US2017304438A1PendingUtilityA1

METHODS OF USING ANTI-CD79b IMMUNOCONJUGATES

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Assignee: GENENTECH INCPriority: Sep 23, 2014Filed: Feb 23, 2017Published: Oct 26, 2017
Est. expirySep 23, 2034(~8.2 yrs left)· nominal 20-yr term from priority
Inventors:Andrew PolsonShang-Fan YuYu-Waye ChuMichael Wenger
A61P 35/00A61K 47/6849C07K 16/2887A61K 2300/00A61K 2039/507A61K 45/06A61K 39/39558A61K 47/6889A61K 2039/54A61K 39/3955C07K 16/3061C07K 2317/24A61K 31/4184A61K 31/635A61K 47/6867A61K 2039/545C07K 16/2803A61K 31/553A61K 31/454A61K 47/68031
57
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Claims

Abstract

Provided herein are methods of treating B-cell proliferative disorders in particular Follicular Lymphoma and/or Diffuse Large B-Cell Lymphoma using immunoconjugates comprising anti-CD79b antibodies in combination with additional therapeutic agents.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method for treating a B-cell proliferative disorder in an individual comprising administering to the individual an effective amount of (a) an immunoconjugate comprising an anti-CD79b antibody linked to a cytotoxic agent, (b) an anti-CD20 antibody, and (c) a BCL-2 inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the anti-CD20 antibody is rituximab. 
     
     
         3 . The method of  claim 1 , wherein the anti-CD20 antibody is a humanized B-Ly1 antibody. 
     
     
         4 . The method of  claim 3 , wherein the humanized B-Ly1 antibody is obinituzumab. 
     
     
         5 . The method of  claim 1 , wherein the anti-CD20 antibody is ofatumumab, ublituximab, and/or ibritumomab tiuxetan. 
     
     
         6 . The method of  claim 1 , wherein the BCL-2 inhibitor is 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide and salts thereof. 
     
     
         7 . The method of  claim 1 , wherein the BCL-2 inhibitor is venetoclax. 
     
     
         8 . The method of  claim 1 , wherein the cytotoxic agent is an antimitotic agent. 
     
     
         9 . The method of  claim 8 , wherein the antimitotic agent is an inhibitor of the polymerization of tubulin. 
     
     
         10 . The method of  claim 1 , wherein the immunoconjugate has the formula Ab-(L-D)p, wherein:
 (a) Ab is the antibody which binds CD79b;   (b) L is a linker;   (c) D is the cytotoxic agent and the cytotoxic agent is selected from an auristatin; and   (d) p ranges from 1-8.   
     
     
         11 . The method of  claim 10 , wherein D has formula D E   
       
         
           
           
               
               
           
         
         and wherein R 2  and R 6  are each methyl, R 3  and R 4  are each isopropyl, R 5  is H, R 7  is sec-butyl, each R 8  is independently selected from CH 3 , O—CH 3 , OH, and H; R 9  is H; and R 18  is —C(R 8 ) 2 —C(R 8 ) 2 -aryl. 
       
     
     
         12 . The method of  claim 10 , wherein D is MMAE. 
     
     
         13 . The method of  claim 10 , wherein the linker is cleavable by a protease. 
     
     
         14 . The method of  claim 13 , wherein the linker comprises a val-cit dipeptide or a Phe-homoLys dipeptide. 
     
     
         15 . The method of  claim 13 , wherein the linker is acid-labile. 
     
     
         16 . The method of  claim 15 , wherein the linker comprises hydrazone. 
     
     
         17 . The method of  claim 10  having the formula: 
       
         
           
           
               
               
           
         
         wherein S is a sulfur atom. 
       
     
     
         18 . The method of  claim 17 , wherein p ranges from 2-5. 
     
     
         19 . The method of  claim 18 , wherein the antibody is a monoclonal antibody. 
     
     
         20 . The method of  claim 19 , wherein the antibody is a human, humanized, or chimeric antibody. 
     
     
         21 . The method of  claim 20 , wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:21; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:22; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:23; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:24; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:25; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:26. 
     
     
         22 . The method of  claim 21 , wherein the antibody comprises (a) a VH comprising the amino acid sequence of SEQ ID NO:19 and (b) a VL sequence comprises the amino acid sequence of SEQ ID NO:20. 
     
     
         23 . The method of  claim 10 , wherein the immunoconjugate is polatuzumab vedotin. 
     
     
         24 . The method of  claim 21 , wherein the antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO:36 and (b) a light chain comprising the amino acid sequence of SEQ ID NO:35. 
     
     
         25 . The method of  claim 21 , wherein the antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO:37 and (b) a light chain comprising the amino acid sequence of SEQ ID NO:35. 
     
     
         26 . The method of  claim 21 , wherein the antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO:36 and (b) a light chain comprising the amino acid sequence of SEQ ID NO:38. 
     
     
         27 . The method of  claim 21 , wherein the B-cell proliferative disorder is cancer. 
     
     
         28 . The method of  claim 27 , wherein the B-cell proliferative disorder is lymphoma, non-Hodgkins 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), or mantle cell lymphoma. 
     
     
         29 . The method of  claim 27 , wherein the B-cell proliferative disorder is NHL, such as indolent NHL and/or aggressive NHL. 
     
     
         30 . The method of  claim 27 , wherein the B-cell proliferative disorder is follicular lymphoma. 
     
     
         31 . The method of  claim 27 , wherein the B-cell proliferative disorder is diffuse large B-cell lymphoma. 
     
     
         32 . The method of  claim 31 , wherein the diffuse large B-cell lymphoma is relapsed/refractory diffuse large B-cell lymphoma. 
     
     
         33 . The method of  claim 30 , wherein the follicular lymphoma is relapsed/refractory follicular lymphoma. 
     
     
         34 . A method of treating relapsed/refractory diffuse large B-cell lymphoma in an individual comprising administering to the individual an effective amount of (a) polatuzumab vedotin, and (b) obinutuzumab, and (c) venetoclax. 
     
     
         35 . A method of treating relapsed/refractory follicular lymphoma in an individual comprising administering to the individual an effective amount of (a) polatuzumab vedotin, and (b) obinutuzumab, and (c) venetoclax. 
     
     
         36 . The method of  claim 34 , wherein polatuzumab vedotin is administered intravenously to the individual at a dose of 1.4 mg/kg or 1.8 mg/kg. 
     
     
         37 . The method of  claim 35 , wherein polatuzumab vedotin is administered intravenously to the individual at a dose of 1.4 mg/kg or 1.8 mg/kg. 
     
     
         38 . The method of  claim 34 , wherein obinutuzumab is administered intravenously to the individual at a dose of 1000 mg. 
     
     
         39 . The method of  claim 35 , wherein obinutuzumab is administered intravenously to the individual at a dose of 1000 mg. 
     
     
         40 . The method of  claim 34 , wherein venetoclax is administered to the individual at a dose of 200, 400, 600 or 800 mg by mouth. 
     
     
         41 . The method of  claim 35 , wherein venetoclax is administered to the individual at a dose of 200, 400, 600 or 800 mg by mouth.

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