Dry powder composition comprising long-chain RNA

Patent metadata

Field	Value
Publication number	US-10517827-B2
Application number	US-201615575284-A
Country	US
Kind code	B2
Filing date	May 20, 2016
Priority date	May 20, 2015
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

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-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 preparing a dry powder comprising a long-chain RNA molecule, wherein the method comprises the steps of:
a) providing a liquid comprising the long-chain RNA molecule,
b) spray-drying the liquid of step a) with a spray-drying device having a drying gas inlet and a drying gas outlet, wherein the drying gas has a temperature at the inlet of at least 85° C., wherein the drying gas has a temperature at the outlet of at least 50° C.,
wherein the dry powder has a residual moisture content of 7% (w/w) or less, wherein the long-chain RNA molecule is in a complex with a cationic or polycationic compound, and wherein the long-chain RNA molecule comprises at least 200 nucleotides.

2. The method according to claim 1 , wherein the liquid of step a) further comprises at least one excipient selected from a cryoprotectant, a lyoprotectant and a bulking agent.

3. The method according to claim 1 , wherein the liquid of step a) does not contain a lipid compound.

4. The method according to claim 1 , wherein the liquid of step a) comprises a spray-drying-compatible solvent.

5. The method according to claim 1 , wherein the liquid of step a) is atomized and a droplet resulting from the atomization of the liquid is characterized by a mass median aerodynamic diameter of 300 nm to 200 μm.

6. The method according to claim 1 , which comprises a plurality of particles.

7. The method according to claim 6 , wherein the median particle size in a volume weighted distribution of the resulting dried powder is at least 1 μm.

8. The method according to claim 6 , wherein the average sphericity of the particles in the resulting dried powder is in a range from 0.7 to 1.0.

9. The method according to claim 1 , wherein the long-chain RNA molecule is present in the form of a free long-chain RNA molecule, or in the form of a complex comprising the long-chain RNA molecule.

10. The method according to claim 1 , wherein the long-chain RNA molecule comprises more than 200 nucleotides.

11. The method according to claim 1 , wherein the long-chain RNA molecule comprises at least one modification.

12. The method according to claim 1 , wherein the liquid of step a) further comprises a suspending agent and/or an osmolality of about 200 mosmol/l to about 400 mosmol/l.

13. The method according to claim 5 , wherein at least a first pressure nozzle is used as an atomizer, optionally wherein the pressure is less than about 1 bar.

14. The method according to claim 1 , wherein (a) the method is performed on bulk material, or the method is performed continuously, and/or (b) the method is performed in an open cycle device, or the method is performed in closed cycle device.

15. The method of claim 1 , wherein the dry powder comprises an average particle size of 1 μm to 20 μm.

Assignees

• Curevac Ag

Inventors

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

Classifications

• A61K48/005 Primary

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

• A61K48/0091

  Purification or manufacturing processes for gene therapy compositions · CPC title

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61K9/1682

  Processes · CPC title