CFAD V. Anacor, IPR2015-01776 ANACOR EX. 2070 - 1/21
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 1/21
`
`

`
`CLINICAL MICROBIOLOGY REVIEWS
`
`VOLUME 11 0 JULY 1998 0 NUMBER 3
`
`Betty A. Forbes, Ea’.-'mr in Ciiief (2Ut}2']
`SUNY Herihli
`.S'cr'cm‘c Cfeiiter
`
`S}-'."£.l(‘£t.S‘€. NJ’.
`
`Lynne S. Garcia. Edi.'r:r- (2003)
`UC'L.«i Medmrl Cerirer
`Los .--'lrigci"c5. C'rri'if;‘I
`
`Kennett: D. Thompson. Ecfiirrr (2002)
`Uiiii-'ersrT_\‘ of C'hic(rgr.: A-i'erlfr.'rrl Center‘
`Cl'i.t'cagr;. Ht’.
`
`Judith E. Dorner (ILFW)
`Kevin Hnzen {l‘)UEi]
`
`EDITORIAL BOA RD
`
`J. Michael Miller [_2[ltl0}
`Andrew Onderdonk t2{ll]t.|)
`Daniel F. Sahm (l9%"}
`
`Steven C. Specter (2001))
`Gregory A. Stnrch (I‘.)()H]
`
`l-’iil:Ir'r'rirto.-.-3 Boom’
`Barhara H. lglcwski. Ci‘-iafnimri.
`Beverley .l. Bennett. Prort'ticrim1 E:li'.'rJr
`
`Linda M. Illig. Ilittwtor. Jourrmt'.r
`Victoria A. Cohen, ,-'i.r.si‘.n'r:rrt P."U(il.t(‘r'lt‘)J'I Erlitor
`
`C.'l'iriit'.{il i\'lit‘i‘ol3i0lrigt.‘ R[".'l(.’ll-'5' corr..\'ia't'rs_,li)r pm‘:li'r.nrioii both solicited mid un.mlir'ired ret-'i‘ew.r and riior:og,»1i:t,zili.r tlerilirtg it-'r't:’i tit’.-' aspect.-3
`of cl'iiiicm' i-riici'oli.«'r:lr.=gv. 1l’i't1t1£!S£‘l't_(?lS, pi'opri.s'uls. rmtl c'r)m’.spoiiclc'ri<‘.t=: regcti‘riiri.g eo'frrJri'r.=t' rmirrers .-rhotrlrl he rirlrJ.'res.terl to tire Erlitur in
`(.'hi'c_,t] Bcit_\'.»‘l. Forbes’. Dcprirtmeiir t.ifC't'iriicr'o' Patlirilragir. S'UNl"Hcoltli .'iefenee Center. 750 Enst.:1rlrmi.r St. S_1;rocii.s'r'. Ni" 2'3.-Nil-2.i'30.
`
`Clinmil .'l‘f:'g';1)bf{Jf0{{\' Revr't=v.=.s (ISSN {I893-t<5l2) is published qumteriy {J:mu-ury. April. July, and October}. one volume per year.
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`CFAD v. Anacor, |PR2015—01776 ANACOR EX. 2070 - 2/21
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 2/21
`
`

`
`Clinical
`
`Microbiology
`
`Reviews
`
`A PubIic.'ari0n of (he Arr-iwicrcrrz .Ԥrm'er_1= for Mic'r()bi0f0g1-'
`
`VOLUME11
`
`0
`
`JULY1998 o NUMBEFI3
`
`CONTENTS/SUMMARIES
`
`405414
`
`Anne H. Rowley and Stanford T. Shulmzm. ..
`Kawasaki Syndrome.
`S:mmm:_1'.' Km-m.s'uki _-.j\‘ndron:(’ ( KS) it rm £.'(’£u‘ft’. a'r.»m:'.':';1u=s (lira! 1-a.vcu:‘f:'i.\‘ o_f‘_\‘umrg c'h:'fdrtw.
`KS has rcpi'c:c':*d m'm‘.'.= rIr:'1rrrra:icfi*1'er m the .|m'J.s'£‘ cmmrmon m:.*.s1-.- rgI'c:c:;t.'.i."m‘ J'rr'm‘! ¢1'.I'sm.-gt in
`chiizfmi in the .'_.’rI:'rm' Srmcs. The i{!'.=rc.s'a' is mam_'f'E.\'Ic'd by 1.-_1:'c:ln:1gc*rf_fin'm-. c‘e'm_j1mr:r:‘1.'rH'
`i:1_j€c'—
`Hun. ermmim-n.
`t.’.1'um'.’::'.-re.
`(.‘I_'\'HIL’J'.!.'£i mm’ .\'I-t-vflirrg ofrlte hcrmix and few. and c1’r1':'a:! cm’wm-p-
`mh_\'.
`'t":'u*.s1' c.'r.’m'('_fi’rIf!m:*_\' of ."Hne_s'.s' are s:'!_,f'—!'.r'n;r:'.'mg. hm ('r'mm.nr_v m'm_1* m‘Jnr2r:m:!i.'.*.n'.x‘ mt‘-pm‘ in
`_-”{}*?+ 0;" umrcn.'c*:I pmicm.s'. The ::ria!og\' of the ."H:1e.s‘.s' ix um'cmJu'n, hm Em‘ c‘:':'rr:'cm’ mm’ epide-
`m:'oIngi¢' f'eun.rr'(!.s' are mo.-;.* crriisisrmir It-‘iii’: cm r]r:_.I'E'c‘n':m.s c'z.'m‘c. Crmrrmm :.‘m'a'."m'r:.m:!r.=:' amm-
`{,fc.srr::inn.x- pf.n|'1c' £!hn'.\'s :'m':'u.r!e JTil".‘r)r.'(.'!'{J'i'I!".5. per.-'m:'rh'r1z' e_[fu.9irJrr. amf mrmrmg‘ nm'n' mmn}-'.\‘m
`fbrnrurfxirr. Trm.'rmwr w.='rJ'1 mnw-'c*:rous gnmmr: glnimliri U l"'C:'G) amt’ m;rJir.".'r u.'£.U'n'n :‘»‘w_,r‘:'m {U
`u'::_\-'.\' of .I'Hm‘.a'.\' rm'rr¢‘('.\' rim _:ar'wm'¢.'n{.'(r of crmrrrcrry m‘r¢'.=_*_.-' ¢:b::::r-r:1::h.'m‘.w _f}-um _‘f_}*'3?.-
`in H'm..\‘é'
`:r'r-um"! Iri.'.’: rr_vp:'.-in m'um= m 4"‘?.'«.. P.<:.'iwu.a' who ¢'J'cJ1-'5-'ir';_,r: wrr.mmj,' u.='m_1_.' u.m:’mj.r.srm'.
