Modified polynucleotides encoding citeD4

• US 9,114,113 B2
• Filed: 12/12/2013
• Issued: 08/25/2015
• 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
• Primary Examiner(s): Ketter, Jim
• Assistant Examiner(s): GALISTEO GONZALEZ, ANTONIO
• Application Number:
  US14/104,556
• Publication Number:
  US 20140186432A1
• Time in Patent Office: 621 Days
• Field of Search: None
• 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
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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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• CPC Class Codes: C07H 21/02 : with ribosyl as saccharide radical
• CPC Class Codes: C07K 14/005 : from viruses
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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. An mRNA encoding SEQ ID NO:

890, wherein said mRNA comprises a coding region having at least 80% identity to SEQ ID NO;

8481.

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 mRNA of claim 1, wherein the coding region is selected from the group consisting of SEQ ID NO:

8481, 8423 and 8438.

10. 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.

11. 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.

12. The method of claim 11, wherein the 5′

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

13. The method of claim 11, wherein the 3′

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

14. The method of claim 11, wherein the 5′

untranslated region and the 3′

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

15. The method of claim 11, wherein the mRNA comprises at least two stop codons.