Claims for Patent: 8,748,573

Summary for Patent: 8,748,573

Title:	Formulations comprising linaclotide
Abstract:	The present invention relates to stable compositions comprising linaclotide, as well as to various methods and processes for the preparation and use of the compositions.
Inventor(s):	Angelika Fretzen, Steven Witowski, Alfredo Grossi, Hong Zhao, Mahendra Dedhiya, Yun Mo
Assignee:	Allergan Pharmaceuticals International Ltd, Ironwood Pharmaceuticals Inc
Application Number:	US12/851,330
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,748,573
Patent Claims:	1. A method of treating chronic constipation or constipation-predominant irritable bowel syndrome in a patient in need thereof, comprising administering to the patient an oral, solid pharmaceutical dosage form comprising: between 100 μg and 300 μg of a peptide consisting of the amino acid sequence Cys1 Cys2 Glu3 Tyr4 Cys5 Cys6 Asn7 Pro8 Ala9 Cys10 Thr11 Gly12 Cys13 Tyr14 (SEQ ID NO:1) or a pharmaceutically acceptable salt thereof, wherein the peptide includes disulfide bonds between Cys1 and Cys6, Cys2 and Cys10, and Cys5 and Cys13; leucine in a molar ratio of leucine to the peptide between 40:1 and 20:1; and Ca2+ or a salt thereof in a molar ratio of Ca2+ the peptide between 70:1 and 50:1. 2. The method of claim 1, wherein the oral, solid pharmaceutical dosage form further comprises a polymer selected from polyvinyl pyrrolidone, polyvinyl alcohol, hydroxylpropyl methyl cellulose and mixtures thereof in an amount between 0.01 wt. % and 2 wt. % relative to the total weight of the oral dosage form. 3. A method of treating chronic constipation or constipation-predominant irritable bowel syndrome in a patient in need thereof, comprising administering to the patient an oral, solid pharmaceutical dosage form comprising a peptide consisting of the amino acid sequence Cys1 Cys2 Glu3 Tyr4 Cys5 Cys6 Asn7 Pro8 Ala9 Cys10 Thr11 Gly12 Cys13 Tyr14 (SEQ ID NO:1) or a pharmaceutically acceptable salt thereof, wherein the peptide includes disulfide bonds between Cys1 and Cys6, Cys2 and Cys10, and Cys5 and Cys13 in an amount between 0.2% by weight and 0.4% by weight, leucine in an amount between 0.5% by weight and 0.8% by weight, and a Ca2+ salt in an amount between 1.4% by weight and 1.65% by weight relative to the total weight of the oral dosage form. 4. The method of claim 3, wherein the leucine is present in the oral pharmaceutical dosage form in an amount between 0.6% by weight and 0.75% by weight, and the Ca2+ salt is present in the oral pharmaceutical dosage form in an amount between in an amount between 1.45% by weight and 1.65% by weight relative to the total weight of the oral dosage form. 5. The method of claim 3, wherein the amino acid is leucine and wherein the Ca2+ salt is in the form of calcium chloride. 6. The method of claim 1, wherein the amino acid is leucine and wherein Ca2+ is in the form of calcium chloride. 7. The method of claim 3, wherein the oral, solid pharmaceutical dosage form further comprises a polymer selected from polyvinyl pyrrolidone, polyvinyl alcohol, hydroxylpropyl methyl cellulose and mixtures thereof in an amount between 0.01 and 2 wt. % relative to the total weight of the oral dosage form. 8. The method of claim 1, wherein the Ca2+ or salt thereof and leucine are present in a molar ratio of at least 1.5:1. 9. The method of claim 1, wherein the dosage form further comprises a hydrolysis product of linaclotide at a concentration between 0.1 and 4 wt. %. 10. The method of claim 3, wherein the dosage form further comprises a hydrolysis product of linaclotide at a concentration between 0.1 and 4 wt. %.