Compositions and methods that inhibit il-23 signaling
US-2024425579-A1 · Dec 26, 2024 · US
US9453072B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9453072-B2 |
| Application number | US-201414205512-A |
| Country | US |
| Kind code | B2 |
| Filing date | Mar 12, 2014 |
| Priority date | Mar 13, 2013 |
| Publication date | Sep 27, 2016 |
| Grant date | Sep 27, 2016 |
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The present invention provides antibodies that bind to interleukin-33 (IL-33) and methods of using the same. The invention includes antibodies that inhibit or attenuate IL-33-mediated signaling. The antibodies of the invention may function to block the interaction between IL-33 and ST2. Alternatively, certain antibodies of the invention inhibit or attenuate IL-33-mediated signaling without blocking the IL-33/ST2 interaction. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human IL-33 with high affinity. The antibodies of the invention are useful for the treatment of diseases and disorders associated with IL-33 signaling and/or IL-33 cellular expression, such as inflammatory diseases, or allergic diseases.
Opening claim text (preview).
What is claimed is: 1. An isolated human monoclonal antibody or antigen-binding fragment thereof that specifically binds human interleukin-33 (IL-33), wherein the antibody or antigen-binding fragment comprises: (a) the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 50, 82, 98, 130, 178, and 274; and (b) the CDRs of a light chain variable region (LCVR) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 58, 90, 106, 138, 186, and 282. 2. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises the heavy and light chain CDRs of a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 50/58, 82/90, 98/106, 130/138, 178/186, and 274/282. 3. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 52-54-56-60-62-64; 84-86-88-92-94-96; 100-102-104-108-110-112; 132-134-136-140-142-144; 180-182-184-188-190-192; and 276-278-280-284-286-288. 4. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 , and a pharmaceutically acceptable carrier or diluent. 5. An isolated human monoclonal antibody or antigen-binding fragment thereof that specifically binds human interleukin-33 (IL-33), wherein the antibody or antigen-binding fragment comprises: (a) a heavy chain variable region (HCVR) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 50, 82, 98, 130, 178, and 274; and (b) a light chain variable region (LCVR) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 58, 90, 106, 138, 186, and 282. 6. The isolated antibody or antigen-binding fragment of claim 5 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 50/58, 82/90, 98/106, 130/138, 178/186, and 274/282. 7. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 50/58. 8. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 82/90. 9. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 98/106. 10. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 130/138. 11. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 178/186. 12. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 274/282. 13. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 7 , and a pharmaceutically acceptable carrier or diluent. 14. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 8 , and a pharmaceutically acceptable carrier or diluent. 15. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 9 , and a pharmaceutically acceptable carrier or diluent. 16. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 10 , and a pharmaceutically acceptable carrier or diluent. 17. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 11 , and a pharmaceutically acceptable carrier or diluent. 18. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 12 , and a pharmaceutically acceptable carrier or diluent. 19. An isolated human monoclonal antibody or antigen-binding fragment thereof that specifically binds human interleukin-33 (IL-33), wherein the antibody or antigen-binding fragment comprises a heavy chain variable region (HCVR) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 50, 82, 98, 130, 178, and 274. 20. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 19 , and a pharmaceutically acceptable carrier or diluent.
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