Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 1 of 118 PageID #: 394
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`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 2 of 118 PageID #: 395
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`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 3 of 118 PageID #: 396
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 3 of 118 PageID #: 396
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`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 4 of 118 PageID #: 397
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 4 of 118 PageID #: 397
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`US 3.114.833 32
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`3mm. WI, 53 {iii pp. {Ii-“LR
`231mm at a?” E'kmrmamxmca! Elmagm Emma; Pammem} Medicalimx.
`mi. L 3nd liiiiiinn. p. 2:13
`
`”‘ cited by exzmmimr
`
`NNVICT00000140
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 5 of 118 PageID #: 398
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 5 of 118 PageID #: 398
`
`US. Patent
`
`[3211143012
`
`sheen of?
`
`Us 3,114,833 32
`
`FIQURE 1
`
`
`
`NNVICT00000141
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 6 of 118 PageID #: 399
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 6 of 118 PageID #: 399
`
`US. Patent
`
`Fem :4, 2m
`
`Sheet 2 0f *3
`
`US 31,114,833 132
`
`FIGURE 2
`
`Mam-mm
`
`NNVICT00000142
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 7 of 118 PageID #: 400
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 7 of 118 PageID #: 400
`
`US. Patent
`
`Fem :4, 2m
`
`Sheet 3 0f *3
`
`US 31,114,833 132
`
`FEGQRE 3
`
`
`
`.“ an”.
`
`fixflhz‘r‘flfi firirzatfuethhumm 35%
`
`~
`
`amflwgmumms «v “-1-
`
`Myra-imam!
`
`Mafia-:8
`
`GEycerol
`
`NNVICT00000143
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 8 of 118 PageID #: 401
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 8 of 118 PageID #: 401
`
`US. Patent
`
`Fem :4, 2m
`
`Sheet 4 0f *3
`
`US 31,114,833 132
`
`FiGURE 4
`
`
`
`Giycine
`
`Lactose
`
`Mannftoi
`
`NNVICT00000144
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 9 of 118 PageID #: 402
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 9 of 118 PageID #: 402
`
`US. Patent
`
`Feb. 14, 2012
`
`$heet 5 of?
`
`Us 3,114,833 32
`
`FiGURE 5
`
`
`
`NNVICT00000145
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 10 of 118 PageID #: 403
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 10 of 118 PageID #: 403
`
`US. Patent
`
`Feb. 14.! 2012
`
`Sheet 6 of?
`
`US 8,114,833 32
`
`FIGURE 6
`
`
`
`NNVICT00000146
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 11 of 118 PageID #: 404
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 11 of 118 PageID #: 404
`
`US. Patent
`
`Feb. 14.! 2012
`
`Sheet 7 of?
`
`US 8,114,833 32
`
`HGURE 7
`
`mam-3!
`
`NNVICT00000147
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 12 of 118 PageID #: 405
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 12 of 118 PageID #: 405
`
`US 8,134,833 B2
`
`1
`Pth?Yi.ENE (33 31301.4TQN‘I’AiNiNf;
`131313171353 FORMULATIONS WHICH A RE
`0PTIthL FOR PRODUCTIQN AND F01? [ESE
`{N INJEICYIION 9161? [CES
`
`U»
`
`CROSS Ri’il‘iiiliiiNCli it} ltiiia‘if'ifif)
`Aiiiii .ft is“ KENS
`
`This; .hppiieatioh is a eetttiattatiaa et’ihtertiatienat Appiiu
`eatieii, eerie} he. l‘CTt‘DKEGOMOKKWQZ fiietl Nev.
`lit. 26‘04
`
`1 ti
`
`and claims; pram}: from U S tippiieatinn Set. Ne. fittiSZ-ttififi
`titted MW. 24. Ztttifi and hem Danish A pplieatitm seriai net. PA
`2&0}; 0127“} flied Nev. 20. 2W3.
`
`FIELD OF THE im‘EWIQN
`
`The present itivehtien reiatea tn pharmaceutical .l’amtttia-
`tines comprising a peptide and ntttpyletie giycni. tn methade
`a t‘ preparing stteh thrtttttlatiens. and tn trees tit” stitch litrtt‘tttittr
`time; in the treattttentnftiiaeaaes and etititiltiehe tar whieh use
`
`al‘ the peptide enntainen in etteh thrmttitttians is intileated.
