111111111111111111111111111111111111 ~IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
`
`US007923536 B2
`
`(12) United States Patent
`Desai et al.
`
`(1U) Pate nt No.:
`(45) Date of Patent:
`
`US 7,923,536 B2
`"'Apr. 12,2011
`
`(54) cO.\tI'OSITIO ."S ANI) M.ET IIO VS OF
`DEI.lVERY OF I'Il A lli\l,\ CO I,oGICA I.
`M-;.~ NTS
`
`(7S)
`
`Inventors: Neil .... Lk-sai, Los Angeles, CA (US);
`P~tric k Soon-Shio ng, [.m Angeles, CA
`(US): Vuong Tri~u, Cnlobasas. C:\. (US)
`
`(73) Assignee: A hra ~ is nifiScience, LLc' Los Angeles,
`CA (US)
`
`( . ) NOIK:c:
`
`Suhject to any disclaimer, the tcnn Oflhi5
`p~lcnl is cXlcndt-d or adjusK-d under 35
`U,S.C.154(b)by Odays.
`
`Ibis patent is subject to a tcmlinaJ dis-
`claimer.
`
`(21 ) App!. No' 12n58,4 13
`
`(22) Filed:
`
`Ap r. 12, 20 10
`
`(65)
`
`Prior Publi.:ution Data
`
`US20 1OJOJ %490AI
`
`Aug_ 5, 2010
`
`Related U.S. Ap pl ka tion 1)>11>1
`
`(63) Continuation of applicatinJ\ No. I I / SB~139, filed on
`Oct. 26. 2006. now J\ll. No. 7,820,788. which is n
`continualion of a pplic:Jtion No. 101731,224. fib..! on
`De.:. 9, 200), nOW abandoned.
`
`(60) Provisio na l application No. 60/432,.'\ 17, filed on Dec.
`9, 2002, provisiollol opplicntioll No. 60/526,544. filed
`on Dec. 3, 2003. provisional
`tlpplicmion No.
`6Qf526,773, !lied on
`lX-.::. 4, 2003, provision .. )
`application No. 6(\1527,177, tiled on Dec . 5, 2003
`
`(51)
`
`(52)
`(58)
`
`(SO)
`
`IIlI.CI.
`C07K 14176
`(2006.01)
`u.s. u .
`530'350; 9771779; 977/906 ; 977/911
`Field o r C I~~sific~l i otl S~~rc h ...... .................. None
`Sec appl ication file for contplete search history.
`
`Referenee"S Ciled
`u.s. PATENT IXXUMENTS
`4,425.319 A
`1119S4 Yokoyam .. c1 .. 1
`21 1987 Tililulsh i c'l ~].
`4.645.660 A
`12.' 1993 U",L1« al
`5.272,1 71 A
`11/ 1994 Des.ai el aI.
`5.362.478 A
`3/ 1995 I.i""rs;tl~ et aI .
`5.399.363 A
`811995 I)csai cl al.
`5.439.686 A
`5.498.421 A
`) 11996 GrinSlalf C!"1.
`4/ 19% Grin~latr et it!.
`5.505.932 A
`4/ 1996 GrinSI. 1f <1 al
`5,508.02 1 A
`« 996 Grinst .. rr <1 al
`5,512.268 A
`10/ 1996 Soon.Shiong ,,1 a1.
`5.560.933 A
`4/ 1997 Kaufman et "I.
`5.616.330 A
`5/ 1997 Brcm et at
`5.616.862 A
`611997 GrinSlatf CI.1.
`5.635.207 A
`6/ 1997 Grin~latf cl aI.
`5.639.473 A
`7.' 1')')7 Grin.lall" c1 ... 1.
`5.650,156 A
`
`'.6$1.9806 "
`5.665.382 A
`5.665,3M3 A
`5,6l!- 1.~4(i "
`5.7 14.52<1 A
`5.71 6.98t A
`5,731 ,355 A
`5,731.356 A
`5.8&6.026 A
`5.916,596 A
`5.945,033 A
`5.977,163 A
`5.99O.t53 A
`5.994.341 A
`5.997,904 A
`6.028. 108 A
`6.096,331 A
`
`6.120.805 A
`
`6.147,122 A
`6.150.423 A
`
`6.326,41){\ 1\1
`6)62,2 34 RI
`6.399,08i BI
`6,441,025 B2
`6,458.373 BI
`
`7' 1997 ~mC\3l.
`9' 1997 GriMlalf d al
`9' 1'J'l7 (jrimtatf d al
`10' 1991 Triue!
`211998 JOOC$ ~1 at
`211998 Humcr d al
`3'199& Jor .. " <:1 at.
`3'199& Jones C\ al.
`3'1999 Hunter C"! 31
`6' 1999 Desai ~~ 111
`8' 1999 Yen
`11' 1999 Li c1 at.
`11' 1999 Woo<\ et a1.
`11' 1999 Hull1~r ~1 ~ I
`1211999 MagJas.i clal
`212000 a-"
`8'2000 Desai ~~ al
`8'2000 PiOjav"," C"! at.
`9'2000 Spcnlehau"," a at.
`
`1t12ooo M ircjovsky d al
`1112000 Carpenler
`1'2001 George cI al
`3'2001 Zhong
`3'2001 W~'Skscn el a1.
`3'2001 SUlIon CI al
`10'2001 ROlhbard el al
`10'2001 Kralz
`12'2001 Dc To mmaso
`}'2002 Hendler
`6'2002 Zhang et.1
`8'2002 Li cl a1.
`10'2002 Lamben C! III
`(Comilllwd)
`
`6.100.302 "
`6.143.276 " 1t12000 Un~r
`6.177.47i '"
`6.197,051 "'
`6.197,349 "'
`6.21)4.054 "'
`6.306.993 "'
`6.310,039 "'
`
`lOP
`
`FORF.IGN PATENT DOCUMENTS
`0227 593 ,\1
`711987
`(Conlinllt'li)
`
`OHlER P UBLICATIONS
`
`Alunayer. P. cl al. (1995). "Propofol Binding 10 I/wnaJl Blood Pro.
`Ic in •. " ArZll<"i~'illei Forschlllll{ Drill{ R'';'earch 45(11)(1 0): 1053- 1056
`
`(Continued)
`
`Primary Examiner - SuW£\nc M Noakes
`Assistant Examiner Marsha M T say
`(74) .,.jf/orne),. Agent, or Firm - Morrison & Foerster LLP
`
`(57)
`
`A BSTIlACT
`
`TIle present in\"~nlion rel,des to a ph"nlrncemical (;omposi,
`lion comprising n pharm~celitic~1 agon! m>d 11 pw.mlllc(.,\,li.
