`

`M. L, Simmons
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`Pre11tice««Ha11,Inc.; Engiewood Cliffs, N. I.
`
`|nnoPharma Exhibit 11090002
`
`

`

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`Prinieci in the United States uf America
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`|nnoPharma Exhibit 11090003
`
`

`

`Ffm'»:é’ .r£c1*:1:E;ra".€Imi§m-3
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`32‘?
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`'3sei:f}1
`1122! n‘1;1k:;: cezfmm the mice 22:21: placeci ham
`poaiiapttmtive train is;
`cieaxgbeddirxgg zmé frrssh f<;-oil 331:3} water s«::« thcziz’ inaunedizite ::m'ire:m1n::er:=: wili
`in-2 s;:<:~21c1uIci\.re: {<3 wick 31ca1irzg and as, minimum nf infections.
`‘I122 xnice sitstmlci
`be gxbservazd r-sgufarigs anti car-zzfxaily, pa1*tia:;uia1*Ey :fc1.§;:xs, sselaicii can becomsrs
`x-‘em lm-3€!E’flf3i}f[2iEv1<fi
`to the aznimai, are used. Clips catazaing, apparent
`«ziis.-»
`a::a::srnf"«:»rt can bar: rammred amil an-:w cues; applied. In :;::-nu: »:::«mz:s, [}i‘{}}3h}’{3CtiC
`tiu-::*apy may be im;iir.'::m3d -:'>wi1":g is iaiemz ir1f12<,:li:>ns :;m«:’£ mm €.%£p¢:l‘i313€i'1fE3.1
`:\‘.'—:21.~50n.~'-:.
`‘§)§;}’E$['t‘2IC§:'<:Ii£1e or ather broad :-:pe~z;tm::11 amibiotics <:.:a-u‘; be piaced
`in the dri11king,wette:.‘ cor avrm fiuslwti into the Eracisiou site. We do not ‘think
`that
`this p1:<J::£:r;£ua‘e
`is o.rciit1ariIy nzzczessary or perhaps»: eve:'1 desirrzxbfe. A
`‘rt.-:<;c:11{ ;:mbli<:mir:»11 on mL1rAi.ne sgpleneasnmly mporting use of am eJe::L:'os:aute1'y
`device 1‘ns;L::ad of Iigatian is; of ini&X‘é:E;L {:ERSIiE<;, 1968}.
`(}iI1e1‘ su1'giez1E Lech
`11iques;g,
`s~;:.:»:.:h as r:1'},*::e:~;u:-gery_, may be used and are pz'»zfi:+21h1jg the methods 0f
`the futurrz. The cryo:=..x.x;'gEcat ztpprflach requires only minimal Iigm:i»::ms.
`
`FLU I. D A DMINISTRATIQN"
`
`mtraperifmteai
`
`intraperitoxaeai a<i1ninisn:atis:m is used far many dii’f1=:x°s=:t1t purpc::asc::.~: in the
`.m<:+u3e. Agjgestlzetics, turgx-:31“ t1'>as1sp§21mis, expeyimexatai c;In.:gs;, zmd mzzmy others
`are :'e:~uti;:eE3s‘
`i:1je::te:€1 by me fntraperitonczai routs. The tc3:¢.:hnEqL1e is simple
`one-:: the basic m»eK:hc>d of picking up and hcslding {he m-:>r.1s:“:
`is mastered.
`We rex::mm1<:~:mi gently ‘mat firmly gmstping the mcruss: by the skin at the back
`at‘ the neck and carefhily gatlueriag the slack skin bpwseaaaix the thtamb and
`f0f€fi11g€E‘.
`Cz1’L1tE01'! mum be taken to avoid pxxmng the fikin too tightly and
`strangiing the mouse. With the skin held praperiy, {he rr1<:eus£a $2111 be lifted
`and 1h: mi} a11C§1»i:»1‘€:d Lbzztween the small finger and palrn of the; hand. The
`moms: is new in as tmsitian ta be easily injected by 21 number of rm2te~:. To
`iiljact intrapariloxzeatiy,
`21 {«-in-zzh 22- is 38-—gaL:ge naetila is. adaqxxeate. The
`size: of the net-2:512 depends. mare an the viswsity 0ftI1<~: xnattzrial ‘aeitxg injecicd
`than an any «csiher r:£:»11s;E«:ier:,1i;i«:m. The needle simuld be Eutruduced on 2: plane
`farming apj3z‘oxi;1121tc':Ey 3 113° angle with the :.~:b<i:::-minaf sztrface amtrl siighiiy
`to €116: right :32‘ lief‘: of the; midiiam The angis:-2 is. important becatzse it is ezzsy tat}
`insert the neecfie info the nrim1:*y bladdsar car inn) the izatesiisxe if 1}1<': amgft: it;
`me great. With Srf}1“1’1& ;:rractic::2, this technique is easily rnztslered.
`
`Irwraznuscular
`
`E11t1‘amLs5cuIz1rir:jectE<_>11s in mice are fairiy diffi¢:u1t i*:e:c2LL:se »:>fti'1»:’: Rick (sf
`a large: rrmsulc nwass. The 1331131 site: for ixxtramuscufal‘ inhscztiaazxs E5
`in 1310
`
`|nnoPharma Exhibit 1109.0004
`
`

