 也巳 '888 patent, and Valeant 8.à r.l. holds an exclusive license to the
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`patent in the United 8t眩目. (8UF 啊 16-17)
`
`13.
`
`Plaintiffsωsert cl创m 9 against Actavis and claim 6 against Alvogen. (See D.I.
`
`221, 223; Tr. at 101, 78-79)
`
`14.
`
`Claims 6 and 9 both depend indirectly from claim 1. Claim 1 recites:
`
`A controlled release oral pharmàceutical composition cönsisting essentially of:
`
`(1) a 切Lblet core consisting essentially of:
`
`a) budesonide in an amount effective to treat
`intestinal inflammatory disease; and
`
`b) a macroscopically homogeneous
`composition ∞mprising at least one
`lipophi1ic excipient, at least one 缸nphiphilic
`excipient, and at least one hydrogel-forming
`hydrophilic excipient other than a gum,
`wherein said budesonide is dispersed in said
`macroscopically homogeneous ∞mposition;
`and
`
`4
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`ο) a c'Oating 'On said tablet c'Ore, said c'Oating
`c'Onsisting essentia11y 'Of a gas仕o-resistant 丑1m
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`σTX-2004 at c'01. 1011. 19-31) (emphasis added)
`
`15.
`
`Claim 6 depends 企'Om c1aim 5. Claim 5 recites: "A c'Ontr'Olled releas巳'Oral
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`pharmaceutica1 c'Omp'Ositi'On acc'Ording t'O claim 1, wherein said at least 'One lip'Ophilic excipient
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`c'Omprises stearic acid 'Or magnesium stearate." (JTX-2004 at c'01. 1011. 44-46) Claim 6 recites:
`
`"A c'Ontr'Ol1ed release 'Ora1 pharmaceutical c'Omp'Ositi'On acc'Ording t 'O c1aim 5, wherein said at least
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`'On巳 hydr'Ogel-f'Orming hydr'Ophi1ic excipient c'Omprises at least 'One hydr'Oxyalkyl ce11ul'Ose."
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`。TX-2004 at c'01. 10 11. 47-50)
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`16.
`
`Claim 9 depends fr'Om c1aim 7. Claim 7 recit曰: "A c'Ontr'Olled relt:ase 'Ora1
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`pharmaceutica1 c'Omp'Ositi'On acc'Ording t'O c1aim 1, wher巳in said at least 'One amphiphilic excipient
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`c'Ompris巳 s leci也in." (JTX-2004 at c'01. 10 日.51-53) Claim 9 recites: "A c'Ontr'Ol1ed release 'Oral
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`pharmaceutica1 c'Omp'Osi世'On acc'Ording t'O c1aim 7, wherein said at least 'One lip'Ophi1ic excipient
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`c'Omprises stearic acid 'Or magnesium stearate." (JTX-2004 at ∞1. 1011. 绍-60)
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`17.
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`Each 'Ofth巳 asserted cJaims recites a limitati'On requiring a "macrosc'Opica11y
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`h'Om'Ogen'Ous c'Omp 'Ositi'On," which the C'Ourt c'Onstrued, in acc'Ordance with Plaintiffs' pr'Op 'Osed
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`c'Onstructi'On, t'O mean 飞 c'Omp'O sl世'On 'Of Ul让f'Orm s位uc切re thr'Ough'Out, as 'Observed by the naked
`
`eye." (D.I. 183 at7-8)
`
`V.
`
`Plain挝ffs' Witnesses
`
`18.
`
`Dr. Davis ís an 巳meritus profess'Or at the Uníversíty 'O fN'Ottingham, England,
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`where he ran a r，巳search gr'Oup studyíng drug delivery systems. (PTX-45 at 1) He has w'Orked ín
`
`5
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`pharmac明.tical sciences and formulation development for nearly 50 years. (Davis Tr. at 66)3 Dr.
`
`Davis provided testimony regarding D巳fendants' alleged in企ing巳ment ofthe '888 patent.
`
`19.
