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US20170368167A9.Pdf THE MAIN TEA ETA USAITOA 20170368167A9 MA MA MA MA MA MAITI ( 19 ) United States ( 10 ) Pub . No .: US 2017/ 0368167 A9 ( 12) Patent Application Publication (48 ) Pub . Date : Dec . 28 , 2017 Agadjanyan et al. CORRECTED PUBLICATION ( 54 ) COMPOSITIONS AND METHODS RELATED (60 ) Provisional application No . 61 /691 ,607 , filed on Aug . TO NEUROLOGICAL DISORDERS 21 , 2012 , provisional application No . 61/ 792 , 770 , filed on Mar. 15 , 2013 . @(71 ) Applicants : The Institute for Molecular Medicine , Huntington Beach , CA (US ) ; VAXINE Publication Classification PTY LTD , Adelaide (AU ) (51 ) Int. Cl. A61K 39 /39 ( 2006 .01 ) @( 72 ) Inventors: Michael Agadjanyan , Huntington A61K 39 /00 ( 2006 .01 ) Beach , CA ( US) ; Anahit Ghochikyan , (52 ) U . S . CI. Huntington Beach , CA ( US ) ; Nikolai CPC . .. .. A61K 39 /39 ( 2013 . 01) ; A61K 39 / 0007 Petrovsky , Adelaide ( AU ) ( 2013 . 01 ) ; A61K 2039 / 55583 ( 2013 .01 ) ; A61K 2039/ 55505 (2013 . 01 ) ; A61K 2039/ 575 @(21 ) Appl. No. : 15 / 174 ,709 ( 2013 . 01 ) ; A61K 2039 /55561 ( 2013 .01 ) (57 ) ABSTRACT @(22 ) Filed : Jun . 6 , 2016 The present technology relates to compositions comprising inulin particles for use in the enhancement of immune Prior Publication Data responses to neuronal self -antigens for treating or preventing ( 15) Correction of US 2017 /0239349 A1 Aug. 24 , 2017 neurodegenerative diseases , in a subject . Also provided are See (63 ) and (60 ) Related U . S . Application Data . pharmaceutically acceptable compositions comprising : par ticles of inulin ; a substance comprising one or more patho (65 ) US 2017 /0239349 A1 Aug . 24 , 2017 gen -associated molecular patterns ( PAMPs) ; and a neuronal self - antigen fused to carrier , and methods and uses of the composition for inducing or modulating an immune Related U . S . Application Data response in a subject, such as modulating an immune (63 ) Continuation - in -part of application No . 14 /628 , 023 , response to a neuronal self - antigen as a vaccine . Also filed on Feb . 20 , 2015 , which is a continuation of provided are vaccine compositions comprising inulin par application No. PCT /US2013 /055877 , filed on Aug . ticles , and an antigen - binding carrier material , and methods 20 , 2013 and uses of the vaccine . Patent Application Publication Dec . 28 , 2017 Sheet 1 of 65 US 2017 /0368167 A9 FIG . IA FIG . ID ALIUON00)* wwws :9 1chd * EIN oda 909 99** N1 ML"Giz 009 TIV = 2000Ali COV*9 ( Bi All 9: 0 * * 003 *HP NEL :3 mil312 900 +Nilm ALL#* . M ALAAIL*09 #12 40 od Nupu + 2014All*109 . vrnirnar . juusemuagakQowwwx) Anti-akustizalgGza(00sm) porting my wwwwwwwwww This Per wonnnnnnnnnnnnnn mininnnnnnnnnnn +19 *AL *. 36 Do do 29 o999 :NIP Ald ALE*HOZ Mai Ald 09 045*WIR árlón909 NIP TH4 TIV*T All #odabraz . All 9400900 MIL Oroz Aodo* B2 #p90 * W ALL- ALL +O2 ..Al * * All # FIG . IB FIG . IC Patent Application Publication Dec . 