IP Library › Granted Patent US 12,365,880
Granted Patent B2
US 12,365,880 · App. 18/365,082 · Granted Jul 22, 2025

Recombinant influenza viruses with stabilized NA

Inventors: Yoshihiro Kawaoka (Middleton, WI); Yuri Furusawa (Tokyo, JP); Seiya Yamayoshi (Kanagawa, JP)
Assignees: The University of Tokyo; Wisconsin Alumni Research Foundation (WARF)
C12N7/00A61K39/145A61K2039/5252A61K2039/552C12N2760/16121C12N2760/16134C12N2760/16151C12N2760/16163
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Quick Facts
Patent No.
US 12,365,880
App. No.
18/365,082
Granted
Jul 22, 2025
Kind
B2
Abstract

Modified influenza virus neuraminidases are described herein that have stabilized NA tetramers which may improve vaccine production efficiency, thus improving the yield of vaccine viruses.

Claims (17)

1. A method of immunizing an avian or a mammal, comprising: administering to the avian or the mammal a composition having an effective amount of an isolated recombinant influenza virus comprising stabilized neuraminidase (NA) tetramers and a NA viral segment encoding a modified NA monomer that forms virions having the stabilized NA tetramers relative to a corresponding influenza virus having a parental NA viral segment encoding an unmodified NA monomer, wherein the modified NA monomer comprises a modified NA stalk that results in the stabilized NA tetramers, wherein the modified NA has a cysteine at position 48 or position 50 or both positions of 48 and 50 relative to the numbering of NA1 of SEQ ID NO:37.

2. The method of claim 1 wherein the mammal is a human.

3. The method of claim 1 wherein the composition is administered intranasally.

4. The method of claim 1 wherein the composition is administered via injection.

5. The method of claim 1 wherein the modified NA stalk further comprises a deletion, an insertion, at least one other amino acid substitution, or any combination thereof.

6. The method of claim 1 wherein the modified NA has a cysteine at position 48.

7. The method of claim 1 wherein modified NA has a cysteine at position 50.

8. The method of claim 1 wherein modified NA has a cysteine at position 48 and position 50.

9. The method of claim 1 wherein the NA stalk is modified within residues 1 to 10 or residues 10 to 20 from the C-terminus of the transmembrane domain.

10. The method of claim 1 wherein the NA is N1, N2, N3 or N5.

11. The method of claim 1 wherein the HA is H1, H3, H5 or H7.

12. The method of claim 1 further comprising administering an adjuvant.

13. The method of claim 12 wherein the adjuvant comprises immunostimulatory DNA sequences, bacterium-derived components, aluminum salt (alum) or a squalene oil-in-water emulsion.

14. The method of claim 1 wherein the composition further comprises an adjuvant.

15. The method of claim 14 wherein the adjuvant comprises immunostimulatory DNA sequences, bacterium-derived components, aluminum salt (alum) or a squalene oil-in-water emulsion.

16. The method of claim 15 wherein the squalene oil-in-water emulsion system comprises MF59 or AS03.

17. The method of claim 1 wherein the virus is chemically inactivated.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2023
From: FURUSAWA, YURI; YAMAYOSHI, SEIYA
To: THE UNIVERSITY OF TOKYO
Reel/Frame 064559/0082 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2023
From: KAWAOKA, YOSHIHIRO
To: WISCONSIN ALUMNI RESEARCH FOUNDATION; THE UNIVERSITY OF TOKYO
Reel/Frame 064559/0162 →
Continuity (3)
Division 17155625 · Jan 22, 2021
Provisional Application 62965225 · Jan 24, 2020
Related Publication 20240010995A1 · Jan 11, 2024
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