Granted Patent B2

US 9,221,891 · App. 14/390,106 · Granted Dec 29, 2015

Inventors: Stephane Bancel (Cambridge, MA); Tirtha Chakraborty (Medford, MA); Antonin de Fougerolles (Waterloo, BE); Sayda M. Elbashir (Cambridge, MA); Matthias John (Cambridge, MA); Atanu Roy (Stoneham, MA); Susan Whoriskey (Belmont, MA); Kristy M. Wood (Cambridge, MA); Paul Hatala (Charlestown, MA); Jason P. Schrum (Philadelphia, PA); Kenechi Ejebe (New York, NY); Jeff Lynn Ellsworth (Lexington, MA); Justin Guild (Framingham, MA)

Assignee: Moderna Therapeutics, Inc.

C07K14/47A61K9/1271A61K31/7115A61K48/0066C07K14/515C07K14/535C07K16/00C12N9/644A61K38/00

Abstract

Claims (15)

1. A method of producing a polypeptide of interest in vivo comprising contacting a mammalian cell, tissue or organism with at least one isolated mRNA encoding the polypeptide of interest, said at least one isolated mRNA comprising

a first region of linked nucleosides, said first region of linked nucleosides encoding SEQ ID NO: 320;

and wherein said first region of linked nucleosides comprise a coding region having at least 80% identity to SEQ ID NO: 321.

2. The method of claim 1 , wherein the isolated mRNA comprises a 3′ tailing sequence of linked nucleosides of approximately 140 nucleotides.

3. The method of claim 1 , wherein the isolated mRNA comprises a 3′ tailing sequence of linked nucleosides of approximately 160 nucleotides.

4. The method of claim 1 , wherein the isolated mRNA comprises a first flanking region located at the 5′ terminus of the first region, wherein said first flanking region comprises at least one 5′ terminal cap, and wherein said at least one 5′ terminal cap is Cap1.

5. The method of claim 1 , wherein the isolated mRNA is formulated.

6. The method of claim 5 , wherein the formulation is a lipoplex formulation.

7. The method of claim 5 , wherein the formulation comprises a lipid and wherein the lipid is selected from DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA and PEGylated lipids and mixtures thereof.

8. The method of claim 5 , wherein the isolated mRNA is administered at a total daily dose of between 1 ug and 150 ug.

9. The method of claim 1 wherein the isolated mRNA is administered in two or more equal or unequal split doses.

10. The method of claim 1 , wherein the isolated mRNA comprises a first flanking region located at the 5′ terminus of the first region and a second flanking region located at the 3′ terminus of the first region, wherein said first flanking region comprises a 5′ untranslated region (5′ UTR) and said second flanking region comprises a 3′ untranslated region (3 ′UTR).

11. The method of claim 10 , wherein the 5′UTR and the 3′UTR of the at least one isolated mRNA are not derived from the same species.

12. The method of claim 10 , wherein at least one of the 5′UTR or the 3′UTR of the at least one isolated mRNA is not derived from beta-globin.

13. The method of claim 1 , wherein the coding region is selected from the group consisting of SEQ ID NOs: 321 and 329-331.

Assignments (3)

Priority Claims (10)

Continuity (52)