US2012183472A1PendingUtilityA1

Immunotherapy of b-cell malignancies using anti-cd22 antibodies

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Assignee: GOLDENBERG DAVID MPriority: Mar 24, 1997Filed: Dec 21, 2011Published: Jul 19, 2012
Est. expiryMar 24, 2017(expired)· nominal 20-yr term from priority
Inventors:David M. Goldenberg
A61K 38/00C07K 16/2803A61P 35/02A61K 39/395A61K 39/39558A61P 35/00A61K 2039/507C07K 16/2887A61K 2039/505
66
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Claims

Abstract

B-cell malignancies, such as the B-cell subtype of non-Hodgkin's lymphoma and chronic lymphocytic leukemia, are significant contributors to cancer mortality. The response of B-cell malignancies to various forms of treatment is mixed. Traditional methods of treating B-cell malignancies, including chemotherapy and radiotherapy, have limited utility due to toxic side effects. Immunotherapy with anti-CD20 antibodies have also provided limited success. The use of antibodies that bind with the CD22 or CD19 antigen, however, provides an effective means to treat B-cell malignancies such as indolent and aggressive forms of B-cell lymphomas, and acute and chronic forms of lymphatic leukemias. Moreover, immunotherapy with anti-CD22 and/or anti-CD19 antibodies requires comparatively low doses of antibody protein, and can be used effectively in multimodal therapies.

Claims

exact text as granted — not AI-modified
1 . A therapeutic composition comprising a pharmaceutically carrier and an immunoconjugate comprising an anti-CD22 antibody or fragment thereof conjugated to one or more therapeutic agents selected from the group consisting of a drug and a radioisotope via a free sulfhydryl group in the hinge region of the anti-CD22 antibody or fragment. 
     
     
         2 . The therapeutic composition according to  claim 1 , wherein the therapeutic agent is a radioisotope. 
     
     
         3 . The therapeutic composition according to  claim 2 , wherein the radioisotope is selected from the group consisting of  198 Au,  32 P,  125 I,  131 I,  90 Y,  186 Re,  188 Re,  67 Cu,  211 At,  213 Bi, and  224 Ac. 
     
     
         4 . The therapeutic composition according to  claim 3 , wherein the radioisotope is  131 I. 
     
     
         5 . The therapeutic composition according to  claim 3 , wherein the radioisotope is  90 Y. 
     
     
         6 . The therapeutic composition according to  claim 1 , wherein the therapeutic agent is attached to a free sulfhydryl group at the hinge region of a reduced antibody component via disulfide bond formation. 
     
     
         7 . The therapeutic composition according to  claim 6 , wherein the therapeutic agent is a radioisotope. 
     
     
         8 . The therapeutic composition according to  claim 7 , wherein the radioisotope is selected from the group consisting of  198 Au,  32 P,  125 I,  131 I,  90 I,  186 Re,  188  Re,  67 Cu,  211 At,  213 Bi, and  224 Ac. 
     
     
         9 . The therapeutic composition according to  claim 8 , wherein the radioisotope is  131 I. 
     
     
         10 . The therapeutic composition according to  claim 8 , wherein the radioisotope is  90 Y. 
     
     
         11 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 antibody or fragment thereof is a human antibody or antibody fragment. 
     
     
         12 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 antibody or antibody fragment is a humanized antibody or antibody fragment. 
     
     
         13 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 antibody or antibody fragment is a chimeric antibody or antibody fragment. 
     
     
         14 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 antibody or antibody fragment is a murine antibody or antibody fragment. 
     
     
         15 . The therapeutic composition according to  claim 1 , wherein the therapeutic agent is  131 I and wherein the therapeutic composition delivers a dose of 15 to 40 mCi when administered to a subject. 
     
     
         16 . The therapeutic composition according to  claim 15 , wherein the dose is 20 to 30 mCi. 
     
     
         17 . The therapeutic composition according to  claim 1 , wherein the therapeutic agent is  90 Y and wherein the therapeutic composition delivers a dose of 10 to 30 mCi when administered to a subject. 
     
