IP Library › Granted Patent US 12,606,804
Granted Patent B2
US 12,606,804 · App. 18/017,374 · Granted Apr 21, 2026

Influenza virus backbone

Inventors: Michael J. Moser (Madison, WI); Yasuko Hatta (Madison, WI); Pamuk Bilsel (Madison, WI); Lindsay Hill-Batorski (Lodi, WI)
Assignee: FluGen, Inc.
C12N7/00A61K39/12C07K14/11A61K2039/522C12N2760/16121C12N2760/16134
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Quick Facts
Patent No.
US 12,606,804
App. No.
18/017,374
Granted
Apr 21, 2026
Kind
B2
Abstract

The invention provides an influenza virus that demonstrates enhanced growth in Vero cells. The influenza virus includes PA, NP, and NS gene segments having selected nucleotides and encoding proteins having amino acid sequences with selected amino aids. The invention also provides a pharmaceutical formulation containing the influenza virus, as well as a method of eliciting an immune response in a mammal by administering the influenza virus to the mammal, and a method for generating the influenza virus.

Claims (31)

1 . An influenza virus comprising PA, NP, and NS gene segments, wherein

(a) the PA gene segment comprises a thymine at nucleotide position 2272;

(b) the NP gene segment encodes a NP protein having an amino acid sequence comprising selected amino acids, wherein the selected amino acids comprise a serine at position 40, an asparagine or glycine at position 161, a threonine at position 204, and optionally a valine at position 93; and

(c) the NS gene segment comprises a guanine at nucleotide position 39, and the NS gene segment encodes an NS1 protein having an amino acid sequence comprising selected amino acids, wherein the selected amino acids comprise a glutamine at position 176.

2 . The influenza virus of claim 1 , wherein the PA gene segment has a nucleotide sequence represented by SEQ ID NO: 10.

3 . The influenza virus of claim 1 , wherein the NP gene segment has a nucleotide sequence represented by SEQ ID NO: 11.

4 . The influenza virus of claim 1 , wherein the PA gene segment encodes a PA protein having an amino acid sequence of SEQ ID NO: 15.

5 . The influenza virus of claim 1 , wherein the NP gene segment encodes an NP protein having an amino acid sequence of SEQ ID NO: 16.

6 . The influenza virus of claim 1 , wherein the NS gene segment has a nucleotide sequence represented by SEQ ID NO: 12.

7 . The influenza virus of claim 1 , wherein the NS gene segment encodes an NS1 protein having an amino acid sequence of SEQ ID NO: 17.

8 . The influenza virus of claim 1 , wherein the selected amino acids are conserved in at least one of the NP and NS proteins after at least ten serial passages in a Vero cell line.

9 . The influenza virus of claim 1 , wherein the selected amino acids are conserved in at least one of the NP and NS proteins after at least ten serial passages in a Vero cell line that stably expresses the BM2 ion channel protein of influenza B virus.

10 . The influenza virus of claim 1 wherein the influenza virus is a recombinant influenza virus.

11 . The influenza virus of claim 1 , wherein the virus further comprises a PB gene segment.

12 . The influenza virus of claim 1 , wherein the virus further comprises a NA gene segment and an HA gene segment.

13 . The influenza virus of claim 12 , wherein the HA gene segment encodes an HA protein having an amino acid sequence comprising at least one amino acid mutation in HA2.

14 . The influenza virus of claim 13 , wherein the at least one amino acid mutation in HA2 is a glutamic acid at position 61.

15 . The influenza virus of claim 13 , wherein the at least one amino acid mutation in HA2 is a glutamic acid at position 112.

16 . The influenza virus of claim 1 , wherein the PA, NP, and NS gene segments are derived from a single influenza strain.

17 . The influenza virus of claim 16 , wherein the HA gene segment is derived from an influenza strain different from the single influenza strain from which the PA, NP, and NS gene segments are derived.

18 . The influenza virus of claim 16 , wherein the NA gene segment is derived from an influenza strain different from the single influenza strain from which the PA, NP, and NS gene segments are derived.

19 . The influenza virus of claim 1 , further comprising a mutant M gene segment.

20 . The influenza virus of claim 19 , wherein the influenza virus does not encode a functional BM2 protein.

21 . The influenza virus of claim 1 , wherein the virus is capable of replication in human cells.

22 . The influenza virus of claim 1 , wherein the virus has enhanced growth as compared to an influenza virus that is the same except without the selected amino acids in Vero cells under the same conditions.

23 . A pharmaceutical formulation comprising the influenza virus of claim 1 .

24 . The pharmaceutical formulation of claim 23 , wherein the pharmaceutical formulation is a vaccine.

25 . The pharmaceutical formulation of claim 24 , wherein the vaccine is formulated as a monovalent vaccine, a bivalent vaccine, a trivalent vaccine, or a quadrivalent vaccine.

26 . A method of eliciting an immune response in a mammal, the method comprising administering the influenza virus of claim 1 to the mammal, thereby eliciting an immune response to the influenza virus in the mammal.

27 . The method of claim 26 , wherein the mammal is a human.

28 . A method of generating the influenza virus of claim 1 , the method comprising serially passaging in influenza virus in a Vero cell line.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 26, 2024
From: MOSER, MICHAEL J.; HATTA, YASUKO; BILSEL, PAMUK; HILL-BATORSKI, LINDSAY
To: FLUGEN, INC.
Reel/Frame 067240/0833 →
Continuity (2)
Provisional Application 63054676 · Jul 21, 2020
Related Publication 20230295582A1 · Sep 21, 2023
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