Granted Patent B2

US 11,708,396 · App. 17/162,061 · Granted Jul 25, 2023

Inventors: Stephen G. Hoge (Brookline, MA); Tirtha Chakraborty (Medford, MA); Joshua P. Frederick (Charlestown, MA); Matthias John (Cambridge, MA); Antonin De Fougerolles (Waterloo, BE)

Assignee: ModernaTX, Inc.

C07K14/47A61K31/711A61K31/7105A61K48/0058C12N15/113C12N15/85A61K38/00C12N2310/141

Abstract

Claims (43)

1. A lipid nanoparticle (LNP) comprising a messenger RNA (mRNA) comprising:

(i) a 5′ cap structure;

(ii) a 5′ untranslated region (5′UTR);

(iii) an open reading frame (ORF) encoding a human OX40L polypeptide comprising the amino acid sequence of SEQ ID NO: 1800 or 1801; and

(iv) a 3′ untranslated region (3′UTR),

wherein each uridine is a 1-methylpseudouridine.

2. The LNP of claim 1 , wherein the 3′UTR comprises at least one microRNA (miR)-122-3p binding site or at least one miR-122-5p binding site.

3. The LNP of claim 2 , wherein the 3′UTR comprises at least one miR-122-3p binding site.

4. The LNP of claim 2 , wherein the 3′UTR comprises at least 2, 3, or 4 miR-122-3p binding sites.

5. The LNP of claim 2 , wherein the miR-122-3p binding site comprises the sequence set forth in SEQ ID NO: 3587.

6. The LNP of claim 2 , wherein the mRNA comprises at least one miR-122-5p binding site.

7. The LNP of claim 2 , wherein the mRNA comprises at least 2, 3, or 4 miR-122-5p binding sites.

8. The LNP of claim 2 , wherein the miR-122-5p binding site comprises the sequence set forth in SEQ ID NO: 3592.

9. The LNP of claim 1 , wherein the ORF comprises a nucleotide sequence at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the nucleotide sequence of SEQ ID NO: 640.

10. The LNP of claim 1 , wherein the mRNA comprises a poly A tail.

11. The LNP of claim 10 , wherein the poly A tail comprises at least 100, at least 120, or at least 140 nucleosides.

12. The LNP of claim 1 , wherein the OX40L polypeptide comprises the amino acid sequence of SEQ ID NO: 1800.

13. The LNP of claim 1 , wherein the OX40L polypeptide comprises the amino acid sequence of SEQ ID NO: 1801.

14. The LNP of claim 1 , wherein the mRNA comprises at least one modified cytidine.

15. The LNP of claim 14 , wherein the at least one modified cytidine is 5-methylcytidine.

16. A LNP comprising a mRNA comprising:

(i) a 5′ cap structure;

(ii) a 5′UTR;

(iii) an ORF encoding a human OX40L polypeptide comprising the amino acid sequence of SEQ ID NO: 1800; and

(iv) a 3′UTR comprising at least one miR-122-5p binding site or at least one miR-122-3p binding site,

wherein each uridine is a chemically modified uridine.

17. The LNP of claim 16 , wherein the ORF comprises a nucleotide sequence at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the nucleotide sequence of SEQ ID NO: 640.

18. The LNP of claim 16 , wherein the mRNA comprises a poly A tail.

19. The LNP of claim 18 , wherein the poly A tail comprises at least 100, at least 120, or at least 140 nucleosides.

20. The LNP of claim 16 , wherein the chemically-modified uridine is selected from 1-methylpseudouridine, 2-thiouridine, pseudouridine, and any combination thereof.

21. The LNP of claim 16 , wherein the chemically modified uridine is 1-methylpseudouridines.

22. The LNP of claim 17 , wherein the chemically-modified uridine is selected from 1-methylpseudouridine, 2-thiouridine, pseudouridine, and any combination thereof.

23. The LNP of claim 17 , wherein the chemically modified uridine is 1-methylpseudouridine.

24. The LNP of claim 16 , wherein the mRNA comprises at least one modified cytidine.

25. The LNP of claim 24 , wherein the at least one modified cytidine is 5-methylcytidine.

26. The LNP of claim 17 , wherein the mRNA comprises at least one modified cytidine.

27. The LNP of claim 26 , wherein the at least one modified cytidine is 5-methylcytidine.

28. The LNP of claim 16 , wherein the mRNA comprises at least one miR-122-5p binding site.

29. The LNP of claim 28 , wherein the mRNA comprises at least 2, 3, or 4 miR-122-5p binding sites.

30. The LNP of claim 28 , wherein the miR-122-5p binding site comprises the sequence set forth in SEQ ID NO: 3592.

31. The LNP of claim 16 , wherein the mRNA comprises at least one miR-122-3p binding site.

32. The LNP of claim 31 , wherein the mRNA comprises at least 2, 3, or 4 miR-122-3p binding sites.

33. The LNP of claim 31 , wherein the miR-122-3p binding site comprises the sequence set forth in SEQ ID NO: 3587.

Assignments (3)

Continuity (10)