`
`Dr.ShenLukhasaPh.D. 恒 chemis句r and is cuirently 出e Chief Scientific Offiωr
`
`of Juniper Pharmaceuticals. (Luk Tr. at 202, 204) Dr. Luk testified that he bisected Defendants'
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`sample tablets (PTX-24; PTX-25) but did not testify r巳E町ding the visual appearance of Actavis'
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`。r Alvogen's tablets (Luk Tr. at 205, 211).
`
`20.
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`Plaintiffs also presented the deposition testimony ofD巳fendants' fact witnesses
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`Dr. Arun Katragadda, Actavis' p血n町 formulator for the accused product (Katragadda Tr. at
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`168-69, 182); Dr. Parag Shah, Actavis' Director ofFormulation Development (Shah Tr. at 182);
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`Dr. Kavitha Koushik Bandi, Alvogen's formulation manager (Bandi Tr. at 196"97; Joshi Tr. at
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`185); and Dr. Mayank Joshi, Alvogen's Vi∞ President ofResearch and Development and
`
`corporate designee (Joshi Tr. at 183回 85). Each ofthese fact witnesses poss田S臼 aPh.D. in 命ug
`
`deliv田y， ph缸mac.eutics， or pharmaceutical sciences.
`
`VI. Actavis' ANDA Product
`
`•
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`22.
`
`Plaintiffs presented no evidence of anyone examining Actavis' tablets wi出 his or
`
`her naked eye to determine wheth巳rth巳 tablets had a "uniform structure throughout." Dr. Davis
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`admitted that observation with the naked eye is an available test to determine whether the
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`macroscopically homogenous limitation is satisfied, but he never performed that observation.
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`3Citationsωtrial testimony are in the form: "([Witness last name] Tr. at [page])."
`
`6
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`Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 9 of 22 PageID #: 9104
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`(Davis Tr. at 115, 141-43)
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`23.
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`Plaintiffs had samples of Actavis' tablets. (PTX-24) Plainti伍s sent s缸nples of
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`Actavis' tabletsωon巳 oftheir experts, Dr. Luk, but asked hini only to bisect them. (Luk Tr. at
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`205) He offered no op凶ion at trial about their structure. (Luk Tr. at 205, 209-10) Dr. Davis did
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`not eJtamine any tablets, either whole or bisωted. (Davis Tr. at 141-42)
`
`24.
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`Dr. Davis reviewed 也emagni丑 ed photograph of a bisected Actavis tablet
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`included in the report ofDr. Alexander Mullen, Actavis' formulation expert on
`
`non-in企ingement， and testified that the photograph 、hows a homogenous structure throughout."
`
`(Davis Tr. at 115-16; PTX-641) Dr. Davis testified that even though Dr. Mullen's photograph
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`was enlarged, he could not s四 anon嗣homogenous dispersion of excipients. (Davis Tr. at 115)
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`Plain咀 ffs introduced no evidence 也就 the photographs reflected the level of detail that can be
`
`observed with the naked eye, and Dr. Davis admitted that he had no way ofknowing whether that
`
`was the case. (Davis Tr. at 155) Dr. Davis did not know the lighting in 也e room when the
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`photographs were taken, the distance between the c缸nera and the tablets, or whether the images
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`Dr. Davis reviewed had been reduced from the full size ofthe original photographs. (Davis Tr.
`
`at 153-54)
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`25.
`
`ln 也e course of performing h缸也因s tests on the ANDA products, Dr. Katragadda
`
`personally saw tablets that had been brokeh. (Katragadda Tr. at 177) Dr. Katragadda testified
`
`that he "didn't see any pockets of excipients" and that the tablet "appe缸'ed to be uniform in
`
`color." (Katragadda Tr. at 177) He also "didn't observe any, any non-uniform distribution in the
`
`brokenp缸t of the tablet or the 一 or the circumference of the tablet. . .. lt alllooked the same
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`"但耐agadda Tr. at 178)
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`7
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`26.
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`Plaintiffs entered bisected Actavis tablets inωeviden四. (PTX-24) The Court
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`observed 吐lat the tablets had "yellow dots that 缸e not uniformly distributed throughout." (Tr. 创
`
`.335)
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`27.
