Modified polynucleotides encoding aryl hydrocarbon receptor nuclear translocator

• US 9,050,297 B2
• Filed: 12/16/2013
• Issued: 06/09/2015
• Est. Priority Date: 04/02/2012
• Status: Active Grant

• Current Assignee: Moderna TX, Inc. (Moderna, Inc.)
• Original Assignee: Moderna Therapeutics, Inc. (Moderna, Inc.)
• Inventors: Chakraborty, Tirtha, de Fougerolles, Antonin, Weiss, Ron
• Primary Examiner(s): Ketter, James
• Assistant Examiner(s): Gonzalez, Antonio Galisteo
• Application Number:
  US14/106,957
• Publication Number:
  US 20140161873A1
• Time in Patent Office: 540 Days
• Field of Search: 514/44.R, 435/69.1
• US Class Current: 1/1
• CPC Class Codes: A61K 31/7115 Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
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• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
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• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61K 48/0066 Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
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Abstract

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

Claims

1. A mRNA encoding SEQ ID NO:

3901, wherein said mRNA comprises a coding region, said coding region having at least 85% identity to SEQ ID NO;

7603.

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. The mRNA of claim 1, wherein said coding region has at least 90% identity to SEQ ID NO:

7603.

8. The mRNA of claim 1, wherein said coding region has at least 95% identity to SEQ ID NO:

7603.

9. The mRNA of claim 1, wherein said coding region consists of SEQ ID NO:

7603.

10. A pharmaceutical composition comprising the codon optimized mRNA of claim 1 and a pharmaceutically acceptable excipient.

11. The pharmaceutical composition of claim 10 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.

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

13. The method of claim 12, 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.

14. The method of claim 13, wherein the 5′

untranslated region is heterologous to the coding region of the mRNA.

15. The method of claim 13, wherein the 3′

untranslated region is heterologous to the coding region of the mRNA.

16. The method of claim 13, wherein the 5′

untranslated region and the 3′

untranslated region are heterologous to the coding region of the mRNA.

17. The method of claim 13, wherein the mRNA comprises at least two stop codons.