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`USOO7820788 B2
`
`(12) United States Patent
`Desai et al.
`
`(1U) Patent No.:
`(45) Date of Patent:
`
`US 7,820,78882
`Ocl. 26, 20 I 0
`
`(:54) CO.\lPOSITIO:-':SA,'li 1) METIJOI)S 011
`DELIVERY OF PHAR..\L\COLOGICAL
`..\\'.~ NTS
`
`(7S)
`
`Invcnto rs:
`
`l'o"ell l', Oe5al. Los Angcl <'S. CA (US);
`Patrick Soon-ShiOJlIg, Lus Angeles, CA
`(US); Vuong Td.,u, Calaixls(ts, CA (US)
`
`(73) Assi~LW: A!Jnt.'li~ nill~dcn~c, LLC, Lo~A.Ilgclc~.
`CA (US)
`
`( .) NOlicc:
`
`SubjCCIIO uuy di;;cbimcr, the term of this
`patent is extended or adjuSK"d under 35
`U ,S.c. 154(b) by 85 days.
`
`(21) Aprl No' 11 /55],.'-19
`
`(21)
`
`Jiiled :
`
`Oct. 26, 2U06
`
`(65)
`
`I'd,,! I'ublkul;oll 0 .. 1"
`
`US 20 1 u/o226~96Al
`
`Scp. 9, 2010
`
`Rdalfd U.S. App lkatioll 1) .. 1 ..
`
`(60)
`
`(6..1) Continuation of appl;cmion No. I flI131 ,224, filed on
`0...-..::.9.2003
`Pru\' i~ iun~1 application Nu. 601432.317. fik...J un ])...'C.
`9, 2002, provisional appliCaTion No. 601526,544, filed
`011 [XX:, .1 2003, provisional applicnlion No. 60/526,
`773. fikxl on IX~. 4. 2003, provision.)1 applicalion No.
`6G'527.177. filt..-d Oil Do."C. 5. 2003.
`
`(5 I)
`
`(52)
`(58)
`
`lilt. Cl.
`(2006.01)
`C07K 14176
`5)O!)50: 9771779: 977/906
`U.S.CI.
`H~ld ofClussitication Scarch
`514!11 12:
`435/7.2: 4241178,1: 5301350: 977/779.
`977/906
`Sec applicalion lile for complele search hi.lOry.
`
`(56)
`
`R,,,ferencl"S <;itcd
`
`US-PArENT LXX.:UMENTS
`
`4.4 25,3 19 A
`4.645.660 A
`5,272. 171 A
`5.362.478 A
`5,399,363 A
`5.439.686 A
`5.498,421 A
`5.505.932 A
`S.50X.02 1 A
`5.512.268 A
`5.560.933 A
`5.616.330 A
`5.626.862 A
`5.63'>.207 A
`5.639.473 A
`5.650.1 56 A
`5.651.986 A
`5.665.382 A
`5.665.3113 A
`5.681.846 A
`5.714.520 A
`5.7t6.981 A
`
`1/ 1 9~ Yok0Y"m~ c1 " I
`21 1987 Tahhm:h i CI a].
`12/ 1993 U~dII CI 81.
`11/ 1994 0.,,,,; ~l ~1.
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`8,' 1995 ]),-~i el al
`3/ 19% GrinSla lf cl a l.
`411996 GrinSla lf cl a l.
`4/ 19% (jrinsl~lr et ~1.
`4/ 1996 Grin~talf el aI.
`10/ 1996 Soon-Shiong L"l al
`4: 1997 KltuliTUlJl C1 !II.
`5: 1997 H",m ~l aI.
`6/ 19\17 Grinslatr el a l.
`61 1997 GrinSlalf cl a l.
`7/ 1997 GrinSlalf c1 a l
`7/ 1997 I3rem cl aJ
`9: 1997 GrinslalT ct aI.
`9/ 1997 Grinst3ff ct aI.
