# US 11,896,665 B2 · Human herpesvirus immunotherapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,896,665 B2 - Document ID: US11896665B2 - Status: Granted - Kind: B2 - Application number: 17/226,929 - Filed: 2021-04-09 - Published: 2021-09-30 - Granted: 2024-02-13 - Earliest claimed: 2012-10-19 - Assignees: The Council of the Queensland Institute of Medical Research - Applicants: The Council of the Queensland Institute of Medical Research - Inventors: Rajiv Khanna; Dasari Vijayendra - Web page: https://patentgrep.com/patent/US11896665B2 ## CPC - A61K 39/245: Herpetoviridae, e.g. herpes simplex virus - A61P 31/22: for herpes viruses - A61P 37/04: Immunostimulants - C07K 14/005: from viruses - C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]} - 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 2039/572: {cytotoxic response} - A61K 2039/6031: {Proteins} - A61K 2039/70: {Multivalent vaccine} - C07K 2319/00: Fusion polypeptide - C07K 2319/21: containing a His-tag - C07K 2319/40: containing a tag for immunodetection, or an epitope for immunisation - C12N 2501/998: Proteins not provided for elsewhere - C12N 2710/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2710/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2710/16222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2710/16234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - 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 An isolated protein comprises respective amino acid sequences of each of a plurality of CTL epitopes from two or more different herpesvirus antigens and further comprises an intervening amino acid or amino acid sequence between at least two of said CTL epitopes comprising proteasome liberation amino acids or amino acid sequences and, optionally, Transporter Associated with Antigen Processing recognition motifs. The isolated protein is capable of rapidly expanding human cytotoxic T lymphocytes (CTL) in vitro and eliciting a CTL immune response in vivo upon administration to an animal as an exogenous protein. Typically, the isolated protein comprises no more than twenty (20) CTL epitopes derived from cytomegalovirus and/or Epstein-Barr virus antigens. ## Claims ### Claim 1 A protein comprising amino acid sequences of a plurality of CTL epitopes, wherein at least two of the CTL epitopes are separated by a sequence consisting of an intervening amino acid sequence, wherein the intervening amino acid sequence is a one or two amino acid sequence that comprises a proteasome liberation amino acid sequence selected from AD, K and R, and wherein the protein is capable of eliciting a cytotoxic T-lymphocyte immune response upon administration to an animal as an exogenous protein. ### Claim 2 (depends on 1) The protein of claim 1, wherein the epitopes are restricted by the HLA class I specificities HLA-A1, -A2, -A3, -A11, -A23, -A24, -A26, -A29, -A30, -B7, -B8, -B27, -B35, -B38, -B40, -B41, -B44, -B51, -B57 and/or -B58. ### Claim 3 (depends on 1) The protein of claim 1, wherein at least one of the CTL epitopes is from a herpesvirus antigen. ### Claim 4 (depends on 3) The protein of claim 3, wherein the herpesvirus is cytomegalovirus (CMV) or Epstein-Barr virus (EBV). ### Claim 5 (depends on 4) The protein of claim 4, wherein the at least one CMV CTL epitope is derived from pp50, pp65, and pp 150 or 1E-1. ### Claim 6 (depends on 1) The protein of claim 1, wherein the protein comprises at least one of the CTL epitope sequences selected from the amino acid sequences set forth in SEQ ID NOS: 1-21. ### Claim 7 (depends on 4) The protein of claim 4, wherein at least one EBV CTL epitope is derived from one or more antigens selected from BMLF1, LMP2a, BRLF1, LMP2, EBNA3A, BZLF1, EBNA3C, EBNA1 and EBNA3B. ### Claim 8 (depends on 1) The protein of claim 1, wherein the protein comprises at least one of the amino acid sequences set forth in SEQ ID NOS: 22-41. ### Claim 9 (depends on 1) The protein of claim 1, wherein the protein comprises a plurality of CTL epitopes selected from the CTL epitope amino acid sequences set forth in SEQ ID NOS: 22-41. ### Claim 10 (depends on 1) A nucleic acid encoding the protein of claim 1. ### Claim 11 (depends on 10) A genetic construct comprising the nucleic acid of claim 10, wherein the genetic construct is operably linked to one or more regulatory sequences in an expression vector. ### Claim 12 (depends on 10) An adenovirus comprising the nucleic acid of claim 10. ### Claim 13 (depends on 11) A host cell comprising the genetic construct of claim 11. ### Claim 14 (depends on 1) A pharmaceutical composition comprising the protein of claim 1, and a pharmaceutically-acceptable carrier, diluent or excipient. ### Claim 15 (depends on 14) The pharmaceutical composition of claim 14, further comprising an immunostimulatory molecule or adjuvant. ### Claim 16 (depends on 15) The pharmaceutical composition of claim 15, wherein the immunostimulatory molecule or adjuvant is one or more TLR agonists that include a TLR4 agonist and/or a TLR9 agonist. ### Claim 17 (depends on 15) The pharmaceutical composition of claim 15, which is a vaccine for eliciting a protective immune response against a herpesvirus in a human. ### Claim 18 A protein comprising amino acid sequences of a plurality of CTL epitopes, wherein each of the CTL epitopes are separated by a sequence consisting of an intervening amino acid sequence, wherein the intervening amino acid sequence is a one or two amino acid sequence comprising a proteasome liberation amino acid sequence selected from AD, K and R, and wherein the protein is capable of eliciting a cytotoxic T-lymphocyte immune response upon administration to an animal as an exogenous protein. ### Claim 19 (depends on 12) A host cell infected with the adenovirus of claim 12.