Manufacture of degarelix

Patent metadata

Field	Value
Publication number	US-11510962-B2
Application number	US-202117154690-A
Country	US
Kind code	B2
Filing date	Jan 21, 2021
Priority date	Jun 1, 2012
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

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, a and processes for providing this lyophilized degarelix drug substance.

First claim

The invention claimed is:

1. A lyophilized degarelix drug substance consisting of degarelix, 4.5% to 10.00% (w/w) acetic acid, up to 10% (w/w) water, and, optionally, impurities due to its production process, wherein the lyophilized degarelix drug substance has a viscosity of up to 3.2 mPas, as determined upon dissolution in an amount of 20 mg degarelix free base in 1 ml of water containing 2.5% (w/V) mannitol.

2. The lyophilized degarelix drug substance of claim 1 , wherein the lyophilized degarelix drug substance has a viscosity ranging from 1.15 to 2.0 mPas, as determined upon dissolution in an amount of 20 mg degarelix free base in 1 ml of water containing 2.5% (w/V) mannitol.

3. The lyophilized degarelix drug substance of claim 2 , wherein the viscosity is determined 240 minutes after production of the lyophilized degarelix drug substance.

4. The lyophilized degarelix drug substance of claim 1 , wherein the lyophilized degarelix drug substance shows an optical density of 0 . 10 AU or less at a concentration of 20 mg degarelix free base/ml in 2.5% (w/V) aqueous mannitol.

5. The lyophilized degarelix drug substance of claim 4 , wherein the optical density is determined 240 minutes after production of the lyophilized degarelix drug substance.

6. A solution of degarelix, prepared by a reconstitution process consisting of reconstituting a lyophilized degarelix drug substance with a solvent consisting of water for injection consisting of water and, optionally, mannitol, to a degarelix concentration selected from 5 mg/ml, 15 mg/ml, 25 mg/ml, and 35 mg/ml of degarelix,
wherein the lyophilized degarelix drug substance consists of degarelix, 4.5% to 10.00% (w/w) acetic acid, up to 10% (w/w) water, and, optionally, impurities due to its production process, wherein the lyophilized degarelix drug substance has a viscosity of up to 3.2 mPas, as determined upon dissolution in an amount of 20 mg degarelix free base in 1 ml of water containing 2.5% (w/V) mannitol.

7. The lyophilized degarelix drug substance of claim 1 , containing impurities due to its production process.

8. The lyophilized degarelix drug substance of claim 1 , consisting of degarelix, 4.5% to 10.00% (w/w) acetic acid, and up to 10% (w/w) water.

9. The solution of claim 6 , wherein the lyophilized degarelix drug substance consists of degarelix, 4.5% to 10.00% (w/w) acetic acid, and up to 10% (w/w) water.

10. The solution of claim 6 , wherein the lyophilized degarelix drug substance contains impurities due to its production process.

11. The solution of claim 6 , wherein the reconstituting solvent consists of water for injection.

Assignees

• Ferring Bv

Inventors

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

Classifications

• A61K9/0024

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K7/06

  having 5 to 11 amino acids · 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

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title