US 11,918,643 B2
RNA vaccine against SARS-CoV-2 variants
Nicole Roth, Tübingen (DE); Diego Chaves Moreno, Tübingen (DE); Hans Wolfgang Große, Tübingen (DE); Dominik Vahrenhorst, Tübingen (DE); and Susanne Rauch, Tubingen (DE)
Assigned to CUREVAC SE, Tübingen (DE); and GLAXOSMITHKLINE BIOLOGICALS SA, Rixensart (BE)
Filed by CureVac SE, Tübingen (DE); and GLAXOSMITHKLINE BIOLOGICALS SA, Rixensart (BE)
Filed on Dec. 21, 2021, as Appl. No. 17/558,257.
Claims priority of provisional application 63/129,395, filed on Dec. 22, 2020.
Claims priority of application No. PCT/EP2021/052455 (WO), filed on Feb. 3, 2021; application No. PCT/EP2021/069626 (WO), filed on Jul. 14, 2021; and application No. PCT/EP2021/069632 (WO), filed on Jul. 14, 2021.
Prior Publication US 2022/0202930 A1, Jun. 30, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); A61K 9/127 (2006.01); A61K 9/51 (2006.01); A61K 31/713 (2006.01); A61K 39/215 (2006.01); A61K 45/06 (2006.01); A61K 47/26 (2006.01); A61K 47/60 (2017.01); A61K 47/69 (2017.01); A61P 31/14 (2006.01); C07K 16/10 (2006.01); C12N 7/00 (2006.01); C12N 15/113 (2010.01)
CPC A61K 39/215 (2013.01) [A61K 9/1272 (2013.01); A61K 9/5123 (2013.01); A61K 31/713 (2013.01); A61K 47/26 (2013.01); A61K 47/60 (2017.08); A61K 47/6933 (2017.08); A61P 31/14 (2018.01); C12N 7/00 (2013.01); C12N 15/1131 (2013.01); A61K 2039/53 (2013.01)] 27 Claims
 
1. A composition comprising
(a) an mRNA comprising:
(i) at least one coding sequence encoding a SARS-CoV-2 spike protein (S) at least 90% identical to SEQ ID NO: 10 that is a pre-fusion stabilized spike protein (S_stab) comprising K986P and V987P stabilizing mutations and 10 or more of the following substitutions relative to SEQ ID NO: 10: A67V, H69del, V70del, T951, G142D, V143del, Y144del, Y145del, N211del, L2121, ins214EPE, G339D, 5371L, S373P, S375F, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K and L981F, and
(ii) at least one heterologous untranslated region (UTR); and
(b) at least one pharmaceutically acceptable carrier,
wherein the mRNA is complexed or associated with a lipid nanoparticle (LNP) and wherein the LNP comprises:
(i) at least one cationic lipid;
(ii) at least one neutral lipid;
(iii) at least one steroid or steroid analogue; and
(iv) at least one PEG-lipid,
wherein (i) to (iv) are in a molar ratio of about 20-60% of the at least one cationic lipid, 5-25% of the at least one neutral lipid, 25-55% of the at least one steroid or steroid analogue, and 0.5-5% of the at least one PEG-lipid.