Ferring B.v.

Polypeptide Laboratories A/s

Jens Fomsgaard

Jon Holbech Rasmussen

Anders Nilsson

Ulf Annby

Birgitta Mörnstam

Anders Tsirk

Grégoire Schwach

Tine Elisabeth Gottschalk Bøving

Stefan Hansen

Palle Hedengran Rasmussen

Wolfgang Oliver Wachs

Palle H Rasmussen

Haixiang Zhang

Gunnar Staerkaer

Wolfgang O Wachs

Tine Elisabeth Gottschalk Boeving

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.

Manufacture of degarelix

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.

Manufacture of Degarelix

The present invention relates to a liquid (or solution)-phase manufacturing process for preparing the decapeptide Degarelix, its protected precursor, and other useful intermediates. The invention further relates to polypeptides useful in the solution-phase manufacturing process and to the purification of Degarelix itself. Degarelix can be obtained by subjecting a Degarelix precursor according to formula (II): (P)AA-AA-AA-AA(P)-AA-AA(P)-AA-AA(P)-AA-AA-NH(II) or a salt or solvate thereof, to a treatment with a cleaving agent in an organic solvent, wherein Pis an amino protecting groups; preferably acetyl; Pis hydrogen or a hydroxy! protecting group, preferably a hydroxyl protecting group; Pis hydrogen or an amino protecting groups; preferably an amino protecting groups; and Pis an amino protecting group.

Process for the manufacture of Degarelix and its intermediates

In a step-wise synthesis of degarelix comprising 0.3% by weight or less of 4-([2-(5-hydantoyl)]acetylamino)-phenylalanine analog on (solid support)-NHa step comprises providing a solution of an amino acid or peptide of which the &#x3b1;-amino group is protected by Fmoc; contacting the support with the solution in the presence of reagent for forming a peptide bond between a carboxyl group of the amino acid or peptide and (solid support)-NH; removing Fmoc by contacting the support with an organic base, in particular piperidine, in an organic solvent. Also disclosed is degarelix of high purity prepared by the method of the invention and the use of Fmoc in the synthesis of degarelix.

Method for the manufacture of degarelix

The peptides Ac-D-2Nal-D-4ClPhe-D-3Pal-OH and Boc-D-2Nal-D-4ClPhe-D-3Pal-OH are intermediates useful in the synthesis of LHRH analogs by coupling with suitable heptapeptides, in particular with the heptapeptides P-Ser(P)-MMeTry(P)-D-Lys(Nic)-Leu-Lys(iPr,P)-Pro-D-AlaNHand P-Ser(P)-NMeTry(P)-D-Asn-Leu-Lys(iPr,P)-Pro-D-AlaNH.

Intermediates for LHRH antagonist synthesis, process for the production, and process for LHRH antagonist production

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Farum, Denmark

Jens Fomsgaard