ANTI-CD22 ANTIBODIES AND IMMUNOCONJUGATES

• US 20140030279A1
• Filed: 07/08/2013
• Published: 01/30/2014
• Est. Priority Date: 07/09/2012
• Status: Abandoned Application

• Current Assignee: MedImmune Ltd. (Astrazeneca PLC), Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG), Spirogen SARL
• Inventors: Polakis, Paul, Polson, Andrew, Flygare, John A., Pillow, Thomas Harden, Howard, Philip Wilson, Masterson, Luke, Spencer, Susan Diane, Yu, Shang-Fan, Gunzner-Toste, Janet L.
• Application Number:
  US13/936,279
• Publication Number:
  US 20140030279A1
• Time in Patent Office: Days
• US Class Current: 424/181.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5517 condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6809 Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6867 the tumour determinant being from a cell of a blood cancer
• CPC Class Codes: A61K 47/6877 the antibody being an immunoglobulin containing regions, domains or residues from different species
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia

Abstract

The invention provides anti-CD22 antibodies and immunoconjugates and methods of using the same.

Claims

1. An immunoconjugate comprising an antibody that binds CD22 covalently attached to a cytotoxic agent, wherein the antibody binds an epitope within amino acids 20 to 240 of SEQ ID NO:

28, and wherein the cytotoxic agent is a pyrrolobenzodiazepine.

2. The immunoconjugate of claim 1, wherein the antibody comprises (i) HVR-H3 comprising the amino acid sequence of SEQ ID NO:

11, (ii) HVR-L3 comprising the amino acid sequence of SEQ ID NO;

14, and (iii) HVR-H2 comprising the amino acid sequence of SEQ ID NO;

10.

3. The immunoconjugate of claim 1, wherein the antibody comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:

9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO;

10, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO;

11.

4. The immunoconjugate of claim 1, wherein the antibody comprises:

a) (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO;

9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO;

10, (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO;

11, (iv) HVR-L1 comprising an amino acid sequence selected from SEQ ID NOs;

12 and 15 to 22, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO;

13, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO;

14;

or

b) (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO;

9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO;

10, (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO;

11, (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO;

15, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO;

13, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO;

14.

5. The immunoconjugate of claim 1, wherein the antibody comprises:

a) (i) HVR-L1 comprising an amino acid sequence selected from SEQ ID NOs;

12 and 15 to 22, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO;

13, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO;

14;

or

b) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO;

15, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO;

13, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO;

14.

6. The immunoconjugate of claim 1, wherein the antibody comprises:

a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

7;

or

b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

8;

or

c) a VH sequence as in (a) and a VL sequence as in (b).

7. The immunoconjugate of claim 6, comprising a VH sequence having the amino acid sequence of SEQ ID NO:

7.

8. The immunoconjugate of claim 6, comprising a VL sequence having the amino acid sequence of SEQ ID NO:

6 or a VL sequence having the amino acid sequence of SEQ ID NO;

8.

10. The immunoconjugate of claim 1, wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

11. The immunoconjugate of claim 1, wherein the immunoconjugate has the formula Ab-(L-D)_p, wherein:

(a) Ab is the antibody;

(b) L is a linker;

(c) D is the cytotoxic agent; and

(d) p ranges from 1-8.

12. The immunoconjugate of claim 11, wherein D is a pyrrolobenzodiazepine of Formula A:

13. The immunoconjugate of claim 12, wherein D has the structure:

14. The immunoconjugate of claim 12, wherein D has a structure selected from:

15. The immunoconjugate of claim 11, wherein D is a pyrrolobenzodiazepine of Formula B:

16. The immunoconjugate of claim 11, wherein the linker is cleavable by a protease.

17. The immunoconjugate of claim 16, wherein the linker comprises a val-cit dipeptide or a Phe-Lys dipeptide.

18. The immunoconjugate of claim 11 having the formula

19. The immunoconjugate of claim 11, wherein p ranges from 1-3.

20. The immunoconjugate of claim 12, comprising the structure:

21. The immunoconjugate of claim 20, comprising a structure selected from:

22. The immunoconjugate of claim 20, comprising the structure:

23. The immunoconjugate of claim 20, comprising the structure:

24. The immunoconjugate of claim 23, wherein Ar¹ and Ar² are each independently selected from optionally substituted phenyl, furanyl, thiophenyl and pyridyl.

25. The immunoconjugate of claim 20, comprising the structure:

26. The immunoconjugate of claim 25, wherein R^V1 and R^V2 are each independently selected from H, phenyl, and 4-fluorophenyl.

31. The immunoconjugate of claim 1, wherein the antibody is a monoclonal antibody.

32. The immunoconjugate of claim 1, wherein the antibody is a human, humanized, or chimeric antibody.

33. The immunoconjugate of claim 1, wherein the antibody is an antibody fragment that binds CD22.

34. The immunoconjugate of claim 1, wherein the antibody binds human CD22.

35. The immunoconjugate of claim 34, wherein human CD22 has the sequence of SEQ ID NO:

28 or SEQ ID NO;

29.

36. A pharmaceutical formulation comprising the immunoconjugate of claim 1 and a pharmaceutically acceptable carrier.

37. The pharmaceutical formulation of claim 36, further comprising an additional therapeutic agent.

38. A method of treating an individual having a CD22-positive cancer, the method comprising administering to the individual an effective amount of the immunoconjugate of claim 1.

39. The method of claim 38, wherein the CD22-positive cancer is selected from lymphoma, non-Hogkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent NHL, refractory NHL, refractory indolent NHL, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, leukemia, hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL), Burkitt'"'"'s lymphoma, and mantle cell lymphoma.

40. The method of claim 39, further comprising administering an additional therapeutic agent to the individual.

41. The method of claim 40, wherein the additional therapeutic agent comprises an antibody that binds CD79b.

42. The method of claim 41, wherein the additional therapeutic agent is an immunoconjugate comprising an antibody that binds CD79b covalently attached to a cytotoxic agent.

43. A method of inhibiting proliferation of a CD22-positive cell, the method comprising exposing the cell to the immunoconjugate of claim 1 under conditions permissive for binding of the immunoconjugate to CD22 on the surface of the cell, thereby inhibiting proliferation of the cell.

44. The method of claim 43, wherein the cell is a neoplastic B cell.

45. The method of claim 44, wherein the cell is a lymphoma cell.

9. An immunoconjugate comprising an antibody that binds CD22 covalently attached to a cytotoxic agent, wherein the antibody comprises (a) a VH sequence having the amino acid sequence of SEQ ID NO:

7 and a VL sequence having the amino acid sequence of SEQ ID NO;

8, and wherein the cytotoxic agent is a pyrrolobenzodiazepine.

27. An immunoconjugate having a formula selected from:

29. The immunoconjugate of claim 27, wherein the antibody comprises a VH sequence of SEQ ID NO:

7 and a VL sequence of SEQ ID NO;

8.

30. The immunoconjugate of claim 29, wherein the antibody comprises a heavy chain of SEQ ID NO:

26 and a light chain of SEQ ID NO;

23.

28. An immunoconjugate having the formula: