IPR Page 1/7
`
`Santen/Asahi Glass Exhibit 2057
`Micro Labs v. Santen Pharm. and Asahi Glass
`IPR2017-01434
`
`

`

`7/9/2018
`
`CAS Registry
`Number
`SMILES
`Inch
`Identifier
`
`130209-82-4
`
`Human Metabolome Database: Showing metabocard for Latanoprost (HMDBO0014792)
`
`CC(C)OC(=0)CCCIC=C/C[C@H]1[C@@H|(0)C[C@S@H)(0)[C@@HN CC[C@@nO)/CCC1=cc=cc=C1
`InChI=1S/C26H4005/c1-19(2)3 1 -26(30)13-9-4-3-8-1 2-22-23(25(29) 18-24(22)28)17-16-21(27)15-14-20-10-6-5-7-11-20/n3,5-8,10-14,1 9.21-25,27-29H,4,9,12-18H2,1-2H3/b8-
`3-t21-,22+,23+,24-25+/m0/s1
`GGXICVAJURFBLW-CEYAHVGTSA-N
`
`InChl Key
`Chemica! Taxonomy
`Description
`
`This compound belongs to the class of organic compounds knownasprostaglandins andrelated compounds. These are unsaturated carboxylic acids consisting of a 20 carbon s
`also contains a five member ring, and are based uponthefatty acid arachidonic acid.
`
`Kingdom
`Super Class
`Class
`Sub Class:
`Direct Parent
`Alternative
`Parents
`
`Substituents
`
`Molecular
`Framework
`External
`Descriptors
`
`Ontology
`Disposition
`
`Organic compounds C3 (http://classyfire.wishartlab. com/tax_nodes/CO000000)
`Lipids and lipid-like molecules ( (hitp://classyfire wishartlab.comitax_nodes/C00000412)
`Fatty Acyls (7 (http://classyfire. wishartlab.com/tax_nodes/CO003909)
`Eicosanoids C4 (http://classyfire.wishartlab.com/tax_nodes/C0000513)
`Prostaglandins and related compounds C& (http.//classyfire wishartlab,com/tax_nodes/C0000514)
`Fatty acid esters G (httpy/classyfire.wishartlab.com/tax_nodes/C0000324)
`Cyclopentanals @ (http://classyfire, wishartlab. com/tax_nodes/C0002938)
`Benzene and substituted derivatives (9 (http.//classyfire. wishartlab.com/tax_nodes/CO002279)
`Cyclic alcohols and derivatives @ (http://classyfire.wishartlab.com/ax_nodes/C0001292)
`Carboxylic acid esters C4 (http://classyfire.wishartlab.com/tax_nodes/C0001238)
`Monocarboxylic acids and derivatives C (nttp:/classyfire wishartlab.com/tax_nodes/C0001137)
`Organic oxides (4 (http://classyfire.wisharllab,com/tax_nodes/CO003940)
`Hydrocarbon derivatives C3 (http://classyfire.wishartlab. com/tax_nodes/C0004 150)
`Carbonyl compounds ( (hitp://classyfire. wishartlab.com/tax_nodes/C0001831)
`
`Prostaglandin skeleton
`Fatty acid ester
`Monacyclic benzene moiety
`Cyclopentanal
`Benzenoid
`Cyclic alcohol
`Carboxylic acid ester
`Secondary alcohol
`Carboxylic acid derivative
`Monocarboxylic acid or derivatives
`Hydrocarbon derivative
`Organic oxide
`Alcohol
`Carbonyl group
`Organic oxygen compound
`Organcoxygen compound
`Aromatic homamonocyclic compound
`
`Aromatic homomonocyclic compounds
`
`carboxylic ester (CHEBI.6384 G (httpAwww ebiac. uk/chebi/searchid.de?chebild=CHEBI:6384))
`prostaglandins Falpha (CHEBI;6384 C (http/www.ebi.ac. uk/chebi/searchid.do?chebild=CHEBI:6384))
`triol (CHEBI:6384 G (httpswenw, ebi_ac.uk/chebi/searchid do?chebild=CHEBI:6384))
`
`Route of exposure:
`Enteral:
`
`e
`
`Ingestion (/metabolite_ontology_terms/4903893)
`
`Source:
`a
`
`Food (/metabolite_ontology_terms/4903892)
`Biologicallocation:
`Biofluid and excreta:
`
`e Urine (/metabolite_ontology_terms/3407383)
`© Blood (/metabolite_ontology_terms/3407384)
`Call and elements:
`
`° Extracellular (/metabolite_ontology_terms/3240349)
`Subcellular.
`s Membrane (/metabolite_ontology_terms/3240350)
`s Cell membrane(/metabolite_ontology_terms/3674477)
`« Cytoplasm (/metabolite_ontology_terms/3835947)
`
`http://www.hmdb.ca/metabolites/HMDB0014792
`
`IPR Page 2/7
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`

