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 for treating a patient in need thereof with a therapeutic antibody or antigen-binding fragment thereof, comprising administering to said patient in an amount effective for treatment a therapeutic antibody or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity.  
     
     
         52 . The method of  claim 51  wherein said antibody or said antibody fragment is humanized.  
     
     
         53 . The method of  claim 51  wherein said antibody or said antibody fragment does not possess O-linked glycosylation.  
     
     
         54 . The method of  claim 51  wherein the nucleic acids encoding said antibody or said antibody fragment have been mutated to prevent N-linked glycosylation.  
     
     
         55 . The method of  claim 51  wherein the N-linked glycosylation of said antibody or said antibody fragment has been modified chemically.  
     
     
         56 . The method of any one of claims  51 - 55  wherein an active agent is conjugated to said antibody or said antibody fragment.  
     
     
         57 . A therapeutic, humanized antibody or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity.  
     
     
         58 . The antibody or antibody fragment of  claim 57  wherein said antibody or said antibody fragment does not possess O-linked glycosylation.  
     
     
         59 . The antibody or antibody fragment of  claim 57  wherein the polynucleotides encoding said antibody fragment have been substituted or deleted to prevent N-linked glycosylation.  
     
     
         60 . The antibody or antibody fragment of  claim 57  wherein the N-linked glycosylation has been chemically modified post expression.  
     
     
         61 . The antibody or antibody fragment of any one of claims  57 - 60  wherein an active agent is conjugated to said antibody or said antibody fragment.  
     
     
         62 . A method of preparing a therapeutic, humanized antibody, or an antigen-binding fragment thereof, with reduced immunogenicity or toxicity, comprising the steps of: 
 (a) selecting an 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 therapeutic, humanized antibody or an antigen-binding fragment thereof.    
     
     
         63 . A method of preparing a therapeutic, humanized antibody, or an antigen-binding fragment thereof, without N-linked glycosylation to reduce immunogenicity or toxicity, comprising expressing in an expression system a nucleotide sequence comprising nucleic acids encoding a therapeutic, humanized antibody or antigen-binding fragment thereof, wherein said expression system does not N-link glycosylate said antibody or said antibody fragment.  
     
     
         64 . The method of  claim 62  or  63  wherein said antibody or said antibody fragment does not possess O-linked glycosylation.  
     
     
         65 . The method of  claim 62  or  63  wherein an active agent is conjugated to said antibody or said antibody fragment.  
     
     
         66 . A method for imaging target cells in an individual, comprising the steps of: 
 (a) administering to an individual in an amount effective for imaging, an antibody specific for target cells or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity; and    (b) detecting said antibody or said antibody fragment, thereby imaging target cells in said individual.    
     
     
         67 . The method of  claim 66  wherein said antibody or said antibody fragment is humanized.  
     
     
         68 . The method of  claim 66  wherein said antibody or said antibody fragment does not possess O-linked glycosylation.  
     
     
         69 . The method of  claim 66  wherein the nucleic acids encoding said antibody or said antibody fragment have been mutated to prevent N-linked glycosylation.  
     
     
         70 . The method of  claim 66  wherein the N-linked glycosylation of said antibody or said antibody fragment has been modified chemically.  
     
     
         71 . The method of any one of claims  66 - 70  wherein an imaging agent is conjugated to said antibody or said antibody fragment.  
     
     
         72 . The method of  claim 71  wherein the imaging agent is a radionuclide.  
     
     
         73 . The method of  claim 72  wherein the radionuclide is  99m Tc,  111 In or  18 F.  
     
     
         74 . A humanized antibody that is useful for imaging target cells or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity, and said antibody or said antibody fragment is useful for imaging target cells.  
     
     
         75 . The antibody or antibody fragment of  claim 74  wherein said antibody or said antibody fragment does not possess O-linked glycosylation.  
     
     
         76 . The antibody or antibody fragment of  claim 74  wherein the polynucleotides encoding said antibody fragment have been substituted or deleted to prevent N-linked glycosylation.  
     
     
         77 . The antibody or antibody fragment of  claim 74  wherein the N-linked glycosylation has been chemically modified post expression.  
     
     
         78 . The antibody or antibody fragment of any one of claims  74 - 77  wherein an imaging agent is conjugated to said antibody or said antibody fragment.  
     
     
         79 . The antibody or antibody fragment of  claim 78  wherein the imaging agent is a radionuclide.  
     
     
         80 . The antibody or antibody fragment of  claim 79  wherein the radionuclide is  99m Tc,  111 In or  18 F.  
     
     
         81 . 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 an 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.    
     
     
         82 . A method of preparing a humanized antibody, or an antigen-binding fragment thereof, without N-linked glycosylation to reduce immunogenicity or toxicity and said antibody or said antibody fragment is useful for imaging target cells, comprising expressing in an expression system a nucleotide sequence comprising nucleic acids encoding a humanized antibody or antigen-binding fragment thereof that is useful for imaging target cells, wherein said expression system does not N-link glycosylate said antibody or said antibody fragment.  
     
     
         83 . The method of  claim 81  or  82  wherein said antibody or said antibody fragment does not possess O-linked glycosylation.  
     
     
         84 . The method of  claim 81  or  82  wherein an active agent is conjugated to said antibody or said antibody fragment.