Pharmaceutical composition containing double-stranded ribonucleic acid inhibiting expression of complement C5

Patent metadata

Field	Value
Publication number	US-12447173-B2
Application number	US-202017768283-A
Country	US
Kind code	B2
Filing date	Dec 24, 2020
Priority date	Dec 26, 2019
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

Disclosed is a pharmaceutical composition comprising a lipid complex, wherein the lipid complex comprises a double-stranded ribonucleic acid comprising a sense strand consisting of a nucleotide sequence set forth in SEQ ID NO: 145 and an antisense strand consisting of a nucleotide sequence set forth in SEQ ID NO: 146, and a pH of a solution of the lipid complex is 5.0 or less, or 7.5 or more.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising:
a lipid complex,
wherein the lipid complex comprises a double-stranded ribonucleic acid comprising a sense strand consisting of a nucleotide sequence set forth in SEQ ID NO: 145 and an antisense strand consisting of a nucleotide sequence set forth in SEQ ID NO: 146, and
a pH of a solution of the lipid complex is 5.0 or less or 7.5 or more.

2. The pharmaceutical composition according to claim 1 , wherein the pH of the solution of the lipid complex is 2.0 or more and 5.0 or less, or 7.5 or more and 11.0 or less.

3. The pharmaceutical composition according to claim 1 , wherein the pH of the solution of the lipid complex is 7.5 or more and 10.0 or less.

4. The pharmaceutical composition according to claim 1 , wherein an average particle size of the lipid complex is 100 nm or less.

5. The pharmaceutical composition according to claim 1 , wherein an average particle size of the lipid complex is 65 nm or more and 100 nm or less.

6. The pharmaceutical composition according to claim 1 , wherein an average particle size of the lipid complex is 80 nm or more and 100 nm or less.

7. The pharmaceutical composition according to claim 1 , wherein a change in an average particle size of the lipid complex after storage for 2 weeks is 10% or less from an average particle size of the lipid complex before the storage.

8. The pharmaceutical composition according to claim 7 , wherein the change in the average particle size of the lipid complex is increase in the average particle size of the lipid complex.

9. The pharmaceutical composition according to claim 1 , wherein the lipid complex comprises:
a cationic lipid; and
at least one lipid selected from the group consisting of neutral lipid, polyethylene glycol-modified lipid, and sterol.

10. The pharmaceutical composition according to claim 9 , wherein the cationic lipid is 2-{9-oxo-9-[(3-pentyloctyl)oxy]nonyl}dodecyl 1-methylpiperidine-4-carboxylate.

11. The pharmaceutical composition according to claim 1 , wherein the lipid complex is a lipid nanoparticle (LNP).

12. The pharmaceutical composition according to claim 1 , wherein the lipid complex encapsulates a double-stranded ribonucleic acid comprising a combination of a sense strand and an antisense strand.

13. A method for treating paroxysmal nocturnal hemoglobinuria, comprising administering the pharmaceutical composition according to claim 1 to a patient in need thereof.

14. A method for treating atypical hemolytic uremic syndrome, comprising administering the pharmaceutical composition according to claim 1 to a patient in need thereof.

15. A method for producing the pharmaceutical composition according to claim 1 , comprising:
adjusting the pH of the solution of the lipid complex to 5.0 or less, or 7.5 or more.

16. The method according to claim 15 , comprising:
adjusting the pH of the solution of the lipid complex to 2.0 or more and 5.0 or less, or 7.5 or more and 11.0 or less.

17. A method for stabilizing the pharmaceutical composition according to claim 1 , comprising:
adjusting the pH of the solution of the lipid complex to 5.0 or less, or 7.5 or more.

18. The method according to claim 17 , comprising:
adjusting the pH of the solution of the lipid complex to 2.0 or more and 5.0 or less, or 7.5 or more and 11.0 or less.

19. The method according to claim 17 , wherein the method for stabilizing the pharmaceutical composition is a method of suppressing a change in an average particle size of the lipid complex in the pharmaceutical composition.

20. The method according to claim 19 , wherein the method of suppressing the change in the average particle size is a method of suppressing increase in the average particle size.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Takemoto Seiji
• Arase Shuntaro
• Suzuki Yuta

Classifications

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61K9/1272

  comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) · CPC title

• A61P13/02 Primary

  of urine or of the urinary tract, e.g. urine acidifiers · CPC title

• A61K31/713 Primary

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title