28, 2017 Sheet 2 of 65 US 2017 /0368167 A9 FIG . 2A FIG . 2B ??????????? ? ? * * ! ?? .Fire ??? ??? * ???? ** ? ???:: ?????: FIG , 2G * * ????? ??????? ??? ??: ?? # " [ar ?? illaha #? ????: ?? ???": .iiii ?? ?? ?? # Flu | # | .?? . ? 43 *4334333334335 ? * 3233333% ? 33% * * 33 " " ???? ? ?? 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SB wwwwwww 08G wwwwwainnainmaalalaban annanna vir *00)910 Swinan wwwwww OMODestan) Anti-katies ???????????????????????????????????????? www wawinan Antimabios mannanna Rodinn Www BIO ouRablo 1001+ SalinaRabius10 Rabia +dIN # *PDI* TOP pusaq # 1011Raba me* 5#Niposaqes line 10x1Raivia +c+IN 1011Rabies +Salitte Toul Kabies #PDM 1061001 Mabies #Saline 1001 Rabies #PDmix : 1Tel win G1(004mm) KotRabias win minnnnnnn www Anti-Rus G2a(00sten gustong A Atttt HowRabies Rabicdin #P Dili 1030Rabies #Pomix ** ToutEtablasttaline 1024Babics =Saline PoulRabies Tol*Saline1021 Rabitudin Rabimnu9Pprin noulRabits #01+Saline3444 Rabimsed 10 ???HowRabiesoforas FIG . SC FIG . 5D 1.2 : : : Patent Application Publication Dec . 28 , 2017 Sheet 6 of 65 US 2017 /0368167 A9 wwwg Total196(OD.sonm) wysoista . LIA. XW0dAL 900x900 Uesowat veUuBuod, Vysowed (w I FIG . 6B6B sx00)Wo1901 wwwwwwwwwwwassenenwaarvan Antinfluenza Saa *LTA XWOd*A 90079d5* vesowkZ WBuuewoon PamCSK4 Patent Application Publication Dec . 28 , 2017 Sheet 7 of 65 US 2017 /0368167 A9 FIG . 6C Jonssoningannaninigasandosimn (uu0$700)190201 ezuantomuy ogamatanoprositoareparing 1 .9002900 wesomez lillVO* FIG . 6D (wuoxo)ezoöleQL Web ZuenguUV V1 XuddAl 900zodo VESOWA veguewody sowest Patent Application Publication Dec . 28 , 2017 Sheet 8 of 65 US 2017 /0368167 A9 FIG . 7A TotalIgG(ODasorm) Anti-influenza *POVE *MPLA) lagellin Prav(U) CSKPok[t : *) MPLA Poly(0) *VALP 00000* FlatéliliaMALP *Home 1961oo)fosy zuenburguy FIG . 7B SOUVE muthaliliilien#MPL Sad* Poly (0 ) PLA ALP Polvuj Plageliin PolveuSOLEREDE hladmin*WALB 9007909 PO zuengumpay IgG2a(ODscann) het nie ????WE )* *#BLA Flagodilo MoltCOGR009)Watcsk w#Polych : )UPLA # Flagaillit MALPA Poly800zodo (U) FIG . 7C romis ) FIG. 70 Patent Application Publication Dec . 28 , 2017 Sheet 9 of 65 US 2017 /0368167 A9 FIG . 8A FIG . 8B *18X(00458) Anti-H6IgG(00450 5POL HSkg g* DIN SH400L + MP *049 HS100ngdi W FIG . 8C FIG . 8D Anti-51961(00480) Antas(gaza0046 !ttt bis30 ilk+CDG 96Bob 8HPgang • din +Co W30100 #foong (OS400) 109400)4295Swauan wwwwwwwwwwminiw ISHOQUE a 1459 d .GoG CASH NIP 10100g #DIN SMBugo WIP 900 15Tag 58licce FIG . SE FIG . 8F Patent Application Publication Dec . 28 , 2017 Sheet 10 of 65 US 2017 /0368167 A9 FIG . 9A horoscoop mit 88 I C00300€ h wanawake * * minimumorigi ironnement orang ** 41*** * * * ** *: 21 B VW ansstorynot variante * woninis wawwwww wwwwwwwwwwwwwwwwww- %Startingbodyweight post-PR8challenge 823 . * * * * * * * * *. .. * * * * * * * * * * * * *** * * * 4444444 writinis pro song version * 0903008 cerimonia Salina 0. ???? ??? ?? ??2 ?? ?? ?? ??? 4? ?? 6 ???? ?? 8 ???? ?? ? ????10 Days after challenge FIG . 