     
         18 . The therapeutic composition according to  claim 15 , wherein the dose is 10 to 20 mCi. 
     
     
         19 . The therapeutic composition according to  claim 1 , wherein said immunoconjugate is a divalent immunoconjugate in which said therapeutic agents are attached to a carbohydrate moiety and to a free sulfhydryl group. 
     
     
         20 . The therapeutic composition according to  claim 19 , wherein said therapeutic agent is a drug. 
     
     
         21 . The therapeutic composition according to  claim 19 , wherein said therapeutic agent is a radionuclide. 
     
     
         22 . The therapeutic composition according to  claim 1 , additionally comprising a therapeutic agent linked through a carbohydrate moiety in the light chain variable region. 
     
     
         23 . The therapeutic composition according to  claim 1 , additionally comprising a therapeutic composition comprising a naked anti-CD20 antibody, packaged for delivery prior to, concurrently with, or after therapy with the anti-CD22 immunoconjugate. 
     
     
         24 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 immunoconjugate is an internalizing anti-CD22 immunoconjugate, which binds specifically to at least one of epitope A, B, C, D and E. 
     
     
         25 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 immunoconjugate is an internalizing specific anti-CD22 immunoconjugate, which binds specifically to epitope B. 
     
     
         26 . The therapeutic composition according to  claim 23 , wherein the anti-CD22 immunoconjugate is an internalizing anti-CD22 immunoconjugate, which binds specifically to at least one of epitope A, B, C, D and E. 
     
     
         27 . The therapeutic composition according to  claim 23 , wherein the anti-CD22 immunoconjugate is an internalizing specific anti-CD22 immunoconjugate, which binds specifically to epitope B. 
     
     
         28 . The therapeutic composition according to  claim 20 , wherein the drug is selected from the group consisting of nitrogen mustards, alkyl sulfonates, nitrosoureas, triazenes, folic acid analogs, pyrimidine analogs, purine analogs, antibiotics, epipodophyllotoxins, and platinum coordination complexes. 
     
     
         29 . The therapeutic composition according to  claim 20 , wherein the drug is a cancer chemotherapeutic drug. 
     
     
         30 . The therapeutic composition according to  claim 1 , wherein the free sulfhydryl group is generated by cleaving disulfide linkages in an antibody with a thiol reducing agent. 
     
     
         31 . The therapeutic composition according to  claim 30 , wherein the antibody or antibody fragment is a Fab′. 
     
     
         32 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 antibody or antibody fragment is attached directly to the free sulfhydryl group in the hinge region. 
     
     
         33 . The therapeutic composition according to  claim 1 , wherein the anti-CD22 antibody or antibody fragment is an LL2 antibody. 
     
     
         34 . The therapeutic composition according to  claim 12 , wherein the anti-CD22 antibody or antibody fragment is an LL2 antibody. 
     
     
         35 . The therapeutic composition according to  claim 13 , wherein the anti-CD22 antibody or antibody fragment is an LL2 antibody. 
     
     
         36 . The therapeutic composition according to  claim 1 , wherein said therapeutic agent is a drug. 
     
     
         37 . The therapeutic composition according to  claim 34 , wherein said therapeutic agent is a drug. 
     
     
         38 . The therapeutic composition according to  claim 35 , wherein said therapeutic agent is a drug. 
     
     
         39 . The therapeutic composition according to  claim 1 , additionally comprising a naked anti-CD19 antibody, packaged for delivery prior to, concurrently with, or after therapy with the anti-CD22 immunoconjugate. 
     
     
         40 . The therapeutic composition according to  claim 1 , additionally comprising a naked anti-CD74 antibody, packaged for delivery prior to, concurrently with, or after therapy with the anti-CD22 immunoconjugate. 
     
     
         41 . The therapeutic composition according to  claim 23 , wherein the therapeutic agent is a cancer chemotherapeutic drug. 
     
     
         42 . The therapeutic composition according to  claim 39 , wherein the therapeutic agent is a cancer chemotherapeutic drug. 
     
     
         43 . The therapeutic composition according to  claim 40 , wherein the therapeutic agent is a cancer chemotherapeutic drug.

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