`10: 1997 Trissel
`2/1 99l'\
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`211998 Hunlcr cl al
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`'.73 1.35' A
`5.731.356 A
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`5.945.033 A
`5,977,163 A
`5.990.153 A
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`6.096.331 A
`
`6.028.108 "
`6.100.302 "
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`6.120.80~ A
`6.143.276 A
`6.147.122 A
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`3'1998 Jo""s ct 3t.
`3'1998 Jo""s ct a t.
`3'1999 Hunln <1 al
`611999 Desai cI al
`8' 199') Ycn
`1111999 Li ct a1.
`11' 1999 Wood ~l al.
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`6,150,423 " 1112000 Carpenter
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`1'2001 George eI al
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`
`6.197.051 HI
`6.11>7.349 81
`
`6.441.025 "2
`
`(Contimlt'd)
`
`FORF.1GN PATENT DOCUMENTS
`
`0227593 AI
`
`ilI987
`
`(Cont inIlL"fI)
`
`OTHER PUI1UCAllONS
`
`Damascclli. H. ct aI 1001 CanC<:T 92(10): 2592.2602,·
`
`(Continued)
`
`Pri",ary Hxa",iner-Maryam Mon;;hipouri
`Assistant Examiner Marsha M Tsay
`(74) AI/orney, Agell/, or Firlll- M'Jffisou & Focn;lcr. LLP
`
`(57)
`
`t\BSTRACT
`
`The present invention relates (0 a phanllac(''Inical composi(cid:173)
`lion compri~in!!. 8 plwrmaccutical agenl mltl a ph:mnaCL"tI!i(cid:173)
`cally aeocptablcearricr, which earricrcomprisesa protein, for
`cx,unplc. humall serum albumin alld/or dcfcroxam inc. The
`human serum lllbllnlin is prL'S('~11 in an amount .. lTL'Cliv .. 10
`reduct· OLle Or mo re sidt· c1k"Cts associawd with administm.
`tion of the pha nnacentical compo;;itioo. Hie inventi on also
`provides melhods for reducing one or more side effL'ClS of
`administration o f the phllnn,l(:euticul COmposi ti on. nwthod.
`lor inhibiting microbial growth and oxidation in the phanlla (cid:173)
`celltic,,1 composition. nnd methods for enhancing Irn n~por1
`and binding ofa plillmmcculical agent to II ccll
`
`12 Cla ims. No Drnwings
`
`Apotex v. Abraxis - IPR20 18-00152, Ex. 1001 , p.O I of24
`
`

`

`u.s. PATENT DOCUMENT S
`10/1002 Lambert eI at
`6.458.373 Bt
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`112003 Desa.i el a l.
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`2003101 !;S!;'J4 AI
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`20051(l()()4002 AI
`2005/000973 1 A I
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`200610073 175 AI
`200610083;82 AI
`20061012 111 9 AI
`2006' 0199248 AI
`200bi02S7326 AI
`
`200610263434 ," 11/2006 0.; ... ; c l al .
`
`2007/0020337 AI
`2007/001128311 AI
`2007/0087022 A I
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`4.'2007
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`
`200110093547 ," 412007 De",idal
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`200110116774 AI
`200110117 ])3 AI
`2001101 17744 AI
`2001101 171162 AI
`2001101 17863 AI
`200110128290 AI
`200110129448 A I
`2007/01663 88 A I
`200')/009~21O A I
`2009/0263483 A I
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`5/ 2007 ))<sai el.t! .
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`6/ 2007 DcAAi c1 a l.
`712007 I)csai ct al.
