# US 2013/0280263 A1 · Toll-Like Receptor 3 Antagonists > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0280263 A1 - Document ID: US20130280263A1 - Status: Published application - Kind: A1 - Application number: 13/798,494 - Filed: 2013-03-13 - Published: 2013-10-24 - Earliest claimed: 2008-10-31 - Assignees: Janssen Biotech, Inc. - Inventors: Mark Cunningham; Yiqing Feng; Katharine Heeringa; Jinquan Luo; Robert Rauchenberger; Mark Rutz; Lani San Mateo; Robert Sarisky; Raymond Sweet; Fang Teng; Alexey Teplyakov; Sheng-Jiun Wu - Web page: https://patentgrep.com/patent/US20130280263A1 ## CPC - C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere} - A61K 39/39533: {against materials from animals} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - A61P 11/00: Drugs for disorders of the respiratory system - A61P 11/02: Nasal agents, e.g. decongestants - A61P 11/06: Antiasthmatics - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/12: Antivirals - A61P 31/16: for influenza or rhinoviruses - A61P 37/00: Drugs for immunological or allergic disorders - A61P 37/02: Immunomodulators - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - C07H 21/04: with deoxyribosyl as saccharide radical - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - C12N 15/117: Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs - A61K 2039/505: {comprising antibodies} - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - C07K 16/18: against material from animals or humans - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 2317/21: from primates, e.g. man - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1 - C07K 2317/515: Complete light chain, i.e. VL + CL - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/55: Fab or Fab' - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/565: Complementarity determining region [CDR] - 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 - C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance - C12N 5/10: Cells modified by introduction of foreign genetic material - C12N 5/12: Fused cells, e.g. hybridomas - C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression - C12N 2310/17: Immunomodulatory nucleic acids - 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) - 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 - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Toll Like Receptor 3 (TLR3) antibody antagonists, polynucleotides encoding TLR3 antibody antagonists or fragments thereof, and methods of making and using the foregoing are disclosed. ## Claims ### Claim 1 A method of treating asthma or asthma exacerbation comprising administering a therapeutically effective amount of an isolated monoclonal antibody or fragment thereof that binds toll-like receptor 3 (TLR3) to a patient in need thereof for a time sufficient to treat asthma or asthma exacerbation, wherein the isolated antibody a. competes for TLR3 binding with a monoclonal antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 216 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 41; b. comprises a heavy chain complementarity determining region (CDR) 1 (HCDR1), 2 (HCDR2) and 3 HCDR3) having the amino acid sequences as shown in SEQ ID NOs: 82, 86 and 84, respectively, and a light chain CDR 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) having the amino acid sequences as shown in SEQ ID NOs: 79, 80 and 87, respectively; c. comprises the VH of SEQ ID NO: 216 and the VL of SEQ ID NO: 41; d. competes for TLR3 binding with a monoclonal antibody comprising a VH having the amino acid sequence of SEQ ID NO: 214 and a VL having the amino acid sequence of SEQ ID NO: 211; e. comprises a HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 70, 77 and 72, respectively, and a LCDR1, LCDR2 and LCDR3 having the amino acid sequences as shown in SEQ ID NOs: 67, 68 and 78, respectively; or f. comprises the VH of SEQ ID NO: 214 and the VL of SEQ ID NO: 211. ### Claim 2 (depends on 1) The method of claim 1, wherein asthma or asthma exacerbation is associated with an infiltration of inflammatory cells in lung, airway hyperresponsiveness, mucus hypersecretion, subepithelial fibrosis or elevated IgE levels. ### Claim 3 (depends on 2) The method of claim 2, wherein the inflammatory cells are eosinophils or neutrophils. ### Claim 4 A method of reducing an infiltration of inflammatory cells in lung comprising administering a therapeutically effective amount of an isolated monoclonal antibody or fragment thereof that binds TLR3 to a patient suffering from a disease