`the present "twentieth farther teiates tn methnds far reducing
`the flaggingel’ihjeetitin devices by a peptide fertnttiatinh and
`[at reducing, tieritisits tin prtidttetieh eattipnient daring pm-
`thietittn hi” a peptide ihmtttiatinn.
`
`RACKURGUND OF '1‘! iii iNh'iiN'tiitliN
`
`"l'he ineittsitin ttt’ istitehieity agents in peptide-centaining
`phannaeetttieai thrtnttlatiahe is widely human and nae {if the
`mere ennitnen teattthie agents used in each ferttiutatieas is
`niahhitei. Iinweven the present iiwetttart; have observed that
`marmitni causes pnthients (hiring. the pmdttetinn at" peptide
`fiirmutatittns as it erystaiiiees resetting in depttsits in the
`prttdttetien equipment anti in the final precinct. Stteh depaeitzt
`increase the need tn elean the fitting equipment tittfittg pm-
`dttetieh (tithe fiiriitutatitin and this; results. in retitteed predat-
`tittt‘t capability. in addititth, sttcit deposits may aisn result in
`retltteeti yield at the final prttdttet sittee Viaisfettrtridgett eati—
`taining the peptide ihrtttttitttinn may need ta be discarded if
`partieies are present. Finaliy.
`the present
`inventars have
`nheewed that in peptide tiiritttilatinns tn be administered by
`injectinn, the presettee (if mamtittii results;
`in flagging a?
`ittieetieit devices.
`Aeenrttingty. it is desirable to idetititjt; an alternative isn-
`tttnie agent tn ittahnit‘el int ineitreittn in peptidemtintaining
`faritittlatietts and in particular. fer inelitsinn in peptide titr-
`mttlalitins which are administered hy injeettttn.
`
`SUM MARY {L3}? ”ii-iii {Nh'iiNTiQN
`
`,_.
`
`'1;
`
`2t:
`
`tn.)'1;
`
`370
`
`33
`
`em
`
`45
`
`The present itwentttrs have dieetwet'ed that peptide Fanati-
`latiens ceritaiaihg pmpylene giyeni at eertain etineentratiens
`1::‘9':
`exhibit reduced tiepeeits in predaetian enttipinent and in the .
`liitai pi‘tidttet and aistt exhibit tedtteed mugging at" injectittn
`devices. the present etinipettitinms may he iitl'ti‘tttiétte‘d with
`any pent ide and are a let": physicai l3; and ehemieaf l3: stable than
`rendering them sheitlstabie and snitahie tar invasive ((3.3.
`ittieetien. etthetitahentts inieetien. intramuscular. iflEmK-‘etttttis
`at iltiija‘itttt} at; welt as hen-invasive (egg. meal that, pttimti~
`nary,
`transdemial ttt‘ ttttttttnmeesal eg. htieeall means a?
`administration.
`
`60
`
`The present inventinit therethre retates tn a pharmaeetitieal
`thrthtilatinh comprising a peptide and pmpyiehe glycol
`where the pmpyiehe glyeni is present in a etineentt‘atitth a?
`1400 tttgz‘ml and titepil (trim: {timittlatitin is lien“: 7. it}. in a
`
`iii?
`
`2
`
`pretence enihndiment, the pitarmaeetttieai fttrttttttatinns til‘
`the intrentian farther eentain a hatter and e pteeemitive.
`the present iti'ttetilitfi‘iztifit} teiatee tn titethnda tier prndtxeittg
`the phanttacetttieai thnttttiatieris at" the inventien.
`In tine emimdiment. the method tier preparing a peptide
`iiirtmtltttiait enittprises:
`a} preparing a first ectftttittn h}! disstiit-‘ing preservative.
`prettyiene giyeel and buffer in water:
`it} preparing a seennd seitttinh by tiit‘ESOittittg the peptide in
`water;
`e} mixing the first and secend snitttintts: and
`ti} adjusting the pii ttt‘tite mixture in e} tn the desired pit.
`in mittthet embed intent, the method iii: preparing a peptide
`thrmttiatian entttprises:
`a} preparing a first snititian by disentving preservative and
`better in water;
`
`in} adding prtipyiene giyenl tn the first attlttticm:
`e} mixing the first etittttian with it second snitttitm mntain-
`ing peptide disttttived in water: and
`{it adittstintg, the pi-i ef the itiixtttre in e) tn the desired pit.
