Reagents and treatment methods for autoimmune diseases

Abstract

The invention concerns treatment methods using anti-CD22 monoclonal antibodies with unique physiologic properties. In particular, the invention concerns methods for the treatment of B-cell malignancies and autoimmune diseases by administering an effective amount of a blocking anti-CD22 monoclonal antibody specifically binding to the first two Ig-like domains, or to an epitope within the first two Ig-like domains of native human CD22 (hCD22).

What is claimed is:  
     
         1 . A method for treating a human patient diagnosed with an autoimmune disease, comprising (1) administering to said human patient an effective amount of a blocking anti-CD22 monoclonal antibody wherein said antibody comprises a heavy chain comprising a V H  sequence having at least about 95% sequence identity with the sequence of amino acids 1 to 100 of SEQ ID NO: 9 (HB22-5 V H  sequence); or amino acids 1 to 97 of SEQ ID NO: 11 (HB22-7 V H  sequence); or amino acids I to 100 of SEQ ID NO: 13 (HB22-13 V H  sequence); or amino acids 1 to 100 of SEQ ID NO: 15 (HB22-23 V H  sequence); or amino acids 1 to 98 of SEQ ID NO: 17 (HB22-33 V H  sequence); or amino acids 1 to 100 of SEQ ID NO: 19 (HB22-196 V H  sequence); and (2) monitoring the response of said autoimmune disease to said treatment.  
     
     
         2 . The method of  claim 1  wherein said antibody comprises a heavy chain comprising a V H  sequence having at least about 95% sequence identity with the sequence of amino acids 1 to 97 of SEQ ID NO: 11 (HB22-7 V H  sequence); or amino acids 1 to 100 of SEQ ID NO: 15 (HB22-23 V H  sequence); or amino acids 1 to 98 of SEQ ID NO: 17 (HB22-33 V H  sequence).  
     
     
         3 . The method of  claim 2  wherein said antibody comprises a V H  sequence selected from the group consisting of amino acids 1 to 97 of SEQ ID NO: 11 (HB22-7 V H  sequence); amino acids 1 to 100 of SEQ ID NO: 15 (HB22-23 V H  sequence); and amino acids 1 to 98 of SEQ ID NO: 17 (HB22-33 V H  sequence).  
     
     
         4 . A method for treating a human patient diagnosed with an autoimmune disease, comprising (1) administering to said human patient an effective amount of a blocking anti-CD22 monoclonal antibody wherein said antibody comprises a light chain comprising a V κ  sequence having at least about 95% sequence identity with the amino acid sequence of SEQ ID NO: 21 (HB22-5 V κ  sequence); or SEQ ID NO: 23 (HB22-7 V κ  sequence); or SEQ ID NO: 25 (HB22-13 V κ  sequence); or SEQ ID NO: 27 (HB22-23 V κ  sequence); or SEQ ID NO: 29 (HB22-33 V κ  sequence); or SEQ ID NO: 31 (HB22-196 V κ  sequence); and (2) monitoring the response of said autoimmune disease to said treatment.  
     
     
         5 . The method of  claim 4  wherein said antibody comprises a light chain comprising a V κ  sequence having at least about 95% sequence identity with the amino acid sequence of SEQ ID NO: 23 (HB22-7 V κ  sequence); or SEQ ID NO: 27 (HB22-23 V κ  sequence); or SEQ ID NO: 29 (HB22-33 V κ  sequence).  
     
     
         6 . The method of  claim 5  wherein said antibody comprises a V κ  sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 23 (HB22-7 V κ  sequence); SEQ ID NO: 27 (HB22-23 V κ  sequence); and SEQ ID NO: 29 (HB22-33 V κ  sequence).  
     
     
         7 . The method of  claim 1  wherein said antibody comprises V H  and V κ  sequences selected from the group consisting of amino acids 1 to 97 of SEQ ID NO: 11 (HB22-7 V H  sequence) and the amino acid sequence of SEQ ID NO: 23 (HB22-7 V κ  sequence); amino acids 1 to 100 of SEQ ID NO: 15 (HB22-23 V H  sequence) and the amino acid sequence of SEQ ID NO: 27 (HB22-23 V κ  sequence); and amino acids 1 to 98 of SEQ ID NO: 17 (HB22-33 V H  sequence) and the amino acid sequence of SEQ ID NO: 29 (HB22-33 V κ  sequence).  
     
     
         8 . The method of  claim 1  wherein said treatment is unaccompanied by any other treatment for the autoimmune disease.  
     
     
         9 . The method of  claim 1  wherein said antibody is a fragment of a complete antibody.  
     
     
         10 . The method of  claim 9  wherein said antibody is selected from the group consisting of Fab, Fab′, F(ab′) 2 , and Fv fragments, diabodies, linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.  
     
