US 11,865,173 B2
Influenza virus hemagglutinin proteins and uses thereof
Peter Palese, New York, NY (US); Adolfo Garcia-Sastre, New York, NY (US); Megan Ermler, New York, NY (US); and Florian Krammer, New York, NY (US)
Assigned to ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI, New York, NY (US)
Filed by ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI, New York, NY (US)
Filed on Jan. 24, 2022, as Appl. No. 17/583,088.
Application 17/583,088 is a division of application No. 16/305,845, granted, now 11,266,734, previously published as PCT/US2017/037384, filed on Jun. 14, 2017.
Claims priority of provisional application 62/355,679, filed on Jun. 28, 2016.
Claims priority of provisional application 62/350,701, filed on Jun. 15, 2016.
Prior Publication US 2022/0257749 A1, Aug. 18, 2022
Int. Cl. A61K 39/145 (2006.01); A61K 39/12 (2006.01); A61K 35/76 (2015.01); C07K 14/005 (2006.01); C07K 14/11 (2006.01); A61K 39/00 (2006.01)
CPC A61K 39/145 (2013.01) [C07K 14/005 (2013.01); A61K 2039/525 (2013.01); A61K 2039/53 (2013.01); A61K 2039/545 (2013.01); A61K 2039/70 (2013.01); C12N 2760/16122 (2013.01); C12N 2760/16134 (2013.01); C12N 2760/16171 (2013.01); C12N 2760/16222 (2013.01); C12N 2760/16234 (2013.01); C12N 2760/16271 (2013.01)] 27 Claims
 
1. A nucleic acid sequence encoding a chimeric hemagglutinin (HA) polypeptide, wherein the chimeric HA polypeptide comprises a hemagglutinin ectodomain from influenza B virus B/Yamagata/16/88, and wherein:
I. a. the following amino acid residues in the 120 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO: 1) are substituted with amino acid residues FIP and KIQLSTKNVINAEHAPGGPYRL (SEQ ID NO: 2);
b. the following amino acid residues in the 150 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin PNVTSRNG (SEQ ID NO: 18) are substituted with amino acid residues PYQGKSS (SEQ ID NO:19);
c. the following amino acid residues in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin RDNKTA (SEQ ID NO: 5) are substituted with amino acid residues KKNSTY (SEQ ID NO: 6); and
d. the following amino acid residues in the 190 helix of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin NKNQMKN (SEQ ID NO: 7) are substituted with amino acid residues NDAAMQT (SEQ ID NO: 8);
II. a. the following amino acid residues in the 120 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO: 1) are substituted with amino acid residues HIP and RIRLSTYNVINAETAPGGPYRL (SEQ ID NO: 51);
b the following amino acid residues in the 150 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin PNVTSRNG (SEQ ID NO: 18) are substituted with amino acid residues NASTGGQS (SEQ ID NO: 52);
c. the following amino acid residues in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin RDNKTA (SEQ ID NO: 5) are substituted with amino acid residues KKKADTY (SEQ ID NO: 53); and
d. the following amino acid residues in the 190 helix of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin NKNQMKN (SEQ ID NO: 7) are substituted with amino acid residues ADAKMQT (SEQ ID NO: 54);
III. a. the following amino acid residues in the 120 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO: 1) are substituted with amino acid residues LIP and KIELSTSNVINAEVAPGGPYRL (SEQ ID NO: 55);
b. the following amino acid residues in the 150 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin PNVTSRNG (SEQ ID NO: 18) are substituted with amino acid residues PFGSSNS (SEQ ID NO:56);
c. the following amino acid residues in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin RDNKTA (SEQ ID NO: 5) are substituted with amino acid residues HQSGTY (SEQ ID NO: 57); and
d. the following amino acid residues in the 190 helix of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin NKNQMKN (SEQ ID NO: 7) are substituted with amino acid residues TTLKMHQ (SEQ ID NO: 58) or ATLKMHQ (SEQ ID NO: 70); or
IV. a. the following amino acid residues in the 120 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin TIP and NIRLSTHNVINAERAPGGPYRL (SEQ ID NO: 1) are substituted with amino acid residues NIP and RIELSTHNVINAEVAPGGPYRL (SEQ ID NO: 59);
b. the following amino acid residues in the 150 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin PNVTSRNG (SEQ ID NO: 18) are substituted with amino acid residues PDKGASS (SEQ ID NO:60);
c. the following amino acid residues in the 160 loop of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin RDNKTA (SEQ ID NO: 5) are substituted with amino acid residues KRGNQY (SEQ ID NO: 61); and
d. the following amino acid residues in the 190 helix of the globular head domain of influenza B virus B/Yamagata/16/88 hemagglutinin NKNQMKN (SEQ ID NO: 7) are substituted with amino acid residues VSTNMAK (SEQ ID NO: 62).