Ultra-pure agonists of guanylate cyclase C, method of making and using same
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.
1. An oral formulation comprising a purified peptide comprising the Guanylate Cyclase-C(GCC) agonist of amino acid sequence of SEQ ID NO: 1, characterized in that the purified peptide has:
a) a bulk density of not greater than 0.1 g/mL;
b) less than 0.25% alpha-Asp-9-plecanatide relative to the weight of the purified peptide; and
c) 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 magnesium stearate.
4. The oral formulation of claim 1 , comprising 0.01 mg to 10 mg of the purified peptide.
5. The oral formulation of claim 1 , comprising 0.1 mg to 5 mg of the purified peptide.
6. The oral formulation of claim 1 , comprising 3 mg of the purified peptide.
7. The oral formulation of claim 1 , wherein the purified peptide has a bulk density of 0.03 to 0.1 g/mL.
8. The oral formulation of claim 1 , comprising 0.1% to 0.5% by weight of topoisomers relative to the weight of the purified peptide.
9. The oral formulation of claim 1 , comprising 0.15% to 0.25% by weight of alpha-Asp-9-plecanatide relative to the weight of the purified peptide.
10. An oral formulation comprising:
(i) a purified peptide comprising the Guanylate Cyclase-C(GCC) agonist of amino acid sequence of SEQ ID NO: 1, characterized in that the purified peptide has:
a) a bulk density of not greater than 0.1 g/mL;
b) less than 0.25% alpha-Asp-9-plecanatide relative to the weight of the purified peptide; and
c) less than 2% by weight of topoisomers relative to the weight of the purified peptide; and
(ii) at least one pharmaceutically acceptable excipient, wherein the at least one pharmaceutically acceptable excipient comprises microcrystalline cellulose.
11. The oral formulation of claim 10 , comprising 0.01 mg to 10 mg of the purified peptide.
12. The oral formulation of claim 10 , comprising 0.1 mg to 5 mg of the purified peptide.
13. The oral formulation of claim 10 , comprising 3 mg of the purified peptide.
14. The oral formulation of claim 10 , wherein the at least one pharmaceutically acceptable excipient further comprises magnesium stearate.
15. The oral formulation of claim 10 , wherein the purified peptide has a bulk density of 0.03 to 0.1 g/mL.
16. The oral formulation of claim 10 , comprising 0.1 to 0.5% by weight of topoisomers relative to the weight of the purified peptide.
17. The oral formulation of claim 10 , comprising 0.15 to 0.25% by weight of alpha-Asp-9-plecanatide relative to the weight of the purified peptide.