Compositions and methods for inducing immune tolerance
AssigneesThe University of Chicago, Anokion SA
InventorsJeffrey A. Hubbell, David Scott Wilson, Kristen Marie Lorentz, Stephan Kontos
Life of this patent
Estimating the term…
Abstract
Several embodiments provided in the present disclosure relate to compositions that carry an antigen to which tolerance is desired, the antigen being coupled, bound, or otherwise joined to a targeting moiety, the targeting moiety configured to direct the composition to the liver of a subject. In several embodiments, the antigen in coupled to the targeting moiety by way of a polymeric linker. In several embodiments, the polymeric linker is configured to liberate the antigen in vivo. Methods of using the compositions to reduce and/or prevent unwanted immune responses against an antigen of interest are also provided.
Claims20
A method for inducing antigen-specific immune tolerance, the method comprising:
- administering to a subject a compound comprising Formula 1:
- where:
- m is an integer from 1 to 100;
- X comprises an antigen or a tolerogenic portion thereof;
- Y is of a linker moiety having a formula selected from the group consisting of:
- wherein:
- n is an integer from 1 to 100;
- q is an integer from 1 to 100;
- k is an integer from 1 to 12;
- i is an integer from 0 to 20;
- v is an integer from 1 to 4;
- R1 is selected from the group consisting of —CH2—, —(CH2)2—C(CH3)(CN)—, —(CH2)2—C(CH3)(CH3)—, —(CH2)2—CH(CH3)—, and —CH(CH3)—;
- and
- Y′ is a random copolymer or block copolymer of W1 and W2, where W1 and W2 are as depicted below:
- wherein the number of repeat units of W1 is denoted as p and wherein p is an integer of at least 1;
- wherein the number of repeat units of W2 is denoted as r and wherein r is an integer of at least 1;
- where R9 is a direct bond, —C(O)—NH—(CH2)2—, or
- —C(O)—NH—(CH2)2— (O—CH2—CH2)t—, where t is an integer from 1 to 5;
- and
- where R10 is —CH2—CH2—OH;
- and
- R2 is selected from the group consisting of:
- where Ar is a substituted or unsubstituted aromatic group, R3 is any carbon-containing linear or heterocyclic moiety, and R11 is hydrogen or an optionally substituted alkyl;
- and
- Z is galactose, glucose, galactosamine, glucosamine, N-acetylgalactosamine, or N-acetylglucosamine.
A method for inducing antigen-specific immune tolerance, the method comprising:
- administering to a subject a compound comprising Formula 1:
- where:
- m is an integer from 1 to 100;
- X comprises an antigen or a tolerogenic portion thereof, wherein X induces an unwanted immune response in a subject;
- where Y is:
- where:
- n is an integer from 1 to 100;
- q is an integer from 1 to 100;
- k is an integer from 1 to 12;
- i is an integer from 0 to 20;
- v is an integer from 1 to 4;
- R1 is selected from the group consisting of —CH2—, —(CH2)2—C(CH3)(CN)—, —(CH2)2—C(CH3)(CH3)—, —(CH2)2—CH(CH3)—, and —CH(CH3)—;
- and
- Y′ is a random copolymer or block copolymer of W1 and W2, where W1 and W2 are as depicted below:
- wherein the number of repeat units of W1 is denoted as p and wherein p is an integer of at least 1:
- wherein the number of repeat units of W2 is denoted as r and wherein r is an integer of at least 1;
- where R9 is a direct bond, —C(O)—NH—(CH2)2—, or
- —C(O)—NH—(CH2)2— (O—CH2—CH2)t—, where t is an integer from 1 to 5;
- and
- where R10 is —CH2—CH2—OH;
- and
- R2 is selected from the group consisting of
- where Ar is a substituted or unsubstituted aromatic group, R3 is any carbon-containing linear or heterocyclic moiety, and R11 is hydrogen or an optionally substituted alkyl;
- and
- Z is one or more of galactose, glucose, galactosamine, glucosamine, N-acetylgalactosamine, or N-acetylglucosamine, and wherein Z is conjugated at its C1, C2 or C6 to Y.
A method for inducing antigen-specific immune tolerance, the method comprising:
- administering to a subject a compound comprising Formula 1:
- where:
- m is an integer from 1 to 100;
- X comprises an antigen or a tolerogenic portion thereof, wherein X induces an unwanted immune response in a subject;
- where Y is:
- where:
- n is 43;
- Vis 2;
- q is 3;
- R1 is —(CH2)2-C(CH3)(CN)—;
- and
- Y′ is a random copolymer or block copolymer of W1 and W2, where W1 and W2 are as depicted below:
- wherein the number of repeat units of W1 is denoted as p and wherein p is an integer of at least 1;
- wherein the number of repeat units of W2 is denoted as r and wherein r is an integer of at least 1;
- where R9 is —C(O)—NH—(CH2)2-(O-CH2-CH2)t-, where t is 1;
- and
- where R10 is —CH2—CH2—OH;
- and
- R2 is selected from the group consisting of:
- where Ar is a substituted or unsubstituted aromatic group, R3 is any carbon-containing linear or heterocyclic moiety, and R11 is hydrogen or an optionally substituted alkyl;
- and
- Z is one or more of galactose, glucose, galactosamine, glucosamine, N-acetylgalactosamine, or N-acetylglucosamine, and wherein Z is conjugated at its C1, C2 or C6 to Y′.
Dependencies are inferred from the claim text.