IP Library › Granted Patent US 12,280,102
Granted Patent B2
US 12,280,102 · App. 17/232,666 · Granted Apr 22, 2025

Alphavirus replicon encoding chimeric SARS-CoV-2 receptor binding domains

Inventors: Wataru Akahata (Kensington, MD); Jonathan F. Smith (Redwood City, CA); Ryuji Ueno (Easton, MD)
Assignee: VLP Therapeutics, Inc.
A61K39/215C07K14/165C07K14/1808C07K2319/02C07K2319/03C12N2770/20034C12N2770/36141
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Quick Facts
Patent No.
US 12,280,102
App. No.
17/232,666
Granted
Apr 22, 2025
Kind
B2
Abstract

Provided herein is an isolated polynucleotide, which encodes alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and a polypeptide comprising a coronavirus protein fused to a signal sequence and/or transmembrane domain. The coronavirus protein may be the receptor binding domain of the S1 subunit of coronavirus spike (S) protein. The polynucleotide such as RNA is useful for as a vaccine against coronavirus infection, especially, COVID-19 infection.

Claims (19)

1. An isolated polynucleotide, which encodes alphavirus non-structural proteins nsP1, nsP2, nsP3, and nsP4 and

a polypeptide comprising a receptor binding domain (RBD) of an S1 subunit in a spike protein of a SARS-CoV2 fused to a transmembrane domain and optionally to a signal sequence,

wherein the alphavirus is Venezuelan Equine Encephalitis Virus or Chikungunya virus, and

wherein the transmembrane domain is heterologous to the SARS-CoV-2.

2. The polynucleotide of claim 1 , wherein the transmembrane domain is derived from Influenza Hemagglutinin (HA) or CD80.

3. The polynucleotide of claim 2 , wherein the transmembrane domain is derived from Influenza Hemagglutinin (HA).

4. The polynucleotide of claim 1 , wherein coronavirus protein is fused to a signal sequence and transmembrane domain.

5. The polynucleotide of claim 1 , wherein the signal sequence is derived from human IL-2 or SARS-CoV-2 spike protein.

6. The polynucleotide of claim 1 , wherein the transmembrane domain and/or signal sequence is fused to the coronavirus protein by a linker.

7. The polynucleotide of claim 1 , wherein the linker is IgG4CH 3 and/or a short linker.

8. The polynucleotide of claim 1 , wherein the polynucleotide encodes an amino acid sequence selected from SEQ ID NOs: 1, 5, 6, 8, 9, 11, 12, 13, 34, 35, 36 and 37-51.

9. The polynucleotide of claim 1 , wherein the polynucleotide is RNA.

10. A vector comprising the polynucleotide of claim 1 .

11. The vector of claim 10 , which further comprises a promoter, 5′ UTR, SG promoter, 3′UTR and poly A tail.

12. A vaccine composition comprising (i) the polynucleotide of claim 1 or an expression vector containing the polynucleotide and (ii) a pharmaceutically acceptable delivery vehicle.

13. The vaccine composition of claim 12 , wherein the delivery vehicle is a particle consisting of one or more alphavirus structural proteins or a lipid delivery system.

14. The polynucleotide of claim 1 , wherein the alphavirus is Venezuelan Equine Encephalitis Virus.

15. A vaccine composition comprising (i) the polynucleotide of claim 1 or an expression vector containing the polynucleotide, and (ii) a pharmaceutically acceptable lipid delivery system.

16. The polynucleotide of claim 1 , wherein the receptor binding domain (RBD) of the S1 subunit in a spike protein of a SARS-CoV2 is SEQ ID NO: 19.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 30, 2021
From: AKAHATA, WATARU; SMITH, JONATHAN F.; UENO, RYUJI
To: VLP THERAPEUTICS, INC.
Reel/Frame 056106/0539 →
Continuity (4)
Provisional Application 63088723 · Oct 7, 2020
Provisional Application 63050442 · Jul 10, 2020
Provisional Application 63011561 · Apr 17, 2020
Related Publication 20210322541A1 · Oct 21, 2021
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