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US 11,504,337 B2Granted
Polynucleotides encoding methylmalonyl-CoA mutase
AssigneeModernaTX, Inc.
InventorsPaolo Martini, Vladimir Presnyak, Kerry Benenato, Stephen Hoge, Iain McFadyen, Ellalahewage Sathyajith Kumarasinghe
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Abstract
The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide.
Claims19
A lipid nanoparticle composition comprising:
- a messenger RNA (mRNA) that comprises an open reading frame (ORF) encoding a methylmalonyl-CoA mutase (MCM) polypeptide, and
- a compound of Formula (IA):
- or a salt or stereoisomer thereof, wherein:
- l is selected from 1, 2, 3, 4, and 5;
- m is selected from 5, 6, 7, 8, and 9;
- M1 is a bond or M′;
- R4 is unsubstituted C1-3 alkyl, or —(CH2)nQ, wherein n is 1, 2, 3, 4 or 5 and Q is OH, —NHC(S)N(R)2, or —NHC(O)N(R)2;
- M and M′ are independently selected from —C(O)O, OC(O), C(O)N(R′), P(O)(OR′)O, an aryl group, and a heteroaryl group;
- R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, and C2-14 alkenyl;
- each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
- each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
- each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
- each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
- and
- each Y is independently a C3-6 carbocycle.
12 more elements
Dependencies are inferred from the claim text.