`cally acccptahlecarricr, which carriercompriscsa protein. for
`ex,ulIple. human serum albumin and/or de feroxamine. The
`human serum .. Ihumin is pn:s(''111 in an ~ mounl cffl'Clivc 10
`reduce one or mo re side elk-cts IIssocilllt-d wilh adminislrJ'
`lion ofthc phannaceutical composi tion. The inven ti on also
`provides mcthods for reducing one or more side effects of
`administt":1tion oflhc phaml.'ICcllIical COmPOSili on. methods
`for ill.hibilillJ,! micrubi .. 1 ~wllt and o xi<i:rlioll in Ih" pharill.a·
`ccutiC:l1 composition, and methods for enhancing lrnnspon
`and hind ing of a phammcculical agent to a cell
`
`16 <':I .. ;m~, N o iJraw;ng.
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 100 1, p.O I of24
`
`

`

`u.s. PATENT DOCUM ENTS
`6.469.069 Bol
`1012002 Mirejo\'Sky el " I.
`6. S06AO~ II I
`112003 ])"s1i el .• .1.
`3/1003 Magdassi d al.
`6.518.067 Bl
`3/2003 Iksai ct aI.
`6.537.579 HI
`51200J Sojomiha,ti" .,1111.
`6. -"6'U142 HI
`6,652.884 112
`1112003 ",!ciani
`
`6.749.868 801
`
`612004 Desai ~I " I.
`
`6,743,826 Bol "- H<'gedll s ct a[
`6.753.006 Bl "- Desai or a1.
`
`6.7 59.43 1 Bl
`7.119,[24 B2
`1.332.568 B2
`
`7.77 1.75 1 "2
`7,820,i SR 112
`20031018589<1 AI
`A'
`
`7/2004 HUDl er ~1 al
`10/ 1006 Hegedu s 01 al.
`212008 Tri cu ,,1 al .
`~120 Hi J.ksai C1 ... 1.
`10120 10 De",; eT . 1.
`10/ 2003 Zenon; ~1 al
`1012003 u nQIli <1 al
`
`" 10/2003 Dc.a,i e l aI.
`"
`
`A'
`A'
`A'
`A'
`
`"
`200110092563 "
`200110093547 "
`
`2007/01 16774 A'
`200110lL713J A'
`200 7/0117i44 A I
`200110129448 AI
`2007/01663!l!$ AI
`2OQI!I(lO()3iZ4 A'
`
`112005 )),) sa.i el al .
`]/2005 I)csai or al.
`3/1005 Hegedus 01 at.
`11/2006 l.ksai c1 011.
`4/2007 Oe ~I al
`412007 0 "",,; eT . 1.
`412007 o.,,,,j el~l.
`412007 De""; e l al .
`512007 Desai or " I.
`5/2007 Trieu cl al .
`512007 I)esai or a1.
`6/2007 Iksai ct aI.
`7!?JJQ7 Desai or ... 1.
`)"2WR 1)0::"'; ~I a l
`
`211009 S""n_Shi" "g L"t .0.1
`4:1009 IXsai CI aI.
`~12()()9 Ix cl III
`1012009 o.,sai <1 a l
`
`2120 10 IX $a..i cl a l.
`I),; ... i <1 a l
`212010
`512010 De$a..i cl a l.
`1120 10 Desai 0 1 a l.
`7120 10 Oesa; et al.
`8120 10 D<'sai ~I a l.
`
`2010i01l2077 AI
`20 lOll) I 66869 A I
`
`200810180981 " 1112008 o., sai et a l.
`2oo9i004833 1 ,"
`1009'0098210 A I
`200wl)1%933 AI
`2009i0263483 A I
`200910304805 " 1212009 IXu,; cl aI .
`20101004&4 <)0) .,
`201010035800 "
`2010102 1575 1 .,
`2010101113128 "
`20101019 1673 ," 11120 10 Harper cr al
`20101029724.1 " 11120 10 ])c$a..i el a l.
`
`FOREIGN PA rENT O<XUME NTS
`0 544 191 A2
`611993
`0 544 29 2 A3
`61 1993
`2 775 900 A l
`911999
`2 1276(l6 CI
`311999
`WO-92/072.'i9 Al
`4/ 1992
`WU-94i 13300 Al
`WO_94i IH954 A I
`WO_94/ 200'l A I
`WO-95/030J6 A I
`WO-%i40l!29 Al
`WO_97/ J0850 A l
`WO-9 8i074 10 A I
`WO-9&'14 I , 4 Al
`WO-98i14175 Al
`WO-99iOO I 13 A I
`WO_99i D 914 A l
`WO-99i39696 A I
`WO -OOi 06152 Al
`WO_OO./1311 7 Al
`WO-OOi 6443 7 Al
`WO-OOi 7 1079 Al
`WO-OOi7 1079 A3
`WO-{lli4926l! AO
`
`£1'
`EP
`FR
`RU
`WO
`wo
`WO
`WO
`WO
`WO
`wo
`wo
`WO
`WO
`wo
`WO
`WO
`WO
`WO
`WO
`\\>"O
`WO
`WO
`wo
`WO-{ll ih'952 2 '"
`WI )"(IZIIJlIl 54$ '"
`WO
`WO
`W0-031096944 A l
`wo W0-2~lOOiS20 A2
`WO
`W()'2~1()()7520 A3
`WO
`W()'2~10 524Q I A2
`WO
`
`.,""
`
`91 I '.194
`9/ 1994
`2/ 1995
`1211996
`3/ 1997
`2/1998
`4/ 1998
`41 1 ~)8
`1/ 19,)')
`3/ 1999
`
`.,'"
`
`212000
`412000
`1112000
`1112000
`1112000
`71200 1
`11/200 1
`I t!21X12
`1112003
`112~
`112~
`&2"'"
`
`W()'200410524QI A3 "''''''
`
`us 7,923,536 82
`Page 2
`
`wo
`WO
`WO
`WO
`
`WO-2OO5/ 1179S1 .'\2
`WO-2oo5/ 1179S2 '\3
`WO-2OO6lO34 147 .'\2
`WO-2006/034 147 .'\3
`
`121200S
`1212005
`312006
`312006
`
`Of HER PUBLICATIONS
`
`A,,"ada. A. (2002 ) ··N ...... Cytolo.~ic Ag~n ls and Molcculou·Targctcd
`Thempi ("S in Ih~ Tr<Xllmenl o f I',lct.u lalic Bre.~SI Cancer:' Trcnds in
`i-;']H'1"/JJlmUJl Gild C/illiClll Metiid llo 12:4·15
`.\w",la. A. d ~1. (2003). " Th~ Pil'di"" "fK .. -w .\nli,an,,,r Ag~nl' r"r
`Urcast Cancer Trealmenl in 2003 ." Crilical R('L'ie»'J ill Ot.cologyl
`Hematology 48:45 -63.
`na y<:.. M el al. (May 2(03) "Galew.Y" roClinic.1 Trials .~ Melltods
`and F;,ulillgs
`in Experiml'llial and C/inical
`l'hal"mllc%gJ'
`25(4) 317-340
`Aielen. S. J . Cf 111. (19%). '"The Effecl o f a Cydo-d<::'<r,in Veh icl eon Ihe
`CamiOVllseular Profile of Propofol in RaIS." AlleSI. AllaiR. 82:920-
`924 .
