Granted Patent B2

US 12,409,135 · App. 18/062,416 · Granted Sep 9, 2025

Inventors: Philip T. Liu (Culver City, CA); Clifford Anders Olson (Culver City, CA); Wade Nichols Richardson (Culver City, CA); Wendy Higashide (Culver City, CA)

Assignee: ImmunityBio, Inc.

A61K9/06A61K38/063A61K41/0028A61K47/36C12N15/1055C12N15/87

Abstract

Claims (14)

1. A method of making a self-assembling mannan nanogel for in vivo delivery of therapeutic agents, the method comprising:

a. oxidizing mannan with periodate (NaIO4);

b. purifying the oxidized mannan;

c. adding aniline to the purified oxidized mannan to produce a mannan derivative with hydrophobic phenylimine groups covalently attached to the mannan, wherein the mannan derivative self-assembles into a mannan nanogel;

d. further reacting the mannan nanogel with succinate dihydrazide (SDH) and 3,3′-Dithiobis(propanoic dihydrazide) (DPDH), thereby introducing dihydrazide crosslinkers into the self-assembled mannan nanogel;

e. further reducing the mannan nanogel disulfide crosslinks with (tris(2-carboxyethyl) phosphine) (TCEP);

f. reducing imines and residual aldehydes in the mannan nanogel with borohydride (NaBH4); and

g. activating thiols in the mannan nanogel with 2,2-dithiopyridine (DTP), thereby preparing the mannan nanogel for loading with thiol-containing cargo.

2. The method of claim 1 , wherein the thiol-containing cargo is loaded onto the DTP-activated nanogel, wherein the cargo is comprised of one or more peptides.

3. The method of claim 1 , wherein dihydrazide crosslinked nanogels are coated with NaIO4-oxidized mannan.

4. The method of claim 1 , wherein the thiol-containing cargo is loaded into the DTP-activated nanogel, wherein the cargo is comprised of one or more peptides, and optionally glutathione (GSH).

5. The method of claim 1 , wherein the thiol-containing cargo is loaded into the DTP-activated nanogel, wherein the cargo is comprised of one or more viral antigens.

6. The method of claim 1 , wherein the thiol-containing cargo is loaded into the DTP-activated nanogel, wherein the cargo is comprised of one or more nucleic acids.

7. The method of claim 6 , wherein the nucleic acids are comprised of thiolated mRNA.

Assignments (2)

Continuity (2)

References Cited (65)