US 12,233,123 B2Granted

Influenza virus hemagglutinin proteins and uses thereof

AssigneeIcahn School of Medicine at Mount Sinai

InventorsPeter Palese, Adolfo Garcia-Sastre, Megan Ermler, Florian Krammer

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Abstract

Provided herein are chimeric hemagglutinin (HA) polypeptides and uses thereof for inducing an immune response (e.g., an antibody response) against influenza virus. Also provided herein are methods of generating antibodies to the chimeric HA polypeptides in a subject.

Claims20

Dependent claims

A method of inducing an immune response against influenza B virus in a subject, comprising administering to the subject an immunogenic composition comprising a chimeric hemagglutinin (HA) polypeptide or a nucleic acid encoding the chimeric HA polypeptide, wherein:

the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues FIP and KIQLSTKNVINAEHAPGGPYRL (SEQ ID NO:
2), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PYQGKSS (SEQ ID NO:19);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKNSTY (SEQ ID NO:
6);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NDAAMQT (SEQ ID NO:
8);
or
II. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues HIP and RIRLSTYNVINAETAPGGPYRL (SEQ ID NO:
51), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NASTGGQS (SEQ ID NO:
52);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKKADTY (SEQ ID NO:
53);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues ADAKMQT (SEQ ID NO:
54);
or
III. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues LIP and KIELSTSNVINAEVAPGGPYRL (SEQ ID NO:
55), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PFGSSNS (SEQ ID NO:56);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 the hemagglutinin ectodomain are substituted with amino acid residues HQSGTY (SEQ ID NO:
57);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues TTLKMHQ (SEQ ID NO:
58) or ATLKMHQ (SEQ ID NO:
70);
or
IV. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NIP and RIELSTHNVINAEVAPGGPYRL (SEQ ID NO:
59), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PDKGASS (SEQ ID NO:60);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KRGNQY (SEQ ID NO:
61);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues VSTNMAK (SEQ ID NO:
62);
or
V. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from an influenza B virus, and wherein:
a. there are 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid substitutions within the 120 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid residues in the 120 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
b. there are 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid substitutions within the 150 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid residues in the 150 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
c. there are 2, 3, 4, 5 or more amino acid substitutions within the 160 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5 or more amino acid residues in the 160 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
and
d. there are 2, 3, 4, 5, 6, 7, 8 or more amino acid substitutions within the 190 helix of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8 or more amino acid residues in the 190 helix of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
or
VI. the nucleic acid comprises:
a. the nucleotide sequence set forth in SEQ ID NO:
20, or a complement thereof;
b. the nucleotide sequence set forth in SEQ ID NO:
22 or SEQ ID NO:
24, or a complement thereof;
or
c. the nucleotide sequence set forth in SEQ ID NO:
43, SEQ ID NO:
45, SEQ ID NO:
47, or SEQ ID NO:
49, or a complement thereof;
or
VII. the chimeric HA polypeptide comprises:
a. the amino acid sequence set forth in SEQ ID NO:
21, or the amino acid sequence set forth in SEQ ID NO:
21 without the signal peptide;
b. the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25, or the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25 without the signal peptide;
c. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
21;
d. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
23 or SEQ ID NO:
25;
e. the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50, or the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50 without the signal peptide;
or
f. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50.

104 more elements

A method of immunizing a subject against influenza virus disease, comprising administering to the subject an immunogenic composition comprising a chimeric hemagglutinin (HA) polypeptide or a nucleic acid encoding the chimeric HA polypeptide, wherein:

I. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues FIP and KIQLSTKNVINAEHAPGGPYRL (SEQ ID NO:
2), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PYQGKSS (SEQ ID NO:19);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKNSTY (SEQ ID NO:
6);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NDAAMQT (SEQ ID NO:
8);
or
II. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues HIP and RIRLSTYNVINAETAPGGPYRL (SEQ ID NO:
51), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NASTGGQS (SEQ ID NO:
52);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKKADTY (SEQ ID NO:
53);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues ADAKMQT (SEQ ID NO:
54);
or
III. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues LIP and KIELSTSNVINAEVAPGGPYRL (SEQ ID NO:
55), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PFGSSNS (SEQ ID NO:56);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 the hemagglutinin ectodomain are substituted with amino acid residues HOSGTY (SEQ ID NO:
57);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues TTLKMHQ (SEQ ID NO:
58) or ATLKMHQ (SEQ ID NO:
70);
or
IV. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NIP and RIELSTHNVINAEVAPGGPYRL (SEQ ID NO:
59), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PDKGASS (SEQ ID NO:60);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KRGNQY (SEQ ID NO:
61);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues VSTNMAK (SEQ ID NO:
62);
or
V. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from an influenza B virus, and wherein:
a. there are 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid substitutions within the 120 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid residues in the 120 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
b. there are 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid substitutions within the 150 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid residues in the 150 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
c. there are 2, 3, 4, 5 or more amino acid substitutions within the 160 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5 or more amino acid residues in the 160 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
and
d. there are 2, 3, 4, 5, 6, 7, 8 or more amino acid substitutions within the 190 helix of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8 or more amino acid residues in the 190 helix of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
or
VI. the nucleic acid comprises:
a. the nucleotide sequence set forth in SEQ ID NO:
20, or a complement thereof;
b. the nucleotide sequence set forth in SEQ ID NO:
22 or SEQ ID NO:
24, or a complement thereof;
or
c. the nucleotide sequence set forth in SEQ ID NO:
43, SEQ ID NO:
45, SEQ ID NO:
47, or SEQ ID NO:
49, or a complement thereof;
or
VII. the chimeric HA polypeptide comprises:
a. the amino acid sequence set forth in SEQ ID NO:
21, or the amino acid sequence set forth in SEQ ID NO:
21 without the signal peptide;
b. the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25, or the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25 without the signal peptide;
c. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
21;
d. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
23 or SEQ ID NO:
25;
e. the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50, or the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50 without the signal peptide;
or
f. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50.