`Arigg s. L. P. cr .0.1. (1 982). '"An Adve rse Rctlcrion 10 Ihe Admini Slralion
`ofDi $Opro fol (Dipri van)." A'IC,e,IJlesi" 37(7) 1099· 110 1
`Calabresi . P. cl al. (19% ). Introduction of ~Cbcmotbcrnp) .. of
`K~la>li ( Di~"aSC>'." s..'Clion X in Good man an,l Gi IJl"'n' ~ TII~
`I'harmar ological iJa.<i .• O/ lIlwal>et<lics. ",. ed .. MC< ;, aw_lJill: New
`York. pp. 1225 ·1 230.
`Campbdl, K. 1. et al. (luI. 20(3 ). '"A Phase I T rial of AB I-007
`"dmin istered Workly for Three Doses Evcry -4 Wccb
`in P"licn IS
`Wilh A,I,".ant:c~1 Non-lJ~,n"l o lo gi c Mal i gnanc i~"S." P rQC£,<·ilinlfS 0/
`the American Associa lion /or e m " .. r Research held on J"I 11_14.
`2003. Was ltinglonCo nvcnrion Cenier. Washington. D. C .. vol.44{2""
`~,lili<>n). p . 1059. ah" tacr No R533 7
`Carter. D.C. c i al. (1994 ). '"Slru~lurcs o f Serum Albumin:' AdV(lIICl'$
`in I',t l/(';" CIto-NlislrJ'. S.:humakcr. V.N., ~.,J. ,\ catkmic Pr~.". Inc.:
`San Diego. CA. 45: IS3-W3.
`CltUllHI!- V. T. G . d ~1. (l<-by 2001 ). hl'baff""""ul ic"l Sh'ucW~' Uli-
`1i:.ing Rocomhinanl ]],,""'n ~'m AII-." nin ." Pharmal'et.'ir ai
`R,'u arcIJ 19(5):569-S 77.
`Curry ct al. ($...1'. 1998). "C rystal StnoCllI'" o f Human Sen,," Albu (cid:173)
`min Compk':'!cd with Fally Acid R ..... ·cal s an t\s)1runctric D istribution
`of Bi nd ing S ires.~ Nat. Slnirt. 8 /015(9 ):827. 83 5.
`CUITY. S. cr al. (t."ov. 21. 19'1') . '"I'arly Ac id Binding ' 10 lI um""
`Scnlm All:oJ.min: N",,' In si ghlS From C rySlaIl Ogl"''Phic Studi cs.~
`Biocltim.Biopltys. Acrr. . 144 1(2_3 ):131_1 40.
`Damasccl li. B. ct a!. (,,'0>. 15. 2001). "lnlnWtcrial Chcmo therapy
`Wilh Poly().~yclhylalc,1 OISlor Oil Fn.., Pad ilJlxd IncorpOf,uul in
`,\ lbum in Nanop,tr1icl c~ (AIlI -007 ~ ~ C"" C(T 92( I 0): 2592 -2602
`Damasccl li. B. C1 al. (Jul. 2(03). hA /IIovel tll1rn.1f1cri al ChenJO(cid:173)
`Iherap}' Using I'aclita.wl
`in Albumin NatJOpMl ick s 10 T,cal
`Ad,·ancoo Squamous Celt Carcinoma of Ihe 'ro ngue : I'rcliminary
`Findings.- AJR Am. J. Roem!l;<',w l . 181(1)25 3_160.
`[)a~ ics. A .F. cr al. (Jun. 2(02). ""ElIi""cy of M icroflltrnti on in
`Decreasing Propofol_lnduccd Pain." AII~eSllles;a 57(6 ):557·561
`De"" i. N.? el a!. (A I'" 19'14 ). "Conl rolled and Targeted J)m S Del iv_
`ery With BiocoJnplltible Prole in Shell Microsphcrc. :' The 10111
`A",,,,,,I M<'f!lilJg ,,/11 ... £Xit'I),/"" 8 i"""" .. " iul • . Bu . ... ",. MA. AI'''
`S-9. 1994. 1'.1 12.
`Dc""i. N.!': ctal.(Oct.-Nov. 1994). htnlmvcnous Targclcd Dclivcry of
`Chemo-th..,rap"ulic Agenls in \'rolcin M icrosp/ler<.'"S ." X VI Intemll_
`tiOlla/ CaJJ(;w I'rogreu. N",,' Delhi. India.. Oct. 3O. :-';ov. 5. 19<)4. P
`2i S
`Dcsai. X I'. c i .0.1. (M.lr. 1995). '"In Vi ... o Drug Delivery With
`nioc(lrnp;l,ihle Prole in S~d l Mic l·<><phcrc<." "The 1/" A",,,,a/ ,\f~e'_
`ing if/lie SocII'IY/Or Biomaleriilfs, San Franci:;.;o. CA Mar. 18-22.
`1 ~5. onc pagc
`tksai. N.I> d al. (Aue . 1995). "I'rotein Microcapsu le; &< DnlJ:i Deliv_
`ery Velticl"".~ 161h Anl/uill },fcctinc of Ilk' R ile Panid e SocieO·.
`Chi cago. 11 " A"g . 22-25. 199 5. (I nc l"' 8C
`Desai. N.P. <.'f al . (Apr._May (997). h p,()Icin_Slabi l i7.ed Kanopaf1idc~
`as [)mglkli\"cry \'chiclcs."1romacti""$: 13"' A",,,,,,/Meer;ugO/IM
`Soci'1y f or BionWlt·rh,/s. Nc· ... Orleans. LA. ,\pr. 30_May 4. 199 7.
`20:172
`
`Apotex v. Abraxis - IPR20 18-0015 3, Ex. 1001 , p.02 of24
`
`

`

`us 7,923,536 82
`Page 3
`
`Desai. N,p. eta]. (ApI. 1998). "Prolein Based Nanop .. utid~ Delivery
`Systems," l&h Ammo! M'~1illg '-'If"" Fi, ... Parf;r/p Sor;"'y. l)alla$,
`TX. Apr, 1-3. 1998. onc pag<:.
`1:Ie ... i. N.I'. '" al. (May2000). "I'ro!ein.lb"",\ NanoJ"'lniciu for I)n'8
`Ddiwry "[P-",,liwcl." 1immlet;oll>' if Ihe Si.tlh World Bio"'aleria/~
`Qmgren. Kamuela, 111. Mny 15·20. 2000. lll(l)'l~ (one page).