`,-mr‘r:'c':n’::::‘{\'
`rimse whr.» tie‘.-'m’¢';;.: gmm L'ur(mm}' m‘rw)' z.'::e:n_}.'.\‘.I1i.s. mar .-;z.'_,|_‘,i"w’ :n_\ruc':n‘.rt'ia! i:.=fur('u'rm secomi'r:r_1*
`I0 I:‘rr'unu'1o.~‘.I'.v 0:'.s'!mr.=.w'.s in the ubsruivrim’ I.'e_s'sc*1',
`.4r1':I'.":."u:mu’ r'e.vcm'rh Io c'¢'¢*ImJ:mc* rho m:.'..\‘e of
`K8 is :.u}:m:!_\' rwea"ed Io nH.«_m=_:‘i':r' i.rnpm1-‘ed dd‘-£J._!;,'ii0.\'£'.S'. mnrc _x'_.oe(‘.i,-’fc‘ rhc'nr_.':;r, am.’ prc1=w:!fm.= of
`the (H.-;-1m'i'e.-‘.
`
`Boni
`Onychomycosis: Pathogenesis, Diagnosis. and Management.
`E. 415429
`.\'mmnm_1=:_.»1Mr:'mg:': rm! !'.{fk‘—.'I:rc*c:£:'ning. 0:1_\*c'.’1mn_v(‘r.=.v.‘_s' (r:_fm.'gw' :'n_.I'Lrc£:'on o_,f'r.’r.e mm’. mm.=!.’_\'
`m:r.w.e*zz' by :3 damm.'c:p!'1_\-'I¢’J' {‘£J!T.\'fff£££r.’S rm E.-nporfcrm _mu'J1'£c‘ hcfcrirfl grmbimr: h¢'c’uu.w r_'1_.I’ its Iiigfr
`pr:.=n:u’¢.=m‘u (afloat: .’f)*'.»".'r- 0_;'”rJ'w L-".3. ,rJ0pu!m'fr::1) mm’ r:s.\‘oc£::.*cd n:ur1'Ii¢'1'."£}‘. The c1'f.mm' um hm'e'
`(';*J1:.*m rregurire ('£IiI5'£‘ql.'i€i:('£’.\' frrr ;m.':'('ur.~'. _mch as pairs, rim." rrrm ,rJc:re:r:‘ic.-1'!_\' 1rm'z’cI:‘r:1:'.-w work
`and .mc':'m’ If-.'m'.
`}']I'iix :'c1‘:'{'w a'i.~‘m.'s.\1'5 ihe L-riznirkgv. 4:’im'.x'.f,-‘f{‘m'i:.m,
`t."fiILL{iIr!_€.3i'. and r.r‘m::1mrJ of
`r.m_'.'cJ'm:rr_'.rmsis. Four [1-'pc5 ofu.'rycfrw:r_\'m_¢.i.w rm’ It-cr.1g;n‘:¢.*:I .’m.x'c:f cm the sire rum’ gmnrem of
`fm:gm" i:m'm'r:u. Dc-‘rmamph_\-*re fimgf are Nu“ prcq.-’onn'muz1 ,r:wJ'mgem'. hm _W¢i's!_\‘
`:"e.\',.r;rt'u'::.-HF.’
`C‘:r:rcI'idr1r cifiiic-1:rz.s'_} and 1rmm'ernmmph_\1e ::10:'ri'3 nlmy (list) he .-'11:,-'J!fc:n'm'.
`.»'{(‘::‘:m:.'e d:'agm:.¢:'.s'
`m;:u'.=w:.i' :h'm'1 n::'cn.:a‘m;_:_\' and fu.r:g:.=I mhnn.'_ The (i:_'fl"k*rm:im" zJ'iz:g::n5'i.v :'m1':.':!:'.s p_\vr:'asis.
`h(’hc.=r p1'amr.\', rm_\'uI:r.>g:_vpJ'2::.\':'.s'. mu.’ um"! mnmm. On_\'('hum_\‘ms.5s is more :.I'i_fl3c’£.n’.' :0 mm: I.-‘mu
`Hi-‘.J_\‘.' dam mr0ph_w:).\1:.=.s b('('aus¢' of!he* .":1hm'n: flan-.' grr_m'rh u_,I"rh::' mm’.
`()I(J'¢3:' rrrrrifirxrlgczf cxgcms
`(kr.'Io¢'cwm::r.=I(' and gr.='.\‘mflu'1'fnJ are :.*.I:.s':.*."!ut'vi'c* 1;.» ow:_u:’I:r).'.=:_1.‘m.vi.s'
`.’.J:=:c.'u:n1* Hf n’ref:' rm'm.I'I'mf_\'
`pom‘ cflim('_r mm’ pr.:r:":m}::J' .rm'w+m- c1fiF:':('r.s'. T.’u1*c r'e('e*r::{}' u'¢'rn'q.rJc'd r:mfm__\'mH'c‘ uger::.\‘ (flu-
`rm-m:0.’v.
`:'r.Iz.'m.I:(::uI:\ mm’ 1'£’!’}Ji.'1:.i'_,(‘}.ii(‘}
`r;_f,Fcr high cure mrcav and gain! 5:':fi*.*_1' pmfiz’¢'.s'.
`In
`z:r1'c'.|'frir.m. tire .suI'mr: rrmrrm*m times {<23 m.rJ.':m.rJ am! :':m=rm.5mrm d(}.$'i!Ig .-it.-’u'dulcs um :’.")‘.'e!'.\‘ In
`c'nfmm:1'-' L:rj:n:ph':'m:‘:-' um! re-'dm‘e' rim wars of rhcmpa-.
`
`l'_'mr!:'rrH:'r.‘ rm _f¢Jf?uI\-1'.-zg pu,1{r
`
`CFAD v. Anacor, |PR2015—01776 ANACOR EX. 2070 - 3/21
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 3/21
`
`

`
`[Tur1r:rrHe(.* ham prt'cr?ri'u:_H prim’
`
`Robert A. Dudas and Ruth
`Respiratory Syncytial Virus Vaccines.
`A.
`
`.'u‘_w1c‘__\-"hid 1-'hm' [RSI-’J is the most hhprmanr -f'(.’£J.i(’. u,"'1‘h'rIl h1u'(':'r£'.s‘;_?i-
`Sunnnrxryx.‘ Rc'.\‘ph'.:.'h:uj\'
`I'|‘.i'I'r'_I|.Pj' tram’ fh'.m.‘.$‘.s' (LRU in 1'.=1_j'Irrm‘.\' (mt! crlrflrlri-fr: I-L'or{d11’fdL‘ mu! m:.'.s'e.'.'