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`10/ 2009 I).:sai ~t al
`
`FOREKiN PATENT IX)(:U MENTS
`o S44 292 A2
`0544292 A3
`2 775900 Al
`2 127606 (;1
`wOn/ OilS9 Al
`W094d3300 Al
`W094118954 Al
`WO-94/ 200,2 Al
`WO-95103036 A I
`WO-%l40 829 Al
`\\'097/ 10850 Al
`W098;0;41O Al
`W098J14 1i4 AI
`W09&'I4Ii5 Al
`W099;OOI13 Al
`WO-99/ 13914 Al
`W099;39696 Al
`WOOO;(Xjlj! Al
`WOOO./2311 7 Al
`WO.oo;644]7 AI
`WOOO; 7 10i9 A2
`WOOI ;89522 AI
`\V0021087545 Al
`\VO 031096944 A I
`WU 2(l().;11OO7520 Al
`\VO 20041052401 A2
`
`61 1993
`61 1993
`911999
`] 1199')
`411992
`61 1 ~)4
`911994
`911994
`21 1995
`1211996
`311997
`111998
`411998
`411998
`111999
`3119<)0)
`& 1999
`WIIOO
`412000
`1112000
`1112000
`111200 1
`1112002
`1112003
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`on ...
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`us 7,820,788 82
`Page 2
`
`wo
`WO
`WO
`
`WO 20061034 147 ;\3
`\VO 20115/ 117952 .'\2
`\VA 2005111 ;952 .'\3
`
`312005
`1212005
`1212005
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`Non·i"inal OfflCcAction mailed On Jun , 12.200);. fo. U, S. App!. /'.'0
`1 L/520.546. c,l<-d ScI' 12. 200(;. eight 1"'11'"'
`Kon·F inai Office,\ction mailed on 1)cc. 2. 2008. for U ,S. AppI, 1\0
`I IIS20.546. fil",! ScI' 12. 2006. e ight I"'g<:<;
`Kon ·Finai OlJkeAction ='Iedon Mar, 28, 2008. for U .s. Appl, 1\0
`1115S3.350. filed Oct, 26. 2006 . six p"!!"S.
`Non· Final Off",eAc! ion maik-..l on 0.:.:. l. 200K fOl U.S. Al'pl , No
`11/S53,350. filli<l Oct. 16. 2(1()(i. six p"gcs
`Kon .l'iMI OOir e Ael ion m .. i\crl On J,m. IR. 2009. 1'0. U. S _ Al'pl. Xo
`11/ 5S3.350. filed Oct, 26. 2()()(i. eight 1"'1;«.
`U,S. AWl. NO . I V271.74~. filed Nov. 14. 200ij. for l)cs.ai d al
`U, S. AWL 1'10. 12133 1.924 . filed Dec, 10.2008. fu, Dc,ai etal
`U.s. Appl. No. IV402.35 S. filed Mar, It . 2009. for Dc C1 a l.
`l i.S. ~fl'1. No t 2l422.0t t. f,tcd Apr. to. 2()()!j , (01' lleui d al
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`U,S. AWl. No. 121479.7 10. liled J un, 5. 2009. for Iks:r i C1 aI .
`U S. All'1. No 121S 13,843. f,l"d M"y 6, 2009. f,,' 1ft",; d "I
`Final Omce "ction mailed on Scp. 17. 2009. for U.S, ,\ppl 1\0
`II IHO.S46. filed Sel'. 12. 2006. eighll"'g ... tot.1
`u.s. AWl. No. 121422.1 92. filed Apr. 10.2009, fot Desai et al
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`
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`I'age.:l
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`M"ll~r. B. G, cta1.(J"", 1996). "AlbuminNano~ph''JCsasCaJJicrs for
`Pa,;~ i"c Drug T"'gcli ng: An OpI imi z ... l Manura<:[Uring T,'Chni'lu~_"
`PlrarwiIlu u,ical Reur.nJ, 13(1):32 .37
`Final OffICe Action maii.xl On MM. 15.2010. for U.S. App1. No.
`1 11553.350, m",i 0.:, 26.2006, 12 P"gc~
`
`U ,S. Appl. No. 121436.697. filed May 6. 2009. for o.,s.,; <II al.
`U,S. " WI. No. 121474.218, f,led May 2~ . 2(109. for Dc"'" c! al
`U,S. ApI'1. NQ. 12/598,406. r.k~Il\-l:Ly $, 2008. fw o.:",i.1 al.
`U.s. APIlI. No. 121600.991. filc<i Jun. 2. 2008. for Desai CI al.