104 more elements

A method of preventing an influenza virus disease in a subject, comprising administering to the subject an immunogenic composition comprising a chimeric hemagglutinin (HA) polypeptide or a nucleic acid encoding the chimeric HA polypeptide, wherein:

I. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues FIP and KIQLSTKNVINAEHAPGGPYRL (SEQ ID NO:
2), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PYQGKSS (SEQ ID NO:19);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKNSTY (SEQ ID NO:
6);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NDAAMQT (SEQ ID NO:
8);
or
II. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues HIP and RIRLSTYNVINAETAPGGPYRL (SEQ ID NO:
51), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NASTGGQS (SEQ ID NO:
52);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKKADTY (SEQ ID NO:
53);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues ADAKMQT (SEQ ID NO:
54);
or
III. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues LIP and KIELSTSNVINAEVAPGGPYRL (SEQ ID NO:
55), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PFGSSNS (SEQ ID NO:56);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 the hemagglutinin ectodomain are substituted with amino acid residues HQSGTY (SEQ ID NO:
57);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues TTLKMHQ (SEQ ID NO:
58) or ATLKMHQ (SEQ ID NO:
70);
or
IV the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NIP and RIELSTHNVINAEVAPGGPYRL (SEQ ID NO:
59), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PDKGASS (SEQ ID NO:60);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KRGNQY (SEQ ID NO:
61);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues VSTNMAK (SEQ ID NO:
62);
or
V. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from an influenza B virus, and wherein:
a. there are 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid substitutions within the 120 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid residues in the 120 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
b. there are 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid substitutions within the 150 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid residues in the 150 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
c. there are 2, 3, 4, 5 or more amino acid substitutions within the 160 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5 or more amino acid residues in the 160 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
and
d. there are 2, 3, 4, 5, 6, 7, 8 or more amino acid substitutions within the 190 helix of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8 or more amino acid residues in the 190 helix of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
or
VI. the nucleic acid comprises:
a. the nucleotide sequence set forth in SEQ ID NO:
20, or a complement thereof;
b. the nucleotide sequence set forth in SEQ ID NO:
22 or SEQ ID NO:
24, or a complement thereof;
or
c. the nucleotide sequence set forth in SEQ ID NO:
43, SEQ ID NO:
45, SEQ ID NO:
47, or SEQ ID NO:
49, or a complement thereof;
or
VII. the chimeric HA polypeptide comprises:
a. the amino acid sequence set forth in SEQ ID NO:
21, or the amino acid sequence set forth in SEQ ID NO:
21 without the signal peptide;
b. the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25, or the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25 without the signal peptide;
c. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
21;
d. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
23 or SEQ ID NO:
25;
e. the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50, or the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50 without the signal peptide;
or
f. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50.

104 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/512,751Filed 17 Nov 2023 · division
Priority: 15 Jun 2016
Published: US 2024/0335524 A110 Oct 2024
Granted: 25 Feb 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
A61K 39/145
Viral antigens: orthomyxoviridae, e.g. influenza virus
A61P 31/16
For RNA viruses: for influenza or rhinoviruses
A61P 37/04
Immunomodulators: immunostimulants