`[)c$lli, K P_~1 al.(2002) "Evidence<! ofEnh",,<e.J in ViVQ EfIicacyat
`M .. , imum Tol"r::It~d [)OS" (.\1TD) ofNanopar1ic!e l'aclila.~el (AB!(cid:173)
`()(J7)and 'laMI in 51 h"DIUlTumor XcnogralisofVarying Sensitiv;ty
`to l'aclil"'~c1." 1002 ASCO Annual Meding Amo:rican Society of
`Clin ical Oncol"i'Y. Orlando. Florida. May2002.Pror.AItI_ SQ{;. CIi"
`Ollcoil l :Abstract No. 462. 4 pages.
`Desai. N. ct al. (Doc, 2(02) "E~ idcncc of a Novel Transporter
`Mcctlanism for a CKmopoo,·F • ...,. l'~cin·Engin(cml l'ad;I .. , .. ]
`(ABI -OO?) and In Vi,o AntilUmor Activity in MX.J Human Breast
`Tumor Xenograft Model." Breo.sr Camx,. ResearNI alld Trt'Illmelll,
`15" Annual San ANonio Brea" Cancer Sympo.ium (SAOCS). San
`'\/ltonio, Tc.~"". i6(SuppI, I) Abstract :"i'D, 524. p. Sl3l.
`Ik.<ai. N, d .>1 . (1)<<, 2(02), "I'redinieal anc1Clin ieaIl'hanMeokinet.
`ies "",I Safety of AI)I.()(l7. a N(",,,I, Crcmophor·F=, Protein·Engi.
`n«red NanOlrnllsfcr o f Paclita."d." Brcas! Callcer RCJcarch a/ld
`riM/"""". 25'" An nu. I San Antonio S'C"" Cancer Symposium
`(SAOCS). San Antonio. Texas 76(Suppl. I) Abstracl No. 523. p.
`Snl.
`Desai. N. « al. (luI. 2(03), "Oral Bioa\lllill\bilily of Padilaxc1 in"(cid:173)
`Novd. Crcmophor d.Frce. Protcin· B....,.1 I'anopaniclc I'rcpara_
`lion." Proc ..... li"8so/lhi- Aml~'ic"" AnocimiOli o/C",u:<'r R .. search
`(AACR) 94" Annua! MCding. Jul. 11· 14. 2003. WaShington Con·
`"calion Center. Washinglon 1},C,44(2"" edition). Abstract N<1. 3673.
`p , 732,
`DeSlli. N. '" al. (luI. 2003). "Pulmonary Delivcry of a Novel,
`C lem" pI'Qr.Frcc. PrQlc i n·B_~1 NanOp'utidc P"'~rati,," "r
`Pac1ita.xel." Prou<'dillgs o/the Amcrirml Associafiotl for Ccmccr
`Re.,earrl, 44(2"" edition). AbSlrnct No. 3672. p, 73 1.
`Desai.N. ~1 ai, (Dec. 20(3). "EvidellCe of Greater AIltilumor Acti"ily
`anc1 Reil Cel l Panitioning and Superior Antimmor Activi ly of
`CI~m"pI'Qr Fltt NanUl'aJtidc P"d; lud (ABI-007) CU"'I'"r~,1 IQ
`Ta.xQI," Breas/ OJJlccr RescM'ch and TrmlJl,elll. 26" Annu.i1 San
`Antonio B~ast Ca..cer Symr<>sillll1 (SAOCS). San Antonio. Te:<lls.
`82(Supp, I): Abslrlcl No, 348. pp. S82.S83
`Desai. N, cl aI. (Feb, I S. 2(06), -lncrcaS<:d Antilumor Activity.
`Inlralu,,"X Plld ;t:a.~d C""cc"trations. a",,1 EmlQlhdial Cd l T r.ul~p'-'rt
`of Crcmop!tor.F"",. All:tl mi n·Bound Paciilaxel. ABI.()(l7. C()m,
`'re""'l'hM.n...s.o:l I':Id ; I,,-~d." '}ill. r'mrer n",<
`[Mra! W;lh
`12(4): 1317. 1324
`o...enickc , AoW. d aJ. (19%), "Reducing Pain During Propofollnjcc·
`tion : Th~ Rok of !he Solwnl.- AII .. ..,It"'·ia & Allalgesia 81 :471474 .
`Dosio. E ela1. (1997). "Prepnralion. Charnctc'l'i7,~tion "",I Proportics
`r n Vilro ant! In Vivo " f a Padit,,-,d. ,\ Ibmnin 'onjugalc."J. r"",. Rid
`4?:293':W4
`Llrugs .oom (Jun. 22. 200<1). "lkfcroMnlinc (Systemic)." located at
`< hlll.:l!WWW.t! ... g •. cvm.~Il\IXlDcf ...... _~.u .. iru:_ M ... yl .. lc.hll •• I>.
`lasl ~ccssci Feb; 4, 200:5, nine pages ,
`Egsling. S, (W03). -Variation on Perc.:nTage Concentration Weight!
`Volwnc ''''rcent Or Manivol umc ''''rcem.'' locala! at bllp: lldJ.
`clackamas.cc.or.uslchI05'()4''''1volpc1.htm>.last visited on Feb, 4.
`1005. "nc P"I!C
`Erlich. R,« al, (Jun, 2002), "American $Qcidy of Clin ical Oneol.
`0$)'- 38'" AnnulI l Meeti ng. ~1 .. y lR·21. 2002. Orlanclo. fL. USA."
`/"vcslig<lliollal Dru/:s JOIlrlmI5(6):49?502.
`I' chskc, K. J, cl ftl. (Jan. I. 1%1). "rhe Locarion of Drug I\ind ing
`Si'e. in Human S,,,,,n Albumin." Hiurht'"licu/ I'hurnwc"'og),
`3~7):687-692
`Finlayson. J.S_ (19110)_ ""Ihumin Pmtlllcl<." S",,,,i llalCfill Tlm''''''''" i,'
`and liI!mwlasls, 1I-lanuncn, E. F, (ed.). Stranon lrue«;Onlincnlal
`Mooiealliook Corporation. NcwYork. NY, 6(2):85· 12Q.
`Floomoy. D, J (J,,1. 1991). "In Vitro AntimicJ<)bial l''''I''''rti~s of
`[)eferoxruninc Mesylmo." E,,~ J. Cli". Microbiol. Itifee/. Dis
`1~7)S97·5911
`Garrid<;. M,J . <>I aI. ( 1994). "Caraelcri~aciQn de la Fijaci6n ,Ic
`Propefol a las l'rOlcinas I'lasm,ilic;u y l'osiblcS l ntcraccioncs," Nt'>:
`J::~. A"""/t'siol, R''<IlIi", 41(6):308.312. with Engli'h abstract (0'""
`page )
`
`Geld~'1hlom. H. ~1 aI. (ScI', 200!), "Cremophor EL: 100 Dra",-backs
`and "dvanlages "fVeh icle Se lecl ion for On,s Formulalion:' E,,~ J.
`Ctmcer 31(13): 159(l·159&.