`

`7/9/2018
`Process
`
`Human Metabolome Database: Showing metabocard for Latanoprost (HMDB0014792)
`
`Naturally occurring process.
`Biological process:
`Biochemical process:
`® Lipid transport (/metabolite_ontology_terms/4903896)
`2 Lipid metabolism (/metabolite_ontology_terms/4903897)
`© Fatty acid metabolism (/metabolite_ontology_terms/4903898)
`Chemical reaction:
`
`© Lipid peroxidation (/metabolite_ontology_terms/4903895)
`Biochemical pathway:
`« Lipid metabolism pathway (/metabolite_ontologyterms/4903894)
`Multicellular process:
`
`Inflammatory response (/metabalite_antology_terms/3835951)
`o
`Immune response (/metabolite_ontolagy_terms/3835952)
`©
`Cellular process
`® Cell signaling (/metabolite_ontology_terms/3449682)
`
`Role
`
`Biologicalrole:
`s Membrane stabilizer (/metabolite_ontology_terms/3674474)
`» Energy source (/metabolite_ontology_terms/3674475)
`® Energy storage (/metabolite_ontology_terms/3674476)
`© Nutrient (/metabolite_ontology_terms/3835948)
`e
`Inflammatory (/metabolite_ontology_terms/3835949)
`Modulator
`
`® Immunomodulatar (/metabolite_ontology_terms/3835950)
`Industrial application;
`® Drug {/metabolite_ontology_terms/3449680)
`© Surfactant (/metabolite_ontology_terms/3674472)
`e Emulsifier (/metabolite_ontology_terms/3674473)
`Pharmaceutical industry
`e Pharmaceutical (/metabolite_ontology_terms/3602520)
`Cardiovascular drug
`® Antihypertensive (/metabolite_ontology_terms/3449681)
`
`Physical Properties
`State
`Liquid
`
`aia Property
`Melting Point
`
`Boiling Point
`
`Water Solubility
`LogP
`
`Value
`Not Available
`
`Not Available
`
`0.013 giL
`44
`
`Reference
`
`Not Available
`
`Not Available
`
`Not Available
`
`Not Available
`
`http://www.hmdb.ca/metabolites/HMDB0014792
`
`IPR Page 3/7
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`
`IPR Page 3/7
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`

