Immunoglobulin variants and uses thereof

Abstract

The invention provides humanized and chimeric anti-CD20 antibodies for treatment of CD20 positive malignancies and autoimmune diseases.

1 - 81 . (canceled) 
     
     
         82 : An isolated nucleic acid encoding an antibody that binds to human CD20 or an antigen-binding fragment thereof, wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8 with amino acid substitutions D56A and N100A and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO:2 with amino acid substitution S92A. 
     
     
         83 : A vector comprising the nucleic acid of  claim 82 . 
     
     
         84 : An isolated host cell comprising the nucleic acid of  claim 82 . 
     
     
         85 : An isolated host cell comprising the vector of  claim 83 . 
     
     
         86 : An isolated host cell comprising a first vector comprising a nucleic acid encoding the heavy chain variable region (VH) of an antibody or antigen-binding fragment thereof, and a second vector comprising a nucleic acid encoding the light chain variable region (VL) of the antibody or antigen-binding fragment thereof, wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8 with amino acid substitutions D56A and N100A and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO:2 with amino acid substitution S92A; and wherein the antibody binds to human CD20. 
     
     
         87 : A method of producing an antibody that binds to human CD20 or an antigen-binding fragment thereof, encoded by the nucleic acid present in the host cell of  claim 84 , comprising culturing the host cell under suitable conditions so that the antibody or antigen-binding fragment thereof is produced. 
     
     
         88 : A method of producing an antibody that binds to human CD20 or an antigen-binding fragment thereof, encoded by the nucleic acid in the vector present in the host cell of  claim 85 , comprising culturing the host cell under suitable conditions so that the antibody or antigen-binding fragment thereof is produced. 
     
     
         89 : A method of producing an antibody that binds to human CD20 or antigen-binding fragment thereof, comprising culturing a host cell under conditions so that the antibody or antigen-binding fragment is produced, wherein the host cell comprises a first vector and a second vector encoding the antibody or antigen-binding fragment thereof, wherein the first vector comprises a nucleic acid encoding the heavy chain variable region (VH) of the antibody, and the second vector comprises a nucleic acid encoding the light chain variable region (VL) of the antibody, wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8 with amino acid substitutions D56A and N100A and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO:2 with amino acid substitution S92A. 
     
     
         90 : An isolated nucleic acid encoding an antibody that binds to human CD20 or an antigen-binding fragment thereof, wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8 with amino acid substitutions D56A and N100A and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO:2 with amino acid substitutions S26A, S56A and S92A. 
     
     
         91 : A vector comprising the nucleic acid of  claim 90 . 
     
     
         92 : An isolated host cell comprising the nucleic acid of  claim 90 . 
     
     
         93 : An isolated host cell comprising the vector of  claim 91 . 
     
     
         94 : A method of producing an antibody that binds to human CD20 or an antigen-binding fragment thereof, encoded by the nucleic acid present in the host cell of  claim 92 , comprising culturing the host cell under suitable conditions so that the antibody or antigen-binding fragment thereof is produced. 
     
     
         95 : A method of producing an antibody that binds to human CD20 or an antigen-binding fragment thereof, encoded by the nucleic acid in the vector present in the host cell of  claim 93 , comprising culturing the host cell under suitable conditions so that the antibody or antigen-binding fragment thereof is produced. 
     
     
         96 : A method of producing an antibody that binds to human CD20 or antigen-binding fragment thereof, comprising culturing a host cell under conditions so that the antibody or antigen-binding fragment is produced, wherein the host cell comprises a first vector and a second vector encoding the antibody or antigen-binding fragment thereof, wherein the first vector comprises a nucleic acid encoding the heavy chain variable region (VH) of the antibody, and the second vector comprises a nucleic acid encoding the light chain variable region (VL) of the antibody, wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8 with amino acid substitutions D56A and N100A and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO:2 with amino acid substitutions S26A, S56A and S92A.