`• cilcd by examiner
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`
`CO.\1POSITIOi'"S AND METIIODS 010'
`nn.l v~~ nv OF I'IIARMACOLOGIC \L
`AGENTS
`
`CROSS-REFERENCE TO RELArED PATENT
`AI'I'LlCATlONS
`
`"Ibis p:.JlI .. 111 application i. ~ CQfllinU<llion or p .. Wlll llpplica·
`lion Sec. No. 101731) 24, which cbilUs the beneti! of U.s.
`Provisional PaWn! App liC<l\iOfl No_ (,()f432,3 11 fil ed 0.."(: 9,
`2002, U.S. Provisional Palenl Application 6&526.544 filed
`Dec. 3. 2003. U.S. I'rovisional 1'::JtC'ntAppJicatiOll 601526 ,773
`flied 0.....:. 4. 2003. and U.S. Provisional F'".J\cnt Application
`60f527, I77lilcd 1Jcc. 5,2003.
`
`HELll OFTJlE INVENTION
`
`n,is ilLvclIli...,,, per.."i"s Iv pharll ... ~"Culic ,,] "')!Hposit;!)"s
`comprising pharmaceutically active agCIlt, tor p;lrt1,lcr,,1 or 20
`mller ;mernal usc, which have the effecl o f reducing certain
`undesirable s ide ,,!flOC! S upon udminislrJtion when compared
`wi lh available fonnulations o f similar drugs.
`
`BACKGROUND OF THE INVTh'TION
`
`2
`reduced pH, drug dcyadation. and discoloration, thereby
`destahilizing the dmg form uill tion li nd/or reduc ing shelf lifc.
`To circumvcnt thc pro bl"ms associmed with administm(cid:173)
`tion -related side effects of drug formulations, a ltemate for(cid:173)
`mul"tiuH~ IIllv" ix."CH allempkd With n:spt.."Ctto propuful. for
`ex,un ple, methods for r~'(\ncing propotol.ind1JC(.-d pain
`include increasing the fat CO ntCnt o fthc solvent (e.g .. long
`chaintriglyceridcs (LeT)). prcm<.-dication. prctrc.1tment with
`non·,lI.:roid:,[ drugs. luc,,1 arw. ... 'St heties. opioids. the addi tion
`to oflidocaine, the addition ofcyclo(\.:.-xtrin, and microfihration
`(see, e.g., Mayeret aI., An<u,srhesisi . 45(1 1), 10112-4 ( 1996),
`Dav ies. CI a l. Anaesthesia, 57, 557-6 I (2002), Docllickc, et
`al.. Ana<!s/h. Ana/g .. 82. 472-4 (1996). Lar.;en et nl.. Anaes (cid:173)
`Ihesili. 50. 842-5 (2001). Li11c y ct al.. Allue.lhesiu, 51. 815-8
`l~ ( 1996), Biclen ct al., Allesth. AIIUI,~., 1)2(5), 920-4 (1 996), and
`Knibbc et al ., Hr. J. Clin. Pharmacol .. 47(6). 65.,-60 ( 1999».
`'Ibese formulations. however, induce other side e ffects (e.g ..
`cardiov3scubr complications). or cause dcstabi1i7..3tion of
`propotol emulsions.
`Jo overcome the prob lem o f b.lc\eri,ll contaminatioa, p ro -
`pofol form ulation, hav" Occll d"vdopcd wilh omibactcrial
`agents. such as an EDTA equivalent (e.g._ edctate). pcntetate.
`ur sulfit ... ·-<:o"t~iJli ng "geJl1l;. <Jr th ... ")' IIllVC ix....,n have bt."'~l
`lormulatl-d with a lower pH (S<.'\.'. c.g., U.S. Pal. Nos. 5,714,
`25 520, 5,7J 1.]55, 5,7] 1 ,]5(,. 6,02R.1OR. 6, 100,]02, 6, 147,122,
`6,177,477.6,399,087.6,469.069. and International Pment
`Application No. WO 99/39(96). Since ooetate and pemetatc
`:Ire metal ionchclntors, how<!Ver, they hnve the pol"ntial to be.
