	US 12,274,785 B2
	Sustained-release pharmaceutical compositions comprising an immunomodulating agent and uses thereof
Keelung Hong, South San Francisco, CA (US); Walter Gwathney, South San Francisco, CA (US); Jonathan Fang, South San Francisco, CA (US); Hao-Wen Kao, South San Francisco, CA (US); and Yi-Yu Lin, South San Francisco, CA (US)
Assigned to TAIWAN LIPOSOME CO., LTD., Taipei (TW); and TLC BIOPHARMACEUTICALS, INC., South San Francisco, CA (US)
Appl. No. 17/285,623
Filed by TAIWAN LIPOSOME CO., LTD., Taipei (TW); and TLC BIOPHARMACEUTICALS, INC., South San Francisco, CA (US)
PCT Filed Oct. 15, 2019, PCT No. PCT/US2019/056186 § 371(c)(1), (2) Date Apr. 15, 2021, PCT Pub. No. WO2020/081485, PCT Pub. Date Apr. 23, 2020.
Claims priority of provisional application 62/746,810, filed on Oct. 17, 2018.
Prior Publication US 2021/0393524 A1, Dec. 23, 2021
Int. Cl. A61K 9/127 (2006.01); A61K 9/1273 (2025.01); A61K 31/137 (2006.01); A61K 31/4245 (2006.01); A61K 47/02 (2006.01); A61K 47/24 (2006.01); A61K 47/26 (2006.01); A61K 47/28 (2006.01); A61K 47/36 (2006.01)

CPC A61K 9/127 (2013.01) [A61K 9/1273 (2013.01); A61K 31/137 (2013.01); A61K 31/4245 (2013.01); A61K 47/02 (2013.01); A61K 47/24 (2013.01); A61K 47/26 (2013.01); A61K 47/28 (2013.01); A61K 47/36 (2013.01)]

8 Claims

1. A pharmaceutical composition, comprising

(a) at least one liposome comprising a bilayer membrane, wherein the bilayer membrane comprises a mixture of about 45 to about 80 mole percent of a first lipid that is selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (HSPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and any combination thereof, about 20 to about 55 mole percent of cholesterol and 0.1-10 mole percent of a second lipid that is selected from the group consisting of N-(carbonyl-methoxypolyethyleneglycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG-DSPE), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPG) and any combination thereof;

(b) a trapping agent selected from the group consisting of triethylammonium sucrose octasulfate, ammonium sulfate, ammonium phosphate, and any combination thereof; and

wherein the molar ratio of the sphingosine-1-phosphate (S1P) receptor agonist to the lipid is higher than about 0.87 and the S1P receptor agonist is encapsulated in the liposome with an encapsulation efficiency higher than about 90%,

wherein when the S1P receptor agonist is fingolimod, the trapping agent is triethylammonium sucrose octasulfate, ammonium sulfate or ammonium phosphate, when the S1P receptor agonist is ozanimod, the trapping agent is ammonium sulfate.