Toll-Like Receptor 3 Antagonists
AssigneeJanssen Biotech, Inc.
InventorsMark 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
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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.
Claims15
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.
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.
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.
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.
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.
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.
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.
Dependencies are inferred from the claim text.