Antibody composition-producing cell

Abstract

The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.

1 - 48 . (canceled)  
     
     
         49 . A glycoengineered, recombinant antibody comprising an Fc region containing N-linked oligosaccharides, wherein said antibody has been engineered to have an increased proportion of nonfucosylated oligosaccharides in the Fc region compared to the corresponding antibody produced by the same host cell that has not been glycoengineered, and wherein said antibody has increased Fc-mediated cellular cytotoxicity as a result of said increased proportion of nonfucosylated oligosaccharides.  
     
     
         50 . A glycoengineered, recombinant antibody comprising an Fc region containing N-linked oligosaccharides, wherein said antibody has been engineered to have an increased proportion of nonfucosylated oligosaccharides in the Fc region compared to the corresponding antibody produced by the same host cell that has not been glycoengineered, and wherein said antibody has increased Fc receptor binding, affinity as a result of said increased proportion of nonfucosylated oligosaccharides.  
     
     
         51 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein the predominant N-linked oligosaccharide in the Fc region is nonfucosylated.  
     
     
         52 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is a chimeric antibody.  
     
     
         53 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is a humanized antibody.  
     
     
         54 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is an antibody fragment that contains a Fc region.  
     
     
         55 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is a fusion protein that includes a Fc region of an immunoglobulin.  
     
     
         56 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein the predominant N-linked oligosaccharide in the Fc region is not a high-mannose structure.  
     
     
         57 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is isolated from an engineered host cell selected from the group consisting of an engineered CHO cell, an engineered BHK cell, an engineered NSO cell, an engineered SP2/0 cell, an engineered yeast cell, and an engineered plant cell.  
     
     
         58 . A glycoengineered, recombinant antibody according to  claim 57 , wherein said antibody is isolated from an engineered CHO cell.  
     
     
         59 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is produced by a host cell that has been genetically manipulated to have altered activity of at least one glycoprotein-modifying glycosyltransferase.  
     
     
         60 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is a therapeutic antibody.  
     
     
         61 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody selectively binds to an antigen expressed by cancer cells.  
     
     
         62 . A glycoengineered, recombinant antibody according to  claim 60 , wherein said antibody is a monoclonal antibody.  
     
     
         63 . A glycoengineered recombinant antibody according to  claim 60 , wherein said antibody is a selected from the group consisting of: an anti-CD20 antibody, an anti-human neuroblastoma antibody, an anti-human renal cell carcinoma antibody, an anti-HER2 antibody, an anti-human colon, lung, and breast carcinoma antibody, a humanized anti-human colorectal tumor antibody, an anti-human melanoma antibody, and an anti-human squamous-cell carcinoma antibody.  
     
     
         64 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is an IgG.  
     
     
         65 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein the majority of the N-linked oligosaccharides in the Fc region of said antibody are nonfucosylated.  
     
     
         66 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said antibody is produced by a process comprising: 
 (a) providing a host cell comprising at least one nucleic acid encoding a recombinant antibody;    (b) genetically manipulating said host cell to alter the activity in said host cell of at least one glycoprotein-modifying glycosyltransferase;    (c) culturing said host cell under conditions which permit expression of the glycoengineered, recombinant antibody; and    (d) isolating said glycoengineered, recombinant antibody.    
     
     
         67 . A glycoengineered, recombinant antibody according to  claim 59 , wherein said antibody is a therapeutic monoclonal antibody having a human Fc region and that selectively binds an antigen expressed by cancer cells, and wherein the majority of oligosaccharides in the Fc region of said antibody are nonfucosylated.  
     
     
         68 . A glycoengineered, recombinant antibody according to  claim 59 , wherein said altered activity comprises altered expression of at least one glycoprotein-modifying glycosyltransferase.  
     
     
         69 . A glycoengineered, recombinant antibody according to  claim 66 , wherein said altered activity comprises altered expression of at least one glycoprotein-modifying glycosyltransferase.  
     
     
         70 . A glycoengineered, recombinant antibody according to  claim 67 , wherein at least 45% of the oligosaccharides in the Fc region are complex structures.  
     
     
         71 . A glycoengineered, recombinant antibody according to  claim 67 , wherein said glycoengineered, recombinant antibody exhibits at least 80% increase in maximal ADCC activity compared to the same antibody produced by the same host cell under identical culture and purification conditions, but which has not been glycoengineered.  
     
     
         72 . A glycoengineered, recombinant antibody according to  claim 49  or  claim 50 , wherein said Fc region containing N-linked oligosaccharides further comprises an increased proportion of GlcNAc residues compared to the corresponding antibody produced by the same host cell that has not been glycoengineered.  
     
     
         73 . A glycoengineered, recombinant antibody comprising an Fc region containing N-linked oligosaccharides, wherein said antibody has been engineered to have an increased proportion of GlcNAc residues in the Fc region relative to the proportion of fucose residues compared to the corresponding antibody produced by the same host cell that has not been glycoengineered, and wherein said antibody has increased Fc-mediated cellular cytotoxicity as a result of said glycoengineering.  
     
     
         74 . A glycoengineered recombinant antibody according to  claim 73 , wherein said GlcNAc residues are bisecting.  
     
     
         75 . A glycoengineered, recombinant antibody according to  claim 73 , wherein said GlcNAc residues are bisecting and wherein said bisected oligosaccharides are of a complex type.  
     
     
         76 . A glycoengineered, recombinant antibody according to  claim 73 , wherein said GlcNAc residues are bisecting and wherein said bisected oligosaccharides are of a hybrid type.  
     
     
         77 . A glycoengineered, recombinant antibody according to  claim 59 , wherein said at least one glycoprotein-modifying glycosyltransferase is GnTIII or Man II.