`.sfgi'1:}'i{.‘rJII:' LR.’ in the
`£'£‘der.’}-' and in hmmm::r;crmzprmrr£.9er£ prm‘eh.:s. The gnaw’ n_,FRSl"1-'m'z‘hr(:rim: it to pl'El-‘Em sc*:'Ec.=u.¢
`RSI-"'-(mm-{me-d LR}. Than‘ are .9;-‘rem! r.:b.shm"es to the dcvefrwprrreari (J,".s::c:'e.\'sfid RSI-" wac-
`ci.=urs,
`irrc‘.-hdirrg J.-"re !I('('d Ia .imnrm1.*'ze reg-' ymmg infinus, us.-‘m :mJ_1-‘ resprjmd iriarieqtlarir.-’y to
`mrcinn.*im1.' rim y.r:'.m+hc:.= afrwa mrrigcnimhjv ¢'h'.s'!fmr.' R.S'I--'_gmu;.1.s'.
`,-'1 am‘! B: and Jim hr'3mr_1' 0}“
`d."sea.s'e enhrrncerncrrr _f0h‘u::whrg rta'rr1.f.v:i.s'm'rrirm nfn fcm1:r.'h':r—h1m'ri1-met.-’ 1-zrmrirre. It is h'kr:l_1' rhm
`more (liar: one type of vmrc:'.rrc 14'lW he needed to prevcm REL’ LR} hi tire wm‘m.*.s‘ pr;puhm'(m.\
`at risk.
`.“lllf:l!('J.'.!gJlI molar cfc=!i1‘€r3-'.11-'sIcn:s.
`_{'.'r:r.«'.Ie.fh' pep.':':'h'.
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`1-'accr'm.-5 have haw in-'u.«'m1I(rd in auinmJ' models. wrh-' the I-'_'.|IJf'I'fl:L'l'l' F p:‘0£ch1 (PFP) ndmrrir
`mcr:hIe.s rmd :"f1*c arrcmmren’ 1-’ar‘c‘r'm’s have been r.=v:u'r.rared in reccm‘ chTr1h.‘nf rrhrls. PFP-2
`
`;;rtm1is.":1g 1-'z.IL'c'Em‘ fhr the cidcnfi-‘ and _f:>r RSI--"-scrc:p0.§hEve cJ'u'Idn‘..=z whh
`zrppmrs to he or
`:.u:rl':*:'Iy:'hg pzrhrmmmrjy :Efsc:.=.\'e. wh¢'.»n=':u- hvu’ cr:l'a'~,rJa.\'.\'uge:£' frp). rc'mpc*ramre-s:%n.§i!h'e (Isl RS1’
`1-'.::ct':'.*I:!.)' (dmnh:d rpm 1-'(:c’{'."n£.\'_J wrmlcl mos: pmbabh-' he :mj,f'u{ in _1-’r)m1g ir{,f'unIs. The mm’!-
`z:h:'l':'fy of cDNA rec.-'::rrJIOg'_u .s'.-’mm’d m"h?M‘ _,f'un'her re,I‘irrenrcnr nfL".r:'.\'.'t'r1.r: live crrrenrtclred (.'p!.\'
`c:'.urmh'zh:rc* I-':rcc:.‘rres Io prorhrce c'.I1g.*'h(ec'red 1-'rtcc:'m°.s‘ Hm.’ am’ sat£.v_f.{:n‘I0:fl_\* arrcn.uamd, frmJI.'m0—
`,_::wu'c‘. and phz':m.r_r;.:icr.!hf_\-' smble.
`
`rzpsaliensisz Waiting in the Wings.
`Campylobacter
`V0011 Loong Chan, and Philip Sherman ...... .
`
`.
`
`.
`
`.
`
`.
`
`Billy Bourke,
`.
`.
`.
`.
`.
`.
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`
`.
`
`440-449
`
`.‘fwrmr:mjr.' Dcwphc .srrrmg ::_:Jr'dcrIric.=hJgical c1':‘n".«:'m'c‘ supporting an impommr nah‘. ._."§9r C:mrp_'.'-
`lrJhaL'r(=r ztp.s':rh.'cr:m'.s as a hmrrmi cmeropa:‘h(;ger:. fr rernainx rehm'1-*e{'.‘ £Nl.hf.Fl:‘}H'.FJ hr the rem"m of
`L-h‘m'-:'al
`rJ1i(‘n'u‘9irJ1'ogy. C‘1'h::'(Iu' srrtrhm imh'c'm'e that
`irrji-criurm 1'.-'.I'Ih
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`i:m"ud.'ing 3pm":-
`rcrncemrx xrhnmhm mm‘ he.-mr)!_wit--uremic symh-ohm.
`.-1:c.em':'_\-' have been 1:ssn:':(‘iat('z£' with humcm
`hr 5:ecr.‘ons. Una'er.s'rm:ch';i,1: of the v.I'mJ'.:=nce pm,.rJer1ies and mo!ec:u’a:' biology‘ a_f(".. e.-psahcrmc is
`l.'1cg:'m::'ng m mrolt-9. Tfrere ix mm-' a premrtg need for r_'on:rr)!h:d. p:'rJspec'h'-.-e cpidc'r:1in!r;gi:'
`.\'.'mhc.< in tldrmllrlll m fim'hcr h1—a’ep.'h h1'.'e-.m‘gm‘hJn ufh'm purrhngem=.s'1'5 af£hf.s' cmeric‘ mn1;1y—
`fobacmr In more prem‘se!_'.-* dcffirrr its role in hmmm dinerzse. FurIhermr';rr:. s."r'.-cc C. up.s'r:I£e.I1.w's is
`.51:-r:.s£r:'1-'c In the zartribicatrts rourirccflv u.s'c.*d in CarrrpylobacrtfrscEecr.51-'c rrrecfirx, Ivide.s‘pr'cm[ ::ppre'-
`Ciatintrrr of-‘the imp0r:‘mu:c? of {Ms w;I;a:1i.mr wifl r‘w'_!-' rm I.-"re 0'91-*cz‘r.»pr:uem of 1w'de{_'.' upph'cal'.1z’e.
`c)jl"t'c*.'."1-'L* Icc.’:rn'qme.¢ for its i.s'u."arhm.
`
`Pathogenesis and Diagnosis of Shiga Toxin-Producing Escherichia cola’
`Infections.
`James C. Paton and Adrienne W. Paton. .
`.
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`45{]—4'?9
`
`.S'u.vm:mr,1-2‘ Sham t.’wh' hlhfc.-I J"E(.'(J.t_,’flh'i(JJI 2()_1-'mrs ago. Shiga m.\’ira-p:'0r1'm'hIg E.sc'hm'c!1ia c.'oh'
`f'STE(_‘) .-m-m'n.\- hr:vc'- L-me.r;;z:.=u' us" an hnmrmm trarrse aj'sc-rir)n.\' fuhmrn ga.vm)in£e.s'rfm:I zf£.\'m.9c'.
