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 a Guanylate Cyclase-C(GCC) agonist of amino acid sequence of SEQ ID NO: 1, wherein the purified peptide has less than 0.25% alpha-Asp-9-plecanatide relative to the weight of the purified peptide.
2. 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.
3. The oral formulation of claim 1 , comprising 0.01 mg to 10 mg of the purified peptide.
4. The oral formulation of claim 1 , comprising 0.1 mg to 5 mg of the purified peptide.
5. The oral formulation of claim 1 , comprising 3 mg of the purified peptide.
6. 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.
7. An oral formulation comprising:
(i) a purified peptide comprising a Guanylate Cyclase-C(GCC) agonist of amino acid sequence of SEQ ID NO: 1, wherein the purified peptide has less than 0.25% alpha-Asp-9-plecanatide 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.
8. The oral formulation of claim 7 , comprising 0.01 mg to 10 mg of the purified peptide.
9. The oral formulation of claim 7 , comprising 0.1 mg to 5 mg of the purified peptide.
10. The oral formulation of claim 7 , comprising 3 mg of the purified peptide.
11. The oral formulation of claim 7 , wherein the at least one pharmaceutically acceptable excipient further comprises magnesium stearate.
12. The oral formulation of claim 7 , comprising 0.15 to 0.25% by weight of alpha-Asp-9-plecanatide relative to the weight of the purified peptide.