IP Library › Granted Patent US 12,233,135
Granted Patent B2
US 12,233,135 · App. 17/047,011 · Granted Feb 25, 2025

Therapeutic constructs for treating cancer

Inventors: Christopher Ullman (Hertfordshire, GB); Christine Anne Carrington (Cambridgeshire, GB)
Assignee: PRECISION MOLECULAR INC.
A61K48/0058A61K9/19A61K38/1774A61K38/208A61K38/45A61K39/3955A61K39/4611A61K39/4631A61K39/464401A61K39/464404A61K39/464406A61K47/59A61P35/00A61K2239/31A61K2239/38A61K2239/55
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Quick Facts
Patent No.
US 12,233,135
App. No.
17/047,011
Granted
Feb 25, 2025
Kind
B2
Abstract

The present disclosure provides nucleic acid constructs for the treatment of cancer, comprising a cancer-specific promoter and one or more therapeutic genes.

Claims (20)

1. A nucleic acid construct for the treatment of cancer comprising an expression cassette, wherein the expression cassette comprises a cancer-specific promoter and nucleic acid sequences encoding one or more tumor antigens, wherein the nucleic acid sequences encoding the one or more tumor antigens are engineered to have a reduced CpG content compared to their wild-type counterparts, the nucleic acid construct comprises a CpG-free plasmid backbone, or a combination thereof.

2. The nucleic acid construct of claim 1 , wherein the cancer-specific promoter is the PEG-3 promoter or a functional derivative thereof.

3. The nucleic acid construct of claim 1 , wherein the one or more tumor antigens is selected from the group consisting of WT1, MUC1, LMP2, HPV E6 E7, EGFRvIII, HER-2/neu, MAGE A3, p53, NY-ESO-1, PSMA, CEA, MelanA/MART1, Ras mutant, gp100, Proteinase3 (PR1), bcr-abl, Tyrosinase, Survivin, PSA, hTERT, EphA2, PAP, ML-IAP, AFP, EpCAM, ERG (TMPRSS2 ETS fusion gene), NA17, PAX3, ALK, Androgen receptor, Cyclin B1, MYCN, RhoC, TRP-2, Mesothelin, PSCA, MAGE A1, CYP1B1, PLAC1, BORIS, ErbB2, Fibroblast activation protein alpha, FR-α, GPC3, IL13-Rα2, Mesothelin, MUC16, PSMA, ROR1, VEGFR2, αvβ6 integrin.

4. The nucleic acid construct of claim 1 , wherein if multiple tumor antigens are encoded, tumor antigen sequences are separated by a picornavirus 2A ribosome skipping sequence, optionally wherein the picornavirus ribosome skipping sequence is P2A or T2A.

5. The nucleic acid construct of claim 1 , wherein the nucleic acid sequences encoding one or more tumor antigens are engineered to have a reduced CpG content compared to their wild-type counterparts and a CpG-free plasmid backbone.

6. A composition for the treatment of cancer comprising the nucleic acid construct of claim 1 .

7. The nucleic acid construct of claim 1 , wherein the expression cassette further comprises one or more therapeutic genes.

8. The nucleic acid construct of claim 7 , wherein the one or more therapeutic genes is a cytokine, a thymidine kinase optionally wherein the thymidine kinase is HSV1-TK or SR39, a toxin, a pathogen-associated molecular pattern (PAMP) optionally wherein the PAMP is flagellin (FliC), a danger-associated molecular pattern (DAMP), an immune checkpoint inhibitor gene, or any combination thereof.

9. The nucleic acid construct of claim 7 , wherein if multiple therapeutic genes are present, the multiple therapeutic genes are separated by a picornavirus 2A ribosome skipping sequence, optionally wherein the picornavirus ribosome skipping sequence is P2A or T2A.

10. The nucleic acid construct of claim 7 , wherein the one or more therapeutic genes is engineered to have a reduced CpG content compared to its wild-type counterpart.

11. The nucleic acid construct of claim 8 , wherein the immune checkpoint inhibitor gene encodes a monoclonal antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA-4 antibody, optionally wherein the immune checkpoint inhibitor gene encodes an immune checkpoint inhibitor fusion protein comprising a PD-1 fusion protein, optionally wherein the PD-1 fusion protein comprises a fusion of PD-1 and an immunoglobulin Fc region.

12. The nucleic acid construct of claim 8 , wherein the cytokine is selected from the group consisting of IL-12, IL-24, IL-2, IL-15, and GM-CSF.

13. The nucleic acid construct of claim 8 , wherein the cytokine is a single chain variant of IL-12 (scIL-12), optionally comprising the amino acid sequence encoded by SEQ ID NO:5.

14. The composition of claim 6 , wherein the nucleic acid construct is formulated into nanoparticles with a cationic polymer, optionally wherein the cationic polymer is linear polyethylenimine.

15. The composition of claim 14 , wherein the nanoparticles are prepared at a N/P ratio of 4 or 6.

16. The composition of claim 14 , wherein the nanoparticles are lyophilized.

17. A method for treating cancer in a subject in need thereof, comprising administering to the subject the nucleic acid construct of claim 1 .

18. The method of claim 17 , wherein the cancer is selected from the group consisting of breast cancer, melanoma, carcinoma of unknown primary (CUP), neuroblastoma, malignant glioma, cervical cancer, colon cancer, hepatocarcinoma, ovarian cancer, lung cancer, pancreatic cancer, and prostate cancer.

19. The method of claim 17 , wherein the nucleic acid construct is delivered systemically.

20. The method of claim 17 wherein the nucleic acid construct is administered in conjunction with one or more additional therapeutic agents, optionally wherein the additional therapeutic agent(s) comprise a therapeutic monoclonal antibody or a one more CAR T cells.

Assignments (3)
MERGER Recorded May 9, 2025
From: PRECISION MOLECULAR INC.; NEURALY INC.
To: NEURALY INC.
Reel/Frame 071070/0332 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2021
From: MORNINGSIDE VENTURE INVESTMENTS LIMITED
To: PRECISION MOLECULAR INC.
Reel/Frame 055932/0677 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 24, 2021
From: ULLMAN, CHRISTOPHER; CARRINGTON, CHRISTINE ANNE
To: CANCER TARGETING SYSTEMS, INC.
Reel/Frame 055390/0924 →
Continuity (2)
Provisional Application 62655926 · Apr 11, 2018
Related Publication 20210154328A1 · May 27, 2021
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