`

`I 23
`
`Tecfxniqrags
`
`yarlzglcrior illjglx l'{§LL!:1(:l¢3}§§F{}L|§3, Ag;-inch E4-gatzgeggugsefile £5 atlflqiltllfi. The same
`general restrainizag technique can be used if crsnlywme 1::-arson is {loving the.
`Wmk. Other metlmcis of rvastraimi fin‘ i11tra:n12$cula:' injecticens §t’}Clt1CltB plastic
`tubes with bales cut in their: large em:sug,l1 L-2:» allow tha lag and thigh ta) be
`gcntly pulled thmugh and injected. Cauli<rsn nmst be used in irmmnuzecular
`izajectians that the needle is net pushed ta deep or toe hard, far it may pass
`<:::«mple3te::ly lihrcaugla the rmzscle mass. T133 zxaedle slmulcfi be dimcteri perpen-
`dicular to the sagitial plane, 0:‘ p0i:'m:d in a v<::'y sliglatly posterim clireciix:«t:.
`
`Sulmltanemts
`
`Subcutaneous illjefitliilltlfi in mice are prubably the easieafi all" all to give.
`The mcmse can be i iljeclifiifil
`!?:l.ll‘)C1!lLaI“3r3()l.t!ill}' on r-.:il;l‘l<:r the
`0|: the ventral
`side. and 2: ~;l«—in<:h 22-g:;1:.:g:3 media is adeqluate far most preparations. If the
`quantity of ixxjecied xna.t~*2z'i;1i is fairly large anti does not ix3terl‘i:z‘e with expmi»
`mezztal pro:-zsccsl, fl11lfli}i‘Jl{3it1j€:Ct§OI1SitES are advisable. The rat»: afabsorption
`is pmbably reduced £:0rl5id$ml:)ly from the fntrapefitoneal er intranmscular
`injectimng. As with caller methods, the restraint of the animal is of great
`importance.
`
`Intratharacic
`
`intrathoracic injectians: can he manila in mice with a slightly hem: or
`rcurved -lwinch 22-gauge rxecdle. It shmtl-:i be izlserted batweerz the ribs at
`approximately the midpcrint {sf the rib cage. Caution musl be: takan ta insert
`it at an angle, thus. preventing injection directly intca lung tissue.
`lntmthoracic
`methods are not used 1'-C!|.1tll1Efl}F, anvil, unless there is a specific exparimemal
`reason its use: the £I1iI;‘l.l1CvCl, the intraperitzuxaeall route is easier and that speed sf
`abserptian is; similar.
`
`Intravenaus
`
`The usual sit-:2 of inlrzwenolxs injectéun in mice ismgfge lateml Lail1»'ei.:1.
`Tim: mice can be restrained in a number of different ways. The simplest is ta
`pass Elle tail through 31 3;-inch slam in a small plasétic shiezlci. If the animals
`lmva been wa1"me£i Lu1r::lea* light bulbs fin‘ ag:»prc»:=:Emately 10 min. ‘clza mains will
`liéiva expanded and inirzwenoits injecticslilii can behacmmplished using,
`a.
`9;-incl‘: E4~g,a:.eg«.2 needle.
`lt is a technique {hm requires pracrice. but can be
`dorm:
`ri::»utinsi§; once: the telcill
`is devaloped. As with all maiczrial
`injected
`iixtravcmzauslys, it slmllld um: contain exlranwus maéerial that rzzaly arc: as 311
`embaslism and kill the zaninml.
`
`|nnoPharma Exhibit 1109.0005
`
`