Humanized antibodies that bind to cd19 and their uses

Abstract

The present invention relates to humanized antibodies or fragments thereof that bind to human CD19. More specifically, the present invention relates to a humanized antibody or fragment thereof that binds to human CD19 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 31 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 32.

1 - 87 . (canceled) 
     
     
         88 . An isolated nucleic acid encoding a humanized antibody or fragment thereof that binds to human CD19 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 31 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 32. 
     
     
         89 . An isolated nucleic acid comprising the heavy chain encoding nucleic acid sequence of a humanized FMC63 variant that binds to human CD19 as deposited in a microorganism with DSMZ having accession No. DSM 23302. 
     
     
         90 . An isolated nucleic acid comprising the light chain encoding nucleic acid sequence of a humanized FMC63 variant that binds to human CD19 as deposited in a microorganism with DSMZ having accession No. DSM 23303. 
     
     
         91 . A vector comprising the isolated nucleic acid of  claim 88 . 
     
     
         92 . A host cell comprising the isolated nucleic acid of  claim 88 . 
     
     
         93 . A method of producing a humanized antibody or fragment thereof that binds to human CD19, said method comprising culturing the host cell of  claim 92  so that the nucleic acid is expressed and the antibody produced. 
     
     
         94 - 97 . (canceled) 
     
     
         98 . A method of inhibiting growth of tumor cells expressing CD19, comprising contacting the cells with a humanized antibody or fragment thereof that binds to human CD19 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 31 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 32 in an amount effective to inhibit growth of the tumor cells. 
     
     
         99 . The method of  claim 98 , wherein said tumor cells are selected from the group consisting of human Burkitt lymphoma cells, human B cell precursor leukemia cells, human B cell leukemia cells or human B-cell lymphoma cells. 
     
     
         100 . A method of depleting B cells in a subject comprising administering to the subject a humanized antibody or fragment thereof that binds to human CD19 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 31 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 32 in an amount effective to deplete B cells from the subject. 
     
     
         101 . A method for treating a CD19 mediated disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of a humanized antibody or fragment thereof that binds to human CD19 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ NO: 29; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 31 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 32. 
     
     
         102 . The method of  claim 101 , wherein the CD19 mediated disorder is selected from the group consisting of autoimmune disorders including rheumatoid arthritis, cancer, non-Hodgkin's lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia, Burkitt's lymphoma, anaplastic large-cell lymphomas (ALCL), cutaneous T-cell lymphomas, nodular small cleaved-cell lymphomas, peripheral T-cell lymphomas, Lennert's lymphomas, immunoblastic lymphomas, T-cell leukemia/lymphomas (ATLL), adult T-cell leukemia (T-ALL), entroblastic/centrocytic (cb/cc) follicular lymphomas cancers, diffuse large cell lymphomas of B lineage, angioimmunoblastic lymphadenopathy (AILD)-like T cell lymphoma, HIV associated body cavity based lymphomas, Embryonal Carcinomas, undifferentiated carcinomas of the rhino-pharynx (e.g., Schmincke's tumor), Castleman's disease, Kaposi's Sarcoma, Multiple Myeloma, Waldenstrom's macroglobulinemia, anti-CD20 antibody resistant B-cell cancers and other B-cell lymphomas and leukemias. 
     
     
         103 . The method of  claim 101 , wherein the CD19 mediated disorder is selected from the group consisting of non-Hodgkin's lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia, rheumatoid arthritis, systemic lupus erythematosus (SLE), and anti-CD20 antibody resistant B-cell cancers. 
     
     
         104 . The method of  claim 101 , wherein the CD19 mediated disorder is a tumorigenic disorder. 
     
     
         105 - 108 . (canceled) 
     
     
         109 . A vector comprising the isolated nucleic acid of  claim 89  or  90 . 
     
     
         110 . A host cell comprising the isolated nucleic acid of  claim 89  or  90 . 
     
     
         111 . A host cell comprising the vector of  claim 91 .