Ultra-pure agonists of guanylate cyclase C, method of making and using same

Patent metadata

Field	Value
Publication number	US-10745441-B2
Application number	US-201816000251-A
Country	US
Kind code	B2
Filing date	Jun 5, 2018
Priority date	Jun 5, 2013
Publication date	Aug 18, 2020
Grant date	Aug 18, 2020

Abstract

The invention provides processes of purifying a peptide including a GCC agonist sequence selected from the group consisting of SEQ ID NOs: 1-251 described herein. The processes include a solvent exchange step before a freeze-drying (lyophilization) step.

First claim

We claim:

1. A purified peptide comprising the Guanylate Cyclase-C(GCC) agonist sequence of SEQ ID NO: 9, wherein the purified peptide has the following characteristics:
a) has a bulk density of not greater than 0.1 g/mL;
b) contains less than 50 ppm acetamide; and
c) less than 0.05% trifluoroacetic acid (TFA) per total weight of the peptide.

2. The purified peptide of claim 1 , wherein the peptide is stable at 25° C. for at least three months.

3. The purified peptide of claim 1 , wherein the peptide has a particle size distribution characterized by:
a) a D10 value of between about 2-15 μm;
b) a D50 value of between about 15-50 μm; and
c) a D90 value of between about 40-80 μm,

when measured by light scattering with liquid dispersant.

4. The purified peptide of claim 1 , wherein the peptide has a bulk density of not greater than 0.06 g/mL.

5. The purified peptide of claim 1 , wherein the peptide has a chromatographic purity of no less than 97%.

6. The purified peptide of claim 1 , wherein the water content of the peptide is less than 10% of the total weight of the peptide.

7. The purified peptide of claim 1 , wherein the peptide contains less than 0.5% per weight of the peptide of one or more impurities selected from the group consisting of acetonitrile, alcohols, ammonium, and acetate.

8. The purified peptide of claim 7 , wherein the peptide contains less than 300 ppm acetonitrile.

9. The purified peptide of claim 7 , wherein the peptide contains less than 1000 ppm isopropanol.

10. The purified peptide of claim 7 , wherein the peptide contains less than 600 ppm isopropanol.

11. The purified peptide of claim 7 , wherein the acetate content of the peptide is less than 0.25% of the total weight of the peptide.

12. The purified peptide of claim 1 , wherein the topoisomer content of the peptide is less than 2% of the total weight of the peptide.

Assignees

• Bausch Health Ireland Ltd

Inventors

• Shailubhai Kunwar
• Comiskey Stephen
• Feng Rong
• Bai Juncai
• Zhang Ruoping
• Jia Jun
• Zhou Junfeng
• Zhao Qiao
• Zhang Guoqing

Classifications

• A61K38/10

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• B01D15/424

  Elution mode · CPC title

• C12Y406/01002

  Guanylate cyclase (4.6.1.2) · CPC title

• C12N9/88

  Lyases (4.) · CPC title

• C07K1/14

  Extraction; Separation; Purification · CPC title