Antibodies that bind to IL1RAP and uses thereof
The present invention relates to antibodies which specifically bind to human IL1RAP and may also bind to cynomolgus monkey and/or mouse IL1RAP. The present invention also relates to the use of such antibodies to diagnose and treat human disease.
1. An anti-IL1RAP antibody comprising a first heavy chain CDR region (CDR-H1), a second heavy chain CDR region (CDR-H2), and a third heavy chain CDR region (CDR-H3), wherein:
(a) CDR-H1 comprises the amino acid sequence of SEQ ID NO: 128;
(b) CDR-H2 comprises the amino acid sequence of SEQ ID NO: 188; and
(c) CDR-H3 comprises the amino acid sequence of SEQ ID NO: 248, and wherein said anti-IL1RAP antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 268.
2. The antibody of claim 1 , wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 58.
3. The antibody of claim 1 , wherein said antibody binds to human IL1RAP with a binding affinity from 1×10 −8 M to 10 −13 M.
4. The antibody of claim 1 , wherein said antibody decreases an IL-1 stimulated signal, an IL-33 stimulated signal, and/or an IL-36 stimulated signal by at least 90%, at least 95%, at least 99%, or 100%; wherein the decrease in signal is measured by a cell-based blocking assay.
5. The antibody of claim 1 , wherein said antibody cross-reacts with a cynomolgus monkey IL1RAP polypeptide of SEQ ID NO: 2.
6. The antibody of claim 1 , wherein said antibody cross-reacts with a mouse IL1RAP polypeptide of SEQ ID NO: 261.
7. The antibody of claim 1 , wherein said antibody is a full-length antibody of class IgG and in particular wherein the class IgG antibody has an isotype selected from lgG1, lgG2, lgG3 and lgG4.
8. The antibody of claim 2 , wherein said antibody is a multispecific antibody.
9. The antibody of claim 1 , wherein the antibody specifically binds to one or more amino acid residues within domain 2 of IL1RAP.
10. The antibody of claim 3 , wherein the binding affinity is measured by equilibrium dissociation constant (KD) to human IL1RAP polypeptide of SEQ ID NO: 1 or 6.
11. A pharmaceutical composition comprising an antibody of claim 1 and a pharmaceutically acceptable carrier.