Therapeutic antibodies

Abstract

A pharmaceutical comprising a therapeutic protein that binds 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 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, the method comprising:
 administering to said animal a modified therapeutic antibody, wherein said modified therapeutic antibody is administered in an amount effective to treat said disease in said animal,   wherein the modified therapeutic antibody comprises 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 method of  claim 35 , wherein the peptide bound to the antibody combining site also is linked to the antibody. 
     
     
         37 . The method 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 method of  claim 35 , wherein the affinity of the modified antibody combined with the peptide for the target antigen is 5 fold less to 100 fold less than the affinity of the unmodified antibody for the target antigen. 
     
     
         39 . The method of  claim 38 , wherein the modified antibody has an affinity for the target antigen that is 20 fold less to 100 fold less than the affinity of the unmodified antibody for the target antigen. 
     
     
         40 . The method of  claim 35 , wherein the antibody is an aglycosylated antibody. 
     
     
         41 . The method of  claim 35 , wherein the Fc portion of the antibody is aglycosylated. 
     
     
         42 . The method of  claim 35 , wherein the antibody does not bind to the Fc receptor. 
     
     
         43 . The method of  claim 35 , wherein the antibody is a non-human antibody. 
     
     
         44 . The method of  claim 35 , wherein the antibody is a chimeric antibody. 
     
     
         45 . The method 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 combining 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 method of  claim 35 , wherein the antibody is a modified alemtuzumab (CAMPATH-1H) antibody. 
     
     
         47 . The method 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 a flexible Glycine4 Serine x2 Linker and (CAMPATH-1H) heavy chain with wild type human IgG1 constant region. 
     
     
         48 . The method 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 a flexible Glycine4 Serine x2 Linker and (CAMPATH-1H) heavy chain with an aglycosyl human IgG1 constant region. 
     
     
         49 . The method 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 a flexible Glycine4 Serine x2 Linker and (CAMPATH-1H) heavy chain with an Fc mutated human IgG1 constant region. 
     
     
         50 . The method 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 method 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 method 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 . The method of  claim 35 , wherein the peptide that is reversibly bound to the antibody combining site of the antibody is displaceable from the antibody combining site in the presence of the target antigen, whereby said target antigen when present displaces the peptide from the antibody combining site as a result of competitive binding.