`
`Actavis' ANDA describes the design ofits ANDA product formulation and its
`
`manufacturlng process, inc1uding testing for blend uniformity and content uniformity.σTX-
`
`175; Davis Tr. at 106-108)
`
`•
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`29.
`
`The blend of Actavis' AND A product is prepared in severa1 steps.σTX圄230 at
`
`41, 96; PTX剖 4 at2)η出严'ocess is designed ωensure a uniform dis阳:bution ofbudesonide
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`and the other tablet c咱也∞mponen也 throughout the blend. (Katragadda Tr. at 174-75; Da'由 Tr.
`
`at 99, 106-08, 109; PTX-230 at 41, 96; PTX惆234 创 2; PTX-125 at 5) Acta刀is' ANDA states 出现
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`"[t]his process ofblending in a se垃es of steps ensured homogene咱us mixing of 9 mg of active
`
`ingredient in 300 mg ofblend as evidenced by blend uniformity data and [content uniformity]
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`data from the core tablet."σTX-230 at 41-42; see also Davis Tr. at 106斗 2; PTX-230 at 72,
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`77-78, 81-82; PTX-232 at 44)
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`30.
`
`Actavis' ANDA describes the fina1 blend as "homogeneous." (PTX-230 at 4;
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`DavisT注目 114)
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`ηlere 缸e no irregnlar pockets of excipients in the fina1
`
`blend. (l王atragadda Tr. at 176-77 ("[Y]ou would not see pock础。f white or yellow powder after
`
`也e 缸al blending has taken place.")) Actavis' formulatortestified that 气he expectation is ω
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`8
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`Case 1:15-cv-00164-LPS Document 272 Filed 01/31/18 Page 11 of 22 PageID #: 9106
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`have uniform distribution. … [o]f each ofthe excipients." (Katragadda Tr. at 176; Davis Tr. at
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`99, 106, 109)
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`31.
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`Actavis p町forms blend uniformity testing at the end of pr。但ssing of 伽e 伍nal
`
`blend before it is ∞mpressed to form tablet cores. (E.g. , PTX-232 at 52; PTX-234 at 5; PTX-
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`230 at 88; Davis Tr. at 112-13) Blend un由rmíty tes出g entai1s sampling the 丑nal blend from
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`di能rent locations within the blender to ensure that the proportionally ∞πect 缸nountof
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`budesonide is pr臼ent in the sampl凶 taken 企'om each location. (Davis Tr. at 148; PTX- 125 at
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`ι7) The results of Actavis' blend 四世 formity testing show that each sample had the correct
`
`amount ofbudesonide with a very narròw standard deviation. (PTX-230 at 42, 88; Davis Tr. at
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`112-.1 3) Because budesonide is mixed with each ofthe other tablet ∞'re ∞mponents during the
`
`manufacturing process, the final blend uniformity tests are also expected to be indicative of the
`
`distribution of excipients in the final blend. (Davis Tr. at 114)
`
`32.
`
`_compressio叼rocess was designed to prevent segregation of the blend ∞mponents
`
`during tabletir毡， which means that the homogeneity reported 也roughout the manufacturirig
`
`process would be ∞ns缸ved. (Katragadda Tr. at 177; Davis Tr. at 99, 108) The compressed
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`tablet cores, thus, have approxÍl.nately the same uniformity and homogeneity as the final blend.
`
`(Katragadda Tr. at 176; Davis Tr. at 99, 106, 108; PTX-230 at 41-42)
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`33.
`
`Following compression ofthe final blend, Actavis performs content uniformity
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`testing on a number of the manufactured 毗lets. (PTX -234 at 5) Content uni岛rinity testing
`
`involves determining 也e amount ofbudesonide present in each ofthose tablets. (Davis Tr. 的
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`9
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`113-14; PTX-232 at 61) As wi出 Actavis' blend uniformity testing, the results of its content
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`uniformity testing are wi伽in its specifications and show that each tablet has 也e correct amount
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`ofbudesonide. (PTX- 232 at 61; PTX-230 at 42, 88; Davis Tr. at 106, 113-14) Actavis'
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`formulator testified 也at based on the active ingredient testing, the active ingredi巳ntand
`
`excipie脚 are expected to be uniformly distributed. (Katragadda Tr. at 178)
`
`34.
