Therapeutic Antibodies

Abstract

A pharmaceutical comprising a therapeutic protein that hinds to a therapeutic target, the protein being modified with a compound that inhibits binding of the protein to the therapeutic target, the modified protein being effective for reducing an immune response against the protein and for producing a therapeutic effect by binding to the therapeutic target. The therapeutic protein may be an antibody that includes an antibody combining site that binds to the therapeutic target.

1 - 34 . (canceled) 
     
     
         35 . A modified therapeutic antibody comprising a cell-binding antibody that includes an antibody combining site that binds to a cell-bound target antigen, said antibody being modified with a peptide that inhibits binding of the antibody to the target antigen, wherein the peptide comprises the target antigen or a domain or mimotope thereof which is reversibly bound to the antibody combining site of the antibody, said modified antibody being effective for reducing an immune response against the antibody and for producing a therapeutic effect by binding to the target antigen. 
     
     
         36 . The modified therapeutic antibody of  claim 35  wherein the peptide bound to the antibody combing site also is linked to the antibody. 
     
     
         37 . The modified therapeutic antibody of  claim 35  wherein the antibody includes a light chain and a heavy chain, and wherein only one of the chains of the antibody has a peptide linked thereto that binds to the antibody combining site. 
     
     
         38 . The modified therapeutic antibody of  claim 35  wherein the avidity of the modified antibody combined with the peptide for the target antigen is at least 4 fold less than the avidity of the unmodified antibody. 
     
     
         39 . The modified therapeutic antibody of  claim 38  wherein the modified antibody has an avidity for the target antigen that is at least 100 fold less than the avidity of the unmodified antibody for the target antigen. 
     
     
         40 . The modified therapeutic antibody of  claim 38  wherein the antibody is an aglycosylated antibody. 
     
     
         41 . The modified therapeutic antibody of  claim 36  wherein the Fc portion of the antibody is aglycosylated. 
     
     
         42 . The modified therapeutic antibody of  claim 36  wherein binding of the antibody to the Fc receptor is essentially eliminated. 
     
     
         43 . The modified therapeutic antibody of  claim 35  wherein the antibody is a non-human antibody. 
     
     
         44 . The modified therapeutic antibody of  claim 35  wherein the antibody is a chimeric antibody. 
     
     
         45 . The modified therapeutic antibody of  claim 35 , wherein the antibody has a peptide reversibly bound to the antibody combining site whereby said target antigen competes for and displaces the peptide from the antibody combing site, said peptide inhibiting binding of the antibody to the target antigen, said modified antibody initially binding to the target antigen in an amount that is lower than the unmodified antibody, with said binding to the target antigen increasing as a result of peptide being displaced from the antibody combining site as the antibody becomes bound to the target antigen. 
     
     
         46 . The modified therapeutic antibody of  claim 36  wherein the antibody is a modified alemtuzumab (CAMPATH-1H) antibody. 
     
     
         47 . The modified therapeutic antibody of  claim 35  wherein the antibody comprises the CD52 mimotope having amino acid sequence QTSSPSAD tethered to alemtuzumab (CAMPATH-1H) light chain V-region by a flexible Glycine4 Serine x2 Linker and (CAMPATH-1H) heavy chain with wild type human IgG1 constant region. 
     
     
         48 . The modified therapeutic antibody of  claim 35  wherein the antibody comprises the CD52 Mimotope having the amino acid sequence QTSSPSAD tethered to alemtuzumab (CAMPATH-1H) light chain V-region by flexible Glycine4 Serine x2 Linker and (CAMPATH-1H) heavy chain with an aglycosyl human IgG1 constant region. 
     
     
         49 . A modified therapeutic antibody of  claim 35  wherein the antibody comprises the CD52 Mimotope having amino acid sequence QTSSPSAD tethered to alemtuzumab (CAMPATH-1H) light chain V-region by flexible Glycine4 Serine x2 Linker and alemtuzumab (CAMPATH-1H) heavy chain with an FcR-mutated human IgG1 constant region. 
     
     
         50 . The modified antibody of  claim 47 , wherein the light chain of the antibody comprises the amino acid sequence of SEQ ID NO 1 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO 2. 
     
     
         51 . The modified antibody of  claim 48 , wherein the light chain of the antibody comprises the amino acid sequence of SEQ ID NO. 1 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO. 2. 
     
     
         52 . The modified antibody of  claim 49 , wherein the light chain of the antibody comprises the amino acid sequence of SEQ ID NO. 1 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO. 2. 
     
     
         53 . A pharmaceutical composition comprising the modified therapeutic antibody of  claim 35 . 
     
     
         54 . A method of treating a disease selected from the group consisting of cancer, rheumatoid arthritis, diabetes, psoriasis, multiple sclerosis, systemic lupus, asthma, myocardial infarction, stroke, and infectious diseases in an animal comprising:
 administering to said animal the modified therapeutic antibody of  claim 35 , wherein said modified therapeutic antibody is administered in an amount effective to treat said disease in said animal.