Compositions and methods of treating lupus nephritis

Abstract

The invention provides methods for treating or delaying progression of lupus nephritis in an individual that has lupus. In some embodiments, the methods comprise administering to the individual an effective amount of a type II anti-CD20 antibody. The invention also provides methods for treating or delaying progression of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in an individual. In some embodiments, the methods comprise administering an effective amount of an anti-CD20 antibody.

1 . A method for treating or delaying progression of lupus nephritis in an individual that has lupus, comprising administering to the individual at least a first antibody exposure to a type II anti-CD20 antibody and a second antibody exposure to the type II anti-CD20 antibody, the second antibody exposure not being provided until from about 18 weeks to about 26 weeks after the first antibody exposure;
 wherein the first antibody exposure comprises one or two doses of the type II anti-CD20 antibody, the first antibody exposure comprising a total exposure of between about 1800 mg and about 2200 mg of the type II anti-CD20 antibody;   wherein the second antibody exposure comprises one or two doses of the type II anti-CD20 antibody, the second antibody exposure comprising a total exposure of between about 1800 mg and about 2200 mg of the type II anti-CD20 antibody; and   wherein the type II anti-CD20 antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:1, HVR-H2 sequence of SEQ ID NO:2, and HVR-H3 sequence of SEQ ID NO:3, and a light chain comprising HVR-L1 sequence of SEQ ID NO:4, HVR-L2 sequence of SEQ ID NO:5, and HVR-L3 sequence of SEQ ID NO:6.   
     
     
         2 . The method of  claim 1 , wherein the first antibody exposure comprises a first dose of between about 900 mg and about 1100 mg of the type II anti-CD20 antibody and a second dose of between about 900 mg and about 1100 mg of the type II anti-CD20 antibody. 
     
     
         3 . The method of  claim 1 , wherein the first antibody exposure comprises a first dose of the type II anti-CD20 antibody and a second dose of the type II anti-CD20 antibody, and wherein the second dose of the first antibody exposure is not provided until from about 1.5 weeks to about 2.5 weeks after the first dose of the first antibody exposure. 
     
     
         4 - 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the second antibody exposure comprises a first dose of between about 900 mg and about 1100 mg of the type II anti-CD20 antibody and a second dose of between about 900 mg and about 1100 mg of the type II anti-CD20 antibody. 
     
     
         8 . The method of  claim 1 , wherein the second antibody exposure comprises a first dose of the type II anti-CD20 antibody and a second dose of the type II anti-CD20 antibody, and wherein the second dose of the second antibody exposure is not provided until from about 1.5 weeks to about 2.5 weeks after the first dose of the second antibody exposure. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the individual has class III or class IV lupus nephritis, or is at risk for developing class III or class IV lupus nephritis. 
     
     
         14 - 18 . (canceled) 
     
     
         19 . The method of  claim 1 , further comprising administering to the individual an effective amount of one or more of the following:
 (a) an immunosuppressive agent, wherein the immunosuppressive agent comprises mycophenolic acid, a derivative thereof, or a salt thereof;   (b) a glucocorticoid or corticosteroid;   (c) an antihistamine;   (d) a non-steroidal anti-inflammatory drug (NSAID);   (e) an antihypertensive agent; and   (f) a standard of care treatment.   
     
     
         20 - 32 . (canceled) 
     
     
         33 . The method of  claim 1 , wherein the method results in one or more of the following:
 (a) a complete renal response (CRR) in the individual; and   (b) depletion of circulating peripheral B cells in the individual.   
     
     
         34 . (canceled) 
     
     
         35 . The method of  claim 33 , wherein the circulating peripheral B cells are CD19+ B cells. 
     
     
         36 . The method of  claim 1 , wherein the type II anti-CD20 antibody is a humanized or human antibody. 
     
     
         37 . The method of  claim 1 , wherein the type II anti-CD20 antibody is afucosylated. 
     
     
         38 . The method of  claim 1 , wherein the heavy chain of the type II anti-CD20 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:7, and wherein the light chain of the type II anti-CD20 antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:8. 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 1 , wherein the type II anti-CD20 antibody is obinutuzumab. 
     
     
         41 - 44 . (canceled) 
     
     
         45 . A kit for treating or delaying progression of lupus nephritis in an individual that has lupus, comprising:
 (a) a container comprising a type II anti-CD20 antibody, wherein the type II anti-CD20 antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:1, HVR-H2 sequence of SEQ ID NO:2, and HVR-H3 sequence of SEQ ID NO:3, and a light chain comprising HVR-L1 sequence of SEQ ID NO:4, HVR-L2 sequence of SEQ ID NO:5, and HVR-L3 sequence of SEQ ID NO:6; and   (b) a package insert with instructions for treating or delaying progression of class III or class IV lupus nephritis in an individual.   
     
     
         46 - 47 . (canceled) 
     
     
         48 . A method for treating or delaying progression of systemic lupus erythematosus (SLE) in an individual, comprising administering to the individual an effective amount of an anti-CD20 antibody, wherein the antibody comprises a heavy chain variable region comprising an HVR-H1 sequence of SEQ ID NO:1, an HVR-H2 sequence of SEQ ID NO:2, and an HVR-H3 sequence of SEQ ID NO:3, and a light chain variable region comprising an HVR-L1 sequence of SEQ ID NO:4, an HVR-L2 sequence of SEQ ID NO:5, and an HVR-L3 sequence of SEQ ID NO:6. 
     
     
         49 . The method of  claim 48 , wherein the antibody is administered intravenously. 
     
     
         50 - 51 . (canceled) 
     
     
         52 . The method of  claim 48 , wherein the antibody is a humanized or human antibody. 
     
     
         53 . The method of  claim 48 , wherein the antibody is afucosylated. 
     
     
         54 . The method of  claim 48 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7, and wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:8. 
     
     
         55 . (canceled) 
     
     
         56 . The method of  claim 48 , wherein the antibody is obinutuzumab. 
     
     
         57 - 61 . (canceled)