Manufacture of Degarelix

Patent metadata

Field	Value
Publication number	US-10172906-B2
Application number	US-201715420156-A
Country	US
Kind code	B2
Filing date	Jan 31, 2017
Priority date	Jun 1, 2012
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

The present invention provides methods for producing a lyophilized degarelix product which, upon reconstitution with water for injection in an amount of 20 mg/ml, shows a viscosity of up to 15 mPas. The present invention also provides a lyophilized degarelix drug substance which shows, upon dissolution in water in an amount of 20 mg/ml, a viscosity of up to 3.2 mPas, and processes for providing this lyophilized degarelix drug substance.

First claim

The invention claimed is:

1. A method for producing a degarelix drug substance comprising:
a. purifying degarelix obtained by solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by high-performance liquid chromatography (HPLC);
b. concentrating the degarelix solution to obtain aggregated degarelix;
c. deaggregating the aggregated degarelix with acetic acid to obtain deaggregated degarelix; and
d. lyophilizing the deaggregated degarelix to provide the degarelix drug substance.

2. The method of claim 1 , wherein concentrating the degarelix solution involves evaporating from the degarelix solution solvent.

3. The method of claim 1 , wherein the purity of the degarelix solution is at least 97.5%.

4. The method of claim 1 , wherein the deaggregated degarelix has an acetic acid concentration of 15 to 35% (v/v).

5. The method of claim 1 , wherein the deaggregated degarelix has a temperature of minus 5 (−5) to 30 degrees centigrade.

6. The method of claim 1 , wherein the deaggregated degarelix has a free base concentration of 10 to 35 g/l.

7. A method for producing a degarelix drug substance comprising:
a. purifying degarelix to obtain a degarelix solution with a purity of at least 95%, as determined by high-performance liquid chromatography (HPLC);
b. loading the degarelix solution onto a chromatographic column;
c. eluting degarelix from the column to provide eluted degarelix;
d. lyophilizing the eluted degarelix to provide the degarelix drug substance.

8. The method of claim 7 , wherein the eluted degarelix is filtered prior to lyophilization.

9. The method of claim 7 , wherein the purity of the degarelix solution is at least 97.5%.

10. The method of claim 7 , wherein the degarelix is deaggregated with acetic acid to form a deaggregated degarelix drug substance.

11. The method of claim 10 , wherein the deaggregated degarelix has an acetic acid concentration of 15 to 35% (v/v).

12. The method of claim 10 , wherein the deaggregated degarelix has a temperature of minus 5 (−5) to 30 degrees Centigrade.

13. The method of claim 7 , wherein the deaggregated degarelix has a free base concentration of 10 to 35 WI.

14. A method for producing a degarelix drug substance comprising:
a. purifying degarelix to obtain a degarelix solution with a purity of at least 95%, as determined by high-performance liquid chromatography (HPLC);
b. adjusting an acetic acid concentration of the purified degarelix solution to 6 to 40% (w/w); and
c. spray-drying the degarelix solution to provide the degarelix drug substance.

Assignees

• Ferring Bv

Inventors

• Schwach Grégoire
• Nilsson Anders
• Gottschalk Bøving Tine Elisabeth
• Rasmussen Jon Holbech
• Mörnstam Birgitta
• Tsirk Anders
• Annby Ulf
• Fomsgaard Jens

Classifications

• A61K38/08 Primary

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/25

  Growth hormone-releasing factor [GH-RF], i.e. somatoliberin · 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

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title