US 11,786,567 B2
Compositions and methods for the treatment of type 1 diabetes
Pieter Rottiers, De Pinte (BE); and Lothar Steidler, Lokeren (BE)
Assigned to INTREXON ACTOBIOTICS N.V., Zwijnaarde (BE)
Filed by INTREXON ACTOBIOTICS N.V., Zwijnaarde (BE)
Filed on Jan. 15, 2021, as Appl. No. 17/150,352.
Application 17/150,352 is a division of application No. 16/069,947, granted, now 10,905,727, previously published as PCT/IB2017/050204, filed on Jan. 13, 2017.
Claims priority of provisional application 62/278,493, filed on Jan. 14, 2016.
Claims priority of provisional application 62/350,472, filed on Jun. 15, 2016.
Prior Publication US 2021/0154247 A1, May 27, 2021
Int. Cl. A61K 35/747 (2015.01); A61K 35/745 (2015.01); A61K 35/744 (2015.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01)
CPC A61K 35/747 (2013.01) [A61K 35/744 (2013.01); A61K 35/745 (2013.01); A61K 39/3955 (2013.01); A61K 2039/523 (2013.01); A61K 2039/542 (2013.01); A61K 2039/545 (2013.01); A61K 2039/55533 (2013.01)] 17 Claims
 
1. A method of treating type 1 diabetes mellitus (T1D) in a mammalian subject in need thereof comprising orally administering to the mammalian subject a therapeutically effective amount of a composition comprising a genetically modified lactic acid bacterium (LAB), wherein the LAB comprises an exogenous nucleic acid encoding human interleukin-2 (hIL-2) polypeptide and an exogenous nucleic acid encoding a type 1 diabetes mellitus (T1D)-specific antigen polypeptide, wherein the T1D-specific antigen polypeptide is human proinsulin (hPINS) polypeptide,
wherein said exogenous nucleic acid encoding said hPINS polypeptide comprises a polycistronic expression unit comprising, in 5′ to 3′ order, glyceraldehyde 3-phosphate dehydrogenase gene (gapB) with its promoter, and usp45 secretion leader (SSusp45) transcriptionally and translationally coupled to the sequence encoding said hPINS polypeptide; and
wherein said exogenous nucleic acid encoding said hIL-2 polypeptide comprises a polycistronic expression unit comprising, in 5′ to 3′ order, phosphopyruvate hydratase gene (eno) with its promoter, and usp45 secretion leader (SSusp45) transcriptionally and translationally coupled to the sequence encoding the hIL-2 polypeptide.