associated with increased infiltration of inflammatory cells in lung for a time sufficient to reduce the infiltration of inflammatory cells in lung, wherein the isolated antibody a. competes for TLR3 binding with a monoclonal antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 216 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 41; b. comprises a heavy chain complementarity determining region (CDR) 1 (HCDR1), 2 (HCDR2) and 3 HCDR3) having the amino acid sequences as shown in SEQ ID NOs: 82, 86 and 84, respectively, and a light chain CDR 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) having the amino acid sequences as shown in SEQ ID NOs: 79, 80 and 87, respectively; c. comprises the VH of SEQ ID NO: 216 and the VL of SEQ ID NO: 41; d. competes for TLR3 binding with a monoclonal antibody comprising a VH having the amino acid sequence of SEQ ID NO: 214 and a VL having the amino acid sequence of SEQ ID NO: 211; e. comprises a HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 70, 77 and 72, respectively, and a LCDR1, LCDR2 and LCDR3 having the amino acid sequences as shown in SEQ ID NOs: 67, 68 and 78, respectively; or f. comprises the VH of SEQ ID NO: 214 and the VL of SEQ ID NO: 211. ### Claim 5 (depends on 4) The method of claim 4, wherein the inflammatory cells are neutrophils or eosinophils. ### Claim 6 (depends on 4) The method of claim 4, wherein the disease associated with increased infiltration of inflammatory cells in lung is asthma, asthma exacerbation, viral infection, influenza virus infection, chronic obstructive pulmonary disease (COPD), allergy, bacterial pneumonia or cystic fibrosis. ### Claim 7 A method of reducing airway hyperresponsiveness comprising administering a therapeutically effective amount of an isolated monoclonal antibody or fragment thereof that binds TLR3 to a patient suffering from a disease associated with airway hyperresponsiveness for a time sufficient to reduce airway hyperresponsiveness, wherein the antibody a. competes for TLR3 binding with a monoclonal antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 216 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 41; b. comprises a heavy chain complementarity determining region (CDR) 1 (HCDR1), 2 (HCDR2) and 3 HCDR3) having the amino acid sequences as shown in SEQ ID NOs: 82, 86 and 84, respectively, and a light chain CDR 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) having the amino acid sequences as shown in SEQ ID NOs: 79, 80 and 87, respectively; c. comprises the VH of SEQ ID NO: 216 and the VL of SEQ ID NO: 41; d. competes for TLR3 binding with a monoclonal antibody comprising a VH having the amino acid sequence of SEQ ID NO: 214 and a VL having the amino acid sequence of SEQ ID NO: 211; e. comprises a HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 70, 77 and 72, respectively, and a LCDR1, LCDR2 and LCDR3 having the amino acid sequences as shown in SEQ ID NOs: 67, 68 and 78, respectively; or f. comprises the VH of SEQ ID NO: 214 and the VL of SEQ ID NO: 211. ### Claim 8 (depends on 7) The method of claim 7, wherein airway hyperresponsiveness is associated with asthma, asthma exacerbation, viral infection, influenza virus infection, chronic obstructive pulmonary disease (COPD), allergy, allergic rhinitis or cystic fibrosis. ### Claim 9 A method of treating inflammatory bowel disease (IBD) comprising administering a therapeutically effective amount of an isolated monoclonal antibody or fragment thereof that binds TLR3 to a patient in need thereof for a time sufficient to treat the gastrointestinal inflammation, wherein the isolated antibody a. competes for TLR3 binding with a monoclonal antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 216 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 41; b. comprises a heavy chain complementarity determining region (CDR) 1 (HCDR1), 2 (HCDR2) and 3 HCDR3) having the amino acid sequences as shown in SEQ ID NOs: 82, 86 and 84, respectively, and a light chain CDR 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) having the amino acid sequences as shown in SEQ ID NOs: 79, 80 and 87, respectively; c. comprises the VH of SEQ ID NO: 216 and the VL of SEQ ID NO: 41; d. competes for TLR3 binding with a monoclonal antibody comprising a VH having the amino acid sequence of SEQ ID NO: 214 and a VL having the amino acid sequence of SEQ ID NO: 211; e. comprises a HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 70, 77 and 72, respectively, and a LCDR1, LCDR2 and LCDR3 having the amino acid