# US 12,594,294 B2 · Therapeutic and prophylactic agent for glioma, brain tumor malignancy marker, brain tumor prognostic marker, method for determining malignancy and prognosis of brain tumor and antibody inhibiting tumor proliferation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,594,294 B2 - Document ID: US12594294B2 - Status: Granted - Kind: B2 - Application number: 17/419,154 - Filed: 2019-12-27 - Published: 2022-04-07 - Granted: 2026-04-07 - Earliest claimed: 2018-12-28 - Assignees: The University of Tokyo; Yamaguchi University - Applicants: The University of Tokyo; Yamaguchi University - Inventors: Kohei Miyazono; Ryo Tanabe; Masato Morikawa; Carl-Henrik Heldin; Bengt Westermark; Koji Tamada - Web page: https://patentgrep.com/patent/US12594294B2 ## CPC - A61K 31/7088: Compounds having three or more nucleosides or nucleotides - C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95} - A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links - A61P 35/00: Antineoplastic agents - C07K 16/18: against material from animals or humans - G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites} - A61K 2039/505: {comprising antibodies} - C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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 A novel agent is for treating or preventing a glioma. A marker for malignancy of a brain tumor and a prognostic marker for a brain tumor can be used in a method for determining malignancy of a brain tumor and a method for determining a prognosis for a brain tumor patient. The agent for treating or preventing a glioma can include an HVEM inhibitor as an active ingredient. The marker for malignancy of a brain tumor and the prognostic marker for a brain tumor can each include an HVEM protein or an HVEM gene. The method for determining malignancy of a brain tumor and the method for determining a prognosis for a brain tumor patient can each include measuring an HVEM expression amount in a biological sample of a subject. ## Claims ### Claim 1 A single variable domain of an immunoglobulin heavy chain which binds to herpesvirus entry mediator (HVEM), said domain comprising a polypeptide with an amino acid sequence having at least 80% identity to the amino acid sequence of any of SEQ ID NOs: 30 to 35 or having at least 85% identity to the amino acid sequence of SEQ ID NO: 29. ### Claim 2 (depends on 1) The single variable domain of the heavy chain according to claim 1, which comprises complementarity determining regions 1 to 3 (CDR1, CDR2 and CDR3), wherein amino acid sequences of CDR1 CDR2 and CDR3 are the following (i), (ii), (iii), (iv), (v), (vi) or (vii): (i) CDR1 comprising an amino acid sequence represented by SEQ ID NO: 36, CDR2 comprising an amino acid sequence represented by SEQ ID NO: 37, and CDR3 comprising an amino acid sequence represented by SEQ ID NO: 38: (ii) CDR1 comprising an amino acid sequence represented by SEQ ID NO: 39, CDR2 comprising an amino acid sequence represented by SEQ ID NO: 40, and CDR3 comprising an amino acid sequence represented by SEQ ID NO: 41, (iii) CDR1 comprising an amino acid sequence represented by SEQ ID NO: 42, CDR2 comprising an amino acid sequence represented by SEQ ID NO: 43, and CDR3 comprising an amino acid sequence represented by SEQ ID NO: 44; (iv) CDR1 comprising an amino acid sequence represented by SEQ ID NO: 45, CDR2 comprising an amino acid sequence represented by SEQ ID NO: 46, and CDR3 comprising an amino acid sequence represented by SEQ ID NO: 47; (v) CDR1 comprising an amino acid sequence represented by SEQ ID NO: 48, CDR2 comprising an amino acid sequence represented by SEQ ID NO: 49, and CDR3 comprising an amino acid sequence represented by SEQ ID NO: 50; (vi) CDR1 comprising an amino acid sequence represented by SEQ ID NO: 51, CDR2 comprising an amino acid sequence represented by SEQ ID NO: 52, and CDR3 comprising an amino acid sequence represented by SEQ ID NO: 53; or (vii) CDR1 comprising an amino acid sequence represented by SEQ ID NO: 54, CDR2 comprising an amino acid sequence represented by SEQ ID NO: 55, and CDR3 comprising an amino acid sequence represented by SEQ ID NO: 56. ### Claim 3 (depends on 2) The single variable domain of the heavy chain according to claim 2, which comprises framework regions (FR1, FR2, FR3 and FR4), wherein amino acid sequences of FR1, FR2, FR3 and FR4 are the following (viii), (ix), (x), (xi), (xii), (xiii) or (xiv): (viii) FR1 comprising an amino acid sequence represented by SEQ ID NO: 57, FR2 comprising an amino acid sequence represented by SEQ ID NO: 58, FR3 comprising an amino acid sequence represented by SEQ ID NO: 59, and FR4 comprising an amino acid sequence represented by SEQ ID NO: 60; (ix) FR1 comprising an amino acid sequence represented by SEQ ID NO: 61, FR2 comprising an amino acid sequence represented by SEQ ID NO: 62, FR3 comprising an amino acid sequence represented by SEQ ID NO: 63, and FR4 comprising an amino acid sequence represented by SEQ ID NO: 64; (x) FR1 comprising an amino acid sequence represented by SEQ ID NO: 65, FR2 comprising an amino acid sequence represented by SEQ ID NO: 66, FR3 comprising an amino acid sequence represented by SEQ ID NO: 67, and FR4 comprising an amino acid sequence represented by SEQ ID NO: 68; (xi) FR1 comprising an amino acid sequence represented by SEQ ID NO: 69, FR2 comprising an amino acid sequence represented by SEQ ID NO: 70, FR3 comprising an amino acid sequence represented by SEQ ID NO: 71, and FR4 comprising an amino acid sequence represented by SEQ ID NO: 72; (xii) FR1 comprising an amino acid sequence represented by SEQ ID NO: 73, FR2 comprising an amino acid sequence represented by SEQ ID NO: 74, FR3 comprising an amino acid sequence represented by SEQ ID NO: 75, and FR4 comprising an amino acid sequence represented by SEQ ID NO: 76; (xiii) FR1 comprising an amino acid sequence represented by SEQ ID NO: 77, FR2 comprising an amino acid sequence represented by SEQ ID NO: 78, FR3 comprising an amino acid sequence represented by SEQ ID NO: 79, and FR4 comprising an amino acid sequence represented by SEQ ID NO: 80; or (xiv) FR1 comprising an amino acid sequence represented by SEQ ID NO: 81, FR2 comprising an amino acid sequence represented by SEQ ID NO: 82, FR3 comprising an amino acid sequence represented by SEQ ID NO: 83, and FR4 comprising an amino acid sequence represented by SEQ ID NO: 84. ### Claim 4 (depends on 1) An antibody or an immunoglobulin multimer, each having variable regions consisting of single variable domains of the heavy chain according to claim 1. ### Claim 5 (depends on 1, 4) A polynucleotide encoding the single variable domain of the heavy chain according to claim 1 or the antibody or multimer according to claim 4. ### Claim 6 (depends on 1, 4) A pharmaceutical composition comprising the single variable domain of the heavy chain according to claim 1 or the antibody or multimer according to claim 4. ### Claim 7 (depends on 6) The pharmaceutical composition according to claim 6, which is formulated for the treatment of a glioma.