Dry-powder peptide medicament

• US 10,925,924 B2
• Filed: 03/17/2015
• Issued: 02/23/2021
• Est. Priority Date: 03/18/2014
• Status: Active Grant

• Current Assignee: Apeptico Forschung und Entwicklung GmbH
• Original Assignee: Apeptico Forschung und Entwicklung GmbH
• Inventors: Fischer, Bernhard
• Primary Examiner(s): Ha, Julie
• Assistant Examiner(s): Hellman, Kristina M
• Application Number:
  US15/126,794
• Publication Number:
  US 20170087207A1
• Time in Patent Office: 2,170 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Disclosed is a dry-powder peptide medicament with a non-typical concentration of carbohydrate excipient, as well as said medicament for use in treatment or prevention of a disease or condition, as well as methods for manufacturing said medicament.

Claims

1. A method for manufacturing a dry-powder medicament, comprising the steps of:

providing a cyclized peptide as an active agent, wherein the peptide consists of 7-17 amino acids and comprises the hexamer TPEGAE (SEQ ID NO;

     2), wherein the peptide is cyclic, and wherein the peptide does not exhibit TNF-receptor-binding activity;

dissolving or diluting the active agent, optionally together with a carbohydrate, in a solvent, wherein the solvent consists of water, thereby yielding a solution with a carbohydrate content of total solids in solution of less than 5% (w/w); and

removing the solvent from said solution by spray drying, spray-freeze-drying, supercritical fluid precipitation, air-jet milling, lyophilisation or rotary evaporation to obtain the dry-powder medicament.

2. The method according to claim 1, wherein the solution has a sugar content of total solids in solution of less than 5% and a sugar alcohol content of total solids in solution of less than 5% (w/w).

3. The method according to claim 1, wherein the solvent is removed by spray drying and the inlet temperature of the spray dryer is between 50-110°

C. and the outlet temperature of the spray dryer is between 20-80°

C.

4. The method according to claim 1, wherein the carbohydrate content of total solids in solution is less than 1% (w/w).

5. The method according to claim 1, wherein the carbohydrate content of total solids in solution is less than 0.1% (w/w).

6. The method according to claim 1, wherein the carbohydrate content of total solids in solution is less than 0.01% (w/w).

7. The method according to claim 1, wherein the total solids concentration before removal of the solvent is between 2-4% (w/v).

8. The method according to claim 3, wherein the solvent is removed by spray drying and the inlet temperature of the spray dryer is between 70-90°

C.

9. The method according to claim 3, wherein the solvent is removed by spray drying and the inlet temperature of the spray dryer is between 75-85°

C.

10. The method according to claim 3, wherein the solvent is removed by spray drying and the outlet temperature of the spray dryer is between 40-60°

C.

11. The method according to claim 3, wherein the solvent is removed by spray drying and the outlet temperature of the spray dryer is between 45-55°

C.

12. The method according to claim 1, wherein the total solids concentration before removal of the solvent is between 1-10% (w/v).

13. The method according to claim 1, wherein the medicament does not contain any excipient.

14. The method according to claim 1, wherein the medicament consists essentially of the peptide.

15. The method according to claim 14, wherein the peptide comprises the amino acid sequence CGQRETPEGAEAKPWYC (SEQ ID NO:

1).

16. The method according to claim 1, wherein the peptide comprises the amino acid sequence CGQRETPEGAEAKPWYC (SEQ ID NO:

1).

17. The method according to claim 1, wherein the medicament consists of powder particles of a mean diameter of 0.5 to 10 micrometers.

18. The method according to claim 17, wherein the medicament consists of powder particles of a mean diameter of 1 to 5 micrometers.

19. The method according to claim 18, wherein the medicament consists of powder particles of a mean diameter of 1 to 3.5 micrometers.

20. A method for manufacturing a dry-powder medicament, comprising the steps of:

providing a cyclized peptide as an active agent, wherein the peptide consists of 7-17 amino acids and comprises the hexamer TPEGAE (SEP ID NO;

2\ wherein the peptide is cyclic, and wherein the peptide does not exhibit TNF-receptor-binding activity;

dissolving or diluting the active agent in a solvent, thereby yielding a solution with the total solids in solution consisting of the peptide; and

removing the solvent from said solution by spray drying, spray-freeze-drying, supercritical fluid precipitation, air-jet milling, lyophilisation or rotary evaporation to obtain the dry-powder medicament.