Variant target binding agents and uses thereof

1. A variant target binding agent conjugate, comprising:

a binding region that comprises an antibody Fv region or an antigen binding fragment thereof that specifically binds to a target antigen, wherein the target antigen is CD33;

at least a portion of a Fc region of a human immunoglobulin IgG1 constant region, comprising an introduced cysteine residue at amino acid position 239, that is S239C, according to the EU index as set forth in Kabat; and

a therapeutic agent conjugated directly or via a linker to the introduced cysteine residue, wherein the therapeutic agent exerts a cytotoxic or cytostatic effect on a cell that expresses CD33.

2. The variant target binding agent of claim 1 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a linker.

3. The variant target binding agent of claim 2 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a maleimide group of the linker.

4. The variant target binding agent conjugate of claim 2 , wherein the therapeutic agent is a cytotoxic agent that exerts a cytotoxic effect on a cell that expresses CD33.

5. The variant target binding agent conjugate of claim 4 , wherein the cytotoxic agent is a DNA minor groove binding agent.

6. The variant target binding agent of claim 5 , wherein the DNA minor groove binding agent is a DNA minor groove alkylating agent.

7. The variant target binding agent conjugate of claim 3 , wherein the therapeutic agent is a cytotoxic agent that exerts a cytotoxic effect on a cell that expresses CD33.

8. The variant target binding agent conjugate of claim 7 , wherein the cytotoxic agent is a DNA minor groove binding agent.

9. The variant target binding agent of claim 8 , wherein the DNA minor groove binding agent is a DNA minor groove alkylating agent.

10. The variant target binding agent conjugate of claim 4 , wherein the cytotoxic agent is an anti-tubulin agent.

11. The variant target binding agent conjugate of claim 1 , wherein the therapeutic agent is an auristatin, an enediyne, a lexitropsin, a duocarmycin, a taxane, a puromycin, a dolastatin, a maytansinoid, or a vinca alkaloid.

12. The variant target binding agent conjugate of claim 1 , wherein the variant target binding agent conjugate is an intact antibody conjugated to a therapeutic agent.

13. The variant target binding agent conjugate of claim 7 , wherein the variant target binding agent conjugate is an intact antibody conjugated to a therapeutic agent.

14. A composition comprising a variant target binding agent comprising a binding region that comprises an antibody Fv region or an antigen binding fragment thereof that specifically binds to a target antigen, wherein the target antigen is CD33;

at least a portion of a Fc region of a human immunoglobulin IgG1 constant region, comprising an introduced cysteine residue at amino acid position 239, that is S239C, according to the EU index as set forth in Kabat; and

a therapeutic agent conjugated directly or via a linker to the introduced cysteine residue, wherein the therapeutic agent exerts a cytotoxic effect on a cell that expresses CD33; and at least one pharmaceutically compatible ingredient.

15. The composition of claim 14 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a linker.

16. The composition of claim 15 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a maleimide group of the linker.

17. The composition of claim 16 , wherein the cytotoxic agent is a DNA minor groove binding agent.

18. The composition of claim 15 , wherein the variant target binding agent conjugate is an intact antibody conjugated to a therapeutic agent.

19. The composition of claim 15 wherein there is an average of two therapeutic agents per antibody in the composition.