Granted Patent B2

US 9,597,380 · App. 14/043,927 · Granted Mar 21, 2017

Inventors: Tirtha Chakraborty (Medford, MA); Stephane Bancel (Cambridge, MA); Stephen G. Hoge (Brookline, MA); Atanu Roy (Stoneham, MA); Antonin de Fougerolles (Brookline, MA); Noubar B. Afeyan (Cambridge, MA)

Assignee: ModernaTx, Inc.

A61K39/00C12N15/67

Abstract

Claims (18)

1. A method of reducing a protein antigen-mediated immune response in a subject, comprising administering to the subject a composition comprising a chemically modified mRNA and a pharmaceutically acceptable carrier, wherein the chemically modified mRNA comprises

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

(b) a region of linked nucleosides encoding said protein antigen;

(c) a 3′ untranslated region (3′ UTR) comprising at least one miR-142-3p microRNA binding site; and

(d) a 3′ tailing region of linked nucleosides,

wherein the chemically modified mRNA comprises fully modified 1-methyl pseudouridine nucleosides, and optionally comprises fully modified 5′ methyl-cytidine nucleosides, thereby reducing the protein antigen-mediated immune response in the subject.

2. The method of claim 1 , wherein the first region of linked nucleosides is codon optimized.

3. The method of claim 1 , wherein the chemically modified mRNA comprises fully modified 1-methyl pseudouridine nucleosides without fully modified 5′ methyl-cytidine nucleosides.

4. The method of claim 1 , wherein the chemically modified mRNA comprises fully modified 1-methyl pseudouridine nucleosides and fully modified 5′ methyl-cytidine nucleosides.

5. The method of claim 1 , wherein the miR-142-3p microRNA binding site comprises the sequence set forth in SEQ ID NO: 1404.

6. The method of claim 1 , wherein the 3′ tailing region of linked nucleosides comprises a poly A tail of at least 100, at least 120, or at least 140 nucleosides.

7. The method of claim 1 , wherein the chemically modified mRNA further comprises a 5′ cap structure.

8. The method of claim 7 , wherein the 5′ cap structure comprises Cap1.

9. The method of claim 1 , wherein the protein antigen is a therapeutic protein, cytokine, growth factor, antibody or fusion protein.

10. The method of claim 1 , wherein the chemically modified mRNA is formulated with a liposome, lipoplex, or lipid nanoparticle.

11. The method of claim 10 , wherein the chemically modified mRNA is formulated with a lipid nanoparticle.

12. The method of claim 11 , wherein the lipid nanoparticle comprises a cationic or ionizable lipid.

13. The method of claim 12 , wherein the cationic lipid is selected from the group consisting of DLin-MC3-DMA, DLin-DMA, C12-200 and DLin-KC2-DMA.

Assignments (3)

Continuity (11)