`(;radi,har. \V.J. <f.>l, (Nov. 1,20(5). "Pita", III Trial ofNa noparlic le
`Albumin-DoIlnd l'aclita.wl Compared with PQlyelhylated Castor
`Oil·Based Padila.~d in Women Wilh Breast CucCl'." J Clill OtlCoi
`23(31):7794.7803
`Green. M, R. ct aI. (Aug. 2006. e-pub, Jun, 1.1(06), "Abrn.'<3neBlA
`NO'o'eI Cremop/lor·Frcc. Albumin-Ilound P~r1iclc Form of l'aclit .. ~d
`for the Trcaunent of Advancoo Non-Smal1-<:el1 Lung Cancer." Ami.
`0"':01,17(8): 1263·1268
`Grinsfaff, M .W. « at (Mar, 1994), "lmravc/tOlJs'farg«ed Ddiveryof
`Ta.~ol in l'rolein Microsphcres.. .. Alls/rac,. ofl'i>jXn ,W?' NaliOlial
`Mrelillg oflht Allleri('a" (1":,,,ical Socie:ly. 199'1. San I)iego. CA.
`Mar. 13-17. 1994.207(1.2). Abst.-act No, 91. one page.
`Guneridg". J,M.e. cl "I. (1981). "lron.l)ioxygcn.l)cpcndcnl
`Ilierg.
`Changes 10 tbe Biolo~ical AClivities of Bleomycin." J
`BiQCllem, 15:349·357.
`(;uneridge. LI.1.C (19!W). "SIrcp!onigrin-I ... lucecl lleoxyrilx>se
`[)cgr:u\alion: Inhibition by Supero.~idc I)i,mutasc. Hydroxyl Radical
`Scavengers ""d Iron Chc1alors." BiochNII. Pllarm, 33(19):3059·
`3062
`Halliwell. B. (1989). "I'rotc.:lionAgainst l it;SUe t).lII\agc in Vivo By
`l)e.fcrrio_""mine: What is It. Me.:hanism of Action'f' Free lIadic_
`Biol_ Med. 7(6):645.65 I
`lIauscr, C '], « Ill. (Jun. 1980), "Oxygen Transpo" Responses to
`Colloids atld Crystalloid. in Critically [[[ Surgical PatienB:' Sw-gery.
`G>,'''c%(,:), amI Obstelrics 150(6):811-8 16 .
`lIawkins. ,\\. 1. ct "I. (20!)4), "l(aliOn,1it. l'redin i",,1 SI'ppon. aIMt
`Clin ical I"roof-of·Corn:cpI for Delivery of Ware/·ln >olttb!c Tltera·
`prulics by It Novcl Nanopan idc A1bumin·Boultd Cl'-'ab) Technology:
`E"I'",i"""", Wilh I':Iditaxd." 0"";,,,- 1""",,_ 22(SIII'''. I):v;ii .x_~vii .
`I-I ll. AbSlrncls from the Chcmothcrnpy FQund.'uion S)mposium
`XXI: In novMive Canc"r Thcrnpy fM TomMlow. Nov 12 · 15. 2003.
`New York. Ne><' York. L'SA. vol. 12. Supplement l. pp, 990100.
`Abstrael 1'0. 19.
`lie. X.M_ ~1 al. (Jul. 16. 1992)_ "Alom;, Sln.;I"", and Chcmi.h),..,f
`lIuJ113n Serum Albumin:' NalUre 358(6383):209·215.
`lle~lthT{)Uch 'Jl Online. (2000). "Defe-roxamine (SY!;lemic )." locat",t
`at <hllp:i/healthtollch .com> . S pag~'S
`Ibrahim. !'Ix. ~'I "I. (2000) "Phase I Study of Cn:mophor·l'rce.
`PI"kin·St.abili~e,l )\an"l,ac1ide F..,,,,., lation " f Padih,d (Abi.
`007) in Solid Tumors." AbSlrncI609F in Pnxeodi"gs o[Thirr)"S;wlt
`AII/IlI"/ M.",lill8 "f ,h .. A",,,,"iraJl SI)('i,,/), if riini""d Ot,t:(>Ing)'. New
`Orleans. Lo uisiana. May 20.2J.1000. p, 155a. Abstracl No, 609F.
`Ibrahim. N. K. ct .. I. (Mny 2002), "Phase land I'hann acokinetic
`Study of ABI -OO?
`a CrcmophQr-f ,,,,,.
`''roki n-Stabili·",d.
`Nanopanic l" formubtion of I':Idiuwl," CIi". Calle.... Res
`1;(5):10)1;_1044
`Ibrahim. N. K. ct aI. (Dec 2002). "Emca.:y and Dosc.l)<-pcntlcnt
`Activity of AllI-007. a t:rcmophor·J'rcc Nanopartidc I·adita.~cl. in
`First·Li"" Mc1astatic BI~ast Canc"r: Inl~w .. k'd Re.uh.of2 Ph""" II
`Trials:' Bft'a51 CalU:i.'r Rcsearch al/d TrealmNI/. lJ" Allllual 5rl1r
`AII/otlio Ilretl51 CalU'.".S)'n,pos;utIJ. i6(Suppl. I): Ahst",cl1\o. 522.
`p. SI3I.
`Ibrahim. N. K. el al. (Scp, 1. 2OU5). "Multicentcr I'baM' II Trial of
`,\1)1-007. all Alblllllin·Rount! Padi t,,-,d . in \\-Qm~n With 1I.kl".la';c
`AreaSI Cancer." J_ eli" Om:ol. 23(25):60 19.6026.
`John. M. C. ~1 .. 1. (MM. 6. 20(2). "A N"vel Preparation 0 1' S)'SIcmic
`Padila.~c1 Reduces In-Slenl R~'Sle nosis in the R:tbbil." Journal of/he
`America" College 0/ Cardiology AlmroCls- ACCIS1/)())
`(Angiography&. llllt"v<'lIlio"uICuit/ioiogy) Ab .. ,a<'( 1\1)_ 1005-6. J>
`SA.
`1",·cn. ru. c1 at (1994) . "Facl"", lhal Inlcrocl ..... ith ,hoc Anli"""le,i .. 1
`Acrion of Thyme Em:nlial O il and iti A~liw Conilituenl s.," J. Appl.
`HaCleriol.76(6):626-631.
`K!~bano!T. SJ, cl al. (Nov, 25. 1989). "O"ygen-based f .-.:e Radical
`Gencmtion by Ferrous 10M and Defero.""",in"." J. Bio. ell"",
`264(13) 19765·19771
`K.nil:tlc. c'A.], "I al. (1999), ·'phanl",~okincti". [n<luetion of
`Anacilhc$ia and Safdy CharactcriSlic~ of l'ropefol b% SAL-,-': n
`Propofol L % SAZN and Dipriv ... n<tl.1Q afier Bolt" Inje.:tion,M & J.