`d.1ngcrous by scavengi ng the essent ial metal ions from the
`:;0 body system. Moreover, the addition of sulphite> to drug
`formnlations pre;entS pot<'ntial ndvL'fSC elft.'CI, 10 the pi.-diat(cid:173)
`ric popu~tion ,md for tllO';c in the gen"ml P-lpulation who arC
`allergic to sul phur.
`ThIlS. there re ma ins a nC(."<1 for a composition and method
`)5 that reduce or eliminate the side effects assoc inted with the
`parentera l or in vivo administr:ltion of drogs. nlere also is a
`n~",-d for a pllllrm<lcemi.al . mnposition that is sterile. <Iud
`melhodS (Jf prcparing such acompositioll.ln addi tion , the re is
`11 nL"Cd for a pharmact-ntical composition a nd method that
`reduce or eliminate oxii1<ttion of phannaceutical formulations
`to pJ"l."vcnt drug dl-stabiliz:dio ll.
`'lbe invention provides such compositions and methods.
`These and ot her IldwlIltllges o f the inventio n, as well as add i(cid:173)
`tional inY"ntivc fcatures, wi11 bc apparent from the descrip(cid:173)
`tion of the invention provided herein.
`
`It is well rcoog.rUud thnt muny drugs for p~rcnternl usc.
`esptxoiaIIy those 3dminis tercd intrJ'"enously. causc undesir(cid:173)
`able ~iJe elT~"Ct~ sm:h as venous irritatiun, phlebitis. buminll,
`and pain on injection, WlIOUS thrombosis, e xtravasation, and
`other administration relnted side effects. Many of these drug s
`nre insoluble in water. and arc thus fonnulated with solubi-
`Ii :ting agents. surfact:lOls .• 01 Vl.:llt •. and/or ~"Illulsi fiefS that <lre
`irritaling, allergenic, or toxic when administ t"R-d to pntients
`(sec, e.g., nrigg.~ t1 nl., Ane.<The .. i.< :\7, 1099 ( 19R2), and
`Wangh et al.. .'1111. J. Hasp. PhamraciSlS. 48, 1520 (1991)).
`Often.. the frl'C dnlgpK'SCnt inthc formulation induces pain or
`irriWtion lIpon adtnin.istm1ion. For example, phlebitis was
`observed in 5tJYo of p<ltients who receiwd periphernl vein
`administmtionof ifosfamidc and vinorclhioc a3 fir>t-linc chc- 40
`mothempy for advanced non-slll3J1 ceJ1lungcarcinoma. (St".
`e.g .. Vallejo et al.. .'1111. J. Cfin. Oneol .. 19(6).584-8 (1996)).
`Morl'OV"r, v~ ncomycill has be..·n showuto induc" sid" I.:ITects
`such as phlehi tis (see, e.g., Lopes Rocha et aI., Hraz. J. Infer/.
`Dis. , 6(4), 196-200 (2002)). The use of cisplatin. gemcitab- 45
`in". and SU5416 in p:lIients with solid tumor.; has resulted in
`adverse events such as d ... ",1' veHUU, thrumbus~s aHd phlebitis
`(S<.'e, t·.g., Kuenen <.1 al.. J. Oin. OIICOI., 20(6). 1657-67
`(2002». In addit ion, pmpofol, an anesthctic agcnt, can induec
`p nin on injtxotion, burning and vein irritation. particularly so
`wh ... 'Il adtnini.tl.:r ... ..r as a lL"Cithin·stabiliZl'l.! fat emulsion (~t.'C.
`e.g, Ta n et aI., Anmht'l'ju, 53, 468-76, (1998)). Other drul!S
`that cxhihit1Klmi ni,lrntion'M!<OCiatl-d ~irle e ffeets inch wl e, fo r
`example. Ta xo l (p<tcJitaxc1) (see. e.g., packa ge inscrt for
`Taxol l.V.). codarone (amiodarone hydrochloride) (sec. e.g .. S3
`P,lCka!;C insert fur Codmulle 1. V.). th" thyroid hormone T3 or
`liothyronioc (commercially avai lable a s Tri ostat). thiotepa.