`
`Howev町， blend uniformity and content uniformity testing do not answer the
`
`question ofwhether Actavis' tablets hav'巳 uniform structure throughout. These tests evaluate
`
`only the amount of active ingredient - not the arrangement of th巳 active ingredient or the
`
`excipients. (Davis Tr. at 145, 148-50) Having active ingr巳:dient "uniformly distributed" in this
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`context refì缸s to each s缸nple ofb1end, or each tablet, having approximately 也es缸ne quantity of
`
`activ巳 ingredient. It says nothing about how the particles of active ingredient (or any excipient)
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`are arranged in the sample. (See, e.g. , Davis Tr. at 148 (飞 80 actually there would be no way
`
`to determine from this test how the API looks in the s缸nple because when you find it, it is in
`
`solution; right? A. Y ou have dissolved it. That' s ∞rrect.")， 149 ("Q. Okay. And when you do
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`也at test on the tablet to get 也e uniformity of contents, you crush the tab1et; correct? A. That
`
`would be a normal process, 1 would imagine. . .. Crush each one and extract them, yes."))
`
`35.
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`P1aintiffs iden世fied only a single docume旧金om Actavis that used the word
`
`"homogeneous," and the statements in that document refer to uniformity studies on the
`
`pre-tab1eted blend, not on the tablets as a whole.σTX-0230 at 4; Tr. at 317)
`
`VII. Alvogen's ANDA Product
`
`36. With respect to A1vogen, Plaintiffs present similar evidence. Alvogen's ANDA
`
`productis a 也blet 也at contains a delayed-release or ent町ic ∞ating and a tablet ∞re that
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`pro飞IÏdes con衍。l1ed release of the active ingredient in a time-dependent m缸mer in the large
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`jntestinalsectors.σTX-176 at 2; Pηι416 at 7; PTX-228 at 11) In its ANDA product, Alvogen
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`刀lUs， Al飞vogen designed its
`
`productωhave..inte呻 ersed in 仕le separa忧 excipient s钉ucture.
`
`37.
`
`Plai丑tif也 presented no evidence ofDr. Davis examining Alvogen's tablets with
`
`his naked 巳:yeωdetermine wheth巳r they had a "uniform structure throughout." (Davis Tr. at 95,
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`150-51) Dr. Davis reviewed pic阳r田 ofbisected Alvogen tablets included in the report ofDr.
`
`Reza Fassihi, Alvog钮， s formulation expert on non-in企ingemel扰， and testified that they showed
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`a uniform dis位ibution of materials; he further testified 也at he did "not see a non-homogeneous
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`dis位ibution" even though the photographs were en1arged. (Davis Tr. at 95-96; PTIι640) Dr.
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`Davis opined that with correctly-sized depictions of Alvogen' s tablets, "one would also see
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`something 1阳t] has homogeneous and uniform [structure]." (Davis Tr. at 96)
`
`38.
`
`Plaintiffs enten:d bisωted Alvogen tablets 扭ω 町idence (Pτχ.-25), which the
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`Court inspected. The Court observed "holes or bumps" or "s创ations" 也at are not evenly
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`distributed throughout 也e 旬blets. (Tr. at 337, 311-12)
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`39.. Alvoge且's ANDA describes the design ofits ANDA product formulation and its
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`manufacturing proc础侃， including testing for blend uni臼rmity and content uni岛rmity. (Pτχ-
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`176 at 29; Da'训s Tr. at 88-89; Joshi Tr. at 190-91, 199-200)
`
`40.
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`•
`
`•
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`43.
