Engineered anti-IL-23R antibodies
View Patent ↗Antibodies to human IL-23R are provided, as well as uses thereof, e.g. in treatment of inflammatory, autoimmune, and proliferative disorders.
1. A binding compound that binds to human IL-23R comprising:
a) an antibody light chain variable domain, or antigen binding fragment thereof, comprising CDRL1, CDRL2 and CDRL3, wherein:
CDRL1 comprises the sequence of SEQ ID NO: 29 or 52;
CDRL2 comprises the sequence of SEQ ID NO: 34; and
CDRL3 comprises the sequence of SEQ ID NO: 39; and
b) an antibody heavy chain variable domain, or antigen binding fragment thereof, comprising CDRH1, CDRH2 and CDRH3, wherein:
CDRH1 comprises the sequence of SEQ ID NO: 14;
CDRH2 comprises the sequence of SEQ ID NO: 19; and
CDRH3 comprises the sequence of SEQ ID NO: 24.
2. The binding compound of claim 1 , further comprising:
a) human germline light chain framework sequences in the antibody light chain variable domain; and
b) human germline heavy chain framework sequences in the antibody heavy chain variable domain.
3. The binding compound of claim 1 , further comprising a γ1 human heavy chain constant region or a variant thereof covalently linked to the antibody heavy chain variable domain, wherein the constant region variant comprises up to 20 conservative amino acid substitutions.
4. The binding compound of claim 1 , further comprising a γ4 human heavy chain constant region or a variant thereof covalently linked to the antibody heavy chain variable domain, wherein the constant region variant comprises up to 20 conservative amino acid substitutions.
5. The binding compound of claim 1 , wherein the binding compound is an antibody fragment selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , and a diabody.
6. A pharmaceutical composition comprising the binding compound of claim 1 in combination with a pharmaceutically acceptable carrier or diluent.
7. A binding compound that binds to human IL-23R, comprising:
a) an antibody light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 48, 49 and 53; and
b) an antibody heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 45, 46 and 47.
8. The binding compound of claim 7 wherein:
a) the light chain variable domain comprises the sequence of SEQ ID NO: 53, and
b) the heavy chain variable domain comprises the sequence of SEQ ID NO: 47.
9. The binding compound of claim 8 comprising:
a) an antibody light chain comprising the sequence of SEQ ID NO: 54; and
b) an antibody heavy chain comprising the sequence of SEQ ID NO: 50.
10. A binding compound that binds to human IL-23R, comprising:
a) an antibody light chain variable domain consisting essentially of a sequence selected from the group consisting of SEQ ID NOs: 48, 49 and 53; and
b) an antibody heavy chain variable domain consisting essentially of a sequence selected from the group consisting of SEQ ID NOs: 45, 46 and 47.
11. An antibody, or antigen binding fragment thereof, that binds to the same epitope as a binding compound comprising:
a) an antibody light chain comprising the sequence of SEQ ID NO: 54; and
b) an antibody heavy chain comprising the sequence of SEQ ID NO: 50.
12. An antibody, or antigen binding fragment thereof, that binds to the same epitope of human IL-23R as the antibody produced by the hybridoma deposited with ATCC under accession number PTA-7801.