`in yet heather enihetlithettt. the thethed fer preparing a
`peptide fimnulatitin ettntpt‘ieettz
`a} preparing a sniutitin by disetilvittg preservative. hatter
`and prtipylene giyenl in water:
`it} adding the peptide in the snitttina tit" step a}; and
`e} attittetihg. the pi-i hi the saititieh at step it} to the desired
`pt].
`"the present invention thither relates: in methods at treat“
`titent aging the phanttaeetttieei iiinntiiatittne at the htvetttieh
`where the etiittpesi tiene are administered in an a ttttitint ei‘t‘em
`tive tn ettthhat the disease. ettitdititin. er dieerder fer which
`adtninistt‘atitin ti l‘the peptide etiiitaiheti in the fitnntitatititt is
`indicated.
`in additien the present invention else relates te a ntethed
`fer redueingt tlepesits an pmttuetintt equipment timing prev
`tittetien at" a peptide fertnttlatien. where the tttethed cant-
`prlses repiaeing the isetnitieitge agent prewittttsiy tlfiii‘lxl‘d in
`staid iitmittlatittn with propylene giyeel at a cttntzenttatien ttl‘
`between 1- till} night}.
`in tine emitndimetit. the redeetien in deposits en the prev
`dttetitin equipment during pmdttetien by the prtipylene giy-
`etil-ettntaining. iiirmttiatinn relative tn that tthservet’l For the
`[ht‘tttttiatinn enntaining the previettsly ntilized isettmieity
`agent is measured it}! a simulated fitting expetitnent.
`The present inventina else relates in a ttiethntl for reducing
`deposits in the final product during pmttttetintt til‘tt peptide
`iitt'mttlat’itm. Where the niethtttf ctthtttt'ises replacing the the»
`tniiieity agent previntteiy utilized in said thnhttttttinh with
`methylene glyeei at a ettneentratien tithe-tween t-itttt ntgftnf.
`in nae ettthntlititettt. the retltietinit itt tiepnsits in the final
`pmttttet is tttcltttttt‘cd by a reduction in the nttmhet' til‘ vials
`anther cartridges; at” the prepyiene giyetil-etintaining termit-
`iatien that must he discarded dtte tn tiepesiti; t‘ttiéttitttfi in name
`he: of visits andhir eartridges at the ihrtttttiation eentaitiihg
`the prtl’t’itttittiy utilized isatanicity agent that must he the»
`carded title in deposits.
`‘lihe present inventien farther reiates {ii a tttethntt {tit techie-
`ing the mugging at ittieetinti devices by a peptide tint-enla—
`tieti. where the ntethed CCtItipt‘iSflS repiaeing the iset‘nhicitga;
`agent pfttifiittttttiy utilized in said femittiatitm with pmpyiene
`glycol at a etineentratinn {timbttti‘Wfifit} Lilli) maximal.
`in one etnhadittient. the reditetiett itt chugging ni‘the inject»
`tine device by the pnipyiene giyeei-eehtaitting thmttilatien
`relative ta that ttbserved for the fitmtttlatian containing. the
`preainasly tttiiitted iaattinieity agent is measured in a eimtt»
`iated in nee study.
`
`NNVICT00000148
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 13 of 118 PageID #: 406
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 13 of 118 PageID #: 406
`
`US 8,134,833 B2
`
`3
`iiRiiiIi-t‘ HHSCRIP’YKDN (JET Tilt-i MGURHS
`
`iiG. 1 sheets it pittitegrttph dfdried, dreplete mt tttit: resettpe
`stides eft‘rrtm tet‘t to right. piueehe {rm peptide} tertttttizttiehe
`ctttttttittirtg mi ietttttttit; agent (e tint}; water, presen’zttitze and
`he Tet}. mettttitei. ettrhittttf xylitttt. etterttse er gtyeemi are the
`iettttmic agent with the titr right siidt: containing mmmittti
`wi it peptide Arg“ ityemtji‘ipwtfywtittt(N“-hexadectttmyi33h
`(ELF-15137}.
`iet't tit
`" Ci. 2 edet tight ittierttecopy pictures ui‘ {mitt
`rig: t smite (3f the dried timpiets; tit piatceho thrmttltttimts
`containing tttmittittti. ttt'giniu, itmsitei tar gt‘ycemi he the iet‘»
`ttmic agent.
