Recombinant anti-cd4 antibodies for human therapy

Abstract

Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability (in vivo half-life).

1 - 36 . (canceled) 
     
     
         37 . A recombinant DNA molecule which encodes for chimeric antibody specific to human CD4 which antibody comprises the variable heavy and light chain sequences of an Old World monkey monoclonal antibody produced against human CD4 and human constant heavy and light domain sequences, wherein the human constant heavy domain sequences are of the gamma 4 isotype mutated at position 236 by the substitution of leucine for glutamic acid. and at position 229 by the substitution of serine for proline. 
     
     
         38 . The recombinant DNA molecule of claim  1 , wherein the antibody does not bind to Old World monkey CD4. 
     
     
         39 . A recombinant DNA molecule comprising the nucleotide sequence set forth in SEQ ID NO: 11. 
     
     
         40 . A recombinant DNA molecule which encodes and provides for the expression of a chimeric antibody according to claim  1 . 
     
     
         41 . A vector comprising the DNA molecule of claim  1 . 
     
     
         42 . A vector comprising the DNA molecule of claim  2 . 
     
     
         43 . A vector comprising the DNA molecule of claim  2 . 
     
     
         44 . A host cell comprising the vector of any one of claims  5 . 
     
     
         45 . A host cell comprising the vector of any one of claims  6 . 
     
     
         46 . A host cell comprising the vector of any one of claims  7 . 
     
     
         47 . A method for producing a chimeric antibody specific to CD4 comprising expressing the recombinant DNA of claim  1  in a recombinant host cell.