# US 8,465,960 B2 · Influenza B viruses with reduced sensitivity to neuraminidase inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,465,960 B2 - Document ID: US8465960B2 - Status: Granted - Kind: B2 - Application number: 12/058,389 - Filed: 2008-03-28 - Published: 2008-11-27 - Granted: 2013-06-18 - Earliest claimed: 2007-03-28 - Assignees: Wisconsin Alumni Research Foundation - Applicants: Yoshihiro Kawaoka; Shuji Hatakeyama - Inventors: Yoshihiro Kawaoka; Shuji Hatakeyama - Web page: https://patentgrep.com/patent/US8465960B2 ## CPC - C07K 14/005: from viruses - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - A61K 35/13: Tumour cells, irrespective of tissue of origin (tumour vaccines A61K39/00) - C12N 2760/16221: Viruses as such, e.g. new isolates, mutants or their genomic sequences - C12N 2760/16222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - G01N 2333/11: Orthomyxoviridae, e.g. influenza virus - 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) - 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) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract An isolated influenza B virus which has reduced sensitivity to one or more neuraminidase (NA) inhibitors, wherein the reduced sensitivity to one or more NA inhibitors is associated with a residue in NA other than Ile at position 222, a residue in NA other than Ser at a position 250, or a residue in NA other than Gly at position 402, as well as methods to detect such a virus or determine agents that inhibit the infection or replication of such as virus, are provided. ## Claims ### Claim 1 A method to select a neuraminidase (NA) inhibitor for a mammal infected with an influenza B virus, comprising: detecting in a sample from the mammal an influenza virus neuraminidase (NA) with a residue other than Ile at position 222, other than Ser at position 250, other than Gly at position 402, or a combination thereof, wherein the numbering for NA residues is that for N2, which residue other than Ile at position 222, Ser at position 250, or Gly at position 402 is associated with reduced sensitivity to peramivir, oseltamivir or zanamivir; and administering a NA inhibitor effective to treat the mammal which inhibitor is selected based on the residue at position 222, at position 250, or at position 402. ### Claim 2 (depends on 1) The method of claim 1 wherein the NA further comprises a residue at position 198 other than Asp. ### Claim 3 (depends on 2) The method of claim 2 wherein the residue at position 198 is Asn. ### Claim 4 (depends on 1) The method of claim 1 wherein the residue at position 222 is Thr. ### Claim 5 (depends on 1) The method of claim 1 wherein the residue at position 250 is Gly. ### Claim 6 (depends on 1) The method of claim 1 wherein the residue at position 402 is Ser. ### Claim 7 (depends on 1) The method of claim 1 wherein the sample is a pharyngeal sample. ### Claim 8 (depends on 1) The method of claim 1 wherein the sample is a nasal sample. ### Claim 9 (depends on 1) The method of claim 1 wherein the sample is cultured in vitro prior to detection. ### Claim 10 (depends on 9) The method of claim 9 wherein MDCK cells are employed to culture the sample. ### Claim 11 A method to select a NA inhibitor for a mammal that has not been treated with a NA inhibitor and is suspected of being infected with an influenza B virus, comprising: providing a sample from the mammal; detecting in the sample an influenza virus NA with a residue other than Asp at position 198, other than Ile at position 222, other than Ser at position 250, other than Gly at position 402, or a combination thereof, wherein the numbering for NA residues is that for N2, which residue other than Asp at position 198, Ile at position 222, Ser at position 250, or Gly at position 402 is associated with reduced sensitivity to peramivir, oseltamivir or zanamivir; and administering a NA inhibitor effective to treat the mammal which inhibitor is selected based on the residue at position 198, at position 222, at position 250, or at position 402. ### Claim 12 A method to select a NA inhibitor for a mammal infected with an influenza B virus, comprising providing a mammalian sample suspected of having influenza virus; detecting in the sample an influenza B virus NA with a Thr at position 222, a Gly at position 250, or a Ser at position 402, or a combination thereof, wherein the numbering for NA residues is that for N2; and administering a NA inhibitor effective to treat the mammal based on whether the virus has a Thr at position 222, a Gly at position 250, or a Ser at position 402. ### Claim 13 A method to select a NA inhibitor for a mammal that has not been treated with a NA inhibitor and is suspected of being infected with an influenza B virus, comprising: providing a sample from the mammal; and detecting in the sample an influenza B virus NA with a Asn at position 198, a Thr at position 222, a Gly at position 250, or a Ser at position 402, or a combination thereof, wherein the numbering for NA residues is that for N2; and administering a NA inhibitor effective to treat the mammal based on whether the virus has Asn at position 198, Thr at position 222, Gly at position 250, or Ser at position 402. ### Claim 14 (depends on 12, 13) The method of claim 12 or 13 wherein the sample is a pharyngeal sample. ### Claim 15 (depends on 12, 13) The method of claim 12 or 13 wherein the sample is a nasal sample. ### Claim 16 (depends on 12, 13) The method of claim 12 or 13 wherein the sample is a human sample. ### Claim 17 A method to treat a human infected with an influenza B virus with reduced sensitivity to a NA inhibitor, comprising: providing a human infected with an influenza B virus having a NA with a Thr at position 222, a Gly at position 250, or a Ser at position 402, or a combination thereof, wherein the numbering for NA residues is that for N2, wherein an influenza B virus NA with a Thr at position 222, a Gly at position 250, or a Ser at position 402 is indicative of a virus with reduced sensitivity to a NA inhibitor; and treating the human with a NA inhibitor that is selected based on whether the virus has Thr at position 222, Gly at position 250, or Ser at position 402.