Claims for Patent: 11,179,367

Summary for Patent: 11,179,367

Title:	Pharmaceutical compositions for treating cystic fibrosis
Abstract:	A pharmaceutical composition comprising Compound I: ##STR00001## Methods of treating cystic fibrosis comprising administering one or more of such pharmaceutical compositions to a patient.
Inventor(s):	Chu; Cathy (Cambridge, MA), Dhamankar; Varsha (Watertown, MA), Dokou; Eleni (Cambridge, MA), Haseltine; Eric L. (Melrose, MA), Moskowitz; Samuel (Waban, MA), Robertson; Sarah (Somerville, MA), Waltz; David (Waban, MA), Chen; Weichao George (San Diego, CA)
Assignee:	Vertex Pharmaceuticals Incorporated (Boston, MA)
Application Number:	16/267,222
Patent Claims:	1. A pharmaceutical composition comprising (a) 15 mg to 250 mg of Compound I: ##STR00102## (b) a first solid dispersion comprising 10 mg to 150 mg of Compound II: ##STR00103## and 10 wt% to 30 wt% of a polymer relative to the total weight of the first solid dispersion; and (c) a second solid dispersion comprising 25 mg to 200 mg of Compound III: ##STR00104## and 10 wt% to 30 wt% of a polymer relative to the total weight of the second solid dispersion. 2. The pharmaceutical composition of claim 1, comprising (a) 50 mg to 125 mg of Compound I; and wherein the first solid dispersion comprises 25 mg to 75 mg of Compound II; and the second solid dispersion comprises 50 mg to 175 mg of Compound III; or (b) 70 mg to 240 mg of Compound I; and wherein the first solid dispersion comprises 30 mg to 120 mg of Compound II; and the second solid dispersion comprises 50 mg to 170 mg of Compound III; or (c) 30 mg to 120 mg of Compound I; and wherein the first solid dispersion comprises 15 mg to 60 mg of Compound II; and the second solid dispersion comprises 20 mg to 90 mg of Compound III; or (d) 30 mg to 120 mg of Compound I; and wherein the first solid dispersion comprises 15 mg to 60 mg of Compound II; and the second solid dispersion comprises 50 mg to 170 mg of Compound III; or (e) 15 mg to 55 mg of Compound I; and wherein the first solid dispersion comprises 10 mg to 50 mg of Compound II; and the second solid dispersion comprises 20 mg to 90 mg of Compound III. 3. A pharmaceutical composition comprising: (a) 10 wt% to 30 wt% of Compound I: ##STR00105## relative to the total weight of the pharmaceutical composition; (b) 8 wt% to 30 wt% of a first solid dispersion relative to the total weight of the pharmaceutical composition, wherein the first solid dispersion comprises 70 wt% to 90 wt% of Compound II relative to the total weight of the first solid dispersion: ##STR00106## and 10 wt% to 30 wt% of a polymer relative to the total weight of the first solid dispersion; and (c) 10 wt% to 45 wt% of a second solid dispersion relative to the total weight of the pharmaceutical composition; wherein the second solid dispersion comprises 70 wt% to 90 wt% of Compound III relative to the total weight of the second solid dispersion: ##STR00107## and 10 wt% to 30 wt% of a polymer relative to the total weight of the second solid dispersion. 4. A single tablet comprising: (a) 25 mg to 125 mg of Compound I: ##STR00108## (b) 60 mg to 65 mg of a first solid dispersion comprising 80 wt% Compound II relative to the total weight of the first solid dispersion: ##STR00109## and 20 wt% of a hydroxypropyl methylcellulose relative to the total weight of the first solid dispersion; and (c) 90 mg to 95 mg, or 180 mg to 190 mg of a second solid dispersion comprising 80 wt% of Compound III relative to the total weight of the second solid dispersion: ##STR00110## 0. 5 wt% of sodium lauryl sulfate relative to the total weight of the second solid dispersion; and 19.5 wt% of a hydroxypropyl methylcellulose acetate succinate to the total weight of the second solid dispersion (d) 85 mg to 275 mg of microcrystalline cellulose; (e) 10 mg to 35 mg of croscarmellose sodium; and (f) 2 mg to 7 mg of magnesium stearate. 5. A single tablet of comprising: (a) 10 mg to 110 mg of Compound I: ##STR00111## (b) 25 mg to 70 mg of a first solid dispersion comprising 80 wt% Compound II relative to the total weight of the first solid dispersion: ##STR00112## and 20 wt% of a hydroxypropyl methylcellulose relative to the total weight of the first solid dispersion; and (c) 85 mg to 195 mg, of a second solid dispersion comprising 80 wt% of Compound III relative to the total weight of the second solid dispersion: ##STR00113## 0. 5 wt% of sodium lauryl sulfate relative to the total weight of the second solid dispersion; and 19.5 wt% of a hydroxypropyl methylcellulose acetate succinate to the total weight of the second solid dispersion (d) 10 mg to 45 mg of croscarmellose sodium; and (e) 95 mg to 280 mg of microcrystalline cellulose; and (f) 2 mg to 7 mg of magnesium stearate. 6. A pharmaceutical composition comprising (a) 12 wt% to 30 wt% Compound I relative to the total weight of the pharmaceutical composition: ##STR00114## (b) 5 wt% to 15 wt% of Compound II relative to the total weight of the pharmaceutical composition: ##STR00115## (c) 10 wt% to 25 wt% of Compound III or Compound III-d relative to the total weight of the pharmaceutical composition: ##STR00116## (d) 20 wt% to 45 wt% of microcrystalline cellulose relative to the total weight of the pharmaceutical composition; (e) 3 wt% - 8 wt% of croscarmellose sodium relative to the total weight of the pharmaceutical composition; and (f) 0.5 wt% to 2 wt% of magnesium stearate relative to the total weight of the pharmaceutical composition. 7. The pharmaceutical composition of claim 1, wherein Compound I is Crystalline Form A. 8. The pharmaceutical composition of claim 7, wherein Compound I Crystalline Form A is in substantially pure form. 9. The pharmaceutical composition of claim 7, wherein Compound I Crystalline Form A is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 6.6 .+-.0.2, 7.6 .+-.0.2, 9.6 .+-.0.2, 12.4 .+-.0.2, 13.1 .+-.0.2, 15.2 .+-.0.2, 16.4 .+-.0.2, 18.2 .+-.0.2, and 18.6 .+-.0.2. 10. A method of treating cystic fibrosis in a patient comprising orally administering to the patient one or more of the pharmaceutical composition of claim 1. 11. The method according to claim 10, wherein said patient having cystic fibrosis is chosen from patients with F508del/minimal function genotypes, patients with F508del/F508del genotypes, patients with F508del/gating genotypes, and patients with F508del/residual function genotypes. 12. A method of preparing the single tablet of claim 4, comprising (a) mixing Compound I and the first and second solid dispersions to form a first mixture; and (b) compressing a tablet mixture comprising the first mixture into a tablet. 13. A method of preparing the single tablet of claim 4, comprising (a) mixing Compound I and the first and second solid dispersions to form a first mixture; (b) mixing the first mixture with said microcrystalline cellulose, croscarmellose sodium and magnesium stearate to form a tablet mixture; and (c) compressing the tablet mixture into a tablet.