US 12,109,271 B2
Microparticle systems and their use for the treatment of multiple sclerosis
Dorina Avram, Tampa, FL (US); Benjamin George Keselowsky, Gainesville, FL (US); Joshua Stewart, Gainesville, FL (US); and Jonathan Joseph Cho, Gainesville, FL (US)
Assigned to UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED, Gainesville, FL (US)
Appl. No. 17/257,731
Filed by UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED, Gainesville, FL (US)
PCT Filed Jul. 3, 2019, PCT No. PCT/US2019/040534
§ 371(c)(1), (2) Date Jan. 4, 2021,
PCT Pub. No. WO2020/010221, PCT Pub. Date Jan. 9, 2020.
Claims priority of provisional application 62/693,619, filed on Jul. 3, 2018.
Prior Publication US 2021/0169904 A1, Jun. 10, 2021
Int. Cl. A61K 47/59 (2017.01); A61K 31/203 (2006.01); A61K 31/436 (2006.01); A61K 31/593 (2006.01); A61K 38/18 (2006.01); A61K 38/19 (2006.01); A61K 38/20 (2006.01); A61K 39/00 (2006.01); A61P 25/00 (2006.01)
CPC A61K 47/593 (2017.08) [A61K 31/203 (2013.01); A61K 31/436 (2013.01); A61K 31/593 (2013.01); A61K 38/1841 (2013.01); A61K 38/1866 (2013.01); A61K 38/193 (2013.01); A61K 38/2066 (2013.01); A61K 39/0008 (2013.01); A61P 25/00 (2018.01)] 16 Claims
 
1. A dual microparticle system for targeting an antigen-presenting immune cell in a subject who is suspected of having, at risk of having or has Multiple Sclerosis, wherein the microparticle system is a composition that comprises: microparticles that are phagocytosable by the antigen-presenting immune cell, and microparticles that are non-phagocytosable by the antigen-presenting immune cell; wherein the phagocytosable microparticles together comprise at least one myelin antigen, the at least one myelin antigen being an antigen involved in pathogenesis of multiple sclerosis, and at least one immunomodulatory agent selected from vitamin D3, vitamin D3 analog, glucocorticoid, estrogen, rapamycin, and retinoic acid; and wherein the non-phagocytosable microparticles comprise at least one immunosuppressive tolerogenic agent selected from IL-10, TGF-p, and nonsteroidal anti-inflammatory drugs (NSAIDs), an agent that recruits the antigen-presenting immune cell of interest selected from GM-CSF, G-CFS, M-CSF, CCL19, CCL20, CCL21, and VEGF-C, wherein the microparticle system further comprises a remyelinating agent selected from clemastine, clobetasol, digoxin, miconazole, phenytoin, and quetiapine.