Modified polynucleotides for the production of oncology-related proteins and peptides

Patent metadata

Field	Value
Publication number	US-9587003-B2
Application number	US-201615015684-A
Country	US
Kind code	B2
Filing date	Feb 4, 2016
Priority date	Apr 2, 2012
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

Abstract

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of oncology-related polynucleotides, oncology-related primary transcripts and oncology-related mmRNA molecules.

First claim

We claim:

1. An mRNA encoding a polypeptide of SEQ ID NO 7572, wherein said mRNA has a coding region having at least 80% sequence identity to SEQ ID NO: 16557.

2. The mRNA of claim 1 , wherein the mRNA comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.

3. The mRNA of claim 2 , wherein the 5′ untranslated region is heterologous to the coding region of the mRNA.

4. The mRNA of claim 2 , wherein the 3′ untranslated region is heterologous to the coding region of the mRNA.

5. The mRNA of claim 2 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the mRNA.

6. The mRNA of claim 2 , wherein the mRNA comprises at least two stop codons.

7. A pharmaceutical composition comprising the mRNA of claim 1 and a pharmaceutically acceptable excipient.

8. The pharmaceutical composition of claim 7 , wherein the pharmaceutically acceptable excipient is selected from a solvent, aqueous solvent, non-aqueous solvent, dispersion media, diluent, dispersion, suspension aid, surface active agent, isotonic agent, thickening or emulsifying agent, preservative, lipid, lipidoids liposome, lipid nanoparticle, core-shell nanoparticles, polymer, lipoplex, peptide, protein, cell, hyaluronidase, and mixtures thereof.

9. The pharmaceutical composition of claim 8 , where the pharmaceutical composition comprises a lipid and wherein said 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.

10. A method of producing a polypeptide of interest in a mammalian cell, tissue or organism comprising contacting said cell, tissue or organism with the mRNA of claim 1 .

11. The method of claim 10 , wherein the mRNA is formulated.

12. The method of claim 11 , wherein the formulation comprises a lipid which is selected from the group consisting of DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA, PEGylated lipids and mixtures or combinations thereof.

13. The method of claim 10 , wherein the contacting is a route of administration selected from the group consisting of intramuscular, intradermal, intravenous and subcutaneous.

14. The method of claim 13 , wherein the route of administration is intramuscular.

15. The method of claim 10 , wherein the mRNA comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.

16. The method of claim 15 , wherein the 5′ untranslated region is heterologous to the coding region of the mRNA.

17. The method of claim 15 , wherein the 3′ untranslated region is heterologous to the coding region of the mRNA.

18. The method of claim 15 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the mRNA.

19. The method of claim 15 , wherein the mRNA comprises at least two stop codons.

Assignees

• Moderna Therapeutics Inc
• Modernatx Inc

Inventors

• Bancel Stephane
• Chakraborty Tirtha
• De Fougerolles Antonin
• Elbashir Sayda M
• John Matthias
• Roy Atanu
• Whoriskey Susan
• Wood Kristy M
• Hatala Paul
• Schrum Jason P
• Ejebe Kenechi
• Ellsworth Jeff Lynn
• Guild Justin

Classifications

• A61K38/4833

  Thrombin (3.4.21.5) · CPC title

• A61K48/0075

  characterised by an aspect of the delivery route, e.g. oral, subcutaneous · CPC title

• A61K47/542

  Carboxylic acids, e.g. a fatty acid or an amino acid · CPC title

• C12N2840/00

  Vectors comprising a special translation-regulating system · CPC title

• C12Y113/12007

  Photinus-luciferin 4-monooxygenase (ATP-hydrolysing) (1.13.12.7), i.e. firefly-luciferase · CPC title