Antibody constant domain regions and uses thereof
The invention provides recombinant protein (e.g., a recombinant antibody or soluble receptor) having (i) a binding domain capable of specific binding to an epitope (for example an antibody variable domains, a receptor, a growth factor, a cytokine, or a fragment of any of the foregoing which is capable of specifically binding the desired epitope) and (ii) an effector domain comprising a constant domain region which is derived from immunoglobulin of a first species which is a companion mammal, e.g. dog, cat, or horse, having engineered substitutions at one or more positions and having an altered interaction with one or more FcRs or other ligands, and optionally enhanced effector function, relative to the parent constant domain region.
1. A recombinant protein comprising
a. a binding domain, or a fragment thereof, that specifically binds to an epitope; the binding domain comprising (i) a non-canine antibody hypervariable region or an epitope-binding fragment thereof, or (ii) a soluble receptor binding domain or an epitope-binding fragment thereof; and
b. an effector domain that provides ADCC and/or CDC effector function to the recombinant protein; the effector domain comprising a constant domain region; wherein the constant domain region comprises SEQ ID NO: 2.
2. The recombinant protein of claim 1 which is a member of the immunoglobulin superfamily comprising an Ig fold.
3. The recombinant protein of claim 1 , wherein the binding domain comprises an antibody variable region.
4. The recombinant protein of claim 1 , wherein the epitope is selected from the group consisting of: a receptor, a growth factor, and a cytokine.
5. The recombinant protein of claim 1 , wherein the effector domain binds to an FcR.
6. The recombinant protein of claim 1 , wherein the recombinant protein has increased ADCC effector function relative to dog gamma globulin.
7. The recombinant protein of claim 1 , wherein the recombinant protein has increased CDC effector function relative to dog gamma globulin.
8. The recombinant protein of claim 1 , wherein the recombinant protein exhibits a TM of at least about the TM of dog gamma globulin.
9. The recombinant protein of claim 1 , wherein the effector domain further comprises a constant domain region of a kappa light chain comprising the sequence set forth in SEQ ID NO:8.
10. The recombinant protein of claim 1 , wherein the effector domain further comprises a constant domain region of a lambda light chain comprising the sequence set forth in SEQ ID NO:9.
11. A recombinant protein according to claim 1 wherein the binding domain comprises hypervariable regions from an antibody from a species other than the companion animal.
12. A recombinant protein according to claim 11 which is a heterochimeric antibody.
13. A pharmaceutical composition comprising the recombinant protein according to claim 1 , in combination or association with a pharmaceutically acceptable diluent of carrier.
14. A recombinant protein comprising SEQ ID NO: 2.