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`Alvogen performs blend uniformity testing on the final blend before it is
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`∞mpressed to form tablet cores. (E.g. , PTX-237 at 21; PTX-176 at 31; Davis Tr. at 92- 93) 白le
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`resu1ts of Alvogen's blend uniformity testing show that each s缸npled location had the correct
`
`amount ofbudesonide wi世1 a narrow standard deviation within the required limits. (PTX-237 at
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`21) B∞ause budesonide is mixed With each of the other tablet ∞re components during the
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`manufacturing process, the final blend uniformity testing suggests 也at each of the excipients is
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`also uniformly distributed throughout the final blend. (Bandi Tr. at 199-200; Davis Tr. at 93 > 95;
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`PTX-176 at 43; PTX-228 at 193)
`
`•
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`45.
`
`FoJlowing compr'田sion ofthe final blend, Alvogen performs content uniformity
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`testing on a number ofthe manufacturèd tablets. (PTX-237 at 23-24, 29) The results of its
`
`content uniformity testing 缸e within its specifications and show that each tablet has the correct
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`amount ofbudesoiride. (Davis Tr. at 93)
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`46.
`
`Plaintiffs identified only one document 企omAlvogen 伽at refì巳:rs to homogeneity,
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`and those statements refer to uniformity studies on the pre-tableted blend, rather than the tablets
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`田 a whole. (PTX-228 at 193; Tr. at 3.17)
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`LEGALSTANDARDS
`
`1.
`
`. Rule 52(c) Motion
`
`UnderFed町al Rule of Cívil Procedure 52(吟， the Court has díscretion to enter judgment
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`on 皿y issue after hearing the evidence. See In re Brimonidine Patent Lit邸， 666 F. Supp. 2d
`
`429, 453 (D. Del. 2009). Rule 52(c) provides that "[i]fa party has been fuJly heard on an issue
`
`du由19 anonjury 忧ial and the court 丑nds against the p缸ty on that issue，也e ∞urt maý enter
`
`judgt卫ent against the p缸tyon a claim or defense 也时， under the controlling law, can be
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`maintained or defea旬d only wíth a favorable :finding on 也at íssue."
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`In considering a motion for judgment under Rule 52(吟，如 Court "applies 世le same
`
`standard of proof and weighs the evidence as it would at 吐le conclusion ofthe tríal." EBC, Inc. V.
`
`ClarkBldg. 吵'8. ， Inc. , 618 F.3d253, 272 (3d Cir. 2010). In doing so, the Court "doesnotview
`
`the evidence 也roughap町ticul缸 lens or draw inferences favorable to either pa吗r." Id. Further,
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`吐le COurt will "make detenninations of witness credibility where appropriate." Id. at 273.
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`II.
`
`Infringement
`
`A patent is infringed when a person "without authority makes, uses, offers to sell, or sells
`
`any patented invention, within the United States . . . dur姐g the tenn ofthe patent." 35 U.S.C.
`
`g271(a). In aHatch-Waxmanc脯， the ANDA itself infonns the 恒的19ement inquiry. Under
`
`35 U.S.C. g 271 (e)(2)(A), the Courtmust determinewhether, ifthe 缸ug were approved based on
`
`世le ANDA, the manufacture, use, or sale of 也at 世ugwouldin企inge 也e patent in the
`
`conventional sense. See Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc. , 731 F.3d 1271, 1278
`
`(Fed. Cir. 2013). Courts employ a two-step analysis in making an in创ngement determination.
`
`SeeMar，加ωn v. Westvtew Instruments, Inc. , 52 F.3d 967, 976 (Fed. Cir. 1995). First, the Court
`
`niust construe the asserted claims. See id. Next, the trier offact must ∞mp缸'e the properly
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`∞'nstrued claims with 加 accused in仕inging product. See id.
