RNA containing composition for treatment of tumor diseases

Patent metadata

Field	Value
Publication number	US-10918740-B2
Application number	US-201816039988-A
Country	US
Kind code	B2
Filing date	Jul 19, 2018
Priority date	Apr 22, 2015
Publication date	Feb 16, 2021
Grant date	Feb 16, 2021

Abstract

The present invention relates to RNA containing compositions for use in the treatment or prophylaxis of tumor and/or cancer diseases, to a pharmaceutical composition, to a kit and to uses of the RNA containing compositions for the treatment or prophylaxis of tumor and/or cancer diseases.

First claim

The invention claimed is:

1. A method of treating solid tumor in a patient in need thereof, the method comprising administering intratumorally to the tumor in the patient a pharmaceutically effective amount of a composition comprising an mRNA encoding IL-23 and having at least about 90% identity to wild-type mature human IL-23, wherein the mRNA encoding IL-23 is complexed with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes.

2. The method of claim 1 , further comprising the administration of at least a second anticancer therapy.

3. The method of claim 2 , wherein the second anticancer therapy is a chemotherapy, a hormone therapy, an immunotherapy, a checkpoint modulator therapy, a cytokine therapy, a radiation therapy, and/or a surgery.

4. The method of claim 3 , wherein the checkpoint modulator therapy is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a LAG3 inhibitor, a TIM3 inhibitor, an OX-40 stimulator, a 4-1BB stimulator, a CD40L stimulator, a CD28 stimulator, and a GITR stimulator.

5. The method of claim 3 , wherein the checkpoint modulator therapy is selected from the group consisting of an agonistic antibody, an antagonistic antibody, a dominant negative receptor, a decoy receptor, and a ligand.

6. The method of claim 5 , wherein the antagonistic antibody is directed against PD-1, PD-L1, or CTLA-4.

7. The method of claim 5 , wherein the decoy receptor is a soluble PD-1 receptor.

8. The method of claim 5 , wherein the checkpoint modulator comprising a mRNA encoding an agonistic antibody, an antagonistic antibody, a dominant negative receptor, a decoy receptor, or a ligand.

9. The method of claim 1 , wherein the G/C content of the coding region of the mRNA is increased compared with the G/C content of the coding region of the wild type mRNA, and wherein the coded amino acid sequence of said G/C-enriched mRNA is not modified compared with the encoded amino acid sequence of the wild type mRNA.

10. The method of claim 1 , wherein the mRNA comprises a 5′-UTR element and/or a 3′-UTR element.

11. The method of claim 10 , wherein the mRNA comprises at least one histone stem-loop.

12. The method of claim 10 , wherein the mRNA comprises a 5′-CAP structure, a poly(A) sequence, and/or a poly(C) sequence.

13. The method of claim 1 , wherein the lipid is a cationic or polycationic lipid.

14. The method of claim 1 , wherein the cancer is prostate cancer, lung cancer, breast cancer, brain cancer, head and neck cancer, thyroid cancer, colon cancer, stomach cancer, liver cancer, pancreas cancer, ovary cancer, skin cancer, urinary cancer, bladder cancer, uterine cancer, lymphoma or cervical cancer.

15. The method of claim 1 , further comprising administering at least a second mRNA encoding a cytokine.

16. The method of claim 15 , comprising administering at least a second mRNA encoding IL-18.

17. The method of claim 1 , wherein the mRNA encoding IL-23 comprises a 5′-CAP structure and a poly(A) sequence, and wherein the composition is administered by injection into tumor tissue.

18. The method of claim 17 , further comprising administering at least a second mRNA encoding IL-18.

19. The method of claim 2 , wherein the second cancer therapy is administering at least a second mRNA encoding OX40L.

Assignees

• Curevac Ag

Inventors

• Fotin-Mleczek Mariola
• Kowalczyk Aleksandra
• Heidenreich Regina
• Baumhof Patrick
• Probst Jochen
• Kallen Karl-Josef

Classifications

• C12Q1/6806

  Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence) · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• A61K38/19

  Cytokines; Lymphokines; Interferons · CPC title

• C12N15/117

  Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title