Methods of use of antibodies with reduced immunogenicity or toxicity

Abstract

Humanized antibodies which bind the NR-LU-13 antigen, conjugates containing such antibodies, and their use in pretargeting methods and conventional antibody therapy and immunodiagnosis are provided.

1 - 50 . (canceled) 
     
     
         51 . A method of reducing immunogenicity or toxicity of a therapeutic antibody or a therapeutic antigen-binding antibody fragment of IgG class, comprising:
 expressing in a plant host system a nucleotide sequence comprising nucleic acid encoding a humanized therapeutic IgG antibody or a humanized therapeutic antigen-binding antibody fragment, wherein said plant host system differentially modifies N-linked glycosylation in the antibody or antibody fragment relative to a mammalian host system so as to yield a humanized therapeutic IgG antibody or a humanized therapeutic antigen-binding antibody fragment with reduced immunogenicity or toxicity.   
     
     
         52 . The method of  claim 51  comprising, prior to the step of expression, the step of selecting a plant host system for the characteristic that said plant host system differentially modifies N-linked glycosylation relative to a mammalian host system, thereby yielding glycoproteins with reduced immunogenicity or toxicity. 
     
     
         53 . The method of  claim 51  wherein said plant host system additionally does not O-link glycosylate the therapeutic antibody or the therapeutic antibody fragment. 
     
     
         54 . The method of  claim 51  wherein said nucleic acid has been mutated to prevent N-linked glycosylation. 
     
     
         55 . The method of  claim 51  wherein said plant host system is from corn. 
     
     
         56 . A method of preparing a humanized antibody, or an antigen-binding fragment thereof, with reduced immunogenicity or toxicity and useful for imaging target cells, comprising the steps of:
 (a) selecting a plant expression system for the characteristic that said system does not N-link glycosylate an antibody or an antibody fragment; and   (b) expressing in said expression system a nucleotide sequence comprising nucleic acids encoding a humanized antibody, or an antigen-binding fragment thereof, that is useful for imaging target cells.   
     
     
         57 . The method of  claim 56  wherein said antibody or said antibody fragment does not possess O-linked glycosylation. 
     
     
         58 . The method of  claim 51  or  56  further comprising isolating the expressed antibody or antigen-binding fragment thereof. 
     
     
         59 . The method of  claim 58  further comprising coupling a radionuclide, drug, antitumor agent, cytokine, hormone or toxin to said antibody or said antibody fragment. 
     
     
         60 . A method of reducing immunogenicity or toxicity of a diagnostic antibody or a diagnostic antigen-binding antibody fragment of IgG class, comprising:
 expressing in a plant host system a nucleotide sequence comprising nucleic acid encoding a humanized diagnostic IgG antibody or a humanized diagnostic antigen-binding antibody fragment, wherein said plant host system differentially modifies N-linked glycosylation in the antibody or antibody fragment relative to a mammalian host system so as to yield a humanized diagnostic IgG antibody or a humanized diagnostic antigen-binding antibody fragment with reduced immunogenicity or toxicity.   
     
     
         61 . The method of  claim 60  further comprising isolating the expressed antibody or antigen-binding fragment thereof. 
     
     
         62 . The method of  claim 61  further comprising coupling a radionuclide, drug, antitumor agent, cytokine, hormone or toxin to said antibody or said antibody fragment. 
     
     
         63 . The method of  claim 60  comprising, prior to the step of expression, the step of selecting a plant host system for the characteristic that said plant host system differentially modifies N-linked glycosylation relative to a mammalian host system, thereby yielding glycoproteins with reduced immunogenicity or toxicity. 
     
     
         64 . The method of  claim 60  wherein said plant host system additionally does not O-link glycosylate the therapeutic antibody or the therapeutic antibody fragment. 
     
     
         65 . The method of  claim 60  wherein said nucleic acid has been mutated to prevent N-linked glycosylation. 
     
     
         66 . The method of  claim 60  wherein said plant host system is from corn. 
     
     
         67 . A method of reducing immunogenicity or toxicity of a humanized antibody or a humanized antigen-binding antibody fragment of IgG class, comprising:
 expressing in a plant host system a nucleotide sequence comprising nucleic acid encoding a humanized IgG antibody or a humanized antigen-binding antibody fragment, wherein said plant host system differentially modifies N-linked glycosylation in the antibody or antibody fragment relative to a mammalian host system so as to yield a humanized IgG antibody or a humanized antigen-binding antibody fragment with reduced immunogenicity or toxicity.   
     
     
         68 . The method of  claim 67  comprising, prior to the step of expression, the step of selecting a plant host system for the characteristic that said plant host system differentially modifies N-linked glycosylation relative to a mammalian host system, thereby yielding glycoproteins with reduced immunogenicity or toxicity. 
     
     
         69 . The method of  claim 67  wherein said plant host system additionally does not O-link glycosylate the antibody or the antibody fragment. 
     
     
         70 . The method of  claim 67  wherein said nucleic acid has been mutated to prevent N-linked glycosylation. 
     
     
         71 . The method of  claim 67  wherein said plant host system is from corn.