`CL 3 ehttwe tight miereeeepy piettaree et‘ciegged tie-titties
`desert with piacehe thttmtltttims containing ittyttimteittti.
`maltesse er giyeemt tie the ietitttttie agent,
`~' (i. 4 shdwe tight micmttcttpy pictures ttf depueits tm
`meet ice dotted with pittcchtt iitrmtttzttittite etitttaittirtg giycitie.
`trimeste- er mamtittti tie the iettttthie agent.
`,, (i. 5 eltdwe tilting equipment after 24 hours Sittiuittted
`tiiiittg with Arg‘mt
`i.yegfithth-{iitt{N*‘-itexztdecttttttyi)3}
`Gui-H13?) medium eeutaiuittg titye-ittdsitei.
`A‘ {in 64 shows; depiisits can fitting eqttiptttertt after 24110ttt'35
`eimttteted titling with it titaimitei—ettttteittittg ptaeehtt Fertilit—
`itttittttt
`
`
`
`,, t}. 7 SitOWS deposits eh steediee darted with tuttuttitdi {trip
`putteit
`tutti prttpytcm: giyctti {httttttm patiei}-etttttaittittg
`Are“,
`igrew{Ni—(1;»I£iitt(N“~itexedecztttttyi§tj-fii.P~l{?-37}
`tiartttu tatittitst
`
`
`
`[)EfitiRiP'HON Q? Tt-iii iNVENTiQN
`
`
`
`”the prettettt invention rcttttes it) a phtttmrteettti ‘Eti i’um‘tuttt-
`ieu edittprisitig 5t peptide er a mixture at peptides; and pre-
`pyteue giyedt where the Final miteetttrzttittu tit‘ prepylette
`giyee! in the titrtttttiatimt is Liam} flight} and the pH at" the
`itritiuizitititt it; in the hinge (if item Hi).
`”the ptttrrtttrteetttittttt
`fiittttttirttitme iii the itttieutitm tire
`’btltttii td he optima} 1hr predttetitttt because they exhibit
`reduced depusits iu prfltfiitlciitm eqttiprttetit retutitie ttt thema-
`ztt inns etttttttihing either iettttitt ieitgst agitate as tttcziettred h}; the
`stimulated fitiittg xtttdiett described in the iixz‘tmpiest ht addi-
`ititt. the pietmteeeutictti
`tiirttittttttimie iii the invention 2th
`’btlttd tit be dptituai for use in irriectittu device; because theyr
`exhihit reduced eirtggittg ttt‘ the injection devices rehative tit
`itrtttttitttittxte t‘tuitttittittg other imtmtieity agents: tie tttettetttcd
`y the eimttiatted in use studies; deecrihed in the iixttmptest
`‘i’he terminations at the present iflvtfit’tiittii may he termit-
`eted with any peptide where examples of such peptides
`itietude, but are net iimited te, gitifiiigttfl: human growth iter-
`mmte {hCii-i}, it‘tsttiitt, uprtttirtitt. tittetttr‘v'ii. theme pittsmtt‘tfir
`gen Etciivt’titir (’E‘i’r’t),
`tittctttrVitzt.
`iiiiR-i’rtetttr‘t’iittt hepari-
`i'ti‘tStL‘i ACTH Heparin Binding i’mteirt. certicetmpitt-
`1::‘9':
`reieaeittg iitctdrt exigitt-teiisiu. Cflicittfllifli giuettgettuiiite .
`peptide-i. gittcztgttnviiitt: peptide-2. it‘tféttiinviikt} grttwth fat»
`terwi. itteuiitt-tiite grttwtit iitetdrwz, iihmhittst gmwth fitment3
`gastric itthihitery peptide, grtiwth itttrtttt‘me-reterteiitg titetttr.
`pitttitary adettyiete eyetase activating peptide.
`secretiit,
`fittiefflgasit‘iflt Sotttttttitstaiitt. smitttteitteditt. parathyrdid her-
`ttitttte. thrttt‘nhttpdietitt. etythrttpttietih. hyptttitetttttiit: reiettee
`in}; thetttt'si pmittetirt, thyrttid stitttuitttittg httrtttmteeg fltidt‘tt"
`phitte. etiitephtttitte, h’z’ifitipi‘etisiit, exymeittt aphids, DP? iii
`iitteriettiziue,
`iiutttttriugitthttiitte,
`eemplemeut
`itihihitore.
`eeritte protease itfltihitttre. eymkiriesi cytdkiue receptors.
