12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 1111 RH 0 HI 010 IIM IV I I 0 101110 Ell 1101E1011H MI 1111 1111 Organization International Bureau (10) International Publication Number International Publication Date ......0\'\'1 WO 2018/078053 Al 03 May 2018 (03.05.2018) WIP0 I PCT (51) (21) (22) (25) Filing Language: (26) (30) (71) International Patent Classification: PEUTICS INC. [CA/CA]; 2714 West 31st Avenue, Van- A61K 39/12 (2006.01) A61K 47/18 (2017.01) couver, British Columbia V6L 2A1 (CA). A61K 39/39 (2006.01) A61K 9/127 (2006.01) (72) Inventors: BAUMHOF, Patrick; Erlenstr. 28, 72144 Dus- A61P 31/16 (2006.01) CO7C 219/06 (2006.01) A61P 31/14 (2006.01) CO7C 229/16 (2006.01) slingen (DE). FOTIN-MLECZEK, Mariola; Chemnitzer A61K 9/51 (2006.01) CO7C 233/18 (2006.01) Weg 10, 71065 Sindelfmgen (DE). HEIDENREICH, A61K 31/225 (2006.01) CO7C 255/24 (2006.01) Regina; BirkenstraBe 15, 72072 Tubingen (DE). HOPE, A61K 9/16 (2006.01) Michael J.; 3550 West 11th Avenue, Vancouver, British Columbia V6R 2K2 (CA). JASNY, Edith; Mohringer Str. International Application Number: 159, 70199 Stuttgart (DE). LAZZARO, Sandra; Michael- PCT/EP2017/077517 str. 9, 72070 Tiibingen (DE). LIN, Paulo Jia Ching; 2837 E. 54th Ave., Vancouver, British Columbia V5S 1Y4 (CA). International Filing Date: LUTZ, Johannes; HauBer Str. 142, 72076 Tiibingen (DE). 26 October 2017 (26.10.2017) MUI, Barbara; 1158 East 11th Avenue, Vancouver, British English Columbia V5T 2G3 (CA). PETSCH, Benjamin; Hagel- Publication Language: English locher Weg 44, 72070 Tubingen (DE). RAUCH, Susanne; Im Winkelrain 18, 72076 Tiibingen (DE). SCHMIDT, Kim Priority Data: Ellen; Talstr. 27, 72135 Dettenhausen (DE). TAM, Ying; PCT/EP2016/075843 3575 West 19th Avenue, Vancouver, British Columbia V6S 26 October 2016 (26.10.2016) EP 1C3 (CA). PCT/EP2016/075929 (74) Agent: PHARMA CONCEPTS GMBH; Unterer Rhein- 27 October 2016 (27.10.2016) EP weg 50, 4057 Basel (CH). PCT/EP2017/064066 09 June 2017 (09.06.2017) EP (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, Applicants: CUREVAC AG [DE/DE]; Paul-Ehrlich- AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, StraBe 15, 72076 Tubingen (DE). ACUITAS THERA- CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, EEEEE 7 S Y, ii 2 , g O -. . s a a an of (54) Title: LIPID 1.1o.- lx1C - c ix106- 1?) E 1,105- 1x10\' - 1x10 .3 NANOPARTICLE MRNA VACCINES PpLuc expression i.m. - 24h , A _ ixioB 'Ix A.R 4 1. A. • .. - § 1 • • .—. 1 , ,p • 118- s 1,10 7 • • - , 3 - 3 Is * ¨ 4 ci, ' c • , g g ix106 • '2 0, s 1,105 o_ o_ 1x10\' 1x10 3 PpLuc expression i.m. - 48h 4.-4,A 41-* • 4 4 * ;1. .• . .. 1 • -W- — ¨ .4. * :70. • • ¨ - 0 4 0 , , 0 ti0 A 4f ,, , > 0 ) .s> 4 ,zs f> , ,> ff 4S s p s Of A A A A A 4 A 4 A A ti ~4 's , • 's , p. 's , , c,,'\' 's ,C) . '' , s p4 , , ,s2 0 , 4 \ p4 . , ,,A , ,s2 , , p,s2 , , y 4 c) , , p4 A • • ;SY . c > t ' ) \'›.. ''). ob . , SO - ' 4: NS ) p' \'; .es.%'' , f,' ' GA 0 R V ' c k e ,o , , ,,, of' , , z sY A N- 0 e \,‘ 0 N . ,' N3- \ O ,o6 ° CP S c FIG. 1A FIG. 113 : The invention relates to mRNA comprising lipid nanoparticles and their medical uses. The lipid nanoparticles of the invention comprise a cationic lipid according to formula (I), (II) or (III) and/or a PEG lipid according to formula (IV), as well mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein. The invention further relates to the said lipid nanoparticles as vaccines or medicaments, in particular with respect to influenza or rabies vaccination. ,—, M un C> VD IN c: : :: , (57) -- -- GC present ,1 as 0 use ei C [Continued on next page] WO 2018/078053 Al MIDEDIMOMOIDEIREIDIONOMMOIREIMOVOIS DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) — with sequence listing part of description (Rule 5.2(a))
LIPID NANOPARTICLE MRNA VACCINES