Granted Patent B2

US 9,616,126 · App. 14/926,450 · Granted Apr 11, 2017

Abstract

Claims (27)

1. A stable liquid pharmaceutical composition, suitable for administration by intravenous injection, subcutaneous injection, or inhalation without reconstitution, comprising:

(a) an alpha-1 proteinase inhibitor (API);

(b) about 0.1M to about 0.3M alanine; and

(c) a pharmaceutically acceptable carrier,

wherein the concentration of API in the composition is at least about 50 mg/ml; wherein the stable liquid pharmaceutical composition exhibits less than 5% aggregation and/or degradation after at least 24 months storage at a temperature between 5° C. and 25° C.; and wherein the percent aggregation and/or degradation is determined by size exclusion high performance liquid chromatography.

2. The composition of claim 1 wherein the pharmaceutically acceptable carrier comprises:

(a) sterile water; and

(b) optionally, one or more buffers or excipients.

3. The composition of claim 2 wherein the one or more buffers are selected from the group consisting of, monobasic sodium phosphate dibasic sodium phosphate, and mixtures thereof.

4. The composition of claim 2 wherein the one or more excipients are selected from the group consisting of sucrose, mannitol, glycerol, sorbitol, dextran, trehalose, hydroxyethyl starch, and 1,2-propanediol.

5. The composition of claim 3 wherein the phosphate is present in an amount to maintain the solution at a pH between 6.9 and 7.1.

6. A stable liquid pharmaceutical composition suitable for administration by intravenous injection, subcutaneous injection or inhalation without reconstitution, consisting essentially of:

(a) an alpha-1 proteinase inhibitor (API);

(b) about 0.1M to about 0.3M alanine; and

(c) a pharmaceutically acceptable carrier;

wherein the concentration of API in the composition is at least about 50 mg/ml; wherein the stable liquid pharmaceutical composition exhibits less than 5% aggregation and/or degradation after at least 24 months storage at a temperature between 5° C. and 25° C.; and wherein the percent aggregation and/or degradation is determined by size exclusion high performance liquid chromatography.

7. The composition of claim 6 wherein the pharmaceutically acceptable carrier consists of:

(a) sterile water; and

(b) a buffer.

8. The composition of claim 7 wherein the buffer is selected from the group consisting of monobasic sodium phosphate, dibasic sodium phosphate, and mixtures thereof.

9. The composition of claim 8 wherein the phosphate is present in an amount to maintain the solution at a pH between 6.3 and 7.4.

10. The composition of claim 8 wherein the phosphate is present in an amount to maintain the solution at a pH between 6.9 and 7.1.

11. A kit comprising the composition of claim 6 suitable for intravenous or subcutaneous injection.

12. A stable liquid pharmaceutical composition, suitable for administration by intravenous injection, subcutaneous injection, or inhalation without reconstitution, consisting essentially of:

(a) an alpha-1 proteinase inhibitor (API); and

(b) about 0.1M to about 0.3M alanine;

wherein the concentration of API in the composition is at least about 50 mg/ml; wherein the stable liquid pharmaceutical composition exhibits less than 5% aggregation and/or degradation after at least 24 months storage at a temperature between 5° C. and 25° C.; and wherein the percent aggregation and/or degradation is determined by size exclusion high performance liquid chromatography.

Assignments (25)