# US 12,594,346 B2 · Crosslinked hydrogel for immune checkpoint blockade delivery > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,594,346 B2 - Document ID: US12594346B2 - Status: Granted - Kind: B2 - Application number: 18/015,232 - Filed: 2021-07-08 - Published: 2023-08-17 - Granted: 2026-04-07 - Earliest claimed: 2020-07-08 - Assignees: Georgia Tech Research Corporation; University of Louisville Research Foundation, Inc. - Applicants: Georgia Tech Research Corporation; University of Louisville Research Foundation, Inc. - Inventors: Andres J. Garcia; Maria M. Coronel; Haval Shirwan; Esma S. Yolcu - Web page: https://patentgrep.com/patent/US12594346B2 ## CPC - A61K 47/6903: {the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel} - A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones - A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol - A61K 47/62: the modifying agent being a protein, peptide or polyamino acid - C07K 14/70521: {CD28, CD152} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Disclosed are PD-L1 presenting compositions. The compositions may be used to effect immunomodulation in a variety of contexts. The compositions may be used to decrease rates of transplant rejection, including pancreatic islet cell transplantation. The compositions are useful for the treatment of type 1 diabetes. ## Claims ### Claim 1 A three-dimensional PD-L1 presenting composition comprising a hydrogel network conjugated to PD-L1 via a biotin/streptavidin complex, wherein the hydrogel is covalently bound to a plurality of biotin residues, the PD-L1 is conjugated to streptavidin; and wherein the composition further comprises an immunosuppressant. ### Claim 2 (depends on 1) The PD-L1 presenting composition according to claim 1, wherein the immunosuppressant comprises rapamycin, cyclophosamide busulfan, fludarabine, methotrexate, sulfasalazine, hydroxychloroquine, azathioprine, tocilizumab, etanercept, adalimumab, anakinra, abatacept, rituximab, certolizumab, golimumab, cyclosporine, dexamethasone, methylprednisolone, prednisone, tacrolimus, and/or triamcinolone. ### Claim 3 (depends on 1) The PD-L1 presenting composition according to claim 1, wherein the immunosuppressant comprises rapamycin. ### Claim 4 (depends on 1) The PD-L1 presenting composition according to claim 1, wherein the hydrogel network composition comprises crosslinked hydrophilic polymers. ### Claim 5 (depends on 1) The PD-L1 presenting composition according to claim 1, wherein the hydrogel network composition comprises crosslinked polyethylene glycol. ### Claim 6 (depends on 1) The PD-L1 presenting composition according to claim 1, wherein the hydrogel network composition has the general formula: wherein ‘polymer’ in each case independently represents a hydrophilic polymer, the encircled C represents a core, Q represents a linker, X represents a crosslinker, Z is null or a linker, and the sum of a+b is from 3-10. ### Claim 7 (depends on 6) The PD-L1 presenting composition according to claim 6, wherein the hydrogel network has the general formula: and each of n and m is independently selected from an integer from 10-50,000. ### Claim 8 (depends on 7) The PD-L1 presenting composition according to claim 7, wherein n is in each case an integer from 15-30,000. ### Claim 9 (depends on 7) The PD-L1 presenting composition according to claim 7, wherein each —(CH2CH2O)n— unit can have an average molecular weight from 1,000-50,000. ### Claim 10 (depends on 7) The PD-L1 presenting composition according to claim 7, wherein m is an integer from 10-1,000. ### Claim 11 (depends on 7) The PD-L1 presenting composition according to claim 7, wherein each —(CH2CH2O)m— unit can have an average molecular weight from 250-50,000. ### Claim 12 (depends on 6) The PD-L1 presenting composition according to claim 6, wherein core can have the general structure: wherein q is an integer from 1-10 and represents a link to the hydrophilic polymer. ### Claim 13 (depends on 6) The PD-L1 presenting composition according to claim 6, wherein Q has the formula: wherein A is independently selected from O or NH, a is independently selected from 0 or 1, B is selected from hydrogen or methyl, and represents a link to the hydrophilic polymer. ### Claim 14 (depends on 1) The PD-L1 presenting composition of claim 1, prepared by a process including the step of reacting a compound of Formula (I): wherein Q1 comprises an electrophilic group, and c is the sum of a+b, with a compound of Formula (2): wherein ‘Nuc’ is a nucleophilic group capable of reacting the Q1, to form a compound of Formula (3): ### Claim 15 (depends on 14) The PD-L1 presenting composition according to claim 14, wherein the molar ratio of the compound of Formula (1) to the compound of Formula (2) is from 10:1 to 1:10. ### Claim 16 (depends on 14) The PD-L1 presenting composition according to claim 14, further comprising the step of reacting the compound of Formula (3) with a crosslinker to give the hydrogel network composition having the formula: wherein X represents a crosslinker. ### Claim 17 (depends on 16) The PD-L1 presenting composition according to claim 16, wherein the crosslinker has the formula: wherein X1 is a is a C1-8alkylene group, optionally substituted one or more times by OH, or X1 is a poly(ethylene)glycol group having from 1 to 20 monomer units. ### Claim 18 (depends on 17) The PD-L1 presenting composition according to claim 17, wherein the crosslinker has the formula: ### Claim 19 (depends on 6) The PD-L1 presenting composition according to claim 6, prepared by further incubating the hydrogel network composition having the formula: with SA-PD-L1. ### Claim 20 (depends on 1) A method of effecting immunomodulation comprising administering to a patient in need thereof the PD-L1 presenting composition according to claim 1.