Anti-cd33 antibodies and method for treatment of acute myeloid leukemia using the same

Abstract

The present invention relates to antibodies that bind CD33. More particularly, the invention relates to anti-CD33 antibodies, fragments and homologues of these antibodies, humanized and resurfaced versions of these antibodies, functional equivalents and improved versions of these antibodies, immunoconjugates and compositions comprising these antibodies, and the uses of same in diagnostic, research and therapeutic applications. The invention also relates to a polynucleotide encoding these antibodies, vectors comprising the polynucleotides, host cells transformed with polynucleotides and methods of producing these antibodies.

1 .- 71 . (canceled) 
     
     
         72 . A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an isolated antibody or epitope-binding fragment thereof that specifically binds CD33, wherein the antibody or epitope-binding fragment thereof comprises:
 (a) a heavy chain (HC) CDR1 comprising the amino acid sequence of GYTFTSYYIH (SEQ ID NO: 58), a HC CDR2 comprising the amino acid sequence of VIYPGNDDIS (SEQ ID NO: 59), and a HC CDR3 comprising the amino acid sequence of EVRLRYFDV (SEQ ID NO: 3); and   (b) a light chain (LC) CDR1 comprising the amino acid sequence of KSSQSVFFSSSQKNYLA (SEQ ID NO: 4), a LC CDR2 comprising the amino acid sequence of WASTRES (SEQ ID NO: 5), and a LC CDR3 comprising the amino acid sequence of HQYLSSRT (SEQ ID NO: 6).   
     
     
         73 . The method of  claim 72 , wherein the antibody or epitope-binding fragment thereof comprises a LC variable region comprising the amino acid sequence of SEQ ID NO: 8. 
     
     
         74 . The method of  claim 72 , wherein the antibody or epitope-binding fragment thereof comprises a LC variable region comprising the amino acid sequence of SEQ ID NO: 10. 
     
     
         75 . The method of  claim 72 , wherein the cancer is selected from acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and pro-myelocytic leukemia (PML). 
     
     
         76 . The method of  claim 72 , wherein the cancer is acute myeloid leukemia (AML). 
     
     
         77 . The method of  claim 72 , wherein the method comprises administering to the subject a therapeutically effective amount of an isolated humanized or resurfaced antibody or epitope-binding fragment thereof that specifically binds to CD33, wherein the antibody or epitope-binding fragment thereof comprises:
 (a) a heavy chain (HC) CDR1 comprising the amino acid sequence of GYTFTSYYIH (SEQ ID NO: 58), a HC CDR2 comprising the amino acid sequence of VIYPGNDDIS (SEQ ID NO: 59), and a HC CDR3 comprising the amino acid sequence of EVRLRYFDV (SEQ ID NO: 3); and   (b) a light chain (LC) CDR1 comprising the amino acid sequence of KSSQSVFFSSSQKNYLA (SEQ ID NO: 4), a LC CDR2 comprising the amino acid sequence of WASTRES (SEQ ID NO: 5), and a LC CDR3 comprising the amino acid sequence of HQYLSSRT (SEQ ID NO: 6); and   wherein the antibody or epitope-binding fragment thereof comprises a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 9 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10, wherein the HC CDR1, CDR2, CDR3 and LC CDR1, CDR2, and CDR3 are unchanged.   
     
     
         78 . The method of  claim 77 , wherein the HC variable region comprises the amino acid sequence of SEQ ID NO: 9 and wherein the LC variable region comprises the amino acid sequence of SEQ ID NO: 10. 
     
     
         79 . The method of  claim 77 , wherein the cancer is selected from acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and pro-myelocytic leukemia (PML). 
     
     
         80 . The method of  claim 77 , wherein the cancer is acute myeloid leukemia (AML). 
     