`eli,,_ PharmaCQi. 47(6):653,660
`
`Apotex v. Abraxis - IPR20 18-0015 3, Ex. 1001 , p.03 of24
`
`

`

`us 7,923,536 82
`I'age.:l
`
`Kolodll-ic. F. D, ~~ al. (Sep . J. 2(02). ''Sustained R~duclion o{[n-Stent
`Nco;o! ;",.1 Gnm1h With the U", o f a Novel Sy~lcJ11jc Nanop.utidc
`Pac1ita.wl," Clrculalioll 106: 11 %-1 198.
`M,,".u-, J. cl al. (Mar. 2()()() . ''Uncxp'''''led Erre,;!. or Albwnin on
`Apoplosis Inductinn hy l>efe",x:tmioe In Vitro," In Vitro Cell f)""
`8iol, Anlm. 36(3): 151·] :5.2
`Kragh.II"n ~n. U. ( 1990) "Stru<ture and ligand Bin'iing PJopcrli~'$
`of Human Sl>rum Altum;n," [)o.1I. ,lied Bull. 37(1):57·84.
`KuenCll. S,c. (MaJ. 15. 2002). "J)Qsc-Findjng and Phanna.:okioctic
`Study of (;isplalin. Gcmcilabinc. and SU5416 ;n Pal ;ents ...... ith Solid
`Tumors." J. Ciin. Ollcol. 20(6): 1651·]661.
`L,, " ocit~. R. e1 .[. (2000). "" Novcllnt,.<I-ArTc ri,,] Chemorh...-.<IpetJ_
`Ii.; Approach (lfSquam(>us Cel l CancerofHead and Nc'Ck Using HiP.
`Do"" C.cmaphOJc, free Pad; la~d/AlbIlJllin Kaoopanidcs (AB!.
`0(7),~ Allllab o/o"co/og)" Secoml Nar;o.tall.-"(mgriC>s of Medical
`o..cology . Oct. 28-3 L 2000, Genova. IHlly. vol. II. Supplc"",nl 2,
`p ""lcr Sc ... inn A. Ab<lr~CI No. A26. p. 7
`Lanoeila R. CI al. (Nov. 2000). '"H igh Dose of Crcmophore_Frl'C
`Padila.~dIAlbu",i "c Nan"l'ar1idcs (AI3I-007) r,-,r a Nuvel ln1l:a_Ar_
`lerial Approach 10 SqlWl'"lOUS Cd l ClIl1ecr of Head and Neck." lO()()
`Sl"i~"'ifir Program . Rad;Q/ogil"~1 Sori~ty of No.-'" Am..,ira, RSNA
`)()()(j, Exp/ort'. 86" Sclmlific Asselnbly ami A""ual ,\.IN:ling. Nov.
`26-I><:c. I. 2000. McCormick I'lace, ChiCAgo. llIinoi., vol. 2 17. p.
`288. AOOI""'l No. )66.
`Lanoe il .. R. ct al. (Nov. 2QOO) . '"Squamous Cancer of Anal CMal
`Inlta_Allc.ial Chelnolhra~"lic Approach U~ ins High I:Io;;e of
`Crcrnapooro-Fr<.'C I'nclila.,c liAlbmnin 1\anopartides (ABl-007)."
`}()IJ() Scienlific Program, Radiologirill S«iely of Norlh America.
`KS'"vA }Q()(), ExplQll', 81/" $cielllijic Anembly and AII/lual Meetill/:.
`Nov. 26-0c<:. I. WOO. McCormick Place. Ch ic,,&o. IHinoi $. vol. 217,
`I' 504. Abslrad N .... 1244
`Larsen. B. ct aI. (.'<ov. lO(1). "Less Pain on Injeclion by a N"ew
`l'onn"lalinn o f I'ropo fo!"?" /M Allam/resis/. 50( 11):l;42-M5.
`Lilley. E.M.M . C1 a1. (S~'P. 1996). uThc Eff~"d of the Addilion of
`Lign(l<:ainc on l'ropofol Emulsion Slability:' A,weSl/oes;a SI :8 1S-
`
`'" Mayer, M. el al. ( 1996). "Propofol ant! Elomi<ia14 lipuro wr
`
`,,"O>Cr
`Ei nleitun g
`AlIg"r.eiMn~S1'he.~i~."
`[),y
`A"a"'l/rcsisI45(l1):I082_I084 an d English lunslalion of absl13cI
`only.
`M~ijs. W E. d al. ( MlI)' 1996). M .. \ Facile Mdhvd f ... r !h ~ labcling o[
`Proteins Wilh Zireonium lS<lfop<'S." X!Jclear Mruici,w & 8iologJ'
`23(4)439-44~
`Micha. J.P. e! al. (Feb. 2006. e"f'llbO;:1. 142(05). "'Aool:-:ane in lhe
`Tre,,!mcnl of Ovarian Canccr: lhe Abscnl\: ofHypcNCnsil ivily Rc1lC(cid:173)
`lions." G)'IWC'" O"co/l00(2)'4JI-4J8
`Moreno_Aspilia. A. Cf al. (0<1. 2005). "Nonh Cenlml CancerTre"l_
`.ncnl Gmlll 1\053 1: Phil.'" I[ T",il of Weekly ,\Iht,min.no.md
`Padil",'<e l (AI3!-OO7, Abra.'<anC®) in CombinaJio n wilh Gel""ilabinc
`in 1'lIlicnls wilh Mdasla1.ic lircasl Lanccr." Cii"ira/ B,ro,'/ Camx!"
`6(4)361-:\64
`MUlier. B,G, ~lal, (Jan, 19%), "Altwnin N"anosphcn:sasCa.rri~rs for
`P~ .. ive r:)fu!, Tars",i "g: An OpIimizoo M"nuf:.clming Technique."
`P/ral'ln. Res. 13(1):32_3 7
`Nyman. LlW. Cl al. (Nov. l. 20(5). "J'hase l and J'hannacokinclics
`Trial Qf AI3!-OO7. a N ..... d NanQI,,,lidc F ... "" uhl ion Qfl'Klilud in
`PalienlS wilh At!vancoo NonhcmalOlogic ).ialignancies," J. Cli"
`Oneol.2 3(31):;7115-;793
`-'II. (2003).
`O·Sha"ghn~'Ssy. J. ct
`''ABl-007 (Abra.xane"'). A
`Nanoprtniclc Albumin-J.lound ("Ilb) P~cl il .. ,<cl l)ctTl()nSlrale$ Supe(cid:173)
`ri "rE/ftc..:yv.la.wl in MSCeA Phaw IllTrial." 8.-..r¥!C",,,,,'Y R .. ¥.
`l"roo/, Proce.:di"gs of Ille }6" A,mulli Sa" A,,/a,ia Brt'asl Cancer
`SY"'I'M;"", (SAHCS). San Anloni". Tc."". IA:,;;. 3-6. 2003, R2(Suppl
`1):3, Ab:itra~l1\o, 44. p, 182,
`Pail, K. C1 nl. (200 I). "IIi gh AlJinily Binding of l'aclila.'<d 10 Iluman
`SCJ"m Albwnin:' E"r. J. Bioc/, .. ",. 26&(1):2187_2191 .