`Piifiiii itit‘t‘tttt‘ necrosis flamers, tttmttr itecrttuie titetttrs recap»
`titre. gmwth {litters end tttiztingttee EtS weii its derivatives;
`
`4
`theretttiiwi‘tere each (if thee: peptides ettnstittttett tin hi tentative
`eitihodimem et‘ the present ittvetttidn.
`in the present appiififliiflih the designation “2m meringue” is
`its-ed tr) designate a peptide wherein one er mere amine acid
`residues tti’ the parent peptide have been substitttted by
`iII'tQii‘ttsf atttim‘t acid residue tittdi’ttt wherein tint”: ttr inert:
`
`U»
`
`amine acid residues: iii the parent peptide have been deieted
`mutter wherein title (it mere utttitto acid residues have been
`
`1 t:
`
`added tr; the parent peptide. Such udditiett euu take piaee
`either at the Nuterrtiittzti end or at the C~tertttitttti end of the
`
`2t:
`
`tn.)'1;
`
`em
`
`£30
`
`parent peptide tit htttit. 'i‘yttimiiy “rm ttttztirrgtte” is; a peptide
`wherein ti ctr ieett amino acids have been stthtttitttted tmdfer
`
`added hustler deleted from the parent peptide, mere pre titr-
`ahiy at peptide wherein 3 m‘ ieee amine acids have been eith-
`etitttted uudi’er added eitdmr deleted item the parent peptide.
`and tttttt-ii’ pretterehiy: a peptide wherein mite amine acid has
`been substituted endfdr added attdfttr deleted frttttt the permit
`peptide.
`In the present apptiezitittn, “u derivative" is; used id desig-
`httte a peptide m eimttigtte thermi’whieti is; ehetttieaiiy modi-
`fied by itttmtitteittg tttt ttrgttttie ettbetitttettt the ester. tiiiryi ttr
`iiptt pitiiie titittctittttttiitiee. 0:1 mm ttr mere Etti‘tii’tt‘?! rteid residues
`tifthe peptide er analogue titereei’.
`in Line ettihdditttent. the peptide it]! he included in the fer-
`tttutzttiert et'the itteetttimt is 21 (Stilt-i ztgeniet where “at (ELF-t
`tigertiet” it; understand ttt refer t0 titty peptide which tittiy ttr
`partial 1y activates the httmttrt (iii iii—i receptdrt In at preterit-d
`ettihmdimmt, the “Cil..P~ t Etgttt‘titii” is; any pept itie that binds; to
`a GLP-i recepter. pret'erah 1;! ed th an affinity eettstattt (KB) or
`it peteuey {iitffifljt pt‘ helm:
`t 3.1M, egg. hetriw me did tit;
`measured by ittetimds human it]
`the em (feet:
`tag. W0
`titti’tiiiiii’t) and exhibits; inettiintitrtipit: activity; where irtetdi—
`hetrttpit: activity may he measured in vim or it: vitrtt aways»;
`kiiewrt tu those of prdirtur}; Shiii in the art. Fer exampie. the
`City-t ageitiet may he rtdtttittietered ttt an attitttei and the
`ittsutitt editcetitrtttiprt measured ever time.
`Methdde for identifying {hit—i ttgtiitiste tire deecrihctt iii
`Wt) {33219275 {New} Nttt‘disk NS} and exampiee {if sttittthie
`CiiiP—i aimittguee and derivatives which cart he used accord-
`ing itt the preeettt itwet’titttt} ineittdee these re titrred m in Wt)
`99/213 785 {New Nttrttiek A38}, WC) 99f43?i)t3 (Newt) Nerdisk
`MS}, WO 99543707 {Nam Nitrdittir: MS}. Wt) ghffitttfii
`{tmetegues with iipfipi‘tiiic etthtttitttettt) and in WO 02345227
`{ttitatdgttes fused td serum atbttittiu or td Fe partied (if au
`igfltfiwu Nitrdisit A33}, WC! 99t437ti8 {New Nttt‘diei; ASS}:
`Wt} LEI-113343 (New: NerdisitAfS}, WU Mittfitfli (The Gem
`ertti iittepitzsi (Rtrprtrtttitmt Wt) 9t}? 1 {2% (“the General tries-
`pittti (imperative). WC} 913t145’? {Bucidey et
`211.3} W0
`9W43658 {Eli Liiiyd: Ce. }. BP (WOBITt’Q—AE {Eli Liiiyda C0. }.