     
         81 . A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an immunoconjugate comprising an antibody or epitope-binding fragment thereof that specifically binds to CD33 linked to a drug or prodrug, wherein the antibody or epitope-binding fragment thereof comprises:
 (a) a heavy chain (HC) CDR1 comprising the amino acid sequence of GYTFTSYYIH (SEQ ID NO: 58), a HC CDR2 comprising the amino acid sequence of VIYPGNDDIS (SEQ ID NO: 59), and a HC CDR3 comprising the amino acid sequence of EVRLRYFDV (SEQ ID NO: 3); and   (b) a light chain (LC) CDR1 comprising the amino acid sequence of KSSQSVFFSSSQKNYLA (SEQ ID NO: 4), a LC CDR2 comprising the amino acid sequence of WASTRES (SEQ ID NO: 5), and a LC CDR3 comprising the amino acid sequence of HQYLSSRT (SEQ ID NO: 6).   
     
     
         82 . The method of  claim 81 , wherein the antibody or epitope-binding fragment thereof comprises a HC variable region comprising the amino acid sequence of SEQ ID NO: 7 and a LC variable region comprising the amino acid sequence of SEQ ID NO: 8. 
     
     
         83 . The method of  claim 81 , wherein the antibody or epitope-binding fragment thereof comprises a HC variable region comprising the amino acid sequence of SEQ ID NO: 9 and a LC variable region comprising the amino acid sequence of SEQ ID NO: 10. 
     
     
         84 . The method of  claim 81 , wherein the drug or prodrug is selected from the group consisting of a maytansinoid, a taxoid, CC-1065, a CC-106 analog, dolastatin, a dolastatin analog, methotrexate, daunorubicin, doxorubicin, vincristine, vinblastine, melphalan, mitomycin C, chlorambucil, and calicheamicin. 
     
     
         85 . The method of  claim 81 , wherein the drug or prodrug is linked to the antibody or epitope-binding fragment thereof through a linking group selected from the group consisting of a disulfide group, a thioether group, an acid labile group, a photolabile group, a peptidase labile group, and an esterase labile group. 
     
     
         86 . The method of  claim 85 , wherein the linking group is a disulfide group. 
     
     
         87 . The method of  claim 81 , wherein the the drug or prodrug is linked to the antibody or epitope-binding fragment thereof through a cleavable linker. 
     
     
         88 . The method of  claim 81 , wherein the cancer is selected from acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and pro-myelocytic leukemia (PML). 
     
     
         89 . The method of  claim 81 , wherein the cancer is acute myeloid leukemia (AML). 
     
     
         90 . The method of  claim 81 , wherein the method comprises administering to the subject a therapeutically effective amount of an immunoconjugate comprising a humanized or resurfaced antibody or epitope-binding fragment thereof that specifically binds to CD33 linked to a drug or prodrug, wherein the antibody or epitope-binding fragment thereof comprises:
 (a) a heavy chain (HC) CDR1 comprising the amino acid sequence of GYTFTSYYIH (SEQ ID NO: 58), a HC CDR2 comprising the amino acid sequence of VIYPGNDDIS (SEQ ID NO: 59), and a HC CDR3 comprising the amino acid sequence of EVRLRYFDV (SEQ ID NO: 3); and   (b) a light chain (LC) CDR1 comprising the amino acid sequence of KSSQSVFFSSSQKNYLA (SEQ ID NO: 4), a LC CDR2 comprising the amino acid sequence of WASTRES (SEQ ID NO: 5), and a LC CDR3 comprising the amino acid sequence of HQYLSSRT (SEQ ID NO: 6); and   wherein the antibody or epitope-binding fragment thereof comprises a HC variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 9 and a LC variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10, wherein the HC CDR1, CDR2, CDR3 and LC CDR1, CDR2, and CDR3 are unchanged.   
     
     
         91 . The method of  claim 88 , wherein the HC variable region comprises the amino acid sequence of SEQ ID NO: 9 and wherein the LC variable region comprises the amino acid sequence of SEQ ID NO: 10. 
     
     
         92 . The method of  claim 88 , wherein the cancer is selected from acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and pro-myelocytic leukemia (PML). 
     
     
         93 . The method of  claim 88 , wherein the cancer is acute myeloid leukemia (AML).