Granted Patent B2

US 12,569,512 · App. 17/744,407 · Granted Mar 10, 2026

Inventors: Katelyn Arnold (Chapel Hill, NC); Jian Liu (Chapel Hill, NC); Rafal Pawlinski (Chapel Hill, NC); Brian Cooley (Chapel Hill, NC)

Assignee: The University of North Carolina at Chapel Hill

A61K31/727A61P1/16A61P7/02

Abstract

Claims (27)

1 . A method of treating a subject suffering from liver ischemia reperfusion (I/R) injury or at risk of suffering liver I/R injury,

the method comprising administering to the subject one or more synthetic heparan sulfate (HS) compounds, wherein:

(i) the one or more synthetic HS compounds comprise a synthetic HS compound having the following structure:

wherein R 1 is —SO 3 H or —COCH 3 and R 2 is —H, alkyl, aryl, substituted alkyl, substituted aryl, or a functional handle;

(ii) the one or more synthetic HS compounds comprise one synthetic HS compound having the structure GlcNS6S-GlcA-GlcNS6S-IdoA2S-GlcNS6S-IdoA2S-GlcNS6S-IdoA2S-GlcNS6S-IdoA2S-GlcNS6S-GlcA-pNP and comprise one synthetic HS compound having the structure:

wherein R is —H, alkyl, aryl, substituted alkyl, substituted aryl, or a functional handle; and

wherein R 1 =H and n=1; R 1 =H and n=2; R 1 =GlcNS- or GlcNS6S- and n=1; or where R 1 =GlcA-GlcNS- or GlcA-GlcNS6S- and n=1; or

(iii) the one or more synthetic HS compounds comprise a synthetic HS compound having the structure:

wherein R 1 is —SO 3 H or —H and R 2 is —H, alkyl, aryl, substituted alkyl, substituted aryl, or a functional handle.

2 . The method of claim 1 , wherein the one or more synthetic HS compounds comprises a synthetic HS compound having the following structure:

wherein R 1 is —SO 3 H and R 2 —H, alkyl, aryl, substituted alkyl, substituted aryl, or a functional handle.

3 . The method of claim 1 , wherein the one or more HS compounds comprises a synthetic HS compound having the following formula:

wherein R 1 is —SO 3 H or —H and R 2 is —H, alkyl, aryl, substituted alkyl, substituted aryl, or a functional handle.

4 . The method of claim 1 , wherein the one or more synthetic HS compounds comprises a synthetic HS compound having the following formula:

wherein R is —H, alkyl, aryl, substituted alkyl, substituted aryl, or a functional handle; and

wherein

R1=H and n=1;

R1=H and n=2;

R 1 =GlcNS- or GlcNS6S and n=1; or

R 1 =GlcA-GlcNS or GlcA-GlcNS6S and n=1.

5 . The method of claim 1 , wherein the one or more synthetic HS compounds comprises a synthetic HS compound having the following formula:

wherein R is —H, alkyl, aryl, substituted alkyl, substituted aryl, or a functional handle.

6 . The method of claim 1 , wherein at least one of the one or more synthetic HS compounds binds HMGB1.

7 . The method of claim 1 , wherein the subject in need of treatment is a mammalian subject.

8 . The method of claim 1 , wherein the one or more synthetic HS compounds is administered as part of a pharmaceutical composition.

9 . The method of claim 8 , wherein the pharmaceutical composition comprises a synthetic HS compound and a pharmaceutically acceptable carrier or adjuvant for administration of the synthetic HS compound.

10 . The method of claim 1 , wherein the administering comprises administering two or more synthetic HS compounds, optionally wherein the two or more synthetic HS compounds are administered separately but at the same time, optionally wherein the two or more synthetic HS compounds are administered at different times, optionally wherein the two or more synthetic HS compounds are administered in a single composition.

Assignments (1)

Continuity (3)

References Cited (400)