AQUEOUS FORMULATION OF ERYTHROPOIESIS STIMULATING PROTEIN STABILISED BY ANTIOXIDANTS FOR PARENTERAL ADMINISTRATION

• US 20140294859A1
• Filed: 06/16/2014
• Published: 10/02/2014
• Est. Priority Date: 11/15/2007
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Sloey, Christopher James, Ko, Jason, Li, Tiansheng
• Granted Patent: US 11,433,134 B2
• Time in Patent Office: Days
• US Class Current: 424/172.1
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0019 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 Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

The present invention relates to stable aqueous protein formulations. In particular, disclosed herein are therapeutic protein formulations suitable for parenteral administration having one or more antioxidants.

Claims

1-91. -91. (canceled)

92. An aqueous formulation suitable for parenteral administration comprising an antibody and a stabilizing concentration of an antioxidant selected from the group consisting of vanillic acid, gallic acid, syringic acid, protocatechuic acid, cinnamic acid, coumaric acid, caffeic acid, ferulic acid, sinapic acid, chlorogenic acid, cytosine, thiamine, pyridoxine, fumaric acid, shikimic acid, glycolic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, catechin, epicatechin, furaneol, sulisobenzone, benzoic acid, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, m-cresol, benzyl alcohol, phenoxyethanol, phenol, a pharmaceutically acceptable salt or ester thereof, and mixtures thereof, wherein, when the antioxidant is benzoic acid, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, m-cresol, benzyl alcohol, phenoxyethanol, or phenol, the stabilizing concentration of the antioxidant is up to about 5 mM.

93. The aqueous formulation of claim 92, wherein,

when the antioxidant is vanillic acid, gallic acid, syringic acid, protocatechuic acid, cinnamic acid, coumaric acid, caffeic acid, ferulic acid, sinapic acid, or chlorogenic acid, the antioxidant is present in the aqueous formulation at a concentration of about 0.1 mM to about 20 mM,

when the antioxidant is benzoic acid, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, m-cresol, benzyl alcohol, phenoxyethanol, or phenol, the antioxidant is present in the aqueous formulation at a concentration of about 0.1 mM to about 5 mM, and

when the antioxidant is cytosine, thiamine, pyridoxine, fumaric acid, shikimic acid, glycolic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, catechin, epicatechin, furaneol, or sulisobenzone, the antioxidant is present in the aqueous formulation at a concentration of about 0.001 mM to about 100 mM.

94. The aqueous formulation of claim 92, comprising:

(i) coumaric acid and sorbitol, sucrose, methionine, or glycerol;

(ii) ferulic acid and sorbitol, sucrose, methionine, or glycerol;

or (iii) chlorogenic acid and sorbitol or sucrose.