Immunoglobulin Formulation and Method of Preparation Thereof

• US 20120328614A1
• Filed: 09/06/2012
• Published: 12/27/2012
• Est. Priority Date: 02/10/2003
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Inventors: Burke, David J., Buckley, Shaun E., Lehrman, Sherwood Russ, O'Connor, Barbara Horsey, Callaway, James, Phillips, Christopher P.
• Granted Patent: US 8,900,577 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/02 Inorganic compounds
• 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: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2839 against the integrin superfamily
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered

Abstract

A stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody, polysorbate 80, a buffer which inhibits polysorbate oxidation is described along with methods of making the preparation. Also described are formulations with high antibody concentrations which maintain fixed volumes and which may be used on patients of variable weight.

Claims

1. A stable, aqueous pharmaceutical formulation comprising from about 20 mg/ml to about 150 mg/ml of natalizumab, polysorbate 80 present in an amount of about 0.0001% to 2% (w/v), about 10 mM phosphate buffer, and about 140 mM NaCl.

2. The formulation of claim 1, comprising about 150 mg/ml natalizumab.

3. The formulation of claim 1, wherein the formulation is isotonic.

4. The formulation of claim 1, wherein the formulation is stable at a temperature of 2°

C. to 8°

C. for at least 6 months.

5. The formulation of claim 1, wherein the formulation has a pH of 3.0 to 7.0.

6. The formulation of claim 4, wherein the pH is 5.5 to 6.5.

7. An article of manufacture comprising a container holding the stable, aqueous pharmaceutical formulation of claim 1.

8. An article of manufacture comprising a container holding the stable, aqueous pharmaceutical formulation of claim 2.

9. An article of manufacture comprising a container holding the stable, aqueous pharmaceutical formulation of claim 3.

10. An article of manufacture comprising a container holding the stable, aqueous pharmaceutical formulation of claim 4.

11. An article of manufacture comprising a container holding the stable, aqueous pharmaceutical formulation of claim 5.

12. An article of manufacture comprising a container holding the stable, aqueous pharmaceutical formulation of claim 6.