RNA encoding a therapeutic protein

Patent metadata

Field	Value
Publication number	US-12227549-B2
Application number	US-202117359902-A
Country	US
Kind code	B2
Filing date	Jun 28, 2021
Priority date	May 4, 2016
Publication date	Feb 18, 2025
Grant date	Feb 18, 2025

Abstract

The present invention relates to an RNA encoding a therapeutic protein. In particular, the present invention relates to RNA suitable for use as a medicament. The present invention concerns such novel RNA as well as compositions and kits comprising the RNA. Furthermore, the present invention relates to the RNA, compositions or kits as disclosed herein for use as a medicament. The present invention also provides the use of the RNA, compositions or kits as disclosed herein for increasing the expression of said encoded protein, in particular in gene therapy.

First claim

The invention claimed is:

1. A method of treating or preventing propionic acidemia wherein, the method comprises administering to a subject in need thereof an effective amount of
a purified RNA comprising at least one coding sequence encoding a PCCA protein that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8175, wherein the coding sequence comprises the nucleic acid sequence of any one of SEQ ID NOs: 34289, 47346, 60403, 21232 and 73460 or a sequence at least 80% identical to the nucleic acid sequence of any one of SEQ ID NOs: 34289, 47346, 60403, 21232 and 73460.

2. The method of claim 1 , wherein the purified RNA comprises a poly(A) sequence of 10 to 200 adenosine nucleotides.

3. The method of claim 1 , wherein the RNA is an mRNA, a viral RNA or a replicon RNA.

4. The method of claim 3 , wherein the RNA is an mRNA.

5. The method of claim 1 , wherein the RNA is a modified RNA.

6. The method of claim 5 , wherein the modified RNA comprises a chemically modified nucleotide.

7. The method of claim 1 , wherein the RNA comprises a 5′-CAP structure, a 5′-untranslated region (5′-UTR), and/or at least one 3′-untranslated region element (3′-UTR).

8. The method of claim 7 , wherein the RNA comprises at least one histone stem-loop.

9. The method of claim 1 , wherein the RNA comprises, in 5′ to 3′ direction, the following elements:
a) a 5′-CAP structure,
b) the at least one coding sequence, and
c) a poly(A) tail.

10. The method of claim 9 , wherein the RNA comprises a 5′-UTR and a 3′-UTR.

11. The method of claim 1 , wherein the at least one coding sequence encodes the amino acid sequence of SEQ ID NO: 8175.

12. The method of claim 1 , wherein the at least one coding sequence comprises a sequence at least 90% identical to the nucleic acid sequence of any one of SEQ ID NOs: 34289, 47346, 60403, 21232 and 73460.

13. The method of claim 9 , further comprising administering an effective amount of a purified RNA comprising at least one coding sequence encoding a PCCB protein that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8176.

14. The method of claim 13 , wherein the at least one coding sequence encodes the amino acid sequence of SEQ ID NO: 8176.

15. The method of claim 13 , wherein the at least one coding sequence comprises a sequence at least 90% identical to the nucleic acid sequence of any one of SEQ ID NOs: 34290, 47347, 60404, 21233 and 73461.

16. The method of claim 9 , further comprising administering an effective amount of
a purified RNA comprising at least one coding sequence encoding a PCCB protein that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8176, wherein the coding sequence comprises the nucleic acid sequence of any one of SEQ ID NOs: 34290, 47347, 60404, 21233 and 73461 or a sequence at least 80% identical to the nucleic acid sequence of any one of SEQ ID NOs: 34290, 47347, 60404, 21233 and 73461.

17. The method of claim 1 , wherein the purified RNA comprises at least one 3′-untranslated region element (3′-UTR), wherein the 3′-UTR element comprises a nucleic acid sequence derived from a 3′-UTR of a gene selected from the group consisting of an albumin gene, an α-globin gene, a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene, and a collagen alpha gene.

18. The method of claim 17 , wherein the 3′-UTR element comprises a nucleic acid sequence derived from a 3′-UTR of an α-globin gene.

19. The method of claim 1 , wherein the purified RNA is formulated in a composition comprising lipid nanoparticles (LNPs).

20. The method of claim 19 , wherein the purified RNA is formulated in a composition comprising LNPs, said LNPs comprising a cationic lipid.

21. The method of claim 19 , wherein the composition is administered by injection.

Assignees

• CureVac SE

Inventors

• Fotin-Mleczek Mariola
• Hoerr Ingmar

Classifications

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N2310/531

  Stem-loop; Hairpin · 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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title