Formulations for delivery of osteogenic proteins

• US 5,385,887 A
• Filed: 09/10/1993
• Issued: 01/31/1995
• Est. Priority Date: 09/10/1993
• Status: Expired due to Term

• Current Assignee: Genetics Institute LLC (Pfizer Inc.)
• Original Assignee: Genetics Institute LLC (Pfizer Inc.)
• Inventors: Schrier, Jay A., Yim, Kalvin W. K., Huberty, Michael C., Northey, Richard P. Jr.
• Primary Examiner(s): Wityshyn, Michael G.
• Assistant Examiner(s): Gromet, Nancy J.
• Application Number:
  US08/119,772
• Time in Patent Office: 508 Days
• Field of Search: 106/645, 106/646, 106/650, 106/651, 106/652, 106/653, 424/78.08, 424/78.37, 424/422, 424/423, 424/424, 424/425, 424/426, 424/529, 514/8, 514/12, 514/21, 530/350, 530/397, 530/399, 530/840, 623/11, 623/16, 623/17, 623/18, 623/19, 623/20, 623/21, 623/22, 623/23
• US Class Current: 514/8.8
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61L 27/025 Other specific inorganic materials not covered by A61L27/04 - A61L27/12
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: Y10S 530/84 Bones; tendons; teeth; cartilage

Abstract

A composition is disclosed comprising a pharmaceutically acceptable admixture of an osteogenic protein; a porous particulate polymer matrix; an osteogenic protein-sequestering amount of blood clot; and a calcium sulfate hemihydrate-containing substance. Also disclosed are formulations of bone morphogenetic proteins with improved solubility and/or stability characteristics.

Claims

1. A composition comprising an osteogenic protein, about 0.1 to about 5.0% (w/v) of a sugar, about 1.0 to about 10.0% (w/v) glycine, and about 1 to about 20 mM of glutamic acid hydrochloride, wherein such composition has a pH of about 4.5.

2. The composition of claim 1, further comprising about 0.01 to about 0.1% (w/v) of a non-ionic surfactant.

3. A composition comprising an osteogenic protein, about 1 to about 10% (w/v) glycine, about 0.1 to about 5.0% (w/v) sucrose, about 0.01 to about 0.1% (w/v) non-ionic surfactant and about 5 to about 10 mM glutamic acid hydrochloride, wherein such composition has a pH less than about 6.0.

4. A composition comprising an osteogenic protein, about 2.5% (w/v) glycine, about 0.5% (w/v) sucrose, about 5 mM glutamic acid hydrochloride, and about 0.01% (w/v) polysorbate 80, wherein such composition has a pH of about 4.5.

5. A composition comprising a lyophilized formulation of about 3.12% to about 24.38% (w/w) BMP;

about 0.52% to about 10.27% (w/w) glutamic acid hydrochloride;

about 38.4% to about 75.7% (w/w) glycine;

about 14.28% to about 47.15% (w/w) sucrose; and

optionally about 0.15% to about 2.94% (w/w) polysorbate 80.

6. A composition according to claim 5 wherein the lyophilized formulation comprises relative weight amounts of about 4.0 mg/ml of BMP-2;

about 0.918 mg/ml of glutamic acid hydrochloride;

about 25 mg/ml of glycine;

about 5 mg/ml of sucrose; and

optionally about 0.1 mg/ml of polysorbate 80.

7. A composition according to claim 5 wherein the lyophilized formulation comprises relative weight amounts of about 2.0 mg/ml of BMP-2;

about 0.918 mg/ml of glutamic acid hydrochloride;

about 25 mg/ml of glycine;

about 5 mg/ml of sucrose; and

optionally about 0.1 mg/ml of polysorbate 80.