Human serum albumin-free stabilized interferon liquid formulations

• US 8,309,069 B2
• Filed: 04/29/2004
• Issued: 11/13/2012
• Est. Priority Date: 05/01/2003
• Status: Active Grant

• Current Assignee: Ares Trading SA (Merck & Co., Inc.)
• Original Assignee: Ares Trading SA (Merck & Co., Inc.)
• Inventors: Samaritani, Fabrizio, Del Rio, Alessandra
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): Hissong, Bruce D
• Application Number:
  US10/554,602
• Publication Number:
  US 20070059285A1
• Time in Patent Office: 3,120 Days
• Field of Search: None
• US Class Current: 424/85.6
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/26 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 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: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A stabilized HSA-free liquid pharmaceutical composition is described, which comprises an interferon (IFN), wherein said formulation is a solution that comprises a buffer, a surfactant, an isotonicity agent and an antioxidant. Preferably the interferon is human recombinant IFN-beta.

Claims

1. A stabilized and preserved aqueous pharmaceutical composition free of human serum albumin, comprising:

interferon-β

1a in an amount of about 10 μ

g/ml to about 800 μ

g/ml;

acetate buffer present in an amount to maintain the pH of the composition within plus or minus 0.5 units of a specified pH, where the specified pH is about 3.0 to about 5.0;

poloxamer 188 surfactant in an amount of about 0.01 mg/ml to about 10 mg/ml;

methionine in an amount of about 0.01 to about 5.0 mg/ml;

benzyl alcohol in an amount of about 0.1% to about 2.0%; and

mannitol in an amount of 0.5 mg/ml to about 500 mg/ml.

2. The composition of claim 1, wherein said acetate buffer is present at a concentration of about 5 mM to 500 mM.

3. The composition of claim 1, wherein said acetate buffer is present at a concentration of about 10 mM.

4. The composition of claim 1 in which the interferon-β

1a is present in an amount of about 44 μ

g/ml.

5. The composition of claim 4, wherein said acetate buffer is present at a concentration of about 5 mM to 500 mM.

6. The composition of claim 4, wherein said acetate buffer is present at a concentration of about 10 mM.

7. The composition of claim 1 in which the interferon-β

1a is present in an amount of about 88 μ

g/ml.

8. The composition of claim 7, wherein said acetate buffer is present at a concentration of about 5 mM to 500 mM.

9. The composition of claim 7, wherein said acetate buffer is present at a concentration of about 10 mM.

10. A stabilized and preserved aqueous pharmaceutical composition free of human serum albumin, consisting essentially of:

interferon-β

1a in an amount of about 10 μ

g/ml to about 800 μ

g/ml;

acetate buffer present in an amount to maintain the pH of the composition within plus or minus 0.5 units of a specified pH, where the specified pH is about 3.0 to about 5.0;

poloxamer 188 surfactant in an amount of about 0.01 mg/ml to about 10 mg/ml;

methionine in an amount of about 0.01 to about 5.0 mg/ml;

benzyl alcohol in an amount of about 0.1% to about 2.0%;

mannitol in an amount of 0.5 mg/ml to about 500 mg/ml; and

water.

11. The composition of claim 10 in which the interferon-β

1a is present in an amount of about 44 μ

g/ml.

12. The composition of claim 10 in which the interferon-β

1a is present in an amount of about 88 μ

g/ml.

13. A stabilized and preserved aqueous pharmaceutical composition free of human serum albumin, consisting of:

interferon-β

1a in an amount of about 10 μ

g/ml to about 800 μ

g/ml;

acetate buffer present in an amount to maintain the pH of the composition within plus or minus 0.5 units of a specified pH, where the specified pH is about 3.0 to about 5.0;

poloxamer 188 surfactant in an amount of about 0.01 mg/ml to about 10 mg/ml;

methionine in an amount of about 0.01 to about 5.0 mg/ml;

benzyl alcohol in an amount of about 0.1% to about 2.0%;

mannitol in an amount of 0.5 mg/ml to about 500 mg/ml; and

water.

14. The composition of claim 13 in which the interferon-β

1a is present in an amount of about 44 μ

g/ml.

15. The composition of claim 13 in which the interferon-β

1a is present in an amount of about 88 μ

g/ml.