IP Library Granted Patent US 12,201,680
Granted Patent B2
US 12,201,680 · App. 17/139,778 · Granted Jan 21, 2025

Nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal for increasing the expression of an encoded pathogenic antigen

Inventors: Andreas Thess (Kusterdingen, DE); Thomas Schlake (Gundelfingen, DE); Jochen Probst (Wolfschlugen, DE)
Assignee: CureVac SE
A61K39/145A61K39/00A61K39/12C12N7/00C12N15/63C12N15/67A61K2039/53A61K2039/64C12N2760/16134C12N2770/20034C12N2830/50Y02A50/30
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Quick Facts
Patent No.
US 12,201,680
App. No.
17/139,778
Granted
Jan 21, 2025
Kind
B2
Abstract

The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a pathogenic antigen or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the treatment of infectious diseases. The present invention further describes a method for increasing the expression of a peptide or protein comprising a pathogenic antigen or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.

Claims (23)

1. A method of stimulating an immune response in a subject comprising administering an effective amount a composition to the subject, said composition comprising a mRNA encoding a Severe Acute Respiratory Syndrome (SARS) coronavirus spike(S) protein coding sequence and a histone stem loop sequence, said mRNA provided in complex with a lipid.

2. The method of claim 1 , wherein the composition is administered by intradermal or intramuscular injection.

3. The method of claim 2 , wherein the composition is administered by intramuscular injection.

4. The method of claim 1 , wherein the mRNA comprises a Poly-A sequence.

5. The method of claim 4 , wherein the mRNA comprises a Poly-A sequence of about 25 to 400 adenosine nucleotides.

6. The method of claim 1 , wherein the mRNA comprises a 5′ untranslated region (UTR) and/or a 3′ UTR.

7. The method of claim 6 , wherein the mRNA comprises a 5′UTR and a 3′ UTR.

8. The method of claim 1 , wherein the lipid comprises a cationic lipid.

9. The method of claim 1 , wherein the coding sequence of the mRNA has a G/C content that is increased compared with the G/C content of the coding sequence of a wild-type RNA.

10. The method of claim 1 , wherein the mRNA comprises a nucleotide analog substitution.

11. The method of claim 10 , wherein the nucleotide analog substation comprises at least one pseudouridine-5′-triphosphate substitution.

12. The method of claim 1 , wherein the mRNA comprises a methylated 5′ cap.

13. The method of claim 1 , further comprising a polyethyleneglycol.

14. The method of claim 1 , further comprising an adjuvant.

15. The method of claim 1 , wherein the mRNA comprises a methylated 5′ cap; a 5′ UTR; a 3′ UTR and a Poly-A sequence of about 25 to 400 adenosine nucleotides.

16. The method of claim 15 , wherein the coding sequence of the mRNA has a G/C content that is increased compared with the G/C content of the coding sequence of a wild-type RNA.

17. The method of claim 16 , wherein the lipid comprises a cationic lipid.

18. The method of claim 1 , wherein the histone stem loop sequence is at least 90% identical to the sequence of SEQ ID NO: 39 or SEQ ID NO: 42.

19. The method of claim 18 , wherein the histone stem loop sequence is at least 90% identical to the sequence of SEQ ID NO: 39.

20. A method of stimulating an immune response in a subject comprising administering an effective amount a composition to the subject, said composition comprising a purified mRNA encoding: a 5′ UTR; a coronaviruses spike(S) protein coding sequence; a 3′ UTR; a Poly-A sequence of 25 to 400 adenosine nucleotides; and a histone stem loop sequence, said mRNA comprising a 5′ Cap, wherein the purified mRNA is provided in complex with a lipid.

21. The method of claim 20 , wherein the composition is administered by intradermal or intramuscular injection.

22. The method of claim 21 , wherein the lipid comprises a cationic lipid.

23. The method of claim 20 , wherein the coding sequence of the mRNA has a G/C content that is increased compared with the G/C content of the coding sequence of a wild-type RNA.

Assignments (1)
CHANGE OF NAME Recorded Jan 11, 2023
From: CUREVAC AG
To: CUREVAC SE
Reel/Frame 062356/0473 →
Continuity (6)
Division 16938136 · Jul 24, 2020
Continuation 15892330 · Feb 8, 2018
Continuation 15465322 · Mar 21, 2017
Continuation 14378538
Continuation PCTEP2012000673 · Feb 15, 2012
Related Publication 20210128716A1 · May 6, 2021
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