US 11,786,505 B2
Methods and compositions for delivering mycophenolic acid active agents to non-human mammals
Michael Klotsman, San Francisco, CA (US); Padmaja Shivanand, Seattle, WA (US); Wayne H. Anderson, Raleigh, NC (US); and Gayatri Sathyan, Karnataka (IN)
Assigned to Okava Pharmaceuticals, Inc., San Francisco, CA (US)
Filed by OKAVA PHARMACEUTICALS, INC., San Francisco, CA (US)
Filed on Sep. 7, 2018, as Appl. No. 16/125,214.
Application 16/125,214 is a continuation in part of application No. PCT/US2018/022266, filed on Mar. 13, 2018.
Claims priority of provisional application 62/503,270, filed on May 8, 2017.
Claims priority of provisional application 62/470,806, filed on Mar. 13, 2017.
Prior Publication US 2019/0201375 A1, Jul. 4, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/365 (2006.01); A61K 9/50 (2006.01); A61K 31/343 (2006.01); A61K 9/20 (2006.01); A61P 37/06 (2006.01); A61P 37/02 (2006.01); A61K 9/16 (2006.01); A61K 9/48 (2006.01)
CPC A61K 31/365 (2013.01) [A61K 9/167 (2013.01); A61K 9/2072 (2013.01); A61K 9/5078 (2013.01); A61K 31/343 (2013.01); A61P 37/02 (2018.01); A61P 37/06 (2018.01); A61K 9/2027 (2013.01); A61K 9/2054 (2013.01); A61K 9/4808 (2013.01)] 20 Claims
 
1. A method for suppressing lymphocyte proliferation in a canine subject, comprising orally administering to the canine subject a single dose of a controlled-release composition per day for 15 or more days, wherein the controlled-release formulation comprises a multiparticulate drug delivery system (MDDS) containing a plurality of particulate subunits that each comprise:
i) a core having a diameter less than about 3 mm;
ii) an active layer disposed over at least a portion of the core and comprising a mycophenolic acid (MPA) active agent, wherein the MPA active agent is sodium mycophenolate;
iii) a controlled-release layer disposed over the active layer;
iv) a protective layer comprising a methacrylate-based polymer disposed over the controlled-release layer; and
achieving an average plasma [MPA] of about 250 ng/ml to about 3000 ng/ml over about 8 hours following a first dose of the controlled-release formulation,
whereupon at 2.5 hours, 4 hours, and 8 hours following the first dose, a percentage of proliferating lymphocytes in a whole blood sample from the subject is reduced by least about 35% as compared to a pre-dose percentage of proliferating lymphocytes in a whole blood sample obtained from the subject 15 or fewer minutes prior to the first dose, as determined using monoclonal antibody Ki-67, and the percentage of proliferating lymphocytes in the whole blood sample from the canine subject is lower than the percentage of proliferating lymphocytes in a whole blood sample obtained from a reference canine subject that received an immediate-release formulation comprising a MPA active agent, and
wherein over the 15 days, the canine subject exhibits a reduced number, a reduced severity, or both, of adverse gastrointestinal events as compared to the reference canine subject that received the immediate-release formulation comprising a MPA active agent, wherein the adverse gastrointestinal event is selected from the group consisting of emesis, diarrhea, and soft stool.