`

`7/9/2018
`Predicted
`Properties
`
`Spectra
`
`Property
`
`Water Solubility
`
`lagP
`
`log
`
`logS
`
`pKa (Strongest Acidic)
`
`pKa (Strongest Basic)
`
`Physiological Charge
`
`Hydrogen Acceptor Count
`
`Hydrogen Donor Count
`
`Polar Surface Area
`
`Ratatable Bond Count
`
`Refractivity
`
`Polarizability
`
`Numberof Rings
`
`Bioavailability
`
`Rule of Five
`
`GhoseFilter
`
`Veber's Rule
`
`MDOR4ike Rule
`
`Human Metabolome Database: Showing metabocard for Latanoprost (HMDB0014792)
`Value
`Source
`
`0.013 g/L
`4.16
`
`3.98
`
`45
`
`14.47
`
`86.99 A*
`
`14
`
`124.34 m?-mol*
`
`50.71 A?
`
`Yes
`
`Yes
`
`Yes
`
`Yes
`
`ALOGPS(http:/www.veclab.org/ab/alogps!)
`
`ALOGPS(http:/www. vcclab, org/lab/alogps/)
`ChemAxon (http://www.chemaxon,com/products/calculator-plugins/property-
`predictors/#logp_logd)
`
`ALOGPS (http:/Awww.veclab.org/ab/alogps/)
`
`ChemAxon (http: (www.chemaxon.com/products/calculator-plugins/property-prec
`
`ChemAxon(http. /www.chemaxon.com/products/calculator-plugins/property-prec
`
`ChemAxon (hitp:/Awww.chemaxon.com/products/calculator-plugins/property-prec
`
`ChemAxon (http:/Avwww.chemaxon.com/products/calculator-plugins/property-
`calculations/#h_bond)
`
`ChemAxon (hito://www.chemaxon.com/praducts/calculator-plugins/property-
`calculations/#h_bond)
`
`ChemAxon (http:www.chemaxon. com/products/calculator-plugins/property-
`calculations##topolgical_surface)
`
`ChemAxon (httpy/www chemaxon. com/products/calculator-plugins/property-
`calculations/#topology_analysis)
`
`ChemAxon (http://www. chemaxon.com/products/calculator-plugins/property-
`calculations/#refractivity)
`
`ChemAxon (http://www. chemaxon.com/products/calculator-plugins/molecular-
`modelling/#polarization)
`
`ChemAxon (httpwww. chemaxon.com/products/calculator-plugins/property-
`calculations#Hopologyanalysis)
`
`ChemAxon (httpy/www.chemaxon.com/products/calculator-plugins/molecular-
`modelling/#polarization)
`
`ChemAxon(httpviwww.chemaxon.com/praducts/calculatar-plugins/molecular-
`modelling/#polarizatian)
`
`ChemAxon (http:tiwww.chemaxon.com/products/calculater-plugins/molecular-
`modelling/#polarization)
`
`ChemaAxon (http./www.chemaxon.com/products/calculator-plugins/molecular-
`modelling/#polarization)
`
`ChemAxon (http:/Awww.chemaxon.com/products/calculator-plugins/molecular-
`modelling/#polarizatian)
`
`http://www.hmdb.ca/metabolites/HMDB0014792
`
`IPR Page 4/7
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`IPR Page 4/7
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`