`bleomycin, a nd diagnostic radiocontmst agcnts.
`Another prookm us:;ociaK..r with the m<lnu(act urcofdrugs
`for iujt;'O;tion, pa rticularly water insoluble drugs, is the assur·
`ance of stcrility. Sterile mauufactnring of dmg emulsio ns!
`dispe rsions can be accomplished by absolute sterili?;ltion of
`all the components before maaufacture, fo llowed by abso(cid:173)
`lutd y <lwptic t ... "CllIliq uc in all sta!l,e:; of m<'Huf""tur". Huw.
`ever, such nwthods are li me consuming and expensive. In
`addition, the oxidation of drog fornlUlations by exposure to
`nir during manufacture or stomgc can lead to. for example.
`
`BRIEF SUMMARY OF THE INVENTION
`
`The in vention pruvidl'l; variOIl~ embodiment~ o f pharma(cid:173)
`c('lltieal compositions. On", $Olll", or all o f th" propcrtil'S of
`the variOlls embodiments c~n he found in different emhodi(cid:173)
`ments of the invention and still fall within the .>Cope o f the
`appended claims.
`'Ibe invention provide, a pharmaceutical composition
`.ompri~ illg a pharmaceuti<.:al agl1u 'Uld a pharm,ll'Cutic:,Jly
`acctl't"b le ealTil.:r, wherein the pMnn;lCeuticall y acccplllblc
`carrier comprises" protl.:;n, such as alhumin, more preferahly
`hnman serum albumin. in an amount ctfective to reduce one
`or more s ide effl-cts of ~dministration o f the phannaccutical
`60 composition into a human, and when>in tIlt' phannaceutically
`acceptahle carrier comprises defemxa mine in an amount
`cfiectivc to inhibit microbial growth in the phannaceutical
`composition. The invention also provides 3 phannaceutical
`eOlllpositiunl'Ulllpri~ing" phannaceutie,,1 agent and ~ pl", r_
`63 maccutically accl.:ptable carrit.,., wherein thl.: pmnnacl .... ti.
`cally acccpl<tb1c carriercompriscs a prole;n, such a, albnmin.
`in on amount eflectivc to rl-duce one or more side effeets of
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`3
`admillistmlioll of the pbannac<::mical composition into a
`human, and wherein the pharmaccutically accepta ble carner
`compriocs dcfcroxmninc in an amount effective to inhibit
`oxid31ion ill the pharmaceutical cOlllposition.
`"Il,e ;IlYc"liull pruviJ~'!; ~ Il.cthud fvr n....JlIciJl)l, um: ur more
`side dk-cts associatL-d with administration of a phanl1an"llti.
`c;J1 composition to a human comprising (a)ndministcring \0 a
`hU1ffil1l a piJ.1mlaCcliticlll composition comprising Il phamm(cid:173)
`ccmical agent and a plll1mlact.'ut;cally m .. :t:L,))lablc clmlcr.
`WhL'rC;1l the pharmaccutical1v acceptable carri"r compriscs 10
`al bumin and dcft"roxamine. Also provided arc methods for
`inhibiting microbial growth, or for inhibiting oxidation. or for
`inhibiting microbia l growth and oxidation ill a phannaccmi-
`c.d cumpositiun. TII~'SC ml1hod s comprise prcparinJ!,:t plmr(cid:173)
`m.1ceUlical 'omposition u>mprising a pharrnaocutical agent t~
`and a phann.1eeutically acceptable carrier, wherein the phar(cid:173)
`maceutically acceplable carrier CQm prises deferoxamine in
`an amount effective for inhibiting microbia l growth or in an
`amount elk";li\"C lor inhibiling oxidl1ion ill lhe phannaccu(cid:173)
`ti el'll composi tion
`rhe invemion also provides a mClhod fo r enhancing lrons(cid:173)
`pon of a phanll:JCeut ical agent 10 the SilO of an infinn ilY.
