HUMANIZED ANTI-IL-1R3 ANTIBODY AND METHODS OF USE
An antibody that specifically binds to IL-1R3, comprising an antibody heavy chain amino acid sequence of SEQ ID NO: 1 and a light chain amino acid sequence of SEQ ID NO: 2. A pharmaceutical composition is provided comprising the said antibody and a pharmaceutically acceptable diluent, carrier or excipient. Also said antibody for use in treating a disease or disorder in a subject in need thereof. The disease or disorder may be an autoimmune or autoinflammatory disease or disorder.
1 .- 15 . (canceled)
16 . An antibody that specifically binds to IL-1R3, wherein the antibody is selected from the group consisting of:
(a) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 24, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 29, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(b) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 25, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 30, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(c) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 25, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 31, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(d) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 25, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 32, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(e) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 26, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 30, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(f) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 26, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 31, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(g) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 26, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 32, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(h) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 27, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 30, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(i) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 27, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 31, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(j) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 27, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 32, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(k) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 28, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 30, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(l) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 28, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 31, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(m) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 28, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 32, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(o) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 33, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 34, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(p) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 35, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 36, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(q) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 37, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 44, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(r) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 38, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 45, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(s) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 39, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 46, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(t) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 40, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 47, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(u) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 41, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 48, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering;
(v) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 42, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 49, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering; and
(w) an antibody comprising an antibody heavy chain variable (VH) domain amino acid sequence of SEQ ID NO: 43, an antibody light chain variable (VL) domain amino acid sequence of SEQ ID NO: 50, and an IgG4 Fc domain, wherein the IgG4 Fc domain comprises an F234A substitution, an L235A substitution, and an S228P substitution, according to EU numbering.
17 . A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable diluent, carrier or excipient.
18 . An isolated nucleic acid molecule encoding the antibody of claim 16 .
19 . An expression vector comprising the nucleic acid molecule of claim 18 .
20 . A host cell comprising the expression vector of claim 19 .
21 . The host cell of claim 20 , which is a Chinese hamster ovary (CHO) cell, preferably wherein the host cell is a CHO DXB11 cell.
22 . A method of manufacturing the antibody of claim 16 , comprising the steps of:
(i) transfecting a host cell using an isolated nucleic acid molecule encoding said antibody or an expression vector comprising a nucleic acid molecule encoding said antibody;
(ii) cultivating the host cell under conditions allowing expression of the antibody;
(iii) recovering the antibody; and
(iv) optionally further purifying and/or modifying and/or formulating the antibody.
23 . The method of claim 22 , wherein the host cell is a Chinese hamster ovary (CHO) cell.
24 . The method of claim 22 , wherein an expression level of the antibody is greater than an expression level of an anti-IL-1R3 antibody comprising a human IgG1 Fc region, wherein the human IgG1 Fc region comprises amino acid substitutions L234A and L235A, according to EU numbering.
25 . A method of treating a disease or disorder in a subject in need thereof comprising administering to the subject an effective amount of the antibody of claim 16 , wherein the disease or disorder is an autoimmune, autoinflammatory, neoplastic, inflammatory, and/or fibrotic disease or disorder.