`

`7/9/2018
`
`Spectra
`
`View in MoNA C (httpu/mona fiehnlabucdavis edu/#/spectra/splash/splash 1 0-D0ki-5469500000-3070e3312¢
`
`splash10-0011-7170196000-
`108246e3e734960ba6id
`
`View in MoNA C4 (httpimona.fiehnlab_ucdavis, edu/#/spectra/splash/splash10-001I-7110196000-1092460367
`
`Le-
`MS/MS
`
`Splash10-052r-1958000000-
`o6S4c9459dbd5a20bSat
`
`View in MoNA CF (http Jimona.fiehniab.ucdavis.edu##/spectra/spiash/splash10-052r- 1 9S5B000000-c604c9459r
`
`Human Metabolome Database: Showing metabocard for Latanoprost (HMDBO01 4792)
`Splash Key
`Spectrum
`Description
`Type
`(http://splash.fiehniab.ucdavis,edu/)
`Predicted Predicted GC-MS
`splash10-00kf-5469500000-
`GC-MS
`Spectrum - GC-MS (Non- 3070e3312e2154427eeb
`denvatized) - 7OeV,
`Positive
`(/spectra/c_msi17619)
`Predicted Predicted GC-MS
`GC-MS
`Spectrum - GC-MS (3
`TMS) - 70eV, Positive
`(/spectra/e_ms/40446)
`LC-MS/MS Spectrum -
`LC-ESI-qTof , Positive
`(/spectraims_ms/3743a4)
`Le- LC-MS/MS Spectrum-,—splash10-052r-19Ss000000-
`
`View in MoNA @ (http.imona.fiehnlab.ucdavis. edu/#/spectra/splash/splash10-052r-1$58000000-cag4c9459¢
`MS/MS
`positive
`089400459db45a20b9at
`(spectra/ms_ms/450974)
`Predicted Predicted LC-MS/MS
`Le-
`Spectrum -10V, Positive
`MS/MS
`(/spectra/ms_ms/63027)
`Predicted Predicted LC-MS/MS
`Lc-
`Spectrum - 20V, Positive
`MS/MS
`(/spectraims_ms/63028)
`Predicted Predicted LC-MS/MS
`Le-
`Spectrum -40¥V, Positive
`MS/MS
`(/spectra/ms_ms/63029)
`splash10-053r-3002900000-
`Predicted Predicted LC-MS/MS
`Lc-
`Spectrum - 10V, Negative 194e702a216b0d2dfe90
`MS/MS
`('spectra/ms_ms/119895)
`splash 10-Oa4i-9104400000-
`Predicted Predicted LC-MS/MS
`Le-
`Spectrum -20V, Negative dBcBOOcGeDbe22batcab
`MS/MS.
`(/spectra/ms_ms/119896)
`splasnh10-Oad4i-9001000000-
`Predicted Predicted LC-MS/MS
`Le-
`Spectrum -40V, Negative d471d19421cS5af96709a
`MS/MS
`Uspectra/ms_ms/119897)
`
`splash 10-014)-1019700000-
`ea3b09b676018f1597e8
`
`splashi0-03di-5119100000-
`970c5bfecae331f19237
`
`splash10-03d)-9123000000-
`71493bbb4bSe38e17db2
`
`View in MoNA @ (http:vim ona. fiehnlab.uedavis.edu/#/spectra/splash/splash1 0-014j-1019700000-ea3bO0obe7e
`
`View in MoNA C (htip:/monafiehnlab uedavis edu/#/spectra/splash/splash10-O03di-5119100000-970cSbfecar
`
`View in MoNA C (http./imona.fiehniab.ucdavis edu/#/spectra/splash/splash10-03dI-9123000000-71493bbb4t
`
`View in MoNA C4 (httpuimona.fienniab.ucdavis edu/#/spectra/splash/splash10-053r-3002900000-19de702a2"
`
`View in MoNA (3 (http:imonafiehniab.ucdavis. edu/#/spectra/splash/splash10-Qa4i-9104400000-dac800cheC
`
`View in MoNA (4 (http://mona.fiehnlab.ucdavis edu/f/spectra/splash/splash10-Dadi-9001 000000-d471d19427
`
`Biological Properties
`Cellular
`Locations
`
`* Extracellular
`* Membrane
`
`Biospecimen
`Locations
`
`= Blood
`« Urine
`
`Tissue
`Locations
`
`Pathways
`
`Not Available
`
`Not Available
`Name
`
`Normal Concentrations
`
`SMPOB/Pathwhiz
`
`KEGG
`
`Taking 21059682 CF (htip:Mw. ncbinim.nih.gowpubmed/21059682)|@& (iconcentr.
`
`Sex
`Age
`Biospecimen Status
`Not
`Not Available
`Blood
`Expected but
`not
`Available
`
`
`drug
`Quantified
`identified
`by
`DrugBank
`entry
`DBOO8S4
`
`Value
`
`Condition Reference
`
`Details
`
`Unne
`
`Expected but
`not
`Quantified
`
`Not Available
`
`Not
`Available
`
`Taking
`drug
`identified
`by
`DrugBank
`entry
`Deooss4
`
`24059662 C3 (http:/www.nebi.nim.nih govipubmed/210596a2)
`
`[fe
`
`(iconcente.
`
`Abnormal Concentrations
`Nat Available
`Associated Disorders and Diseases
`Disease
`None
`References.
`Associated
`OMIM IDs.
`
`None
`
`http://www.hmdb.ca/metabolites/HMDB0014792
`
`IPR Page 5/7
`
`5/7
`
`IPR Page 5/7
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`

