Patent SG-11201807378S-A (SG)
Title: Trans-replicating rna
Inventor: BEISSERT TIM
IPC: A61K48/00
Filed: 2017-03-13
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/162461 Al 28 September 2017 (28.09.2017) WIPO I PCT (51) International Patent Classification: C12N 15/86 (2006.01) C12N 5/10 (2006.01) C12N 15/40 (2006.01) A61K 48/00 (2006.01) (21) International Application Number: PCT/EP2017/055813 (22) International Filing Date: 13 March 2017 (13.03.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: PCT/EP2016/056160 21 March 2016 (21.03.2016) EP (71) Applicants: BIONTECH RNA PHARMACEUTICALS GMBH [DE/DE]; An der Goldgrube 12, 55131 Mainz (DE). TRON - TRANSLATIONALE ONKOLOGIE AN DER UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ GEMEIN- NUTZIGE GMBH [DE/DE]; Freiligrathstr. 12, 55131 Mainz (DE). (72) Inventors: BEISSERT, Tim; Edith-Stein-Weg 4, 64521 Gross-Gerau (DE). SAHIN, Ugur; Philipp-von-Za- bern-Platz 1, 55116 Mainz (DE). PERKOVIC, Mario; Falkenweg 1, 60437 Frankfurt (DE). (74) Agent: SCHNAPPAUF, Georg; ZSP Patentanwalte PartG mbB, Hansastrasse 32, 80686 Miinchen (DE). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, 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)) = (54) Title: TRANS-REPLICATING RNA Fig. 1 A SFV genome SGP (incl C\"E3) CSE4 MINV., aped & glyeopostelns -7300-1 -3700nt -11400nt cis-replicon L Gene of interest CSE1,2 SGP iCSE4 --poIyA -770.0nt transreplicon replicase encoding mRNA CSE1S2 SGP te , CSE4 polyA -1500nt (57) : The present invention generally relates to systems and methods suitable for high-level protein production. While one or more elements of the present invention are derived from an alphavirus, the present invention does not require propagation of virus particles. In particular, a system comprising two separate RNA molecules is foreseen, each comprising a nucleotide sequence derived from an alphavirus: one RNA molecule comprises a RNA construct for expressing alphavirus replicase, and one RNA molecule comprises a RNA re pi icon that can be replicated by the replicase in trans. The RNA construct for expressing alphavirus replicase comprises a 5'-cap. It was surprisingly found that the 5'-cap is suitable for efficiently driving expression of a transgene from the repl - icon in trans. The system of the present invention enables expression of a protein of interest in a cell or organism, but is not associ - ated with undesired virus-particle formation. Therefore, the present invention is suitable for efficiently and safely producing a pro - tein of interest, e.g. a therapeutic protein or an antigenic protein, such as a vaccine, in a target organism. Respective methods of pro - tein production in vitro and in vivo as well as medical uses are provided herein. The present invention also provides DNA encoding the RNA molecules of the invention, and cells comprising the RNA molecules of the invention. 1111111111111101110111111111110101111101110111111110101111111111011111111111110111111 W O 20 17 / 16 246 1 Al