IPR Page 1/6
`
`Santen/Asahi Glass Exhibit 2056
`Micro Labs v. Santen Pharm. and Asahi Glass
`IPR2017-01434
`
`

`

`7191201 8
`
`Human Metabolome Database: Showing metabocard for Tafluprost (HMDBODlSTDA)
`
`Chemical Taxonomy
`Description
`
`This oompound belongs to the class of organic compounds Known as prostaglandins and related compounds. These are unsaturated carbonylic acids consisting of a 20 carbon 5
`also contains a five member ring, and are based upon the latty acid eradtidonio acrd.
`Organic corn pounds (3 (httptflclassyfiremisharliao oomrtax_nodaslcnm0000t
`Lipids and iioidJlike molecules 3 [i'lltpflclassyfils wisharllab comllax_nodesl'00000012l
`Fatty Acyis f5 [htlo'i‘iclasswirewishartlab oomitax_nodearCDDDSBDQ)
`Eioosanoids G lnlto'rlciassyfirewisharliab comilex_nodeelCDDDOS1 3}
`
`Kingdom
`Super C! as
`Ctaae
`Sub Class
`Direct Parent
`Alternative
`Parents
`
`Substituenta
`
`Molecular
`Framework
`External
`Descriptors
`
`Ontology
`Disposition
`
`Prostaglandins and related compounds l3 [hltpflciaosytireWishai'tlab.oomrtax_nodele000051 4)
`. Pnenoxy compounds 6 [http'flclassyi'irewishaniab comilax_nodeslc 0004742]
`- Phenol atheism {http'flclassy‘lire.wishartiab.oomltax_nodesl00002341l
`- Folly acid esters l3 (htlpwolassyriira wrshartiab.cornilax_nodesl‘C 0000324)
`I Aikyi aryt elt'iers G (hltp:l.tolassyfire wishartlab comllax_node5ICUDDD1‘EBi
`. Cyclopentanois l3 {http:floia say-fire wohartlabeornrl axinooesrcooozem:
`. cyclic alcohols and derivatives [5 [mtpflciassyiire.wiehartlab comrtax_nodale0001292}
`- Carboxylio acid esters ['3 [http'lrolassyfire.wiehartlaboornFtex_nodesfcuoo12BB)
`- Monocarboxylic acrds and derivatives (3 (http irclassyfirewishanlab.oornitaxhnodeslcoflm13?)
`- Organol‘luon‘des f3 [http:li‘classyl'ire wishanlao comilax_nodesiCOOOt 517]
`. Organic oxides G [http:l‘iolassy‘fire wishenleboomrtaxiriodesicmottmD)
`- Hydrocarbon derivatives [5 [nttpnliclassyfirewishartlab mmltax_nodeleDDU4150]
`- Carbonyl compounds 13 lhlto'iiolassyfire wishartlab comrlax_nodeeiCDDOi 831]
`- Alkyl fluorides l3 {http:flolassmre wisharllao.comllax_nodes!CDDD‘l 02?)
`
`- Prostagiandinskeleton
`o Phenoxy compound
`» Phenol ether
`- Alkyiarylelher
`- FattyI acid ester
`- Benzenoid
`- Monooydio benzene moiety
`- Cyciooentanot
`. Cyclic aioohol
`- Secondary aEcohol
`- Cartoxyiio acid ester
`- Camoxylic acrd derltraiive
`. Monorarooxylii: acid or derivatives
`- Enter
`- Organooxygenmpound
`- Alkyl fluoride
`. Alcohol
`. Organohalogen compound
`- Organofluoiide
`- Carbonylgrouo
`- Hydrocarbon derivative
`I Alkyi halide
`. Organic oxygen compound
`- Organic oxide
`- Aromatic homomonooyclic compound
`
`Aromatic homomonocyclic compounds
`
`- organofiuorine compound (CHEBI'EGBQQ (‘1'(httpiMwwebi.acukl‘cheoii‘searcnld.do7chebild=CHEBifiEB|39n
`a carboxylic ester (CHEBI:66899 ('5 (http lmwvwebiac.ukrcneoilsearohld.do’?chebild=CHEBI 66399))
`. oroataglandins Falotta [CHEBHBEBQQ 6 film p. irwww ebi ac uki'chebilsaarchld.do'?cheoild =CH EBt 653991]
`
`Route of exposure
`Enteral:
`
`n
`
`ingestion Umetaoolite_ontology_tamar485854ut
`
`Source
`
`1: Food Umelabolila_onlology_lermsf4558539t
`Biological location:
`Suboeilutar-
`
`:- Membrane (imetabol'rte_ontolongarmsBZ-i1642i
`u Cell membrane Urnelaboiile_onloIogy_term5i35?5827]
`u Cytoplasrn Urnetel:olite_ontom\gy_lermsr3536229)
`Siofiuid and excreta:
`
`n Urine{JmetaboiiteLonlologLIerm513395340)
`a Blood Urnetabotite_ontology_lermsi33§5341}
`
`http:riwwwhmdbcalmetabolitesfHMDBOD15754
`
`IPR Page 2/6
`
`215
`
`IPR Page 2/6
`
`