`

`7/9/2018
`External Links
`
`Human Metabolome Database: Showing metabocard for Latanoprost (HMDB0014792)
`
`0800654 @ (nitp://www.drugbank. ca/drugs/DBO0654)
`Not Available
`
`DrugBank ID
`Phenol
`Explorer
`Compound
`ID
`FoodDBID Not Available
`
`Not Available
`
`4470740 CF (http./www.chemspider.com/Chemical-Structure.4470740.ntm!)
`
`Not Available
`
`Not Available
`Not Available
`
`Latanoprast GF (http:/len.wikipedia.org/wiki/Latanoprost)
`
`Not Available
`
`6311221 © (http://pubchem.nebinim.nih,gov/summary/summary.cgi?cid=5311221)
`
`Not Available
`
`6384 (3 (http:/vww.ebi_ac, uk/chebilsearchid,de?chebild=6384)
`
`Not Available
`
`Not Available
`
`1. Hara T: [Increased iris pigmentation after use of latanoprost in Japanese brown eyes]. Nippon Ganka Gakkai Zasshi, 2001 May, 105(5):314-21,
`[PubMed:11406947 ( (http:/Avww.nebi.nim.nih.gow/pubmed/11406947)]
`2. SimonsK, ToomreD:Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct,1(1):31-9. [PubMed 11413487 G (bttp/Awww.nebi.nim.nih.gowpubmed/11413487
`3, Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global appreach tolipid analysis in biological sy
`Lipid Res. 2006 Oct;47(10):2101-11, Epub 2006 Aug 10. (PubMed: 16902246 G (http:waww.ncbi.nim.nih.gov/pubmed/16802246)]
`4, Sethi JK, Vidal-Puig AJ: Thematic review series; adipocyte biology, Adiposetissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6): 12!
`2007 Mar 20. [PubMed:17374880 C (http:!www.nebi.nim,nih.gov/pubmed/17374880)]
`5. Lingwood D, Simons K:Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1/327(5961) 46-50. doi: 10.1126/science.1174621
`[PubMed;20044567 ( (http://www,ncbi_nim.nih.gow/pubmed/20044567)]
`6 Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). Thelipid handbook with CD-ROM. CRC Press
`
`KNApSAcK
`ID
`
`Chemspider
`ID
`KEGG
`Compound
`ID
`
`BioCyc ID
`BIGGID
`
`Wikipedia
`Link
`METLIN ID
`
`PubChem
`Compound
`PDBID
`
`ChEBIID
`References
`
`Synthesis
`Reference
`Material
`Safety Data
`Sheet
`(MSDS)
`
`General
`References
`
`Enzymes
`
`1, Prostaglandin F2-alpha receptor(/proteins/HMDBP01950)
`General function:
`Involved in G-protein coupled receptor protein signaling pathway
`Specific function:
`Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phasphatidylinasitol-calcium second messenger system
`Initiates luteolysis in the corpus luteum
`Gene Name:
`PTGFR
`Uniprot ID;
`P43088 CF (http:/www.uniprot.org/uniprot/P 43088)
`Molecular weight:
`400541
`
`“$B Enzyme Details (/proteinsiHMDBPO1850) |
`
`References
`
`1, Ota T, Aihara M, Narumiya S, Araie M; The effects of prostaglandin analogues on IOP in prostanoid FP-receptor-deficient mice. Invest Ophthaimol Vis Sci. 2005 Nov:46(11):4159-
`83. [PubMed:16249494 (4 (http:/Avww.ncbi.nim.nih.gow/pubmed/16249494)]
`2. Nakajima T, Matsugi T, Goto W, Kageyama M, Mon N, Matsumura Y, Hara Hi New flucroprostaglandin F(2alpha)derivatives with prostanoid FP-receptor agonistic activity as potent
`ocular-hypotensive agents. Biol Pharm Bull. 2003 Dec:26(12):1691-5 [PubMed:14646172 (http:/Awww.ncbinim.nih.gowpubmed/14646172)]
`3. Takagi Y, Nakajima T, Shimazaki 4, Kageyama M, Matsugi 7, Matsumura Y, Gabelt BT, Kaufman PL, Hara H; Pharmacological charactenstics of AFP-168 (tafluprost), a new
`prostanoid FP receptor agonist, as an ocular hypotensive drug. Exp Eye Res. 2004 Apr-78(4):767-76. [PubMed 15037111 @ (http://www ncbi.nim.nih.gowpubmed/15037111))
`4. Ocklind A: Effect of latanoprost on the extracellular matrix of theciliary muscle. A study on cultured cells and tissue sections, Exp Eye Res. 1998 Aug(67(2):179-91
`[PubMed:9733584 © (https/www.ncbi.nim.nih.gov/pubmed/9733584)]
`5. Maxey KM, Johnson JL, LaBrecque J: The hydrolysis of bimatoprost in comeal tissue generates a potent prostanoid FP receptor agonist. Surv Ophthalmol, 2002 Aug.47 Suppl
`4:534-40, [PubMed:12204699 (8 (http:/Avww.nebi.nim nih.gow/pubmed/12204699))
`6, Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1/30(1):412-5. [PubMed:11752352 C (http://www. ncbinim.nih.gov/pubmed/11 752352)
`
`http://www.hmdb.ca/metabolites/HMDB0014792
`
`IPR Page 6/7
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`6/7
`
`IPR Page 6/7
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`

