Granted Patent B2

US 12,383,617 · App. 17/250,015 · Granted Aug 12, 2025

Inventors: Jeffrey A. Hubbell (Chicago, IL); David Scott Wilson (Chicago, IL); Kym Brünggel (Chicago, IL); Kristen Marie Lorentz (Ecublens, CH)

Assignees: The University of Chicago; Anokion SA

A61K39/385A61K39/0008A61K39/001154A61K39/001158A61K39/4611A61K39/4644A61K47/549A61K47/60A61P37/06C07D249/16C08F220/58C08G65/332C08G65/3344C08G81/025A61K2039/6087A61K2039/6093A61K2239/38

Abstract

Claims (54)

1. A compound of Formula 1:

X—[Y(Z) p ] m —R 2    Formula 1

where:

X comprises an antigen, a tolerogenic portion thereof, or a mimetic thereof;

Y comprises a linker moiety;

Z comprises a moiety that specifically targets a mannose receptor;

p is an integer from 2 to 250;

m is an integer from 1 to 100;

R 2 is any of functional groups I-III:

where Ar is a substituted or unsubstituted aromatic group and one or more of:

R 3 is C 1-6 -alkyl; or

R 11 is C 1-6 -alkyl.

2. The compound of claim 1 , wherein the moiety that specifically targets a mannose receptor is selected from the group consisting of α-linked mannose, β-linked mannose, substituted mannose, mannose-6-phosphate, N-acetyl mannosamine, and mannan having β(1-4), α(1-6), α(1-2), and/or α(1-3) linkages.

3. The compound of claim 1 , wherein Y is a linker resulting from reaction of at least one of a N-hydroxysuccinamidyl linker, maleimide linker, PEG linker, vinylsulfone linker, pyridyl di-thiol-poly (ethylene glycol) linker, pyridyl di-thiol linker, n-nitrophenyl carbonate linker, NHS-ester linker, and nitrophenoxy poly (ethylene glycol) ester linker.

4. The compound of claim 3 , wherein Y is covalently bound to X.

5. The compound of claim 1 , wherein —[Y(Z) p ]— is represented by one of Formula Ya to Yr:

where

n is an integer from 1 to 100;

q is an integer from 1 to 44;

k is an integer from 1 to 12;

i is an integer from 0 to 20;

v is an integer from 1 to 4;

p is an integer from 2 to 250;

r is an integer from 0 to 250;

R 1 is —CH 2 —, —(CH 2 ) 2 —C(CH 3 )(CN)—, —(CH 2 ) 2 —C(CH 3 )(CH 3 )—, —(CH 2 ) 2 —CH(CH 3 )— or —CH(CH 3 )—;

W 1 and W 2 are as defined below:

R 9 is a direct bond, —(CH2)2-NH—C(O)— (an ethylaceetamido group or “EtAcN”) or —(CH2)2-(O—CH2-CH2)t-NH—C(O)— (a pegylated ethylacetamido group or “Et-PEGt-AcN”)

t is an integer from 1 to 5;

Z is mannose or a mannose receptor-targeting moiety; and

R 10 is an aliphatic group, an alcohol, an aliphatic amine-containing group, or an aliphatic alcohol.

6. The compound of claim 1 , wherein Y is an antibody, antibody fragment, peptide or other ligand that binds to X.

7. The compound of claim 1 , wherein X is an antigen against which a patient may develop or has developed an unwanted immune response.

8. The compound of claim 7 , wherein the antigen is a foreign transplant antigen, an alloantigen, an autoimmune antigen, a food antigen, an animal antigen, a plant antigen, an environmental antigen, a therapeutic antigen, a synthetic self-antigen, or a tolerogenic portion thereof.

9. The compound of claim 8 , wherein X is an asparaginase antigen or an ovalbumin antigen.

10. The compound of claim 1 , wherein the mannose receptor is mannose-6-phosphate receptor.

11. The compound of claim 1 , wherein Y and X are connected through a bond configured to cleave when the compound reaches a target area.

12. The compound of claim 1 , wherein Ar is selected from:

where each instance of R″, where present, is independently selected from an optionally substituted C 1-6 -alkyl, optionally substituted C 1-6 alkoxy, optionally substituted amino, OH, or halogen and wherein, X″ is a heteroatom.

13. The compound of claim 12 wherein X″ is N.

14. The compound of claim 1 , wherein R 11 is —CH 3 .

15. A composition comprising the compound of claim 1 .

16. A method of inducing immunological tolerance to an antigen target comprising administering to a subject a composition Formula 1:

X—[Y(Z) p ] m —R 2    Formula 1

where:

X comprises an antigen, a tolerogenic portion thereof, or a mimetic thereof;

Y comprises a linker moiety;

Z comprises a moiety that specifically targets a mannose receptor;

p is an integer from 2 to 250;

m is an integer from 1 to 100;

R 2 is any of functional groups I-III:

where Ar is a substituted or unsubstituted aromatic group and one or more of:

R 3 is C 1-6 -alkyl; or

R 11 is C 1-6 - alkyl.

17. The method of claim 16 , wherein the moiety that specifically targets a mannose receptor is selected from the group consisting of α-linked mannose, β-linked mannose, substituted mannose, mannose-6-phosphate, N-acetyl mannosamine, and mannan having β(1-4), α(1-6), α(1-2), and/or α(1-3) linkages.

Assignments (2)

Continuity (2)

References Cited (400)