`

`"#912015
`Process
`
`Role
`
`Human Metabolome Database: Showing melabocald for Tafiuprosl (HMDBOO15?D4)
`
`Naiuratiy occuning process:
`Biological process:
`Biochemical process:
`a Lipid lranspori Urnelaboiile_onloiogy_temid4858543]
`n Lipid metabolism [i‘melabolilaAantolugyJErm514551544)
`a Fatly and metabolism Hmatabolrte_onloiogy_tenn5:4358545)
`Chemical reaction
`
`n Lipid peroxidatinn iimelabolrle_antolugy_temi5M658542)
`Biochemical palhway.
`u Lipid metabolism pathway (1meiaooliteiontulogyilemsm553541l
`Multicellulaf process
`
`lnflammalory response :rmetaoolitejniuingyftemsraaafizfia}
`a
`Immune response [Imelalzioiite_ontolugy_tsnnsJ3836234]
`=-
`Callulat prune 55:
`n (3 Eli Signaling Um maboliiegmIologyalermsflflsfizssn
`
`Biological role
`a Nulrienl (Fm embolita_onlo IogLIei-m 55836230}
`9
`Inllammaiory timetabohle_onlolngy_1arm9333623I}
`a Energy storage {lmetabnritgonioiogyJem #4855545)
`a Energy sci UfCE t.frnelabnlila_onloIngy_terms.f4855547i
`Membrane stabilizer UmelabnEite_anulog yulermsmBSBSd B}
`Modulator:
`
`lmmunomudulator(ln'ielabnlila_Dnluiugy_lerrn5J3835232i
`n
`Industriai application.
`9 Drug tFmelabolile_onlolagy_lerm93451451)
`Pharmaceutical iflduslry:
`0 Pharmaceutical [lmeiaho|ile_ontology_iams!3603354)
`Cardiovascular drug:
`a Antihyperlansrve Urn alaboiile_onlology__tenn #3451452]
`
`Physical Properties
`Slate
`Liquid
`
`Exparimo ntal
`Proparfies
`
`Property
`
`Wain!
`Boiling PDII'Ii
`
`Water Soiubility
`LugP
`
`Valua
`
`Wailable
`No! Availaola
`
`D 0053 gi'L
`N01 Avaliable
`
`Referennl
`
`Rufumie
`Nut Available
`
`Not Available
`
`Noi Available
`
`hflp:lew.hmdbcafmelaboliteslHM[130015704
`
`SEE
`
`IPR Page 3/6
`
`IPR Page 3/6
`
`