`Palelli. G. CI aI . (2002). "'Eff"",iwncss ofinu"'IJI", ial ChcJn<>lhCJapy
`hy T~""nc ,h~ rgcd Alhtrm;r.e NaMp.'Tlicl"."n A,h"nccd Squ~m''''.
`Cd l CanccrofOrnl Cavity ant! Oropharyn.~:' l!IIenUlli",,,,1 J()IJrIlal
`QjCauca- Ill" UICC Inlcrnational Cancer l:o ng.rc $S. Jun. 3U-Jul. 5,
`2002.0,10. No,way.Abstract B<>ok, S"ppl~n"'nl 13. Ab:i!Jacl N". p .
`371. p. 258.
`
`Ibckground and UJe.~
`
`PUrcell. M . ct 31. (2000) . ~Inlcr .. clion ofTa.~ol wilh Human Serum
`'\hun;n." Bi<X/rim. 8iQplJ)'S. A'-I<! 147861-68
`RiloV, V. B. '" al. (lun. 20(1). "'Hexokinase [so>:},m. Dislribmion in
`Iluman Skel.tal Mu""I.," J)ir.i>eles SO: 1253_1262
`R"cha. 1. L. l..,1 a1. (,\ ug . 2(02). '"l' ncmrunon VlU>I:ornyc in-lnducoo
`Si<lc EffccIS,~ 11Je Brazil. J "ifecl Disl'fl$c$ 6{4):1%-200
`Shimon;. E. d
`,,]. (Jun
`1994) ·'Anl;"~i.tllnl
`Propc:Tl i c~ of
`Dcfero~amine." JAOCS71(6):64L-644.
`Singh. N, 1'. el ~1. (Nov. 21. 2(M)[) "Sd«livc 'lo~iC;ly or
`Dihydruart~'ITlisininand H"lutransfcrrin Toward H"man BreaSl Can (cid:173)
`cer Ce ll s,~/'ifo' Sci. 70(1):49_56.
`S,,",rc1:oom, A d al. (Feb. 11. 1995). ··0..1e.minalioo o f J'lldilll~d
`and Mdabolitl!S in Mouse Plasma. TissU<'s. Urine and Faeces by
`Scm i- i\" lomMe.t l( cvcrscd-Ph.Mc lligh-Pc.fonnanec Liq \lid Chro(cid:173)
`rnalogr.tphy." J. OJromatogr. B. Bimm:d. Appl. 664(2):383.391
`Sp,."..,boom. i\ . el al. (lun. I. 2(05). ''Comparnlive l'Icd inical ant!
`Clinicll ll'hafJnacolcin~1ic. of a CJcnlOphOJ -f '''''. Nano"anic1e Albu_
`min_Boun t! l'adita~c\ (ARJ-007) and P,,,,lila~cl Fonnulaloo in
`Crernophor (la.~ol)." Cii". C""cer Re.'. 11(11):4136-4 14]
`Sugio, S. C1 al. (1999). "Cryslal Sl,ruc(UrcofHuman SerumAlbtunin
`al 2.5 A Resolution." Proteill Ellg. 12(6):439-446
`Tan. C. U. d "I. (May 1998) -'Pa in On !njc<:lion of Prof>Oful ,~
`AJ1a<'SI/resia 53(5):468-476.
`'1:'yIOJ. C. d aI. (Ik.:. 20(2). "I'rdiminary Evidence of Antitumor
`ACl ivily of A13[-007. CreJnophor_Frl'C Kanopal1ide l'adila.xcL in
`PalionlS Prcvioulsy Exposed 10 T .. ""nes," 8,..,a$1 Cancel" ReSl'llrch
`,",,1 Tt .. a/mm/. 25" Annual San Anlonio Breast Ca8~Cr S)'rnpo~i lJm
`(SABCS). San Anlonio. T",,,"'iS 76(Supp1. I) AbstracI 1'--0. 525. p
`S13 2.
`Tonner. p, 11, el ai , (Nov, 1992), " f hc(}cncra] Ancslhe!k POI~llI:yof
`Propofol and hs l)cpcndenccon Hyriros1nlic Pressure: ' AII41}""io/(cid:173)
`"ID' 77(5):926-93 1
`Tullis. J. L. (Jan. 24. 1977). "Albumin'
`JAMA 237(4 ):355-360.
`Tullis. J. L. (Jan. 31. 1977). hAlb"min 2. Gui<lclin~s for C liniul
`usc." JAJ1A 237(5):46(1463
`uriCH. S. ct al. ()"'by 19%). ·'[)oo.;cla.",,1 SClwn l'IQlcin Bilxli"l! w;lh
`lligh Affinity of Alpha , _Ac id G lycoprotein." """'51. Nell' Dru1;$
`14(2): 147_151
`Villkjo. C. e! aI. (0....,. 1996). "[fosfam ide and Vinorelbill e as Firs!_
`line C hemolherapy fOf Ad'ancoo Non-Small Cdl Lung Care i(cid:173)
`numa." Am. J. CIi". ()'J<''''. 19(6):SiM -588
`Vorum. n. (Nov. 1999). "Reversible Ligand Binding 10 lIuman
`Scmm Al humin." nGlr. Med. H"IL 46(5):379-399
`Waugh. W.N. el al. (J111. 1991). "S/:ability. Compatibi lily. and PI:w i(cid:173)
`cizcr E.,lmclion orrll.,ol (NSC-12 5'J73) Injection Di lu lOO in Infu sion
`So}"li"no anJ SlofCd in Various C"nlai""".-· AJHP 48(7): I no_
`1524 .
`Y~ng. Y. 7.. d AI. (1991). M,\lkyllllion of Ih"mn Alhumin hy Ihe
`Anlimalarial Anemisinin." 8iot:/,em Pharln.46(2):336-339.
`Yans.. A. C1 al. (J"I. 2(03). -'I'IIlmoniuy Uclivery of a .'Iovel.
`... r
`I'rQ!c;H
`I).a~<~l Nan"'l',ut idc P"'pardli ... n
`Crcl11Ul'hQr_Fr<...,.
`Pa~lila.xd." Procffdillg:s of tile American .1ssocialiwJ cf Callccr
`ResoomJ (AAC R)94" Ann"al Mccling. Ju1. 11_14. 2003_ Washing_
`Ion Con"enlion Cenler. Washinglon D.C. 44(2"'" edilion). Abslracl
`No. 3672. p. 73 1
`u.s All'1. Nu 121479.710. f,lcd 1m, S. 2009. f ... ,l)c,ai "I al
`u.s. A]lIlI. No. 121818.099, flloo Jun 17_ 2010 for Dc e1 al.