`which hm)‘ mu.-ll in h'r2»-rlrrearmirzg c0.Inp.'ic:m‘0ns 51m’: as h.2:rz(;.{1-Tic’-:m'r1:£c .s’_1-':za‘r0me*. Fond-
`bomc outbreaks raj" STECT (h'.s'easc appear to be :'r:crec'£smg and, when Hms.s'-p:‘odm:‘c‘u' am!
`n1rzs.s'—rhLm'£b:tredfood‘: are ::onccrm:d. cam irn'o!'1-'6 hrrge m.*mbem of,-Jc*n_m"c. Del-'n'.'opr1:cm of
`rher;'::;mr:fc' mm’ prmrurrrrrrive .s'!rn£egh:.s' to crohu'm.' STEC di.9erI.s'r.' n=qm'r:e.9 :1 I.-’-mmugh m1a'er-
`Smrm'.5r1_g of tire nm:l":mH'5n:5 by -.1-'.’:."ch 3 TEC 0rgam'sm.s cohJm'2e .h"1e hxmtrm .i:1m.m'mn’ Irucr and
`£'(I££S-:" {c:c‘¢a'I and sf:-'s!r:mh' par!m.’ugh.'m' chr:r1gr'.s'. While our k!I0'|-1’hT{1':E¢‘. rL'mm'hs hnr0h1p:'erL'.
`rwem 5mrJ'.*'r.'..v ham.’ frwrprawrf our ttrrdersfrrrrcfirwg of rhe.\'¢= ;Jn';ccs:.‘es. pani€:.*J'rJ:'E_1‘ {he c‘omph*.\
`imemcrfrm I;-cm-'(acH .S’:'u'ga rarhrs arm‘ has! (His. wa"ri('h is central‘ (0 the ;.1rm’10gw1c‘s'i.\' ofSTEC
`di.s'e:m'. hr mhhhnu. .vc=1=rer':n’prtrr:r:'w.= accessriry viru.-’€nce facmrs J':.<rI-'8 been idc:'::."}'?ed m:dpm1:’y
`chrsr-crcrrsa-fzezf. The mpachy In iimir flat’ scah’ um"! .vcI-wit)‘ of .S'}"EC diamasc is also dependent
`upon mpid mm’ .\'u:'.*i.w'!i1-I’ dfagrw.s‘!r'(' ;Jroccc.-'m'e.\‘ .f'h:' mIa¢'y.~'is of :‘mrmm .\‘cm1p:"c.s‘ mm" .mspecr
`1-'m'riL‘J'r:s. The ."m'.Im.\'crI :.r_pp{ic‘a.*fnu ufurh-'am.'ec.-’ .vm:h:c'u.’m' r:rc.'.-‘mo.-'ugi:r.s' in (.'h‘ru1-al :'aIJur'r:Jr;r':1'rs
`has sfgm]‘imnIIy im_.rmJv:‘a' om’ Capt.-ri:‘_v m :'I'icr,_2hrJ.s-9 STEC i::f¢'c£ir)rr
`enr¢’_I,= in the r.‘rJm“.\‘{’ of
`rh'.':cr:.ve amf m clumcrr hm‘ hrw.-is of ¢='n1'.-‘r0.-ahrmtaf cm:rmu.im:I.'m.':. This. in rmn. has cr'.r:(:mf .:
`p0n'm'h7! I1-'im:hm-' oj'.«':_:.>p0r£:r;ri{y jir.-.r_,"itHrrz' I.-’1erupc::ric :'hr('n*c:;rn'rm.
`
`CFAD v. Anacor, |PR2015-01776 ANACOR EX. 2070 - 4/21
`
`{.mm.'1m*u' rm ;r.'ru‘h:n'mg prigtr
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 4/21
`
`

`
`:’_"orttt'rtm'ci' from pt'ut'e'rI'ttt.se: ].'tt_t{c’
`
`Dengue and Dengue Hemorrhagic Fever.
`
`Duane J. Gubler. .. .
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`48lJ—4%
`
`.5mmmtt_1': £)cttgt.te ;‘i:'r:"t'. it l't’t'_‘.-‘ oht rtt'm:t_\'c. that rcretitrtgcrt to the pct.-rt 2t}yeot:s' with an (‘J.'_.'7tttt(J"L’{t'
`gt-'(tgt’£tp:’ttI‘
`tt't'.~rtribttttott of both the 1'int.v(.*s
`tom’ the m(!.5'(j'ttH{J
`'.'t.‘t‘fUt‘.\‘_
`t'm‘t'c:tscct'
`:'pt'(h=ttth'
`at‘ttl’ll'_}’, the th*1-'ct'oprtt.9t1t of h_i-'pcremh?ntict'ty (the L‘(J(.’h*‘{Tlth'¢'!tfltt oj'nutt'tt'ph* _rc'r'tJt\-'pexJ'. and the
`c*tt1c:gem'e ofctettgue lteotorrttogit‘_ft=1-erht mm-*gco_§:t'u,o)':t'c' tt'gt'r:tt.\‘. ht 29993‘ tt£t.‘|'tJ'ttJ.s'qttttt}—tT(L:rtit-'
`£l'i.5‘t_Jct.\'(.' is the most tt3Ip0t‘t£tt!t‘ tt'opimJ' thf’e't"thJtts' tit'.s‘co.\'c otter tattttittitt, with on csttttitttctt I00
`mt'h‘t'oh c'o5c_\' of thmgtte fiwcr, 5UtJ_0I90 crises ofttettgtte t'teototT."tctgr'cfever. and 25,000 :h'ott':.\'
`otttttttthfr. The t'1‘:‘t£St_Jt1.\‘f'}t' this t‘{’.S'tiI‘gt‘.’tIt'c' and etttctgcttce of(t'c=t1gtt(' t'mtttot1‘ttr1gic_fc1'et' hr the‘
`n'ont't1g _i-'t3or..~‘ of the 20th t.’.‘(?t'l'fttt'_\-‘ are cotttptex ttmi not _htz":'y i.mch=t:s‘tooct. hut rtetttcigrtiptrtc.
