# US 11,992,525 B2 · Chimeric influenza vaccines > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,992,525 B2 - Document ID: US11992525B2 - Status: Granted - Kind: B2 - Application number: 18/501,578 - Filed: 2023-11-03 - Published: 2024-03-28 - Granted: 2024-05-28 - Earliest claimed: 2020-05-08 - Assignees: Academia Sinica - Applicants: Academia Sinica - Inventors: Chi-Huey Wong; Hsin-Yu Liao; Shih-Chi Wang; Yi-An Ko; Kuo-I Lin; Che Ma; Ting-Jen Cheng - Web page: https://patentgrep.com/patent/US11992525B2 ## CPC - A61K 39/12: Viral antigens - A61K 39/145: Orthomyxoviridae, e.g. influenza virus - A61P 31/16: for influenza or rhinoviruses - C07K 14/005: from viruses - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 2039/55505: {Inorganic adjuvants} - A61K 2039/55572: {Lipopolysaccharides; Lipid A; Monophosphoryl lipid A} - A61K 2039/572: {cytotoxic response} - A61K 2039/575: {humoral response} - A61K 2039/58: {raising an immune response against a target which is not the antigen used for immunisation} - C12N 2760/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2760/16171: Demonstrated in vivo effect - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present disclosure relates to a chimeric influenza virus hemagglutinin (HA) polypeptide, comprising one or more stem domain sequence, each having at least 60% homology with a stem domain consensus sequence of H1 subtype HA (H1 HA) and/or H5 subtype HA (H5 HA), fused with one or more globular head domain sequence, each having at least 60% homology with a globular head domain consensus sequence of H1 subtype HA (H1 HA) or H5 subtype HA (H5 HA). ## Claims ### Claim 1 An immunogenic composition comprising a monoglycosylated chimeric influenza virus hemagglutinin (HA) polypeptide and an adjuvant; wherein the monoglycosylated chimeric influenza virus HA polypeptide comprising an amino acid sequence of SEQ ID NO: 4; wherein the monoglycosylated chimeric influenza virus HA polypeptide has only N-Acetylglucosamine (GlcNAc) at N28, N40, N182, N292, and N497; and wherein the adjuvant is selected from the group consisting of Al(OH)3, AlPO4, an analog of α-galactosylceramide (α-GalCer), squalene and QS21. ### Claim 2 (depends on 1) The immunogenic composition of claim 1, wherein the monoglycosylated chimeric influenza virus HA polypeptide further comprises only N-Acetylglucosamine (GlcNAc) at N171 and N303. ### Claim 3 (depends on 1) The immunogenic composition of claim 1, wherein the adjuvant is Al(OH)3. ### Claim 4 (depends on 1) The immunogenic composition of claim 1, wherein the analog of a-galactosylceramide is C34. ### Claim 5 (depends on 1) The immunogenic composition of claim 1, wherein the monoglycosylated chimeric influenza virus HA polypeptide is existed as a trimer. ### Claim 6 (depends on 1) A method of immunizing a subject against influenza virus or preventing an influenza virus disease comprising administering an effective amount of the immunogenic composition of claim 1 to the subject. ### Claim 7 (depends on 6) The method of claim 6, wherein the method elicits CD4+ and CD8+ T-cell immune responses. ### Claim 8 (depends on 6) The method of claim 6, wherein the method induces stem-specific antibodies, with higher antibody-dependent cellular cytotoxicity (ADCC), better neutralizing and stronger cross-protection activities against H1, H3, H5 and H7 strains and subtypes. ### Claim 9 (depends on 6) The method of claim 6, wherein the method enhances the vaccine efficacy with more IFN-γ, IL-4 and CD8+ memory T cells produced. ### Claim 10 A method for preparing a chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5, having one or more stem domain sequence fused with one or more globular head domain sequence, comprising: composing H1 as HA1 (amino acids 1-327 of SEQ ID NO: 8) And H5 as HA2 (amino acids 328503 of SEQ ID NO: 8) giving H1 as globular head and [H1+H5 (HA2)] as stem. ### Claim 11 (depends on 10) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 of claim 10, wherein one or more glycosites on the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 are monoglycosylated. ### Claim 12 (depends on 11) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 of claim 11, wherein the monoglycosylated HA polypeptide Swap H1/5 has only N-Acetylglucosamine (GlcNAc) on each glycosite. ### Claim 13 (depends on 10) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 of claim 10, wherein the chimeric influenza virus HA polypeptide Swap H1/5 comprises the amino acid sequence of SEQ ID NO: 8. ### Claim 14 A method for preparing a chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1, having one or more stem domain sequence fused with one or more globular head domain sequence, comprising: composing H5 as HA1 (amino acid 1-330 of SEQ ID NO: 12) And H1 as HA2 (amino acid 331-506 of SEQ ID NO: 12) giving H5 as globular head and [H5+H1 (HA2)] as stem. ### Claim 15 (depends on 14) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 of claim 14, wherein one or more glycosites on the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 are monoglycosylated. ### Claim 16 (depends on 15) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 of claim 15, wherein the monoglycosylated HA polypeptide Swap H5/1 has only N-Acetylglucosamine (GlcNAc) on each glycosite. ### Claim 17 (depends on 14) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 of claim 14, wherein the chimeric influenza virus HA polypeptide Swap H5/1 comprises the amino acid sequence of SEQ ID NO: 12. ### Claim 18 A method for preparing a chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1, having one or more stem domain sequence fused with one or more globular head domain sequence, comprising: (a) constructing the globular head domain with the amino acid sequence between residues C42 and C274 of SEQ ID NO: 4 (H3 numbering); and (b) constructing the stem domain with portions of HA1 and HA2 subunits (amino acids 1˜41 of SEQ ID NO: 4 and 275-511 of SEQ ID NO: 4). ### Claim 19 (depends on 18) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 of claim 18, wherein one or more glycosites on the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 are monoglycosylated. ### Claim 20 (depends on 19) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 of claim 19, wherein the monoglycosylated HA polypeptide chimeric H5/1 has only N-Acetylglucosamine (GlcNAc) on each glycosite. ### Claim 21 (depends on 18) The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 of claim 18, wherein the chimeric influenza virus HA polypeptide chimeric H5/1 comprises the amino acid sequence of SEQ ID NO: 4.