     
         11 . The method of  claim 1  wherein said antibody comprises antigen-specificity and is effective to bind to the first two Ig-like domains of a CD22 molecule, or to bind to an epitope within the first two Ig-like domains of native human CD22 (hCD22) of SEQ ID NO: 1, and further has an additional antigen-specificity.  
     
     
         12 . The method of  claim 10  wherein said antibody is a bispecific antibody.  
     
     
         13 . The method of  claim 12  wherein said antibody additionally binds to another epitope of CD22.  
     
     
         14 . The method of  claim 1  wherein said antibody is chimeric.  
     
     
         15 . The method of  claim 1  wherein said antibody is humanized.  
     
     
         16 . The method of  claim 1  wherein said antibody is human.  
     
     
         17 . The method of  claim 1  wherein said antibody is administered intravenously.  
     
     
         18 . The method of  claim 17  wherein said antibody is administered by weekly intravenous infusions.  
     
     
         19 . The method of  claim 1 , wherein said human patient is further administered an anti-CD20 antibody.  
     
     
         20 . The method of  claim 7  wherein said antibody is chimeric.  
     
     
         21 . The method of  claim 7  wherein said antibody is humanized.  
     
     
         22 . The method of  claim 7  wherein said antibody is human.  
     
     
         23 . The method of  claim 4  wherein said treatment is unaccompanied by any other treatment for the autoimmune disease.  
     
     
         24 . The method of  claim 4  wherein said antibody is a fragment of a complete antibody.  
     
     
         25 . The method of  claim 24  wherein said antibody is selected from the group consisting of Fab, Fab′, F(ab′) 2 , and Fv fragments, diabodies, linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.  
     
     
         26 . The method of  claim 4  wherein said antibody comprises antigen-specificity and is effective to bind to the first two Ig-like domains of a CD22 molecule, or to bind to an epitope within the first two Ig-like domains of native human CD22 (hCD22) of SEQ ID NO: 1, and further has an additional antigen-specificity.  
     
     
         27 . The method of  claim 25  wherein said antibody is a bispecific antibody.  
     
     
         28 . The method of  claim 27  wherein said antibody additionally binds to another epitope of CD22.  
     
     
         29 . The method of  claim 4  wherein said antibody is chimeric.  
     
     
         30 . The method of  claim 4  wherein said antibody is humanized.  
     
     
         31 . The method of  claim 4  wherein said antibody is human.  
     
     
         32 . The method of  claim 4  wherein said antibody is administered intravenously.  
     
     
         33 . The method of  claim 32  wherein said antibody is administered by weekly intravenous infusions.  
     
     
         34 . The method of  claim 4 , wherein said human patient is further administered an anti-CD20 antibody.  
     
     
         35 . An isolated nucleic acid molecule comprising nucleic acid encoding an antibody heavy chain variable region comprising a V H  sequence having at least about 95% sequence identity with the sequence of amino acids 1 to 100 of SEQ ID NO: 9 (HB22-5 V H  sequence); or amino acids 1 to 97 of SEQ ID NO: 11 (HB22-7 V H  sequence); or amino acids 1 to 100 of SEQ ID NO: 13 (HB22-13 V H  sequence); or amino acids 1 to 100 of SEQ ID NO: 15 (HB22-23 V H  sequence); or amino acids 1 to 98 of SEQ ID NO: 17 (HB22-33 V H  sequence); or amino acids 1 to 100 of SEQ ID NO: 19 (HB22-196 V H  sequence).  
     
     
         36 . An isolated nucleic acid molecule comprising nucleic acid encoding an antibody light chain variable region comprising a V κ  sequence having at least about 95% sequence identity with the amino acid sequence of SEQ ID NO: 21 (HB22-5 V κ  sequence); or SEQ ID NO: 23 (HB22-7 V κ  sequence); or SEQ ID NO: 25 (HB22-13 V κ  sequence); or SEQ ID NO: 27 (HB22-23 V κ  sequence); or SEQ ID NO: 29 (HB22-33 V κ  sequence); or SEQ ID NO: 31 (HB22-196 V κ  sequence).  
     
     
         37 . An isolated nucleic acid molecule comprising nucleic acid encoding a V H  sequence selected from the group consisting of amino acids 1 to 97 of SEQ ID NO: 11 (HB22-7 V H  sequence); amino acids 1 to 100 of SEQ ID NO: 15 (HB22-23 V H  sequence); and amino acids 1 to 98 of SEQ ID NO: 17 (HB22-33 V H  sequence).  
     
     
         38 . An isolated nucleic acid molecule comprising nucleic acid encoding a V κ  sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 23 (HB22-7 V κ  sequence); SEQ ID NO: 27 (HB22-23 V κ  sequence); and SEQ ID NO: 29 (HB22-33 V κ  sequence).