Dry powder composition comprising long-chain RNA

Patent metadata

Field	Value
Publication number	US-11534405-B2
Application number	US-202016904993-A
Country	US
Kind code	B2
Filing date	Jun 18, 2020
Priority date	May 20, 2015
Publication date	Dec 27, 2022
Grant date	Dec 27, 2022

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 method for producing an RNA powder, wherein the method comprises the following steps:
a) providing a template DNA comprising a nucleic acid sequence encoding an RNA comprising at least 200 nucleotides in length;
b) in vitro transcribing the template DNA in order to obtain a liquid comprising the RNA;
c) purifying the liquid comprising the RNA obtained in step b);
d) formulating the RNA of step c) to form a complex with a cationic or polycationic compound to produce a formulated RNA; and
e) drying the liquid formulated RNA of step d) by spray-freeze drying to produce an RNA powder, wherein the powder comprises 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.

2. The method of claim 1 , wherein the drying comprises a step of spray-freezing and a step of lyophilization.

3. The method of claim 1 , wherein the spray-freeze drying comprises a step of atomization of the liquid at a temperature below −50° C.

4. The method according to claim 3 , wherein the droplets resulting from the atomization of the liquid are characterized by a mass median aerodynamic diameter of 300 nm to 200 μm.

5. The method of claim 1 , wherein the RNA powder has an average sphericity of the particles is in a range from 0.7 to 1.0.

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

7. The method of claim 1 , wherein the liquid comprising the RNA further comprises at least one excipient selected from a cryoprotectant, a lyoprotectant, and a bulking agent.

8. The method of claim 1 , wherein the liquid comprising the RNA does not contain a lipid compound.

9. The method of claim 1 , wherein the RNA comprises more than 500 nucleotides.

10. The method of claim 1 , 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.

11. The method of claim 1 , wherein the RNA molecule comprises at least one open reading frame (ORF) encoding a protein or a peptide.

12. The method of claim 1 , wherein the RNA molecule is an mRNA molecule.

13. The method of claim 1 , wherein the RNA molecule is a single-stranded RNA molecule.

14. The method of claim 1 , wherein the RNA molecule comprises at least one modification.

15. The method of claim 1 , wherein the RNA powder comprises at least one excipient.

16. The method of claim 1 , wherein upon reconstitution of the dry powder in a suitable solvent, the complexed long-chain RNA molecule is present in the solvent in the form of nanoparticles having a size of about 50 to 500 nm.

17. The method of claim 7 , wherein the at least one excipient comprises a free carbohydrate.

18. The method of claim 17 , wherein the at least one excipient comprises lactose, sucrose or trehalose.

Assignees

• Curevac Ag

Inventors

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

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K9/1682 Primary

  Processes · 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

• A61P37/02

  Immunomodulators · CPC title