`which mcth<.><i comprise, aW ni ni,tering 10 0 humou .. plmr.
`maceutical composi tion U>lllp ri sing a pharmaceutical agent
`anel ~ pham' 3ceul ically 3cccpt,)hle <;.1lTier, wherein the ph ur. 25
`maceutically acceptable carrier CQmprises albumin. and
`wherein the rat io of 31bumin to phannaceu tical agent ia the
`pharm:1Ceulical compositiou i~ about 18; 1 Or IC6 •. The inven·
`ti on funher provides a method for enhancing binding of a
`pMrmaceulical agent to u cell in vitro or in v;'u, which :;0
`mNhodcompriscs odministering to said cell in vilrl) orin vivo
`a pilannaccUliC<l1 eQmposi ti Qn compri.ing a phonnacL'tltiC<l1
`agent and a pharnmceutically acce plablc calTier, wherein the
`pharmfICeul ieally acccptahle carrier comprises nlhumin, nnd
`wherein the mtio of albumin 10 phammceUlical ag<'nt in thc )5
`phannaceutical compos ilion is about 18: 1 o r less.
`TIle invention also prov kks:t pllllrmal"CUlicol composition
`comprising a pharmaceutica l ')gen t Imd a phnnn~ccut i c"lly
`accL-pt ah le carrier, wherL-1n the pharmaceulicoliy accL-plal!le
`carrier comp ri ses albumin in an amount efTl'Ctive to increase 40
`tra nsport of the druJ:! to thc site of inlirrnity in a human. and
`whcre in the ratio o f albumin to pharmacemical agent is aboul
`I R: I or less.
`[be invention funher provides II melhod for increasing the
`lranspon ofa phannaceutical agent loa cell in vitroor in vivo
`by L·{.lJtlbitlin)o! said ~)o!.,nt with 0 pro t,-,itl. wherei n :;<lid pl1) tL~"
`binds a specific cdl -surface receptor on said cell, wherein
`said hinding of thc pmtc in-pharmaccmical agcnt combina(cid:173)
`tion with the said rL"<:eptor caU!;('""S th e transpon to occur. and
`wherein the mtio or protein to phill"nUJC,-,utic al ~~enl i. ~bout
`18: I Or less.
`
`DETAILED DESCRIPTION OF THE II\'VEI\'TION
`
`TIle inven tion pru vides a pharma(;'-'lnical composition
`comprising 11 pharmaceutica l ')gen t Imd a phann~ccut i c"lly
`acceptahle tarrier, wherein the pharmaceutically accc'ptahic
`carrier compris.es a prote in such as albumin. preferably
`human seru m albumin. in an ,UllOUll1 eflh:live 10 n.'llUl"C one
`or mort' side .. lleelS o f administration of the phannaceutical
`composilion to a huma n, and wherein lhe phannaceutical1y
`acceptablc carrier CQmpriscs dcferoxaminc in ru) amoum
`effoctive to inhibi t microbial growth in lh ... phannaeeutical
`c'.lJnposi tion. 'n,e invention olw pft)vi.k~ 0 plmmlllCL'tltical
`composi tion com prising a pharm3Ct.'lItical agent "'ld a phur.
`lllaceuticaily ac<:cplllble carricr, wherein the pharmacl'Uti·
`c:llly acceptab le carrier comprises a protein such as a lbumin
`
`4
`in an amount efleetivc to reduce one or more side c ll";x:ts of
`administration of th e pha rmaceutical compositio n to a
`human. and wher<'in the pharnmceutically occcplable carrier
`comprises d<'feroxamine in an amount effoclive 10 inhibil
`oxid.atiOJl in 11.., phammL"CuticlIl compositi<Kl.
`Any suitnble phannacL'utical agent can be ust.--d in the
`invcntive phammccutical co mposi tion. Suitablc ph.a mmccu(cid:173)
`tical agents include. but <Ire not limilt-d to, antic,1ncer agen