sequences as shown in SEQ ID NOs: 67, 68 and 78, respectively; or f. comprises the VH of SEQ ID NO: 214 and the VL of SEQ ID NO: 211. ### Claim 10 (depends on 9) The method of claim 9, wherein IBD is ulcerative colitis (UC) or Crohn's disease (CD). ### Claim 11 A method of treating sepsis comprising administering a therapeutically effective amount of an isolated monoclonal antibody or fragment thereof that binds TLR3 to a patient in need thereof for a time sufficient to treat the sepsis, wherein the isolated antibody a. competes for TLR3 binding with a monoclonal antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 216 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 41; b. comprises a heavy chain complementarity determining region (CDR) 1 (HCDR1), 2 (HCDR2) and 3 HCDR3) having the amino acid sequences as shown in SEQ ID NOs: 82, 86 and 84, respectively, and a light chain CDR 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) having the amino acid sequences as shown in SEQ ID NOs: 79, 80 and 87, respectively; c. comprises the VH of SEQ ID NO: 216 and the VL of SEQ ID NO: 41; d. competes for TLR3 binding with a monoclonal antibody comprising a VH having the amino acid sequence of SEQ ID NO: 214 and a VL having the amino acid sequence of SEQ ID NO: 211; e. comprises a HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 70, 77 and 72, respectively, and a LCDR1, LCDR2 and LCDR3 having the amino acid sequences as shown in SEQ ID NOs: 67, 68 and 78, respectively; or f. comprises the VH of SEQ ID NO: 214 and the VL of SEQ ID NO: 211. ### Claim 12 A method of treating or preventing viral infection comprising administering a therapeutically effective amount of an isolated monoclonal antibody or fragment thereof that binds TLR3 to a patient in need thereof for a time sufficient to treat or prevent viral infection, wherein the isolated antibody a. competes for TLR3 binding with a monoclonal antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 216 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 41; b. comprises a heavy chain complementarity determining region (CDR) 1 (HCDR1), 2 (HCDR2) and 3 HCDR3) having the amino acid sequences as shown in SEQ ID NOs: 82, 86 and 84, respectively, and a light chain CDR 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) having the amino acid sequences as shown in SEQ ID NOs: 79, 80 and 87, respectively; c. comprises the VH of SEQ ID NO: 216 and the VL of SEQ ID NO: 41; d. competes for TLR3 binding with a monoclonal antibody comprising a VH having the amino acid sequence of SEQ ID NO: 214 and a VL having the amino acid sequence of SEQ ID NO: 211; e. comprises a HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 70, 77 and 72, respectively, and a LCDR1, LCDR2 and LCDR3 having the amino acid sequences as shown in SEQ ID NOs: 67, 68 and 78, respectively; or f. comprises the VH of SEQ ID NO: 214 and the VL of SEQ ID NO: 211. ### Claim 13 (depends on 11) The method of claim 11, wherein viral infection is influenza virus or human rhinovirus infection. ### Claim 14 A method of treating rheumatoid arthritis comprising administering a therapeutically effective amount of an isolated monoclonal antibody or fragment thereof that binds TLR3 to a patient in need thereof for a time sufficient to treat rheumatoid arthritis, wherein the isolated antibody a. competes for TLR3 binding with a monoclonal antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 216 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 41; b. comprises a heavy chain complementarity determining region (CDR) 1 (HCDR1), 2 (HCDR2) and 3 HCDR3) having the amino acid sequences as shown in SEQ ID NOs: 82, 86 and 84, respectively, and a light chain CDR 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) having the amino acid sequences as shown in SEQ ID NOs: 79, 80 and 87, respectively; c. comprises the VH of SEQ ID NO: 216 and the VL of SEQ ID NO: 41; d. competes for TLR3 binding with a monoclonal antibody comprising a VH having the amino acid sequence of SEQ ID NO: 214 and a VL having the amino acid sequence of SEQ ID NO: 211; e. comprises a HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 70, 77 and 72, respectively, and a LCDR1, LCDR2 and LCDR3 having the amino acid sequences as shown in SEQ ID NOs: 67, 68 and 78, respectively; or f. comprises the VH of SEQ ID NO: 214 and the VL of SEQ ID NO: 211. ### Claim 15 (depends on 1) The method of claim 1, wherein the isolated monoclonal antibody or fragment thereof that binds TLR3 is human or human-adapted.