Caninized human antibodies to human IL-4R alpha
The present invention provides caninized human anti-human IL-4Rα antibodies that have specific sequences and a high binding affinity for canine IL-4Rα. The invention also relates to use of these antibodies in the treatment of dogs against atopic dermatitis.
1. An isolated caninized antibody or antigen binding fragment thereof that specifically binds interleukin-4 receptor alpha (IL-4Rα) comprising a canine IgG heavy chain and a canine kappa light chain; wherein the canine kappa light chain comprises three light chain complementary determining regions (CDRs): CDR light 1 (CDRL1), CDR light 2 (CDRL2), and CDR light 3 (CDRL3); and the canine IgG heavy chain comprises three heavy chain CDRs: CDR heavy 1 (CDRH1), CDR heavy 2 (CDRH2) and CDR heavy 3 (CDRH3):
(a) wherein CDRL1 comprises the amino acid sequence of SEQ ID NO: 43;
(b) wherein CDRL2 comprises the amino acid sequence comprising SEQ ID NO: 44;
(c) wherein CDRL3 comprises the amino acid sequence of SEQ ID NO: 45;
(d) wherein CDRH1 comprises the amino acid sequence of SEQ ID NO: 46;
(e) wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 47; and
(f) wherein CDRH3 comprises the amino acid sequence of SEQ ID NO: 48.
2. The isolated caninized antibody of claim 1 , wherein the IgG heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 28, SEQ ID NO: 30, and SEQ ID NO: 32.
3. The isolated caninized antibody of claim 2 , wherein the kappa light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 34, SEQ ID NO: 36, and SEQ ID NO: 38.
4. The isolated caninized antibody of claim 1 , or antigen binding fragment thereof, wherein said caninized antibody or antigen binding fragment thereof binds to canine IL-4Rα at one or more amino acid residue from the amino acid sequence selected from the group consisting of SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42 and any combination thereof.
5. The isolated caninized antibody of claim 4 , wherein when bound to canine IL-4Rα said antibody binds to one or more amino acid residues of SEQ ID NO: 4 selected from the group consisting of T 27 , Y 37 , S 164 , T 165 , K 167 , and any combination thereof.
6. The isolated caninized antibody of claim 1 , or antigen binding fragment thereof which binds canine IL-4Rα and blocks the binding of canine IL-4Rα with canine Interleukin-4 (IL-4).
7. A pharmaceutical composition comprising the antibody of claim 1 , and a pharmaceutically acceptable carrier or diluent.
8. The isolated caninized antibody of claim 5 , wherein when bound to canine IL-4Rα said antibody binds to the tyrosine residue at amino acid position 37, (Y 37 ).
9. The isolated caninized antibody of claim 4 , or antigen binding fragment thereof, wherein said caninized antibody or antigen binding fragment thereof binds to canine IL-4Rα at one or more amino acid residue from the amino acid sequence SEQ ID NO: 39.
10. The isolated caninized antibody of claim 3 , wherein the IgG heavy chain comprises the amino acid sequence of SEQ ID NO: 30 and the kappa light chain comprises the amino acid sequence of SEQ ID NO: 36.