`

`"17912018
`Pmdicled-
`Properties
`
`Spectra
`
`Properly
`
`Whter Sumbulity
`
`iagP
`
`lug?
`
`logs
`
`pKa (Strongest Acidic)
`
`pKa (Slmngesl Basic}
`
`Physiological Charge
`
`Hydrogen Aocapmr Count
`
`Hydrogen Donor Count
`
`Po‘ar Surface Area
`
`Rotalabla Band Counl
`
`Reflectivity
`
`Pculanzabilil}.I
`
`Number of Rings
`
`Blomailabllily
`
`Rule at Five
`
`Ghnse leler
`
`Usher's Rule
`
`MODE—lake Rula
`
`Human Metabolome Database: Showing metabocard for Tafiuprost (HMDBDO15704)
`50mm
`
`Value
`
`0 0053 gfL
`446
`
`4.29
`
`.4 9
`
`14.51
`
`729
`
`75.99 A‘
`
`13
`
`120.59 m'fl‘lol ‘
`
`43 55 A'
`
`YE5
`
`YES
`
`Yes
`
`Yes
`
`ALOGPS {htlpilfhvwwmcciab orgflabralugpsi]
`
`ALOGPS {ht'lp'flwww vcclabnrgrlablalogpsl}
`
`ChemAxnn Ehtlp‘wa.chemaxun.wmlpmn‘uclslcalcu‘ator—pluglnsipropeny-
`prauiuotsfmugp_logd]
`
`ALOGPS {hrlp‘lrwwwvcclanorgrlabiaIogpsi]
`
`ChamAxan {hltpiIMww.chemaxun com!produdsicalwlaIDr-pluginslpmperly-prec
`
`ChsmAxun (hup-IMww chemaxon‘camipmduclsicalcu|ator-p!uginsfproperlyrprec
`
`ChemAxon [http:flwww.chemaxnn wmlpmdunlslca\c-ulator-pluginslpropany-pre:
`
`ChemAxan [http:fiwww.charnaxon comfprududslm‘culator-plminsfprapeny-
`calculaliansmhrbund]
`
`ChemAxon {hlthMwwcnemaxon comrpmducts.1calwiaior-piugunsfpraperly—
`calcu‘atiun swhflband)
`
`ChemAxun (hug:F1www.chemaxon.wmlwoduclslcaIculatariplugmsfproparty-
`calcu‘auonsfiflupalgicaI_sufiace}
`
`ChemAxnn (him:”www.chernaxon.mmlprcductsfcalculalnr-plugmsrproparly-
`calculalIonsimopolugyéanarysis]
`
`ChamAxun (hltp'waw chemamn comiproductsfcalculater-piuginsrproperty-
`:alwlalionsflrefraclivnty)
`
`ChernAxun {nupflwww chem axon.mmfproduclslcaIcutatur-plugInsrmnlecular-
`madallingh‘lpokarization]
`
`ChamAxnn [h1lp:.waw chemaxan.I:Dmv‘producisfcalcuIaIUI-plugmsrpmperly-
`ca‘wlauonsm‘lopoiogLanalysus5
`
`Chem-Exxon :hlthMwwchemaxon comfpmdumsfcalouIaiowiugnnsfmmecular-
`madallmgflpolanzalxon:
`
`ChemAxu n (httpzmrww mam axon comfproduclslcalculator—p‘uginslmnlacular—
`modelhngflpulanzauan]
`
`ChernAxun {htlp waw chem axon on m Fprnductsrcalculalnr-piuginsimulacular-
`modelhngrflpolanzamn}
`
`ChemAxon (nflp:flww.chernaxon.comrpruductsrralw\alor-pluginsima‘ecular-
`modeilmglflpolarization)
`
`ChemAxon (nnp:.erw.chamaxon.comiprnduclsfcaIcuLatur-plugjnslmmecuiar-
`modellingmpolarizallunl
`
`http:I!mm~.hmdb.cafmeiaboliteslH MDBDU15704
`
`IPR Page 4/6
`
`4J5
`
`IPR Page 4/6
`
`

