Antibodies to canine interleukin-4 receptor alpha
The present invention provides antibodies to canine IL-4 receptor alpha that have a high binding affinity for canine IL-4 receptor alpha, and that can block the binding of canine IL-4 and/or IL-13 to canine IL-4 receptor alpha. The present invention further relates to epitopes of canine IL-4 receptor alpha that bind to the antibodies to canine IL-4 receptor alpha. The present invention further provides the use of the antibodies for the treatment of atopic dermatitis in dogs.
1 . An isolated mammalian antibody or antigen binding fragment thereof that binds canine interleukin-4 receptor α (IL-4R α ) comprising a set of six complementary determining regions (CDRs), three of which are heavy chain CDRs: a CDR heavy 1 (HCDR1), a CDR heavy 2 (HCDR2), and a CDR heavy 3 (HCDR3) and three of which are light chain CDRs: a CDR light 1 (LCDR1), a CDR light 2 (LCDR2), and a CDR light 3 (LCDR3); wherein
(i) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 12;
(ii) the HCDR2 comprises the amino acid sequence of SEQ ID NO: 14;
(iii) the HCDR3 comprises the amino acid sequence of SEQ ID NO: 16;
(iv) the LCDR1 comprises the amino acid sequence of SEQ ID NO: 18;
(v) the LCDR2 comprises the amino acid sequence of SEQ ID NO: 20; and
(vi) the LCDR3 comprises the amino acid sequence of SEQ ID NO: 22.
2 . The isolated mammalian antibody or antigen binding fragment thereof of claim 1 , wherein the antibody and antigen binding fragment thereof bind canine IL-4Ra and block the binding of canine IL-4Ra to canine interleukin-4.
3 . The isolated mammalian antibody or antigen binding fragment thereof of claim 1 , that is a caninized antibody or a caninized antigen binding fragment thereof.
4 . The caninized antibody or caninized antigen binding fragment thereof of claim 3 , comprising a hinge region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9.
5 . The caninized antibody or caninized antigen binding fragment thereof of claim 3 , comprising a heavy chain comprising a modified canine IgG-B (IgG-Bm) comprising the amino acid sequence of SEQ ID NO: 10.
6 . The caninized antibody or caninized antigen binding fragment thereof of claim 5 , comprising a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42.
7 . An isolated caninized mammalian antibody or caninized antigen binding fragment thereof that binds canine interleukin-4 receptor α (IL-4R α ), comprising a light chain comprising the amino acid sequence SEQ ID NO: 39 and a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42.
8 . An isolated caninized mammalian antibody or caninized antigen binding fragment thereof that binds canine interleukin-4 receptor α (IL-4R α ), comprising a light chain comprising the amino acid sequence SEQ ID NO: 44 and a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42.
9 . An isolated nucleic acid that encodes the heavy chain of the caninized antibody or caninized antigen binding fragment thereof of claim 3 .
10 . An isolated nucleic acid that encodes the light chain of the caninized antibody or caninized antigen binding fragment thereof of claim 3 .
11 . An expression vector comprising the isolated nucleic acid of claim 9 .
12 . A host cell comprising the expression vector of claim 11 .
13 . A pharmaceutical composition comprising the caninized antibody or caninized antigen binding fragment thereof of claim 3 , and a pharmaceutically acceptable carrier or diluent.
14 . A method of aiding in the blocking of inflammation associated with atopic dermatitis, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 13 .
15 . An expression vector comprising the isolated nucleic acid of claim 10 .
16 . A host cell comprising the expression vector of claim 15 .
17 . A pharmaceutical composition comprising the caninized antibody or caninized antigen binding fragment thereof of claim 8 , and a pharmaceutically acceptable carrier or diluent.
18 . A method of aiding in the blocking of inflammation associated with atopic dermatitis, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 17 .
19 . A pharmaceutical composition comprising the caninized antibody or caninized antigen binding fragment thereof of claim 7 , and a pharmaceutically acceptable carrier or diluent.
20 . A method of aiding in the blocking of inflammation associated with atopic dermatitis, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 19 .