`iii” fldtifitfititinm (tilii {iii}? {it Cd}. WC) 0139833} {iiii tuiiiy &
`(fit.
`
`tme emht’itiimmtt the (HP-t egttniet it: selected item the
`I
`gm 3p miteistiitg of tiLt“~i(’?—36}-umide. Cit.t’~i(?~3?}, a
`Cit, -i {i-iitit-atttide uneteguet a tiLi’~t(7-37‘} z-ittttltigtte~ er a
`derivative tilw an}! di‘theeet
`i t (the cmhttttitttettt, the (ii .i’~t agttttiet is a derivative ttf
`{iii i-it7-36i-ztmide, GLP- K7137},
`at (iiP-ififit’fi-tttttide
`itttzt ttgtte er at {ELF-mid?) Etttztitftgttet which comprises a
`iipophiiic suhstitttent.
`in this ertttmdirttettt Mitre itwerttitttt, the City-t derivative
`pre iL‘t'ttbi}; hate three iipttphiiit: Qtthetitttcttte, mere pret‘ertthiy
`two iipdphiiie Subfitiittfittt’g! and meet preferahiy Dita iipt’)“
`phi it: etthetiment attached to the parent peptide {iii flittt’wi ('i~
`Edi—amide. (ELF-16%?) it (it.P-t(7-3ti}~emide attttiegtte or
`a {ii,,i’—i(?-37} ttttaittgtie}, where each iipttphitit: substituettt
`is} ateliemhiy [the 4.41:) cztrhtttt meme, mere pretbttthiy mu
`
`
`
`NNVICT00000149
`
`

`

`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 14 of 118 PageID #: 407
`Case 1:17-cv-00227-JFB-SRF Document 39-1 Filed 01/29/18 Page 14 of 118 PageID #: 407
`
`US 8,134,833 B2
`
`:3
`
`earhitn stems, even mere preferably 8-25 carbon tit-ems. even
`there preferably 12-25 earberi atheist and meet pretertthiy
`Lint 8 eitrheh attome
`
`is tt
`
`hi ene enihetiiiitent. the lipephiiie stibstitttent eemprises e
`partisan}; er eompieteiy hydrogenated eyeinpetttttttopheiizttit~
`rene shetettin.
`hi ttttether eittheditttenh the iiptiphiiie snhstittteht
`straight—chain or branches aikyl gents
`in yet enether enthrittiittettt. the iipnphiiir: stthstitttent is ah
`seyi group (ifs straight—chain or hrahehed [titty acid Preter-
`“My: the iipnpitiiie snhstitttent is en trey} group havittg the
`iiirttinitt CHRKTHEJWCQ»»»»»—. wherein n is an integer time at to
`38. preterehty an integer item 12 to 38 and rhnst pret‘erahty
`is (fii3tt.’1i2ft[2(7{)-----. (3113(CTi-i2i MCI} - t£_TI-13{C’ii2)m(7(,i- '.
`(fittBttfiigmtfe »
`tit ifitrtttztmtt‘o
`this
`(shifting
`22th} »»»»»» t in a: mere preferred ettthtttiiinettt. the iipephiiic sitti-
`stitttent is tett‘ttdtmtthoyi. inn meet preterred ettihedittieht. the
`tittepitiiie stihstitneitt is hexadecannyi.
`in t: thither enthedimettt (tithe present twentieth. the iipri-
`phiiie stthstitttettt has a grtittp whieh is negatimt}t ehztrged
`such as it earhnsyiie said group. {tor estimpie. the iipnnhitie
`stibstitttetn may he an hey! greet) hi it straightehnih or
`hm tiehed n litane mortiiettrbmtyi it: acid at the termini: HOOK
`({TttzimtlT} --, wherein m is an integer item :1 to 38, preter-
`shiy an integer them 1?: ts 323. and must pret'ershiy is i i003
`(“{3}”th»»»»»»»»»»,
`t’iQOCTtCH’izilfiCO»»»»»»»» . titjtmftifiigimtfti»»»»»»»»,
`iifilii‘rtftfifiiigmfit)»»»»»»»»» er iiQO’CitC‘iifitzztht»»»»»»—.
`in the {ii,.»i"~i derivatives 211’ the inventietti the iipnrthiiie
`stthstiteentts} contain a theetit‘thei