Family

Application62/350,701Us provisional application · filed 15 Jun 2016
Application62/355,679Us provisional application · filed 28 Jun 2016
PCT/US2017/037384Parent of this division · filed 14 Jun 2017
Application17/583,088Parent of this division · filed 24 Jan 2022
US 11,266,734 B2Parent of this division · filed 8 Mar 2022
US 2024/0335524 A1Pre-grant publication · published 10 Oct 2024
US 11,865,173 B2Parent of this division
Application16/305,845Parent of this division
US 2019/0314485 A1Published application
US 2022/0257749 A1Published application
US 12,233,123 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues FIP and KIQLSTKNVINAEHAPGGPYRL (SEQ ID NO:
2), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PYQGKSS (SEQ ID NO:19);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKNSTY (SEQ ID NO:
6);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NDAAMQT (SEQ ID NO:
8);
or
II. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues HIP and RIRLSTYNVINAETAPGGPYRL (SEQ ID NO:
51), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NASTGGQS (SEQ ID NO:
52);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KKKADTY (SEQ ID NO:
53);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues ADAKMQT (SEQ ID NO:
54);
or
III. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues LIP and KIELSTSNVINAEVAPGGPYRL (SEQ ID NO:
55), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PFGSSNS (SEQ ID NO:56);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 the hemagglutinin ectodomain are substituted with amino acid residues HQSGTY (SEQ ID NO:
57);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues TTLKMHQ (SEQ ID NO:
58) or ATLKMHQ (SEQ ID NO:
70);
or
IV. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
a. amino acid residues TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO:
1) in the 120 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues NIP and RIELSTHNVINAEVAPGGPYRL (SEQ ID NO:
59), respectively;
b. amino acid residues PNVTSRNG (SEQ ID NO:
18) in the 150 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues PDKGASS (SEQ ID NO:60);
c. amino acid residues RDNKTA (SEQ ID NO:
5) in the 160 loop of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues KRGNQY (SEQ ID NO:
61);
and
d. amino acid residues NKNQMKN (SEQ ID NO:
7) in the 190 helix of the globular head domain of the influenza B virus B/Yamagata/16/88 hemagglutinin ectodomain are substituted with amino acid residues VSTNMAK (SEQ ID NO:
62);
or
V. the chimeric HA polypeptide comprises a hemagglutinin ectodomain from an influenza B virus, and wherein:
a. there are 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid substitutions within the 120 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid residues in the 120 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
b. there are 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid substitutions within the 150 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8, 9 or more amino acid residues in the 150 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
c. there are 2, 3, 4, 5 or more amino acid substitutions within the 160 loop of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5 or more amino acid residues in the 160 loop of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
and
d. there are 2, 3, 4, 5, 6, 7, 8 or more amino acid substitutions within the 190 helix of the globular head domain of the influenza B virus hemagglutinin ectodomain, wherein the amino acid substitutions substitute 2, 3, 4, 5, 6, 7, 8 or more amino acid residues in the 190 helix of the globular head of the influenza B virus hemagglutinin ectodomain with amino acid residues found in a corresponding region of the globular domain of an influenza A virus hemagglutinin;
or
VI. the nucleic acid comprises:
a. the nucleotide sequence set forth in SEQ ID NO:
20, or a complement thereof;
b. the nucleotide sequence set forth in SEQ ID NO:
22 or SEQ ID NO:
24, or a complement thereof;
or
c. the nucleotide sequence set forth in SEQ ID NO:
43, SEQ ID NO:
45, SEQ ID NO:
47, or SEQ ID NO:
49, or a complement thereof;
or
VII. the chimeric HA polypeptide comprises:
a. the amino acid sequence set forth in SEQ ID NO:
21, or the amino acid sequence set forth in SEQ ID NO:
21 without the signal peptide;
b. the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25, or the amino acid sequence set forth in SEQ ID NO:
23 or SEQ ID NO:
25 without the signal peptide;
c. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
21;
d. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
23 or SEQ ID NO:
25;
e. the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50, or the amino acid sequence set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50 without the signal peptide;
or
f. the amino acid sequence of the influenza virus hemagglutinin ectodomain set forth in SEQ ID NO:
44, SEQ ID NO:
46, SEQ ID NO:
48, or SEQ ID NO:
50.

104 more elements

Facts

Application

18/512,751Filed 17 Nov 2023 · division

Priority

15 Jun 2016

Published

US 2024/0335524 A110 Oct 2024

Granted

25 Feb 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
A61K 39/145
Viral antigens: orthomyxoviridae, e.g. influenza virus
A61P 31/16
For RNA viruses: for influenza or rhinoviruses
A61P 37/04
Immunomodulators: immunostimulants

Family

Application62/350,701Us provisional application · filed 15 Jun 2016

Application62/355,679Us provisional application · filed 28 Jun 2016

PCT/US2017/037384Parent of this division · filed 14 Jun 2017

Application17/583,088Parent of this division · filed 24 Jan 2022

US 11,266,734 B2Parent of this division · filed 8 Mar 2022

US 2024/0335524 A1Pre-grant publication · published 10 Oct 2024

US 11,865,173 B2Parent of this division

Application16/305,845Parent of this division

US 2019/0314485 A1Published application

US 2022/0257749 A1Published application

US 12,233,123 B2This patent

From the US filing history. Foreign family members aren’t listed.