Humanized anti-cd22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease

Abstract

The present invention provides chimeric and humanized versions of anti-CD22 mouse monoclonal antibody, HB22.7. The anti-CD22 antibodies of the invention comprise four human or humanized framework regions of the immunoglobulin heavy chain variable region (“VH”) and four human or humanized framework regions of the immunoglobulin light chain variable region (“VK”). The invention further comprises heavy and/or light chain FW regions that contain one or more backmutations in which a human FW residue is exchanged for the corresponding residue present in the parental mouse heavy or light chain. Human or humanized VH framework regions of antibodies of the invention may comprise one or more of the following residues: a valine (V) at position 24 of framework region 1, a glycine (G) at position 49 of framework region 2, and an asparagine (N) at position 73 of framework region 3, numbered according to Kabat. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human CD22 antigen and that preferably mediate human ADCC, CDC, and/or apoptosis for: the treatment of B cell diseases and disorders in human subjects, such as, but not limited to, B cell malignancies, for the treatment and prevention of autoimmune disease, and for the treatment and prevention of graft-versus-host disease (GVHD), humoral rejection, and post-transplantation lymphoproliferative disorder in human transplant recipients.

1 - 17 . (canceled) 
     
     
         18 . A method of treating a B cell malignancy in a human, comprising administering to a human in need thereof a therapeutically-effective amount of a humanized anti-CD22 monoclonal antibody comprising a heavy chain and a light chain, wherein the heavy chain variable region (“VH”) comprises three complementarity determining regions, VH CDR1, VH CDR2, and VH CDR3, and four framework regions, VH FW1, VH FW2, VH FW3, and VH FW4, in the order VH FW1-VH CDR1-VH FW2-VH CDR2-VH FW3-VH CDR3-VH FW4;
 wherein VH CDR1 comprises the amino acid sequence DYGVN (SEQ ID NO:62), VH CDR2 comprises the amino acid sequence IIWGDGRTDYNSALKS (SEQ ID NO:63), and VH CDR3 comprises the amino acid sequence APGNRAMEY (SEQ ID NO:64); 
 wherein the light chain variable region (“VK”) comprises three complementarity determining regions, VK CDR1, VK CDR2, and VK CDR3, wherein VK CDR1 comprises the amino acid sequence KASQSVTNDVA (SEQ ID NO:65), VK CDR2 comprises the amino acid sequence YASNRYT (SEQ ID NO:66), and VK CDR3 comprises the amino acid sequence QQDYRSPWT (SEQ ID NO:67), and wherein 
 (i) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTFS (SEQ ID NO:81); or 
 (ii) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLD (SEQ ID NO:82); or 
 (iii) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLS (SEQ ID NO:83) and VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO:84); or 
 (iv) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLS (SEQ ID NO:83) and VH FW3 comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:86). 
 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 18 , wherein the VH FW2 of the humanized anti-CD22 monoclonal antibody comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO:84). 
     
     
         22 . The method of  claim 18 , wherein the VH FW3 of the humanized anti-CD22 monoclonal antibody comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:86). 
     
     
         23 . The method of  claim 18 , wherein the VH FW4 of the humanized anti-CD22 monoclonal antibody comprises the amino acid sequence WGQGVLVTVS (SEQ ID NO:88). 
     
     
         24 . The method of  claim 18 , wherein VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTFS (SEQ ID NO:81), VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO:84), VH FW3 comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:86), and VH FW4 comprises the amino acid sequence WGQGVLVTVS (SEQ ID NO:88). 
     
     
         25 . The method of  claim 18 , wherein VH FW2 of the humanized anti-CD22 monoclonal antibody comprises the amino acid sequence WIRQAPGKGLEWVG (SEQ ID NO:85), and wherein
 (i) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTFS (SEQ ID NO:81); or   (ii) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLD (SEQ ID NO:82); or   (iii) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLS (SEQ ID NO:83) and VH FW3 comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:86).   
     
     
         26 . The method of  claim 18 , wherein the VH FW3 of the humanized anti-CD22 monoclonal antibody comprises the amino acid sequence RLTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:87), and wherein
 (i) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTFS (SEQ ID NO:81); or   (ii) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLD (SEQ ID NO:82); or   (iii) VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLS (SEQ ID NO:83) and VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO:84).   
     
     
         27 . The method of  claim 18 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 59. 
     
     
         28 . The method of  claim 24 ,
 wherein the VK comprises four framework regions, VK FW1, VK FW2, VK FW3, and VK FW4, in the order VK FW1-VK CDR1—VK FW2-VK CDR2—VK FW3-VK CDR3-VK FW4;
 wherein VK FW1 comprises the amino acid sequence DIVMTQSPSSLSASVGDRVTITC (SEQ ID NO:117), VK FW2 comprises the amino acid sequence WYQQKPGKAPKLLIY (SEQ ID NO:118), VK FW3 comprises the amino acid sequence GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:119) or GVPDRFSGSGYGTDFTLTISSLQPEDFATYFC (SEQ ID NO:126), and VK FW4 comprises the amino acid sequence FGGGTKVEIKRT (SEQ ID NO:127). 
   
     
     
         29 . A polynucleotide molecule comprising a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 55, SEQ ID NO: 57, or SEQ ID NO: 59. 
     
     
         30 . The polynucleotide molecule of  claim 29 , wherein the nucleic acid sequence is SEQ ID NO: 58. 
     
     
         31 . The polynucleotide molecule of  claim 29 , wherein the nucleic acid sequence encodes the amino acid sequence of SEQ ID NO: 59. 
     
     
         32 . The polynucleotide molecule of  claim 31 , which comprises a nucleic acid sequence of a humanized anti-CD22 heavy chain variable region encoded by a plasmid deposited with the American Type Culture Collection having accession deposit no. PTA-7373. 
     
     
         33 . A vector comprising the polynucleotide molecule of  claim 31 . 
     
     
         34 . A mammalian cell comprising the vector of  claim 33 .