Anti-IL-1R3 antibodies for use in inflammatory conditions
The present invention relates to methods for treating medical conditions and/or disorders characterized by uncontrolled or abnormal expression of members of the IL1R3 signaling pathway such as IL-1α, IL-1ß, IL-33, IL-36, IL1RA and/or IL1R3, as well as variants thereof. More specifically, the present invention relates to anti-IL1R3 antibodies for use in the treatment of an IL1R3-mediated inflammatory condition and/or disorder in a subject. Such conditions and disorders include but are not limited to inflammatory diseases, immune disorders, fibrotic disorders, eosinophilic disorders, infection, pain, a central nervous system disorder, an ophthalmologic disorder, Hereditary Systemic Inflammatory Diseases, and Systemic and Local Inflammatory Diseases and cancer associated chronic inflammation.
1 . A method for treating a neutrophilic inflammatory disorder in a subject, comprising administering to the subject an antibody, or antigen binding fragment thereof, that specifically binds IL-1R3, wherein the antibody or antigen binding fragment comprises: a) a heavy chain variable region (VH) comprising the complementarity determining regions comprising CDR-H1, CDR-H2, and CDR-H3, wherein the CDR-H1 region comprises an amino acid sequence set forth in SEQ ID NO: 79, wherein the CDR-H2 region comprises an amino acid sequence set forth in SEQ ID NO: 96, and wherein the CDR-H3 region comprises an amino acid sequence set forth in SEQ ID NO: 113; and b) a light chain variable region (VL) comprising the complementarity determining regions comprising CDR-L1, CDR-L2, and CDR-L3, wherein the CDR-L1 region comprises an amino acid sequence set forth in SEQ ID NO: 130, wherein the CDR-L2 region comprises an amino acid sequence set forth in SEQ ID NO: 147, and wherein the CDR-L3 region comprises an amino acid sequence set forth in SEQ ID NO: 175, thereby treating the neutrophilic inflammatory disorder in the subject.
2 . The method of claim 1 , wherein the antibody comprises a human IgG1 Fc region.
3 . The method of claim 2 , wherein the human IgG1 Fc region comprises at least amino acid substitutions L234A and L235A, wherein the numbering of amino acid residues in the Fc region is according to the EU numbering system.
4 . The method of claim 1 , wherein the VH region is at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 28, and the VL region is at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 174.
5 . The method of claim 1 , wherein the antibody comprises a human IgG4 Fc region.
6 . The method of claim 5 , wherein the human IgG4 Fc region comprises at least amino acid substitutions S228P and L235E, wherein the numbering of amino acid residues in the Fc region is according to the EU numbering system.
7 . A method for attenuating neutrophil activation in a subject, comprising administering to the subject an antibody, or antigen binding fragment thereof, that specifically binds IL-1R3, wherein the antibody or antigen binding fragment comprises: a) a heavy chain variable region (VH) comprising the complementarity determining regions comprising CDR-H1, CDR-H2, and CDR-H3, wherein the CDR-H1 region comprises an amino acid sequence set forth in SEQ ID NO: 79, wherein the CDR-H2 region comprises an amino acid sequence set forth in SEQ ID NO: 96, and wherein the CDR-H3 region comprises an amino acid sequence set forth in SEQ ID NO: 113; and b) a light chain variable region (VL) comprising the complementarity determining regions comprising CDR-L1, CDR-L2, and CDR-L3, wherein the CDR-L1 region comprises an amino acid sequence set forth in SEQ ID NO: 130, wherein the CDR-L2 region comprises an amino acid sequence set forth in SEQ ID NO: 147, and wherein the CDR-L3 region comprises an amino acid sequence set forth in SEQ ID NO: 175, thereby attenuating neutrophil activation in the subject.
8 . The method of claim 7 , wherein the antibody comprises a human IgG1 Fc region.
9 . The method of claim 8 , wherein the human IgG1 Fc region comprises at least amino acid substitutions L234A and L235A, wherein the numbering of amino acid residues in the Fc region is according to the EU numbering system.
10 . The method of claim 7 , wherein the VH region is at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 28, and the VL region is at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 174.
11 . The method of claim 10 , wherein the human IgG4 Fc region comprises at least amino acid substitutions S228P and L235E, wherein the numbering of amino acid residues in the Fc region is according to the EU numbering system.
12 . The method of claim 7 , wherein the antibody comprises a human IgG4 Fc region.