Treatment of B-cell associated diseases such as malignances and autoimmune diseases using a cold anti-CD20 antibody/radiolabeled anti-CD22 antibody combination

• US 20020039557A1
• Filed: 06/20/2001
• Published: 04/04/2002
• Est. Priority Date: 06/20/2000
• Status: Active Grant

• Current Assignee: Biogen, Inc.
• Original Assignee: Biogen, Inc.
• Inventors: White, Christine
• Granted Patent: US 6,846,476 B2
• Time in Patent Office: Days
• US Class Current: 424/1.49
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 51/1027 against receptors, cell-surface antigens or cell-surface determinants
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Treatment of B-cell associated diseases including autoimmune and B-cell malignancies such as leukemias, lymphomas, using the combination of an anti-CD20 antibody, preferably RITUXAN® and a radiolabeled anti-CD22 antibody, preferably an ⁹⁰Y labeled humanized anti-CD22 antibody, is described. These therapeutic regimens provide for enhanced depletion of B cells, and therefore reduce the risk in B cell malignancy treatment of relapse associated with RITUXAN® and, moreover, provide for prolonged immunosuppression of B-cell immune responses, especially in the context of autoimmune diseases and transplant.

Claims

1. A method of treating a disease or condition wherein suppression and/or depletion and/or blocking the function of B-cells is therapeutically beneficial, comprising the steps of:

(i) administering a therapeutically effective amount of cold (non-radiolabeled) anti-CD20 monoclonal antibody having B cell depleting activity substantially equivalent to Rituxan®

; and

(ii) administering a therapeutically effective amount of a hot (radiolabeled) anti-CD22 antibody or fragment thereof;

wherein said anti-CD20 antibody and said radiolabeled anti-CD22 antibody or fragment are administered separately or in combination, and in either order.

2. The method of claim 1, which is used to treat a B-cell malignancy, leukemia or lymphoma.

3. The method of claim 1, which is used to treat an autoimmune disease.

4. The method of claim 2, wherein said disease is non-Hodgkins lymphoma.

5. The method of claim 2, wherein said malignancy, leukemia or lymphoma is selected from the group consisting of low grade/follicular non-Hodgkin'"'"'s lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade/follicular NHL, intermediate grade diffuse NHL, chronic lymphocytic leukemia (CLL), high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small noncleaved cell NHL, bulky disease NHL, mantle cell lymphoma, AIDS-related lymphoma and Waldenstrom'"'"'s Macroglobulinemia.

6. The method of claim 1, wherein the amount of said cold anti-CD20 antibody ranges from 0.1 mg to 500 mg/m² per week.

7. The method of claim 6, wherein the amount of said cold anti-CD20 antibody is at least about 500 mg/m² weekly.

8. The method of claim 7, wherein said dosage is about 375 mg/m² weekly for four weeks.

9. The method of claim 1, wherein said radiolabeled anti-CD22 antibody or fragment is an yttrium-labeled anti-CD22 antibody or fragment.

10. The method of claim 6, wherein said radiolabeled anti-CD22 antibody fragment is a Fab₂, Fab, Fv, or domain deleted antibody.

11. The method of claim 9, wherein said anti-CD22 antibody is a ⁹⁰Y labeled humanized LL2 antibody.

12. The method of claim 11, wherein the dosage of said radiolabeled antibody ranges from 10 to 30 mCi.

13. The method of claim 12, wherein said radiolabeled anti-CD22 antibody is administered about a week after an RITUXAN®

antibody therapeutic regimen has been completed.

14. The method of claim 13, which further includes administration of a chemotherapeutic agent.

15. The method of claim 13, which further includes administration of a cytokine.

16. The method of claim 1 wherein the anti-CD20 antibody is Rituxan®

.

17. The method of claim 16 wherein the condition treated is a B cell malignancy, leukemia or lymphoma.

18. The method of claim 5 wherein the anti-CD20 antibody is Rituxan®

.

19. The method of claim 16 wherein the disease is transplant.

20. The method of claim 16 wherein the condition is cell therapy.

21. The method of claim 16 wherein the disease is an autoimmune disease.

22. The method of claim 21 wherein the autoimmune disease is a B cell related autoimmune disease.

23. The method of claim 1 wherein the condition is cell therapy.

24. The method of claim 1 wherein the condition is allergy.

25. The method of claim 1 wherein the condition is a treatment involving the administration of an antigenic moiety.

26. The method of claim 25 wherein the antigenic moiety is a therapeutic protein.

27. The method of claim 1 wherein the disease is a solid tumor wherein B cells promote tumor growth but are not themselves the origin of the tumor.