`\1.S. '\]lIl1. No. 121824.014. filed J UlI 25.20 10 fo. Desai,;;1 ~l.
`\1.S. A]lIlI. No. 121874.965. fik-d Sep. 2. 2010. for Dc el a l.
`U.s. A]lIlI. No. 121832.876. filed J ul. 8, 2010, for Ucsai CI al
`u.s. App!. lola 121910.693. f,lc~i Q.;c 22. 1010. r"r De,..i d al
`Non·Final O!ToceAclion mailed On Jun. 12.2008. fOl U.S . Appl. 1\0
`11IS20.S46. fil",! Scp 12. 2006. ninCf"gco
`Non-Final Offi(e A~lion mail~ on Dc<; , 2. 2008, ror U.S, Appl.1\o,
`1 LI~20.S46. filed Scp. 12. 20Q{i. eight pag.C>!.
`Final OlfLw AClion mailoo on s..V. 17.2009. fo. U.S. Appl. 1\0
`11/ 520.546. filed Sep. 12. 2006. 8 P"!l<'S 10lal
`Inlcmal;on~1 Surd Rcpnn mailct! N"v. 30. 2004.]>(1 Appl i~Mi'm
`1\0. PCTIUS0313894 I filed Dc<;. 9, 20(H, publi sh"'! as WO 20041
`0$2401 On Jun. 24. 2004. to: pagcs
`Iksai. N. d aI. (0....,. 2003). "E .. id.,nc~ "fG.cah:r Amilumo, ACli"i ly
`ofCrcmophor<!'-F.ce Nanopar1iclc !\lbumin,Bound ("ab) Padil!l~el
`
`Apotex v. Abraxis - IPR20 18-0015 3, Ex. 1001 , p.04 of24
`
`

`

`us 7,923,536 8 2
`Page 5
`
`(Abrn.",'nc) Comparoo [0 T.Ml: Role of a Novel Albumin Trans(cid:173)
`porter Mochanism." I'"Sle. p resenled 01.1 26'" ,\nn"al San Antoni"
`Br~asI Can"~r Sympvsil.lm (SABCS) hdd on D<.~ 3-6. 2003, San
`Antonio, Tc.~aJI. one page (PoSlcr).
`
`Bechcr(J 965 ). Em,,/siOl's. lll00/y and Proclice. 2nd cdition. Arneri(cid:173)
`"M Chcmicill Socidy. Mooograph Scr;e~.I(cinoold I>u blishi ng Cor(cid:173)
`porallon. Ncwy", k. USA. Table ()f C()JUcnl~ on p. xi, f<,,, a 101,,1 of)
`pages.
`
`Apotex v. Abraxis - IPR20 18-00 IS3 , Ex. 100 1, p.OS of24
`
`

`

`us 7,923,536 B2
`
`CO.\1POSITIOi'"S AND METIIODS 0 10'
`OHIVE RY O F PI1ARM.ACOLOG IC \L
`AG ENTS
`
`CRUSS-RH' EKENCE TO RELAfED PAlENI'
`APrl JCATIONS
`
`"Ibis p:.JlI .. 111 application i. ~ CQn1inU<llion or p .. Wlllllpplica·
`lion S.n. No.1 lfSSJ,339, m"" <XI. 26, 2006, now issu~u as
`US. Pal. No. 7,R20,7RR; which is ~ oool;"''''\;On of pMenl
`application Scr. No. I on)l ,224, filed J::)cc, 9. 2(0); which
`cbims the benefit of U.S. Provisionall'atent Applicmion Scr.
`Nu. 601432.317. fikd Dt.'C. 9, 2002; U.S. Provisional Pal<..111
`A pplication Scr. No. 601526,544, filed Dec. 3, 2003; U.S.
`l'rovisional Palen! Application Scr. No. 601526,773, filed
`Dec. 4. 2003; and U.s. Provisionall'mcnt Application Scr.
`Nu. 60/527.177. fikd Dt.'C. 5, 2003.
`
`FIELD OF THE INVENTION
`
`"Ibis illvcmion pertains to pharmaceutical oomJXlsitions
`comprising pharmOCclltically active agents for parenteml or
`other interlml usc. which hav~ the effect of reducing certuin
`undcsirnble side effe(;ts upon administr:nion when compared
`wilh ~vailablc f")flllulalium; o f ~imilar dru8-s.
`
`BACKGROUND OF THE INVEJ\'T[ON
`
`N
`
`"
`
`2
`addition, thc oxidation of drug formulations by exposure to
`air during manulac1I1re or storage can lead to, lor cxample,
`r<--duccd pH, drug dcgradmion, and discolorntion, thereby
`dcstabilizing the dmg formuilltion Il ndlo r reduc ing shelf life.
`To circumvent the problems associmed with administra(cid:173)
`tion-related side effects of drug formulations.. a!tenmte for(cid:173)
`lllulations haw oc'Cn attcmpted. With rcspoxt to prol'% J, for
`example, methods for rcdLlcing propolol_ioduC(,d pain
`include increasing the fm content of the solvent (c.g .. long
`to chain triglyccridcs (LCT». prcnK'dication. prctrc.1lmcnl with
`non-.tcroid<il drugs. Joeal atlal'Sthctics. opioids. lhe addi tion
`oflidoc:.ine, the addition ofcyclock'Xtrin, and micro liltmtion
`(sec, e.g., Mayer et aI., A""esrhe.ris/. 45( 11), 10112-4 ( 1990),
`Davies. CI al. Anaesthesia, 57, 557-61 (2002), Docnickc, cl
`t~ al.. Anae,frh. Alia/g .. 82. 472-4 (1996). Larsen t1 al.. Anaes(cid:173)
`Ih('~'ili~' 50. 842-5 (2001). lillcy cl ... 1.. Antl('Slhl.i~·itl, 51,815-11
`(1996), IJicienet aJ., A,,<'s lh.AJUl/g., 82(5), 920 -4 (1996), and
`Knihbc ct al ., Hr. J. Clin. Ph(JrJlltlCoi .. 47(6). 65.,-60 ( 1999».
`These formulations. llOWt'Ver. induce other side effects (e.g ..
`cardiovascul<lr complic<ltions). or c<luse dl'Slllbilisati()n of
`propolol emulsions.
`To overcome the pmhlem ofhacterial contamina tion, pm(cid:173)
`pofol formulations havc oc'Cn developed with antibnckrial
`agents. such as an E[)TA equivalent (e.g .. edctate). pcntetate.
`ur sulfi ll· ..... :ont~ining "gcnll;, <Jr thl")' IlavC oc'Cn have bt-><-~.
`fommbted with a lowcr pll (see. e.g., US. 1'n1. Nos. 5,; 14,
`520,5.7:> 1.355.5,731 ,35(,.6.0211.1<»1.6.100.302.6, 147,122.
`6,177,4 71, 6,399,081, 6,469,069, and IntcmatioJ