9B kurdistangomitopitongA A PR8PR8+ + diNd NCog/ + CPG 11 %StartingBodyweight moting Sains www on PRS * Saline PR8 * CpG 0 2 4 6 8 10 Days post challenge Patent Application Publication Dec . 28 , 2017 Sheet 11 of 65 US 2017 /0368167 A9 Hemagglutination inhibition and neutralizing antibody Uters during vaccination Hemagglutination - nhbition Antibody at booster dose , Day - 21 prior to challenge 512 seis 256susitikimas H H JobVH H 8 Sestdienas H 22.54g+Ad1pm ow+Bis27.50g*Ad1 apy+Bits27.5ug“Ad2 zoX+Bilg'a VaccineNoAd ONO ZpYongzz 225ugAd2Once Group FIG . 10A Patent Application Publication Dec . 28 , 2017 Sheet 12 of 65 US 2017 /0368167 A9 Hemagglutination - Inhbition Anibody on Day 7 prior to challenge E + k 101VH sweet 2 H I HH +A15u822. Onuo 7.519+Ad17Adte*g57. Ad2+54g7.A02549*7. 22.5ug*Adi zou+busz VaccineNoAd 22.500Ad2Once HOND a FIG . 10B Patent Application Publication Dec . 28 , 2017 Sheet 13 of 65 US 2017 /0368167 A9 Microneutralization antibody at booster dose , day 21 prior to challenge 2048 JauuogezjemnalogW 7.6ugAdi 7.5vg+Ad2 22.6ug*Adt 22.54g*Ad2 Vaccine*NoAd Oudoo 22519-A02Once Group FIG . 10C Patent Application Publication Dec . 28 , 2017 Sheet 14 of 65 US 2017 /0368167 A9 Microneutralization antibody at booster dose . day - 21 prior to chalenge H + MicroneutralizationTiter He + * * * oooooooooooooo 750gAd)von Onuo 7.5ugAd2 22.5ug*Adil zov+Bigzz Vaccine*NoAd 22.500 226ug*Ad2Once Group FIG . 10D Patent Application Publication Dec . 28 , 2017 Sheet 15 of 65 US 2017 /0368167 A9 100%:22.5ugInadz(once) OnsZpYuk. 100%.7,5ugnAdi aurpes*oricca:%29 *100%22.5ugnadieienaaris100%22.5ugsnsd2 kinge009. companiesnoiementS22629ONQuest . mesto ELI wwww HOWCACAOC Steinman Dosorown L w 000000 00000 OLL A wwwDay6Saline*InAdi Day5,25:Salinesnad2 inw ogooo000000dinniwwwwwwww 6 incon.Day6SalineSaline n 8 o w wamework 2 StudyDay Kawin i ndooooooooM AMA 000000 ?????????????????????????????????oo?????????????????????????????????????? book wwwwwwwwwww ** * * d seccovering wwwww too Survivalproportions W 9 wwwmero0000000wwwiinanaman € ainimiininanini 7 wamininiai000winning FIG.11 100 onmintainininn i vidio da ????????????????????????????????????????????0 survival Percent Patent Application Publication Dec . 28 , 2017 Sheet 16 of 65 US 2017 /0368167 A9 FIG . 12A 22 . 5 ug + Ad1 * * * * * * * * * * * * * * * * * * Www xvWWW ? ? ? ? ? ? ? ? ? ? percentweightchange Birmingham 11 13 7 . 5 ug + Ad1 ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? S mimpinning percentweightchange trand 1113 DPI FIG . 12C Patent Application Publication Dec . 28 , 2017 Sheet 17 of 65 US 2017 /0368167 A9 FIG . 12B in 22 .5 ug * Adt percentweightchange . .. * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * TTTTT WeightChangeafterchallenge DA 7 . 5 mg * Ad2 YYYYYYYYYYY TITI percentweightchange 77 7 OPI FIG . 12D Patent Application Publication Dec . 28 , 2017 Sheet 18 of 65 US 2017 /0368167 A9 Lord : : : : : : 22. 5 g
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