`
`h仕ingement is a question of fact. See Hilgraeve Corp. v. Symantec Corp. , 265 F.3d
`
`1336, 1341 (Fed. Cir. 2001). In order to establish literal in企ingement， "every limitation set forth
`
`in a clainl must be found in an accused product, exactly." Southwall Techs. , Inc. v. CardinalIG
`
`Co. , 54 F.3d 1570, 1575 (Fed. Cir. 1995). 咀le plaintiffhas 也eburd∞ of proving in企ingement
`
`by a preponderance öf the evidence. See Siemens Med. Sols. USA, Inc. v. Saint-Gobain Ceramics
`
`&Plastics, Inc. , 637 F.3d 1269, 1279-80σed. Cir. 2011). "A patentee may prove in企ingement
`
`by any method ofanalysis that is probative ofthe fact ofin企ingement， and circumstantial
`
`evidence may be su伍cient." Martek Biosciences Corp. v. Nutrinova, Inc. , 579 F.3d 1363, 1372
`
`(Fed. Cir. 2009).
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`DlSCUSSION
`
`Having considered Plaintiffs' testimonial, documentary, and other evidenc白， aswell as 也e
`
`p缸ties' 缸guments ， the Court finds that Plaintiffs have fai!ed to meet their burden of proving
`
`in企ingement ofthe asserted claims ofthe '888 patent by a_preponderance ofthe evidence.
`
`ηle on1y c1aim limitation at issue is whether Defendants' ANDA products have a
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`"macros∞.pical1y homogeneous composition." During c1aim construction, the Court adopted
`
`Plainti岱， proposed construction of this term, construing it to mean 飞 composition ofuniform
`
`structure 也roughout， as observed by the naked eye." (D.I. 183 at 7-8) Whi1e this construction
`
`does not imppse any particu1町 requirement for how to det旺minewh巳ther a composition is
`
`mactos∞.pically homogeneous, it does at least imply an appropriate starting point for 也。
`
`in企ingement inquiry: what the tablet' s composition looks like when observed by the naked eye.4
`
`N evertheless, for reasons that 缸e ∞tirely unexplained on 吐le record,s Plaintif也 didnot
`
`provide samples ofthe accused products to their in企ingement expert, Dr. Da-飞ris， -so Dr. Da-飞ris did
`
`not observe them with his naked eye. (See Davis Tr. at 141-42, 150-51) Instead, Dr. Davis only
`
`reviewed photographs ofthe tablets taken by Defendants' non-in企ingement expertS. (Davis Tr.
`
`4Defendants contend that th巳c1aim construction requires an e印刷 to observe the accused
`products by 也e naked eye and makes all other testing irrelevant. (See D.1. 234 at 咱 23) (citing
`Chimie v. PPG Indus., Inc. , 402 F.3d 1371, 1380-82 (Fed. Cir. 2005); Genentech, Inc. v.
`Wellcome Found. Ltd. , 29 F.3d 1555, 1563, 1566 (Fed. Cir. 1994))ηle Court disagrees. Unlike
`也e c1aims in Chimie and Genentech, the construction here does not demand a particul缸 type of
`quantitative testing. Instead "macroscopically homogeneous composition" is, by its construction,
`qualitative and may be amenable to various obs缸vation techniques. Accordingly, the Court has
`considered all 也e evidence presen时 by Plainti能 in determining that 也eyhavenotc缸口创也巳ir
`burden to prove in企ingement.
`
`5See Tr. at 293 (Court: "[I]s there an:抖ung in the record as to why the plaintiffs didn't
`just simply have their own expert do his own naked eye test?" Counsel for Plaintiffs: "There is
`nothing in the record asωwhy the Plaintiffs did not do that.")
