Dry powder composition comprising long-chain RNA

Patent metadata

Field	Value
Publication number	US-12138348-B2
Application number	US-202217676586-A
Country	US
Kind code	B2
Filing date	Feb 21, 2022
Priority date	May 20, 2015
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

Abstract

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-freeze drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

First claim

The invention claimed is:

1. A dry powder composition comprising long-chain RNA molecules having a length of 500 to 20,000 nucleotides, said composition produced by a method comprising:
a) providing a liquid comprising the long-chain RNA molecules, wherein the long-chain RNA molecules are in a complex with a cationic or polycationic compound,
b) drying the liquid provided of step a) by spray-freeze drying, wherein the spray-freeze drying comprises a step of atomization of the liquid at a temperature below −50° C., thereby producing the dry powder composition,

wherein the dry powder composition has a residual water content of 7% (w/w) or less,
wherein the dry powder composition comprises a plurality of particles having a mean diameter of about 100 μm to about 200 μm.

2. The dry powder RNA composition of claim 1 , wherein the dry powder composition comprises a plurality of particles having an average sphericity of the particles in a range from 0.7 to 1.0.

3. The dry powder RNA composition of claim 1 , wherein the drying b) comprises a step of spray-freezing and a step of lyophilization.

4. The dry powder RNA composition of claim 1 , wherein the dry powder composition has a residual moisture content of 3% (w/w) or less.

5. The dry powder RNA composition of claim 1 , wherein the dry powder composition has a residual moisture content of 1% (w/w) or less.

6. The dry powder RNA composition of claim 1 , wherein the dry powder composition comprises a carbohydrate component.

7. The dry powder RNA composition of claim 6 , wherein the cationic or polycationic compound is a cationic or polycationic polymer, a cationic or polycationic peptide or protein, and/or a cationic or polycationic lipid.

8. The dry powder RNA composition of claim 7 , wherein the cationic or polycationic compound is a cationic or polycationic lipid.

9. The dry powder RNA composition of claim 8 , wherein the carbohydrate component comprises glucose, mannose, lactose, maltose, sucrose, trehalose and/or cellobiose.

10. The dry powder RNA composition of claim 8 , wherein the dry powder composition has a residual moisture content of 3% (w/w) or less.

11. The dry powder RNA composition of claim 8 , wherein the long-chain RNAs are mRNAs that comprise an open reading frame encoding a protein.

12. The dry powder RNA composition of claim 11 , wherein the mRNAs comprise a 5′ Cap and a Poly(A) sequence of 40 to 200 adenine nucleotides.

13. The dry powder RNA composition of claim 12 , wherein the mRNAs further comprise a 5′ untranslated region (UTR) and a 3′ UTR.

14. The dry powder RNA composition of claim 12 , wherein the long-chain RNA molecules comprise at least one nucleotide modification selected from the group consisting of pseudouridine and 1-methyl-pseudouridine.

15. The dry powder RNA composition of claim 8 , wherein the long-chain RNA molecules are complexed with a lipid nanoparticle comprising cationic lipids.

16. The dry powder RNA composition of claim 8 , wherein the dry powder composition comprises cationic lipids, neutral (phospho)lipids and cholesterol.

17. The dry powder RNA composition of claim 8 , wherein the liquid comprising the long-chain RNA molecules comprises about 0.5 to about 10% (w/w) of the carbohydrate component.

18. The dry powder RNA composition of claim 8 , wherein the long-chain RNA molecules have a relative integrity is at least 75% after storage at room temperature for one month.

19. The dry powder RNA composition of claim 8 , wherein the dry powder composition comprises a plurality of particles having an average sphericity of the particles in a range from 0.7 to 1.0.

20. A dry powder composition comprising long-chain mRNA molecules having a length of 500 to 20,000 nucleotides, said molecules comprising a 5′ Cap, a 5′ UTR, an ORF encoding a protein, a 3′ UTR and a Poly(A) sequence of 40 to 200 adenine nucleotides,
wherein the long-chain mRNA molecules are in a complex with a cationic or polycationic compound,
said dry powder comprising a plurality of particles having a mean diameter of about 100 μm to about 200 μm and a residual moisture content of 3% (w/w) or less.

Assignees

• CureVac SE

Inventors

• Eber Fabian Johannes
• Yazdan Panah Benyamin
• Sewing Stefanie
• Ketterer Thomas
• Mutzke Thorsten
• Roos Tilmann
• Sonntag Michael
• Wiggenhorn Michael
• Kolland Katharina

Classifications

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K48/0091

  Purification or manufacturing processes for gene therapy compositions · CPC title

• A61K48/005 Primary

  characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title