`

`mama
`
`Spectra
`
`Spectrum
`Till”
`Predicted
`GEMS
`
`Predicted
`GCVMS
`
`Predicted
`LC-
`MSMS
`Predicted
`LC-
`MSJMS
`Predicted
`LC-
`MSI'MS
`Predicted
`Ll:-
`MSIMS
`Predicted
`LC-
`MSFMS
`Predicted
`LC-
`MEWS
`
`Description
`Predicted GC-MS
`Spectrum - GC-MS {Nori-
`dertvalizedi - rue»:
`Positive
`ifspectran:_msi1?:l77)
`Predicted GC-MS
`Spectrum - (EC-MS (2
`TMS) - New, Pogitive
`Uspeclrarc_msl4fl??2}
`Predicted LGMSFMS
`Spectmm - 10V. Positive
`[ispectrafmgmsiazmzl
`Predicted LC-MSMS
`Spectrum - 20V, Positive
`Uspe:lralms_mei92014]
`Predicted LC-MSIMS
`Spectrum - 40V. Positive
`ilspectrai‘i'ris_msi92l1l5}
`Predicted LCVMSJMS
`Spectrum v 1W Negative
`Uspeclrafmsfimsrtssfiflt
`Predicted LC—MSIMS
`Spectmm - 2W. Negative
`(Ispectrall'nsimsfi 55551]
`Predicted LC—MSJMB
`Spectrum — 4W, Negative
`tispeclialms_msl155552)
`
`Biological Properties
`Cellular
`Locations
`
`- Membrane
`
`Biuepecimen
`Locations
`
`- Blood
`- Urine
`
`Tissue
`Locations
`
`Pathways
`
`Not Available
`
`Not Available
`Name
`
`Normal Concentrations
`
`Human Metabolome Database: Showing metabocard for Tatiuprost (HMDI300157041
`S pl: eh Key
`|llttp:iispla iih.fiehnlab.u:davla.edul}
`splasht easy-«3970mm
`EFQDZeBElSTZFficcSQ3
`
`View in Mom (3 [http:flmonaiie hnlab.ucdavis.edui'flspeclraispiashtsplasn1 0-052l-44 SQTOODUDVEWUESSSFS}
`
`splash t B-Dm I—720U590000-
`5373b078t32l edEIQEana
`
`splash10-ODW40159DDODD-
`cSSfiSESrfibZrfiSSifiZglb
`
`spl ash'l 0433117511 9200000-
`4d3e13131945c7345704
`
`splash10-03dj-BD11EIUDUUD-
`01 DbBGSce-EQEDFEUQQAE
`
`spi ash‘l fl-ODOE-QDDHZEIDEIOU-
`02451 S2MeZBdc5bBl6h
`
`splash‘lO-OOUSBODDUDDOUD-
`35b6|74a§c34571333T5
`
`splasht D-Dadl-SOOOODOUDU-
`921114 351DD382656029
`
`View in MONA U {http:iii-nona.iiei'lniabundavts ediii‘iflsuewai'spiashisplash‘t0-00ll-‘i’QDDBBUDUO—Baflbflisar
`
`View In MoNA G {http:ilmona.fiehniab.undone.adum'spectralsplashi‘spiaahtfl-flflkv-am 5900000—688592563
`
`View in MoNA G (title Hmonatiehnlab Liadavis edumspeclraisplaahisplashlO-Eladp-fi1192DDODfl-463eie131e-
`
`V’iew in MDNA G (http.i‘imona fiehnlab ucdaws edurtli'spectraisplasnlsplash1[1703017901loDBnOD-O'IODESBW
`
`View in MONA l3 ihtlpn‘lmona fiehnlab uodawsedutflspactrarsplashleplashlD-DDDE-QODDZUDDDUUMS‘ISZOR
`
`View in MuNA {5 (http Hmong fiehnleb.ucdavis enmispeciiarsptasnisplaeh1U—OGDB-QDODODODaD-afihsfldafii
`
`View in MeNA [3“ (http limor'ia fiennlabucdavis edumspamraisplasniepiasm 0—DathSOUUUODDOO-921114351 I:
`
`SMPDEi‘Pathwhi:
`
`KE GG
`
`Value
`
`Biospecimen status
`Blood
`Expected but
`no!
`Quantified
`
`Ago
`Nat Available
`
`Sc!
`Not Avaalable
`
`Urine
`
`Expected but
`not
`Quantified
`
`Nut fiveiiable
`
`Nol Available
`
`Condition Reference
`
`Details
`
`21D59632 U thitp.i'Mww.ncbi nlm mhguw‘punmedflmSBeaZl @
`
`(Iconcemr
`
`21059682 [5 (httpfrwww nail nlrii nih uovipuomedizt 059682) 0
`
`{Jmncimtr
`
`Taking
`drug
`identified
`by
`DmgBank
`Entry
`DBUBB19
`Taking
`drug
`identified
`by
`Drugaank
`entry
`DBUEB1 5
`
`Abnormal Concentrations
`Not Available
`Associated Disardals and Diseases
`Disease
`None
`References
`Associated
`DMIM IDs
`External Links
`
`None
`
`DrugBanl: ID DEDBBt El [3 [hitp'wawdmgbankoatdmgerBDElatQ]
`Phenol
`Not Ava i labia
`Explorer
`Campou rid
`3D
`
`http:iiww.hmdb.calmetabolitesiHMDElllflt 5704
`
`IPR Page 5/6
`
`516
`
`IPR Page 5/6
`
`