`.\-o.L't'ctot'. ittttt ptthth‘ ht'ot'tt't t'nf"o..\‘tt'm'tut'c cfttottgcs to the post 30 _\'cott+_.' t':oI.-:1’ cotthfhtttcd grcttthn
`This paper rtweucs the chrmgtttg E_t)fdt'tttt£}iOg\‘ of durigrte rota’ ttettgttc h:ztttort')'trtgic fa!-'t:r by
`g£‘t'Jgt‘t'tph'tE' ttrgiotr, the tmtttmf hi\‘tor_v omit tt‘t}'tl5ttttS.\‘t()tt {'_l-’C‘¢"(.’.§. chtttcttt rttrtgttosis ofhottt tieogttc
`fever and dctigi.-c’ hentorthogtc’ f(.'1-':'.’t‘. sflologhs (ttttt' i.=t't'oh)gi.'.' hit'>m'otorj.' thogttttses. prttttrig¢*tte_\is.
`5ttt1Jct:'t'rmt:r.*. pt‘t.'l't?ttIhSlJ"t. tmd cotttrot'. .-‘I rtmjor ct'1ttZh?ttge_tbt' ptthh'c hmt'th o_{fict'at'.\' it: oh’ troptl-of
`mmx of the world is to o'c-.-'h.'np om! tfthplemcrtt sttstrttnrthh‘ pt‘£’l-'£’tit'.h3'tt rota’ r.'mttr'r_3t progtzrttix
`that n-Eh.’ tZ’1-'tL't”.\‘C the mam! oj'etm'tge=ht ttcttgttc .ht’ntot1hogt:' fever.
`
`Epidemiology of Group B Streptococcal Disease in the United States:
`Shifting Paradigms.
`Anne Schuchat. .
`.
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`497-513
`
`Stttmnorjt-': Since its (’.tm?t“gt.’tl'('(' 25 _v:.'m'.x ago. group H .\‘tt'£’pttJc’U{’L‘t.tS has .-‘vccomc t'et*og1ttz:’:i' as
`at
`['fl£t.5‘t.’ of .s'ct1'tJtt.s'
`t't't'm=.s's
`in tit.-‘I-t-'b0t‘h‘.\‘. pregnant W0t?It_’tt, amt ttthttts with C’ht'{ittt{' mezt't'cot'
`t.'otuh'tioh.\'. H'£’tI1-’_';-' cohatttzotiott ofthc gctiitof t't'(t(‘i‘ with gt-(mp B _\‘fl‘t;’piti{'0tTtTHS also t}ILTrEtt.\‘C.€
`the
`t'fb‘h' that o wommt M-'iIItt'ct'i1-'ct'
`.1 pt't°.'t(?t"tl"t I011--fittth1vet'_2ht ihjottt. Ectrt_\'-rmset Ettfecttoh.§ (o.-:::to'-
`mtg at <7 ct'o_\‘s of age’) are os.\'ot:tt:t:='o' wit.-‘I
`t?:I'ttt‘h hm-‘er fotohty than wtiett
`t'h't?_l' were first
`dc-‘sL‘t‘t'bc?r!. out! their trt(.'fd£‘ttC[’ is fihat’h' dcrrrct.-.vt'ttg {IS the ttse of pt'evt:.rtti1-‘t’ ttt1tt.htott'c5 :t.'urhtg
`:‘ltt]’tiht't‘ttt
`it1ci't.’o.\‘e5' among wc.-titer: at rick. New sr:rot_-.'p(.=..\“ of gt'r}Ifl_.(} B Su't‘tI‘p!t?CtJ[.‘Ctt.§' Firm.-
`ctmrrgm‘ as fmpot't.:tht _mrthogc*m: to :td'ttt'ts- and tit-M-"harm". Ch‘.-1t't;'o( amt h2bot'r.rtoty ptrtt.-tires—itt
`ot)st::=ti't'<15‘. pechtttrms-. and t‘hr1t'(ro! tnt‘crobiot'og_\-'—Jt:tv(-‘ on impcrct on ttiserm’ mzdtot’ its )‘Jt‘é’i-‘£.'tt—
`ttott. arid pt'otocot's t:st:thz’ish(’rt at the htsttttttiotrot 181-‘cf appear to he crt'tt'r-ht’ toot: for the
`rcrtttrticitt r:f',rJct'tt-iota! dl.5‘{.'rt.3‘fl chic to ,g,'t‘mtp B stt'eptocr;rctts. Since t'tth'oportom tJttttbtDth".T n.'t'h'
`pram-‘wit or best om’)-’ a portion of‘ the fith’ h1t."£h'.’t! of gtmtp B streptococcal.’ :t'.r'sctts:'. c.-rt'tt'coi
`dg;.:¢:toprr1¢'ttt.s ht 1-'occ'ht(.* m'ttht:ttt'oh.
`iric‘htrt't'hg 3tm1_v of pt';h-‘.s‘occhm't¢'t'€-pmteio cotijttgote 'l'tt(‘-
`chm. ojfcr the potential for etttittticed prcwnttott th the rct':tti1'e:‘_\= tIt."tI'J" fittitrc.
`
`Serum Therapy for Tuberculosis Revisited: Reappraisal of the Role of
`Antibody-Mediated Immunity against Mycobacterium tubercutosis.
`Aharona Glatman-Freedman and Arturo Casadevall .
`.
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`514—532
`
`Sttt?l'mtl't}'.' Féfty _}-‘ears tt}i.«:*r the ihtt‘o:'!ttrtfoo of the _,fi.r.§t cjfetrtii-'6 otititttirrobhtt ogcttts agaihxt
`ti-1;.-'coboc'tct'tt.tot tubm'tthJ.9t'.s'. this pothogett crmtt‘.-mc.\‘ to be a trt=tm'mtrJtt.i pitbhc .-‘health pm!)-
`hzm. The rise in the ottmber of rmtstotrt stntihs ohd the tt{fhr;'tttti:'.\' ihi-‘oh-‘ed in the fht’t'£'tp}’ of
`tttbet‘ctth'ist.\' to intoutttoc‘otttprc:mf.rea' AIDS prtth=.ttts htti-’(‘ ttfttcwcttt the thtcrmt in the dL=1't*top—
`omit t2fa{ffi.'t.'tt'.'c 1-’.:tcc’t't'te.s'. To evohttttc wt'tett'tt:t' tt potutrtiot 1'£t{'£‘ttt.(’ (tgoittst tut.wct‘cutosts rottht
`ptwettt it1_ft’L'tton t‘1_\n:'.-’tc‘ittttg ct pt‘otcc'tt‘1-'9 otttihody t'e.s‘pot1.s'r:. we rt'1.-‘tcwect' thehi.vtot}'ofttti.t.ibm1{‘.‘-
`tttc'a"iotert' tttt.t?ttttttt_\' ogofhst ttt.’J:2rctttt).vi.s‘. Rm-'t‘crn' of the htmttttrc of the pro‘! !0()_veitt‘s demoti-
`stmtcs that then’ is .s'ufiictr_-‘tit e1'to.’ettc'c to {‘0ttt‘htthf‘ that or:tt'htJ.rh=—ot¢‘diotctt t'mmtmtt).' (‘mt tt'todtf1‘
`the t:’(.=to:s‘e ofittfi'ctt'ott to t.‘t_’t‘!(tttI stttttttiotts. Brtsetf on ottt‘fihc2’h1gs and oh what is t'(hou-‘tr ht
`other S]’.§‘£t’t'?‘i5, we ptrtposw that the role of ztt:tihot{1'-tticdittttld hhmut.=it_'.-‘ to M.
