Compounds for the induction of antigen-specific immune tolerance

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

• an antigen to which tolerance is desired or a tolerogenic portion thereof;
• wherein the antigen to which tolerance is desired, when presented alone to the subject is capable of inducing an unwanted immune response in the subject;
• a polymeric linker that does not include a dithiobenzoate, trithiocarbonate, or a xanthate, the linker comprising:
• a copolymer or a random copolymer, wherein the copolymer or random copolymer comprises of first acrylyl unit and a second acrylyl unit, the first acrylyl unit comprising a first C-amido or C-carboxy functionality and the second acrylyl unit comprising a second C-amido or C-carboxy functionality;
• wherein the second C-amido or C-carboxy functionality is conjugated to an aliphatic group, an alcohol, or an aliphatic alcohol;
• wherein the polymeric linker is bonded to the antigen to which tolerance is desired or tolerogenic portion thereof via a disulfide bond or a disulfanyl ethyl ester,
• wherein the disulfide bond or the disulfanyl ethyl ester are each configured to be cleaved upon administration of the compound to the subject and to release the antigen to which tolerance is desired or tolerogenic portion thereof from the polymeric linker;
• wherein the polymeric linker comprises an end-capping group that improves the stability of the compound in solution by at least 20% as compared to a linker that includes a dithiobenzoate-containing, trithiocarbonate containing, or a xanthate-containing end-capping group;
• and
• a liver-targeting moiety;
• wherein the liver targeting moiety is connected to the first acrylyl unit through the first C-amido or C-carboxy functionality and a polyether.

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

• an antigen to which tolerance is desired;
• wherein the antigen to which tolerance is desired, when presented alone to the subject is capable of inducing an unwanted immune response in the subject;
• a polymeric linker comprising:
• a copolymer comprising a first acrylyl unit and a second acrylyl unit, the first acrylyl unit comprising a first C-amido or C-carboxy functionality and the second acrylyl unit comprising a second C-amido or C-carboxy functionality;
• wherein the second C-amido or C-carboxy functionality is conjugated to an aliphatic group, an alcohol, or an aliphatic alcohol;
• 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 polymeric linker comprises a terminal end unit lacking each of a dithioester and a dithiobenzoate (DTB) and wherein the terminal end unit confers improved stability to the compound when in solution;
• and
• a liver-targeting moiety;
• and
• wherein the liver targeting moiety is connected to the first acrylyl unit through the first C-amido or C-carboxy functionality and a polyether.