`

`WQIZDlB
`FoooDB in
`
`KNA pSAcK
`iD
`
`Chemspider
`ID
`KEGG
`Compound
`ID
`
`along”: in
`BIGG ID
`
`Wikipadia
`Link
`HETLIN ID
`
`PubCham
`Compound
`PDB ID
`
`GhEBI ID
`Refer-noes
`
`Synthesis
`Reference
`Material
`Safety Data.
`sheet
`{M503}
`
`General
`References
`
`Human Metabolome Database: Showing metabocard for Tailuprosl (HMD30015704)
`
`Not Available
`
`Nol Available
`
`3044132 B (http'thw.chems oideroomlchornioatesiru olureflflmtazmml}
`
`Not Availabie
`
`Not Available
`Not Available
`
`Tafluprost f5 thltputten.wikipedia.urgrw1kflailu orost}
`
`Not Available
`
`9853491 U (hl‘lp rlpuoonern nobinlm.ningovtsurnmaryi'summaryog”61129353491 )
`
`Not Available
`
`66599 L’ (titre:{nameplaeuldohebitsearcnld.oo?chabiio=56l393)
`
`Not Available
`
`Not Availaoia
`
`. Takagi Y. Nakajima T Shimazaki A. Kageyama M, Malsugi T. Malsumura 'r, Gabalt ET, Kaulman PL, Hera H‘ Pnannacologioat characteristics at AFF-168 (talluprostt. a net
`FP receptor agonist. as an ocular hypotenaiue dmg Exp Eye Res. 2004 Apr;?8(4]‘?5?7?6. [PubMed.15037111 G {http:erw ndsinlrn nih gowpubrneoh 513371115]
`Pantcheva MB, Seibold LK, Awadailah NS. Kahook MY: Tafluorosi: a novel prostaglandin analog for treatment of glaucoma. Adv Ther. 2011 Sep;20(§]:707-15. doi 10.1003
`0055-3. Epub 2011 Aug 18. [Pounded-21358491 G {hltp'lew ncbi nlm.nih govipuomedrztasfittstn
`Fukano Y, Kawazu K Disposition and metabolism of a novel prostanoid antigtauooma medication. lal’luprost. fotlawing ocular administration to rats Drug Metab Diopoa. 20
`Aug:37tB):1622—34 dbl: 10.1124ldmd.108.024535. Epub 2009 May za [PuhMed 19477945 r5 (hltoJNnvw n:hi.n|m.nlh.govlpubmadl19477945)]
`Papadia M. Bagnis A, Sootlo R. Traverse CE: Tafluprost for glaucoma Expert Donn Pnam'iaoother. 2011 0ct.12t15).2393-401 ooi 10 1517l14655565.2011_606510. [Pooh
`I3 (http.ii\.vww.nciai.nimmingourpubmearzieisrBBi]
`. Simone K, Toornra D‘ Lipid rafts and signal transdudion Nat Rev Mol Cell Biol. 2000 Dct;l(1]‘3179. [PubMad:11413-157 3' [http ttwww.ncbi.nlrri nih.govl'pubmedl'1141348?
`. Watson AD Thematic review series: systems biology approaches to metaoolio and cardiovascular disorders Lrpidomics: a global approach to lipid analysis In biologicat sy
`Res zoos 0m.4?{10}2101-11. Epub zoos Aug 10 [PuhMed'1690224-5 i3 (httpmvww nobinlm ninguvipubmedneaozmon
`Selhl JK, Uidal—F‘uig AJ' Thematic review series adipocyte biology. Adipose tissue function and plasllcfly orchestrate nutritional adaptation J Lipid Res. 200? Jun;48(6]‘12.'
`EDD? Mar 20. [PubMed‘1TST4BflD U [http:erw ncbi nlrn nih gow‘pubmadfl ‘i‘SNBBOJI
`Linwood D. Simons K. Lipid rafts as a membrane-organizing prinoiple. Seience 2010 Jan 1;32?[5961):46-50. doi
`{PubMed20044567 L’i' ifhttp.t!ww.ncbi.nlrn'.nih.govrouomeorZOOMSSTJ]
`. Gunstone. Frank 0.. John L. Haniiiood. and Albert .J Dijkstra {2010?}. The iipid handbook with CDROM. CRC Press.
`
`to 1126iscience ”le21
`
`
`
`This project is
`
`supported by
`the Canada"
`institutes of
`
`to?
`"'
`CIHR m5;
`
`
`“ring;fjwwwlcihr.irsc_gc_ca) . TM IC The Metabolumics [hltouwwwmelaboloniicsoentra cal
`Innovation Centre
`
`' '
`
`{3
`p
`g
`.
`.
`l $33329;
`[http:i‘rgenomeoanaoaoa}
`lhl‘lp'figfiflflmehc ca} J
`tnltthrgenornealberla ca} (3'
`lhl‘lp'lMWw aihealthsolutions ca} J
`I Health
`Research
`GHiome ..- ~1-
`Morn-i
`[mum-i9
`1| Smutinns
`{hltpfllwwucinrrirsooo ca) [award #111062}. Alberta lnnovates - Heatlh Solutions thltp-waw aiheallhsolulionsoa], and by The Metabolornics Innovation Centre lTMlCl
`[http:flwwwmetabolomicscentre can. a nationally-funded research and core facility that supports a wide range of cutting-edge metabolornic studies TMIC is funded by Genome Alberta
`[hltp-i’twww genomealbanaoal. Genome British Columbia [nltpthwwgenoi-nebocat). and Genome Canada {http:rlwww gen omecanada ca}, a not-for—profll organization that is leading
`Canada's national genomics strategy with $900 million in funding from the lederal government
`HMDB Version 4.0 —— Conlact Us {lwfoontacl}
`
`httpflwwwhmdbeai’metabolitestHM030015704
`
`are
`
`IPR Page 6/6
`
`IPR Page 6/6
`
`