`tttt'icrct1t'o.w'.¢ be
`rcctotttittco’. trxittg oo'vuttceo‘ ttrt:!tttotug\'.
`
`Quantitation of Cytomegalovirus: Methodologic Aspects and Clinical
`Applications.
`Michael Boeckh and Guy Boivin .
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`is on t'mpot'toot pttttiogctt in trohsphmt rt'ct'picttts oust’
`(CMI-’)
`5tm1motj.'.' C_1-'tr.}tncg:1tovh'tts
`httttmtt to-tmttttorttfficictzci-' 1-*t't‘t.:s t H! Ir")-r”.It__i"(*t“.tL-‘II ttm't'1'i:'tttoI.\'. Mttjot‘ flt’I(.'_I{t'£’.\‘_§‘ has hem t'.'”.'tTt:"(‘ ht
`t'te1-'5'.-'opt'ttg q'tJtl'JIftIttttl'£’ tt't.’f£.‘(‘:‘lOtL' tttet»"t0o’.s' for CM I-" or t‘t’(’{ftJ'f _'.':?rtrs. Doc to th'{’tt' high scti:.'ttt'1-'tt_1'.
`
`L IH'i”.fiHI'I! rm fk;t.hm't'tt,:z _ttugt‘
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 5/21
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 5/21
`
`

`
`I.-Ilfiii-r'lUl.'(iI ,I'i'n.m‘ Jr-'JI.‘('i.'rr'J'.‘l!.:
`
`,r_.:(:.:.::'
`
`i'H(.‘_\’ he :i_s-tjflii in pn‘dicri.=:g Fifi’ ;.=i.'.*i¢'irI '3
`firm:-’ m-.m_r.s mi: {i:'it'L'.’ C'.’l—l‘l-" m.-rir. mm’ :,rmii1.*i.'nr.'iuii
`.r'i_\'i\'. _,fi:1i'
`:1‘.-‘_\‘m_w.’ mil‘! in i'l'li}ilil0l‘ii£|£; me glee: aJr"rinti1'irm" .'iit=i‘up_'.'. Tili.\' r't’|'i(’Il'
`tl'i.\'i‘ii_s'.\‘.v5 mm’:-
`irdiritagimi ci.\‘pet‘I.~' of (‘m"!‘(.‘IIli_}' imeii qmmiii.-:ui1'c :i.x‘.wi1‘.\'fi'ii‘ C'il-fl" (i.e.. rim! cuinm' i(‘(‘iHliqIIc'.N.
`:':m‘igen {'it’fi.’L'ii{'J!'l‘ r£.\‘.\'t':)’.\'. DNA :.icret'iirJir ms-cr_1*s im‘iiiriii1gPC.‘R. bW.'!l(’il'£’Ei-.ON.‘l m‘.\‘i:_1'. mm‘ rim
`UN.-‘l
`ii_ri?i'ia'
`[‘(l'pll'u‘l"t‘ u.s:.w_\-‘J mm’ r.f(i(ii‘(‘.§'.‘a'(.‘.\' the .:.'ui‘rw'ri:iriii
`r.»j,f' .s'_v.sIcii1i:; {'H'I(i
`.s'iit=-\',i;t.*ci'Jr'iu:.' (“Ml-"
`iomi am! (Ml-' :ii.m'i.~;e in d'i,f';"ci‘:rrn‘ piJpuiarim:s of iiIII.’HH.'(?.W.‘ppl'tf.T.Yt?(i p(u‘.'i{‘.'lIS Ii'.\' u-1'1? as file‘
`re.gi;0ir.<c‘ in :mm 'imi r.Imimeur. Tb dare. dirt-'r‘ir:r1Iigc'ir :h;'*ie('rirm cmci iirriiiririiir :ct'lmiqm'.s' .-'mI'c
`lz:.=7.:(‘i\' :t'p1'm‘¢-‘cl nmii.'.='imm' r.-ulr:ii‘c-im.s'c*:l rc’c'lrirz'qric*.r_f-hr CM!--" qrimirimiirjii.
`.-‘ii gt'i1:?ml.
`Ii‘ iiigii
`.¢_1'.m'irric CM!-" lama’ is cmrei.:iic.:i wirir CMI-" r!i.\"ec':.§'e. This‘ rr_m'e!arir_m is .-xrmiig in the’ H:'l-"-
`iii_,I"ec'!L"d _(mp:.'i:i£im‘r mm’ in .§rJii:i~i;rg:Iii .f."t.'n.s'_.'IIu.n.' rc*i'ipient.9 iml l'c'.s‘.s" rl't'm' in t:z"z'rJgei1£'i(' inm?'iJw
`m.'i.-_vpim:.' iwi,-')."eiir.s'. M:'ci.vm‘iirg the rim! icmrl‘ an .\‘pcci,fi.'_‘ mm.'r_;ri11ic' _\-ir:=.s- rmI_1‘ in’ cm t1ilL’l‘.'ltHil-‘L’
`11-'u_\‘ in rim-.\'_s' :ii.s'm.\'e m"£i1-‘ilj-‘ in .\'imm'irm.s -.w’it-.'it.- lire .s'_y-‘sic:-.'iic 1-‘irui :"m.rd ("om-irr!rr.s p(mriy‘ wiria
`:ii'.s'm.\'e i:c.'irii_1-'.
`.-rl
`i‘erlm‘riw:
`r)_';“ :‘i'l{’
`..~'_'.‘.~;reiJ:ic' CW1’ I-’ {mid riixu coi'i‘ei:ne.\' 11-‘iii:
`I.‘
`res_m'.=m'e Io
`:im'h'irm' !l"L.'(JH.’l{.‘.’Fi'_. hm U!'(}.FI.‘
`i"(.'.\‘L’(I."-'.‘il is .Fl(’(’(it’[i fr) (.'l'tl'il'n‘{¢‘:‘l-F rim mic .q,r"1‘ir:u' lurid m‘ I.’
`.\'iimJ_giiI¢'
`Hl(J'i‘kL’i"_ii.'J.r' iiitig r'e.vi.r.'iiir('e.
`.’)m.- in die wides,i.Ji'mi.i use r;gfr,ri.mmitririve ("Ml-"deiec1ioir .'echniq.ties
`in ciircw (H'L'{'i moiairor timivimi iJ"(.'th'l'IiL‘II:'.
