	US 12,281,322 B2
	RNA replicon for versatile and efficient gene expression
Tim Beissert, Gross-Gerau (DE); Ugur Sahin, Mainz (DE); and Mario Perkovic, Frankfurt (DE)
Assigned to Biontech SE, Mainz (DE); and Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz Gemeinnützige GmbH, Mainz (DE)
Filed by BIONTECH SE, Mainz (DE); and TRON-Translationale Onkologie an der Universitätsmedizin der Johanne Gutenberg-Universität Mainz gem, Mainz (DE)
Filed on Oct. 5, 2021, as Appl. No. 17/494,601.
Application 17/494,601 is a continuation of application No. 16/086,157, granted, now 11,168,337, previously published as PCT/EP2017/055808, filed on Mar. 13, 2017.
Prior Publication US 2022/0033852 A1, Feb. 3, 2022
Int. Cl. C12N 15/86 (2006.01)

CPC C12N 15/86 (2013.01) [C12N 2770/36143 (2013.01)]

13 Claims

1. A pharmaceutical composition comprising an RNA replicon and a pharmaceutically acceptable carrier or excipient,

wherein the RNA replicon comprises

(a) a 5′ replication recognition sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 5, wherein the 5′ replication recognition sequence is characterized in that it comprises the removal of all initiation codons compared to the native alphavirus 5′ replication recognition sequence as set forth in SEQ ID NO: 4, and

(b) a first open reading frame encoding a first transgene which is not derived from an alphavirus, wherein the 5′ replication recognition sequence and the open reading frame do not overlap and wherein the initiation codon of the open reading frame is the first initiation codon in the 5′ to 3′ direction of the RNA replicon.