Polyphosphazene polyelectrolytes and uses thereof

Patent metadata

Field	Value
Publication number	US-11584828-B2
Application number	US-202017111043-A
Country	US
Kind code	B2
Filing date	Dec 3, 2020
Priority date	Jul 6, 2016
Publication date	Feb 21, 2023
Grant date	Feb 21, 2023

Abstract

Polyphosphazenes polyelectrolytes. The polyphosphazenes can be prepared by substituting pendant groups (e.g., ionic groups or pendant groups that can form ionic groups) onto a reactive macromolecular precursor for example, by reaction between the reactive chlorine atoms on the backbone of poly(dichlorophosphazene) and appropriate organic nucleophiles. In certain examples, one or more charged pendant groups of a polyphosphazene is/are further modified to introduce desired counterions, which can be hydrophobic counterions. The polyphosphazenes can activate distinct Toll-Like Receptors (TLRs) and can be used in methods of stimulating an immune response.

First claim

What is claimed is:

1. A polyphosphazene having the following structure:

wherein
Y + is independently at each occurance in the polyphosphazene is an cationic group selected from the group consisting of H + , Na + , K + , Ca 2+ , N-protonated spermine groups, N-protonated spermidine groups, N-protonated imidazoquinoline groups, N-protonated substituted imidazoquinoline groups, N- and/or S-protonated thiaimidazoquinoline groups, and N- and/or S-protonated substituted thiaimidazoquinoline groups,
with the proviso that at least one of the Y + groups is a N-protonated imidazoquinoline group, N-protonated substituted imidazoquinoline group, N- and/or S-protonated thiaimidazoquinoline group, or a N- and/or S-protonated substituted thiaimidazoquinoline group,
R − is independently at each occurance in the polyphosphazene an anionic group, and n is an integer from 10 to 500,000.

2. The polyphosphazene of claim 1 , wherein R − is selected from the group consisting of carboxylic acid groups, sufonic acid groups, phosphonic acid groups, and deprotonated forms thereof.

3. The polyphosphazene of claim 1 , wherein one or more Y + is:

wherein
R 1 is independently at each occurance in the polyphosphazene is —H,

and
R 2 is independently at each occurance in the polyphosphazene is —H, —CH 3 , —CH 2 —CH 2 —CH 3 ,

4. The polyphosphazene of claim 3 , wherein one or more Y + is:

5. The polyphosphazene of claim 1 , wherein R − is

and Y + is

6. The polyphosphazene of claim 1 , wherein the polyphosphazene has the following structure:

wherein
X is independently at each occurance in the polymer a linking moiety.

7. The polyphosphazene of claim 6 , wherein in the linking moiety has independently at each occurance one of the following structures:

8. The polyphosphazene of claim 1 , wherein the polyphosphazene has one of the following structures:

9. A composition comprising a polyphosphazene of claim 1 .

10. The composition of claim 9 , wherein the composition further comprises a pharmaceutically acceptable carrier.

11. The composition of claim 9 , wherein the composition comprises a polyphosphazene, vaccine antigen and, optionally, a pharmaceutically acceptable carrier.

12. The composition of claim 9 , wherein the composition comprises a polyphosphazene, an immunomodulating compound and/or TLR agonist, and, optionally, a pharmaceutically acceptable carrier.

Assignees

• Univ Maryland

Inventors

• Andrianov Alexander K
• Fuerst Thomas R
• Fusco Peter
• Marin Alexander

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• C08G79/025 Primary

  Polyphosphazenes · CPC title

• A61P37/04 Primary

  Immunostimulants · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title