`there is {J gl"t’(U Jl(’{’t.l for rm t'.l.s'.§'t'.\'.§'IH£’H'.f of rile
`i't.-pm:im'ibiiii_'.' ufrc.-ii rr.=5ul'£s mm’ heifer xiiiiitirirdizsrnoir 0_f’r.i'1t'
`(.I.'£.\‘r?_'.'.\'.
`
`and Guillain-Barré
`Species
`Campyiobacter
`Nachamkin. Ban Mishu A1103, and Tony Ho
`
`Syndrome.
`.
`.
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`.
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`.
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`.
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`Irving
`.
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`.'5im'e the emdimrim: uf'_.«mliu ii: nm..\‘.f ptH"I'..\‘ of fire u'oi'M. Guiiiaiii-Brirré .~j-*i£dnJirtc= (OBS) Em.»
`hi.-‘mule the mm‘! L'r.r.Ii1mrm crmw of £1-f.'£H(' flr.'t'('id pm'iuf_\-'.\“i.t. GBS is rm mimiimmiiic ili.wm'L'i' (if
`the pi.-n'pirr'i‘m" .lI(.’i'|-’:‘)H.\' .sj'.\':‘em c.-‘rm-air-:er.=;ed by u-'mime._\‘.s'.
`:t.s'zm:"{v,= 5_-..-ipmmrm-;;.(, {J1.’0il'iJ'Ig m.-,«_»;- 9
`p¢ri‘ir)(i [l_r.\’L"'l.-'{_-!l"£J'11 iic.'_v.s' m’ .'JJUJ"[’.
`.§’i.r1(.'{.’ iztlzimilnm-'.1' began in i.\'c.-."r:e‘:'{’ (‘IiiH.f)I}-'.’{Jb(l{'ft’r S,-'_n't‘i(.'.¢ lfir;-in
`.-wool .s'_m'('in?(."it_s' same 2()_1'c.m:s- ago.
`.'i'iere have .-‘ween nm'.FI_l’ rspum of CBS fuiiowirrg C.'ai1ip_p.
`i0i'!II'[‘i£'i’ infeciioia. (Jmfi‘ ritiriiig rim pm‘:jtm-'_1-'e't'ri3' i1tl.\"_\'l.r‘tJrlg e1*ia"enL't' .mp_nor.'ing riiix u.s‘.\'r.=cimimi
`dc.-I'eiupm'. C'mn,r?_\'ir..~e'Jm'ier iiifc.*m'iJii
`is mm-‘ kimwir {H the .s-ingz’¢' imm iciciriifiiible mu‘ece:ienI
`iri,f'ecii0i1 cissracirrred wiiii tire de1-'eiopim*m‘ of GBS. CrIii1;.1_1'ir)iJzit‘m' is riirmghi in L"(u'li.\'£’ this
`uumimimiiic ¢ii.s't':m.= ihrrmgii ti iiictn"i:ii.=i.vIn miicri iiraieciiiiirmimic‘ij.'. wimeiry C:im_uylnbm'.'e.I'
`(‘{J}:f£Ji??.§‘ g:mglim'i':lc-like-’ q.uiInpr.=._~: in .-‘he iljlflflillil-'S(I(.'(’iltifidt’ .’JIOi£’i_‘.-' rim: e.-’."t'ii am'rmi.Iiib9ziie.s'
`ri.=m.':iirg with pl.’l‘ip,lI(‘n'!i news’ i:ii*gei.s:
`(."mripj.-'iciiJucm" is ti.-;.mi.'i':iieci with set-mrirri
`,'JiiiimiqL_,ri'c
`_;'i:rim.\' {if CBS. ii:(‘.r'ur!'ing the darn)-‘iriiizcitiirg fricmre infliiiiriiwrirnijn-' dei11_1-eiimrriiig pui_viiei.inJp:ariI_'.'J
`mm’ rLrrmm' (cimie iJl‘(JI()I‘r1ll‘f)l'.l(Ii n'etii'npuil1_\')_,flum:.v. i)i_3%rei:r srrciiiis of(":i.=Ji;iw’0brirh!i' us web’
`(15 imsi fi.':'iur3'
`iii(:’i__1' play an impormm role in u'ei¢9i'iJ:iiriirg who a'c1*elr;p.s‘ (_}‘B.5‘ a..\' mad’! as the
`i"l'{’J"l'£’ iiii;gt'r.~' _,"i.ir the iiasi immL.me m‘mci't' c2f,i)ei‘i,')irerrii i1ei1‘e.\', The piii}m.s'<! of this" rel-'ieIr is m
`.§‘Efl'm.iItl'l"i31E‘ our (.'u.i?'{’H.'
`i<.=iuv.-"ledge about ihi: crii'ni¢‘t'ii. upi:lemiuiqtgimi. ptirirrizzierrceric. aim’ fur’:-
`rmifory crspmrs nf canipyIrubricr.rei'—as_mciared OBS.
`
`For yeixr convenience, the full text of the 1998 CMR issues will be available online by late July
`1998. Access will be free for all of 1998. Please visit www.journals.asm.0rg for more information.
`
`CFAD v. Anacor, |PR2015-01776 ANACOR EX. 2070 - 6/21
`
`l"r1in‘iiim-'u' UH p‘UNr:il'il'l_J_g lpn_-.::'
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 6/21
`
`

`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`t\=tn_ir.on|:n.om R: vnzws. July Itllis, p. 4l:‘s-42*!
`(‘1.1.-x'u..\t
`I IH‘-a"_l-‘$5 I 2raa.r'SI 14.1}! I + r I
`
`Copyright‘ (C3
`
`l‘l‘4ll-l. Aittericali Society for lVllL'l't1l‘IlllltJg__\. All Rights Rescuer}.
`
`Onychomyeosis: Pathogenesis, Diagnosis,
`and Management
`BONI E. ELEWSK|*
`
`t.t‘nin-'er.~'ii_i= Ho.spirrit\' of C,'lei'e!m1t'.-’.
`l)epm'm1eiir of [_Jw'ii3.:irrJirJgt-',
`Ca.-.1» I-l-"esrcm ."\’e.s'ei'i-1+ L-‘iii:-rsizvin-*.
`("lt*1-‘teittrttl. Ohio
`
`lN'I‘ROlJU(.'Tl()N
`ONYCI-IOMYCOSlS..........
`
`no¢nI|o|Iu||u0 ..............nu...no............
`
`Definition and Clinical Impact
`Epidemitiltigy and Risk Factors
`DERMATOPHYTES AND ONYCTHONIYCOSIS
`CLINICAL TERMINOLOGY................................
`...-noun...