`

`7/9/2018
`
`Human Metabolome Database: Showing metabocard for Latanoprost (HMDB0014792)
`
`Transporters
`
`1, Solute carrier organic anion transporter family member 281(iproteins/HMDBP02021)
`Generalfunction:
`Invalved in transporter activity
`Specific function:
`Mediates the Na{+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2,leukotriene C4, thromboxane B2 and iloprast
`Gene Name:
`SLCO2B1
`UniprotID:
`034956 CG (http://www. uniprot.orgfuniprovOS4956)
`Molecular weight:
`76697.9
`
`Enzyme Details (/proteins/HMOBPO2021)
`
`References
`
`1, Kraft ME, Glaeser H, Mandery K, Konig J, Auge D, Fromm MF, Schiotzer-Schrehardt U, Welge-Lussen U, Kruse FE, Zolk O: The prostaglandin transporter OATP2A1 is expressed
`in human oculartissues and transports the antiglaucoma prostanoid latanoprost, Invest Ophthalmol Vis Sci, 2010 May.51(5):2504-11. doi: 10.1167/iovs.09-4290. Epub 2009 Dec
`17, [PubMed:20019365 C (http:/Awww.nebi,nim.nih.gov/pubmed/20019368)]
`
`wieeg
`he
`R IRS¢
`CIH
`ee
`
`
`
`This project is
`supported by
`(http:/Avww.cihr-irse.ge.ca) "eTM| C The Metabolomics (http:/www.metabolomicscentra.ca)
`the Canadian
`Institutes of
`2
`nace)
`2
`¢
`[tit
`Heath
`(http/genomecanada.ca)
`(htip.genomebe.ca)
`(hitpiwww.aihealthsolutions.ca) &
`Health
`Research
`(http://genomealberta.ca) 5
`ove
`Genomet
`Solutions
`Genome
`Genome!
`(http:/Avww cihr-irsc.gc.ca) (award #111062), Alberta Innovates - Health Solutions (http:/Avww, aihealthsolutions.ca), and by The Metabolomics Innovation Centre (TMIC)
`(http://www. metabolomicscentre,ca/), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta
`(http://www. genomealberta,ca), GenomeBritish Columbia (http:/www.genomebe.ca/), and Genome Canada (http: /www.genomecanada.ca), a not-for-profit organization that is leading
`Canada's national genomics strategy with $900 million in funding from the federal government,
`HMDEB Version 4.0 — Contact Us (/w/contact)
`
`Innovation Centre
`
`http:/www.hmdb.ca/metabolites/HMDB0014792
`
`IPR Page 7/7
`
`77
`
`IPR Page 7/7
`
`