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

Patent metadata

Field	Value
Publication number	US-11319346-B2
Application number	US-202117478027-A
Country	US
Kind code	B2
Filing date	Sep 17, 2021
Priority date	Jun 5, 2013
Publication date	May 3, 2022
Grant date	May 3, 2022

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. An oral formulation comprising:
a purified peptide comprising the Guanylate Cyclase-C (GCC) agonist of amino acid sequence of SEQ ID NO: 1,
wherein the formulation comprises less than 2% by weight of topoisomers relative to the weight of the purified peptide.

2. The oral formulation of claim 1 , comprising less than 0.5% by weight of topoisomers relative to the weight of the purified peptide.

3. The oral formulation of claim 1 , wherein the formulation further comprises at least one pharmaceutically acceptable excipient, wherein the at least one pharmaceutically acceptable excipient comprises microcrystalline cellulose.

4. The oral formulation of claim 1 , comprising 0.01 mg to 10 mg of the purified peptide.

5. The oral formulation of claim 4 , comprising 0.1 mg to 5 mg of the purified peptide.

6. The oral formulation of claim 5 , comprising 3 mg of the purified peptide.

7. The oral formulation of claim 1 , wherein the formulation further comprises at least one pharmaceutically acceptable excipient, wherein the at least one pharmaceutically acceptable excipient further comprises magnesium stearate.

8. An oral formulation comprising:
(a) a purified peptide comprising the Guanylate Cyclase-C(GCC) agonist of amino acid sequence of SEQ ID NO: 1, wherein the purified peptide comprises less than 0.1% trifluoroacetic acid (TFA) by weight of the purified peptide; and
(b) one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients comprise microcrystalline cellulose.

9. The oral formulation of claim 8 , comprising 0.01 mg to 10 mg of the purified peptide.

10. The oral formulation of claim 8 , comprising 0.1 mg to 5 mg of the purified peptide.

11. The oral formulation of claim 8 , comprising 3 mg of the purified peptide.

12. The oral formulation of claim 8 , wherein the one or more pharmaceutically acceptable excipients further comprises magnesium stearate.

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

• B01D15/424

  Elution mode · CPC title

• C12N9/88

  Lyases (4.) · CPC title

• C07K1/14

  Extraction; Separation; Purification · CPC title

• A61K38/10

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

• C12Y406/01002

  Guanylate cyclase (4.6.1.2) · CPC title