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`PHIGENIX
`PHIGENIX
`Exhibit 1003
`Exhibit 1003
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`

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`
`Journal: OE Cir‘nicol’ Onwfcgy, ‘v’oE 15, No 8 {August}, 3839?: pp EQ‘EMQ’E‘OA
`
`. No other uses without permission.
`Downloaded from jco.ascopubs.org on April 7, 2014. For personal use only
`Copyright © 1997 American Society of Clinical Oncology. All rights reserved.
`
`PHIGENIX
`
`Exhibit 1003-01
`
`

`

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`
`. No other uses without permission.
`Downloaded from jco.ascopubs.org on April 7, 2014. For personal use only
`Copyright © 1997 American Society of Clinical Oncology. All rights reserved.
`
`PHIGENIX
`
`Exhibit 1003-02
`
`

`

`28(1713
`
`PRESE ET AL
`
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`{3112‘ Mi} 52150.R‘ 01121311320 11; 1th; 5051.131- 1 111111132111011 111111313;
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`
`01:31:»; 1001111111213 161;; atium'e 21 (11311511338535 21R:""‘s:mcm: of gene.
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`1311-:
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`12.12131 1131:" 1312121: 110: lcus
`
`Fluorcwem 51133111131; £1211 HERQJRM 13,0110 9.1113 chroma.-
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`
`1113011113 in 1:01:31 of 11 5111105; 111'p1'1‘1grcssdyeiy E21100: $£1£T1§3E115~2
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`
`. No other uses without permission.
`Downloaded from jco.ascopubs.org on April 7, 2014. For personal use only
`Copyright © 1997 American Society of Clinical Oncology. All rights reserved.
`
`PHIGENIX
`
`Exhibit 1003-03
`
`

`

`HER-27mm fiMPLiFlCATFC‘N 8? HSH
`
`28??
`
`
`
`fin
`Ida—Effie 332439. imafizad £2}: green flooresmni‘ signufs. umfi nipi‘rwscleiiém 8N)!» of chromosome 1?, imaiixed 532126 fiuarewem sign-315.,
`Fig 3.,
`Maugham genial a? breasr cartimmo wiis {Mae},
`ilk? Ema» mar-em imking PIER-Near: gem. empiifimrian civmumrmw (rim narmui dipioid mime”? of
`Nikr’za’aw sigrmia gm:- nutiaus. {£1} finest camera wirh low ievurlls of Hfikfifnmr gene nmpiificrflism anew an intranet} number e§ iifii’éfifnw gene copies
`wil'i's HE’RQIfleww‘nhmwswe :1? Sigma? mm?!) i.'> 3.5}, {Ci Emmi! (armors wiih high [Lewis n15 HER'QXMU gone amflifimfimx (rim flaw {in immersed
`number m‘: HER-2r‘m gems «Apia: wish 548%ijwere-chromosome 1? signal “Bim- :> 1G.
`
`
`.
`‘ of'czases would he mamziizigguowi3; arraigned s;
`
`
`
`amplified or Hil’lliEliflffliiiifi-L‘i
`e' "reg" wining;
`ii} rm 2,.
`fl“??-
`
`aifier scoring 13 rmeiei, 314*
`area? ’3} zmciei, 932% after
`953*}. after 9541: nuclei. and. 99% sitar Eli} 23.02.1103,.
`
`No Liz’ffez'c 10m in ciagaiiirzniiun occurred when HER—Cf
`
`rm»: Ei‘i-k‘tfélgt‘: 000,053; in the first ’35,} iii.r3‘3r3eif»r:fl,ii nuclei were
`compared Wérh 000an in tire i203: LEG nuclei and with counts:
`of the: entire. 801 of 300 miciei, ii’uifiiieifrrmm, after semiz'zg
`iii} rumor-ca}? nuclei. ail rasey were Cr}fi£€ii}* categorized
`as arnpiiifimi a}: nonalmpliiicri ii' the {Iii was. {geared and
`{mi}! rise s:i:3:n‘spci.rfii5£m of rim ratio to aim Vidal: 2.0 was
`considered.
`
`Gama empiifizxrfirm by 3733?? with and wider/m: {fireman
`
`
`.3?
`:77 Women? E'Ufi‘filfi.
`{Staring . “iii 2'11
`swarm;
`.
`.
`
`
`of {he Mai trellis:
`rims cases. we mi).
`.rsrcrl relatively- iirrle
`variation in £3162. air-wage number a}? r;hmrna:mozrnc 57‘ men"
`
`'ifiqe range of chromo-
`ifiift3‘itfi‘fiffi mg“ {armor-{rail namieus.
` 1.1.
`some i? monomers: aw ages in 1mm radians Was: {iii
`in 32’ mm more than 965.3% averaging '1‘ or fewer chrome»-
`
`:smnrt
`ii“! {tr-:mzrmrmas par i.umz>r—a:<:-li nucleus Unexpect»
`«213332. 0031:: of the Cases.
`in Kids group of ifrrcziisi: writer};
`riemanszrsrrmi a parallel mamas: in mm tiu-rumsrmm 3,?
`maintainers meal HER-Efrem copies. which suggesrs ritual:
`none: fifths» ii'icrxiaxcd i—iicZR—Ez’rwri copies was (ire: to 30m»
`yield}; 231mm. 53mm. alumnusome i? mrz’rrcrmems windb—
`med little: and 3252MB: i311R~2122w mums; Li-ranrzribuicd gzz'rsaiijx
`{in liar: assessment of amplifi-starim'x. iiziaiyyis of HER-Erma;
`ff
`{one alone appeared 10 provide am Hammer. assessment of
`33¢.
`arm ampfiféeazim. During rim GE phase of? the call cycle.
`t';
`Clix wiii regaiirzaie each gene. 'E‘imrcrm'e. a gem: rim is
`present m. the 0522i at. ’3 or lime: armies: would be: firm-reared
`in shite. (23' four only dining; ilk-33¢.“ phases of the. cal} cyuie.
`5% tall. with an average of more main rem- copies. of HEMR
`may wouls‘i be expcrrrmi to new: as: abnomzaiig mfmifiitfid
`number of copies. 3e. germ a;12;;«iificaz:i0n. We reanaiyxed
`our date for iHEE-Z.v2im?m mp}; monkey wiihrmi: chromo-
`some i? ogmr‘rmnem my}! BBmhdr 05mg iii? an; sire pain:
`of .zsepaz-zuimz for non.<zr1’3piified am} érz‘aplii‘ied cases to new.
`
`
`termini: ii" Kiri
`simpimr approach prmidar’i 3000:2332: r:
`‘
`fixation of i-iél'fipii-BS. All x'ziiiriarim'z cases were dassified
`rim. name. as when using cirrorrrosr‘zme l’lf‘. fiinm: gfrztorurru
`game i? canizmmem (imam; yrm’iried no additional infer
`
`raisin 'l. Hereijnau Amplification Asseased by So‘lizi'Mciri: Mailing;
`
`
`Erwin-mi :‘x imam l-lyix. . an «x:
`am;
`
`
`Ampiificfl
`MN :smpiiiir-x.‘
`Total
`
`2i?
`‘5’ E
`W} '3 AG
`
`
`
`
`
`l
`39
`
`Downloaded from jco.ascopubs.org on April 7, 2014. For personal use only. No other uses without permission.
`Copyright © 1997 American Society of Clinical Oncology. All rights reserved.
`
`PHIGENIX
`
`Exhibit 1003-04
`
`

`

`13.161111
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`PHIGENIX
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`PHIGENIX
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