Glycotargeting therapeutics

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 liver-targeting moiety;
• and
• a polymeric linker comprising:
• where
• the right bracket “)” indicates a bond between the linker and a corresponding reversible addition-fragmentation chain transfer (RAFT) polymerization agent;
• the bottom bracket “” indicates a bond between the linker and a liver targeting moiety;
• W is a copolymer or a random copolymer of the W1 and W2 having p repeat units, where:
• where:
• p is an integer from 2 to 150;
• R9 is a direct bond, —C(O)—NH—CH2—CH2—, or —C(O)—NH—(CH2—CH2—O—)t—CH2—CH2—;
• t is an integer from 1 to 5;
• R10 is an aliphatic alcohol;
• Y′ comprises:
• where
• n is an integer from 1 to 100;
• the left bracket “(” of Y′ indicates the bond between the antigen and linker;
• the right bracket “)” of Y′ indicates a bond between Y′ and the remainder of the polymeric linker;
• wherein the polymeric linker is bonded 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 cleave after administration of the composition to the subject and to release the antigen to which tolerance is desired from the polymeric linker.

A composition for the induction of antigen-specific immune tolerance in a subject, the composition comprising:

• one or more antigens to which tolerance is desired,
• wherein the one or more antigens to which tolerance is desired is capable of inducing an unwanted immune response in the subject;
• wherein the one or more antigens to which tolerance is desired comprises:
• one or more antigens associated with multiple sclerosis, or
• one or more antigens associated with Type I Diabetes;
• a liver targeting moiety, wherein the liver targeting moiety comprises N acetylgalactosamine;
• a polymeric linker comprising:
• where
• the right bracket “)” indicates a bond between the linker and a corresponding reversible addition-fragmentation chain transfer (RAFT) polymerization agent;
• the bottom bracket “” indicates a bond between the linker and a liver targeting moiety;
• W is a copolymer or a random copolymer of the W1 and W2 having p repeat units, where:
• where:
• p is an integer from 2 to 150;
• R9 is a direct bond, —C(O)—NH—CH2—CH2—, or —C(O)—NH—(CH2—CH2—O—)t—CH2—CH2—;
• t is an integer from 1 to 5;
• R10 is an aliphatic group, an alcohol or an aliphatic alcohol;
• Y′ comprises:
• where
• n is an integer from 1 to 100;
• the left bracket “(” of Y′ indicates the bond between the antigen and linker;
• the right bracket “)” of Y′ indicates a bond between Y′ and the remainder of the polymeric linker;
• wherein the polymeric linker is bonded to the one or more antigens via a disulfide bond or a disulfanyl ethyl ester,
• wherein the disulfide bond or the disulfanyl ethyl ester are each configured to cleave after administration of the composition to the subject and to release the one or more antigens from the polymeric linker.