`ANATOMY OF THE NAIL
`CLASSIFICA'|'I()N OF (}N\‘('HOlV1Y."O-(ISIS............
`..u......o.-u--....... .
`Distal Suhungual On_vehon1_veosis
`Proximal Sultungual Onychomycosi
`White Superficial Onye|Iont_\-‘crisis
`Candida Infections of the Nail
`
`......................
`
`.....................
`
`....."416
`...........-'-llt')
`
`Total Dystrophic Ollychotttyeusis
`DIAGNOSIS OF ONYCHOMYCOSIS
`Dilferential Diagnosis...............
`Collecting the Nail Specimen........
`Distal subungual onychomycosis
`Proximal subungual lIIl‘l_W.!l1llI'l'I_\-'l.'(}Si5..............
`....unus..
`White superficial anychomycosis
`Crmrlida onyclmtnycosis ....
`.... ..
`Specimen Analysis ..........................................
`..............
`ANTLFUNGAL SUSCEPTIBILITY TESTING ........
`ANTIMYCOTIC AGENTS USED TO TREAT ONYCHOMYCOSIS..............
`........... --«......u...u........n.uq.uu....u... ..u....... .
`Limitations of Traditional Antifungal Agents
`Griseofialvin
`..
`K(£lt'lC(|l'I11I(.0lE ................
`...................... ..
`
`..
`
`Advantages of Newer Antifungal Agents
`Fluconazole
`Itraconazole
`Terbinafine................ ..
`ANTIFUNGAL THEI{APY............. ..
`
`II1IICIQIIIIIIIIIIIIOIIIIIIQII
`
`Comparative Trials of Antifungal Agents" .................. ..
`Adjuncts to Systemic 'l‘|Ierap_v .............
`
`........-'-I20
`
`....420
`
`Selection of an Appropriate Therapg-'.......
`cu
`Clinical Management of Treated Patients ............ ..
`Educating Patients about Their Role in Treatment.
`CONCLUSlON................... .................
`REFERENCES .......
`......................
`
`................
`
`.....
`
`INTRODUCTION
`
`Most cutaneous iiilections are the work of the Iiomogeneous
`group of keratinophilic lungi known
`derlitattophyle-S. The
`d:-.'rn1uI'opl1yte }'i'iclmpJ'.=_\'.'r'iii i'm'1i'mi.= is the major cause ol" tinea
`petlis and U[‘l_\_-'L‘llUT1l_\’CUSlH (El). Alter ori:__rin-ating in West Africa.
`Southeast Axial. Intlonesia. and NoI'thern x"\tI.‘I+irEtliiJ... T. mhr.-mi
`spread to liurope and North and South America in the late
`llrlth and early Ellth centuries, where it fountl Lt niche within a
`
`l-Inspi-
`l_.'Ill\'t:l”:iil_\-
`" Mailing address: F}epartment' of Der1'nato|og_v.
`tals of Cleveltmd.
`llllltl liucliti Ave- Cleveland, OH -1-4ll'Il'1-5|L’t‘i.
`Plume: {Ito} Hzlél-31?? [-ax: {Elli} Hal-1-:-{W}. E-mail: BEELEWSKI
`to .r\Ol_..C()i\«'l.
`
`reeenllvx-' shotl populace {S}. Subsetplent Zllth century develop-
`ments including wars, the i‘l'It‘It.ll.'l'I’l health movelnent and the
`associated use of occlusive |ootwea1' and locker rooms. and
`migration of people since the invention of the jumbo jet. pro-
`moted an increasecl incidence of tinea peclis and o11ye|1omvco-
`sis (El).
`Derrnatophytoses of the fingernails and toenails. in contrast
`to those at other hod_v sites. are p;-1rlicular|_v ditlicult to eradi-
`cate with drug treatment. This is the eonsequeitcc of [actors
`intrinsic to the nail—the llill'l.l. protective nail plate. sequest1‘a-
`Lion of patliogcns between the nail bed and plate. and slow
`growth of the nail—as well as of the relatively poor etiicaey of
`the early pliarrtracologic agents.
`Recent years, however, liave \vitne1i.scclt|1e development of a
`
`J15
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`CFAD V. Anacor, |PR2015-01776 ANACOR EX. 2070 - 7/21
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`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2070 - 7/21
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`
`-llfi
`
`!:.|_.|:.WSl~il
`
`L"i-ir~.-. Mu l{ttltlIJL. R1-v.
`
`new generation of -antifungal drttgs that produce impressive.
`long-lasting cure rates with shorter treatment times and better
`safety profiles than ketoconazole and griseolulvin. In this pa-
`per. current knowledge of the pathogenesis. diagnosis. and
`management of onycltornycosis with these new agents is re-
`viewed and evaluated.
`
`ONYCHOMYCOS IS
`
`Definition and Clinical Impact
`
`“Onychomyeosis“ tratlitiottally referred to a nondermato—
`phytic infection of the nail but is now used as a general term to
`denote any fungal nail
`infection (63) [linear unguium specifi-
`cally describes a dermatophytic invasion of the nail plate"). In
`spite of the clearly diseased appearance associated with this
`condition- onychontycosis is all too often regarded as merely a
`cosmetic problem of relatively minor importance that is hardly
`worth the effort to resolve. This belief may ltave been sup-
`ported by the adverse cheats and long dosing courses associ-
`ated with some of the earlier atttitungal agents.
`In fact. onychornycosis can have sigtiiticant negative effects
`on patients‘ ernotional. social. and occupational functioning
`and can. in addition. consume a sizable proportion of health
`care dollars. Affected patients may experience embarrassment
`in social and work situations. where they feel blighted or tin-
`ciean. unwilling to allow their hands or feet to be seen. Patients
`may fear that they will transmit their infection to family mem-
`bcos. friends. or coworkers. tears that can lead to dirninished
`sell"-esteeirt and the avoidance oi’ close relationsltips (55). Em-
`ployment suffers if employers are relttetant to hire individuals
`with abnormal nails. particularly torjobs such as food handling
`or modelling or where iittei'action with the public is required.
`A more tangible barrier to work success is the discomfort some
`patients experience that prevents them from carrying otit work-
`related tasks such as prolonged standing, writing. or typing.
`Finally. onyehontycosis can compel worl-ters to take periodic
`sick leave.
`:1 problem even for treated patients if therapy is
`inetfectivc andior long-lasting (55). This lack of success.
`in
`turn. can cause patients to feel discouraged or even to stop
`treatment. resigning themselves to permanent disfigurement
`and discornhirt.
`
`On_vchot'nycosis in inimunoeontpromised patients. such as
`those infected with human intmunodetieieney virus {I [IV]. can
`pose a more serious health problem (55). Not only does the
`di|l'tcult—t'o—treat infection serve as a constant Ientinder to