`
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`也t 95-96, 115-16) Al也ough the phot'Ographs may be representative 'Of the tablets, reviewing a
`
`phot'Ograph is not a go'Od substitute for examining the tablets themselves in 白.e c'Ontext 'Of this
`
`case. Among 'O th町也ings， the ph'Ot'Ographs 缸e magnified many times (alth'Ough precisely how
`
`magnified is unkn'Own), and the appe缸ance 'Of 也e ph'Ot'Ographed tablets may have been affected
`
`by factors like lighting and distan∞仕om 也e caínera.6
`
`Plaintiffs, h'Owever, did 'Offer Defendants' tablets int'O evidence (pTX-24; PTX-25), and
`
`invited the C'Ourt to l'Ook at 也em itself. (See Ti. at 294; see also id. at 300, 304 (Defendants not
`
`objωting)) Alth'Ough Defendants c'Ontend 也at issues 'Of in企ingement must be evaluated 企''Om the
`
`perspective 'Of a pers'On 'Of skill in 也e art, see Sundance, Inc. v. DeMonteFabricating Ltd. , 550
`
`F.3d 1356, 1361 & n.3 (Fed. Cir. 2008), it was appr'Opriate f'Or the C'Ourt t'O all'Ow ~lainti能 ω
`
`submit the tablets f'Or lay 'Ob阳vati'On by the naked eye, even unassisted by expe时 testim'Ony asω
`
`h'Ow an ordinarily-skilled artisan w'Ould understand the structure 'O,f the bisected tablets. The
`
`Federal Circuit has "repeatedly appr'Oved th巳 use 'Ofexp巳rt testim'Ony t'O establish in创ngement"
`
`but has declined ω"state a'per se rule that exp甜 testim'Ony is required t'O prove in缸ngement
`
`when the art is c'Omplex." Centricut, LLCv. Esab Grp., Inc. , 390 F.3d 1361, 1369-70 (Fe况1. Cir.
`
`2004) (emphasis added). Thus, whi1e it w'Ould have been preferable f'Or Plaintiffs t'O have
`
`pr'Ovided expert guidance 'On what an 'Ordinarily-skilled artisan sees when l'O'Oking at 也e accused
`
`tablets with the naked eye, the C'Ourt performed its 'Own 'Observati'Ons and used them as p缸t 'Ofits
`
`6Plaintiffs presented evidence 'Of 'Obs缸vati'Ons by Dr. Ka仕agaddareg缸ding Actavis
`tablets br'Oken during hardness testing. (See Katragadda Tr. at 177-78) Alth'Ough Dr. Katragadda
`n'Oted that the broken tablet c'Ores l'O'Oked the s田ne t'O him, his 'Observati'Ons 缸'O se in the c'Ontext 'Of
`testing f'Or hardness. Thus, his 'Obs町vati'Ons were n'Ot f'Ocused 'On whether the t丑blets 缸。
`macrosc'Opica11y hom'Ogene'Ous, and there is n'O indicati'On 也at he had in mind the claim language
`at issue here when he viewed the tablets. Dr. Katragadda's testim'Ony, theref'Ore, is 丑。t
`persuasive evid∞∞'Ofin企ingement.
`
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`ca1culus as to what a person of ordinary'skill in the art would see had she looked at the product
`
`with her naked eye. See generally Centricut, 390 F.3d at 1370 (recognizing pitfalls ofplaintiffs
`
`f血lure to supplement complex subject matter with expert opinion).
`
`In viewing Actavis' tablets, the Court found that they do not, to a lay observer at least,
`
`a即阳 to be a ∞mposition ofuniform structure throughout. The Court observed yellow dots 也at
`
`were not uniformly distributed throughout the bisected tablets.7 (See Tr. at 335) Wi也 respectto
`
`Alvogen's tablets, the Court similarly found that 也.ey did not, to a lay observer, appe缸 to be a
`
`composition ofuniform structure throughout. Instead, Alvogen's tablets app巳ared to have holes
`
`or bumps that were not evenly distributed 也roughout the bisected tablets. (See Tr. at 337)
`
`Thus，也.e Court's observation ofDefendants' tablets, in combination with the lack of
`
`obse凹ation of the tablets by Plaintif弛， expert, is evidence that Defendants' tablets are not
`
`macroscopica11yhomogeneous. See, e.g. , Gumbs v. Int'[ Harvester, Inc. , 718 F.2d 88, 96 (3d
`
`Cir. 1983); Tzu Wei Chen Food Co. v. Chia-ChiBnters., Inc. , 73 F.3d 379, 1995 WL 714589，就
`
`*6 (Fed. C亿 Dec. 5, 1995).
`
`Plaintiffs' other evidence does not persuade 由e Court to reach a different conc1usion.
`
`Plainti配 h企ingement theory rests primarily