Anti-CD22 antibody-maytansine conjugates and methods of use thereof

1. A conjugate that includes at least one modified amino acid residue with a side chain of formula (I):

wherein

W 2 is an anti-CD22 antibody.

2. The conjugate of claim 1 , wherein the anti-CD22 antibody constant region comprises a sequence of the formula (II):

X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein

FG1y′ is the modified amino acid residue of formula (I);

Z 20 is either a proline or alanine residue;

Z 30 is a basic amino acid or an aliphatic amino acid;

X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and

X 2 and X 3 are each independently any amino acid.

3. The conjugate of claim 2 , wherein the sequence is L(FG1y′)TPSR (SEQ ID NO: 11).

4. The conjugate of claim 2 , wherein

Z 30 is selected from R, K, H, A, G, L, V, I, and P;

X 1 is selected from L, M, S, and V; and

X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

5. The conjugate of claim 1 , wherein the modified amino acid residue is positioned at a C-terminus of a heavy chain constant region of the anti-CD22 antibody.

6. The conjugate of claim 5 , wherein the heavy chain constant region comprises a sequence of the formula (II):

X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein

FG1y′ is the modified amino acid residue of formula (I);

Z 20 is either a proline or alanine residue;

Z 30 is a basic amino acid or an aliphatic amino acid;

X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and

X 2 and X 3 are each independently any amino acid, and

wherein the sequence is C-terminal to the amino acid sequence SLSLSPG (SEQ ID NO: 12).

7. The conjugate of claim 6 , wherein the heavy chain constant region comprises the sequence SPGSL(FG1y′)TPSRGS (SEQ ID NO: 13).

8. The conjugate of claim 6 , wherein

Z 30 is selected from R, K, H, A, G, L, V, I, and P;

X 1 is selected from L, M, S, and V; and

X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

9. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a light chain constant region of the anti-CD22 antibody.

10. The conjugate of claim 9 , wherein the light chain constant region comprises a sequence of the formula (II):

X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein

FG1y′ is the modified amino acid residue of formula (I);

Z 20 is either a proline or alanine residue;

Z 30 is a basic amino acid or an aliphatic amino acid;

X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and

X 2 and X 3 are each independently any amino acid, and

wherein the sequence is C-terminal to the sequence KVDNAL (SEQ ID NO: 14), and/or is N-terminal to the sequence QSGNSQ (SEQ ID NO: 15).

11. The conjugate of claim 10 , wherein the light chain constant region comprises the sequence KVDNAL(FG1y′)TPSRQSGNSQ (SEQ ID NO: 16).

12. The conjugate of claim 10 , wherein

Z 30 is selected from R, K, H, A, G, L, V, I, and P;

X 1 is selected from L, M, S, and V; and

X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

13. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a heavy chain CH 1 region of the anti-CD22 antibody.

14. The conjugate of claim 13 , wherein the heavy chain CH 1 region comprises a sequence of the formula (II):

X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein

FG1y′ is the modified amino acid residue of formula (I);

Z 20 is either a proline or alanine residue;

Z 30 is a basic amino acid or an aliphatic amino acid;

X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and

X 2 and X 3 are each independently any amino acid, and

wherein the sequence is C-terminal to the amino acid sequence SWNSGA (SEQ ID NO: 17) and/or is N-terminal to the amino acid sequence GVHTFP (SEQ ID NO: 18).

15. The conjugate of claim 14 , wherein the heavy chain CH 1 region comprises the sequence SWNSGAL(FG1y′)TPSRGVHTFP (SEQ ID NO: 19).

16. The conjugate of claim 14 , wherein

Z 30 is selected from R, K, H, A, G, L, V, I, and P;

X 1 is selected from L, M, S, and V; and

X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

17. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a heavy chain CH2 region of the anti-CD22 antibody.

18. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a heavy chain CH3 region of the anti-CD22 antibody.

19. A pharmaceutical composition comprising:

a conjugate of claim 1 ; and

a pharmaceutically acceptable excipient.

20. A method comprising:

administering to a subject an effective amount of a conjugate of claim 1 .

21. A method of treating a leukemia or a lymphoma in a subject, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a conjugate of claim 1 , wherein the administering is effective to treat the leukemia or the lymphoma in the subject.

22. A method of delivering a drug to a target site in a subject, the method comprising:

administering to the subject a pharmaceutical composition comprising a conjugate of claim 1 , wherein the administering is effective to release a therapeutically effective amount of the drug from the conjugate at the target site in the subject.

23. The conjugate of claim 1 , wherein the modified amino acid residue is positioned at a C-terminus of a heavy chain CH3 region of the anti-CD22 antibody.

24. The conjugate of claim 5 , wherein the heavy chain constant region comprises a sequence of the formula (II):

X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein

FG1y′ is the modified amino acid residue of formula (I);

Z 20 is either a proline or alanine residue;

Z 30 is a basic amino acid or an aliphatic amino acid;

X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and

X 2 and X 3 are each independently any amino acid, and

wherein the sequence is C-terminal to the amino acid sequence SLSLSPG (SEQ ID NO: 12).

25. The conjugate of claim 6 , wherein the heavy chain CH3 region comprises the sequence SPGSL(FG1y′)TPSRGS (SEQ ID NO: 13).

26. The conjugate of claim 6 , wherein

Z 30 is selected from R, K, H, A, G, L, V, I, and P;

X 1 is selected from L, M, S, and V; and

X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

27. The method of claim 21 , comprising treating the leukemia.

28. The method of claim 27 , wherein the leukemia is a B-cell derived leukemia.

29. The method of claim 27 , wherein the leukemia is hairy cell leukemia, B-cell acute lymphoblastic leukemia, acute lymphoblastic leukemia, or chronic lymphocytic leukemia.

30. The method of claim 21 , comprising treating the lymphoma.

31. The method of claim 30 , wherein the lymphoma is a B-cell derived lymphoma.

32. The method of claim 30 , wherein the lymphoma is Burkitt's lymphoma, Hodgkin's lymphoma, non-Hodgkin's B cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, or marginal zone lymphoma.