US 12,257,267 B2
Click-modified mRNA
Thomas Frischmuth, Frischmuth (DE); Sascha Serdjukow, Kiefersfelden (DE); Birgit Graf, Munich (DE); and Stefano Croce, Munich (DE)
Assigned to BASECLICK GMBH, Neuried (DE)
Filed by BASECLICK GMBH, Neuried (DE)
Filed on Oct. 12, 2022, as Appl. No. 18/046,020.
Application 18/046,020 is a continuation of application No. 16/955,837, abandoned, previously published as PCT/EP2018/085676, filed on Dec. 18, 2018.
Claims priority of application No. 17209585 (EP), filed on Dec. 21, 2017; application No. 18157703 (EP), filed on Feb. 20, 2018; and application No. 18202542 (EP), filed on Oct. 25, 2018.
Prior Publication US 2023/0226094 A1, Jul. 20, 2023
Int. Cl. C07H 21/02 (2006.01); A61K 31/7115 (2006.01); C12N 15/85 (2006.01)
CPC A61K 31/7115 (2013.01) [C12N 15/85 (2013.01)] 20 Claims
 
1. A pharmaceutical composition comprising a modified messenger RNA (mRNA) comprising a 5′-cap structure, a 5′-untranslated region (5′-UTR), an open reading frame region (ORF), a 3′-untranslated region (3′-UTR) and a poly (A) tail region as an active agent, optionally in combination with a pharmaceutically acceptable adjuvant or excipient and/or contained in a pharmaceutically acceptable carrier, wherein the modified mRNA contains at least one of an alkyne- or azide modification in at least one nucleotide in
a) the ORF, the 5′-UTR, and the 3′ UTR,
b) the ORF, the 5′-UTR, the 3′-UTR, and the poly (A) tail region, or
c) only the poly (A) tail region,
wherein at least one of the following conditions applies:
(i) the mRNA does not contain a chain-terminating alkyne- or azide-modification at the 3′-ribose position in the poly (A) tail region,
(ii) at least one of the four standard types of nucleotides is present in modified form compared to the non-modified form in a ratio of 1:4 to 4:1;
(iii) the modified mRNA contains a functional molecule introduced via a click reaction of the modified mRNA with an alkyne-functional molecule corresponding to an azide modification of the modified mRNA or with an azide-functional molecule corresponding to an alkyne modification of the modified mRNA, which functional molecule is a tissue or cell specific targeting group or ligand, or
(iv) in the ORF and UTRs at least one nucleotide is alkyne-modified and at least one nucleotide is azide-modified.