IP Library › Granted Patent US 12,618,074
Granted Patent B2
US 12,618,074 · App. 17/602,951 · Granted May 5, 2026

CD40 specific DNA aptamers as vaccine adjuvants

Inventors: Adil Sabr Al-Ogaili (Wasit, IQ); Tieshan Jiang (Fayetteville, AR); Christine N. Vuong (Fayetteville, AR); Rohana Liyanage (Fayetteville, AR); Jackson O. Lay, Jr. (West Fork, AR); Suresh Kumar Thallapuranam (Fayetteville, AR); Luc R. Berghman (College Station, TX); Young Min Kwon (Lincoln, AR); Billy Hargis (Fayetteville, AR)
Assignees: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ARKANSAS; THE TEXAS A&M UNIVERSITY SYSTEM
C12N15/115A61K39/39A61K2039/55561C12N2310/16C12N2310/17C12N2310/3513C12N2320/30
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Quick Facts
Patent No.
US 12,618,074
App. No.
17/602,951
Granted
May 5, 2026
Kind
B2
Abstract

The present invention provides immunostimulatory nucleic acids that have an affinity to a specific target protein. The present invention also provides templates and methods for making and using the immunostimulatory nucleic acids. Further, methods for linking the immunostimulatory nucleic acids to antigens and using the resulting complexes to enhance an immune response are provided.

Claims (18)

1 . An immunostimulatory nucleic acid comprising a protein-binding sequence having at least 95% identity to any one of SEQ ID NOs: 1-8, wherein the immunostimulatory nucleic acid binds to CD40.

2 . An immunostimulatory nucleic acid comprising a plurality of protein-binding units; wherein each of the protein-binding units comprise a first protein-binding sequence, a second protein-binding sequence, and a spacer sequence therebetween; wherein the second protein-binding sequence is a different sequence than the first protein-binding sequence; wherein (a) the first protein-binding sequence has at least 95% identity to any one of SEQ ID NOs: 1-8, (b) the second protein-binding sequence has at least 95% identity to any one of SEQ ID NOs: 1-8, or (c) both the first protein-binding sequence and the second protein-binding sequence have at least 95% identity to any one of SEQ ID NOs: 1-8; and wherein the immunostimulatory nucleic acid binds to CD40.

3 . The immunostimulatory nucleic acid of claim 2 , wherein the first and the second protein binding sequence are selected from SEQ ID NO: 3 and SEQ ID NO: 4.

4 . The immunostimulatory nucleic acid of claim 2 , wherein the immunostimulatory nucleic acid induces a CD40 signaling response when it is bound to CD40.

5 . The immunostimulatory nucleic acid of claim 2 , further comprising a binding tag.

6 . A method of binding CD40, the method comprising contacting CD40 with the immunostimulatory nucleic acid of claim 1 .

7 . A template for producing a plurality of protein-binding units comprising in order from 5′ to 3′: i) a 3′ end of a primer-binding sequence, ii) a reverse complement of a second protein-binding sequence, iii) a reverse complement of a spacer sequence, iv) a reverse complement of a first protein-binding sequence, and v) a 5′ end of a primer-binding sequence, wherein the 5′ end of the primer-binding sequence and the 3′ end of the primer-binding sequence form a primer-binding site when the template is circularized.

8 . The template of claim 7 , wherein the first protein-binding sequence comprises a sequence having at least 95% identity to any one of SEQ ID NOs: 1-8, wherein the second protein-binding sequence comprises the sequence having at least 95% identity to any one of SEQ ID NOs: 1-8, or wherein both the first protein-binding sequence and the second protein-binding sequence comprise the sequence having at least 8095% identity to any one of SEQ ID NOs: 1-8, and wherein the plurality of protein-binding sequences bind to CD40.

9 . The template of claim 7 , wherein both the first protein-binding sequence and the second protein-binding sequence have an affinity for an immune response signaling protein.

10 . The template of claim 9 , wherein the immune response signaling protein is CD40.

11 . A method of producing an immunostimulatory nucleic acid comprising (a) providing the template of claim 7 , (b) circularizing the template, and (c) amplifying the circularized template to produce the immunostimulatory nucleic acid.

12 . The method of claim 11 , further comprising partially or completely hybridizing a complementary sequence to the spacer sequence of the immunostimulatory nucleic acid.

13 . The method of claim 11 , wherein step (a) comprises (i) identifying two or more protein-binding sequences with an affinity for an immune response signaling protein and (ii) selecting the complement of the first protein-binding sequence and the complement of the second protein-binding sequence from the identified sequences.

14 . A method of producing an immunostimulatory complex comprising: (a) amplifying the template of claim 7 to produce an immunostimulatory nucleic acid, (b) tagging the immunostimulatory nucleic acid with a binding tag, and (c) linking the immunostimulatory nucleic acid to an antigen.

15 . An immunostimulatory complex comprising an adjuvant and an antigen, wherein the adjuvant is the immunostimulatory nucleic acid of claim 1 , and wherein the adjuvant and the antigen are linked.

16 . The immunostimulatory complex of claim 15 , wherein the antigen is a bacterial antigen, viral antigen, or fungal antigen.

17 . The immunostimulatory complex of claim 15 , wherein the antigen is a peptide.

18 . A method for enhancing an immune response in a subject comprising administering an effective amount of the immunostimulatory complex of claim 15 to the subject.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2022
From: BERGHMAN, LUC R.
To: THE TEXAS A&M UNIVERSITY SYSTEM
Reel/Frame 059456/0664 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2022
From: JIANG, TIESHAN; VUONG, CHRISTINE N.; LIYANGE, ROHANA; LAY, JACKSON O., JR.; THALLAPURANAM, SURESH KUMAR; KWON, YOUNG MIN; HARGIS, BILLY M.; AL-OGAILI, ADIL SABR
To: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ARKANSAS
Reel/Frame 059456/0235 →
Continuity (3)
Provisional Application 62952802 · Dec 23, 2019
Provisional Application 62832725 · Apr 11, 2019
Related Publication 20220186224A1 · Jun 16, 2022
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