US 12,214,083 B2
Pharmaceutical composition and administrations thereof
Eleni Dokou, Cambridge, MA (US); Shahla Jamzad, Belmont, MA (US); John P. Caesar, Jr., Lancaster, MA (US); Majed Fawaz, Foxboro, MA (US); Laura Das, Charlestown, MA (US); Chong-Hui Gu, Waban, MA (US); Patricia Nell Hurter, Harvard, MA (US); Meghna Jai Israni, Boston, MA (US); Meghan M. Johnston, Wakefield, MA (US); Dragutin Knezic, Watertown, MA (US); Andrew G. Kuzmission, Shrewsbury, MA (US); and HongRen Wang, Lexington, MA (US)
Assigned to Vertex Pharmaceuticals Incorporated, Boston, MA (US)
Filed by Vertex Pharmaceuticals Incorporated, Boston, MA (US)
Filed on Jul. 20, 2023, as Appl. No. 18/355,475.
Application 18/355,475 is a continuation of application No. 17/475,622, filed on Sep. 15, 2021, granted, now 11,752,106.
Application 17/475,622 is a continuation of application No. 16/299,675, filed on Mar. 12, 2019, granted, now 11,147,770, issued on Oct. 19, 2021.
Application 16/299,675 is a continuation of application No. 15/181,114, filed on Jun. 13, 2016, granted, now 10,272,046, issued on Apr. 30, 2019.
Application 15/181,114 is a continuation of application No. 14/715,682, filed on May 19, 2015, abandoned.
Application 14/715,682 is a continuation of application No. 14/510,507, filed on Oct. 9, 2014, abandoned.
Application 14/510,507 is a continuation of application No. 14/286,856, filed on May 23, 2014, granted, now 8,883,206, issued on Nov. 11, 2014.
Application 14/286,856 is a continuation of application No. 13/779,654, filed on Feb. 27, 2013, abandoned.
Claims priority of provisional application 61/710,352, filed on Oct. 5, 2012.
Claims priority of provisional application 61/603,882, filed on Feb. 27, 2012.
Prior Publication US 2024/0156738 A1, May 16, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/20 (2006.01); A61K 9/14 (2006.01); A61K 9/16 (2006.01); A61K 9/48 (2006.01); A61K 31/47 (2006.01); A61K 47/02 (2006.01); A61K 47/12 (2006.01); A61K 47/20 (2006.01); A61K 47/26 (2006.01); A61K 47/38 (2006.01); A61P 1/10 (2006.01); A61P 1/16 (2006.01); A61P 1/18 (2006.01); A61P 3/00 (2006.01); C07D 215/56 (2006.01)
CPC A61K 9/205 (2013.01) [A61K 9/143 (2013.01); A61K 9/145 (2013.01); A61K 9/146 (2013.01); A61K 9/1611 (2013.01); A61K 9/1617 (2013.01); A61K 9/1623 (2013.01); A61K 9/1652 (2013.01); A61K 9/2009 (2013.01); A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2054 (2013.01); A61K 9/2072 (2013.01); A61K 9/2077 (2013.01); A61K 9/4808 (2013.01); A61K 9/485 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61K 31/47 (2013.01); A61K 47/02 (2013.01); A61K 47/12 (2013.01); A61K 47/20 (2013.01); A61K 47/26 (2013.01); A61K 47/38 (2013.01); C07D 215/56 (2013.01)] 20 Claims
 
1. A pharmaceutical composition in a unit dose form comprising a plurality of granules or mini-tablets, wherein the composition comprises:
a) a solid dispersion in an amount from about 30 to about 40 percent by weight of the composition, wherein the dispersion comprises:
i. about 80 wt % of amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion,
ii. about 19.5 wt % of hydroxypropylmethylcellulose acetate succinate (HPMCAS) by weight of the dispersion, and
iii. about 0.5 wt % of sodium lauryl sulfate (SLS) by weight of the dispersion;
b) mannitol and lactose in an amount from about 30 to about 60 percent by weight of the composition, wherein mannitol and lactose are present in a ratio of about 1:3 mannitol to lactose;
c) sucralose in an amount from about 0.1 to about 5 percent by weight of the composition;
d) croscarmellose sodium in an amount from about 1.5 to about 8 percent by weight of the composition;
e) colloidal silicon dioxide in an amount from about 0.1 to about 5 percent by weight of the composition; and
f) magnesium stearate in an amount from about 0.1 to about 7 percent by weight of the composition;
wherein the unit dose form comprises at least about 5 mg of amorphous Compound 1, and
wherein less than about 15 wt % of the Compound 1 is crystalline.
 
13. A method of treating or lessening the severity of CFTR mediated disease in a pediatric patient comprising administering to the patient a pharmaceutical composition of claim 1.