US 11,654,188 B2
Glycotargeting therapeutics
Jeffrey A. Hubbell, Chicago, IL (US); David Scott Wilson, Lausanne (CH); Stephane Kontos, Boston, MA (US); Kristen Marie Lorentz, Boston, MA (US); and Shuning Gai, Gland (CH)
Assigned to Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (CH); and Anokion, SA, Ecublens (CH)
Filed by Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (CH); and Anokion SA, Ecublens (CH)
Filed on Dec. 20, 2019, as Appl. No. 16/723,757.
Application 16/723,757 is a continuation of application No. 14/859,292, filed on Sep. 19, 2015, granted, now 10,946,079.
Application 14/859,292 is a continuation in part of application No. 14/627,297, filed on Feb. 20, 2015, granted, now 10,821,157.
Claims priority of provisional application 61/942,942, filed on Feb. 21, 2014.
Prior Publication US 2020/0129601 A1, Apr. 30, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); A61K 39/385 (2006.01); A61K 39/35 (2006.01); A61K 47/54 (2017.01); A61K 38/38 (2006.01); A61K 38/28 (2006.01); A61K 38/00 (2006.01)
CPC A61K 39/001 (2013.01) [A61K 38/28 (2013.01); A61K 38/38 (2013.01); A61K 39/0002 (2013.01); A61K 39/0005 (2013.01); A61K 39/35 (2013.01); A61K 39/385 (2013.01); A61K 47/549 (2017.08); A61K 47/555 (2017.08); A61K 38/00 (2013.01); A61K 2039/555 (2013.01); A61K 2039/577 (2013.01); A61K 2039/60 (2013.01); A61K 2039/6093 (2013.01); A61K 2039/627 (2013.01); C07K 2319/01 (2013.01)] 20 Claims
 
1. A composition for the induction of antigen-specific immune tolerance in a subject, the composition comprising:
an antigen to which tolerance is desired;
wherein the antigen to which tolerance is desired is capable of inducing an unwanted immune response in the subject;
a polymeric linker;
wherein the polymeric linker is coupled to the antigen to which tolerance is desired via a disulfide bond or a disulfanyl ethyl ester;
wherein the disulfide bond or the disulfanyl ethyl ester are each configured to be cleaved after administration of the composition to the subject and to release the antigen to which tolerance is desired from the polymeric linker;
a liver-targeting moiety;
wherein the polymeric linker comprises the following structure:

OG Complex Work Unit Chemistry
where
the right bracket “)” indicates a bond between the linker and a corresponding reversible addition-fragmentation chain transfer (RAFT) polymerization agent;
the bottom bracket “custom character” indicates a bond between the linker and the liver targeting moiety;
Y′ comprises a remaining portion of the polymeric linker:

OG Complex Work Unit Chemistry
n is an integer from 1 to 100;
p is an integer from 2 to 150;
R9 comprises —C(O)—NH—CH2—CH2—;
the left bracket “(” indicates the bond between the antigen and linker;
the bottom bracket “custom character” indicates the bond between the linker and the liver targeting moiety; and
wherein the liver-targeting moiety comprises a galactosylating moiety or glucosylating moiety.